Abstract: Disclosed herein are anti-EGFR antibodies conjugated with maytansinoid drugs for targeted delivery to disease tissues. Methods related to the preparation and uses of such antibody drug conjugates to treat EGFR positive cells in cancers are provided.

Abstract: Disclosed herein are anti-ERB B2/NEU antibodies conjugated with maytansinoid drugs for targeted delivery to disease tissues. Methods relating to the preparation and uses of such drug conjugates to treat ERB B2/NEU positive cells in cancers are provided.

Abstract: Provided are efficient methods for direct coupling of a maytansinoid with a carboxylic acid to prepare a maytansinoid C-3 ester in high yield using a rare earth metal-based or trifluoromethanesulfonate-based Lewis acid catalyst and a base together with a coupling reagent. Also provided are compositions used in such methods.

Abstract: Disclosed herein are maytansinoid drug linker derivatives which can be linked to a antigen binding unit (Abu), and maytansinoid drugs linked with an antigen binding unit (Drug-Linker-Antigen binding Unit: D-L-Abu), for targeted delivery to disease tissues. D-L-Abu, D-L-Abu derivatives, and methods relating to the use of such drug conjugates to treat antigen positive cells in cancers and immunological disorders are provided.

Abstract: Disclosed herein are maytansinoid drug linker derivatives which can be linked to a antigen binding unit (Abu), and maytansinoid drugs linked with an antigen binding unit (Drug-Linker-Antigen binding Unit: D-L-Abu), for targeted delivery to disease tissues. D-L-Abu, D-L-Abu derivatives, and methods relating to the use of such drug conjugates to treat antigen positive cells in cancers and immunological disorders are provided.

Abstract: Provided are efficient methods for direct coupling of a maytansinoid with a carboxylic acid to prepare a maytansinoid C-3 ester in high yield using a rare earth metal-based or trifluoromethanesulfonate-based Lewis acid catalyst and a base together with a coupling reagent. Also provided are compositions used in such methods.

Abstract: Disclosed herein are anti-ERB B2/NEU antibodies conjugated with maytansinoid drugs for targeted delivery to disease tissues. Methods relating to the preparation and uses of such drug conjugates to treat ERB B2/NEU positive cells in cancers are provided.

Abstract: Disclosed herein are anti-CD20 antibody conjugated with maytansinoid drugs for targeted delivery to disease tissues. Methods related to the preparation and uses of such antibody drug conjugates to treat CD20 positive cells in cancers are provided.

Abstract: The present invention relates to the medical use of nitrites, such as inorganic nitrites, or any pharmaceutically acceptable salts, solvates, compositions, or prodrugs thereof, in the treatment of conditions that benefit from increased cerebral vascular flow. The pharmaceutical compositions used in these methods, which can be formulated for oral administration, can provide immediate release or extended release of the nitrite ion (NO2?).

Abstract: The cell-based assays described in the present invention can be used to directly assess the sensitivity and specificity of the gene annotation reagent against its target, mapping genes and to determine if a non-targeted gene participates in a pathway of interest or is functionally linked to another gene or protein. Preferred assay embodiments include fluorescence or luminescence assays in intact (live or fixed) cells. Such fluorescence or luminescence assays include high-throughput or high-content assays for protein activity, subcellular localization, post-translational modifications, or interactions of proteins. Suitable assays may include protein-protein interaction assays; protein translocation assays; and post-translational modification assays. The invention can be used to assess the efficacy of any gene silencing experiment, and to map novel genes into biochemical pathways, and to identify novel pharmaceutical targets.

Abstract: The present invention provides protein fragment complementation assays for drug discovery, in particular to identify compounds that activate or inhibit cellular pathways. Based on the selection of an interacting protein pair combined with an appropriate PCA reporter, the assays may be run in high-throughput or high-content mode and may be used in automated screening of libraries of compounds. The interacting pair may be selected by cDNA library screening; by gene-by-gene interaction mapping; or by prior knowledge of a pathway. Fluorescent and luminescent assays can be constructed using the methods provided herein. The selection of suitable PCA reporters for high-throughput or high-content (high-context) assay formats is described for a diversity of reporters, with particular detail provided for examples of monomeric enzymes and fluorescent proteins.

