Abstract: Articles and methods for delivering a therapeutic agent to a subject are described. These articles and methods may be useful, in some cases, for the delivery of therapeutic agents to the colon of a subject. In some embodiments, an article is configured to release a secretion inducing agent e.g., to stimulate the release of intestinal fluids. The article, in some embodiments, comprises a therapeutic agent such that the stimulated release of intestinal fluid increases the amount of therapeutic agent available for absorption by the colon. For example, in some embodiments, the articles and methods described herein advantageously promote increased absorption of therapeutic agents in subjects as compared to traditionally administered therapeutic agents without additional components such as a secretion inducing agent. In some embodiments, articles and methods described herein may increase the motility of the colon of a subject.

Abstract: The subject matter disclosed herein is generally directed to compositions and methods for treating diffuse gliomas with histone H3 lysine27-to-methionine mutations (H3K27M-gliomas). Disclosed herein are gene signatures specific for tumor cell types and compositions for treatment of H3K27M gliomas. In one embodiment, PRC1 is targeted in a treatment regimen for H3K27M-gliomas.

Abstract: Described herein is a semiconductor structure, comprising: a drain region; a drift region comprised of a wide band gap material disposed over the drain region; and a channel structure disposed over the drift region. In some embodiments, the channel structure comprises: an optically active material disposed over the drift region, wherein the optically active material generates charge carriers in response to an optical signal; and a source region disposed over the optically active material, wherein in an off state charge carriers in the optically active material are depleted to turn off the semiconductor structure, and in an on state charge carriers in the optically active material conduct a current in the semiconductor structure when an electric field is applied across the source region and drain region, causing the current to substantially flow directly between the source region and the drain region.

Abstract: Programmable photonic circuits of reconfigurable interferometers can be used to implement arbitrary operations on optical modes, providing a flexible platform for accelerating tasks in quantum simulation, signal processing, and artificial intelligence. A major obstacle to scaling up these systems is static fabrication error, where small component errors within each device accrue to produce significant errors within the circuit computation. Mitigating errors usually involves numerical optimization dependent on real-time feedback from the circuit, which can greatly limit the scalability of the hardware. Here, we present a resource-efficient, deterministic approach to correcting circuit errors by locally correcting hardware errors within individual optical gates. We apply our approach to simulations of large-scale optical neural networks and infinite impulse response filters implemented in programmable photonics, finding that they remain resilient to component error well beyond modern day process tolerances.

Abstract: Component errors prevent linear photonic circuits from being scaled to large sizes. These errors can be compensated by programming the components in an order corresponding to nulling operations on a target matrix X through Givens rotations X?T†X, X?XT†. Nulling is implemented on hardware through measurements with feedback, in a way that builds up the target matrix even in the presence of hardware errors. This programming works with unknown errors and without internal sources or detectors in the circuit. Modifying the photonic circuit architecture can reduce the effect of errors still further, in some cases even rendering the hardware asymptotically perfect in the large-size limit. These modifications include adding a third directional coupler or crossing after each Mach-Zehnder interferometer in the circuit and a photonic implementation of the generalized FFT fractal.

Abstract: Described herein are systems, methods, and apparatus for automatically identifying and recovering individual cells of interest from a sample of biological matter, e.g., a biological fluid. Also described are methods of enriching a cell type of interest. These systems, methods, and apparatus allow for coordinated performance of two or more of the following, e.g., all with the same device, thereby enabling high throughput: cell enrichment, cell identification, and individual cell recovery for further analysis (e.g., sequencing) of individual recovered cells.

Abstract: The systems, devices, and methods presented herein use a heart pump to obtain measurements of cardiovascular function. The heart pumps described herein can operate in parallel with and unload the heart. The system can quantify the functioning of the native heart by measuring certain parameters/signals such as pressure or motor current, then calculate and display one or more metrics of cardiovascular function. These metrics, such as left ventricular end diastolic pressure (LVEDP), left ventricular pressure, and contractility, provide valuable information to a user regarding a patient's state of heart function and recovery.

Abstract: The present disclosure provides new prime editor guide RNAs for prime editing, constructs for prime editing, and methods for using same. In addition, the present disclosure provides compositions and methods for conducting prime editing of a target DNA molecule (e.g., a genome) that enables the incorporation of a nucleotide change and/or targeted mutagenesis (e.g., insertion or deletion). The nucleotide change can include a single-nucleotide change (e.g., any transition or any transversion), an insertion of one or more nucleotides, or a deletion of one or more nucleotides. More in particular, the disclosure provides fusion proteins comprising nucleic acid programmable DNA binding proteins (napDNAbp) and a polymerase (e.g., reverse transcriptase), which is guided to a specific DNA sequence by a prime editor RNA (PEgRNA).

Abstract: A method of polynucleotide synthesis includes a series of enzymatic reactions for restriction, ligation, and amplification using a machine and system that provide efficient droplet-based reactions. The method enables hierarchical assembly with minimal handling in order to address challenges associated with traditional polynucleotide synthesis methods, such as high cost, limited throughput, long synthesis times, and limited ability to synthesize long sequences.

Abstract: Meta-optic systems are described that include multi-function metasurfaces formed from a plurality of meta-atoms. A multi-function metasurface can exhibit two or more different optical functions for two or more different states of light incident on the metasurface. Different states of light include different polarizations, different wavelengths, and different angles of incidence. Different optical functions include distance sensing, converging, diverging, image formation, and patterned light formation. The multi-function metasurface can selectively impart different phase profiles to an incident beam depending on the incident beam's state of light.

