Abstract: An optical component comprises a metasurface comprising nanoscale elements. The metasurface is configured to receive incident light and to generate optical outputs. The geometries and/or orientations of the nanoscale elements provide a first optical output upon receiving a polarized incident light with a first polarization, and provide a second optical output upon receiving a polarized incident light with a second polarization that is different from the first polarization.

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 CRJSPR-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 CR.ISPR-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: As described below, the present invention features compositions, panels of biomarkers, and methods for characterizing chronic lymphocytic leukemia (CLL) for prognosis and selection of a subject for a treatment and/or inclusion in a clinical trial.

Abstract: Described herein are polypeptides, compositions, kits, and analyte detection systems for the detection of the presence or absence of small molecules (e.g. histamine and/or histidine) in a test sample.

Abstract: Described herein are methods of generating a programmable multicellular organoid and/or a 3D organ-specific tissue. Also, described are the programmable multicellular organoid and/or a 3D organ-specific tissue produced by the described methods. Also, described herein are in vitro methods of generating functional human tissue construct.

Abstract: The present invention generally relates to systems and methods for imaging or determining nucleic acids, for instance, within cells. In some embodiments, the transcriptome of a cell may be determined. Certain embodiments are directed to determining nucleic acids, such as mRNA, within cells at relatively high resolutions. In some embodiments, a plurality of nucleic acid probes may be applied to a sample, and their binding within the sample determined, e.g., using fluorescence, to determine locations of the nucleic acid probes within the sample. In some embodiments, codewords may be based on the binding of the plurality of nucleic acid probes, and in some cases, the codewords may define an error-correcting code to reduce or prevent misidentification of the nucleic acids. In certain cases, a relatively large number of different targets may be identified using a relatively small number of labels, e.g., by using various combinatorial approaches.

Abstract: The invention provides agents that inhibit L-Phe in cytoplasmic phenylalanine tRNA-synthetase (cFRS), methods for identifying them, compositions comprising such agents, and therapeutic methods of using such agents.

Abstract: Provided herein are methods and compositions related to the treatment of a neurodegenerative disease or an ocular disease.

Abstract: Some aspects of this disclosure provide compositions, methods, systems, and kits for controlling the activity of RNA-programmable endonucleases, such as Cas9, or for controlling the activity of proteins comprising a Cas9 variant fused to a functional effector domain, such as a nuclease, nickase, recombinase, deaminase, transcriptional activator, transcriptional repressor, or epigenetic modifying domain. For example, the inventive proteins provided comprise a ligand-dependent intein, the presence of which inhibits one or more activities of the protein (e.g., gRNA binding, enzymatic activity, target DNA binding). The binding of a ligand to the intein results in self-excision of the intein, restoring the activity of the protein.

Abstract: The present invention generally relates to systems and methods for imaging or determining nucleic acids, for instance, within cells. In some embodiments, the transcriptome of a cell may be determined. Certain embodiments are directed to determining nucleic acids, such as mRNA, within cells at relatively high resolutions. In some embodiments, a plurality of nucleic acid probes may be applied to a sample, and their binding within the sample determined, e.g., using fluorescence, to determine locations of the nucleic acid probes within the sample. In some embodiments, codewords may be based on the binding of the plurality of nucleic acid probes, and in some cases, the codewords may define an error-correcting code to reduce or prevent misidentification of the nucleic acids. In certain cases, a relatively large number of different targets may be identified using a relatively small number of labels, e.g., by using various combinatorial approaches.

Abstract: The instant specification provides for evolved base editors which overcome deficiencies of those in art (including increased efficiency and/or decreased requirement for specific sequence-context at an editing site) and which are obtained a result of a phage-assisted continuous evolution (PACE) system. In particular, the instant specification provides for evolved cytidine base editors (e.g., based on APOBEC1, CDA, or AID cytidine deaminase domains) which overcome deficiencies of those in art (including increased efficiency and/or decreased requirement for specific sequence-context at an editing site) and which are obtained a result of a phage-assisted continuous evolution (PACE) system.

