Biotech SMART Report Summarized Multipurpose Articles on Research and Technology (SMART) BIOTECHNOLOGY INDUSTRY RESEARCH ASSISTANCE PROGRAM A program of Department of Biotechnology, Ministry of Science and Technology, Government of India In partnership with ABLE and BCIL APR - JUN 2011 Volume: 08 VOL 08 APR - JUN 2011 Biotech SMART Report (Summarized Multipurpose Articles on Research and Technology) Biotech SMART Report is a Quarterly publication from BIRAP, a programme of DBT, Govt. of India which is dedicated to nurture, incubate and discover innovative research in the Biotechnology Industry. The Report is an assemblage of updated news reports from company websites, e-newspapers, emagazines and market report updates in the area of Biotechnology for a period of 03 months from 01 APR вЂ“ 30 JUN 2011. BIOTECHNOLOGY INDUSTRY RESEARCH ASSISTANCE PROGRAM A program of Department of Biotechnology, Ministry of Science and Technology, Government of India In partnership with ABLE and BCIL Published by: BIRAP A вЂ“ 254, 3rd Floor, Bhisham Pitamah Marg, Defence Colony New Delhi вЂ“ 110024 I N D I A Web : www.birapdbt.nic.in | Email : birap.dbt@nic.in Compiled By: Suryakant Pathak I & D Officer, BIRAP Tel: +91-11-47744500 вЂ“ 510 | Fax: +91-11-47744511 Direct Line: 011-47744522 | Cell: +91 9555 469 237 Email : spathak.birap@nic.in | Bhawna Kaushik DEO, BIRAP Note: The Biotech SMART Reports have been reproduced as such from various sources and BIRAP does not authenticate the validity of the same. PAGE 2 OF 124 Contents Section A: Agriculture .................................................................9 Headline1: Nitrogen-Fixing Bacterial Symbiont Promises Trove of Natural Products ................. 9 Headline2: Importing grains cannot solve food shortage problems .......................................... 10 Headline3: Managing papaya mealybug through bio control .................................................... 11 Headline4: New technique for artificial photosynthesis ............................................................ 12 Headline5: Improving Photosynthesis? Solar Cells Beat Plants at Harvesting Sun's Energy, for Now ............................................................................................................................. 13 Headline6: Genomes of Fungi That Threaten Wheat, Poplars Sequenced ................................ 15 Headline7: Harnessing the Energy of the Sun: New Technique Improves Artificial Photosynthesis ............................................................................................................ 16 Headline8: GM maize contaminates non-GM crops in Uruguay ................................................ 17 Headline 9: Could crop ancestors feed the world? .................................................................... 19 Headline 10: Onion variety that yields well and is drought resistant ........................................ 20 Headline 11: Bt Maize trials shown red signal ........................................................................... 22 Section B: Healthcare & Clinical Research .................................. 24 Headline 1: Single gene controls development of many forms of polycystic disease................ 24 Headline 2: Study of biomarker development in mice provides a roadmap for a similar approach in humans .................................................................................................... 25 Headline 3: Researchers use human vaccine to cure prostate cancer in mice .......................... 27 Headline 4: Generx DNA-Based Angiogenic Therapy Receives Clearance for Late-Stage Registration Clinical Study for Coronary Artery Disease ............................................. 28 Headline 5: FDA clears Siemens Biograph mMR ........................................................................ 30 PAGE 3 OF 124 Headline 6: Dengue Virus Circulating Between Monkeys and Mosquitoes Could Emerge to Cause Human Outbreaks ............................................................................................. 31 Headline 7: Human Adult and Embryonic Stem Cell Research is Complementary, According to Social Scientists ........................................................................................................... 33 Headline 8: ImmunoCellular Therapeutics Ltd. Expands Phase II Trial of ICT-107 ..................... 35 Headline 9: Life Technologies Negotiates License to TAL Effector Gene Control Technology ... 36 Headline 10: Shingles May Be Related to Elevated Risk of Multiple Sclerosis ........................... 37 Headline 11: Pharmasset Announces the Expansion of the ELECTRON Trial in Chronic Hepatitis C................................................................................................................................... 37 Headline 12: Pfizer Conducts First "Virtual" Clinical Trial Allowing Patients to Participate Regardless Of Geography ............................................................................................ 38 Headline 13: Stem cells with bone-regenerating hormone help mend fractures ...................... 40 Headline 14: Panacea Biotec partners with GAVI....................................................................... 41 Headline 15: Novel First-In-Class Anti-Cancer Agent in Development by Niiki Pharma Shows Promising Phase I Results ............................................................................................ 42 Headline 16: Ampio Pharmaceuticals, Inc. Announces Initiation of Phase 1B Clinical Trial for Its Anti-inflammatory Drug Ampionв„ў .............................................................................. 43 Headline 17: Better vaccines thanks to RNA .............................................................................. 44 Headline 18: Herbal Remedies Offer Hope as Novel Antibiotics................................................ 45 Headline 19: Changing the Indian Culture in Reporting Adverse Drug Reactions...................... 46 Headline 20: Patients with Rheumatoid Arthritis Receive Less Protection from Pandemic Influenza with H1N1 Vaccine, Study Shows ................................................................ 47 Headline 21: Is It Ethical To Use Placebo In Rheumatoid Arthritis Clinical Trials? ..................... 48 Headline 22: Transgenomic, Inc. Acquires Exclusive Worldwide License to Predictive Markers for Cancer Drug Response ........................................................................................... 49 PAGE 4 OF 124 Headline 23: Gene-modified stem cells help protect bone marrow from toxic side effects of chemotherapy ............................................................................................................. 51 Headline 24: Investigators Pour Doubt on Accepted Understanding of DNA-to-RNA Sequence Equivalence ................................................................................................................. 52 Headline 25: Researchers Figure Out How to Selectively Correct Mutations in Patient-Derived Human iPSCs................................................................................................................ 54 Headline 26: FDA approves oral hepatitis c virus protease inhibitor ......................................... 57 Headline 27: Irregular practices in Private TB Drug market: Study ............................................ 58 Headline 28: New Discoveries about Tumor-Suppressing Protein Could Help Reduce Treatment Side Effects .................................................................................................................. 59 Headline 29: Trillium raises funds to advance urology program into clinical trials.................... 61 Headline 30: Scientists Claim TIF1-Gamma Levels Could Represent Biomarker of Response to Leukemia Therapy ....................................................................................................... 62 Headline 31: New Gene Therapy Technique on iPS Cells Holds Promise in Treating Immune System Disease ............................................................................................................ 64 Headline 32: Hepatitis B Virus Reemerges With Long-Term Nucleoside Analog Treatment, Study Suggests............................................................................................................. 66 Headline 33: Enigma Announces the Start of US Clinical Trials for Its Influenza A/B Detection Assay............................................................................................................................ 67 Headline 34: Vaccine for Transplant Infection Shows Promise in Phase II Trial......................... 68 Section C: Microbial .................................................................. 70 Headline 1: Cholesterol boosts antibiotic resistance in H. Pylori ............................................... 70 Headline 2: Nitrogen-Fixing Bacterial Symbiont Promises Trove of Natural Products .............. 71 Headline 3: E. coli Bacteria More Likely to Develop Resistance after Exposure to Low Levels of Antibiotics ................................................................................................................... 72 PAGE 5 OF 124 Headline 4: Non-Independent Mutations Present New Path to Evolutionary Success.............. 72 Headline 5: Cystic Fibrosis-Associated Bacteria Could Help Fight Back Against Antibiotic Resistance.................................................................................................................... 74 Headline 6: Potential Human Exposure to Prion Diseases Assessed .......................................... 75 Headline 7: Genetically Modified Bacteria Filters Out Toxic Vapors .......................................... 77 Headline 8: Filtering out Pesticides with Genetically Modified Bacteria ................................... 77 Section D: Nano Technology ..................................................... 79 Headline 1: Novel nanoparticles communicate to target tumors more efficiently ................... 79 Headline 2: Nanoparticles help scientists harvest light with solar fuels .................................... 80 Headline 3: Nanoparticles may help inhibit Alzheimer's disease and other neurodegenerative disorders...................................................................................................................... 82 Headline 4: Nanoparticle therapeutics might help people suffering from hearing disorders ... 83 Headline 5: Safety of nanoparticles in food crops is still unclear ............................................... 84 Headline 6: Sharpening the Nanofocus ...................................................................................... 84 Headline 7: BMS Expands Deal to Evaluate TekmiraвЂ™s RNAi Delivery Technology ..................... 86 Headline 8: BMS Expands Deal to Evaluate TekmiraвЂ™s RNAi Delivery Technology ..................... 88 Headline 9: Silver Cycle: New Evidence for Natural Synthesis of Silver Nanoparticles .............. 89 Headline 10: NanoBio and GSK Commence Phase 3 Studies of Nanoemulsion-Based OTC Treatment for Cold Sores ............................................................................................ 90 Headline 11: Inverting a Standard Experiment Sometimes Produces Different Results............ 91 Headline 12: New Solar Cell Technology Greatly Boosts Efficiency ........................................... 93 Headline 13: Shrink Nanotechnologies to Acquire Nanopoint for Live Cell Imaging Capabilities ..................................................................................................................................... 94 PAGE 6 OF 124 Section E: Pharmaceuticals ....................................................... 96 Headline 1: Cubist might stay clear of Ph3 for antibiotic, analyst says ...................................... 96 Headline 2: Constellation Pharma takes different route than rival in hot epigenetics field ...... 96 Headline 3: Regeneron Drug Called Effective in FDA Review ..................................................... 97 Headline 4: FDA Says Diabetes Drug Might Raise Cancer Risk ................................................... 99 Headline 5: FDA approves Glaxo, Valeant's epilepsy drug ....................................................... 100 Headline 6: Par Pharmaceutical to Acquire Edict Pharmaceuticals ......................................... 101 Headline 7: Cell Biosciences Pays $9M to Acquire Brightwell Technologies for Micro-Flow Imaging Platform ....................................................................................................... 102 Headline 8: EMA approves Biogen Avonex Pen ....................................................................... 102 Section F: Energy & Environmental ......................................... 104 Headline 1: USB's "See for yourself" tour includes biodiesel stop ........................................... 104 Headline 2: Miniature Power Plants for Aircraft Bodies .......................................................... 105 Headline 3: Scientists at wheat symposium suggest growing risk to wheat crops .................. 106 Headline 4: Planet's Soils Are Under Threat, Expert Warns ..................................................... 109 Headline 5: Developing Advanced Biofuels: Researchers Counteract Biofuel Toxicity in Microbes.................................................................................................................... 110 Headline 6: Study: 'E-waste pollution' a threat to human health ........................................... 112 Headline 7: Bio-plastic bags trying to change the face of carry bag market ............................ 113 Headline 8: Green and Lean: Secreting Bacteria Eliminate Cost Barriers for Renewable Biofuel Production ................................................................................................................. 114 Headline 9: Teaching Algae to Make Fuel: New Process Could Lead to Production of Hydrogen Using Bioengineered Microorganisms ...................................................................... 116 PAGE 7 OF 124 Headline 10: Scientists Generates Hydrogen as an Energy Source from Ethanol and Sunlight ................................................................................................................................... 117 Headline 11: New Green Technology for Hydrogen Production .............................................. 118 Headline 12: Global warming 'has reduced maize and wheat yields' ...................................... 119 Headline 13: Background radiation and radioactivity in India ................................................. 120 Headline 14: Green technology to tackle water pollution ....................................................... 122 Headline 15: Using the Energy in Oil Shale without Releasing Carbon Dioxide in a Greenhouse World......................................................................................................................... 123 Headline 16: Toward a More Efficient Use of Solar Energy...................................................... 123 PAGE 8 OF 124 Section A: Agriculture Headline1: Nitrogen-Fixing Bacterial Symbiont Promises Trove of Natural Products Published By: ScienceDaily Date of Publication: June 27, 2011 Source: http://www.sciencedaily.com/ Soil-dwelling bacteria of the genus Frankia have the potential to produce a multitude of natural products, including antibiotics, herbicides, pigments, anticancer agents, and other useful products, according to Bradley S. Moore of the Scripps Oceanographic Institute, La Jolla, and his collaborators in an article in the June 2011 issue of the journal Applied and Environmental Microbiology. The researchers found genetic structures in this bacterium that resemble those of various valuable natural product categories through bioinformatics and genome mining. "This tremendous biosynthetic capacity is reminiscent of many industrially important bacteria such as those belonging to the genus, Streptomyces that produce the majority of the natural antibiotics used as drugs," says Moore. "To see this capacity in a well-known microbe not previously exploited for its chemical richness was very rewarding from both an applied and basic science point of view," says Moore. Frankia are nitrogen-fixing bacteria that live in symbiosis with actinorhizal plants (whose ranks include beech and cherry trees, and various gourd-producing plants). "Since the vast majority of the deduced [biosynthetic] pathways are unique to Frankia, it suggests that they employ a very complex and specialized communication with their plant host to establish and maintain their symbiosis. So lots to discover there." Frankia have not previously been exploited partly because these bacteria are difficult to grow in the lab. But new genetic methods make it easier to transplant genes for promising natural products from Frankia into "more user-friendly host bacteria for production," says Moore. Moreover, genome mining, a recent technique that involves searching for genetic sequences, was critical to the results, and "complementary to the far more laborious traditional natural product drug discovery that has gone unchanged for decades," says Moore. A greater understanding of how complex organic molecules are synthesized in nature laid additional groundwork for this, and for "a new revolution in the discovery of natural chemicals that will fuel new research into what functions these chemicals play in nature, and how they can be used to benefit society," says Moore. The project grew out of a graduate class that Moore and Daniel Udwary (then his post-doc, now at the University of Rhode Island) taught on "Microbial Genome Mining," says Moore. Each student in the class researched a group of biosynthetic gene clusters that Moore and Udwary preselected. The students -- who are the majority of coauthors on the paper -- annotated their genes and based on PAGE 9 OF 124 biosynthetic principles, and predicted pathways leading to putative natural products. They then worked with the laboratories of Pieter Dorrestein at the University of California, San Diego (a mass spec specialist) and Lou Tisa at the University of New Hampshire (a Frankia biologist) to conduct preliminary proteomic and metabolomic analyses to probe whether the predicted pathways were operative, and whether small molecule chemistry was evident. Headline2: Importing grains cannot solve food shortage problems Published By: The Hindu Date of Publication: June 20, 2011 Source: http://www.thehindu.com вЂњIt is a universally acclaimed fact, that importing food cannot solve the problem of food shortage. Modern technologies do offer vast prospects for crop improvement but that alone need not make it popular among small and marginal farmers,вЂќ says farmer Mr. Mahavir Singh Arya, from Churu district of Rajasthan. Despite facing acute problem of water shortage, Mr. Mahavir, an advocate of organic farming, developed numerous varieties of wheat and mustard, and claims that he never used any inorganic fertilizer to grow crops and still managed to generate good yield. Ignorant вЂњUrban people do not seem to know the real problem we farmers face,вЂќ he says and adds: вЂњTo them it becomes an issue only during price hike. Though farming being an important area вЂ” a large section of the public view agriculture as something involving the government and it becomes a job for elected persons to resolve the farmers' problems. вЂњThe fact, that we import food to cater to domestic demand, besides large scale migration to cities does not seem to cause any serious concern in the urban manвЂ™s mind.вЂќ Real life According to him, though urban people may be fascinated by the simple village life, in reality life isnвЂ™t all that easy in villages. вЂњThe aspiration of rural folks to seek out greener pastures in nearby metros, educate their kids and push them out of the village. Hence statistically, food supply is dwindling and demand is shooting up вЂ” we are all sitting on a volcano ready to erupt anytime,вЂќ he feels. вЂњA farmerвЂ™s life is a tale of continuous experimentation and struggle for existence and even getting a good price for the produce is difficult for us,вЂќ he explains. Different odds PAGE 10 OF 124 Inspite of all the odds, inquisitiveness made him visit Hissar Agriculture University to see some breeding experiments in crop varieties and learn the method of selection and crossing between different varieties. He returned to start experimenting in the fields. Encouraged by the success, he got interested in breeding and thereafter he made it a point to visit various research institutions and universities, to keep himself updated. The farmer developed more than 10 varieties of mustard by crossing the varieties available in Delhi region. The maturity period of all these varieties varies from 130 to 150 days and the yield from about 1.8 tonnes to 2.4 tonnes per hectare. All the varieties are disease resistant and high yielding, according to him. He chanced upon a variety of tall and high yielding wheat and crossed it with a locally popular variety. The next year, the farmer observed that the crops grew taller, bore bolder grains that were resistant to disease. He selected plants possessing characteristics like height of the plant, resistance to disease, etc., every year and developed the variety вЂ�Mahavir Kisan Mahan.вЂ™ Different varieties In the same way, he kept on crossing varieties obtained from different regions with other local varieties and successfully developed more than 15 varieties of wheat. The maturity period of all the wheat varieties varies from 135-160 days, except one, named Mahavir Kishan Pragati, a short duration dwarf variety developed by him that comes to harvest in 95-110 days. The yield of these varieties varies from 4-8 tonnes for a hectare. Extra effort вЂњFor a farmer every available area of space needs to be utilised so that some sort of income can be generated. In places like ours where water is a scarce commodity, extra effort is needed to obtain even average yield. Government should look into the cause of the millions of farmers like Mr Mahavir who toil day in and day out to feed the over billion plus population of the country.вЂќ says Sundaram Verma, a progressive farmer himself and Honey Bee Network collaborator ofRajasthan. Mr. Mahavir mentions that the government may be trying its best,but an extra effort towards providing enough support to the farmers would go a long way in making India a self reliant country in food crops. Headline3: Managing papaya mealybug through bio control Published By: The Hindu Date of Publication: June 03, 2011 Source: http://www.thehindu.com PAGE 11 OF 124 Outbreak of papaya mealy bug, Paracoccus marginatus was noticed during 2008 on papaya, mulberry, tapioca, jatropha, vegetables, fruits, cotton, plantation crops, spices and flowers crops in different parts of Tamil Nadu causing extensive damage upto 90 per cent. Three parasitoids Acerophagus papayae, Anagyrus loecki and Pseudleptomastix mexicana were imported through NBAII (National Bureau of Agriculturally Important Insects) from US. Field trials According to Dr. P. Murugesa Boopathi, Vice Chancellor, Tamil Nadu Agriculture University, We obtained the nucleus culture of the parasitoids from NBAII for multiplication. Subsequently the parasitoids were released as field trials in the University campus. He says: вЂњTraining on mass multiplication of mealybug parasitoids was given to plant protection scientists from seven colleges, 36 research stations and 14 KVKs within a fortnight to take up mass production throughout the state immediately. Short time frame вЂњWithin a period of six months, 5,65,000 parasitoids were mass multiplied in a war footing manner and released in farmers field at 100 parasitoids / field / village or block in all districts of Tamil Nadu except Nilgiris. Since, no mealybug incidence was noticed in Nilgiris, the parasitoids were not released.вЂќ вЂњThe technology is very well received by the farmers. Previously, on an average 2 sprays were given for a single crop of mulberry and 20-24 sprays in papaya and ten sprays in cassava by the farmers. Amount saved вЂњAn amount of Rs.122 crores has been saved by rural farmers for not advocating pesticide application for the past six months in papaya, mulberry and cassava. Due to release of mealybug parasitoidan amont of Rs.435 crores have been saved from loss due to the invasive pest in above three crops,вЂќ adds Dr. Boopathi Two thousand parasitoids were also given to Kerala Agricultural University for release. Anticipation вЂњWe anticipate further flare up of mealybugs, since summer is in progress. In order to prevent mealybugs damage all the research stations were asked to gear up mass production of parasitoids to meet out the demand and release the parasitoids wherever there is infestation,вЂќ says Dr. Boopathi Headline4: New technique for artificial photosynthesis Published By: The Hindu Date of Publication: May 25, 2011 Source: http://www.thehindu.com PAGE 12 OF 124 This discovery will make it possible to improve photoelectrochemical cells. In the same way that plants use photosynthesis to transform sunlight into energy; these cells use sunlight to drive chemical reactions that ultimately produce hydrogen from water. The process involves using a light-sensitive semi-conducting material such as cuprous oxide to provide the current needed to fuel the reaction. Although it is not expensive, the oxide is unstable if exposed to light in water. Research by Adriana Paracchino and Elijah Thimsen, published May 8, 2011 in the journal Nature Materials, demonstrates that this problem can be overcome by covering the semiconductor with a thin film of atoms using the atomic layer deposition (ALD) technique. Under the supervision of Professor Michael GrГ¤tzel in EPFL's Laboratory of Photonics and Interfaces, the two scientists achieved this remarkable feat by combining techniques used at the industrial scale, and then applying them to the problem of producing hydrogen. With their process, cuprous oxide can be simply and effectively protected from contact with water, making it possible to use it as a semiconductor. The advantages are numerous: cuprous oxide is abundantly available and inexpensive; the protective layer is completely impermeable, regardless of the roughness of the surface; and the process can easily be scaled up for industrial fabrication. The research team developed the technique by вЂњgrowingвЂќ layers of zinc oxide and titanium oxide, one atom-thick layer at a time, on the cuprous oxide surface. By using the ALD technique, they were able to control the thickness of the protective layer down to the precision of a single atom over the entire surface. This level of precision guarantees the stability of the semiconductor while preserving all of its hydrogen-producing efficiency. The next step in the research will be to improve the electrical properties of the protective layer. Headline5: Improving Photosynthesis? Solar Cells Beat Plants at Harvesting Sun's Energy, for Now Published By: ScienceDaily Date of Publication: May 20, 2011 Source: http://www.sciencedaily.com In a head-to-head battle of harvesting the sun's energy, solar cells beat plants, according to a new paper in Science. But scientists think they can even up the playing field, says researcher David Kramer at Michigan State University. Plants are less efficient at capturing the energy in sunlight than solar cells mostly because they have too much evolutionary baggage. Plants have to power a living thing, whereas solar cells only have to send electricity down a wire. This is a big difference because if photosynthesis makes a mistake, it makes toxic byproducts that kill the organism. Photosynthesis has to be conservative to avoid killing the organisms it powers. PAGE 13 OF 124 "This is critical since it's the process that powers all of life in our ecosystem," said Kramer, a Hannah Distinguished Professor of Photosynthesis and Bioenergetics. "The efficiency of photosynthesis, and our ability to improve it, is critical to whether the entire biofuels industry is viable." The annually averaged efficiency of photovoltaic electrolysis based on silicon semiconductors to produce fuel in the form of hydrogen is about 10 percent, while a plant's annually averaged efficiency using photosynthesis to form biomass for fuel is about 1 or 2 percent. Plants, following the path of evolution, are primarily interested in reproducing and repairing themselves. The efficiency at which they produce stored solar energy in biomass is secondary. Still, things can change. Just as early Native Americans manipulated skinny, non-nutritious Teosinte into fat, juicy kernel corn, today's plants can be manipulated to become much better sources of energy. Researcher Arthur J.Nozik, a NREL senior research fellow, and Senior Scientist Mark Hanna working at DOE's National Renewable Energy Laboratory (NREL), recently demonstrated how a multijunction, tandem solar cell for water splitting to produce hydrogen can provide higher efficiency -more than 40 percent -- by using multiple semiconductors and/or special photoactive organic molecules with different band gaps arranged in a tandem structure. The coupling of different materials with different gaps means photons can be absorbed and converted to energy over a wider range of the solar spectrum. "In photovoltaics, we know that to increase power conversion efficiency you have to have different band gaps (i.e., colors) in a tandem arrangement so they can more efficiently use different regions of the solar spectrum," Nozik said. "If you had the same gap, they would compete with each other and both would absorb the same photon energies and not enhance the solar conversion efficiency." Photosynthesis does use two gaps based on chlorophyll molecules to provide enough energy to drive the photosynthesis reaction. But the two gaps have the same energy value, which means they don't help each other to produce energy over a wider stretch of the spectrum of solar light and enhance conversion efficiency. Furthermore, most plants do use the full intensity of sunlight but divert some of it to protect the plant from damage. Whereas photovoltaics use the second material to gain that photoconversion edge, plants do not, Nozik noted. PAGE 14 OF 124 One of NREL's roles at the DOE workshop was to help make it clear how the efficiency of photosynthesis could be improved by re-engineering the structure of plants through modern synthetic biology and genetic manipulation based on the principles of high efficiency photovoltaic cells, Nozik said. In synthetic biology plants can be built from scratch, starting with amino acid building blocks, allowing the formation of optimum biological band gaps. The newly engineered plants would be darker, incorporating some biological pigments in certain of nature's flora that would be able to absorb photons in the red and infrared regions of the solar spectrum. As plants store more solar energy efficiently, they potentially could play a greater role as alternative renewable fuel sources. The food that plants provide also would get a boost. And that would mean less land would be required to grow an equivalent amount of food. The new information in the Science manuscript will help direct the development of new plants that have a better propensity for reducing carbon dioxide to biomass. This could spur exploration of blue algae, which not only comprise about one quarter of all plant life, but are ideal candidates for being genetically engineered into feedstock, because they absorb light from an entirely different part of the spectrum compared to most other plants. "It would be the biological equivalent of a tandem photovoltaic cell," said Robert Blankenship, one of the lead authors in the Science paper who studies photosynthesis at Washington University in St. Louis. "And those can have very high efficienc Headline6: Genomes of Fungi That Threaten Wheat, Poplars Sequenced Published By: ScienceDaily Date of Publication: May 14, 2011 Source: http://www.sciencedaily.com An international team of researchers co-led by a U.S. Department of Agriculture (USDA) scientist has sequenced the genomes of two fungal pathogens-one that threatens global wheat supplies and another that limits production of a tree crop valued as a future source for biofuel. The sequencing of the genetic codes of wheat stem rust pathogen (Puccinia graminis) and poplar leaf rust pathogen (Melampsora larici-populina) is expected to help researchers develop control strategies to address worldwide threats to wheat fields and tree plantations. The study, published in the Proceedings of the National Academy of Sciences, was a six-year collaborative effort of USDA's Agricultural Research Service (ARS), the U.S. Department of Energy Joint Genome Institute, the National Science Foundation, the Broad Institute of Harvard and the Massachusetts Institute of Technology, the University of Minnesota and the French National Institute for Agricultural Research. PAGE 15 OF 124 "The threats these pathogens pose to two essential agricultural products are very real, and that makes it important to learn everything we can about them, from their molecular underpinnings to how they survive and spread infection," said Edward B. Knipling, administrator of ARS, USDA's principal intramural scientific research agency. The research supports the USDA priority of developing new sources of bioenergy and promoting international food security. Wheat stem rust causes major epidemics of both barley and wheat worldwide. A strain known as Ug99 has spread across Africa and into Central Asia, and has been able to overcome most of the stem-rust-resistant wheat varieties developed over the past 50 years. Poplar leaf rust can cause significant losses in poplar tree plantations. Poplar is an important crop for the wood industry and is becoming increasingly important to the biofuel industry in the United States and Europe because of its rapid and significant production of biomass. The study represents the first genome-wide characterization of any rust fungus, a diverse group of more than 6,000 species, according to Les Szabo, a lead researcher on this project. Szabo works at the ARS Cereal Disease Laboratory in St. Paul, Minn. Rust fungi depend on living tissue of their hosts for survival. The pathogens secrete proteins that enable them to block the host plant's defenses and steal nutrients. The research uncovered evidence that both pathogens have large numbers of such "effector" proteins, an indication that they likely coevolved with their host plants, according to the study authors. Because they need a plant host to survive, the pathogens can't be cultured in a laboratory and are notoriously hard to study. But the genetic sequencing opens a window into the never-ending arms race between these pathogens and their hosts, Szabo said. The team's sequence data has been released in GenBank, a genetic database administered by the National Center for Biotechnology Information at the National Institutes of Health. Headline7: Harnessing the Energy of the Sun: New Technique Improves Artificial Photosynthesis Published By: ScienceDaily Date of Publication: May 11, 2011 Source: http://www.sciencedaily.com Transforming solar energy into a usable form is a real challenge. One technique is to use semiconductors to store the energy as hydrogen. Unfortunately, the most efficient semiconductors are not the most stable. An EPFL team has just discovered that it is possible to protect the semiconductor with a uniform layer just a few nanometers thick. PAGE 16 OF 124 This discovery will make it possible to improve photoelectrochemical cells. In the same way that plants use photosynthesis to transform sunlight into energy; these cells use sunlight to drive chemical reactions that ultimately produce hydrogen from water. The process involves using a light-sensitive semi-conducting material such as cuprous oxide to provide the current needed to fuel the reaction. Although it is not expensive, the oxide is unstable if exposed to light in water. Under the supervision of Professor Michael GrГ¤tzel in EPFL's Laboratory of Photonics and Interfaces, the two scientists achieved this remarkable feat by combining techniques used at the industrial scale, and then applying them to the problem of producing hydrogen. With their process, cuprous oxide can be simply and effectively protected from contact with water, making it possible to use it as a semiconductor. The advantages are numerous: cuprous oxide is abundantly available and inexpensive; the protective layer is completely impermeable, regardless of the roughness of the surface; and the process can easily be scaled up for industrial fabrication. A promising technique The research team developed the technique by "growing" layers of zinc oxide and titanium oxide, one atom-thick layer at a time, on the cuprous oxide surface. By using the ALD technique, they were able to control the thickness of the protective layer down to the precision of a single atom over the entire surface. This level of precision guarantees the stability of the semiconductor while preserving all of its hydrogen-producing efficiency. The next step in the research will be to improve the electrical properties of the protective layer. Using widely available materials and techniques that can be easily scaled up will help the "green" photoelectrochemical production of hydrogen meet the needs of industry. Headline8: GM maize contaminates non-GM crops in Uruguay Published By: Scidev Date of Publication: May 5, 2011 Source: http://www.scidev.net/ Contamination of traditional maize crops planted near genetically modified (GM) maize fields may be common in Uruguay, where the cultivation of GM maize has been permitted since 2003, scientists have said. A study published in Environmental Biosafety Research (25 March) has found GM seedlings in three traditional maize fields. It is said to be the first report of cross-fertilisation between GM and non-GM maize in South America. Studies on the unplanned presence of GM maize and the contamination of non-GM crops in Latin America have led to some controversial cases, such as a retracted 2001 Nature study from Mexico PAGE 17 OF 124 and a 2007 Peruvian study that led to a libel case against one of the scientists who challenged the findings and a subsequent campaign for freedom of speech for scientists. And Monsanto's GM maize trial in Mexico has recently re-ignited the debate in the country that boasts the most diverse maize genetic resources. But, unlike Mexico and Peru, Uruguay permits the cultivation of GM maize. The varieties MON810 and Bt11 were approved for commercial planting in 2003 and 2004, respectively. Governmental regulations specify that GM and non-GM crop fields should be more than 250 metres apart to avoid cross-fertilisation and ensure their "regulated coexistence", and that 10 per cent of the field should be non-GM to provide a refuge area for biodiversity. In the latest research, scientists from Uruguay's University of the Republic analysed five pairs of commercial maize п¬Ѓelds where farmers planted GM maize at about the same time as a nearby non GM crop. Studying commercial fields is better than using experimental plots, which may not correspond to the real-life situation, the scientists argue. In three cases they detected foreign genes from GM maize, the 'transgenes', in seedlings produced by seeds taken from the non-GM crops. The transgenes were presumably blown over in pollen from the GM fields. The highest percentage of transgenic seedlings was 0.83 per cent in a field 100 metres from the GM maize field. In one case, the cross-fertilisation occurred despite a Eucalyptus tree barrier (12 metres high, 30 metres wide) separating the fields, and another case involved cross-fertilisation between fields more than 250 metres apart. Cross-fertilisation may therefore be "a common situation in Uruguay", the authors said, adding that the area planted with GM maize in the country is increasing. "These results also show that the current regulation in Uruguay is insufficient and that the actual 'coexistence policy' is not well known among farmers," Pablo Galeano, the study's lead author, told SciDev.Net. "I think that to talk about 'regulated coexistence' without the necessary tools to make it viable is nothing more than rhetoric." But Galeano cautioned that the findings may not necessarily apply to other crops or other countries. PAGE 18 OF 