Abstract: Methods, systems, and devices for automated feature selection and model generation are described. A device (e.g., a server, user device, database, etc.) may perform model generation for an underlying dataset and a specified outcome variable. The device may determine relevance measurements (e.g., stump R-squared values) for a set of identified features of the dataset and can reduce the set of features based on these relevance measurements (e.g., according to a double-box procedure). Using this reduced set of features, the device may perform a least absolute shrinkage and selection operator (LASSO) regression procedure to sort the features. The device may then determine a set of nested linear models—where each successive model of the set includes an additional feature of the sorted features—and may select a “best” linear model for model generation based on this set of models and a model quality criterion (e.g., an Akaike information criterion (AIC)).

Abstract: A method is provided for treating a recipient with a biological product obtained from at least one donor that may be the same as, or different from, the recipient. The method includes identifying a targeted level of gene expression of a first gene in a biological product to be transferred from at least one donor to a recipient; treating the at least one donor to achieve the targeted level of gene expression of the first gene in the biological product; and transferring the biological product from the at least one donor to the recipient.

Abstract: This disclosure provides methods for determining relative abundance of one or more non-host species in a sample from a host. Also provided are methods involving addition of known concentrations of synthetic nucleic acids to a sample and performing sequencing assays to identify non-host species such as pathogens. Also provided are methods of tracking samples, tracking reagents, and tracking diversity loss in sequencing assays.

Abstract: Provided herein are highly sensitive compositions and methods for detection of at least one specific nucleic acid molecule in a sample. The presence of a specific nucleic acid provides a positive indicator of a pathogenic agent, contaminant, non-canonical bases, and/or wild-type or mutated genes in a sample or a cell. Applications for which the compositions and methods are particularly well suited include point-of-care disease diagnosis or cellular RNA imaging.

Abstract: Disclosed are arrays of nucleic acid molecules, kits, methods of genotyping and marker assisted bovine breeding methods using SNPs on genes of the bovine interferon tau signaling pathway for improved bovine fertilization rate, or embryo survival, or both.

Abstract: An analyzer of a component in a sample fluid includes an optical source and an optical detector defining a beam path of a beam, wherein the optical source emits the beam and the optical detector measures the beam after partial absorption by the sample fluid, a fluid flow cell disposed on the beam path defining an interrogation region in the a fluid flow cell in which the optical beam interacts with the sample fluid and a reference fluid; and wherein the sample fluid and the reference fluid are in laminar flow, and a scanning system that scans the beam relative to the laminar flow within the fluid flow cell, wherein the scanning system scans the beam relative to both the sample fluid and the reference fluid.

Abstract: Provided herein is technology relating to isolating nucleic acids. In particular, the technology relates to methods and kits for extracting nucleic acids from problematic samples such as stool.

Abstract: The present invention is based, in part, on the discovery of galectin 1 (Gal1) epitopes against which anti-Gal1 agents can neutralize Gal1 function, as well as anti-Gal1 agents and methods useful for neutralizing Gal1 function.

Abstract: The presently claimed invention offers programmable and precise regulation of Cas9 functions by utilizing a set of compact Cas9 derivatives created by deleting conserved HNH and/or REC-C domains based on the structural information across variant class 2 CRISPR effectors. In addition, a novel strategy for engineering the dimeric gRNA-guided nuclease by splitting the mini-dSaCas9 and fusing the FokI domain right after the split point is claimed to increase the on-target DNA cleavage efficiency and potentially reduce the off-target effect because of a closer proximity of dimeric Fold nuclease to the target sequence. By combining the optimized and compact gRNA expression cassette and the downsized SaCas9 derivatives, the entire CRISPR/Cas system with different effector domains for transactivation, DNA cleavage and base editing is loaded into a single AAV virus. Such an all-in-one AAV-CRISPR/Cas9 system will be particularly appealing in biomedical applications that require safe and efficient delivery in vivo.

Abstract: This disclosure provides chips, systems and methods for sequencing a nucleic acid sample. Tagged nucleotides are provided into a reaction chamber comprising a nanopore in a membrane. An individual tagged nucleotide of the tagged nucleotides can contain a tag coupled to a nucleotide, which tag is detectable with the aid of the nanopore. Next, an individual tagged nucleotide of the tagged nucleotides can be incorporated into a growing strand complementary to a single stranded nucleic acid molecule derived from the nucleic acid sample. With the aid of the nanopore, a tag associated with the individual tagged nucleotide can be detected upon incorporation of the individual tagged nucleotide. The tag can be detected with the aid of the nanopore when the tag is released from the nucleotide.

