Better World Project

Food Storage Technology Improves Consumer Satisfaction

North Carolina State University

 Food Storage Technology Improves Consumer Satisfaction

To provide consumers with the freshest, highest-quality fruits and vegetables, researchers have long been interested in managing the production of ethylene, which is a naturally occurring hormone in fruit that causes ripening, and eventually, softening and rot. Effective quality control methods would mean benefits to consumers such as improved overall tartness and taste.

North Carolina State researchers from the College of Agriculture and Life Sciences, Edward C. Sisler, Ph.D., and Sylvia M. Blankenship, Ph.D., have discovered the secret to keeping fruits and vegetables juicy, crisp and harvest-quality-fresh through storage and the trip to the marketplace. They uncovered 1-MCP (1-methylcyclopropene), a patented technology that provides a method of inhibiting the ethylene response of fruits and vegetables, thereby regulating the ripening process and lengthening the shelf life of produce.

Researchers have discovered the secret to keeping fruits and vegetables juicy, crisp and harvest-quality-fresh through storage and the trip to the marketplace.

Rohm and Hass Company recognized the commercial potential of the university’s discovery and worked with the Office of Technology Transfer to license the ethylene-inhibiting technology. Rohm and Hass formed AgroFresh to develop its product platform. Based on this successful union, AgroFresh developed a product called SmartFresh® a synthetic produce enhancer. Ethylene-sensitive crops such as apples, avocados, bananas, broccoli, cucumbers, leafy vegetables, mangoes, melons, pears, plums and tomatoes are now candidates for longer life spans and fresher taste. SmartFresh® helps drive growth in the produce industry by ensuring that fresh food crops get to market, which means consumers can expect fresher fruits and vegetables year-round.

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Once-a-Day HIV Meds Improve Quality of Life and Hold Promise for Developing Countries

Emory University

Once-a-Day HIV Meds Improve Quality of Life and Hold Promise for Developing Countries

Not so long ago, HIV sufferers took 10 to 15 pills a day and still the outcome was often bleak. Today, more than 80 percent of HIV patients take at least one of the drugs developed by Emory scientists in a single tablet, once a day. Although it’s not a cure, the treatment restores life as it lowers the daily drug regimen burden, diminishes side effects, relieves disease symptoms, and adds longevity.

“They are what we call DNA chain terminators,” explains Liotta. “Think of viral DNA as a line of rail boxcars, the drugs destroy the hitch so no more cars are added. The virus accepts the compounds and mistakes them for normal nucleotides, but they lack a function group necessary to copy the RNA to DNA.”

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Typically, HIV sufferers take a three-drug combination, with Emtriva being one of the three. “Special credit goes to the scientists at Gilead,” says Liotta. “They are the unsung heroes that developed a compression technique to fit a full day’s dosage of all three drugs in a single tablet, and it’s not a ‘horse’ pill.”

“That’s the thing, thousands of people make contributions to the ultimate success of this drug,” says Liotta. Indeed, many people have persevered at getting the drugs to patients around the globe. Gilead and Bristol-Myers Squibb gained FDA approval in 2006 for the first once-a-day, single tablet regimen for adults with HIV called Atripla®. Atripla contains three drugs—efavirenz (Sustiva®), emtricitabine (Emtriva®), and tenofovir disoproxil fumarate (Viread®), combined in one tablet and hence can be used as a stand-alone therapy in patients. Atripla reduces pill burden and simplifies dosing schedules, which not only makes things easier and more tolerable for patients, but also greatly eases storage, transport and distribution of the drug to places with less than ideal conditions.

“Gilead did a tremendous amount of work in stability studies to increase the shelf stability of the drugs in hot, humid climates and poor storage conditions typical in third world countries,” says Liotta.

Atripla is marketed jointly by Gilead and Bristol-Myers Squibb in United States, Canada and Europe, but in much of the developing world, marketing and distribution is handled by Merck & Co., Inc. In addition, Gilead established partnerships with 10 Indian companies to produce and distribute quality, low-cost generic versions of Gilead’s HIV medications in 95 developing countries.

Other industry collaborations include local manufacturing and distribution by South Africa’s Aspen Pharmacare and a manufacturing collaboration in the Bahamas with PharmaChem Technologies and the Grand Bahama Port Authority.

Meanwhile, Gilead is hard at work clearing the political and regulatory paths in developing world countries.

“If you work with import waivers you might get products into a country one month, but not the next,” explains Clifford Samuel, senior director of International Access Operations at Gilead. “We prefer to take the high road and pursue full regulatory approval in each country so that patients have sustainable access to the antivirals they need on an uninterrupted schedule.”

This is no easy task as the regulatory process varies greatly by country and not all governments are motivated by humanitarian concerns. Nonetheless, Samuel and his team continue to push their way through the various regulatory challenges in Africa, Eastern Europe, China, Southeast Asia, Latin America and the Caribbean.

While these highly coordinated efforts seem brilliant in their simplicity, the history of FTC, like other new discoveries, is a bit more convoluted. FTC was licensed by Emory in 1996 to Triangle Pharmaceuticals, a biotech company founded by Schinazi and others in 1995. In 2003, Gilead acquired Triangle for $482 million and in the same year, Emtriva was approved by the FDA. In 2002, Shire and GlaxoSmithKline jointly licensed Emory’s patents related to 3TC, now used in at least 5 products. In 2005, Gilead Sciences and Royalty Pharma signed a deal with Emory to buy its royalty interest for FTC for $525 million. Gilead obtained approval for Truvada®, a fixed-dose combination of Emtriva and Viread in 2004. Today’s combined efforts of Emory, Gilead, Merck and Bristol-Myers have saved millions of lives worldwide.

Although these results are very gratifying, this is far from the end of the story. Emory researchers are expanding their search for more lifesaving drugs.

The new Emory Institute for Drug Discovery will open either late fall or early winter of 2009. Within its walls, scientists will attack several diseases with an unfailing determination to stop their trek across human lives.

“We may not make a fortune, but we will make a difference,” said Liotta.

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Web-based Software Uses Math to Grade Students’ Writing

Univeristy of Colorado, Boulder

Web-based Software Uses Math to Grade Students’ Writing

After 10 years of research, Thomas K. Landauer, Ph.D., a psychology professor at University of Colorado in Boulder, Peter Foltz, Ph.D., a psychology professor at New Mexico State University, and Darrell Laham, Ph.D., a graduate student at University of Colorado, invented Intelligent Essay Assessor (IEA). IEA is Web-based and conducts sophisticated mathematical and statistical evaluations of the semantic content of writing to issue a grade that correlates closely with what teachers or test examiners would give.

IEA automatically assesses and critiques electronically submitted essays providing feedback to both the student and instructor.

IEA allows teachers to assign more writing assignments to students without additional grading time and gives students opportunities to practice and improve their writing abilities.

The software relies on Latent Semantic Analysis to evaluate the quality of the semantic content of writing. Computer modules are used to conduct a mathematical analysis of the semantic space, evaluate the words in the text, compare sections of the essay and integrate the scores from each module to arrive at a final score. IEA can also identify areas of weakness, recommend instructional materials and identify sections in need of rewriting.

Initial funding came through a series of research grants from the National Science Foundation, the Defense Advanced Research Projects Agency, the U.S. Army and the U.S. Air Force. IEA was invented in 1997 and patented in 2002 by Knowledge Analysis Technologies, LLC, a company formed by Landauer, Foltz and Laham. The company was acquired by Pearson Education in 2004 at which time it became known as Pearson Knowledge Technologies. IEA has scored more than two million student essays.


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Molecular Biomarkers Improve Treatment of Colorectal Cancers

University of Southern California USC

Molecular Biomarkers Improve Treatment of Colorectal Cancers

Surgery has always been the most accepted treatment for early-stage colorectal cancers, but a groundbreaking discovery from the Keck School of Medicine at the University of Southern California will likely provide physicians with more treatment options.

In 1998 associate professor of medicine Heinz-Joseph Lenz, M.D., and colleagues David Park, Ph.D., Jan Stoehlmacher, Ph.D., Sheeja Thankappan-Pullarkat, M.D. and Yi Ping Xiong, M.D. discovered a group of biomarkers that are associated with colorectal cancer.

Detecting biomarkers specific to a disease can aid in the identification, diagnosis, and treatment of affected individuals, as well as people who may be at risk but do not yet exhibit symptoms.

Officially called “Medical Diagnostic Predictors of Therapy Response Rate,” this technology will help scientists predict therapy response rates and overall outcomes and survival for patients with colorectal cancer, helping caregivers immediately determine the best methods for treatment.

In 2007 the technology was licensed to Abraxis Bioscience, a biotechnology company located in Los Angeles. The goal of continued research is to combine prognostic markers with specific therapeutic agents, which will allow clinicians to tailor therapy to the molecular profile of the patient while minimizing life-threatening toxicities.

The end result has the potential to improve the overall outcome and survival rate for patients with colorectal cancer.

To see available technologies from research institutions, click here to visit the AUTM Innovation Marketplace.

Synthetic Vitamin D Protects Bone Strength in Kidney Failure Patients

University of Wisconsin Madison

Synthetic Vitamin D Protects Bone Strength in Kidney Failure Patients

A serious side effect from kidney failure is the depletion of vitamin D hormone, which is manufactured by the kidneys and regulates calcium absorption from the intestines. Without adequate levels of vitamin D hormone in the bloodstream, the body cannot process enough calcium from digested food and instead must draw calcium into the blood from the skeleton. Over time this leads to weakened, brittle bones that break easily. To fight this condition, in the early 1990s, scientists at the University of Wisconsin-Madison invented paricalcitol, a synthetic form of vitamin D hormone that regulates calcium in the bloodstream.

Biochemistry professor Hector DeLuca, PhD, led the research team that discovered paricalcitol (now sold commercially as Zemplar™). Initial funding for the research was provided by the National Institutes of Health.

When calcium levels in the blood are low, the parathyroid gland produces parathyroid hormones that trigger calcium release from the bones. During kidney failure the parathyroid gland is in a state of over-production known as secondary hyperparathyroidism. Paricalcitol suppresses the activity of the parathyroid gland and the overproduction of parathyroid hormone by increasing calcium levels in the blood. Paricalcitol is also safer than other vitamin D hormone therapies because it has lower risk for elevating blood calcium to dangerous levels.

Nearly 80 percent of patients on kidney dialysis now receive vitamin D hormone compared to approximately 60 percent in 1999.

The use of vitamin D hormone therapy in chronic kidney disease patients has increased since paricalcitol was commercialized as Zemplar™. Paricalcitol generates more than $30 million each year in royalties for the University of Wisconsin, where research continues for clinical applications of vitamin D in psoriasis, osteoporosis, cancer and a variety of autoimmune/inflammatory diseases.

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Serving a Better Cup of Coffee

University of Guelph

Serving a Better Cup of Coffee

In recent years, the popularity of single-serve coffee makers has increased dramatically. The handy appliances — commonplace in many homes, office break rooms and hotels — provide convenience for consumers, but at a high cost to the environment

The single-serve pods used by these machines generate enormous amounts of waste. Such concerns prompted officials in Hamburg, Germany to ban the purchase of single-serve pods for government buildings. But elsewhere, sales flourish and the pods usually end up in landfills. One estimate suggests that the volume of pods sold each year for one of the most popular brands — the Keurig K-Cup — could circle the globe more than 10 times. Because of that massive waste problem, the K-Cup’s inventor has said publicly that he sometimes regrets his creation.  

Thanks to researchers at University of Guelph, there’s a much more earth-friendly coffee pod available now— one that’s not only compostable, but also incorporates material that coffee roasters would often haul to landfills.
By 2011, Canada’s largest supermarket chain, Loblaws, realized that although consumers loved single-serve coffee, they didn’t love the idea of creating so much waste. Loblaws turned to its supplier, Club Coffee, to identify someone who could create a compostable coffee pod. After two years, Club Coffee still couldn’t find a solution — so the CEO asked Ontario’s deputy minister of agriculture if she knew anyone who might help.
That led to a meeting in January 2014, where Club Coffee explained its predicament to Amar Mohanty, Ph.D., director of University of Guelph's Bioproducts Discovery and Development Centre. Atul Bali, CEO of Competitive Green Technologies, also attended that meeting. He and Mohanty had worked together on previous projects to commercialize university technologies, and they shared an overarching goal: reduce the world’s dependence on petroleum-based plastics by developing bio-based materials made with natural fibers or fillers.
To develop the compostable coffee pod, the biggest challenge was creating the bio-material for the ring that secures the coffee pod’s pouch. That’s because Mohanty needed to design something that was compostable and cost-effective. At the time, Club Coffee’s pods had rings made from polypropylene, a petroleum-based plastic that costs significantly less than typical bio-degradable plastic. “People are very interested in being green, but they aren’t interested in paying more,” says Mohanty, who has studied bio-polymers for more than 25 years. To create a ring that didn’t exceed Club Coffee’s cost requirements, Mohanty knew he would need to add an inexpensive natural fiber to the bio-degradable plastic. He wasn’t sure which fiber he would use — but the material would have to be readily available in large quantities.
After about four months of talking with companies in the coffee industry, Mohanty found his answer. He learned that before coffee beans are roasted, the skin of the bean is removed. It's called chaff, and coffee roasters consider it a waste product. They pay companies to haul chaff away and spread it in fields, dump it in landfills, or burn it. When Mohanty heard that, something clicked. “If I see something going to waste, my mind starts wondering, ‘How can I utilize that?’”
With coffee chaff, Mohanty had an ideal inexpensive natural fiber. The coffee roasters were glad to have their chaff hauled away for free, so Mohanty and his researchers could use it. By September 2014, he had a ring formulation with bio-degradable plastic that consisted of about 25 percent chaff. That allowed Mohanty to reduce the cost sufficiently. What’s more, chaff represented a natural fiber that wouldn’t encounter supply shortages. It’s an important consideration, since supply-chain problems often create big hurdles for bio-based composite materials. Within Canada and the United States alone, Mohanty estimates that roasters produce more than 10 million pounds of chaff each year. His approach has the added benefit of finding value in discarded industrial material. As Bali puts it: “The use of chaff is totally ideal from a waste management perspective — turning waste to value.”
In March 2015, University of Guelph's Catalyst Centre filed a patent on Mohanty’s innovation and exclusively licensed the technology to Competitive Green Technologies in June 2015. It took less than a month to negotiate that license, says Steve De Brabandere, associate director for the University of Guelph's Catalyst Centre. “We’ve done four licensing agreements with them, and we anticipate doing more in the future."
Says Mohanty: “The [Catalyst Centre] was instrumental in making this project a great success. The support we received in commercializing the technology is essential in a project like this. It improves the patenting process and the licensing agreement."
De Brabandere observes that Mohanty’s formulation creates a virtuous circle — it helps keep chaff out of landfills and that chaff allows cost-effective production of compostable pods. He’s also struck by the close working relationship between Mohanty’s research center and Bali’s company, Competitive Green Technologies. It played a critical role in the commercialization of the formulation, he says. “For anything like this, it’s not the type of technology where you make it in a lab and then throw it over the wall,” says De Brabandere. “It’s not like we’ve developed a pharmaceutical drug that isn’t going to change.” Instead, it requires plenty of willingness to tweak.  
Bali agrees. “When you prepare a new material in a laboratory, maybe you use four pounds of it in experiments,” he says. "When you now take that to the real world, the customer is looking for a trial run of 1,000 pounds to put in big molding machines.” That can entail considerable changes to fit real-life manufacturing conditions.
When Mohanty’s formulation first ran through a large molding machine, it didn’t work properly, says Bali. “But we did three iterations and by the third time, we nailed it." By November 2015, Competitive Green Technologies was able to use a mold that produced 64 of the rings every 10 seconds. “Right now, the molder is molding half million rings a day,” says Bali.
The compostable coffee pod that includes the ring is called PurPod100 — it’s a Club Coffee product that is now supplied to large retailers in Canada and the United States, including Loblaws, Kroger, Walmart and Costco. When the Biodegradable Polymer Institute tested the PurPod100 to provide compostable certification, it found that the pod was 100 percent composted in about 45 days. Without the help of several researchers at his center, Mohanty notes that it would have taken much longer to develop the compostable pod. “For this type of product, one person might be able to do it in three or four years if they work very hard,” says Mohanty. “Our team of researchers was able to complete this in less than 18 months."
The single-serve coffee maker at his research center uses the compostable pods — but don’t expect Mohanty to make beverages with those. He’s an avid tea drinker, and one of his next projects involves developing a compostable single-serve pod for tea (it won’t include coffee chaff, because the coffee odor would permeate the tea).
“I’m a nature loving guy,” says Mohanty. “We are trying to save the world from greenhouse gases — so anything I do, I try to focus on being more environmentally friendly.”

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3D Prototyping Technology Cuts Manufacturing Time, Costs

Bowling Green State University

3D Prototyping Technology Cuts Manufacturing Time, Costs

Ceramics are typically manufactured using prototype negative molds. Creating the mold is a time-consuming step that adds extra cost to the manufacturing process.

Faculty at Bowling Green State University (BGSU) in Bowling Green,  Ohio, have developed a rapid prototyping technology that uses a digital file to directly create durable ceramic products that can be glazed and fired in a kiln, without the need for a negative mold. 

This technology eliminates the need for an eleborate manufacturing process while enabling the production of a wide variety of ceramic parts. 

The construction of ceramic objects from digital models technology was developed in 2005-2006 by John Balistreri, Sebastien Dion and Amber Reed. Funding of $50,000 was provided by the BGSU Office of Sponsored Programs and Research. The research team invented specific ceramic recipes and binders that, when used in a rapid prototyping machine, produce fully functional and durable ceramic objects. This technology eliminates the need for negative molds in the manufacturing process. It can produce an unlimited variety of precision, inert and heatresistant ceramic parts, including insulators, gaskets, filters and engine parts.

Architects and designers can create ceramic components directly from digital drawings of portions of walls, floors, and details of custom patterns in 3-D relief without going through  an elaborate production process.  Archaeologists, paleontologists, and  restorers can also use this technology to  quickly complete, reconstruct, or repair ancient fossils or artifacts through 3-D scanning and modeling techniques.  

To see available technologies from research institutions, click here to visit the AUTM Innovation Marketplace.

3-D Virtual Colonoscopies: Changing Attitudes, Reducing Cancer

SUNY Stony Brook

3-D Virtual Colonoscopies: Changing Attitudes, Reducing Cancer

Colorectal cancer is a leading cause of cancer-related deaths worldwide and claims about 677,000 men and women annually, according to the World Health Organization. This cancer burden can be decreased if cases are detected and treated early. Unfortunately, most individuals over 50 avoid the unpleasant and invasive tests that can screen for colorectal cancer or precancerous growths—until now.

A new 3-D Virtual Colonoscopy, also known as computed tomography (CT) colonography, is changing the way people view colorectal screening. It is expected to become more commonly used than a conventional optical colonoscopy thanks to its non-invasive nature. The procedure takes less than 15 minutes and typically requires the patient to drink a contrast solution, which eliminates the need for a harsh purgative prior to the scanning. The patient, without being sedated and after a small tube is inserted in the rectum to inflate the colon with CO2, lays on his/her back and stomach while a CT scan takes pictures of the abdomen and pelvis in several seconds.

This fast, safe and cost effective procedure is based on patented diagnostic 3-D imaging software, techniques and a computer system developed by a Stony Brook University research team led by its inventor, Arie E. Kaufman, a Distinguished Professor and Chairman of the Department of Computer Science who pioneered the field of “volumetric representation.” Unlike an ordinary 2-D computer image, a 3-D volumetric representation is a stack of 2-D images laid on top of each other forming a continuous 3-D space. Development of volumetric representation, which was funded by the National Science Foundation, has led to a number of advances in software for graphics display and graphics acceleration hardware.

By offering the capability to screen lots of people quickly, easily, inexpensively and noninvasively, the  virtual colonoscopy can change the way people throughout the world view colorectal screening and start to save thousands of lives worldwide through early detection and treatment,
Arie E. Kaufman

In the case of the 3-D Virtual Colonoscopy, approved for use in the United States by the Food and Drug Administration, this innovative computer graphics technology puts the CT images together into a high quality 3-D computerized image of the colon so a physician can see 100 percent of its surface vs. the estimated 77 percent with a conventional colonoscopy. After the exam a radiologist can actually “fly through” the patient’s virtual colon, from beginning to end, and around all folds, thoroughly searching for polyps that are as small as a few millimeters. By contrast, a conventional colonoscopy using a fiber optic endoscope is invasive and expensive, and requires a day of preparation involving laxatives and usually a day for the procedure since the patientmust be sedated. A conventional colonoscopy also carries the risk of perforation of the colon wall and even a small risk of death.

To date, more than 100 potentially lifesaving 3-D Virtual Colonoscopy systems have been used in the United States to screen thousands of patients. In 2008, both Siemens Healthcare of Germany and GE Healthcare of General Electric Company signed non-exclusive licenses for the portfolio of innovations developed by Kaufman and his team.


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Assay Pinpoints Natural Killer Cells To Improve Transplant Outcomes

St. Jude Children's Research Hospital

Assay Pinpoints Natural Killer Cells To Improve Transplant Outcomes

A bone marrow or stem cell transplant in which stem cells from a donor (called allogeneic) are transplanted into a patient is often the best chance for a cure for patients with recurrent or resistant cancers such as leukemia and lymphoma.

However, of the roughly 25,000 patients who receive a stem cell transplant each year worldwide, only about half survive, according to the Worldwide Network for Blood & Marrow Transplantation. And until recently, researchers could not accurately predict the outcome of the costly and high-risk transplant procedure.

Insight Genetics hopes to reduce that uncertainty — and increase the success rate of stem cell transplants — by offering a new test to help identify the optimal stem cell donor. The assay, developed by researchers at St. Jude Children’s Research Hospital, provides information on both the patient’s cancer cells and the makeup of receptors on specialized immune cells called natural killer (NK) cells from donor candidates.

This test helps take the guesswork out of donor-patient matching for allogeneic stem cell transplants," says JonEric Pettersson, manager of commercial development at Insight Genetics.

The researcher behind the assay is Wing Leung, M.D., Ph.D., chair of St. Jude’s Department of Bone Marrow Transplant and Cellular Therapy.

The use of the new test will change the choice of stem cell donors in as many as 20,000 of the 25,000 transplants performed each year.
Wing Leung

Using the Immune System to Fight Cancer

Stem cells, which live in the spongy center (called marrow) of certain bones in the body, produce the body’s blood cells — including NK cells — that play a critical role in the immune system to fight off invading germs and cancer cells.A stem cell transplant essentially recruits a whole new defense against the disease by infusing stem cells from a well-matched donor into the patient to attack the cancer.

The Stem Cell Transplant

The majority of stem cell transplants are performed on patients with cancers that originate in blood cells, including leukemia, multiple myeloma and some lymphomas, that are highly resistant to standard treatments.

The stem cell transplantation procedure (also called a bone marrow or cord blood transplant) is typically preceded by chemotherapy and radiation therapy to eliminate as much of the cancer as possible.

“The chemo and radiation are harsh, but if it is effective, you eradicate 99.99 percent of the cancer cells,” says Stephan W. Morris, M.D., chief scientific officer at Insight Genetics. “However, that leaves a tiny percentage of cells that are able in some cases to re-grow and cause a recurrence. In a successful transplantation, the donor cells seek out the latent cancer cells, eradicate them, and you have the potential for a cure.” 

This desired characteristic of the donor cells is called the graft-versus-tumor (GVT) reaction.

Unfortunately, not all transplantations are a success. In some patients, the GVT reaction is robust — but in others, the effect is suboptimal. To better understand the molecular mechanisms that influence GVT in bone marrow transplants, Leung and his colleagues began studying the genetic makeup of NK cells in 2004.

Understanding Natural Killer Cells

Each NK cell has proteins extending from its surface called killer-cell immunoglobulin-like receptors (KIRs) that regulate the cell’s activity. Before NK cells attack and eliminate foreign cells in the body, these receptors must first recognize and bind to proteins or ligands (known as human leukocyte antigens or HLAs) on foreign cells.

Using a specially developed molecular assay to determine the genetic makeup of KIRs, Leung discovered that a specific KIR receptor — KIR2DL1 — varies from person to person. What’s more, he found that this variation in the NK cell’s gene content, as well as the matching between the donor KIR and recipient HLA, affects the strength of the cells’ immune response and its cancer-killing ability following transplantation.

Using the test to retrospectively analyze the outcomes of previous transplant procedures, Leung’s research team determined that NK cells expressing the stronger version of KIR2DL1 destroy cancer cells more effectively than cells expressing the weaker version of KIR2DL1. In a study by Leung and his colleagues published in the Journal of Clinical Oncology, the researchers demonstrated that children with leukemia were much more likely to survive their transplant and their disease was significantly less likely to progress when bone marrow transplants came from donors whose NK cells expressed the stronger form of KIR2DL1.

“It’s a three-fold difference, which is huge,” says Leung.

When HLA ligands in the patient’s body bind to KIRs on the donor’s NK cells, the receptor sends a signal to the NK that either activates or inhibits the attack mechanism. The balance between these activating and inhibiting signals plays an important role in the ability of NK cells to mount an effective GVT response.

Leung and his team also developed a second test to determine the type of HLA ligands present in the patient. The optimal stem cell recipient does not have ligands that will inhibit the donor’s NK cells, a situation referred to as a KIR-KIR ligand mismatch.

Accordingly, Leung had discovered that he could match donor stem cells that express the stronger form of KIR2DL1 with recipients that were less likely to inhibit those cells in order to greatly increase the stem cell transplantation success rates.

A Friend and Partner in Insight Genetics

After filing the patents for the KIR/KIR-ligand assay, St. Jude’s Office of Technology Licensing approached Insight Genetics as they knew the company’s scientific founder well.

Morris co-founded Insight Genetics in 2007 after working as a clinician and researcher on St. Jude’s staff for 25 years — helping to discover and characterize a number of oncogenes (including anaplastic lymphoma kinase, ALK, among others) — before beginning his commercial venture dedicated to providing companion diagnostics to the increasingly personalized treatments for cancer.

“After nearly 30 years in academic medicine I finally decided to scratch my entrepreneurial itch,” says Morris, who left St. Jude and joined the company full-time as chief scientific officer in 2012.

Insight Genetics obtained exclusive, worldwide licensing rights to KIR2DL1 coding sequences and the KIR/KIR-lligand assay, including unique probe and primer designs for developing the test.

The KIR/KIR-Ligand Assay

Now 20 employees strong, the company has been refining the assay for clinical use and plans to begin processing blood samples from donor candidates in its Nashville-based laboratory, Insight Molecular Labs, during the second quarter of 2014.

Depending on demand for the assay, the company may also develop a testing kit that can be sold to individual laboratories and bone marrow registries across the country so they can perform the assay on their own.

The automated KIR/KIR-ligand assay is a quantitative real-time polymerase chain reaction (qPCR)-based test that amplifies, or makes multiple copies of, the specific molecules of interest with a fluorescent label that is detected by an instrument common to clinical laboratories. The company hopes to return test results — indicating the optimal donor based on the presence of the stronger KIR receptor and a KIR-KIR ligand mismatch — within 48 hours.

“There’s a clear utility for this assay for leukemia patients,” says Morris. “But it also has potential for other diseases that are treated with bone marrow transplants.”

Leung says that more and more physicians are referring patients for stem cell transplants earlier in the cancer treatment process, not just at the end-stage of the disease.

“The stem cell transplant has become much safer as the technology has advanced,” he says. “Plus, stem cell transplantation is curative and more patients have access to transplant centers in 42 states now.”

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A Novel Partnership Tackles Meningitis

National Institutes of Health (NIH)

A Novel Partnership Tackles Meningitis

In the middle of 2003, Marc LaForce was having trouble sleeping. As the director of the Meningitis Vaccine Project (MVP), he was missing a vital piece of a difficult puzzle. The MVP sought to commercialize a vaccine that would help prevent Africa’s devastating epidemics of meningococcal meningitis, a bacterial infection of the brain and spinal cord. The largest documented outbreak, in 1996, sickened 250,000 people in Africa and caused 25,000 deaths. In 2002, a single West African country (Burkina Faso) had 13,000 meningitis cases and at least 1,500 deaths.

To succeed, the MVP needed a vaccine production method with two essential qualities: very effective and very affordable. But in mid-2003, that search hit a dead end. "All projects have their ups and downs," says LaForce, M.D. "We were in the downest of downs."

Then, in June 2003, LaForce had a pivotal conversation with Carl Frasch, Ph.D., a Food and Drug Administration (FDA) researcher. Frasch  offered a new method for vaccine production developed by one of his colleagues, Robert Lee. It ultimately led to an unconventional licensing arrangement. The National Institutes of Health (NIH)—FDA's sister agency, responsible for FDA’s technology transfer—didn’t license the production method to a company. Instead, it transferred the technology to PATH, one of the nonprofit organizations that collaborated on the MVP. The result would be a vaccine—MenAfriVac—that could dramatically reduce the meningitis rate in Africa. What’s more, the product-development partnership that emerged could serve as a collaboration model for effectively tackling other public health issues in developing nations.

Debilitating Effects on Patients and Communities

The quest for a better, affordable vaccine began in 2001 with a $70 million grant from the Bill and Melinda Gates Foundation. That funded the creation of the MVP — a partnership between the World Health Organization and PATH, a Seattle, Wash., nonprofit with a public health focus. The MVP’s goal was no small matter, considering the meningitis epidemics that had plagued Africa for decades. The hardest-hit area is known as the African Meningitis Belt, consisting of about 20 countries stretching across the top of sub-Saharan Africa. From 1991 to 2010, nearly 1 million meningitis cases were reported in that area, along with about 100,000 deaths. Other parts of the world did not have the same grim figures. In the United States, for example, there were about 3,200 cases reported from 1998 to 2007, with less than 500 deaths from the disease.

Even when patients receive early diagnosis and treatment for meningitis, a full recovery is not guaranteed. As many as 10 percent of patients do not survive, and up to 20 percent of those who do survive are left with hearing loss, learning disabilities, or brain damage. 

In sub-Saharan African, meningitis is particularly debilitating, even beyond the individuals it infects. That’s because meningitis tends to strike people age 30 and younger, who are often a household's main wage-earner. Says Steven Ferguson, deputy director, licensing and entrepreneurship at the NIH's Office of Technology Transfer: "The disease is quite significant, not only in terms of mortality, but also the economic impact for the patients and their families."

Veering From the Traditional Licensing Path

Vaccines have been available in the African Meningitis Belt for more than 30 years, but they typically provided short-term immunity that sometimes only lasted for several months, and did not help children younger than 2 years old. The MVP wanted to improve this by providing a conjugate vaccine, a particular type of vaccine proven to be more effective. Originally developed by NIH scientists, conjugate vaccines take a polysaccharide molecule from the outer layer of a disease-causing bacteria (in this case,the group A meningococcal bacterium), and attach it to a "carrier" protein. This boosts immunity to the pathogen, helping the immune system to swiftly attack the pathogen even if it invades several years later.  

At the project's outset, LaForce and WHO staff visited Africa to talk with public health officials there. It soon became clear that a more-effective vaccine would not be enough. It had to be affordable — and to African public health officials, that meant a conjugate vaccine costing no more than 50 cents a dose.

It was an audacious goal. In the United States, for example, conjugate vaccines often cost $150 or more, says LaForce.

A Game-Changing Conversation

In early 2003, the MVP leadership thought they had lined up a partnership with a lab that would transfer a conjugation method for the vaccine. But, as LaForce puts it, "It was an arrangement that did not work out." That left the MVP in a precarious spot. In June 2003, LaForce stood in front of a WHO panel in Geneva and informed them that the $70 million project still had no conjugation method. At that moment, the vaccine project did not exactly seem poised for success.

But before he left, LaForce met someone who also happened to be visiting Geneva: Carl Frasch, Ph.D., chief, Laboratory of Polysaccharides, Division of Bacterial Products at the FDA's Center for Biologics Evaluation and Research. LaForce described his predicament, and Frasch told him about a scientist in his lab, Robert Lee, Ph.D., who had developed a new conjugation method. “He said, ‘Why don’t you come and see us?’” says LaForce. "It was a game-changer."  Three days later, LaForce was in Washington, D. C., at the FDA, marveling at what the researchers had developed.

The chemistry used in the conjugation method is not new — it is an existing reaction that has been used for other scientific applications since the 1960s, as Lee is quick to point out. But it had not been used for conjugate vaccine production, due to reliability and reproducibility concerns. The major problem was precipitation in the vaccine, which resulted in the formation  of unwanted solids.

"I was bothered by that,” says Lee. “But then I thought, ‘Hey, there is no reason why it cannot be overcome.’" After more than a year, Lee solved the precipitation problem by keeping the solution pH between 10 and 11. Lee’s refinements led to an extremely efficient method that aligned perfectly with MVP’s goals. As LaForce points out:

If you're going to make vaccine for 250 million people and you're aiming at a cost that's less than 50 cents a dose, you better make sure that the method is one that yields the most product for the amount of raw material that you put in.
Robert Lee

Conjugation methods for vaccines represent highly prized, highly protected intellectual property for pharmaceutical companies. So when the FDA’s conjugation method was licensed to PATH, one of the two organizations behind MVP, it represented a dramatic turning point for the project.

The nonexclusive license transfer to PATH was handled by NIH’s Office of Technology Transfer, which played a vital role, says LaForce.  "When you're developing contracts, they can go on forever," he says. But with the NIH, it only took about four months. “They were enormously helpful in getting this facilitated,” says LaForce, who retired from his MVP director position in 2012. "The whole process moved flawlessly." Conducting these license negotiations on behalf of NIH was Peter Soukas, a technology licensing specialist in the NIH Office of Technology Transfer.

Thanks to the efficient and expedient technology transfer process, the vaccine project finally had the right method, but PATH still needed a manufacturer to produce the vaccine for less than 50 cents per dose. That company turned out to be Serum Institute of India Ltd. (SII), one of the largest suppliers of vaccines globally. SII told LaForce and his colleagues that the company would have to take on significant business risks to manufacture this new vaccine at such a low price. But SII also decided the benefits far outweighed the risks, considering the expertise the company would gain from making this new vaccine and the contribution it would make in solving a substantial public health problem.

As part of the agreement, the FDA shared its conjugate vaccine know-how in a truly collaborative way. Instead of receiving written guidance for the production technique, two scientists came to the FDA lab in December 2003 to gain expertise in person. "For three weeks, we worked side by side, day and night, and produced 12 small vaccine batches," says Lee. "They had never been in the field of conjugated vaccines, so this was a very good head start for them."

A Model to Emulate

After clinical trials demonstrated that the vaccine (named MenAfriVac) was safe and effective, vaccinations began in Africa in 2010. MenAfriVac quickly delivered on its promise of improved immunity. In 2011, three countries that had been involved in the vaccine’s initial rollout — Burkina Faso, Mali, and Niger — had the lowest number of group A meningitis cases ever recorded during an epidemic season.

By the end of 2012, more than 100 million people in Africa had received the vaccine.

Immunity from a single dose is expected to last up to 10 years — compared to previous meningitis vaccines in Africa, where immunity sometimes lasted less than 12 months.

MenAfriVac probably would not have become a 50-cents-per-dose reality without the public-private partnership that unfolded, one that veered from the traditional path of licensing to a pharmaceutical or biotech company. It's a glimpse of the future, one that the NIH wants to facilitate. "This case inspired us to put together a template agreement on our website, so other NGOs [nongovernmental organizations] can see what the general outline would be for an agreement like this,” says Ferguson. “That way, they can seriously consider this pathway in terms of meeting their goal as an organization. Particularly for products that don't have an immediate market in Western countries, we have to think differently in terms of commercialization strategies.”


To see available technologies from research institutions, click here to visit the AUTM Innovation Marketplace.

Abilex Device Restores Patients’ Ability to Speak, Swallow

University of Western Ontario

Abilex Device Restores Patients’ Ability to Speak, Swallow
A man injured in a car crash was able to eat by mouth for the first time in five months after using Abilex. A woman left without speech for three years after her stroke used Abilex and is now able to swallow and speak.
The Abilex device may look simple, but this life-changing product is backed by considerable design, engineering, and research expertise to help people who have difficulty swallowing or speaking exercise and strengthen their jaw, tongue and mouth.

It is the brainchild of Ruth Martin, Professor and Associate Dean for Graduate and Postdoctoral Programs in the Faculty of Health Sciences at Western University in London, Ontario. During her early career as a speech language pathologist in a neuro-rehabilitation clinic, Martin often worked with people who had difficulty swallowing because of strokes, brain injuries or throat and mouth cancers. Therapy was often slow and difficult, with few devices available to retrain both the tongue and the brain that controlled them.
In her later postdoctoral research, Martin worked on the hypothesis that electrical stimulation of the brain could promote swallowing in people who had lost that ability. That’s where her ‘eureka’ moment happened: what if there were an easy-to-use therapy that patients could use to exercise their tongue and jaw, and at the same time help re-wire the ‘swallowing’ parts of their brains?
It had to be lightweight so it wouldn’t overload the jaw; malleable at one end so with little pressure people could get some movement even if they had little muscle control; and have a shape and form that would, without risking their health, help patients stimulate their ‘natural’ ability to wet food into a little ball in their mouths to make it easier to swallow.
It’s this last point that’s key. People with swallowing difficulties often lack the ability to create a swallow-able food ball – sometimes causing them to choke, or aspirate food into their lungs, leading to pneumonia.
Martin’s lab tested several prototypes of various shapes and sizes.  Clinical studies, including functional MRIs at Robarts Research Institute to test the device performance, took place from 2004-09.
WORLDiscoveries, the technology transfer office for Western University, helped Martin secure patents and development funding for the technology and promoted the device to potential licensing partners. In 2009, London-based medical innovator Trudell Medical International picked up the license for the device, which it now makes and markets as Abilex.

To see available technologies from research institutions, click here to visit the AUTM Innovation Marketplace.

Portal Infuses Technology Into K-12 Classrooms

PLS 3rd Learning
Univeristy at Buffalo Office of Science, Technology Transfer and Economic Outreach
University at Buffalo

Portal Infuses Technology Into K-12 Classrooms

If Don Jacobs gets his wish, K-12 classrooms soon will be transformed by disruptive and innovative new teaching methods. He also hopes to be part of that change, through his own innovation: web-based systems that offer teachers a searchable curriculum database, resources and professional development — and certainly through the company he helped establish to commercialize the systems, PLS 3rd Learning.

I hope schools look completely different in 10 years, blending old-fashioned learning with technology,
Don Jacobs, CEO

Becoming an Early Adopter

Jacobs is himself a blend of teacher and techie. When he graduated with a degree in art education from Buffalo State College in 1981, teaching jobs were scarce; the market for personal computers, however, was just emerging. Out of sheer necessity, Jacobs taught himself to use the new technology, which helped him land a position “automating” a New York education service agency.

“That position allowed me to dabble in all areas of the organization, including designing instructional technologies projects,” says Jacobs, who simultaneously completed a doctorate in 1992 at the University at Buffalo (UB) Graduate School of Education of The State University of New York (SUNY) system. “And that led me to want to create a research center at SUNY that focused on using technology to advance K-12 education.”

He went on to establish and direct the Center for Applied Technologies in Education first at Buffalo State College and then at the UB SUNY, from 1995 through 2007.

“We did projects all over the world to advance K-12 education with technologies,” he says.

As the center began focusing on the World Wide Web in the mid 2000s, Jacobs and managing director Paulette Gandel built a web portal to organize New York’s academic learning standards for K-12 with funding from the New York State Department of Education/U.S. Department of Education.