124 "Cross-fertilisation depends on topography, size and orientation of fields, type of maize, wind direction during the flowering time, temperature and humidity, so it is hardly possible to generalise our results to other crops, areas or countries," he said. Daniel Bayce, manager of Uruguay's National Seed Institute, told SciDev.Net that the findings were not representative because cross-fertilisation was detected mostly where the fields were too close, and even then "the frequency of GM contamination was very low Headline 9: Could crop ancestors feed the world? Published By: COSMOS Magazine Date of Publication: April 26, 2011 Source: http://www.cosmosmagazine.com The race is on to develop and test improved crop varieties to feed the world's growing population вЂ” and help may lie in Syria's wild plants. Many of the first crops emerged in Syria, where humans are thought to have first discovered agriculture some 11,000 years ago. Emmer wheat, barley, chickpea, pea and lentil crops all originated here. Researchers from around the world are flocking to the Arabian desert to create crops for an increasingly bleak future, as obstacles to food production stack up, according to COSMOS Magazine. Climate change; depletion of phosphorous supplies; the drying out of water basins; competition with biofuels for land; and the reliance on oil for nitrogen fertiliser production are all challenging the status quo, according to Kenneth Street, an agriculturalist and genetic resource scientist at the International Centre for Agricultural Research in Dry Areas (ICARDA) . As a result, many researchers have turned to breeding techniques that import useful traits from wild varieties вЂ” the ancestors of domestic crops. Although humans have only ever bred small numbers of the best-yielding varieties of crops, hundreds of thousands of species that our ancestors didn't pick contain genes that have enabled them to grow in one of the world's harshest climates, enduring droughts, high salinity and temperature variations. If some of these genes could now be introduced to high-yielding crops they could provide them with an urgently needed boost. To speed up this process, which normally takes up to 12 years, researchers are now looking at new technologies. For example, the Focussed Identification of Germplasm Strategy approach informs researchers where to look for certain traits by examining the environment from which the seed was collected. PAGE 19 OF 124 "For example, if we're looking for a drought resistant crop, we're going to look in low rainfall environments in which the seasonal rainfall is highly variable вЂ” this type of environment may have forced local populations to evolve towards physiological drought tolerance," says Street. Another initiative is to look for new molecular markers, which are common for some crops, such as wheat and barley, but largely unknown for others, such as chickpeas. Genetic modification could also help reduce the length of time to breed new varieties, from 12 to two years, he said, but public concerns over the consequences for health and the environment may mean it never takes off. "[GM] technology will never replace normal breeding вЂ” you're only going to use [it] when you don't have any other way of getting the trait," says Muhammad Imtiaz, senior chickpea breeder at ICARDA. Headline 10: Onion variety that yields well and is drought resistant Published By: The Hindu Date of Publication: April 20, 2011 Source: http://www.thehindu.com Government's version of trying to control price rise is not helping, an onion cannot be dismissed as just another vegetable. вЂњIn fact no other vegetable seems to be backed by a strong lobby like the humble onion. Especially in our country, Governments can be toppled and unseated if the vegetable records a meteoric price rise. When onion price fluctuates it becomes front page news,вЂќ says Mr. Manaram Chowdhary from Sikar, Rajasthan. Decade of work The farmer developed an onion variety after nearly a decade of trial and error and says these ones yield well, are drought resistant, and fetch a better price compared to the other local varieties. Named Rashidpura, the variety attained wide popularity in the northern states of Rajasthan, Delhi, Punjab, and Haryana for its distinctive taste and strong smell. вЂњI tried cooking them and found them delicious. But their shelf life was short. I then preserved some bulbs by drying them and sowed them in the next season. Water scarcity PAGE 20 OF 124 вЂњThough I did cultivate the local varieties, acute water shortage made me experiment with a variety, whose requirement of water was less and which could survive the drought conditions that are prevalent in our area,вЂќ he adds. The three wells in his 10-acre farm were unsuitable for growing wheat, bajra, and other crops in addition to onions. He says that he observed that the plants from this particular variety were maturing earlier (110-115 days ) than the other varieties (125- 135 days) and yielded well вЂ” 40,000 kg bulbs per hectare вЂ” than the commercially cultivated varieties (25,000-30,000 kg per hectare), even under water-stress and low irrigation conditions. He stabilised the characteristics over a period of ten years (1983 to 1993) by performing repeated selection. Once he was satisfied with the yield stability of the variety, and the drought resistant characteristic of the variety, he named it Rashidpura. Consumer awareness вЂњAs of now the availability and awareness among consumers for this particular variety are relatively low compared to the other popular ones. This variety can also fetch a good price like the other local ones and farmers should realise this and start cultivating it,вЂќ says the farmer, adding, вЂњthis variety is usually used to spice soups, salads and pizzas due to its peculiar taste. вЂњUrban consumers seem to prefer these varieties and the requirement for this type of onion is also expected to increase. Farmers would definitely benefit from growing this variety of onionвЂќ. Appreciation Officials from the agriculture extension department in Sikar and research station, Durgapur (Jaipur) appreciated the variety developed by Mr. Choudhary. вЂњSeveral onion farmers end up ploughing their crops back into the soil in frustration as they are not able to get a good price for their produce. The weather also creates problems for us. вЂњIt suddenly starts raining during peak summer and sometimes there is little rain for years together,вЂќ says Mr. Sundaram Verma, Honey Bee Network collaborator Rajasthan. False claim вЂњThe transport cost to the mandis does not even make up for our investment expenditure. The Government's claim of trying to control the rise does not seem to be of much help to poor farmers. PAGE 21 OF 124 вЂњThe media must also throw light on plight of onion cultivators, their problems, and new methods if any, to increase area of cultivation and encourage other farmers to start cultivating onion, instead of just reporting on price rise and how it affects consumers and the Government's reply and control mechanism to the same,вЂќ adds Mr. Manaram. Headline 11: Bt Maize trials shown red signal Published By: Biospectrum India Date of Publication: April 12, 2011 Source: http://www.biospectrumindia.com The stopping of of Bt Maize trials in Bihar by the Environment Ministry has raised several grave questions. The absence of a clear policy regarding the commercial utilization of the outcome of huge investments into R&D of various crops, is seen as a major hindrance to the agri-biotech sector. Bt crops has once again found itself admist controversies in India. Mr Jairam Ramesh, the minister for forest & environment, had during March, directed the Genetic Engineering Appraisal Committee (GEAC) to immediately cancel field trials for Bt maize in Bihar. Maize is IndiaвЂ™s 3rd largest cereal crop. Mr Ramesh intervened after Bihar chief minister Nitesh Kumar put his strong objections on the trials before the Environment Ministry. In a letter written to the GEAC, Mr Ramesh also instructed the GEAC to give state governments a month's time to agree or disagree with the field trials of GM food crops. The ministry's decision to overlook the GEAC has also raised questions on the powers of the regulatory body. Earlier the GEAC, which is under the ministry of environment and forests, had allowed US-based biotech giant, Monsanto, to conduct field trials of Bt maize. However, the voices coming from the agri-biotech industry are very clear this time. The industry wants the government to come up with a clear mandate and allow Bt crops in India. The Indian Maize Development Association (IMDA) expressed its apprehensions over the decision. Dr Sain Dass, president, IMDA said, вЂњWith the success maize has achieved over the years and with the potential the crop has to offer, there is significant scope to repeat the Bt cotton story with maize and put India on the world Bt map.вЂќ The Association of Biotechnology Led Enterprises-Agriculture Group (ABLE-AG) while labeling the development as unfortunate, observed that the industry will continue to engage in constructive dialogue with several regulatory authorities, including GEAC, Department of Biotechnology, State Agriculture Universities and farmers amongst others to develop technologies and products in India that are important and relevant to the countryвЂ™s agriculture needs. вЂњWe are confident that our countryвЂ™s science-based regulatory system will continue to support research-led innovations in agriculture and PAGE 22 OF 124 will help improve crop productivity, thereby benefitting Indian farmers, consumers, environment and our nation as a whole,вЂќ said VR Kaundinya, Chairman, ABLE-AG. The safety of Bt maize has been established through detailed tests and studies. So what seems to be the problem with Bt maize in Indian? Industry experts are baffled at the fact that decisions surrounding Bt maize are being taken due to political interference and not based on scientific reasoning. Many independent bio-agri consultants like Dr TM Manjunath believe that regulatory committees comprise eminent scientists who use their collective knowledge and wisdom in taking a decision on such issues based on science. вЂњOur politicians are best advised to be guided by the eminent scientific bodies on such issues and not misled by self-styled environmentalists.вЂќ says Dr Manjunath, who is a consultant at Agri-Biotechnology & Integrated Pest Management. Raising far more serious questions, Dr KK Narayanan, managing director, Metahelix, asks, вЂњHow can we afford not to have the latest technologies in this crop? The sudden halting of the trials instills further uncertainty in the road towards commercializing of not just Bt maize, but all other crops as well. Unless there is a clearly laid out path towards commercial utilization of the outcome of such investments, all investments will amount to a mere waste of the nationвЂ™s resources and scientific talent.вЂќ However Dr B Mazumdar, vice-President, Bejo Sheetal Seeds takes this as an isolated case. Dr Mazumdar says, вЂњThis is a special case and we feel that this is not generalized directive for all the GM trials.вЂќ The increased productivity in maize can turn India into a dominant exporter of maize particularly in Asia due to low cost of production and advantages in transportation. Therefore, it is high time for the Indian government to clear the air on Bt crops because it cannot continue to overlook the aspirations of the Indian agri-biotech industry. PAGE 23 OF 124 Section B: Healthcare & Clinical Research Headline 1: Single gene controls development of many forms of polycystic disease Published By: Physorg Date of Publication: June 19, 2011 Source: http://www.physorg.com Cysts riddle a kidney from a patient with polycystic kidney disease. Credit: courtesy Yale University A single gene is central in the development of several forms of polycystic kidney and liver disease, Yale School of Medicine researchers report in the June 19 issue of Nature Genetics. The findings suggest manipulating activity of PKD1, the gene causing the most common form of polycystic kidney disease, may prove beneficial in reducing cysts in both liver and kidney. "We found that these conditions are not the result of an all or nothing phenomenon," said Stefan Somlo, the C.N.H. Long Professor of Medicine and Genetics and Chief, Section of Nephrology and senior author of the study. "The less PKD1 is expressed, the more cysts develop. Conversely, expressing more PKD1 can slow the process." The most common form of this condition is called autosomal dominant polycystic kidney disease (ADPKD), a condition passed on to children from one parent affected with the disease that is found in 600,000 people in the United States alone. Two genes, PKD1 and PKD2, are responsible for the onset of this condition. PKD patients also develop cysts of the liver and Somlo and colleagues had previously identified families with identical cysts found only in the liver. They found two different genes were responsible for this related condition. The researchers wanted to know how liver-only polycystic disease was related to ADPKD. In a series of experiments using both genetically engineered mouse models and biochemical studies, they found that the activity of only one of the four genes, PKD1, controlled cyst formation in the other forms of the disease. Experiments in mice showed that modulating dosage of PKD1 could slow disease progression. "The data suggest the exciting possibility that targeting the activity of PKD1 may be beneficial for treatment of isolated polycystic liver disease, childhood recessive polycystic kidney disease and even a subset of adult ADPKD," said Somlo. PAGE 24 OF 124 Yale is a leader in the investigation of PKD. For instance basic scientific research conducted at Yale has been crucial in helping to identify cilia, the tiny thread-like structure that extends from a cell's surface, as a critical component in cyst forming pathways. Yale has been the home of one of the four NIH-funded national centers of excellence in PKD research since 1999. In addition, the laboratory of Craig Crews, Lewis B. Cullman Professor of Molecular, Cellular, and Developmental Biology and Professor of Chemistry and of Pharmacology, has identified a compound that has shown promise in reducing number of cysts in some mouse models of PKD. Headline 2: Study of biomarker development in mice provides a roadmap for a similar approach in humans Published By: Physorg Date of Publication: June 19, 2011 Source: http://www.physorg.com Researchers at Fred Hutchinson Cancer Research Center have demonstrated in mice that the performance of a novel biomarker-development pipeline using targeted mass spectrometry is robust enough to support the use of an analogous approach in humans. The findings, by principal investigator Amanda Paulovich, M.D., Ph.D., an associate member of the Hutchinson Center's Clinical Research Division, are published in Nature Biotechnology. Paulovich and colleagues demonstrated that a staged, targeted pipeline approach using mass spectrometry to prioritize and validate proteins of interest enabled them to test a far larger number of biomarker candidates than would have been possible using conventional technologies, making a substantial improvement over the current state of biomarker evaluation. "If, as we hope, this approach enables more efficient translation of novel biomarkers into use as diagnostic tests, the effect will be an improved ability to personalize medicine by optimizing our treatment of individual patients, thus improving patient outcomes and also helping to contain health care costs," Paulovich said. The researchers undertook this proof-of-concept study in an attempt to accelerate and streamline the process of biomarker candidate testing because, over nearly a decade, hundreds of millions of dollars have been spent on the discovery of promising protein biomarkers of human diseases, particularly biomarkers found in the blood. Despite this significant investment, the number of new FDA-approved blood-based biomarkers has remained very low. Several factors have contributed to this low return on investment. Each promising biomarker must be further studied in clinical trials, which requires researchers to measure the abundance of each candidate biomarker in hundreds of patient samples. Because the odds are extraordinarily low that any one biomarker candidate will provide clinically useful information, large numbers of candidates must be tested if there is to be any hope of identifying a clinically useful biomarker. PAGE 25 OF 124 "Unfortunately, there is a major bottleneck in the biomarker-development pipeline because there are no quantitative tests for the majority of human proteins," Paulovich said. "As a result, tests must be developed from scratch for clinical analysis of candidate biomarkers, and this process is prohibitively expensive for testing large numbers of candidate proteins. As a result, few promising biomarkers undergo rigorous validation, and the literature is replete with lists of candidates that have not been thoroughly tested." For the project, Paulovich and colleagues used a highly sensitive and targeted analytical technology вЂ“ selected reaction monitoring mass spectrometry. This type of mass spectrometry is not new вЂ“ it has been used for years in clinical laboratories worldwide to measure drug metabolites and small molecules associated with inborn errors of metabolism. What is new is their pioneering use of this technology in a pipeline to test candidate protein biomarkers. Unlike traditional mass spectrometry, which attempts to detect all proteins in a biological sample in a scattershot fashion, this technology is highly targeted, allowing researchers to calibrate the equipment to specifically look for peptides, or protein fragments, of interest, filtering out the rest as white noise. Targeted mass spectrometry methods, particularly when combined with antibody-based enrichment of target proteins, provide a technology platform for highly specific, reproducible and sensitive quantification of many proteins from a small drop of blood. Mass spectrometry-based tests have several advantages over traditional technologies, and they can be performed more quickly and at a lower cost. "We aimed to test the possibility that a staged biomarker pipeline based on targeted mass spectrometry would enable the prioritization and testing of very large numbers of candidate biomarkers in preclinical trials. The hope was that this would enable more comprehensive testing of candidate biomarkers and thus a greater success rate for clinical validation." Stage one of the biomarker discovery pipeline involved using targeted mass spectrometry to detect candidate biomarker proteins in the blood. Stage two sought to determine whether these proteins were elevated in the blood of mice with breast cancer as compared to healthy mice. Stage three involved developing blood tests that could be used in preclinical trials to detect the most promising protein candidates associated with early breast cancer development. Although previous work, including that of Paulovich and colleagues, had analyzed the performance of the individual stages in isolation, these components had never before been assembled into a pipeline, and the numbers of proteins tested in previous studies were generally too small to demonstrate the feasibility of translating to clinical use. PAGE 26 OF 124 For the study, the researchers tested 80 blood samples from healthy control mice and mice harboring preclinical or clinically apparent breast cancers. They also studied a group of mice that experience conditions that commonly affect the results of cancer screening tests. The researchers found 36 blood biomarkers of breast cancer in this mouse model. Of these, two were elevated in the blood of tumorbearing mice before the tumors could be seen or felt, indicating that they enabled early detection of the cancers. The purpose of the study was not to find biomarkers for breast cancer that would be of use in humans, but rather to develop and test technologies in a preclinical model before embarking on human studies. "It remains to be tested whether any of the specific biomarkers identified in the mouse will be of use in humans, where disease and biological variation will be much greater than in a mouse model. It is more likely that we have developed a road map for conducting more effective biomarker studies in humans," Paulovich said. Headline 3: Researchers use human vaccine to cure prostate cancer in mice Published by: Medical Express Date of Publication: June 19, 2011 Source: http://medicalxpress.com University of Leeds researchers, funded by Cancer Research UK, have used a library of DNA to create a vaccine that could be used to treat cancer, according to a study published in Nature Medicine. Before now, 'gene therapy' vaccines have often delivered just one gene to stimulate the immune system. It produces a protein, called an antigen, which activates the immune system to destroy cancer cells. It has been difficult to develop successful cancer vaccines because each tumour has specific proteins and identifying the right antigens has been a huge challenge. Scientists have also tried to boost the effectiveness of vaccines by using several genes to increase the chances of producing successful antigens. But a worry has always been that the immune system's response would be too strong for the body to handle. But now researchers, working with the Mayo Clinic in Rochester, US, have solved this problem in experiments involving mice. The team used doses of a vaccine made from a virus which contained a 'library' of DNA, containing multiple fragments of genes and therefore many possible antigens. This approach did not send the immune system into overdrive, which had been a concern. Instead the range of DNA meant the vaccine was able to target the tumour through many routes. Importantly, the DNA library was harvested from the same organ as the tumour. This meant that the immune system 'self-selected' the cancer antigens to respond to and did not react against other healthy parts of the body. Also, the process of self-selection was triggered when the vaccine was PAGE 27 OF 124 injected into the bloodstream, an approach to vaccination that is far more practical than injecting directly into tumours. The researchers delivered a library of DNA taken from healthy prostate tissue in mice. When delivered in a virus, the vaccine successfully treated mice with prostate cancer. University of Leeds' Professor Alan Melcher, co-author of the study, said: "This is the first time we've been able to use a whole library of DNA in a viral vaccine successfully. "The biggest challenge in immunology is developing antigens that can target the tumour without causing harm elsewhere. "By using DNA from the same part of the body as the tumour, inserted into a virus, we may be able to solve that problem." The vaccine was made by putting the DNA library inside a vesicular stomatitis virus (VSV), which stimulates an immune response that can then track down and kill tumour cells. Professor Peter Johnson, Cancer Research UK's chief clinician, said: "This is an interesting and significant study which could really broaden out the field of immunotherapy research. "Although the vaccine didn't trigger the immune system to overreact and cause serious side effects in mice, it will need to be further developed and tested in humans before we can tell whether this technique could one day be used to treat cancer patients." Headline 4: Generx DNA-Based Angiogenic Therapy Receives Clearance for Late-Stage Registration Clinical Study for Coronary Artery Disease Published By: Medical News today Date of Publication: June 15, 2011 Source: http://www.medicalnewstoday Cardium Therapeutics (NYSE Amex: CXM) today announced that it has received clearance from the Russian Ministry of Health and Social Development to commence a Phase 3 registration study for the Company's Generxв„ў (alferminogene tadenovec, Ad5FGF-4) biologic product candidate. Generx is a new and innovative DNA-based angiogenic therapy designed for the potential treatment of myocardial ischemia due to coronary artery disease. The Russian Health Authority has assigned Generx the therapeutic drug trade name of Cardionovoв„ў for marketing and sales in Russia. The new YouTube video "Cardium Generx Cardio-Chant" provides an overview of the Company's Generx product candidate, here. This newly approved clinical study (ASPIRE) is a randomized, controlled, parallel group, multi-center study designed to evaluate the safety and efficacy of Cardium's Generx product candidate using PAGE 28 OF 124 SPECT imaging to measure improvements in microvascular cardiac perfusion following a one-time, non-surgical, catheter-based administration of Generx DNA-based angiogenic therapy. As designed, the ASPIRE clinical study is expected to enroll approximately 100 men and women with myocardial ischemia due to coronary artery disease at up to three leading medical centers in Moscow. The study's primary efficacy endpoint will be the improvement in reversible perfusion defect size as measured by SPECT imaging. The ASPIRE study will represent the fifth clinical study under Generx's clinical development program that when completed will have enrolled more than 750 patients at over 100 medical centers throughout the U.S., Canada, South America, Western Europe and Russia. Based on the specified clearance for the Russian Health Authority, with positive safety and efficacy data from this single registration study, Cardium's Russian sponsor and development partner, Advanced Biosciences Research, an affiliate of the contract research organization bioRASI, would be in a position to consider the submission of an application for marketing and sales of Generx in the Russian Federation, and to advance forward with applications and submissions seeking approval for marketing and sales of Generx in certain other countries of the Commonwealth of Independent States, comprising former republics under the Soviet Union. The ASPIRE study could also provide additional clinical evidence regarding the safety and effectiveness of Generx that would be useful for optimizing and broadening commercial development pathways in other industrialized countries. Positive results from the prior Phase 2a clinical study (Grines et al., J Am Coll Cardiol 2003; 42:133947) showed that Generx improved myocardial blood flow in the ischemic region of the hearts of men and women following a single intracoronary infusion as measured by the objective efficacy endpoint of SPECT imaging. As noted in the publication, the mean change observed in Generx-treated patients was a 4.2% absolute reduction (which represents a 20% relative reduction) in the reversible perfusion defect size from baseline at eight weeks (p<0.001), while the placebo group showed only a 1.6% absolute reduction from baseline (not significant) at eight weeks following treatment. The observed treatment effect for patients receiving Generx was similar in magnitude to that reported in the literature for patients undergoing angioplasty/stent or revascularization procedures with reversible perfusion defects of comparable size at one year following these procedures. An independent long-term study published in Circulation (Meier et al, Circ. 2007; 116:975-983) provided key evidence indicating that men and women with more recruitable collateral circulation have a better chance of surviving a heart attack than patients who have less developed collateral circulation. This important study quantitatively evaluated coronary collateral blood flow in 845 patients with coronary artery disease during a 10-year follow-up period and showed that long-term cardiac mortality was approximately 66% lower in patients with a highly developed collateral vessel blood supply (p=0.019). For the first time, this study showed the importance of collateral circulation beyond simply the relief of angina and provided further support of the potential for long term benefits from angiogenic therapy. PAGE 29 OF 124 "We are pleased to receive clearance from the Russian Ministry of Health and Social Development and look forward to initiating our ASPIRE study with the assistance of the bioRASI organization. From a global perspective, it is expected that over 80% of the future increase in coronary heart disease mortality will occur outside the U.S., and the economic burden of heart disease is no longer confined to the industrialized world. With the exception of sub-Saharan Africa, cardiovascular disease is the leading cause of death in the developing world as a result of accelerating tobacco use, diet and lifestyle changes. There is a need for innovative and cost-effective advanced cardiovascular care to meet the accelerating levels of cardiovascular disease affecting global markets. A new video "Cardium Generx Cardio-Chant" provides an overview of our Generx product candidate here. We believe that Generx may offer the potential for a one-time, non-surgical cost-efficient treatment option for patients with myocardial ischemia due to coronary artery disease," stated Christopher J. Reinhard, Cardium's Chairman and Chief Executive Officer. Generx Product Candidate Generx (Alferminogene tadenovec, Ad5FGF-4) is a DNA-based angiogenic growth factor therapeutic product candidate representing a new class of cardiovascular biologics as a treatment for patients with advanced coronary artery disease. Generx is designed to stimulate and promote the growth of supplemental collateral vessels to enhance myocardial blood flow (perfusion) following a one-time intracoronary administration from a standard cardiac infusion catheter in patients who have insufficient blood flow due to atherosclerotic plaque build-up in the coronary arteries. Generx has progressed through four randomized, placebo controlled clinical studies at over 100 medical centers in the United States and Western Europe that have enrolled over 650 patients. The ASPIRE study (A Randomized, Controlled, Parallel Group, Multi-center Study To Evaluate The Efficacy And Safety Of Ad5FGF-4 Using Adenosine SPECT Myocardial Perfusion Imaging In Patients With Stable Angina Pectoris) will evaluate the safety and efficacy of Generx using adenosine SPECT imaging at leading medical centers in Moscow. The Russian Health Authority has assigned Generx with the therapeutic drug trade name of Cardionovo for marketing and sales in Russia. Headline 5: FDA clears Siemens Biograph mMR Published By: Biospectrum India Date of Publication: June 14, 2011 Source: http://www.biospectrumindia.com The US FDA cleared the Siemens Biograph mMR system, the first device to simultaneously perform a positron emission tomography scan, commonly known as PET scan, and a magnetic resonance imaging (MRI) scan. PAGE 30 OF 124 PET scans allow physicians to see how the organs and tissues inside the body are actually functioning by injecting a radioactive chemical tracer into the patientвЂ™s bloodstream. MRI uses magnetic fields and radiowaves to produce detailed images of organs, soft tissues, bone and other internal body structures. Previously, physicians could use a PET and computer tomography (CT) scanner to image the body. Advantages of the Siemens Biograph mMR system over current systems include simultaneous imaging, reduced radiation dose, and increased soft tissue contrast. "The Siemens PET/MRI system allows two tests to run simultaneously without having to move the patient to a different scanning system," Dr Alberto Gutierrez, director of the Office of In Vitro Diagnostic Device Evaluation and Safety in the FDAвЂ™s Center for Devices and Radiological Health. "Minimizing changes in a patient's position between tests allows physicians to compare images more easily and helps them get the most accurate information possible." The Biograph uses MRI rather than CT to produce detailed images of the internal structures of the body. Because MRI makes images based mainly on the concentration of water in the body, it can produce greater detail of nearly all the internal structures of the body as compared with CT, which uses X-rays to make images. This could provide the physician with additional information about a patientвЂ™s condition. Additionally, the Biograph mMR system allows physicians to acquire images at a significantly lower radiation dose compared to a PET/CT system. Although the radiation dose from the PET exam remains unchanged, MRI does not use ionizing radiation, so the entire ionizing radiation dose from the CT scan is eliminated. The decreased radiation dose is especially significant for sensitive populations, such as children or patients who are receiving multiple scans. The FDA cleared the Siemens system based on bench tests that compared the device with a predicate PET/CT device. The Biograph mMR system is indicated for anyone who needs diagnostic PET or MRI imaging. However, people with pacemakers, defibrillators or other implanted electronic devices should not be scanned with the Biograph mMR system unless those devices are specifically indicated for use in the MRI environment, because the strong magnetic fields of the MRI system may interfere with those devices. Headline 6: Dengue Virus Circulating Between Monkeys and Mosquitoes Could Emerge to Cause Human Outbreaks Published By: Science Daily Date of Publication: June 13, 2011 PAGE 31 OF 124 Source: http://www.sciencedaily.com/ More than a thousand years ago, somewhere in Southeast Asia, a fateful meeting occurred between a mosquito-borne virus that infected mainly monkeys and a large, susceptible group of humans. The result: the world's first outbreak of dengue fever. Today, dengue virus -- which can produce high fever, excruciating joint pain and even death -- has spread throughout tropical Asia, Africa and South America, and in 2008 it re-appeared in the Florida Keys. It could be even more widespread along the U.S. Gulf Coast but there is no surveillance in place to detect it. Annually dengue strikes about 100 million people and causes an estimated 50,000 deaths, thriving in the urban environments infested by Aedes aegypti, the mosquito species primarily responsible for human dengue transmission. Meanwhile, the virus' forest-dwelling counterpart -- known as "sylvatic dengue" -- continues to flourish in Southeast Asia and West Africa, cycling between non-human primates and the mosquitoes that feed on them. Since the 1970s, sylvatic dengue has received very little scientific attention -- a situation that badly needs to be remedied, according to the authors of "Fever from the forest: Prospects for the continued emergence of sylvatic dengue virus and its impact on public health," an article published online June 13 in Nature Reviews Microbiology. "This virus continues to circulate in the forests, and now economic and ecological pressures are driving more and more people into the forests in Africa and Southeast Asia," said University of Texas Medical Branch at Galveston assistant professor Nikos Vasilakis, lead author of the paper. "In the last 10 years we've seen a number of outbreaks of disease with real public health impact caused by what we call zoonotic viruses, viruses that start out in wild animals but can also be transmitted to humans -look at SARS, Nipah and Hendra, for example. Sylvatic dengue could be capable of a similar emergence -- or rather, re-emergence, since we know previous dengue spillovers into urban and near-urban settings have occurred." Dengue virus may also be capable of movement from the widespread urban cycles into primates and forest mosquitoes of Latin America, which would establish a new reservoir for human infections in the New World. In the paper, Vasilakis and his collaborators identify two factors that make a dengue re-emergence a "clear and present danger": rapid human population growth near and in tropical forests, and the fact that little or no genetic change would be needed for sylvatic dengue to adapt to human hosts and urban mosquitoes. PAGE 32 OF 124 "Experiments show that there is little or no adaptive barrier to the emergence of sylvatic dengue into human populations," Vasilakis said. "In other words, the virus can emerge from its current environment at any time, without further adaptation." The article also presents additional reasons for boosting research into sylvatic dengue, among them the possibility that its behavior in nonhuman primate animal models might offer critical new perspectives on the pathology of human dengue. (Most monkeys tested so far show no clinical signs of the disease, limiting their usefulness as experimental models.) Another significant issue is the possibility that vaccines against human dengue, which could be licensed in as little as five years, might push the virus to the brink of eradication in the urban, human transmission cycle, leaving an ecological opening that could be filled by sylvatic dengue. "We see a precedent for this with yellow fever, where we have a very good vaccine -- urban yellow fever has been nearly eliminated in some regions -- but we don't have good vector control programs, and especially in South America we now have outbreaks fueled by sylvatic yellow fever," Vasilakis said. "If we eradicate human dengue and then stop vaccinating, as we often do after the disease disappears, we could see a re-emergence of dengue from a sylvatic source." With the exception of a research program in Malaysia that ended in 1975, fieldwork on sylvatic dengue has been minimal, according to Vasilakis. In the article, he and his fellow authors call for new surveillance programs to monitor mosquitoes, non-human primates and humans in areas where sylvatic dengue is endemic, as well as the development of new diagnostic tools that will enable researchers to more easily accomplish those studies. (One such surveillance effort is now underway in Senegal, funded by the National Institutes of Health and led by UTMB professor Scott Weaver, the paper's senior author.) "Of all the viruses with the potential to shift from animals into humans, the most likely to do so are those that, like sylvatic dengue, are carried by the non-human primates and/or bats," Vasilakis said. "For our own good, we need to know as much as we can about this virus." Other authors of the paper include Jane Cardosa of the Universiti Sarawak Malaysia, Kathryn Hanley of New Mexico State University and Edward Holmes of Pennsylvania State University. The National Institutes of Health supported this work. Headline 7: Human Adult and Embryonic Stem Cell Research is Complementary, According to Social Scientists Published By: Medical News Today Date of Publication: June 12, 2011 PAGE 33 OF 124 Source: http://www.medicalnewstoday.com New research says studying both adult and embryonic stem cells can benefit medical science, but banning the study of either type could harm studies of the other. Researchers from the University of Michigan, Stanford University and the Mayo Clinic in Rochester, Minn. recently investigated whether the increased number of studies with a certain type of adult stem cell has changed the overall course of research in the field. The researchers analyzed more than 2,000 scientific papers and found adult stem cells are not replacing human embryonic stems cells in the laboratory. Instead, the two cell types have proven to be complementary and any disruption of federal funding, they say, would negatively impact stem cell research overall. "This is an important study that systematically examines the co-authorship networks of stem cell research articles and uses those to understand the interactions between two complementary areas of research," says Julia Lane, program director for Science of Science & Innovation Policy at the National Science Foundation (NSF), which funded the study. "It is particularly interesting because it uses new analytical techniques to advance our understanding of how the implementation of policy in one area can affect scientific research in another area." "The incentives to use both types of cell in comparative studies are high," says Jason Owen-Smith, a sociologist at University of Michigan. He notes the science behind adult stem cells that can be "reprogrammed," called human induced pluripotent stem cells (hiPSCs), is still in its infancy, having become widely available in 2007. "As a result, induced pluripotent stem cells do not offer an easy solution to the difficult ethical questions surrounding embryonic stem cell research," he says. Pluripotent stem cells are those capable of differentiating into any type of tissue, hence the attractiveness of embryonic stem cells, or hESCs, also called ES cells, which are also pluripotent. The researchers examined stem cell research papers published between 1998 and 2010. They found the proportion of papers using human adult and human embryonic stem cells together is growing faster than those using adult stem cells alone. In 2008, only 15 or 5.1 percent of all papers examined in the study reported using adult stem cells, and only three of those papers combined the use of human adult and human embryonic stem cells. By 2010, some 161 of 574 or 28 percent of papers reported on studies of both cell technologies, and 62.1 percent of those papers paired adult and embryonic cell lines. PAGE 34 OF 124 Because use of the two cell types has become so intertwined, any federal policy that would deny funding for embryonic stem cell research "would derail work with a nascent and exciting technology," says Owen-Smith. If federal funding stops for human embryonic stem cell research, it would have a serious negative impact on adult stem cell research, says Stanford University bioethicist Christopher Scott, one of the paper's co-authors. "We may never be able to choose between iPS and ES cell research because we don't know which type of cell will be best for eventual therapies." "The whole point with science policy is to have a more scientific basis to understand the impacts of policy decisions on science if and when those decisions are made," says Lane. In addition to NSF, this research was funded by grants from the National Institutes of Health, and the Stanford Institute for Stem Cell Biology and Regenerative Medicine. Headline 8: ImmunoCellular Therapeutics Ltd. Expands Phase II Trial of ICT-107 Published By: Medicalnew today Date of Publication: June 10, 2011 Source: http://www.medicalnewstoday.com ImmunoCellular Therapeutics, Ltd. ("ImmunoCellular" or the "Company") (OTCBB: IMUC), a biotechnology company focused on the development of novel immune-based cancer therapies, today announced the expansion of sites for its Phase II clinical trial of ICT-107. ICT-107 is the Company's dendritic cell based cancer vaccine candidate targeting multiple tumor antigens for the treatment of glioblastoma multiforme (GBM). The Company had initially planned to conduct the study, which is now underway, at up to 15 clinical centers, but has increased the number of anticipated sites to 20 or more. ImmunoCellular has qualified 21 sites so far and has submitted the trial to 12 prospective sites' Institutional Review Board (IRB) for approval. Of these 12 sites, 6 have received their IRB approval. The Phase II trial of ICT-107 is a double-blind, placebo-controlled, 2:1 randomized study designed to evaluate the safety and efficacy of ICT-107 in patients with newly diagnosed GBM. The study is enrolling patients at medical institutions in collaboration with leading experts and opinion leaders in neuro-oncology at those sites. "We are excited to accelerate and expand site enrollment of our Phase II clinical trial for ICT-107," said Manish Singh, Ph.D. president and CEO of ImmunoCellular Therapeutics. "With this trial we look forward to generating data in support of the safety and efficacy of ICT-107 in the treatment of GBM and to further support the promising outcomes reported in our Phase I study." PAGE 35 OF 124 In the Phase I clinical study of ICT-107 in GBM, 16 newly diagnosed patients who received the vaccine in addition to standard of care of surgery, radiation and chemotherapy demonstrated a one year overall survival of 100 percent and a two year survival of 80 percent. The study's median progression free(PFS) survival of 16.9 months compared favorably to the historic median PFS of 6.9 months. 