Abstract: The invention is directed to compositions and methods for treating or reducing the likelihood of the development of epilepsy in an individual. The method comprises administering to the central nervous system of an individual in need of such treatment a therapeutically effective amount of an agent capable of increasing the expression and/or activity of miR-128.

Abstract: The invention provides for delivery, engineering and optimization of systems, methods, and compositions for manipulation of sequences and/or activities of target sequences. Provided are delivery systems and tissues or organ which are targeted as sites for delivery. Also 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 to ensure enhanced specificity for target recognition and avoidance of toxicity and to edit or modify a target site in a genomic locus of interest to alter or improve the status of a disease or a condition.

Abstract: This invention concerns anti-inflammatory agents, compositions, and methods for treating inflammatory disorders.

Abstract: Pyranoyrazoles and pyrazolopyridines of formula I or formula II are disclosed: These compounds inhibit Coagulation Factor XIIa in the presence of thrombin and other coagulation factors. They are useful to treat autoimmune diseases.

Abstract: This invention concerns anti-inflammatory agents, compositions, and methods for treating inflammatory disorders.

Abstract: An imaging signal extraction apparatus comprising: an interface; a processing device, the processing device operatively coupled to the interface; and a computer readable medium comprising instructions that, when executed by the processing device, perform operations comprising: a) generating a two-dimensional image from imaging information obtained from the interface, thereby estimating ballistic component of the imaging information; b) generating a three-dimensional image by remapping the two-dimensional image; c) identifying a candidate object in the three-dimensional image; d) obtaining an estimated spatial forward model of the candidate object by mapping the three-dimensional image of the candidate object with a point-spread-function associated with the imaging apparatus; e) obtaining background-corrected data by using the estimated spatial forward model of the candidate object and estimated temporal components; and f) iteratively updating the estimated spatial forward model and estimated temporal componen

Abstract: The present invention provides methods and compositions for the remote control of cell function based on the use of radiofrequency waves to excite nanoparticles targeted to specific cell types. The nanoparticles may be applied to the target cell extracellularly and/or expressed intracellularly. The cell type of interest expresses a temperature sensitive channel wherein excitation of the nanoparticles results in a localized temperature increase that is transduced into a cellular response. Such cellular responses may include, for example, increases in gene expression resulting in production of one or more physiologically active proteins. The expression of such proteins can be used to treat a variety of different inherited or acquired diseases or disorders in a subject. Accordingly, the invention provides a generic approach for treatment of any disease associated with a protein deficiency.

Abstract: The present invention provides methods and compositions for the remote control of cell function based on the use of a magnetic field to excite paramagnetic nanoparticles targeted to specific cell types. The cell type of interest expresses an ion channel wherein excitation of the paramagnetic nanoparticles results in a physical change that is transduced into a cellular response. Such cellular responses may include, for example, increases in gene expression resulting in production of one or more physiologically active proteins. The expression of such proteins can be used to treat a variety of different inherited or acquired diseases or disorders in a subject.

Abstract: The present disclosure provides antibody-drug conjugates comprising (i) antibodies that specifically bind to Mer Tyrosin Kinase (MERTK) (e.g., human MERTK, or both human and mouse MERTK), and (ii) cytotoxic agents conjugated directly to the antibodies or conjugated to the antibodies via linkers, and compositions comprising such antibody-drug conjugates, wherein the antibodies contained in the antibody-drug conjugates agonize MERTK signaling of endothelial cells. The present disclosure also provides methods for treating cancer, by administering an antibody-drug conjugate that comprises (i) an antibody that specifically binds to MERTK and agonizes MERTK signaling of endothelial cells, and (ii) a cytotoxic agent conjugated directly to the antibody or conjugated to the antibody via a linker.

Abstract: Provided are compositions and methods based in part on the discovery that Enterococcus faecium heterologous secreted antigen A (SagA)-produced peptidoglycan fragments are protective against enteric bacterial infections. Modified bacteria that are engineered to express heterologous SagA are provided, and are included a nutraceutical, pharmaceutical, and probiotic formulations, and as components of food products, including dairy products. The modified bacteria include modified Lactobacillus bacteria that express heterologous SagA. The disclosure includes a method that involves introducing into an individual modified bacteria of that express and secrete heterologous SagA.