The database, called NYLearns, was first offered for free, and then for a fee to New York school districts, which in turn gave their teachers free access to the web portal.

“We found good resources available through nonprofit organizations and wrote agreements to use those and put them on the web,” says Jacobs. “We were able to put thousands of resources aligned to standards on the site.”

Providing Curriculum Resources

Using NYLearns, a fourth grade math teacher in the Bronx can log on to the web portal and find not only a listing of mathematic concepts students are expected to know by the end of the year, but also sample curricula tied to those academic learning standards.

“There are companies that provide curriculum mapping to inform teachers what has to happen between September and June at every grade level,” says Jacobs. “We also do that, but we add the search feature that makes those standards searchable by grade level, course and subject.”

Over time, the center expanded NYLearns with additional teacher resources, including best practicesand online tools. Using the web portal, English teachers can find time-tested ways to teach the concept of foreshadowing, and math instructors have access to an online whiteboard to show students how moving the parentheses in an order of operations problem changes the calculation.

Arming Teachers With High-Tech Tools

The center staff, which eventually grew to 25 people, equally split between teachers and programmers, also added a point-and-click website builder for teachers to communicate weekly assignments to students and parents and an electronic portfolio tool where instructors can collect ideas and information gleaned from the web.

NYLearns also helps teachers assess how well their teaching methods are working. When the state of New York released 13 years worth of test questions used to assess students — some 30,000 questions — the center attached each question to its academic standard and compiled it all into a searchable database.

“[Using this feature], a teacher can search and find the handful of questions associated with foreshadowing or order of operations and create a practice assessment unit with psychometrically developed questions,” says Jacobs.

Time to Spin Out

After a decade of success with NYLearns — and growing interest in the curriculum and academic standards management system from other states — UB SUNY encouraged Jacobs to consider commercializing the software.

“That launched a conversation with Jeff Dunbar, and then three of us jumped out,” says Jacobs, who was joined in the commercial venture by Michael Horning, Jr., and Robert Daunce.

“It doesn’t happen very often that a faculty member leaves to start an enterprise,” says Jeff Dunbar, director of technology transfer for the UB Office of Science, Technology Transfer and Economic Outreach (STOR). “But Dr. Jacobs was willing because he saw such a great opportunity. He was already running a business within the university; he just had to move it out operationally.”

UB STOR assisted Jacobs’ center with obtaining copyrights and trademarks for its intellectual property, including the database design, portal design and web tools.  In 2007 the technology transfer office also negotiated and executed the license to the new company, which was funded by and became a subsidiary of a private company called Performance Learning Systems (PLS).

“We encouraged Don to work with an attorney but explained the licensing process and milestones and structuring of royalty rates,” says Dunbar.

Initial projects in the company’s pipeline included building a web portal modeled after NYLearns for the state of Pennsylvania called the Standards Aligned System (SAS) and a similar system for the state of Texas now being used by 850 school districts.

Enhancing the Teaching Profession

By accepting sample curricula from teachers, PLS 3rd Learning is able to continually build content for its portals, while supporting and sharing the work of teachers. Contributions are reviewed by three or more instructors who teach at the same grade level and subject. Submitters receive anonymous feedback and after any necessary tweaking, the sample curriculum goes live.

Although the PLS 3rd Learning databases contain more than 40,000 teaching items, Jacobs is quick to point out that the real value of each system lies in the teacher’s ability to contextualize the data.

“Google how to measure the circumference of a circle and you’ll get 8 billion hits, the value of which is 0,” says Jacobs. “We contextualize [that information], so that if you’re teaching fourth grade math in the Bronx to bilingual students, you will find methods for teaching circumference that meet your state’s standards. That puts value through the roof.”

A Boost for Buffalo

In just seven years, PLS 3rd Learning is posting sales of $10.5 million and has grown to a staff of 70, which recently required an expansion of the company’s headquarters in downtown Buffalo.

“Seeing the number of jobs created has been fantastic for Buffalo and its efforts to revitalize,” says Dunbar. “Our licensing fee revenue is just icing on the cake compared to the company’s contribution to the Buffalo economy.”

The company has also been receiving accolades from teachers and administrators using its web portals.

“We have all kinds of really positive feedback, it’s one of the very gratifying things about what we do,” says Jacobs. “After seeing the Pennsylvania web portal, one of the state’s top education policymakers said it made her want to go back into the classroom and teach again.”

In 2012, Jacob’s company merged with PLS and took over management of the parent company, which specialized in professional development.

“Online professional development is a big growth area for us,” says Jacobs.

In addition to providing online courses to educators in Turkey, Switzerland and Portugal, PLS 3rd Learning has recently partnered with the European Council of International Schools to provide professional development to schoolteachers across Europe. The company is also working with the New York State Council of Superintendents to help NY schools prepare to implement novel teaching methods such as the “flipped classroom,” in which students work independently with online materials and then work with the teacher on interactive exercises during class time.

Jacobs is excited to be playing a role in the evolution from classroom-based learning to anywhere, anytime learning.

“Part of it is providing the websites to help teachers and part is the professional development that provides a conceptual framework to prepare teachers for the shift,” he says. “Having the skills and expertise on a systemic level will determine how fast [school systems] get there.”

The Goal: Blended Learning

When Jacobs started his career, the technologies we all take for granted today had not yet transformed the business world.

“Schools are struggling to catch up,” he says. “The transition is now happening in education, and it’s what we call blended learning — the infusion of technology in the classroom.”

It’s just a matter of time, says Jacobs, before technology is ubiquitous in teaching and learning.

“Eventually, calling it blended learning will be redundant. It will just be learning,” he says.

Photo caption: Don Jacobs
Credit: PLS 3rd Learning Staff


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Acadia’s Pest v. Pesticide Challenge

Partnership Seeks “Green” Ways to Save Trees, Crops

Acadia University
Dalhousie University
University of New Brunswick

Acadia’s Pest v. Pesticide Challenge

If insects had their way, you wouldn’t be able to see the forest or the trees.

Every year bugs, beetles and like-minded pests chomp their way through millions of hectares of forest and farmland, according to Canadian government figures. But with rising concerns about the adverse environmental and health effects of traditional pesticides, a major push is under way to develop more “green” approaches to pest management—and not just in Canada but around the world.

Researchers at Acadia University in Nova Scotia are in the forefront of this movement. The effort is led by biology professor Kirk Hillier, an internationally recognized expert in how insects use naturally produced semiochemicals such as pheromones to communicate with one another. Pheromones can signal alarm, attract prey, repel enemies and lure potential mates.

It’s that last category that interests those working to protect the country’s crops and forests. Hillier’s team and its partners have developed and marketed several products that disrupt the mating behaviours of targeted groups of pests, among them the brown spruce longhorn beetle, the emerald ash borer and the jack pine budworm. These products include traps, lures and sprays to attract, repulse or confuse the intended recipients.

In 2017 Canada committed nearly $3 million from the Atlantic Canada Opportunities Agency to the project, which supporters hope will reduce the billions of dollars in damage caused by native and foreign insects, while simultaneously protecting the environment.

Acadia’s key partners include Forest Protection Limited (FPL), a nonprofit company that operates customized aircraft used for firefighting and aerial surveys in addition to vegetation and pest management. FPL says field trials of sex pheromones and biological insecticides using its state-of-the-art delivery techniques “allow us to optimize low-volume delivery with the maximum benefit to the forest and people.

Other partners include National Resources Canada, the University of New Brunswick and Dalhousie University.

Federal Environment Minister Catherine McKenna said the research “has the potential to create effective and environmentally responsible, pheromone-based products that will be marketed in Canada and internationally.

To see available technologies from research institutions, click here to visit the AUTM Innovation Marketplace.

ACE Inhibitors Found to Treat Diabetic Nephropathy

Brigham & Women's Hospital

ACE Inhibitors Found to Treat Diabetic Nephropathy

For those with high blood pressure, angiotensin-converting enzyme inhibitors (ACE inhibitors) are a dream come true. By opening arteries, these drugs lower blood pressure and the resultant strain on the heart.

But it turns out that ACE inhibitors yield other medical benefits as well. Barry Brenner, M.D., of Brigham and Women’s Hospital in Boston and Ronald D. Smith, M.D., formerly of Merck & Co., Inc. found that ACE inhibitors can benefit those suffering from diabetic nephropathy.

Diabetic nephropathy is one of the potentially serious complications associated with diabetes, and it stems from uncontrolled high blood sugar. High blood sugar levels can damage nephrons — the miniscule tube-like units that filter fluid and other substances from the blood stream. If left unchecked, diabetic nephropathy can lead to kidney failure.

Diabetic nephropathy is the leading cause of kidney failure in Americans, affecting up to 40 percent of those with diabetes.

The scientists discovered that by lowering blood pressure, one could also lower pressure in the glomerulus — the cluster of capillary blood vessels that filter blood in the kidney. As a result, kidney life can be prolonged indefinitely in many patients suffering from diabetic nephropathy. Today, kidney patients around the world are treated with ACE inhibitors.


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Activated-Carbon Fabric Garments Absorb Viruses, Toxins and Other Deadly Contaminants

Feng Chia University

Activated-Carbon Fabric Garments Absorb Viruses, Toxins and Other Deadly Contaminants

What can help people resist the SARS virus, or protect them from contaminated water and air, or electromagnetic waves? The answer is a highly absorbent material called “PAN-Based Activated Carbon Fabrics” that was invented at Feng Chia University in Taiwan.

The development of this material, discovered by professor Tse-Hao Ko in 1995, was funded in part by the Taiwan National Science Council. It was licensed in 1996 to Taiwan Carbon Technology Co., CCTeks Co. and CeTech Co.

Polyacrylonitrile (PAN)based activated carbon fibers are superior to pitch-based, cellulose-based, and Phenol resin-based activated carbon fibers for mechanical strength and absorbency.

The proprietary process that transforms activated carbon powder to carbon fiber results in a high density of air holes in the carbon fiber, creating higher absorbency. The PAN-based fiber bundles are oxidized first and then activated in a carbon dioxide atmosphere at a temperature of 1,652 degrees Fahrenheit (900 degrees C.)

Garments containing activated carbon fabrics are 40 percent lighter than other protective clothing worn by U.S. soldiers in Iraq.

PAN-based activated fibers can be woven into yarn, thread or cloth. This highly absorbent fabric can be used in a variety of ways, including in disposable respirators, medical protective garments that guard against virus transmission, protective gear for nuclear and biochemical attacks, as well as filters for air and drinking water. 

To see available technologies from research institutions, click here to visit the AUTM Innovation Marketplace.

Activator Puts the Brakes on Cancer

University of California, Berkeley (UC Berkeley)

Activator Puts the Brakes on Cancer

As a kid, James Allison loved to figure out how things worked.

“I wanted to be the first person on the planet to know something before anyone else,” says Allison, who prepared for a life of discovery by pursuing a bachelor’s degree in microbiology and a doctorate in biological sciences.

After 20 years of intense laboratory research studying the body’s immune system, he got his wish.

Using Allison’s pioneering work, the biotechnology company, Medarex, in partnership with Bristol-Myers Squibb, developed Yervoy, the first drug ever shown to significantly improve overall survival for patients with advanced metastatic melanoma, the deadliest form of skin cancer.

Twenty-five percent of patients treated with Yervoy are still alive four-and–a-half years later, We can’t call it a cure, but what we’re seeing is a durable response.
James Allison

Melanoma: Rare but Lethal

Melanoma, the most dangerous form of skin cancer, is caused by uncontrolled growth in pigment-producing skin cells.

Highly curable in the early stages, melanoma can often be surgically removed. However, the disease is more likely than other skin cancers to metastasize, or spread to other parts of the body, making treatment more difficult. In the late stages of metastatic melanoma, the average survival rate is just six months.

According to the American Cancer Society (ACS), melanoma accounts for less than 5 percent of all skin cancer cases, but the vast majority of skin cancer deaths. The ACS estimates that in 2012, 76,250 Americans will be diagnosed with melanoma, and 9,180 will die from the disease.

“Metastatic melanoma is one of the most aggressive forms of cancer and, despite the rising incidence, no new treatments had been approved in more than a decade before Yervoy,” says Sarah Koenig, spokesperson for Bristol-Myers Squibb.

Harnessing the Immune System

Unlike chemotherapy, which treats the tumor directly, Yervoy is part of an emerging class of treatments known as immunotherapy, which harnesses the body’s own immune system to fight tumors.

In a healthy immune system, foreign bacteria and viruses as well as transformed cancer cells bear molecular structures called antigens that identify them to the immune system as dangerous. A type of immune cell called the T-cell plays a key role in the body’s defensive response to these dangers. However, T-cells attack antigen-bearing targets only when given a green light to do so. To prevent the body from attacking its own normal cells, the immune system has a series of checkpoints that operate like traffic lights, sending signals that either activate or inhibit T-cells.

As a professor in the Division of Immunology and director of the Cancer Research Laboratory at the University of California, Berkeley (UCB), Allison devoted himself to studying the immune response to cancer — and how the disease proliferates by selectively suppressing T-cell activation.

In 1995, he showed that a checkpoint molecule called cytotoxic T lymphocyte antigen-4 (CTLA-4) puts the brakes on T-cell responses. Block CTLA-4, theorized Allison, and the immune system could be activated, unleashing a robust antitumor response. In preclinical experiments, he successfully demonstrated that he could bind a special type of protein called a monoclonal antibody to CTLA-4, preventing it from interfering with T-cell activation.

Finding a Commercial Partner

For help in the patenting process and finding a commercial partner, Allison turned to UCB’s Office of Intellectual Property (IP) and Industry Research Alliances. It turned out to be a long and winding road to commercialization.

“In the early ‘90s, companies were not interested in commercializing IP rights due to lack of what’s known as ‘proof of clinical mechanism,’” says Carol Mimura, Ph.D., assistant vice chancellor, IP and Industry Research Alliances. “As a university without a medical school, we couldn’t advance the opportunity beyond preclinical stages, but we took a risk on pursuing a broad patent portfolio because Dr. Allison convinced us that we had a world-changing opportunity.

“Essentially, we were betting on Dr. Allison and his research team, just as a venture capitalist bets on the management team of a startup company,” explains Mimura.

The technology was originally licensed to NeXstar Pharmaceuticals, which merged with the biopharmaceutical company, Gilead Sciences Inc.  Gilead sublicensed the rights to Medarex, which developed a human monoclonal antibody and began testing in partnership with Bristol-Myers Squibb.  Bristol-Myers Squibb acquired Medarex in 2009.

“Two startup companies took the risk of performing lengthy and expensive R&D [research and development] for more than a decade on an unproven opportunity,” Mimura says of NeXstar and Medarex. “Entrepreneurship and dogged determination resulted in a product that the pharmaceutical industry was able take to the finish line.”

In clinical trials, the antibody — named ipilimumab — added months to the survival rates of patients with advanced melanoma, something no other drug had been able to achieve. Based on the results of a randomized, double-blind Phase III study, the drug was fast-tracked and approved from the U.S. Food and Drug Administration in March of 2011.

“Yervoy provided a critical missing piece to the cancer immunotherapy armamentarium and was a game-changer not only for melanoma patients who desperately needed new treatment options, but also for the entire field of cancer immunotherapy,” says Jill O’Donnell-Tormey, Ph.D., CEO and director of scientific affairs for the Cancer Research Institute in New York. “We expect Yervoy and other types of treatments that block the immune system’s ‘off switches’ will potentially help patients with any type of cancer, and if used in combination with cancer vaccines or conventional cancer treatments, could help a much larger percentage of patients.”

Unleashing T-Cells on Cancer

To date, more than 10,000 cancer patients have received Yervoy in clinical trials to treat advanced melanoma and other types of cancer, either alone or in combination with other drugs. Immunotherapy is a key area of focus at Bristol-Myers Squibb, which is also testing the use of Yervoy to treat specific prostate cancers and both small-cell and non-small-cell lung cancer.

“This treatment is unique in that it recruits the immune system to fight the cancer,” says Mimura. “It’s also nonspecific to a given tumor type. Clinical trials are now under way for prostate, breast, lung and other cancers.”

Allison says that unlike other drug therapies, which have short half-lives, T-cells, once activated, stay in the body for decades or maybe even a lifetime.

“One of the reasons so-called miracle drugs don’t work is because they only last in the system a short amount of time, and 85 percent of the time the cancer comes back because you can’t get every cancer cell,” says Allison. “If you try to kill cancer, it’ll beat you every time because it mutates.”

Over the years, Allison has had the opportunity to meet several patients who, thanks to Yervoy, have survived much longer than expected.

 “I met a woman who participated in our very first clinical trial 12 years ago,” he says. “That’s one of the hallmarks of immunotherapy. Once it works, it’s permanent.”

Funding Fundamental Research

Mimura and Allison say the success of Yervoy underscores the importance of conducting and funding basic research.

“Dr. Allison transformed the field of immunology and achieved clinical success by performing basic research on T-cells,” says Mimura. Adds Allison, “It’s satisfying that I could come up with this only by getting under the hood and seeing how things work.”

According to Mimura, both federal dollars — through National Institutes of Health — and later, private funding from the Howard Hughes Medical Institute, played critical roles in Allison’s discovery.

“We hit several valleys between federal grants that could have spelled death for the project,” she says. “A vital $50,000, no-strings-attached grant from Michael Milken’s CaP CURE  (now the Prostate Cancer Foundation) provided Dr. Allison’s laboratory with much-needed bridge funding at a very critical time.”

The tenacity of everyone involved paid off when it came time to negotiate a drug royalty monetization agreement with Bristol-Meyers Squibb: UCB received an upfront payment of $87.5 million — the biggest win to date for the university’s IP office — with the possibility of additional future payments if sales achieve certain pre-specified levels. The university directed funds toward a myriad of scientific research needs, from faculty retention, new biology teaching labs and equipment for the cancer research lab to a new building devoted to stem cell research.

Today, Allison is chair of the Immunology Program at the Sloan-Kettering Institute in New York City, where he is working side by side with physicians to increase the number of patients who respond to Yervoy by combining it with other cancer treatments.

“I believe we can increase survival rates by using cancer treatments that shrink the tumor, and then coming in behind them and taking the brakes off the immune system,” he says. “It’s just a matter of finding the appropriate pairing of therapies.”

Allison’s lifelong quest for new discoveries also continues: He’s currently on the hunt for other molecules that interfere with the body’s natural immune response.

“I’m proud to have turned a scientific finding into something that benefits a lot of people,” he says. “I hope to do it again.”

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Acuvane: Maximizing wind turbine clean-electricity generation

École de technologie supérieure

Acuvane: Maximizing wind turbine clean-electricity generation
Wind farm in Gaspésie - Québec

It might not look like it to peer at the large blades of a wind turbine, but if one vane is misaligned by just five degrees, the resulting energy could blow away millions of dollars. This problem often makes the production of clean electricity still more expensive than producing fossil-fuel energy.

For a 100-megawatt wind farm of 150 turbines, this could represent $20 million in losses over 20 years,” said Francis Pelletier, PhD in wind-energy production at Montréal's École de technologie supérieure (ETS).
As the world faces an ecological crisis and unprecedented economic challenges, Pelletier and his academic supervisor, Souheil-Antoine Tahan from ETS’s Department of Mechanical Engineering, agreed to adapt existing technology to solve this problem. Their research revealed that a wind turbine misaligned by five degrees can cause a 1% energy loss, and the idea of an alignment process to calibrate wind turbine blades caught on.
“It must also be robust, feasible and cheap,” Tahan said.

After five years of effort, the researchers invented the first laser wind-vane aligner. This new technology enables wind turbines to be oriented as precisely as possible in the wind direction, enabling energy savings of 1 to 2%; for one 100-megawatt wind farm this powers an additional 200 to 250 homes. The improved precision considerably reduces stress on mechanical components and extends their lifespan. In the future, Francis hopes that wind energy alone will be enough to power all major cities around the world.
In 2011, the invention was declared to Aligo Innovation, the outside technology-transfer firm that took the lead to protect the intellectual property and undertake the process of licensing it.
It was exclusively licensed to TECHÉOL, a company specializing in technical services for wind farms, to use, manufacture and sell the laser wind-vane alignment system. The technology is now marketed under the name ACUVANE™.

“TECHÉOL is very proud to be the exclusive distributor of this invention, which already allows us to export this service outside Québec, in addition to helping us promote our other services to our customers,” said Evan Mulrooney, Founder and co-owner of TECHÉOL.

Patent Number(s): US: 14,067,206; Canadian: CA 2,832,070; Mexican: MX a,2013,012718

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Adaptive Technologies Ideal for Small, Adjustable Camera Lenses

University of Central Florida

Adaptive Technologies Ideal for Small, Adjustable Camera Lenses

A scientist at the University of Central Florida’s Center for Research and Education in Optics and Lasers (CREOL) in Orlando has invented adaptive lenses that change their light focusing properties in response to stimulus such as electrical current and mechanical pressure. Adjusting the pressure in the lens changes the level of magnification without having to rely on moving, mechanical parts the way standard cameras do.

The first patent application for professor Shin-Tson Wu’s “Adaptive Liquid Crystal Lens” was submitted in 2002. Funding for the research, which has been ongoing for five years, is provided by the U.S. Air Force, the University of Central Florida, and the private sector. Wu’s portfolio of adaptive lens technologies have been licensed by Holochip Corp., in Albuquerque.

Unlike conventional cameras that use mechanical controls to adjust focus, the Adaptive Liquid Crystal Lens uses liquid crystal technology to provide the focus and zoom capability, without the need for moving mechanical parts.

The excitation of the liquid crystal through electrical current works like a LCD monitor in that the electrical current decides the shape of the lens, thus producing the effect of zooming or focusing.  As a second approach, Wu’s fluidic lens uses a transparent fluid encapsulated by a transparent elastic membrane.  Mechanical compression of the fluid causes the membrane surface to bulge, thereby changing its curvature and the focal length of the lens.

These technologies make it possible to produce very small lenses, something that is prohibitively expensive for conventional mechanical lenses.

The liquid crystal and fluidic lenses are ideal for cell phone cameras and other image-capturing systems, including surveillance equipment for the military. Medical applications are also of interest, such as implantable lenses for eyes, or replacement lenses, that are made from biocompatible materials.

To see available technologies from research institutions, click here to visit the AUTM Innovation Marketplace.

Adenocard Helps Patients with Abnormally Rapid Heartbeats

University of Virginia

Adenocard Helps Patients with Abnormally Rapid Heartbeats

Paroxysmal supraventricular tachycardia (PSVT) can best be described as an abnormally rapid series of heartbeats that can last anywhere from a few minutes to a few hours. It typically surfaces for the first time in childhood or early adulthood, although the first episode may manifest itself at any age, and it is not indicative of an abnormal heart condition.

Patients experience the disturbing sensation of a heart pounding from 140 to 200 beats or more per minute.

While the number of people affected by this heart disturbance is not known, its consequences can be serious. Since the heart is beating so rapidly, it cannot rest between beats, and as a result, the heart’s chambers cannot contract sufficiently or become filled with enough blood, leading to inadequate supplies of blood to the body. When this occurs, the patient experiences dizziness and/or breathlessness.

Research conducted at the University of Virginia yielded an effective treatment for PSVT: Adenocard®. By slowing down the heart’s electrical conduction, Adenocard® — an injection-based treatment — in turn slows the heart rate. It was developed by the late Robert M. Berne, M.D., a professor emeritus of physiology, and Luiz Belardinelli, M.D., and was first patented in 1982. Today, Adenocard® is used widely in hospitals and emergency vehicles around the world.

To see available technologies from research institutions, click here to visit the AUTM Innovation Marketplace.

Invention Holds the Promise of Earlier, More Accurate Alzheimer's Detection

University of Glasgow

Invention Holds the Promise of Earlier, More Accurate Alzheimer's Detection

Diagnostic Potentials Ltd., a spin-off from the University of Glasgow, has completed a pivotal clinical trial demonstrating that the ADEPT System can detect Alzheimer’s at an early stage. Coupling dense array EEG with a computer program designed to test patient’s cognitive skills, this technology may revolutionize the way clinicians diagnose a degenerative and highly debilitating disease.

It looks like an elaborate hairnet, or a strange wig of wires, and those who place it on their heads work at a computer terminal. While it sounds like the setup for some kind of virtual reality game, in fact it is not.

This cutting-edge technology that may hold the key to the early and accurate diagnosis of a dreaded disease.

Alzheimer’s, a progressive and degenerative disease, continues to stymie clinicians, drain nations’ economies and shatter many lives. Currently, the diagnosis of early stage Alzheimer’s dementia is difficult because affected individuals display symptoms that appear to be part of the normal aging process. Yet it is during the early phase in the disease’s development that an accurate diagnosis would be most beneficial and allow for more effective intervention.

Diagnostic Potentials, located in Glasgow, Scotland, is on track to develop the missing diagnostic tool. A spin-off from the University of Glasgow’s department of psychology, the company has gotten off the ground with the help of funding from United Kingdom government research trust funds. With the completion of the first clinical trial to evaluate its leading technology — the ADEPT system — the founders of Diagnostic Potentials are optimistic.

ADEPT uses EEG (electroencephalogram) to measure the electrical activity of the brain while an individual performs a set of computerized cognitive tasks designed to assess intellectual function. The goal of the technology is to identify differences in the electrical signals in individuals with fully functioning brain activity, and individuals exhibiting early stages of Alzheimer’s. In the latter case, memory function becomes impaired and can be measured through changes in EEG patterns.

Chief scientific officer and co-founder of Diagnostic Potentials, Kerry Kilborn, Ph.D., says this technology is less invasive and claustrophobic than other forms of brain scans presently used to probe for signs of Alzheimer’s. The EEG array sensor net is designed like a spongy hairnet and patients undergoing the test simply place it on their heads. The critical difference between the sensor net used with ADEPT and conventional EEG nets is the number of sensors used to measure brain activity — 128 rather than 12. This provides a tremendous advantage because by covering most of the upper brain, the dense array produces higher resolution maps of electrical fields on the scalp and can better capture brain function.

A Clinician’s Dream

Alan Hughes, M.D., geriatric psychiatrist and honorary senior clinical lecturer at Inverclyde Royal Hospital in Greenock, Scotland, was involved in the first clinical trial of ADEPT. As a clinician who treats elderly patients, he understands the present limitations of diagnosing Alzheimer’s and realizes how essential it is to make the proper diagnosis early in the disease when treatment is more effective.

“The most useful time of diagnosis, from the patients’ point of view, is when they can do the most about their illness — when they can participate in decisions about their treatment, make their wishes known, and discuss them with family members,” says Dr. Hughes.

Technically speaking, Dr. Hughes says the development of this technology is significant because current tools for Alzheimer’s dementia such as computerized axial tomography (CAT) scans simply provide a picture of what the brain looks like at a specific time. An early stage Alzheimer’s brain often looks the same as the brains of individuals affected with other diseases.

“This approach, looking at brain function, allows us to be more accurate and gives us more valuable information,” he says.

Generous Help from the Public and Private Sectors

The transfer of the ADEPT technology from a psychology laboratory at the University of Glasgow initially presented some intellectual and financial challenges according to Professor Kilborn. Commercialization support from the Scottish Biomedical Research Trust and the Department of Trade and Industry for commercial, legal and intellectual property work were the critical components in the 1999 launch of Diagnostic Potentials. The Scottish Technology Fund, along with private investors, helped the founders to raise £384,000 (approximately $618,000 U.S.) to commence the development phase of the company and support three full-time employees.

The fledgling company devoted the next two years to achieving the ADEPT technology’s proof of concept while occupying a small space in the Scottish Enterprise research incubator. They reached their goal and filed for a patent by 2001.

Although buoyed by this breakthrough, the company faced an uphill battle over the next few years.

“We had used most of the funding that was raised by that time,” recalls Professor Kilborn, “so we had to write a new business plan and attract more potential investors for a second round of funding.”

Despite a real turndown in the market at that time, the company persevered and eventually found support from several sources — the Wellcome Trust Fund charity, Scottish Executive, and Scottish Enterprise — totaling over £800,000 (more than $1.3 million U.S.).

Kevin Cullen, Ph.D., director of research and enterprise for the University of Glasgow, points out that Diagnostic Potentials is an excellent example of how long it takes to move good university science out of the lab and into the marketplace.

“The story of Diagnostic Potentials demonstrates the process of university commercialization and how necessary it is to find those little pots of money to keep a project alive at times when the academics are under pressure,” he says. “The process requires a highly motivated, enthusiastic and determined academic in a supportive academic environment to make it work.”

With a second round of funding secured, Professor Kilborn and his colleagues focused on designing a full-scale clinical trial — one that necessitated rebuilding the ADEPT technology and software from the ground up. In the last several years they launched and completed the first multi-site clinical trial involving 148 patients at four different centers across the United Kingdom. Publication of the results is pending, and Professor Kilborn hints that they are promising.

The trials are demonstrating that the ADEPT technology can identify Alzheimer’s disease in cases where it might not be easily diagnosed. Cullen is focusing on the trial’s implications beyond the primary findings and expresses hope that the technology will be capable of mass applications — especially given our society’s aging population.

“The ADEPT approach is creative, and from the commercial perspective, we hope to convince those in the company to look into other markets and explore other applications,” he says.



To see available technologies from research institutions, click here to visit the AUTM Innovation Marketplace.

Advanced Urine-Testing System Delivers Test Results in Hours

George Mason University

Advanced Urine-Testing System Delivers Test Results in Hours

A process can go no faster than the slowest step in that process. In urine culture testing, one of the slowest steps takes up to two days to deliver results.

However, scientists at George Mason University in Fairfax, Va., have invented an innovative new technology that can reduce this step to hours instead of days, while providing highly accurate results.

Disclosed in 1997, the "QuikiCult Rapid UTI Detection System" detects urinary tract infections much faster by identifying high concentrations of infectious bacteria using light spectrophotometry and automated computer-driven analysis. The research was funded by the university and the private sector.

Doctors and patients benefit from faster reporting times — as little as three hours for most negative samples, compared to 24-48 hours using current testing methods.

The QuikiCult System makes it possible to test larger samples, increased protection from contamination, fewer false positives and reduced labor costs for operators.

Because the system is portable and easy to operate, QuikiCult System is ideal for non-laboratory health care settings, including hospitals, doctors’ offices, rural or remote clinics and nursing homes. By operating the system at the point of collection, fresh samples can be tested quickly and provide more accurate results. 

The technology was licensed in 2004 to Maryland-based Macrobionetics, which supplies customized testing equipment for industrial companies and government agencies. The company is selling the QuikiCult System under the name "CultureStat" to health care facilities and reference laboratories across the United States and Canada.

To see available technologies from research institutions, click here to visit the AUTM Innovation Marketplace.

Sealing Heating and Air Conditioning Leaks from the Inside Out

Lawrence Berkeley Natl Lab

Sealing Heating and Air Conditioning Leaks from the Inside Out

Aeroseal, now a division of Carrier Corp., revolutionized the process of searching for, and sealing, hidden leaks in heating and air ducts.

Move over duct tape, a new competitor on the market is getting the job done faster and with more energy savings.

Long thought to be the right solution for stopping leaks around hot or cold air ducts, fabric-backed duct tape fails to seal leaks in ducts and pipes, according to Lawrence Berkeley National Laboratory in Berkeley, Calif.

Instead, Aeroseal duct-sealing technology, invented and developed by the Energy Performance of Buildings Group at Lawrence Berkeley National Laboratory, is making waves for its ability to seal more leakage because of its unconventional method of getting at inaccessible leaks.

Each year about $5 billion of energy escapes into thin air due to leaky ducts in American homes.

The new technology stops the leaks from the inside of the ducts by coating the leaks with tiny sealant particles. The discovery can benefit virtually anyone with a heating and cooling system by offering increased energy savings and comfort.

Mark Modera, Ph.D., inventor and principal investigator for the research group that developed the technology, is also the principal engineer with Carrier Aeroseal. He points out why it’s challenging to maintain a comfortable environment if there are duct leaks.

“You won’t have the same degree of comfort in a two-story home that you’re  trying to cool in summer when you have duct leaks,” he explains. “But the Carrier Aeroseal technology allows more air and cooling upstairs and ultimately provides more comfort.”

Addressing Energy Costs

Viviana Wolinsky, licensing manager at Berkeley Lab says, “Even in the very early stages of the development, we could see that the duct-sealing technology had far-reaching benefits for everyone interested in decreasing energy costs.”

Wolinsky points out that no one wants to pay more for their energy bills than they have to, but when leaky ducts mean you’re paying to heat or cool the air outside your home or office, it’s doubly frustrating.

“The prospect of being able to make homes and commercial buildings more energy efficient by sealing ducts from the inside, and at the same time making interior environments more comfortable, was exciting from a technology standpoint,” she says.

Idea Comes to Life

The first concept for the technology came to Modera in 1987 when it was apparent that the current methods for sealing leaks weren’t effective.

“It’s difficult, often impossible, to seal duct leaks from the outside when the ducts are in inaccessible locations,” says Modera. “When exploring technologies to seal leaks from the inside, I found that sealing leaks in straight pipes is one thing, but too often there are bends and junctions in the ducts and that’s where the problem lies.”

Modera used his skills as a research scientist to gain information about duct sealing. When he saw a newspaper advertisement touting a company’s ability to seal duct leaks, he set up a duct system and invited the company to take a look at it.

“I discovered their method didn‘t seal the system I showed them,” he recalls. “That‘s when I decided that maybe I could design a technology that would seal ducts from the inside.”

Invention Driven by Marketplace Needs

In 1990, the original funding came as part of a multi-year, multi-million dollar Department of Energy (DOE)-sponsored Cooperative Research & Development Agreement between Berkeley Lab and the California Institute for Energy and the Environment, $50,000 of which was for developing duct technology. Subsequent funding of more than $1 million was provided by the Environmental Protection Agency, DOE and the Electric Power Research Institute.

For three years, Modera and a graduate student worked on developing the technology, and in 1993, Modera says, “We figured it out.”

Modera explains how the technology works using the analogy of a car driven at high speeds.

“If a car is driven at 90 miles per hour in the city, it will skid out and crash going around the first sharp turn. Similarly, our technology works by using airborne adhesive particles injected into the ducts so that, when they speed up trying to go through a leak, they ‘pile up’ or ‘crash’ into the sides of the leak and seal it.”

Carrier Seals the Deal

In 1997, the technology was licensed for use in the residential market as well as for small commercial buildings. The logical next step was to create a business so the technology could reach customers who needed it. By 1997, Dr. Modera began spending about half of his time in the lab so that he could devote enough time to starting the company.

The marketing of Aeroseal, which is the name of the company as well as the product, was initially done through franchises primarily sold to heating and cooling dealers.

In 2001, the business was sold to Carrier Corp., which in turn created the subsidiary, Carrier Aeroseal. Two years later the company obtained a license from Lawrence Berkeley National Laboratory for improved nozzles and was able to offer the same product and service to the non-residential market.

Hospital Sees Benefits from Duct Sealing

When Cleveland’s MetroHealth Medical Center hired Karpinski Engineering as a consultant to improve the heating, ventilation and air conditioning systems in its Central Sterilization Department, the firm specified that the Carrier Aeroseal method of duct sealing should be utilized for a portion of existing ductwork on the project.

A previous balance report had shown significant leakage in the hospital’s ductwork in this part of the facility.

“We felt that the Carrier Aeroseal technology would be ideal for this project,” says Nathan Anderson, a project engineer with Karpinski. “The hospital has an exhaust fan on the roof and ductwork that was originally installed in the 1970s. When originally constructed, this ductwork was enclosed in a shaft and after the leakage was revealed, the duct was inaccessible for sealing.”

The first steps involved Modera taking measurements and sealing off the existing exhaust grills, and a sealant was injected from the inside of the ducts.

The technology can block off existing exhaust openings that range from a quarter inch to a half inch in size. The time varies from a few hours to a few days depending on the characteristics of individual heating and cooling systems.

“With Carrier Aeroseal, it’s a computerized, high-tech process,” says Anderson. “Once the openings were blocked off, sealing ducts from the inside took just about 30 minutes.”

The “after sealing” report at the time the project was completed in April 2006, showed about 85 percent of the leakage had been plugged — 1,570 cubic feet per minute (cfm) leakage prior to sealing, 230 cfm leakage after sealing.
“By specifying Carrier Aeroseal, we accomplished our goal, which was to improve the exhaust airflow rates,” says Anderson. “If we had not sealed off the ducts from the inside, there would have been significant demolition work involved to accomplish sealing from the outside because of the inaccessibility to the ductwork.”

Meeting the goals of the hospital was paramount for the engineering firm.

“By using this new technology, which has a 10-year warranty, we saved the  hospital time and money,” says Anderson.

The engineering firm is so satisfied with the technology, it has specified Carrier Aeroseal to seal 21 ducts in another significant Cleveland building.

“The technology is simple, easy and relevant to today’s world,” says Wolinsky. “Customers realize a demonstrable payback. When they see how much air is escaping in the before-test when compared to after the ducts are sealed, it’s a powerful visual.”

Between 2003 and 2006 Carrier Aeroseal sealed 20 large buildings ranging from offices to hospitals. The company intends to focus on promoting the technology via a larger launch into commercial markets during 2007 and 2008.

“The driving forces are energy savings and building/system performance improvement,” Modera points out. “During the past four years of accelerated testing, the technology has never failed.”

To see available technologies from research institutions, click here to visit the AUTM Innovation Marketplace.

Aguru Images Shines Light on Digital Imaging

New York University
University of Southern California

Aguru Images Shines Light on Digital Imaging

In the world of academic technology transfer, one contact often leads to another, ultimately resulting in new discoveries that enter the marketplace.

That is the story of Aguru Images, which merged brilliant academic discoveries from universities on opposite sides of the United States — New York University (NYU) and the University of Southern California (USC).

The result is creating a buzz in the computer graphics community because the technology can be used in a variety of applications. They range from making strikingly accurate digital images in motion pictures, videos and computer games to improving renderings by interior, fashion, architectural and industrial designers.

In fact, just about anyone who wants realistic lighting on everything from faces to brushed aluminum to fabrics may be able to benefit from Aguru’s technology.

The Virginia-based company now sells equipment and services and will eventually add software and a library of illumination data to its products. Appropriately, one of the meanings of Aguru in the Sanskrit language is light. Steve Gray, the chief technical officer and executive producer of Vykarian, a Shanghai-based game developer, says Aguru has made a great leap forward.

“It’s pretty remarkable what they’ve done working with NYU and USC,” says Gray, who formerly was the executive producer for Electronic Arts’ “Lord of the Rings” video games.

The Right Mix of Technologies

In the computer graphics world, getting textures right is extremely difficult, Gray points out.

“But along came Aguru, working with NYU, which has a scanner that uses a kaleidoscopic array,” says Gray. “You can stick anything on it and it basically figures out how the light, including light that is being scattered below the surface, is reflected. That’s something.”

Next, in conjunction with USC, he notes, Aguru added a dome that is a three-dimensional scanner.

“It essentially takes pictures simultaneously from many different angles,” Gray explains. “Then, using image-based modeling techniques, allows you to reconstruct a 3-D model of the thing that was inside the dome. One of the first applications was scanning people’s faces and it achieved really, really high resolution. It uses five million polygons, which is essentially more resolution than can be rendered back with film.”

The third component, also from USC, is called the Linear Light Source (the Aguru Scanner). It is a larger type of scanner that captures flat object reflection, the different colors of shine and the surface bumpiness, among other features.

The technologies work together well, Gray says, because the USC dome recreates the subtleties of 3-D shapes and textures for really difficult objects and materials, like the human face, while the NYU and USC scanners capture the properties of countless other materials.

