Abstract: The invention relates to the identification of genetic signatures and expression profiles that are a part of the Base Excision Repair (BER) pathway, a major DNA repair pathway that modifies base lesions. In one embodiment, the present invention provides a method of determining responsiveness of treatment by BER inhibitors for malignant glioma by determining the presence of a low level of expression of Apex 1, a low level of expression of Apex 2, and a high level of expression of MPG.

Abstract: Methods and compositions are provided for improving specificity during amplification of a target DNA sequence. The methods and compositions rely upon the use of an RNase H enzyme, a polymerase, and RNase H enzyme-sensitive, blocked-cleavable oligonucleotide primers in the amplification reactions, wherein the reaction mixtures include either an optimized final concentration of a divalent metal salt comprising 2.0 mM or less of free Mg++ cation and/or an optimized final concentration of a non-ionic detergent comprising at least about 0.001% polyethylene glycol hexadecyl ether.

Abstract: This disclosure relates to analyzing the end-to-end sequence and the relative distributions in heterogeneous mixtures of polynucleotides and methods and enabling reagents related thereto. In certain embodiments this method relates to the complete full length sequencing and quantitative profiling of mRNAs present in the transcriptomes of cells or tissues of but not limited to, higher multicellular organisms that possess interrupted genes subject to complex post-transcriptional RNA processing.

Abstract: Methods and kits for qualifying the analysis of cell free DNA in e.g. plasma and serum samples are provided, based on the identification of contaminating DNA from B lymphocytes. Quantitative PCR (qPCR) can be used to detecting or determining the level of clonally rearranged immunoglobulin heavy-chain (IGH) genes, immunoglobulin kappa chain (IGK) genes, or immunoglobulin lambda-chain (IGL) genes, or a combination of any thereof. Samples identified as containing contaminating DNA can thus be identified and excluded or corrected, improving the accuracy of cf DNA determinations as a diagnostic, prognostic and treatment monitoring tool.

Abstract: A method for identifying any of the presence, location and phasing of modified cytosines (C) in long stretches of nucleic acids is provided. In some embodiments, the method may comprise (a) reacting a first portion of a nucleic acid sample containing at least one C and/or at least one modified C with a DNA glucosyltransferase and a cytidine deaminase to produce a first product and/or reacting a second portion of the sample with a dioxygenase, optionally a DNA glucosyltransferase and a cytidine deaminase to produce a second product and; (b) comparing the sequences from the first and optionally the second product obtained in (a), or amplification products thereof, with each other and/or an untreated reference sequence to determine which Cs in the initial nucleic acid fragment are modified. A modified TET methylcytosine dioxygenase with improved efficiency compared to unmodified TET2 at converting methylcytosine to carboxymethylcytosine is also provided.

Abstract: A continuous throughput microfluidic system includes an input system configured to provide a sequential stream of sample plugs; a droplet generator arranged in fluid connection with the input system to receive the sequential stream of sample plugs and configured to provide an output stream of droplets; a droplet treatment system arranged in fluid connection with the droplet generator to receive the output stream of droplets in a sequential order and configured to provide a stream of treated droplets in the sequential order; a detection system arranged to obtain detection signals from the treated droplets in the sequential order; a control system configured to communicate with the input system, the droplet generator, and the droplet treatment system; and a data processing and storage system configured to communicate with the control system and the detection system.

Abstract: Methods of treating a wound in a subject are provided comprising administering to the subject an amount of an inhibitor of Fidgetin-like 2. Compositions and pharmaceutical compositions comprising an amount of an inhibitor of Fidgetin-like 2 are also provided. Methods are also provided for identifying an inhibitor of Fidgetin-like 2.

Abstract: The present disclosure provides analyte-specific binding reagents conjugated with a platinum-containing moiety, e.g., cisplatin, and methods, compositions, and kits for their production and use in assays for analyte detection.

Abstract: The present invention relates to an RNAi-inducing nucleic acid molecule having a new structure and the use thereof, and more particularly to a novel nucleic acid molecule having a structure comprising a first strand, which is 24-121 nt in length and comprises a region complementary to a target nucleic acid, and a second strand which is 13-21 nt in length and has a region that binds complementarily to the region of the first strand, which is complementary to the target nucleic acid, so that the nucleic acid molecule inhibits the expression of a target gene with increased efficiency, and to a method of inhibiting the expression of a target gene using the nucleic acid molecule. The nucleic acid molecule structure of the present invention increases the efficiency with which the nucleic acid molecule inhibits the target gene.