Abstract: We describe a strategy for designing and implementing protein-fragment complementation assays (PCAs) to detect biomolecular interactions in vivo and in vitro. The design, implementation and broad applications of this strategy are illustrated with a large number of enzymes with particular detail provided for the example of murine dihydrofolate reductase (DHFR). Fusion peptides consisting of N- and C-terminal fragments of murine DHFR fused to GCN4 leucine zipper sequences were coexpressed in Escherichia coli grown in minimal medium, where the endogenous DHFR activity was inhibited with trimethoprim. Coexpression of the complementary fusion products restored colony formation. Survival only occurred when both DHFR fragments were present and contained leucine-zipper forming sequences, demonstrating that reconstitution of enzyme activity requires assistance of leucine zipper formation. DHFR fragment-interface point mutants of increasing severity (Ile to Val, Ala and Gly) resulted in a sequential increase in E.

Abstract: The present invention is directed to Protein-fragment Complementation Assays (PCAs) and assay compositions based on fluorescent proteins. The invention provides methods for fragmenting fluorescent proteins and generating mutant fragments with desired spectral characteristics for PCA. The invention encompasses assays and compositions based on fluorescent proteins from the species Aequorea, Anemonia and Anthozoa. In particular, the invention is directed to fragments of mutant fluorescent proteins having improved spectral properties over the wild-type proteins. The invention encompasses fragments of mutant versions of A. Victoria green fluorescent protein (GFP), in particular yellow fluorescent proteins (EYFP and super-EYFP), ‘Venus’, cyan, ‘citrine’, blue, cyan-green, and photoactivatable variants of GFP The invention also encompasses red fluorescent PCAs based on Discosoma red fluorescent protein (RFP PCA) and a kindling fluorescent protein PCA (KFP1 PCA) derived from Anemonia sulcata.

Abstract: Systems and methods that could reduce the potential for side effects while delivering a reduced amount of light energy and non-light energy to a patient while providing a desired therapeutic effect that might otherwise only be achievable with a higher dose of either the light energy or non-light energy administered alone are disclosed. In certain embodiments, disclosed is a system and method for treating a patient, by administering a combination of light therapy from a light energy source in addition to one, two, or more other non-light energy modalities to a target region of a patient for a synergistic therapeutic effect.

Abstract: A system used for controlling a position of a patient's tongue includes an implant having at least one electrode configured to deliver selective stimulation to particular fascicles of the Hypoglossal nerve to stimulate at least one muscle of the tongue and a controller coupled to the implant.

Abstract: The present invention provides functional annotation of novel genes by detection of interactions of their encoded proteins with known proteins followed by assays to validate that the gene participates in a specific cellular function. The instant invention also provides an experimental strategy that allows for detection of protein interactions and functional assays with a single reporter system. Interactions among network component proteins are detected and probed with stimulators and inhibitors of the network and subcellular location of the interacting proteins is determined. Additionally, applicants' use this strategy to map a signal transduction network that controls the G0 to G1 transition in eukaryotes. Analysis of 148 combinations of 65 protein pairs in mammalian cells allows applicants' to propose a model of network architecture. The results demonstrate the feasibility of employing this strategy in genome-wide functional annotation efforts.

Abstract: The present invention generally provides processes for purification of Inter-alpha inhibitor proteins (I?Ip) and compositions thereof from blood.

Abstract: The present invention describes a method for detecting biomolecular interactions said method comprising: (a) selecting an appropriate reporter molecule selected from the group consisting of a protein, a fluorescent protein, a luminescent protein and a phosphorescent protein; (b) effecting fragmentation of said reporter molecule such that said fragmentation results in reversible loss of reporter function; (c) fusing or attaching fragments of said reporter molecule separately to other molecules; followed by (d) reassociation of said reporter fragments through interactions of the molecules that are fused to said fragments; and (e) detecting said biomolecular interactions by reconstitution of activity of the reporter molecule.

Abstract: The present invention describes an assay method comprising: (A) generating (1) at least a first fragment of a reporter molecule linked to a first interacting domain and at least a second fragment of a reporter molecule linked to a second interacting domain, or (2) nucleic acid molecules that code for (A)(1) and subsequently allowing said nucleic acid molecules to produce their coded products; then, (B) allowing interaction of said domains; and (C) detecting reconstituted reporter molecule activity, where said reporter molecule can react with a penicillin- or a cephalosporin-class substrate.

Abstract: An optical assembly includes an output optical element having a thermally conductive and optically transmissive material and a thermal conduit in thermal communication with the output optical element and having at least one surface configured to be in thermal communication with at least one heat dissipating surface of a light delivery apparatus. The optical assembly further includes a coupling portion configured to be placed in at least two states. In a first state, the coupling portion is attached to the apparatus such that the at least one surface of the thermal conduit is in thermal communication with the at least one heat dissipating surface. In a second state, the coupling portion is detached from the apparatus after having been attached to the apparatus in the first state and in which the coupling portion is configured to prevent re-attachment of the coupling portion to the apparatus.