It’s exciting stuff, and it’s 99.9 percent photorealistic. It makes it cheaper, faster and unlocks these capabilities for everyone, like small game developers and boutique studio effects studios.
Steve Gray

Collaborating With Researchers on Two Coasts

Aguru’s story began in 2005, when Saul Orbach was hired by ANGLE Technology Ventures, a publicly traded British firm, as its entrepreneur in residence. Back then, Orbach knew little about computer graphics, kaleidoscopic technologies, properly illuminating textured surfaces or getting the light right when scenes with real actors are meshed with virtual backgrounds.

Nor did he know that the quest for truly photorealistic digital images had long been the holy grail of the three-dimensional computer graphics industry.

In the past two years, however, he has become something of an expert of sorts in the field of virtual lighting — thanks in large part to researchers at NYU’s Courant Institute of Mathematical Sciences and USC’s Institute for Creative Technologies.

Orbach is modest about what he put together.

“I’m no scientist,” says Orbach, a serial entrepreneur. “When I started out, my job was to find technologies that we could commercialize and turn into a company. So I looked at a lot of things.”

Because of his NYU connections — Orbach earned undergraduate and M.B.A. degrees from the university — he met with Robert Fechter, associate director of the NYU Office of Industrial Liaison, who led him to the Courant Institute.

Fechter introduced him to Ken Perlin, a computer science professor, and Jeff Han, a research scientist at Courant. They showed Orbach a variety of computer graphics projects they were working on.

“One was the kaleidoscopic technology that was capturing reflectance data for textured materials,” Orbach says. “This was exciting stuff.

“In fact, it was a ‘Eureka!’ moment,” he said. “The existing methodologies for doing the same thing were very complicated. But Ken had come up with a simple, brilliant device with no moving parts that was quick and easy to operate.

“I like simple, innovative solutions to problems that no one has thought of,” he said. “This was really cool.

“Ken’s device allowed you to capture all angles of illumination. Then you could look them up from his database. His device could capture all those angles in 15 seconds. Learning about that was what started it all.”

Appropriately, Perlin was a fan of kaleidoscopes as a child.

“Wasn’t everyone?” Perlin asks. “As part of my research, I learned that the kaleidoscope was invented by Sir David Brewster in the early 1800s. It was so wildly successful that it became the symbol of science and progress. It was the iPod or computer of its time.”

Prior to this invention, in order to see a surface from multiple points of view you either needed an array of cameras or to mechanically move a single camera to different locations.

“I thought, ‘Why not use a tapered kaleidoscope to do the same thing?’” Perlin recalls. “Then I talked to my colleague Jeff Han and we set about to build it.”

As part of his due diligence, Orbach says he learned everything he could about the industry and the difficulty of getting realistic lighting on computer generated images.

“Along the way, I talked to 50 people and companies who were possible users of this technology. I got a good feel for the market, what the applications were, how much and for what price,” notes Orbach.

Orbach also met with Paul Debevec, a research associate professor at USC’s Institute for Creative Technologies Graphics Lab and a friend of Perlin’s who had come up with a complementary technology.

Debevec’s Light Stage 2 process was used by Sony Pictures Image Works to create photorealistic digital actors as part of its Academy Award-winning visual effects in “Spider Man 2,” the Academy Award-nominated visual effects in “Superman Returns,” and most recently “Spider Man 3.”

Debevec, who most recently led the development of a Light Stage dome that measures 26 feet in diameter, says his research began in 1999 and is funded by movie studios and digital imaging corporations. The institute’s basic research funding came from the U.S. Army.

“The goal of our institute is to foster collaboration between academic researchers and the entertainment industry to develop the next generation of simulation and virtual environments,” Debevec explains.

“With Aguru commercializing some of our technologies and pushing them further forward, that will help meet these goals,” he says. “It will allow more people to benefit from these physically based rendering and realistic model acquisition techniques. Aguru is going to take proven technologies, make them more robust, more economical and will adapt and evolve them to better meet the specific needs of the industry. And that will inspire our group to work on the next generation of these technologies.”

Making Its Marketplace Debut

Aguru Images was launched in March 2007 with an initial $1 million in financing from ANGLE. NYU licensed its technology to Aguru in exchange for equity and revenue. USC negotiated a similar deal.

By August 2007, Aguru was ready to show its products at the 2007 SIGGRAPH trade show in San Diego. (SIGGRAPH stands for Special Interest Group for Graphics and Interactive Techniques.)

John Sweet, a senior licensing associate at USC’s Stevens Institute for Technology Commercialization, calls working with Aguru Images a “pleasure.”

“Saul Orbach is an experienced entrepreneur and has assembled a good group of guys,” he says. “It’s nice to collaborate with people like that who know what they are doing.”

Orbach estimates the company will have revenues of between $5 to $7 million in 2008. And after that, who knows?

“As for future applications, we quickly came up with a short list of 15 or 16 that includes online commerce, cosmetics, catalog shopping, medical applications and even military stuff,” says Orbach.

“There is no shortage of how this technology could be used,” he muses. “The sky’s the limit.” 

To see available technologies from research institutions, click here to visit the AUTM Innovation Marketplace.

ALEKS Tutors Students in Learning to Succeed

University of California, Irvine (UC Irvine)

ALEKS Tutors Students in Learning to Succeed

The groundbreaking intelligent tutoring system developed at the University of California, Irvine, equalizes educational opportunities because it knows exactly what the student knows and what the student is ready to learn.

“Alan,” a student at Hilltop Middle School in Chula Vista, Calif., knows firsthand that when it comes to learning, one size doesn’t fit all.

He was getting Ds and Fs on his seventh-grade report card when his father called Gary Oakland, a teacher at his school, saying he didn’t know how to help his son.

Over the past five years, Oakland has had great success with ALEKS (Assessment and LEarning in Knowledge Spaces), a groundbreaking technology developed at the University of California, Irvine (UCI) in the mid-1990s. The revolutionary artificial intelligence technology, now used by hundreds of thousands of students in more than 1,000 schools, was developed by Jean Claude Falmagne, Ph.D., chairman and founder of ALEKS and emeritus professor of cognitive science at the University of California, Irvine, along with and a team of researchers.

Oakland suggested Alan try working with ALEKS. Using his home computer, Alan started getting excited about learning. Pretty soon he finished 100 percent of the state’s standard Grade 7 math requirements. Oakland, who has trained all of the math teachers and math department heads in his school district on ALEKS, says, “Over this past summer, Alan, who is now in eighth grade, completed 85 percent of an algebra course all on his own without ever spending a day in an algebra class.”

ALEKS has revolutionized learning because it interacts with students at a highly individual level of readiness instead of teaching to the “fat part of the curve.” Subjects such as math, chemistry and accounting, have been traditionally taught in a linear method — in a start-to-finish sequence.

“But the reality is not everyone learns at the same pace, and not everyone can afford a tutor,” Oakland says. “You should be able to achieve success by teaching in a logical, sequential manner, but it doesn’t work that way. Everyone learns differently.”

Anyone who has worked with ALEKS knows it is all about outcomes. Students are taken on a fantastic voyage of learning, and in the process, ALEKS helps them achieve academic success, often for the first time in their lives.

ALEKS Unveiled

In 1993, Falmagne says researchers at UCI received a “lucky break.”

“We received a $2.4 million grant from the National Science Foundation to develop the software that would become ALEKS,” he explains.

The technology is based on Knowledge Space Theory, a milestone in cognitive  psychology and applied mathematics. Its origin goes back to the early 1980s when Falmagne, along with Dr. Jean-Paul Doignon of the Free University of Brussels in Belgium, and scientists at New York University and other universities, began to develop Knowledge Space Theory.

“Knowledge Space Theory is not only about finding out what someone knows, but that knowledge acquisition takes place in a ‘learning space,’” says Falmagne who notes the extremely complex software took 10 years and millions of lines of code to create.

In 1997, the UCI Office of Technology Alliances licensed the technology to ALEKS Corp. Two years later, McGraw-Hill became the distributor of ALEKS in higher education.

“In 1999, our first commercial products of Basic Math and Beginning Algebra for two-year colleges got off the ground,” notes Falmagne. “Our partnership with McGraw-Hill has also allowed us to develop many other products.”

Classroom Dynamics

From the moment the computer screen lights up, ALEKS takes students on a rewarding journey. The technology can be used for independent learning — students can get ahead on their own by accessing ALEKS from any computer or the software can be used for specific courses as well as in school computer labs.

In November 2006, Oakland made a presentation to the California Math Council showing how ALEKS can help students with varying scholastic aptitudes succeed beyond their wildest dreams.

Oakland’s school, located about 15 miles from Mexico, has a student population that is about 75 percent Hispanic.

ALEKS is fully bilingual in Spanish and English for math through Grade 9, with instantaneous “one click” translation.

In 2001, when the school received a flyer about ALEKS, Oakland was teaching an after-school algebra recovery program to seventh- and eighth-grade students (to help them “recover” their grades from failing the class the year before).

“The students have to make up 60 hours to repeat or ‘recover’ a class,” Oakland says. “Some of our students weren’t even coming to school.”

On top of failing grades, he says behavioral issues created a nightmare atmosphere for both students and teachers. But there was hope in the form of ALEKS.

“The more they use ALEKS, the more apt they are to get good grades,” Oakland comments. “When they get their first ‘A’ it’s a heady experience — there’s no stopping them.”

“First off, ALEKS does an assessment to determine precisely which topics the student has already mastered,” says R.G. Wilmot Lampros, president of ALEKS Corp., Tustin, Calif. “ALEKS avoids multiple choice questions. There are no lucky guesses — it’s not geared to finding out how good a test taker a person is. The student has to know how to solve a problem.”

Oakland’s school didn’t have a computer lab, but he was determined to build one so his students could use ALEKS. Oakland, along with an information technology staffer from the school, brought in 60 old computers that didn’t work.

“Together we repaired and rebuilt the computers, bought inexpensive keyboards, and repaired tables and chairs,” he recalls. “In the end we had our computer lab complete with 34 computers.”

Oakland saw positive results from ALEKS from the start. He willingly made the long drive from the mountains where he lives to teach the algebra recovery classes on weekends and during the summer in addition to after school classes, which are now math support classes.

Lampros notes that ALEKS was not developed around the idea of using technology to maximize high-end graphics.

“That’s one of the reasons why ALEKS’ success is so fascinating,” he says. “We use graphics where they are pedagogically useful. Students fall in love with ALEKS not because of its visuals, but because using it enables them to learn and excel.” They also see an immediate assessment of what they know and how to do a problem right.

“They tell me they love ‘seeing’ what they know,” says Oakland, referring to the program’s popular pie chart feature. “When students click on it, ALEKS shows them not only what they can do but, what they are ready to do next. They love seeing where their knowledge is growing.”

Learning Comes Alive

Harold Baker, Ph.D., director of customer support, has been with ALEKS since before it became a commercial product. From early on, he recalls a vivid image of how ALEKS makes math come alive.

“A student with developmental disabilities was sitting at her computer at a community college unable to type like other students, but she was so caught up in learning math from ALEKS, that she used her pencil’s eraser to enter numbers and letters from her keyboard,” he says.

What ALEKS is not, he says, is a program that just gives more homework online.

“There are possibilities for deep customization with ALEKS — it has many features tomake sure teachers are successful as well as students,” he says.

“Studies have shown that early failure in math, particularly in Algebra 1 and 2 is often a predictor of failures in other disciplines,” say Baker. “If a student has failed before, he will likely fail again. ALEKS breaks the cycle of repeated failure.”

ALEKS offers another classroom benefit. It frees up teacher time and allows teachers to spend more time with individual students (or small groups) and do more creative things. “Instead of just teaching math and other subjects, teachers can have fun teaching students the applications of math such as how math is used in building bridges,” notes Baker.

What’s next for ALEKS? The company will launch an elementary chemistry program in early 2007. Recently, a study by researchers at the University of Memphis, showing how an ALEKS statistics program can eliminate racial disparities, was accepted by the American Educational Research Association for presentation at its annual meeting.

Summing up why students like ALEKS, Falmagne says, “It talks directly to them, and it always rewards their time and effort.”

While ALEKS has made a difference in many students’ lives, more will benefit in the future. “The potential for success for students throughout the world is unlimited,” says Baker. “ALEKS is an intelligent tutoring system that really works.”

To see available technologies from research institutions, click here to visit the AUTM Innovation Marketplace.

Partnership Yields Revolutionary Cancer Drug

Eli Lilly and Co.
Princeton University

Partnership Yields Revolutionary Cancer Drug

The brimstone butterfly adorns the business cards of Edward C. Taylor, Ph.D. A fitting homage to his life’s work, the butterfly symbolizes Taylor’s inspiration to develop the anticancer drug Alimta (pemetrexed).

Alimta is currently approved in the United States to treat recurrent, or second-line, non-small cell lung cancer, the most common form of lung cancer. It is also approved in combination with another drug called cisplatin for the treatment of malignant pleural mesothelioma, a cancer often associated with exposure to asbestos.

The development of Alimta dates back to 1946 when Taylor, now a retired distinguished professor and organic chemist at Princeton University in Princeton, N.J., entered graduate school and was looking for a thesis topic. He came across an article describing the discovery of a compound found in human liver that, bizarrely, possessed a structure of which a portion was identical to the structure of pigments in the wings of butterflies. Taylor’s curiosity about this unexpected discovery eventually led him to make a major advancement in the fight against cancer.

The compound from the liver was later determined to be folic acid, a vitamin that plays an essential role in making cell division possible. “It was found that folic acid is essential for all forms of life,” says Taylor.

It was then he saw the potential for an anticancer agent. Like all cells, tumor cells need folic acid, or folates, to divide and multiply, allowing the tumor to grow. “If you could inhibit it, you would have a good way of arresting the growth of tumors,” he says. “The challenge was to inhibit the growth of the tumor and not healthy human cells. People tried for years, but no one succeeded.”

Trust is Essential to Success

In the 1970s Taylor resumed work on an antifolic agent that might selectively target tumor cells. After years of work, he came up with a promising compound called Dideazatetrahydrolic acid (DDATHF). But he knew his work could only be carried so far at Princeton, and he needed help. “I needed facilities and expertise that Princeton didn’t have,” he says. “If I wanted this compound thoroughly looked at, who would do it?”

Taylor enlisted the help of Eli Lilly and Co. in Indianapolis. At the time, Taylor had already been consulting with Lilly for years, and had established close relationships with the company, so in the early 1980s he sent DDATHF to them.

The compound turned out to be one of the most effective antitumor agents that Eli Lilly had seen.
Edward C. Taylor

Knowing they might be on the brink of a major breakthrough, Taylor (through Princeton) and Lilly in the mid-1980s set up a collaborative effort to explore the potential of what appeared to be an extremely promising new area of cancer research. During the following four years, approximately 800 new drug candidates were synthesized and evaluated through this collaboration. DDATHF, the original lead, eventually failed clinically because of toxicity, but another compound finally emerged that proved to be the compound of choice for development, and that compound became the drug named Alimta®.

This was also a pioneering time for technology transfer at Princeton.

By this time, Princeton had a well organized technology transfer arm, but at the time of the project’s initiation, the partnership was forged out of mutual trust.

The Princeton-Lilly joint research project that culminated in the discovery of Alimta“was the first big collaboration that Princeton had undertaken, and it proved to be a major success because there was complete trust and integrity on both sides,” according to Taylor.

Partnership, Perseverance Overcome Obstacles

As a pharmaceutical company, Lilly focused on understanding how the compounds behaved in humans. “Our role was to conduct evaluations and animal studies to determine which compounds were candidates for clinical trial,” says Joe Shih, Ph.D., a distinguished research fellow at Lilly.

A key part of Lilly’s role was to understand the compounds’ toxicity in humans and how to mitigate it. That turned out to be a crucial element.

Early clinical trials with Alimta® were plagued by unpredictable toxicity issues. Although the majority of patients in the trials responded well, some experienced serious, life threatening side effects. While the drug’s clinical benefits were clear, these problems threatened to end the project. That’s when another member of Lilly’s team saved the project.

Clet Niyikiza, Ph.D., at the time a statistician and mathematician with Lilly, stepped forward to solve the problem. “He said, ‘Give me three weeks,’” recalls Taylor, “and he would solve the problem.”

Scouring the clinical data to find the common thread among patients who experienced the side effects, Niyikiza, determined that the patients who experienced side effects had a pre-existing folic acid deficiency. Researchers had not anticipated this problem, since they were attempting to inhibit folic acid activity. But Niyikiza’s work led to changing the protocol to co-administering folic acid and vitamin B-12 to patients, and this amended treatment saved the drug.

“It tipped the balance critically,” says Taylor.

“Alimta is a single compound that targets the utilization of many folate based processes essential for the growth of tumor cells,” Taylor explains. “Other cancer drugs usually can target only one specific biological process, making it attractive for patients to receive a ‘cocktail’ of several drugs. But this strategy also means that the patient is subject to the combined toxicities of each component of this cocktail.

“Since Alimta is a single drug that has multiple targets, it is harder for tumors to develop resistance to it,” he continues. “That is part of the reason Alimta is one of the least toxic cancer drugs known.”

Since its approval in the U.S., Alimta has gone on to be approved by regulatory authorities in more than 85 countries. Unlike most chemotherapy treatments for cancer, Alimta is easy to administer, requiring only a 10-minute infusion every three weeks.

Collaboration is the Cornerstone

Alimta’s development is the result of decades of work and partnership between Taylor and the research team at Lilly, without which the drug would have never made it to initial trials.

“The attrition rate in drug development is enormous,” says Taylor, citing that only one out of every 5,000 to 10,000 potential candidates ever becomes a drug. “It’s a discouraging and extraordinarily expensive process.”

He added that Lilly’s agreement to collaborate with Princeton, and to help develop the drug, demonstrated Lilly’s trust in Taylor and in the promise the early compounds held.

From Taylor’s perspective, the partnership with Lilly and its evaluations of drug candidates, gave him, as well as his Lilly colleagues, the feedback needed to continue research in the direction that eventually led to the discovery of Alimta.

“In drug development, you have to evaluate constantly what you are making so you don’t go in the wrong direction,” he explains. “Such feedback is not available in an organic synthesis lab.”

It was the willingness of Lilly to perform extensive biological testing that made Alimta possible.

Shih views the development of Alimta as a model of how a pharmaceutical company and a university can work together.

“The science is being conducted all over the world at top research institutions like Princeton,” he says. “Big pharmaceutical companies don’t have the resources to conduct research at that scale. These institutions help us to identify interesting discoveries that can lead to new drugs.”

Lilly is working with many institutions worldwide in the research and development of drugs for oncology, diabetes and neuroscience.

Summing up the importance of partnerships between research institutions and the private sector, Shih comments, “Collaboration is a cornerstone of this process.”

Taylor says Lilly’s help was invaluable. “Without this kind of collaboration, Alimta would still be a curious compound sitting on a shelf in my lab.” 


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The Birth of Allegra: Nothing to Sneeze at

Georgetown University

The Birth of Allegra: Nothing to Sneeze at

When Georgetown University’s Raymond Woosley discovered fexofenadine’s role as a safe and effective allergy medicine – you know it as Allegra – he didn’t realize it would transform the science of drug development. Today, Allegra is one of the most popular antihistamines in the world, restoring an otherwise unattainable quality of life for serious allergy sufferers.

Woosley, the chairman of pharmacology at Georgetown University Medical Center, was part of the scientific team called-in to investigate problems occurring with Seldane (terfenadine), a drug introduced to the market in 1985 as the first “non-drowsy” allergy medicine. He found previously overlooked reports of arrhythmias and deaths that suggested an interaction between Seldane and other common drugs could cause serious heart rhythm disorders, sometimes leading to sudden death.

It was during his research that Woosley discovered that a breakdown product of Seldane—fexofenadine—was the actual ingredient that suppressed allergy symptoms, with no serious side effects.

Woosley’s work transformed the drug development process at an international level. Based on his studies, the FDA and other regulatory agencies published guidelines requiring testing of new drugs for their potential to cause heart arrhythmias. These guidelines are essentially the same tests and protocols that Woosley conducted on terfenadine.

With the help of Georgetown University’s Office of Technology Commercialization, Woosley went on to patent fexofenadine as a non-toxic allergy medicine. OCT played a critical role in the deal, managing key language in the development agreement.

Following its approved by the FDA in 1996, the drug was commercialized and marketed as Allegra by Sanofi-Aventi. Shortly afterward the FDA pulled terfenadine from the market, soon followed by over a dozen other medications that were found to pose similar risks.

The FDA approved over-the-counter (OTC) sales of Allegra in 2011. In 2016 Allegra totaled $221.6 million in OTC sales, placing it among the top-five-selling OTC allergy medicines in the U.S..
Allegra aside, Woosley’s work transformed the drug development process at an international level.
Based on his studies, the FDA and other regulatory agencies published guidelines requiring testing of new drugs for their potential to cause heart arrhythmias. These guidelines are essentially the same tests and protocols that Woosley conducted on terfenadine and are now required for almost all new drugs being developed today.

Woosley has continued his mission to make drugs safer. He is founding president of the Arizona Center for Education and Research on Therapeutics, a nonprofit organization dedicated to the safe use of medications. The center analyzes evidence and maintains lists of drugs that are categorized according to their risk of causing dangerous cardiac arrhythmias. This information is accessed online by thousands of researchers and healthcare providers every year.

"Patients are dying needlessly from drugs and drug combinations that are often taken to treat common, relatively trivial illnesses,” said Woosley. “Although these kinds of side effects resulting in death are rare, they are preventable and even one death is unacceptable."

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Increasing Mobility for Amputees

Bloorview Research Institute
Holland Bloorview Kids Rehabilitation Hospital
University of Toronto

Increasing Mobility for Amputees

Worldwide, about 30 million people require a prosthetic device to walk, yet only 10 percent of those individuals have access to the devices. Prosthetic devices available in developing countries are often rudimentary and do not offer the functionality of advanced prostheses, which can cost up to $50,000.

Inventor Jan Andrysek, Ph.D., a scientist at Bloorview Research Institute at Holland Bloorview Kids Rehabilitation Hospital and an assistant professor at the University of Toronto, has created a more affordable solution for individuals for whom advanced prosthetics are out of reach.

Amputees fitted with the All-Terrain Knee can engage in everyday activities more quickly and efficiently, whether that’s working or taking care of family.
Jan Andrysek

The All-Terrain Knee is an innovative, mechanical prosthetic knee joint that is stable, durable and waterproof. The invention includes a proprietary stance-phase control mechanism (the AutoLock) and a swing-phase control mechanism that allows the knee to securely lock itself without impeding natural movement. The prosthetic knee is easy to fit and maintain, and can be used in harsh environments.

Andrysek established partnerships with rehabilitation centres to develop fitting procedures and teamed with the International Committee of the Red Cross to conduct clinical studies with the All-Terrain Knee. The inventor says the study results provide strong empirical evidence that the device provides users with a greater feeling of security and a reduction in falls.

In 2014, the technology was licensed to LegWorks Inc., a for-profit social enterprise established to commercialize the artificial knee joint. Today, the company offers four versions of the All-Terrain Knee with various features appropriate for different users, from sedentary to more athletic patients. LegWorks has reached patients in 28 countries, tiering its pricing to help reach underserved patient populations.

To see available technologies from research institutions, click here to visit the AUTM Innovation Marketplace.

Innovative Bandage Saves Lives

University of North Carolina Chapel Hill

Innovative Bandage Saves Lives

Severe blood loss is one of the leading causes of death in traumatic injury cases. Despite the abundant research that exists on ways to stop surface bleeding (hemostasis), little work has been done to develop special materials that can be applied to wounds to staunch bleeding. This is especially critical in combat casualty care, where control of non-compressible bleeding is one of the biggest unmet needs in military emergency medicine. Blood loss through gauze dressings is a major factor in the death of wounded soldiers on the battlefield.

The unique fabric activates the body’s own hemostatic systems when applied to a wound.

To reduce death and injury from substantial blood loss, a joint research team from the University of North Carolina at Chapel Hill and East Carolina University in Greenville, N.C., developed a technology consisting of a fabric of woven specialty fibers, including glass, silk, bamboo, cotton, flax, hemp and zeolite. Additional co-factors such as thrombin, RL platelets, RL blood cells, fibrin, fibrinogen, and other hemostatic agents can be  incorporated into the textile. The fabric is soft, strong, and absorbent, can be cut to any needed size or shape, is temperature-stable, and may be used to support other hemorrhage-control methods.

This technology was licensed to Entegrion, a University of North Carolina startup company. In 2007 Entegrion received Food and Drug Administration approval for its hemostatic textile technology called Stasilon™. AlphaBandage™, the company’s emergency bandage that promotes blood coagulation and reduces bleeding, was distributed to battlefield medics and performed well during pilot testing.

The product has demonstrated the ability to reduce blood loss as compared with gauze by improving rates of clot formation. Entegrion is developing other wound-dressing products for military and commercial markets in the United States.


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An Accurate and Definitive Diagnose: the Promise of Altropane®

Harvard University

An Accurate and Definitive Diagnose: the Promise of Altropane®

A fortuitous discovery of a molecule that can differentiate between normal and abnormal levels of brain cells that bear dopamine transporters may hold the key to more accurate and early diagnoses of Parkinson’s disease and attention deficit hyperactivity disorder. 

Imagine waking up one morning with a sudden and unexplained twitch in your little finger. Too persistent to ignore, you go to your general practitioner where you learn that you may have some kind of movement disorder. The twitches, tremors and shakes may not go away — in fact they may get worse. Even scarier, there is a good chance that your condition will be misdiagnosed, and the treatment you really need is not necessarily the one that will be prescribed. 

Welcome to the frustrating world of movement disorders. Doctors who treat patients with these symptoms face this conundrum every day. Patients with Parkinson’s Disease — a highly debilitating neurodegenerative disease — as well as patients with other disorders that appear to be the same thing but are actually of a very different etiology suffer because of a lack of accurate and reliable diagnostic tools.

Approximately 140,000 people in the U.S. alone come to their physicians every year with new, undiagnosed movement disorders like Parkinson’s Disease and essential tremor. Medical journals report misdiagnosis rates of 30 to 40 percent, if not higher. 

“There has been a crying need for a long time now for earlier and more accurate diagnosis of Parkinson’s disease,” says Ken Rice, executive vice president and chief financial officer of Boston Life Sciences Inc., a Boston-area company that is playing a huge role in helping to solve this problem. Research into the progression of Parkinson’s disease has shown that by the time a patient is symptomatic, 70 to 80 percent of the neurons that control movement in the substantianigra part of their brain have died. Because there is no cure for the disease, all that is available to patients and their families is a plan for managing the symptoms — and even this phase is relatively short. “That is why earlier detection and intervention of PD can make a big difference,” Rice says. “It would allow for an extension of the symptom management phase and translate into better quality of life for patients.” 

Understanding Diseases on a Molecular Level

That’s where Altropane®, a highly specific imaging agent presently undergoing evaluation in Phase III clinical trials, comes in. The groundwork for Altropane® was laid in the late 1980s, when Bertha Madras, Ph.D., professor of psychobiology at Harvard University, was researching the action of cocaine in the brain. Madras fortuitously discovered that a certain molecule, by virtue of selectively binding to a protein — the dopamine transporter — could accurately differentiate between particular cells in the brain. A somewhat simple concept, but the information it revealed was quite powerful. “I’ll never forget that moment,” Madras recalls. “When the lab technician showed me the results of the experiment, I nearly fell off my seat. I immediately realized the impact of these results, and it sent off a cascade of ideas in my mind.” 

This binding molecule, called a tropane, was the first to accurately identify neurons in the brain that bear dopamine transporters, specialized  proteins that transport the chemical dopamine into cells. Neurons that don’t have dopamine transporters on their cell surface were clearly and cleanly ignored when introduced to the tropane. The implication for Parkinson’s patients is that those with the disease have very low levels of dopamine transporter-producing cells; they mysteriously die off. So, the brains of Parkinson’s patients, compared with normal brains, as well as those with non-Parkinson’s movement disorders like essential tremor, look very different when put to this test. 

The clinical application of this discovery involved joining forces with a team of chemists who specialize in modifying molecules to make them imaging agents, or proteins that become detectable by nuclear medicine tests such as positron emission tomography, or PET, scans. Collaboration with fellow Harvard scientist, chemist and inventor David Elmelah, Ph.D., helped to overcome this hurdle, and the team was ready to find a partner to support product development. They enlisted the expertise of Peter Meltzer, Ph.D., scientist and president of Organix in nearby Woburn, Mass., and the collaboration between academic and industry science led to the further development of Altropane®. 

The final version of Altropane® includes a radioactive label (Iodine-123), enabling its visualization by clinicians in live humans when imaged by single photon emission computed tomography, or SPECT. SPECT imaging is more widely available and less expensive than conventional PET scans, making it accessible to most hospitals with nuclear medicine departments. Moreover, SPECT can provide imaging of Altropane® almost immediately after it is injected, enabling quick and accurate diagnoses. 

Early Diagnosis Can Slow Progression of Disease

The technology transfer office at Harvard University worked with the scientists as they recognized the potential of Altropane®, and Boston Life Sciences, headquartered in Hopkinton, Mass., acquired the rights to develop, manufacture and commercialize the agent. Following the completion of several large earlystage trials, Altropane® is now in pivotal Phase III trials specifically designed to test the molecule’s ability to differentiate between Parkinson’s Disease and other non-Parkinsonian movement disorders manifested by shaking and tremors. 

“We’re very excited about Altropane® and its promise in reducing the high error rate associated with the diagnosis of PD and other movement disorders,” says Rice of Boston Life Sciences. The company is very committed to bringing the product to market and has made a substantial investment in the clinical development of Altropane®. “First and foremost, the Parkinson’s community is a very dedicated group of people who want nothing more than to find a cure,” Rice says. “Anything we can do to help alleviate the uncertainty by providing a more accurate tool for diagnosis is hugely important.”

Clinicians who diagnose and treat Parkinson’s patients say Altropane® could have a significant impact. “In terms of a patient’s quality of life, it is so important to get the appropriate medicine early on,” says Burton Scott, Ph.D., M.D., associate clinical professor in medicine and neurology at the Movement Disorders Center at Duke University Medical Center. “We want to eventually use neuroprotective drugs for those patients who are susceptible to PD. That goal has been the Holy Grail in PD research for quite some time. In the foreseeable future, when we have effective therapies that can slow down the progression of PD — and I’m confident that they will be forthcoming — the correct diagnosis of the disorder will be even more critical.”

The acceptance of Altropane® also promises a more widespread means of identifying and diagnosing Parkinson’s Disease patients so that they receive adequate treatment earlier. “Altropane® allows more clinicians to make an accurate diagnosis without requiring movement disorder specialists,” says Alan Fischman, M.D., director of nuclear medicine at the Massachusetts General Hospital and an investigator involved in clinical trials of Altropane® in Parkinson’s Disease patients. “By allowing doctors who are not necessarily experts in the field of movement disorders to make a definitive diagnosis, it moves the treatment out of major academic centers and out into the community. Because of this, Altropane® can significantly augment the field.”

Attention deficit hyperactivity disorder, or ADHD, is another highly prevalent medical problem characterized by abnormal levels of dopamine transporter-producing neurons in the brain. Like Parkinson’s Disease, the level of dopamine transporters in the brains of ADHD individuals differs from those without the disorder. In the case of ADHD however, dopamine transporters levels are elevated, not reduced. Boston Life Sciences is now sponsoring Clinical trials to test the accuracy of Altropane® in diagnosing this disorder.

ADHD, which affects more than 5 million children in the United States and as many as 2 to 4 percent of adults, has been a controversial medical issue because of inconsistencies in the clinical diagnosis and concern about the reported abuse of behavior-modifying medications for the disorder.

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From Diagnostic to Vaccine: The Fight Against Tropical Disease Continues

University of Virginia
University of Virginia Patent Foundation

From Diagnostic to Vaccine: The Fight Against Tropical Disease Continues

Each year, more than 3 million children around the world die of diarrhea and other gastrointestinal ailments, primarily in developing countries.

Scientists at the University of Virginia (U.Va.) and TechLab, a medical diagnostic manufacturer based in Blacksburg, Va., are working together to make a dent in the disease and, if all goes well, come up with a vaccine against amebiasis, or amebic dysentery.

The story begins in 1989, when Dr. William Petri, a trombone-playing researcher at U.Va. received a National Institutes of Health (NIH) grant to study a protein on the surface of Entamoeba histolytica, a parasite that causes dysentery. Petri is the chief of the Division of Infectious Diseases and International Health at U.Va. in Charlottesville.

With the help of colleague and longtime friend, Dr. Barbara Mann, they were able to successfully clone the surface protein so it could be used to develop antibodies that would result in an accurate diagnostic test. This test, which has been cleared by the U.S. Food and Drug Administration (FDA), identifies the E. histolytica organism in children and adults suffering from diarrhea and dysentery. It was licensed by the U.Va. Patent Foundation to TechLab in 1992.

The company is now collaborating with Petri to develop a low-cost dipstick-like device similar to a home pregnancy test that changes color when used to analyze infected fecal matter. The dipstick, which is being tested in Bangladesh, uses TechLab’s diagnostic technology. But it will deliver it in a simpler form, Petri says.

Providing such a low-cost kit would allow the most impoverished nations to have greater access to the technology, thereby allowing for proper diagnosis and treatment of dysentery.

Petri says he believes FDA clearance of the dipstick test may occur by the end of 2008. The current form of the test is a bit more complicated, but can also be used in the field, he says.

Debi Hudgens, a licensing associate at the U.Va. Patent Foundation, calls the collaboration between her school and TechLab “extremely productive.”

Joel Herbein, who heads TechLab’s parasitology section, says working with Petri is important because he has collaborators all over the world and can set up clinical evaluations in places where gastrointestinal diseases are endemic.

“We want our products to be used in very simple settings to diagnose disease without a lot of supplemental expensive equipment,” says Herbein, who earned his Ph.D. in cell biology from Duke University in Durham, N.C.

“There is always a push for these tests to become simpler and cheaper, faster to run and more sensitive.”

TechLab came into being in 1989, when it was spun out of the Virginia Tech Anaerobe Laboratory in Blacksburg, Va. It was founded by microbiologists Tracy Wilkins and David Lyerly, whose work had focused on Clostridium difficile, a bacteria that can also cause gastrointestinal illnesses. The company now has 72 employees and more than 15 products on the market, including the E. histolytica test. Lyerly said TechLab is always trying to push basic research to improve its products.

“We go to the top institutions in the country,” he says. “That’s why we started the collaboration with U.Va., because it is a top-notch university doing work that dovetails perfectly with what we do here.”

A Chance Meeting Leads to Collaboration

Petri and Wilkins crossed paths in 1992 when Petri made a presentation at an American Society of Microbiology chapter meeting held at Virginia Tech.

“Very fortunately for me, Tracy happened to be there,” says Petri. “The presentation was about our attempts to make a better diagnostic test for amebiasis. We’d had some limited success doing that, but Tracy and his company were and still are today, the world’s experts in how to make diagnostic tests for intestinal infectious diseases.”

The pair spoke during the meeting and decided to work together.

“There were no research grants or anything,” he recalls. “We agreed to take some of the antibodies that we had made against this parasite and turn it into a diagnostic test that would work and could pass muster at the FDA.”

Petri calls the importance of the collaboration between the two “enormous for the field of tropical medicine and amebiasis. There still is no other diagnostic test specifically for E. histolytica. Since then, it has gone through three generations of FDA approval, with each one better than the last generation.”

Petri says the importance of the collaboration goes well beyond simply having a good diagnostic test.

“We have been able since 1999 to work with a cohort of 500 children in Dhaka, Bangladesh, who have been monitored every other day for diarrheal illness,” he says. “With their tests, we have been able to quickly ascertain when the children have diarrhea if it is due to amebiasis, which often leads to malnutrition. And malnutrition in turn is the most common cause of death in children in the developing world.”

Before there was a good diagnostic test for amebiasis, Petri says no one knew how common it was or if those who had it were resistant to being reinfected.

“A number of very fundamental questions were unresolved,” he says. “If you don’t have a good way of reliably diagnosing an infection, there is no way to study it in humans. All this was made possible by the TechLab test.”

Petri and his colleagues in Bangladesh learned that amebiasis is quite common in the children they are following.

“About 40 percent of Bangladeshi children we are following are infected with this parasite every year,” he says. “We also discovered that the infection is linked to malnutrition. So if you are malnourished, you are four times more likely to become infected.”

Hope for a Vaccine

Petri and his team learned that when the body creates antibodies against this parasite, reinfection is less likely. In other words, they discovered that these intestinal antibodies can lead to immunity to the infection.

“We can use this information to try to rationally develop a vaccine against the infection,” he says. “All because of the TechLab test. Without that, none of this work would have gone forward. This has been the perfect collaboration where both parties benefit equally. This has been win-win from the very beginning.”

Petri said his current work with TechLab is being supported by the National Institutes of Health through cooperative research agreements that are part of the Vaccine Initiative and with Small Business Technology Transfer program funding.

But the work Petri is most devoted to is the amebiasis vaccine.

Petri said he believes the vaccine will be tested on humans by 2011.

“If I can help achieve a vaccine against amebiasis, I will be overjoyed,” he says. “That will be a huge accomplishment by many people working together.”

“The biggest winners, I think, are going to be children in the developing world,” he says.

Malnutriation is the biggest killer of children in the first five years of life. ​What is coming out of all this is a better way of understanding what contributes to malnutrition in the developing world.
Dr. William Petri

What we have discovered so far from this work is the contribution of cryptosporidiosis, amebiasis and giardiasis to malnutrition. Having a better way of diagnosing means you have a better way of treating it to try to help prevent malnutrition.

“And it’s malnutrition that makes children so susceptible to the other diseases like pneumonia that kill so many of them around the globe.” 

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Ohio University Researcher Discovers Key to Producing Cheap Hydrogen Fuel

Ohio University

Ohio University Researcher Discovers Key to Producing Cheap Hydrogen Fuel

What do nuclear submarines and petrochemical plants have in common?

Both use ammonia.

Ben Schafer learned about this colorless, pungent gas during a stint as a submariner — or “bubble head” — in the U.S. Navy. Gerardine Botte, an associate professor of chemical and biomolecular engineering at Ohio

University in Athens, became familiar with it from her studies and while working in her native Venezuela.

The two ended up putting their heads together after attending a Denver meeting of the Electrochemical Society in December 2005. Botte was there representing her university’s Russ College of Engineering and Technology, while Schafer was attending on behalf of his company, the Hydra Fuel Cell Corp.

The result — less than two years later — was a collaborative private sector-university partnership to develop inexpensive hydrogen from ammonia, while also producing clean wastewater in the process. This partnership led to the establishment of a new company, American Hydrogen Corp. in the Ohio University Innovation Center, which aims to produce inexpensive hydrogen from ammonia and clean wastewater in the process.

Schafer, a computer engineer, was scouting for a cheap source of hydrogen to power small electric generators made by the Hydra Fuel Cell Corp., a subsidiary of American Security Resources Corp. (ASRC). “I’d been looking for six months,” says Schafer. “I was continually being pinged (a submariner term) by people asking me ‘where you gonna get the hydrogen?’” he says.

“Like all fuel cell companies, we’d kind of ducked the question and said the problem will get solved eventually,” he recalls. “But I was getting tired of the questions.”

Schafer knew that nuclear submarines had used ammonia in their reactors’ coolant. “We used lots of it and I was exposed to its chemistry back then,” says Schafer, a proud bubble head for seven years.

An Auspicious Lunch

Fast forward 30 years to the conference in Denver. Schafer encountered Botte and the two sat down for lunch. It was an auspicious meeting.

