Abstract: Provided herein are methods for determining the ploidy state of one or more chromosome in a developing fetus. The subject methods provide for increased accuracy by utilizing information about the mosaicism level of one or more chromosomes of interest in the mother of fetus. The mosaicism level of one or more chromosomes of interest is determined for the maternal tissue that is used as the source of nucleic acid for genetic analysis that are used to determine the ploidy state of the fetal chromosome or chromosomes of interest. Utilization of the mosaicism data can be used to increase the reliability and accuracy of the determination of the ploidy state of a chromosome of interest.

Abstract: Methods and systems for identifying and quantifying molecular biomarkers and for predicting patient response to cancer therapy are provided. The disclosed methods and systems make use of artificial intelligence to capture morphometric changes from histopathology tissue that correlate with molecular changes. The system may analyze molecular markers which are predictive of tumor response and have no defined correlation with morphological features. The system may use artificial intelligence to correlate morphometric changes with critical gene modifications and molecular changes.

Abstract: Compositions useful as poliovirus immunogens are provided along with methods and compositions for preparing the same. Compositions comprising poliovirus immunogens can enable a host response that includes virus-neutralizing antibodies which can protect the host from infection and/or disease.

Abstract: Disclosed herein are high Tm RNA nanostructures that can be composed of one or more modules or motifs to build RNA nanostructures with or without layers. The RNA nanostructures can have a core domain and three or more double-stranded arms and formulations thereof to conjugate high copy numbers of therapeutics, pH responsive or enzyme cleavable drug cargo. Also described herein is a design strategy for generation of synthetic RNA oligonucleotides that can self assemble into highly thermostable RNA structures. Also described herein are uses of the RNA nanostructures described herein.

Abstract: This invention relates to methods for screening for a genotype for loss of antigen presentation via MHC class I in a subject and/or respectively detecting a subject's increased risk of resistance against immunotherapy such as against vaccination.

Abstract: The invention provides a method for preparing an expanded renal (kidney) tissue sample suitable for microscopic analysis. Expanding the kidney sample can be achieved by binding, e.g., anchoring, key biomolecules to a polymer network and swelling, or expanding, the polymer network, thereby moving the biomolecules apart as further described herein. As the biomolecules are anchored to the polymer network, isotropic expansion of the polymer network retains the spatial orientation of the biomolecules resulting in an expanded, or enlarged, kidney sample.

Abstract: Genetically modified non-human animals which are deficient in expression of an endogenous GPC3 polypeptide and express a human GPC3 polypeptide at a physiologically adequate level; methods for producing the non-human animals; and methods for evaluating test substances using the non-human animals. Furthermore, methods for evaluating test substances regarding their safety, therapeutic effects on diseases, pharmacokinetics, in vivo distribution, and such, using the non-human animals as models.

Abstract: The present disclosure relates to a PCR detection kit for rapidly identifying Salmonella of specific serotypes. The kit includes primers for detecting tcpS gene, the primers for detecting the tcpS gene including a forward primer having a nucleotide sequence as set forth in SEQ ID NO. 1 and a reverse primer having a nucleotide sequence as set forth in SEQ ID NO. 2. The kit can identify Salmonella of enteritidis, pullorum/gallinarum, and dublin serotypes rapidly and in a high throughput, which can be used as an auxiliary method for the conventional serotyping of Salmonella.

Abstract: A technique for learning and steering evolutionary dynamics may include initializing a bioreactor including a population of evolving organisms; determining selection pressures; (a) applying the selection pressures to the population; (b) determining the population state and storing it in a population dataset; (c) detecting whether the population has reached a stable state; (d) if the population has reached the stable state: obtaining data representing the stable state, redetermining the selection pressures based on a selection pressure policy, and storing the data and the redetermined selection pressures in a stable state dataset; (e) determining whether one or more stopping criteria have been met; and repeating steps (a)-(e) until at least one of the stopping criteria is met.

Abstract: 8-Hydroxy quinoline derivative compounds for enhancing telomerase reverse transcriptase (TERT) expression, and methods for using the same, are provided. These compounds and methods find use in a variety of applications in which increased expression of telomerase reverse transcriptase is desired.