Abstract: The present invention discloses novel agents and methods for diagnosis and treatment of melanoma. Also disclosed are related arrays, kits, and screening methods.

Abstract: Tetrahydronaphthyridines of formula are disclosed. These compounds selectively inhibit ?V?3 without activating the ?V?3 receptor. They are useful for treating osteoporosis, acute myelogenous leukemia, sickle cell disease, focal segmental glomerulosclerosis, fibrosis, supravalvular aortic stenosis associated with Williams syndrome, tumors expressing ?V?3, tumor metastasis, bone resorption, T-cell lymphoma, retinal disease, age-related macular degeneration, diabetic retinitis, and herpes simplex virus infection. They may also be used for inhibiting tumor angiogenesis.

Abstract: The present invention relates to methods and agents for preventing the establishment of HIV-1 latent reservoirs or for reducing the size of the reservoirs. Specifically, the disclosure provides methods and agents for preventing the establishment of HIV-1 latent reservoirs or for reducing the size of the reservoirs, the methods comprising administering to the subject a therapeutically effective amount of an isolated anti-HIV antibody, and administering to the subject two or more viral transcription inducers in effective amounts to induce transcription of an HIV provirus in the cells. Further provided are antibodies and viral transcription inducers used in the methods.

Abstract: Provided are compositions and methods for selectively reducing the amount of antibiotic resistant and/or virulent bacteria in a mixed bacteria population, or for reducing any other type of unwanted bacteria in a mixed bacteria population. The compositions and methods involve targeting bacteria that are differentiated from other members of the population by at least one unique clustered regularly interspaced short palindromic repeats (CRISPR) targeted DNA sequence. The compositions and methods can be readily adapted to target any bacteria or any bacteria plasmid, or both.

Abstract: Provided are tri-specific fusion antibodies created to target multiple epitopes of the Human Immunodeficiency Virus (HIV). The fusion antibodies provide improved potency and breadth against HIV as compared to monospecific and bispecific antibodies, and additionally provide a high barrier against viral resistance. Also disclosed are pharmaceutical formulations and therapeutic methods utilizing such fusion proteins.

Abstract: Compounds of formula: are useful as antitumor agents. In these compounds, R10 is (a) (C1-C10) hydrocarbyl, (C1-C10)halohydrocarbyl, (C1-C6)hydroxyalkyl, or or R10 is (b) in which Q and A are linkers and Ar is optionally substituted monocyclic or bicyclic aryl or heteroaryl.

Abstract: The present invention relates to broadly neutralizing anti-HIV-1 antibodies and isolated antigens. Also disclosed are related methods and compositions.

Abstract: Embodiments of the present invention are directed to compositions and methods for anti-HIV (anti-CD4 binding site) potent VRC01-like (PVL) antibodies targeted to gp120 having an amino acid substitution at a residue in the anti-CD4 binding site PVL antibody that is equivalent to Phe43 in CD4, these antibodies having improved potency and breadth.

Abstract: The present invention relates to methods and compositions for use in modulating, including inhibiting the growth and/or reducing the virulence of, gram-positive bacteria. The present invention provides methods and compositions for disrupting the cell wall and/or cell membrane in gram-positive bacteria such that cell wall or cell membrane target(s) are rendered exposed or accessible and sensitive to a modulation thereof. Methods for modulation of one or more gram-positive bacterial cell wall or cell membrane targets in a gram-positive bacteria are provided comprising disrupting the cell wall such that the cell wall or cell membrane target, which is particularly a sortase, is rendered exposed or accessible and sensitive to a modifying, modulating or binding agent, which is particularly an antibody or fragment thereof, wherein the cell wall or cell membrane target is inaccessible or relatively insensitive to the modifying, modulating or binding agent in the absence of cell wall disruption.

Abstract: Acinetobacter lysin polypeptides and variants peptides with killing activity against gram negative bacteria. Methods for treating bacterial infections or bacterial colonization using Acinetobacter lysin polypeptides.