“I said I worked for a fuel cell company and was trying to fi nd ways to provide hydrogen,” he recalls. “She asked if I’d considered ammonia, and I told her I had, but hadn’t found a way to reduce it to nitrogen and hydrogen. She said ‘let’s talk’ and that’s how it started. It wasn’t long before we were communicating near the speed of a couple of Cray super computers.”

In a nutshell, Botte had developed a patent-pending ammonia catalytic electrolyzer (ACE) technology to efficiently convert ammonia into hydrogen.

Botte, director of Ohio University’s Electrochemical Engineering Research Laboratory came up with the idea of passing ammonia through the electrolyzer after attending a Honda Initiation Grant Conference in Columbus, Ohio, in 2002.

“One of the presenters at the conference said fuel cells are great because you start with clean water, clean energy, and in return you can produce clean water and clean power,” she recalls.

“I went back into my lab after that conference and spent the whole night doing calculations and realized that the thermodynamics of the reaction were wonderful. I said I have to work on this right away,” she says.

Botte did the initial experiments herself and then got her students involved.

“In the beginning it was like using a magnifying glass to look at little bubbles of what we have right now, which is a process that produces tons and tons of hydrogen,” she says (figuratively speaking).

“I started with an idea and a small piece of paper, which had the potential for a commercial application. And now it has become a company.”

Room Temperature

One of the things Schafer liked about Botte’s discovery is that it takes place at room temperature and under low pressure, requiring less energy and expense than high-pressure, high temperature processes.

The cost is also reasonable, too, he says.

It’s not the horse that costs you, it’s the feed. And in this case, ammonia is inexpensive. A tremendous amount of it goes into the environment as waste and we see that as a tremendous potential for recovery in energy use.
Ben Schafer

Schafer figures Botte’s process involving the ammonia catalytic electrolyzer will be able to process a kilo of hydrogen for $2, far less than the $8 to $10 it costs in today’s market. And a kilo of hydrogen, he notes, is the equivalent of one gallon of gas.

Schafer explains, “It’s our intention to take the ACE to market in conjunction with our Hydra Fuel Cell products as the first commercial ammonia-to-energy process in the one-to-five kilowatt range.

“We also have the grander dream of really getting the hydrogen economy moving by using ammonia as the feedstock to run stationary fuel cells to supply electricity to sites and also to dispense hydrogen for hydrogen powered vehicles.

“What you store locally is ammonia and then convert it to hydrogen for your vehicle,” he says. “Or you store ammonia in a gas tank and convert it onboard to feed an electric fuel cell.”

Environmental Benefits and Profitable Solutions

The sources of ammonia are wide ranging, according to Botte.

“There is a lot of ammonia in the waste slurry from animals, for example, and it is a byproduct of plenty of other processes,” she says. But on the drive back from the Columbus conference in 2002 to her Ohio University campus in Athens, she says she had an epiphany.

“I said ‘wow,’ ammonia from wastewater would be a wonderful source to produce hydrogen because it is abundant and independent of fossil fuels,” she says.

“And if I put the wastewater through an electrolyzer. I remove the ammonia waste from the water and produce clean power and clean water,” she says. “It is a beautiful picture.”

Besides the obvious environmental benefits of removing ammonia from wastewater, there are great benefits for companies that have to dispose of ammonia they use or produce as a byproduct in their manufacturing processes. In some cases, this disposal can be costly, and can require additional time and resources. But now there’s an alternative.

Instead of spending money on ammonia disposal, these companies could potentially use the ammonia catalytic electrolyzer to remove ammonia and resell it to companies that can use it to produce hydrogen, or they might even convert it to hydrogen themselves and resell it. Bottom line, it amounts to transforming a costly waste item into a profitable commodity.

“The great thing about this is that it can go so many places. It could drive a car or even be in a shuttle in a mission to Mars in the future,” she says. Botte says the ACE technology dovetailed with other work she had been doing in her lab during the past several years, such as hydrogen storage.

Schafer, who likes to move fast, visited Ohio University not long after the Denver conference. He toured Botte’s facilities and went back to his board seeking $50,000 to fund a project to scale up her “lab project” from 250 milliwatts to five watts.

The results, he says, were “impressive.”

Fruitful Negotiations = Collaborative Relationship

Ohio University’s Technology Transfer Office and ASRC soon entered negotiations to license Botte’s technology. As a result, the university had a substantial license package, including up-front payment, minimum annual licensee payments, running royalties for fuel cells and hydrogen production, and a sizable equity stake in ASRC for the Ohio University Foundation. And, just as important, Botte’s lab had a two-year, $600,000 sponsored research contract to support her ACE-related research and development project.

At the same time, ASRC created American Hydrogen Corp., which has exclusive worldwide rights to commercialize the technology for hydrogen production and fuel cell applications, and set up the new company in Athens at the Ohio

University Innovation Center, further strengthening the collaborative ties between ASRC and the university.

Robert Malott, associate director for technology commercialization at the university, says gaining equity in ASRC was a key to the deal. In addition to American Hydrogen and Hydra Fuel Cell, ASRC also owns a third company called American Wind Power. ASRC may also make more acquisitions in the energy field, he said.

Malott says the collaboration between the university and ASRC and American Hydrogen Corp. has gone well.

“We liked Ben’s demeanor and found him and the others we dealt with to be straightforward and down-to-earth, the kind of people we like to do business with,” Malott recalls. “There was no “smoke and mirrors” or any game-playing.”

Schafer agrees.

“It’s been great dealing with the Ohio University folks,” he says. “And their Innovation Center, especially if you are in the early stages of starting up a company, is super. The flexibility is nice and you can’t beat the cost in terms of services that are available. It takes a lot of the pain out of being a startup, that’s for sure.”

Botte, a consultant for American Hydrogen, is pleased, too. Not only is her future research being solidly funded, but her graduate students are finding work at the fledgling company.

“There is a lot of interaction between their personnel, myself and my students,” she says. “And I’m advising them on different market and R&D opportunities for the project.

“I think I will always be a professor,” she says. “But I have some ideas for the future of additional things I’d like to start.” 


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An Effective Therapeutic for Sickle Cell Disease

Virginia Commonwealth University

An Effective Therapeutic  for  Sickle Cell Disease

Donald Abraham’s quest to find a new drug to treat sickle cell disease (SCD) has all the intrigue and plot twists of a suspense novel: It’s a decades-long, against-all-odds pursuit filled with overwhelming obstacles, false starts, uncanny timing, dogged determination, international collaborations and not one, but two chance meetings.

Some 40 years after he began looking for a way to alter the underlying molecular mechanism of SCD, the compound Abraham discovered at Virginia Commonwealth University (VCU), is now a drug candidate being evaluated in clinical trials.

“I threw everything, my whole heart and science into sickle cell disease,” says the retired Abraham, who served as professor of medicinal chemistry and director of VCU’s Institute for Structural Biology and Drug Discovery at from 1988 to 2007. “For a long while it wasn’t the wisest thing to do. But since my postdoctoral days in 1963, my great desire was to use structural biology to discover a drug.”

Structure-Based Drug Design

Structural biology, or structure-based drug design, uses X-ray crystallography or nuclear magnetic resonance spectroscopy to obtain information on a three-dimensional structure — the drug target — to aid in the search for a small molecule to bind to the target in a way that achieves a therapeutic benefit.

“You can think of the structure as the puzzle with a piece missing,” explains Abraham, who was one of the first scientists to attempt to use structural biology for drug design. “You know what the piece has to look like to fit in.”

Abraham chose to work on SCD because it provided him with a ready-made puzzle.

The molecular structure of hemoglobin, a protein inside red blood cells that carries oxygen throughout the body, was the first protein to be decoded — along with a genetic mutation found in people with SCD. When mutant or “sickle” hemoglobin releases its oxygen, it sticks to other sickle hemoglobin (a process called polymerization), creating rigid rods that distort red blood cells from their typically round shape into narrow crescents. These sickle cells stick to each other and to blood vessel walls, causing anemia, organ damage and overwhelming pain.

Searching for a Missing Piece

In 1975, despite a lack of funding and support for SCD research, Abraham launched what would become a decades-long search for a molecule — the missing puzzle piece — to bind to sickle hemoglobin and prevent the polymerization process and the consequent sickling action.

“I was told that I had 0 percent chance of solving this,” says Abraham, who remained undeterred. “I went into this field with the hope of one day discovering a new drug to relieve human suffering.”

Sickle cell disease occurs in about 1 out of every 500 African American births. Millions of people are affected by the disease worldwide,

According to the Centers for Disease Control and Prevention, SCD is a hereditary disease that mainly affects African Americans: Less than 100,000 people suffer from SCD in the United States — too few to warrant a billion-plus-dollar research program from major pharmaceutical companies.

Pursuing a rare or orphan disease meant Abraham would lose his funding from the National Institutes of Health (NIH) and his research team. But a chance meeting with a professional baseball player fundraising for SCD research led to new funding sources and, eventually, the opportunity to collaborate with Max Perutz at the Medical Research Council Laboratory of Molecular Biology in Cambridge, UK, who had won a Nobel Prize for his work unraveling hemoglobin. Their research, which spanned an eight-year period, in turn attracted a team of graduate students and postdoctoral fellows to Abraham’s VCU lab.

Building Momentum

By the late 1980s, Abraham’s research team had identified a number of compounds that inhibited polymerization in the test tube, but all proved to be too toxic for use in humans.

“Sickle cell patients have almost a pound of hemoglobin,” explains Abraham. “So in the early 1990s we shifted gears and began searching for a food-like agent that could be tolerated at high doses throughout a patient’s lifetime.”

The common flavoring agent vanillin proved promising at first but metabolized too quickly in the body, leaving Abraham and his researchers at a dead end.

Food-Based Agents

Fate intervened once more when Abraham and his wife were on a train trip across Italy and shared a train cabin with a British food chemist.

“I asked him if he knew of any nontoxic food agents like vanillin that might be suitable candidates to test,” says Abraham. “It was a last ditch effort because I had no idea what else could be out there.”

The chemist sent Abraham a list of possible compounds that included a byproduct of browning sugar called 5-Hydroxymethylfurfural (5-HMF). Basic animal studies of the compound, conducted at Children’s Hospital of Philadelphia, confirmed the efficacy of the compound.

In 2002, Abraham, Martin K. Safo, Ph.D., and Richmond Danso-Danquah, Ph.D., disclosed their discovery to VCU’s Innovation Gateway. Safo, a former postdoctoral fellow in Abraham’s group, is leading the ongoing sickle cell disease drug discovery effort at the Institute for Structural Biology and Drug Discovery.  

“I don’t think any of this would have happened if it weren’t for [former VCU] President Eugene Trani,” says Abraham. “He had a real can-do attitude and an interest in advancing science and our work through commercialization.”

VCU’s Innovation Gateway filed the first patent on 5-HMF in 2004 and licensed the compound to a startup company. When that company failed, a second startup based in Newton, Mass., AesRx, acquired the rights to the preclinical molecule in 2009 and renamed it Aes-103.

“The compound was the most attractive opportunity I had ever seen,” says AesRx CEO Steve Seiler. “There is a crying need for a novel intervention for SCD that is disease modifying. SCD was first described in 1910, and more than 100 years later, there is still no drug to treat it except an anticancer drug that has side effects and compliance issues.”

Ivelina Metcheva, executive director of VCU’s Innovation Gateway, says Seilerprovided a great example of how to communicate with a technology transfer office.

“He continually kept us apprised of where he was in the development process and the obstacles he was facing,” she says. “As a result, we modified the license agreement to give him some breathing room to grow the business.”

Connecting With TRND

With the economy in a tailspin, financing was a major issue for AesRx until 2010, when Seiler connected with the National Heart, Lung and Blood Institute (NHLBI) and the Therapeutics for Rare and Neglected Diseases (TRND) program, part of the NIH’s National Center for Advancing Translational Sciences.

“We created a multiphase, multi-institute, public-private research collaboration with researchers from the NHLBI and TRND,” says Seiler.

Within a year, AesRx was able to apply to the Food and Drug Administration for an investigational new drug application and move into early stage clinical trials, which showed that patients who took one dose of Aes-103 experienced significantly less pain.

A phase II trial designed to test dosing and efficacy began in London in 2013. The NIH provided $5 million in funding to support the collaborative research effort, and AesRx also secured additional financing in the form of a Massachusetts Life Sciences Center Accelerator Loan.

Seiler credits the cooperation among highly skilled researchers, VCU’s Innnovation Gateway and TRND’s business model for the quick progress made on Aes-103.

Derisking Drug Development

“The NIH played a prominent role in getting the clinical data to derisk further development of this drug so it would be appealing to venture capitalists and pharmaceutical companies that could take it the rest of the way,” says Seiler. “You need good science, but you also need good people to associate with. We had good partners.”

In July 2014, the biopharmaceutical company Baxter International acquired Aes-103 and is continuing clinical development activities required for regulatory approval and commercialization, including completing Phase II and III trials.

“From a professional perspective, this was the most satisfying thing I’ve ever done,” says Seiler. “It’s really encouraging and I hope to see it work for patients.”

If Aes-103 is able to improve the lives of SCD patients, it will not only provide a storybook ending for Abraham, it could a start a new chapter for other rare and underfunded diseases.

“The business model that TRND proposed works and can be used for other orphan diseases,” says Seiler. “So there’s an impact beyond the SCD, focus and that’s something we should all be proud of.”


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A Promising Tool Against Prostate Cancer

University of Maryland Baltimore

A Promising Tool Against Prostate Cancer

Prostate cancer is the most common type of cancer in America (skin cancers excluded) affecting one in six men. In fact, more than 234,000 men in the United States will be diagnosed with prostate cancer this year, according to the Prostate Cancer Foundation. Prostate cancer can cause pain, difficulty in urinating, erectile dysfunction and other symptoms.

Now, a team of researchers at the University of Maryland, Baltimore, offer a promising weapon in the fight against prostate cancer. Angela Brodie, Ph.D., and Vincent C. O. Njar, Ph.D., both researchers at the university, developed a cadre of proprietary compounds that functionally inhibit the growth of prostate cancer cells.

These inhibitors block the interaction between androgen, a steroid made by the body, and its receptors. Androgen receptors are thought to play a critical role in prostate cancer growth.

Androgren synthesis inhibitors offer patients a much-needed potential therapy for prostate cancer.

The research was supported with a grant from the National Institutes of Health.

Tokai Pharmaceuticals, Inc., located in Cambridge, Mass., is the exclusive licensee of the androgen synthesis inhibitor technology.

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From Pilot Study to Market in Less than 4 Years, Angiotensin II Stabilizes Critically Ill Patients

George Washington University

From Pilot Study to Market in Less than 4 Years, Angiotensin II Stabilizes Critically Ill Patients
GIAPREZA helps patients hospitalized with septic shock that are urgently in need of critical care.

By targeting a new route to raise blood pressure, the first and only FDA-approved drug of its kind, angiotensin II (trade name GIAPREZA™), may save patients’ lives.

An infection (sepsis), allergic reaction, or severe accident can decrease blood flow to the brain, heart, and other vital organs. Hormones that target different blood pressure regulation pathways have been in use for years but are not effective for many patients. 

The George Washington University (GW) School of Medicine and Health Sciences’ Professor Lakhmir Chawla, M.D., tested peptide hormone angiotensin II on 20 patients in a 2014 pilot study. Dr. Chawla found that angiotensin II effectively narrowed blood vessels to increase dangerously low blood pressure in patients with septic shock. 

Because Dr. Chawla’s promising results could significantly improve the safety or effectiveness of treating, diagnosing, or preventing a serious condition, the FDA allowed angiotensin II to proceed directly from the pilot study to a phase III clinical trial. It also provided Priority Review, meaning the FDA intends to act on a New Drug Application within just six months, so a treatment can reach patients sooner than usual.

It is extremely rare to have a pharmaceutical come out of a university and go straight into a phase III clinical trial," said Steve Kubisen, Managing Director of GW's Technology Commercialization Office (TCO).

GW’s TCO managed patent filings using outside patent prosecution counsel, and managed licensing of the exclusive rights to the patents to the La Jolla Pharmaceutical Co. (LJPC) in 2015. They started with an option agreement and negotiated the exclusive license that followed. GW TCO also managed the royalty monetization process, utilizing a well-known royalty monetization structuring agent.

The FDA approved GIAPREZA™ in 2017, and LJPC began selling the drug in 2018.

GW’s TCO also obtained broad international patent protection for GIAPREZA™ which will help provide incentive for LJPC to distribute the drug to patients in need globally.

 “In 2019, the European Commission approved GIAPREZA™ and GW’s European patent was granted.  This provides an opportunity to help patients outside the US,” Kubisen said.

Also in 2019, GW struck a deal with financial services firm Barings LLC to sell a portion of its US royalty rights, a common practice for high-value drugs. GW plans to reinvest this game-changing cash infusion into strategic priorities.

“The money could accelerate commercialization in orthopedics, cancer drugs, cardiac devices, diagnostics, and other products GW is developing or licensing out,” Kubisen said.  

“This is an extraordinary example of GW research and innovation at its best,” said GW President Thomas LeBlanc. “A treatment developed here will improve clinical care and save lives, while at the same time provide resources for our university to reinvest in research for the next big discovery. Our impact on society will only continue to grow.”

Patent Number(s): 9,572,856; 9,867,863; 10,500,247; 10,322,160; 10,335,451; 10,548,943; 9,220,745; 10,028,995; 10,493,124

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Crash-Test Software Saves Lives and Money

Wayne State University

Crash-Test Software Saves Lives and Money

Because dummies are not human, the crash-test data that automobile manufacturers rely on to make design decisions is not as relevant to human safety as it could be. Professor King H. Yang, Ph.D., director of the Bioengineering Center at the College of Engineering at Wayne State University in Detroit, decided to come up with a more “human” way to test car safety.

Using crash-test dummies is a good way to make cars safer for dummies — but not necessarily people.

In the early 1990s Yang, along with professor Albert I. King, Ph.D., and a team of graduate students developed a software program called Anthropomorphic Numerical Surrogate for Injury Reduction (ANSIR). The Centers for Disease Control and the automotive industry supported the research, which exceeded $10 million.

The technology was disclosed in 1995 and licensed in 1998 to Toyota Motor Co. ANSIR is a software program that uses computerized models to demonstrate the detailed effects of car crashes on the human body. The models are based on tests using cadavers and reveal how various crash angles, velocities and car sizes affect the human body, especially internal organs. ANSIR presents far more detailed and accurate information compared to data derived from crash tests with dummies.

Toyota is currently developing its own variation of ANSIR and requires first-tier suppliers to use human models to check the safety performance of the parts they supply. ANSIR technology has been licensed around the world and is expected to save millions of dollars in crash-testing vehicles, improve vehicle safety, and reduce injuries. The software also has applications for designing sports and military helmets, body armor, and for pre-neurosurgical planning.


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Promising New Antibiotics Effective Against Infections Resistant to and Tolerant of Current Treatments

St Jude Children's Research Hospital
St. Jude Children's Research Hospital

Promising New Antibiotics Effective Against Infections Resistant to and Tolerant of Current Treatments

For over 100 years, antibiotics have been used to fight bacterial infection and disease. However, bacteria are increasingly developing resistance to front line antibiotics,and new therapies are needed to treat these bacterial strains. Dr. Richard Lee, Ph.D., a member of the St. Jude Department of Chemical Biology and Therapeutics, is developing two new classes of compounds to be effective in treating strains that are no longer effectively treated with current therapies. One compound is an adaptation of an old antibiotic- Spectinomycin, which is modified using structure based drug design. The other compound is designed to treat chronic infections and biofilms caused by persister cells that have become tolerant of existing antibiotics. Both compound classes are described below:

Treating resistant bacteria

Dr. Lee’s laboratory designed a promising new class of antibiotics, called aminomethyl spectinomycins, which follows his work on Spectinomycin analogs for treating tuberculosis. In this case a new series of spectinomycin analogs has been developed for treating a broad spectrum of respiratory tract infections including S. pnuemoniae, the most common pathogenic bacteria associated with this type of infection. The aminomethyl spectinomycins are active against drug resistant strains. In collaboration with Dr. Jason Rosch in the Infectious Diseases department, the robust efficacy of this compound series has been demonstrated at low compound dosing levels, further validating this series. These compounds have been licensed by Microbiotix, a privately-held, clinical stage biopharmaceutical company engaged in the discovery and development of novel small molecule anti-infectives.

“This study demonstrates how classic antibiotics derived from natural products can be redesigned to create semi-synthetic compounds to overcome  drug resistance.” - Richard Lee, Ph.D.

Treating tolerant bacteria

Dr. Lee and his collaborators developed another set of compounds designed to treat bacteria, fungi and parasites that develop multidrug tolerance by becoming dormant.
Small subpopulations of tolerant microbial cells are called persister cells, because they can survive the antimicrobial treatments that kill their genetically identical siblings.

When persister cells are left behind, they become a reservoir from which an infection can recur. Examples of chronic infections include endocarditis, urinary tract infections, gingivitis, middle ear infections, fatal lung disease (cystic fibrosis) and infections produced by biofilms.

These infections are often associated with implanted medical devices, such as catheters and artificial joints. Multidrug tolerant infections account for more than 60% of all microbial infections, are hard to treat and subject to infection relapse. Traditional antibiotics kill active cells via inhibition; however, this new set of compounds acts to kill dormant cells. They could be used to treat infections caused by biofilms; and other infections caused by chronic bacteria persister cells. These compounds have been licensed to Arietis, a Boston-based biotechnology company, focused on the discovery and development of novel antimicrobial agents.

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Antimicrobial Coating for Implaned Medical Decices Reduces Risk of Post-Op Infections

Columbia University

Antimicrobial Coating for Implaned Medical Decices Reduces Risk of Post-Op Infections

Infections are a growing problem in health care settings. According to the Centers for Disease Control, there are 4.5 hospital infections for every 100 patient admissions, and nearly 100,000 deaths annually from hospital infections.

To fight this problem, department of surgery researchers at Columbia University in New York, N.Y. have developed an antimicrobial coating for implanted medical devices that reduces the risk of post-operative infection. From 1984 to 1987 Shanta Modak, M.D., Charles Fox, M.D., and Lester Sampath, M.D. developed the method and technology for applying an antimicrobial coating to medical devices and surfaces, making them infection-resistant.

The coating consists of a polymeric matrix containing antimicrobial silver sulfadiazine and chlorhexidine. Initially funded with $500,000 from Daltex Medical Sciences, early experiments involved coating urinary catheters, gauze dressings, soft tissue patches, arterial grafts, catheters, wound covers, gloves, mask, contraceptive devices and implantable pumps.

Studies have shown a 50-80 percent reduction in catheter-related infection and a 60 percent reduction in bloodstream infection when this antimicrobial coating is used.

Columbia University licensed this technology to Daltex Medical Sciences in 1987, which later sublicensed it to Arrow International. Arrow International has sold more than five million central venous catheters that utilize this technology.

W.L. Gore also incorporates this coating in manufacturing the only  hernia repair material that inhibits bacterial colonization in the hernia repair patch for up to two weeks after its implantation. Current research also indicates a lower risk of microorganisms developing resistance to antimicrobialcoated surfaces compared to non-coated implanted medical devices, making them a better long-term solution for patients.

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Anti-Sway Control System Improves Crane Safety, Saves Time

National University of Singapore

Anti-Sway Control System Improves Crane Safety, Saves Time

Industrial crane operators typically manipulate the independent motions of trolley, hoisting and traverse when they are moving payloads. This, however, can result in an uncontrolled swaying motion, which slows down the construction process because extra time is required to let the swaying motion come to a stop. Uncontrolled swaying is also a safety issue that can result in serious injury. 

Led by associate professor Ong Chong Jin, researchers at the National University of Singapore’s Mechanical Engineering Department have developed a highly effective solution to the control of payload sway in industrial crane and crane-like structures. The “Anti-Sway Control of a Crane Under Operator’s Command” technology was developed in 2000.

The use of this technology on construction sites improves safety; labor costs are also reduced because operators spend less time waiting for swaying motions to cease.

In response to the operator’s command for trolley, hoist and traverse motions, this software program utilizes a family of differential equations to calculate the precise counter-adjustments necessary for canceling out sway. The differential equations are solved in real time, using sensory measurement of the cable length and its time derivative.

The program also responds immediately to the operator’s commands under simultaneous trolley/hoisting and traverse/hoisting motions. The software takes into account the acceleration, velocity, and span limits of the drive system of the crane to ensure the anti-sway control is not compromised when these limits are reached.


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From Hardware Store to Operating Room

University of British Columbia

From Hardware Store to Operating Room

Healthcare facilities in the developing world lack many resources, including access to expensive surgical equipment. As a result, some 5 billion people lack access to safe surgery because surgeons do not have access to the right medical equipment.

Case in point: orthopedic drills needed to perform surgery on serious bone and muscle injuries cost upwards of $30,000. That leaves orthopedic surgeons in low-resource areas with two options — they can use non- sterile hardware drills which increase the  risk of infection, or use sterile, hand-cranked drills that are labor- intensive and  lack precision.

Working with surgeons from Canada and Uganda, graduate students in biomedical engineering at the University of British Columbia (UBC) created a third and more appealing option — a reusable drill cover that transforms a drill purchased at a hardware store into a sterile surgical instrument.

Transforming off-the-shelf hardware into surgical equipment has helped reduce the rate of infection, improve patient outcomes and reduce operating times for low-resource environments in 20 countries.

UBC assigned the patented drill cover to Arbutus Medical. The company’s flagship product, the Arbutus Drill Cover, has been used in more than 12,000 surgeries in 20 countries. Use of the sterilizable and reusable drill cover has  helped reduce the rate of infection, improve patient outcomes and reduce operating times.

Arbutus Medical named the company after the Arbutus tree, an evergreen tree native to the southwest coast of British Columbia that thrives in harsh environments. Like its namesake, the company is working with surgeons around the world to develop safe, affordable and appropriate medical equipment for low-resource environments.

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Designing Devices for Africa's Rural Poor

University of Georgia
University of Georgia Research Foundation

Designing Devices for Africa's Rural Poor

In industrialized countries, a milk cooler is where shoppers grab a gallon of milk at the grocery store. A nutcracker is something people use to pry open a pecan.

But in developing countries, those two devices can look quite different. In some countries, a milk cooler is something a dairy farmer uses to keep his cows’ milk from spoiling. A nutcracker is a person with a rock.

Thanks to William Kisaalita, Ph.D., a professor and tissue engineer at the University of Georgia (UGA) in Athens, storing and harvesting food has become much easier for farmers in Uganda and Morocco. The milk cooler and nutcracker he developed give an economic boost to those who struggle to make a living.

The Uganda-born Kisaalita worked with UGA engineering students to develop these two devices. And though the innovations may be made of metal, a lot of heart goes into the invention process.

The professor, who grew up just outside Kampala, Uganda, is now a U.S. citizen. He and his wife, an accountant, have four children who are healthy and successful. His current surroundings are a stark contrast to the place where he grew up: a house made of reeds and mud, lit by kerosene and heated with wood.

Kisaalita left Uganda, earned his doctoral degree in Canada, and joined UGA’s College of Agricultural and Environmental Sciences in 1991. After asking himself what he could do to help people like those he had grown up with, he set up a program in which engineering students can go overseas and design products to help the poor.

The first product they came up with was a milk cooler about the size of a dishwasher. Farmers along Uganda’s “cattle corridor,” a 50,000-square-mile dry-land area stretching north to south, are now using that cooler.

That region is home to more than 2.5 million dairy farms. Most farmers have between two and five cows. Farmers milk the cows, which produce an average of 50 liters of milk a day, in the morning and evening.

In the past, lack of refrigeration forced farmers to pour about 40 percent of their income potential down the drain each night.

During the day, farmers sell the milk to local vendors who transport the milk to cooling stations. But those markets are closed in the evening. So, in the past, farmers had no way to cool the milk produced in the evening. The

So Kisaalita and 15 of his undergraduate students came up with a power-independent cooler for short-term milk storage. The cooler uses a vacuum system and a mineral called zeolite to help keep the milk cold.

Research funding came from a number of sources: the University of Georgia Research Foundation Inc., the World Bank, U.S. National Science Foundation, U.S. Department of Agriculture and U.S. Environmental Protection Agency.

After the first prototype of the cooler didn’t work well enough to market, Kisaalita found an unlikely partner: a German company called Cool-System KEG GmbH, which had designed a selfcooling keg for beer drinkers. After some redesign, Cool-System produced a cooler called CoolChurn. The keglike cooler chills15 liters of milk within three or four hours, and keeps it cold for a full day.

But instead of resting on his laurels, Kisaalita has continued to engineer practical, simple solutions for Africa’s rural poor. So when a colleague approached him in 2005 on behalf of people in rural Morocco, Kisaalita took up the challenge.

The professor and his students were determined to crack the mystery of how to help the Moroccans. Women and children in Morocco used rocks to manually open argan nuts, which contain oil-rich seeds. When cracked open, those seeds yield argan oil, which gourmands around the world use as a cooking ingredient. The oil also serves as a rich source of vitamin E for cosmetics.

Cracking those nuts using rocks was not only labor-intensive, it was unsafe. Workers engaged in this work sometimes broke fingers. Sustaining such an injury meant women and children faced periods of inactivity and lost income from one of the few economic activities available to them. Given the lack of proper medical care, those broken fingers often resulted in poorly healed bones. That could lead to hand or finger deformity — even permanent injury.

So Kisaalita and students Max Neu, Meghan Samberg, Jonathan Dunn and Phillip Jones designed a simple metal-and-wood structure that cracks one nut at a time and is three times faster than cracking with rocks. The device is much sturdier than a nutcracker a consumer in the United States might use for something like an almond because argan nuts are incredibly hard to crack. Kisaalita’s nutcracker maximizes safety, thereby eliminating injuries while greatly increasing productivity and income.

The University of Georgia Research Foundation Inc. and the University of Georgia Office of the Vice President for Public Service and Outreach both funded the technology, which is now in use in Morocco.

Someone who lives in an industrialized country may not always think about where the food comes from before it arrives on a dinner plate. But for William Kisaalita and his students, the question of how farmers will get food on the table is one they won’t be forgetting anytime soon.


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Bovine Intervention: Sleeping Sickness a Thing of the Past

University of Greenwich

Bovine Intervention: Sleeping Sickness a Thing of the Past

One of Africa’s most harmful pests, the tsetse fly, has been all but eradicated from parts of the continent thanks to a novel artificial cow developed by an international group of researchers, including scientists from the University of Greenwich.

Today, sleeping sickness is virtually unheard of.

The artificial cows attract tsetse — which can infect humans and  cattle with fatal sleeping sickness — by emitting chemicals (kairomones) to mimic the smell of real cattle. The fake cattle are impregnated with insecticides that kill the tsetse attracted to them.

The cows were introduced to Zimbabwe in the mid-1980s, when thousands of cattle were infected with nagana (the equivalent to human sleeping sickness), transmitted by tsetse.

Cases of sleeping sickness in Zimbabwe have plummeted to practically zero, largely due to the use of artificial cows.

Cases of nagana in Zimbabwe been virtually zero for the last five years with the help of nearly 60,000 articificial cows. The fake cows also act as an effective barrier to stop tsetse re-invading areas cleared of flies.

Not only are artificial cows highly successful in controlling tsetse, but their use also results in a dramatic reduction in the amount of insecticide necessary to control the pest.

With only four artificial cows needed per square kilometre to ensure effective pest control, the use of insecticide is far more targeted than conventional widespread aerial and ground spraying, resulting in a greatly reduced environmental impact.


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Artificial Lung Helps Patients Breathe Easier

University of Pittsburgh

Artificial Lung Helps Patients Breathe Easier

A 76-year-old woman with chronic emphysema was admitted to a hospital in India earlier this year. She was complaining of shortness of breath and was diagnosed as being in respiratory failure, meaning she had a buildup of carbon dioxide in her lungs and couldn’t take deep enough breaths to push it out and suck in oxygen instead.

Normally doctors would put such a patient on a mechanical ventilator, which would mean sedating her so they could insert a breathing tube down her throat. Instead, her doctors decided she was the ideal person to be enrolled as the first patient in a study of a new artificial lung initially developed by researchers at the University of Pittsburgh, called the Hemolung.

The device is connected to a patient by a catheter. It pumps blood out of the patient, runs it across a bundle of fibers that pull out carbon dioxide and infuse oxygen, then sends the blood back into the patient, thus doing about 50 percent of the work of the person’s failing lungs.

The woman was hooked up to the Hemolung and quickly began breathing more easily. By the time it was removed three days later, her carbon dioxide levels were down, and she could breathe on her own. Equally importantly, she had avoided needing to be put on a mechanical ventilator and, therefore, spent her time in the hospital alert and able to eat and talk with her family.

“It was very rewarding to see that happen,” says Nick Kuhn, chief operating officer (COO) of ALung Technologies, the Pittsburgh company developing the Hemolung. ALung is hoping to finish its first clinical trial on patients in Europe and

India early next year and then apply for approval in the United States. The goal is to be able to help the 450,000 people in this country and millions more worldwide avoid temporary hookup to a ventilator, thus granting them a shorter and more comfortable stay in the hospital.

Carbon Dioxide out and Oxygen in

The innovation grew out of work in the Medical Devices Laboratory at the University of Pittsburgh. The external device now known as the Hemolung has changed shape considerably, having started as an internal device. Professors Brack Hattler, M.D., Ph.D., and William Federspiel, Ph.D., designed what they called the Hattler catheter in the mid-1990s. The catheter held a series of tiny hollow fiber tubes that were bundled together and was inserted into a patient’s large vein during respiratory failure. The tubes had oxygen running through them, so when the patient’s blood ran across them, it picked up oxygen and left behind carbon dioxide.

ALung is focusing on two types of potential patients, those with chronic obstructive pulmonary disease (COPD) and those with acute respiratory distress syndrome (ARDS). COPD patients, who often have emphysema, have trouble breathing deeply because the airways in their lungs are restricted, having grown stiff or swollen over the years. ARDS patients’ lungs have been damaged as a result of another disease or accident, and they tend to develop ARDS while in the hospital.

In its first trial, ALung is looking at the Hemolung’s effect on people with COPD who have a sudden drop in respiratory function.

“They could get a cold or a flu or anything that puts these patients over the edge,” Federspiel explains. “If you or I get a bad cold in the winter, we don’t have to go to the intensive care unit because we breathe fine. If they get a bad cold, they can’t breath.”

The artificial lung is a temporary device needed to get them through that period of acute need, usually three to four days. “Eventually the cold or flu resolves itself and they get better,” he says.

Starting a Company

Hattler, who died in 2008, and Federspiel patented the catheter-based artificial lung with the help of the University of Pittsburgh’s Office of Technology Management (OTM) and founded ALung in 1997. They didn’t have any plans to commercialize the device at the time, but needed to work with a company to apply for grants. The research has been funded by the National Institutes of Health, the U.S. Department of Defense and the U.S. Army.

By 2001, they were presenting their idea at scientific conferences and had started generating enthusiasm for an actual catheter-based device, Federspiel says. They couldn’t find an established company interested in licensing the technology, so they decided to set out on their own.

But first they needed to negotiate a one year licensing option with the university, explains Maria Vanegas, OTM technology licensing associate. The office generally grants options to startups because this strategy is a simpler and less expensive way to investigate whether there really is a market for the product. Startups can use that year to perform due diligence on the technology and to start fundraising, she says.

They also brought in an outside chief executive officer for the first time, choosing Kuhn (who switched to COO in 2009), a veteran of other medical device companies. Kuhn worked at raising money, while Hattler and Federspiel toiled in the lab to make the catheter as small as possible. After the one-year option was up, the company fully licensed the technology.

In 2005, they found that the miniaturization of the catheter device topped out at about 1 centimeter in diameter. While it worked well in animal studies, the scientific advisory board assembled by Kuhn opined that such a large a catheter would be unappealing to many medical professionals.

“It became obvious that we needed to make a change,” Kuhn says.

After much deliberation, they decided to scrap the Hattler catheter and turned to a related innovation — the one that eventually became the Hemolung.

Breathing New Life Into the Project

Federspiel had been working on another iteration of the technology that used the same fiber bundle but positioned it outside the body. Because the bundle didn’t have to get inside the person’s vein, the catheter size dropped to 5 millimeters in diameter, the same size used in kidney dialysis.

There was a precedent for an external artificial lung. A technology called extracorporeal membrane oxygenation (ECMO) is used at a small number of hospitals in the country. It removes a patient’s blood, adjusts the gas levels and then pumps it back into the body. But, because it removes two to three liters of blood a minute, the patient has to be very carefully monitored.

“If there’s a complication in the line, they could bleed out,” Federspiel says. “The technology is considered very invasive and complex.”

Federspiel figured that if he could come up with a way to remove sufficient carbon dioxide using a much smaller amount of blood per minute, the technology would be a far more attractive. But removing less blood meant that the artificial lung had to be more efficient in restoring the correct carbon dioxide and oxygen levels to have the same desired effect.

That’s when he had the idea of rotating the fibers. Spinning the fibers allows them to come into contact with more blood as it’s pumped out and so it works more efficiently, Federspiel explains. The Hemolung removes about 400 milliliters of blood a minute, or between a 5th and a 10th as much as the ECMO machine. ALung changed the design while retaining the concept so that the blood now rotates around stationary fibers rather than the opposite.

ALung is now focusing exclusively on the Hemolung. While this switch has slowed down the company’s plans for generating a product, everyone agrees that it has made the device much more marketable. Vanegas applauds Hattler and Federspiel’s determination to see the project succeed, despite the initial setback.

“It’s unique when you find dedicated inventors who don’t get frustrated with the process, especially when they had one device and then had to switch,” she says.

For patients like the woman in India, the device’s long evolution was definitely worth it, both for the medical care it provides and the ability to avoid being hooked to a ventilator.

“They’re able to move around, get out of bed,” Federspiel says. “They have the ability to eat normally, talk normally and express how they’re feeling. It’s a significant quality-of-life improvement.”


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Emory Researchers at the Forefront of HIV Antivirals

Emory University

Emory Researchers at the Forefront of HIV Antivirals

More than 90 percent of people in the U.S. who have HIV, and many around the world, take at least one of the drugs invented by Emory researchers Ray Schinazi, Dennis Liotta, and Woo-Baeg Choi.

In the early 1990s, Schinazi, an infectious disease and antiviral expert, Liotta, a chemist, and Choi, who was a postdoctoral research associate in Liotta's lab at the time, announced the discovery of an unusual molecule, FTC (emtricitabine, sold alone as Emtriva®, with the "Em" standing for Emory) and a chemically similar compound, 3TC (lamivudine, sold alone as Epvir®).
"In addition to being quite effective, Emtriva® is one of the safest antiretroviral agents available," says Liotta. "This is quite important because AIDS patients have to take their drug regimens every day of their lives."
Both drugs are in the class known as nucleoside reverse transcriptase inhibitors, which work against the enzyme that copies HIV RNA into new viral DNA.