Abstract: The present invention is directed to improved methods for conducting immunoassays. The methods are designed to amplify signals in immunoassays and anchor immunoassay complexes employed therein.

Abstract: Systems and methods that analyze blood-based cancer diagnostic tests using multiple classes of molecules are described. The system uses machine learning (ML) to analyze multiple analytes, for example cell-free DNA, cell-free microRNA, and circulating proteins, from a biological sample. The system can use multiple assays, e.g., whole-genome sequencing, whole-genome bisulfite sequencing or EM-seq, small-RNA sequencing, and quantitative immunoassay. This can increase the sensitivity and specificity of diagnostics by exploiting independent information between signals. During operation, the system receives a biological sample, and separates a plurality of molecule classes from the sample. For a plurality of assays, the system identifies feature sets to input to a machine learning model. The system performs an assay on each molecule class and forms a feature vector from the measured values.

Abstract: Disclosed herein are methods and compositions for targeted, nuclease-mediated insertion of transgene sequences into the genome of a cell.

Abstract: The disclosure features systems and methods for measuring and diagnosing target constituents bound to labeling particles in a sample. The systems include a radiation source, a sample holder, a detector configured to obtain one or more diffraction patterns of the sample each including information corresponding to optical properties of sample constituents, and an electronic processor configured to, for each of the one or more diffraction patterns: (a) analyze the diffraction pattern to obtain amplitude information and phase information corresponding to the sample constituents; (b) identify one or more particle-bound target sample constituents based on at least one of the amplitude information and the phase information; and (c) determine an amount of at least one of the particle-bound target sample constituents in the sample based on at least one of the amplitude information and the phase information.

Abstract: The present invention is directed to kits for improving assay specificity and performance in binding assays.

Abstract: There is provided a paper-based colorimetric sensor kit for quickly and simply diagnosing mercury in situ with a naked eye. The paper-based colorimetric sensor kit includes: a circular template for rolling circle amplification (RCA); a primer that does not hybridize to the circular template when a mercury ion is bonded to a primer that hybridizes to the circular template; a DNA polymerase; a sensing material kit including a nanoparticle probe labeled to a DNA coil formed in the circular template for RCA; and a radial chromatography paper.

Abstract: A combination of an electrochemical device for delivering reducing equivalents to a cell, and engineered metabolic pathways within the cell capable of utilizing the electrochemically provided reducing equivalents is disclosed. Such a combination allows the production of commodity chemicals by fermentation to proceed with increased carbon efficiency.

Abstract: The present invention relates to biomarkers associated with the clinical response to an FGF-18 compound before or during treatment of a cartilage disorder. The present invention more particularly relates to specific proteins present in the blood, serum, synovial fluid or in the urine, which can be used for the diagnosis and treatment of cartilage disorders. The invention further discloses specific proteins that are related to cartilage response to an FGF-18 compound treatment as well as diagnostic tools and kits based on their expression profile. Thus, the invention can be used in predicting the response to an FGF-18 compound treatment, before starting the treatment with FGF-18 or during the treatment. It could be used for selecting/identifying subjects to be treated by intra-articular administration of an FGF-18 compound. The use of these biomarkers in diagnostics could result in increased benefit and reduced risk in subjects.

Abstract: Provided herein, in some embodiments, are methods and compositions for highly multiplexed in situ signal amplification via hairpin-mediated concatemerization.

Abstract: The present invention relates generally to a method of monitoring pharmacodynamic responses mediated by in vivo administration of glucocorticoids. More specifically, the present invention relates to a method of using a change in gene signature as a pharmacodynamic marker of glucocorticoid exposure.

