Abstract: The invention features methods for rapidly and sensitively identifying molecular targets in medical, industrial, and environmental samples. The invention labels target molecules and then images them using large area imaging. Diagnostic tests based on the invention can be rapid, ultrasensitive, quantitative, multiplexed, and automated. A broad range of infectious agents (e.g., bacteria, viruses, fungi, and parasites) and molecules (e.g., proteins, DNA, RNA, hormones, and drugs) can be detected by the methods. The invention enables rapid, ultra-sensitive, cost-effective, and portable assays. The ability of the invention to detect low levels of target molecules rapidly and cost-effectively results from the combination of high intensity labeling, formats that facilitate rapid reaction kinetics, and large area imaging based using either instrumentation made from off-the-shelf commercial components or no instrumentation at all.

Abstract: Methods of inserting genes into defined locations in the chromosomal DNA of cultured mammalian cell lines which are subject to gene amplification are disclosed. In particular, sequences of interest (e.g., genes encoding biotherapeutic proteins) are inserted proximal to selectable genes in amplifiable loci, and the transformed cells are subjected to selection to induce co-amplification of the selectable gene and the sequence of interest. The invention also relates to meganucleases, vectors and engineered cell lines necessary for performing the methods, to cell lines resulting from the application of the methods, and use of the cell lines to produce protein products of interest.

Abstract: Disclosed herein is a genetically-modified cell comprising in its genome a modified human T cell receptor alpha constant region gene, wherein the cell has reduced cell-surface expression of the endogenous T cell receptor. The present disclosure further relates to methods for producing such a genetically-modified cell, and to methods of using such a cell for treating a disease in a subject.

Abstract: Disclosed herein, in certain instances, are methods for the diagnosis, prognosis and determination of cancer progression of a cancer in a subject. Further disclosed herein, in certain instances, are methods for determining the treatment modality of a cancer in a subject. The methods comprise expression-based analysis of targets. Further disclosed herein, in certain instances, are probe sets for use in assessing a cancer status in a subject.

Abstract: Disclosed are synthetic nanocarrier methods, and related compositions, comprising B cell and/or MHC Class II-restricted epitopes and immunosuppressants in order to generate tolerogenic immune responses, such as the generation of antigen-specific regulatory B cells.

Abstract: Provided herein are compounds and related composition and methods that may be used to raise an antibody response to nicotinic compounds, in some embodiments.

Abstract: Provided are methods of use of compounds comprising a self-immolative group, which compounds may include a protein (for example, an oligopeptide, a polypeptide, an antibody, or the like) having substrate-specificity for a target and an active agent (for example, a drug, a toxin, a ligand, a detection probe, or the like) having a specific function or activity.

Abstract: The present invention belongs to the fields of pharmacology, medicine and medicinal chemistry. The present invention provides novel pharmaceutical compositions composed of solid nanoparticles dispersed in aqueous medium of substantially water insoluble pharmaceutical substances such as docetaxel with reduced Ostwald ripening.

Abstract: Disclosed herein is a genetically-modified cell comprising in its genome a modified human T cell receptor alpha constant region gene, wherein the cell has reduced cell-surface expression of the endogenous T cell receptor. The present disclosure further relates to methods for producing such a genetically-modified cell, and to methods of using such a cell for treating a disease in a subject.

Abstract: A microfluidic device includes a three-dimensional slat structure having a plurality of interstices configured to generate a high power, high flow rate of fluids by electroosmotic flow. The microfluidic device includes a housing for holding and moving fluids through the slat structure, and a plurality of electrodes that generate an electric field within the plurality of interstices.

Abstract: Heterocyclic modulators of lipid synthesis are provided as well as pharmaceutically acceptable salts thereof; pharmaceutical compositions comprising such compounds; and methods of treating conditions characterized by dysregulation of a fatty acid synthase pathway by the administration of such compounds.

Abstract: The disclosure relates to isolated microorganisms—including novel strains of the microorganisms—microbial consortia, and compositions comprising the same. Furthermore, the disclosure teaches methods of utilizing the described microorganisms, microbial consortia, and compositions comprising the same, in methods for modulating the production and yield of milk and milk components in ruminants. In particular aspects, the disclosure provides methods of increasing desirable components of milk in ruminants. Furthermore, the disclosure provides for methods of modulating the rumen microbiome.

Abstract: A subject is inoculated from a disease by exposing a biopsy of a tumor or other abnormal growth to a nanosecond pulsed electric field (nsPEF). A sufficient treatment can be confirmed by detecting calreticulin on the tumor cell membranes, which indicates apoptosis occurring in the tumor cells. Treated tumor cells from the biopsy are then reintroduced into the subject. The calreticulin-exhibiting tumor cells activate the subject's immune system against the tumor, and any other like tumors in the body, and effectively vaccinates the subject against the disease. The treatment can be combined with CD47-blocking antibodies, doxorubicin, CTLA-4-blocking antibodies, and/or PD-1-blocking antibodies. The immune response may be measured at a later time. Specific electrical characteristics of the nsPEF treatments can be based on the type and/or strength of the tumor.

Abstract: The present disclosure provides a method of covalently modifying a biological macromolecule, the method comprising subjecting a reaction mixture comprising: (a) a biological macromolecule comprising one or more thiol groups; and (b) a molecule comprising one or more olefin or alkyne moieties to a radical reaction under conditions sufficient to produce the covalently modified biological macromolecule. The present disclosure also provides a method of covalently modifying a biological macromolecule, the method comprising subjecting a reaction mixture comprising: (a) a molecule comprising one or more thiol groups; and (b) a biological macromolecule comprising one or more olefin or alkyne moieties to a radical reaction under conditions sufficient to produce the covalently modified biological macromolecule. The present disclosure further provides a covalently modified biological macromolecule prepared by any of the disclosed methods.

Abstract: Compounds having a structure of formula (I), including stereoisomers and pharmaceutically acceptable salts and solvates thereof: wherein R1 is as defined herein. Such compounds are inhibitors of the vesicular monoamine transporter 2 (VMAT2) and have utility for treating, for example, hyperkinetic disorders. Also disclosed are compositions containing these compounds in combination with a pharmaceutically acceptable carrier or diluent, as well as methods relating to the use in a subject in need thereof.

Abstract: The invention provides bispecific fusion proteins that inhibit activation of complement pathway and vascular endothelial growth factor (VEGF) pathway and methods for using these fusion proteins.

Abstract: Disclosed are synthetic nanocarrier methods, and related compositions, comprising administering immunosuppressants and MHC Class I-restricted and/or MHC Class II-restricted epitopes that can generate tolerogenic immune responses (e.g., antigen-specific T effector cell deletion).

Abstract: This disclosure relates to an in vivo treatment of a skin lesion of a mammal comprising application of electrical energy to the skin lesion in a form of electrical pulses. At least one electrical pulse is applied. The pulse duration may be at least 1 nanosecond at the full-width-half-maximum. This treatment may prevent at least growth of the lesion.

Abstract: Disclosed herein are new compounds and compositions and their application as pharmaceuticals for the treatment of diseases. Methods of inhibition of KDM1A, methods of increasing gamma globin gene expression, and methods to induce differentiation of cancer cells in a human or animal subject are also provided for the treatment of diseases such as acute myelogenous leukemia.

Abstract: Polypeptides, such as a multi-valent polypeptide designated svD2, useful in pharmaceutical compositions for stimulation of the adaptive arm of the immune system. svD2 demonstrated in vivo activity in a syngeneic mouse model. svD2 is biologically active at nanomolar concentrations. These properties are believed to result as a consequence of the ability of svD2 to cross-link cell-surface receptors.