Abstract: This disclosure relates to variant Factor VIII polypeptides comprising an amino acid substitution at one or more positions within one or both of the thrombin cleavage site and the activation loop. In certain embodiments, the variant Factor VIII polypeptide comprises one or more amino acid substitutions within both the thrombin cleavage site and the activation loop. In further embodiments, the variant factor VIII polypeptide further comprises one or more amino acid substitutions within the A1-A2 domain interface and the A2-A3 domain interface. The present disclosure further relates to methods of producing and/or using such variant Factor VIII polypeptides; nucleic acids encoding the polypeptides; vectors and/or recombinant cells, tissues, or organisms containing such nucleic acids; and kits and pharmaceutical compositions containing such polypeptides and/or nucleic acids.

Abstract: This disclosure relates to variant Factor VIII polypeptides comprising an amino acid substitution at one or more positions within one or both of the thrombin cleavage site and the activation loop. In certain embodiments, the variant Factor VIII polypeptide comprises one or more amino acid substitutions within both the thrombin cleavage site and the activation loop. In further embodiments, the variant factor VIII polypeptide further comprises one or more amino acid substitutions within the A1-A2 domain interface and the A2-A3 domain interface. The present disclosure further relates to methods of producing and/or using such variant Factor VIII polypeptides; nucleic acids encoding the polypeptides; vectors and/or recombinant cells, tissues, or organisms containing such nucleic acids; and kits and pharmaceutical compositions containing such polypeptides and/or nucleic acids.

Abstract: This disclosure relates to variant Factor VIII polypeptides comprising an amino acid substitution at one or more positions within one or both of the thrombin cleavage site and the activation loop. In certain embodiments, the variant Factor VIII polypeptide comprises one or more amino acid substitutions within both the thrombin cleavage site and the activation loop. In further embodiments, the variant factor VIII polypeptide further comprises one or more amino acid substitutions within the A1-A2 domain interface and the A2-A3 domain interface. The present disclosure further relates to methods of producing and/or using such variant Factor VIII polypeptides; nucleic acids encoding the polypeptides; vectors and/or recombinant cells, tissues, or organisms containing such nucleic acids; and kits and pharmaceutical compositions containing such polypeptides and/or nucleic acids.

Abstract: Methods, systems, and apparatus, including computer programs encoded on a computer storage medium, for analyzing queries. One of the methods includes obtaining a plurality of queries submitted from a plurality of different client devices; determining a source geographic location for each of the plurality of queries based on information associated with a client device from which the query was submitted; determining a destination geographic location for each of the plurality of queries based on the respective first text portion of the query; determining a vertical market category for each of the plurality of queries; receiving a request to analyze queries according to a first vertical market category and at least one of a source geographic location or a destination geographic location; using one or more indexes to identify queries responsive to the request; and presenting data describing the queries responsive to the request.

Abstract: This disclosure relates to variant Factor VIII polypeptides comprising an amino acid substitution at one or more positions within one or both of the thrombin cleavage site and the activation loop. In certain embodiments, the variant Factor VIII polypeptide comprises one or more amino acid substitutions within both the thrombin cleavage site and the activation loop. In further embodiments, the variant factor VIII polypeptide further comprises one or more amino acid substitutions within the A1-A2 domain interface and the A2-A3 domain interface. The present disclosure further relates to methods of producing and/or using such variant Factor VIII polypeptides; nucleic acids encoding the polypeptides; vectors and/or recombinant cells, tissues, or organisms containing such nucleic acids; and kits and pharmaceutical compositions containing such polypeptides and/or nucleic acids.

Abstract: The present invention relates to the generation of replication-competent viruses having therapeutic utility. The replication-competent viruses of the invention can express proteins useful in the treatment of disease.

Abstract: The present invention relates to the generation of replication-competent viruses having therapeutic utility. The replication-competent viruses of the invention can express proteins useful in the treatment of disease.

Abstract: The present invention provides an improved, expression system for the regulated expression of an encoded protein or nucleic acid therapeutic molecule in the cells of a subject, for use in the treatment of disease. In particular, the present invention provides an improved, regulated gene expression system, and pharmaceutical compositions and uses thereof for treatment of disease.

Abstract: The present invention relates to the generation or replication-competent viruses having therapeutic utility. The replication-competent viruses of the invention can express proteins useful in the treatment of disease.