10 of the 16 patients continue to survive. This compares favorably with historical 61.1 percent one-year and 26.5 percent two-year survival based on the standard of care alone. The data shows 6 out of the 16 (37.6%) newly diagnosed patients who received ICT-107 continue to show no tumor recurrence, with 3 of these patients (18.8%) remaining disease-free for almost four years while the other 3 patients have gone more than 2 and a half years disease-free. No treatment related serious adverse events have been observed to date. Headline 9: Life Technologies Negotiates License to TAL Effector Gene Control Technology Published By: Gen News Date of Publication: June 10, 2011 Source: http://www.genengnews.com Firm claims platform allows the precise programming and control of genetic circuitry. Life Technologies signed an exclusive license agreement for a technology that effectively allows the programming and control of genetic circuitry in engineered pathways and organisms. The Transcription Activator-Like (TAL) Effector Technology enables the design of proteins that specifically target and bind to a desired sequence of DNA, allowing the delivery of elements that control or modify specific aspects of cellular function, Life Technology explains. The firm initially plans to make the TAL Effector technology available through its Geneart gene synthesis portfolio. However, it says the platform will have far broader applications in fields such as bioproduction, stem cell research, and drug discovery. In August 2010, Life Technologies purchased about 59% of GermanyвЂ™s Geneart, which concentrates on DNA engineering and processing. It provides custom gene-synthesis and gene-optimization services to its customers. Life Technologies now owns a 74% stake in that company. The TAL Effector platform was originally developed by scientists at the Martin-Luther-UniversitГ¤t Halle-Wittenberg in Germany and previously licensed to the Two Blades Foundation (2Blades) for all applications in plants. Life Technologies' license, signed with with the inventors and the Two Blades Foundation, gives the firm research use for plant applications. Rights to commercial applications of the technology in plants have been retained by 2Blades. PAGE 36 OF 124 Headline 10: Shingles May Be Related to Elevated Risk of Multiple Sclerosis Published By: Science Daily Date of Publication: June 09, 2011 Source: http://www.sciencedaily.com Taiwanese investigators have found that there can be a significantly higher risk of multiple sclerosis (MS) occurring in the year following a shingles, or herpes zoster, attack. The findings, which support a long-held view on how MS may develop, are published in The Journal of Infectious Diseases and now available online. MS is an autoimmune disease that affects the brain and spinal cord, leading to inflammation and nerve damage as the body's immune cells attack the nervous system. Possible causes that may trigger the inflammation include environmental, genetic, and viral factors. One virus that has been associated with MS is varicella zoster virus, the cause of herpes zoster. In a study conducted by Herng-Ching Lin, PhD, and colleagues at Taipei Medical University in Taiwan, 315,550 adults with herpes zoster and a control group of 946,650 subjects were tracked and then evaluated for MS occurrence during a one-year follow-up period. The control group was selected randomly from a pool of subjects who had not been diagnosed with herpes zoster or other viral diseases. After adjusting for monthly income and geographic region, the authors found that the group with herpes zoster had a 3.96 times higher risk of developing MS than the control group. The authors noted that this risk, although increased, was still low, as is the frequency of MS in general. The study also noted an interval of approximately 100 days between a herpes zoster event and occurrence of MS. Although the study was limited almost entirely to Han Chinese adults, the large scope of this nationwide case-controlled study, 1.26 million sampled patients, provides strong epidemiological evidence for a possible role for herpes zoster in the development of MS. The authors also point out that MS has a lower prevalence in Asian compared to Western populations and, thus, it may be difficult to project their findings to other populations. In an accompanying editorial, Teresa Corona, MD, and Jose Flores, MD, of the National Institute of Neurology and Neurosurgery in Mexico noted that "The evidence provided in this studyвЂ¦allows us to better understand the role of these viral factors as an MS risk among certain genetically susceptible individuals," and that the study should be corroborated in other parts of the world to help clarify the role of this and other viruses in MS. Headline 11: Pharmasset Announces the Expansion of the ELECTRON Trial in Chronic Hepatitis C Published By: Medical News Today PAGE 37 OF 124 Date of Publication: June 09, 2011 Source: http://www.medicalnewstoday.com Pharmasset, Inc. (Nasdaq: VRUS) announced the addition of three treatment cohorts to the ELECTRON trial of PSI-7977, a nucleotide analog polymerase inhibitor, for the treatment of chronic hepatitis C (HCV). The rapid and consistent antiviral effects and high barrier to resistance demonstrated with PSI-7977 to date provide the rationale for additional exploratory regimens in this setting. This amendment will add one arm exploring 12 weeks of PSI-7977 monotherapy (without peginterferon and ribavirin) and two arms of interferon-sparing therapy: one for 8 weeks of PSI-7977 plus peginterferon and ribavirin (Peg-IFN/RBV) in patients with HCV genotype 2 (GT2) or 3 (GT3) and one for 12 weeks of PSI-7977 plus Peg-IFN/RBV in patients with HCV genotype 1 (GT1) prior null responses. "The combination data reported at EASL demonstrated that SVRs were achievable with two oral DAAs in the absence of peginterferon and ribavirin," stated Bill Symonds, PharmD, Pharmasset's Senior Vice President of Clinical Pharmacology and Translational Medicine, "We continue to explore the potential for removing peginterferon and ribavirin from the HCV treatment regimen. Given the encouraging data we are seeing in ELECTRON, we have decided to expand the study to investigate PSI-7977 monotherapy, as well as shorter treatment regimens based on the promising data we reported at EASL from PROTON." Pharmasset anticipates reporting results from the first four arms of the trial (n=40) during the second half of 2011. We have submitted a number of abstracts to the 2011 American Association for the Study of Liver Diseases (AASLD) meeting, including data from the ELECTRON and PROTON trials. Headline 12: Pfizer Conducts First "Virtual" Clinical Trial Allowing Patients to Participate Regardless Of Geography Published By: Medicalnewstoday Date of Publication: June 08, 2011 Source: http://www.medicalnewstoday.com Pfizer Inc. announced today that it is conducting the first-ever randomized clinical trial under an investigational new drug (IND) application that manages study participation entirely using electronic tools and allows patients to participate in the clinical trial regardless of their proximity to clinical sites. The pilot project, initiated following review from the U.S. Food and Drug Administration (FDA), uses mobile phone and web-based technology to collect necessary data for the trial without clinic visits. The Research on Electronic Monitoring of OAB Treatment Experience - REMOTE - is a U.S.-based Participatory Patient-Centered (PPC) clinical trial designed to assess the safety and efficacy of Detrol LA (tolterodine tartrate), a treatment for overactive bladder (OAB). Pfizer and its research partners hope to determine whether the results of the pilot REMOTE "virtual trial" can replicate the results of a PAGE 38 OF 124 previously completed Phase IV Detrol LA trial, and in this way begin to validate virtual, patientcentered approaches to clinical research. "With the REMOTE virtual trial pilot, for the first time we can make it possible for patients to participate in clinical trials without having to visit physical sites," said Pfizer Executive Vice President and Chief Medical Officer Freda Lewis-Hall, M.D., who announced the new trial today during remarks at the National Library of Medicine (NLM) Clinical Trials Conference in Bethesda, MD. "Studies like REMOTE could make biomedical science much more accessible to people who have long been excluded from or under-represented in clinical trials. Putting research within reach of more diverse populations has the potential to advance medical progress and lead to better outcomes for more patients." The REMOTE trial is the first-ever randomized "virtual" clinical trial under an IND application to secure patient consent online using video/multimedia and online testing. Study investigators will ship all blinded study medication to patients at home rather than dispensing it at a clinic visit. Researchers will manage study conduct remotely, and share clinical trial data and results with patients, enabling them to add them to their own personal health records. Investigators in the REMOTE trial plan to enroll about 600 patients from about 10 states across the United States. Enrolled patients will participate in the study screening process through the Internet, actively manage their own trial activity and report results directly to a trial investigator who keeps close oversight of patient eligibility and safety. As a result, researchers expect to save time and obtain better quality, more reliable data through increased patient compliance, lower withdrawal rates and real-time data collection. "This approach, if proven successful, holds considerable promise in speeding up clinical trials while improving their quality," said Briggs W. Morrison, M.D., Pfizer's senior vice president of Worldwide Medical Excellence. "This program and similar programs that may follow could lead to an entirely new way for patients to participate in trials and contribute to biomedical research." The REMOTE clinical trial pilot is consistent with the mission of the FDA's Clinical Trials Transformation Initiative (CTTI) to improve the quality and efficiency of clinical trials. Pfizer has been an active participant in multiple CTTI projects. "Modernization of clinical trials is a key initiative of FDA. We commend Pfizer's progress on the REMOTE pilot and encourage all manufacturers considering other novel ideas in advancing clinical trials to have prospective discussions with the Agency regarding trial design and oversight," said Janet Woodcock, M.D., director, Center for Drug Evaluation and Research at FDA. "This virtual method enables scientists to conduct trials more efficiently. Additionally, as more people participate in trials conveniently from home, the results of trials may apply to a broader patient PAGE 39 OF 124 population," said Dr. Steven Cummings, M.D., Emeritus Professor of Medicine at the University of California San Francisco. Pfizer has reviewed the study approach with the FDA and two institutional review boards have approved the study. Physicians will carefully monitor patient data and patient safety throughout the trial. Patients will be able to interact with study physicians remotely 24 hours a day. Headline 13: Stem cells with bone-regenerating hormone help mend fractures Published By: The Times of India Date of Publication: June 06, 2011 Source: http://www.timesofindia.indiatimes.com An animal study has shown that transplantation of adult stem cells, enriched with a bone-regenerating hormone, can help mend bone fractures that are not healing properly. Anna Spagnoli, MD, associate professor of paediatrics and biomedical engineering led researchers at the University of North Carolina at Chapel Hill School of Medicine. They demonstrated that stem cells manufactured with the regenerative hormone insulin-like growth factor (IGF-I) become bone cells and also help the cells within broken bones repair the fracture, thereby speeding the healing. "This problem is even more serious in children with osteogenesis imperfecta, or brittle bone disease, and in elderly adults with osteoporosis, because their fragile bones can easily and repeatedly break, and bone graft surgical treatment is often not successful or feasible," Spagnoli said. Fractures that do not mend within the normal timeframe are called non-union fractures. Using an animal model of a non-union fracture, a "knockout" mouse that lacks the ability to heal broken bones, Spagnoli and her colleagues studied the effects of transplanting adult stem cells enriched with IGF-I . "More excitingly, we found that stem cells empowered with IGF-I restored the formation of new bone in a mouse lacking the ability to repair broken bones," she said. "This is the first evidence that stem cell therapy can address a deficiency of fracture repair," she stated. PAGE 40 OF 124 This success in an animal model of fracture non-union, Spagnoli said, "is a crucial step toward developing a stem cell-based treatment for patients with fracture non-unions". IGF-I is currently approved for treatment of children with a deficiency of this hormone, causing growth failure Headline 14: Panacea Biotec partners with GAVI Published By: Biospectrumasia Date of Publication: June 06, 2011 Source: http://www.biospectrumasia.com New Delhi-based Panacea Biotec, Indias one of the biggest vaccine manufacturers who introduced worlds first fully liquid Pentavalent vaccine EasyFive in 2005, has pledged to support the cause of GAVI alliance by further reducing the cost of its Pentavalent Vaccine EasyFive to the tune of 10 percent to15 percent in coming years, thereby increasing access of vaccines to more millions of children. After introduction of EasyFive in developing countries in year 2008, price of Pentavalent vaccine was brought down by 18percent in 2010. The new vaccine price reductions are expected to help to some extent on donor support for GAVI & contribute to reducing GAVIs funding challenge. Commenting on this initiative, Dr Rajesh Jain, joint. managingdirector, Panacea Biotec Ltd, said, We are very happy to extend our continued, unequivocal and unstinted support to GAVI for this noble social cause as developing countries are facing severe challenges in saving childrens lives and protecting people health. The combined demand of all combination pediatric vaccines worldwide is estimated to grow up to $1.6 billion by 2012. Pentavalent vaccine market is estimated to cross a mark of$1 billion out of which UN agencies are likely to procure vaccines worth more than $425 million in 2011. Making vaccines affordable as demands grow is the only model which can create sustainable interest with Governments, Donors and other International Agencies to ensure each child is immunized from protectable disease", added Dr. Rajesh Jain. Panacea Biotec has a long term agreement with UNICEF to supply 75 million doses for the year 2010, 2011 and 2012. EasyFive is worlds first fully liquid pentavalent vaccine developed by Panacea Biotec and introduced in India in January 2005, which immunizes children against five dreadful diseases (Diptheria+ Tetanus+ whole cell Pertussis+ Hepatitis B+ Hemophilus Influenza Type b) of early childhood. PAGE 41 OF 124 Panacea Biotec is considered to be the largest vaccine producer in India has been ranked as the 3rd largest biotechnology company. The product portfolio of the Company includes highly innovative prescription products in important therapeutic areas such as pain management, diabetes management, renal-disease management, anti-osteoporosis, anti-tubercular, gastro-intestinal care products and vaccines. Launched in 2000, the GAVI Alliance is a global health partnership representing stakeholders in immunisation from both private and public sectors: developing world and donor governments, private sector philanthropists such as the Bill & Melinda Gates Foundation, the financial community, developed and developing country vaccine manufacturers, research and technical institutes, civil society organisations and multilateral organisations like the World Health Organization (WHO), the United Nations Children's Fund (UNICEF) and the World Bank. Headline 15: Novel First-In-Class Anti-Cancer Agent in Development by Niiki Pharma Shows Promising Phase I Results Published By: Medicalnewstoday Date of Publication: June 02, 2011 Source: http://www.medicalnewstoday.com Niiki Pharma announced that it will present interim data from the ongoing Phase I clinical study for its lead product, NKP-1339, at the 2011 American Society for Clinical Oncology meeting in Chicago, IL. NKP-1339 is a novel transferrin targeted ruthenium based anti-cancer compound. The intracellular targets of NKP-1339 include GRP78, a key regulator of mis-folded protein processing. In preclinical studies, in vivo and in vitro activity has been demonstrated against multiple tumor types, including those resistant to other anti-cancer agents. The NKP-1339 Phase I trial is a dose-ascending trial and determines the safety, tolerability, maximum tolerated dose (MTD) and pharmacokinetics of NKP-1339. A total of 16 patients with metastatic solid tumors resistant to standard therapies have been treated to date at six different dose levels. NKP1339 treatment has been generally well tolerated, with the most common drug related side effects of grade 1-2 fever and mild flu-like symptoms. MTD has not been reached and NKP-1339 dose escalation continues. Signs of anti-tumor activity (stable disease greater than or equal to four months; tumor regression) have been observed. A patient with a neuroendocrine tumor (NET) of the small intestine has been on NKP-1339 therapy for over 13 months with a continuing minor response. The patient remains on NKP-1339 therapy. Another patient with the metastatic gastrinoma NET exhibited six months stable disease, and two patients with metastatic non-small cell lung cancer exhibited four months stable disease. PAGE 42 OF 124 The NKP-1339 Phase I trial is being led by Dr. Daniel Von Hoff, Translational Genomics Institute, Arizona, and Dr. Howard Burris, Sarah Canon Research Institute, Tennessee. Reflecting on NKP1339's novel mechanism of action, Dr. Von Hoff noted "Resistance to anti-cancer therapy remains a major challenge in treatment of patients with metastatic cancer. First-in-class drugs, like NKP-1339, can take us one step further to address this high unmet need." While Dr. Burris commented, "The results to date indicate that NKP-1339 could be a promising new agent that would enhance our anticancer armamentarium." Headline 16: Ampio Pharmaceuticals, Inc. Announces Initiation of Phase 1B Clinical Trial for Its Anti-inflammatory Drug Ampionв„ў Published By: Medicalnewstoday Date of Publication: June 1, 2011 Source: http://www.medicalnewstoday.com Ampio Pharmaceuticals, Inc. (NASDAQ: AMPE)("Ampio") announced that it received ethics board approval for a Phase 1B clinical trial in Australia of its biologic anti-inflammatory agent, Ampionв„ў. Patients are now being recruited for first dosing in the three arm, placebo controlled, 60 patient trial designed to demonstrate efficacy in the treatment of osteoarthritis of the knee as well as to confirm patient safety and tolerance. The present "standard of care" treatment for this condition is the injection of a short acting local anesthetic agent combined with a long acting steroid into and around the joint. In the Ampion trial the mitigation of pain and loss of function caused by osteoarthritis will be assessed at intervals from the time of injection. Patients will be evaluated for 72 hours and various parameters will be followed to demonstrate that Ampionв„ў is well tolerated and provides pain relief through decreased inflammation as well as demonstrated improvement in the range of motion of the knee. Dr. David Bar-Or, MD, Ampio's Chief Scientific Officer, noted, "We discovered this molecule in patients with severe head injury who experienced decreased immune/inflammatory function. The molecule is produced in the body from our own serum albumin and is the most abundant protein in human plasma. We realized from our studies in human tissue that this molecule is an integral part of the innate control of inflammation. We know of many molecules made by our body that increase inflammation but of very few that decrease it. We are hopeful that Ampionв„ў, with few or no side effects, will provide real relief for patients suffering from chronic inflammatory conditions," stated Dr. Bar-Or. Ampio CEO Don Wingerter noted, "Since Ampionв„ў is a biologic product made by our bodies, we believe there is the probability of markedly greater safety than steroids or other anti-inflammatory PAGE 43 OF 124 drugs. We anticipate this clinical trial will demonstrate sufficient proof of safety and efficacy to allow longer term studies in which relief may be obtained without prolonged use of steroids, especially when knee replacement is not an option. We are hopeful this drug will provide clinical utility and safety greater than products now selling in the multi-billion dollar market for anti-inflammatories." Vaughan Clift, MD, Ampio's Chief Regulatory Officer added, "We are very grateful to our Australian Principal Investigators, Dr. Peter Lewis and Dr. Andrew Comley, who helped in the design of the trial and approval process and whose leadership has resulted in encouraging support from local General Practitioners who are also identifying and referring patients into this AIK (Ampion in knee) trial. We expect the trial results will form the basis for submissions to various regulatory agencies to conduct Phase II/III studies of the active component in numerous inflammatory conditions. We believe the nature of the compound and its human origin should facilitate a faster regulatory approval path in most countries compared to the traditional new drug therapies." Headline 17: Better vaccines thanks to RNA Published By: Medicalexpress Date of Publication: May 30, 2011 Source: http://medicalxpress.com Vaccination can be just as effective with dead bacteria as with live ones, as long as you inject them with the RNA of live bacteria. This finding was published in Nature by a team of American, French, Amsterdam and Wageningen researchers, and has been available online (AOP) since on 22 May. Doctors have known for some time that you obtain the best immunity after vaccination with live bacteria. The immune system recognizes certain parts of the bacteria and remembers them, so that you become immune to them. That is, if you survive the vaccination. Because someone who is injected with live pathogens runs the risk of falling prey to the very disease they aim to ward off. So for safety reasons, doctors usually work with dead bacteria. Safer but also less effective. Michael Muller, professor of Nutrition and Nutrigenomics at Wageningen University, is co-author of the publication. He used genomics techniques and advanced computer analyses to study the difference in the response of the immune system to dead and to live bacteria. His team was looking for the answer to the big question: how can the immune cell know whether bacteria are dead or alive? Which substance is missing in dead bacteria, causing an incomplete immune response? And: Do you get complete immunity if you add that substance to the vaccine based on dead pathogens? In order to identify the mystery substance, the research team embarked on a 'killing mission', killing off bacteria in various different ways. They used alcohol, UV light, antibiotics and a type of formaldehyde. The idea was that different killing methods would destroy different substances in the bacteria. The PAGE 44 OF 124 dead bacteria were then worked into a vaccine and injected into people. As expected, almost all the dead bacteria produced an incomplete immune response. Except for the group killed with formaldehyde: these bacteria did produce a complete response. Formaldehyde was the only killing method that left the Messenger RNA, a DNA-like molecule, intact, and this suggests that the RNA is the missing substance. Mission accomplished? "Not quite," says the professor. "To make the evidence conclusive and really show that the RNA is responsible for the complete immune response, we have added RNA to a vaccine based on dead pathogens.' After vaccination, this cocktail did turn out to give a complete immune response. The results of this research not only led to more effective vaccines, but are also extremely useful for the nutrition research done by MГјller and his group. 'In our nutrigenomics research we are especially interested in how unhealthy eating derails the immune system and thus causes chronic inflammation and eventually disease, as well as in how healthy diet prevents that', explains MГјller. 'We know from research at Wageningen and elsewhere that we carry large numbers of live bacteria in and on our bodies, including our intestinal flora. Because we now know more about exactly how the immune response to bacteria works at molecular level, in the longer term we may be able to keep infections under control." Headline 18: Herbal Remedies Offer Hope as Novel Antibiotics Published By: BiotechDaily Date of Publication: May 30, 2011 Source: http://www.biotechdaily.com A new study investigates the potency of 10 Indian wild plants against bacterial and fungal infections in the mouths of oral cancer patients. Researchers at Pt. B.D.S. Health University (Rohtak, India; uhsr.ac.in/) took blood and oral swab cultures from 40 oral cancer patients undergoing treatment in the radiotherapy unit. Isolates were identified by general microbiological, staining, and biochemical methods, and absolute neutrophile counts were done using standard methods. The medicinal plants selected for antimicrobial activity analysis were Asphodelus tenuifolius Cav., Asparagus racemosus Willd., Balanites aegyptiaca L., Cestrum diurnum L., Cordia dichotoma G. Forst, Eclipta alba L., Murraya koenigii (L.) Spreng. , Pedalium murex L., Ricinus communis L. and Trigonella foenumgraecum L. The antimicrobial efficacy of the medicinal plants was evaluated by modified Kirby-Bauer disc diffusion method. The results showed that the prevalent bacterial pathogens isolated were Staphylococcus aureus (23.2%), Escherichia coli (15.62%), Staphylococcus epidermidis (12.5%), Pseudomonas aeruginosa (9.37%), Klebsiella pneumonia (7.81%), Proteus mirabilis (3.6%), and Proteus vulgaris (4.2%); the fungal pathogens were Candida albicans (14.6%) and Aspergillus fumigatus (9.37%). Out of 40 cases, 35 (87.5%) were observed as neutropenic. Eight medicinal plants (including wild asparagus, desert date, false daisy, curry tree, castor oil plant, and fenugreek) showed significant antimicrobial activity against most of the isolates, with Pseudomonas aeruginosa observed as the highest PAGE 45 OF 124 susceptible bacteria (46.6%) on the basis of susceptible index. The study was published on May 20, 2011 in the BioMed Central open access journal Annals of Clinical Microbiology and Antimicrobials. вЂњNatural medicines are increasingly important in treating disease and traditional knowledge provides a starting point in the search for plant-based medicines,вЂќ said lead author Jaya Parkash Yadav, MD. вЂњImportantly, we found that the extraction process had a huge effect on both the specificity and efficacy of the plant extracts against microbes. Nevertheless, several of the plants tested were broadspectrum antibiotics able to combat bacteria including E. coli, S. aureus, and the fungi Candida and Aspergillus. Both desert date and castor oil plant were especially able to target bacteria, such as Pseudomonas aeruginosa, which are known to be difficult to treat with conventional antibiotics.вЂќ Cancer treatments often have the side effect of impairing the patient's immune system. This can result in life-threatening secondary infections from bacteria and fungi, especially since many bacteria, like Staphylococcus aureus, are becoming multidrug resistant. Headline 19: Changing the Indian Culture in Reporting Adverse Drug Reactions Published By: Prnewswire Date of Publication: May 29, 2011 Source: http://www.prnewswire.com Adverse Drug Reactions (ADRs) are the sixth global leading cause of death among hospitalised patients and the incidence of serious ADRs in hospitalised patients is 6.7 per cent (Joshi et al). India is the world's second most populated country with over one billion potential drug consumers, and a value of US $ 1 billion worth of clinical trials, therefore it is very important to focus the attention of the medical community on the importance of the adverse drug reporting to ensure maximum patient health. Dr. Viraj Suvarna, Medical Director at Boehringer Ingelheim who is speaking at the Pharmacovigilance India Summit has said that while multinational Pharmaceutical companies which operate in India clearly have very stringent adverse event reporting requirements, doctors are reluctant to report adverse events. "Doctors in India don't really understand the difference between an adverse event and an adverse drug reaction. So they believe that they need to report only if that particular event has a causal relationship to that product in question. Despite the fact that we've trained so many doctors over so many years, one will still find them to be a little uneducated or a little hesitant to report because sometimes they feel that they could land into a medical-legal complication because once they report, then they think that that report will be processed and it could go against them", added Dr Suvarna. PAGE 46 OF 124 This culture of reluctance in reporting is now changing as The Ministry of Health in India has launched a complete roadmap for a proactive pharmacovigilance system which will increase the awareness about the benefits of adverse event reporting. This programme is called the National Pharmacovigilance Programme and it is funded by the WHO to foster the reporting culture in India and make sure that people are receiving safe medicine. This first edition of Pharmacovigilance India taking place from 27-29 June 2011 at the Hilton Mumbai International Airport will explore the National Pharmacovigilance Programme in further detail and provide an opportunity for industry stakeholders to meet, network, do business and share industry best-practices. Pharmacovigilance India Summit features informative presentations and case-studies from high profile speakers, including Dr. Y. K. Gupta, National Coordinator of Pharmacovigilance Programme of India and other key speakers from organisations such as International Society of Pharmacovigilance, UK, Bayer Healthcare Global R & D Centre, China, Boehringer Ingelheim, Baxter Healthcare, Asia Pacific, Takeda Pharmaceuticals International, USA, Panacea Biotec, Wockhardt, Novartis Healthcare, Astellas Pharma, India, Bayer Healthcare, UCB, India, and Biocon, India.. Headline 20: Patients with Rheumatoid Arthritis Receive Less Protection from Pandemic Influenza with H1N1 Vaccine, Study Shows Published By: Science Daily Date of Publication: May 28, 2011 Source: http://www.sciencedaily.com Individuals with rheumatoid arthritis taking disease modifying anti-rheumatic drugs, showed significantly less protection from pandemic influenza after receiving the H1N1 vaccine compared to healthy individuals, according to data presented at the EULAR 2011 Annual Congress. A Brazilian hospital-based study assessed responses to flu vaccines in 340 RA patients in regular follow-up compared to 234 healthy patients. Measures of protection obtained by vaccination (seroprotection rate (SP)) after immunization was over 20% lower for RA patients compared to healthy individuals (60.1% vs. 82.9% comparatively (p<0.001)). Tests to determine levels of detectable antibodies to microorganisms in the blood serum as a result of infection and immunization with the flu virus (seroconversion rate (SC)) showed a similar pattern with 53.4% of RA patients and 76.9% of healthy controls having antibodies present respectively (p<0.001). "This study has highlighted that there are differences in the level of protection between the H1N1 vaccine and the seasonal influenza vaccine so healthcare professionals should not assume that immune response will be the same with different vaccines" said Professor A. Ribeiro of the University of Sao Paolo. "In planning for future pandemic outbreaks, healthcare professionals should consider PAGE 47 OF 124 specific immunization strategies to ensure this large population of patients are as fully protected as possible from the risk of contracting pandemic flu." The vaccination's impact on disease activity (DAS28*) was also measured and nine patients (2.6%) reported worsening of symptoms with the mean disease activity score changing from 3.66 to 5.15 (p<0.05) after the H1N1 vaccination. No serious adverse events were seen across either patient group, although more subjects in the RA patient group reported more adverse events, 42% versus 30.8% with a rate of 140 events/100 patients versus 87/100 control group (p<0.005). *DAS28 (Disease Activity Score) is an index used by physicians to measure how active an individual's RA is. It assesses number of tender and swollen joints (out of a total of 28), the ethroycyte sedimentation rate (ESR, a blood marker of inflammation), and the patient's 'global assessment of global health'. A higher score indicates more active disease. Headline 21: Is It Ethical To Use Placebo In Rheumatoid Arthritis Clinical Trials? Published By: Eurekalert Date of Publication: May 27, 2011 Source: http://www.eurekalert.org The results of this study, conducted in Germany, re-open the debate on whether it is ethical to conduct placebo-controlled studies where patients in the placebo-group are at a serious disadvantage compared to patients taking the new treatments. The study analysed current study designs, for new therapies such as abatacept (OrenciaВ®), golimumab (SimponiВ®) or tocilizumab (ActemraВ®), and showed that patients in the placebo group experienced no change in medication, having to continue with their former, ineffective treatment plus placebo. "According to the Helsinki-Declaration of the World Medical Association*, a placebo-controlled study design is deemed to be ethically acceptable when there is no other effective treatment," said Dr. Juche, Johanniter-Hospital, Treuenbrietzen, Germany. "However, this analysis confirms that patients in the placebo-group are at a disadvantage as they are given no change in medication to reduce their active inflammatory condition or halt disease progression. Our recommendation is that future clinical trials should include an active comparator group to ensure that all patients receive effective treatments to improve their quality of life." In the analysis, researchers used studies from the European Public Assessment Report (EPAR) of the European Medicines Agency (EMA) for abatacept, golimumab and tocilizumab as samples. The PAGE 48 OF 124 studies chosen had to be placebo controlled at the beginning and state clinical relevant outcome criteria (e.g. DAS28**, ACR20***, Health Assessment Questionnaire and joint erosion scores). Headline 22: Transgenomic, Inc. Acquires Exclusive Worldwide License to Predictive Markers for Cancer Drug Response Published By: Prnewswire Date of Publication: May 26, 2011 Source: http://www.prnewswire.com Transgenomic, Inc. (OTC/BB: TBIO) announced today that it has acquired an exclusive worldwide license to Montefiore Medical Center's (Bronx, NY, US) patent application, "Method of Determining the Sensitivity of Cancer Cells to EGFR Inhibitors including cetuximab, panitumumab and erlotinib". The invention relates to the discovery by Montefiore scientists and collaborators that tumor-specific mutations in the genes PIK3CA and PTEN can aid in predicting patient non-response to epidermal growth factor receptor (EGFR) inhibitors, a widely prescribed class of cancer drugs. Transgenomic is incorporating the PIK3CA and PTEN gene assays into its rapidly expanding menu of cancer profiling tests available through its clinical reference laboratories and is developing testing kits for sale to other labs. Testing of these genes is also being offered to support drug development research by pharmaceutical companies that have been expressing great interest in these genes and in Transgenomic's proprietary, ultra-sensitive mutation-detection technologies. At the American Association for Cancer Research meeting in April of this year, Transgenomic described methods for detecting tumor-specific mutations at such low levels that it may be possible to identify them in patients' blood samples, not just in surgically obtained tumor tissues. "This exclusive license from Montefiore strengthens our cancer-related diagnostic test portfolio and is integral to the continued development of our leadership position in oncology," said Craig