Abstract: A casting core used in the manufacture of a cast engine component for a turbine engine, the cast engine component having a first area, a second area, a fluid passage wall separating the first area and the second area, and a connecting fluid passage extending through the fluid passage wall and interconnecting the first area and the second area. The connecting fluid passage having a turn with a radius (R). The casting core having a first core and a second core. The first core and the second core being defined by a set of geometric characteristics having a first minimum equivalent diameter (D1eqmin) of the first core and a second minimum equivalent diameter (D2eqmin) of the second core. A first flexible geometry factor (FGF1) being equal to: ( D ? 1 eq ? min D ? 2 eq ? min ) ? ( R D ? 2 eq ? min ) .

Abstract: The present disclosure relates to genetically modified T cells comprising a transgene encoding an engineered antigen specific receptor, wherein expression of an endogenous gene selected from MNK1, MNK2, or both are inhibited in the genetically modified T cell in order to enhance central memory T cell subsets in cellular immunotherapy compositions.

Abstract: The present disclosure provides compositions and methods for improving an antitumor response against non-inflamed solid tumors. Methods of this disclosure include use of an eIF4A inhibitor to promote infiltration of antitumor lymphocytes into a non inflamed solid tumor. Methods of treating cancer associated with a non-inflamed solid tumor are also provided.

Abstract: The present disclosure relates to genetically modified T cells comprising a transgene encoding an engineered antigen specific receptor, wherein expression of an endogenous gene selected from MNK1, MNK2, or both are inhibited in the genetically modified T cell in order to enhance central memory T cell subsets in cellular immunotherapy compositions.

Abstract: The present disclosure provides methods for the treatment of a subject having BRAF-mutated cancer cells comprising administering an effective amount of an eIF4E inhibitor, which may be optionally used in combination with other therapies, such as RAF inhibitors. Furthermore, BRAF mutational status can be used to select for patients that would clinically benefit from eIF4E inhibition, such as patient with BRAF-mutated cancer cells that are resistant to RAF kinase inhibitors.

Abstract: The present disclosure relates to methods for ameliorating or treating an eIF4A dependent condition or disease in a subject in need thereof. The methods of the disclosure comprise administering to the subject a therapeutically effective amount of at least one eukaryotic translation initiation factor 4A (eIF4A) inhibitor and a therapeutically effective amount of at least one cyclin-dependent kinase (CDK) inhibitor.

Abstract: The present disclosure relates to genetically modified T cells comprising a transgene encoding an engineered antigen specific receptor, wherein expression of an endogenous gene selected from MNK1, MNK2, or both are inhibited in the genetically modified T cell in order to enhance central memory T cell subsets in cellular immunotherapy compositions.

Abstract: The present disclosure relates to the use MNK-specific inhibitors to inhibit immunosuppression components, such as immune checkpoint proteins PD-1, PD-L1, LAG3, and/or immunosuppressive cytokines, such as IL-10, in order to inhibit or release immune suppression in certain diseases, such as cancer and infectious disease.

Abstract: The present disclosure relates to genetically modified T cells comprising a transgene encoding an engineered antigen specific receptor, wherein expression of an endogenous gene selected from MNK1, MNK2, or both are inhibited in the genetically modified T cell in order to enhance central memory T cell subsets in cellular immunotherapy compositions.

Abstract: The present disclosure relates to the use MNK-specific inhibitors to inhibit immunosuppression components, such as immune checkpoint proteins PD-1, PD-L1, LAG3, and/or immunosuppressive cytokines, such as IL-10, in order to inhibit or release immune suppression in certain diseases, such as cancer and infectious disease.

Abstract: The present disclosure provides compositions and methods for improving an antitumor response against non-inflamed solid tumors. Methods of this disclosure include use of an eIF4A inhibitor to promote infiltration of antitumor lymphocytes into a non inflamed solid tumor. Methods of treating cancer associated with a non-inflamed solid tumor are also provided.

Abstract: The present disclosure relates to genetically modified T cells comprising a transgene encoding an engineered antigen specific receptor, wherein expression of an endogenous gene selected from MNK1, MNK2, or both are inhibited in the genetically modified T cell in order to enhance central memory T cell subsets in cellular immunotherapy compositions.

Abstract: The present disclosure relates to the use MNK-specific inhibitors to inhibit immunosuppression components, such as immune checkpoint proteins PD-1, PD-L1, LAG3, and/or immunosuppressive cytokines, such as IL-10, in order to inhibit or release immune suppression in certain diseases, such as cancer and infectious disease.

Abstract: Compounds of the formula and pharmaceutically acceptable salts thereof, wherein R1 and A are defined herein, are protein kinase inhibitors and are useful in the treatment of proliferative diseases, for example, cancer, inflammation and arthritis. They may also be useful in the treatment of Alzheimer's disease and cardiovascular disease.

Abstract: The compounds of the invention are protein kinase inhibitors and are useful in the treatment of proliferative diseases. Compositions and methods are provided for the synergistic treatment of proliferative disorders.

Abstract: The invention provides a method for preventing or treating alopecia induced by chemotherapy or radiotherapy by administering to a mammalian specie in need thereof a therapeutically effective amount of a compound of formula I or II or a pharmaceutically acceptable salt thereof.

Abstract: The present invention describes compounds of formula I: and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4, R5, m and n are as defined in the specification. The compounds of formula I are protein kinase inhibitors and are useful in the treatment of proliferative diseases, for example, cancer, inflammation and arthritis. They may also be useful in the treatment of Alzheimer's disease, chemotherapy-induced alopecia, and cardiovascular disease.

Abstract: Compounds of the formula 1

Abstract: The present invention describes compounds of formula I: 1

Abstract: Compounds of the formula and pharmaceutically acceptable salts thereof are provided.