20 April 2016. Energy use by Americans in their homes and businesses declined in 2015 from the previous year, due to a sharp drop in coal burned for electric power, among other factors. The findings were published in an annual accounting of national energy supply and demand by Lawrence Livermore National Laboratory, based on data from the Department of Energy’s Energy Information Administration.
Overall, Americans used 97.5 quadrillion British Thermal Units, or quads, of energy, a reduction of 0.8 quads from 2014. British Thermal Units or BTUs are an international unit of energy, with 3,600 BTUs equivalent to 1 kilowatt-hour. At the same time, Americans use of energy from renewable sources increased in 2015, led by gains of 25 percent in utility-scale solar energy, and 11 percent more use each of residential solar and geothermal power. Use of wind energy also gained by 5 percent in 2015.
While renewables gained, fossil fuel use had a mixed record in 2015. Burning of coal for electrical power declined by 12 percent in 2015 to 15.7 quads, while natural gas use increased by 3 percent, reflecting a continuing shift in sources by utilities. A.J. Simon, group leader of the Livermore Lab’s energy program, notes in a statement that “much of the overall decrease in energy consumption can be traced to the shift from coal to gas, because modern gas-fired plants may use up to 46 percent less energy to produce the same amount of electricity.”
Petroleum use in 2015 increased by 2 percent compared to 2014, which Livermore Lab says is a result of economic growth, reflected in more driving for work and recreation, as well as increased deliveries of goods. Energy produced from all sources for electric power generation decreased slightly to 38 quads in 2015.
The largest single energy consumer in the U.S. in 2015 was transportation, which accounted for 27.7 of the 97.5 quads produced, about the same as 2014, followed by industrial, residential, and commercial uses. Residential, commercial, and industrial energy use in 2015 registered decreases compared to 2014, with residential use of natural gas declining by 0.5 quads in 2015, which Livermore Lab attributes to milder winter.
Wasted energy — power produced but not consumed by the economy — declined from 59.4 quads in 2014 to 59.1 in 2015, a reduction of 1 percent. Livemore Lab attributes at least some of that wasted energy reduction to more efficient electrical power production, including utility-scale solar farms.
U.S. energy accounting flow chart; click on image for full-size display (Lawrence Livermore National Laboratory)
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(National Human Genome Research Institute, NIH)
19 April 2016. A new computer program detects genetic variations in individual cells, rather than current methods that require analyzing DNA in millions of cells. The program, named Monovar, is described by geneticists and bioinformatics specialists at M.D. Anderson Cancer Center in the 18 April issue of the journal Nature Methods (paid subscription required).
Monovar is designed to provide more precise depictions of genetic alterations, including those leading to cancer, than next generation sequencing, or NGS, the current state of the art in genomic analysis. “NGS technologies have vastly improved our understanding of the human genome and its variation in diseases such as cancer,” says Ken Chen, professor of bioinformatics and a lead author of the paper in an M.D. Anderson statement. “However, because NGS measures large numbers of cells, genomic variations within tissue samples are often masked.”
The emergence of single-cell sequencing, say the authors, offers better tools for understanding characteristics of tumors, and has already made an impact on cancer research and other areas of biology. Monovar provides computational tools for single-cell sequencing to detect slight alterations in individual cells, known as single nucleotide variants or SNVs. Co-lead author Nicholas Navin, a genetics professor at M.D. Anderson, adds that “Monovar is a novel statistical method able to leverage data from multiple single cells to discover SNVs and provides highly detailed genetic data.”
In their paper, Chen, Navin, and colleagues tested Monovar against standard algorithms on three human tumor data sets. The researchers report Monovar performed better at identifying driver mutations — genetic variations implicated in cancer development — and the structure of cloned DNA, than the standard algorithms.
The M.D. Anderson team, based in Houston, believes Monovar can be applied directly to cancer diagnosis and treatment, particularly in precision medicine, where identification of small genetic variations is important for an individual patient’s care. The software can also be applied to pre-natal genetic diagnosis, and with further refinements, to diseases other than cancer.
The Monovar software is available from Bitbucket.org, with pricing determined by the size of team.