Tuttle, CEO of Transgenomic. "At Transgenomic, we are uniquely equipped to maximize the value of these genetic discoveries by combining them with the unparalleled sensitivity of our proprietary mutation- detection technologies. Our exclusive access to this new intellectual property will enable us to provide the most comprehensive analysis for predicting response to cancer treatment in the current market." About PIK3CA and PTEN Monoclonal antibody therapeutics that target the epidermal growth factor receptor (EGFR) are new and often highly effective treatments for metastatic colorectal cancer and other aggressive cancers. Unfortunately, some patients do not benefit from these drugs because their cancers have mutations in genes within the EGFR pathway. The American Society of Clinical Oncology has recommended that colorectal cancer patients who are candidates for anti-EGFR therapy should be tested for mutations in PAGE 49 OF 124 the gene K-RAS as patients with mutations in K-RAS do not benefit from these therapies. Studies from Montefiore Medical Center and elsewhere have demonstrated that mutations in PIK3CA and PTEN can also cause anti-EGFR therapies to be ineffective. A diagnostic panel that comprehensively tests all these genes has the potential to greatly improve the tailored use of these cancer treatments. About Transgenomic Transgenomic, Inc. (www.transgenomic.com) is a global biotechnology company advancing personalized medicine in cancer and inherited diseases through its proprietary molecular technologies and world-class clinical and research services. The company has three complementary business divisions: Transgenomic Pharmacogenomic Services is a contract research laboratory that specializes in supporting all phases of pre-clinical and clinical trials for oncology drugs in development. Transgenomic Clinical Laboratories specializes in molecular diagnostics for cardiology, neurology, mitochondrial disorders, and oncology. Transgenomic Diagnostic Tools produces equipment, reagents, and other consumables that empower clinical and research application in molecular testing and cytogenetics. Transgenomic believes there is significant opportunity for continued growth across all three businesses by leveraging their synergistic capabilities, technologies, and expertise. The company actively develops and acquires new technology and other intellectual property that strengthen its leadership in personalized medicine. About Montefiore Medical Center As the University Hospital for Albert Einstein College of Medicine, Montefiore is a premier academic medical center nationally renowned for its clinical excellence and scientific discovery; compassionate, patient-centered model of care; commitment to its community; and medical education, including the second largest residency program in the country. Montefiore is recognized among the top hospitals nationally and 6th out of 180 in the New York metro area by U.S. News & World Report. The Children's Hospital at Montefiore has consistently ranked in U.S. News "Americas Best Children's Hospitals," and is 2nd among those in the New York metro area. As an integrated health system, it is comprised of four hospitals, has 1491 beds and 93,000 annual hospital discharges, and is seamlessly linked by advanced technology. State-of-the-art primary and specialty care is provided through a network of nearly 100 locations across the region, including the largest school health program in the nation and a home health program. Inspired by its patients and its community, Montefiore is on the frontlines of developing innovative approaches to care and is a national model for excellence. www.montefiore.org and www.montekids.org Forward-Looking Statements Certain statements in this press release constitute "forward-looking statements" of Transgenomic within the meaning of the Private Securities Litigation Reform Act of 1995, which involve known and PAGE 50 OF 124 unknown risks, uncertainties and other factors that may cause actual results to be materially different from any future results, performance or achievements expressed or implied by such statements. Forward-looking statements include, but are not limited to, those with respect to management's current views and estimates of future economic circumstances, industry conditions, company performance and financial results, including the ability of the Company to grow its involvement in the diagnostic products and services markets. The known risks, uncertainties and other factors affecting these forward-looking statements are described from time to time in Transgenomic's filings with the Securities and Exchange Commission. Any change in such factors, risks and uncertainties may cause the actual results, events and performance to differ materially from those referred to in such statements. Accordingly, the Company claims the protection of the safe harbor for forward-looking statements contained in the Private Securities Litigation Reform Act of 1995 with respect to all statements contained in this press release. All information in this press release is as of the date of the release and Transgenomic does not undertake any duty to update this information, including any forward-looking statements, unless required by law. Headline 23: Gene-modified stem cells help protect bone marrow from toxic side effects of chemotherapy Published by: Physrog Date of Publication: May 21, 2011 Source: http://www.physorg.com Although chemotherapy is used to kill cancer cells, it can also have a strong toxic effect on normal cells such as bone marrow and blood cells, often limiting the ability to use and manage the chemotherapy treatment. Researchers at Fred Hutchinson Cancer Research Center reported at today's annual meeting of the American Society of Gene and Cell Therapy in Seattle that one possible approach to reduce this toxic effect on bone marrow cells is to modify the cells with a gene that makes them resistant to chemotherapy. Hans-Peter Kiem, M.D., a member of the Hutchinson Center's Clinical Research Division, and colleagues Jennifer Adair, Ph.D., a research associate in the Clinical Research Division, and Maciej Mrugala, M.D., Ph.D., M.P.H., a neuro-oncololgist at the Seattle Cancer Care Alliance and the University of Washington, presented data from a clinical trial in which bone marrow stem cells from patients with brain tumors were removed and modified with a retrovirus vector to introduce the chemotherapy-resistant gene. The cells were then re-infused into the patients. In the trial, which was designed to evaluate safety and feasibility, patients were safely administered gene-modified blood stem cells that persisted for more than one year and did not show any apparent harmful effects. This approach was first attempted in patients with a terminal form of brain cancer called glioblastoma. Currently, median survival for glioblastoma patients is just 12 to 15 months. The prognosis for glioblastoma patients is poor not only because no curative treatment is available but because doctors PAGE 51 OF 124 cannot effectively use the treatment that does exist. Glioblastoma cells make a large amount of a protein called MGMT that makes them resistant to chemotherapy, so doctors use a second drug, called benzylguanine, to knock down MGMT and make the tumor cells susceptible to the chemotherapy. However, this potent one-two punch is not limited to the brain tumor cells. Benzylguanine also disables MGMT in normal blood and bone marrow cells, leaving them also susceptible to the effects of chemotherapy. The effects on patients' blood and bone marrow can be pronounced and often limit the ability to effectively administer the chemotherapy. "Our initial results are encouraging because our first patient is still alive and without evidence of disease progression almost two years after diagnosis," Kiem said. The results of the trial suggest the administration of the modified cells represent a safe method for protecting marrow and blood cells from the harmful effects of chemotherapy in brain tumor patients. Future clinical trials will be done to determine whether this combination chemotherapy will also improve the survival of patients with glioblastoma. Headline 24: Investigators Pour Doubt on Accepted Understanding of DNAto-RNA Sequence Equivalence Published By: Gen News Date of Publication: May 19, 2011 Source: http://www.genengnews.com Team suggests disease susceptibility studies should focus on mRNA sequence variations as well as DNA polymorphisms. The finding that one stretch of coding DNA doesnвЂ™t necessarily get transcribed into a matching stretch of RNA has led researchers to query whether RNA sequence variation could impact disease susceptibility or manifestation. Studying factors related to disease susceptibility at the genetic level has to date largely focused on looking at variations in the genes themselves or measuring levels of corresponding protein production. Studies by Vivan G. Cheung, Ph.D., at the University of Pennsylvania School of Medicine in Philadelphia, and colleagues, suggest, however, that RNA sequence variations may also be relevant. When the researchers compared the RNA sequences in human B cells with the corresponding DNA sequences in the same cells, they found 28,766 DNA-RNA mismatch events at over 10,000 exonic sites in 4,741 genes. Each specific mismatch was observed in the B cells of at least two individuals PAGE 52 OF 124 from the original cohort of 27 people and was subsequently identified in primary skin cells and brain tissues from a separate set of individuals. All 12 possible categories of discordances were observed, and in a number of cases peptides were generated from the discordant RNAs that didnвЂ™t correspond to the DNAs. The researchers report their results in Science Express in a paper titled вЂњWidespread RNA and DNA Sequence Differences in the Human Transcriptome.вЂќ It is widely assumed that a sequence of an mRNA exactly reflects that of the DNA from which it was transcribed, and this assumed precision is important given that mRNA serves as the template for protein synthesis, Dr. Cheung and colleagues explain. Although errors in transcription can occur they are relatively rare, and RNA-DNA differences that are known to occur as a result of RNA editing are effected by enzymes that target the mRNA post-trancriptionally. As a result of the expected one-to-one relationship between DNA and its mRNA transcript, studies into the genetics of disease susceptibility have focused largely on DNA sequence polymorphisms, while the analysis of mRNA and proteins has centered largely on levels of their expression, rather than on any potential RNA sequence differences among individuals. The researchers have now poured significant doubt on this basic tenet of DNA-to-RNA sequence equivalence. They compared the DNA and mRNA sequences from B cells in 27 unrelated individuals who are part of the International HapMap Consortium and 1000 Genomes Projects. Of the 28,766 events identified, nearly 7,000 were A-G events, which could be the result of deamination by ADAR, and another 1,220 were C-T differences which could also be mediated by a deaminase, the researchers admit. However, 43% if the differences (12,507) were transversions at 10,210 exonic sites, which couldnвЂ™t have resulted from classic deaminase-mediated editing. The mechanisms behind these sequence differences, which they termed RNA-DNA differences (RDDs) remains unknown. Significantly, the researchers add, вЂњthese sites where RNA sequences differ from the corresponding DNA sequences appear to be non-random since the identical differences were found in multiple individuals.вЂќ In fact, 80% of the RDD sites were found in at least 50% of the test individuals. Also of importance was the mass spectrometry-based confirmation that sequences corresponding to at least some of the RNAs were translated into peptides. Interestingly, the mismatched DNA and RNA sequences were not spread evenly across the 10,210 exonic sites. Chromosome 19 had the most and chromosome 13 the fewest. The average number of exonic DNA-RNA mismatches per person among the Gencode genes was just over a thousand but in some people it was in the low-100s and in others nearly 2,000. PAGE 53 OF 124 The team validated its findings experimentally by Sanger sequencing of both DNA and RNA at 12 randomly selected sites in the B cells, primary skin, and brain cortex from multiple individuals as well as in tumor cells. B cells from the subjects were also regrown and DNA and mRNA extracted from the same aliquots of cells. The consistent pattern of the observations suggests that the RDDs have biological significance and are not just noise, the authors conclude. At nearly all RDD sites, we observed only one RDD type across cell types and in different individuals. вЂќ At present, however, the underlying mechanisms for these events remain largely unknown," the investigators admit. вЂњFor most of the cases we do not know yet whether a different base was incorporated into the RNA during transcription or if these events occur post-transcriptionally.вЂќ Headline 25: Researchers Figure Out How to Selectively Correct Mutations in Patient-Derived Human iPSCs Published By: Gen News Date of Publication: May 19, 2011 Source: http://www.genengnews.com Tests suggest approach can efficiently replace large, transcriptionally inactive genomic stretches. Researchers report on what they claim is an accurate and efficient method for selectively correcting disease-causing mutations in human induced pluripotent stem cells (hIPSCs) or adult stem cells generated from patients with genetic diseases. Using hIPSCs derived from a patient with HutchinsonGilford progeria syndrome (HGPS) as an example, the team showed that a single helper-dependent adenoviral vector (HDAdV) was capable of selectively correcting the lamin A gene (LMNA) mutation responsible for HGPS. Targeted correction of LMNA led to the restored expression of wild-type lamin A and to the abolishment of progerin expression. This in turn corrected the disease-associated cellular phenotypes, decelerated cell senescence, and restored normal nuclear morphology. In fact, the team claims, using the HDAdV technique it was possible to correct different mutations spanning a substantially large region of the LMNA gene with very high efficiency and without causing any obvious genetic or epigenetic abnormalities. The multidisciplinary team, at the Salk Institute for Biological Sciences, the University of California at San Diego (UCSD), the Scripps Research Institute, and the Center for Regenerative Medicine in Barcelona, report their findings in Cell Stem Cell. The paper, which will be published in June but is PAGE 54 OF 124 now available online, is titled вЂњTargeted Gene Correction of Laminopathy-Associated LMNA Mutations in Patient-Specific iPSCs.вЂќ Gene-editing methodologies reported to date for human cells suffer from technical problems. Classical nonviral vectors and delivery approaches are associated with low efficiency of gene targeting in human pluripotent stem cells, especially for transcriptionally silenced genomic loci. Additionally the need to generate double-stranded DNA breaks carries the potential for unexpected and unwanted mutations and chromosomal aberrations. Moreover, the researchers note, вЂњfor genes bearing mutational вЂ�hotspots,вЂ™ efficient tools targeting multiple sites spanning a large DNA sequence still need to be developed.вЂќ The HDAdV approach developed by Dr. BelmonteвЂ™s team is designed to address these issues to allow targeted gene editing in stem cells. Fortunately, the researchers had at hand a recently established LMNA-based iPSC model of disease in which to test the technology. LMNA is a known transcriptionally inactive locus in pluripotent cells. This coupled with the fact that over 300 mutations in the gene have already been reported means LMNA represented an ideal candidate for the study of hot-spot gene corrections using single vectors targeting large genomic regions, the authors explain. LMNA mutations are associated with a range of human laminopathies, including the premature aging disease HGPS, which is caused by a specific LMNA mutation that results in production of an abnormal progerin protein. Scientists have now generated iPSCs from HGPS patient fibroblasts. The HDAd-based gene correction vector tested on the HGPS iPSCs had previously been shown to mediate efficient and precise gene editing in human embryonic stem cells, without the requirement for artificial double-stranded DNA breaks, the team notes. The vector retains no viral genes, so shows low cytotoxicity, but retains a large cloning capacity and allows for insertion of long homologous DNA regions designed to facilitate targeted integration of the delivered gene via homologous recombination. Dr. BelmonteвЂ™s team first confirmed that their LMNA-c-HDAdV vector could correct the specific HGPSassociated LMNA mutation in the hIPSCs. The overall system used positive and negative drug resistance selection steps to choose the cells in which the correct gene had been targeted by the vector. In this first round of tests the researchers found that the vector targeted the correct gene in 78-100% of cells, and in 46% of the drug-resistant colonies the HGPS mutation had been successfully corrected. Genome-wide SNP genotyping demonstrated that the genetic background of the corrected HGPS-iPSCs was the same as the parental HGPS fibroblasts, while copy number variant analysis suggested there were no apparent duplications or deletions in the HGPS-iPSC cells, compared with the original fibroblasts. PAGE 55 OF 124 Additional genome-wide DNA methylation analysis indicated the cHGPS-iPSCs showed a highly similar methylation profile to their parental iPSCs. вЂњThus, our gene-correction approach effectively maintained genetic and epigenetic cell integrity,вЂќ the authors claim. To see whether correcting the LMNA mutation in HGPS-iPSCs could prevent the development of disease-associated phenotypes, they differentiated the HDAdV-corrected cells into vascular smooth muscle cells and fibroblasts, which are known to be affected by HGPS. These differentiated cells demonstrated no progerin mRNA or progerin protein, which correlated with a significant rescue of the senescence phenotype. The corrected HGPS-iPSC-derived fibroblasts also showed a more than 60% reduction in the number of abnormal nuclei compared with their non-corrected counterparts. Dr. BelmonteвЂ™s achieved similarly encouraging results when they tested the technique on iPSCs derived from a patient with atypical Werner syndrome AWS, which is caused by a different LMNA mutation. Moreover, additional analyses of the corrected AWS iPSCs showed the vector had inserted a long enough stretch of the wild-type LMNA gene into the AWS iPSCs to replace two additional SNPs located in the LMNA gene 3.3 kb and 4.4 kb downstream of the original target insertion site. вЂњThus, our method could potentially be used to correct more than 200 different mutations described to accumulate in the LMNA locus,вЂќ they claim. As a final evaluation, the researchers tested whether the HDAd-based vector could be used to edit genes in human adult mesenchymal stem cells. Focusing on olfactory ectomesenchymal stem cells (OE-MSCs), which represent a potentially attractive population for clinical applications, they confirmed that the LMNA-c-HDAdV demonstrated a gene-editing efficiency of 54% in wild-type OE-MSCs without disrupting normal lamin A/C expression. вЂњOur results demonstrate that the long homology arms used in HDAdVs have the capability to edit the targeted genomic locus without off-target effects and/or introduction of additional mutations, thus presenting an advantageous alternative to the use of other gene-editing technologies,вЂќ the authors conclude. They point out that while bacterial artificial chromosome-mediated vectors also use long homology arms, the ability of these constructs to target the genome appears restrictred to transcriptionally active loci. вЂњThus, the HDAdV represents a robust and versatile tool that could be applied toward the correction of multiple monogenic diseases. Finally, this approach could serve to generate appropriate genotype-matched iPSC lines in disease modeling and drug discovery studies.вЂќ PAGE 56 OF 124 Headline 26: FDA approves oral hepatitis c virus protease inhibitor Published By: Biospectrum India Date of Publication: May 16, 2011 Source: http://www.biospectrumindia.com Merck has announced that the U.S. Food and Drug Administration (FDA) has approved Victrelis (boceprevir), the company's innovative new medicine for the treatment of chronic hepatitis C (CHC). Victrelis is approved for the treatment of CHC genotype 1 infection, in combination with peginterferon alfa and ribavirin, in adult patients (18 years of age and older) with compensated liver disease, including cirrhosis, who are previously untreated or who have failed previous interferon and ribavirin therapy. Victrelis must not be used as monotherapy and should only be used in combination with peginterferon alfa and ribavirin. Victrelis efficacy has not been studied in patients who have previously failed therapy with a treatment regimen that includes Victrelis or other HCV NS3/4A protease inhibitors. Victrelis in combination with peginterferon alfa and ribavirin has not been studied in patients documented to be historical null responders (less than a 2 log HCV-RNA decline by treatment week 12) during prior therapy with peginterferon alfa and ribavirin. The clinical studies included patients who were poorly interferon responsive. Patients with less than 0.5 log HCV-RNA decline in viral load at treatment week 4 with peginterferon alfa plus ribavirin alone are predicted to have a null response (less than a 2 log HCV-RNA decline by treatment week 12) to peginterferon alfa and ribavirin therapy. Poorly interferon responsive patients who were treated with Victrelis in combination with peginterferon alfa and ribavirin have a lower likelihood of achieving a sustained virologic response (SVR)(1), and a higher rate of detection of resistance-associated substitutions upon treatment failure, compared to patients with a greater response to peginterferon alfa and ribavirin. Victrelis is the first in a new class of medicines known as hepatitis C virus (HCV) protease inhibitors approved for use in combination with peginterferon alfa and ribavirin, which is the current standard therapy, for the treatment of chronic hepatitis C. "This is an exciting day for physicians and patients because Victrelis is the first major advancement for the treatment of chronic hepatitis C approved in a decade," said Bruce Bacon, professor of internal medicine, Saint Louis University School of Medicine, and a clinical investigator for Victrelis. "Compared to current standard therapy, VICTRELIS can significantly increase a patient's chance of achieving undetectable levels of the virus, thereby obtaining an SVR. For many patients, VICTRELIS may allow for a shorter total duration of treatment." "Merck is deeply committed to innovation in bringing forward new medicines that significantly address unmet medical needs, and Victrelis is a shining example of our commitment being realized," said Kenneth C. Frazier, president and chief executive officer, Merck. "We look forward to building on our PAGE 57 OF 124 legacy in the fight against infectious diseases, and to being a part of this exciting new era in the treatment of chronic hepatitis C." Merck will begin shipping Victrelis to pharmacies within a week so that patients will have access to this new medication as soon as possible. In addition, the company is expanding its support of public awareness and education programs for chronic hepatitis C. Headline 27: Irregular practices in Private TB Drug market: Study Published By: Biospectrumasia Date of Publication: May 14, 2011 Source: http://www.biospectrumasia.com Tuberculosis is widely considered public health concern and its treatment a public sector responsibility. But according to a recent study, the private sector for TB treatment is ignored at our peril.The first detailed study of the private tuberculosis (TB) drug market, published in the latest edition of PLoS ONE journal, finds that it is surprisingly large, and has irregular practices that could be driving treatment failures and contributing to the emergence of multi-drug resistant TB (MDR-TB). The research, conducted by the TB Alliance and IMS Health, examined 10 high-burden countries where 60 percent of the worldвЂ™s TB burden is present. These included India, Indonesia, Phillipines, Pakistan, China, Thailand, Russia, Vietnam, Bangladesh and South Africa. Across 10 high-burden countries, there is as much TB drug volume in the private sector as in the public sector and at least one third of all private sector closages of first-line TB drugs fall outside of national and international treatment recommendations. Any resulting misuse could be responsible for many treatment failures and for escalating the emergence of MDR-TB, which is further worsening the TB epidemic. According to the study report, previously, TB treatment was thought to take place primarily in the public sector. However, there is as much TB drug volume in the private sector as in the public sector, implying massive overtreatment and retreatment of the disease. More than one-third (35%) of all TB treatment in the private sector fall outside national and international treatment recommendations, and constitute non-recommended strengths. There were 111 different first-line TB drug dosages and combinations detected in the private sector, compared to the 14 deemed necessary. The report further blames the chaos surrounding the standard treatment which in turn can contribute to escalating rates of MDR-TB and further worsening of the TB epidemic. India has the largest private drug market by far, estimated to hold enough drugs to treat more than 2 million cases. Nearly 60% of dosing strengths in the Indian private markets do not correspond with standard TB treatment guidelines nearly twice the average of the other countries studied. MDR-TB treatment rates are low PAGE 58 OF 124 within the private sector, showing that the private market has not stepped in to fill the growing gap in treatment for patients in need. According to Dr. William Wells, Director of Market Access at the TB Alliance and lead author of the study, вЂњThe private sector is keeping the confusion that existed previously in the public sector alive. With this new baseline understanding of the TB drug market, we can no longer ignore the private sectorвЂ™s critical role in the access equation for TB treatment. We must dedicate more efforts toward ensuring rational prescribing in the private sector if we are to protect both current drugs and new regimens, which are now in the latest stages of testing, from the development of resistance.вЂќ During the past decade, the world has seen a rewakening of TB drug development efforts, and the first wave of new TB tretments will be introduced within the next few years,вЂќ said Dr. Mel Spigelman, President and CEO of the TB Alliance. вЂњThis study fills a critical gap in our knowledge base.вЂќ Mario Raviglione, Director, Stop TB Department, WHO, said, вЂњGeater government and international support is needed for these efforts and also for improved regulatory oversight and quality assurance of TB drugs. A dual track approach of collaboration and regulation is the logical way forward. We ought to make privat providers responsible partners of the private sector in controlling TB and MDRTB.вЂќ Headline 28: New Discoveries about Tumor-Suppressing Protein Could Help Reduce Treatment Side Effects Published By: ScienceDaily Date of Publication: May 12, 2011 Source: http://www.sciencedaily.com Researchers at the Stanford University School of Medicine have untangled two distinct ways in which a common, naturally occurring "tumor-suppressor" protein works. The separation of these two functions -- which can have quite different consequences -- could enhance efforts to develop treatment approaches that mitigate the sometimes-devastating side effects of radiotherapy and chemotherapy. The protein, p53, is mutated or missing in more than half of all human cancers, and most cancers involve at least some compromise in its function. Cancer is caused by two categories of mutations: those that activate oncogenes, whose protein products drive cells into overzealous replication, and those that disable tumor-suppressor genes, which code for proteins that sense this abnormal behavior and put the brakes on it. PAGE 59 OF 124 "We knew that p53 responds to two different types of signals: DNA damage and oncogene activity," said Laura Attardi, PhD, associate professor of radiation oncology and of genetics. "We wanted to know if p53 responds to both in the same way." Attardi is senior author of a study to be published May 13 in Cell that throws light on crucial molecular details about how p53 works. It is widely understood that p53 can temporarily or permanently shut down cell division in response to either acute damage to a cell's DNA or biochemical signals within a cell that suggest it's prone to becoming a cancer cell. In extreme cases, p53 convincingly counsels the cell to commit suicide, thereby preventing the possibility of a tumor arising. Attardi and her colleagues created bioengineered mice in which various parts of p53 were incapacitated. This allowed them to determine which genes are activated by different parts of the protein, and to show that p53's aggressive DNA-damage response and its gentler tumor-suppression response are separable functions. "We've determined, for the first time, that the gene expression program p53 requires in its tumorsuppression role is distinct from that which it requires in the context of acute DNA damage," Attardi said. "Separating these responses may allow the identification of ways to inhibit the detrimental effects of radiotherapy and chemotherapy -- both of which damage DNA -- without putting a patient at risk for developing new tumors." While most tumors lack a working p53 protein, radiotherapy and chemotherapy activate the p53 present in healthy tissues, producing serious side effects by destroying cells in the gastrointestinal tract, blood, hair follicles and brain. That's because these treatments cause profound DNA damage, a trigger for p53 action. It's known that p53 is a transcription factor: a protein that can regulate the production of numerous other proteins inside a cell. According to scientists, p53 recognizes and perches upon a particular DNA sequence found near large numbers of genes. Once p53 has seated itself near such a gene, two different regions of the protein, called TAD1 and TAD2, can serve as landing beacons that attract mammoth molecular copying machines to the gene -- a key early step in protein generation. But the response is very different depending on which of the two beacons, TAD1 or TAD2, is calling in the copying machinery. Attardi's group used bioengineered mice in which TAD1, TAD2 or both had been disabled by mutations. This allowed the investigators to show that these two beacons flag different sets of genes. The genes that TAD1 turns on are the ones involved in p53's show-stopping response to DNAdamage. More than 100 such genes had already been identified. PAGE 60 OF 124 But when the investigators disabled TAD1 while leaving TAD2 intact, they were able to unmask a set of 50 or so genes turned on by TAD2. These genes, the team showed, mediate p53's ability to stimulate cells' somewhat more nuanced tumor-suppression response, which shuts down a cell only upon sensing oncogene activity, a more direct sign of potential cancer than mere DNA damage. "When we treated the TAD1-disabled mice with high-dose radiation, they didn't suffer the DNAdamage-induced side effects that we saw in wild-type mice," said the study's lead author, Colleen Brady, a PhD student in Attardi's lab. "But TAD1-disabled mice were resistant to tumor development." "This is an important advance," said molecular biologist and oncologist Arnold Levine, PhD, a professor at the Institute of Advanced Studies in Princeton, N.J. "The team has uncovered half of what the biggest player in human cancers does." Levine, who didn't participate in the study but is familiar with it, is one of three scientists credited for p53's discovery in 1979. The finding that p53 can suppress tumors, even when the part of it that shuts down cells in response to DNA damage has been disabled, holds significant implications for therapy. If the two distinct activities of p53 in healthy cells can be decoupled -- say, by a drug impairing TAD1's function but sparing TAD2's -- it might be possible to avoid the massive healthy-cell die-off responsible for nausea, hair loss, immune deficiency and nerve damage that usually occur during radiotherapy or chemotherapy, without promoting new tumor development. Disabling p53's TAD1 region would allow cells that have sustained DNA damage in the course of these therapies to live to another day, but TAD2's still-intact tumor-suppressor function in those otherwise normal cells would guard against those cells becoming cancer cells. The study was funded by the American Cancer Society, the Leukemia & Lymphoma Society and the National Institutes of Health. Other Stanford co-authors were postdoctoral researchers Dadi Jiang, PhD; Stephano Spano Mello, PhD; Daniela Kenzelmann Broz, PhD; Lesley Jarvis, MD, PhD; and Shashwati Basak, PhD; medical students Margaret Kozak and Thomas Johnson, PhD; and research assistant Eunice Park, all of Attardi's lab. Jarvis is now an assistant professor of medicine at Dartmouth-Hitchcock Medical Center, and Basak is scientific manager at BBRC Syngene International Ltd. Headline 29: Trillium raises funds to advance urology program into clinical trials Published By: PRNewswire Date of Publication: May 12, 2011 Source: http://www.prnewswire.com Trillium Therapeutics Inc., a privately-held biopharmaceutical company, announced today that it has raised $1 million from a new undisclosed investor. The funds will be used to advance its lead PAGE 61 OF 124 program, TTI-1612, into clinical trials for the treatment of interstitial cystitis (IC), also known as bladder pain syndrome. The first trial is projected to start in the second half of this year. "We are very excited about this new investment, since it will allow us to transform Trillium into a clinical company, while continuing to advance our broad preclinical immunoregulatory platform", commented Trillium CEO, Dr. Niclas Stiernholm. "Adding to last August's $2 million round from our existing shareholders, this new investment is timely and critical for the company's future. With clinical data in hand by year end, we should gain wider access to new capital, as well as to potential pharma partners, in 2012." Interstitial cystitis is a chronic, debilitating and poorly treated bladder disease affecting millions of women in the US alone. It is believed to develop as a result of dysfunction in the protective epithelial layer lining the bladder. TTI-1612, a locally-delivered recombinant growth factor, is being developed to correct this dysfunction and restore the bladder epithelium to a normal, healthy state. Working with a premier advisory group of leading urologists, Trillium is in the final stages of completing the preclinical toxicology studies required for testing in humans, and plans to submit a clinical trial application later this year. The company intends to secure additional financing and/or a development partner prior to the start of randomized phase II studies in 2012. "Remarkably little progress has been made in developing effective treatments for IC, and patients and physicians are desperately seeking new therapeutic approaches", added Dr. Bob Uger, Trillium's Vice President R&D. "TTI-1612 is aimed at correcting the underlying cause of IC, and is arguably one of the most innovative therapeutics currently under development for this disease. This program could fundamentally alter how IC is treated and have a significant impact on millions of patients' lives." Headline 30: Scientists Claim TIF1-Gamma Levels Could Represent Biomarker of Response to Leukemia Therapy Published By: Gen News Date of Publication: May 2, 2011 Source: http://www.genengnews.com TIF1Оі transcripts were found to be missing in cells from 35% of CMML patients studied. Scientists have identified transcription intermediary factor 1Оі (TIF1Оі) as a tumor suppressor in hematopoietic cells. The team suggests changes in expression of the protein could represent a biomarker for measuring response to demethylating agents and other chromatin structure modifiers such as HDAC inhibitors in development for treating chronic myelomonocytic leukemia (CMML). PAGE 62 OF 124 The researchers, led by Jean-NoГ«l Bastie, Ph.D., and Laurent Delva, Ph.D., at Inserm UMR 866, the University of Burgundy, found that deletion of the TIF1Оі gene in the hematopoietic tissues of experimental mice led to the animals developing an age-dependent myeloproliferative disorder that mimicked the essential characteristics of human CMML. They separately found that TIF1Оі was almost undetectable in leukemic cells of 35% of CMML patients evaluated and that demethylating agents restated its expression. The results are published in the Journal of Clinical Investigation. The paper is titled вЂњTranscription intermediary factor 1Оі is a tumor suppressor in mouse and human chronic myelomonocytic leukemia.