Abstract: The present invention provides compositions and methods based on genetic polymorphisms that are associated with vascular diseases such as stroke. In particular, the present invention relates to genetic polymorphisms that have utility for such uses as predicting disease risk or predicting an individual's response to a treatment such as statins, including groups of polymorphisms that may be used as a signature marker set for such uses, as well as nucleic acid molecules containing the polymorphisms, variant proteins encoded by such nucleic acid molecules, reagents for detecting the polymorphic nucleic acid molecules and proteins, and methods of using the nucleic acid and proteins as well as methods of using reagents for their detection.

Abstract: The present disclosure relates a low magnification dark-field microscope system and method for producing a dark-field image. The method includes transferring a biological specimen to a surface of a sample plate, and pre-treating the biological specimen using one or more pre-treatment steps selected from (1) heating the biological specimen using a heating device; (2) applying ultrasound energy using an ultrasound transducer and ultrasound generator; and (3) doping the biological specimen with a metallic nanoparticle. Following pre-treatment, the method includes imaging a region of interest the biological specimen on the sample plate using a dark-field microscope to generate a dark-field image of the biological specimen.

Abstract: A method of characterizing biological sequences includes: preparing a library of sequences; subjecting the sequences in the library to at least one screening experiment to obtain an experiment outcome of each of the sequences; creating a first dataset comprising identities of the sequences and the experiment outcomes of the sequences; and training a first neural network using the first dataset to extract first sequence features from the sequences in the first dataset. A second neural network may be additionally be trained using a second dataset based on an external database to generate a pre-trained model, which is used extract additional features from the first dataset.

Abstract: Provided are compositions and methods for expressing a transgene in plant cells and/or plant tissues using regulatory elements, including the promoters, 5?UTR, 3? UTRs, and/or terminators isolated from Glycine max chlorophyll binding Ab genes.

Abstract: The present invention addresses the issue of providing a target base sequence detection method, etc., whereby a determination can be readily made regarding whether or not a target base sequence is present in a nucleic acid sample. A fluorescent-labeled detection probe and a competitive probe are added to a nucleic acid sample and caused to hybridize with the nucleic acid in the sample, the fluorescence intensity is measured while changing the temperature of the reaction sample, and first order differentiation is performed on a temperature-fluorescence intensity curve.

Abstract: The present disclosure discloses a gold/quantum dot nanoprobe for detecting active ricin in a complex matrix and application thereof. The gold/quantum dot nanoprobe is a nanoprobe formed by utilizing gold nanoparticles and quantum dots, which are modified by single strand oligodeoxynucleotides (ssODN), to form double strand oligodeoxynucleotides in a base pairing hybridizing mode and assembling the gold nanoparticles and the quantum dots into a core-satellite structure. According to the present disclosure, the gold/quantum dot nanoprobe is used for detecting the active ricin, has a limit of detection of 7.46 ng/mL, is high in accuracy and good in reliability, and does not require large-scale equipment and complex operations. In order to further eliminate the false positive result, the present disclosure further provides a method for enriching ricin in a complex sample by utilizing magnetic beads.

Abstract: The present invention relates to a plasma reactor and more specifically to an plasma microreactor comprising a support, made at least partially of a dielectric material, the support comprising a gas inlet, a liquid inlet, at least a fluid outlet, a liquid microchannel in the support, a gas channel, at least a ground electrode, at least a high voltage electrode, separated from the gas channel by the dielectric material of the support, wherein said ground electrode and said high voltage electrode are arranged on opposite sides of the gas channel so as to be able to create an electric field inside the gas channel, wherein the liquid microchannel and the gas channel are contiguous and at least an opening is arranged between the liquid microchannel and the gas channel so as to form a fluid channel and to cause the liquid flow contact the gas flow and wherein the liquid flow is retained within the liquid microchannel by capillarity action.

Abstract: The present invention relates to, among other things, probes, compositions, methods, and kits for simultaneous, multiplexed detection and quantification of protein and/or nucleic acid expression in a user-defined region of a tissue, user-defined cell, and/or user-defined subcellular structure within a cell that are adaptable for use with existing sequencing technologies.

