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Cyanide, Sulfide, Methane-Thiol Antidote

Cyanide is a highly toxic agent that inhibits mitochondrial cytochrome-c oxidase, thereby depleting cellular ATP. Cyanide exposure contributes to smoke inhalation deaths in fires and could be used as a weapon of mass destruction. Cobalamin (vitamin B12) binds cyanide with a relatively high affinity and is used to treat smoke inhalation victims. Cobinamide, the penultimate compound in cobalamin biosynthesis, binds cyanide with about 1010 greater affinity than cobalamin and is 5-10 times more potent than cobalamin in rescuing animals from cyanide poisoning. Cobinamide is also an effective intra- and extracellular nitric oxide scavenger. Currently, three cyanide antidotes are currently available in the United States: nitrites, thiosulfate, and hydroxocobalamin. All three drugs are approved only for intravenous (IV) administration, and thus are not suitable for treating mass casualties as could occur after a major industrial accident or a terrorist attack. Thus, new formulations for cyanide exposure treatment that are faster and easier to administer are needed.

Multistrain Population Control Systems and Methods in Bacteria

Microbial ecologists are increasingly turning to small, synthesized ecosystems as a reductionist tool to probe the complexity of native microbiomes. Concurrently, synthetic biologists have gone from single-cell gene circuits to controlling whole populations using intercellular signaling. 

Probing and Measurement Tool for Silicon Photonics Technology

Silicon photonics is the melding of traditional high-density/high-throughput silicon wafer processes with electro-optical systems at wafer scale and production volumes. Today, silicon photonics is transforming the design and operation of data centers, enabling 100G connectivity with the goal of 400G in the next couple of years. According to Intel, the explosive growth of network traffic has pushed silicon photonics past the tipping point for widespread adoption, with future uses cases extending into many other technology sectors, including: autonomous vehicles, aviation, Internet of Things, Artificial Intelligence, classical and quantum computing and sensing.   BCC Research projects the global market for photonic integrated circuits to grow from $539M in 2017 to $1.8B in 2022, a combined annual growth rate of 27.5%. Now while data-centers are making ready use of this new technology, much research and development opportunity remains to be solved as silicon photonics begins to penetrate the broader market for IC’s.

Targeting CAFs: New Treatment for Pancreatic Cancer by Blocking Fibrotic Pathways

Pancreatic ductal adenocarcinoma (PDAC), the most common type of pancreatic cancer, is currently the third- leading cause of cancer death in the United States, and is predicted to be the second such cause by 2020. The current 5-year survival rate of PDAC is ~8%. Factors that contribute to this high death rate include the early, asymptomatic phase of the disease, such that at the time of diagnosis, many patients have locally advanced or metastatic disease. Surgical resection, the only curative treatment, is feasible in <20% of patients. Chemotherapy of PDAC has had limited impact. The EGFR inhibitor erlotinib is the only approved targeted therapy and produces minimal clinical benefit. New, effective treatments of pancreatic cancer are thus a major, unmet medical need. G protein-coupled receptors (GPCRs), the largest family of cell signaling receptors (~3% of the human genome), are seven transmembrane receptors that respond to numerous types of extracellular signals and regulate many physiological processes. Emerging evidence implicates GPCRs in cancer: certain GPCRs have increased expression in tumors and are involved in cancer initiation and/or progression. GPCRs can contribute to fibroblast myofibroblast conversion and increases in cellular cAMP (a second messenger for certain GPCRs) can blunt the myofibroblastic phenotype. Little is known regarding the role of GPCRs in pancreatic cancer-associated fibroblasts (CAFs).

Identification of Novel Regulatory CD8 T Cells in Control of Inflammation in the Gut

A dynamic set of complex interactions between intestinal microbes, intestinal epithelial cells and intestinal immune cells are key in maintaining normal intestinal homeostasis as well as in the etiology of Inflammatory Bowel Disease (IBD). It is becoming clear that regulatory T cell-mediated control of inflammation is critical for the maintenance of immune tolerance in gut. Since 1970s, it has been suggested that CD8+ regulatory T cells play an important role in immune regulation of autoimmune diseases, transplant tolerance, and homeostasis of cellular and humoral immune responses. Among Treg subpopulations, an important role for Foxp3+CD4+ Treg and Foxp3- IL-10-secreting CD4+ T cells has been elucidated, while the function of CD8+ regulatory T cells in the gut has been hampered by an inability to distinguish them from conventional CD8+ T cells. Normally specific cytokines and transcription factors are the driving factors for maintaining the expression of a particular T cell phenotype.

Targeting Kidney Stones: A Neutraceutical Formulation / Functional Food containing Bioactives

Changing diets and lifestyles are causing dramatic increases in painful kidney stones. Tastes for high-salt processed foods, high-sugar foods and drinks, and poor hydration are all causes. It is estimated that 10-20% of the population will develop a kidney stone, resulting in extreme pain, which may require surgical intervention. Alongside direct medical procedures, patients are often given potassium citrate pills as an adjunct therapy, but these are poorly-tolerated due to gastrointestinal side effects and large size of the pills, all of which decrease patient compliance. These current formulations require a twice-a-day dosing regimen, which only exacerbates the compliance problem. However, beyond these citrate pills, sadly few effective medical alternatives exist. To remedy this problem, UC San Diego physicians have recently developed a neutraceutical formulation, specifically designed to comprise precise balance of bioactives within a well-tolerated functional food, supporting the targeted relief of kidney stones.

Ex Vivo Maintenance and Expansion Of Hematopoietic Stem Cells

Hematopoietic stem cell (HSC) transplants are used to treat patients with a broad spectrum of hematological malignancies, immune disorders and genetic blood diseases. Unfortunately, even after decades of use and research, there is a significant shortage of histocompatible HSCs available for transplants. Transplanting larger numbers of HSCs increases the likelihood and speed of successful engraftment, which can reduce the risk of complications such as anemia and infection, and more effectively treat underlying disease. The inability to efficiently maintain adult HSCs ex vivo is also a significant barrier for the wider development and implementation of gene therapies for diverse blood diseases and a major obstacle for engineering HSC derived cellular products for immunotherapy. One approach to overcome this challenge is to develop a means to maintain and expand HSCs in culture. Unfortunately, there is no well-defined reproducible means to maintain or expand HSCs. Even short culture times in optimized conditions are deleterious to HSCs. Ex vivo HSC maintenance and expansion could significantly enhance their clinical utility in a wide range of human diseases, providing a new platform for testing drugs, enabling more efficient gene editing within stem cells, and developing into a widely-used tool for the research community.

Composition Of Matter And Method For Leptospirosis Vaccine

Leptospirosis is one of the most widespread diseases estimated to infect up to 7-10 million people per year worldwide (2014) that can be transmitted from animals to humans. The most common transmission is via the urine of rodents or domestic animals that contaminates water or soil. Unfortunately, it can cause severe infection and currently there is not an efficient vaccine present to combat this disease. The disease is caused by Leptospira, a genus of the spirochaete bacteria of which there are ~13 pathogenic species that effect humans. The signs and symptoms of the disease are quite variable and can range from mild headaches, muscle pains, and fevers to the more severe form which causes bleeding from the lungs.