Abstract: The present invention relates to the field of stem cell biology, in particular the lineage specific differentiation of pluripotent or multipotent stem cells, which can include, but is not limited to, human embryonic stem cells (hESC) in addition to nonembryonic human induced pluripotent stem cells (hiPSC), somatic stem cells, stem cells from patients with a disease, or any other cell capable of lineage specific differentiation. Specifically described are methods to direct the lineage specific differentiation of hESC and/or hiPSC into floor plate midbrain progenitor cells and then further into large populations of midbrain fate FOXA2+LMX1A+TH+ dopamine (DA) neurons using novel culture conditions.

Abstract: The presently disclosed subject matter provides for antigen-recognizing receptors that specifically target uPAR and cells comprising such uPAR-targeted antigen-recognizing receptors. The presently disclosed subject matter further provides uses of the uPAR-targeted antigen-recognizing receptors for treatment.

Abstract: In one aspect, the invention relates to substituted 1-phenyl-3-(piperidin-4-yl)urea analogs, derivatives thereof, and related compounds, which are useful as inhibitors of the DCN1-UBC12 interaction inhibitors of DCN1-mediated cullin-RING ligase activity, methods of making same, pharmaceutical compositions comprising same, methods of treating disorders using the disclosed compounds and compositions, methods of treating disorders associated with a DCN1-UBC12 interaction dysfunction, methods of treating disorders associated with a DCN1-mediated cullin-RING ligase activity dysfunction, methods of male contraception comprising the disclosed compounds and compositions, and kits comprising the disclosed compounds and compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Abstract: The presently disclosed subject matter provides for antigen-recognizing receptors that specifically target uPAR and cells comprising such uPAR-targeted antigen-recognizing receptors. The presently disclosed subject matter further provides uses of the uPAR-targeted antigen-recognizing receptors for treatment.

Abstract: The presently disclosed subject matter provides for in vitro methods of inducing differentiation of human stem cells into neural crest, cranial placode or non-neuro ectoderm precursors, and cells generated by such methods. The presently disclosed subject matter also provides for uses of such cells for treating neurodegenerative and pituitary disorders.

Abstract: The present technology relates to methods for treating, preventing, and/or ameliorating kinase mutation-associated neurodegenerative diseases, including BRAFV600E-associated neurodegenerative diseases, in a subject in need thereof. In particular aspects, the present technology relates to the use of BRAF, MEK, and/or CSF-1R inhibitors to treat, prevent, and/or ameliorate kinase mutation-associated neurodegenerative diseases, including BRAFV600E-associated neurodegenerative diseases.

Abstract: The present invention provides a novel anti-DLL3 antibody-pyrrolodiazepine derivative and a novel anti-DLL3 anti-body-pyrrolodiazepine derivative conjugate using the same.

Abstract: It is an object of the present invention to provide an antibody-drug conjugate of an antibody binding to DLL3 and a drug having antitumor activity, a pharmaceutical composition comprising the antibody-drug conjugate and having therapeutic effects on a tumor, a method for treating a tumor using the antibody-drug conjugate or the pharmaceutical composition, and the like. The present invention provides an antibody-drug conjugate of an antibody binding to DLL3 and a drug having antitumor activity, a pharmaceutical composition comprising the antibody or the antibody-drug conjugate, and a method for treating a tumor.

Abstract: The presently disclosed subject matter provides antibodies or antigen-binding fragments thereof that bind to uPAR and methods of using such antibodies or antigen-binding fragments thereof same.

Abstract: Single chain peptides comprising either a cell penetrating HIV-TAT peptide sequence and a MYB:CBP complex interfering peptide sequence from MYB, or compsiring a cell penetrating HIV-TAT peptide sequence, a CBP binding peptide sequence from CREB and a MYB:CBP complex interfering peptide sequence from MYB, are provided for use in preventing MYB:CBP complex formation and downstream events leading to cancer, in particular a leukemia. Both L-amino acid single chain peptides and retro-inverso single chain peptides are provided.