Abstract: A DNA sequencing device having a first conductor electrically insulated from a second conductor, a voltage source and an amplifier electrically connected in series with the first conductor and the second conductor, a DNA polymerase attached to the first conductor and to the second conductor with matching biotinylated tag molecules, and an electric current monitor. A non-discriminating electrical signal is provided by the polymerase during pairing, which signal can be used as a marker to indicate that transcription is occurring between a single-type of free nucleotide and a base nucleotide of a template DNA strand.

Abstract: In certain aspects, the invention disclosed herein relates to the isothermal amplification of probe linkage products to generate specific amplified signals. In some aspects, the invention provides methods, reagents, and kits for carrying out such amplification via the isothermal chain reaction (ICR).

Abstract: Provided herein are methods and kits for labeling endonuclease-treated cells. The methods comprise: contacting the cells to be labelled with at least one endonuclease suitable for targeting a genomic region of interest, and first and second nucleic acids suitable for introducing one or more silent (or optionally non-silent) mutation(s) in the genomic region by homology-directed repair (HDR). The mutation(s) introduced by the first nucleic acid differ from the mutation(s) introduced by the second nucleic acid.

Abstract: A biomolecule analysis method including: feeding a reagent into a reaction container which includes a plurality of wells and filing the reagent in the plurality of wells, the reagent being for causing an enzymatic reaction with regard to a target substance of analysis; feeding an oil sealing solution over the plurality of wells and sealing the reagent into the plurality of wells with the oil sealing solution so that the plurality of wells become a plurality of independent reaction containers; performing the enzymatic reaction by incubating the reaction container; and detecting a signal amplified by the enzymatic reaction.

Abstract: The purpose of the present invention is to provide a method for treating biomolecules and a method for analyzing biomolecules with which it is possible to effectively suppress the clog of nanopores. The present invention is a method for treating biomolecules for analysis in which nanopores are used, wherein the method includes a step for preparing a sample solution that includes ammonium cations represented by a prescribed formula and biomolecules in which at least a portion of the higher-order structure has been fused.

Abstract: Compositions and methods are provided for rapid characterization of Cas endonuclease systems and the elements comprising such systems, including, but not limiting to, rapid characterization of PAM sequences, guide RNA elements and Cas endonucleases. Type II Cas9 endonuclease systems originating from Brevibacillus laterosporus, Lactobacillus reuteri Mlc3, Lactobacillus rossiae DSM 15814, Pediococcus pentosaceus SL4, Lactobacillus nodensis JCM 14932, Sulfurospirillum sp. SCADC, Bifidobacterium thermophilum DSM 20210, Loktanella vestfoldensis, Sphingomonas sanxanigenens NX02, Epilithonimonas tenax DSM 16811, Sporocytophaga myxococcoides are described herein. The present disclosure also describes methods for genome modification of a target sequence in the genome of a cell, for gene editing, and for inserting a polynucleotide of interest into the genome of a cell.

Abstract: Disclosed herein include systems, methods, compositions, and kits for molecular barcoding on the 5?-end of a nucleic acid target. After barcoding a nucleic acid target using an oligonucleotide barcode comprising a target binding region and a molecular label to generate a barcoded nucleic acid molecule, an oligonucleotide comprising a complement of the target binding region can be added to generate a barcoded nucleic acid molecule comprising the target-binding region and the complement of the target-binding region. A stem loop is formed with intra-molecular hybridization of the barcoded nucleic acid molecule, which can be extended to generate an extended barcoded nucleic acid molecule comprising the molecular label and a complement of the molecular label.

Abstract: Disclosed are methods and systems for determining the three-dimensional structure of chromatin in eukaryotic cells. More specifically, disclosed are methods and systems for obtaining chromatin structural information by surface immobilization that includes tethering crosslinked protein:DNA complexes and/or ligated DNA complexes to media such as beads, gels, and or matrices during the conformation capture assay.

Abstract: The invention provides compositions containing cargo molecules attached to elements that improve the function of the cargo molecules in the body of a subject. The compositions are useful for therapeutic and diagnostic purposes. Furthermore, the invention outlines ways in which these compositions can be produced; the core molecule can be functionalized, via bioorthogonal click chemistry, in such a way as to impart modular characteristics. This functionalization simultaneously allows for loading of biologically relevant cargo and provides stabilization to the overall structure of the molecule.

Abstract: This disclosure describes materials and methods for effectively performing serial multiplexed FISH analysis.

