Abstract: This application describes compounds and methods that can inhibit Scavenger receptor class B, type I (SR-BI) activity, which compounds and methods can be used, for example, to mediate high-density lipoprotein (HDL) lipid uptake and treat hepatitis C viral infections. The compounds have the formula: wherein R1 and R2 are independently H, halogen, cyano, haloalkyl, haloalkyloxy or OMe; or R1 and R2 together are —O—CH2— or —O—CF2—O—; R3 is H, halogen, cyano, haloalkyl or haloalkyloxy; R4 is C1-6alkyl, C3-6cycloalkyl, C3-6cycloalkylmethyl or C3-6cycloheteroalkyl, wherein the heteroatom is N or O; R5 is H or CH3; R6 is C1-6alkyl or C3-6cycloalkyl; and A, B, D and E are each, independently, CH, N, O or S, wherein at least one of A, B, D and E is N, and another of A, B, D and E is N, O or S.

Abstract: The specification relates generally to methods of detecting, diagnosing, and/or identifying pathogens, e.g., infectious disease pathogens and determining their drug sensitivity and appropriate methods of treatment. This invention also relates generally to methods of monitoring pathogen infection in individual subjects as well as larger populations of subjects.

Abstract: The invention relates to a compound of Formula I: F1—X1-L1-X2—P1—X3-G1??(Formula I).

Abstract: The invention provides for systems, methods, and compositions for manipulation of sequences and/or activities of target sequences. Provided are vectors and vector systems, some of which encode one or more components of a CRISPR complex, as well as methods for the design and use of such vectors. Also provided are methods of directing CRISPR complex formation in eukaryotic cells and methods for selecting specific cells by introducing precise mutations utilizing the CRISPR/Cas system.

Abstract: Disclosed herein are methods and compositions useful in targeting a payload to, or editing a target nucleic acid, where a governing gRNA molecule is used to target, optionally inactivate, a Cas9 molecule or a Cas9 molecule/gRNA complex.

Abstract: Proteomic methods for identifying cancer related proteins and related products and kits are provided. The cancer specific proteins are extracellular matrix proteins that are associated with various aspects of cancer. Panels or signature sets of proteins useful in the detection, diagnosis and treatment of cancers as well as monitoring therapeutic progress in a cancer patient are provided herein along with methods for their detection and for their use in targeting imaging and/or therapeutic agents to the tumors via binding to the specified proteins. The proteins were identified using proteomics analyses of tissue samples taken from cancer patients. In certain aspects the proteins are particularly useful in colon cancer patients.

Abstract: The invention provides for systems, methods, and compositions for manipulation of sequences and/or activities of target sequences. Provided are vectors and vector systems, some of which encode one or more components of a CRISPR complex, as well as methods for the design and use of such vectors. Also provided are methods of directing CRISPR complex formation in eukaryotic cells and methods for selecting specific cells by introducing precise mutations utilizing the CRISPR/Cas system.

Abstract: The present invention relates to clonal expansion of somatic cells in subjects, and acquired selective advantage of cell clones during the lifetime of a subject. In particular, the invention relates to methods for predicting the development of cancer based on the observation of specific genetic mutations in somatic cell clones, as well as to methods for treating or preventing cancer in a subject, in which clonal expansion of cells comprising specific modifications is observed.

Abstract: The invention provides for systems, methods, and compositions for targeting nucleic acids. In particular, the invention provides non-naturally occurring or engineered DNA or RNA-targeting systems comprising a novel DNA or RNA-targeting CRISPR effector protein and at least one targeting nucleic acid component like a guide RNA.

Abstract: The invention generally provides a sieve valve including: a substrate defining a channel; a flexible membrane adapted and configured for deployment at an intersection with the channel; and one or more protrusions extending into the channel from the substrate or the flexible membrane. The one or more protrusions define a plurality of recesses extending beyond the intersection between the channel and the flexible membrane; A microfluidic circuit including one or more sieve valves. In particular embodiments, the circuit comprises one or more input/output valves. The one or one or more input/output valves can include one or more input valves and one or more output valves. The microfluidic circuit can further include a mixing circuit. At least one of the sieve valves can be positioned between the one or more input/output valves and the mixing circuit. The invention further provides methods of using the device for the analysis of samples comprising cells.

