Abstract: The present invention relates to methods and systems that result in high quality, reproducible, thermal melt analysis on a microfluidic platform. The present invention relates to methods and systems using thermal systems including heat spreading devices, including interconnection methods and materials developed to connect heat spreaders to microfluidic devices. The present invention also relates to methods and systems for controlling, measuring, and calibrating the thermal systems of the present invention.

Abstract: The invention provides antibodies, and antigen-binding fragments thereof, that specifically bind to ROBO2, as well as uses, and methods thereof.

Abstract: The present inventors discovered that antibodies having weaker antigen-binding activity at the early endosomal pH in comparison with that at the pH of plasma are capable of binding to multiple antigen molecules with a single antibody molecule, have long half-lives in plasma, and have improved durations of time in which they can bind to antigen.

Abstract: A method for synthesizing a target double stranded (ds) polynucleotide by providing an oligonucleotide library within an array device that has a diversity of oligonucleotide library members, each of which has a different nucleotide sequence and is contained in a separate library containment in an aqueous solution. The library includes single stranded oligonucleotides and double stranded oligonucleotides with at least one overhang and covers at least 10,000 pairs of matching oligonucleotides. In a first step, transferring at least a first pair of matching oligonucleotides transferred from the library into a first reaction containment using a liquid handler and the matching oligonucleotides are assembled, thereby obtaining a first reaction product comprising at least one overhang.

Abstract: The present invention relates to high-throughput methods comprising direct infusion electrospray ionization mass spectrometry (ESI-MS), multistep tandem mass spectrometry (MSn), consecutive reaction monitoring (CRM), ion mobility spectrometry mass spectrometry (IMS-MS), high-resolution MS, and IMS-MS, for genome-wide (whole cell or tissue) profiling of DNA and RNA nucleotides/nucleosides having a wide variety of variant structural modifications. In particular, these methods are contemplated for providing a specific profile of variant DNA and/or RNA chemically modified nucleic acids (i.e. structures) associated with specific medical conditions. Medical conditions may include, but are not limited to: cancer; including prostate, lung, uterus, larynx, ovary, breast, kidney, and many other types of cancers; specific stages of cancer; bacterial infections; viral infections; genetic and metabolic disorders; and any condition involving changes in DNA and/or RNA structural modifications.

Abstract: Disclosed herein are nucleic acid molecules comprising one or more nucleic acid sequences that encode a mutated consensus LEMD1 antigen. Vectors, compositions, and vaccines comprising one or more nucleic acid sequences that encode a mutated consensus LEMD1 antigen are disclosed. Methods of treating a subject with a LEMD1-expressing tumor and methods of preventing a LEMD1-expressing tumor are disclosed. Mutated consensus LEMD1 antigen is disclosed.

Abstract: A method of treating a subject can include administering to a subject in need thereof an effective amount of a killer cell lectin-like receptor G1 (KLRG1)/ligand binding agent, thereby disrupting KLRG1 signaling and activating CD8+ cytotoxic T and/or NK cells. A method of treating cancer can include administering to a subject in need thereof an effective amount of a killer cell lectin-like receptor G1 (KLRG1)/ligand binding agent. The methods can treat various cancers, for example melanoma, lung cancer, pancreatic cancer, glioma, breast cancer, and ovarian cancer.

Abstract: The present invention relates to the field of resorbing biodegradable medical and cosmetic compositions.

Abstract: Methods of treating fibrotic diseases and disorders including Systemic sclerosis (SSc) are provided. Methods include, for example, administering to a subject an effective amount of an antagonist/inhibitor of PTP4A1 protein expression or activity to treat a fibrotic disease or disorder such as SSc, or an associated pathology such as organ or skin fibrosis.

Abstract: Provided are a multispecific protein drug and a library thereof, a preparing method therefor and an application thereof. Specifically, a protein drug library is provided and comprises C different protein drug monomers, wherein the protein drug monomer comprises a protein drug component part and a nucleic acid component part connected with the protein drug component part, and the nucleic acid component part of one protein drug monomer establishes a double-stranded paired structure with a nucleic acid component part of at least one different protein drug monomer by means of complementation, thereby constituting a protein drug polymer, wherein C is a positive integer greater than or equal to 2.

Abstract: Compounds of Formula (I) are provided herein. Such compounds, as well as pharmaceutically acceptable salts and compositions thereof, are useful for treating diseases or conditions, including conditions characterized by excessive cellular proliferation, such as cancer and tumors, as well as viral infections such as HIV.