Abstract: The present invention relates to a novel method for analyzing nucleic acid sequences based on real-time detection of DNA polymerase-catalyzed incorporation of each of the four nucleotide bases, supplied individually and serially in a microfluidic system, to a reaction cell containing a template system comprising a DNA fragment of unknown sequence and an oligonucleotide primer. Incorporation of a nucleotide base into the template system can be detected by any of a variety of methods including but not limited to fluorescence and chemiluminescence detection. Alternatively, microcalorimetic detection of the heat generated by the incorporation of a nucleotide into the extending template system using thermopile, thermistor and refractive index measurements can be used to detect extension reactions.

Abstract: The present disclosure provides a novel approach for shifting or distributing various information (e.g., protocols, analysis methods, sample preparation data, sequencing data, etc.) to a cloud-based network. For example, the techniques relate to a cloud computing environment configured to receive this information from one or more individual sample preparation devices, sequencing devices, and/or computing systems. In turn, the cloud computing environment may generate information for use in the cloud computing environment and/or to provide the generated information to the devices to guide a genomic analysis workflow. Further, the cloud computing environment may be used to facilitate the sharing of sample preparation protocols for use with generic sample preparation cartridges and/or monitoring the popularity of the sample preparation protocols.

Abstract: The present invention relates to a novel method for analyzing nucleic acid sequences based on real-time detection of DNA polymerase-catalyzed incorporation of each of the four nucleotide bases, supplied individually and serially in a microfluidic system, to a reaction cell containing a template system comprising a DNA fragment of unknown sequence and an oligonucleotide primer. Incorporation of a nucleotide base into the template system can be detected by any of a variety of methods including but not limited to fluorescence and chemiluminescence detection. Alternatively, microcalorimetic detection of the heat generated by the incorporation of a nucleotide into the extending template system using thermopile, thermistor and refractive index measurements can be used to detect extension reactions.

Abstract: Provided herein are systems and methods for whole genome amplification and sequencing. In particular, provided herein are systems and methods for detection of nucleic acid variants (e.g., rare variants) in limited samples.

Abstract: Provided are methods for labeling transfer RNA comprising replacing the uracil component of a dihydrouridine of said transfer RNA with a fluorophore. The disclosed methods may comprise fluorescent labeling of natural tRNAs (i.e., tRNAs that have been synthesized in a cell, for example, in a bacterium, a yeast cell, or a vertebrate cell) at dihydrouridine (D) positions, or fluorescent labeling of synthetic tRNAs. In another aspect, the present invention provides methods for assessing protein synthesis in a translation system comprise providing a tRNA having a fluorophore substitution for the uracil component of a dihydrouridine in a D loop of the tRNA; introducing the labeled tRNA into the translation system; irradiating the translation system with electromagnetic radiation, thereby generating a fluorescence signal from the fluorophore; detecting the fluorescence signal; and, correlating the fluorescence signal to one or more characteristics of the protein synthesis in the translation system.

Abstract: Compositions, kits, cells and methods for treating cardiovascular (e.g., myocardial ischemia and heart failure), immunological, and inflammatory diseases or disorders involve the use of the mature and precursor sequences of microRNAs 142-5p, 142-3p, 17-5p, 17-3p, 374, and 20a, and of antisense molecules complementary to these sequences, to manipulate processes relevant to, for example, the cardiac response to stress, including survival signaling, angiogenesis, stem cell differentiation along muscle or vascular lineages, and repression or promotion of cardiac myocyte growth. Also described are methods to treat cardiovascular, immunological and inflammatory diseases by engineering cells containing specific micro-RNAs or antagomirs against specific mRNAs. The engineered cells can then be used to treat patients with such diseases by autologous stem cell therapy.

Abstract: Small molecule fluorescent probes for established drug targets such as nucleic acids including DNA and RNA has been developed and disclosed herein. These nucleic acid probes bind to multiple DNA and RNA structures, and to sites crucial for nucleic acid function, such as DNA and RNA major grooves. Displacement of the probes by other binders such as small molecule compounds and/or proteins illicits a fluorescence change in the probe that once detected and analyzed provide binding information of these other binders of interest. Similarly, changes in fluorescence upon binding of the probes to nucleic acid have been applied to screen nucleic acid of different sequence and conformation. The nucleic acid probes and method of uses disclosed herein are advantageously suitable for high-through put screening of libraries of small molecule compounds, proteins, and nucleic acids.

