Abstract: Methods of generating fusion protein variants are provided that comprise introducing sequence diversity at the junction region or regions in the fusion and allows for the generation of variants having a desired activity. Examples include immunoglobulins comprising a domain or polypeptide inserted into, or replacing, a CDR. Also provided are polynucleotides encoding a fusion protein and comprising two or more RSSs, and compositions and host cells comprising same, as well as fusion proteins variants produced by the described methods.

Abstract: In a computing device, when a user requests to carry out an operation, the device determines the type of operation requested and the time period since the user was last authenticated. The operation is enabled only if the determined time period does not exceed a threshold for the requested operation.

Abstract: A receptor is provided having a heterologous binding site that activates, when bound, a signaling domain related to the TNF receptor superfamily. Methods/uses of the foregoing in whole cell biosensors are also provided. There is also provided a library comprising a plurality of unique biosensor cells for binding unknown binding substrates. Each unique biosensor is a host cell having a receptor which signals production of a positive selectable marker and/or a negative selectable marker in response to the receptor being bound. Also provided is a method of identifying biosensor cells from a library that is specifically activated by a target, involving (a) contacting the library with the target substrate under positive selection conditions; (b) contacting the library with a control substrate under negative selection conditions; and (c) identifying biosensor cells which survive (a) and (b) as biosensor cells which are specifically activated by the target.

Abstract: There is provided a single variable domain T-cell receptor (svd-TCR) comprising a first TCR variable domain, the first TCR variable domain specifically binding to an epitope, that is not a superantigen, in the absence of a second TCR variable domain. Also provided are compositions and cells comprising the svd-TCR as well as methods of identifying the svd-TCR.

Abstract: Methods of generating fusion protein variants are provided that comprise introducing sequence diversity at the junction region or regions in the fusion and allows for the generation of variants having a desired activity. Examples include immunoglobulins comprising a domain or polypeptide inserted into, or replacing, a CDR. Also provided are polynucleotides encoding a fusion protein and comprising two or more RSSs, and compositions and host cells comprising same, as well as fusion proteins variants produced by the described methods.

Abstract: Methods of generating fusion protein variants are provided that comprise introducing sequence diversity at the junction region or regions in the fusion and allows for the generation of variants having a desired activity. Examples include immunoglobulins comprising a domain or polypeptide inserted into, or replacing, a CDR. Also provided are polynucleotides encoding a fusion protein and comprising two or more RSSs, and compositions and host cells comprising same, as well as fusion proteins variants produced by the described methods.

Abstract: In a computing device, when a user requests to carry out an operation, the device determines the type of operation requested and the time period since the user was last authenticated. The operation is enabled only if the determined time period does not exceed a threshold for the requested operation.

Abstract: In a computing device, when a user requests to carry out an operation, the device determines the type of operation requested and the time period since the user was last authenticated. The operation is enabled only if the determined time period does not exceed a threshold for the requested operation.

Abstract: Methods of generating fusion protein variants are provided that comprise introducing sequence diversity at the junction region or regions in the fusion and allows for the generation of variants having a desired activity. Examples include immunoglobulins comprising a domain or polypeptide inserted into, or replacing, a CDR. Also provided are polynucleotides encoding a fusion protein and comprising two or more RSSs, and compositions and host cells comprising same, as well as fusion proteins variants produced by the described methods.

Abstract: Methods of generating fusion protein variants are provided that comprise introducing sequence diversity at the junction region or regions in the fusion and allows for the generation of variants having a desired activity. Examples include immunoglobulins comprising a domain or polypeptide inserted into, or replacing, a CDR. Also provided are polynucleotides encoding a fusion protein and comprising two or more RSSs, and compositions and host cells comprising same, as well as fusion proteins variants produced by the described methods.

Abstract: Methods of generating sequence diversity in a protein, such as a ligand-binding protein, are provided. The methods comprise targeted introduction of two or more recombination signal sequences (RSSs) into the protein coding sequence and introduction of the modified protein coding sequence into a recombination-competent host cell, specifically a recombination-competent host cell that is capable of expressing at least RAG-1 and RAG-2, thereby allowing for recombination of the protein coding sequence and expression of variant proteins. Also provided are polynucleotides comprising a nucleic acid sequence encoding a target protein, such as a ligand-binding protein, and comprising two or more RSSs, and compositions and host cells comprising same.

