Abstract: The present disclosure provides compositions comprising a lyn kinase activator and TRPM8 agonist, and to methods of: reducing blood glucose levels, weight gain, or fat depot levels; treating metabolic syndrome, Syndrome X, obesity, prediabetes, type II diabetes, type I diabetes; treating hypercholesterolemia, hypertension, coronary heart disease, diabetic neuropathy, lipodystrophy, diabetic retinopathy, erectile dysfunction, kidney disease, dyslipidemia, dyslipoproteinemia, a peroxisome proliferator activated receptor-associated disorder, septicemia, a thrombotic disorder, or pancreatitis; inducing the beiging of adipocytes; and preventing pancreatic beta cell degeneration.

Abstract: Aspects of the disclosure relate to compositions, systems, and methods for evolving nucleic acids and proteins utilizing continuous directed evolution in the periplasm of a host cell. In some embodiments, the methods comprise passing a nucleic acid from cell-to-cell in a desired, function dependent manner. The linkage of the desired function and passage of the nucleic acid from cell-to-cell allows for continuous selection and mutation of the nucleic acid.

Abstract: In some embodiments, a mass spectrometry tag may comprise a linker region, a mass balance region, and a reporter region. The mass spectrometry tag may be configured to fragment in a mass spectrometer via an energy dependent process to produce multiple reporter molecules. For example, the reporter region of the tag may be configured to produce at least two reporter molecules via fragmentation. In some embodiments, one or more regions of the tag may comprise at least one heavy isotope. In some such embodiments, the ability to fragment into multiple reporter molecules as well as the placement and/or number of heavy isotope(s) allows the mass spectrometry tag to be distinguished from other similar mass spectrometry tags. In some such embodiments, the ability to distinguish between tags having the same or substantially similar total mass to charge ratio and reporter region mass may allow the system to have a greater multiplexing capacity than conventional systems.

Abstract: Provided herein are systems, compositions, kits, and methods for the suppression of pain (e.g., chronic pain). Genes encoding ion channels (e.g., SCN9A) responsible for the propagation pain signals in neurons (e.g., DRG neurons) may be edited using a genome editing agent (e.g., a nucleobase editor). In some embodiments, loss-of-function ion channel mutants are generated, leading to pain suppression. In some embodiments, the genome editing agent is administered locally to the site of pain or to the nerves responsible for propagation of the pain signal.

Abstract: Acute myeloid leukemia (AML) is a clonal disorder of hematopoietic stem and progenitor cells. It is a devastating disease with a poor prognosis and an average 5-year survival rate of about 30%. Disclosed herein are composition and methods for treating leukemia with a biomaterial comprising a polymer scaffold, a dendritic cell activating factor, a dendritic cell recruitment factor, and at least one leukemia antigen. The biomaterial-based vaccine disclosed herein promotes a potent, durable and transferable immune response against acute myeloid leukemia to prevent cell engraftment and synergizes with chemotherapy to prevent relapse.

Abstract: The present invention generally relates to microscopy, and to systems and methods for imaging or determining nucleic acids or other desired targets, for instance, within cells. In certain aspects, a sample is contained within an expandable material, which is expanded and imaged in some fashion. Expansion of the material improves the effective resolution of the subsequent image. This may be combined, for example, with other super-resolution techniques, such as STORM, and/or with techniques such as MERFISH for determining nucleic acids such as mRNA within the sample, for example, by binding nucleic acid probes to the sample. Other aspects are generally directed to compositions or devices for use in such methods, kits for use in such methods, or the like.

Abstract: The disclosure provides amino acid sequence variants of Botulinum neurotoxin (BoNT) proteases that cleave (VAMP1, VAMP2, VAMP7, VAMP8, SNAP25, SNAP23, PTEN, etc.) and methods of evolving the same. In some embodiments, proteases described by the disclosure are useful for cleaving proteins found in a cell, that is in an intracellular environment. In some embodiments, proteases described by the disclosure are useful for treating diseases associated with increased or aberrant VAMP7, VAMP8, SNAP23 or PTEN expression or activity, for example, cancer and neurological disorders. Some aspects of this disclosure provide methods for generating BoNT protease variants by continuous directed evolution.