Abstract: The present disclosure provides for genetically modified organisms that provide numerous health benefits but also have an improved flavor profile and a more palatable aroma for the consumer of the organism.

Abstract: The present disclosure relates to systems and methods for classifying data sets using associated functions from neural networks. In one example, a system for classifying data sets by corresponding functions includes at least one processor and at least one non-transitory memory storing instructions that, when executed by the at least one processor cause the system to perform operations including: obtaining a neural network associated with a data set, the neural network being trained to generate synthetic data sets related to the data set; selecting a test set of inputs to the neural network; obtaining a corresponding set of outputs by applying the neural network to the test set of inputs; estimating one or more functions describing the test set of inputs and the corresponding set of outputs; and indexing the estimated one or more functions to the data.

Abstract: A method of promoting the generation of oligodendrocytes from oligodendrocyte precursor cells by enhancing their survival and/or maturation includes administering to the cell an effective amount of an agent that enhances and/or induces accumulation of ?8,9-unsaturated sterol intermediates of the cholesterol biosynthesis pathway in the oligodendrocyte precursor cells.

Abstract: Methods and compositions for modulating repeat non-ATG protein (RAN protein) translation are provided. In some aspects, the disclosure provides methods of inhibiting RAN protein translation by contacting a cell with an effective amount of an inhibitor of eIF2 phosphorylation or an inhibitor of protein kinase R (PKR). In some embodiments, methods described by the disclosure are useful for treating diseases associated with RAN protein translation, such as certain neurodegenerative diseases.

Abstract: A process of quantifying the extent of degradation present in a human DNA sample is described. The process makes use of a real time PCR system to separately quantitate within a sample a first retrotransposon interspersed element and a relatively longer second retrotransposon interspersed element, where the longer element is expected to be disrupted at a faster pace than is the shorter element as the sample degrades. In one embodiment, the process makes use of the appearance of the relatively young (on an evolutionary scale) Alu Yb-lineage subfamily sequences appearing in every human genome and their virtual absence in non-human samples. In a preferred embodiment, the process quantifies longer 290 bp sequences of “SVA” elements and shorter 80 bp sequences of Alu Yb8-lineage. Newly designed primers and TaqMan probes that are useful in the process are presented. A related process additionally quantifies male specific human DNA.

Abstract: A pig intestinal tract epithelium cell line with METTL3 gene knocked out and a construction method therefor. A gene interference vector for METTL3 form a pig is also provided.

Abstract: The present invention relates to compounds, compositions, and methods for the study, diagnosis, and treatment of traits, diseases and conditions that respond to the modulation of PHD2 gene expression and/or activity, and/or modulate a beta-catenin gene expression pathway. Specifically, the invention relates to double-stranded nucleic acid molecules including small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA) molecules that are capable of mediating or that mediate RNA interference (RNAi) against PHD2 gene expression.

Abstract: The invention provides improved methods for synthesizing polynucleotides, such as DNA and RNA, using renewable initiators coupled to a solid support. Using the methods of the invention, specific sequences of polynucleotides can be synthesized de novo, base by base, in an aqueous environment, without the use of a nucleic acid template.

Abstract: The present invention generally relates to methods and compositions used delivery of gene editing compositions including transcriptional effectors with parvovirus and preferred methods for making same.

Abstract: The present invention relates to improved methods for epigenetic blood and immune cell counting, and respective uses and kits.

Abstract: The present embodiments provide methods, compounds, and compositions useful for inhibiting DGAT2 expression, which may be useful for treating, preventing, or ameliorating a disease associated with DGAT2.

Abstract: Methods for controlling for non-systematic error in an amplification-based next generation sequencing (NGS) library preparation are described, which method includes using an internal amplification control (IAC) sharing identical priming sites to a native nucleic acid target template of interest in a NGS library preparation.

Abstract: A method of sequencing nucleic acids is provided using sequencing by ligation and/or sequencing by hybridization.

Abstract: Some aspects of this disclosure provide compositions, methods, systems, and kits for controlling the activity and/or improving the specificity of RNA-programmable endonucleases, such as Cas9. For example, provided are guide RNAs (gRNAs) that are engineered to exist in an “on” or “off” state, which control the binding and hence cleavage activity of RNA-programmable endonucleases. Some aspects of this disclosure provide mRNA-sensing gRNAs that modulate the activity of RNA-programmable endonucleases based on the presence or absence of a target mRNA. Some aspects of this disclosure provide gRNAs that modulate the activity of an RNA-programmable endonuclease based on the presence or absence of an extended DNA (xDNA).

