Abstract: Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload promotes the expression or activity of a functional dystrophin protein. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide, e.g., an oligonucleotide that causes exon skipping in a mRNA expressed from a mutant DMD allele.

Abstract: Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload promotes the expression or activity of a functional dystrophin protein. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide, e.g., an oligonucleotide that causes exon skipping in a mRNA expressed from a mutant DMD allele.

Abstract: A system for indexing, updating, and search haplotypes for genetic genealogical discovery in genotype databases. The system includes a pool of genetic indexes, a haplotype ingestion engine, and a haplotype query engine. The haplotypes of a number of individuals in a genotype database are indexed by a pool of multiple panels, and each panel pool can be dynamically updated by the insertion or deletion of individual haplotypes. A genetic genealogical search of a query haplotype against the database is achieved by first projecting the query onto a subset of panels in the pool, then conducting long match queries over each panel, and finally aggregating the identified long matches into Identical-by-Descent segments, i.e., DNA matches, between the query and the haplotypes in the database.

Abstract: Provided are: a method for modifying a target nucleic acid in the genome of a cell using a novel PAM sequence; and a cell in which a target nucleic acid in the genome is modified thereby. Accordingly, genome editing can be performed by targeting a position that could not be previously targeted as a target for genome editing, and thus the range of applications of genome editing can be expanded.

Abstract: Methods, compositions, kits, and uses are provided herein for detecting a subject nucleic acid in various samples.

Abstract: Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload promotes the expression or activity of a functional dystrophin protein. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide, e.g., an oligonucleotide that causes exon skipping in a mRNA expressed from a mutant DMD allele.

Abstract: Disclosed herein are methods of treating cholangiocarcinoma in a patient comprising: evaluating a biological sample from the patient for the presence of one or more FGFR mutants including at least the mutation FGFR3 R397C; or one or more FGFR mutants including at least the mutation FGFR3 L608F; or one or more FGFR mutants including at least the fusion FGFR2-TACC2; and treating the patient with an FGFR inhibitor if one or more FGFR mutants including at least the mutation FGFR3 R397C; or one or more FGFR mutants including at least the mutation FGFR3 L608F; or one or more FGFR mutants including at least the fusion FGFR2-TACC2 are present in the sample.

Abstract: The present invention provides methods, compositions and devices for stabilizing the extracellular nucleic acid population in a cell-containing biological sample using an apoptosis inhibitor, preferably a caspase inhibitor, a hypertonic agent and/or a compound according to formula 1 as defined in the claims.

Abstract: Sharing data is disclosed. In some cases, sharing data includes receiving a request to share data from a first account to a second account, receiving an indication of a plurality of first account profiles associated with the first account to share with the second account, and establishing sharing from the plurality of first account profiles to the second account, wherein sharing comprises the second account having read access to a subset of nonpublic data associated with the plurality of first account profiles.

Abstract: The present invention relates to methods for the selection of a stable producer cell line expressing one or more protein(s) of interest (POIs), comprising the stable transfection of cells with a gene encoding a constitutively active variant of a growth factor receptor, respective methods for the expression of one or more POIs in such stable producer cell lines, and uses of a constitutively active variant of a growth factor receptor as selection marker in the cultivation of cells.

Abstract: Provided are a computer program product, system and method for restoring volumes in a data storage system. A virtual restoration of a volume of data stored in storage is performed using a target volume. In one embodiment, the virtual restoration includes configuring metadata associated with the target volume, to map the target volume to the recover volume as a virtual restoration of the recover volume. In response to a request by a host for data stored on the recover volume, physical restoration of data of the recover volume is performed using the target volume. In one embodiment, the physical restoration includes transferring data to the target volume from the recover volume to which the target volume is mapped by the virtual restoration. In addition, transferred data is relabeled as target volume data instead of recover volume data.