Abstract: A method for determining the presence, absence or amount of two or more target polynucleotides in a sample comprising additional components, the method comprising: (i) contacting the sample with a panel of two or more probes under conditions suitable for hybridisation of the target polynucleotides to the probes, wherein: (a) each probe comprises a non-hybridisation region and a hybridisation region that specifically hybridises to one of the target polynucleotides to form a hybridised probe; and (b) the hybridisation region of a probe of the panel comprises one or more non-natural nucleotides; (ii) contacting the sample prepared in step (i) with a transmembrane pore through which a single stranded polynucleotide but not a double stranded polynucleotide can pass and applying a potential difference to the transmembrane pore such that the hybridised probes in the sample interact with the pore; (iii) measuring current blockades having a duration within a defined window, wherein: (a) the one or more non-natural nuc

Abstract: The present invention provides expression vectors for use in an inducible coexpression system, capable of controlled induction of expression of each gene product.

Abstract: Bispecific aptamers having a first end that specifically binds to a first tumor specific marker, tumor antigen, or viral protein and a second end that specifically binds to a second tumor specific marker, tumor antigen, or viral protein are provide. The bispecific aptamers can be used to treat cancer or virally infected cells. Generally, the bispecific aptamers bind to two surface proteins, preferably different proteins, on the same cell. In a preferred embodiment the bispecific aptamers bind to two different tumor markers, tumor antigens, tumor specific proteins and combinations thereof.

Abstract: Methods are provided for nucleic acid analysis wherein a target nucleic acid is mixed with a dsDNA binding dye to form a mixture. Optionally, an unlabeled probe is included in the mixture. A melting curve is generated for the target nucleic acid by measuring fluorescence from the dsDNA binding dye as the mixture is heated. Dyes for use in nucleic acid analysis and methods for making dyes are also provided.

Abstract: The present invention relates to methods of providing a biomass residuum and compositions thereof. In particular examples, the biomass residuum includes one or more high value amino acids, even after removal of mixed alcohol components. In particular, the methods include implementing pre-treatment conditions and employing fermentation conditions including modified organisms.

Abstract: The present invention provides novel methods of diagnosing and determining treatment strategies for Lyme disease and other tick-borne illnesses.

Abstract: Systems and methods are provided for provided for automatic evaluation of a human embryo. An image of the embryo is obtained and provided to a neural network to generate a plurality of values representing the morphology of the embryo. The plurality of values representing the morphology of the embryo are evaluated at an expert system to provide an output class representing one of a current quality of the embryo, a future quality of the embryo, a likelihood that implantation of the embryo will be successful, and a likelihood that implantation of the embryo will result in a live birth.

Abstract: Method of tracking a plurality of objects comprising: focusing an image of the objects on an imaging element using an optical system; capturing the image of the objects using an imaging element comprising a plurality of pixels; measuring at least one characteristic of the objects from the captured image using an image processor; wherein the field of view is set be the widest field of view for which the image processor is able to measure the at least one characteristic.

Abstract: There is disclosed a composition of an aqueous solution comprising, consisting or consisting essentially of a flap endonuclease, a bulking agent and an organic buffer, wherein the aqueous solution has an inorganic salt concentration of 5 mM or less and wherein the composition is substantially free of glycerol.

Abstract: The present disclosure relates to chemical compositions, kits, and apparatuses and methods for using these compositions, kits and apparatuses in various assays.

Abstract: A sensor apparatus for testing a biological sample, a system making use thereof and a method for testing a biological sample with the sensor apparatus and system.

Abstract: Devices and methods for recording dynamics of cellular and/or biochemical processes, including a device including one or more dispersive elements configured to receive a pulsed laser beam with a spectrum of different wavelengths and disperse the spectrum of the pulsed laser beam; and one or more first elements configured to receive the dispersed spectrum of the pulsed laser beam, and generate a multiphoton excitation area in a biological sample by re-overlapping in time and space the dispersed spectrum of the pulsed laser beam on an area in the biological sample, wherein the device is configured to record at high speed changes of cellular and biochemical processes of a population of cells of the biological sample based on generation of the multiphoton excitation area in the biological sample.