Abstract: Provided are compositions and methods for cleaving a DNA sequence in a cell. The methods involve comprising introducing into a cell a recombinant vector containing a clustered regularly interspaced short palindromic repeats (CRISPR) system. The system includes a CRISPR RNA (crRNA) targeted to a DNA sequence in the cell that is operatively linked to a promoter; and CRISPR-associated enzymes (Cas) 10, Cas6, and at least one Csm protein. The Cas 10 cleaves the DNA sequence only during transcription of the DNA sequence that is operatively linked to the promoter. Also provided are recombinant vectors for modifying cells, cells that contain the recombinant vectors and modifications introduced by them, and kits that include the modified vectors.

Abstract: The invention relates to a mediator probe comprising a probe region and a mediator region. Furthermore, the invention relates to a system comprising a mediator probe and a detection molecule, use of that system and a method for detection of at least one target molecule.

Abstract: The present invention relates to a nucleic acid detection kit and a nucleic acid detection method, which use nanoparticles. More specifically, the present invention relates to: a nucleic acid detection method comprising a step of amplifying and labeling nucleic acids, and then capturing the same by using nanoparticles and centrifuging the same; and a nucleic acid detection kit using the method. The present invention is effective since a negative or positive determination for a particular disease can be made, through the nucleic acid detection method not comprising a separation step, in a more rapid, simple, sensitive, and highly reliable manner.

Abstract: Techniques for measuring sequences of nucleic acids are provided. Time-based measurements (e.g., forming a histogram) particular to a given sequencing cell can be used to generate a tailored model. The model can include probability functions, each corresponding to different states (e.g., different states of a nanopore). Such probability functions can be fit to a histogram of measurements obtained for that cell. The probability functions can be updated over a sequencing run of the nucleic acid so that drifts in physical properties of the sequencing cell can be compensated. A hidden Markov model can use such probability functions as emission probabilities for determining the most likely nucleotide states over time. For sequencing cells involving a polymerase, a 2-state classification between bound and unbound states of the polymerase can be performed. The bound regions can be further analyzed by a second classifier to distinguish between states corresponding to different bound nucleotides.

Abstract: The invention provides methods for simultaneously amplifying multiple nucleic acid regions of interest in one reaction volume as well as methods for selecting a library of primers for use in such amplification methods. The invention also provides library of primers with desirable characteristics, such as minimal formation of amplified primer dimers or other non-target amplicons.

Abstract: Analytical standards can allow one to detect and/or measure sampling, processing, and/or amplification errors in a sample that includes a plurality of polynucleotide molecules. The analytical standards can provide an internal control to detect errors in the representation of the original sample reflected in data obtained after manipulating and/or processing of sample molecules.

Abstract: The present disclosure provides methods, kits, and compositions for generating DNA molecules encoding CRISPR/Cas guide RNAs (e.g., Cas9 single guide RNAs or Cas9 targeter RNAs). A library of such DNA molecules can be generated from any DNA source. The methods include a step of contacting target DNA with one or more DNA endonucleases that specifically bind to and cleave within a recognition sequence that includes a PAM sequence, to generate a plurality of cleavage fragments, to which a DNA adapter can be attached. A distal-cleaving DNA endonuclease can be used that specifically binds to a recognition sequence in the DNA adapter and cleaves at a site within the attached DNA cleavage fragments to generate a library of CRISPR/Cas guide sequences. After removal of all or a portion of the DNA adapter, a constant region of a guide RNA can be attached to generate DNA molecules encoding CRISPR/Cas guide RNAs.

Abstract: Provided herein is a method for sequencing a polynucleotide molecules. The method includes the steps of providing a plurality of polynucleotide molecules attached to a surface, wherein a first portion of each polynucleotide molecule is attached to a first location of the surface and a second portion of each polynucleotide molecule is attached to a second location of the surface, the relative proximity of the first and second locations being correlated with the probability that the first and second portions are paired, separating the first and second portions of the polynucleotide molecules on the surface, determining the sequences of the first and second portions of the polynucleotide molecules and comparing the relative proximities and the sequences to determine which first and second portions are paired and to determine the sequence of the target polynucleotide molecules.