Abstract: The present invention discloses a sensor based on a field effect transistor (FET) with nano-tapes of a carbon-based material, especially graphene (GNR), a semiconductor joint, electrodes and a base gate composed of a carbon-based metallic material for the detection and measurement of low concentrations (nM-pM) of metabolites (biomarkers) in living organisms. The device features a unique nano-tape configuration of a carbon-based material, especially armchair-type graphene (GNR) (Armchair) in the semiconductor gasket and electrodes, which favors the manufacture of high-density nanosensor arrangements. The device features bifunctional ligaments based on pyrene compounds bound to the semiconductor joint and covalently the target analyte, generating the mechanical, chemical and electronic stability of the detected signal.

Abstract: Provided herein are compositions and methods for the treatment of conditions such as benign prostatic hyperplasia (BPH), Lower Urinary Tract Symptoms (LUTS), chronic prostatitis (CP) and/or chronic pelvic pain syndrome (CPPS). In particular, provided herein are combination therapies comprising a mast cell inhibitor and a histamine receptor antagonist.

Abstract: A system for indexing, updating, and search haplotypes for genetic genealogical discovery in genotype databases. The system includes a pool of genetic indexes, a haplotype ingestion engine, and a haplotype query engine. The haplotypes of a number of individuals in a genotype database are indexed by a pool of multiple panels, and each panel pool can be dynamically updated by the insertion or deletion of individual haplotypes. A genetic genealogical search of a query haplotype against the database is achieved by first projecting the query onto a subset of panels in the pool, then conducting long match queries over each panel, and finally aggregating the identified long matches into Identical-by-Descent segments, i.e., DNA matches, between the query and the haplotypes in the database.

Abstract: Compositions and methods are provided for the identification of peptide sequences that are ligands for a T cell receptor (TCR) of interest, in a given MHC context.

Abstract: Various methods and systems are provided for bicuspid valve detection with ultrasound imaging. In one embodiment, a method comprises acquiring ultrasound video of a heart over at least one cardiac cycle, identifying frames in the ultrasound video corresponding to at least one cardiac phase, and classifying a cardiac structure in the identified frames as a bicuspid valve or a tricuspid valve. A generative model such as a variational autoencoder trained on ultrasound image frames at the at least one cardiac phase may be used to classify the cardiac structure. In this way, relatively rare occurrences of bicuspid aortic valves may be automatically detected during regular cardiac ultrasound screenings.

Abstract: Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload promotes the expression or activity of a functional dystrophin protein. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide, e.g., an oligonucleotide that causes exon skipping in a mRNA expressed from a mutant DMD allele.

Abstract: The disclosure provides a method for detecting a target analyte in a biological sample including contacting the sample with one or more probe sets each comprising a primary probe and a linker, contacting the sample with an initiator sequence, contacting the sample with a plurality of fluorescent DNA hairpins, wherein the probe binds the target molecule, the linker connects the probe to the initiator sequence, and wherein the initiator sequence nucleates with the cognate hairpin and triggers self-assembly of tethered fluorescent amplification polymers, and detecting the target molecule by measuring fluorescent signal of the sample.

Abstract: IL33 antagonists alone or in combination with IL-4R antagonists can be used to treat or inhibit eosinophilic asthma, eosinophilic COPD, eosinophilic ACOS, and nasal polyps in a subject having one or more risk alleles in the intronic IL1RL1 variant rs1420101, in the IL33 variant rs1342326, in both, or in variants in linkage disequilibrium thereof.

Abstract: Sharing data is disclosed. In some cases, sharing data includes receiving a request to share data from a first account to a second account, receiving an indication of a plurality of first account profiles associated with the first account to share with the second account, and establishing sharing from the plurality of first account profiles to the second account, wherein sharing comprises the second account having read access to a subset of nonpublic data associated with the plurality of first account profiles.

Abstract: Methods of treating cancer are provided along with nucleic acids and nucleic acid analog sequences of a long-non-coding RNA (lncRNA), and reagents useful for knocking down the lncRNA.

Abstract: The invention relates to a method for generating a unique identifier of a subject from a genotyped DNA sample from said subject, the method comprising the steps of: obtaining a number N?2 of genomic positions of interest, said obtained genomic positions being such that, in a population of M subjects, these genomic positions exhibit a polymorphism of at least one nucleotide having an allelic frequency of between 25% and 35%, for the minority allele; combining in pairs the obtained genomic positions by means of logical functions so as to obtain a binary code bc.

