Abstract: Methods and composition related to the engineering of a novel protein with methionine-?-lyase enzyme activity are described. For example, in certain aspects there may be disclosed a modified cystathionine-?-lyase (CGL) comprising one or more amino acid substitutions and capable of degrading methionine. Furthermore, certain aspects of the invention provide compositions and methods for the treatment of cancer with methionine depletion using the disclosed proteins or nucleic acids.

Abstract: Methods and compositions relating to the engineering of an improved protein with methionine-?-lyase enzyme activity are described. For example, in certain aspects there may be disclosed a modified cystathionine-?-lyase (CGL) comprising one or more amino acid substitutions and capable of degrading methionine. Furthermore, certain aspects of the invention provide compositions and methods for the treatment of cancer with methionine depletion using the disclosed proteins or nucleic acids.

Abstract: Methods for determining the VH:VL antibody repertoire from cells, such as antigen-specific B cells, in a high throughput manner. In some aspects, methods are provided for the capture of mRNA transcripts from single B cells that secreted antigen-specific antibodies followed by sequencing of the corresponding cDNAs encoding antibody VH and VL sequences. Libraries of antibodies produced by such methods are also provided.

Abstract: Methods and compositions related to the use of a protein with kynureninase activity are described. For example, in certain aspects there may be disclosed a modified kynureninase capable of degrading kynurenine. Furthermore, certain aspects of the invention provide compositions and methods for the treatment of cancer with kynurenine depletion using the disclosed proteins or nucleic acids.

Abstract: Methods and compositions involving polypeptides having an aglycosylated antibody Fc domain are provided. In certain embodiments, polypeptides have an aglycosylated Fc domain that contains one or more substitutions compared to a native Fc domain. Additionally, some embodiments involve an Fc domain that is binds some Fc receptors but not others. For example, polypeptides are provided with an aglycosylated Fc domain that selectively binds C1q, and optionally activating Fc receptors, but that is significantly reduced for binding to the inhibitory Fc?RIIb receptor. Furthermore, methods and compositions are provided for promoting complement dependent cytotoxicity (CDC) using a polypeptide having a modified aglycosylated Fc domain and a second non-Fc binding domain, which can be an antigen binding region of an antibody or a non-antigen binding region. Some embodiments concern antibodies with such polypeptides, which may have the same or a different non-Fc binding domain.

Abstract: A cryogenically cooled boring tool design reduces the effect of cryogen coolant on a workpiece caused by coolant leakage and coolant exhaust. A tool body has a cartridge for holding a cutting tool insert and a coolant supply path through the tool body and the cartridge for supplying cryogenic coolant to the tool insert. A feed transfer tube connects the coolant supply path in the tool body to the coolant supply path in the cartridge. Insulating tubes line portions of the coolant supply paths in the tool body and the cartridge. The shrinkage rates of the feed transfer tube and the insulating tubes cause the press fit of the insulating tubes to tighten the seal between the insulating tubes and the feed transfer tube when cryogenic coolant flows through the supply path. The exhaust ports on the tool for boiled-off cryogen remains outside of a workpiece bore.

Abstract: Methods and compositions related to the engineering of a protein with L-cyst(e)ine degrading enzyme activity are described. For example, in certain aspects there may be disclosed a modified cystathionine-?-lyase comprising one or more amino acid substitutions and capable of degrading L-cyst(e)ine. Furthermore, certain aspects of the invention provide compositions and methods for the treatment of cancer with L-cyst(e)ine using the disclosed proteins or nucleic acids.

Abstract: Provided are methods for the identification of mutant kinases that are resistant to inhibition by a kinase inhibitor. In some embodiments, the methods may be used to assess a test compound or kinase inhibitor for the risk of the development of resistance in vivo, e.g., during clinical administration to treat a disease such as a cancer.

Abstract: Methods and compositions relating to the engineering of an improved protein with methionine-?-lyase enzyme activity are described. For example, in certain aspects there may be disclosed a modified cystathionine-?-lyase (CGL) comprising one or more amino acid substitutions and capable of degrading methionine. Furthermore, certain aspects of the invention provide compositions and methods for the treatment of cancer with methionine depletion using the disclosed proteins or nucleic acids.

Abstract: In some aspects, mutant or variant Fc domains are provided that exhibit increased binding to FcRn and increased half-life after administration in vivo. The Fc domain may be comprised in a glycosylated or aglycosylated antibody. Methods for using the mutant or variant Fc domains or polypeptides comprising the mutant or variant Fc domains are also provided.

Abstract: Methods and compositions for identification of candidate antigen-specific variable regions as well as generation of antibodies or antigen-binding fragments that could have desired antigen specificity are provided. For example, in certain aspects, methods for determining amino acid sequences of serum antibody CDR3 and abundancy levels are described. In some aspects, methods for determining nucleic acid sequences of antibody variable region sequences and the frequency thereof in biological samples are provided. Furthermore, the invention provides methods for identification and generation of antibodies or antigen-binding fragments that comprise highly-represented CDR domains.