Abstract: Methods and compositions for synthesizing nucleic acid sequences in an emulsion are provided.

Abstract: The present invention relates to a method of preparation of substrates for nucleic acid sequencing reactions. More specifically, the present invention provides a new method of preparing hairpins using force-induced strand invasion. Hairpins prepared by this method and methods of nucleic acid analysis using these hairpins are also part of the present invention.

Abstract: Improved compositions for and methods of processing and analyzing samples are described. In particular, the compositions and methods liberate nucleic acids from a biological sample allowing direct downstream processing of the nucleic acids in microfluidic systems. These compositions, methods and kits are useful in diagnosing, staging or otherwise characterizing various biological conditions.

Abstract: Novel compositions and methods for engineering wireframe architectures and scaffolds of increasing complexity by creating gridiron-like DNA structures (FIG. 1). A series of four-arm junctions are used as vertices within a network of double-helical DNA fragments. Deliberate distortion of the junctions from their most relaxed conformations ensures that a scaffold strand can traverse through individual vertices in multiple directions. DNA gridirons, ranging from two-dimensional arrays with reconfigurability to multilayer and three-dimensional structures and curved objects, can be assembled according the methods presented herein.

Abstract: Methods for the rapid detection of the presence or absence of mecC-containing Staphylococcus aureus (mecC-MRSA) in a biological or non-biological sample are described. The methods can include performing an amplifying step, a hybridizing step, and a detecting step. Furthermore, primers, probes targeting the genes for mecC-MRSA, along with kits are provided that are designed for the detection of mecC-MRSA.

Abstract: Provided herein are a novel Zn-DPA complex compound and an siRNA delivery system including the same as a transporter, the Zn-DPA complex compound including: a phosphate-directing functional part of zinc (II)-dipicolylamine (“Zn-DPA”); a cell membrane-directing functional part; and a linker part that links the phosphate-directing functional part and the cell membrane-directing functional part. The Zn-DPA complex compound has low toxicity and efficiently delivers siRNA to cells, thereby useful in various ways for various studies and diagnosis and treatment of diseases, which use siRNA.

Abstract: Some embodiments of the present application relate to novel modified nucleotide linkers for increasing the efficiency of nucleotide incorporation in Sequencing by Synthesis applications. Methods of preparing these modified nucleotide linkers are also provided herewith.

Abstract: Therapies and assays to screen for small molecules that can have therapeutic use in the control of neurodegenerative diseases such as Parkinson's and other alpha-synucleinopathies.

Abstract: A lipid membrane structure encapsulating an siRNA inside thereof and containing a lipid compound of the formula (I) as a lipid component (R1 and R2 represent CH3—(CH2)n—CH?CH—CH2—CH?CH—(CH2)m—, n represents an integer of 3 to 5, m represents an integer of 6 to 10, p represents an integer of 2 to 7, and R3 and R4 represent a C1-4 alkyl group or a C2-4 alkenyl group.

Abstract: The present invention provides methods for immobilizing target nucleic acids on a solid support utilizing combinatorial capture probe pairs. These pairs contain first and second capture oligonucleotides that each comprise a target binding region, a capture region and a stem region positioned between the target binding and capture regions. The target binding regions comprise nucleic acid sequences that allow them to hybridize to adjacent regions on the target nucleic acid. The stem regions have nucleic acid sequences that are complementary to each other and the capture regions each comprise a sequence that when positioned adjacent to one another produce a combined nucleic acid sequence that is complementary to a portion of an oligonucleotide bound to a solid support.

Abstract: Methods are provided that operate on raw dissociation data and dissociation curves to generate calibrations of the detected data and to further improve analysis of the data. The data can be taken from each support region of a multi-region platform, for example, from each well of a multi-well plate. Each support region can be loaded with portions of the same sample. In some embodiments, a dissociation curve correction can be calibrated for the sample, prior to a run of an experiment using such sample. In some embodiments, a method is provided for generating a melting transition region of dissociation curves that show the melting characteristics of the sample. In some embodiments, dye temperature dependence correction can be performed on the dissociation curve data to further improve analysis. In some embodiments, a feature vector can be derived from the melt data, and the feature vector can be used to further improve genotyping analysis of the dissociation curves.

Abstract: The present invention provides a novel assay that allows high-throughput screening of chemical compounds for the inhibition of binding between EF-Tu and tRNA.

Abstract: The invention provides methods, compositions, kits and devices for the detection of target molecules. In some embodiments, the invention allows for multiplexed target molecule detection.

