One-Step Random Amplification Method to Detect Extremely Low Input Nucleic Acids for Virome, Microbiome, and Metagenomics in Clinical and Biological Specimens

Clinical and biological specimens often contain microbial nucleic acid in extremely low quantities, presenting a significant challenge for the detection of viral and bacterial pathogens. This also prevents direct sequencing of non-culturable samples using next-generation sequencing (NGS). Currently, NGS library preparation on most platforms requires 0.1 ng to 10 µg of DNA or cDNA, while microbial or viral nucleic acids in clinically relevant specimens, such as blood, serum, respiratory secretions, cerebral spinal fluid, and stool, often contain less than 0.1 ng.

Potent Nucleotide Inhibitors of Ecto-5'-Nucleotidase (CD73)

These small molecules are novel nucleotide derivatives, containing either a purine or pyrimidine nucleobase, that competitively block the enzyme CD73, also known as ecto-5'-nucleotidase. This enzyme converts extracellular AMP (not a potent activator of adenosine receptors) to adenosine (the native activator of 4 subtypes of adenosine receptors. CD73 inhibitors are being used, in clinical trials and preclinical research, in conjunction with cancer immunotherapy.

Novel Codon-Optimized Gene Therapeutic for Methylmalonic Acidemia

Methylmalonic Acidemia (MMA) is a metabolic disorder characterized by increased acidity in the blood and tissues due to toxic accumulation of protein and fat by-products resulting in seizures, strokes, and chronic kidney failure. A significant portion of MMA cases stem from a deficiency in a key mitochondrial enzyme, methylmalonyl-CoA mutase (MUT), required to break down amino acids and lipids. Currently, there are no treatments for MMA and the disease is managed primarily with dietary restriction of amino acid precursors and liver-kidney transplantation in severe cases.

Heterocyclic Compounds for the Treatment of Hepatitis C Virus

The vast majority of people infected with Hepatitis C Virus (HCV) will have chronic infection. Over decades, this can lead to liver disease and liver cancer. In fact, HCV infection is the leading cause of liver transplants in the U.S. Several new drugs have recently come into the market that have changed the HCV treatment paradigm. However, the effectiveness of these new drugs can vary depending on the HCV genotype. Furthermore, all oral, interferon free therapeutic regimens for HCV infection will need combinations of drugs that target different aspects of the HCV life cycle.

High-Titer, Fast-Growth Chimeric Dengue/West Nile Viruses for Vaccine and Diagnostics Development

Mosquito-transmitted dengue virus is one of the leading causes of illness in the tropics and subtropics. There is currently no vaccine available and a number of DENV diagnostic and research applications depend on the production of large amounts of these viruses. However, due to the slow growing nature of DENVs these protocols are very time-consuming.

Mobile Instrumentation for the Detection and Sampling of Aerosol Particles

Hazardous airborne particles pose a risk for health and safety in a variety of environments and thus detection of these small particles is essential. Current particle magnification systems are bulky and require a lot of power for operation, making them unsuitable to easily detect and analyze small particles in mobile and personal settings.

Microscopy System for Distinguishing Stimulated Emissions as a Means of Increasing Signal

The invention pertains to a system and method for distinguishing stimulated emissions as a means of enhancing signal strength of fluorescent markers in fluorescence microscopy applications. The system is arranged such that an excitation beam (e.g., laser beam) illuminates a sample along some axis exciting the fluorescent markers used in the sample. A second light beam, a stimulation beam, illuminates the sample along another axis, possibly the same as that of the excitation beam.

Therapeutic and Diagnostic Targets for Severe RSV Infection

Respiratory Syncytial Virus (RSV) infects nearly all children by their second birthday. RSV usually causes mild respiratory illness, however, a subset of patients experience severe infection that require hospitalization. Successful host defense against viral pathogens requires rapid recognition of the virus and activation of both innate and adaptive immunity. Toll-Like Receptors (TLRs) are responsible for mounting an innate immune response and genetic variations within TLRs modulate severity of infection.

Monoclonal Antibodies Against Bacillus Anthracis Antigens

Anthrax, whether resulting from natural or bioterrorist-associated exposure, is a constant threat to human health. Bacillus anthracis is the causative agent of anthrax. It is surrounded by a polypeptide capsule of poly-gamma-D-glutamic acid (gamma-D-PGA), which is essential for virulence, is poorly immunogenic and has anti-phagocytic properties. Antibodies to the capsule have been shown to enhance phagocytosis and killing of encapsulated bacilli.

Assay for Predicting the Time of Onset of Niemann-Pick Disease Type C (NPC)

Niemann-Pick Disease, type C (NPC) is a rare, autosomal recessive, neurodegenerative disease. Approximately 95% of patients with NPC have mutations in NPC1, a gene implicated in intracellular cholesterol trafficking. Mutation of NPC1 causes intracellular accumulation of unesterified cholesterol in late endosomal/lysosomal structures and marked accumulation of glycosphingolipids, especially in neuronal tissue. Thus, NPC patients generally present with hepatosplenomegaly (enlargement of liver and spleen) and neurological degeneration.