Abstract: Transcriptomes of individual neurons provide rich information about cell types and dynamic states. However, it is difficult to capture rare dynamic processes, such as adult neurogenesis, because isolation from dense adult tissue is challenging, and markers for each phase are limited. Here, Applicants developed Nuc-seq, Div-Seq, and Dronc-Seq. Div-seq combines Nuc-Seq, a scalable single nucleus RNA-Seq method, with EdU-mediated labeling of proliferating cells. Nuc-Seq can sensitively identify closely related cell types within the adult hippocampus. Div-Seq can track transcriptional dynamics of newborn neurons in an adult neurogenic region in the hippocampus. Dronc-Seq uses a microfluidic device to co-encapsulate individual nuclei in reverse emulsion aqueous droplets in an oil medium together with one uniquely barcoded mRNA-capture bead. Finally, Applicants found rare adult newborn GABAergic neurons in the spinal cord, a non-canonical neurogenic region.

Abstract: The present invention provides a robotic locomotive device (1) that is capable of driving itself forwards and backwards, anchoring and steering itself whilst inside a tubular structure (200), for example, the human colon, or any structure comprising two opposing walls (202, 204). In this respect, the device is made up of two or three segments (102, 104, 106) covered in an elastic material and driven by an internal actuating mechanism. All of the segments (102, 104, 106) have a concertina configuration that enable a shortening and lengthening motion. As well as contracting and extending in length, at least one of the end segments (102, 106) is capable of bending at an angle away from the longitudinal axis such that it becomes wedged or jammed between the walls (202, 204) of the tubular structure (200). That is, the end segments (102, 106) are capable of both a bending action and a contracting and extending action.

Abstract: A system and a method for predicting susceptibility of genus Klebsiella to amikacin are provided. The system includes a calculating unit containing a computer-readable storage medium stored with a computer program; the computer program is used to, when is executed by a processor, implement a calculation method for an Exp(?k) power value, and the calculation method for the Exp(?k) power value includes: step 1, calculating a k value according to formula I; and step 2, calculating the Exp(?k) power value with an Euler's constant e as a base and a ?k value as an exponential; and C1 to C5 are respectively copy numbers of an arr-2 gene, an acrB gene, an armA gene, an oqxB gene, and a rmtB gene in to-be-predicted Klebsiella strains. When the method and the system are adopted to predict the susceptibility of the genus Klebsiella to amikacin, an accuracy rate is about 98.8%.

Abstract: An imaging apparatus for imaging a sample (7) comprises an array of electronically addressable pixels (6) wherein each pixel is arranged to support a surface plasmon resonance therein to generate an evanescent electromagnetic field. This field extends transversely from the pixel so as to be salient from the array at a first side of the array for illuminating the sample at said first side. A light source (15) is arranged to illuminate the array with excitation light therewith to generate said surface plasmon resonance. An optical detector (12A, 12B, 12C) is arranged at a second side of the array which is opposite to said first side of the array for detecting optical radiation returned from the array in response to illumination of the array by said excitation light. A processing unit (4) is arranged to associate the detected optical radiation with the address of the pixel or pixels within the array at which the surface plasmon resonance was generated.

Abstract: Cellulose nanofibers (CNF) act as a dispersing agent to directly exfoliate graphite in an aqueous solution using sonication. The resulting suspension has graphite flakes, each having 2-20 monolayers, a relatively large lateral dimension, and a plurality of CNF decorating its surfaces and edges. The dispersing effect of the CNF allows the graphite-CNF suspension to be stored without degradation until desired use. The graphite-CNF suspension can be used to form various composite structures, such as by spraying, coating, pouring, extruding, or printing the suspension, and then drying the suspension. The resulting composite structures have improved tensile strength and toughness due to hydrogen bond interactions between the CNF and graphite.

