Abstract: The present disclosure provides methods for expanding tumor-infiltrating lymphocytes (TILs), such as tumor-infiltrating T cells, utilizing an agonist of PGC1? in vivo, ex vivo, or both. Exhausted T cells present in the TIL population fail to effectively proliferate, produce cytokines, or kill target cells. The present disclosure provides methods to correct these defects through the use of pharmacologic agents to reprogram the metabolism of the exhausted intratumoral T cells. Exemplary agonists of PGC1? include proliferator-activated receptor (PPAR)-gamma agonists (e.g., a thiazolidinedione (TZD), aleglitazar, farglitazar, muraglitazar, or tesaglitazar), AMPK activators (e.g., 5-aminoimidazole-4-carboxamide ribonucleotide, AICAR), and sirtuin activators (e.g., resveratrol, SRT1720, SRT2104, SRT2183, SRT1460). Also provided are kits can compositions that can be used with such methods.

Abstract: An agent comprising: an algin crosslinked with acetal linkages; and at least one cation coupled to the crosslinked algin.

Abstract: Methods are disclosed herein for identifying a compound of use in treating a condition treatable by metformin. The methods include determining if the test compound binds a subunit of the mitochondrial electron transport complex IV, and/or alters the function of the mitochondrial electron transport complex IV. Methods for treating a subject with a condition treatable by metformin, are also disclosed. In some embodiments, the condition is type II diabetes.

Abstract: Interferon-?-inducible protein 10 (IP-10) peptides, IP-10 peptide variants and in silico designed C—X—C chemokine receptor 3 (CXCR3) peptide agonists are described. The small peptides can be used for inhibiting pathological tissue remodeling and treating fibrosis in a subject, such as a subject with fibrosis of the heart, lung, liver, kidney or skin. The peptide agonists can also be used to treat cardiovascular disease, including myocardial infarction and ischemia-reperfusion injury. Also described are in silico designed peptide antagonists that bind CXCR3 or ligands of CXCR3. These antagonist peptides block CXCR3 signaling by disrupting interaction of CXCR3 with its ligand. Antagonist peptides can be used, for example, to treat myocarditis and atherosclerosis. In additional embodiments agonists and antagonists of CXCR4 are disclosed.

Abstract: The present invention provides methods and compositions for identifying patients at risk of kidney injury. A risk score, which is a composite of a urinary concentration of IGFBP7 (insulin-like growth factor-binding protein 7) and a urinary concentration of TIMP-2 (tissue inhibitor of metalloproteinase 2), is determined obtained from the patient, and is used to manage patient treatment.

Abstract: Provided herein are compositions and methods for treating pulmonary vascular disease in a subject comprising administering to the subject a therapeutically effective amount of a YAP/TAZ inhibiting composition and/or a GLS1 inhibiting composition.

Abstract: In vitro and in vivo methods of removing carbon monoxide from hemoglobin in blood or animal tissue are described. Methods of treating carboxyhemoglobinemia (carbon monoxide poisoning) in a subject are also described. The methods include administering natural or artificial oxygen carriers that are in their reduced form. Methods of producing a reduced oxygen carrier are further described. Methods of treating cyanide poisoning or hydrogen sulfide poisoning with oxygen carriers are also described.

Abstract: An energy harvesting device includes a housing (2), a moveable device (12) disposed within the housing and including a first surface including a first material (15) and a second surface including a second material (17), wherein the moveable device is operable to move to bring the first and second surfaces together and apart to cause contact and separation between the first and second materials, a first strap (4) attached to the housing, a second strap (6) coupled to the moveable device, wherein movement of the second strap causes operation of the moveable device, and electronic circuitry (20) structured to harvest energy from the electrical charge generated by the contact between the first and second materials.

Abstract: The invention provides a method for ameliorating chronic pain signaling involving transient receptor potential cation channel subfamily V member 1 (TRPV1) by expressing PP1? in neurons. The invention also provides HSV vectors for expressing PP1? within neurons and compositions comprising such vectors.

Abstract: The present invention relates to methods for treating patients having cancer or a premalignant or neoplastic condition. It is based, at least in part, on the discovery that a genome editing technique that specifically targets a fusion gene can induce cell death in a cancer cell other than a prostate cancer cell, e.g., a hepatocellular cancer cell, having the fusion gene. The present invention provides methods for treating cancer patients that include performing a genome editing technique targeting a fusion gene present within one or more cells of a subject to produce an anti-cancer effect.

