Abstract: The invention provides monoclonal antibodies and antigen-binding fragments thereof specific for TNFR2, and methods of using the same to treat cancer or autoimmune disorder, including combination therapy with antagonists of the PD-1/PD-L1 immune checkpoint.

Abstract: A long-endurance self-powered ocean buoy includes a buoy body, a power generation device and a gas bag base; the power generation device is mounted at a lower end of the gas bag base and includes a housing, a first power generation assembly, a second power generation assembly and a storage battery; the first power generation assembly includes a plurality of mutually-communicated gas chambers, hydraulic bags and control integration units. The lowest gas chamber is filled with a volatile working medium which can generate gas pressure by volatilization to drive power generation fans in turbines on a vent pipe communicating adjacent gas chambers for power generation. The second power generation assembly includes a plurality of temperature difference energy modules with one end surrounded by a phase change material and the other end in contact with the housing, so as to increase the power generation efficiency.

Abstract: A long-endurance self-powered ocean buoy includes a buoy body, a power generation device and a gas bag base; the power generation device is mounted at a lower end of the gas bag base and includes a housing, a first power generation assembly, a second power generation assembly and a storage battery; the first power generation assembly includes a plurality of mutually-communicated gas chambers, hydraulic bags and control integration units. The lowest gas chamber is filled with a volatile working medium which can generate gas pressure by volatilization to drive power generation fans in turbines on a vent pipe communicating adjacent gas chambers for power generation. The second power generation assembly includes a plurality of temperature difference energy modules with one end surrounded by a phase change material and the other end in contact with the housing, so as to increase the power generation efficiency.

Abstract: The invention provides monoclonal antibodies and antigen-binding fragments thereof specific for TNFR2, and methods of using the same to treat cancer or autoimmune disorder, including combination therapy with antagonists of the PD-1/PD-L1 immune checkpoint.

Abstract: The invention features compositions and methods for inhibiting the Pin1 protein, and the treatment of disorders characterized by elevated Pin1 levels.

Abstract: The invention features compositions and methods for inhibiting the Pin1 protein, and the treatment of disorders characterized by elevated Pin1 levels.

Abstract: The invention features all-trans retinoic acid (ATRA)-related compounds capable of associating with Pin1 and methods of treating a proliferative disorder characterized by elevated Pin1 marker levels, Pin1 degradation, and/or reduced Pin1 Ser71 phosphorylation in a subject by administering an ATRA-related compound. The invention also features methods of treating proliferative disorders, autoimmune diseases, and addiction conditions (e.g., diseases, disorders, and conditions characterized by elevated Pin1 marker levels) by administering an ATRA-related compound in combination with another therapeutic compound.

Abstract: The invention features methods of treating a proliferative disorder characterized by elevated Pin1 marker levels and/or reduced Pin1 Ser71 phosphorylation in a subject by administering a retinoic acid compound. Additionally, the invention features methods of treating proliferative disorders (e.g., proliferative disorders characterized by elevated Pin1 marker levels) by administering a retinoic acid compound in combination with another anti-proliferative compound. Finally, the invention also features methods including high-throughput screens for discovering and validating Pin1 inhibitors.

Abstract: The invention features compositions and methods for inhibiting the Pin1 protein, and the treatment of disorders characterized by elevated Pin1 levels.

Abstract: Biomarkers and driver mutations for diagnosis and prognosis of Pin 1-associated diseases are disclosed. In one embodiment, the methods for diagnosis of Pin 1-associated diseases may include detecting the level of Pin1 to stage abnormal cell growth, such as breast or prostate cancer. In another embodiment, the methods include evaluating the efficacy of a treatment of abnormal cell growth, such as cancer, by monitoring the levels of Pin1. In another embodiment, the methods include using driver mutations to determine the pharmacogenetics of abnormal cell growth, such as cancer. In the present disclosure, elevated active monomeric Pin1 levels may be detected by Pin1 biomarkers, which may include Pin1 Q33K or E100D driver mutations, Pin1 protein or transcript overexpression, dephosphorylation of Pin1 on Ser71, dephosphorylation of S16, phosphorylation of S65, phosphorylation of S138, deacetylation of Pin1 on K13 and deacetylation of K46, and/or desumoylation of Pin1 on K6 and desumolation of K63, among others.

Abstract: The invention features methods of treating a proliferative disorder characterized by elevated Pin1 marker levels and/or reduced Pin1 Ser71 phosphorylation in a subject by administering a retinoic acid compound. Additionally, the invention features methods of treating proliferative disorders (e.g., proliferative disorders characterized by elevated Pin1 marker levels) by administering a retinoic acid compound in combination with another anti-proliferative compound. Finally, the invention also features methods including high-throughput screens for discovering and validating Pin1 inhibitors.

