Abstract: The invention provides deimmunized mutant proteins having reduced immunogenicity while exhibiting substantially the same or greater biological activity as the proteins of interst from which they are derived, as exemplified by mutant L-asparaginase that comprises amino acid substitutions compared to wild type L-asparaginase. The invention further provides methods for screening mutant deimmunized proteins that have substantially the same or greater biological activity as a protein of interest, and methods for reducing immunogenicity, without substantially reducing biological activity, of a protein of interest. The invention's compositions and methods are useful in, for example, therapeutic applications by minimizing adverse immune responses by the host mammalian subjects to the protein of interest.

Abstract: Methods and compositions for the screening and isolation of ligand-binding polypeptides, such as antibodies. In some aspects, methods of the invention enable the isolation of intact soluble antibodies comprising a constant domain. Screening methods that employ genetic packages such as bacteria and bacteriophages enable high through-put identification of ligand binding molecules.

Abstract: A method, system, and medium are provided for managing bandwidth associated with a communication session characterized by a plurality of data packets being transmitted from a sender to a receiver. The receiver can include functions that monitor communication sessions and determine bandwidth adjustments corresponding thereto for optimizing the user's experience. The receiver can communicate feedback messages to senders that include requests for bandwidth adjustments. According to embodiments, senders can include well-known feedback listening ports through which feedback messages are received, enabling out-of-band user experience optimization.

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 CDR and abundancy level are described. In some aspects, methods for determining nucleic acid sequences of antibody variable region sequences and frequency are provided. Furthermore, the invention provides methods for identification and generation of antibody or antigen-binding fragments that comprise highly-represented CDR.

Abstract: Methods and compositions for the screening and isolation of ligand-binding polypeptides, such as antibodies. In some aspects, methods of the invention enable the isolation of intact soluble antibodies comprising a constant domain. Screening methods that employ genetic packages such as bacteria and bacteriophages enable high through-put identification of ligand binding molecules.

Abstract: Mobile switching centers (MSCs) in serving systems are interconnected by gateways for tandem free operation. The serving systems route calls involving two mobile stations that use the same compressed digital format through the gateways. The gateways carry the media exchanged during the call in the compressed digital format in order to avoid tandem transcoding. When a serving system hands off a mobile station involved in a tandem free call, the call pathway is extended through the gateways so that the call remains tandem free.

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: The invention overcomes the deficiencies of the prior art by providing antibody compositions having improved affinities for Bacillus anthracis antigens. The compositions have important thereapeutic and diagnostic applications, including treatment or detection of infection by Bacillus anthracis.

Abstract: Methods and composition for the preparation of gene libraries of antibodies or parts of antibodies which contain the variable domains. For example, in certain aspects methods for providing polynucleotide library involving annealing and extending are described. Furthermore, the invention provides polynucleotide or antibody fragment libraries prepared by the methods.

Abstract: The invention provides methods for using the Twin Arginine Translocation pathway in bacteria to produce heterologous polypeptides that have multiple disulfide bonds. Methods of screening polypeptide libraries produced by secretion through the TAT pathway are also provided. The invention provides improved methods for production of heterologous polypeptides having at least one disulfide bond.

Abstract: The invention overcomes the deficiencies of the prior art by providing a rapid approach for isolating binding proteins capable of binding small molecules and peptides via “display-less” library screening. In the technique, libraries of candidate binding proteins, such as antibody sequences, are expressed in soluble form in the periplasmic space of gram negative bacteria, such as Escherichia coli, and are mixed with a labeled ligand. In clones expressing recombinant polypeptides with affinity for the ligand, the concentration of the labeled ligand bound to the binding protein is increased and allows the cells to be isolated from the rest of the library. Where fluorescent labeling of the target ligand is used, cells may be isolated by fluorescence activated cell sorting (FACS). The approach is more rapid than prior art methods and avoids problems associated with the surface-expression of ligand fusion proteins employed with phage display.