Abstract: Described are concepts, systems, structures and techniques for metal filling an open channel (12) in a baseplate (19). In embodiments, metal filling of an open baseplate channel is achieved using vacuum pressure impregnation (VPI). In embodiments, a compression plate (14a) is disposed over an open baseplate channel (12) to be filled with a molten metal. In embodiments, gaskets (97) are disposed between the compression plate (14a) and a surface of the baseplate (10) proximate the baseplate channel (12). In embodiments, a channel cap (26) is disposed over the open channel. In embodiments, the channel cap (26) has a solder flow channel (29, 32) provided in a surface thereof. In the embodiments, the solder flow channel (29, 32) has a meandering shape. In embodiments, a solder flow channel (29, 32?) is provided in the compression plate (14a) and/or the baseplate (10).

Abstract: A system comprising a processor and a non-transitory computer-readable medium communicatively coupled to the processor is provided. The medium stores instructions configured to cause the processor to perform operations including receiving, from a user, a search request comprising one or more keywords related to a desired item, determining that the user is a participant in a closed-loop recycling program based on a user setting, identifying, based on the determination and the keywords, one or more item results, at least one qualifying result of the one or more item results having a packaging meeting a predetermined level of recyclability, and providing to the user in a prioritized manner, the at least one qualifying result.

Abstract: Provided herein are oligonucleotides, trimeric peptides, and peptide-oligonucleotide-conjugates. Also provided herein are methods of treating a muscle disease in a subject in need thereof, comprising administering to the subject oligonucleotides, trimeric peptides, and peptide-oligonucleotide-conjugates described herein.

Abstract: Systems and methods for predicting a trajectory of a moving object are disclosed herein. One embodiment downloads, to a robot, a probabilistic hybrid discrete-continuous automaton (PHA) model learned as a deep neural network; uses the deep neural network to infer a sequence of high-level discrete modes and a set of associated low-level samples, wherein the high-level discrete modes correspond to candidate maneuvers for the moving object and the low-level samples are candidate trajectories; uses the sequence of high-level discrete modes and the set of associated low-level samples, via a learned proposal distribution in the deep neural network, to adaptively sample the sequence of high-level discrete modes to produce a reduced set of low-level samples; applies a sample selection technique to the reduced set of low-level samples to select a predicted trajectory for the moving object; and controls operation of the robot based, at least in part, on the predicted trajectory.

Abstract: Disclosed herein are circular zymogens of RNase 1 that have a proteolytic cleavage site and are activated by a specific protease. These circular zymogens are useful for treatment of disorders that are characterized by a specific protease (e.g., HTV-1 protease).

Abstract: The invention provides for systems, methods, and compositions for altering expression of target gene sequences and related gene products. Provided are structural information on the Cas protein of the CRISPR-Cas system, use of this information in generating modified components of the CRISPR complex, vectors and vector systems which encode one or more components or modified components of a CRISPR complex, as well as methods for the design and use of such vectors and components. Also provided are methods of directing CRISPR complex formation in eukaryotic cells and methods for utilizing the CRISPR-Cas system. In particular the present invention comprehends optimized functional CRISPR-Cas enzyme systems. In particular the present invention comprehends engineered new guide architectures and enzymes to be used in optimized Staphylococcus aureus CRISPR-Cas enzyme systems.

Abstract: Aspects of the disclosure relate to non-naturally occurring constructs for the activation of Shank3 gene expression, AAV vectors comprising the constructs, and gene therapy methods.

Abstract: A method for operation of AOFP circuits includes accepting data arriving at any phase of a clock cycle, synchronizing the data to a known phase of a subsequent clock cycle, and providing the synchronized data to an AQFP circuit during the known phase of the subsequent clock cycle. The accepting and synchronizing of the data may be performed by a phase synchronizer and/or by a token-passing circuit. An asynchronous AOFP device includes at least one AQFP circuit and an activation phase synchronizer and/or token-passing circuit. The phase synchronizer may comprise a multiplexed array of QFP Buffers that samples each input phase of the clock cycle through a weak constant zero cell and outputs the logical OR of all input clock phases, propagating an input signal on any activation phase to a first phase output of the next activation cycle.

Abstract: Articles and systems for dark microscopy and related methods are generally described.

Abstract: Computational and functional analysis identified the neuropeptide receptor Nmur1 as selectively expressed on Type 2 innate lymphoid cells (ILC2s). While both IL-33 and IL-25 promote ILC activation in vivo, IL-33 induces robust ILC proliferation, whereas ILCs activated with IL-25 do not proliferate as robustly and up-regulate Nmur1 expression. Treatment with neuromedin U (NMU), the neuropeptide ligand of Nmur1, had little effect on its own. Co-administration of IL-25 with NMU, however, dramatically amplified allergic lung inflammation and induced the proliferation and expansion of specific ILC2 subsets, characterized by a molecular signature unique to pro-inflammatory ILC2s. The results demonstrate that Nmur1 signaling strongly modulates IL-25-mediated ILC2 responses, resulting in highly proliferative pro-inflammatory ILCs, and highlights the importance of neuro-immune crosstalk in allergic inflammatory responses at mucosal surfaces.