Abstract: The invention features compounds (e.g., macrocyclic compounds) capable of modulating biological processes, for example through binding to a presenter protein (e.g., a member of the FKBP family, a member of the cyclophilin family, or PIN1) and a target protein (e.g., a eukaryotic target protein such as a mammalian target protein or a fungal target protein or a prokaryotic target protein such as a bacterial target protein). These compounds bind endogenous intracellular presenter proteins, such as the FKBPs or cyclophilins, and the resulting binary complexes selectively bind and modulate the activity of intracellular target proteins. Formation of a tripartite complex among the presenter protein, the compound, and the target protein is driven by both protein-compound and protein-protein interactions, and both are required for modulation of the targeted protein's activity.

Abstract: The invention features compounds (e.g., macrocyclic compounds) capable of modulating biological processes, for example through binding to a presenter protein (e.g., a member of the FKBP family, a member of the cyclophilin family, or PIN1) and a target protein such as CEP250. These compounds bind endogenous intracellular presenter proteins, such as the FKBPs or cyclophilins, and the resulting binary complexes selectively bind and modulate the activity of the target protein. Formation of a tripartite complex among the presenter protein, the compound, and the target protein is driven by both protein-compound and protein-protein interactions, and both are required for modulation of target protein activity.

Abstract: A glenoid implant (100) is disclosed. The glenoid implant including a plurality of bone fixation pegs (130, 140, 150) extending from a back or medial surface thereof. The bone fixation pegs including one or more features in the form of fins (132) and grooves (160) arranged and configured to provide increased fixation to the patient's bone thus minimizing the likelihood of the implant loosening.

Abstract: Interleukin-2 (IL-2) conjugates comprising at least one or more amino acid substitutions that bias binding to the IL-2 receptor ??c dimer over binding the IL-2 receptor ???c trimer and a non-natural amino acid at or near the N-terminus conjugated to a water-soluble polymer are described. The IL-2 conjugates are useful for treatment and prevention of cell proliferation and cancer in a patient.

Abstract: Interleukin-2 (IL-2) conjugates comprising at least one or more amino acid substitutions that bias binding to the IL-2 receptor ??c dimer over binding the IL-2 receptor ???c trimer and a non-natural amino acid at or near the N-terminus conjugated to a water-soluble polymer are described. The IL-2 conjugates are useful for treatment and prevention of cell proliferation and cancer in a patient.

Abstract: Anti-cancer combination therapies comprising a CTLA-4 blocking agent and a PD-1 blocking agent are disclosed. In particular, combination therapies are disclosed wherein the CTLA-4 blocking agent is an effector-silent anti-CTLA-4 antibody or effector-silent anti-CTLA-4 antibody fragment and the PD-1 blocking agent is an anti-PD-1 or anti-PD-L1 antibody, or antibody fragment thereof.

Abstract: The present invention provides molecules, such as ISVDs and Nanobodies, that bind to PD1 and LAG3 and, optionally to human serum albumin. These molecules have been engineered so as to reduce the incidence of binding by pre-existing antibodies in the bodies of a subject administered such a molecule. Methods for increasing immune response, treating cancer and/or treating an infectious disease with such molecules are provided.

Abstract: The present invention provides molecules, such as ISVDs and Nanobodies, that bind to PD1 and LAG3 and, optionally to human serum albumin. These molecules have been engineered so as to reduce the incidence of binding by pre-existing antibodies in the bodies of a subject administered such a molecule. Methods for increasing immune response, treating cancer and/or treating an infectious disease with such molecules are provided.

Abstract: The present invention provides molecules, such as ISVDs and Nanobodies, that bind to PD1 and LAG3 and, optionally to human serum albumin. These molecules have been engineered so as to reduce the incidence of binding by pre-existing antibodies in the bodies of a subject administered such a molecule. Methods for increasing immune response, treating cancer and/or treating an infectious disease with such molecules are provided.

Abstract: Interleukin-2 (IL-2) conjugates comprising at least one or more amino acid substitutions that bias binding to the IL-2 receptor ??c dimer over binding the IL-2 receptor ???c trimer and a non-natural amino acid at or near the N-terminus conjugated to a water-soluble polymer are described. The IL-2 conjugates are useful for treatment and prevention of cell proliferation and cancer in a patient.