вЂќ TIF1Оі affects human hematopoietic progenitor cell response to cytokines of the TGF-ОІ superfamily through various mechanisms, the authors write. To further explore the role of TIF1Оі in hematopoiesis, Drs. Bastie and DelvaвЂ™s team examined the effects of hematopoietic tissue-targeted deletion of theTif1g gene in mice. They found that knockout mice younger than six months old did not display any macroscopic or blood peripheral abnormalities but did show changes in the proportions of hematopoietic progenitors. The proportion of granulocyte/monocyte progenitors was increased by about 400%, at the expense of common myeloid progenitors and megakaryocyte-erythroid progenitors. Conversely, knockout mice older than six months developed a CMML-like myeloproliferative disease with monocytic features. When bone marrow cells were taken from four month old knockout mice and transplanted into control animals, the recipients also developed the same myeloproliferative disease. The researchers also tested whether Tif1Оі could regulate expression of Csf1r (M-CSFR), Csf3r (GCSFR), and Csf2ra (GM-CSFR), three genes known to participate in monocyte or granulocyte differentiation. They found that knockout mice had significantly reduced expression of Csf1r specifically, which they suggest could account for the altered production of peritoneal macrophages observed in the knockout animals. Moving on to humans, the team subsequently found the TIF1Оі transcript was almost undetectable in peripheral blood monocytes sorted from 21 of the 60 patients (35%) with CMML. Immunocytochemical analysis confirmed decreased expression of the protein in monocytes and neutrophils of these patients. Low levels of TIFIG in cells from these patients correlated strongly with Csf1r expression, which had previously been identified in the knockout mouse cells. Interestingly, sequencing of all the TIF1G exons in monocytes from the 66 CMML patients failed to identify any mutation in the coding sequence, whatever the levels of TIF1Оі mRNA and protein levels were expressed. Rather, they found that the TIF1G promoter of CMML patients expressing low levels of TIF1Оі was methylated, while none of the DNA from either normal human monocytes or from CMML monocyte sample with normal TIF1G mRNA levels was methylated. PAGE 63 OF 124 This promoter hypermethylation appeared to be corrected on administration of demethylating agents. Exposing CMML peripheral blood monocytes with initially downregulated TIF1G expression to decitabine for three days restored TIF1Оі expression. Gene expression was also reestablished in the peripheral blood monocytes of a CMML patient who responded to decitabine in vivo. The researchers say cytosine methylation in the TIF1G promoter sequence, which they had identified in the monocytes of these patients before decitabine treatment, was no longer detected after seven cycles of decitabine, which correlated with Tif1Оі mRNA re-expression. Headline 31: New Gene Therapy Technique on iPS Cells Holds Promise in Treating Immune System Disease Published By: Science Daily Date of Publication: April 28, 2011 Source: http://www.sciencedaily.com Researchers have developed an effective technique that uses gene therapy on stem cells to correct chronic granulomatous disease (CGD) in cell culture, which could eventually serve as a treatment for this rare, inherited immune disorder, according to a study published in Blood, the Journal of the American Society of Hematology. CGD prevents neutrophils, a type of white blood cell of the immune system, from making hydrogen peroxide, an essential defense against life-threatening bacterial and fungal infections. Most cases of CGD are a result of a mutation on the X chromosome, a type of CGD that is called "X-linked" (XCGD). While antibiotics can treat infections caused by X-CGD, they do not cure the disease itself. Patients with X-CGD can be cured with a hematopoietic stem cell (HSC) transplant from healthy bone marrow; however, finding a compatible donor is difficult. Even with a suitable donor, patients are at risk of developing graft-versus-host disease (GVHD), a serious and often deadly post-transplant complication that occurs when newly transplanted donor cells recognize a recipient's own cells as foreign and attack the patient's body. Another treatment option under development for X-CGD is gene therapy, a technique for correcting defective genes responsible for disease development that involves manipulation of genetic material within an individual's blood-forming stem cells using genetically engineered viruses. However, this gene therapy has so far proved to be inefficient at correcting X-CGD. In addition, these engineered viruses insert new genetic material at random locations in the blood-forming stem cell genome, putting patients at significantly higher risk for developing genetic mutations that may eventually lead to serious blood disorders, including blood cancer. PAGE 64 OF 124 In order to develop a more effective and safer gene therapy for X-CGD, researchers from the National Institute of Allergy and Infectious Disease (NIAID) at the National Institutes of Health (NIH) and The Johns Hopkins University School of Medicine embarked on a study using a more precise method for performing gene therapy that did not use viruses for the gene correction. Researchers removed adult stem cells from the bone marrow of a patient with X-CGD and genetically reprogrammed them to become induced pluripotent stem cells (iPS cells). Like embryonic stem cells, these patient-specific iPS cells can be grown and manipulated indefinitely in culture while retaining their capacity to differentiate into any cell type of the body, including HSCs. "HSCs that are derived from gene corrected iPS cells are tissue-compatible with the patient and may create a way for the patient's own cells to be used in a transplant to cure the disease, removing the risk of GVHD or the need to find a compatible donor," said Harry L. Malech, MD, senior study author, Chief of the Laboratory of Host Defenses and Head of the Genetic Immunotherapy Section of NIAID at the NIH. "However, turning iPS cells into a large number of HSCs that are efficently transplantable remains technically difficult; therefore, our study aimed at demonstrating that it is possible to differentiate gene corrected iPS cells into a large number of corrected neutrophils. These corrected neutrophils, grown in culture, are tissue-compatible with the patient and may be used to manage the life-threatening infections that are caused by the disease." Typically, iPS cells from a patient with an inherited disorder do not express disease traits, despite the fact that the iPS cell genome contains the expected mutation. The researchers were able to prove, in culture, that iPS cells from a patient with X-CGD could be differentiated into mature neutrophils that failed to produce hydrogen peroxide, thus expressing the disease trait. This is the first study in which the disease phenotype has been reproduced in neutrophils differentiated from X-CGD patient-specific iPS cells. After discovering that the disease could be reproduced in cell culture, the researchers then sought to correct the disease and produce healthy neutrophils in culture. They used synthetic proteins called zinc finger nucleases (ZFNs) to target a corrective gene at a specifically defined location in the genome of the X-CGD iPS cells. The iPS cells were then carefully screened to identify those containing a single copy of the corrective gene properly inserted only at the safe site. The researchers observed that some of the gene-corrected iPS cells could differentiate into neutrophils that produced normal levels of hydrogen peroxide, effectively "correcting" the disease. "This is the first study that uses ZFNs in specific targeting gene transfer to correct X-CGD," said Dr. Malech. "Demonstrating that this approach to gene therapy works with a single-gene disease such as X-CGD means that the results from our study offer not only a potential treatment for this disease, but more importantly, a technique by which other single-gene diseases can be corrected using specifically targeted gene therapy on iPS cells." PAGE 65 OF 124 Headline 32: Hepatitis B Virus Reemerges With Long-Term Nucleoside Analog Treatment, Study Suggests Published By: Science Daily Date of Publication: April 27, 2011 Source: http://www.sciencedaily.com/ A recently published study revealed that virological breakthrough (VBT) is common in patients receiving nucleoside analogs (NUCs) for chronic hepatitis B. Nearly 40% of the VBTs found were not related to antiviral drug resistance. Details of this retrospective study are published in the May issue ofHepatology, a journal published by Wiley-Blackwell on behalf of the American Association for the Study of Liver Diseases. VBT is the first manifestation of antiviral drug resistance during NUC therapy of chronic hepatitis B. NUC drugs approved for treatment of chronic hepatitis B include lamivudine (LAM), adefovir (ADV), entecavir (ETV), telbivudine (TBV), and tenofovir (TDF). While the medications suppress the virus with few side effects, they do not eradicate HBV and require long-term treatment to provide clinical benefit. With long-term NUC therapy, studies have shown an increasing risk of drug resistance particularly with monotherapy regimens. In the current study, Anna Lok, M.D. and colleagues from the University of Michigan Health System examined the incidence of VBT and genotypic resistance (GR) in 148 patients with chronic hepatitis B who were treated with NUCs between January 2000 and July 2010. The mean age of study participants was 45 years and 73% were male. Researchers reviewed medical records and recorded patient demographics, hepatitis B virus (HBV) markers, liver panel, blood counts and liver histology. Results showed that during a mean follow-up of 38 months, 39 (26%) patients had at least one VBT, and upon retesting, 15 (38%) of these patients did not have a VBT and 10 had no evidence of GR. Researchers reported the probability of VBT, confirmed VBT, and GR at five years was 46%, 30%, and 34%, respectively. "Our analysis showed an alarmingly high rate of VBT in clinical practice and the only factor significantly linked to VBT was failure to achieve undectectable HBV DNA," said Dr. Lok. HBV DNA decreased in the ten patients who initially experienced a VBT, but who did not have confirmed VBT or GR, when the same drug regimen was maintained. Nine of these patients had undetectable HBV DNA at the most recent follow-up, a mean of 7 months after the initial VBT. These data suggest that nonadherence to medication may be a common cause of VBT. "Counseling patients with chronic hepatitis B on the importance of medication adherence, and confirming reemergence of the virus and genetic mutations that cause resistance, can help to avoid unnecessary changes to antiviral treatments," advised Dr. Lok. PAGE 66 OF 124 Headline 33: Enigma Announces the Start of US Clinical Trials for Its Influenza A/B Detection Assay Published By: Medical New Today Date of Publication: April 11, 2011 Source: http://www.medicalnewstoday.com Enigma Diagnostics announced today that it has commenced clinical trials for its intended point of care EnigmaВ® ML Influenza A/B detection assay. Enigma will submit its application to the U.S. Food and Drug Administration (FDA) for approval of the assay in 2012. The EnigmaВ® ML instrument platform combines fully-automated sample extraction with real-time PCR amplification and detection system which has been specifically designed for the particular needs of infectious disease testing. The starting material for analysis is a capped tube containing universal transport medium and a swab which uniquely is inserted directly into the consumable cartridge. The test is anticipated to take less than 1 hour to perform and results are displayed in a number of simple to interpret formats by the integrated touch-user interface screen. Current methods for viral detection often require many manipulative steps for sample handling and subjective interpretation from highlyskilled laboratory technicians which can take several days to process from the time of collection. The EnigmaВ® ML system was specifically designed as a rapid fully automated system enabling "raw sample to result" testing with uncomplicated read-outs and allowing for lower technical skill users. Clinical trial site initiations and the enrollment of subjects for the US based trial began in late March after Enigma worked closely with the FDA on the clinical trial design for both 510(k) clearance and potential CLIA-waiver of the system. Up to 8 clinical study sites across the United States will participate in patient enrollment and onsite testing of the EnigmaВ® ML system. The clinical trial design consists of two phases. The first phase includes the collection of nasopharyngeal samples at the end of the 2010-2011 flu season. The second phase will include additional collection of samples alongside testing on the EnigmaВ® ML system during the 2011-2012 flu season. A total of 1,100 subjects including both adult and pediatric patients will be enrolled in the trial. John McKinley, Chairman and CEO, said, "It is estimated that over 12 million influenza tests are performed yearly in the USA and typically between 5 and 20 percent of the US population are infected with seasonal flu every year. Faster and more accurate tests are needed to satisfy this growing market and the features of the EnigmaВ® ML instrument make it ideally suited to meet this demand. With increasing market recognition of the importance of achieving CLIA Waiver, we are pressing ahead with the clinical trials and anticipate completion of our EU and USA regulatory accreditation processes within 2012 to include FDA consideration of the appropriateness of the EnigmaВ® ML system to achieve CLIA Waiver status." PAGE 67 OF 124 Headline 34: Vaccine for Transplant Infection Shows Promise in Phase II Trial Published By: Medical News Today Date of Publication: April 07, 2011 Source: http://www.medicalnewstoday.com/ A major infectious problem after organ transplantation, cytomegalovirus (CMV), could potentially be targeted with a vaccine, according to new results from a clinical trial led by scientists from UCL and doctors at the Royal Free Hospital. The results of this Phase II proof-of-concept study, published in The Lancet today, show that a vaccine preparation moderated the severity of CMV infection in patients waiting for kidney and liver transplants and, in some cases, may have interrupted transmission of the virus from donor to recipient. CMV is part of the herpes family of viruses and is one of the most common viral infections. It is estimated that around 6 of every 10 adults in the UK have been infected by CMV, usually through contact with young children. It is typically unnoticed in healthy people because their lymphocytes keep the virus under control. However, the virus can be serious when it develops or reoccurs in certain vulnerable groups, particularly those with weakened immune systems such as organ transplant recipients, people with HIV and unborn babies. CMV is sometimes referred to as the 'Toll of Transplantation' because of the high level of serious disease it can cause in this patient group - including pneumonia, lung complications and liver infection. Congenital CMV, when a woman becomes infected during pregnancy and passes the infection on to her unborn baby, can also have serious consequences. About 7 babies in every 1000 will be born with congenital CMV. More than 10 per cent of babies born with the virus will have symptoms at birth, such as learning difficulties and hearing loss. These same problems will develop in at least another 10 per cent of babies, even though they appeared to be normal at birth. The study's lead author Professor Paul Griffiths, UCL Centre for Virology and Honorary Consultant at The Royal Free, said: "Many scientists thought that it would be impossible to make a vaccine against CMV because the virus works by evading the immune system, so they reasoned it would also evade a vaccine. However, this study shows that at least one vaccine preparation can moderate the severity of CMV infection, even in patients given immunosuppressive drugs and exposed to CMV in a transplanted organ. Although this trial just examines the vaccine in transplant patients, we expect that a vaccine could help other groups vulnerable to CMV such as pregnant women." PAGE 68 OF 124 140 Royal Free patients awaiting transplantation of a kidney or of a liver were recruited to the trial. Half of these patients had had natural infection in the past, whereas half had never seen CMV before. After informed consent, they were randomised to receive the vaccine or a placebo. 78 of them proceeded to transplant and so had their CMV biomarkers measured following the operation. All 67 patients given the vaccine responded by making antibodies against the CMV protein (glycoprotein B; gB) contained in the vaccine. The average quantity of antibodies made by the vaccine group was very significantly increased compared to the recipients of placebo. The level of these antibodies declined a little with time, but the vaccine recipients still had antibody levels which were significantly greater than the placebo recipients when they were called to transplant. After transplant, the biomarkers of CMV were all reduced in those who had received the vaccine compared to recipients of placebo. The study was not designed to provide significant differences between these biomarkers in each of the four different subgroups of patients. However, the reduction in biomarkers was statistically significant in the patients in the highest risk category (recipients who had never seen CMV in the past who received organs from patients infected with CMV). In five such high risk cases, the study results show that the vaccine may have interrupted transmission of virus from donor to recipient, because their biomarkers remained undetectable at all times after transplant. Professor Griffiths continued: "Based on these results, we conclude that it could be possible to make a vaccine against CMV that is able to protect against this important pathogen for transplant patients, as well as women of childbearing age whose unborn babies can be damaged by CMV. We hope these results will encourage multiple pharmaceutical companies to accelerate development of their CMV vaccine candidates for both groups of patients." PAGE 69 OF 124 Section C: Microbial Headline 1: Cholesterol boosts antibiotic resistance in H. Pylori Published By: Physorg Date of Publication: June 23, 2011 Source: http://www.physorg.com New research suggests that cholesterol boosts resistance in Helicobacter pylori both to many antibiotics and to the endogenous antimicrobial peptide, LL-37. A complete understanding of the pathway of cholesterol uptake might lead to novel strategies thwarting H. pylori by blocking that pathway, says corresponding author David McGee of Louisiana State University. The research is published in the June 2011 issue of the journal Antimicrobial Agents and Chemotherapy. H. pylori infects one third of Americans, causing gastritis and peptic ulcers, and costing $10 billion annually. Antibiotic therapy is recommended, but resistance, often leading to treatment failures, is becoming increasingly common, even following the now-standard triple drug therapy. In the study, the investigators grew H. pylori in the presence or absence of cholesterol, and treated the bacteria with different classes and concentrations of antibiotics, comparing the populations of surviving bacteria. вЂњWe found that H. pylori grown with cholesterol displayed a very dramatic increase in resistance to many antibiotics, bismuth, and to LL-37,вЂќ says McGee. вЂњIt would be important to learn whether we can manipulate the ability to clear H. pylori infections in animals and humans by lowering cholesterol either through dietary means or cholesterol-lowering drugs (statins),вЂќ says McGee. вЂњThere are already data showing that H. pylori-infected patients have elevated serum cholesterol levels, suggesting the bacteria manipulate the human host to produce more cholesterol.вЂќ Additionally, he says, a study of 500 patients found that taking statins lowered the severity of chronic gastritis, which is also caused by H. pylori. But some statins work, and others donвЂ™t, he says. And so far, no studies have combined antibiotics with statins. Thus, it is too soon to make recommendations to patients on their use to lower cholesterol, he says. Interestingly, McGee says his research would not have been possible without the help of a high school student. Alika George, now an undergraduate at the University of Louisiana, collected some of the data, and urged McGee to include pepto bismol (bismuth) in the study, while taking part in a summer enrichment program for minority high school students, which was supported by Louisiana State UniversityвЂ™s Office of Multicultural Affairs. вЂњI feel it is vital to be supportive of programs like this to give students opportunities they otherwise would not have had,вЂќ says McGee. PAGE 70 OF 124 Headline 2: Nitrogen-Fixing Bacterial Symbiont Promises Trove of Natural Products Published By: Science Daily Date of Publication: June 19, 2011 Source: http://www.sciencedaily.com Soil-dwelling bacteria of the genus Frankia have the potential to produce a multitude of natural products, including antibiotics, herbicides, pigments, anticancer agents, and other useful products, according to Bradley S. Moore of the Scripps Oceanographic Institute, La Jolla, and his collaborators in an article in the June 2011 issue of the journal Applied and Environmental Microbiology. The researchers found genetic structures in this bacterium that resemble those of various valuable natural product categories through bioinformatics and genome mining. "This tremendous biosynthetic capacity is reminiscent of many industrially important bacteria such as those belonging to the genus, Streptomyces that produce the majority of the natural antibiotics used as drugs," says Moore. "To see this capacity in a well-known microbe not previously exploited for its chemical richness was very rewarding from both an applied and basic science point of view," says Moore. Frankia are nitrogen-fixing bacteria that live in symbiosis with actinorhizal plants (whose ranks include beech and cherry trees, and various gourd-producing plants). "Since the vast majority of the deduced [biosynthetic] pathways are unique to Frankia, it suggests that they employ a very complex and specialized communication with their plant host to establish and maintain their symbiosis. So lots to discover there." Frankia have not previously been exploited partly because these bacteria are difficult to grow in the lab. But new genetic methods make it easier to transplant genes for promising natural products from Frankia into "more user-friendly host bacteria for production," says Moore. Moreover, genome mining, a recent technique that involves searching for genetic sequences, was critical to the results, and "complementary to the far more laborious traditional natural product drug discovery that has gone unchanged for decades," says Moore. A greater understanding of how complex organic molecules are synthesized in nature laid additional groundwork for this, and for "a new revolution in the discovery of natural chemicals that will fuel new research into what functions these chemicals play in nature, and how they can be used to benefit society," says Moore. The project grew out of a graduate class that Moore and Daniel Udwary (then his post-doc, now at the University of Rhode Island) taught on "Microbial Genome Mining," says Moore. Each student in the class researched a group of biosynthetic gene clusters that Moore and Udwary preselected. The students -- who are the majority of coauthors on the paper -- annotated their genes and based on biosynthetic principles, and predicted pathways leading to putative natural products. They then PAGE 71 OF 124 worked with the laboratories of Pieter Dorrestein at the University of California, San Diego (a mass spec specialist) and Lou Tisa at the University of New Hampshire (a Frankia biologist) to conduct preliminary proteomic and metabolomic analyses to probe whether the predicted pathways were operative, and whether small molecule. Headline 3: E. coli Bacteria More Likely to Develop Resistance after Exposure to Low Levels of Antibiotics Published By: Science Daily Date of Publication: June 16, 2011 Source: http://www.sciencedaily.com E. coli bacteria exposed to three common antibiotics were more likely to develop antibiotic resistance following low-level antibiotic exposure than after exposure to high concentrations that would kill the bacteria or inhibit their growth, according to a timely article in Microbial Drug Resistance, a peerreviewed journal published by Mary Ann Liebert, Inc. E. coli bacteria in food and water supplies have been responsible for disease outbreaks and deaths around the world in recent years. The current outbreak in Europe has sickened thousands of individuals and caused multiple deaths and life-threatening complications in hundreds of persons infected with a new strain of E. coli. Bacterial resistance to commonly prescribed antibiotics is an enormous and growing problem, largely due to misuse of antibiotics to treat non-bacterial infections and environmental exposure of the bacteria to low levels of antibiotics used, for example, in agriculture. In the article "De Novo Acquisition of Resistance to Three Antibiotics by Escherichia coli," the authors studied the mechanisms by which E. coli acquire resistance to three common antibiotics: amoxicillin, tetracycline, and enrofloxacin. Depending on the antibiotic and the level of exposure, different mechanisms may come into play. The authors report that exposure to antibiotics at relatively low levels--below those needed to inhibit growth of the bacteria--are more likely to result in the development of antibiotic resistance. "Exposure to low levels of antibiotics therefore clearly poses most risk," a finding that "contradicts one of the main assumptions made questioning the threat of usage of antibiotics in food animals," conclude the authors. Headline 4: Non-Independent Mutations Present New Path to Evolutionary Success Published By: Science Daily Date of Publication: June 03, 2011 Source: http://www.sciencedaily.com PAGE 72 OF 124 Mutations of DNA that lead to one base being replaced by another don't have to happen as single, independent events in humans and other eukaryotes, a group of Indiana University Bloomington biologists has learned after surveying several creatures' genomes. And, the scientists argue, if "point mutations" can happen in twos, threes -- even nines -- large evolutionary jumps are possible, especially when problems caused by a single point mutation are immediately compensated for by a second or third. The work appears in the latest issue of Current Biology. "A similar phenomenon had been observed in bacteria," said Matthew Hahn, the project's principal investigator. "And the idea that this might be happening in eukaryotes has been around for a while. We are the first ones to use exhaustive genomic studies to show it's actually happening, and happening in a big way." Hahn and two members of his lab, Ph.D. student Daniel Schrider and undergraduate Jonathan Hourmozdi, surveyed the disparate genomes of yeast (Saccharomyces cerevisiae), roundworm (Caenorhabditis elegans), fruit fly (Drosophila melanogaster), the model plant Arabidopsis thaliania and humans, and found that across the board, about three percent of new mutations are "multinucleotide mutations," or MNMs, perhaps the result of a single, error-prone DNA polymerase making two or more mistakes as it made its way down the chromosome. The group also studied human trios of parent-parent-offspring DNA, as well as the complete genomes of a Yan Chinese (YH01) and J. Craig Venter, cofounder of (and donor to) the Human Genome Project. The researchers found tens of thousands of likely MNMs. MNMs were essentially defined by the proximity of two or more point mutations. Since mutations are rare, the statistical likelihood of finding two mutations within 20 or 100 bases of each other after a few generations (or a few replication events in the germ line) is low enough to assume two nearby mutations have a near-100 percent likelihood of being caused by the same mutational event. Three percent of new mutations may not sound like a lot, but even rare genetic phenomena can be very powerful if they impact a creature's fitness, the measure of an individual's ability to survive and reproduce. "There are cases where an organism could improve its fitness if it acquired multiple mutations that would each reduce fitness if they occurred individually," Schrider said. "In cases like this, the organism would not be able to reach the improved fitness state, as the less-fit intermediate states would be eliminated by natural selection. Cases like this are referred to as 'fitness valleys.' The exchange of a single base within a gene can have drastic consequences for the behavior of the protein that gene encodes. Sickle cell anemia, for example, which causes red blood cells to become PAGE 73 OF 124 rigid, sharp-edged, and resistant to oxygen absorption -- and is the cause of listlessness and excruciating pain in the humans who have it -- is caused by a point mutation. The idea, Hahn and Schrider say, is that whatever problems a point mutation causes could be ameliorated by a second, with one point mutation compensating for the other in between generations. The scientists admit they expect this would be a very rare event. But possible. "The most exciting implication of our work is that it raises the possibility that organisms could leap across fitness valleys and reach a higher-fitness state by acquiring multiple mutations simultaneously," Schrider said. Hahn says he does not yet know of examples of genes in which valley leaping might have occurred, but that he and other researchers are eager to investigate. "Our work provides evidence for a possible new mechanism of adaptation," Hahn said. "It also raises questions about whether thousands of supposedly independent mutations others have observed in important genes are truly independent. Some of these genes will need to be reanalyzed, because the recognition that some of these mutations are actually MNMs could have an impact on many analyses of DNA sequences." But first, Hahn's group will try to see whether the MNMs they've found in humans conform to the mechanism geneticists have observed in humans' faultier DNA polymerases. "It's satisfying to be able to be able to show that this is real," Hahn said. "I talked about this at a recent conference, and no matter who we talked to, they said the same sorts of things: 'Oh yeah I've seen those before, but I just thought it was a statistical anomaly.' People have seen the phenomenon but they just didn't know it was meaningful. We hope this gets people excited to go back and look at their old sequence data." This work was supported by grants from the Sloan Foundation, the National Science Foundation, and the Indiana University Cox Scholarship Program. Headline 5: Cystic Fibrosis-Associated Bacteria Could Help Fight Back Against Antibiotic Resistance Published By: Science Daily Date of Publication: May 28, 2011 Source: http://www.sciencedaily.com A bacteria which infects people with cystic fibrosis could help combat other antibiotic-resistant microbes, according to a team from Cardiff and Warwick Universities. Continuous use of existing PAGE 74 OF 124 antibiotics means that resistant bacteria are now causing major health problems all over the world. New antibiotics are urgently needed to combat the emergence of multidrug-resistant bacteria such as the MRSA superbug. Now a surprising source of hope has emerged in the form of Burkholderia, a group of bacteria which can cause severe lung infections in people with the genetic disorder cystic fibrosis. However, the Cardiff and Warwick team has now discovered antibiotics from Burkholderia are effective against MRSA and even other cystic fibrosis infecting bacteria. Dr Eshwar Mahenthiralingam, of Cardiff University's School of Biosciences, Cardiff University, has been studying Burkholderia for the last decade. Using forensic fingerprinting tests to genetically identify the bacteria, Dr Mahenthiralingam's research group has tracked strains all over the world and helped develop guidelines to prevent it spreading. By the summer of 2007, Dr Mahenthiralingam had built up a large collection of Burkholderia bacteria. He and his team then decided to screen them for antibiotics active against other bacteria, particularly drugs with the potential to kill other bacteria that infect cystic fibrosis patients. Over the next two years, Dr Mahenthiralingam's team discovered that around one quarter of Burkholderia bacteria have very strong antibiotic activity on multidrug-resistant pathogens such as MRSA. One particular strain, Burkholderia ambifaria, was found to produce two very potent antibiotics active on resistant bacteria, in particular Acinetobacter baumanii. The chemical structures of the antibiotics, called enacyloxins, were determined by Professor Gregory Challis and Dr. Lijiang Song at the University of Warwick, demonstrating that they belong to one of the most successful families of natural product drugs, the polyketides. Other examples of polyketides include erythromycin, which is used to cure many bacterial infections, and doxorubin, used as an anticancer drug. Professor Challis commented: "The combination of enzymes used by Burkholderia to make the enacyloxins is very unusual. Our insights into this process should allow us to use cutting edge synthetic biology techniques to produce novel enacyloxin analogues with improved pharmaceutical properties." The team's findings have now been published in the journal Chemistry and Biology. Dr Mahenthiralingam commented: "Burkholderia are soil bacteria like Streptomyces, which are the source of most of our current antibiotics. Our research therefore offers real hope of a completely new source for the identification and engineering of highly potent antibiotics. With antibiotic resistant bacteria causing great suffering around the world, these new sources are urgently needed." Headline 6: Potential Human Exposure to Prion Diseases Assessed Published By: Science Daily Date of Publication: May 23, 2011 PAGE 75 OF 124 Source: http://www.sciencedaily.com Researchers from the Centers for Disease Control and Prevention (CDC) have examined the potential for human exposure to prion diseases, looking at hunting, venison consumption, and travel to areas in which prion diseases have been reported in animals. Three prion diseases in particular -bovine spongiform encephalopathy (BSE or "Mad Cow Disease"), variant Creutzfeldt-Jakob disease (vCJD), and chronic wasting disease (CWD) -- were specified in the investigation. The results of this investigation are published in the June issue of the Journal of the American Dietetic Association. "While prion diseases are rare, they are generally fatal for anyone who becomes infected. More than anything else, the results of this study support the need for continued surveillance of prion diseases," commented lead investigator Joseph Y. Abrams, MPH, National Center for Emerging and Zoonotic Infectious Diseases, CDC, Atlanta."But it's also important that people know the facts about these diseases, especially since this study shows that a good number of people have participated in activities that may expose them to infection-causing agents." Although rare, human prion diseases such as CJD may be related to BSE. Prion (proteinaceous infectious particles) diseases are a group of rare brain diseases that affect humans and animals. When a person gets a prion disease, brain function is impaired. This causes memory and personality changes, dementia, and problems with movement. All of these worsen over time. These diseases are invariably fatal. Since these diseases may take years to manifest, knowing the extent of human exposure to possible prion diseases could become important in the event of an outbreak. CDC investigators evaluated the results of the 2006-2007 population survey conducted by the Foodborne Diseases Active Surveillance Network (FoodNet). This survey collects information on food consumption practices, health outcomes, and demographic characteristics of residents of the participating Emerging Infections Program sites. The survey was conducted in Connecticut, Georgia, Maryland, Minnesota, New Mexico, Oregon, and Tennessee, as well as five counties in the San Francisco Bay area, seven counties in the Greater Denver area, and 34 counties in western and northeastern New York. Survey participants were asked about behaviors that could be associated with exposure to the agents causing BSE and CWD, including travel to the nine countries considered to be BSE-endemic (United Kingdom, Republic of Ireland, France, Portugal, Switzerland, Italy, the Netherlands, Germany, Spain) and the cumulative length of stay in each of those countries. Respondents were asked if they ever had hunted for deer or elk, and if that hunting had taken place in areas considered to be CWDendemic (northeastern Colorado, southeastern Wyoming or southwestern Nebraska). They were also asked if they had ever consumed venison, the frequency of consumption, and whether the meat came from the wild. The proportion of survey respondents who reported travel to at least one of the nine BSE endemic countries since 1980 was 29.5%. Travel to the United Kingdom was reported by 19.4% of respondents, higher than to any other BSE-endemic country. Among those who traveled, the median duration of travel to the United Kingdom (14 days) was longer than that of any other BSE-endemic country. Travelers to the UK were more likely to have spent at least 30 days in the country (24.9%) compared to travelers to any other BSE endemic country. The prevalence and extent of travel to the UK indicate that health concerns in the UK may also become issues for US residents. The proportion of survey respondents reporting having hunted for deer or elk was 18.5% and 1.2% reported having hunted for deer or elk in CWD-endemic areas. Venison consumption was reported by PAGE 76 OF 124 67.4% of FoodNet respondents, and 88.6% of those reporting venison consumption had obtained all of their meat from the wild. These findings reinforce the importance of CWD surveillance and control programs for wild deer and elk to reduce human exposure to the CWD agent. Hunters in CWDendemic areas are advised to take simple precautions such as: avoiding consuming meat from sickly deer or elk, avoiding consuming brain or spinal cord tissues, minimizing the handling of brain and spinal cord tissues, and wearing gloves when field-dressing carcasses. According to Abrams, "The 2006-2007 FoodNet population survey provides useful information should foodborne prion infection become an increasing public health concern in the future. The data presented describe the prevalence of important behaviors and their associations with demographic characteristics. Surveillance of BSE, CWD, and human prion diseases are critical aspects of addressing the burden of these diseases in animal populations and how that may relate to human health." Headline 7: Genetically Modified Bacteria Filters Out Toxic Vapors Published By: Medical News Today Date of Publication: April 19, 2011 Source: http://www.medicalnewstoday.com Genetically modified bacteria could be used in air filters to extract pesticide vapors from polluted air thanks to work by researchers in China published this month in the International Journal of Environment and Pollution. The bacteria Escherichia coli is perhaps best known as a bacterium that can cause food poisoning and in one form, the O157:H7, can damage the kidneys and even be lethal. However, E coli, is commonly used in biological research as a model organism for a wide range of beneficial experiments. Now, researchers in China have discovered that a genetically modified form of the bacteria can be used in a biofilter to extract the toxic pesticides, parathion and methyl parathion from the air. Junxin Liu of the Chinese Academy of Sciences in Beijing, and colleagues have demonstrated average removal efficiencies of 95.2% for parathion and 98.6% for methyl parathion using a biofilter based on the engineered bacteria E coli BL21. Optimization of the system might allow up to 100% removal. The team explains that compared to conventional biofilters, their system was far more effective, especially in the initial stages of filtering. The pesticides are broken down to p-nitrophenol as well as nitrate and sulfate byproducts. These byproducts are then quickly "mineralized" by other naturally occurring microbes present in the biofilter. Organophosphorus pesticides, including parathion and methyl parathion, are highly effective agrochemicals amounting to more than a third of agricultural crop protection worldwide. Unfortunately, they can accumulate in the environment and pose a risk to human health under some conditions. Bioremediation of water and soil using bacteria that can break down these compounds is being developed. However, Liu and colleagues have focused on air purification using biofilters. Headline 8: Filtering out Pesticides with Genetically Modified Bacteria Published By: ScienceDaily PAGE 77 OF 124 Date of Publication: April 14, 2011 Source: http://www.sciencedaily.com Genetically modified bacteria could be used in air filters to extract pesticide vapors from polluted air thanks to work by researchers in China published this month in the International Journal of Environment and Pollution. The bacteria Escherichia coli is perhaps best known as a bacterium that can cause food poisoning and in one form, the O157:H7, can damage the kidneys and even be lethal. However, E coli, is commonly used in biological research as a model organism for a wide range of beneficial experiments. Now, researchers in China have discovered that a genetically modified form of the bacteria can be used in a biofilter to extract the toxic pesticides, parathion and methyl parathion from the air. Junxin Liu of the Chinese Academy of Sciences in Beijing, and colleagues have demonstrated average removal efficiencies of 95.2% for parathion and 98.6% for methyl parathion using a biofilter based on the engineered bacteria E. coli BL21. Optimization of the system might allow up to 100% removal. The team explains that compared to conventional biofilters, their system was far more effective, especially in the initial stages of filtering. The pesticides are broken down to p-nitrophenol as well as nitrate and sulfate byproducts. These byproducts are then quickly "mineralized" by other naturally occurring microbes present in the biofilter. Organophosphorus pesticides, including parathion and methyl parathion, are highly effective agrochemicals amounting to more than a third of agricultural crop protection worldwide. Unfortunately, they can accumulate in the environment and pose a risk to human health under some conditions. Bioremediation of water and soil using bacteria that can break down these compounds is being developed. However, Liu and colleagues have focused on air purification using biofilters. PAGE 78 OF 124 Section D: Nano Technology Headline 1: Novel nanoparticles communicate to target tumors more efficiently