Abstract: The application generally relates to olfaction as a biomarker, more particularly as a prognostic biomarker or biological predictor, of neurosensory disease or disorder and/or of neurocognitive disease or disorder, in subjects whose nervous system has been infected by an infectious agent, such as by a neurotropic virus, bacterium, protozoan parasite, fungus or prion, more particularly by a neurotropic virus.

Abstract: A circuit implementing a spiking neural network that includes a learning component that can learn from temporal correlations in the spikes regardless of correlations in the rates. In some embodiments, the learning component comprises a rate-discounting component. In some embodiments, the learning rule computes a rate-normalized covariance (normcov) matrix, detects clusters in this matrix, and sets the synaptic weights according to these clusters. In some embodiments, a synapse with a long-term plasticity rule has an efficacy that is composed by a weight and a fatiguing component. In some embodiments, A Hebbian plasticity component modifies the weight component and a short-term fatigue plasticity component modifies the fatiguing component. The fatigue component increases with increases in the presynaptic spike rate. In some embodiments, the fatigue component increases are implemented in a spike-based manner.

Abstract: A lateral flow assay device comprising a conjugate pad for receiving a quantity of fluid, and a membrane comprising a test line for determining whether the fluid comprises a target analyte. The device includes an actuator connected to a moving element comprising a shaft or a wheel. A first magnet is connected to the backing of the membrane. Second and third magnets are connected to the moving element. The actuator moves the moving element between first and second positions. In the first position, the opposite poles of the first and second magnets attract each other and maintain a gap between the membrane and the conjugate pad separate. In the second position, the similar poles of the first and third magnets repel each other and close the gap between membrane and the conjugate pad, allowing the fluid to flow from the conjugate pad into the membrane and the test line.

Abstract: The present invention relates to compositions and methods using protein reporters as imaging agents in 129Xe NMR and MRI applications. It is described that bla and MBP are genetically-encoded proteins that induce a detectable chemical shift during 129Xe NMR, allowing for use as protein reporters in research and clinical applications.

Abstract: Disclosed is a method for isolating, amplifying, and sequencing infectious agents' nucleic acids from an acellular fraction of a biological fluid using detergents and nucleic acids-digesting enzymes. Also disclosed is a kit-of-parts including detergents and nucleic acids-digesting enzymes for the implementation of the methods described.

Abstract: Provided herein are recombinant fungal or bacterial cells comprising a heterologous L-lactate dehydrogenase, and processes of preparing L-lactic acid employing such cells.

Abstract: The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules.

Abstract: Differentially expressed miRNA or small mRNA in the culture media of embryos were found to correlate to and affect embryo developmental fate. Accordingly the present invention provides a method for selecting a bovine embryo for implantation into a female bovine animal for further development based on the levels of specific miRNA or small mRNA. Also provided are methods of improving bovine embryo development fate by reducing in the culture medium the level of selected miRNAs.

Abstract: In some embodiments, an electrochemical sensing system includes a working electrode and a reference electrode. At least a portion of the working electrode includes rhodium. An electrical circuit is electronically coupled to the working electrode and the reference electrode. The electrical circuit is configured to bias the working electrode at voltage of less than about 0.4 V which is sufficient to electrochemically decompose a target analyte, and to measure a current corresponding to the concentration of the target analyte. In some embodiments, a biosensing molecule can be disposed on the working electrode and is operative to catalytically decompose a non-electroactive target analyte to yield and an electroactive by-product. In some embodiment, the reference electrode can include rhodium and its oxides.

Abstract: A biomolecule analysis kit includes a reaction container configured to perform an enzymatic reaction, the reaction container including a base portion which has a container-shaped portion and a low-adsorption structural portion which is provided on at least the inner surface of the container-shaped portion, the low-adsorption structural portion having an adsorption rate lower than the base portion at which at least one of a sample which becomes a target of analysis in the enzymatic reaction and a reagent for the enzymatic reaction is adsorbed thereonto, wherein a signal resulting from the enzymatic reaction is configured to be detected when the enzymatic reaction is performed in the reaction container.

Abstract: A peptide sequence of a guide protein for the production of a peptide of interest; a peptide sequence that has a similarity of at least 90% to SEQ. ID. NO 1; a nucleotide sequence encoding the guide protein; an expression vector comprising the nucleotide sequence; a host cell that expresses a fusion protein comprising a peptide of interest; a method of production of a peptide of interest, comprising the steps of A) constructing an expression vector; B) inserting the expression vector into a host cell; C) expressing the fusion protein, culturing the host cell in a culture medium; D) recovering the accumulated fusion protein in the host cell; E) cleaving the fusion protein; F) purifying the peptide of interest.