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(Oleg Savitsky, Wikimedia Commons)
19 April 2016. A technique for masking allergy or asthma treatments in biodegradable nanoparticles is shown in lab mice to quickly build a tolerance in the immune system for offending allergens. A medical and engineering team at Northwestern University in Chicago published its findings yesterday, 18 April, in Proceedings of the National Academy of Sciences (paid subscription required).
Researchers led by immunologist Stephen Miller are seeking a solution to underlying causes of asthma, a chronic condition where the airways become inflamed and narrow, causing people with asthma to experience wheezing, shortness of breath, tightness in the chest, and coughing for periods of time. Centers for Disease Control and Prevention estimates that in 2010 some 18.7 million adults had asthma, along with 7 million children.
Most asthma treatments relieve symptoms or try to build a tolerance over time for pollen, air pollution, or dust mites that trigger the airway inflammation in asthma. Among people with asthma, normal immune system mechanisms that make it possible to adapt to these allergens do not function. The approach taken by Miller and colleagues from Northwestern and University of Michigan is to quickly develop a tolerance for the allergen that bypasses the immune system, thus avoiding adverse reactions.
The team’s techniques encase proteins similar to the allergens in nanoscale particles made of poly lactic-co-glycolic acid or PLGA, a biocompatible and biodegradable polymer often used in medical devices and for drug delivery. The PLGA coating masks the allergen from the immune system, allowing macrophages — white blood cells in the immune system that ingest foreign matter — to take in the particles without causing a reaction. Miller’s lab assessed this approach previously in preclinical research with treatments for the autoimmune disorders celiac disease and multiple sclerosis, but not for allergies or asthma.
In their paper, the researchers tested the process on lab mice induced with a respiratory allergy to egg proteins like asthma. When the protein was injected into the lungs, the mice created antibodies causing a reaction with inflammation in the lungs similar to asthma. After receiving injections of the nanoparticles, which were well tolerated, the mice no longer reacted to the allergens.
In addition, the team found mice receiving the nanoparticles developed more immune system cells that react normally, rather than adversely, to potential allergens. After the nanoparticle treatments, mice produced more regulatory T-cells, white blood cells in the immune system that respond routinely to possible allergic substances, than Th2 or helper T-cells that generate a strong immune response.
Miller’s lab is testing the techniques to treat other allergies. “It’s a universal treatment,” says Miller in a university statement. “Depending on what allergy you want to eliminate, you can load up the nanoparticle with ragweed pollen or a peanut protein.”
Cour Pharmaceutical Development Co. in Chicago licensed the technology from Northwestern and is developing treatments for allergies, celiac disease, and inflammatory disorders. Miller and co-author Lonnie Shea are scientific advisers to the company.
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Pseudomonas aeruginosa bacteria (National Institute of Environmental Health Sciences, NIH)
18 April 2016. A bandage that sends a mild electric current through wounds was shown in tests with pigs to disrupt and reduce films of bacteria that form over wounds, to improve healing. Tests of the electric wound dressing, made by Vomaris Innovations in Tempe, Arizona, were reported at the Wound Healing Society conference that ended yesterday in Atlanta, Georgia.
Vomaris Innovations is a medical device company with a technology that sends a weak electric current from tiny batteries through dressings that the company says disrupts colonies of bacteria that can form in wounds. The batteries, made with silver and zinc, are arranged in a matrix in the wound dressing, between layers of adhesive and foam. The electric current is carried through hydrogel or saline solutions applied with the dressing, or the moisture from the wound itself.
The company’s technology is designed to prevent the build-up of bacterial biofilms in the wounds. Biofilms are communities of microbes that connect and expand through a matrix of organic matter. These microbe colonies also stick tightly to surfaces, including the skin, making them difficult to treat, because of their persistence and ability to resist conventional antibiotics. When biofilms cause skin infections, the bacteria are further protected by the outermost layer of the skin.