Abstract: The present disclosure provides methods of treating subjects having hearing loss, methods of identifying subjects having an increased risk of developing hearing loss, and methods of detecting Kelch Domain Containing 7B (KLHDC7B) variant nucleic acid molecules and variant polypeptides.

Abstract: Provided herein are reagents and kits for detection of multiple target sequences in a single-tube, single-color assay, and methods of use thereof. In particular, multiplex assays are provided for the detection of Mycobacterium tuberculosis complex target sequences (e.g., katG, rpoB, inhA promotor, pncA, etc.).

Abstract: A diagnostic assay strip includes a first layer that includes an iron mobile labelled specific binding partner that will bind to and iron biomarker from a sample and produce an iron complex and a vitamin A mobile labelled specific binding partner that will bind to a vitamin A biomarker from the sample and produce a vitamin A complex. A second layer includes iron and vitamin A test regions, and a control region. The iron test region has immobilized specific binding partners that will bind to the iron complex. The vitamin A test region has immobilized vitamin A biomarker that will bind to vitamin A mobile labelled specific binding partner, which is not bound to the vitamin A biomarker, passing from the first layer to the second layer. The control region has a moiety which will non-specifically bind to and immobilize the iron and vitamin A labelled specific binding partners. Methods of using the diagnostic assay strip are also discussed.

Abstract: Probe systems and methods are provided for detecting nucleic acid targets using labeled polynucleotide probes and antiprobes that interact together and with complementary targets. These interactions result in signaling changes that indicate target frequency and provide error-checking functions that facilitate single base discrimination. These probe:antiprobe compositions enable real-time PCR detection, end-point detection and microarray detection of microbial species, drug resistant mutants, and cancer related variants. The probe:antiprobe may be an internal probe between two primers or may be a primer-probe. The probe also may be modified by introducing a base mismatch to increase thermodynamic discrimination of a correct versus incorrect target differing by a single base. Probe systems also are provided for use in methods of increasing target amplification and detecting specific single base variants.

Abstract: The present invention relates to RNAi constructs and their use in gene silencing. RNAi constructs associated with the invention contain a double stranded region connected to a single stranded region of phosphorothioate modified nucleotides.

Abstract: This invention relates to compounds, compositions, and methods useful for reducing AT3 target RNA and protein levels via use of dsRNAs, e.g., Dicer substrate siRNA (DsiRNA) agents.

Abstract: A novel maize variety designated PH4DR4 and seed, plants and plant parts thereof are provided. Methods for producing a maize plant comprise crossing maize variety PH4DR4 with another maize plant are provided. Methods for producing a maize plant containing in its genetic material one or more traits introgressed into PH4DR4 through backcross conversion and/or transformation, and to the maize seed, plant and plant part produced thereby are provided. Hybrid maize seed, plants or plant parts are produced by crossing the variety PH4DR4 or a locus conversion of PH4DR4 with another maize variety.

Abstract: In certain embodiments, the present invention provides a modified transfer RNA (tRNA) comprising a T-arm, a D-arm, and anticodon-arm and an acceptor arm, wherein the T-arm comprises nucleotides that interact with the elongation factor 1 alpha protein, and methods of use thereof.

Abstract: Disclosed are luciferase polypeptides with improved light-emitting activity and their encoding nucleic acids. These molecules are useful in a range of assays including luciferase-based gene reporter assays, bioluminescence resonance energy transfer assays, protein complementation assays and other applications in which luciferase enzymes are utilized as detectable and/or quantifiable labels. Also disclosed are methods and compositions for increasing the sensitivity and/or improving the kinetics of luciferase-catalyzed reactions as well as decreasing the impact of undesirable variables.

Abstract: Embodiments of the present disclosure provide a target capturing apparatus and a manufacturing method thereof, and a target detecting method. The target capturing apparatus includes a cavity structure, the cavity structure includes: an inlet portion, an outlet portion and a capture region positioned between the inlet portion and the outlet portion, and the capture region includes a capture component, and a combination specifically combined with a to-be-captured target is included in the capture component so as to capture the target in a sample entering the cavity structure.