Abstract: The present invention provides methods for amplifying a nucleic acid from a sample containing a mixture of nucleic acids utilizing a solid support. Methods are provided utilizing user-defined primer oligonucleotides for directional amplification that assists in further manipulation of the target nucleic acid, such as sequencing. Methods are also provided utilizing blocker and displacer oligonucleotides for generating amplified target nucleic acids of defined length. One of these methods provides a first oligonucleotide and a second oligonucleotide affixed to a solid support or separate solid supports. The first oligonucleotide is blocked to prevent extension from the 3?-terminus and has a sequence complementary to a first portion of a target nucleic acid. The second oligonucleotide has a sequence that is identical to a second portion of the target nucleic acid. In this method, a sample is applied to the solid support and the target nucleic acid within the sample binds said first oligonucleotide.

Abstract: This invention includes ionizable compounds, and compositions and methods of use thereof. The ionizable compounds can be used for making nanoparticle compositions for use in biopharmaceuticals and therapeutics. More particularly, this invention relates to compounds, compositions and methods for providing nanoparticles to encapsulate active agents, such as nucleic acid agents, and to deliver and distribute the active agents to cells, tissues, organs, and subjects.

Abstract: The present invention relates to a method of biological labeling that occurs via a free radical chain reaction. The labeling occurs due to deposition of a detectable reporter molecule from a media comprising a substance comprising at least two moieties of a peroxidase enzyme substrate (termed herein ‘cross-linker’) in a target site comprising peroxidase activity and a biological marker. The labeling reaction described herein may generally be used to detect targets in a host of experimental schemes for detecting and visualizing a biological or chemical target, including immunohistochemistry (IHC), in situ hybridization (ISH), antibody-based staining methods such as ELISA, Southern, Northern, and Western blotting, and others.

Abstract: The invention provides methods of detecting an analyte by multi-stage mass spectrometry with improved S/N ratio. An analyte is labeled with a positively-charged mass tag to form a precursor ion that leads by anchimeric assistance to a greatly enhanced, analyte-characteristic first product ion that can, in turn, lead to a greatly enhanced, analyte-characteristic second product ion in a mass spectrometer. Either a three stage mass spectrometer (true MS3) or a two-stage mass spectrometer (MS2) operated in a pseudo MS3 mode can be used. The precursor ion is split via an anchimeric-assisted reaction to form a first product ion, which in turn can be fragmented to form the second product ion. The methods offer extreme ultrasensitivity, at the low amol level. The invention also provides anchimeric mass tags for use in the methods. A wide variety of previously undetectable analytes of biological or environmental origin can be detected and quantified.

Abstract: Nucleic acid compositions, methods of making and using such compositions that comprise modular functional groups that can be configured to provide desired functionality to different nucleotide types through a swappable and preferably non-covalent linkage component. Such compositions are useful in a variety of applications including nucleic acid analyses.

Abstract: A method of preparing a nucleic acid sample with target enrichment uses a reaction vessel (11), within which is added a chelating agent to a sample with heating to about 99° C. to provide a crude lysate. A PNA probe is provided at a concentration sufficient for binding and capture of discernible levels of target nucleic acid. The PNA probe may be attached to beads (26) which are initially embedded in a wax body (17) and are released during the heating so that they are free to move and come into contact with the PNA probe and target DNA. After binding has occurred, the beads are magnetically attracted back into a pocket (16) along with the wax (17), which is allowed to solidify before they are removed from the reaction vessel.

Abstract: A composition and method for improving plant growth, wherein the composition includes at least one live strain of bacteria of the Lactobacillus rhamnosus species.

Abstract: Methods of barcoding nucleic acids, such as genomic DNA, are provided herein. In some embodiments, a fragment of genomic DNA may comprise a first and a second barcode.

Abstract: Multimeric protected fluorescent reagents and their methods of synthesis are provided. The reagents are useful in various fluorescence-based analytical methods, including the analysis of highly multiplexed optical reactions in large numbers at high densities, such as single molecule real time nucleic acid sequencing reactions. The reagents contain fluorescent dye elements, that allow the compounds to be detected with high sensitivity at desirable wavelengths, binding elements, that allow the compounds to be recognized specifically by target biomolecules, and protective shield elements, that decrease undesirable contacts between the fluorescent dye elements and the bound target biomolecules and that therefore decrease photodamage of the bound target biomolecules by the fluorescent dye elements. The reagents also contain coupling elements connect monomeric compounds into multimeric forms, thereby increasing brightness.

