Abstract: Provided herein, in some embodiments, are methods and compositions for identifying combinations of transcription factors, for example, those involved in cell type conversion processes, such as cell differentiation.

Abstract: The present invention relates to chimeric antigen receptor (CAR)-T cells, and particularly, although not exclusively, to anti-T-cell receptor (TCR) V-beta CARs, and to their use in immunotherapy, and for treating, preventing or ameliorating cancer, such as T-cell lymphomas, various microbial infections, such as HIV and TB, and also autoimmune disease. The invention is especially concerned with the use of CAR-engineered mucosal-associated invariant T (MAIT) cells, and to novel methods for stimulating, isolating and expanding highly purified MAIT cells, which can then be engineered into such CAR-MAIT cells. The invention extends to genetic constructs per se, and to their use in generating the CAR-MAIT cells, and to transduced CAR-MAIT cells per se. The invention also extends to various medical uses of the constructs and transduced CAR-MAIT cells, and to pharmaceutical compositions comprising these constructs and CAR-MAIT cells.

Abstract: The present disclosure provides glycosyl hydrolases (e.g., OGA) comprising a ligand-dependent intein. The present disclosure also provides pharmaceutical compositions comprising the glycosyl hydrolases disclosed herein, as well as polynucleotides, vectors, cells, and kits. Methods of using the disclosed intein-containing glycosyl hydrolases are also provided herein, including methods of deglycosylating a target protein. Methods of treating a glycosylation-associated disease in a subject, as well as methods of sensitizing a cell to a desirable therapeutic outcome, are also provided herein.

Abstract: Some aspects of this disclosure provide a fusion protein comprising a guide nucleotide sequence-programmable DNA binding protein domain (e.g., a nuclease-inactive variant of Cas9 such as dCas9), an optional linker, and a recombinase catalytic domain (e.g., a tyrosine recombinase catalytic domain or a serine recombinase catalytic domain such as a Gin recombinase catalytic domain). This fusion protein can recombine DNA sites containing a minimal recombinase core site flanked by guide RNA-specified sequences. The instant disclosure represents a step toward programmable, scarless genome editing in unmodified cells that is independent of endogenous cellular machinery or cell state.

Abstract: Forced expression of a handful of transcription factors (TFs) can induce conversions between cell identities; however, the extent to which TFs can alter cell identity has not been systematically assessed. Here, we assembled a human TFome, a comprehensive expression library of 1,578 human TF clones with full coverage of the major TF families. By systematically screening the human TFome, we identified 77 individual TFs that induce loss of human-induced-pluripotent-stem-cell (hiPSC) identity, suggesting a pervasive ability for TFs to alter cell identity. Using large-scale computational cell type classification trained on thousands of tissue expression profiles, we identified cell types generated by these TFs with high efficiency and speed, without additional selections or mechanical perturbations. TF expression in adult human tissues only correlated with some of the cell lineage generated, suggesting more complexity than observation studies can explain.

Abstract: Some aspects of this disclosure relate to strategies, systems, methods, compositions, and kits that are useful for production (e.g., evolution) of cytidine deaminase protein variants that are characterized by increased soluble expression and/or stability relative to the wild-type cytidine deaminase protein from which they are evolved. In some embodiments, evolved cytidine deaminase variants described by the disclosure are useful for incorporation into targeted nucleic acid editing proteins, for example in fusion proteins with a Cas9 domain or variant thereof.

Abstract: The present invention relates to chimeric antigen receptor (CAR)-T cells, and particularly, although not exclusively, to their use in immunotherapy, and for treating, preventing or ameliorating cancer, such as T-cell lymphomas, various microbial infections, such as HIV and TB, and also autoimmune disease. The invention is especially concerned with the use of CAR-engineered mucosal-associated invariant T (MAIT) cells, and to novel methods for stimulating, isolating, and expanding highly purified MAIT cells, which can then be engineered into such CAR-MAIT cells. The invention is also concerned with methods for expansion of MAIT cells in vitro.

Abstract: Disclosed herein are an apparatus for electrically assessing and/or manipulating cells. One aspect is directed to electrically mapping cells on the surface of the semiconductor substrate via cross-electrode impedance measurements. Further according to some aspects, the electrode array allows for spatially addressable electrical stimulation and/or recording of electrical signals in real-time using the CMOS circuitry. Some of these aspects are directed to using an electrode array to perform cell patterning through electrochemical gas generation, and extracellular electrochemical mapping.

Abstract: The present disclosure generally relates to sugar reduction in foods and, in some aspects, to enzyme-polymer conjugated particles for food and other applications. Certain aspects of the disclosure are directed to compositions for reducing sugar content and/or producing dietary fiber within food products during or after consumption (e.g., in a subject's gastrointestinal (GI) tract), while maintaining the sweetness and flavor of the sugar in food products upon consumption (e.g., in a subject's mouth). For example, in one set of embodiments, a composition may comprise a particle comprising an enzyme capable of converting a sugar into a relatively non-digestible form (e.g., a polymer), optionally an inhibitor that reversibly inhibits the enzyme from converting the sugar, and optionally an additive capable of associating with the inhibitor. The composition may be used for in situ conversion of sugars upon exposure to an environment condition (e.g., pH and/or temperature) in the GI tract.

