Abstract: Disclosed are compounds, methods, reagents, systems, and kits for the preparation and utilization of monomeric or polymeric metal-based compounds. These metal-based compounds are organometallic catalysts composed of substituted dipyrrin ligands bound to transition metals. C—H bond functionalization catalysis can be performed with the disclosed organometallic catalysts to yield C—N bonds to generate substituted bicyclic, spiro, and fused nitrogen-containing heterocycles, all common motifs in various pharmaceutical and bioactive molecules.

Abstract: Described herein are targeting moieties that can be capable of specifically targeting muscle cells and can include an n-mer motif. In some embodiments, the n-mer motif contains an RGD motif. Also described herein are vector systems, particles, polypeptides that can encode and/or contain one or more targeting moieties. Also described herein are methods of delivering a cargo to a cell, such as a muscle cell, using one or more of the targeting moieties described herein.

Abstract: Some aspects of this disclosure provide strategies, methods, and reagents for determining nuclease target site preferences and specificity of site-specific endonucleases. Some methods provided herein utilize a novel “one-cut” strategy for screening a library of concatemers comprising repeat units of candidate nuclease target sites and constant insert regions to identify library members that can been cut by a nuclease of interest via sequencing of an intact target site adjacent and identical to a cut target site. Some aspects of this disclosure provide strategies, methods, and reagents for selecting a site-specific endonuclease based on determining its target site preferences and specificity. Methods and reagents for determining target site preference and specificity are also provided.

Abstract: Small molecules acting through the ligand binding domain of nuclear receptor TLX (NR2E1) are disclosed, as well as the use thereof for promoting neurogenesis and treating disorders associated with nuclear receptor TLX, including neurological disorders such as Alzheimer's disease. In certain embodiments, the invention provides compounds according to Formula II as described herein, and pharmaceutically acceptable salts or isomers thereof.

Abstract: Genetic circuits that control transgene expression in response to pre-defined transcriptional cues would enable the development of smart therapeutics. The present disclosure relates to engineered programmable single-transcript RNA sensors in which adenosine deaminases acting on RNA (ADARs) autocatalytically convert trigger hybridization into a translational output. This system amplifies the signal from editing by endogenous ADAR through a positive feedback loop. Amplification is mediated by the expression of a hyperactive, minimal ADAR variant and its recruitment to the edit site via an orthogonal RNA targeting mechanism. This topology confers high dynamic range, low background, minimal off-target effects, and a small genetic footprint. The circuits and systems disclosed herein leverage an ability to detect single nucleotide polymorphisms and modulate translation in response to endogenous transcript levels in mammalian cells.

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: A fluidized solidified soil based on gold tailings includes the following raw materials in parts by mass: 75 parts to 80 parts of gold tailings, 5.2 parts to 13 parts of a dispersant solution, and 9 parts to 16 parts of a solidifying material. A preparation method includes the following steps: mixing the gold tailings with the dispersant solution, and then stirring to obtain a suspension slurry of the gold tailings; and adding the solidifying material, and stirring to obtain the fluidized solidified soil. In the present disclosure, the gold tailings are used as a main material, combined with a special dispersant solution and a special solidifying material, and a fluidized solidified soil is prepared with fluidity suitable for pumping and a certain strength after hardening. The fluidized solidified soil prevents the pollution caused by gold tailings landfilling, and can be used as a filling material for various construction projects.

Abstract: Disclosed are highly active cationic cobalt phosphine complexes, both mono- and bimetallic, that can catalyze hydroformylation reactions. The disclosed catalysts can be utilized in methods that provide reaction processes that are hundreds of times faster than high pressure HCo(CO)4 or phosphine-modified HCo(CO)3(PR3) catalysts and operate at considerably lower pressures and temperatures. Also disclosed are methods of hydroformylation using the described transition metal complexes. 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 disclosure.

Abstract: Proteins, nucleic acids encoding the proteins, compositions comprising the proteins, and methods are provided. The proteins have the ability to be self-targeted to ICAM-1 and, if desired, enzymatically-released at acidic pH. The ICAM-1-targeting peptides are provided as single copies or multiples repeats, and can be separated by linkers from the enzyme segment, from which the ICAM-1 targeting peptides can be released, if desired, at acidic pH. These fusion proteins enhance the activity of the enzyme segment within or liberated from the fusion protein, and provide increased recognition and targeting of diseased organs, transport from the bloodstream across the endothelium into said diseased organ, and intracellular uptake and lysosomal trafficking by cells in them, both in peripheral tissues and the central nervous system. Representative nucleotide and amino acid sequences of these fusion proteins, as well as in vitro, cellular, and in vivo animal data are provided.