Abstract: The present invention provides a method for improving the loading of nucleic acid on a solid support by contacting the solid support with a poloxamer-containing reagent. The present invention also provides a method for improving the stability of a nucleic acid on a solid support, comprising contacting a nucleic acid molecule with a partially double-strand oligonucleotide before or after loading the nucleic acid molecule on a solid support, so as to cause the nucleic acid molecule to hybridize with the oligonucleotide. The present invention also provides a combined use of the two methods.

Abstract: The present invention provides a method and a pharmaceutical composition for the treatment of the NDO comprising the viral expression vector carrying a transcription cassette that harbors transgene(s) inhibiting/silencing neurotransmission or synaptic transmission of afferent neurons.

Abstract: The invention provides an AMH-INH-GNIH tri-expression gene vaccine capable of improving fecundity of animals and a preparation method of engineering strain thereof. The engineering strain was deposited in China Center for Type Culture Collection on Aug. 15, 2018, with deposit No.: CCTCC NO:M 2018544. When the engineering strain is used for direct immunization of animals or immunization of animals after being mixed with DNA vaccine adjuvant, the fecundity of the animals can be effectively improved. The tri-expression gene is a tri-expression non-resistant DNA plasmid of Mullerian duct resisting hormone, inhibin and gonadotropin release restraining hormone, which can be used for direct immunization of the animals through mucosa immunization to generate antibodies in the manner of being sprayed to noses, orally administered, blended into feeds and the like.

Abstract: The invention provides aptamer-gene modulator conjugates, where the aptamer and the gene modulator are linked together. The invention further provides a method for cell-specific delivery of gene modulators to hard to transfect cells such as CD4+ cell.

Abstract: The present application describes methods for accurate and cost-effective categorization of DNA samples into different types of in vitro generated DNA or different types of natural DNA such as from different tissues and/or physiological/pathological states. The invention achieves categorization by comparing “signal ratios” that are correlated to ratios of methylation levels at specific genomic loci, but does not rely on calculation of actual methylation levels at any genomic locus. Therefore the disclosed inventive method eliminates the requirement for external DNA species and controls, thereby simplifying and increasing the accuracy of the assay. The described inventive technology also enables performing the categorization of DNA together with DNA profiling in the same reaction, thereby allowing for concomitant categorization and determination of identity of the samples.

Abstract: The present invention provides methods for modulating SET activity by contacting SET with a binding agent such as an ApoE peptide derivative. In one embodiment of the invention, a pharmaceutical composition capable of modulating SET activity is administered to a patient for the treatment of an inflammatory or neurological condition. In another embodiment of the invention, compounds efficacious for the treatment of inflammatory and neurological conditions are identified by screening for a binding agent capable of competing with or inhibiting the binding of an ApoE derivative to SET.

Abstract: The present invention relates to imprinted polymer nanoparticles. In particular, the present invention provides imprinted polymer nanoparticles polymerized in the presence of a target molecule (e.g., peptide), wherein the imprinted polymer nanoparticles comprise vinyl, acryl, and/or methacryl monomers, wherein the monomers have affinity for the target molecule. The present invention also relates to methods of using imprinted polymer nanoparticles in biomacromolecular purification methods (e.g., to purify monoclonal antibodies or hormones), in toxin elimination methods (e.g., hemoperfusion), in diagnostics, in research, as well as in therapeutic methods (e.g., therapeutic methods where antisera or monoclonal antibodies are normally employed).

Abstract: The present invention is directed toward pharmaceutical compositions comprising an isolated polypeptide and a pharmaceutically acceptable carrier. The present invention also discloses an antibody or an antigen-binding portion thereof that bind to the isolated polypeptide. Methods of inhibiting cancer cells growth are also disclosed, comprising administering the isolated polypeptide or the antibody described herein to a subject in need thereof.