Abstract: Compositions and methods for the treatment of cancer are described, and, more preferably, to the treatment of cancers that do not express, or are otherwise deficient in, argininosuccinate synthetase, with enzymes that deplete L-Arginine in serum. In one embodiment, the present invention contemplates an arginase protein, such as a human Arginase I protein, comprising at least one amino acid substitution and a metal cofactor, said protein comprising an increased catalytic activity when compared with a native human Arginase I.

Abstract: Methods and compositions related to the use of a protein with kynureninase activity are described. For example, in certain aspects there may be disclosed a modified kynureninase capable of degrading kynurenine. Furthermore, certain aspects of the invention provide compositions and methods for the treatment of cancer with kynurenine depletion using the disclosed proteins or nucleic acids.

Abstract: A rotating cutting tool that is internally cooled by cryogenic coolant, the rotating cutting tool has a cylindrical body including: a central bore that extends along a longitudinal axis of the cylindrical body; a plurality of cold flow delivery paths formed from radial bores that fluidly communicate with and extend radially-outwardly from the central bore; longitudinal grooves that are formed along an outer surface of the cylindrical body extending along the longitudinal axis and fluidly communicating with the radial bores; a bushing having an inner diameter closely conforming to the outer surface of the cylindrical body allowing the bushing to concentrically fit over the cylindrical body and the longitudinal grooves to form longitudinal passageways extending from the radial bores to one or more exhaust ports formed in the bushing proximate a rear face of the cylindrical body; and a plurality of flutes for cutting a workpiece each having a cutting edge formed from the bushing.

Abstract: A cryogenically cooled boring tool design reduces the effect of cryogen coolant on a workpiece caused by coolant leakage and coolant exhaust. A tool body has a cartridge for holding a cutting tool insert and a coolant supply path through the tool body and the cartridge for supplying cryogenic coolant to the tool insert. A feed transfer tube connects the coolant supply path in the tool body to the coolant supply path in the cartridge. Insulating tubes line portions of the coolant supply paths in the tool body and the cartridge. The shrinkage rates of the feed transfer tube and the insulating tubes cause the press fit of the insulating tubes to tighten the seal between the insulating tubes and the feed transfer tube when cryogenic coolant flows through the supply path. The exhaust ports on the tool for boiled-off cryogen remains outside of a workpiece bore.

Abstract: Methods and compositions relating to the engineering of an improved protein with homocyst(e)inase enzyme activity are described. For example, there are disclosed modified cystathionine-?-lyase (CGL) enzymes comprising one or more amino acid substitutions and capable of degrading homocyst(e)ine. Furthermore, provided are compositions and methods for the treatment of homocystinuria or hyperhomocysteinemia with homocyst(e)ine depletion using the disclosed enzymes or nucleic acids.

Abstract: Methods and compositions related to the engineering of a protein with L-cyst(e)ine degrading enzyme activity are described. For example, disclosed are modified cystathionine-?-lyases comprising one or more amino acid substitutions and capable of degrading L-cyst(e)ine. Furthermore, compositions and methods are provided for the treatment of cancer and cystinuria using the disclosed modified enzymes or nucleic acids encoding said enzymes.

Abstract: Compositions and methods for the treatment of cancer are described, and, more preferably, to the treatment of cancers that do not express, or are otherwise deficient in, argininosuccinate synthetase, with enzymes that deplete L-Arginine in serum. In one embodiment, the present invention contemplates an arginase protein, such as a human Arginase I protein, comprising at least one amino acid substitution and a metal cofactor, said protein comprising an increased catalytic activity when compared with a native human Arginase I.

Abstract: A rotating cutting tool that is internally cooled by cryogenic fluid has a generally cylindrical outer shape. At least one flute is formed on the cutting tool and a cutting edge is formed on an outer edge of the flute for cutting a workpiece. An internal cold flow delivery path for cryogenic coolant is in proximity to the cutting edge. A coolant cavity is formed in the cutting tool for supplying cryogenic coolant to the internal cold flow delivery path and a return path for cryogenic coolant is downstream from the cold flow delivery path. An exhaust port is coupled to the return path for exhausting cryogenic coolant to atmosphere. The exhaust port is remote from the cutting edge so that the cryogenic coolant is exhausted away from the cutting edge and away from a workpiece so that the cryogenic coolant does not cool and toughen the workpiece.

Abstract: Methods and composition related to the engineering of a novel protein with methionine-?-lyase enzyme activity are described. For example, in certain aspects there may be disclosed a modified cystathionine-?-lyase (CGL) comprising one or more amino acid substitutions and capable of degrading methionine. Furthermore, certain aspects of the invention provide compositions and methods for the treatment of cancer with methionine depletion using the disclosed proteins or nucleic acids.