Abstract: Described herein are methods and computer systems for classification of CD8 T-cell topology using a patient response-based linear cutoff model. A plurality of histology images of tissue samples in a plurality of patients are received by a computer system. An image analysis of the plurality of histology images is performed to obtain a CD8+ T-cell abundance in the tumor parenchyma and stroma in each of the plurality of histology images. Real inflammation scores and tumor infiltration scores are determined based on a polar coordinate transformation of the CD8+ T-cell abundance in the tumor parenchyma and stroma. Based on the real inflammation scores and tumor infiltration scores, a feature space is generated, and linear boundaries or linear cutoffs between a plurality of classifications in the feature space are identified based on the real inflammation scores, the tumor infiltration scores, and patient response data.

Abstract: The invention provides a method of treating a tumor in a human patient comprising (i) identifying a patient as having a LAG-3 positive tumor and (ii) administering to the patient a PD-1 pathway inhibitor, a combination of a PD1 pathway inhibitor and an immune checkpoint inhibitor, a combination of a LAG-3 inhibitor and a PD-1 pathway inhibitor, or an anti-CTLA4 antibody. In some embodiments, the method further comprises identifying the patient as having a LAG-3 positive PD-L1 positive tumor. In some embodiments, the LAG-3 inhibitor is an anti-LAG-3 antibody and the PD-1 pathway inhibitor is an anti-PD-1 antibody. The methods of the invention can improve response rates to treatment with a PD-1 pathway inhibitor, a combination of a PD1 pathway inhibitor and an immune checkpoint inhibitor, or a combination of a LAG-3 inhibitor and a PD-1 pathway inhibitor.

Abstract: The invention provides a method of treating a tumor in a human patient comprising (i) identifying a patient as having a LAG-3 positive tumor and (ii) administering to the patient a PD-1 pathway inhibitor, a combination of a PD1 pathway inhibitor and an immune checkpoint inhibitor, a combination of a LAG-3 inhibitor and a PD-1 pathway inhibitor, or an anti-CTLA4 antibody. In some embodiments, the method further comprises identifying the patient as having a LAG-3 positive PD-L1 positive tumor. In some embodiments, the LAG-3 inhibitor is an anti-LAG-3 antibody and the PD-1 pathway inhibitor is an anti-PD-1 antibody. The methods of the invention can improve response rates to treatment with a PD-1 pathway inhibitor, a combination of a PD1 pathway inhibitor and an immune checkpoint inhibitor, or a combination of a LAG-3 inhibitor and a PD-1 pathway inhibitor.

Abstract: Described herein are methods and computer systems for classification of CD8 T-cell topology using artificial intelligence and machine learning. A plurality of histology images of tissue samples in a plurality of patients are received by a computer system. An image analysis of the plurality of histology images is performed to obtain a CD8+ T-cell abundance in the tumor parenchyma and stroma in each of the plurality of histology images. A machine learning algorithm is then trained using results of the image analysis and the CD8+ T-cell abundance in the tumor parenchyma and stroma. Based on the training, a machine learning feature space comprising a plurality of classifications is generated, and boundaries between the plurality of classifications in the machine learning feature space are identified.

Abstract: The present disclosure provides methods of identifying a subject suitable for an anti-PD-?PD-L1 antagonist therapy comprising measuring assay CD8 localization and PD-L1 expression in a tumor sample obtained from the subject. In some aspects, method further comprises administering (i) an anti-PD-?PD-L1 antagonist therapy or (ii) an anti-PD-?PD-L1 antagonist and anti-CT-LA-4 antagonist combination therapy to a subject identified as having a tumor exhibiting an excluded CD8 localization phenotype, wherein the tumor is PD-L1 negative.

Abstract: This disclosure provides a method for treating a subject afflicted with tumor, which method comprises administering to the subject an antibody or an antigen-binding portion thereof that specifically binds to a Programmed Death-1 (PD-1) receptor and inhibits PD-1 activity. In some embodiments, the tumor is derived from a non-small cell lung cancer (NSCLC). In some embodiments, the tumor expresses Programmed Death Ligand 1. In some embodiments, the subject carries a wild-type STK11 gene.