Abstract: A method comprising applying an object recognition pipeline to frames of video data. The object recognition pipeline provides a mask output of objects detected in the frames. The method includes fusing the mask output of the object recognition pipeline with depth data associated with the frames of video data to generate a map of object instances, including projecting the mask output to a model space for the map of object instances using a camera pose estimate and the depth data. An object instance in the map of object instances is defined using surface-distance metric values within a three-dimensional object volume, and has an object pose estimate indicating a transformation of the object instance to the model space. The object pose estimate and the camera pose estimate form nodes of a pose graph for the map of model instances.

Abstract: The present application provides methods for preparing soluble lipidated ligand agents comprising a ligand entity and a lipid entity, and in some embodiments, provides relevant parameters of each of these components, thereby enabling appropriate selection of components to assemble active agents for any given target of interest.

Abstract: A transdermal formulation for the delivery of one or more active agents to a subject is provided. The formulation can be applied to the treatment of various diseases or conditions associated with an elevated CD38 level.

Abstract: The present invention generally relates to systems and methods for imaging or determining nucleic acids or other desired targets, for instance, within cells or tissues. In one aspect, a sample is exposed to a plurality of nucleic acid probes that are determined within the sample. In some cases, however, background fluorescence or off-target binding may make it more difficult to determine properly bound nucleic acid probes. Accordingly, other components of the samples that may be contributing to the background, such as proteins, lipids, and/or other non-targets, may be “cleared” from the sample to improve determination. However, in certain embodiments, nucleic acids or other desired targets may be prevented from also being cleared, e.g., using polymers or gels within the sample. Other aspects are generally directed to compositions or kits involving such systems, methods of using such systems, or the like.

Abstract: A bioink for extrusion-based printing includes an extracellular matrix (ECM) precursor comprising an uncrosslinked polymer, and sacrificial microparticles dispersed in the ECM precursor. The sacrificial microparticles have a melting temperature above a crosslinking temperature of the uncrosslinked polymer. A method of fabricating a tissue/organ model or therapeutic construct comprises extruding a bioink comprising a first ECM precursor and first sacrificial microparticles through a nozzle moving relative to a deposition bath, and depositing an extruded filament comprising the bioink into the deposition bath as the nozzle moves. After deposition, the first ECM precursor is crosslinked to form a first ECM material, and after the crosslinking, the first sacrificial microparticles are melted to form pores in the first ECM material. The pores may have a width or diameter comparable to that of individual cells.

Abstract: The invention provides ultrasensitive methods for detection and quantification of target analytes in samples. The methods can be multiplexed to allow simultaneous detection and quantification of multiple target analytes. The methods can achieve an attomolar limit of detection. The invention also provides related compositions and kits.

Abstract: Provided herein are engineered nucleic acids (e.g., expression vectors, including viral vectors, such as lentiviral vectors, adenoviral vectors, AAV vectors, herpes viral vectors, and retroviral vectors) that encode OCT4; KLF4; SOX2; or any combination thereof that are useful, for example, in inducing cellular reprogramming, tissue repair, tissue regeneration, organ regeneration, reversing aging, or any combination thereof. Also provided herein are recombinant viruses (e.g., lentiviruses, alphaviruses, vaccinia viruses, adenoviruses, herpes viruses, retroviruses, or AAVs) comprising the engineered nucleic acids (e.g.

Abstract: Disclosed are kits and methods for detecting the presence of tumor sites that are active in tumor cell dissemination and uses thereof for determining the risk of tumor cells undergoing hematogenous metastasis, for assessing the prognosis of a subject undergoing treatment for a localized tumor, for determining a course of treatment for a localized tumor, and for identifying agents to treat or prevent hematogenous metastasis.