Abstract: The present invention provides compositions and methods for regulating expression of nucleotide sequences in fungi. Compositions are novel nucleotide sequences for a tissue preferred promoter isolated from the Agaricus bisporus lectin gene. The sequences drive expression preferentially to fruit body tissue. A method for expressing a nucleotide sequence in fungi using the regulatory sequences disclosed herein is provided. The method comprises transforming a fungal cell to comprise a nucleotide sequence operably linked to one or more of the regulatory sequences of the present invention and regenerating a stably transformed fungus from the transformed cell.

Abstract: A method for generating antibodies preferable to either a normal protein and a mutated form of the normal protein, respectively, where a mutation associated with the mutated form includes either a single point mutation or a small number of point mutations where the method includes creating first and second antigenic peptides of a predetermined length corresponding respectively to common regions of the normal target protein and the mutated form, where the common regions are identical to one another except for the point mutation of the mutated form, obtaining first and second antibodies by multiplying the first and second antigenic peptides via hybridoma methods, and identifying the respective affinities of the first and second antibodies for the normal target protein and the mutated form. Also included are methods of using the first and second antibodies to detect and quantify respective amounts of a normal target protein and a mutated form of the target protein.

Abstract: Methods for identifying a subject at risk for developing AMD are disclosed, as are kits which can be used to practice the methods. The methods include identifying specific protective or risk polymorphisms or genotypes from the subject's genetic material, including polymorphisms in the BF, C2 and/or CFH genes. Microarrays and kits for use in these methods are also provided.

Abstract: A method for the measurement of the amount or difference in the amounts of 2 or more nucleic acid targets in a sample, the method comprising the steps of attaching to nucleic acids present in the sample (1) a tag which allows the nucleic acids to be captured to a solid support; and (2) a labelled probe for a first nucleic acid target present in the sample and a labelled probe for second nucleic acid target present in the sample, and then measuring the amount of each labelled probe or difference in the amount of labelled probes; wherein the probe is not a single labelled nucleotide.

Abstract: The present disclosure relates to methods of determining a treatment course of action. In particular, the present disclosure relates to mutations in the gene encoding estrogen receptor and their association with responsiveness to estrogen therapies for cancer.

Abstract: Genetic markers associated with intellectual disability as well as compositions, methods and kits for screening for genetic markers of intellectual disability, diagnosing intellectual disability and identifying individuals with a predisposition for offspring suffering from intellectual disability are provided.

Abstract: Disclosed herein are methods and reagents for determining the responsiveness of cancer to an epidermal growth factor receptor (EGFR) targeting treatment. The detection of these mutations will allow for the administration of gefitinib, erlotinib and other tyrosine kinase inhibitors to those patients most likely to respond to the drug.

Abstract: The present invention provides compositions and methods of treatment of HCV infected subjects that are not sensitive to interferon treatment. Further, compositions and methods are provided for prevention of organ transplant rejection. The compositions of the invention comprise an anti microRNA-122 oligonucleotide, and are made for administration to a primate.

Abstract: Disclosed are kits and methods for diagnosing a person with, or assessing a person's risk for developing, sarcoidosis and/or complicated sarcoidosis.

Abstract: A polynucleotide primer comprising at least the final six nucleotides of one of the following primer sequences, or a sequence complementary thereto: SEQ. ID NOS. 1 to 18, 21 to 45 or 74 to 77.

Abstract: The present invention relates to a method for diagnosing a myeloid cancer in a subject, which comprises the step of analyzing a biological sample from said subject by determining the presence or the absence of a mutation in the ASXL1 (additional sex combs like 1) gene coding for the polypeptide having the sequence SEQ ID No 2. A kit for diagnosing myeloid cancer in a subject comprising at least one nucleic acid probe or oligonucleotide or at least one antibody, which can be used in a such a method.

Abstract: The present invention provides nucleic acid sequences that are used for identification, classification and diagnosis of specific types of cancers. The nucleic acid sequences can also be used for prognosis evaluation of a subject based on the expression pattern of a biological sample.

