Abstract: Engineered transcriptional activator-like effectors (TALEs) are versatile tools for genome manipulation with applications in research and clinical contexts. One current drawback of TALEs is that the 5? nucleotide of the target is specific for thymine (T). TALE domains with alternative 5? nucleotide specificities could expand the scope of DNA target sequences that can be bound by TALEs. Another drawback of TALEs is their tendency to bind and cleave off-target sequence, which hampers their clinical application and renders applications requiring high-fidelity binding unfeasible. This disclosure provides methods and strategies for the continuous evolution of proteins comprising DNA-binding domains, e.g., TALE domains. In some aspects, this disclosure provides methods and strategies for evolving such proteins under positive selection for a desired DNA-binding activity and/or under negative selection against one or more undesired (e.g., off-target) DNA-binding activities.

Abstract: The invention provides rechargeable batteries including a solid state electrolyte (SSE) containing an alkali metal disposed between two electrodes. The batteries are volumetrically constrained imparting increased stability under voltage cycling conditions, e.g., through microstructure mechanical constriction on the solid state electrolyte and the electrolyte-electrode interface. These batteries of the invention are advantageous as they may be all-solid-state batteries, e.g., no liquid electrolytes are necessary, and can achieve higher voltages with minimal electrolyte degradation.

Abstract: Therapeutics and methods for treating a stroke in a human comprising administering a therapeutic to the patient, wherein the therapeutic comprises one of immortalized human placenta mesenchymal stem cells (hPMSCs) and a product from the immortalized hPMSCs. Methods and therapeutic products comprising extracellular vesicles (EVs) isolated from of immortalized hPMSCs. Therapeutics and methods of treating COVID-19 disease vascular injury comprising administering a therapeutic to the patient, wherein the therapeutic comprises one of hPMSCs and a product from the hPMSCs.

Abstract: Provided herein, in some embodiments, are methods for detecting a level of asparaginase (ASNS) in a sample obtained from a subject having or at risk for stomach cancer or liver cancer, and methods of treating the subject.

Abstract: The invention relates to methods of altering expression of a genomic locus of interest or specifically targeting a genomic locus of interest in an animal cell, which may involve contacting the genomic locus with a non-naturally occurring or engineered composition that includes a deoxyribonucleic acid (DNA) binding polypeptide having a N-terminal capping region, a DNA binding domain comprising at least five or more Transcription activator-like effector (TALE) monomers and at least one or more half-monomers specifically ordered to target the genomic locus of interest, and a C-terminal capping region, wherein the polypeptide includes at least one or more effector domains, and wherein the polypeptide is encoded by and translated from a codon optimized nucleic acid molecule so that the polypeptide preferentially binds to the DNA of the genomic locus.

Abstract: Provided herein are mutant reverse tetracycline transactivator (rtTA) proteins and engineered nucleic acids (e.g., viral vectors, including lentiviral vectors, adenoviral vectors, AAV vectors, herpes viral vectors, and retroviral vectors, and non-viral vectors, including RNA and plasmid DNA) that encode a mutant rtTA that are useful, for example, in regulating gene expression, inducing cellular reprogramming, tissue repair, tissue regeneration, organ regeneration, reversing aging, treating a disease (e.g., acute injuries, neurodegenerative disease, chronic diseases, proliferative diseases, cardiovascular diseases, genetic diseases, inflammatory diseases, autoimmune diseases, neurological diseases, hematological diseases, painful conditions, psychiatric disorders, metabolic disorders, cancers, aging, age-related diseases, and diseases affecting any tissue in a subject), or any combination thereof. Also provided herein are recombinant viruses (e.g.

Abstract: A heart valve therapeutic device (1) comprises a coaptation assist valve (20) comprising a conduit (2) with an outer surface (3) for coaption with the native leaflets, and a prosthetic flow valve (5) mounted within the conduit (2) to allow one-way flow through the conduit (2). Support for the coaptation assist valve (20) is provided by a support (10) for positioning the conduit (2) across the native leaflets, and connectors (15) attaching the conduit (2) to the support (10).

Abstract: Methods and compositions of altering mitochondrial DNA of a eukaryotic cell are provided using one or more of a mitochondrial specific adeno-associated virus to deliver one or more nucleic acids encoding CRISPR system including a Cas9 protein or its nuclease inactive variant and a guide RNA into a mitochondria for expression within the mitochondria. The Cas9 system can cut, nick or regulate a target mitochondrial nucleic acid.

Abstract: The present disclosure provides, in some embodiments, methods and compositions for single-molecule detection.