Abstract: This disclosure provides a method for treating a subject afflicted with tumor, which method comprises administering to the subject an antibody or an antigen-binding portion thereof that specifically binds to a Programmed Death-1 (PD-1) receptor and inhibits PD-1 activity. In some embodiments, the tumor is derived from a non-small cell lung cancer (NSCLC). In some embodiments, the tumor expresses Programmed Death Ligand 1. In some embodiments, the subject carries a wild-type STK11 gene.

Abstract: The disclosure provides LAG-3 antagonists and methods comprising the same for treating a cancer in a subject based on a LAG-3 density score and/or a LAG-3 proportion score in a tumor sample from the subject. The disclosure also provides methods of identifying a subject responsive to a LAG-3 antagonist therapy.

Abstract: This disclosure provides a method for treating a subject afflicted with tumor, which method comprises administering to the subject an antibody or an antigen-binding portion thereof that specifically binds to a Programmed Death-1 (PD-1) receptor and inhibits PD-1 activity. In some embodiments, the tumor is derived from a non-small cell lung cancer (NSCLC). In some embodiments, the tumor expresses Programmed Death Ligand 1 (PD-L1), Serine/Threonine Kinase 11 (STK11), or both PD-L1 and STK11.

Abstract: The invention provides a method of treating a tumor in a human patient comprising (i) identifying a patient as having a LAG-3 positive tumor and (ii) administering to the patient a PD-1 pathway inhibitor, a combination of a PD1 pathway inhibitor and an immune checkpoint inhibitor, a combination of a LAG-3 inhibitor and a PD-1 pathway inhibitor, or an anti-CTLA4 antibody. In some embodiments, the method further comprises identifying the patient as having a LAG-3 positive PD-Ll positive tumor. In some embodiments, the LAG-3 inhibitor is an anti-LAG-3 antibody and the PD-1 pathway inhibitor is an anti-PD-1 antibody. The methods of the invention can improve response rates to treatment with a PD-1 pathway inhibitor, a combination of a PD1 pathway inhibitor and an immune checkpoint inhibitor, or a combination of a LAG-3 inhibitor and a PD-1 pathway inhibitor.

Abstract: A method of electricity production using water thermal energy includes compressing an enclosed working fluid at a first vertical position relative to a surface of a body of water to cause the fluid to move to a second vertical position relative to the surface and subsequently move to the first position in a closed loop, an external environment at the second position having a greater temperature than an external environment at the first position such that the fluid transitions between a liquid phase at the first position and a vapor phase at the second position, the compressing using power from a battery, and expanding the fluid at the second position to generate electricity to charge the battery. The first and second positions may be two depths of the body of water or a height of an atmosphere above the body of water and a depth of the body of water.

Abstract: This disclosure provides a method for treating a subject afflicted with tumor, which method comprises administering to the subject an antibody or an antigen-binding portion thereof that specifically binds to a Programmed Death-1 (PD-1) receptor and inhibits PD-1 activity. In some embodiments, the tumor is derived from a non-small cell lung cancer (NSCLC). In some embodiments, the tumor expresses Programmed Death Ligand 1 (PD-L1), Serine/Threonine Kinase 11 (STK11), or both PD-L1 and STK11.

Abstract: This disclosure provides a method for treating a subject afflicted with tumor, which method comprises administering to the subject an antibody or an antigen-binding portion thereof that specifically binds to a Programmed Death-1 (PD-1) receptor and inhibits PD-1 activity. In some embodiments, the tumor is derived from a non-small cell lung cancer (NSCLC). In some embodiments, the tumor expresses Programmed Death Ligand 1. In some embodiments, the subject carries a wild-type STK11 gene.

