Abstract: The invention features pancreatic islet and pancreatic organoids, and cell cultures and methods that are useful for the rapid and reliable generation of pancreatic islet and pancreatic islet organoids. The invention also features methods of treating pancreatic diseases and methods of identifying agents that are useful for treatment of pancreatic diseases, such as type 2 diabetes and pancreatic cancer, using the pancreatic islet and pancreatic organoids of the invention.

Abstract: Provided herein are CRISPR/Cas methods and compositions for targeting RNA molecules, which can be used to detect, edit, or modify a target RNA.

Abstract: The present disclosure provides FGF1 mutant proteins, such as those having an N-terminal deletion, point mutation(s), or combinations thereof, which can reduce blood glucose in a mammal. Such mutant FGF1 proteins can be part of a chimeric protein that includes a ?-Klotho-binding protein, an FGFR1c-binding protein, a ?-Klotho-binding protein and a FGFR1c-binding protein, a C-terminal region from FGF19 or FGF21. In some examples, mutant FGF1 proteins have reduced mitogenic activity. Also provided are nucleic acid molecules that encode such proteins, and vectors and cells that include such nucleic acids. Methods of using the disclosed molecules to reduce blood glucose levels are also provided.

Abstract: Provided herein are CRISPR/Cas methods and compositions for targeting RNA molecules, which can be used to detect, edit, or modify a target RNA.

Abstract: Image similarity searching can be achieved by improving utilization of computing resources so that computing power can be reduced while maintaining accuracy or accuracy can be improved using a same level of computing power. Such a similarity search can be achieved via an expansion matrix that expands the number of dimensions in an input feature vector of a query image. Dimensionality of an input feature vector can be increased, resulting in a higher dimensional hash. Sparsification can then be applied to the resulting higher dimensional hash. Sparsification can use a winner-take-all technique or setting a threshold, resulting in a hash of reduced length, but can still be considered of the expanded dimensionality. Matching the query image against a corpus of sample images can be achieved via nearest neighbor techniques via the resulting hashes to find sample images matching the query image.

Abstract: Provided herein is the use of compounds that modulate the activity of inhibitor of apoptosis proteins (IAPs), alone or in combination with other therapeutic agents, in the treatment of human immunodeficiency virus (HIV). Described herein is the use of IAP antagonists in the treatment of human immunodeficiency virus (HIV) in a mammal, alone or in combination with other therapeutic agents used in HIV therapy. In one aspect, provided herein is a method of treating human immunodeficiency virus (HIV) in an individual in need thereof comprising administering a therapeutically effective amount of at least one inhibitor of apoptosis proteins (IAP) antagonist.

Abstract: Novel compounds having a formula embodiments of a method of making the same, and of a composition comprising them are disclosed herein. Also disclosed are embodiments of a method of treating or preventing a metabolic disorder in a subject, comprising administering to a subject (e.g., via the gastrointestinal tract) a therapeutically effective amount of one or more of the disclosed compounds, thereby activating FXR receptors in the intestines, and treating or preventing a metabolic disorder in the subject. Additionally disclosed are embodiments of a method of treating or preventing inflammation in an intestinal region of a subject, comprising administering to the subject (e.g., via the gastrointestinal tract) a therapeutically effective amount of one or more of the disclosed compounds, thereby activating FXR receptors in the intestines, and thereby treating or preventing inflammation in the intestinal region of the subject.

Abstract: The present disclosure provides FGF1 mutant proteins, which include an N-terminal deletion, point mutation(s), or combinations thereof. In some examples, the mutant FGF1 proteins have reduced mitogenic activity. Also provided are nucleic acid molecules that encode such proteins, and vectors and cells that include such nucleic acids. The disclosed FGF1 mutants can reduce blood glucose in a mammal, and in some examples are used to treat a metabolic disorder.

Abstract: The method provides methods and compositions for treating metabolic disorders such as impaired glucose tolerance, elevated blood glucose, insulin resistance, dyslipidemia, obesity, and fatty liver.

Abstract: This disclosure concerns compositions and methods for immunoenhancement and/or immunosuppression. In certain embodiments, the disclosure concerns methods of using a TAM receptor inhibitor for immunoenhancement, for example as a vaccine adjuvant, for the treatment of sepsis, or for treating an immunocompromised subject. Also disclosed are methods of screening for immunoenhancing agents. In other embodiments, the disclosure concerns methods of using a TAM receptor agonist for immunosuppression, for example as a treatment for an autoimmune disorder, for the treatment of an allergy, or for treating graft-versus-host disease in a subject. Also disclosed are methods of screening for immunosuppressive agents.