Abstract: The present invention relates generally to a method of screening for the onset, predisposition to the onset and/or progression of a neoplasm. More particularly, the present invention relates to a method of screening for the onset, predisposition to the onset and/or progression of a neoplasm by screening for changes to the methylation levels of a panel of gene markers including BCAT1, IKZF1, IRF4, GRASP and/or CAHM. The method of the present invention is useful in a range of applications including, but not limited to, those relating to the diagnosis and/or monitoring of colorectal neoplasms, such as colorectal adenocarcinosis.

Abstract: A computer-implemented method, system, and apparatus for providing interactive and analytical components that provide a comprehensive and dynamic tool for therapies to prevent and cure dementia-related diseases. The invention includes one or more computers that receive and store personal information for people, including personal background information, pre-existing conditions, current medications, genomic data and diagnostic information. The computers also generate synergic data containing compounded probability data specifying an expected adjustment of individual biological mechanisms from particular combinations of therapies. For each person, the computers process personal information and identify a subset of biological mechanisms that are principally affected by dementia-related diseases or the substantial risk of dementia-related diseases.

Abstract: We determined the sequence of ATRX and DAXX in 447 cancers from various sites. We found mutations most commonly in pediatric glioblastoma multiformae (GBM) (11.1%), adult GBM (6.5%), oligodendrogliomas (7.7%) and medulloblastomas (1.5%); and showed that Alternative Lengthening of Telomeres (ALT), a telomerase-independent telomere maintenance mechanism found in cancers that have not activated telomerase, perfectly correlated with somatic mutations of either gene. In contrast, neuroblastomas, and adenocarcinomas of the ovary, breast, and pancreas were negative for mutations in ATRX and DAXX. Alterations in ATRX or DAXX define a specific molecular pathway that is closely associated with an alternative telomere maintenance function in human cancers.

Abstract: The method involves drying down dye-conjugated reagents in separate locations in a reaction vessel so that the dyes don't non-specifically interact with each other during drying. This invention thus improves multiplex binding assays by eliminating erroneous results caused by dyes' being non-specifically attached to each other when dried down together.

Abstract: The present invention relates to a method for producing dextran polymer-based amplified nucleic acid aptamer nanoconstructs which efficiently and selectively capture a specific target molecule, the method comprising linking a short nucleic acid sequence or a complementary sequence for formation of nanoconstructs and a nucleic acid aptamer sequence for capture of the specific target molecule to a dextran polymer by a chemical reaction, mixing the resulting polymer/nucleic acid substances with each other to form nanostructures, subjecting the nanostructures to rolling circle amplification, thereby forming a nucleic acid aptamer having a repeated structure. The dextran polymer-based amplified nucleic acid aptamer nanoconstructs have the effect of efficiently and selectively capturing a specific target molecule.

Abstract: A computer aided diagnostic system and automated method to classify a kidney utilizes medical image data and clinical biomarkers in evaluation of kidney function pre- and post-transplantation. The system receives image data from a medical scan that includes image data of a kidney, then segments kidney image data from other image data of the medical scan. The kidney is then classified by analyzing at least one feature determined from the kidney image data and the at least one clinical biomarker.

Abstract: A circuit implementing a spiking neural network that includes a learning component that can learn from temporal correlations in the spikes regardless of correlations in the rates. In some embodiments, the learning component comprises a rate-discounting component. In some embodiments, the learning rule computes a rate-normalized covariance (normcov) matrix, detects clusters in this matrix, and sets the synaptic weights according to these clusters. In some embodiments, a synapse with a long-term plasticity rule has an efficacy that is composed by a weight and a fatiguing component. In some embodiments, A Hebbian plasticity component modifies the weight component and a short-term fatigue plasticity component modifies the fatiguing component. The fatigue component increases with increases in the presynaptic spike rate. In some embodiments, the fatigue component increases are implemented in a spike-based manner.

Abstract: The invention relates to a novel hetero-dimeric multi-specific format of multiple antibody variable domains comprising a core of two split variable domain pairs wherein both variable light domains and the two cognate variable heavy domains are positioned in tandem on two separate protein chains, respectively.

Abstract: A novel use of ligands of B7h receptor in the treatment of osteoporosis or osteopenia is disclosed as well as the use of B7h receptor as target for the screening of pharmaceutical active agents useful in the treatment of osteopenia or osteoporosis.