Abstract: A method of electricity production using water thermal energy includes compressing an enclosed working fluid at a first vertical position relative to a surface of a body of water to cause the fluid to move to a second vertical position relative to the surface and subsequently move to the first position in a closed loop, an external environment at the second position having a greater temperature than an external environment at the first position such that the fluid transitions between a liquid phase at the first position and a vapor phase at the second position, the compressing using power from a battery, and expanding the fluid at the second position to generate electricity to charge the battery. The first and second positions may be two depths of the body of water or a height of an atmosphere above the body of water and a depth of the body of water.

Abstract: A method of electricity production using water thermal energy includes compressing an enclosed working fluid at a first vertical position relative to a surface of a body of water to cause the fluid to move to a second vertical position relative to the surface and subsequently move to the first position in a closed loop, an external environment at the second position having a greater temperature than an external environment at the first position such that the fluid transitions between a liquid phase at the first position and a vapor phase at the second position, the compressing using power from a battery, and expanding the fluid at the second position to generate electricity to charge the battery. The first and second positions may be two depths of the body of water or a height of an atmosphere above the body of water and a depth of the body of water.

Abstract: A method of electricity production using water thermal energy includes compressing an enclosed working fluid at a first vertical position relative to a surface of a body of water to cause the fluid to move to a second vertical position relative to the surface and subsequently move to the first position in a closed loop, an external environment at the second position having a greater temperature than an external environment at the first position such that the fluid transitions between a liquid phase at the first position and a vapor phase at the second position, the compressing using power from a battery, and expanding the fluid at the second position to generate electricity to charge the battery. The first and second positions may be two depths of the body of water or a height of an atmosphere above the body of water and a depth of the body of water.

Abstract: A system and method are disclosed for providing a mobile persona environment hosted by a network accessible server that can be activated by network connected client device. The client device points the portion of its file system used by the operating system to configure the desktop environment to a persona container hosted by the server. The persona container includes user data, applications and operating system settings or policies that are used to configure the operating system of the client device to provide the mobile persona environment. The client device obtains user profile information and connection information from a persona reference object stored on the client device. Applications are executed locally on the client device while the data remains secure in the network accessible server.

Abstract: A chemical mechanical polishing composition contains 1) water, 2) optionally an abrasive material, 3) an oxidizer, preferably a per-type oxidizer, 4) a small amount of soluble metal-ion oxidizer/polishing accelerator, a metal-ion polishing accelerator bound to particles such as to abrasive particles, or both; and 5) at least one of the group selected from a) a small amount of a chelator, b) a small amount of a dihydroxy enolic compound, and c) a small amount of an organic accelerator. Ascorbic acid in an amount less than 800 ppm, preferably between about 100 ppm and 500 ppm, is the preferred dihydroxy enolic compound. The polishing compositions and processes are useful for substantially all metals and metallic compounds found in integrated circuits, but is particularly useful for tungsten.

Abstract: A method of polishing a substrate with a polishing composition comprising an oxidizing agent and abrasive particles having a surface, said surface of the abrasive particles being at least partially modified with 1) at least one stabilizer compound comprising aluminum, boron, tungsten, or both, said stabilizer compound being bound via a covalent bond to said abrasive particles, and 2) an organic chelating compound, said chelating compound being bound via a covalent bond to said stabilizer compound. The organic chelating compounds include one or more of 1) a nitrogen-containing moiety and between one and five other polar groups; 2) a sulfur-containing moiety and between one and five other polar groups; and 3) between two and five polar groups selected from carboxylic acid groups or salts thereof and hydroxyl groups.

Abstract: A chemical mechanical polishing composition contains 1) water, 2) optionally an abrasive material, 3) an oxidizer, preferably a per-type oxidizer, 4) a small amount of soluble metal-ion oxidizer/polishing accelerator, a metal-ion polishing accelerator bound to particles such as to abrasive particles, or both; and 5) at least one of the group selected from a) a small amount of a chelator, b) a small amount of a dihydroxy enolic compound, and c) a small amount of an organic accelerator. Ascorbic acid in an amount less than 800 ppm, preferably between about 100 ppm and 500 ppm, is the preferred dihydroxy enolic compound. The polishing compositions and processes are useful for substantially all metals and metallic compounds found in integrated circuits, but is particularly useful for tungsten.