Abstract: The present disclosure describes how all-retinoic acid (ATRA) binds and inhibits Pin1 activity and induces degradation of the activated Pin1 monomer selectively in cancer cells. Identification of the binding mechanism of ATRA with Pin1 confirm ATRA binding specificity to Pin1 residues in the PPIase active site, thus demonstrating that drug-induced Pin1 ablation has potent anticancer activity, such as in acute promyelocytic leukemia (APL), by inducing PML-RARa degradation, as well as against other types of cancer and diseases that are associated with Pin1 overexpression, such as aggressive triple negative breast cancer, lupus, asthma, cocaine addiction, among others, due to their unique ability to simultaneously block numerous cancer-driving pathways, with relatively lower toxicity. The present disclosure also provides a rationale for developing sustained released ATRA-containing formulations.

Abstract: The invention features all-trans retinoic acid (ATRA)-related compounds capable of associating with Pin1 and methods of treating a proliferative disorder characterized by elevated Pin1 marker levels, Pin1 degradation, and/or reduced Pin1 Ser71 phosphorylation in a subject by administering an ATRA-related compound. The invention also features methods of treating proliferative disorders, autoimmune diseases, and addiction conditions (e.g., diseases, disorders, and conditions characterized by elevated Pin1 marker levels) by administering an ATRA-related compound in combination with another therapeutic compound.

Abstract: The invention features compositions and methods for inhibiting the Pin1 protein, and the treatment of disorders characterized by elevated Pin1 levels.

Abstract: The invention features compositions and methods for inhibiting the Pin1 protein, and the treatment of disorders characterized by elevated Pin1 levels.

Abstract: The present disclosure describes how all-retinoic acid (ATRA) binds and inhibits Pin1 activity and induces degradation of the activated Pin1 monomer selectively in cancer cells. Identification of the binding mechanism of ATRA with Pin1 confirm ATRA binding specificity to Pin1 residues in the PPIase active site, thus demonstrating that drug-induced Pin1 ablation has potent anticancer activity, such as in acute promyelocytic leukemia (APL), by inducing PML-RARa degradation, as well as against other types of cancer and diseases that are associated with Pin1 overexpression, such as aggressive triple negative breast cancer, lupus, asthma, cocaine addiction, among others, due to their unique ability to simultaneously block numerous cancer-driving pathways, with relatively lower toxicity. The present disclosure also provides a rationale for developing sustained released ATRA-containing formulations.

Abstract: Biomarkers and driver mutations for diagnosis and prognosis of Pin 1-associated diseases are disclosed. In one embodiment, the methods for diagnosis of Pin 1-associated diseases may include detecting the level of Pin1 to stage abnormal cell growth, such as breast or prostate cancer. In another embodiment, the methods include evaluating the efficacy of a treatment of abnormal cell growth, such as cancer, by monitoring the levels of Pin1. In another embodiment, the methods include using driver mutations to determine the pharmacogenetics of abnormal cell growth, such as cancer. In the present disclosure, elevated active monomeric Pin1 levels may be detected by Pin1 biomarkers, which may include Pin1 Q33K or E100D driver mutations, Pin1 protein or transcript overexpression, dephosphorylation of Pin1 on Ser71, dephosphorylation of S16, phosphorylation of S65, phosphorylation of S138, deacetylation of Pin1 on K13 and deacetylation of K46, and/or desumoylation of Pin1 on K6 and desumolation of K63, among others.

Abstract: The invention features all-trans retinoic acid (ATRA)-related compounds capable of associating with Pin1 and methods of identifying the same. The invention also provides methods of treating a condition selected from the group consisting of a proliferative disorder, an autoimmune disease, and an addiction condition characterized by elevated Pin1 marker levels, Pin1 degradation, and/or reduced Pin1 Ser71 phosphorylation in a subject by administering a retinoic acid compound. Additionally, the invention features methods of treating proliferative disorders, autoimmune diseases, and addiction conditions (e.g., diseases, disorders, and conditions characterized by elevated Pin1 marker levels) by administering a retinoic acid compound in combination with another therapeutic compound. The invention also features a co-crystal including Pin1 and a retinoic acid compound.

Abstract: The invention features compositions and methods for inhibiting the Pin1 protein, and the treatment of disorders characterized by elevated Pin1 levels.

Abstract: The invention features methods of treating a proliferative disorder characterized by elevated Pin1 marker levels and/or reduced Pin1 Ser71 phosphorylation in a subject by administering a retinoic acid compound. Additionally, the invention features methods of treating proliferative disorders (e.g., proliferative disorders characterized by elevated Pin1 marker levels) by administering a retinoic acid compound in combination with another anti-proliferative compound. Finally, the invention also features methods including high-throughput screens for discovering and validating Pin1 inhibitors.