Abstract: Methods of generating sequence diversity in a protein, such as a ligand-binding protein, are provided. The methods comprise targeted introduction of two or more recombination signal sequences (RSSs) into the protein coding sequence and introduction of the modified protein coding sequence into a recombination-competent host cell, specifically a recombination-competent host cell that is capable of expressing at least RAG-1 and RAG-2, thereby allowing for recombination of the protein coding sequence and expression of variant proteins. Also provided are polynucleotides comprising a nucleic acid sequence encoding a target protein, such as a ligand-binding protein, and comprising two or more RSSs, and compositions and host cells comprising same.

Abstract: In a computing device, when a user requests to carry out an operation, the device determines the type of operation requested and the time period since the user was last authenticated. The operation is enabled only if the determined time period does not exceed a threshold for the requested operation.

Abstract: Peptide-grafted antibodies having agonist activity against a Class B GPCR and their uses, and methods for identifying same. Mammalian cell lines for high-throughput screening for agonists of a Class B GPCR are also provided that comprise a stably integrated recombinant nucleic acid construct comprising a reporter gene under control of a cAMP responsive promoter, the reporter gene encoding a cell surface expressed protein, and a stably integrated recombinant nucleic acid construct comprising a sequence encoding a Class B GPCR under control of a constitutive promoter.

Abstract: Methods of generating sequence diversity in a protein, such as a ligand-binding protein, are provided. The methods comprise targeted introduction of two or more recombination signal sequences (RSSs) into the protein coding sequence and introduction of the modified protein coding sequence into a recombination-competent host cell, specifically a recombination-competent host cell that is capable of expressing at least RAG-1 and RAG-2, thereby allowing for recombination of the protein coding sequence and expression of variant proteins. Also provided are polynucleotides comprising a nucleic acid sequence encoding a target protein, such as a ligand-binding protein, and comprising two or more RSSs, and compositions and host cells comprising same.

Abstract: Methods of generating fusion protein variants are provided that comprise introducing sequence diversity at the junction region or regions in the fusion and allows for the generation of variants having a desired activity. Examples include immunoglobulins comprising a domain or polypeptide inserted into, or replacing, a CDR. Also provided are polynucleotides encoding a fusion protein and comprising two or more RSSs, and compositions and host cells comprising same, as well as fusion proteins variants produced by the described methods.

Abstract: Compositions and methods are disclosed for generating immunoglobulin structural diversity in vitro, and in particular, for reducing biases in V region and J segment gene utilization, and for generating immunoglobulin V-D-J recombination events in a manner that does not require D-J recombination to precede V-DJ recombination. Selection of advantageous combinations of immunoglobulin gene elements, including introduction of artificial diversity (D) segment genes and optimization of recombination signal sequence (RSS) efficiency, are disclosed.

Abstract: An in vitro system for generating sequence, and thus structural, diversity in proteins is described. The system can be constructed using appropriately selected nucleic acid molecules that encode regions of a selected protein or proteins and recombination signal sequences (RSS). The selected protein(s) can be, for example, immunoglobulin (Ig) V, D, J and/or C regions, regions of a non-immunoglobulin (non-Ig) protein, or a combination of Ig regions and non-Ig regions. Assembly of such appropriately selected components and their introduction into suitable recombination-competent host cells allows for recombination between the RSS sequences and introduction of sequence and structural diversity into the protein(s).

Abstract: Compositions and methods are disclosed for generating immunoglobulin structural diversity in vitro, and in particular, for reducing biases in V region and J segment gene utilization, and for generating immunoglobulin V-D-J recombination events in a manner that does not require D-J recombination to precede V-DJ recombination. Selection of advantageous combinations of immunoglobulin gene elements, including introduction of artificial diversity (D) segment genes and optimization of recombination signal sequence (RSS) efficiency, are disclosed.

Abstract: Compositions and methods are disclosed for generating immunoglobulin structural diversity in vitro, and in particular, for reducing biases in V region and J segment gene utilization, and for generating immunoglobulin V-D-J recombination events in a manner that does not require D-J recombination to precede V-DJ recombination. Selection of advantageous combinations of immunoglobulin gene elements, including introduction of artificial diversity (D) segment genes and optimization of recombination signal sequence (RSS) efficiency, are disclosed.