Abstract: The technology described herein is directed to methods, kits, compositions, and systems for detecting a target RNA, such as a small amount of viral RNA. In one aspect, described herein are methods of detecting the target RNA, using primers comprising at least one barcode region. In other aspects, described herein are kits, compositions, and systems suitable to practice the methods described herein to detect the target RNA.

Abstract: A device includes a first mode converter and a second mode converter that define a region between the first mode converter and the second mode converter. The region can contain a plurality of orthogonal modes of a wave. The wave, when sent from outside the region and when propagating from the first mode converter towards the second mode converter, can include a first mode of the plurality of orthogonal modes. The second mode converter can convert the wave from the first mode of the plurality of orthogonal modes, to a second mode of the plurality of orthogonal modes that is different from the first mode. The first mode converter can convert the wave to the first mode of the plurality of orthogonal modes.

Abstract: Provided herein, in some embodiments, are artificial secretion peptides capable of directing secretion from Lactobacillus for use, for example, in producing heterologous proteins, including therapeutic proteins.

Abstract: The technology described herein is directed to an anterior nares swab that is automation compatible. In one aspect, the swab comprises a cap, a threaded portion, a neck, and a sample collection head. The cap can be integrally and/or monolithically formed with any one or more of the threaded portion, the neck, and the sample collection head; or can be removably coupled to any one or more of the threaded portion, the neck, and the sample collection head. In additional aspects, described herein are kits comprising said swabs and methods of using said swabs.

Abstract: Systems and methods related to the operation of wearable robotic systems are disclosed. In one embodiment, a wearable robotic system may be calibrated by correlating a measured joint angle and an actuation pressure. In another embodiment, a wearable robotic system may be operated to provide gravity compensation by operating one or more actuators of the system based on an estimated current pose of a first body portion associated with a joint and calibration parameters of the system to support at least a portion of a weight of the first body portion.

Abstract: Described herein are compositions and methods for inducing Type I interferon production. The compositions described comprise immunostimulatory oligonucleotide duplexes including a 5? terminal monophosphate-CUGA-3? (SEQ ID NO. 1) sequence. Compositions comprising the immunostimulatory oligonucleotide duplexes described can be used for the treatment of diseases or disorders that respond to interferons.

Abstract: The present disclosure provides adenine base editors (ABEs) that are variants of known adenine base editors. The adenosine deaminase domain of a known ABE was modified to produce adenosine deaminase variants. The deaminase variants provided herein have broader compatibility with diverse napDNAbp domains, such as Cas homologs, for base editing applications. The ABEs provided herein comprise a deaminase variant and a napDNAbp domain. The ABEs provided herein exhibit reduced off-target editing effects while retaining high on-target editing efficiencies. These ABEs exhibit reduced off-target DNA editing effects and reduced off-target editing effects in cellular mRNA. In addition, methods for targeted nucleic acid editing are provided. Further provided are pharmaceutical compositions comprising the ABEs. Also provided are vectors and kits useful for the generation and delivery of the ABEs, including vector systems for engineering the ABEs through directed evolution.

Abstract: Methods, systems, compositions and strategies for the use of ARMM-mediated delivery of molecules (e.g., biological molecules, small molecules, proteins, and nucleic acids (e.g., DNA, RNA), DNA plasmids shRNA, mRNA) to cells of the nervous system (e.g., central nervous system and peripheral nervous system).

Abstract: Systems and methods are disclosed to objectively identify sub-second behavioral modules in the three-dimensional (3D) video data that represents the motion of a subject. Defining behavioral modules based upon structure in the 3D video data itself—rather than using a priori definitions for what should constitute a measurable unit of action—identifies a previously-unexplored sub-second regularity that defines a timescale upon which behavior is organized, yields important information about the components and structure of behavior, offers insight into the nature of behavioral change in the subject, and enables objective discovery of subtle alterations in patterned action. The systems and methods of the invention can be applied to drug or gene therapy classification, drug or gene therapy screening, disease study including early detection of the onset of a disease, toxicology research, side-effect study, learning and memory process study, anxiety study, and analysis in consumer behavior.