Abstract: Methods and compositions for digital profiling of nucleic acid sequences present in a sample are provided.

Abstract: An insertable catheter device includes a shaft including a proximal end and a distal end, an expandable balloon, and an actuator configured to expand and retract the expandable balloon. The actuator includes a fluid conduit that extends through the shaft and is coupled with the expandable balloon to enable inflation and retraction of the expandable balloon via injection or withdrawal of a fluid to or from the expandable balloon via the fluid conduit. The expandable balloon is displaceably retractable into the shaft and extendable from the shaft. A fluid pump is coupled with the fluid conduit to pump the fluid through the fluid conduit. A patch is positioned to be displaced by the expandable balloon when the expandable balloon is inflated, and the expandable balloon is displaceably retractable into the shaft and displaceably extendable from the shaft.

Abstract: The present invention provides reagents and methods for breast cancer detection.

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, wherein the guide sequence is modified by secondary structure to increase the specificity of the CRISPR-Cas system and whereby the secondary structure can protect against exonuclease activity and allow for 5? additions to the guide sequence.

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.

Abstract: Some aspects of this disclosure relate to systems, apparatuses, compositions (e.g., isolated nucleic acids and vectors), and methods for improving the stability and/or solubility of proteins evolved using phage-assisted continuous evolution (PACE). In some embodiments, vectors described herein comprise nucleic acids encoding selection systems (e.g., positive and/or negative selection systems) that link expression of genes required for production of infectious phage particles to a desirable physiochemical (e.g., stability or solubility) and/or desired function of an evolved protein.

Abstract: Provided herein are methods of preparing new 14-membered ketolides via coupling of an eastern and western half moiety, followed by macrocyclization, and optional functionalization. Intermediates in the synthesis of these ketolides including the eastern and western halves are also provided. Pharmaceutical compositions and methods of treating infectious diseases and inflammatory conditions using these ketolides are also provided.

Abstract: A strain sensor comprising a conductive member having a plurality of elements arranged adjacent to one another, and a non-conductive and elastically deformable material encapsulating the conductive member, wherein, in an equilibrium state, compressive forces cause at least one of the plurality of elements to contact at least a portion of an adjacent element, and wherein, when a strain is applied, a resulting elastic deformation causes at least one of the plurality of elements to space apart from an adjacent element such that the contacted portion decreases or is eliminated. A multi-axis force sensor comprising a sensing array comprising at least two planar sensors arranged radially on a planar substrate in antagonistic pairs, and a compressible member positioned between the substrate and a central portion of the sensing array, the compressible member acting to displace the central portion of the sensing array away from the substrate.

Abstract: The disclosure provides methods, base editors, vectors encoding base editors and cognate gRNAs, and compositions and kits comprise said components, for installing nucleobase edits to the SMN2 locus to increase the activity and/or amount and/or stability of SMN2 protein in a cell, thereby treating Spinal Muscular Atrophy. In certain aspect, the disclosure provides compositions and methods to edit C840T of exon 7 of the SMN2 gene, or installing another one or more nucleobase edits which have the effect of removing or inactivating a degron, such as the C-terminal portion of the region encoded by exon 6 or the 4-amino acid region encoded by exon 8 (i.e., the EMLA (SEQ ID NO: 466)-tail) so as to remove or limit their degron activity to reduce, mitigate, or eliminate the intracellular degradation of the SMN2 protein.

Abstract: The embodiments disclosed herein utilized RNA targeting effectors to provide a robust CRISPR-based diagnostic with attomolar sensitivity. Embodiments disclosed herein can detect broth DNA and RNA with comparable levels of sensitivity and can differentiate targets from non-targets based on single base pair differences. Moreover, the embodiments disclosed herein can be prepared in freeze-dried format for convenient distribution and point-of-care (POC) applications. Such embodiments are useful in multiple scenarios in human health including, for example, viral detection, bacterial strain typing, sensitive genotyping, and detection of disease-associated cell free DNA.

Abstract: Microfluidic structures and methods for manipulating fluids, fluid components, and reactions are provided. In one aspect, such structures and methods can allow production of droplets of a precise volume, which can be stored/maintained at precise regions of the device. In another aspect, microfluidic structures and methods described herein are designed for containing and positioning components in an arrangement such that the components can be manipulated and then tracked even after manipulation. For example, cells may be constrained in an arrangement in microfluidic structures described herein to facilitate tracking during their growth and/or after they multiply.

Abstract: Disclosed herein are universal donor stem cells and related methods of their use and production. The universal donor stem cells disclosed herein are useful for overcoming the immune rejection in cell-based transplantation therapies. In certain embodiments, the universal donor stem cells disclosed herein do not express one or more MHC-I and MHC-II human leukocyte antigens. Similarly, in certain embodiments, the universal donor stem cells disclosed herein do not express one or more human leukocyte antigens (e.g., HLA-A, HLA-B and/or HLA-C) corresponding to MHC-I and MHC-II human leukocyte antigens, thereby rendering such cells hypoimmunogenic.

Abstract: The technology described herein is directed to methods and compositions for inhibition of ClbP and the treatment and/or prevention of cancer, e.g., colorectal cancer, a urinary tract cancer, a squamous cell carcinoma, an oral squamous cell carcinoma, or a head-and-neck cancer.

Abstract: Disclosed are methods for detecting spatial proximity relationships between nucleic acid sequences in a cell. The methods include: providing a sample of one or more cells comprising nucleic acids; fragmenting the nucleic acids present in the cells, wherein the fragmented nucleic acids have ends capable of joining to other fragmented nucleic acids; joining ends of fragmented nucleic acids to other ends fragmented nucleic acid to create at least one nucleic acid concatemer having at least one junction between the joined fragmented nucleic acids, and wherein the at least one nucleic acid concatemer encodes the information about the proximity of the DNA sequences in the cell; and determining the sequence at least one junction of the at least one nucleic acid concatemer, thereby detecting spatial proximity relationships between nucleic acid sequences in a cell.

Abstract: The technology described herein is directed to adjuvants comprising ionic liquids, as well as compositions and methods utilizing or comprising such adjuvants.

Abstract: Described herein are compositions comprising polymers conjugated to at least one immunomodulator, e.g., a) a retinoid and an imidazoquinoline, b) a retinoid and a HDAC inhibitor, or c) a HDAC inhibitor and an imidazoquinoline. Further described herein are methods of using said compositions, e.g., in modulating immune responses and/or treating a disease such as cancer.

Abstract: The technology described herein is directed to compositions comprising CAGE and at least one active compound, e.g., for oral or parenteral administration.

Abstract: The present invention relates to clonal expansion of somatic cells in subjects, and acquired selective advantage of cell clones during the lifetime of a subject. In particular, the invention relates to methods for predicting the development of cancer based on the observation of specific genetic mutations in somatic cell clones, as well as to methods for treating or preventing cancer in a subject, in which clonal expansion of cells comprising specific modifications is observed.

Abstract: Methods and compositions for rejuvenating skeletal muscle stem cells are disclosed.

Abstract: 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. 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 modified guide RNA, named an PEgRNA.