Abstract: The present invention provides molecules, such as ISVDs and Nanobodies, that bind to PD1 and LAG3 and, optionally to human serum albumin. These molecules have been engineered so as to reduce the incidence of binding by pre-existing antibodies in the bodies of a subject administered such a molecule. Methods for increasing immune response, treating cancer and/or treating an infectious disease with such molecules are provided.

Abstract: Methods and apparatus to cool a vehicle heat source are disclosed herein. An example apparatus includes a first tank and a second tank. The first tank and the second tank are disposed on a vehicle. The second tank is in fluid communication with the first tank. An engine of the vehicle is to be supplied with fuel from at least one of the first tank or the second tank. The example apparatus also includes a cooling system disposed on the vehicle to cool the fuel flowing from the first tank to the second tank. The example apparatus further includes a heat exchanger operatively coupled to a heat source disposed on the vehicle. The fuel from the second tank is to flow to the first tank via the heat exchanger to cool the heat source.

Abstract: Systems, methods and computer-readable media for initiating, facilitating and/or performing financial transactions are disclosed. A request associated with a financial transaction may be received on behalf of a requestor. At least one financial account to be debited and at least one financial account to be credited in connection with the financial transaction may be identified based on information included or provided in association with the request. Respective payment networks that provide access to the financial accounts may be identified. One or more of the financial accounts may be accessible in real-time via a respective payment network. A respective debit or credit instruction may be transmitted to each of the identified payment networks to post a debit or credit to a corresponding financial account. Corresponding debit and/or credit status information may be received, and various status indications may be generated and transmitted, potentially for presentation to the requestor.

Abstract: The present invention provides multispecific molecules, e.g., comprising more than one ISVD or Nanobody, that bind to PD1 and CTLA4. These molecules have been engineered so as to reduce the incidence of binding by pre-existing antibodies in the bodies of a subject administered such a molecule. Methods for increasing immune response, treating cancer and/or treating an infectious disease with such molecules are provided.

Abstract: The present invention provides molecules, such as ISVDs and Nanobodies, that bind to PD1 and LAG3 and, optionally to human serum albumin. These molecules have been engineered so as to reduce the incidence of binding by pre-existing antibodies in the bodies of a subject administered such a molecule. Methods for increasing immune response, treating cancer and/or treating an infectious disease with such molecules are provided.

Abstract: The present invention provides molecules, such as ISVDs and Nanobodies, that bind to PD1 and LAG3 and, optionally to human serum albumin. These molecules have been engineered so as to reduce the incidence of binding by pre-existing antibodies in the bodies of a subject administered such a molecule. Methods for increasing immune response, treating cancer and/or treating an infectious disease with such molecules are provided.

Abstract: The present invention provides molecules, such as ISVDs and Nanobodies, that bind to PD1 and LAG3 and, optionally to human serum albumin. These molecules have been engineered so as to reduce the incidence of binding by pre-existing antibodies in the bodies of a subject administered such a molecule. Methods for increasing immune response, treating cancer and/or treating an infectious disease with such molecules are provided.

Abstract: Systems, methods and computer-readable media are disclosed for generating integrated data records by correlating source data records stored at different registry source data repositories. A set of source data records is retrieved based on execution of one or more search queries against a set of registry source data repositories. A data record matching rule is selected for execution on the set of source data records. The matching rule specifies one or more input properties, each of which specifies at least one data field designator, and optionally, a matching algorithm and an input property match threshold value. The matching rule is executed on pairwise combinations of source data records to obtain a set of matched source data records. An integrated data record is generated and populated with respective data from each of one or more of the matched source data records. The integrated data record is linked to each source record.

Abstract: The present invention provides molecules, such as ISVDs and Nanobodies, that bind to PD1 and LAG3 and, optionally to human serum albumin. These molecules have been engineered so as to reduce the incidence of binding by pre-existing antibodies in the bodies of a subject administered such a molecule. Methods for increasing immune response, treating cancer and/or treating an infectious disease with such molecules are provided.

Abstract: Systems, methods and computer-readable media are disclosed for generating integrated data records by correlating source data records stored at different registry source data repositories. A set of source data records is retrieved based on execution of one or more search queries against a set of registry source data repositories. A data record matching rule is selected for execution on the set of source data records. The matching rule specifies one or more input properties, each of which specifies at least one data field designator, and optionally, a matching algorithm and an input property match threshold value. The matching rule is executed on pairwise combinations of source data records to obtain a set of matched source data records. An integrated data record is generated and populated with respective data from each of one or more of the matched source data records. The integrated data record is linked to each source record.