Abstract: Oligonucleotides are provided herein that inhibit MARC1 expression. Also provided are compositions including the same and uses thereof, particularly uses relating to treating diseases, disorders and/or conditions associated with MARC1 expression.

Abstract: The present disclosure provides small hairpin nucleic acid molecules capable of stimulating interferon production. The nucleic acid molecules of the present disclosure has a double-stranded section of less than 19 base pairs and at least one blunt end. In certain embodiments, the molecule comprises at least one 5?-triphosphate and/or at least one 5?-diphosphate. In certain embodiments, compounds and/or compositions of the disclosure are useful for treating, ameliorating, and/or preventing SARS-CoV-2 viral infection, and/or ameliorating, minimizing, reversing, and/or preventing persistent SARS-CoV-2 viral infection, and/or minimizing or preventing SARS-CoV-2 viral infection-derived mortality and/or lethality, in a subject. In certain embodiments, compounds and/or compositions of the disclosure are useful for treating, ameliorating, and/or preventing SARS-CoV-2 viral infection in a tumor-bearing subject.

Abstract: Described herein is a chemical sensing system that can be deployed in an environment and automatically monitor the environment. The chemical sensing system includes one or more chemical sensing units with sensing elements that sense chemicals in the environment. The chemical sensing system analyzes measured values output by the sensing elements to identify patterns indicative of events. After identifying an event, the chemical sensing system may generate an inference about the environment using measured values output by the sensing elements during the event.

Abstract: Described herein are methods of enhancing chromosomal homologous recombination to stimulate a loss of heterozygosity at a gene locus of interest in a living cell. These methods are driven by an enhancer component and a target-specific endonuclease component and proceed through a mechanism whereby: exogenous donor DNA that is homologous to the gene locus of interest is not introduced into the living cell; the desired allele of the gene locus of interest remains uncleaved; and the undesired allele is either uncleaved, cleaved at a single location, or cleaved at multiple locations. These methods have numerous applications, including the repair of risk alleles for disease prevention, the correction of heterozygous mutations in dividing cells, the design of cancer therapeutics, and the design of novel gene-drive strategies.

Abstract: The disclosure provides a method of inhibiting proliferation of a cell, inhibiting m3C formation in a cell, inhibiting activity of Mettl8 in a cell, or activating ATM and p53 in a cell, the method comprising contacting the cell with a Mettl8 inhibitor. The disclosure also provides a composition comprising a cell with a reduced expression or activity of Mettl8. In another aspect, the disclosure provides methods of rendering a tumor cell sensitive to a cancer therapy.

Abstract: Disclosed herein are methods for the detection of the presence of sperm DNA fragmentation in a semen sample. The methods include embedding of sperm cells of the semen sample in a gel, denaturing DNA of the sperm cells, and lysing the nuclear proteins of the sperm cells. The present method includes an ionic surfactant sodium dodycyl sulfate (SDS) and a chaotropic agent urea in the lysis solution for releasing DNA from protamine of chromosome, which significantly reduces the time required for lysis. A kit for detecting sperm DNA fragmentation in a semen sample is also disclosed.

Abstract: The present disclosure provides a diagnostic method based on pairwise comparison of cancers using transcriptome expression data. In one embodiment, the method comprises the steps of: obtaining a first gene expression profile of a first cancer sample having a first cancer type; obtaining a second gene expression profile of a second cancer sample having a second cancer type, wherein the second cancer type is different from the first cancer type; comparing said first gene expression profile with said second gene expression profile; and selecting N genes that are most differentially expressed in the first and the second gene expression profiles to generate pairwise differentially expressed genes (DEGs), wherein N is an integer between 10 and 100.

Abstract: Provided herein is a lateral flow diagnostic device and methods of using thereof. The device comprises a substrate and a first end, wherein the first end comprises a sample loading portion. The first end may further comprise a first region loaded with a detectable ligand, a CRISPR effector system, a detection construct, a first test band comprising a biotin ligand, and a second test band comprising a capture molecule for the detectable ligand. The detection construct may comprise an RNA oligonucleotide, having a first molecule such as FITC on a first end and a second molecule such as FAM on a second end. Contacting the sample loading portion with a sample causes the sample to flow from the sample loading portion of the substrate towards the first and second capture regions, thereby generating a detectable signal, which may be indicative of a disease state.