In their conference paper, a research team led by Ohio State University surgery professor Chandra Sen reported on tests of the Vomaris device with full thickness burns on pigs that destroy both the dermis and epidermis layers of skin. The burns were also infected with biofilms of Pseudomonas aeruginosa and Acinetobacter bacteria, which present serious problems for patients in hospitals, especially in intensive care units or with weak immune systems. The animals were randomly assigned to receive treatments twice a week for 56 days with either Vomaris or placebo dressings.
The results show wounds treated with Vomaris dressings had less bacterial biofilm colonization on the wound surface, compared to the placebo dressings. In addition, wounds treated with the Vomaris dressings showed more new tissue regrow and stronger skin barrier over the wound than those treated with placebos.
Sen notes in a Vomaris statement that the electric current in the dressings could help prevent development of resistance to treatments, a growing problem with traditional antibiotics. “Electrical forces and activity are central to the assembly and integrity of bacterial biofilm,” says Sen. “These microbes cannot evade electrodynamic forces as they do pharmacological drugs, making electroceutical intervention a smart choice.”
FDA cleared the Vomaris device, with the brand-name Procellera, for use with humans in June 2013.
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Carcinoid lung tumor (Yale Rose, Flickr)
18 April 2016. An experimental treatment was shown in lab mice to enhance immune system cells that can help immunotherapy drugs to reduce solid tumor growth. Researchers from Memorial Sloan Kettering Cancer Center in New York and Infinity Pharmaceuticals in Cambridge, Massachusetts presented their findings yesterday (17 April) at the annual meeting of American Association for Cancer Research in New Orleans.
Infinity Pharmaceuticals is developing cancer treatments that target the phosphoinositide-3-kinase, or PI3K, signaling pathways associated with a wide range of cancers in humans. The therapy in this case, code-named IPI-549, is a small-molecule or low molecular weight treatment designed to limit PI3K-gamma signals that block immune system cells from acting on tumor growth. In particular, PI3K-gamma signals promote the support system that protect tumors from immune cells.
The team from Sloan Kettering and Infinity tested IPI-549 given as oral treatments to mice induced with human lung cancer. The results show mice given IPI-549 had lower levels of myeloid cells that support the ability of tumors to suppress immune system cells. Mice given IPI-549 also reported higher levels of CD8+ or cytotoxic T-cells in the immune system that attack tumors, which with the reductions in myeloid cells, indicate the treatments can disrupt the protective environment built up by tumors.
In separate findings on a poster at the AACR meeting, Infinity reported that IPI-549 treatments given with immunotherapy treatments to lab mice induced with solid tumor cancers had less tumor growth than mice given the immunotherapies alone. The company tested IPI-549 with a type of immunotherapy known as checkpoint inhibitors that limit the actions of tumor cells to block the immune system.
The results show mice receiving IPI-549 with immunotherapy treatments had more complete responses, less tumor growth, and greater survival than those getting immunotherapy alone. Mice with IPI-549 and immunotherapy having complete responses also reported little or no tumor growth when tumors were regrafted, suggesting a continuing effect of the treatments.
Infinity is testing the safety and effects on the body of IPI-549 in an early-stage clinical trial with individuals having advanced cases of non-small cell lung cancer and melanoma. The company is recruiting 150 participants, who will be given IPI-549 alone, or with pembrolizumab, a checkpoint inhibitor approved by FDA to treat those cancer types.
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15 April 2016. A challenge on InnoCentive is asking for new techniques to deliver drugs to specialized kidney cells in patients with kidney damage caused by diabetes. The competition has a total purse of $20,000 and a deadline of 13 May 2016 for submissions. The sponsor of the challenge, pharmaceutical company Boehringer Ingelheim, is also seeking research plans related to the challenge proposals, with funding of up to $200,000 selected separately.
The competition is conducted by InnoCentive in Waltham, Massachusetts that conducts open-innovation, crowdsourcing competitions for corporate and organization sponsors. Free registration is required to see details of the competition. In November 2015, Boehringer Ingelheim revealed that it planned to make more use of crowdsourcing for R&D ideas through InnoCentive and others.