Abstract: The present invention provides a method of diagnosing the existence or risk of hyperthyroidism in a feline comprising measuring the level of expression of one or more biomarkers selected from the group consisting of e.g., IYD, TG, SLC5A5, NIS, TPO, TSHR, DUOX1, DUOX2 (ThOX), TGFB1, CSTD, DCN and SEPP1 and the expression products thereof, in a biological sample from the feline, wherein elevated expression of the one or more biomarkers in the sample relative to a control value for expression in a sample from a normal feline or feline population, or a baseline value from the feline, indicates the existence or risk of hyperthyroidism; a method of treating a feline so diagnosed; and compositions, reagents and kits for carrying out the specified methods.

Abstract: The present invention provides a method for treating a human subject afflicted with multiple sclerosis or a single clinical attack consistent with multiple sclerosis with a pharmaceutical composition comprising glatiramer acetate and a pharmaceutically acceptable carrier, comprising the steps of: (i) determining a genotype of the subject at a location corresponding to the location of one or more single nucleotide polymorphisms (SNPs) selected from the group consisting of: Group 1, (ii) identifying the subject as a predicted responder to glatiramer acetate if the genotype of the subject contains one or more A alleles at the location of Group 2, one or more C alleles at the location of Group 3, one or more G alleles at the location of Group 4, or one or more T alleles at the location of kgp18432055, kgp279772, kgp3991733 or kgp7242489; and (iii) administering the pharmaceutical composition comprising glatiramer acetate and a pharmaceutically acceptable carrier to the subject only if the subject is identif

Abstract: Detection probes are provided that are capable of detecting a sequence to be detected containing a mutation even when a sequence not to be detected containing no mutation coexists with the sequence to be detected containing a mutation, which are different only in a single base from each other. At least one oligonucleotide selected from the group consisting of SEQ ID NOs: 2˜16 is used as a probe. Even in a sample containing an abl gene in which a mutation has occurred and an abl gene in which no mutation has occurred, the use of such probes in, for example, Tm analysis allows the mutation to be detected.

Abstract: Treatment of prostate cancer by regional and prolonged release of one or more nucleotide-based RNAi agents is provided.

Abstract: The invention comprises reagents and methods for detecting cancer-associated mutations in the human EZH2 gene. Further, a method of detecting the mutations and a method of treatment are disclosed.

Abstract: In Caenorhabditis elegans, lin-4 and let-7 encode 22- and 21-nucleotide RNAs, respectively, that function as key regulators of developmental timing. Because the appearance of these short RNAs is regulated during development, they are also referred to as “small temporal RNAs” (stRNAs). We show that many more 21- and 22-nt expressed RNAs, termed microRNAs, (miRNAs), exist in invertebrates and vertebrates, and that some of these novel RNAs, similar to let-7 stRAN, are also highly conserved. This suggests that sequence-specific post-transcriptional regulatory mechanisms mediated by small RNAs are more general than previously appreciated.

Abstract: There is disclosed a photocleavable sense-antisense nucleobase polymer complex capable of modulating gene expression comprising an unnatural antisense nucleobase polymer that targets an mRNA, and a photocleavable sense nucleobase polymer noncovalently bound to the antisense nucleobase polymer, wherein the photocleavable sense nucleobase polymer comprises a plurality of nucleobase polymers connected by a photocleavable linkage. There is also disclosed a method for controlling the time and spatial position of gene expression comprising selecting a target mRNA, introducing the photocleavable sense-antisense nucleobase polymer complex into a cell, and selectively irradiating the cell with light.

Abstract: A system (100) for classifying a biological test sample, including a database (112) populated with reference expression data. The reference expression data includes expression levels of a plurality of molecules (polynucleotides or polypeptides), including a set of marker molecules, in a plurality of reference samples. Each reference sample has a pre-assigned value for each of one or more clinically significant variables. The system includes at least one processor (110) and at least one storage medium containing program instructions for execution by said processor (110). The program instructions cause the processor to accept (122) input expression data including a test vector of expression levels of the marker molecules in the biological test sample; and pass the input expression data to one or more analysis programs (130a, 130b, 35).