Abstract: Provided herein are double strand DNA molecules comprising inverted repeats, expression cassette and one or more restriction sites for nicking endonucleases, the methods of use thereof, and the methods of making therefor.

Abstract: There is a method for selective translation of a desired protein. The method has the steps of (a) providing a modified nucleic acid enzyme, including two half cores of a minimized 9DB1 deoxyribozyme split between nucleotides 35 and 39, wherein each half core includes a pendant assembly arm of a strand of nucleic acids extending therefrom and a separate, pendant binding arm extending therefrom of a strand of nucleic acids; (b) binding a nucleic acid ligand to each of the two assembly arms to form an intermediate; (c) binding the intermediate to (i) a first substrate of ribonucleic acid sequences capped at one end, (ii) a second substrate of a strand of ribonucleic acids having a 5? triphosphate region at one end and a region of polyadenylated nucleotides at the other end and wherein the second substrate codes for the desired protein, (iii) join the two half cores to form a core in order to form a ligated product; and (d) allowing the translation for the desired protein to proceed from the ligated product.

Abstract: Optical device for optical fluorescence microscopy, comprising a spatial modulator (1), a microscope objective (2), a beamsplitter (3) and a camera (4), wherein the beamsplitter (3) is placed between the spatial modulator (1) and the microscope objective (2), wherein the beamsplitter (3) is placed between the camera (4) and the microscope objective (2), and wherein a prism (5) is placed between the beamsplitter (3) and the camera (4).

Abstract: The present disclosure provides oligomeric compounds (including oligomeric compounds that are antisense agents or portions thereof) comprising a modified oligonucleotide having at least one modified internucleoside linking group.

Abstract: Provided herein are compositions and methods of reducing adduct formation.

Abstract: The present invention is a method for measuring the amount of at least one molecule in a biological sample, the method comprising a) combining the sample, or a derivative thereof, with one or more aptamers and allowing one or more molecules in the sample to bind to the aptamer(s); b) separating bound from unbound molecules; and c) quantifying the molecule(s) bound to the or each aptamer, wherein quantification of the bound molecule(s) is carried out by sequencing at least part of the or each aptamer. Uses of and products derived from the method are also contemplated.

Abstract: The present invention provides a system for receiving biological sequence information and activating the synthesis of a biological entity. The system has a receiving unit for receiving a signal encoding biological sequence information transmitted from a transmitting unit. The transmitting unit can be present at a remote location from the receiving unit. The system also has an assembly unit connected to the receiving unit, and the assembly unit assembles the biological entity according to the biological sequence information. Thus, according to the present invention biological sequence information can be digitally transmitted to a remote location and the information converted into a biological entity, for example a protein useful as a vaccine, immediately upon being received by the receiving unit and without further human intervention after preparing the system for receipt of the information.

Abstract: Nucleic acid memory strands encoding digital data using a sequence of homopolymer tracts of repeated nucleotides provides a cheaper and faster alternative to conventional digital DNA storage techniques. The use of homopolymer tracts allows for lower fidelity, high throughput sequencing techniques such as nanopore sequencing to read data encoded in the memory strands. Specialized synthesis techniques allow for synthesis of long memory strands capable of encoding large volumes of data despite the reduced data density afforded by homopolymer tracts as compared to conventional single nucleotide sequences.

Abstract: Methods and compositions for attaching cell-specific barcodes without formation of partitions is provided.

Abstract: The invention relates to novel maize plants, seeds and compositions, as well as improvements to maize plant breeding and methods for creating modifications in maize plant genomes.

Abstract: The methods described herein provide a means of producing an array of spatially separated proteins. The method relies on covalently attaching each protein of the plurality of proteins to a structured nucleic acid particle (SNAP), and attaching the SNAPs to a solid support.