Boehringer Ingelheim is seeking new ways to address diabetic nephropathy, damage to kidneys resulting from diabetes. In people with diabetes, basic components of kidneys known as nephrons, thicken and become scarred, leaking albumin proteins into the urine. Damage can occur and continue for years before symptoms develop, with diabetic nephropathy now considered a major cause of sickness and death among people with diabetes, often requiring dialysis or a kidney transplant.
Because of the rising number of people with diabetes worldwide — World Health Organization estimates 422 million people have diabetes, leading to 1.5 million deaths each year — new tools and techniques are urgently needed to battle its effects. Boehringer Ingelheim cites data indicating the 5-year survival rate of people with diabetes in dialysis is only 25 percent, with diabetic nephropathy also a major risk factor for cardiovascular disease.
In this challenge, the sponsor is seeking solutions that target cells in the kidney known as podocytes that filter waste from the blood. Podocytes are found in the Bowman’s capsule of the kidney that surrounds a tangled cluster of capillaries called the glomerulus, and are part of the kidney’s filtration system. Because of the key role played by podocytes, Boehringer Ingelheim seeks new ways to address these cells in people with chronic cases of diabetic nephropathy.
InnoCentive calls this type of competition an ideation challenge, which requires a brief (two-page) proposal. Ideation proposals can contain ideas originating from the participants, the public domain where no restrictions are applied, or third-parties where participants have the rights to propose solutions with those ideas. Participants are asked not to submit confidential information in their proposals.
Boehringer Ingelheim says it plans to award the entire $20,000 challenge purse, with at least one award being no smaller than $5,000 and no award being smaller than $3,000. The sponsor also indicates that submitting a proposal grants the sponsor a non-exclusive, perpetual, and royalty-free license to use any information in the proposal. An exclusive transfer of intellectual property rights to the sponsor, however, is not required.
Participants in the competition with their own research facilities can apply for funding to carry out the research plan in their challenge proposals. Boehringer Ingelheim says these research plans should not exceed two years nor request more than $200,000. The company says the optional research proposals will be considered separately from the challenge submissions, but still have a 13 May 2016 deadline.
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Pancreatic cancer device inventors, L-R, Matteo Ligorio, Laura Indolfi, and Elazer Edelman (Bryce Vickmark, MIT)
15 April 2016. An engineering and medical research team developed an implanted device that in lab mice delivers chemotherapy directly to cancerous tumors in the pancreas. The device, designed in a biomedical engineering lab at Massachusetts Institute of Technology and Harvard University, is described in an article appearing 31 March 2016 in the journal Biomaterials (paid subscription required).
The technology, created in the lab headed by engineering and medical professor Elazar Edelman, seeks to offer people with pancreatic cancer more and better therapeutic options. Pancreatic cancer is often difficult to diagnose in its early stages, due to few unique symptoms associated with the disease, as well as the pancreas being hidden among other organs in the body. As a result, it is often diagnosed in later, more advanced stages of the disease, with generally a poor prognosis for survival. American Cancer Society estimates more than 53,000 people in the U.S. will be diagnosed with pancreatic cancer this year, leading to nearly 42,000 deaths.
Another characteristic of pancreatic cancer is a thick fibrous coating that builds up on tumors, making it more difficult for drugs to penetrate. In addition, tumors in the pancreas have fewer blood vessels, limiting the routes available to deliver drugs.
The overcome these obstacles, MIT postdoctoral researcher Laura Indolfi in the Edelman lab, with David Ting and Matteo Ligorio at Massachusetts General Hospital, affiliated with Harvard Medical School, developed a flexible plastic film, loaded with chemotherapy drugs that fits over a tumor in the pancreas. The film itself is made from poly lactic-co-glycolic acid or PLGA, a biocompatible and biodegradable polymer often used in medical devices and for drug delivery.
Because of its flexibility, the film can be rolled up and delivered with a catheter to the cancer site, which unfolds and wraps around the tumor, or surgically implanted. The film is first loaded with enough chemotherapy drugs for 60 days, and programmed to release the drugs over that period. In addition, the device emits the drugs only from the side of the film facing the tumor, to limit damage to other organs.