Abstract: Provided herein are methods and compositions relating to the synthesis of isoprenoid diphosphates using a mutated isopentenyl phosphate kinase.

Abstract: In certain aspects, the invention provides a method for treating a disease or condition in a subject, the method comprising co-administering to a subject in need thereof a therapeutically effective amount of at least one ULK1-inhibiting pyrimidine, and a therapeutically effective amount of an mTOR inhibitor.

Abstract: Methods, systems, and devices are disclosed for evaluating vulnerability, disease progression, and treatments in neuropathologies. In one aspect, a method to provide an assessment related to a neurological or neuropsychiatric disorder includes selecting a profile category indicative of one or more aspects of cognitive or sensory functions associated with a neurological or neuropsychiatric disorder, presenting a sequence of stimuli to a subject, in which the sequence of stimuli is based on the selected profile category, acquiring physiological signals of the subject before, during, and after the presenting of the sequence of stimuli to produce physiological data, and processing the physiological data to generate an information set including one or more quantitative values associated with the selected profile category.

Abstract: The present disclosure provides compositions that include a nanoparticle and a compound that increases the biological activity of the vitamin D receptor (VDR) (e.g., a VDR agonist), and methods of using such compounds to increase retention or storage of vitamin A, vitamin D, and/or lipids by a cell, such as an epithelial or stellate cell. Such methods can be used to treat or prevent fibrosis.

Abstract: Provided herein are compounds I, II or III and compositions useful in increasing PPAR8 activity. The compounds and compositions provided herein are useful for the treatment of PPAR8 related diseases (e.g., muscular diseases, vascular disease, demyelinating disease, and metabolic diseases).

Abstract: Novel compounds having a formula embodiments of a method of making the same, and of a composition comprising them are disclosed herein. Also disclosed are embodiments of a method of treating or preventing a metabolic disorder in a subject, comprising administering to a subject (e.g., via the gastrointestinal tract) a therapeutically effective amount of one or more of the disclosed compounds, thereby activating FXR receptors in the intestines, and treating or preventing a metabolic disorder in the subject. Additionally disclosed are embodiments of a method of treating or preventing inflammation in an intestinal region of a subject, comprising administering to the subject (e.g., via the gastrointestinal tract) a therapeutically effective amount of one or more of the disclosed compounds, thereby activating FXR receptors in the intestines, and thereby treating or preventing inflammation in the intestinal region of the subject.

Abstract: Provided herein are CRISPR/Cas methods and compositions for targeting RNA molecules, which can be used to detect, edit, or modify a target RNA.

Abstract: Recombinant herpes simplex virus (HSV)-1 capable of selectively replicating in alternative lengthening of telomeres (ALT)-dependent tumor cells are described. The recombinant HSV-1 are ICP0-deficient, such as by complete deletion of the ICP0 gene, or mutation of the ICP0 gene sufficient to diminish or eliminate E3 ubiquitin ligase activity of ICP0. In some cases, the recombinant HSV-1 further include additional gene deletions or mutations, such as those that render the virus glycoprotein C (gC) deficient, or include a heterologous gene, such as a gene encoding an immunostimulatory molecule. Methods of treating ALT-dependent cancer, and methods of selectively killing ALT-dependent tumor cells are also described.

Abstract: Provided herein are compounds of formula (I) useful for the treatment of PPAR-delta related diseases (e.g. mitochondrial diseases, muscular diseases, vascular diseases, demyelinating diseases and metabolic diseases).

Abstract: Methods, systems, and devices are disclosed for acquiring and analyzing physiological signals. In one aspect, a physiological sensor device includes a substrate formed of an electrically insulative material and structured to allow physical contact of the device with the frontal region of the head of a user, a recording electrode configured at a first location on the substrate to acquire an electrophysiological signal of the user, a reference electrode configured at a second location on the substrate to acquire a reference signal to the electrophysiological signal, and a ground electrode configured at a third location at least partially between the first and the second locations on the substrate, in which the first location is posterior to the second and third locations, and in which the device is operable when electrically coupled to an electrical circuit to detect physiological signals of the user.