Abstract: This invention provides novel azido linkers for deoxynucleotide analogs having a detectable marker attached thereto.

Abstract: A method for lysing cells is disclosed. The method includes stirring cells with a magnetic stir element in the presence of a plurality of cell lysis beads at a speed sufficient to lyse the cells. Also disclosed is a device for lysing cells. The device includes a container having a magnetic stir element and a plurality of cell lysis beads disposed therein. The container is dimensioned to allow rotation of the magnetic stir element inside the container.

Abstract: Some embodiments described herein relate to modified nucleotide and nucleoside molecules with novel 3?-hydroxy protecting groups. Also provided herein are methods to prepare such modified nucleotide and nucleoside molecules and sequencing by synthesis processes using such modified nucleotide and nucleoside molecules.

Abstract: Provided are a mismatch-specific cleavage reaction using a novel heat-resistant mismatch nuclease, a method for removing errors in a nucleic acid amplification reaction using the mismatch nuclease, a method for inhibiting the amplification of a nucleic acid having a specific base sequence during a nucleic acid amplification reaction, and a method for detecting a nucleic acid having a single-base polymorphic mutation using this inhibition method.

Abstract: The present disclosure provides methods and kits for isolating miRNAs from biological fluids.

Abstract: According to the present teachings, methods and compositions are provided that utilize at least one reference dye of formula (I): In some embodiments, a method comprises measuring a detection signal of a reporter dye and at least one reference dye of formula (I). In some embodiments, a composition comprises a reference dye of formula (1), a buffer, a selection of nucleotides and a protein.

Abstract: The invention relates to double-stranded ribonucleic acid (dsRNA) compositions targeting the ALAS1 gene, and methods of using such dsRNA compositions to alter (e.g., inhibit) expression of ALAS1.

Abstract: Systems and methods are used to display data obtained from a qPCR instrument. Each of two or more samples is probed with a first labeling probe and a second labeling probe. A first data set is received from a qPCR instrument at a first cycle number that includes for each sample a first labeling probe intensity, and a second labeling probe intensity. A second data set is received at a second cycle number that includes for each sample a first labeling probe intensity and a second labeling probe intensity. A first plot of first labeling probe intensity as a function of second labeling probe intensity is created using the first data set. A second plot of first labeling probe intensity as a function of second labeling probe intensity is created using the second data set. The first plot and the second plot are displayed in response to user defined input to provide dynamic and real-time analysis of genotyping data.

Abstract: The present invention relates to a pharmaceutical composition for preventing or treating atopic dermatitis, the pharmaceutical composition including, as an active ingredient, X-shaped DNA (XL-DNA) formed by complementary binding of oligonucleotides having nucleotide sequences of SEQ ID NO: 1 to SEQ ID NO: 4. When the pharmaceutical composition is subcutaneously injected into an animal model of atopic dermatitis, effects of easing skin lesions, such as erythema, bleeding and edema, and the like, and ear edema, and reducing expression of immunoglobulin E (IgE) are exhibited. In this regard, the composition can be used as a pharmaceutical composition, a health food, or a cosmetic for atopic dermatitis.

Abstract: Methods for multiplex amplification of a plurality of targets of distinct sequence from a complex mixture are disclosed. In one aspect targets are circularized using a single circularization probe that is complementary to two regions in the target that flank a region to be amplified. The targets may hybridize to the circularization probe so that 5? or 3? flaps are generated and methods for removing flaps and circularizing the resulting product are disclosed. In another aspect targets are hybridized to dU probes so that 5? and 3? flaps are generated. The flaps are cleaved using 5? or 3? flap endonucleases or 3? to 5? exonucleases. The target sequences are then ligated to common primers, the dU probes digested and the ligated targets amplified.

Abstract: Compositions, reaction mixtures, and methods for performing an amplification reaction, including multiplex amplification reaction, wherein the method comprises using one or more amplification oligomer complexes comprising linked first and second amplification oligomer members. In one aspect, the amplification oligomer complex is hybridized to a target nucleic acid, the target nucleic acid with hybridized amplification oligomer complex is then captured, and other components are washed away. Target sequences of the target nucleic acids are pre-amplified to generate a first amplification product. The first amplification product is amplified in one or more secondary amplification reactions to generate second amplification products.

Abstract: The invention relates to double-stranded ribonucleic acid (dsRNA) compositions targeting the ALAS1 gene, and methods of using such dsRNA compositions to alter (e.g., inhibit) expression of ALAS1.