Abstract: The present invention relates to the generation of replication-competent viruses having therapeutic utility. The replication-competent viruses of the invention can express proteins useful in the treatment of disease.

Abstract: The present invention provides an improved, expression system for the regulated expression of an encoded protein or nucleic acid therapeutic molecule in the cells of a subject, for use in the treatment of disease. In particular, the present invention provides an improved, regulated gene expression system, and pharmaceutical compositions and uses thereof for treatment of disease.

Abstract: The present invention provides an improved, expression system for the regulated expression of an encoded protein or nucleic acid therapeutic molecule in the cells of a subject, for use in the treatment of disease. In particular, the present invention provides an improved, regulated gene expression system, and pharmaceutical compositions and uses thereof for treatment of disease.

Abstract: The present invention provides an improved, expression system for the regulated expression of an encoded protein or nucleic acid therapeutic molecule in the cells of a subject, for use in the treatment of disease. In particular, the present invention provides an improved, regulated gene expression system, and pharmaceutical compositions and uses thereof for treatment of disease.

Abstract: The present invention provides an improved, expression system for the regulated expression of an encoded protein or nucleic acid therapeutic molecule in the cells of a subject, for use in the treatment of disease. In particular, the present invention provides an improved, regulated gene expression system, and pharmaceutical compositions and uses thereof for treatment of disease.

Abstract: This invention provides novel transcriptional regulatory elements from the human TRPM4 (Transient Receptor Potential-Melastatin 4) gene. These promoter and enhancer elements preferentially activate transcription in prostate tumor cells and tissues as compared to other tissues. Methods and compositions are provided to employ TRPM4 promoter elements for prostate tumor-specific expression of therapeutic molecules. Prostate tumor-restricted replicating adenoviral vectors are also provided.

Abstract: The present invention relates to the generation of replication-competent viruses having therapeutic utility.

Abstract: An intervertebral disk prosthesis includes a first anchoring device for anchoring the prosthesis to a first vertebral body and a second anchoring device for anchoring the prostheses to a second vertebral body. The two anchoring devices are moveably coupled to each other. The coupling between the two anchoring devices may include at least one deformable element. The coupling may be constructed as a single piece integrally with the first anchoring device and/or with the second anchoring device.

Abstract: A mobile ergospirometry system including a portable measurement unit that can be attached to a subject and that incorporates a mouthpiece or mask to collect respiratory gas, a sensor for the volume or amount of gas as well as sensors to determine the CO2/O2 concentration in the respiratory gas, a signal processing unit, and a telemetry module. The system further includes a computer-assisted base station having a telemetry unit to create a wireless connection to the telemetry module. In the system a bidirectional transmission route to the telemetry unit is set up by the telemetry module to transmit data and commands, for which purpose a transmitter and receiver subassembly is provided in each case, so that from the base station it is possible to communicate to the subject online information or requirements for operation of the measurement unit and/or the progress of the test.

Abstract: The invention relates to a catalyst component and a catalyst system for the preparation of high molecular weight ethylene or alpha-olefin homopolymers, ethylene-alpha-olefin copolymers, terpolymers or tetrapolymers, in a polymerization process, which is expediently effected in solution, at elevated temperature, preferably at least 80 DEG C. The catalyst system comprises a group 4-6 metal, preferably group 4 metal, a cyclic ligand (such as a cyclopentadienyl-type ligand), which forms a delocalized pi-bond with the metal M, a monohapto bonded 1,3-diaza-2-imino heterocyclic ligand (such as an iminoimidazolidine-type ligand) and anionic ligands and a catalyst activator coupound.

Abstract: The invention relates to a catalyst component and a catalyst system for the preparation of high molecular weight ethylene or alpha-olefin homopolymers, ethylene-alpha-olefin copolymers, terpolymers or tetrapolymers, in a polymerization process, which is expediently effected in solution, at elevated temperature, preferably at least 80 DEG C. The catalyst system comprises a group 4-6 metal, preferably group 4 metal, a cyclic ligand (such as a cyclopentadienyl-type ligand), which forms a delocalized pi-bond with the metal M, a monohapto bonded 1,3-diaza-2-imino heterocyclic ligand (such as an iminoimidazolidine-type ligand) and anionic ligands and a catalyst activator coupound.