Abstract: Novel oligonucleotides that are fully chemically stabilized are provided. Methods of using oligonucleotides that are fully chemically stabilized are also provided.

Abstract: A primer set includes a terminal primer A including, in its 3?-terminal part, a nucleotide sequence that hybridizes to a 3?-terminal part of a complementary sequence of a first target nucleic acid sequence, a k-th double-headed primer including two polynucleotides linked at their 5? terminal sides, wherein one of the two polynucleotides includes, in its 3?-terminal part, a nucleotide sequence that hybridizes to a 3?-terminal part of a nucleotide sequence of a k-th target nucleic acid, and the other polynucleotide includes, in its 3?-terminal part, a nucleotide sequence that hybridizes to a 3?-terminal part of a complementary sequence of a (k+1)th target nucleic acid, and a terminal primer B including, in its 3?-terminal part, a nucleotide sequence that hybridizes to a 3?-terminal part of a nucleotide sequence of a N-th target nucleic acid.

Abstract: The present invention relates to compositions and methods for increasing the rate of nuclease-mediated site specific insertions of donor DNA sequence to the genome via recombination. More specifically, the method utilizes a non-naturally occurring nuclease-homology directed repair (HDR) protein chimeras for genome editing applications. Physically tethering the activity of a DNA nuclease to an HDR protein results in significant increase in the fraction of nuclease induced DNA breaks that are repaired by homologous recombination and provides higher accuracy and specificity of genome editing.

Abstract: The invention provides methods for generating pools of variants of DNA templates, and methods of using pools of variants to identify sequences involved in conferring sensitivity or resistance to environmental factors.

Abstract: Disclosed herein, inter alia, are compounds, compositions, and methods of use thereof in the sequencing a nucleic acid.

Abstract: The invention generally relates to capturing, amplifying, and sequencing nucleic acids. In certain embodiments, copies of the sense and antisense strands of a duplex template nucleic acid are captured using linked capture probes and multiple binding and extension steps to improve specificity over traditional single binding target capture techniques. Methods of seeding sequencing clusters with sense and antisense strands of a target nucleic acid are also disclosed including identifying the strands using sense-specific barcodes and confirming base calls using two sense-specific sequencing reads. Linked adapters may be used to increase adapter ligation selectively or efficiency and yield.

Abstract: High throughput personal genomic testing has created a need for robust quality control mechanisms to track sample identity, reagent integrity, and other factors with significant influence on assay performance. A method of massively parallel sequencing using an accompanying barcoded molecular standard enables one to track nucleic acid analytes to identify them by project, lot, batch, or patient. The molecular standard contains sequences present in the analyte, allowing it to be processed simultaneously without any other additional reagents. Within the molecular standard, a calibrator sequence permits assessment of fidelity of sequence determination. Additional sequences in the molecular standard may be used to manipulate the molecular standard separate from the analyte. The molecular standard can be used to benchmark sequencing platforms and assess error rates.

Abstract: The present disclosure relates to methods of treating EPAS1-related diseases such as cancer, metastases, astrocytoma, bladder cancer, breast cancer, chondrosarcoma, colorectal carcinoma, gastric carcinoma, glioblastoma, head and neck squamous cell carcinoma, hepatocellular carcinoma, lung adenocarcinoma, neuroblastoma, non-small cell lung cancer, melanoma, multiple myeloma, ovarian cancer, rectal cancer, renal cancer, clear cell renal cell carcinoma (and metastases of this and other cancers), gingivitis, psoriasis, Kaposi's sarcoma-associated herpesvirus, preeclampsia, inflammation, chronic inflammation, neovascular diseases, and rheumatoid arthritis, using a therapeutically effective amount of a RNAi agent to EPAS1.

Abstract: Methods and compositions for the detection and quantification of nucleic acids are provided. In certain embodiments, methods involve the use of primers or probes that comprise a non-natural nucleotide linked to a reporter. Target nucleic acids are detected by the polymerization of a complementary probe or primer that incorporated a cognate non-natural nucleotide linked to a quencher.

Abstract: Methods, compositions, and kits are provided for CRISPR/Cas mediated transcriptional modulation.