Preparation of Substituted Diarylpropanamides as RORgt Antagonists for the Treatment of Th17-related Autoimmune Diseases

This technology includes a series of diphenylpropanamides as potent and selective RORgt inhibitors for the treatment of Th17-related autoimmune diseases. The retinoic acid-related orphan receptor RORgt plays an important role in the differentiation of thymocytes, lymphoid tissue inducer cells, and inflammatory T helper-expressing interleukin 17a (Th17) cells. Small molecule RORgt inhibitors may provide means to regulate Th17 mediated immune response. The novel molecules have potential to treat Th17-related autoimmune diseases.

Discovery of imidazo[1,2-b]pyridazines with Anticancer Properties

This technology includes a series of imidazo[1,2-b]pyridazines that display potent inhibition of FLT3, as well as potent binding and activity against FLT3 tyrosine kinase domain and gatekeeper mutations. This chemotype exhibits superior anti-leukemic activity against the common clinically-relevant FLT3-mutant acute myeloid leukemia (AML) in vitro and in vivo. Tyrosine kinase domain mutations are a common cause of acquired resistance to FLT3 inhibitors used to treat FLT3-mutant AML.

Gene Therapy for Cobalamin C Deficiency (cblC) with Viable Mouse Models

Cobalamin C deficiency (cblC) is the most common inborn error of intracellular cobalamin metabolism and is caused by mutations in MMACHC, a gene responsible for processing and trafficking dependent enzymes: intracellular cobalamin, resulting in elevated methylmalonic acid and homocysteine and methionine deficiency. Disease manifestations include growth failure, anemia, cardial defects and progressive blindness.

MiR-193b and MiR-365-1 are Not Required for the Development and Function of Brown Fat in the Mouse

This technology includes the discovery that two specific microRNAs are not required for the development and function of brown fat in mice. Effects of inactivating microRNAs in cell culture in vitro have not always been reproduced in vivo. The paper tests the effect of inactivating two microRNAs, miR-193b and miR-365-1 on the differentiation, function and development of brown adipose tissue. In contrast to positive results previously observed in vitro, the mouse in vivo studies failed to demonstrate significant effects.

Field-Adapted Spot Test for Evaluating Materials Treated with Permethrin Insect Repellent

Military uniforms and mosquito nets are treated with permethrin, a repellent and insecticide used for personal protection against biting flies, mosquitoes, and other disease-carrying insects. Vector-borne diseases such as malaria, leishmaniasis (a parasitic infection spread by sandflies), Zika virus, West Nile virus, Lyme disease, and more can be diminished if treated nets or clothing containing the proper amount of permethrin are utilized. Washing and wear depletes the insecticide on the material, eventually rendering it ineffective.

Handwipe Disclosing Method for Detecting the Presence of Lead

Lead (Pb) exposure can cause serious health concerns including abdominal pain, headaches, loss of appetite, memory loss, weakness, and other symptoms. Lead residues on human skin, especially on the hands of workers can be a significant health risk since such residues may be ingested during normal activities (e.g. eating, drinking, and smoking). A key component to reducing lead exposure is being able to identify areas of lead contamination.

Molecular Nanotags for Detection of Single Molecules

Biological nanoparticles, like extracellular vesicles (EVs), possess unique biological characteristics making them attractive therapeutic agents, targets, or disease biomarkers. However, their use is hindered by the lack of tools available to accurately detect, sort, and analyze. Flow cytometers are used to sort and study individual cells. But, they are unable to detect and sort nanomaterials smaller than 200 nanometers with single epitope sensitivity.

Optical Configuration Methods for Spectral Scatter Flow Cytometry

Multi-parameter flow cytometry has been extensively used in multiple disciplines of biological discoveries, including immunology and cancer research. However, the disadvantage of traditional flow cytometry platforms using excitation lasers and fluorescence detectors is spectral overlap when using multiple dyes on the same biological sample. Metaethical compensation of spectral overlap could only be effective to a certain degree. Mass cytometry is advantageous compared to flow cytometry but is pricey and requires highly skilled operators. 

Exo-Clean Technology for Purifying Extracellular Vesicle Preparations from Contaminants

Extracellular Vesicles (EVs), including exosomes and microvesicles, are nanometer-sized membranous vesicles that can carry different types of cargos, such as proteins, nucleic acids and metabolites. EVs are produced and released by most cell types. They act as biological mediators for intercellular communication via delivery of their cargos. This unique ability spurred translational research interest for targeted delivery of therapeutic molecules to treat a wide range of diseases. EVs also contain interesting information of their specific cellular origin.

Mouse Lines with Fluorescently Labelled Membrane Proteins Regulating Cellular Motility and Membrane Trafficking

Cell motility and membrane trafficking play important roles in regulating cell division, cell migration, cell death and autophagy. Impairment of these processes can result in enhanced cell proliferation and survival and increased migration and invasion leading to cancer. Several proteins involved in cell motility and membrane trafficking have been shown to be dysregulated in various cancers. There is therefore a need for development of animal models for studying the roles of these proteins in cancer and their responses to drug treatment in vivo.

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