Abstract: The present invention is based, in part, on the identification of methods of modulating PD-1 expression and/or activity in regulatory T cells (Tregs) to thereby regulate effector immune responses in effector T cells (Teffs).

Abstract: The present disclosure provides a distributed and anonymous approach to demand response of an electricity system. The approach conceptualizes energy consumption and production of distributed-energy resources (DERs) via discrete energy packets that are coordinated by a cyber computing entity that grants or denies energy packet requests from the DERs. The approach leverages a condition of a DER, which is particularly useful for (1) thermostatically-controlled loads, (2) non-thermostatic conditionally-controlled loads, and (3) bi-directional distributed energy storage systems. In a first aspect of the present approach, each DER independently requests the authority to switch on for a fixed amount of time (i.e., packet duration). The coordinator determines whether to grant or deny each request based electric grid and/or energy or power market conditions. In a second aspect, bi-directional DERs, such as distributed-energy storage systems (DESSs) are further able to request to supply energy to the grid.

Abstract: The present disclosure provides fusion proteins comprising a nanobody and a glycan modifying enzyme. Also provided herein are methods of glycosylating a protein and methods of removing a sugar from a protein. Further provided in the present disclosure are methods of treating and/or diagnosing diseases. Also provided herein are kits, polynucleotides, vectors, and cells.

Abstract: An apparatus for generating a blood pressure estimation model includes: a signal acquirer configured to receive input a first signal and a second signal from a user; and a processor configured to obtain a pulse transit time (PTT) as a first predictor variable value based on the first signal and the second signal, to extract at least one feature from the second signal, to obtain a second predictor variable value based on the extracted at least one feature, and to generate a blood pressure estimation model based on the first predictor variable value and the second predictor variable value.

Abstract: In certain aspects, disclosed herein are novel compositions and methods related to either the enhancement or inhibition of erythropoiesis that are useful, for example, in the treatment of anemia or erythrocytosis.

Abstract: The invention provides compositions and methods to form pores in situ within hydrogels following hydrogel injection. Pores formed in situ via degradation of sacrificial porogens within the surrounding hydrogel facilitate recruitment or release of cells. Disclosed herein is a material that is not initially porous, but which becomes macroporous over time.

Abstract: Techniques are disclosed for providing a thumbnail scrubber mode in electronic devices, such as a touch screen device. In an embodiment, a thumbnail scrubber may be displayed to the user in response to a distinguishable touch screen gesture, or in response to a toolbar command. A toolbar may be displayed on the device including a scrubber bar, and the thumbnail scrubber mode may be invoked when a user interacts with the scrubber bar. The thumbnail scrubber displays multiple thumbnail images of pages of digital content and allows the user to preview and scroll through the digital content while continuing to display the current page in the main viewer of the device. After scrubbing through the digital content pages, the user may select one of the thumbnail images in the scrubber in order to access that page of the digital content.

Abstract: The present disclosure relates to the prediction of physiological parameters, such as glucose levels. A training input is received, the training input comprising time-series values of a physiological parameter and time-series values of one or more further parameters. Training examples are generated form the training input, wherein each training example comprises a training dataset and a corresponding training label, wherein each training dataset is generated from the training input with time-series values restricted to a time interval, and wherein each corresponding training label represents the value of the physiological parameter a prediction period after the end of that time interval. A neural network is then trained using the training examples.

Abstract: The present invention embodies an effective teeth whitening composition that utilizes bromelain enzymes as the primary active ingredient and the main source of whitening. Further, the invention is a method for preparing the effective teeth whitening composition. The composition of an effective teeth whitener includes a sugar alcohol, calcium carbonate, a binder, an anionic detergent, a fluoride agent, sodium benzoate, and bromelain.

Abstract: The invention provides flow batteries including an anthraquinone and methods of discharging the batteries that reduce loss of capacity. The loss of capacity of anthraquinones may be mitigated by controlling the state of charge and/or oxidizing the negolyte.

Abstract: An automatic door handle/panel sanitizer dispensing assembly comprising a frame, a control unit including a processor, an actuator assembly controlled by the processor, the actuator assembly includes one of a pump and a valve, a first sensor operatively connected to the processor, a power storage unit powering the control unit, the actuator assembly, and the first sensor, a first nozzle and a second nozzle, both fluidly connected to the actuator assembly, a container coupled to the frame, for storing disinfectant, a threaded hook to hang the assembly onto the door handle, a tray having an arcuate shape and being arranged abutting a roof of the frame and being supported by the frame, a plurality of threaded tray holes extending through the tray arranged proximate to a rear end of the tray.