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 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 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: Technologies are provided for correlating alert messages using placeholder correlation records. When a network alert message is received, a network component associated with the alert can be identified and a correlation record can be created that is associated with the identified network component. A model of the computer network can be used identify another network component that is related to the identified network component. If a correlation record for the related component does not exist, then a placeholder correlation record for the related component can be created. If another alert message is received that is associated with another component that is also related to the same component, then the placeholder correlation record can be used to correlate the alert messages. An event message can be generated that indicates an occurrence of a network event involving the related component associated with the placeholder correlation record.

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: Technologies are provided for correlating alert messages using correlation domains. Alert messages can be received that are related to computer network components. The alert messages can be partitioned using separate correlation domains and analyzed by separate alert processors. When an alert message is received, it can be analyzed to determine a correlation domain with which the alert message is associated. The alert message can then be correlated with other alert messages associated with the correlation domain, and alert messages that are not associated with the correlation domain can be ignored. Groups of alert messages associated with different correlation domains can be correlated independently by different alert processors. Events generated by an alert processor can include correlation domain information. Events associated with different correlation domains can be handled differently.

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: 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: 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: Methods are provided for identifying tumor-specific antibodies and/or T-cell receptors by paired mRNA sequencing from individual immune cells in sentinel lymph nodes and comparison of these sequences with corresponding mass spectroscopy data from a subject having a cancer. Novel tumor-specific antibodies (e.g., NY-ESO-1-binding antibodies) are also provided.

Abstract: Methods and composition for the screening and isolation of aglycosylated antibody Fc domain polypeptides. For example, in certain aspects methods for identifying aglycosylated Fc domains that bind to Fc receptors or preferentially bind to particular Fc receptors are described. Furthermore, the invention provides aglycosylated Fc domains that bind to Fc receptors with high affinity. Enhanced methods and media for prokaryotic based interaction screening are also provided.

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 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: The present disclosure generally relates to sequencing two or more genes expressed in a single cell in a high-throughput manner using reverse transcriptases. More particularly, the present disclosure relates to a method for high-throughput sequencing of pairs of transcripts co-expressed in single cells (e.g., antibody VH and VL coding sequence) to determine pairs of polypeptide chains that comprise immune receptors.

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: 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 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 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: In some aspects, mutant or variant Fc domains are provided that can exhibit increased affinity or selectivity for Fc?RIIB. The variant Fc domain may be a mutant IgG1 Fc domain. In some embodiments, a mutant or variant Fc domain may be present in a therapeutic antibody such as, e.g., an agonistic antibody. Additional methods for using and identifying mutant Fc domains are also provided.