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"Everyone was intrigued but skeptical about our work—no one realized the importance of what we had found," Schinazi says. "We pushed Emory University very hard to file patent applications to protect these inventions (FTC and 3TC). Emory finally did, and received the rewards less than ten years later."
This would culminate in a $540 million deal, the largest royalty sale at the time in higher education.
FTC was licensed in 1996 to Triangle Pharmaceuticals, a biotech company founded by Schinazi in 1995. In 1999 and again in 2002, Emory resolved patent disputes with various third parties to consolidate intellectual property rights and clear the path to market for FTC.
In 2003, Gilead acquired Triangle for $482 million; in the same year, FTC was approved by the FDA. Shire and GlaxoSmithKline jointly licensed Emory's patents related to 3TC, which is contained in at least five FDA-approved therapeutics (including a drug to treat chronic hepatitis B).
In 2005, Gilead Sciences and Royalty Pharma signed a deal with Emory to buy its FTC royalty interest for $525 million. Gilead paid Emory an additional $15 million to alter the terms of the license as it relates to the company's plans for developing the compound for use against another disease. Emory College and the School of Medicine were major beneficiaries of the $540 million sale, along with the departments of chemistry and pediatrics and the laboratories of Liotta and Schinazi. Choi left Emory to found the drug-discovery company FOB Synthesis Inc. The three scientists shared 40 percent of the sale.
In August 2004, Gilead obtained approval for Truvada®, a fixed-dose combination of Emtriva® and Viread® for use by people infected with HIV. (In July 2012, the FDA also approved the use of Truvada® to help uninfected people at high risk for the AIDS virus. Truvada® was the first HIV drug to be approved by the FDA for preventative use.)
In July 2006, Gilead and Bristol-Myers-Squibb gained approval for the first once-a-day, single tablet regimen for adults with HIV— Atripla® —from the FDA. Atripla® is intended either as a stand-alone therapy or to be used in combination with other antiretrovirals.
By combining the three drugs, efavirenz (Sustiva®), emtricitabine (Emtriva®) and tenofovir disoporxil fumarate (Viread®), Atripla® reduces pill burden and simplifies dosing schedules, easing compliance, storage, transport and distribution. In North America and Europe, Atripla® is marketed jointly by Gilead and BMS, but in much of the developing world, marketing and distribution is handled by Merck & Co. Merck announced that it will lower the cost of the drug in countries with high HIV prevalence, and will use a sliding scale based on each country's wealth. It is registering Atripla® in forty-five countries in the Middle East and Africa and in nine countries in Latin America, the Caribbean and Asia.
Schinazi is the Frances Winship Walters Professor of Pediatrics at Emory and director of the Laboratory of Biochemical Pharmacology. Liotta is the Samuel Candler Dobbs Professor at Emory and Executive Director of the Emory Institute for Drug Development.
"It's very gratifying to see that our work has helped so many people all over the world," Schinazi says. "HIV is no longer a death sentence."

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Automation Technology Speeds DNA Analysis

Lawrence Livermore Natl Lab

Automation Technology Speeds DNA Analysis

In the event of a disease outbreak or biochemical terrorist attack, identifying the pathological agents as quickly as possible is critical for mitigating losses. Technology developed at Lawrence Livermore National Laboratory in Livermore, Calif., now automates the molecular analytical process.

The technology reduces the time spent obtaining DNA identification from several hours to several minutes.

Lawrence Livermore National Laboratory (LLNL) is a U.S. Department of Energy research laboratory managed by the University of California. The new automation technology, involving a micro-machined chemical reaction chamber with rapid and precise thermal control, was developed from 1994-1995 by LLNL researchers Allen Northrup, Raymond Mariella, Anthony Carrano and Joseph Balch. Initial funding was provided by the Defense Advanced Research Projects Agency, an arm of the U.S. Department of Defense.

What makes this technology unique is the improvement in the thermal control over the reaction occurring in the reaction chamber. Before this technology was developed, a single heating/cooling cycle for copying a DNA strand could take up to four to five minutes, and 30-40 cycles would require several hours for full amplification and identification. Not only do long cycle times delay the DNA identification, but they also permit extraneous reactions to occur in the sample and interfere with the analysis. LLNL technology is a more efficient way to reproduce exact copies of DNA sequences, decreasing the cycle time to as little as several seconds to copy a single strand of DNA, and the full amplification process to a matter of minutes.

The technology was licensed by LLNL to Cepheid, a California-based startup company founded in 1997 to develop and commercialize genetic analysis systems for the clinical assessment, biothreat and life sciences markets. Core products being marketed today by Cepheid that are licensed under this technology are Smart Cycler®  and GeneXpert real-time thermocyclers, which can quickly perform a variety of genetic tests. Cepheid is to continue developing a broader array of tests for the scientific and medical communities.

Smart Cycler®  and GeneXpert are trademarks of Cepheid.

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A Better View of Cancer Treatment

Emory University

A Better View of Cancer Treatment

In 2003, the Office of Technology Transfer licensed the patents to Nihon Mediphysics — a Japanese joint venture owned by Sumitomo and GE Healthcare — which had provided funding for Goodman’s research for 10 years beginning in 1994. In 2008, GE Healthcare licensed the fluciclovine F-18 imaging compound from Nihon Mediphysics. But then GE concentrated its efforts on a different imaging compound — one for Alzheimers’ — and fluciclovine F-18 languished. That frustrated not only Emory researchers but also a few GE employees, including David Gauden.

“GE has a lot of options about where it can invest its money,” says Gauden. “It was clear to some of us that this particular project was not going to be a priority for them,” he says. “But we believed in the product. We could see an unmet need.” When prostate cancer spreads, it often goes to lymph nodes and bone. Fluciclovine F-18 could more accurately detect cancer in those areas, says Gauden, compared to other types of diagnostic scans that had trouble spotting cancer if it wasn’t a large tumor mass.

To help that innovation reach the marketplace, Gauden and several of his colleagues left GE and formed Blue Earth Diagnostics in 2014. The company’s founding investor was Syncona, an investment company aligned with the Wellcome Trust and Cancer Research UK.

In 2014, GE licensed fluciclovine F-18 to Blue Earth Diagnostics, which now markets the compound under the name Axumin. “We continue to have a productive collaboration with GE,” says Gauden, now CSO at Blue Earth Diagnostics. “They make some of the raw materials for us for product manufacturing.”

He notes that the licensing history of the compound involves three continents — with companies in the United States, Japan and UK— and Emory’s tech transfer office played a critical role along the way. “It’s a fairly complicated licensing chain, and Emory’s tech transfer has done a lot of work to keep everyone happy,” says Gauden. “We also work very collaboratively with Emory to strengthen the patent portfolio on this product.”

Axumin received FDA approval in May 2016 and marketing authorization from the European Commission came one year later. "The FDA gave us an expedited review. … I think because they could perceive the unmet need," said Gauden.

With U.S. headquarters in Burlington, Mass., and global headquarters in Oxford, Blue Earth Diagnostics now has more than 50 employees and hopes to expand Axumin’s use for other cancers. That includes brain cancer — which originally prompted the development of fluciclovine F-18 at Emory — as well as breast cancer, ovarian cancer, and bladder cancer. Those possibilities are being investigated clinically, says Gauden.

In the last year, thousands of men and their families, and doctors, have benefited from better information about the location of their prostate cancer recurrence and more informed decision making about treatment.
David Gauden

"To have that kind of impact already is great, and we look forward to much more of that in the future," says Gauden. “It’s just great to sit here and think, we are able to actually progress a technology that may not have progressed otherwise,” 

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“Magic Bullet” Azedra Gives Hope to Patients with Rare Adrenal Cancer

University of Western Ontario

“Magic Bullet” Azedra Gives Hope to Patients with Rare Adrenal Cancer
Western University Chemistry Professor Emeritus Duncan Hunter gets a little choked up when it’s noted the work he began more than three decades ago will now, finally, be applied to saving hundreds of lives in the form of the drug Azedra.
Hunter describes Azedra as “a bit like a magic bullet” for rare adrenal tumors that can’t be surgically removed and require systemic anti-cancer therapy.

In 2018 the new compound, developed by Progenics Pharmaceuticals, became the first FDA-approved therapy for this use, offering hope to patients with rare adrenal gland tumors. It decreases the need for blood pressure medication and reduces the size of tumors in about one-quarter of patients – people who had exhausted all other medical options.
Adrenal cancers affect about 1,000 people in the United States each year. 
Hunter developed the compound with his Western lab team 30 years ago and then, after years of further development, applied for the patent.
The compound is highly radioactive and, once injected intravenously is specifically absorbed by, and then attacks the tumor, while the kidneys flush out the material it doesn’t use. Key to Azedra’s success is the use of a radioactive pharmaceutical called metaiodobenzylguanidine (MIBG), a compound designed to target only the tumor.
“Essentially, every molecule of MIBG has a radioactive iodine (iodine-131) on it. It gets absorbed where you want it to, it irradiates where you want it to and then it decays,” Hunter said.
While a form of MIBG has been used for years, one of the main stumbling blocks has been to find a method to produce MIBG in which every molecule carries the radioactive isotope. The Hunter lab developed a specific resin that would hold the precursor to the radioactive material until ready to be converted into the radiopharmaceutical for use by the body.
“There were very few companies in the world that specialize in radiopharmaceuticals. It’s highly specialized work,” Hunter said.
WORLDiscoveries, the technology transfer office for Western University, located in London, Ontario, helped Hunter apply for patents and coordinated license agreements with Molecular Insight and later Progenics Pharmaceuticals.
At the eleventh hour, Molecular Insight, a Boston-based company, picked up the license on the patent and began development, and then clinical trials.
It is a process that requires a lot of resources, and when Molecular Insight couldn’t stay financially afloat, it appeared as if the project might be over before its time. In stepped Progenics Pharmaceuticals, which secured the license and rescued the research, resuming clinical trials at several specialized centers in the US. Progenics’ results confirmed the effects and benefits of the pharmaceutical, now named Azedra (iobenguane 131).

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Improved Diagnostic Test Targets Hard-to-Detect Bacteria

North Carolina State University

Improved Diagnostic Test Targets Hard-to-Detect Bacteria

By the time Edward Breitschwerdt was in 9th grade, he knew he wanted to become a veterinarian. After turning that childhood dream into a degree, Breitschwerdt, D.V.M., expected to spend his career taking care of the local animals in Maryland, where he had grown up on a small farm. Instead, he has dedicated years to teaching young veterinarians, practicing internal medicine and performing infectious disease research that has implications for global health. His research has led to a diagnostic test that dramatically improves the detection of Bartonella — a bacteria that infects a range of animals. In humans, Bartonella infection has been documented in patients with a startling range of chronic diseases, including rheumatoid arthritis, fibromyalgia and multiple sclerosis.

Bartonella has wreaked havoc on humans for centuries — it infected as much as 20 percent of Napoleon's army. The trench fever epidemic from World War I has also been attributed to a species of Bartonella that’s still prevalent in homeless populations.

A Microorganism with Many Disguises

Scientists have discovered more than 30 Bartonella species so far, and about half of those cause disease. These bacteria are primarily transmitted by tiny insects like ticks, fleas, lice and biting flies — and also through the bites and scratches of other animals, such as cats (cat scratch fever is one disease example).

Because Bartonella are slow-growing bacteria that hide within cells, they often elude detection. When conventional testing is used on a patient’s blood sample, the result too often is a false negative. Patients can have many common symptoms like persistent headaches, chronic fatigue or muscle pain. “It doesn’t have a signature,” says Anupama Ahuja, Ph.D., licensing associate at North Carolina State University’s Office of Technology Transfer. As  a result, many patients infected by Bartonella are misdiagnosed or not diagnosed at all.

The Search for Fertile Ground

In the early 1990s, Breitschwerdt’s research laboratory at North Carolina State University’s College of Veterinary Medicine studied vector-borne infectious diseases like those carried by fleas, ticks or mosquitoes. “As time went on, my research laboratory went from putting 90 percent of effort into other known vector-transmitted organisms to putting 90 percent of our research effort into Bartonella.”

Bartonella are known as fastidious bacteria. Basically, they are picky about where they live, and often need a complex set of nutrients to grow to detectable levels in patient specimens. In 1993, Breitschwerdt isolated the first Bartonella species from a dog with endocarditis (an infection of the heart valve), but subsequently wasn’t able to culture the bacteria from other dogs thought to be infected.

His research lab attempted to culture it using mammalian cell-based media — that’s what microbiologists always did if a type of bacteria was pathogenic for mammals. But Bartonella’s comfort zone seemed to be in insects, the most common carriers of the bacteria. With that in mind, someone suggested a different approach: Instead of using media derived from mammals, why not use insect cells? “No one had ever asked that question in that manner,” says Breitschwerdt. “Those two biochemical compositions — mammals vs. insects — are extremely different.” This novel culture method worked.

With co-inventor Sushama Sontakke, Ph.D. (and support of internal funds from North Carolina State University), Breitschwerdt led the development of BAPGM — shorthand for Bartonella alpha Proteobacteria Growth Medium. It is a medium made to support the growth of insect cells and optimized chemically to enhance growth of Bartonella. Subsequently, Ricardo Maggi, Ph.D., research associate professor at the College of Veterinary Medicine, led efforts to optimize the medium for growing Bartonella and other fastidious bacteria.

Because it significantly improved the detection of Bartonella, BAPGM upended conventional  wisdom that Bartonella didn’t cause a chronic bloodborne infection. Some researchers, like Breitschwerdt, had suspected that Bartonella could remain in patients’ bloodstream for many years. But no one could really prove it, until BAPGM came along. “We are demonstrating that there are individuals with chronic symptoms that are persistently infected with Bartonella in their bloodstream,” he says. “I think the rest of the world is starting to catch on to the fact that could be a big deal.”

Testing the Business Potential

In 1999, North Carolina State University saw that BAPGM filled an unmet need and filed a patent application. Not everyone saw BAPGM’s potential, though. That became clear after Breitschwerdt approached several major diagnostic companies, in an effort to find a corporate partner. Even with his long list of credentials — including his role as former president and subsequently the chairman of the board of the American College of Veterinary Internal Medicine — he could not convince any companies to invest.

Breitschwerdt had no plans to start a company. But, his oldest son had enrolled in a class that required the development of a business plan as a project. He led a team that featured BAPGM. To turn that plan into reality, Breitschwerdt and his co-founders secured a company inception loan from the North Carolina Biotechnology Center. The funding allowed Galaxy Diagnostics Inc., based in Research Triangle Park, N.C., to obtain an exclusive license for the BAPGM technology from North Carolina State University and open its doors in 2009.

“The tech transfer office played an important role in getting the technology patented,” says Amanda Elam, Ph.D., president of Galaxy Diagnostics. “They don’t patent everything … they do their own due diligence.That’s an important step in the process, early on in the innovation.”

The Office of Technology Transfer continues to be involved with the advancement of Galaxy Diagnostics.The company was included in the 2012 inaugural class of NC State Fast 15 program, a venture launch support and mentoring program run by New Venture Services in the Office of Technology Transfer.The program helped Galaxy Diagnostics build connections in the growth capital community.

The test offered by Galaxy Diagnostics is called Bartonella ePCR. The e refers to enrichment — that’s BAPGM’s role, and it’s critical when diagnostically dealing with a slow-growing bacteria like Bartonella. “You’re looking for minute amounts of foreign bacterial DNA in a patient sample,” says Elam. By giving Bartonella more fertile ground to grow, BAPGM increases the chance of identifying the bacteria with the use of PCR (polymerase chain reaction) — a highly sensitive technology that can make millions of copies of a DNA sequence. Previous conventional Bartonella PCR tests only detected about 20 percent of cases. With BAPGM, now 80 percent of infected individuals can be diagnosed.

In 2009, the company launched Bartonella ePCR testing services for the veterinary market.Two years later, it began offering testing services for physicians. The company and its four employees are developing a test kit that could be used in hospitals around the world.

Before they receive a Bartonella diagnosis, patients often see more than a half-dozen medical specialists and can end up with a spectrum of diagnoses, ranging from arthritis to serious neurological problems, like seizures and loss of feeling or motor ability in arms and legs. The symptoms of cat scratch disease (caused by Bartonella henselae) can closely resemble lymphoma. Elam recalls talking with one physician who said the ability to make a cat scratch disease diagnosis meant he could send a patient home with antibiotics, instead of a referral to an oncologist and the possibility of two years of chemotherapy.

Says Breitschwerdt,“Doctors, whether physicians or veterinarians, can’t diagnose and treat what they don’t know exists.” For many years, he has taught veterinary students, interns and internal medicine residents that, “The kindest form of therapy is an accurate diagnosis.”

Identifying More Culprits Behind Chronic Disease

It can take quite a while for the medical importance of a microorganism to gain widespread acceptance. Breitschwerdt points to Helicobacter pylori, a bacterium known to cause most gastric ulcers in people. After that disease association was first proposed by researchers in Australia, it still took many decades to change the belief that ulcers were caused only by stress.

Using BAPGM, ePCR has already enhanced understanding of the scope of Bartonella infection. “With all the case studies they’ve collected and published, I feel like every correct diagnosis is a life changed,” says Ahuja. Symptoms can be debilitating — but it’s not just physical distress that’s alleviated with correct diagnosis. “Many of these patients are already struggling to convince even their physicians that the symptoms are real,” she says. “Even people around them are saying, ‘It’s all in your head.’”

Accurate testing could do more than alleviate patient suffering. It may also have a dramatic effect on healthcare costs. For U.S. rheumatoid arthritis patients alone, some estimates show annual healthcare costs could exceed $8 billion, and costs of other rheumatoid arthritis consequences (such as lost work productivity) were $10 .9 billion. Even if Bartonella only accounted for a small percentage of rheumatoid arthritis cases, it could save the healthcare system a lot of money.

Breitschwerdt readily acknowledges the big “if” in that scenario. The more complex a disease, the less likely a single factor (or bacteria) is solely responsible for the patient’s symptoms. That’s why he emphasizes the need for more research to establish that Bartonella actually causes or contributes to the development of certain chronic diseases. With ePCR, that research is now possible. He also suspects the usefulness of BAPGM may extend beyond Bartonella. “In the future, I think what we will ultimately find that BAPGM is going to allow us to find other bacteria in humans and animals that cause chronic intravascular infections that we didn’t know existed.”

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Berkeley-Darfur Stoves Improve Women’s Safety and Feed Refugees

Engineers Without Borders
Lawrence Berkeley Natl Lab
University of California, Berkeley (UC Berkeley)

Berkeley-Darfur Stoves Improve Women’s Safety and Feed Refugees

The humanitarian crisis in the Darfur region of western Sudan has displaced nearly 2.3 million people. While many of these individuals live within the safe confines of refugee camps, they are not always out of harm’s way.

Women must venture outside camps to collect firewood to cook for their families. The sudden and drastic increase of people relying on the camps’ surrounding land has taken a toll on the environment.Deforestation has left the area surrounding camps barren, and the lack of firewood causes more than 50 percent of families to miss one or more meals a week. As women spend more time outside of the camps in search of wood (a typical trip can last up to seven hours), they put themselves at risk of being raped or subjected to genital mutilation by the Janjaweed militia.

When Dr. Ashok Gadgil, Senior Scientist and Group Leader for the Environmental Energy Technologies Division at Lawrence Berkeley National Laboratory, was contacted by an officer of the United States Agency for International Development (USAID) to help refugees in Darfur, he knew little about the daily lives of refugees and wondered how a group of scientists could help better their lives.

The initial USAID proposal was to develop a compactor to turn sun-dried kitchen waste into a fuel source. On his first trip to Darfur, Gadgil concluded that there was not enough kitchen waste to provide an adequate fuel source for cooking fires. He did note that refugees cooked over three-stone fires, which transfer just five percent of heat to food.

This inefficient cooking method inspired Gadgil to develop a field test in Darfur to study the efficiency of various cooking stove designs.

Researchers assessed the factors of cooking in Darfur. They worked closely with women, taking note of what they liked and didn’t like about each stove in the trial. Other factors they considered included the size and shape of the pots used, how the stove was manned and the cooking environment-either outdoors, in close proximity to neighbors, or inside refugees’ small shelters.

The team also took note of the types of food cooked. One of the staple foods of Darfur is assida, a bread that is cooked in a pot and must be continuously stirred. As the assida cooks, it becomes viscous and requires the cook to use the leverage of the pot to stir-stability is crucial to ensure the pot and stove do not tip over. Mulah is a sauce served with the assida. Cooks must fry onions, a cooking technique that requires a higher heat output from the fire than other techniques such as boiling water.

Back in the United States, Gadgil and students at the University of California, Berkeley designed a stove that would address the specific needs of refugees in Darfur. The resulting Berkeley-Darfur Stove is four times more efficient than a three-stone fire and features customized engineering to benefit the refugees.

A tapered wind collar increases fuel-efficiency in the gusty Darfur environment and allows for multiple size pots. Wooden  handles allow for the stove to be handled while hot. Metal tabs accommodate a flat plate to bake bread. Internal ridges create the optimum space between the stove and pot for maximum fuel efficiency. Feet provide stability, and optional rods can be pounded into the earth for more stability. Nonaligned air openings between the outer stove and inner firebox prevent too much airflow, and a small firebox opening prevents cooks from using more fuel wood than necessary.

Berkeley-Darfur Stoves use 25 percent of the fuel used in three-stone fires. The stoves have more combustion efficiency (how well energy is converted into heat) and better heat transfer (how heat gets to the pot).

The design also minimizes the changes required of the refugees. It allows them to prepare the same kinds of food as before in the same amount of time, something not guaranteed by other options such as solar stoves. With the design in place, the next step was to devise a plan to produce and distribute the stoves. The Berkeley group partnered with the San Francisco Professionals Chapter of Engineers Without Borders to develop a manufacturing system with Darfur’s infrastructure in mind. Led by Ken Chow, this group of engineers revisited the stove design to make it simpler to build by reducing the number of parts and streamlining the assembly without compromising the design of the stove.

The Berkeley-Darfur Stove is metal, instead of clay, because metal provided better quality control when producing mass quantities. Sheet metal is stamped and cut to the exact dimensions shown to provide the most efficiency.

These flat kits are shipped to Darfur and assembled by local workers. In cooperation with CHF International, a pilot production facility has been set up in Darfur. The facility currently produces between 200 and 500 stoves per month, not nearly enough to provide for the estimated 400,000 stoves needed. The facility is currently working to increase production by increasing days of operation and adding a second shift. The project hopes to open more facilities in the future.

The manufacturing sites will create new jobs in Darfur, just one of the economic benefits of the Darfur Stoves Project. Families who use the stove will save $250 a year on firewood. Women will spend less time looking for firewood and will be able to pursue entrepreneurial activities such as weaving mats. An influx of money to the Darfur economy will improve the living conditions of refugees. Each stove costs $25. Since this is an outrageous amount for refugees to pay, international nongovernmental agencies underwrite the stoves.

Amy Callis, Executive Director of the Darfur Stoves Project, works with organizations such as The Hunger Site to distribute the stoves and provide training to ensure the most efficient cooking. There has already been a high demand for the stoves. During a three-week trial, 50 stoves were distributed and assessed. After the study, the stoves were offered for sale, and each one was bought.

This successful program could not have been possible without the collaboration of experts from various fields—Gadgil and his scientific team, Chow and his engineers and Callis’ networking and communication skills. The project was executed almost entirely by volunteers. Each had their own specialty and none worked exclusively.

“We’re doing what we can to relieve them from suffering, but the humanitarian crisis is extreme,” said Chow. “The stoves will improve the situation but will not be an answer to the crisis.” For more information visit

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Better Plantlets for Better Plants

Washington State University
Washington State University Office of Commercialization

Better Plantlets for Better Plants

Using a proprietary growing method developed at Washington State University (WSU), start-up company Phytelligence is producing plants and trees faster than ever, offering a fresh alternative to tree farmers in an industry overripe for innovation.

We can produce in one year what is typically produced in three years: a 10-foot tall tree.
 Amit Dhingra, Associate Professor of Horticultural Genomics and Biotechnology at WSU

The company’s soil-less multiplication system — which requires less water and no pesticides — combined with genetic analysis services to ensure the identity of tree species offers tree farmers a way to improve profitability and reduce their environmental impact.

“The company’s plant multiplication method can produce 250,000 plants in one year from a single plant in five-week intervals,” says Preeti Malik-Kale, Ph.D., Technology Licensing Associate in WSU’s Office of Commercialization. “DNA testing prior to shipment guarantees the authenticity of the fruit tree or plant species being supplied to growers.”

Tree Growing 101

Most trees are not grown from seed, but rather grafted on rootstocks — the root system and about 18” of tree stem — that are traditionally propagated in the ground at specialty nurseries. Once the rootstock is large enough, a branch from another tree representing a commercial plant variety (called a scion) selected for its fruit or another attribute is then inserted — or grafted — into the woody stem of the rootstock. After one or two years of growing time, the tree is uprooted and shipped to an orchard, where it takes an additional two to three years before the tree bears fruit.

“Nurseries are confined by the amount of land they have to grow with; 100 acres is a lot. It’s a limiting factor and [space for new trees] only opens up every two to three years,” says Dhingra.

Dhingra says traditional tree propagation is lengthy and rife with inefficiency: About 10 to 40 percent of rootstocks may eventually die, and 10 to 20 percent are not even the variety ordered — a nasty surprise that may come to light years after planting forcing the farmer to rip out trees from random spots in an orchard.

“This results in millions of dollars of loss to the industry,” Dhingra told attendees at a TEDxWSU event in 2014. “It’s a commonly accepted norm.”

Indian-Born Botanist

Dhingra had an affinity for plants at an early age, but growing up in India furthered his resolve to work in agriculture and plant sciences.

“There were food shortages in the early ‘80s in India and seeing people dying from famine made a big impression on me,” he says.

He earned bachelor’s and master’s degrees in botany in India followed by a doctorate in plant molecular biology from University of Delhi, India, and Rutgers University, New Jersey in 2000. Before joining WSU, he worked as a researcher at Rutgers, the University of Central Florida and University of Florida.

“From 1994 to 2015 my work has been in the broad area of photosynthesis, trying to change how plants grow and to produce them faster,” he says.

When Dhingra joined WSU in 2006, there was little gene-based information on apples, pears and cherries, so he mapped the genome of each in collaboration with colleagues from Chile and Europe.

“I was like a kid in a candy store; the field was wide open,” he says.

Meeting Farmers

Dhingra also traversed the states of Washington, Oregon and California — top producers of apples, cherries, raspberries and grapes — which gave him a better understanding of the problems faced by nurseries, farmers and fruit packagers.

“There were common themes everywhere,” he says. “Farmers would tell me they were waiting for a million plants and they’d maybe get 10,000.”

Neither traditional propagation nor a newer alternative called plant tissue culture or micropropagation were able to meet the demand for rootstocks. In micropropagation, cultivation occurs not in soil but in the laboratory, where a small amount of tree tissue (called an explant) is added to a sterile container filled with a gel-based mixture of nutrients and placed under artificial light.

“Apple trees multiply in soil slowly, and tissue culture wasn’t efficient because they were using a one-size-fits-all approach,” he says. “A lot of tissue culture labs were using compounds formulated for tobacco. I knew that wouldn’t work, so I began developing my own formulations.”

Growing Formulations

Dhingra and students in his horticultural genomics laboratory went to work experimenting with different compounds in agar-based media in which explants of various plant species would quickly multiply.

“I was fortunate to have students who were open to a city kid from New Delhi who told them to come along with him and meet with farmers and who wanted to have a practical impact beyond learning,” he says.

Tyson Koepke was just beginning his doctoral work in Dhingra’s lab in 2007 when he was asked to work on a growing medium for sweet cherries alongside other graduate and doctoral students assigned to different plants. Five-and-a-half years later, the group had perfected four media packages and growing processes for apple, pear, cherry and grape species, each of which included specially customized compounds for four growth stages.

During each five-week growing period, explants multiply three- to five-fold and are divided and placed into containers with a new mix of customized nutrients. After several months in a carefully controlled laboratory environment, the plants are moved to a greenhouse where they continue growing for approximately 4-6 months.

“There are other tissue culture labs out there, but [our] group figured out how to make cultures more viable and developed protocols for growing higher quality plants,” says Koepke.

Going Commercial

When a pair of undergraduate students suggested that Dhingra explore commercializing the multiplication method, he met with representatives of WSU’s Office of Commercialization to discuss the intellectual property management and commercialization plan. Because the growing compounds developed in Dhingra’s lab were essentially recipes, the Office decided to classify the intellectual property as trade secrets.

In 2012, Dhingra, four students and a laboratory manager founded Phytelligence — the first plant-focused biotechnology startup to come out of the university — and licensed the media packages and protocols as well as the software for verifying plant identity through high-resolution genetic analysis.

“When we started the company, it wasn’t just me, it was a group of co-founders,” says Dhingra, who now serves as CEO of Phytelligence. “It changed the paradigm on campus because this was the first group of graduate students to start a company in plant science. It has become motivation for other Ph.D. students to form companies.”

WSU’s Office of Commercialization also connected Dhingra with experts who could help draft a business plan as well as potential investors — 70 percent of the company’s $1 million in start-up funding came from Washington growers and nurseries.

From Researcher to Entrepreneur

Two weeks after Koepke completed his doctorate, he became the director of operations at Phytelligence and began outfitting the lab and building the company’s team, which has grown from three full-time employees in early 2014 to 24 employees today.

After shipping 110,000 plants last year, the company is on track to deliver up to 300,000 plants in 2015. In addition to performing genetic testing on each plant it produces to ensure the rootstocks are true to type, Phytelligence also offers genetic analysis services to farmers and nurseries.

“Because of our genome sequencing and analysis expertise, we know how to assure each plant is true to type so it doesn’t have to be dug out of the ground and present a problem to a farmer a few years later,” says Dhingra.

Koepke says the company has also been able to achieve propagation rates that are in some cases two to five times faster than those of competing tissue culture labs.

“We’re able to improve the business cycle for the average apple farmer,” says Dhingra. “They get trees to plant one to two years after ordering, 95 percent survive and all rootstocks are as ordered, resulting in 20 percent extra income annually for the farmer.”

In addition to benefitting tree farmers, the Phytelligence multiplication system has significant environmental benefits: The process requires no insecticides, pesticides or fungicides and, compared to traditional propagation, uses 50 to 80 gallons less water per tree produced.

Fruits to Nuts to Forests

Phytelligence is now exploring ways to expand, including franchising or establishing partnerships with other tissue culture labs. Long-term, the company hopes to apply its soil-free multiplication technology to citrus trees, nuts and forestry. In addition to introducing a new media package for raspberry plants, the company continues to research growing compounds for other plant species.

“There’s an art and science to developing superior formulations, and we have to work all the time at improving, and now we have the engine doing that,” says Dhingra. “We’ve just started scraping the surface of how to improve growing trees.  The secret is to keep on innovating and leading the field with cutting-edge research.”

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BevShots Takes Flight with Cocktail Imagery

Florida State University

BevShots Takes Flight with Cocktail Imagery

Michael Davidson, of the FSU Magnetic Laboratory, created images of mixed drinks photographed using a light microscope and polarized light. The photo galleries of the pictures were first used by Stonehenge Inc in NYC, a NeckTie business, to create and sell a cocktail collection of silk Neckties. These ties were trademark branded by Stonehenge with the images copyright protected by FSU.

Casual Fridays in the early 2000's shrank sales dramatically.

What emerged was Lester Hutt, a young Tallahassee entrepreneur who used the cocktail gallery of images and created a series of drink related products — wall art as well as a line of women's beach clothing accessories and men's clothing accessories.


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BeadChip Types Platelets for Better Transfusion Outcomes

BioArray Solutions
BloodCenter of Wisconsin

BeadChip Types Platelets for Better Transfusion Outcomes

In a hospital birthing suite, a mother’s labors are rewarded, and a new life enters the world. But the baby appears to be severely bruised, almost as if it had been beaten in the womb. How could this have happened?

In another hospital, a cancer patient who has received multiple transfusions shows a dangerously low platelet count. He receives yet another platelet transfusion. Hours later the platelet count remains seriously depleted, despite the transfusion. The new platelets seem to have mysteriously disappeared. Where did they go?

Both the newborn and the cancer patient are examples of immune-related platelet disorders. Almost everyone knows that humans have different ABO blood types and that, before transfusion, blood must be properly matched between donor and recipient to prevent serious complications. Few, however, are aware that platelets — the little disks in the blood that are essential for clotting — also have "types" that, when mismatched, can produce immune reactions such as those seen in the newborn and the cancer patient.

The newborn that appeared to be bruised is bleeding beneath the skin. That is caused by a low platelet count resulting from a mismatch between the platelet types of the mother and father. The medical term for this condition is neonatal alloimmune thrombocytopenia or NATP. According to the BloodCenter of Wisconsin, in the United States about 3,000 babies are born each year with NATP, which can result in bruising, intracranial bleeding and, in some cases, death.

In the case of the cancer patient, the newly transfused platelets are disappearing because the body’s immune system is attacking them because of a mismatch of platelet types. About 10 million platelet transfusions are given each year in the United States. No one knows for sure how often immune problems resulting from transfusion mismatches may occur.

The good news is that both the newborn and the cancer patient can be helped with platelet transfusions that have been properly typed and matched to them.

The Road to Finding out "Why"

When doctors first saw what happened to the ‘bruised" newborn and the cancer patient with disappearing platelets, they were puzzled. "The antigens that cause blood types have been recognized for almost 100 years, but for many years nothing was known about platelet types," says Richard Aster, M.D., professor of medicine at the Medical College of Wisconsin and senior investigator at the BloodCenter of Wisconsin’s Blood Research Institute. "Typing platelets didn’t become important until people began transfusing platelets in the 1950s and 60s."

Over the years, a team of researchers at the Blood Research Institute would identify a number of platelet antigens critical to patient health. "I got involved at the very beginning," Aster says, "when we were defining platelet antigens using antibodies identified in individual patients."

Later, Aster and Peter J. Newman, Ph.D., now vice president for research at the BloodCenter of Wisconsin and associate director of the Blood Research Institute, would identify the molecular basis for various platelet antigens. "We were able to identify the single nucleotide polymorphism (SNP) that creates individual antigens. Knowing that opens the door to a fast, accurate test for platelet typing," Newman says. "It’s a little like knowing which key opens which lock."

What was needed now was a fast, convenient way of executing such a test.

The Genesis of the BioArray BeadChip

In the early 1990s, researchers in New Jersey had the germ of a concept for such a test. The idea was to make a beadchip for complex nucleic acid and protein analysis. After some patents were filed on the concept and Small Business Innovation Research funding was secured, BioArray Solutions was formed. The company would eventually be acquired by Immucor in 2009, but much work had to be completed.

"To make the BeadChip work, many novel elements had to be developed in-house," says Sukanta Banerjee, senior director of research and development at BioArray. "This includes software for reading the chips, an associated microscope for examining the BeadChips and an entire system for manufacturing an array of BeadChips bonded to glass slides. None of these elements, with the exception of the microscope, which we heavily customize—can be bought off the shelf."

Banerjee adds that while they were developing the technology for the complete system that comprises the BioArray BeadChip, there was a question constantly in the back of their minds: "There are lots of things that the BeadChip could test for, but where is there a demand for a platform like this? The answer was in blood. Now we have separate BeadChips for detailed analysis and typing of red blood cells, platelets and white blood cells."

To make their Human Platelet Antigen (HPA) BeadChip work, BioArray licensed the markers for human platelet antigens from the BloodCenter of Wisconsin.

Transferring the Technology

"In 2006, BioArray Solutions approached the BloodCenter of Wisconsin. We had a meeting in which BioArray explained what their base technology was and how it worked," says Laura Savatski, technology transfer officer for the BloodCenter of Wisconsin’s Blood Research Institute. "They were interested in licensing our Human Platelet Antigens and in collaborating on samples that would give them access to positive controls to confirm that their system was working."

Savatski notes that while the agreement was executed in 2006, it took a couple of years to get the final product working and market-ready. "Now sales are growing, and we are getting royalties," she says, "which have actually taken off in the past two years."

Putting it All Together

At the heart of the BioArray BeadChip system are tiny silicon chips that measure just 300 micrometers by 300 micrometers, smaller than the period at the end of this sentence. Hard to see with the naked eye, 96 BeadChips fit on a glass slide, which means that 96 different samples can be tested at once. Each of the 96 BeadChips is seeded with 4,000 microparticle "probes" for detecting the various Human Platelet Antigens.

The sample to be tested is prepared by taking whole blood from the person to be analyzed, extracting genomic DNA from it and performing PCR (polymerase chain reaction) amplification for the target areas of interest. The sample is put onto an individual BeadChip, and when there is a match between the sample DNA and the BeadChip, there is a fluorescent reaction, which can be seen and analyzed using a special microscope and software that is part of the BeadChip system. The entire test, including sample preparation, takes place within a single work shift and shortens the process of typing platelets by more than two days.

According to Banerjee, the BeadChip is widely used in Europe and is considered the test of record there for platelet typing. The BeadChip currently is available for research use only in the United States.

Aster says, "From our viewpoint, the key benefit of the BioArray BeadChip is that it can be used to type large numbers of donors to create prescreened and typed platelet units.

"So when a baby with NATP or a cancer patient with the low platelet count needs a transfusion, we can give them platelets without fear of adverse reactions."

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Diagnostic: Nano Biosensors Help Identify and Slow Spread of Major Diseases

Argonne Natl Lab

Diagnostic: Nano Biosensors Help Identify and Slow Spread of Major Diseases

Throughout history, human migration has contributed greatly to the spread of infectious diseases. Trade caravans, religious pilgrimages and military maneuvers spread many diseases such as influenza, plague and smallpox.

Today, epidemics continue at an accelerated rate thanks to an internationally mobile population with unprecedented access to quick, global travel.

This increased international mobility has created the potential for a serious and costly health crisis, prompting world health authorities to seek rapid, high-throughput disease surveillance and reporting programs as a first line of defense. A solution needs to identify, manage and contain highly communicable infectious diseases such as tuberculosis (TB), human immunodeficiency virus (HIV), hepatitis, influenza and severe acute respiratory syndrome (SARS).

Infectious diseases can be separately diagnosed with existing highly effective gold-standard diagnostic tests such as culture and/or polymerase chain reaction (PCR). But, the most sensitive and accurate tests conducted in clinical labs usually take days to provide an answer, while the very rapid tests that require only a few minutes are usually less sensitive and inaccurate.

Performing individual tests for each of these diseases at a reasonable cost, though, creates formidable logistical and financial challenges. A more innovative solution that cuts down the number of tests is needed.

Next Generation Disease Screening

One possible solution that shows great promise is a high-throughput diagnostic system, which is commercially available from Akonni Biosystems, a private molecular diagnostic company based in Frederick, Md. Called TruSentry, the system can extract DNA and/or RNA directly from either a tiny spot of dried blood or whole blood and then subject the single sample to testing for 10 to 20 of the most prevalent diseases at the same time. Results are available in less than five hours — fast enough to allow the analysis of thousands of samples per day.

The TruSentry diagnostic system can also be deployed in a single national reference lab, processing millions of samples per year or as part of a larger network of separate satellite facilities that are at, or closer to, the point where samples are collected. Other configurations can be deployed remotely in the field, for example, at the point of an infectious disease outbreak.

At the heart of the TruSentry system is nanoscale biosensor technology on three dimensional gel-drops licensed from Argonne National Laboratory in Illinois. Known as a biochip, this high-throughput form resembles a 96-well microtiter plate but in a 1 centimeter by 1 centimeter area that contains several dozen to several hundred “dots” or small drops. These biochips also are available in a microscope slide-size format for use in point of care settings. Each serves as a miniature laboratory with a unique protein, antibody or nucleic acid that will attach to a particular DNA sequence or antigen to identify infectious diseases such as TB, multidrug-resistant TB, HIV, viral hepatitis B, hepatitis C, syphilis and influenza.

“What Akonni has been able to do with the innovations licensed from Argonne is a very fascinating success story,” says Yash Vaishnav, Ph.D., M.B.A, senior manager, intellectual property development and commercialization, Division of Technology Development and Commercialization (TDC), at Argonne National Laboratory. “It illustrates what can happen when innovative technologies, developed by two international research facilities, with cultural and geopolitical differences, fit well together, and a technology transfer office and licensee work together to overcome challenges.”

