Compositions and methods are provided for the inhibition of the function of RNA guided endonucleases, including the identification and use of such inhibitors. Methods of identifying inhibitor compounds of RNA guided nucleases, assays for detecting nuclease activity and compounds for use therein are also provided.

Bacterial systems for screening for small molecule agents are disclosed herein. Kits for carrying out the screening are also disclosed.

Methods of treating, preventing and/or managing cancer as well as and diseases and disorder associated with, or characterized by, undesired angiogenesis are disclosed. Specific methods encompass the administration of an immunomodulatory compound alone or in combination with a second active ingredient. The invention further relates to methods of reducing or avoiding adverse side effects associated with chemotherapy, radiation therapy, hormonal therapy, biological therapy or immunotherapy which comprise the administration of an immunomodulatory compound. Pharmaceutical compositions, single unit dosage forms, and kits suitable for use in methods of the invention are also disclosed.

The present invention provides workflows for the discovery of nonallosteric sirtuin activation compounds. Workflows enable drug discovery of novel sirtuin activating compounds with prescribed effects on the binding in pockets near the active site interacting with flexible protein degrees of freedom around the active site. Novel kinetic models are used to confirm hit compounds and to improve their properties.

The present invention relates to methods of immune modulation. In particular, the present invention relates to regulation of inflammation and immune responses by modulation of ABCF1. Modulation of ABCF1 may be useful in the treatment of sepsis, autoimmune diseases, cancer or infections.

The invention generally relates to methods for quantifying an amount of enzyme molecules. Systems and methods of the invention are provided for measuring an amount of target by forming a plurality of fluid partitions, a subset of which include the target, performing an enzyme-catalyzed reaction in the subset, and detecting the number of partitions in the subset. The amount of target can be determined based on the detected number.

The present invention relates to agents for use in the prophylactic or therapeutic treatment of myopia in a subject, wherein said agents are capable of decreasing epidermal growth factor receptor (EGFR) signaling and/or signaling of another receptor susceptible for amphiregulin in a subject in a direct or indirect manner. The present invention further relates to agents for use in the prophylactic or therapeutic treatment of hyperopia in a subject, wherein said agents are capable of increasing epidermal growth factor receptor (EGFR) signaling and/or signaling of another receptor susceptible for amphiregulin in a subject. Furthermore, the present invention relates to methods for the diagnosis of myopia or hyperopia in a subject, comprising the steps of (a) providing a biological sample from the subject; (b) determining the amphiregulin level in said sample; (c) comparing the level determined in step (b) to the amphiregulin levels found in emmetropic subjects or subjects going to be emmetropic; and (d) determining that the subject has myopia or is predisposed for the development of myopia in case the level determined in step (b) is higher than the amphiregulin levels found in emmetropic subjects or subjects going to be emmetropic; and determining that the subject has hyperopia or is predisposed for the development of hyperopia in case the level determined in step (b) is lower than the amphiregulin levels found in emmetropic subjects or subjects going to be emmetropic. Finally, the present invention relates to a method for identifying agents which associate with amphiregulin or fragments or variants thereof.

The present invention provides: an assay method that uses a compound represented by formula (I) as a fluorescent probe molecule and that is for detecting the lipid peroxidation suppression activity of a test compound; an assay kit that uses the assay method; a screening method that uses the assay method; and a pharmaceutical composition that is for the treatment, etc. of diseases (such as age-related macular degeneration) that are induced by lipid peroxidation reactions.

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A high-throughput screening methods for identifying candidate anticancer medicinal agents is described herein. The candidate anticancer medicinal agents are arylfluorosulfate compounds derived from phenolic compounds. The method involves in situ generation of the arylfluorosulfate compounds in multi-well plates by reaction of phenolic compounds in DMSO with a saturated solution of SO.sub.2F.sub.2 dissolved in a solvent such as acetonitrile, in the presence of an organic base, followed by reaction of generated fluoride ion with trimethylsilanol to form volatile trimethylsilyl fluoride. Solvents, organic base, and silyl compounds are then removed, in vacuo, to afford the arylfluorosulfate compounds suitable for biological screening in cancer cell lines without further purification.

This disclosure pertains to methods and compositions for tolerizing a mammal's brain to exogenously administered acid sphingomyelinase polypeptide by first delivering an effective amount of a transgene encoding the polypeptide to the mammal's hepatic tissue and then administering an effective amount of the transgene to the mammal's central nervous system (CNS).