Abstract: Provided herein are recombinant peptides useful for inhibiting the function of autophagy-related 8 (Atg8) proteins. The recombinant peptides can be used in the preparation of imaging agents for monitoring autophagy in a cell or subject and treating autophagy related diseases, such as cancer.

Abstract: Provided herein is a method for making an cDNA library, comprising adding an affinity tag-labeled GMP to the 5? end of targeted RNA species in a sample by optionally decapping followed by incubating the sample with an affinity tag-labeled GTP and a capping enzyme, enriching for RNA comprising the affinity tag-labeled GMP using an affinity matrix that binds to the affinity tag, reverse transcribing the enriched RNA to produce a population of cDNAs, and adding a tail to the 3? end of the population of cDNAs using a terminal transferase, to produce an cDNA library.

Abstract: The present invention relates to a method for genotyping single nucleotide polymorphisms (SNPs) using a lateral flow test device. The invention also relates to a kit comprising said lateral flow test device and also to the use thereof for genotyping single nucleotide polymorphisms (SNPs).

Abstract: Recombinantly expressed variant antibodies that have enhanced affinity for TL1A and enhanced potency relative to the parent antibody from which they were derived are provided. The antibodies inhibit the interaction between TL1A and the death receptor 3 (DR3). The antibodies, or a composition thereof, may be used to treat one or more of asthma, COPD, pulmonary fibrosis, cystic fibrosis, inflammatory bowel disease, a gastrointestinal disease associated with cystic fibrosis, Crohn's disease, colitis, ulcerative colitis, irritable bowel syndrome, eosinophilic esophagitis, atopic dermatitis, eczema, scleroderma, arthritis, or rheumatoid arthritis.

Abstract: Provided are compositions, kits, and methods for the identification of Listeria. In certain aspects and embodiments, the compositions, kits, and methods may provide improvements in relation to specificity, sensitivity, and speed of detection.

Abstract: The modification of biomolecules, small molecules, and other agents of via conjugation of excipients, tags, or labels is of great importance. For example, the modification of therapeutic agents can confer improved stability, solubility, duration of action, or pharmacological properties. Supramolecular chemistry utilizes specific, directional, reversible, non-covalent molecular recognition motifs in order to achieve organization of molecules, and can be used to complex tags to agents of interest (e.g., insulin, glucagon, antibodies). The present invention provides useful supramolecular complexes wherein an agent of interest is specifically bound to a host via non-covalent interactions, and wherein the host is conjugated to a tag. The present invention also provides methods and compounds useful in preparing supramolecular complexes, and methods of treating diseases using the supramolecular complexes.

Abstract: Described herein is the finding that increasing the frequency of Zscan4 activation in mouse ES cells not only enhances, but also maintains their developmental potency in long-term cell culture. As the potency increases, even a whole animal can be produced from a single ES cell injected into a 4N blastocyst at an unexpectedly high success rate. The studies disclosed herein indicate that ES cells acquire higher potency by going through the transient Zscan4 activation state more frequently than the regular state. Particularly disclosed herein is the finding that the constitutive presence of Zscan4-ERT2, even in the absence of its usual activator tamoxifen, can increase the frequency of endogenous Zscan4 activation in ES cells, resulting in the increase of developmental potency of the ES cells. Accordingly, provided herein are Zscan4-ERT2 fusion proteins and nucleic acid molecules and vectors encoding Zscan4-ERT2 fusion proteins.

Abstract: The present invention relates to a compound inhibiting the expression and/or the activity of maternally expressed 3 (Meg3) for use in treating or preventing cardiac remodelling.

Abstract: The present invention relates to a process for determining in vitro the immune status of an individual according to which: (a) a blood sample from the individual is provided, (b) at least two reagents specific to at least two products of expression of at least two target genes are provided; (c) the expression of said at least two target genes is determined, and (d) the expression of said at least two target genes respectively is compared with a reference expression, with a change in the expression of said at least two target genes relative to their reference expression indicating that the individual's immune status has changed, and a correlation between the expression of said at least two target genes with their reference expression indicating that the individual's immune status is normal; as well as a kit for determining said immune status of the individual.

Abstract: The present disclosure provides methods for determining the ploidy status of a chromosome in a gestating fetus from genotypic data measured from a mixed sample of DNA comprising DNA from both the mother of the fetus and from the fetus, and optionally from genotypic data from the mother and father. The ploidy state is determined by using a joint distribution model to create a plurality of expected allele distributions for different possible fetal ploidy states given the parental genotypic data, and comparing the expected allelic distributions to the pattern of measured allelic distributions measured in the mixed sample, and choosing the ploidy state whose expected allelic distribution pattern most closely matches the observed allelic distribution pattern. The mixed sample of DNA may be preferentially enriched at a plurality of polymorphic loci in a way that minimizes the allelic bias, for example using massively multiplexed targeted PCR.