International Collaboration Leads to Biochip

The special nanoscale biosensor technology is the result of an international research collaboration originally started in 1988 by the late Professor Andrei Mirzabekov, Ph.D., and his team at the Engelhardt Institute of Molecular Biology in Moscow and subsequently advanced via a joint research agreement in 1995 with Argonne National Laboratory. Argonne is one of the U.S. Department of Energy’s (DOE) oldest and largest national laboratories for science and engineering research.

One of the many inventors who worked on developing this innovative technology is Daniel Schabacker, Ph.D., team leader, Bio-Detection Technologies at Argonne, where he is the lead scientist for the development of the biochip portfolio. Schabacker helped develop the technology for manufacturing the biochips in a commercial setting.

“When I joined the Argonne team, many aspects of manufacturing and scalability of biochips had not been worked out,” Schabacker says. “It was interesting, with a lot of capabilities, but there was no manufacturing mindset — the manufacturing process needed to be scalable to be commercially viable.

“We really developed a package of standard operating procedures and a cost analysis that showed how our biochips could be marketable and manufactured in a commercial environment. We also transitioned from the original gel-pad concept to gel drops, which increased efficiency and produced a robust product.”

Since this international group of researchers started collaborating in 1993, development of the biochip has been supported with $22 million in funding from government and private sponsors — U.S. National Institutes of Health, DOE, U.S. Department of Defense, U.S. National Institute of Allergy and Infectious Disease, Centers for Disease Control, Motorola Inc., and Packard Instrument Co.

The Argonne National Laboratory biochip point-of-care diagnostic portfolio contains 29 issued U.S. patents with six pending applications, and the Argonne TDC has granted three exclusive licenses with defined fields of use to:

  • Safeguard Biosystems — focusing on veterinary diagnostics
  • Aurora Photonics — developing biochip imager for research and diagnostics
  • Akonni Biosystems — developing human diagnostics

Innovations Licensed to Startup

Akonni first approached the Argonne TDC in 2003 after hearing Mirzabekov talk about detecting TB in human samples. As a startup biotech company, Akonni wanted to license the strong portfolio of intellectual property relating to this innovative microarray technology to raise funds.

After submitting a business plan and completing a licensing questionnaire, Argonne worked with Akonni to identify key patents and exercise an option agreement to negotiate a license prior to the request for seed funding. After the funding was obtained, they entered into license negotiations.

Argonne’s Vaishnav says the first exclusive license included biochips for TB and a few other infectious diseases, a reasonable upfront fee and royalty rates, and due diligences based on sales and commercialization activity. As the relationship matured, it became clear to both that they needed a more dynamic agreement beyond standard licensing. The result was a collaborative research approach with the guidelines that allowed for advancing the technology and developing prototype applications of the biochip.

Over the years, many of them filled with time-consuming processes and difficult challenges, Vaishnav says both parties took a flexible approach that resulted in the agreements to evolve so they could overcome risks, attract more investors and collaborators, and take advantage of growth opportunities.

Today, the relationship is guided by a fine-tuned license that includes an equity stake for Argonne in Akonni and a cooperative research and development agreement. The result is a successful relationship: So successful, in fact, that former Argonne staff, including a key biochip researcher, have joined Akonni, and both entities are working constructively with others to bring the technology to the marketplace.

“This technology adds a molecular diagnostic solution where the current technology, while good, simply can’t perform,” says Kevin Banks, vice president of sales and marketing at Akonni Biosystems. Unlike today’s real-time PCR-based platforms, the Akonni TruSentry system, Banks says, can rapidly screen a sample for hundreds of disease markers at one time by using hundreds of molecular biosensors in a microarray the size of a fingernail thanks to all the work, not only at Argonne and Akonni, but the original research started by Mirzabekov and his team.

Akonni, which is deploying the technology in both point-of-care and high throughput screening settings, is in the process of attaining U.S. Food and Drug Administration approval for its diagnostic tests. Banks says this is a major milestone on the road to clinical trials and eventual clearance to market it as a commercially available diagnostic system.

“At the end of the day, what we have developed together is a third-generation molecular diagnostic solution that can provide truly accurate and trusted results, combined with alert detection and reporting on the world’s most prevalent and dangerous infectious diseases,” Banks says. “It represents the future of molecular diagnostics — a rapid, cost effective diagnostic system can greatly help immigration and health care officials identify and slow the spread of potentially dangerous diseases and would benefit all people.”

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3D Bone Implants Developed to Improve Skull Repair

National University of Singapore

3D Bone Implants Developed to Improve Skull Repair

“Brain injury occurs more frequently than breast cancer, AIDS, multiple sclerosis and spinal cord injury,” remarks Allan I. Bergman, president and chief executive officer of the Brain Injury Association.

Standard treatment to prevent brain injury caused by pressure on the brain following stroke or trauma involves drilling burr holes into the skull to relieve pressure. Typically the holes are closed with a titanium plate or bone grafts. These approaches each have drawbacks. The use of a titanium in either mesh or plate form can be expensive, and bone grafts are difficult to perform, painful and prone to infection. Each of these techniques can lead to deformity of the skull curvature.

A team of doctors and engineers from the National University of Singapore (NUS) and the National University Hospital, collaborating with Temasek Polytechnic, saw the need for something better. Inventors Swee Hin Teoh, Dietmar Hutmacher, Kim Cheng Tan, Kock Fye Tam and Iwan Ziein developed a biocompatible polycapolactone polymer-based implant for the burr holes that provides a base for the bone of the skull to regenerate after repair at half the cost of a titanium mesh or plate. The invention is currently licensed to Osteopore International Pte Ltd., a NUS spinoff.

This approach is not only economical but minimizes infection.

The technology works by rapid prototyping and design of a 3D patient-specific burr plug. It uses fused deposition modeling and enables the fabrication of the exact shape needed for the patient without a mold. This invention has received support from various organizations, including the Ministry of Education, the National Medical Research Council and the Tote Board.

One of the first patients treated was a 23-year-old man who suffered an injury on the job. The engineering team fashioned a precise scaffold infusing some of his living bone cells into the scaffold to “seed” the growth process. The bone plug has achieved wonderful results, and two years later the scaffold has fused with the surrounding tissue, with no trace of the original hole. His hair has even grown back.

Teoh indicated in the Far Eastern Economic Review (Oct. 21, 2004) that this new technology might be used in developing countries, where medical imaging equipment is scarce, causing doctors to drill multiple holes in a patient’s skull before they may find the correct entry point. Other anticipated applications for this technology include treatment of patients with facial injuries and uses in cardiovascular, orthopedic and dental treatment. 

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Biodegradable Boards Made From Plant Fibers Provide Alternative to Standard Materials

Cornell University

Biodegradable Boards Made From Plant Fibers Provide Alternative to Standard Materials

Composite materials, such as particleboard, fiberglass and carbon-fiber products, are held together with a moldable glue or resin. Unfortunately, most glues are not safe for the environment, are not biodegradable, and are often toxic.

Many of the polymers used in composites are petroleum-based — a nonrenewable, high cost resource. Engineered wood products also contain formaldehyde, a known carcinogen that degasses slowly over time, creating indoor air quality problems. Huge amounts of engineered wood products are thrown into landfills every year, both from tear-downs and new construction projects.

Scientists at Cornell University in Ithaca, N.Y., have invented an alternative to standard composite materials — biodegradable composites made entirely from plant materials.

This biodegradable composite technology is stronger, cheaper and safer for the environment.

Developed by Anil Netravali, a professor of fiber science and apparel design at Cornell University, the process binds together renewable fibers from fast-growing plants with a proprietary soy protein-based resin. This material is then processed into sheets. Many of these fibers, such as bamboo, kenaf, and flax, can be grown on marginal or unused farmlands. Other advantages include a high strength-to-weight ratio, no petrochemical content, and lower overall cost compared to traditional composite materials.

e2e Materials LLC, an Ithaca company founded on this new technology, is developing biodegradable composites with a wide range of strength properties, reaching as high as midrange steels, for different industries and applications. Biodegradable composites manufactured by e2e Materials are currently being used in skateboard decks and office furniture. The company is also developing advanced composites that are stronger than steel but almost six times lighter, which will be suitable for a variety of structural applications, such as I-beams.

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Biodegradable Inks Make Tattoo Removal Easy, Affordable

Massachusetts General Hospital

Biodegradable Inks Make Tattoo Removal Easy, Affordable

People get tattoos for lots of reasons that seem great at the time — but as life and love change, tattoos, especially if they are highly visible, may cause problems. Removing a tattoo can be painful and expensive and may lead to permanent skin damage and scarring. But that doesn’t have to be the case.

Massachusetts General Hospital in Boston has developed a safe, removable ink that is both biodegradable and bioabsorbable.

Rox Anderson, M.D., of Massachusetts General Hospital’s Wellman Center of Photomedicine, became interested in the chemistry of tattoo ink when one of his patients developed a severe reaction to a permanent tattoo. After several years of research, Anderson invented microencapsulated biodegradable and bio-absorbable dyes within safe, colorless polymer beads. The dyes are made from natural pigments and enclosed in tiny beads several microns in diameter, which are injected under the skin. To remove the tattoo, a laser is passed over the tattoo, which ruptures the beads and releases the inks, which are then safely absorbed by the body.

This technology is licensed to Freedom-2 Inc., a startup company founded in 1999 by Anderson to commercialize biodegradable Freedom-2™ tattoo inks. The company is continuing to research and develop new engineered ink products using well-established, safe, biocompatible materials that provide both high-quality art and easy removability.

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Bioengineered, Insect-Resistant Variety of Eggplant Developed

Cornell University

Bioengineered, Insect-Resistant Variety of Eggplant Developed

Eggplant is an essential crop in many tropical countries around the world, including India  and the Philippines. However, eggplant fields are often attacked by the eggplant fruit and shoot borer (EFSB), an insect that can causes widespread crop damage. These losses hurt the food supply chain, as well as the regional economies where eggplant is a staple food source. They also force farmers to spread expensive chemical pesticides, to which the EFSB is gradually becoming resistant. 

In an effort to strengthen crop yields, Cornell University,  Ithaca, N.Y., and Sathguru Management Consultants in India have partnered with a private enterprise Mahyco seed company and a consortium of public research institutions to introduce a bioengineered, EFSB-resistant variety of eggplant to Asia. They coordinated the pro bono use of Monsanto – Mahyco technology, which was licensed to a public/private research and development consortium to develop this new variety of eggplant. The work was funded by the U.S. Agency for International Development’s Agriculture Biotechnology Support Project and the governments of India, Bangladesh and the Philippines.

Bioengineered eggplant allows farmers to reduce their dependence on pesticides, it's safe for the environment, and maximizes farm yields and creates more stable income for farming families.

Monsanto’s insect-resistance technology is based on the cry1Ac protein from Bacillus thuringiensis (Bt), a soil bacterium. This unique organism produces crystal proteins that are toxic to a variety of insects, including EFSB. The technology bioengineers the cry1Ac gene into the eggplant, creating a hybrid variety with plant leaves that are toxic to EFSB but safe for human consumption. 

Transgenic Bt-hybrid eggplant will be available commercially in India, Bangladesh and the Philippines in 2008.

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Antibody-Based Kits Detect Nut Contamination in Food Processing Machinery

Florida State University

Antibody-Based Kits Detect Nut Contamination in Food Processing Machinery

BioFront Technology's MonoTrace ELISAs represent the first line of monoclonal antibody-based kits (MABs) for detecting nut contamination in food matrices. Precisely defined MABs targeting major allergenic proteins help insure sensitive, specific, and reproducible results. 

The company offers a series of diagnostics test kits for ground nut and tree nut allergy tests.

In an increasingly allergic world, these kits make a difference.

Companies manufacturing food which include such nuts need to ensure that their machinery is meticulously clear before beign used for non-nut containing foods. Slight contamination can lead to very expensive food recalls.

Prior to this, available test kits used polyclonal antibodies which have high cross reactivioty and high false positives.

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Biomarkers and Blood Test Breathe New Life into Diagnosis and Treatment of Mental Illness

Cambridge Centre for Neuropsychiatric Research
University of Cambridge

Biomarkers and Blood Test Breathe New Life into Diagnosis and Treatment of Mental Illness

 Early detection and proper care is a common message used by health care organizations in their efforts to educate people and governments throughout the world about winning the war against certain cancers and other chronic diseases.

But does this message offer the same real hope of change for individuals and caregivers who live with the chronic and disabling affects of schizophrenia and other mental and neurological disorders? Early detection and proper care is less than assured. This is especially true when general practitioners and psychiatrists must rely on a century-old, highly subjective and time consuming verbal diagnosis that hopefully will help them identify the exact  sychosis that is causing the delusions, hallucinations, disorganized thinking and other psychotic symptoms. This process often delays treatment and extends the suffering of millions throughout the world.

About 24 million people suffer worldwide from schizophrenia. Treatment is more effective in the initial stages of the disease, but more than 50 percent of persons with this disorder are not receiving appropriate care.

Existing diagnosis and treatments are failing too many people who suffer from schizophrenia and other mental and neurological disorders, as well as contributing to runaway global health care costs.

But in early 2009, Rules-Based Medicine Inc. (RBM), the leading multiplexed biomarker testing laboratory based in Austin, Texas, plans to sell worldwide a reliable and objective blood test for the diagnosis of schizophrenia. This diagnostic blood test, which relies on RBM’s comprehensive protein biomarker assay and technology platform, is based in large part on proprietary biomarkers that are a signature for schizophrenia.

The identity of these biomarkers are the result of 12 years of ground-breaking research by Sabine Bahn, M.D., Ph.D., MRCPsych, of the Cambridge Centre for Neuropsychiatric Research (CCNR) at the Institute of Biotechnology, University of Cambridge in the United Kingdom. Aided by funding from Stanley Medical Research Institute, the National Alliance for Research on Schizophrenia and Depression and University/Higher Education Innovation Fund, Bahn and her team of researchers tested spinal fluid and analyzed post-mortem tissues of schizophrenic brains in their quest for a scientific approach that can enable more appropriate and timely therapeutic intervention.

A psychiatrist by training, Bahn cofounded Psynova Neurotech in 2005 to develop and commercialize novel biomarkers—genes or proteins in tissues, blood and body fluids—that can distinguish schizophrenia from Alzheimer’s disease, bipolar disorder, manic depression or dementia. The founding intellectual property of her ground-breaking work is licensed on an exclusive worldwide basis by Psynova from Cambridge Enterprise Limited, the University of Cambridge’s technology transfer company.

The last piece to fall in place came in June 2008 when Psynova and RBM agreed to partner in the validation, regulatory approval and manufacture of a diagnostic blood test.

This first blood test for the diagnosis of schizophrenia is a scientific tool that can help general practitioners and psychiatrists diagnose patients much sooner, say Bahn and RBM’s Chief Executive Officer, Craig Benson, both of whom have witnessed first hand the suffering of a family member with a mental disorder. It also offers the potential to identify disease subtypes, develop proper treatment options, monitor patient responses and discover novel drug approaches.

“Our diagnostic blood test represents new hope for the millions of individuals throughout the world with schizophrenia,” says Bahn, “not only for early detection and proper care but more personalized treatments that would make the trial and error approach they now know obsolete.” 

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Biomarkers Identify Best Options for Leukemia Patients

University of California, Los Angeles (UCLA)

Biomarkers Identify Best Options for Leukemia Patients

In 2001 the Federal Drug Administration (FDA) approved the drug Gleevec™ as a firstline therapy for treating chronic myeloid leukemia (CML). To date results have been impressive.

Over 90 percent of the patients who received Gleevec responded well to treatment, with many experiencing complete remission. Yet the remaining 10 percent failed to respond at all to Gleevec, or experienced slight improvement before developing a resistance to the drug and relapsing.

Researchers at the University of California, Los Angeles, have discovered key mutations that are predictive of Gleevec activity and resistance. Disclosed in 2001, the Gleevec Pharmacogenomic Test was developed by Mercedes Gorre, Neil Shah, John Nicoll, and Charles Sawyers. Initial research was funded by the National Institutes of Health.

The Gleevec Pharmacogenomic Test can be used to accurately determine whether CML patients will respond favorably to Gleevec. In 2005 the university licensed this biomarker technology to Genzyme, which manufactures a diagnostic test that can quickly identify patients who are likely to respond to Gleevec, as well as those who are likely to develop resistance to the drug. Physicians and clinicians using this test will be able to make earlier and more effective treatment decisions for their patients regarding Gleevec therapy. 

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Technology Converts Agricultural “Leftovers” into Useful Products

University of Western Ontario

Technology Converts Agricultural “Leftovers” into Useful Products

A new technology developed at the University of Western Ontario in London, Canada, enables farmers to convert biomass “leftovers” into valuable commodities such as heating oil, pharmaceuticals and food additives.

Department of biochemical engineering professors Franco Berruti, Ph.D., Cedric Briens, Ph.D., and Ron Golden, Ph.D., developed the apparatus and process for the pyrolysis of agricultural biomass in 2005. Initial funding of $100,000 was provided through the Ontario Centers of Excellence. Agri-Therm, a University of Western Ontario spin-off company, was created to commercialize and market the technology.

The portable device converts agricultural biomass, such as leftover crop material, into bio-oil, carbon char and non-condensable gases through a process that rapidly heats the biomass to temperatures hotter than 932 degrees Fahrenheit (500 degrees Celsius).

The chemical bonds of biomass compounds are broken, releasing the constituent components. The resulting hot, smoky gas is filtered and rapidly cooled to condense liquid bio-oil from the gas stream. Combustible gases such as methane, hydrogen, and ethane are recovered and burned as a partial replacement for natural gas used to heat the pyrolysis process, or to dry out biomass feedstocks. The solid “char” can also be burned as fuel, applied as fertilizer, or used to filter contaminated air streams.

While the process can convert any carbon-based material, or biomass, each feedstock produces a unique combination of solids, bio-oil, and gases depending on its chemical makeup. Fuel, fertilizer, pesticide, pharmaceutical, food and specialty chemical uses are all possible when appropriate feedstocks  are matched with the desired end-use product. The truck-mounted mobility of the device allows farmers to economically process the biomass residue on-site in their fields.


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Bio-Material Improves Heart Surgery Outcomes

Purdue Research Foundation

Bio-Material Improves Heart Surgery Outcomes

More than 650,000 open heart surgeries are performed every year. During open heart surgery, the thin sac or casing surrounding the heart is cut open and sometimes even damaged. It’s usually left unrepaired because a compatible repair material is not readily available. This increases the risk of developing scar tissue or adhesions, which may result in difficult follow-up surgery.

In the late 1980s and early 1990s researchers at Purdue University, West Lafayette, Ind., in  partnership with Cook Biotech Inc. in Purdue Research Park, developed the CorMatrix  ECM Patch for closing the pericardial sac during surgery. Further cardiovascular applications were developed by Rob Matheny, M.D. of CorMatrix Cardiovascular Inc. in Sunnyvale, Calif.

The CorMatrix® ECM Patch is made from a pig’s small intestine submucosa,  which has been used for years in general soft tissue reconstruction and repairing wounds. This same material is now being used by heart surgeons.

The CorMatrix®  ECM Patch provides surgeons with a way to repair or reconstruct the sac surrounding the heart. This also helps restore the natural barrier between the back of breastbone and the heart and can also protect underlying grafts.

In 2006 the first CorMatrix®  ECM Patch was implanted to close the pericardial sac. To date more than 2,000 pericardial closure implants have been successfully performed in the United States. CorMatrix® Cardiovascular Inc. continues to research and develop new cardiovascular applications for this innovative technology.

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Biorefinery Technologies Maximize the Value of Renewable Resources

Research Foundation of SUNY

Biorefinery Technologies Maximize the Value of Renewable Resources

Forest biorefinery is defined as the full conversion of wood biomass into fibers, chemicals and energy. For decades pulp mills have burned or discarded wood sugars and chemicellulose, which can be used in the manufacturing of plastics, ethanol and acetic acid. Now new processes developed at the State University of New York’s College of Environmental Science and Forestry (SUNY ESF) in Syracuse make it much easier to exploit these co-products.

A suite of “Forest Biorefinery” technologies were developed by Thomas E. Amidon, Ph.D., Gary M. Scott, Ph.D., Bandaru V. Ramarao, Ph.D., Raymond Francis, Ph.D., Christopher D. Wood and Jeremy Bartholomew. The technologies are designed to extract value from trees in new and unique ways.  The Empire State Paper Research Institute was the primary funding source. Wood chips are pretreated with selected enzymes, which make the lignin, sugars, and hemicellulose easier to extract. Once extracted and concentrated, the sugars and hemicellulose are converted to acetic acid and ethanol, two valuable commodities. This enables pulp mills, chipboard plants and other businesses that utilize trees (or forest biomass) to better extract economic value from their current production processes. 

It is estimated that the extracted lignin, sugar and hemicellulose will yield as much revenue from downstream chemical products as the fiber or fuel that is traditionally extracted yields in the production of paper products or energy.

Acting on behalf of SUNY ESF, The Research Foundation of State University of New York is in the early stages of licensing and commercialization.  Licensees and potential licensees are testing these technologies in small-scale pilot operations throughout the country. In 2007 New York State Department of Agriculture and Markets dedicated $10.8 million to the construction of pilot and demonstration plants in New York, first at SUNY ESF and then transferring the pilot plant to Lyonsdale Biomass, LLC, a wood-burning power plant on  the Moose River, Lewis County. The first full-size biorefinery is scheduled for completion in early 2009 in the state of New York.  

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Small, Biodegradable Spheres May Have Big Impact on Tumor Treatments

University of Minnesota

Small, Biodegradable Spheres May Have Big Impact on Tumor Treatments

Jafar Golzarian, M.D., has spent nearly 20 years redirecting traffic — not for vehicles, but for blood flow.

Golzarian works in University of Minnesota's Department of Radiology as an interventional radiologist, a specialist who uses imaging techniques like ultrasound and fluoroscopy to pinpoint and treat areas with precision, and without surgery. That includes procedures like opening blocked arteries with stents or angioplasty. But sometimes, doctors strategically block blood vessels to improve patients’ health.

Arterial embolization — millions of tiny spheres injected into a blood vessel and clogging it — is an effective way to control bleeding in trauma patients while controlling some types of tumors by blocking the blood flow to tumor cells and letting them starve to death.

Embolization is often used on benign tumors in the uterus, known as uterine fibroids. It’s a non-invasive way to eliminate the tumor. But when Golzarian recommended this treatment to his uterine-fibroid patients, some of them refused — even though the technique has a proven track record. For nearly two decades, embolization has been used to treat uterine fibroids. (And it's been used on other tumors for nearly 50 years). When patients said no to the procedure, it often happened after they asked this question about the embolization microspheres: How long will they stay in my body? The answer: Forever. The particles are made of materials that can’t be absorbed by the body. Golzarian would explain to patients that studies didn’t show any serious side effects from the microspheres. Still, patients remained unconvinced. They didn’t want to carry around millions of tiny beads for the rest of their lives.

“I understand the mentality of the patient,” says Golzarian. “’If there’s no need for the material to stay in my body, why can’t you use something that’s resorbable?’”

He’s devoted the past five years to answering  that question. His research led to the launch of a startup, EmboMedics Inc., based in Maple Grove, Minn., which hopes to earn FDA approval for a different type of microsphere — one made of natural materials that the human body can absorb within days and  could improve treatment for tumors and also for cancer and other medical problems. These tiny spheres have the potential to make a big difference.

Building a Better Sphere

Most women have uterine fibroids — some estimates suggest as many as 75 percent of women do.  And most women will never know it, because they don’t have symptoms. For those who do experience symptoms, uterine fibroids can bring misery, including back pain and pelvic pain. About 10 to 20 percent of women who have fibroids require treatment. When they are treated with arterial embolization, the radiologist uses real-time X-ray imaging to guide a catheter (a thin tube about the size of a spaghetti strand) into position. The microspheres are loaded into a saline-filled syringe and injected through the catheter to a precise spot, where they clump together and block blood flow to the fibroid. Some studies show that after the procedure, nearly 90 percent of patients report significant or total relief from their symptoms.

After the microspheres create the blockage, it only takes a few hours for the fibroid to die. If they can eliminate fibroids so effectively, why not have microspheres that disappear after their work is done, instead of lingering? That’s the challenge Golzarian began tackling in 2008. With internal funding, he set up a lab at the University of Minnesota and enlisted the help of polymer chemist Lihui Weng, Ph.D. 

Their criteria included  natural — not synthetic — materials that would be absorbed by the body and materials that could be manufactured with consistent quality and shape. That’s no easy task when creating particles measured in microns (one millionth of a meter), and Golzarian knew he would need to make some of the microspheres as small as 100 microns. For comparison, the period at the end of this sentence is about 500 microns.

They also wanted materials that were easy to synthesize, without a hefty price tag. “We didn’t want fancy expensive material, because that would be costly for the end user,” says Golzarian.

After testing hundreds of substances, they found a combination that worked: chitosan, made from shells of shrimp and other crustaceans, and cellulose, the main component in plant cell walls. Cellulose is also on the ingredient list of many grocery items (it prevents clumping in prepackaged shredded cheese and makes low-fat ice cream seem creamier).  When it’s in the bloodstream, the chitosan-and-cellulose compound eventually breaks downs into carbon dioxide and water — things the body can easily dispose of.

With this material, the microspheres can be manufactured in various sizes (larger spheres work better for large arteries). That’s not the only customizable aspect of the material. Using a chemical process, Golzarian and Weng  were able to control the rate at which the body absorbs the microspheres, ranging from three days to 30 days.

Moving Beyond the Lab

The researchers knew they had developed a useful polymer. But was it patentable? To determine that, the University of Minnesota’s Office of Technology Commercialization  (OTC) conducted rigorous research on existing polymer patents — including hiring a patent attorney — in  2009.

“We spent more than the average amount of time trying to figure out whether this was patentable,” says Karen Kaehler, technology strategy manager for life sciences at University of Minnesota’s OTC. That effort paid off. Submitted in 2010, the 50-page patent, #8,617, 132, was issued in December 2013, with all of its 44 claims. That same month, a European patent (2485777) was issued. More patents are likely on the way — applications have been submitted in Australia, Canada, China, Hong Kong, and Korea.

In addition to patent assistance, the OTC helped with the search for a commercial partner to license the technology. “We talked with a lot of different companies,” says Kaehler. “And we heard a lot of comments like, ‘That sounds interesting. Let us know when you get it further along.’”

In this case, “further along” meant launching a startup to continue development of the embolization microspheres. Golzarian didn’t want to lead a company, so the OTC vetted potential entrepreneurs in 2012. That search lead to Omid Souresrafil, who became cofounder  and CEO of the startup, EmboMedics (the university owns 25 percent of the company).  “I’ve worked with medical devices for more than 20 years, so I know a good idea when I see it,” saysSouresrafil.

After a six-month process, the OTC  licensed the technology to EmboMedics in April 2013. “They were always very helpful about getting things to the next level,” says Golzarian, who is also EmboMedic’s cofounder and chief medical officer. Souresrafil echoes that sentiment, noting the OTC played a vital role in obtaining the startup’s most valuable asset:  the patent. “[The OTC] also introduced us to people who could invest in the company,” says  Souresrafil. “They did a very good job.”

Treating Liver Cancer

EmboMedics plans to call its product “resorbeads” — a nod to the shape (bead) and key attribute (resorbable). In March, the company began the application process for FDA approval. EmboMedics is also seeking regulatory approval for the microspheres in Europe and China. In addition to treating benign tumors, Golzarian and Souresrafil envision other uses. The microspheres could help stabilize patients with severe bleeding caused by trauma or ulcers — and after they served that purpose, the tiny beads would break down.

But the most dramatic way EmboMedics’ microspheres could make a difference is by treating liver cancer. Liver cancer caused 745,000 deaths worldwide in 2012, making it second only to lung cancer. Arterial embolization is already being used to treat liver cancer. The microspheres act as tiny sponges loaded with cancer-fighting drugs. When the microspheres are injected, they deliver a one-two punch: They close off the arteries that feed to the liver’s cancerous tumor and also gradually release the drugs.

Here’s the problem with the current microspheres used for this treatment: Because they stay in the body, they continue to release the chemotherapy drugs even after they’re taken care of the tumor. Also, the permanent particles may block the access to the tumors if the patient needs another treatment. That’s not ideal, says Golzarian — and there is some data suggesting that the unnecessary drug release may provoke side effects. “It makes more sense that when tumor is dead, the spheres go away and don’t release drugs anymore.”

Golzarian would like to see EmboMedics’ product used for this purpose, but that goal is still years away and would require clinical trials for FDA approval. In the meantime, he’s hoping EmboMedics can change the conversation around arterial embolization, by making the absorbable material widely available. 

When patients ask, “How long will these microspheres stay in my body,” the doctors can finally give an answer they want to hear.  

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BIOX Technology Makes Biodiesel Faster to Manufacture, Cheaper

University of Toronto

BIOX Technology Makes Biodiesel Faster to Manufacture, Cheaper

A University of Toronto chemistry professor’s research that began with sewage sludge oils has led to breakthroughs in producing biodiesel — a cleaner form of fuel for diesel engines.

Oil and water don’t mix, as any elementary school science teacher will tell you. That basic concept is the foundation of a University of Toronto chemistry professor’s discovery.

This innovation significantly cuts the time and cost for creating biodiesel — a renewable fuel for diesel engines derived from natural oils like soybean oil and a variety of other feedstocks such as animal fats, greases and used cooking oils.

It also led to the creation of an Ontario firm called BIOX Corp., which has 33 employees and is headed by Chief Executive Officer Tim Haig. BIOX recently built a $24 million plant in the steel-making city of Hamilton.

The facility is capable of producing 60 million liters (18 million gallons) of biodiesel a year and shipped its first batch of fuel to the United States in late 2006. Over time, the company hopes to build plants throughout North America and Europe.

BIOX’s Beginnings

The BIOX story goes back more than a decade to when David Boocock, Ph.D., then head of the University of Toronto chemical engineering department, was looking into the oils that were produced when sewage sludge was heated. He is now a professor emeritus at the school.

“I was investigating the technology of using pyrolysis to turn the sludge into a liquid fuel,” he recalls. Pyrolysis is the use of heat to break down complex chemical substances into simpler substances.

“I identified that there were good oils and bad oils,” he explains. “The bad came from the proteins and the good came from the lipids.” Lipids are also known as fats.

That led Boocock — an organic chemist by training — to biodiesel that was being manufactured in Germany.

“I knew that it was lipid-like, so I looked at the literature and came to the conclusion that most of what was being published was wrong,” he notes.

The people making biodiesel believed that methanol and vegetable oils and animal fats, plus a catalyst, would mix, he said.

“They don’t,” says Boocock. “Chemical engineers call this a mass transfer problem. They were trying to measure the rates of reactions, but it was based on a faulty premise.”

To cut to the quick, Boocock came up with an inert co-solvent to add to the oil and methanol. The three melded and became one.

“It was clear and you could see through it,” he comments. “And when it was mixed, the reactions speed up and go a lot further.”

That, in a nutshell, was the technology that launched BIOX. Boocock continued to refine his discovery, and in 1999, it began to look like the technology had a business application. The Natural Sciences and Engineering Research Council of Canada provided funding for Boocock’s research underlying BIOX.

Biodiesel’s Growing Importance

Cyril Gibbons is the commercialization director for physical sciences and engineering for Innovations at University of Toronto (IUT), a group of professionals charged with commercializing innovations developed by University of Toronto researchers and its health care partners. He commented that there was not a lot of interest in the technology until the cost of fuel began its upward swing.

Boocock said the discovery of mad cow disease in Canadian cattle several years ago also made producing biodiesel cheaper. 

“It is the cost of the feedstocks that largely control what it costs to make biodiesel,” he says. “And when mad cow disease appeared, this resulted in a dramatic falling in prices of ‘refurbished’ waste fats and oils (from animals).” 

Regulations cut off transfer of those materials between countries, essentially wiping out the foreign market, so the BIOX process also helps solve a waste problem, he said.

Gibbons adds: “From the environmental side, there are many reasons to use biodiesel because it is significantly cleaner, emitting 80 percent fewer hydrocarbons, 60 percent less carbon dioxide and 50 percent less particulate matter than petroleum diesel.”

He says that Innovations helped Boocock patent his discovery and retains a small interest in BIOX.

Moreover, scientists say high quality biodiesel blends easily with petroleum diesel in any proportion, requires no engine modification, and is actually good for the engine.

“Before 1999, biodiesel was considered too expensive too produce,” he says. “But the cost of oil is now about double what it was back then, so the economics shifted strongly in our favor.”

Growth Opportunities for BIOX

In 2000, Innovations found a Toronto investor willing to put up the money to build a prototype plant. The company, Madison Ventures Ltd., introduced Haig to Innovations, and BIOX was off and running.

Haig, an engineer who had worked with wind farms and other renewable energy sources, said he was fascinated by the simplicity of Dr. Boocock’s discovery. Instead of applying more heat or pressure to the process — what Haig called the “sledgehammer” approach — Boocock went back to the first principles.

“David is a finesse guy,” says Haig. “Rather than using brute force, he found a way to make the liquids — oil and alcohol — go together by adding a co-solvent that made the two want to stay in one phase until the reaction was complete.”

Haig worked with Scott and Joe Monteith, the principals behind Madison Ventures, who also happened to make grease traps for restaurants.

“It was a lot for what was then just an idea,” says Haig. “But Joe Monteith was a chemist, too, and he saw elegance in the technology.”

Haig also got about $500,000 in grant money from the Canadian government to help build the pilot plant.

“Prior to that, we had no idea if it would be scalable,” explains Haig, adding that the pilot was finished in April of 2001.

“We ran that for some time and found out there was a fine line between making soap and biodiesel,” he recalls. “As you would expect, we had some issues. But our first plant, in Oakville, ultimately proved the chemistry.”

Haig then “beat the pavement” to find more high net worth investors so the company could buy the University of Toronto biodiesel intellectual property outright and build another plant in Boston.

“The second plant proved efficient separation,” he says. “In the first, you had a concoction of a whole batch of carbon chains. In the second, we proved we could separate carbon chains into the right bucket at the right price.”

With that hurdle passed, they scaled up to build the big new plant in Hamilton.

“We finished it this summer and it is working well,” Haig says confidently. “We raised another $48 million this summer and we intend to build three, four or five more plants in the next few years, selling to companies that want to mix what we are producing with regular diesel — probably at blends of 2 to 5 percent.

“And you know the ironic thing about all this?” Haig asks. “Rudolph Diesel invented the diesel engine to run on vegetable oil.”

Pierre Schuurmans, chief operating officer of Birch Hill Equity Partners Management, Inc., said his company put up $48 million so BIOX can continue to grow.

“We think they have a low-cost technology in process that puts them in a good position to meet the growing demand,” Schuurmans explains. “With mandates and subsidies in some places, BIOX is very competitive.”

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Black Silicon Revolutionizes How Light is Captured and Stored

Harvard University

Black Silicon Revolutionizes How Light is Captured and Stored

In 1999 Harvard University physics professor Eric Mazur accidentally created a remarkable new material in his laboratory by subjecting gray silicon to ultra-short bursts of energy from a high-intensity laser. He discovered the surface of the now-blackened silicon was covered by billions of tiny, needle-like spikes of silica only one-hundredth the diameter of a human hair.

Mazur and his research team quickly realized this new material, which he named black silicon, had excellent light-absorbing properties. Funding for additional research was provided by the U.S. Army Research Office, National Science Foundation, and the U.S. Department of Energy.

Black silicon can absorb 96 to 98 percent of the light that hits it — giving it highly sensitive and unique optical and electronic properties.

Black silicon can absorb visible light and infrared radiation (heat) at unprecedented levels. For comparison, normal gray silicon absorbs only about 60 percent of sunlight that strikes its surface.

This technology is currently being developed by Massachusetts-based Sionyx, Inc. Possible applications include manufacturing very sensitive and inexpensive photodetectors for high resolution cameras, day/night cameras for security and surveillance, and high-sensitivity detectors and imagers for biotechnology applications. Because it also absorbs heat, black silicon is an excellent detector of clouds, pollution, water vapor and other atmospheric effects that influence climates. Other possible products include disposable chemical/biological sensors and improved thin-screen displays.

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Bloodchip Technology Could Change the Face of Blood Testing

University of the West of England, Bristol

Bloodchip Technology Could Change the Face of Blood Testing

Bloodchip® is a new approach to testing blood groups that could save many lives and significantly improve patient care in Europe and worldwide.

The new test is intended to replace traditional methods of blood grouping with a highly accurate genetic test, giving a much clearer picture of the many different and often small variations in blood types. This will enhance the accuracy with which blood donors are matched with recipients (patients). The Bloodchip testing solution will be particularly beneficial to patients who are receiving multiple blood transfusions and require perfectly matched blood types. Over time these patients develop antibodies that reject imperfectly matched blood transfusions, a process known as alloimmunization, which can lead to serious illness and life-threatening side effects.

Particular beneficiaries of Bloodchip® include those affected by sickle cell disease and thalassemias, which are hereditary disorders involving defective hemoglobin production, and result in low production and destruction of red blood cells.

The Bloodchip test will help ensure people with sickle cell disease or thalassemias receive perfectly matched blood to enable them to better manage their conditions.

Bloodchip has been developed by the panEuropean Bloodgen consortium led by scientists at the University of the West of England, Bristol. The consortium is a mixture of academic institutions, national blood transfusion services and commercial organizations involving the following participants:

  • University of the West of England, Bristol 
  • Progenika Biopharma S.A.
  • Sanquin, Amsterdam
  • Bristol Institute for Transfusion Sciences
  • University Hospital Blood Centre, Lund
  • Transfusion Centre and Tissue Bank (CTBT), Barcelona
  • Institute of Haematology and Blood Transfusion (UHKT), Prague
  • Biotest A G

The European Union’s Fifth Framework Program, which promotes research and technological development, funded the consortium’s work. 

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BluePRO Water Filtration System: Saving Water Resources and Money

University of Idaho

BluePRO Water Filtration System: Saving Water Resources and Money

Municipalities and industrial plants are under pressure to meet increasingly stringent clean-water regulations, which often are costly to implement. But they may get some assistance from a cutting-edge firm that has commercialized an innovative water treatment process developed at the University of Idaho.

Municipalities and industrial plants across the United States are finding themselves between a rock and  hard place.

On the one hand, they’ll need to spend millions of dollars to improve their water treatment systems to comply with new clean water regulations. On the other hand, the existing technology to upgrade water treatment systems is not highly effective.

Much of their dilemma revolves around regulations to reduce nutrients such as phosphorus in discharged water by as much as 95 percent. Phosphorus, a vital nutrient in all living things, can be harmful when excessive amounts are in lakes and streams. Too much phosphorus causes rampant algae growth, which further diminishes the quality of water and can kill fish and other organisms vital to aquatic ecosystems.

Conventional water treatment systems may be capable of reducing phosphorous levels to as low as 500 parts per billion. But in certain parts of the country, such as the Spokane River in the northwest United States, new phosphorous reduction regulations allow for only 50 parts per billion — far below the water cleaning capabilities of conventional systems.

Luckily, a new water treatment technology has entered the marketplace — and not a moment too soon.

It’s called BluePRO™, a low-cost, low maintenance solution that is highly effective in removing phosphorus and other contaminants from water.

Scrubbing Wastewater With Coated Sand

The BluePRO™ filtration system is based on the pioneering research of Professor Greg Möller, Ph.D., and Remy Newcombe, Ph.D. The two conducted initial work on the technology at the University of Idaho in Moscow, under the sponsorship of the U.S. Environmental Protection Agency and other U.S. government agencies. In 2003, Blue Water Technologies Inc., based in Hayden, Idaho, was founded to commercialize the technology; it also obtained the license to the technology underlying BluePRO™.