Abstract: The present invention relates to compounds of formula (I) or a pharmaceutically acceptable salt, hydrate, solvate, or prodrug thereof, wherein X1, X2, X3, X4, X5, W1, W2, W3, and W4 are as described. The present invention relates generally to inhibitors of histone deacetylase and to methods of making and using them. In one aspect, the invention relates to selective HDAC3 inhibitors useful for protecting ?-cells and improving insulin resistance. The selective HDAC3 inhibitors are also useful for promoting cognitive function and enhancing learning and memory formation.

Abstract: The invention relates to methods of treatment and diagnosis of subjects with cancer. In some aspects, the invention relates to methods of treatment and diagnosis of subjects with cancer, wherein the cancer is characterized by a Notch pathway activation mutation or by resistance to a Notch pathway inhibitor.

Abstract: The invention relates to methods for the identification of compounds, peptides and proteins that can act as substrates for histone deacetylases. The invention further relates to compounds of Formula I: F1-X1-L1-X2-P1-X3-G1??(Formula I) The invention relates to the treatment of diseases or disorders mediated by ARID1A (BAF250A).

Abstract: The present invention is related to genomic nucleotide sequencing. In particular, the invention describes a paired end sequencing method that enables the sequencing of unique read pairs by co-localizing both 5? ends on a single emulsion polymerase chain reaction bead. The method may use a customized forked adaptor primer pair that is compatible with massively parallel sequencing techniques. The compositions and methods disclosed herein contemplate sequencing complex genomes, amplified genomic regions, as well as detecting chromosomal structural rearrangements.

Abstract: The present invention provides novel compounds (e.g., compounds of Formula (I)), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, prodrugs, and compositions thereof. Also provided are methods and kits comprising the inventive compounds, or compositions thereof, for treating and/or preventing a fungal or protozoan infection, inhibiting the activity of a fungal or protozoan enzyme, killing a fungus or protozoon, or inhibiting the growth of a fungus or protozoon. The fungus may be a Candida species, Aspergillus species, or other pathogenic fungal species. The compounds of the invention may inhibit the activity of fungal or protozoan cytochrome b and/or fungal or protozoan Hsp90. The present invention also provides synthetic methods of the inventive compounds.

Abstract: The present disclosure provides methods of treating and/or preventing inflammatory bowel disease (IBD) and graft-versus-host disease (GVHD) using salt-inducible kinase (SIK) inhibitors, such as macrocyclic SIK inhibitors of Formula (I), imidazolyl SIK inhibitors of Formula (II), and urea and carbamate SIK inhibitors of Formula (III-A) (e.g., urea and carbamate SIK inhibitors of Formula (III)).

Abstract: The present invention relates to compounds of formula (I): or a pharmaceutically acceptable salt, hydrate, solvate, or prodrug thereof, wherein U, J, V, X, R1a, R2b, R2c, R5 and t are as described herein. The present invention relates generally to inhibitors of histone deacetylase and to methods of making and using them. These compounds are useful for promoting cognitive function and enhancing learning and memory formation. In addition, these compounds are useful for treating, alleviating, and/or preventing various conditions, including for example, neurological disorders, memory and cognitive function disorders/impairments, extinction learning disorders, fungal diseases and infections, inflammatory diseases, hematological diseases, and neoplastic diseases in humans and animals.

Abstract: The invention relates to tuberculosis diagnostic methods and devices that measure particular biomarker profiles in subjects and identify a subject having tuberculosis based on such profiles.

Abstract: The invention relates to compounds of Formula I or a pharmaceutically acceptable salt, ester or prodrug thereof:

Abstract: The present invention provides nucleic acid constructs that encode fusion peptides comprising a bioluminescent protein and a precursor of a secreted peptide or protein expressed at the cell surface and high throughput screening assays using same.