The researchers tested the device on lab mice grafted with human pancreatic tumors. Some of the mice received the implanted device with the chemotherapy drug paclitaxel often given to treat sold tumor cancers, while the other mice received injections of paclitaxel, similar to current chemotherapy delivery methods, for 4 weeks.
After 4 weeks, mice with the device-delivered drugs had 5 times higher concentrations of paclitaxel in their tumors than mice receiving the drug through injections. Moreover, mice with the devices were found with 12 times less tumor growth, and in some cases shrinkage of tumors, than those with injected drugs. In addition, mice receiving drugs through the device had less metastasis, or spreading, of the cancer to other organs.
The authors say this drug delivery technology may have other uses. People with pancreatic tumors sometimes encounter blockages in their bile ducts from the spread of the cancer, a painful condition that interferes with digestion. Combining the drug-coated film with a stent could relieve the blockage and prevent the cancer spreading again to the duct, extending the lifetime of the stent. The device could also treat other solid tumor cancers that are difficult to reach and those needing high doses of chemotherapy, but would be too toxic to patients if delivered with conventional infusions.
Indolfi, Ting, and Edelman founded PanTher Therapeutics in 2014, a company in Boston commercializing the drug delivery technology. Indolfi is PanTher’s CEO and co-author Ligorio is the company’s lead clinician. PanTher is planning clinical trials of its device and is seeking partners to expand the technology to other disorders.
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Western diamondback rattlesnake (H. Krisp, Wikimedia Commons)
14 April 2016. A new treatment for rattlesnake bites, designed as emergency first-aid until reaching a clinic, is being developed at University of Arizona medical school in Tucson. The therapy, still in preclinical stages, is the work of anesthesiology professor Vance Nielsen and toxicologist Leslie Boyer, founder and director of Arizona’s Viper Institute — short for Venom Immunochemistry, Pharmacology and Emergency Response — also part of the university’s health sciences department.
From 7,000 to 8,000 people get bitten by snakes in the U.S. each year, according to Centers for Disease Control and Prevention. The risk to most people from snakebites is considered minor, but some people will have an allergic reaction, leading to a small number of deaths, about 5 in the U.S. each year.
The new treatment is designed to help people bitten by a class of snakes called pit vipers that are found in much of North and South America, and parts of Europe and Asia. Pit vipers include venomous rattlesnakes and copperheads that inhabit dry land, and water moccasins and cottonmouth snakes living in water. The snakes have a sensitive heat sensor in a pit between their eyes and nostrils, thus their name, that give them the ability to detect and hunt warm-blooded prey.
Among the effects of pit viper venom is its damage to fibrinogen, a protein in blood that combines with platelets, that makes it possible for blood to coagulate in case of wounds or injury. While many people bitten by pit vipers or other venomous snakes may not have allergic reactions, they can still suffer excessive bleeding when the venom damages fibrinogen.
The therapy being developed by Nielsen and Boyer aims to temporarily restore fibrinogen levels in people attacked by rattlesnakes until they can reach a clinic to receive medical attention. The proposed treatment, still in discovery and early development stages, combines carbon monoxide and iron, which if given soon enough after the bite, can block the effects of venom by bolstering fibrinogen in the blood.
Nielsen earlier published research on the effects of carbon monoxide and iron on coagulation, which led to his interest in developing a treatment for snakebite that addresses the risk of excessive bleeding. While he and Boyer have worked on the new drug for about a year, they already engaged the services of Tech Launch Arizona, the university’s technology commercialization arm to protect their intellectual property and move the discoveries to market.
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Red blood cells (geralt, Pixabay)
14 April 2016. A new process is shown to regenerate therapeutic coatings on implanted medical devices in lab tests and with animals, possibly extending the devices’ lifetimes in patients. The techniques, developed in the lab of Harvard University biomedical engineering professor Elliot Chaikof, are described in the 13 April 2016 issue of the journal Nature Communications.
Chaikof and colleagues at Beth Israel Deaconess Medical Center, affiliated with Harvard Medical School, and the Wyss Institute of Biologically Inspired Engineering also at Harvard, address a problem with newer implanted medical devices, such as stents and heart valves, in regular contact with blood. These devices have thin-film coatings of molecules or drugs to prevent clots or inflammation, such as restenosis where inflammation blocks arteries after bare-metal stents are implanted.