Published By: Physorg Date of Publication: June 19, 2011 Source: http://www.physorg.com For decades, researchers have been working to develop nanoparticles that deliver cancer drugs directly to tumors, minimizing the toxic side effects of chemotherapy. However, even with the best of these nanoparticles, only about 1 percent of the drug typically reaches its intended target. Now, a team of researchers from MIT, the Sanford-Burnham Medical Research Institute, and the University of California at San Diego have designed a new type of delivery system in which a first wave of nanoparticles homes in on the tumor, then calls in a much larger second wave that dispenses the cancer drug. This communication between nanoparticles, enabled by the body's own biochemistry, boosted drug delivery to tumors by over 40-fold in a mouse study. This new strategy could enhance the effectiveness of many drugs for cancer and other diseases, says Geoffrey von Maltzahn, a former MIT doctoral student now at Cambridge-based Flagship VentureLabs, and lead author of a paper describing the system in the June 19 online edition of Nature Materials. "What we've demonstrated is that nanoparticles can be engineered to do things like communicate with each other in the body, and that these capabilities can improve the efficiency with which they find and treat diseases like cancer," says von Maltzahn. Senior author of the paper is Sangeeta Bhatia, the John and Dorothy Wilson Professor of Health Sciences and Technology and a member of MIT's David H. Koch Institute for Integrative Cancer Research. Von Maltzahn and Bhatia drew their inspiration from complex biological systems in which many components work together to achieve a common goal. For example, the immune system works through highly orchestrated cooperation between many different types of cells. "There are beautiful examples throughout biology where at a system scale, complex behaviors emerge as a result of interaction, cooperation, and communication between simple individual components," says von Maltzahn. PAGE 79 OF 124 The MIT team's approach is based on the blood coagulation cascade - a series of reactions that starts when the body detects injury to a blood vessel. Proteins in the blood known as clotting factors interact in a complex chain of steps to form strands of fibrin, which help seal the injury site and prevent blood loss. To harness the communication power of that cascade, the researchers needed two types of nanoparticles - signaling and receiving. Signaling particles, which make up the first wave, exit the bloodstream and arrive at the tumor site via tiny holes in the leaky blood vessels that typically surround tumors (this is the same way that most targeted nanoparticles reach their destination). Once at the tumor, this first wave of particles provokes the body into believing that an injury has occurred at a tumor site, either by emitting heat or by binding to a protein that sets off the coagulation cascade. Receiving particles are coated with proteins that bind to fibrin, which attracts them to the site of blood clotting. Those second-wave particles also carry a drug payload, which they release once they reach the tumor. In a study of mice, one system of communicating nanoparticle systems delivered 40 times more doxorubicin (a drug used to treat many types of cancer) than non-communicating nanoparticles. The researchers also saw a correspondingly amplified therapeutic effect on the tumors of mice treated with communicating nanoparticles. To pave the path for potential clinical trials and regulatory approval, the MIT researchers are now exploring ways to replace components of these cooperative nanosystems with drugs already being tested in patients. For example, drugs that induce coagulation at tumor sites could replace the signaling particles tested in this study. Headline 2: Nanoparticles help scientists harvest light with solar fuels Published By: Physorg Date of Publication: May 19, 2011 Source: http://www.physorg.com The humble alga, hated by boaters and pool owners, may someday help provide us with the raw machinery to power our appliances. Utschig and Tiede are part of Argonne's Photosynthesis Group, which has worked for fifty years to understand photosynthesisвЂ”one of the most mysterious and wonderful chemical processes in the world. Photosynthesis built a green Earth out of the bare, meteor-blistered planet which had sat empty PAGE 80 OF 124 for a billion years; it tipped the composition of the atmosphere towards oxygen, allowing all kinds of life to blossom, including us. The chemistry group is part of a larger effort to develop efficient ways to produce what are termed solar fuels. Most people think of solar panels when they think of solar energy, but the energy that solar panels generate has to be used right awayвЂ”they directly create electricity, which can't be stored easily. The alternative is solar fuels, which pull energy from the sun to create fuel that can be stored for later, such as hydrogen. Hydrogen, a promising fuel in the effort to reduce carbon dioxide emissions, is appealingly clean: when it's burned as fuel, water is the byproduct. But we have yet to discover a lowcost way to manufacture large amounts of hydrogen. "Basically, we've been reverse-engineering photosynthesis," said Argonne chemist David Tiede, who co-authored the paper. "If we understand how Nature does it, we can tweak the process to produce hydrogen." Most solar fuel efforts focus on a type of protein complex called Photosystem I, or PSI, which is the first half of the photosynthetic duo found in all green plants. When light strikes the PSI complex, it momentarily knocks an electron into an "excited" state. The goal is to separate this electron from its home atomвЂ”leaving behind a "hole" of positive chargeвЂ”and channel it to an artificial catalyst to make hydrogen. But the electron only remains excited for the tiniest fraction of a second; the catalyst needs to grab it during this tiny window. With co-author Nada Dimitrijevic, the team designed platinum nanoparticle catalysts. These catalysts have a size and surface chemistry that allows them to stick to PSI molecules at the point where the light-generated electrons accumulate. When the modified platinum nanoparticles and PSI are mixed in water, the two link together. "The platinum nanoparticles have the same size and surface charge as the molecule that PSI would bind to naturally," Tiede said. Because the study design used platinum as a catalyst, which is too expensive to be cost-effective, the research serves as proof-of-concept. Further studies hope to improve the method's efficiency, reliability and economics. "The next step we'll take is experimenting with non-platinum catalysts," Utschig said. "Hopefully we can find a catalyst that can be made with a cheaper metal, which would make the process much more attractive on a large scale." PAGE 81 OF 124 The paper, "Photocatalytic Hydrogen Production from Noncovalent Biohybrid Photosystem I/Pt Nanoparticle Complexes," was published in the Journal of Physical Chemistry Letters and is available online. Headline 3: Nanoparticles may help inhibit Alzheimer's disease and other neurodegenerative disorders Published By: Physorg Date of Publication: June 14, 2011 Source: http://www.physorg.com Nanoparticles of the right dimensions and shape may be the key in combating the plaque that destroys neurons and leads to symptoms associated with Alzheimer's disease, a new report shows. University of Michigan chemical engineering professor Nicholas Kotov says the nanotechnology means can attract and capture the longer fibrils that are known to form plaque related to neurodegenerative disorders. "Both amyloid peptides and nanoparticles exhibit a strong ability to self-assemble into fibrils," Kotov said. "We were open to any possible effect of nanoparticles on the amyloid fibrillation. We were very pleased to see amazing inhibitory effect on amyloids fibrillation which opens the door for new approaches to the development of drugs to prevent Alzheimer's disease." By introducing tetrahedral nanoparticle that were comparable in size with growing fibrils, he discovered that the dangerous plaque readily bonded to them, and their geometry was strongly distorted. Such drastic change in shape results in complete inhibition of their further fibrillation. Typical Alzheimer drugs bond to amyloid peptides in 1:1 ratio. This is known to be inefficient. The nanoparticles can inhibit the amyloid peptide fibrillation in minute quantities with much greater efficiency. One nanoparticle can capture more than 100 amyloid peptides. This high efficiency of fibrillation inhibition makes nanoparticles similar to some proteins that human body uses to protect itself against the progression of Alzheimer's disease. The implication here is that if a likely human compatible particle, for example, were introduced then the effect could help clear, or at least contain, the growth of the debilitating plaque. Cadmium is toxic to humans, but the revelations from this work indicate a big step forward in combating diseases like Alzheimer's. Kotov's laboratory is working toward engineering of such nanoparticles and better understanding their metabolism. PAGE 82 OF 124 Headline 4: Nanoparticle therapeutics might help people suffering from hearing disorders Published By: Physorg Date of Publication: June 13, 2011 Source: http://www.physorg.com For millions of people hearing disorders make a negative impact on their lives. Scientists are looking into new ways of treating hearing disorders, by using different sorts of nanoparticles as original inner ear delivery devices. Their hope is that nanoparticles will be able to deliver drugs that can improve or restore hearing. Due to different anatomic and physiological barriers it is hard to treat hearing disorders by using conventional systemic drug delivery. Therefore scientists are investigating different ways to locally apply drugs using nanoparticles. Researchers at Guangdong Pharmaceutical University in China highlight that several nanoparticles have a combination of properties, such as target specificity, stability in vivo, biocompatibility and capacity to incorporate the encapsulated drugs into the cell, making it possible to use smaller doses and reduce the side effects of therapeutic agents. They anticipate that nanoparticles will play an extremely important role in the development of drug delivery systems, which can find the desired target sites and release the drugs in a controlled way within the cell. In the European Commission-funded project NANOEAR, scientists from several countries in Europe are studying where different nanoparticles go within the inner ear and if these nanoparticles could be harmful or useful in therapeutics. They are currently testing eight nanoparticle classes, for example, biodegradable liposomes, micelles and lipid-core nanocapsules, regarding their delivery of genes, peptides, corticosteroids, siRNA and shRNA. Since nanoparticles also have properties that separate them, the researchers need to find the best carrier for each drug. The projectвЂ™s researchers are working on nanoparticles targeted towards hair cells, neurons and supporting cells. They have identified fundamental peptides helping the nanoparticles to avoid being trapped and dysfunctionalized by the lysosomal enzymes in the cellвЂ™s endosome system, so the nanoparticles are able to deliver the therapeutic drugs to their targets. Nanoparticles can be modified with coatings to escape immune responses. Three of NANOEARвЂ™s partners are focusing on safety and they have not observed any adverse reactions. Within the consortium, researchers at the Medical University of Innsbruck in Austria studied nanoparticles conjugated with a neurotrophin-derived peptide ligand. They found that these nanoparticles selectively targeted the mouse inner ear cells and can potentially be used as inner ear drug delivery devices. PAGE 83 OF 124 Many research projects are in the early stage development. There will be rigorous controls and take years until patients may be helped by the innovations. However, if the researchers manage to make these nanoparticles do exactly what they are made to do, nanoparticle therapeutics will radically change the way hearing disorders are treated. Headline 5: Safety of nanoparticles in food crops is still unclear Published By: Science Daily Date of Publication: June 01, 2011 Source: http://www.sciencedaily.com/ With the curtain about to rise on a much-anticipated new era of "nanoagriculture" вЂ” using nanotechnology to boost the productivity of plants for food, fuel, and other uses вЂ”scientists are reporting a huge gap in knowledge about the effects of nanoparticles on corn, tomatoes, rice and other food crops. Their article appears in ACS' Journal of Agricultural and Food Chemistry. Jorge Gardea-Torresdey and colleagues at The University of Texas at El Paso, a co- investigator for the NSF/EPA University of California Center for Environmental Implications of Nanotechnology, note that nanoparticles, which are 1/50,000th the width of a human hair, are used in products ranging from medicines to cosmetics. The particles also could end up in the environment, settling in the soil, especially as fertilizers, growth enhancers and other nanoagricultural products hit the market. Some plants can take-up and accumulate nanoparticles. But it is unclear whether this poses a problem for plants or for the animals (like humans) that eat them. So, the researchers sorted through the scientific literature looking for evidence to settle the safety question. In the article, the scientists analyzed nearly 100 scientific articles on the effects of different types of nanoparticles on edible plants. They found that the uptake and build-up of nanoparticles varies, and these factors largely depend on the type of plant and the size and chemical composition of the nanoparticles. "This literature review has confirmed that knowledge on plant toxicity of [nanomaterials] is at the foundation stage," the article states, noting that the emerging field of nanoecotoxicology is starting to tackle this topic. Headline 6: Sharpening the Nanofocus Published By: Science Daily Date of Publication: May 18, 2011 Source: http://www.sciencedaily.com/ Such highly coveted technical capabilities as the observation of single catalytic processes in nanoreactors, or the optical detection of low concentrations of biochemical agents and gases are an important step closer to fruition. Researchers with the U.S. Department of Energy (DOE)'s Lawrence PAGE 84 OF 124 Berkeley National Laboratory (Berkeley Lab), in collaboration with researchers at the University of Stuttgart in Germany, report the first experimental demonstration of antenna-enhanced gas sensing at the single particle level. By placing a palladium nanoparticle on the focusing tip of a gold nanoantenna, they were able to clearly detect changes in the palladium's optical properties upon exposure to hydrogen. "We have demonstrated resonant antenna-enhanced single-particle hydrogen sensing in the visible region and presented a fabrication approach to the positioning of a single palladium nanoparticle in the nanofocus of a gold nanoantenna," says Paul Alivisatos, Berkeley Lab's director and the leader of this research. "Our concept provides a general blueprint for amplifying plasmonic sensing signals at the single-particle level and should pave the road for the optical observation of chemical reactions and catalytic activities in nanoreactors, and for local biosensing." Alivisatos, who is also the Larry and Diane Bock Professor of Nanotechnology at the University of California, Berkeley, is the corresponding author of a paper in the journal Nature Materials describing this research. The paper is titled "Nanoantenna-enhanced gas sensing in a single tailored nanofocus." Co-authoring the paper with Alivisatos were Laura Na Liu, Ming Tang, Mario Hentschel and Harald Giessen. One of the hottest new fields in technology today is plasmonics -- the confinement of electromagnetic waves in dimensions smaller than half-the-wavelength of the incident photons in free space. Typically this is done at the interface between metallic nanostructures, usually gold, and a dielectric, usually air. The confinement of the electromagnetic waves in these metallic nanostructures generates electronic surface waves called "plasmons." A matching of the oscillation frequency between plasmons and the incident electromagnetic waves gives rise to a phenomenon known as localized surface plasmon resonance (LSPR), which can concentrate the electromagnetic field into a volume less than a few hundred cubic nanometers. Any object brought into this locally confined field -- referred to as the nanofocus -- will influence the LSPR in a manner that can be detected via dark-field microscopy. "Nanofocusing has immediate implications for plasmonic sensing," says Laura Na Liu, lead author of the Nature Materials paper who was at the time the work was done a member of Alivisatos' research group but is now with Rice University. "Metallic nanostructures with sharp corners and edges that form a pointed tip are especially favorable for plasmonic sensing because the field strengths of the electromagnetic waves are so strongly enhanced over such an extremely small sensing volume." Plasmonic sensing is especially promising for the detection of flammable gases such as hydrogen, where the use of sensors that require electrical measurements pose safety issues because of the potential threat from sparking. Hydrogen, for example, can ignite or explode in concentrations of only four-percent. Palladium was seen as a prime candidate for the plasmonic sensing of hydrogen because it readily and rapidly absorbs hydrogen that alters its electrical and dielectric properties. PAGE 85 OF 124 However, the LSPRs of palladium nanoparticles yield broad spectral profiles that make detecting changes extremely difficult. "In our resonant antenna-enhanced scheme, we use double electron-beam lithography in combination with a double lift-off procedure to precisely position a single palladium nanoparticle in the nanofocus of a gold nanoantenna," Liu says. "The strongly enhanced gold-particle plasmon near-fields can sense the change in the dielectric function of the proximal palladium nanoparticle as it absorbs or releases hydrogen. Light scattered by the system is collected by a dark-field microscope with attached spectrometer and the LSPR change is read out in real time." Alivisatos, Liu and their co-authors found that the antenna enhancement effect could be controlled by changing the distance between the palladium nanoparticle and the gold antenna, and by changing the shape of the antenna. "By amplifying sensing signals at the single-particle level, we eliminate the statistical and average characteristics inherent to ensemble measurements," Liu says. "Moreover, our antenna-enhanced plasmonic sensing technique comprises a noninvasive scheme that is biocompatible and can be used in aqueous environments, making it applicable to a variety of physical and biochemical materials." For example, by replacing the palladium nanoparticle with other nanocatalysts, such as ruthenium, platinum, or magnesium, Liu says their antenna-enhanced plasmonic sensing scheme can be used to monitor the presence of numerous other important gases in addition to hydrogen, including carbon dioxide and the nitrous oxides. This technique also offers a promising plasmonic sensing alternative to the fluorescent detection of catalysis, which depends upon the challenging task of finding appropriate fluorophores. Antenna-enhanced plasmonic sensing also holds potential for the observation of single chemical or biological events. "We believe our antenna-enhanced sensing technique can serve as a bridge between plasmonics and biochemistry," Liu says. "Plasmonic sensing offers a unique tool for optically probing biochemical processes that are optically inactive in nature. In addition, since plasmonic nanostructures made from gold or silver do not bleach or blink, they allow for continuous observation, an essential capability for in-situ monitoring of biochemical behavior." Headline 7: BMS Expands Deal to Evaluate TekmiraвЂ™s RNAi Delivery Technology Published By: Genengnews Date of Publication: May 17, 2011 Source: http://www.genengnews.com PAGE 86 OF 124 Tekmira Pharmaceuticals expanded its current multiyear collaboration with Bristol-Myers Squibb (BMS) to include evaluation of TekmiraвЂ™s newly developed lipid nanoparticle (LNP) formulations designed for delivery to tumors and other tissues outside the liver. In addition, the two companies are expanding ongoing target validation work. вЂњWe have been successfully collaborating with Bristol-Myers Squibb for several years,вЂќ comments Mark J. Murray, Ph.D., TekmiraвЂ™s president and CEO. вЂњLast year, we signed a multiyear target validation agreement under which Tekmira provides Bristol-Myers Squibb with LNP formulations designed to validate the function of certain genes. вЂњWe are now expanding that work to include further evaluation of TekmiraвЂ™s proprietary LNP technology to identify formulations capable of targeting tumors and certain tissues outside of the liver. The new work also includes additional cellular targets that were beyond the scope of the original agreement,вЂќ Dr. Murray adds. вЂњBristol-Myers Squibb will continue to share the data from this research with Tekmira.вЂќ Under the original target validation agreement, BMS paid $3 million to use siRNA molecules formulated by Tekmira in LNPs to silence target genes of interest. BMS is conducting the preclinical work to validate the function of certain genes and is sharing the data with Tekmira. Bristol-Myers Squibb will have a first right to negotiate a licensing agreement on certain RNAi products developed by Tekmira that evolve from gene targets that it validates. TekmiraвЂ™s LNP technology (formerly referred to as stable nucleic acid-lipid particles, or SNALP) encapsulates siRNAs in uniform lipid nanoparticles that have demonstrated the ability to deliver RNAi therapeutics to disease sites in preclinical models. LNP formulations comprise several lipid components that can be adjusted to suit the specific application. The technology relies on the enhanced permeability and retention effect, which occurs because these nucleic acid-containing particles have a long circulation time in the blood. These results in increased accumulation at sites of vascular leaks, such as those found at sites of tumor cell growth, infection, or inflammation. Once at the target site, cells take up the LNP through endocytosis and the nucleic acid payload is delivered inside the cell. Besides BMS, Tekmira has partnerships focused on using its LNP delivery technology with Alnylam Pharmaceuticals, Pfizer, Roche, and Takeda Pharmaceuticals. While Pfizer, Roche, and TakedaвЂ™s work is at the discovery-to-preclinical stage, Alnylam has two clinical-stage candidates that use TekmiraвЂ™s platform. ALN-VSP is in Phase I as a treatment for patients with advanced solid tumors with liver involvement including hepatocellular carcinoma. ALN-TTR is also in early-stage clinical trials for TTR amyloidosis. PAGE 87 OF 124 Alnylam also has a third LNP formulation candidate; ALN-PCS is in preclinical development for hypercholesterolemia. Tekmira is conducting a Phase I trial with its TKM ApoB (previously ApoB SNALP) in patients with high LDL cholesterol. Also in development by Tekmira is cancer drug TKM PLK1 for cancer and TKM Ebola, both in preclinical studies. Headline 8: BMS Expands Deal to Evaluate TekmiraвЂ™s RNAi Delivery Technology Published By: Gen News Date of Publication: May 17, 2011 Source: http://www.genengnews.com Firm will now test lipid nanoparticle formulations in cancer, over and above using them for target validation. Tekmira Pharmaceuticals expanded its current multiyear collaboration with Bristol-Myers Squibb (BMS) to include evaluation of TekmiraвЂ™s newly developed lipid nanoparticle (LNP) formulations designed for delivery to tumors and other tissues outside the liver. In addition, the two companies are expanding ongoing target validation work. вЂњWe have been successfully collaborating with Bristol-Myers Squibb for several years,вЂќ comments Mark J. Murray, Ph.D., TekmiraвЂ™s president and CEO. вЂњLast year, we signed a multiyear target validation agreement under which Tekmira provides Bristol-Myers Squibb with LNP formulations designed to validate the function of certain genes. вЂњWe are now expanding that work to include further evaluation of TekmiraвЂ™s proprietary LNP technology to identify formulations capable of targeting tumors and certain tissues outside of the liver. The new work also includes additional cellular targets that were beyond the scope of the original agreement,вЂќ Dr. Murray adds. вЂњBristol-Myers Squibb will continue to share the data from this research with Tekmira.вЂќ Under the original target validation agreement, BMS paid $3 million to use siRNA molecules formulated by Tekmira in LNPs to silence target genes of interest. BMS is conducting the preclinical work to validate the function of certain genes and is sharing the data with Tekmira. Bristol-Myers Squibb will have a first right to negotiate a licensing agreement on certain RNAi products developed by Tekmira that evolve from gene targets that it validates. PAGE 88 OF 124 TekmiraвЂ™s LNP technology (formerly referred to as stable nucleic acid-lipid particles, or SNALP) encapsulates siRNAs in uniform lipid nanoparticles that have demonstrated the ability to deliver RNAi therapeutics to disease sites in preclinical models. LNP formulations comprise several lipid components that can be adjusted to suit the specific application. The technology relies on the enhanced permeability and retention effect, which occurs because these nucleic acid-containing particles have a long circulation time in the blood. This result in increased accumulation at sites of vascular leaks, such as those found at sites of tumor cell growth, infection, or inflammation. Once at the target site, cells take up the LNP through endocytosis and the nucleic acid payload is delivered inside the cell. Besides BMS, Tekmira has partnerships focused on using its LNP delivery technology with Alnylam Pharmaceuticals, Pfizer, Roche, and Takeda Pharmaceuticals. While Pfizer, Roche, and TakedaвЂ™s work is at the discovery-to-preclinical stage, Alnylam has two clinical-stage candidates that use TekmiraвЂ™s platform. ALN-VSP is in Phase I as a treatment for patients with advanced solid tumors with liver involvement including hepatocellular carcinoma. ALN-TTR is also in early-stage clinical trials for TTR amyloidosis. Alnylam also has a third LNP formulation candidate; ALN-PCS is in preclinical development for hypercholesterolemia. Tekmira is conducting a Phase I trial with its TKM ApoB (previously ApoB SNALP) in patients with high LDL cholesterol. Also in development by Tekmira is cancer drug TKM PLK1 for cancer and TKM Ebola, both in preclinical studies. Headline 9: Silver Cycle: New Evidence for Natural Synthesis of Silver Nanoparticles Published By: ScienceDaily Date of Publication: May 12, 2011 Source: http://www.sciencedaily.com/ Nanoparticles of silver are being found increasingly in the environment -- and in environmental science laboratories. Because they have a variety of useful properties, especially as antibacterial and antifungal agents, silver nanoparticles increasingly are being used in a wide variety of industrial and consumer products. This, in turn, has raised concerns about what happens to them once released into the environment. Now a new research paper adds an additional wrinkle: Nature may be making silver nanoparticles on its own. PAGE 89 OF 124 A team of researchers from the Florida Institute of Technology (FIT), the State University of New York (SUNY), Buffalo, and the National Institute of Standards and Technology (NIST) reports that, given a source of silver ions, naturally occurring humic acid will synthesize stable silver nanoparticles. "Our colleague, Virender Sharma, had read an article in which they were using wine to form nanoparticles. He thought that, based on the similar chemistry, we should be able to produce silver nanoparticles with humic acids," explains FIT chemist Mary Sohn. "First we formed them by traditional methods and then we tried one of our river sediment humic acids. We were really excited that we could see the characteristic yellow color of the nanoparticles." Samples were sent to Sarbajit Banerjee at SUNY Buffalo and Robert MacCuspie at NIST for detailed analyses to confirm the presence of silver nanoparticles. "Humic acid" is a complex mixture of many organic acids that are formed during the decay of dead organic matter. Although the exact composition varies from place to place and season to season, humic acid is ubiquitous in the environment. Metallic nanoparticles, MacCuspie explains, have characteristic colors that are a direct consequence of their size. (The effect is called "surface plasmon resonance" and is caused by surface electrons across the nanoparticle oscillating in concert.) Silver nanoparticles appear a yellowish brown. The team mixed silver ions with humic acid from a variety of sources at different temperatures and concentrations and found that acids from river water or sediments would form detectable silver nanoparticles at room temperature in as little as two to four days. Moreover, MacCuspie says, the humic acid appears to stabilize the nanoparticles by coating them and preventing the nanoparticles from clumping together into a larger mass of silver. "We believe it's actually a similar process to how nanoparticles are synthesized in the laboratory," he says, except that the lab process typically uses citric acid at elevated temperatures. "This caught us by surprise because a lot of our work is focused on how silver nanoparticles may dissolve when they're released into the environment and release silver ions," MacCuspie says. Many biologists believe the toxicity of silver nanoparticles, the reason for their use as an antibacterial or antifungal agent, is due to their high surface area that makes them an efficient source of silver ions, he says, but "this creates the idea that there may be some sort of natural cycle returning some of the ions to nanoparticles." It also helps explain the discovery, over the past few years, of silver nanoparticles in locations like old mining regions that are not likely to have been exposed to humanmade nanoparticles, but would have significant concentrations of silver ions. Headline 10: NanoBio and GSK Commence Phase Nanoemulsion-Based OTC Treatment for Cold Sores 3 Studies of Published By:Medical News Today PAGE 90 OF 124 Date of Publication: May 12, 2011 Source: http://www.medicalnewstoday.com NanoBioВ® Corporation today announced the initiation of two Phase 3 multicenter trials evaluating NB001 as a topical treatment for cold sores, a step forward in their OTC licensing agreement with GlaxoSmithKline Consumer Healthcare (GSK CH). In December 2009, GSK CH licensed exclusive rights in the United States and Canada to NB-001 for the OTC treatment of cold sores. GSK currently offers the market-leading cold sore treatment Abreva, the only OTC medicine approved by the Food & Drug Administration (FDA) to shorten cold sore healing time. The two trials of NB-001 will be conducted in 1700 subjects at 72 clinical sites and will evaluate the effectiveness of NB-001 to reduce cold sore healing time. "Based on the efficacy of NB-001 in Phase 2, we are very optimistic about these trials and the path to FDA approval," said Mary Flack, MD, Vice President of Clinical Research, NanoBio. "Cold sores are painful and embarrassing for the roughly 20 percent of the US population that suffer from them. The initiation of these trials marks a significant step towards the commercialization of a new treatment offering for cold sores, as well as potential other new offerings to come from our nanoemulsion-based platform technology." Headline 11: Inverting a Standard Experiment Sometimes Produces Different Results Published By: ScienceDaily Date of Publication: May 1, 2011 Source: http://www.sciencedaily.com Nanoparticles will soon be used as tiny shuttles to deliver genes to cells and drugs to tumors in a more targeted way than was possible in the past. But as the scientists prepare to use the nanoparticles in medicine, concerns have arisen about their potential toxicity. Studies of both the applications of nanoparticles and their toxicity rely on the ability of scientists to quantify the interaction between the nanoparticles and cells, particularly the uptake (ingestion) of nanoparticles by cells. In the standard laboratory tests of the biological activity of nanoparticles, cells are plated on the bottom of a dish and culture medium containing nanoparticles is poured on top of them. It seems straightforward enough. But recently Washington University in St. Louis scientist Younan Xia started to worry about the in vitro experiments his lab was doing with gold nanoparticles. PAGE 91 OF 124 What if the cells were upside down, he wondered? Would that make a difference? Would it change their uptake rate? "People assumed that if they prepared a suspension, the suspension was going to have the same concentration everywhere, including at the surface of the cells," says Xia, PhD, the James M. McKelvey Professor in the Department of Biomedical Engineering. A battery of experiments in Xia's lab with both the standard and upside-down setups showed that nanoparticles above certain sizes and weights will settle out. So concentrations of the nanoparticles near the cell surfaces are different from those in the bulk solution and cellular uptake rates are higher. As the scientists conclude in the Nature Nanotechnology article describing the experiments, "Studies on the cellular uptake of nanoparticles that have been conducted with cells in the upright configuration may have given rise to erroneous and misleading data." Topsies and Turveys Scientists have felt they could safely assume that the concentration of nanoparticles in the fluid next to the cells, which drives cellular uptake, was the same as the initial concentration of nanoparticles in the medium because the particles are small enough to be easily lofted by Brownian motion, the random motion of the molecules in the liquid. Gravity, by this accounting, did not override this force for diffusion and the nanoparticles stayed in solution instead of settling out. "We started to wonder, however, because our nanoparticles are made of gold," Xia says. "Gold is nontoxic but it is also very heavy, so it was conceivable relatively large nanoparticles might settle." Since it is impossible to measure the exact concentration of gold nanoparticles at the surface of a cell, Xia and coworkers designed a simple experiment to test whether settling changed the concentration there and the cellular uptake. Xia's lab tested gold nanospheres of three sizes, nanocages of two edge lengths, and nanorods, some with surface coatings that picked up serum proteins in solution and others coated with a chemical that acts as an antifouling agent. After the cells were incubated in the nanoparticle-bearing medium, the concentration of the nanoparticles in the medium was measured spectroscopically and the number of particles each cell had taken up was calculated from the difference in the concentrations. In the literature, Xia says, there are reports that the cellular uptake of nanoparticles depends on the nanoparticles' size, shape and surface coating. PAGE 92 OF 124 His lab's experiments showed that these characteristics are secondary, relevant only insofar as they affect the sedimentation and diffusion velocities of the nanoparticles. For small, light particles, there was no disparity between the cells in the upright and the upside-down configurations. In the case of larger, heavier particles, however, sedimentation dominated, and the upright cells took in more nanoparticles than the upside-down cells. "All earlier work may need to be re-evaluated to account for the effects of sedimentation on nanoparticle dosimetry," the authors conclude. "It's no different from medicines that have to be shaken to suspend a powder in water. If you don't shake the bottle," Xia says, "you end up under- or overdosing Headline 12: New Solar Cell Technology Greatly Boosts Efficiency Published By: Science Daily Date of Publication: April 29, 2011 Source: http://www.sciencedaily.com/ With the creation of a 3-D nanocone-based solar cell platform, a team led by Oak Ridge National Laboratory's Jun Xu has boosted the light-to-power conversion efficiency of photovoltaics by nearly 80 percent. The technology substantially overcomes the problem of poor transport of charges generated by solar photons. These charges -- negative electrons and positive holes -- typically become trapped by defects in bulk materials and their interfaces and degrade performance. "To solve the entrapment problems that reduce solar cell efficiency, we created a nanocone-based solar cell, invented methods to synthesize these cells and demonstrated improved charge collection efficiency," said Xu, a member of ORNL's Chemical Sciences Division. The new solar structure consists of n-type nanocones surrounded by a p-type semiconductor. The ntype nanoncones are made of zinc oxide and serve as the junction framework and the electron conductor. The p-type matrix is made of polycrystalline cadmium telluride and serves as the primary photon absorber medium and hole conductor. With this approach at the laboratory scale, Xu and colleagues were able to obtain a light-to-power conversion efficiency of 3.2 percent compared to 1.8 percent efficiency of conventional planar structure of the same materials. PAGE 93 OF 124 "We designed the three-dimensional structure to provide an intrinsic electric field distribution that promotes efficient charge transport and high efficiency in converting energy from sunlight into electricity," Xu said. Key features of the solar material include its unique electric field distribution that achieves efficient charge transport; the synthesis of nanocones using inexpensive proprietary methods; and the minimization of defects and voids in semiconductors. The latter provides enhanced electric and optical properties for conversion of solar photons to electricity. Because of efficient charge transport, the new solar cell can tolerate defective materials and reduce cost in fabricating next-generation solar cells. "The important concept behind our invention is that the nanocone shape generates a high electric field in the vicinity of the tip junction, effectively separating, injecting and collecting minority carriers, resulting in a higher efficiency than that of a conventional planar cell made with the same materials," Xu said. Research that forms the foundation of this technology was accepted by this year's Institute of Electrical and Electronics Engineers photovoltaic specialist conference and will be published in the IEEE Proceedings. The papers are titled "Efficient Charge Transport in Nanocone Tip-Film Solar Cells" and "Nanojunction solar cells based on polycrystalline CdTe films grown on ZnO nanocones." The research was supported by the Laboratory Directed Research and Development program and the Department of Energy's Office of Nonproliferation Research and Engineering. Other contributors to this technology are Sang Hyun Lee, X-G Zhang, Chad Parish, Barton Smith, Yongning He, Chad Duty and Ho Nyung Lee. Headline 13: Shrink Nanotechnologies to Acquire Nanopoint for Live Cell Imaging Capabilities Published By: Gen News Date of Publication: April 12, 2011 Source: http://www.genengnews.com Shrink expects firmвЂ™s products will complement its solutions for drug discovery. Shrink Nanotechnologies is planning on buying Nanopoint, a biomedical instrumentation and microfluidics company. Nanopoint has developed extended time-lapse live-cell imaging solutions, which Shrink believes will complement its own stem cell-based research tools. PAGE 94 OF 124 Nanopoint's cellTRAYВ® line of products includes the cellTRAY imaging system, cellTRAY microfluidics system, cellTRAY mini-microscope system, and associated consumables including cellTRAY slide and cellTRAY dish. These provide an automated microfluidics delivery system, onstage incubation system, and imaging software solutions for drug discovery, assisted reproductive technologies, lab-on-a-chip, stem cell research, and biodetection. Nanopoint CEO Cathy Owen states, "Nanopoint has spent six years and over $6 million building a world-class extended live-cell imaging platform and refining that platform along with our customers to meet the unique requirements of the assisted reproduction, drug discovery, and stem cell research markets.