Abstract: A method for quantifying an amount of fat contained in a liver or other tissue of a subject in vivo includes varying the temperature of a target area in a subject, imaging thermal strain of the target area using an ultrasound scanner, and quantifying the amount of fat in the targeted area based on the thermal strain imaging. In some embodiments, the thermal strain imaging is performed using high-resolution, phase-sensitive speckle tracking to differentiate between fat-based tissue and water-based tissue.

Abstract: Various embodiments of this invention are directed to pharmaceutical compositions and methods for treating disease. The compositions of such embodiments include reversible nitroxide derivatives of nitroalkenes. The methods of various embodiments include administering an effective amount of any of these pharmaceutical compositions to a patient in need of treatment.

Abstract: Various embodiments of this invention are directed to pharmaceutical compositions and methods for treating disease. The compositions of such embodiments include thiolated nitro fatty acids. The methods of various embodiments include administering an effective amount of any of these pharmaceutical compositions to a patient in need of treatment.

Abstract: Disclosed herein are various bioreactor devices that mimic the mammalian joint. The bioreactor device can include a series of bioreactor chambers that contain different components of the joint, such as bone, cartilage, synovium, nerve and ligament. At least two different nutrient fluid circulation systems connect subsets of the bioreactor chambers to differentially supply nutrient fluids at concentrations optimized for the tissue that the fluid nourishes. For example, relatively hypoxic fluid can be supplied to synovium and cartilage to mimic oxygenation in the joint compartment, but normoxic fluid can be supplied to the bone and other components that have an arterial supply that provides higher oxygen concentrations. One or more or all of the bioreactor chambers can be supplied with separate inlets through which perturbation agents (such as drugs or other agents) can be introduced to model the effect of the perturbations on different components of the system.

Abstract: Compounds of formula I and their metabolites are potent mediators of an inflammatory response: where a, b, c, d, e, f, V, W, X, Y, Ra, Rb, Rb?, Rc, and Rc? are defined herein. In particular, the compounds of the invention are candidate therapeutics for treating inflammatory conditions.

Abstract: In one embodiment, the invention provides a herpes simplex virus (HSV) vector that does not express toxic HSV genes in non-complementing cells and which comprises a genome comprising one or more transgenes, wherein the vector is capable of expression of a transgene for at least 28 days in non-complementing cells. The invention also relates to viral stocks of the inventive vectors, compositions thereof suitable for use therapeutically or for in vitro applications, and methods relating thereto. In another aspect, the invention provides a complementing cell engineered to express ICP4 and ICP27 when the cell is infected with HSV for the production of the inventive vector.

Abstract: The invention provides an isolated nucleic acid encoding a receptor, other than an immunoglobulin, wherein the receptor binds to a MUC 1 tumor antigen independently of an major histocompatibility complex (MHC).

Abstract: Nitro oleic acid and related metabolites are agonists of PPAR-?. Surprisingly, nitro oleic acid is a more potent agonist of PPAR-?, relative to nitro linoleic acid. Thus, nitro oleic acid and its metabolites, as well as their pharmaceutically acceptable salts and prodrug forms, are candidate therapeutics for the treatment of type-2 diabetes, which results from insulin resistance accompanying the improper functioning of PPAR-?.

Abstract: A method of estimating relative change of the 3D position of an object (e.g., sample drift in a microscopy system) having fiduciary markers that have an asymmetric joint point spread function distribution includes generating a plurality of calibration curves for each of the markers during a calibration phase including first calibration curves for a PSF width and second calibration curves for lateral bias. The method further includes capturing a first image of the markers during a acquisition phase, generating a first joint 3D position for the markers using the first image, the first calibration curves and the second calibration curves, capturing a second image of the markers during the data acquisition phase, generating a second joint 3D position for the markers using the second image and the first and second calibration curves, and estimating the sample drift using the first joint 3D position and the second joint 3D position.

Abstract: A catalytic glycosylation method comprising: installing thioether to an anomeric carbon of a carbohydrate; and catalytically activating the thioether with a non-oxophilic Lewis acid. The thioether may comprise an anomerically stable thioether leaving group. The catalytic glycosylation method may further comprise: utilizing an acid-sensitive ester protecting group as permanent protecting group or using a reactivity-based one-pot glycosylation that employs a single-component catalyst to accelerate an oligosaccharide assembly process. A protecting group to mask hydroxyl functionalities in the production of oligosaccharides, natural products or any molecule having a hydroxyl group comprising an acid-labile ester protecting group.