Abstract: Methods and compositions involving polypeptides having an aglycosylated antibody Fc domain. 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 Fe domain that selectively binds Fc?RI at a level within 2-fold of a glycosylated Fc domain, but that is significantly reduced for binding to other Fc receptors. Furthermore, methods and compositions are provided for promoting antibody-dependent cell-mediated toxicity (ADCC) 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 different non-Fc binding domain.

Abstract: The present invention provides artificial enzymes comprising, e.g., an N-terminal domain derived from E. coli FkpA that allows for dimerization and provides a substrate binding region, and a C-terminal thioredoxin domain derived from E. coli DsbA. Similar to DsbC, such de novo designed chimeric (hybrid) FkpA-DsbA enzymes function, as disulfide reductases, oxidases, or isomerases, and chaperones in vivo and in vitro, despite lacking similarity to DsbC-related polypeptide sequence.

Abstract: The invention provides composition and methods for producing proteins of interest which comprise at least one disulfide bond, include proteins which in their mature form do not contain disulfide bonds, but whose precursor molecule contained at least one disulfide bond. The methods employ a host cell modified to more efficiently produce properly folded disulfide bond containing proteins. The host cells generally contain a mutation in one or more reductase genes, and can be further genetically modified to increase their growth rate, and are further optionally modified to increase the expression of a catalyst of disulfide bond formation. Host cells, methods for u sing such to produce proteins of interest, proteins of interest produced by these methods are within the scope of the invention.

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: The invention overcomes the deficiencies of the prior art by providing a rapid approach for isolating polypeptides capable of anchoring heterologous polypeptides to a bacterial inner membrane. In the technique, libraries of candidate anchor polypeptides are expressed as fusions with a heterologous polypeptide that is capable of being detected when bound to the inner membrane. In bacteria expressing a functional anchor sequence, the heterologous polypeptide becomes bound to outer face of the inner membrane. Bacteria with the functional anchor sequence can be identified by removing the outer membrane to remove non-anchored heterologous polypeptide followed by detection of anchored heterologous polypeptide. Such bacteria may be detected in numerous ways, including use of direct fluorescence or secondary antibodies that are fluorescently labeled, allowing use of efficient techniques such as fluorescence activated cell sorting (FACS).

Abstract: The present invention discloses the engineering of a human enzyme with arginine hydrolytic activity suitable for human therapy. An enzyme comprising of a human sequence is not likely to induce adverse immunological responses and thus is expected to constitute a superior therapeutic. Since the human genome does not encode arginases with the proper high affinity catalytic properties (i.e., for example, a low Km and high catalytic activity, kcat) an appropriate arginase can be engineered by modifying an enzyme with related catalytic activity. For example, the human enzyme PAD4 can hydrolyze arginine in peptide substrates but does not have activity for free arginine. First, a high throughput assay was developed for detecting arginine activity by monitoring the formation of the hydrolytic product citrulline. Then, using a combination of rational design and iterative mutation and screening PAD4 mutants were identified and isolated exhibiting high affinity free arginine metabolic activity.

Abstract: The present invention relates to compositions and methods for analyzing and modulating (e.g., enhancing or inhibiting) protein-protein interactions. In particular, compositions and methods of the present invention find use in identifying, reconstituting and characterizing protein-protein interactions, identifying binding subunits, and drug screening. The methods and compositions of the invention may also be used to identify agents that may agonize or antagonize a protein-protein interaction (e.g., using test compounds).

Abstract: A comprehensive signalling node is provided according to an embodiment of the invention. The comprehensive signalling node includes a signalling interface adapted for transmitting and receiving signalling communications and a storage system configured to store a Media Gateway Controller (MGC) routine, to store a Session Initiation Protocol (SIP) routine, to store a Session Border Controller (SBC) routine, to store a Push-To-Talk (PTT) routine, to store a H.323 routine, to store a Wide Area Network (WAN) compression routine, and to store a Communication Assistance for Law Enforcement (CALE) routine. The comprehensive signalling node further includes a processing system that is configured to receive a signalling communication through the signalling interface, process the signalling communication with the MGC routine if appropriate, with the SIP routine if appropriate, with the SBC routine if appropriate, with the PTT routine if appropriate, with the H.

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.