вЂќ Shrink develops nanotechnology components and systems for various industries using its NanoShrinkв„ў plastic and associated ShrinkChip Manufacturing Solutionв„ў. According to its letter of intent to acquire 100% of the equity interests in Nanopoint, Shrink will exchange 25,750,000 shares of its common stock. Additional stock payments of up to 40,000,000 shares will be made upon Nanopoint meeting certain sales and EBITDA targets by June 30, 2012, and December 31, 2013. Shrink expects to retain all critical Nanopoint employees. At closing Nanopoint will operate as a wholly owned subsidiary of Shrink. вЂњWe believe that there is tremendous synergy between our respective productsвЂ”StemDisc and Cell Align, in particularвЂ”along with work that we are doing with the Corning modular microfluidics platform, and we believe that the Nanopoint distribution group is a terrific way for Shrink to leverage on the relationships that Nanopoint has been able to build,вЂќ says Shrink CEO Mark L. Baum. Owen notes that Nanopoint has established a network of distributors in Australia, Asia, and Europe. PAGE 95 OF 124 Section E: Pharmaceuticals Headline 1: Cubist might stay clear of Ph3 for antibiotic, analyst says Published By: Fiercebiotech Date of Publication: June 27, 2011 Source: http://www.fiercebiotech.com While Cubist Pharmaceuticals ($CBST) is mulling over whether to advance its antibiotic against C. difficile infections into late-stage development, an analyst says the developer might not pursue the studies after Phase II data didn't show the drug could be clearly differentiated from the growing number of such treatments. Cubist reported yesterday it would decide later this year whether to conduct further trials of the antibiotic, classified as CB-183,315, while the firm moves ahead with late-stage development of a separate antibiotic, CXA-201. With CB-183,315, the Lexington, MA-based firm's Phase II study showed the treatment's ability to treat diarrhea associated with C. diff bugs on par with vancomycin, the long-used antibiotic for such infections. Yet the experimental antibiotic didn't show it was superior to vancomycin in treating a particularly dangerous strain of C. diff called NAP-1, something that might have separated Cubist's drug from the latest crop of similar treatments--including Optimer Pharmaceuticals' recently approved antibiotic Dificid, Needham analyst Alan Carr wrote in a note to investors yesterday. "Cubist had previously indicated that efficacy against NAP-1 may be a key area of potential differentiation from Dificid," Carr said. "Hence, we believe there is a possibility that Cubist may not pursue further development of (CB-183,315)." Of course, Cubist has found a way to share in Optimer's ($OPTR) recent win with Dificid, with its deal to co-promote the drug with the San Diego-based company to U.S. hospitals, where C. diff often camps out and can spread to patients. Yet the future of its internal candidate against the bug seems awfully uncertain right now. Headline 2: Constellation Pharma takes different route than rival in hot epigenetics field Published By: FierceBiotech Date of Publication: June 25, 2011 Source: http://www.fiercebiotech.com PAGE 96 OF 124 With plenty of science to explore but limited funds, a biotech startup often faces the challenge of where to focus its time and money. At Constellation Pharmaceuticals, CEO Mark Goldsmith tells Xconomy that his firm is placing bets on three areas of the emerging epigenetics field, believing that promising drug targets for cancer and other diseases exist in all of them. The Cambridge, MA-based firm's strategy to spread its research efforts across three classes of epigenetic enzymes--which are involved in turning on or off certain disease genes and modulating chromatin structures--provides a clear point of differentiation from its crosstown rival Epizyme. Epizyme, another venture-based start-up, has been focusing its research efforts on one class of epigenetic enzymes called histone methlytransferases (HMTs). There are certainly merits to both the firms' strategies. With its focus on HMTs, Epizyme has landed two deals this year with GlaxoSmithKline ($GSK) and Eisai Pharmaceuticals that have brought the start-up a total of $26 million in upfront money and potential milestone payments of more than $800 million. While Constellation (a 2008 Fierce 15 company) hasn't revealed any such Big Pharma pacts, the firm is building up deep scientific expertise in epigenetics that could potentially provide a greater wealth of targets than its counterpart down the road. In an endorsement of the startup's progress, Constellation's venture backers added $15 million to its Series B round announced earlier this month, giving the company more financial firepower to move ahead with its multiple research programs. And Goldsmith, whose company also has an HMT program, told FierceBiotech earlier this month that the firm hopes to enter the clinic with its lead compound by the end of 2012. "We think it will be more powerful to take a holistic view of chromatin," Goldsmith told Xconomy in today's report. Headline 3: Regeneron Drug Called Effective in FDA Review Published By: The Wall Street of Journal Date of Publication: June 22, 2011 Source: http://online.wsj.com Food and Drug Administration reviewers confirmed that Regeneron Pharmaceuticals Inc.'s proposed eye drug was effective in the treatment of a vision-deteriorating condition. The drug agency, which released a review of the product on its website Wednesday, didn't raise any major safety concerns about the drug prior to an FDA advisory panel meeting that is set for Friday. The panel is expected to recommend the FDA approve the product. PAGE 97 OF 124 The drug, called VEGF Trap-Eye, is designed to treat wet age-related macular degeneration. The FDA based its review on company-funded studies that compared the drug to Roche Holding AG's Lucentis, the leading treatment for the condition. The FDA said the Regeneron drug, whose proposed brand name is Eylea, was equally effective as Lucentis, when comparing the proportion of patients who maintained their vision. In Wednesday trading, shares of Regeneron rose 5.1% to $57.82 on the Nasdaq Stock Market. The stock is up more than 50% in the last three months. Wall Street analysts viewed the documents as positive or neutral, with many projecting annual sales of the drug to eventually exceed $1 billion. The FDA's documents contain a proposed label for the drug if it is approved, something that multiple analysts viewed as a positive sign for the drug's review prospects. Citigroup analyst Yaron Werber expects approval of the drug, but cautioned that some uncertainty remains as the documents contain little insight into FDA's actual thinking about the drug. VEGF Trap-Eye, which is administered by direct injections into the eye, works by binding to and inhibiting numerous proteins that are believed to play a critical role in the formation of new blood vessels. That mechanism is similar to Lucentis and Roche's cancer drug Avastin, which is also used by some doctors to treat age-related macular degeneration. Novartis AG sells Lucentis outside the U.S. Roche reported U.S. sales of Lucentis of about $1.7 billion last year. VEGF Trap-Eye is designed to be administered about every two months, compared with monthly injections for Lucentis. That could be an advantage for the Regeneron drug if the less frequent dosing strategy is approved. The FDA panel will be asked to discuss the frequency of dosing with VEGF Trap-Eye and whether patients should still be monitored every four weeks. On Friday, the panel will also be asked to vote on whether it thinks VEGF Trap-Eye is safe and effective. The agency said there have been reports of elevations in intraocular pressure following repeated dosing of products like Lucentis and Avastin and that it was seen "in low frequency" among patients in the VEGF Trap-Eye studies. The panel will be asked if it has any recommendations for ways to handle the issue. PAGE 98 OF 124 Most market observers see Regeneron's drug gaining the panel's recommendation and FDA approval by Aug. 20. Should VEGF Trap-Eye get final approval, Regeneron will face off against Roche in the market and possibly in the courtroom. Germany's Bayer AG has rights to sell VEGF Trap-Eye outside the U.S. A Roche spokesman said Tuesday that Lucentis has "set a high bar for both safety and efficacy" and been studied in 18 completed clinical trials. The company is studying a higher dose version and different dosing regiments, along with sustained delivery technology that may cut the number of injections. Wet age-related macular degeneration gradually destroys central vision by damaging the macula, which is located in the back of the eye and allows sharp vision of fine detail. It occurs when abnormal blood vessels from behind the retina, often leaking blood and fluid and displacing the macula. Headline 4: FDA Says Diabetes Drug Might Raise Cancer Risk Published By: The Wall Street of Journal Date of Publication: June 19, 2011 Source: http://online.wsj.com The use of Takeda Pharmaceutical Co.'s diabetes drug Actos for more than one year might increase the risk of bladder cancer, the U.S. Food and Drug Administration said. In a posting on its website Wednesday, FDA said the product label would be updated to include information about the risk of bladder cancer along with a so-called medication guide that is meant for patients. About 2.3 million prescriptions were filled for Actos and medicines containing the same active ingredient from January 2010 through October, FDA said. The agency said Actos shouldn't be used in patients with active bladder cancer and urged "caution" in using Actos in patients with a history of bladder cancer. In September the FDA announced a safety review of Actos that was prompted by preliminary, fiveyear data from an ongoing, 10-year study involving the drug. The FDA said Wednesday that five-year results didn't show an overall association between Actos and the risk of bladder cancer. However, the agency said there was an increased risk of bladder cancer in patients with the longest exposure to Actos and in those with the highest cumulative dose of the drug. PAGE 99 OF 124 The agency also said it was aware of a study conducted in France that suggests an increased risk of bladder cancer, which recently prompted French health authorities to suspend use of Actos. Germany has recommended against starting Actos in new patients. FDA said it would conduct a comprehensive review of the French study. Takeda has said the final result from the 10-year study will provide a better understanding of any risk of bladder cancer. Actos is in the same class of drugs as GlaxoSmithKline PLC's Avandia. Use of Avandia was sharply restricted by the FDA last year because of concerns the drug might increase the risk of heart attacks and strokes. The 10-year Actos study involves 193,099 patients with diabetes who are members of the Kaiser Permanente Northern California health plan. The study is being funded by Takeda and is designed to address bladder safety concerns raised in earlier studies. Headline 5: FDA approves Glaxo, Valeant's epilepsy drug Published By: Biospectrum India Date of Publication: June 16, 2011 Source: http://www.biospectrumindia.com Valeant Pharmaceuticals International and GlaxoSmithKline announced that the US Food and Drug Administration has approved Potiga (ezogabine) Tablets, a potassium channel opener, as adjunctive treatment of partial-onset seizures in patients aged 18 years and older. "We are so pleased to reach such an important milestone with the U.S. approval of Potiga by the FDA," stated Susan Hall, PhD, head of research and development at Valeant. "We believe this product will play a needed role in the management of partial onset seizures in appropriate patients who are uncontrolled on their current medications." FDA has recommended that ezogabine be scheduled as a controlled substance under the Controlled Substances Act (CSA). Final classification is still under review by the Federal Drug Enforcement Administration (DEA) and ezogabine will not be available until this process is complete. Ezogabine is expected to be available in U.S. pharmacies by the end of the year. The efficacy of ezogabine as adjunctive therapy in partial onset seizures was established in 3 controlled clinical studies involving 1,239 adult patients. The primary endpoint was percent change in seizure frequency from baseline in the double-blind treatment phase. PAGE 100 OF 124 FDA has determined that a Risk Evaluation and Mitigation Strategy (REMS) will be necessary for ezogabine, with the goal of informing healthcare professionals of the risk of urinary retention and the symptoms of acute urinary retention. Ezogabine caused urinary retention in clinical trials. Urinary retention was reported as an adverse event in 29 out of 1,365 (approximately 2 percent) patients treated with ezogabine. In all studies of patients with partial-onset seizures, including openlabel studies, five patients required catheterization (four on ezogabine and one on placebo). Headline 6: Par Pharmaceutical to Acquire Edict Pharmaceuticals Published By: Prnewswire Date of Publication: May 25, 2011 Source: http://www.prnewswire.com Par Pharmaceutical Companies, Inc. (NYSE: PRX) announced today that it entered into a definitive agreement to acquire privately-held Edict Pharmaceuticals, an India-based developer and manufacturer of generic pharmaceuticals, for up to $37.6 million in cash and Par's repayment of certain additional pre-close indebtedness. The transaction is expected to be accretive in 2013. Edict Pharmaceuticals is a Chennai, India-based developer and manufacturer of solid oral dosage generic pharmaceuticals with a highly-skilled research and development team and strong product pipeline focused on niche first-to-file, first-to-market formulations. Edict currently has seven ANDAs filed with the U.S. FDA and one ANDA filed in the name of a development partner with an additional 14 products in development. Commenting on the acquisition, Paul V. Campanelli, President of Par Pharmaceutical, said, "This transaction enhances Par's already successful research and development infrastructure and demonstrates Par's intention to continue to build out our product development platform. Also, Edict's facility adds significant operational capacity and provides business continuity protection for our Spring Valley, NY facility." Mr. Campanelli continued, "Par has a long-standing relationship with Edict's CEO, Muthusamy 'Samy' Shanmugan, having collaborated on numerous current Par products. He shares Par's highly entrepreneurial culture and cost-efficient approach to product development. I am very excited to welcome Samy and his experienced and dedicated team to Par." The acquisition is subject to customary conditions and approvals. Par expects to complete the transaction by the end of the year. PAGE 101 OF 124 Headline 7: Cell Biosciences Pays $9M to Acquire Brightwell Technologies for Micro-Flow Imaging Platform Published By: Gen News Date of Publication: May 15, 2011 Source: http://www.genengnews.com Firm says deal will bolster its position in the protein therapeutics analytics field. Protein analysis specialist Cell Biosciences has bought Canada-based Brightwell Technologies for $9 million in cash to acquire the firmвЂ™s digital-image based Micro-Flow ImagingTM (MFITM) platform for protein analysis. The MFI platform has been developed to allow the analysis of subvisible particles in biotherapeutics, and it has applications at every stage of drug development and manufacturing, Brightwell claims. The technology can be applied to measure protein aggregates and particulates, air bubbles, silicone oil droplets, and contaminants in the subvisible and visible ranges. Cell Biosciences develops protein-analysis instrumentation systems, software, and assay products for applications in research, biotherapeutics production, and biomarker discovery. The firm moved into the protein-therapeutics market in October 2010, with the $12 million acquisition of Convergent Biosciences. Convergent has pioneered the development of whole-column detection capillary isoelectric focusing for protein characterization. Cell Biosciences says the acquisition of Brightwell will significantly bolster its position in the protein therapeutics analysis field, with the ability to offer a second platform that is targeted to the same customer set. вЂњThis is our fourth acquisition in 18 months and it represents another important step in our plan to build a highly focused and differentiated protein analysis pure-play,вЂќ comments Tim Harkness, Cell BiosciencesвЂ™ president and CEO. Last month Brightwell launched its latest line of MFI instruments, the MFI 5000 series. Building on the success of the 4000 series, the new instruments feature additional automation to further streamline the setup process, as well as a smaller benchtop footprint. Headline 8: EMA approves Biogen Avonex Pen Published By: Biospectrumasia Date of Publication: April 20, 2011 Source: http://www.biospectrumasia.com Biogen announced that the European Medicines AgencyвЂ™s Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion recommending the approval of AVONEX PEN for patients with relapsing multiple sclerosis (MS) and patients with a single demyelinating event. The CHMP recommendation provides the basis for a European Commission licensing decision, which is expected within 75 days from the opinion. The company also announced an authorization for AVONEX PEN from Health Canada. AVONEX PEN is designed to be the first single-use, once-a-week, fully integrated intramuscular autoinjector available for use with AVONEX treatment. It has been designed to improve convenience PAGE 102 OF 124 of AVONEX administration, while also reducing injection anxiety. The CHMP decision was based, in part, on a phase IIIb study in which the overall success rate in using AVONEX PEN in patients with MS was 89 percent. In the study, 94 percent of patients expressed a preference for AVONEX PEN over the AVONEX Prefilled Syringe. "AVONEX is currently one of the most prescribed first-line treatments for people living with MS and has more than 1.4 million patient years of experience. For many patients and their caregivers, AVONEX PEN is a significant advancement, especially for those who desire a more convenient method of administration,вЂќ said Dr Douglas E Williams, executive vice president, research and development at Biogen. вЂњThis positive CHMP opinion and authorization in Canada is a testament to our commitment to not only develop new treatments for the MS community, but our continued drive to further improve patientsвЂ™ experience with our existing industry-leading therapies." PAGE 103 OF 124 Section F: Energy & Environmental Headline 1: USB's "See for yourself" tour includes biodiesel stop Published By: Biodieselmagazine Date of Publication: June 15, 2011 Source: http://www.biodieselmagazine.com In July a group of U.S. soybean farmers will have the opportunity to see their checkoff dollars in action as part of the United Soybean BoardвЂ™s fourth annual вЂњSee for YourselfвЂќ program. The soybean checkoff has selected 10 farmers to participate in this yearвЂ™s event, which will include tours of several facilities that utilize soybeans and soybean oil. вЂњThere is no better way to show someone the value of their investment than to show them the results firsthand,вЂќ said Rich Stern, USB Audit & Evaluation program chair and a soybean farmer from Cream Ridge, N.J. The program Farmers taking part in the program will learn about the use of soy biodiesel at LambertSt. Louis International Airport, travel on a barge that transports U.S. soy and visit a company that makes soy ink, before heading to the number one market for U.S. soybean meal - Mexico - to get a firsthand look at the massive PROAN farm in the western Mexican state of Jalisco. They will visit the state-of-the-art facility and hear why PROAN chooses to source soybean meal from the United States over the countries. They will also visit an aquaculture farm and a refinery that produces soy and palm oil. According to Stern, the program has included a biodiesel stop each year. One reason the Lambert-St. Louis International Airport was an attractive option for this yearвЂ™s tour is that the facility has been a huge supporter of biodiesel, both advocating and promoting use of the fuel, Stern continued. The airport fuels its maintenance vehicles with biodiesel blended fuel, and servers as a great example of large-scale use of the fuel. The fact that the Lambert-St. Louis International Airport is using biodiesel with such success really sends a strong message to the public about the benefits of the fuel, Stern said. The goal of the program is to have the participating farmers walk away with a level of comfort regarding how their checkoff dollars are spent. вЂњThe checkoff is really a great program and the farmers that are spending the checkoff dollars really take this personally and have a passion to make sure the money is being spent properly,вЂќ Stern said. вЂњThey are using the checkoff dollars to really further the soybean industry.вЂќ PAGE 104 OF 124 Headline 2: Miniature Power Plants for Aircraft Bodies Published By: ScienceDaily Date of Publication: June 14, 2011 Source: http://www.sciencedaily.com Sensor networks are supposed to pervade the body shell of airplanes in the future -- much like a nervous system. Thanks to a joint research project of EADS Germany and the Vienna University of Technology, these sensors do not require any external power supply. Aircraft maintenance can be time consuming and expensive. It is much simpler if the airplane itself reports, where maintenance is required. The best solution is a sensor system, which even has its own power supply and is therefore independent of electrical wiring -- and this is what has now been developed by EADS Germany, in cooperation with the Institute of Sensor and Actuator Systems at Vienna University of Technology (TU Vienna). For each individual sensor, electricity is produced by a thermoelectric generator with a small water tank, storing thermal energy. The electricity is simply generated from the temperature difference between the icy cold air in high altitudes and the air close to the ground. This new sensor technology could not only facilitate aircraft maintenance, but also increase comfort for travellers. Energy from the "Energy Harvester Module" Even small collisions can easily lead to damage in the body of the aircraft. On aluminum bodies, a slight dent may be visible -- but on modern carbon materials, it is much harder to detect damage. Tiny, invisible cracks may appear, which are very hard to detect. With suitable sensors connected directly to the body of the aircraft, this could be constantly monitored. "A major problem with these sensors is the energy supply. Wiring up hundreds of sensors in the aircraft body is complicated and expensive," professor Ulrich Schmid from the Institute for Sensor and Actuator Systems at TU Vienna explains. For this reason, he -- together with Dominik Samson and professor Thomas Becker (EADS Germany) -- developed the idea of the "thermoelectric energy harvester" as an energy source, in order to be completely independent of batteries and wiring. Electrical Current from Differences in Temperature When an airplane rises to an altitude of thousands of meters, the exterior wall cools down. "From the temperature difference between the exterior and the interior, we can harvest energy for the sensor element, using a thermoelectric generator," Dominik Samson explains. In the energy-harvester module, there is a little water tank which can store the ground temperature for a while. Water is especially well suited for this task, because it can store large quantities of energy in terms of heat. The inner part of the module with the water tank is connected to the cold exterior wall via the thermoelectric generator. Therefore, a gradient in temperature arises at the generator, which can be PAGE 105 OF 124 used to create electrical voltage. During landing, it works the other way around: The plane heats up again, whereas the inner part of the module is still cold -- and again, electricity can be produced. Whenever there is no thermoelectric current, for instance right after takeoff and during the landing, sophisticated electronics controls storage and transfer of electrical energy. The electronics and the components which create electricity only take up very little space: They fit on the palm of a hand and can easily be integrated into the aircraft body. The size can be adjusted for the individual energy demand of different applications. No Wires, no Batteries The data collected by the sensor can be transmitted wirelessly. Wireless technology does not only make maintenance easier, it also minimizes potential causes of defect and it reduces the weight of the airplane. During one flight, the energy harvester can provide the energy of eight to ten milliwatt hours -- which is sufficient for a wireless sensor. "A plane has a durability of roughly thirty years. If the sensors were operated with batteries, each of them would use up about one hundred batteries during this time," Dominik Samson estimates. Using a large number of sensors, this would not only require costly maintenance but it would also create unnecessary amounts of waste. The concept of generating electricity in the airplane by utilizing differences in temperature could also be used for other purposes. Sensors could monitor whether the passengers have fastened their seatbelts or whether the tables are in an upright position. At the push of a button, a wireless signal could be transmitted to the flight attendants -- without expensive and complicated wiring, just powered by the body heat of the passengers. "The first and most important step has been taken. We are confident that this wireless sensor technology will travel on board of many airplanes soon," Ulrich Schmid says. Headline 3: Scientists at wheat symposium suggest growing risk to wheat crops Published By: Greenbio Checkbiotech Date of Publication: June 10, 2011 Source: http://www.greenbio.checkbiotech.org Five years after the launch of a global effort to protect the worldвЂ™s most important food crop from variants of Ug99, a new and deadly form of wheat rust, scientists say they are close to producing super varieties of wheat that will resist the potent pathogen, while boosting yields by as much as 15 percent. According to research to be presented at a global wheat rust symposium in Minneapolis starting June 13, scientists report that variants of the Ug99 strain of stem rust are becoming increasingly virulent PAGE 106 OF 124 and are being carried by wind beyond the handful of countries in East Africa where they had been identified. New data show that key Ug99 variants have now been identified across all of eastern and southern Africa and that it may only be a matter of time before the spores travel to India or Pakistan, and even Australia and the Americas. вЂњWe are facing the prospect of a biological firestorm, but itвЂ™s also clear that the research community has responded to the threat at top speed, and we are getting results in the form of new varieties that are resistant to rust and appealing to farmers,вЂќ said Ronnie Coffman, who heads the Durable Rust Resistance in Wheat (DRRW) project at Cornell University, which is coordinating the fight against the disease. вЂњBut the job of science is not over. Declining support for public agricultural research got us into this problem with Ug99. Unless that changes, the problem is likely to arise again in a few years. We are dealing with a constantly-evolving pathogen, and we need to stay at least one step ahead of it at all times.вЂќ Coffman and his colleagues note that significant obstacles will have to be overcome before the new varieties of wheat can replace susceptible varieties that cover most of an estimated 225 million hectares of wheat fields throughout the breadbaskets of South Asia, the Middle East, China, Europe, Australia and North America. вЂњNow itвЂ™s a question of whether nations are willing to invest the political and economic capital necessary for agricultural research to secure the worldвЂ™s wheat supply,вЂќ Coffman said. Norman Borlaug created the Borlaug Global Rust Initiative, or BGRI, in 2005, after confirming that a new stem rust strain called Ug99 could overcome a crucial resistance gene (Sr31) that had been widely used in the worldвЂ™s wheat breeding programs to protect the worldвЂ™s wheat crop from the disease. Borlaug sounded the alarm as only he could. The Nobel Laureate had taken on stem rust in the past, succeeding in breeding high-yielding, rust-resistant wheat in the 1950s and 1960s, after the pathogen had claimed 40 percent of the wheat crop in the US and Canada. Borlaug is credited with saving millions of people from starvation worldwide with rust-resistant varieties that improved yields at the same time. Up to 90 percent of wheat now in production, including most wheat grown in the Americas, Asia and Africa - is susceptible to Ug99 and its variants. Concern that damage could be inflicted on wheat fields around the world has prompted a vigorous international response spearheaded by the BGRI as scientists contemplate unprecedented losses to a crop that is the main source of sustenance for millions of people. PAGE 107 OF 124 Researchers at Penn State and the US Department of Agriculture (USDA) are adapting a system that was used to forecast soybean rust movements to track how Ug99 might travel from Africa by winds into the wheat-growing regions of the US. Strategies for Spurring Introduction of Ug99-Resistant Wheat The move to protect the world from Ug99 is focused not on creating a single variety of wheat that can withstand the disease, but, rather, on conferring genetic resistance in wheat and transferring these traits to local varieties. Two factors could accelerate widespread adoption of Ug99-resistant wheat: the rapid spread of yellow rust and the high food prices and grain shortages that have played a role in the political volatility that has roiled the Middle East. Ravi Singh, a wheat breeding expert at the Mexico-based International Maize and Wheat Improvement Center (known by its Spanish acronym, CIMMYT), and colleagues from the Kenya Agricultural Research Institute, the Ethiopian Institute of Agricultural Research (EIAR) and the USDA will report this week on new varieties of wheat under development at CIMMYT that have resistance to all three rusts of wheat: stem rust, yellow rust and leaf rust. Some of the new varieties yield 10 to 15 percent more than current cultivars. вЂњWe have made tremendous progress on the science side but now we need to see progress on the development side,вЂќ Singh said. вЂњScientists can only do so much. We need to see national governments making the investments in seed systems development, including seed production and distribution. In many areas there will need to be support and leadership from wealthy countries and international institutions to carry these innovations into farmersвЂ™ fields.вЂќ New data being presented at the conference will confirm that yellow rust is now common in the worldвЂ™s wheat-growing regions, causing up to 40 percent of losses in countries in the Middle East and Africa, for example. Scientists from the International Center for Agricultural Research in the Dry Areas (ICARDA) will present new research that shows that yellow rust epidemics have spread rapidly in major wheatproducing regions over the last few years. Yellow rust appears to be adapting to warmer conditions and moving into areas where the disease has not previously caused economic losses. Scientists see the growing demand for yellow rust-resistant wheat as an opportunity to disseminate new high-yield varieties resistant to multiple pathogens, including yellow rust and stem rust. PAGE 108 OF 124 For instance, investigators from the EIAR will report that a particularly destructive bout of yellow rust in August 2010 greatly accelerated work in Ethiopia to develop and distribute locally-adapted varieties that had resistance to both yellow and stem rust. Headline 4: Planet's Soils Are Under Threat, Expert Warns Published By: ScienceDaily Date of Publication: June 08, 2011 Source: http://www.sciencedaily.com The planet's soils are under greater threat than ever before, at a time when we need to draw on their vital role to support life more than ever, warns an expert from the University of Sheffield in the journal Nature. Professor Steve Banwart from the University's Kroto Research Institute, will be helping to tackle this challenge as part of a new programme of international research, called Critical Zone Observatories (CZOs), funded initially by the USA National Science Foundation and the European Commission. In some parts of the world, losses due to erosion are greatly outstripping the natural rate of soil formation; and the intensity of human activity is impacting the ability of soil to produce food, store carbon from the atmosphere, filter contamination from water supplies and maintain necessary biodiversity. Because of growing demand for food, intensification of agriculture alone will put a huge strain on soils over the next few decades, and climate change adds to the challenge. Soils are at the heart of Earth's 'critical zone', the life-supporting veneer of the planet from the top of tree canopies to the bottom of drinking water aquifers that support much of humankind. CZOs are international magnets that draw together multidisciplinary experts from around the world, to focus their combined efforts to solve this soils challenge. There are now over 30 CZOs in many different countries and they are starting to work together. One goal of this international effort is to develop mathematical models to predict how soil and the services it provides will change as humans intensify the use of soil. The aim is to pro-actively design solutions, for example to increase crop yields without compromising the other roles of soil. This could be done by laying out alternative ways to raise crops and calculate the effects, to find the best solutions before soils deteriorate, and then implement these to maintain soil quality and potentially improve it. CZOs are developing this predictive capability from fundamental scientific principles and combining data from the sites to test the models. Key requirements that are identified to accelerate this research effort are greater international collaboration between national research programmes, and getting companies involved in research planning to help move from research to practical solutions. Given the possible doubling in food demand by 2050, critical zone scientists are arguing that we need to have this capability operational within a decade. Professor Banwart argues: "The challenge is clear. We need rigorous forecasting methods to quantify and best utilise soil's natural capital, to assess options for maintaining or extending it, and to determine how declines can be reversed. And we need these things well within a decade." The news follows significant research already being carried out at the University of Sheffield in the areas of global change and food security as part of Project Sunshine. Led by the Faculty of Science at the University of Sheffield, Project Sunshine aims to unite scientists across the traditional boundaries PAGE 109 OF 124 in both the pure and applied sciences to harness the power of the Sun and tackle the biggest challenge facing the world today: meeting the increasing food and energy needs of the world's population in the context of an uncertain climate and global environment change. It is hoped that Project Sunshine will change the way scientists think and work and become the inspiration for a new generation of scientists focused on solving the world's problems Headline 5: Developing Advanced Biofuels: Researchers Counteract Biofuel Toxicity in Microbes Published By: Science Daily Date of Publication: June 05, 2011 Source: http://www.sciencedaily.com Advanced biofuels -- liquid transportation fuels derived from the cellulosic biomass of perennial grasses and other non-food plants, as well as from agricultural waste -- are highly touted as potential replacements for gasoline, diesel and jet fuels. Equally touted is the synthesis of these fuels through the use of microbes. However, many of the best candidate compounds for advanced biofuels are toxic to microbes, which present a "production versus survival" conundrum. Researchers at the U.S. Department of Energy (DOE)'s Joint BioEnergy Institute (JBEI) have provided a solution to this problem by developing a library of microbial efflux pumps that were shown to significantly reduce the toxicity of seven representative biofuels in engineered strains of Escherichia coli. "Working with all available microbial genome sequence data, we generated a library of largely uncharacterized genes and were able to devise a simple but highly effective strategy to identify efflux pumps that could alleviate biofuel toxicity in E. coli and, as a consequence, help improve biofuel production," says Aindrila Mukhopadhyay, a chemist with JBEI's Fuels Synthesis Division, who led this research. Mukhopadhyay, who also holds an appointment with the Lawrence Berkeley National Laboratory (Berkeley Lab)'s Physical Biosciences Division, is the corresponding author on a paper published in the journal Molecular Systems Biology. Co-authoring the paper with Mukhopadhyay were Mary Dunlop, Zain Dossani, Heather Szmidt, Hou-Cheng Chu, Taek Soon Lee, Jay Keasling and Masood Hadi. Research efforts are underway at JBEI and elsewhere to engineer microorganisms, such as E. coli, to produce advanced biofuels in a cost effective manner. These fuels, which encompass short-tomedium carbon-chain alcohols, such as butanol, isopentanol and geraniol, can replace gasoline on a gallon-for-gallon basis and be used in today's infrastructures and engines, unlike ethanol. Biofuels made from branched carbon-chain compounds, such as geranyl acetate and farnesyl hexanoate, would also be superior to today's biodiesel, which is made from esters of linear fatty acids. Cyclic alkenes, such as limonene and pinene, could serve as precursors to jet fuel. Although biosynthetic pathways to the production of these carbon compounds in microbes have been identified, product toxicity to microbes is a common problem in strain engineering for biofuels and other biotechnology applications. "In order for microbial biofuel production to be cost effective, yields must exceed native microbial tolerance levels, necessitating the development of stress-tolerant microbe strains," Mukhopadhyay PAGE 110 OF 124 says. "It is crucial that we improve tolerance in parallel with the development of metabolic pathways for the production of next-generation biofuels." Microbes employ various strategies for addressing cell toxicity but perhaps the most effective are efflux pumps, proteins in the cytoplasmic membrane of cells whose function is to transport toxic substances out of the cell. This is done actively, using proton motive force. However, to date very few of these have been characterized for efficacy against biofuel like compounds. "Sequenced bacterial genomes include many efflux pumps but remain a largely unexplored resource for use in engineering fuel tolerance," Mukhopadhyay says. "We took a systematic approach to screen a library of primarily uncharacterized heterologous pumps for engineering biofuel tolerant host strains. We were then able to demonstrate that expression of a heterologous pump can increase the yield of a biofuel in the production strain." Since all known solvent-resistant efflux pumps in Gram-negative bacteria fall into the hydrophobe/amphiphile efflux (HAE1) family, Mukhopadhyay and her colleagues constructed a datab ase of all HAE1 pumps from sequenced bacterial genomes. They then performed a bioinformatics screen to compare regions predicted to be responsible for substrate specificity to those of TtgB, a well-characterized solvent-resistant efflux pump. "This metric allowed us to rank the