Similar to existing water filtration systems, BluePRO™ uses sand as a key filtering agent. But it’s not just ordinary sand that you might find at the beach.

Instead, it’s coated with iron oxide, a rust-like property that is particularly absorbent. The specially coated sand scrubs phosphorus and other undesirable properties in wastewater that flows through large tanks. As the sand sinks from the top of the tank to the bottom, the iron oxide detaches and absorbs the phosphorus. Next, the water, sand and iron oxide are separated from each other by density. The clean water is pumped out, the sand is separated and removed for reuse and the waste solid containing iron oxide/phosphorous particles is removed for disposal.

“The sand filter is the core of our product,” explains Tom Daugherty, president of Blue Water Technologies Inc. “These filters have no moving parts, so they’re easy to maintain. And only up to 10 percent of the sand must be replaced annually over the 20-year life cycle of the filters. These are a few of the reasons why BluePRO is so cost-effective.”

Depending on the size of the community involved, use of the BluePRO™ system can cost as little as $12 per household annually for about 20 years.

In cases like the Spokane River where conventional systems are incapable of reducing phosphorus to lower levels required by the EPA, other exotic systems involving reverse osmosis and membrane filtration could conceivably do the job, Daugherty says. “But their cost would be many times more than that of the BluePRO™ system,” he says. And cost efficiency definitely is a critical issue when considering the scale of phosphorous reduction needed in the United States.

As much as half of the country’s waters do not adequately support life because of excessive phosphorus and other nutrients, according to the EPA. To meet the EPA’s lower phosphorous levels in these bodies of water, an effective, relatively inexpensive solution like BluePRO™ would help thousands of cash-strapped municipalities responsible for water treatment.

Putting BluePRO™ to the Test

In view of increasing regulatory requirements for cleaner water, it’s no surprise that numerous potential customers have shown an interest in purchasing the BluePRO™ filtration system, especially given its affordability and ease of use. In fact, Blue Water Technologies Inc. created a portable trailer-mounted water treatment system to demonstrate the value of BluePRO™ filtration systems at various locations throughout the Northwest.

However, a number of companies and communities have been reluctant to invest millions to upgrade their wastewater treatment systems with BluePRO™, noting that it has been demonstrated only on a small scale — not in large-scale applications.

Undaunted, Blue Water Technologies Inc. teamed up with the town of Hayden, Idaho, to create a 1,200-square foot, $1 million dollar test facility connected to Hayden’s wastewater treatment plant, capable of treating 1.5 million gallons of contaminated wastewater every day. Launched in May 2005, the Hayden Wastewater Research Facility showcases BluePRO™ technology in a real-life setting.

“The Hayden facility gives researchers at the University of Idaho and other institutions a full-sized environment in which trials and demonstrations of other experimental water treatment processes can be conducted,” says Gene Merrell, interim director of the Idaho Research Foundation at the University of Idaho, and assistant vice president and chief technology transfer officer at the University of Idaho’s University Research Office.

The main focus of the Hayden Wastewater Research Facility is phosphorous removal, given the EPA’s regulatory push to reduce phosphorous levels in water.

“When it comes to phosphorus, natural water should have less than 40 parts per billion, and 20 parts per billion is even better,” notes Möller.  In late 2005 the Hayden facility dramatically surpassed clean water requirements.

The BluePRO™ system can lower phosphorous levels from 3,000 parts per billion to 10 parts per billion — a 99.7 percent reduction.

Researchers at the Hayden facility are setting out to prove that a modified BluePRO™ process can remove other harmful substances besides phosphorus. These include arsenic, heavy metals and endocrine disrupters commonly found in detergents, birth control pills and other personal care and pharmaceutical products that are flushed down toilets or put down the drain. Endocrine disrupters are particularly worrisome, as they can cause cancer and birth defects, and can adversely affect immune and reproductive systems in humans and animals.

Improving the environment while saving money in the process may seem like a dream to most taxpayers and business executives. Yet this dream is quickly becoming a reality, thanks to the University of Idaho’s groundbreaking scientific discoveries that are being perfected, commercialized and marketed by Blue Water Technologies Inc.



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Body Sensor Networks Monitor Physical Data Wirelessly in Real Time

Imperial College London

Body Sensor Networks Monitor Physical Data Wirelessly in Real Time

Professor Guang-Zhong Yang and his team at the Department of Computing, Imperial College London have developed Body Sensor Networks (BSNs) that effectively monitor readouts of heart-rate, blood oxygen levels, temperature and physical activity with relative ease. 

The miniature wearable microsensors and wireless communication technology can be used wherever real-time monitoring is required — from managing patients’ chronic diseases in medical facilities to monitoring the health of people living on their own.

The e-AR (ear-worn activity recognition) sensor developed by the team has been tested with patients recovering from surgery at St. Mary’s Hospital in London.

Beyond medical applications, a team from Imperial College’s Tanaka Business School demonstrated BSNs also could be used for personal fitness monitoring. So the Royal College of Art was tasked with designing a wearable sensor directed at the elite athlete and fitness sector. The end result: a device that can monitor an athlete’s performance and transmit the information to his or her mobile phone, personal digital assistant device or computer.

Professor Yang and his team are now working with the Engineering and Physical Sciences Research Council, which is the United Kingdom’s governmental agency for funding university research grants for engineering and physical sciences projects, and UK Sport, the leading government agency promoting sports in the United Kingdom, in piloting the e-AR sensor for training potential UK medallists. Imperial Innovations, a technology commercialization and investment  company based at Imperial College London, has formed the company Sensixa to commercialize the many applications of BSNs. Various government grants were used to fund the initial research underlying the patented BSN technology.

Additional information is available at

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Planting Seeds to Faster Recovery

Emory University

Planting Seeds to Faster Recovery

Angioplasty has come a long way. In the early days of the procedure, stainless steel stents were used to keep the patient's artery from reclosing after the angioplasty balloon restored blood flow. But about a fifth of these patients developed restenosis—the growth of scar tissue in and around the stent. The results were chest pain, repeat procedures to reopen the clogged artery, and sometimes death from heart attack.

To remedy this situation, in the late 1990s Emory University physician/scientists Ian Crocker, MD, Spencer King, MD, Keith Robinson, PhD and Ron Waksman, MD along with engineers from Novoste Corporation, developed the Beta-Cath™ System, which uses vascular brachytherapy to prevent the artery from re-closing.

With brachytherapy, tiny “seeds” of radiation are placed within the coronary artery at the site of the angioplasty, and are left in the artery for less than five minutes before being removed. The radioactive seeds minimize the growth of cells at the site, which reduces the amount of scar tissue that may develop. Patients’ exposure is less than 1 percent of the radiation they would be exposed to by a typical chest X-ray.

The Beta-Cath™ System was licensed to Novoste and received FDA approval in 2000. It was the first commercially available vascular brachytherapy device in the U.S. and Europe. A few years later, Novoste received FDA approval for its smaller diameter Beta-Cath™ 3.5F System and its Beta-Cath™ System that uses a 60mm radiation source. The company also began clinical trials of its CORONA™ System for treatment of peripheral vascular disease and restenosis of arterial-venous dialysis grafts. In 2006, Novoste (now NOVT) sold all of its vascular brachytherapy assets to Best Vascular, Inc.

What sets Beta-Cath™ apart from other technologies such as drug-eluting stents, is its proven track record.

When standard stainless steel stents are used, 15 to 20 percent of patients experience restenosis as well as bouts of angina and chest pain. Drug-eluting stents, which are coated with medicines that interfere with reblocking, show a complication rate of 8 percent, while Beta-Cath™ has shown complication rates as low as 3.8 percent.

Fewer procedures mean less expense for the patient, less of a burden on the nation's health care system, and longer and better lives for patients. Beta-Cath™ is backed by data and the experience of interventional cardiologists, who have used it to treat more than 50,000 patients worldwide.

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Researchers Realize a Vision to Help the Blind

Wisconsin Alumni Research Foundation (WARF)

Researchers Realize a Vision to Help the Blind

Sometimes the path technology takes to the marketplace is dotted with people who raise a quizzical eyebrow and say, You want to do what? In the case of the Brainport vision device, some of the first people to do so were two of the co-inventors.

The innovation started with Paul Bach-y-Rita, M.D., who was an early pioneer in the field of neuroplasticity — the idea that the brain can be trained to process information in a new way. In the 1960s, he became interested in using that concept to design a device that would transfer the sense of sight into touch, a process known as sensory substitution. He did this by creating a machine out of an old dentist chair with a camera attached. Four hundred little rods popped in and out against a person’s back mimicking the patterns of the objects the camera was seeing.

Though Bach-y-Rita proved that the system worked, not much happened with that invention. When he came to the University of Wisconsin in the 1980s he picked up the idea of sensory substitution again. He was particularly interested in using electrical pulses instead of manual stimulation to represent shapes.

Bach-y-Rita, along with Kurt Kaczmarek, Ph.D., then a staff scientist at the university, designed a system that translated black-and-white images into electrical pulses against a blind person’s fingertip. The strength of the pulse depended on how black, white or gray an object appeared on a computer screen. The device worked well, but it was bulky and cumbersome. Still, it gave people with no sight a way to visually perceive objects for the first time.

“These are truly visual tasks and they did them without their eyes,” says Kaczmarek, now a senior scientist in the university’s Tactile Communication and Neurorehabilitation Lab.

That rudimentary device eventually turned into the Brainport vision device — giving blind people a way to “see” their surroundings through electrical pulses.

Transferring to Tongues

But that device needed to get much smaller, which led to a switch away from fingertip stimulators and the first round of skepticism.

Bach-y-Rita started talking to Kaczmarek and another research colleague, Mitchell Tyler, about using people’s tongues instead of fingertips. His reasoning was that the tongue is super sensitive, a large part of the brain is devoted to processing information from the tongue, and except for when we’re eating and talking, the tongue doesn’t do a whole lot.

“We looked at him kind of funny,” Kaczmarek says. “Mitch and I thought he was being a little crazy.”

Bach-y-Rita, it turned out, was onto something. He spent a couple years mulling over ways to use the tongue for sensory substitution. Kaczmarek and Tyler finally acquiesced and agreed to give it a try. They took the fingertip device, and stuck it on their tongues. The pulses it delivered were comfortable and effective. People have described it as feeling like champagne bubbles are painting a picture in their mouth. The researchers did some preliminary studies and proved that people could recognize basic geometric shapes while wearing it, and it performed as well as the fingertip version.

One of the key “aha moments” Kaczmarek recalls was realizing that the tongue required much less circuitry than fingertip devices. The surface of our skin changes depending on whether we’re hot, cold or sweating. Tongues stay uniformly wet and warm. So the electrical circuitry needed to generate and control the pulses is much simpler, meaning the device can be much smaller. Kaczmarek, who designed the first tactile tongue display, got the hardware down to the size of a shoebox. It would eventually become the size of a cell phone.

Road to Commercialization

The group published its results in 1998 and approached the school’s private, nonprofit technology transfer organization, the Wisconsin Alumni Research Foundation (WARF), about patenting the invention. WARF eagerly proceeded. Then it started looking for companies interested in licensing the technology. It found none.

“It was a little off the wall — thinking about seeing with your tongue,” says Jeanine Burmania, a licensing manager with WARF. She says the market didn’t fully appreciate the device’s potential at the time.

Or, as Kaczmarek says: “We were viewed as those crazy people in Madison who were doing things with the tongue.”

So Bach-y-Rita, who passed away in 2006, decided to found a company called Wicab, after his wife’s maiden name.

“It’s a good example of the passion of an inventor who wanted to see his technology commercialized,” Burmania says.

WARF exclusively licensed the technology to Wicab in 1999. WARF received equity from Wicab in lieu of an upfront licensing fee, an arrangement WARF frequently makes with startups, Burmania says.

“Sometimes, technologies developed at universities need further development prior to attracting interest from existing companies,” she continues. “This development is often outside the scope of traditional university funding mechanisms and no longer feasible within the university setting. The Brainport technology is an example of a device that could have languished in the lab from lack of exposure, but was able to make it out of the university because of Wicab.”

For the first several years, Wicab operated mostly as a research and development company, and the personnel overlapped entirely with the university staff.

A couple years into their work with Wicab, the team discovered a new way to use the tactile tongue display. Tyler had a bad inner-ear infection, which caused him to have balance problems. The group decided to try putting a sensor on a helmet that monitored tilt and then translated that information to people’s tongue via electrical pulses that let them know if they were off balance. After seeing that it worked, they started developing a balance device in addition to the vision device.

In 2005, Robert Beckman took over as chief executive officer of Wicab. A veteran of other medical device companies,

Bach-y-Rita invited him to helm the still fledgling company. Beckman realized that the commercial viability of the Brainport balance device was much higher than the vision device because there are many more people with balance problems than those who are totally blind. So they pushed ahead aggressively with the balance device, using much of the $10 million he raised from angel investors during his first year on the job. The vision device was still being developed, mostly with the help of funding from the National Institutes of Health, the National Eye Institute, the Defense Advanced Research Projects Agency and the State of Pennsylvania.

Then Wicab got some bad news. The company had received approval in Europe and Canada to sell the device, but that process is based only on proving the safety of the device not its efficacy. During U. S. Food and Drug Administration (FDA) trials earlier this year, the company discovered that its balance device, while effective 60 percent of the time, was not more effective than the “sham device” that half of the people in the study used. Beckman believes the benefit came from the training and exercises that both groups of users went through in conjunction with their participation in the clinical study. Kaczmarek isn’t convinced that it was the training and exercises alone that helped 60 percent of the people in the study and is trying to puzzle this out in his lab.

Either way, Beckman says of the results: “It’s good for science. It’s bad for commercialization.”

Independence Through Improved Sight

Wicab’s full attention has now turned to the vision device, which could get FDA approval as early as the end of the year, Beckman says. They have proved that the device works by testing it on more than 100 people who have had great success with it.

While there are 300,000 people with no sight in the United States, the company is focusing only on the 100,000 who are not elderly and, therefore, probably more receptive to new technology. He’s also interested in the potential market in China and India.

The device has shrunk considerably since its days in the University of Wisconsin lab. Users now wear a pair of sunglasses with a camera mounted on the nose bridge. A lollipop-sized square, which has 400 electrodes in it, sits on their tongue. The stimulation pattern of those electrodes mimic whatever the camera is picking up, essentially acting as the camera’s pixels. So if the camera is seeing white, the user gets a stronger pulse, gray gets a medium pulse and black gets no pulse. A cell phone-sized control box is attached by a wire to the camera and allows the user to zoom in and out on specific objects. Beckman says the next step is to make the device wireless.

Users get trained for 10 hours on the device, and almost all are very comfortable with it at the end and eager to take it outside or use it at home, says Aimee Arnoldussen, Ph.D., a neuroscientist with Wicab. They’ve listed the many tasks and activities they would love to use the device for, from simply reaching directly for a cup of coffee on the table instead of having to feel around for it to being able to run a marathon by following a guide instead of having to be tethered to him.

“They talk about the independence that the devices can give them,” Arnoldussen says. Unlike many devices for the blind that read aloud the information people can’t see, the Brainport allows people to dictate what they want to pay attention to.

“The user gets to control this technology and what information they’d like to understand,” she says. “They get to decide where their attention is drawn.”

In a video on Wicab’s Web site, blind adventurer Erik Weihenmayer demonstrates how he can rock climb while wearing the device. Weihenmayer, who lost his vision as a teenager, has climbed Mount Everest and scaled El Capitan since losing his sight. He also performs some less daring feats in the video, such as playing tic-tac-toe with his daughter while wearing the Brainport.

Some of the most emotional users, Arnoldussen says, are military personnel who lost their sight in explosions in Iraq and Afghanistan. “In many ways they’ve given up having visual perception, and we can provide that for them,” she says.

The Rotary Foundation has bought early versions of the vision device to help blind children in Central and South America. “Can you imagine the experience of a child who hasn’t had sight before being able to comprehend objects around them?” Arnoldussen says.

Who would raise a quizzical eyebrow to that?


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BRCA1 and BRCA2: Predictive Gene Testing Lets Women Know if They Are at Risk for Developing Breast Cancer

University of Utah

BRCA1 and BRCA2: Predictive Gene Testing Lets Women Know if They Are at Risk for Developing Breast Cancer

Every year, nearly 200,000 women are diagnosed with breast cancer. Research has shown that about 10 percent of these cases occur in women who have inherited higher-risk factors from their parents. Knowing this early in their lives can help them take a preventive approach to their health care, including more frequent screenings.

Two genes, BRCA1 and BRCA2, normally help the body fight off breast cancer. But an inherited mutation of these genes can make women more at risk for developing breast cancer. In fact, by age 70, women who carry the BRCA1 or BRCA2 mutation are nearly 10 times more susceptible to developing breast cancer.

BRCA1 and BRCA2, and their mutations, were discovered in the mid-1990s by a research team led by Mark Skolnick, Ph.D., a professor in the department of medical informatics at the University of Utah in Salt Lake City and executive vice president of research and development for Myriad Genetics. The research was conducted in collaboration with the University of Utah and others.

The number of women being tested for BRCA1 and BRCA2 is growing by 40 percent every year.

Since that time Myriad has become an international leader in preventive medicine and discovering disease-related genes. In 2007 Myriad Genetics expects to analyze more than 70,000 tests, which have become an accepted part of medical care among women.

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Breast CT: A New Alternative to Mammography

University of California, Davis (UC Davis)

Breast CT: A New Alternative to Mammography

Computed tomography (CT) is used extensively to identify tumors and other abnormalities in the brain, abdomen and pelvis. In contrast to medical X-rays, which produce a single-layer 2-D image, a CT scan records hundreds of images of multiple tissue layers and assembles them into a 3-D representation.

A team working at University of California Davis Cancer Center has developed a breast CT device they believe provides a more comfortable and potentially more sensitive alternative to X-ray based mammography to detect breast cancer.

The breast CT device, currently in a Phase II investigational trial, is the invention of Drs. John Boone, professor of radiology at UC-Davis, and Thomas R. Nelson, professor of radiology at University of California, San Diego. CT has not typically been applied to breast cancer detection because of concerns over the radiation dose required. The inventors solved this problem by designing a CT device that scans each breast while the patient lies face down on a special table. The radiation exposure in the breast is equivalent to that of a traditional mammogram, and the thoracic cavity is not irradiated at all, as it would be in a conventional CT scanner.

The first 21 patients in the ongoing clinical trial reported that the CT breast scan, which does not require breast compression, caused them less discomfort than mammography. The CT detected 19 of the 21 tumors initially identified by mammography, and Dr. Lindfors believes the prototype machine and method of scanning can be modified to improve on this detection rate. Once the Phase II trial is complete, a trial directly comparing breast CT and mammography will be the next step in moving the technology forward.


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Crop Protection Gets a Boost with Biotechnology

University of Georgia
University of Georgia Research Foundation

Crop Protection Gets a Boost with Biotechnology

Big problems can come in small packages. Case in point: The insect pests that feed on crops. Each year, these tiny creatures cause large-scale agricultural devastation around the world. For farmers, that erodes revenue worth billions of dollars and also contributes to steeper food prices. This poses a particularly worrisome trend in developing nations, where growing populations already struggle to afford the sustenance they need.

InsectiGen Inc. plans to help squash that bug problem.

The scientific discovery has led to increased effectiveness of widely used biopesticides and genetically modified crops — without damaging the environment.  

On the Farm, Bacteria Lend a Hand

To understand how InsectiGen’s product, BtBooster, can improve insect control, it helps to know a little about the type of pesticide it enhances: Bacillus thuringiensis, or Bt.

Bt is a form of bacteria commonly found in soil. Thousands of Bt strains exist today, and these bacteria have a valuable property. When eaten by certain insect larvae, Bt proteins turn toxic, killing the larvae within a couple days. That function was discovered a century ago, and farmers have used Bt toxins to help protect their crops for decades. Worldwide, it represents the most commonly used biopesticide. Considering the benefits Bt offers, it’s easy to understand why.

Unlike some pesticides, Bt doesn’t kill haphazardly. That’s because each Bt strain works like a lock and key, matching up with gut receptors in different insect larvae. As a result, it can target specific pests and let helpful insects thrive. Bt is also biodegradable, so it avoids problems linked to conventional chemical pesticides, such as potential harm to nearby livestock or wildlife or contamination of soil and water.

In the mid-1990s, farmers began planting cotton and corn crops that contained the Bt gene. These genetically modified plants produce the Bt protein that kills insect larvae. Since the introduction of Bt plants, their use has grown dramatically. In 1997, Bt crops represented 8 percent of U.S. corn acreage and 15 percent of U.S. cotton acreage, according to the U.S. Department of Agriculture. By 2010, those figures had surged to 63 percent for corn and 73 percent for cotton.

Giving Bt a Much-Needed Boost

While Bt has significant benefits — like the ability to selectively kill insects — it hasn’t eradicated agriculture pests. To glimpse the problem’s enormity, consider that for U.S. farmers, the cost of insect treatments and crop loss due to the corn rootworm can reach $1 billion annually, according to a Journal of Economic Entomology article. And that’s just the toll taken by one insect species, in one country.

Several shortcomings have kept Bt from making a bigger dent in the pest problem. It works well on some insects but has little effect on others. Concerns about Bt’s effectiveness have grown, as insects show signs of building resistance (one recent documented case is the fall armyworm, a well-known corn and cotton pest). Plus, Bt is a relatively expensive biopesticide, so it’s costly for farmers.

InsectiGen addresses those challenges with BtBooster. The aptly named product gives a boost to Bt’s effectiveness, in both spray form and genetically modified crops. According to InsectiGen, tests have demonstrated BtBooster’s ability to increase Bt’s potency by 20-fold or more. This creates several advantages for insect control. The heightened potency allows current Bt products to more effectively kill the insects they target. It also allows the development of new Bt products aimed at a wider range of pests.

What’s more, the extra-potent Bt diminishes insects’ ability to develop resistance to it — and farmers can use smaller amounts of Bt when it’s paired with InsectiGen’s product. As a result, BtBooster provides a twofold benefit for agriculture: It not only makes Bt more effective, but less costly too.

All of those advancements sprang from a happy accident — basically, a failed hypothesis that led to a scientific breakthrough.

A Path to Serendipity

“In the lab, you learn to look for ‘eureka’ moments,” says Michael Adang, Ph.D, professor of entomology and biochemistry and molecular biology at University of Georgia in Athens. That’s exactly what he found in October 2003.

At the time, Adang sought answers to a fundamental question: What makes certain Bt toxins kill one caterpillar and not another? With several patents for genetically modified Bt plants and more than 25 years of research, Adang was already well-versed in the science of Bt. But he needed to dig deeper.

To that end, Adang and his colleagues did an experiment using fragments of an insect’s receptor for Bt toxin. They took the fragments, mixed them with Bt toxin, and fed it to larvae. The researchers thought the fragments would neutralize Bt’s effects and block the toxin from binding to the insect’s gut. Instead, they got a startling result that defied their expectations. The receptor fragment didn’t protect the insects at all — it caused them to die from lower-than-usual doses of Bt toxin.

“We thought, ‘This is really unusual,’” says Adang. “At first we didn’t believe it.” Adang and his team — Gang Hua, Ph.D, Jiang Chen, and Mohd Amir Abdullah, Ph.D — repeated the experiment several times. When they got the same results again and again, they started believing. “We said, ‘This is real.’ It was a serendipitous discovery.”

A Business Takes Root

To commercialize that happy accident, Adang co-founded InsectiGen in 2003 with Clifton Baile, Ph.D. With BtBooster, they envisioned a new strategy for insect control: A product that doesn’t replace Bt, but augments it. “The BtBooster has no toxicity itself because it’s just part of an insect protein. It bindsto the Bt, and preserves its bioactivity,” says Baile, InsectiGen’sCEO. Previously, he served as a director of research and developmentat Monsanto, one of the largest agricultural biotechcompanies in the world. But he’s no stranger to the struggles ofa small business. Before InsectiGen, Baile helped launch nineother biotech startups.

When InsectiGen needed to create a business plan, the not-forprofit Georgia Research Alliance helped pay for a professional to write it. Funding from the U.S. Department of Agriculture and the National Institutes of Health helped Adang conduct research to further develop the company’s nontoxic protein. In 2003, InsectiGen licensed BtBooster’s initial technology from University of Georgia Research Foundation, the university’s technology transfer group. Since then, Adang’s lab has done additional patent-worthy research for BtBooster. “We jointly own some of the patents with InsectiGen, which is a little bit unusual,” says Rachael Reiman Widener, Ph.D, technology manager at the University of Georgia Research Foundation.

The company has close ties to the university; InsectiGen is currently based on campus at the university’s BioBusiness Center, which serves as an incubator for faculty startups. Widener notes that not all academics are natural entrepreneurs — and that sets InsectiGen apart from other startups she’s observed.

“It is not unusual to have struggles with faculty startup companies,” she says. That hasn’t been the case with InsectiGen. “They make it easy,” says Widener. “Mike and Cliff have a good sense of what it means to run a company, versus running a lab. So we’ve been able to work with them without any hiccups.”

Even before his BtBooster invention, Adang says the University of Georgia Research Foundation played a helpful role. “I’ve filed other patent applications previously, and our technology transfer group here is very faculty friendly,” he says. “They’re supportive of faculty that have entrepreneurial ambitions.” He also appreciates the level of trust shown by the technology transfer group. “When I asked to work with a patent attorney I’ve known for more than 15 years, they said ‘Great, go with it,’” says Adang. “They could have insisted on using a local attorney, but they didn’t.”

Baile echoes those sentiments regarding the technology transfer group’s support. “We consider them members of the team,” says Baile, who is also a professor in University of Georgia’s Departments of Animal and Dairy Science and Foods and Nutrition. “They’ve been very good in nourishing the commercialization activity of the company.”

InsectiGen’s Next Steps

Soon, the company plans to take BtBooster’s commercialization a step further. It’s working toward registering the product with the Environmental Protection Agency. “We’ve been doing field trials for several years on combinations of BtBooster with Bt biopesticides,” says Adang. “I think we could have it registered in the next two or three years.”

The product has already caught the attention of large companies.A subsidiary of DuPont, Pioneer Hi-Bred, is using BtBooster under a licensing agreement to develop better geneticallyengineering Bt crops. “It’s the only one we have publiclyannounced, but we have other agreements with companies,”says Baile.

In its present form, BtBooster is designed to thwart agriculture infestations, but InsectiGen won’t stop there. Ultimately, Adang wants to broaden the scope of insects that Bt kills — and not just pests that damage crops. His current research includes BtBooster’s effect on the darkling beetle, which can transmit Salmonella in commercial poultry houses. He has other pests in the crosshairs too.

“Some of our more interesting work is trying to find a more effective way to make biopesticides for mosquito control,” says Adang. He has applied for a National Institutes of Health grant to conduct field trials in this area. If he’s able to curb mosquito populations with BtBooster, it could have widespread effects on world health issues by preventing the spread of lethal diseases. Malaria is one example — according to the World Health Organization, at least 1 million people die each year from malaria transmitted by mosquitoes.

Adang knows the rewards of taking a discovery from the lab to the marketplace. Each year, he helps plant that seed in students’ heads by teaching a biotechnology course at University of Georgia (one of the guest lecturers the patent attorney who works on BtBooster). “I think he’s really able to get the point across to students that there is another world beyond academia,” says Widener.

BtBooster has officially entered that other world. It evolved from a “eureka” moment in the lab to a product that could dramatically improve pest control.

“It’s very gratifying,” says Adang. “But this isn’t the first time I’ve had this experience.” In 1982, he started developing technology for engineering Bt genes into plants. InsectiGen continues to build on those decades of research. With a boost in potency, Bt toxins can help reduce the damage insects do to plants, and the disease they cause in humans. The potential significance isn’t lost on Adang. “It’s a motivating force in my career,” he says, “that you can continue to make discoveries that will have value for society.”


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Helping Newborns and Their Parents Breathe Easier

Rice University

Helping Newborns and Their Parents Breathe Easier

Each year, millions of babies are born with an urgent struggle: breathing. It’s particularly common for premature babies who don’t have fully developed lungs, and one solution that can save lives is a machine called a bubble CPAP (which stands for “continuous positive airway pressure”).

Originally developed more than 40 years ago, it’s widely available throughout hospitals in developed nations. That’s not the case in most developing countries, where the World Health Organization estimates that almost 800,000 neonatal deaths occur each year due to acute respiratory infections. A typical bubble CPAP machine can cost more than $6,000 dollars, placing it out of reach for low-resource facilities. That’s changing, thanks to a low-cost bubble CPAP machine called Pumani (which means “breathe easy” in Chichewa, the national language of Malawi).

Initially developed at Rice University, this affordable, durable, and easy-to-use device has already proven it can dramatically improve infant survival rates.  
The idea behind Pumani emerged from Rice 360° Institute for Global Health Technologies — a program where Rice faculty and students develop low-cost health technology to address the needs of developing nations. As part of that program, students, and their advisors collaborate extensively with Queen Elizabeth Hospital in Malawi. As co-founder and director of Rice 360, Rebecca Richards-Kortum, Ph.D. visits the hospital three times a year and sees the resource challenges first-hand. "In the neonatal ward, you might find 60 or 70 babies with only two nurses to take care of them. And it's not uncommon to see up to four babies sharing a single bed,” says Richards-Kortum, who is also Malcolm Gillis University Professor.
When Rice 360 participants asked clinicians to identify gaps in their ability to deliver care, the main request was the development of a robust, affordable bubble CPAP system. An air tube extends from the baby’s nostrils to a column of water in the machine — the air flow in the system creates water bubbles, and the machine helps increase lung pressure and keeps airways open for lungs that haven’t fully developed yet.  
In 2009, a team of senior Rice undergraduate students began working on the problem, with initial funding from the Howard Hughes Medical Institute, the U.S. Agency for International Development (USAID), and the National Collegiate Inventors and Innovators Alliance (now called VentureWell). “We looked at the main components of a CPAP which provide pressure and flow — and tried to determine the best way to provide those in a low-cost, durable way,” says Jocelyn Brown, who was part of that student team. After considering several off-the-shelf pumps and fans, the team discovered that aquarium pumps would work well for their prototype, which took about nine months to complete.
"I was still an undergraduate student, and I really had very little idea of what is actually required to bring a medical device to market,” says Brown. "In my mind, it didn't seem like a possibility at the time.” That changed after she went to Rwanda with other Rice students to meet with doctors in major hospitals and demonstrate the prototype. Then something unexpected happened: One of the hospital administrators tried to buy the prototype from the team. ”It was very encouraging in a certain way, but also really evident to me that there was such a desperate need for equipment like this,” she says. “That experience really showed me that there was huge potential for the device."
To help refine how the device would be designed and manufactured for a reasonable price, Rice University enlisted the services of 3rd Stone Design, a product design and development company. The San Rafael, Calif.-based firm had worked with the Rice 360 program on two previous projects. “Every now and then, students come up with something that isn’t just a good student project, but is potentially a good product,” says Robert Miros, founder of 3rd Stone Design.
Although he calls the students’ use of the aquarium pump “a stroke of genius,” the Pumani design changes included a different pump to maximize product durability. “We found that with aquarium pumps, sourcing might be problem to get the adequate amount consistent to our required specifications.” The current pump is one that’s commonly used in fountains "to keep them from getting slimy,” says Miros. Data shows those pumps can run continuously for nine years, while the aquarium pumps might only last for a few years.
For a high-volume production unit, most companies invest in expensive tooling to make injection-molded parts, says Miros. Instead, 3rd Stone Design focuses on lower-cost tooling production methods. That includes sheet metal — which makes the product heavier, but also more durable. “With higher-tech stuff, [the manufacturers] know it isn’t going to last forever, so they design that way. We’re designing something that will last five to 10 years in the field,” he says.
In 2013, Miros hoped that Rice would find a commercialization partner to license and produce the Pumani long-term — but he wasn’t keenly interested in that role. “There are global distribution challenges, and it costs a fair amount to develop it, and there are regulatory reviews and other additional overhead. Honestly, I was not certain it was a good fit for us."
He reached a turning point later that year, after visiting Queen Elizabeth Hospital and other clinics in Malawi.  “There’s an extreme disparity between what you see there and what you might see in a U.S. hospital,” he says. "What they showed me was, with the Pumani hooked up, these babies are breathing and they're going to make it— without it, the chances are not as good. That really changed my attitude,” he says. “I decided we should figure out a way to do it. And it's worth any added headache and financial cost, because it really is going to have this tremendous impact."
The university’s Office of Technology Transfer (OTT) had discussions with several potential licensees before talks began in earnest with Miros’ firm in October 2013. "The licensing process was a bit different than most, in that we were working with a company that was aiming to produce and sell products in developing markets.  The licensing structure and royalties were negotiated to facilitate entry into these low resourced markets,” says Andy Castillo, Licensing Associate, Biological Division at the Office of Technology Transfer.
By the end of May 2014, the device was exclusively licensed by Rice to Hadleigh Health Technologies, LLC., a subsidiary of 3rd Stone Design. “This is something that, frankly, is never going to make a tremendous amount of money,” says Miros. “The OTT was flexible and willing to consider variations on what is probably the standard formula for licensing,” he says. “And they were also able to realize that we are a smaller entity, and they were willing to hear me out on what was reasonable from our perspective, in terms of assurances and payments."
Hadleigh Health Technologies, LLC., also has assistance from one of the device’s creators: Jocelyn Brown, who works as product manager at the firm. "She spent two years living in Malawi, and I saw she was best person to have here as product manager, to help expand its presence in the world,” says Miros.
One study has already demonstrated Pumani's life-saving potential. Under a seed grant from USAID’s Saving Lives at Birth program, a clinical trial conducted at the Queen Elizabeth Hospital in Malawi showed that the device improved the survival rate of newborns with severe respiratory illness, from 44 percent to 71 percent. For babies with low birth weight and sepsis, survival rates more than tripled after treatment with the device. The United Nations has also taken note of Pumani. In September 2013, it named the device as one of 10 “Breakthrough Innovations That Can Save Women and Children Now.”
With funding from USAID, Pumani bCPAPs are now being placed in all government hospitals in Malawi, and units are also being distributed in hospitals in 12 other African countries, along with Pakistan, Indonesia, Haiti, and Cambodia. Hadleigh Health has received interest from more than 100 hospitals worldwide, as well as NGOs like UNICEF and Doctors Without Borders, says Miros. The units sell for no more than $800, and may even have potential customers in developed countries, he says. Although the initial market of Pumani will amount to hundreds of devices, Miros says that ultimately, it could encompass tens of thousands of devices — maybe even hundreds of thousands. His firm may be able to support distribution to several countries, but Miros knows the need for a device like Pumani covers a wider territory.  “To get to 100 countries, we may need to partner with a larger company.” he says.
It's not unusual for undergraduates to have good ideas about how to change the world, says Yousif Shamoo, Vice Provost for Research at Rice’s Office of Research. Fortunately, Pumani has moved far beyond the "good idea” stage. "A lot of times, good ideas don't go anywhere because there's not a network, or a framework, to bring them to market,” he says. "The role that tech transfer has is to give them the opportunity and the ability to get the technology out there."

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Buffalograss May Bring Relaxation Back to Your Summer

University of Nebraska

Buffalograss May Bring Relaxation Back to Your Summer

For hundreds of years, hearty, drought-resistant buffalograsses have thrived on the Great Plains of America. The search for improved, urbanized buffalograsses that could be used for lawns, golf courses, parks, and other commercial turf applications throughout the country was accomplished when scientists at University of Nebraska-Lincoln (UNL) developed new and improved turf buffalograsses.

The urbanized buffalograsses require up to 50 percent less water than the commonly used Kentucky bluegrass.

The grasses are as tough as their prairie ancestors while requiring far less mowing and fertilization than traditional turf, can grow successfully in poor soil, and are especially useful in water-short areas.

The UNL research team developed the environmentally friendly buffalograsses over 18 years. Research was first headed by Terrance Riordan and now by Robert Shearman, both professors of agronomy and horticulture at the university. Ten improved turf buffalograss cultivars have been released since the research began. Major research funding has come from the United States Golf Association (USGA), which has provided more than $1 million to support this research. Cultivars developed through this research have generated more than $1 million in royalties.

Turf buffalograsses are sold as seed, sod or as the UNL-developed, pre-rooted plugs, which allow the grass to become established faster than by seeding. UNL has licensing agreements with several companies for various turf buffalograsses.

While different UNL turf buffalograss cultivars grow best in differing climates and conditions, all share some important characteristics. They are easy on the eye as well as the environment. All are darker green and denser, and maintain their color longer than conventional buffalograsses, making them well suited for home and commercial turf applications.

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BullEx Digital Safety Makes Hot Product Out of Fire Extinguisher Training

Rensselaer Polytechnic Institute

BullEx Digital Safety Makes Hot Product Out of Fire Extinguisher Training

Not all technology breakthroughs spring from the brains and laboratories of those with a Ph.D. Sometimes undergraduates have pretty darn good ideas, too.

That’s the whole point of the Inventor’s Studio at Rensselaer Polytechnic Institute (RPI) in Troy, N.Y., where students came up with a live fire extinguisher training simulator that ultimately led to the founding of BullEx Digital Safety.

The goal of the course is to define problems that most people don’t even know exist. And then invent and patent solutions.
Burt Swersey, RPI faculty member

But the students in Swersey’s class didn’t start out seeking to create what has come to be known as the Intelligent Training System™, a safe and relatively inexpensive technology that can detect the accuracy of trainees’ sweeps of compressed air and water from its SmartExtnguishers™ onto what looks like an oversized camping stove.

Company officials say the system that evolved is an ideal teaching tool, thanks to an onboard control system that realistically and automatically varies the propane-fed flames to simulate a variety of fire types. The system also allows the trainer to control the flame range, score and rate trainees, and vary the degree of difficulty.

Experts note that fires account for more than $9 billion in property loss in the  U.S. each year. Yet the majority of these fires can be stopped before growing too large with a single extinguisher, operated by a trained user.

Better training in the use of fire extinguishers is greatly needed, they say, because most homeowners — if they have them at all — don’t know how to use them. In addition, federal law requires industries to train workers how to use their fire extinguishers.

Students as Inventors

Swersey, who has been teaching in the Inventor’s Studio for the past eight years in the department of mechanical, aerospace and nuclear engineering, gives most of the credit for the Intelligent Training System to two former students — Paul Darois and Steve Galonska — who began working on a related project when they were sophomores at RPI several years ago. Swersey is also listed as a co-inventor on the patent application, as are former RPI students John Blackburn and Travis Bashaw.

“I believe this product will save lives and prevent property damage. That’s a pretty great thing,” says Swersey, who has started and run several medical device companies in New York. A Cornell University graduate, he began his career at Polaroid and is a devotee of Edwin Land, who pushed employees to find unrecognized needs and create products to solve them.

Swersey says Darois and Galonska first designed a cook stove that would turn itself off if a fire erupted. But many other inventors had worked on that problem and obtained patents. So they toyed with making race cars and airplanes safer from fires. Eventually, they looked at fire extinguishers and found that the system for training users could be improved significantly.

“Basically, the state of the art was to ignite kerosene in a container in a parking lot and have trainees use a fire extinguisher to put out the fire. It’s expensive, $20 plus to recharge the extinguisher, makes a mess and provides no metrics of the test,” he says. “And that’s how it’s still done around much of the world.”

Swersey says it was important that Darois and Galonska did not “fall in love” with their first idea.

“Iteration is the key,” he states. “Rarely is the first idea the winner. You need successive iterations and they kept working until they created a design that was far better than what exists.”