Abstract: Provided herein are methods, systems, kits, and compositions useful for determining small molecule-protein interactions and protein-protein interactions. The photo-click tags provided herein can be conjugated to a small molecule or amino acid analog to provide compounds that can be integrated into a protein through photo-conjugation, allowing for identification of a small molecule-protein interaction or protein-protein interaction to elucidate the small molecules mechanism of action or the protein targeted by the small molecule. In some embodiments, the photo-click tags comprise a photo-conjugation moiety and a click chemistry handle, allowing for the attachment of various functional groups (e.g., affinity tags) to the small molecule or amino acid analog.

Abstract: Methods and apparatus for modulating light using a tunable light modulation device. The tunable light modulation devices comprises an elastomer structure including at least one elastomer layer, a compliant electrode network of conducting fibers arranged on a first surface of the at least one elastomer layer, a patterned electric conductor arranged on a second surface of the at least one elastomer layer opposite the first surface. The patterned electric conductor includes a plurality of individually-addressable sections, and the compliant electrode network is configured to compress the at least one elastomer layer in the presence of an electric field between the compliant electrode network and one or more of the individually-addressable sections of the patterned electric conductor to produce a voltage-dependent roughening of the at least one elastomer layer.

Abstract: The present disclosure provides systems, compositions, and methods for simultaneously editing both strands of a double-stranded DNA sequence at a target site to be edited. Further provided herein are pharmaceutical compositions, polynucleotides, vectors, cells, and kits for simultaneously editing both strands of a double-stranded DNA sequence.

Abstract: A medical instrument port is described for use with a surgical mask or other protective face covering. The medical instrument port provides a sealed pathway through which a medical instrument can be passed without exposing the clinician to aerosolized droplets expelled from the patient's respiratory system when the medical instrument is introduced into the patient's nasal and/or oral passages.

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: An apparatus for measuring a characteristic of a sample using a centrifuge and optical components is disclosed. The centrifuge may be a standard benchtop centrifuge. The optical components may be sized and dimensioned to fit, along with the sample, inside the centrifuge.

Abstract: A set of interlocking blocks consists a plurality of first blocks and a plurality of second blocks capable of forming kinematic interlock. Each of the first blocks and second blocks comprise at least one male joint and female joint for mating with its counterpart. The motion of the first blocks and second blocks are constrained by joints. Subsequent first blocks and/or second blocks reinforce and immobilize prior first blocks and/or second blocks. Assembly of an interlock structure consisting the set of interlocking blocks may be performed via translation motions.

Abstract: A system for training a neural network includes a neural network configured to receive a training input in an image space and produce an enhanced image. The system further includes an error signal generator configured to compare the enhanced image to a ground truth and generate an error signal that is communicated back to the neural network to train the neural network. Additionally, the system includes a neural input enhancer configured to modify the training input in response to receiving at least one of an output from the neural network or the error signal. Modifying the training input improves one of an efficiency or a training result of the neural network beyond the communication of the error signal to only the neural network.

Abstract: The present disclosure generally relates to systems and methods for multi-focal imaging, for example, for determining nucleic acids in cells or other samples. In some cases, multiple focal planes may simultaneously be determined, e.g., by using a plurality of detectors, such as a plurality of cameras, which image the same sample, but at least some of which are focused on different focal planes within the sample. Thus, the sample may be imaged in 3 dimensions, e.g., without sample refocusing. In certain cases, this may improve the resolution of imaging, in space and/or time. Various embodiments can be used to increase imaging throughput and/or resolution in image-based approaches, e.g., for single-cell molecular profiling such as multiplexed error robust fluorescence in situ hybridization (MERFISH), or for other applications.

Abstract: The present invention generally relates to a controlled fluidic device to develop spatially complex environments to enhance the rate of evolution in cell populations. The method further provides an enhanced understanding in the emergence, for example, drug resistance during cancer chemotherapy.

Abstract: In ultra-wideband or impulse radio terahertz wireless communication, the electromagnetic signal may experience group delay dispersion (GDD). Without correction, this can degrade the achievable data transmission rate. An apparatus comprising a stratified structure having a front portion and a back portion is disclosed. The structure comprises a plurality of adjacent layers of differing refractive indices, wherein each layer has a refractive index different from an immediately adjacent layer. The structure further includes a backing layer at the back portion. The structure defines a GDD, which can be adjusted, and the structure is configured to introduce the GDD to an incident electromagnetic signal and thereby produce a dispersion-compensated electromagnetic signal when the incident signal is reflected by the structure. The GDD of the structure is configured to substantially cancel out the dispersive effects experienced by the electromagnetic signal in the signal path.