complete set of pumps and select a subset that represented a uniform distribution of candidate genes," says Mukhopadhyay. "To construct the library, we amplified efflux pump operons from the genomic DNA of the selected bacteria, cloned them into a vector, and transformed the vector into an E. coli host strain." In a series of survival competitions, the two microbial efflux pumps that performed best were the native E. coli pump AcrAB and a previously uncharacterized pump from a marine microbe Alcanivorax borkumensis. "We focused on the A. borkumensis pump and tested it in a strain of host microbe engineered to produce the limonene jet fuel precursor," Mukhopadhyay says. "Microbes expressing the pump produced significantly more limonene than those with no pump, providing an important proof of principle demonstration that efflux pumps that increase tolerance to exogenous biofuel can also improve the yield of a production host." Mukhopadhyay and her JBEI colleagues have begun evaluating microbial efflux pumps for other important compounds as well as inhibitors present in the carbon source from lignocellulose. They are also looking to improve the A. borkumensis pump and other high performers in their current library, and to optimize the systems by which pump genes are expressed in engineered biofuel-producing microbial strains. "We believe our bioprospecting strategy for biofuel tolerance mechanisms is going to be a valuable and widely applicable tool in the biotechnology field for engineering new microbial production strains," Mukhopadhyay says. This research was supported by JBEI through the DOE Office of Science. PAGE 111 OF 124 Headline 6: Study: 'E-waste pollution' a threat to human health Published By: Physorg Date of Publication: May 30, 2011 Source: http://www.physorg.com In addition to its damaging effect on the environment and its illegal smuggling into developing countries, researchers have now linked e-waste to adverse effects on human health, such as inflammation and oxidative stress вЂ“ precursors to cardiovascular disease, DNA damage and possibly cancer. In a study published today, Tuesday 31 May, in IOP Publishing's journal Environmental Research Letters, researchers took air samples from one of the largest e-waste dismantling areas in China and examined their effects on human lung epithelial cells. E-waste, or electronic waste, describes end-of-life electrical goods such as computers, televisions, printers, and mobile phones. Each year between 20тє Ђ million tons of e-waste is generated worldwide, 100,000 tons of which is exported from UK shores, according to a recent BBC Panorama programme. A large proportion of worldwide e-waste is exported to China. Due to the crude recycling process, many pollutants, such as persistent organic pollutants and heavy metals, are released from e-waste, which can easily accumulate in the human body through the inhalation of contaminated air. After exposing the cultured lung cells to the organic-soluble and water-soluble constituents of the samples, the researchers tested for the level of Interleukin-8 (IL-8), a key mediator of inflammatory response, and Reactive Oxygen Species (ROS), chemically reactive molecules that can cause extensive damage in excess. The samples were also tested for the expression of the p53 gene вЂ“ a tumour suppressor gene that produces a protein to help counteract cell damage. If there is evidence of this gene being expressed it can be seen as a marker that cell damage is taking place. The results showed that the samples of pollutants caused significant increases in both IL-8 and ROS levels вЂ“ indicators of an inflammatory response and oxidative stress respectively. Significant increases were also observed in the levels of the p53 protein with the risk of organic-soluble pollutants being much higher than water-soluble pollutants. Co-author of the study Dr Fangxing Yang, of Zhejiang University, said, "Both inflammatory response and oxidative stress may lead to DNA damage, which could induce oncogenesis, or even cancer. Of course, inflammatory response and oxidative stress are also associated with other diseases, such as cardiovascular diseases." In this study, the researchers took samples of the air from Taizhou of Zhejiang province вЂ“ a dismantling complex that involves more than 60,000 people and dismantles more than two million tons of e-waste to recycle metals each year. To obtain the samples, the researchers used two sampling sites that were located downwind of a dismantling industrial park in Taizhou, set up by the local government in 2004. PAGE 112 OF 124 It is well known that inflammatory response and oxidative stress can lead to DNA damage and therefore activate the p53 gene to counteract this damage. The study did not find any significant correlation between IL-8 and ROS and p53 expression; however the researchers suggest that this may be due to the various other endpoints, not examined in this study, which can damage DNA. A further study will attempt to characterise the components present in the polluted air and identify the key contributors to these adverse effects. Dr Yang continued, "From these results it is clear that the 'open' dismantlement of e-waste must be forbidden with more primitive techniques improved. As the results show potential adverse effects on human health, workers at these sites must also be given proper protection. Headline 7: Bio-plastic bags trying to change the face of carry bag market Published By: The Hindu Date of Publication: May 29, 2011 Source: http://www.thehindu.com Billimoria,Founder and CEO of Earthsoul India, displaying one of Natural Biopolymer Product which was launched in New Delhi. With the Supreme Court coming down heavily on the use of plastic pouches for вЂ�gutkaвЂ™ and a number of States banning plastic carry bag, an eco-friendly bio-plastic bag is trying to replace the ubiquitous polythene bag in the retail markets in India. The compostable bio-plastic bags are produced out of non-edible vegetable oils and starch unlike the traditional polythene material that is oil-based. вЂњOil is scarce and expensive and this movement towards bio-plastic could well shift focus from oil wells to oil farms with cultivators increasingly going for vegetable oilseeds,вЂќ Stefano Facco, a top executive of an Italian bio-polymer firm, told PTI. вЂњI am happy to see the increased focus on environment friendly products in India,вЂќ said Mr. Facco, who is in India at the invitation of Earthsoul India, which launched the bio-plastic bags six years ago. These bags are water-proof, transparent and hygienic and come in varied sizes to hold domestic wet garbage of 2 kg to 5 kg and large trash of 15 kg to 20 kg. Enquiries have already come in from some State agriculture departments for packaging seeds in small to large bags, he said. Unlike polymer bags which remain in the soil and harm it in the process, the bio-plastic material is naturally compostable and does not harm the nature at all, Perses Billimoria, Founder and CEO of Earthsoul, said. Mr. Billimoria welcomed the initiative taken by large institutions like Tirupati Tirumala Devasthanams of the famous Balaji temple, which have recently floated tenders for bio-plastic bags. PAGE 113 OF 124 Some States like Andhra Pradesh, Himachal Pradesh and Rajasthan have totally banned plastic bags and others are moving towards that вЂњbut it is still miles to go,вЂќ he said. Talking about the popularity of bio-plastic in Europe, Mr. Facco, who is the New Business development Director of Novamont S.p.A, said that at least 5,000 municipal authorities in the continent were using the product in varied sizes and the market is growing at 20 to 30 percent. He said there could be a socio-economic angle to the bio-plastic movement, apart from the environmental issue. Farmers could also benefit by cultivating vegetable oilseeds like castor as the industry grows. For instance, NovamontвЂ™s bio-refinery is integrated with the local farming community, he added. The characteristics of the product include: completely biodegradable in various environments through composting, or in soil, fresh and salt water, suitable for use with existing industrial technology for traditional plastics with no drop in productivity, printable using standard inks and printing technologies, without corona pre-treatment, can be coloured using biodegradable master batches, intrinsic antistatic properties and Gamma-ray sterilisation. Apart from the carry bags, the bio-plastic can also find application in agriculture, toys, cutlery, nappies, sanitary towels, catering and so on, Mr. Facco said. As part of its social responsibility, Earthsoul and its partner Novamont have decided not to supply their bio-plastic material to the Rs 40,000 crore Gutka industries. Headline 8: Green and Lean: Secreting Bacteria Eliminate Cost Barriers for Renewable Biofuel Production Published By: Science Daily Date of Publication: May 27, 2011 Source: http://www.sciencedaily.com A Biodesign Institute at Arizona State University research team has developed a process that removes a key obstacle to producing low-cost, renewable biofuels from bacteria. The team has reprogrammed photosynthetic microbes to secrete high-energy fats, making byproduct recovery and conversion to biofuels easier and potentially more commercially viable. "The real costs involved in any biofuel production are harvesting the goodies and turning them into fuel," said Roy Curtiss, of the Institute's Center for Infectious Diseases and Vaccinology and professor in the School of Life Sciences. "This whole system that we have developed is a means to a green recovery of materials not requiring energy dependent physical or chemical processes." Curtiss is part of a large, multidisciplinary ASU team that has been focusing on optimizing photosynthetic microbes, called cyanobacteria, as a renewable source of biofuels. These microbes PAGE 114 OF 124 are easy to genetically manipulate and have a potentially higher yield than any plant crops currently being used for the production of transportation fuels. But, until now, harvesting the fats from the microbes has required many costly additional processing steps that contribute up to 70 to 80 percent of the total cost of their renewable biofuel production, making them uncompetitive compared with petroleum production costs. Cyanobacteria have a tough, protective set of outer membranes that help the bacteria thrive in even harsh surroundings, creating the pond scum often found in backyard swimming pools. Like plants, they are dependent upon sunlight, water and carbon dioxide for growth. To get cyanobacteria to more readily release their precious, high fat cargo, Curtiss and postdoctoral researcher Xinyao Liu, placed a suite of genes into photosynthetic bacteria that produced enzymes to degrade membrane lipids, poking holes in the membranes to release free fatty acids into the water. In a clever feat of genetic reprogramming of the cells, the enzymes are only produced when carbon dioxide -- a vital ingredient of bacterial growth -- is removed from their environment. "We first freed up fatty acids by triggering self-destruction of the bacteria by adding nickel," Liu said, "but this is not so good for the environment. So, this time we did it in a smarter way -- by stopping carbon dioxide supply. The strategy of adding nothing for recovering fuels from biomass is designed to drastically reduce processing costs." "Genetics is a very powerful tool," added Liu, who recently presented the results at the 3rd Annual World Algae Summit in San Diego, California. "We have created a very flexible system that we can finely control. After teaching cyanobacteria to excrete fuels, we don't want to waste the useful lipids in the photosynthetic membranes, so we developed a greener way to recycle the remaining value of the biofactory." The team tested fat-degrading enzymes, called lipases, from bacterial, fungal and guinea pig sources to see which would work best. These lipases are able work like molecular scissors, clipping off the fatty acids from the photosynthetic membranes. They also worked to optimize the growth conditions of their green recovery method, testing variables such as the cell culture density of the microbes, light intensity and agitation of the cultures. The team's ingenuity rests in part with their ability to utilize the full repertoire of nature's toolkit. "Due to rapid DNA sequencing and public gene databases, we can now use this vast and ever-increasing store of gene sequences with powerful computer search methods to identify the best genes and proteins with optimal functions and capabilities independent of their origin in microbes, plants and animals," said Curtiss. "It is like being a kid in a candy store the size of the State of Arizona and finding the most delicious candy treat almost in the time to snap your fingers!" The project is also a prime example of the multidisciplinary, collaborative spirit of ASU research combining the expertise of bacteriologists, molecular biologists and engineers. Other key contributors were Biodesign colleagues Sarah Fallon and Jie Sheng. Next, the group will test their results in large-scale photobioreactors, which are being designed by engineers in the institute's Swette Center for Environmental Biotechnology to optimally capture the free fatty acids. Ultimately, the team hopes to achieve development of a new, economical and environmentally friendly, carbon neutral source of biofuels. "We are optimistic that we can make the system even better, leading to the commercialization of our green recovery method bundled with other technologies," said Liu. PAGE 115 OF 124 The project has been part of the state of Arizona's strategic research investments to spur new innovation that may help foster future green and local industries. The state's abundant year-round sunshine and warm temperatures are ideally suited for growing cyanobacteria. The work was supported by Biodesign Institute seed funding and a $5 million grant from the U.S. Department of Energy Advanced Research Projects Agency. Headline 9: Teaching Algae to Make Fuel: New Process Could Lead to Production of Hydrogen Using Bioengineered Microorganisms Published By: ScienceDaily Date of Publication: May 26, 2011 Source: http://www.sciencedaily.com Many kinds of algae and cyanobacteria, common water-dwelling microorganisms, are capable of using energy from sunlight to split water molecules and release hydrogen, which holds promise as a clean and carbon-free fuel for the future. One reason this approach hasn't yet been harnessed for fuel production is that under ordinary circumstances, hydrogen production takes a back seat to the production of compounds that the organisms use to support their own growth. But Shuguang Zhang, associate director of MIT's Center for Biomedical Engineering, and postdocs Iftach Yacoby and Sergii Pochekailov, together with colleagues at Tel Aviv University in Israel and the National Renewable Energy Laboratory in Colorado, have found a way to use bioengineered proteins to flip this preference, allowing more hydrogen to be produced. "The algae are really not interested in producing hydrogen, they want to produce sugar," Yacoby says -- the sugar is what they need for their own survival, and the hydrogen is just a byproduct. But a multitasking enzyme, introduced into the liquid where the algae are at work, both suppresses the sugar production and redirects the organisms' energies into hydrogen production. The work is described in a paper being published online this week in the Proceedings of the National Academy of Sciences, and was supported in part by a European Molecular Biology Organization postdoctoral fellowship, the Yang Trust Fund and the U.S. Department of Energy's National Renewable Energy Laboratory. Adding the bioengineered enzyme increases the rate of algal hydrogen production by about 400 percent, Yacoby says. The sugar production is suppressed but not eliminated, he explains, because "if it went to zero, it would kill the organism." The research demonstrates for the first time how the two processes carried out by algae compete with each other; it also shows how that competition could be modified to favor hydrogen production in a laboratory environment. Zhang and Yacoby plan to continue developing the system to increase its efficiency of hydrogen production. PAGE 116 OF 124 "It's one step closer to an industrial process," Zhang says. "First, you have to understand the science" -- which has been achieved through this experimental work. Now, developing it further -- through refinements to produce a viable commercial system for hydrogen-fuel manufacturing -- is "a matter of time and money," Zhang says. Ultimately, such a system could be used to produce hydrogen on a large scale using water and sunlight. The hydrogen could be used directly to generate electricity in a fuel cell or to power a vehicle, or could be combined with carbon dioxide to make methane or other fuels in a renewable, carbon-neutral way, the researchers say. In the long run, "the only viable way to produce renewable energy is to use the sun, [either] to make electricity or in a biochemical reaction to produce hydrogen," Yacoby says. "I believe there is no one solution," he adds, but rather many different approaches depending on the location and the end uses. This particular approach, he says, is simple enough that it has promise "not just in industrialized countries, but in developing countries as well" as a source of inexpensive fuel. The algae needed for the process exist everywhere on Earth, and there are no toxic materials involved in any part of the process, he says. Headline 10: Scientists Generates Hydrogen as an Energy Source from Ethanol and Sunlight Published By: Science Daily Date of Publication: May 26, 2011 Source: http://www.sciencedaily.com A team of researchers from the Universitat PolitГЁcnica de Catalunya, the University of Aberdeen (Scotland) and the University of Auckland (New Zealand) uses ethanol and sunlight to generate hydrogen as an energy source. The results of the study have been published in Nature Chemistry. Jordi Llorca, director of the Institute of Energy Technology and researcher at the Universitat PolitГЁcnica de Catalunya's Nanoengineering Research Centre, is one of the authors of the study, which represents a major step towards using hydrogen as an alternative to fossil fuels. In the framework of the research, a fully scalable powder photocatalyst was created that makes the hydrogen production process simpler and cheaper as it takes place at ambient temperature and pressure. A solid photocatalyst is placed in a container with ethanol and exposed to ultraviolet light by agitation, simulating the most energetic part of the solar spectrum. The device contains a titanium dioxide semiconductor that in contact with sunlight generates electrons captured by metallic gold nanoparticles, which react with the alcohol molecules to produce hydrogen. According to Llorca, the semiconductor's structure and the contact with the nanoparticles are crucial features in the design of the photocatalyst. PAGE 117 OF 124 The amount of hydrogen and energy generated depends on the amount of catalyst used and the area exposed to solar radiation. Researchers have generated up to 5 litres of hydrogen per kilogram of catalyst in one minute. If 9 kg of catalyst were put in an ethanol tank and exposed to sunlight and the hydrogen generated were used to power a fuel cell, 3 kW of electricity would be obtained, an amount similar to that which is used in a home. Llorca plans to design reactors with real-life applications such as providing electricity to the home, which he sees as an important step towards introducing hydrogen as an energy vector and gradually gaining independence from fossil fuels. One of the advantages of hydrogen compared with electricity is that it can be stored. An economical process based on renewable resources Until now, solar-generated hydrogen techniques have largely relied on water. However, despite water being cheap and abundant, these techniques have garnered poor results and the materials they require are expensive. As an alternative, the researchers suggest using ethanol, a renewable and economical resource that is easily obtained from agricultural and forest waste (100 grams of glucose generate approximately 50 grams of ethanol). The photocatalyst is also much cheaper and simpler to use than the materials employed in techniques with water as it uses very small gold particles, ranging in size from 2 to 12 nanometres (1 metre = 1 million nanometres). These nanoparticles capture the free electrons generated when titanium oxide -used as a support base -- comes into contact with sunlight. During the process, which is based on solar energy, the team also discovered that the size of the gold nanoparticles has no influence on the production of hydrogen, unlike what occurs during the more widespread processes in which the catalyst powder must be heated to reaction temperature (usually over 500ВєC) and therefore incurs an energy cost. In addition, the catalyst is more durable because it works at ambient temperature and pressure. Headline 11: New Green Technology for Hydrogen Production Published By: ScienceDaily Date of Publication: May 12, 2011 Source: http://www.sciencedaily.com Researcher Mohamed Halabi of Eindhoven University of Technology demonstrates a proof-of-concept for a new and clean technology to produce high purity hydrogen from natural gas. This allows hydrogen to be produced in an elegant technique at much lower temperatures, and without releasing CO2 into the atmosphere. Hydrogen is a valuable feedstock for the petrochemical industry and it may play a big role in the energy supply of the future, as a green, non-polluting, and efficient energy carrier. If it is burnt, only water is formed. However, the conventional technology for hydrogen production from natural gas ('steam reforming') is a highly energy intensive process, operated at high pressures (up to 25 bar) and o high temperature (850 C), with multistage subsequent separation and purification units. Moreover, huge amounts of CO2 have to be handled in post-processing steps. TU Eindhoven has now developed a new and improved technology called "sorption enhanced catalytic reforming of methane," using novel catalyst/sorbent materials. Halabi, working in collaboration with the Energy Research Centre of the Netherlands (ECN), has demonstrated the PAGE 118 OF 124 feasibility of producing hydrogen through such a process at much lower temperatures (400 to 500 degrees Celsius). The process is performed in a packed bed reactor using a Rhodium-based catalyst and a Hydrotalcite-based sorbent as a new system of materials. Hydrogen is produced on the active catalyst and the cogenerated CO2 is effectively adsorbed on the sorbent, hence preventing any CO2 emissions to the atmosphere. Halabi: "Direct production of high purity hydrogen and fuel conversion greater than 99.5% is o experimentally achieved at low temperature range of (400 -- 500 C) and at a pressure of 4.5 bar with a low level of carbon oxides impurities: less than 100 ppm." The enormous reduction of the reactor size, material loading, catalyst/sorbent ratio, and energy requirements are beneficial key factors for the success of the concept over the conventional technologies. Small size hydrogen generation plants for residential or industrial application operated at a relatively low pressure, of less than 4.5 bar, seem to be feasible. Dr. Mohamed Halabi received his PhD on May 9, 2011, at TU Eindhoven based on his dissertation "Sorption Enhanced Catalytic Reforming of Methane for Pure Hydrogen Production -- Experimental and Modeling." He conducted his research at the laboratory of Chemical Reactor Engineering, under the supervision of Prof. Jaap Schouten. Headline 12: Global warming 'has reduced maize and wheat yields' Published By: The Times of India Date of Publication: May 6, 2011 Source: http://www.timesofindia.indiatimes.com Global warming has already reduced the global yields of key crops, say scientists. Maize and wheat production have been 3.8 and 5.5 per cent lower, respectively, than they would have been without the temperature rises associated with climate change since the 1980s, according to the statistical analysis. Rice and soya yields have dropped in some parts of the world and risen in others, so overall the warming has not changed their net global production. Linking climate change to food prices for the first time, the scientists, led by David Lobell of Stanford University, United States, have shown that these losses have probably led to at least a six per cent rise in food prices between 1980 and 2008. The news comes as the UN this week (3 May) revised upwards its population prediction for the planet вЂ” to 10.1 billion by 2100. "Without successful adaptation, and given the persistent rise in demand for maize and wheat, the sizeable yield setback from climate change is likely incurring large economic and health costs," said the team, whose work was published in Science yesterday (5 May). The team developed two models of crop productivity using data from countries around the world. Both models included complex factors such as the increases in yield from technological advances in farming, PAGE 119 OF 124 but one included the actual increase in global temperatures between 1980вЂ“2008, while the other kept the temperature constant at 1980 levels. For maize, warming was linked with a reduced yield of around eight per cent in Brazil and seven per cent in China, but an increase of about one per cent in India. In Africa, there were significant yield drops in Egypt, Mozambique and Uganda, but substantial increases, linked to temperature drops, in Kenya, Tunisia and Zambia. Wheat productivity in the developing world was significantly reduced in Afghanistan, Brazil, Iraq, Libya and Morocco. And, although the global productivity of soya remained level, Brazil experienced a drop of five per cent, and Paraguay 7.5 per cent, while Argentina showed a 2.5 per cent increase. The study did not take into account the fertilising effect of extra carbon dioxide in the atmosphere вЂ” thought to increase yields for rice and soy but have no effect on maize and wheat. "We are not saying climate change is the only or even a major cause of price increases for major commodities," Lobell told SciDev.Net. "Most people would say biofuel and trade policies are probably more important for food price rises. But what we are saying is that climate change is also a factor." Gerald Nelson, a senior research fellow at the International Food Policy Research Institute in the United States said the results demonstrated that "the way climate plays out in individual locations in the future is going to be very important for global effects". For developing countries it underlined the urgency of adapting agriculture to climate change вЂ” and building better infrastructure so that farmers can benefit from higher prices for their crops, he said. Headline 13: Background radiation and radioactivity in India Published By: The Hindu Date of Publication: May 05, 2011 Source: http://www.thehindu.com Every time we eat a banana, we are introducing 14 Bq of K-40 into our body. The body retains only the amounts in the normal range essential for its functioning. We live in a sea of radiation. In any city, an unsuspecting owner of a 0.1 acre backyard garden may not know that the top one metre of soil from his garden contains 11,200 kg of potassium, 1.28 kg which is of potassium- 40 (K-40, a radioactive isotope of potassium), 3.6 kg of thorium and one kg of uranium. These values may be higher or lower depending on the soil. Uranium and thorium decay through several radio-nuclides to lead, a stable element. The presence of radioactive nuclides does not pose any significant risk. Total dose The total annual external dose from sources in soil and cosmic rays in Mumbai, Kolkata, Chennai, Delhi and Bengaluru is 0.484, 0.81, 0.79, 0.70 and 0.825 milligray respectively. Gray is a unit for absorbed dose; when the radiation energy imparted to a kg of material is one joule, it is called a gray. PAGE 120 OF 124 Since gray is very large, milligray (one thousandth of a gray), and microgray (one millionth of a gray), are commonly used. Cosmic rays come from outer space. Their intensity at a place depends on the altitude. Cosmic rays alone contribute 0.28 milligray at the first three cities as they are at sea level; the column of air helps to reduce their intensity. At high altitudes, the protection from the column of air is less. The cosmic ray contributions are higher at 0.31 milligray and 0.44 milligray respectively at Delhi and Bengaluru as these cities are at altitudes of 216 metre and 921 metre. Air passengers receive 5 microgray per hour from cosmic rays. Parts of Kerala and Tamil Nadu are high background radiation areas (HBRA) because of the presence of large quantities of monazite in the soil. Thorium content in monazite ranges from 8-10.5 per cent. Researchers found that the radiation levels in 12 Panchayats in Karunagappally varied between 0.32 to 76 milligrays per year; the levels in 90 per cent of over 71,000 houses were more than one milligray per year. The average value of population dose in HBRA is 3.8 milligray per year. One milligray is the average value for areas of normal background radiation. The units milligray and millisievert are the same in these instances. Study at the HBRA during 1990-99 by the researchers from the Regional Cancer Centre and Bhabha Atomic Research Centre did not show any health effect attributable to radiation. Radon, which occurs in uranium series present in soil seeps into homes. In temperate areas radon decay products build up in air due to poor ventilation and deliver high doses to the lungs of millions of people. In tropics ventilation is adequate to disperse radon .In the United Kingdom persons in 5 per cent of the homes are exposed to doses above 23.7 mSv/year. One per cent of the population receives doses above 55.8 mSv/year. The highest estimated dose was 320 mSv/year in Cornwall. All foodstuffs contain potassium-40 (K-40). We need potassium for sustenance. K-40 is 0.012 per cent of potassium. Once ingested, most of the potassium enters the blood stream directly and gets distributed to all tissues and organs. Homeostatic control The potassium content in the human body is strictly under homeostatic control. The body retains only the amounts in the normal range essential for its functioning; it is independent of the variations in the environmental levels. The body excretes excess amounts with a biological half life of 30 days. K-40 delivers a constant annual radiation dose of 0.18 mSv to soft tissue. This dose is unavoidable as potassium is an essential element. Every time we eat a banana, we are introducing 14 Bq of K-40 in to our body. Trucks containing bananas have triggered radiation alarms at border posts in the U.S. Brazil nut Brazil nut is probably the most radioactive food. Scientists have measured 700Bq of radium per kg of Brazil nut. The roots of the Brazil nut tree pass through acres of land; They have a tendency to concentrate barium; along with barium, the roots collect radium as well. Radium appears in the nuts. Many vegetables like brinjal, carrot etc. also contain the radioactive isotope. PAGE 121 OF 124 Indian researchers have measured polonium-210 in fish and other marine organisms. Our whole body is hit by particles coming from all sides. Radiation is a part of our life. We cannot avoid eating food just because it contains radioactivity. Headline 14: Green technology to tackle water pollution Published By: The Hindu Date of Publication: April 25, 2011 Source: http://www.thehindu.com Union Minister for Environment and Forests Jairam Ramesh has launched a вЂњbioremediation technologyвЂќ project to curb pollution caused by sewerage and industrial effluents in the Buddah Nallah of Ludhiana in Punjab. The project is estimated to cost Rs. 16 crore in the initial phase and it will be borne by The National River Conservation Directorate of the Union government. It is expected to take one year for completion. Relief to thousands The project will provide relief to thousands living along the Sutlej river and canals off the Harike barrage in Punjab and Rajasthan. Water pollution has caused severe disorders among them. Flowing parallel to the Sutlej, the 31-km-long Buddah Nallah, of which about 14 km falls in Ludhiana, has, for decades, been polluted by industrial effluents, sewage water, solid waste from dairies, leather and electroplating industries and dumping of garbage. It merges with the Sutlej near Moga, from where the polluted water is carried downstream. In September last, on the invitation of Ludhiana MP Manish Tiwari, Mr Ramesh travelled along the Nallah to make an assessment of the pollution levels. Fatal disorders In March, The Hindu highlighted the plight of at least 40 villages of Ferozepur district, where children needed more wheelchairs than toys, as they are succumbing to disorders caused by high levels of toxicity in the Sutlez water that had seeped into the aquifers. Talking to presspersons after laying the foundation for the project near Haibowal on Saturday, Mr. Ramesh expressed concern over the environmental degradation in Ludhiana district. вЂњLudhiana is among the richest districts of the country but it is not as clean as it should be.вЂќ He sought more attention to overall cleanliness of the city and its surrounding areas. Detailing about the project, the Minister said temporary barricades, вЂ�Green bridges', fortified with microbial consortia would be erected at regular intervals depending upon the flow and quantum of water in the Nallah. There would be reduction in вЂ�biochemical oxygen demand' (BOD) and вЂ�chemical oxidation demand' (COD) levels in the water passing through the green bridges. Through this completely green technology, the microbial consortia would chew away the organic load and industrial pollutants. The benefit of this technology would be visible within three months, Mr. Ramesh said, adding the micro-organisms deployed in this technology were harmless and indigenously found in nature. No genetically modified organisms would be used in the project, which PAGE 122 OF 124 would run on an environmentally benign process that had no harmful impact on the ecosystem and on human or animal health. The project would be closely monitored not only by the Ministry but also by experts, public representatives and the media. He expressed the hope that the Punjab government would implement other projects too which was proposed by Chief Minister Parkash Singh Badal and Deputy Chief Minister Sukhbir Singh Badal when they met him in New Delhi recently. Headline 15: Using the Energy in Oil Shale without Releasing Carbon Dioxide in a Greenhouse World Published By: Science Daily Date of Publication: April 20, 2011 Source: http://www.sciencedaily.com New technology that combines production of electricity with capture of carbon dioxide could make billions of barrels of oil shale -- now regarded as off-limits because of the huge amounts of carbon dioxide released in its production -- available as an energy source in a greenhouse world of the future. That's the conclusion of a report on "electricity production with in situ carbon capture" (EPICC) in ACS' journal Energy & Fuels. Adam Brandt and Hiren Mulchandani explain that almost 3 trillion barrels of oil are trapped in the world's deposits of oil-shale, a dark-colored rock laden with petroleum-like material. The United States has by far the world's largest deposits in the Green River Formation, which covers parts of Colorado, Utah, and Wyoming. Estimates put that total domestic oil resource at 1.2 trillion to 1.8 trillion barrels. Limiting potential use of those deposits are concerns over the large amounts of the greenhouse gas carbon dioxide released with current methods for extracting oil from shale. That's why the researchers tried to find a new way to get energy from oil shale without producing greenhouse gases. Their answer is EPICC -- a self-fueled method that generates electricity, as well as the heat needed to produce that electricity from shale. The report describes how EPIC could generate large amounts of electricity without releasing into the atmosphere carbon dioxide from burning the shale. That carbon would be captured and stored underground as part of the production process. Headline 16: Toward a More Efficient Use of Solar Energy Published By: Science Daily Date of Publication: April 14, 2011 Source: http://www.sciencedaily.com The exploitation and utilization of new energy sources are considered to be among today's major challenges. Solar energy plays a central role, and its direct conversion into chemical energy, for example hydrogen generation by water splitting, is one of its interesting variants. Titanium oxidebased photocatalysis is the presently most efficient, yet little understood conversion process. In cooperation with colleagues from Germany and abroad, scientists of the KIT Institute for Functional PAGE 123 OF 124 Interfaces (IFG) have studied the basic mechanisms of photochemistry by the example of titania and have presented new detailed findings. Even though hydrogen production from water and sunlight by means of oxide powders has been studied extensively for several decades, the basic physical and chemical mechanisms of the processes involved cannot yet be described in a satisfactory way. Together with colleagues from the universities of St. Andrews (Scotland) and Bochum and Helmholtz-Forschungszentrum Berlin, scientists at KIT's Institute for Functional Interfaces, headed by Professor Christof WГ¶ll, have succeeded in gathering new findings on the fundamental mechanisms of photochemistry on titanium dioxide (TiO2). Titanium dioxide, or titania, is a photoactive material occurring in nature in the rutile and anatase modifications, the latter of which being characterized by a ten times higher photochemical activity. When the white TiO2 powder, which is also used as a pigment in paints and sunscreens, is exposed to light, electrons are excited and can, for example, split water into its components oxygen and hydrogen. The hydrogen produced in that way is a "clean" energy source: No climate-killing greenhouse gases are generated but only water is produced during combustion. Titanium dioxide is also used to manufacture self-cleaning surfaces from which unwanted films are removed through photochemical processes triggered by incident sunlight. In hospitals, this effect is used for sterilizing specially coated instruments by means of UV irradiation. So far, the physical mechanisms of these photochemical reactions on titania surfaces and especially the reason for the much higher activity of anatase could not be explained. The powder particles used in photoreactors are as tiny as a few nanometers only and are thus too small for use in studies by means of the powerful methods of surface analysis. By using instead mm-sized single-crystal substrates, the researchers were for the first time able to precisely study photochemical processes on the surface of titanium dioxide by means of a novel infrared spectrometer. Using a laser-based technique, the scientists, in addition, determined the lifetime of light-induced electronic excitations inside the TiO2 crystals. According to Professor Christof WГ¶ll, Head of the IFG, exact information about these processes is of great importance: "A short lifetime means that the excited electrons fall back again at once: We witness some kind of an internal short circuit. In the case of a long lifetime, the electrons remain in the excited state long enough to be able to reach the surface of the crystal and to induce chemical processes." Anatase is particularly well suited for the latter purpose because it is provided with a special electronic structure that prevents "internal short circuits." Knowledge of this feature will allow the researchers to further optimize shape, size, and doping of anatase particles used inside photoreactors. The objective is to develop photoactive materials with higher efficiencies and longer lifetimes: "The results obtained by Professor WГ¶ll and his co-workers are of great importance regarding the generation of electrical and chemical energy from sunlight, and especially regarding the optimization of photoreactors," says Professor Olaf Deutschmann, spokesman of the Helmholtz Research Training Group on "Energy-related Catalysis." PAGE 124 OF 124