Abstract: A method of reducing a symptom of a clinical disorder characterized by aberrantly elevated circulating aP2 is carried out by administering to a subject an inhibitor of secreted aP2, secretion of aP2, or a serum aP2 blocking agent. For example, glucose intolerance is reduced following administration of such an inhibitor or agent. Exemplary compositions inhibit cellular secretion of aP2 or bind to circulating aP2, thereby reducing the level or activity of aP2 in blood or serum.

Abstract: Materials for electrochemical cells are provided. BaZr0.4Ce0.4M0.2O3 compounds, where M represents one or more rare earth elements, are provided for use as electrolytes. PrBa0.5Sr0.5Co2?xFexO5+? is provided for use as a cathode. Also provided are electrochemical cells, such as protonic ceramic fuel cells, incorporating the compounds as electrolytes and cathodes.

Abstract: The present invention discloses a pneumatic-controlled pitch-adjustable telescopic mechanism used for a robotic arm, which belongs to the technical field of robotic arm pneumatic control movement, comprising a sliding block, a fixed block and a driving device, the fixed block is in a fixed position; the sliding block slides relative to the fixed block according to a predetermined movement track, which is used to adjust the distance between the sliding block and the fixed block; the driving device is used to provide power to drive; a sliding bar is disposed between the driving device and the sliding block, one end of the sliding bar is fixedly connected to the driving device, and the other end is slidingly connected to the sliding block, which is used to drive the sliding block to slide; the fixed block is provided with a fixed base and a guide mechanism, the fixed base is used to restrict the sliding bar from moving in a direction non-parallel to the predetermined movement track; the guide mechanism is used t

Abstract: Activators of BAX and their uses in cancer therapy are disclosed.

Abstract: The present disclosure relates to a device, comprising a base and a plurality of microneedles attached to the base, wherein each microneedle has an outer surface; the outer surface of at least one microneedle being coated with a composition comprising at least one polymer and least one Peptide Nucleic Acid (PNA). The present disclosure additionally relates to a method of detecting an analyte in interstitial fluid (ISF), comprising contacting the device to a subject, for example, to human skin.

Abstract: Methods of detecting, probing, mapping and directed sequencing of target nucleic acids are provided using a guide RNA and a Cas9 protein. Methods for detecting the binding of the guide RNA/Cas9 complex to a target nucleic acid where the guide RNA includes a 3? tail sequence that can hybridize to a probe are provided. Methods for detecting the binding of the guide RNA/Cas9 complex to a target nucleic acid where the complex is physically detected are provided.

Abstract: A method of altering a eukaryotic cell is provided including transfecting the eukaryotic cell with a nucleic acid encoding RNA complementary to genomic DNA of the eukaryotic cell, transfecting the eukaryotic cell with a nucleic acid encoding an enzyme that interacts with the RNA and cleaves the genomic DNA in a site specific manner, wherein the cell expresses the RNA and the enzyme, the RNA binds to complementary genomic DNA and the enzyme cleaves the genomic DNA in a site specific manner.

Abstract: Provided herein are fluorogenic sensors which can be used to detect targets (e.g., antigens). In general, the fluorogenic sensors provided herein comprise a protein (e.g., antibody, nanobody, mini-protein) and a fluorogenic small molecule conjugated to the target-binding domain (e.g., antigen-binding domain) of the protein. Upon binding of the protein to said target (e.g., antigen), the fluorogenic small molecule may increase or decrease in fluorescence or exhibit a change in fluorescence lifetime (i.e., “turn on”), thereby indicating the presence of the target (e.g., antigen).

Abstract: The invention provides aminoacyl-tRNA synthetases, compositions thereof, and methods for use thereof.

Abstract: Disclosed is a video summarisation method that includes converting an input video file to a video transcript using speech recognition, segmenting the video transcript into a plurality of paragraphs using a transformer based model, performing relevance ranking of the plurality of paragraphs by assigning a paragraph importance score to each paragraph, based on relevance of each paragraph to an overall content of the video transcript, creating a plurality of candidate summaries from the plurality of paragraphs, each candidate summary comprising two or more paragraphs, performing coherence reranking of the plurality of candidate summaries based on a combination of coherence and relevance of each candidate summary, and selecting a summary based on the coherence reranking.

Abstract: Embodiments of the present disclosure pertain to compositions that include a metal-organic framework. The metal-organic framework includes a plurality of metals and a plurality of ligands coordinated with the plurality of metals, where the plurality of metals include bismuth, and the plurality of ligands include a plurality of hydroxy moieties that are not part of carboxyl groups. At least some of the hydroxy moieties are coordinated with bismuth to form Bi—O bonds. The metal-organic framework is in the form of a conductive and interconnected network. Additional embodiments of the present disclosure pertain to methods of utilizing the compositions to detect analytes in a sample and shield various objects from radiation.