Abstract: Described is an approach for tracking 3D organ motion in real-time using magnetic resonance imaging (MRI). The approach may include offline learning, which may acquire signature and 3D imaging data over multiple respiratory cycles to create a database of high-resolution 3D motion states. The approach may further include online matching, which may acquire signature data only in real-time (latency less than 0.2 seconds). From a motion state and motion signature database, the 3D motion state whose signature best (or sufficiently) matches the newly-acquired signature data may be selected. Real-time 3D motion tracking may be accomplished by performing time-consuming acquisition and reconstruction work in an offline learning phase, leaving just signature acquisition and correlation analysis in an online matching step, minimizing or otherwise reducing latency. The approach may be used to adapt radiotherapy procedures based on tumor motion using a magnetic resonance linear accelerator (MR-Linac) system.

Abstract: The present disclosure provides methods and compositions for enhancing the immune response toward cancers and pathogens. It relates to an immunoresponsive cell comprising an antigen-recognizing receptor (e.g., a chimeric antigen receptor (CAR) or a T cell receptor (TCR)), and expressing increased level of IL-36. In certain embodiments, the engineered immunoresponsive cells are antigen-directed and have enhanced immune-activating properties.

Abstract: Described herein are 3D single-molecule super-resolution imaging systems and methods. The provided systems and methods use modulation interferometry and phase-sensitive detection techniques that achieve less than 2 nanometer axial localization precision, which is well below the 5-10-nanometer-sized individual protein components. To illustrate the capability of this technique in probing the dynamics of complex macromolecular machines, (1) movement of individual multi-subunit E. coli RNA Polymerases were visualized through the complete transcription cycle, (2) kinetics of the initiation-elongation transition were dissected, (3) the conformational changes from the open initiation complex to the elongation complex were analyzed, and (4) the fate of ?70 initiation factors during promoter escape were determined.

Abstract: The present disclosure relates to methods of treating a vascular malformation in a subject expressing a gain-of-function mutation in a PIK3CA gene comprising administering, to the subject, an effective amount of an agent that inhibits phosphoinositide 3-kinase (“PI3K”).

Abstract: The present application relates generally to identifying regions of interest in images, including but not limited to whole slide image region of interest identification, prioritization, de-duplication, and normalization via interpretable rules, nuclear region counting, point set registration, and histogram specification color normalization. This disclosure describes systems and methods for analyzing and extracting regions of interest from images, for example biomedical images depicting a tissue sample from biopsy or ectomy. Techniques directed to quality control estimation, granular classification, and coarse classification of regions of biomedical images are described herein. Using the described techniques, patches of images corresponding to regions of interest can be extracted and analyzed individually or in parallel to determine pixels correspond to features of interest and pixels that do not.

Abstract: The present invention provides immunoresponsive cells, including T cells, cytotoxic T cells, regulatory T cells, and Natural Killer (NK) cells, expressing at least one of an antigen recognizing receptor and one of a chimeric costimulatory receptor. Methods of using the immunoresponsive cell include those for the treatment of neoplasia and other pathologies where an increase in an antigen-specific immune response is desired.

Abstract: The presently disclosed subject matter provides novel T cell receptors (TCRs) that target a mutated RAS protooncogene. The presently disclosed subject matter further provides cells comprising such TCRs, and methods of using such cells for treating cancers associated with RAS.

Abstract: The presently disclosed subject matter provides methods and compositions for enhancing the immune response toward cancers and pathogens. It relates to novel designs of chimeric antigen receptors (CARs) and engineered immunoresponsive cells comprising the same. The engineered immunoresponsive cells comprising the novel CARs are antigen-directed and have extended persistence without compromising function.

Abstract: Described herein is a method of induced cell death via ferroptosis by nanoparticle ingestion. Moreover, the present disclosure describes the administration of high concentrations of ultrasmall nanoparticles at multiple times over the course of treatment in combination with a nutrient-depleted environment, thereby modulating cellular metabolic pathways to induce cell death by the mechanism ferroptosis. Ferroptosis involves iron, reactive oxygen species, and a synchronous mode of cell death execution.

Abstract: The presently disclosed subject matter provides antibodies that bind to GPRC5D and methods of using the same.