Abstract: A Western Blot assay is performed by performing a probing process on a membrane containing target proteins, by contacting the membrane with a fluorescent resonant energy transfer (FRET) solution and allowing the probing process to proceed for a probing time period. The probing process results in a target protein becoming labeled with both a donor chromophore and an acceptor chromophore, which are effective as a donor-acceptor pair for FRET when so linked to the target protein. While performing the probing process, the labeled target proteins are measured by irradiating the membrane with an excitation light to excite the donor chromophores, wherein in each labeled target protein, the excited donor chromophore transfers energy to the acceptor chromophore by FRET and, in response, the labeled target protein emits an emission light. The intensity of the emission light is then measured. The light measured may be light emitted from the donor chromophore and/or light emitted from the acceptor chromophore.

Abstract: A computer-implemented method for spectroscopic analysis of biological material is provided that includes analyzing samples of biological material from a plurality of sources, and delivering samples of biological material to at least one flow cell for spectroscopy, and determining whether the spectroscopic analysis for each sample of the plurality of samples is or is predicted to be ambiguous in that it is affected by at least two non-discriminable factors. If such a determination is made, a disambiguating step can be performed.

Abstract: The invention relates to a plasmid, a DNA assembly method and its application recombinant strain. The plasmid has single adjacent Type IIP and Type IIS RE recognition sites. The plasmid combines the properties of Type IIP and Type IIS REs to achieve recursive cycling, SCAR-free and repeat sequence assembly.

Abstract: Disclosed herein are engineered oligonucleotides for selective inhibition of polypeptide expression and activity. Also disclosed herein are methods of selectively inhibiting polypeptide expression and activity contacting an engineered oligonucleotide with a polynucleotide encoding the polypeptide.

Abstract: Compositions comprising multiple hydrogel particles having substantially the same diameter, but with each subgrouping of particles from the multiple hydrogel particles having different associated values for one or more passive optical properties that can be deconvoluted using cytometric instrumentation. Each hydrogel particle from the multiple hydrogel particles can be functionalized with a different biochemical or chemical target from a set of targets. A method of preparing hydrogel particles includes forming droplets and polymerizing the droplets, with optional functionalization.

Abstract: Methods and systems described herein involve using long cell-free DNA fragments to analyze a biological sample from a pregnant subject. The status of methylated CpG sites and single nucleotide polymorphisms (SNPs) is often used to analyze DNA fragments of a biological sample. A CpG site and a SNP are typically separated from the nearest CpG site or SNP by hundreds or thousands of base pairs. Finding two or more consecutive CpG sites or SNPs on most cell-free DNA fragments is improbable or impossible. Cell-free DNA fragments longer than 600 bp may include multiple CpG sites and/or SNPs. The presence of multiple CpG sites and/or SNPs on long cell-free DNA fragments may allow for analysis than with short cell-free DNA fragments alone. The long cell-free DNA fragments can be used to identify a tissue of origin and/or to provide information on a fetus in a pregnant female.

Abstract: This invention provides methods of amplifying genomic DNA to obtain an amplified representative population of genome fragments. Methods are further provided for obtaining amplified genomic DNA representations of a desired complexity. The invention further provides methods for simultaneously detecting large numbers of typable loci for an amplified representative population of genome fragments. Accordingly the methods can be used to genotype individuals on a genome-wide scale.

Abstract: The present invention may provide a small RNA detection sensor comprising: at one end thereof, a first sensing region comprising nucleotides having a sequence complementary to target small RNA; and a PCR-capable region that is coupled to the first sensing region, the small RNA detection sensor to synthesize a replication region complementary to the PCR-capable region by a DNA polymerase by using the target small RNA as a primer, and amplify the PCR-capable region and the replication region.

Abstract: Aspects of the invention include methods for preparing sequencing libraries, performing sequencing procedures that can correct for process-related errors, and identifying rare variants that are or may be indicative of cancer.

Abstract: Provided herein are methods and compositions for synthesizing 5?Capped RNAs wherein the initiating capped oligonucleotide primers have the general form m7Gppp[N2?Ome]n[N]m wherein m7G is N7-methylated guanosine or any guanosine analog, N is any natural, modified or unnatural nucleoside, “n” can be any integer from 0 to 4 and “m” can be an integer from 1 to 9.

Abstract: The invention relates to a combination and its use for the treatment of diseases. The instant disclosure provides a combination of a so-called T-cell regulator selected from the group comprising PD1, PD-L1, OX40, TIM-3, LAG3, CD137(4-1BB) and a non-coding immunomodulating DNA.