Abstract: Drug targets, pathways, kits and methods for treating conditions related to neurodegeneration or ocular disease, are disclosed.

Abstract: This document provides methods and materials involved in assessing samples (e.g., cancer cells) for the presence of a loss of heterozygosity (LOH) signature. For example, methods and materials for determining whether or not a cell (e.g., a cancer cell) contains an LOH signature are provided. Materials and methods for identifying cells (e.g., cancer cells) having a deficiency in homology directed repair (HDR) as well as materials and methods for identifying cancer patients likely to respond to a particular cancer treatment regimen also are provided.

Abstract: A method for extracting pharmacogenetic DNA from dried blood that is retained in a solid resin collection device includes one or more of the steps of combining the dried blood and at least a portion of the solid resin collection device in a first vessel, sonicating the first vessel containing the dried blood and at least a portion of the solid resin collection device, moving at least some of the contents of the first vessel including the portion of the solid resin collection device to a solid resin spin column, adding an elution buffer to the solid resin spin column, centrifuging the solid resin spin column so that at least some of the contents of the solid resin spin column are transferred to a second vessel, and processing the contents of the second vessel by conducting one of capillary electrophoresis, Next-Generation Sequencing, DNA sequencing or genotyping, and mass spectrometry-based sequencing on the contents of the second vessel.

Abstract: Several embodiments provided for relate to methods of using of anti-CD19 CAR expressing immune cells in immunotherapy. Provided for herein in several embodiments are immune cell-based (e.g., natural killer (NK) cell) compositions comprising CD19-directed chimeric antigen receptors. In some, embodiments the anti-CD19 binder portion of the CAR is humanized. In several embodiments, the humanized anti-CD19 CAR expressing cells exhibit enhanced expression of the CAR as well as enhanced cytotoxicity and/or persistence.

Abstract: Methods for purifying RNA from a sample, comprising one or more steps of tangential flow filtration, hydroxyapatite chromatography, core bead flow-through chromatography, or any combinations thereof. These techniques are useful individually, but show very high efficiency when used in combination, or when performed in particular orders. The methods can purify RNA in a highly efficient manner without unduly compromising potency or stability, to provide compositions in which RNA is substantially cleared of contaminants. Moreover, they can be performed without the need for organic solvents.

Abstract: Disclosed are methods for modulating splicing of Tau mRNA in an animal with Tau antisense compounds. Also disclosed herein are methods for reducing expression of Tau mRNA and protein in an animal with Tau antisense compounds. Such compounds and methods are useful to treat, prevent, or ameliorate neurodegenerative diseases in an individual in need thereof. Examples of neurodegenerative diseases that can be treated, prevented, and ameliorated with the administration Tau antisense oligonucleotides include Alzheimer's Disease, Fronto-temporal Dementia (FTD), FTDP-17, Progressive Supranuclear Palsy, Chronic Traumatic Encephalopathy, Epilepsy, and Dravet's Syndrome.

Abstract: Methods, systems, and apparatus determine whether a first chromosomal region exhibits a deletion or an amplification associated with cancer in a sample from a subject (e.g., where the sample includes a mixture of cell-free DNA from tumor cells and non-malignant cells. Nucleic acid molecules of the biological sample are sequenced. Respective amounts of a clinically-relevant chromosomal region and of background chromosomal region(s) are determined from results of the sequencing. A parameter derived from these amounts (e.g. a ratio) is compared to one or more cutoff values, thereby determining a classification of whether first chromosomal region exhibits a deletion or an amplification associated with cancer.

Abstract: The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules.

Abstract: A multiplex slide plate device is provided, including a slide plate, a sacrificial layer, and a housing. The slide plate has reaction vessels arranged in an array. The sacrificial layer has a microfluidic channel, which has an injection channel, a main channel, and a distal channel connected to each other. The housing is used to accommodate the slide plate and the sacrificial layer, and is composed of a cover and a tray, and the cover has an injection hole, an exhaust hole, and a storage tank. A sample solution and an oil are injected from the injection hole into the injection channel, wherein the sample solution is pushed by the oil. The sample solution loads into each of the reaction vessels while flowing through the main channel. Excess waste liquid flows from the exhaust hole into the storage tank, and is covered by the oil and cannot reflow.