Swersey says he distinctly remembers the day a few years back when Galonska came into his class and proudly showed him a sensor he had purchased for about $7.

“He said ‘Hey, look at this’ and proceeded to demonstrate it,” he recalls.

Galonska stood 15 feet from his partner Darois and ignited a cigarette lighter. When Galonska pointed the sensor at the flame, “low and behold” the simple little circuit he had built went off, Swersey says.

“The sensor could see the cigarette lighter 15 feet away,” he says. “That was a key moment. And it resulted from their attitude — constantly striving for improvement and taking initiative, rather than waiting to be told what to do. They attacked problems with optimism and confidence that they could learn any new technology on their own and would do whatever was needed to succeed. That is the most important lesson.”

They continued improving the mechanical and electronic design and running a succession of tests. And rather quickly, the training system, which uses advanced sensors embedded in the burner in combination with the control system to determine the students’ technique, was ready to be shown to users.

BullEx: “An Inspiration”

Other key players in the BullEx story are volunteer firefighter Ryan O’Donnell, who is now the company’s CEO, and John Blackburn, electrical engineer and head of technology. O’Donnell and Blackburn took over the company, when Galonska and Darois chose to pursue other careers after they graduated. O’Donnell and Blackburn were also in Swersey’s class and overlapped with the original inventors.

Phil Weilerstein also played an important role. He is the executive director of the National Collegiate Inventors and Innovators Alliance (NCIIA), which gave out grants worth nearly $30,000 to the fledgling company. NCIIA is supported by the Lemelson Foundation. Its namesake, Jerome Lemelson, was a prolific inventor.

“BullEx is an inspiration that we have broadcast widely in our network to make it clear to other faculty that they need to do the kinds of things that were done for this team and to look for students who can be nurtured the way these students have,” Weilerstein says.

“They killed a lot of birds with one stone and went from the classroom to a company,” he says. “O’Donnell pulled together a team, took a great idea and made this happen with determination and know-how. But it wouldn’t have happened without the RPI environment.

“Their story exemplifies the opportunities that are there for students in higher  education for locally funded and developed innovations that can have a positive impact on the local economy without any large federal grants or venture capital funding,” he says.

Charles Rancourt, who heads Rensselaer’s Office of Technology and Commercialization, says he, too, is inspired by the success of BullEx and its student entrepreneurs. Rancourt’s office helped the inventors with the patenting process and coordinated the licensing of the technology to BullEx.

“They were very successful at winning business plan competitions to help launch the company,” he says. “But the thing I would emphasize is that this was a student project. They took an invention that had commercial potential and then had the initiative to start a company that is the ‘real deal’ with customers all over the country.”

O’Donnell, who remains a volunteer fireman, said the company earned about $150,000 in grants and awards from the NCIIA and a number of state and local business plan competitions. It also took out a “significant” loan to get off the ground in 2005.

BullEx, which is based in Albany, N.Y., has 30 employees and is making a profit, he says. It now has customers in virtually every market and industry group, including the U.S. Army, General Electric, Harvard University and the state of Alaska.

“We’re making a difference in a lot of positive ways,” says O’Donnell, who earned his degree from RPI in engineering. “From here, our aim is to keep growing, capitalize on new innovations and offer systems similar to the fire extinguisher training technology that can provide a real and cost-effective benefit to customers.”

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Emory Expands Existing Tech to Build COVID Symptom Checker

Emory University

Emory Expands Existing Tech to Build COVID Symptom Checker
Feeling feverish? Wondering if it’s coronavirus? Visit, a free online symptom checker that can help anyone assess the likelihood they’ve contracted COVID-19.
“We’re all fighting, in ways big and small, to keep our loved ones out of harm’s reach. But the anxiety and uncertainty around the best way to do that can result in crowded emergency departments that will have difficulty managing the surge,” said Dr. Justin Schrager, emergency medicine physician at Emory University Hospital and co-founder of Vital. “Our goal with is to prevent that from happening, while also making it super simple for people to understand and follow CDC guidelines.”

Based on the answers to questions about signs and symptoms, age and more, a person is directed to guidance based on CDC guidelines and is placed into one of three risk categories: high (needs immediate medical attention), intermediate (can contact their doctor for guidance), or low (can likely administer self-care or recover at home). Participants are never dissuaded from seeking professional medical advice or contacting their healthcare provider for more guidance.

Emory Department of Emergency Medicine’s Health DesignED Center physicians, including Chair Dr. David Wright and Dr. Anna Quay Yaffee, assistant professor and director of Global Health in Emergency Medicine Section at Emory University School of Medicine; and Emory Office of Critical Event Preparedness and Response’s Dr. Alex Isakov, executive director and co-author of the SORT algorithm guided Vital, a software company focused on emergency department workflow, in designing the site and further developing SORT, an existing Emory technology originally designed for the H1N1 outbreak in 2009. The site is for educational purposes and not a replacement for a healthcare provider evaluation. Emory is working with its faculty and partners for options to deploy the tool to other parts of the world, even where mobile internet is lacking.

The ongoing relationship required substantial input from Emory’s Tech Transfer office to help address concerns of deploying university technology through Vital during the pandemic, including the use of the Emory trademarks and collection of individual’s data.

Emory’s OTT negotiated and executed a Cooperative Research and Development Agreement between Emory, USUHS, and Vital to develop and validate the technology and launch the Emory-Vital cobranded website. Vital is not charging the public for use of the symptom checker. Users can opt to share a zip code to contribute to research tracking the geographic spread and eventual recovery from the pandemic.

“Through this partnership, Emory and its academic colleagues also gain access to valuable epidemiological data that come from the public use of the website,” said John Nicosia, a Licensing Associate for Emory’s OTT. “Emory is currently partnering with Vital to have this technology deployed for use by individual state-level governments and health departments and for any commercial entity wishing to deploy the symptom checker to their employees.”

Vital was founded by Schrager and Aaron Patzer, founder of, and launched in 2019, before the coronavirus pandemic, to help offset the already overloaded work of Emergency Departments.

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Tumor Marker Assay Helps Identify the Recurrence of Breast Cancer

Dana-Farber Cancer Institute

Tumor Marker Assay Helps Identify the Recurrence of Breast Cancer

The monitoring of breast and other types of cancer with blood tests is critical for improving the odds of successful treatment. Discovering cancer markers that identify the progression of cancer at early stages is a research goal for many medical institutions.

Based on their research conducted in the late eighties and early nineties, Dr. Donald W. Kufe, M.D., and colleagues at the DanaFarber Cancer Institute in Boston, developed a monoclonal antibody that recognizes the MUC1 glycoprotein. MUC1 is aberrantly overexpressed by most carcinomas of the breast, lung, ovary and other sites. Dr. Kufe’s research showed that MUC1 is released by tumor cells into the blood and that the level of MUC1 in the circulation reflects the extent of disease.

This highly accurate blood analysis is regarded as one of the most sensitive tests for detecting breast disease.

Today the blood test, also known as the CA15-3 radioimmunoassay, is commercially available to the clinical community under a license granted by the Dana-Farber Cancer Institute. Measured over time, CA15-3 can detect the recurrence of cancer, more quickly than standard methods of follow-up testing, especially for patients already treated for Stage II or Stage III breast cancer. CA15-3 is supported by more than 2,000 peer-reviewed studies and is one of the most widely used cancer detection markers in the world.

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Campath: Collaborations Across Continents Prove Successful

University of Cambridge

Campath: Collaborations Across Continents Prove Successful

It is fitting that the promising cancer therapy called Campath® begins with the letter “C” — the same letter that starts the word “collaboration” (not to mention “continents” and “commitment.”) For the story behind Campath is characterized by collaborative efforts that span several countries and involve hundreds of committed individuals.

Backed by several decades of research and development and then subjected to a dizzying series of mergers and acquisitions during its commercialization, Campath’s history is both long and winding. Yet in the end, the personal stories like those of Juliana Oliveri, a chronic lymphocytic leukemia (CLL) patient successfully treated with Campath, are what matter the most.

One Grateful Patient’s Story

The last thing a busy professional like Oliveri had time for in her life was a chronic disease. A former society singer and performer in major cities across the U.S., she had since switched the focus of her career and was working 16-hour days for the luxury goods industry in New York City. When a routine physical by her internist revealed an alarmingly high white blood cell count five years ago, Oliveri had no intention of slowing down, especially since she felt physically fine. Additional tests indicated that although asymptomatic, Oliveri had CLL, the most common form of adult leukemia.

Her doctors adopted a “watch and monitor” approach, and for the next three years Oliveri continued to work long hours, travel, and cater to demanding celebrity clients. The symptoms struck quite suddenly on her 49th birthday in July 2005, and they were serious enough to warrant admission to the hospital and the initiation of therapy. At the time she was first diagnosed, Oliveri had learned about a promising CLL therapy called Campath, and she took a proactive approach in helping her physicians formulate a treatment plan. Campath was the therapy she felt she needed, and fortunately that is what she received.

For six months Oliveri checked into the hospital three mornings a week as an outpatient. There she would endure routine blood work, followed by intravenous administration of Campath, and after an hour of close monitoring, she would leave the hospital to begin a full day of work “tending to the rich and famous.” Recalls Oliveri, “I had no side effects during treatment — it was amazing.” She has remained in full remission since completing Campath therapy in January 2006 and continues to lead a life as busy and demanding as ever.

Oliveri’s experience with CLL has taught her many valuable lessons such as the importance of teaming up with health care specialists who understand cutting edge treatments. But overall, she credits her health to the availability of Campath.

Knowing I had Campath to go to when the time came for treatment was the best thing that could have happened to me.
Juliana Oliver

A Long and Winding History

The discovery of Campath, a monoclonal antibody that targets cancerous blood cells, began in the 1970s in the laboratory of Herman Waldmann, Ph.D., at the University of Cambridge in Cambridge, England. Waldmann, a pioneer in the field of monoclonal antibody production, first sought to develop the proteins to treat problems associated with bone marrow transplantation. Through Britain’s Medical Research Council (MRC), money was raised to establish research projects along these lines. Joining him in those efforts in the early 1980s were two ambitious researchers in Cambridge’s department of pathology — Mike Clark, Ph.D., and Geoff Hale, Ph.D.

The team of scientists spent years searching for monoclonal antibodies effective in targeting human immune cells. Eventually, they successfully discovered several. One of the next critical steps involved gaining the technical expertise to use the antibodies in human patients. With the help of colleague Greg Winter, Ph.D., they learned how to humanize antibodies, and in 1988, they successfully treated their very first lymphoma patient using the humanized antibody. The promising molecule, which binds to a specific target called CD52 on cell surfaces and directs the body’s immune system to destroy those CD52-bearing cells, was named Campath, for Cambridge University Department of Pathology.

The commercialization potential of Campath had meanwhile generated discussion between Cambridge and the British government’s technology transfer arm, the National Research and Development Corporation (now renamed the British Technology Group, or BTG). Richard Jennings, Ph.D., director of technology transfer and consultancy at the University of Cambridge, was involved in the negotiations at that stage and recalls that they represented a rather complex nexus of interest between different people and different organizations.

“It was a really fascinating project to work on, and it was driven by fantastic enthusiasm on the part of the academic inventors who showed a long-standing motivation to get new types of therapies to market for patients,” says Jennings. “They remained driven, and this impressed us.”

When Clark recounts the early phases in Campath’s development, the power of collaboration is what stands out above and beyond everything else. “We had already established that the antibody worked clinically, but we now needed to convince those involved that it was a commercially viable product,” he says. “That initial direct collaboration between researchers and clinicians has been the key to the success of this entire project.”

Through the work of Jennings’ office and the BTG the Campath team connected with The Wellcome Foundation (which became Glaxo- Wellcome and is now part of GlaxoSmithKline). Campath was licensed to the company in 1985 and efforts to commercialize it for use in the treatment of lymphoma and leukemia, as well as an immunosuppressive agent in rheumatoid arthritis patients, began in earnest. By the mid-1990s Phase II trial results were demonstrating that Campath showed potential for treatment of lymphoma and CLL patients.

The results of rheumatoid arthritis clinical trials however were unimpressive. Thus began the rollercoaster ride for Campath and its inventors. In 1995, around the time that Wellcome was considering a merger with pharmaceutical company Glaxo, it announced it was abandoning the project.

Yet the strength of scientific connections served to rescue the faltering project. Waldmann contacted Harvard University pathologist Timothy Springer, Ph.D., a colleague whose path he had first crossed when the two were learning monoclonal antibody technology in the MRC laboratory of Nobel Laureate scientist César Milstein, Ph.D. Springer had since returned to the U.S. and had founded a startup company, LeukoSite, in the Boston area. LeukoSite, it turned out, was in a position to license the rights to Campath from BTG.

By 1997 LeukoSite had negotiated a new licensing deal for Campath and clinical trials designed to test the therapy in CLL patients were back on track. Yet again the route of Campath was altered by a series of commercial mergers and acquisitions. Within two years LeukoSite announced its merger with another Boston area company, Millennium Pharmaceuticals, Inc. While the company quickly gained Food and Drug Administration (FDA) approval of Campath for the treatment of B-cell CLL patients who fail conventional chemotherapy, Millennium eventually transferred the rights to ILEX Oncology, Inc. In 2004 Genzyme Oncology, Inc. acquired ILEX and gained the production rights to Campath. While Campath’s history with ILEX was short-lived, it was beneficial, as Genzyme investors recognized the therapy’s potential at a time when it was looking to expand its prognostic and diagnostic portfolio in the treatment of hematological cancers.

According to Terry Murdock, Genzyme senior vice president and general product manager of Campath, the gain of Campath as a therapy in the treatment of CLL was the perfect platform for the company in which to leverage a diagnostic tool and a targeted therapy. “In hematological malignancies like CLL, the need to eradicate residual disease in patients is important as relapses are often related to the residual nature of the disease,” says Murdock.

The merging of ILEX and Genzyme was ideal as the strengths and directions of the two companies complemented one another. “ILEX had a strong clinical operating route University of Cambridge and a strong base of experience in getting clinical trials completed. It also had a solid track record of getting drugs developed,” says Murdock. “Genzyme has a strong academic and clinical physician base, as well as experience with regulatory approval and manufacturing. Putting those two things together, we provide a solid base to move forward with Campath.”

A Bright Future Ahead

Under the protection of Genzyme, Campath remains the first and only monoclonal antibody approved by the FDA for the treatment of patients with B-cell CLL. In the fall of 2007 the FDA granted a label expansion and approved Campath as a first-line treatment for the disease. Along with Bayer Healthcare Pharmaceuticals, which markets Campath, Genzyme is also developing the therapy as a treatment for multiple sclerosis. The latest news reports successful results in Phase II trials of Campath for multiple sclerosis patients; Phase III trials are now underway.

Reflecting on the long history and sometimes uncertain future of the therapeutic protein to which Clark has devoted much of his life, he recognizes certain recurrent themes. Most significant he claims were the collaborations that existed between clinicians and university research groups that provided the dedicated Campath researchers with the confidence necessary to push for its commercialization.

Hale echoes those sentiments and points to the unusually strong tie between himself, Clark and Waldmann — the original three behind the discovery of Campath.

“One of the greatest things about this project is that while the three of us have been working on it going back to the early 1980s, we’ve all remained very close,” says Hale. “And there have been hundreds of other scientists, clinicians and patients who have helped along the way and made this project successful. Everyone has been very loyal every step of the way.”

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Campus Incident Tracking System Supports Campus Security

Boston University

Campus Incident Tracking System Supports Campus Security

Campus safety is a top priority among college and university administrators. When director Peter Schneider and associate director Ron Slade of Boston University’s Office of Environmental Health and Safety (OEHS) realized there was no software package designed to track and analyze “incidents” on campus, they decided to create one.

Schneider and Slade developed the “Campus Incident Tracking System  (CITS)” from 2000-2005 with $60,000  in funding from Boston University. CITS is a user friendly, Internet-based system that logs, tracks, analyzes, reports, and follows up incidents that occur on university, college and medical campuses. 

The software captures critical information about each incident, and allows for trend and root-cause analysis. It is also a highly effective tool for recording information from multiple sources, such as police and fire officials, public safety personnel and eyewitnesses. Major risks can be identified and mitigated to improve campus safety, and speed up response time. The recorded data and reports can also be used to support lawsuits and internal audits.

By analyzing trends and root causes, and implementing corrective actions, OEHS personnel have significantly improved campus safety.

Since it began using CITS, OEHS has tracked 800 incidents, and the university has licensed the software to Boston-based  Axim Systems, which markets and sells  CITS worldwide. 

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New Test Kit Improves In Vitro Fertilization Success Rates

McGill University

New Test Kit Improves In Vitro Fertilization Success Rates

In vitro fertilization (IVF) can be an emotional roller coaster for many couples, one that often ends in disappointment; using current methods, about 85 percent of healthy-looking embryos transferred through IVF fail to result in pregnancy. Aside from the emotional toll this takes, IVFs are expensive and not always covered by health insurance.

Researchers at McGill University in Montréal, Canada, have developed a rapid, noninvasive test for determining compatibility between an embryo and a potential mother. Professors David Burns, Ph.D., and James Posillico, Ph.D., at McGill’s department of chemistry developed Via-Test™-E in 2006-2007. Funding was provided by The Natural Sciences and Engineering Research Council of Canada, Canadian Institutes of Health Research, and Molecular Biometrics, a medical technology company.

ViaTest™-E targets in vitro biomarkers of oxidative metabolism (OM) that are indicative of embryo viability. The degree of OM is basically a measure of the level of oxidative stress in the cells.

Embryos and gametes that are highly stressed are less likely to result in pregnancy. ViaTest™-E enables the rapid, simultaneous identification and analysis of multiple OM biomarkers in a single sample. This methodology leads to the accurate detection of viable embryos of high reproductive potential.

Current practices grade and select embryos for implantation based on their morphology, or how they look. This is a subjective and inaccurate practice that leads to high failure rates. To counter this, a common practice is transferring multiple embryos. This, in turn, results in higher incidences of multiple births and increased health care risks to mothers and infants. When combined with morphology, ViaTest™-E provides the most accurate method for identifying the healthiest and most compatible embryos.

Molecular Biometrics has licensed the technology from McGill University and is marketing the test kit. This product is the first of its kind and has generated interest around the world. Long-term use of ViaTest™-E is expected to increase pregnancy rates, lower multiple births, and reduce health risks to mothers and babies.

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Carbon Nanotechnology Lowers Cost of Hydrogen Fuel Cell

Florida State University

Carbon Nanotechnology Lowers Cost of Hydrogen Fuel Cell

To keep the world’s growing army of cell phone towers constantly powered so mobile phone users can enjoy ubiquitous service, telecommunication providers are scrambling to find viable solutions to supplement unstable power grids or meet new regulations for alternative energy sources in remote areas. 

According to a report by Navigant Research, there are approximately 5 million cell phone towers (also called mobile base stations) worldwide, including 640,000 off-grid base stations at the end of 2012, most of which are powered by  generators using diesel fuel.

Using nanotechnologies developed at Florida State University (FSU), Bing Energy hopes its hydrogen fuel cell that features a cutting-edge, high-performance material called buckypaper will become the cell tower power of choice in many countries around the world.

The Hydrogen Fuel Cell

The hydrogen fuel cell (also known as a proton exchange membrane fuel cell or PEM) is similar to the lead-acid battery in that it generates electricity through a chemical reaction. However, unlike a battery, which requires recharging once its stored energy is consumed, this fuel cell not only keeps producing electricity as long as it has a supply of fuel, but it is also free from the environmental hazards associated with lead–acid batteries.

The basic components of a PEM fuel cell include a channel on one side that allows hydrogen to flow in to the anode electrode, where a catalyst causes the hydrogen to split into positive ions and negatively charged electrons. On the other side of the fuel cell, oxygen flows into the cathode electrode. A membrane in the middle allows only the positively charged ions to pass through to the cathode, while blocking and forcing the electrons to travel to the cathode via an external circuit or load, creating the electrical energy. When the electrons and ions eventually meet at the cathode, they combine with the oxygen to form water, an environmentally safe by-product..

Collectively, the anode and cathode electrodes and membrane form membrane-electrode assemblies, or MEAs.

“The fuel cell is a small stationery unit that consumes the most common element in the universe (hydrogen) to generate electricity, producing a waste product of water,” says R. Dean Minardi, chief financial officer of Bing Energy.

Until now, one of the limitations to the hydrogen fuel cell — whether it is used to power an automobile or as a stationery unit of backup power — has been cost. It’s typically because of it’s expensive platinum or other precious metals that are used to strip the electrons off hydrogen gas in the anode and reduce oxygen to water in the cathode.

As a result, scientists — including James P. Zheng, Ph.D., a professor in the Center for Advanced Power Systems at FSU — have been searching for ways to lower the cost of the fuel cell by reducing the amount of platinum it requires or finding alternative catalysts.

The Carbon Nanotube and Buckypaper

Zheng knew that his FSU colleagues, Richard Liang and Ben Wang in FSU’s High Performance Materials Institute, had been working with a new material called buckypaper, made from a unique form of pure carbon. Over lunch with his fellow scientists, they theorized that the properties of buckypaper could provide an excellent material for the MEA in the PEM fuel cell.

Depending on how its atoms are bound together, carbon can take on a variety of forms. Arranged in a tetrahedral lattice, carbon atoms form a diamond. But a single layer of carbon atoms arranged in a honeycomb or hexagonal shape results in graphene. Rolled into a cylindrical shape, graphene becomes a carbon nanotube 50,000 times thinner than a human hair.

Although carbon nanotubes occur naturally, they can be created with a carbon source, such as sugar cane or corn with the help of heat and a catalyst. Carbon nanotubes can then be synthesized into a thin film, stacked and compressed to create buckypaper, a conductive material 250 times stronger than steel yet 10 times lighter.

Zheng and his colleagues decided to hire a postdoctoral student in 2007 to test buckypaper for the fuel cell application. Nine months later, the team had a viable proof of concept.

“The gradient structure of the buckypaper improved gas flow and the effectiveness of the catalysts,” says Zheng, who began working with the Florida State University Office of Commercialization to start the patenting process.

“There are 50 to 60 patents in the United States on Dr. Zheng’s buckypaper work,” says John Fraser, executive director of the FSU Office of Commercialization. “Dr. Zheng is a super star at FSU, and we have high hopes for him and this technology.”

Initial funding for FSU buckypaper-based fuel cell research came from the U.S. Army and was followed by support from the FSU Research Foundation Gap Grant Program, which provided $50,000 to help scale the invention for commercialization, and the U.S. Department of Energy.

Startup Company Bing Energy

In 2010, FSU entered into an exclusive licensing deal with Bing Energy, a spinoff company led by Richard Hennek, to create PEM fuel cells with MEAs made with buckypaper. Hennek relocated the company from California to Florida to be closer to Zheng, who serves as technical adviser to the company, and received $300,000 from the Florida Institute for the Commercialization of Public Research to help develop the technology.

“FSU’s Office of Commercialization has been extraordinarily helpful,” says Minardi. “We wouldn’t be here if it weren’t for that office.”

At the company’s new Tallahassee headquarters, Bing began its buckypaper-based MEA production.

“We embed platinum in the buckypaper as the anode, but it requires 70 percent less platinum and performs the same [as a fuel cell made without buckypaper],” says Minardi. “The MEA looks like a furnace filter with platinum on the filter fibers to provide a reactive surface.”  The large decrease in the amount of platinum that needs to be mined is another environmentally significant improvement of the buckypaper technology. 

Each fuel cell requires a number of MEAs stacked together, depending on the amount of energy that needs to be generated. Today there are 15 employees in Tallahassee working to produce 300 MEAs during each eight-hour shift — a number that will soon grow to several thousand per shift when the facility is semi-automated.

Once completed, the MEAs are sent to the company’s second facility in Ragao, China, just outside Shanghai, for final production. Zheng, a native of Shanghai, worked with Chinese authorities to establish an enterprise zone for the factory and a dormitory. Thirty-five employees in Ragao place end caps around the MEAs, affix aluminum hoses and pipe-fittings, and finally, place the unit inside a box cabinet to create the final fuel cell product.

Powering China Telecom’s Cell Towers

The first commercial application of Bing’s fuel cells will be in China, where they will replace lead-acid batteries in isolated cell phone towers owned by China Telecom, an international telecommunications company. The PEM fuel cell will be placed at the foot of each cell tower in a rain-proof metal locker with a 5-foot tall steel cylinder nearby to hold the hydrogen fuel.

“China Telecom needs backup power desperately,” says Minardi. “They have a very unstable grid and the country is trying to ban acid batteries. It’s the same situation in India, which is seeing significant telecom industry growth.”

China Telecom’s off-grid cell phone towers, each with a 3-kilowatt generator, will require the electrical output of 40 hydrogen fuel cells.

The Market for Stationery Fuel Cells

Smaller, lighter, quieter, lower environmental impact,  and lower cost are just a few of the advantages Bing Energy says it offers with its new PEM fuel cell.

“There’s a sweet spot in the market for distributing stationery fuel cells to replace existing battery or diesel backup power,” says Minardi.

He says even cell phone towers that are connected to an electrical power grid need backup power  when the grid goes down, a common occurrence in developing countries.

There are 1.3 million cell towers in China alone, and they all are converting to this technology.
R. Dean Minardi

Minardi says Bing’s fuel cell stacks up well against other energy alternatives, such as lead-acid batteries (which are being phased out in China due to environmental waste issues) and diesel-powered generators. While batteries need to be constantly charged, diesel powered generators require a significant amount of fuel and frequent maintenance — and both will last only 18 to 60 months before they will need to be swapped out for new equipment. Conversely, he says Bing’s fuel cells have no emissions, fans or pumps and have a 20-year lifecycle.

 “The durability of our fuel cell and low platinum usage is being embraced by the market,” he says. “There is a place in the energy world for distributed hydrogen power.”

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Carbovir Compounds Offer New Alternatives for AIDS Patients

University of Minnesota

Carbovir Compounds Offer New Alternatives for AIDS Patients

When the National Institutes of Health requested that he patent his discovery, Dr. Robert Vince, professor of medicinal chemistry and director of the Center for Drug Design at the University of Minnesota, realized the impact his anti-HIV Carbovir compounds could have on AIDS patients.

In December 1998, the Food and Drug Administration approved Carbovir-based Ziagen®, which was developed through a license with a pharmaceutical company. It inhibits HIV’s ability to reproduce in the white blood cells called T cells, which regulate the body’s immune system.

In order to reproduce, HIV attaches to a protein on a T cell’s surface. The virus is then able to enter the cell and replicate. Like other nucleoside analogues, Carbovirs interfere with the enzyme HIV uses to manufacture new viral particles within an infected cell. They work by incorporating into the elongating DNA strands and terminating the extension process. Carbovirs work earlier in the HIV replication process compared to the well-known protease inhibitors and therefore offer a more attractive option in early treatment.

Today, medications containing Carbovir compounds, including Ziagen®, Trizivir®, and Epzicom™, contribute to the treatment of hundreds of thousands of AIDS patients worldwide.

The sale of these medications has generated more than $200 million in royalties for the University of Minnesota. Portions of this royalty have been re-invested back into the university through the establishment of the Center for Drug Design to do further research in the drug development arena.

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Ultrasound Technology Helps Maximize Beef Production

Kansas State University

Ultrasound Technology Helps Maximize Beef Production

A more efficient and profitable form of beef production became possible with the invention of the innovative carcass ultrasound technology invented by Kansas State Professor John Brethour.

The technology offers beef producers a fast, non-invasive way to predict and measure cattle carcass characteristics in live cattle. In 1995, the university licensed the technology to Cattle Performance Enhancement Co., based in Oakley, Kansas. The technology revolutionized the beef industry by allowing producers a cost efficient way to measure intramuscular fat in livestock.

The technology, which estimates the fat, muscle and body composition of cattle, enables beef producers to raise premium beef without over feeding the cattle —  a cost savings for the producers and a healthier end product for consumers.

Achieving a premium grade of beef is typically linked to overly fat cattle, but with Brethour’s ultrasound technology, the selection and management of livestock helps predict carcass yield and quality. Brethour’s technology is based on two U.S. patents. The first is for a system that accurately allows breeders to measure the intramuscular fat in live cattle. The second patent provides an assessment of how long cattle should be maintained on feed for maximum profit by projecting future carcass merit.

In 2003, when the Kansas State Agricultural Research Center-Hays (ARCH) entered 80 Angus steers in the Best of Breed Angus Challenge at the National Cattlemen’s Beef Association annual convention and trade show, they came away with the $100,000 top prize. Illustrating that the university’s livestock research is top notch, ARCH steers were graded 100 percent Choice beef or better and 91 percent earned the prestigious Certified Angus Beef award.


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Visual Acuity Test Helps Determine Vision Problems in Young Children, the Intellectually Impaired

Cardiff University

Visual Acuity Test Helps Determine Vision Problems in Young Children, the Intellectually Impaired

When people cannot express in words what they see, it is difficult for health care professionals to determine the nature of visual problems they may have. That’s why Professor Maggie Woodhouse, Ph.D., at the Cardiff University School of Optometry and Vision Sciences, with university funding, designed the Cardiff Acuity Test.

Announced in 1993, the Cardiff Acuity Test measures acuity in toddlers ages one through three, as well as individuals with intellectual impairment.

Historically this is considered a hard-to-test group because these individuals cannot communicate well enough to describe the familiar symbols and images they are shown.

Children do not need to name, or even recognize, the images used during the test. Instead the observer relies on the technique of “preferential looking” and records the subject’s eye movements to determine how much of the image is actually being seen.

The Cardiff Acuity Test comes in a simple, quick, durable, and easy-to-use format, which is important when dealing with toddlers and individuals with intellectual impairment. Users find it is easy to interpret the results.

To date about 2,100 test kits have been sold in the United Kingdom and the United States. The royalty income has allowed Woodhouse to develop the Cardiff Near Test and the Cardiff Contrast Test. Find more information, here.

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Electronic Career Portfolio Reports Skills, Not Just Jobs

Florida State University

Electronic Career Portfolio Reports Skills, Not Just Jobs

Oftentimes what makes or breaks students’ success in getting a job is their ability to demonstrate that they have obtained knowledge, skills, and abilities necessary for the required position throughout their college experience. The standard resume showing work experiences may not necessarily reflect what they are now able to do or how they are able to think critically or strategically.

To keep up with the growing demand of capturing and tracking this experience, Jeff Garis, Jill Lumsden, and the Career Center team at the Florida State University (FSU) developed a Web-based application called Career Portfolio. This career resource enables students to showcase the skills they have developed by allowing them to input information into five experience categories — coursework, memberships and activities, volunteer work, jobs and internships.

This online portfolio serves both the students and the prospective employers. Students can see which skills they have developed so far and which skills they may want to concentrate on in the future. By keeping all of the information centralized, employers can gain access to additional electronic information that is not included on a typical resume or curricula vita and use it to more effectively direct their decision making process.

More than 40,000 students have used the Career Portfolio system since its inception.

It has become part of the academic and student service culture at FSU. In fiscal year 2005, Career Portfolio was licensed to three major colleges — University of California, San Diego, Montclair University and Georgia Technical Institute — and a private  company based in Japan. The invention of the FSU Career Portfolio changed the national landscape regarding how college students prepare for their careers and apply for jobs. The FSU Career Portfolio is recognized nationally as a new leading innovative career service and is contributing to an international trend in the development of ePortfolios.

For more information visit

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CaseNEX Brings Research to Life in Classrooms Everywhere

University of Virginia

CaseNEX Brings Research to Life in Classrooms Everywhere

The University of Virginia developed CaseNEX in early 2000 — a research-based methodology that educators apply during case study analysis. The CaseNEX methodology represents the type of jobembedded professional development required by the federal “No Child Left Behind” legislation.

The technologically blended, case-based approach provides educators the opportunity to read cases, view streamed video and follow links to a virtual library of current research. The expectation is that teachers and administrators who can perform the steps of case-based analysis are likely to repeat the process when faced with similar situations in their classrooms.

The CaseNEX problem-solving model is engaging, collaborative and effective, offering more than 150 multimedia, Web-based cases, or “slices of life,” that form a bridge between best practices and the complex school environment.

School district and university partners across the country integrate the CaseNEX learning model and access the library of case studies to enhance, enliven, and extend their existing programs. Teachers can join the collaborative online learning cohorts to satisfy professional development requirements, earn graduate credits, and complete master's degree programs.


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CATCH: Comprehensive Assessment for Tracking Community Health

University of South Florida

CATCH: Comprehensive Assessment for Tracking Community Health

Three University of South Florida professors from the colleges of Public Health, Computer Information Sciences and Business Administration joined forces more than 10 years ago to use their combined expertise to develop a tool for assessing community health.

Capitalizing on a unique combination of practical experience and research expertise in information technology, James Studnicki, Alan Hevner and Donald Berndt developed the Comprehensive Assessment for Tracking Community Health, or CATCH, which  uses a data warehouse to assess the health status of community populations. CATCH Reports use more than 250 health care indicators in conjunction with an innovative comparative framework and weighted evaluation process to produce a ranked list of community health.

For health care providers, community organizations and public agencies, the assessments can be used as a tool to determine resource allocation and health care policy formation.

Individuals and whole communities benefit from the improved efficiency and effectiveness in how health care services, including medical and surgical procedures are provided. Moreover, health issues among defined populations can be better assessed and evaluated to determine smarter health care strategies for those group.

The product is licensed to a start-up company called Medegy which is run by the inventors. Customers include hospitals, health departments and managed care organizations, with a large number of CATCH Reports being delivered to government-run and private health care agencies.

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Colorful Hybrids Brighten Gardens Across America

University of Connecticut

Colorful Hybrids Brighten Gardens Across America

Millions of home gardeners have beautified their yards with colorful flowers developed by Professor Ron Parker, Ph.D., at the University of Connecticut-Storrs. Parker’s plant-breeding work was highly unusual in that he made extensive use of naturally growing wild plants from around the world — most notably Catharanthus and Impatiens.

Catharanthus is an annual flower that can withstand extremes of heat and sunlight, making it a favorite among gardeners. Although hardy, it was available in only two or three rather bland colors. In 1991, after 12 years of plant development at the University of Connecticut, Parker released three varieties with striking pink and rose-colored blossoms: “Pretty in Pink,” “Parasol” and “Pretty in Rose.” The flowers feature glossy green foliage and large pink, deep rose, magenta or bright white blossoms. Annual sales of seeds for these varieties of Catharanthus have reached as much as $1 million a year.

All three flowers won All-America Selection awards, the horticultural equivalent of winning an Oscar.

Impatiens, another top-selling bedding plant for commercial growers and home gardeners, was also known for its limited color options. With funding from the Bodger Seed Co., Professor Parker and Maryke Cleland developed Impatiens hybrids with pale yellow to gold-yellow petals and profuse branching. These hybrids were transferred to Bodger Seed under a development and sales agreement, and four of the University of Connecticut hybrids are the subject of separate U.S. plant patents. Bodger used the new plants as the foundation for developing a colorful series of Impatiens that was introduced to the market in 1998 that included yellow, apricot, peach and tangerine hues. These plants continue to be sold in 2007.


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Scientific Visualization Leads to the CAVE

University of Illinois, Chicago

Scientific Visualization Leads to the CAVE

Imagine being able to stand inside a human heart and watch blood flow around you. Or, imagine test-driving a car, before it actually has been built.

Through the wonders of the CAVE (Cave Automatic Virtual Environment), the first technology to widely exploit immersive virtual reality (VR) environments, people can do just that. The “wow” technology was pioneered at the University of Illinois at Chicago’s (UIC) Electronic Visualization Laboratory (EVL). CAVE is a trademark of the Board of Trustees of the University of Illinois. EVL is an interdisciplinary graduate research laboratory that combines art and computer science with advanced networked visualization and collaboration tools and technologies. Since the early 1970s, the lab has been recognized for its leadership in computer graphics. EVL, a unique collaboration between UIC’s College of Engineering and the School of Art and Design, is one of the oldest formal interdisciplinary efforts between art and engineering in the U.S. Through its combination of the two disciplines — engineering and art — EVL serves as an excellent example of collaborative university research.

CAVE Adaptations

From the CAVE’s development at EVL, other products and services have emerged, ranging from immersive virtual rooms, to software libraries to desktop/office-sized displays to anatomical teaching devices for medicine. Its success in the marketplace is due to its unique collaborative components — science, coupled with vision, design and computational steering. Together they are helping solve complex problems. The CAVE name was first commercialized and licensed to Pyramid Systems and is currently licensed to Mechdyne Corp. of Marshalltown, Iowa.

In immersive CAVE environments, people walk inside a room surrounded by large wall-size projection screens, wearing special glasses that allow the CAVE 3-D graphics to be seen with three-dimensional depth. The glasses are synchronized with the projectors so the images appear to be in front of their eyes. People then can walk around virtual objects, see objects float by, as well as peer inside a world where reality and illusion come together. The ImmersaDesk®, which was developed in 1995 at EVL, is a derivative of the CAVE system. This system uses one screen, positioned at an angle, like a drafting table — people look forward and down instead of all around. The system was less expensive than the original CAVE since it didn’t require building a room within a room. Pyramid Systems commercialized the ImmersaDesk system, which also followed through to Mechdyne Corp.

Software Solutions

Researchers at the University of Calgary’s Sun Center of Excellence for Visual Genomics have taken CAVE technology in a new direction. Viewers who study the Sun Center’s life-sized, human model called CAVEman, are looking at a marvel of visual reality technology. The anatomical digital atlas offers students, scientists and medical personnel a high-resolution view inside the human body. The technology has been used at the University of Calgary since 2002.

Christoph Sensen, Ph.D., professor at the Centre for Advanced Technologies, University of Calgary Faculty of Medicine, says, “We are developing a Java 3D™-based human body model for research, education and clinical applications.” The final result of the virtual reality development will be a next generation 4-D (designating space and time) visual window that will show genetic components of diseases like cancer, diabetes and Alzheimer’s.

Sensen says, “Using our CAVE models, we will soon be able to simulate diseases for which we have no examples here in Alberta and teach our students how to treat them.” CAVE technology is also used to treat various phobias, including the fear of heights and spiders. Since people absorb most of their information through visual stimuli, a CAVE experience, which is being used in multiple ways in industry, can be a phenomenal way to impart information. An in-depth CAVE experience, for example, involves a basic four-screen (three walls and a floor) immersive room and a small graphics computing cluster.

Jeff Brum, vice president of marketing and business development at Mechdyne Corp., says, “While the costs can go into the millions of dollars for complex, six-sided, high- resolution rooms, the result in any CAVE is a compelling experience. When we have navigated to the edge of a virtual building or stood on the virtual space station looking down at Earth, many first-time CAVE users experience a real sense of vertigo.”

Virtual Manufacturing

The CAVE’s virtual applications allow people to address a wide range of challenges like creating better crops for improved harvests and better safety features on cars.

Designers can sit in life-sized vehicles and create better sight-lines and other safety components. It also allows manufacturers to “see” production lines before the products are rolled out so potential changes can be built in early in the planning process.
Jeff Brum

Car companies have incorporated these features by developing virtual prototypes that help get the products into the marketplace sooner. The technology is also a cost benefit since virtual prototypes give companies an excellent alternative to building expensive physical prototypes.

Conceiving the World’s First Projection-Based Technology with Walls and a Floor

It was a long journey from the development at EVL in the 1990s to the wonders of today’s virtual reality applications. Tom DeFanti, Ph.D., a distinguished professor emeritus at UIC now a research scientist at the University of California, San Diego’s California Institute of Telecommunications and Information Technology (Calit2), co-conceived the CAVE system in 1991 with fellow UIC researcher and art professor Daniel Sandi