But these coatings have limited lifetimes, which only temporarily delay the need to replace the devices. “Not only do they have a finite reservoir of bioactive agents,” says Chaikof in a Beth Israel statement, “but the surface components of the thin films also degrade or lose their effectiveness when exposed to the physiological environment over time. Presently the only solution is to replace the entire device.”
The new technique developed by Chaikof and co-author David Liu, a Harvard chemistry professor, harnesses an engineered form of the enzyme Staphylococcus aureus Sortase A, which in its wild form can act as a catalyst to link sequences of peptides, or short protein chains. The engineered form, known as eSrtA, boosts that catalytic ability 120-fold. Moreover, eSrtA can break apart as well as link the peptide sequences, and repeat those functions over and over.
The researchers first tested eSrtA with thrombomodulin, a protein with anti-clotting properties, attached to simulated device surfaces. Results show adding eSrtA was able to regenerate thrombomodulin activity on the device surfaces in whole blood, with the thrombomodulin still able to produce anti-clotting factors for as long as 28 days.
The team then added eSrtA to thrombomodulin coatings on venous access catheters, first in lab mice, then in the jugular veins of rats. After 7 days, coatings on the catheters in rats were still charging, stripping, and recharging thrombomodulin. “We found that through a two-step process of removing and replacing bioactive coatings,” notes Liu, “eSrtA enables rapid, repeated thin-film regeneration in the presence of whole blood in vitro and in vivo.”
While these proof-of-concept findings were promising, the authors say much work remains. Since eSrtA is derived from bacteria, its ability to generate an immune reaction needs to be determined. The entire lifetime of device coatings with eSrtA also needs to be measured, along with the number of times coatings can be regenerated, and whether interactions with other biological processes allow bioactive coatings to be accessed over time.
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Sung Poblete, president and CEO of Stand Up to Cancer (standup2cancer.org)
13 April 2016. The charitable group Stand Up to Cancer unveiled today a new program to spur research on cancer treatments begun by pharmaceutical companies. The program known as Catalyst will harness funds and products from participating companies that will be bid out to the research community at large for further research and development.
Charter members of Catalyst include the pharmaceutical companies Merck, Bristol-Myers Squibb, and Roche, through its biotechnology subsidiary Genentech. The companies will provide cancer treatments under development, or currently approved drugs for study to treat other disorders, as well as diagnostic or medical devices. Financial or in-kind commitments from these companies for Catalyst were not disclosed.
The Catalyst program itself will be administered by American Association for Cancer Research. Based on participants’ donations, American Association for Cancer Research will issue a request-for-proposal for translational researchers to respond with novel ideas leading to drugs or devices for detecting, preventing, or treating cancer. The request will outline the compounds and other materials provided by the companies, research priorities, estimated number of projects supported, and funds available.
Proposals are expected to follow Stand Up to Cancer’s collaborative model that puts together teams that cross industry and sector boundaries. This team approach, says the organization, brought together 1,100 researchers at 131 institutions, as well as 69 pharmaceutical, biotech, and diagnostics companies. The teams so far produced more than 160 clinical trials planned, underway, or completed.
Sung Poblete, president and CEO of Stand Up to Cancer (SU2C), says Catalyst aims to speed up the rate at which new treatments are being developed. “The Catalyst program,” says Poblete in an organization statement, “is a perfect fit with the SU2C mission of accelerating the pace of groundbreaking translational research that provides new therapies to patients quickly. This will be a nimble program that will help speed up the rate at which we discover what works.”
The Catalyst program will be supervised by an executive board chaired by Phillip Sharp, professor of cancer research at MIT and 1993 Nobel laureate, who also chairs Stand Up to Cancer’s scientific advisory committee. A steering committee of academic and industry representatives will review proposals and recommend awardees.
Stand Up to Cancer, in Los Angeles, is an initiative of Entertainment Industry Foundation. The charity was formed in 2008 by film and media executives who use the industry’s resources to encourage a more collaborative model for cancer research.
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