Abstract: A nucleic acid integrated detection method and detection reagent tube are provided, separating a lysis solution, a cleaning solution and a reaction solution in a detection reagent tube by providing a plurality of separation plugs in an over-under arrangement and disposing a hydrophobic layer in liquid or solid phase on each separation plug; adding a sample into the lysis solution; extracting nucleic acid in the sample using magnetic nanobeads; and then driving the magnetic nanobeads carrying the nucleic acid to sequentially pass through each hydrophobic layer along a magnetic bead channel and into the cleaning solution and the reaction solution to realize a cleaning and amplification for the nucleic acid, and finally, detecting the nucleic acid of the sample by an external device using an optical detection method, thus realizing a plurality of steps of nucleic acid extraction, cleaning and amplification reactions in the same detection reagent tube.

Abstract: The present invention provides compounds, compositions, and methods for detecting, diagnosing and treating cancers such as glioblastoma multiforme.

Abstract: A recombinant cell and a method of producing itaconic acid using such recombinant cell. The recombinant cell is of the genus Methylorubrum and includes a first polynucleotide sequence as defined in SEQ ID NO: 1 or a homologue thereof operably linked to a regulatory sequence.

Abstract: A method for simulating a biochemical environment utilizes a heterogeneous process model, which evaluates both a flux balance analysis and one or more detailed models each on a different but overlapping sets of molecules in the biochemical environment. The heterogeneous process model evaluates the flux balance analysis based on a stoichiometric matrix, a flux vector including initial internal exchange flux values, and an objective function. The heterogeneous process model evaluates the one or more detailed models based on an initial set of molecule concentrations and a plurality of detailed model parameters. The results are then used to update the exchange fluxes and molecules concentrations. The process is repeated thereby integrating the results of the flux balance analysis with the one or more detailed models.

Abstract: Disclosed herein are methods and systems for identifying targets for distinguishing cell types. In some embodiments, the method comprises: hierarchically clustering expression profiles of cells to generate a dendrogram with each leaf representing the expression profile of a different individual cell. The dendrogram can be pruned by eliminating invalid splits (and their children). The remaining leaves in the dendrogram can be merged, independent of their locations in the dendrogram, based on their distances to one another to generate clusters of expression profiles. The method can identify targets for distinguishing cell types based on targets that are expressed differentially in the clusters.

Abstract: The invention relates to a method of characterising a target polynucleotide using a single-stranded binding protein (SSB). The SSB is either an SSB comprising a carboxy-terminal (C-terminal) region which does not have a net negative charge or a modified SSB comprising one or more modifications in its C-terminal region which decreases the net negative charge of the C-terminal region.

Abstract: A kit of parts and methods for determining the presence and quantity of one or more therapeutic monoclonal antibody drugs and/or therapeutic monoclonal antibody inhibitor drug antibodies in a biological sample, the method including providing a reaction liquid comprising the sample, a first conjugate with the target of the therapeutic monoclonal antibody and a first conjugated moiety and a second conjugate with the target of the therapeutic monoclonal antibody and a second conjugated moiety, followed by detecting the change in spectrophotometric signal when the complex between the therapeutic monoclonal antibody drug, the first conjugate and a the second conjugate forms.

Abstract: The disclosure provides for methods to form compact cross-linked polynucleotide/protein structures that can then be labeled using a barcoded oligonucleotide array in order to reconstruct physical linkage and/or genomic proximity (and phase) of polynucleotide fragments.

Abstract: The present invention relates to a kit of parts and methods for determining the presence and quantity of one or more TNF-? inhibitor drugs and/or anti-TNF-? inhibitor drug antibodies in one or more biological samples each comprising less than 200 ?l, the method comprising the steps of providing a reaction liquid comprising the sample, a first TNF-? conjugate comprising TNF-? and a first conjugated moiety and a second TNF-? conjugate comprising TNF-? and a second conjugated moiety, said second moiety being capable of generating or ameliorating a detectable signal in the presence of a molecular complex comprising a TNF-? inhibitor, followed by detecting the change in signal when the complex between the TNF-? inhibitor drug, the first TNF-? conjugate and a the second TNF-? conjugate forms.

Abstract: The present invention provides a method for identifying a synthetic classifier including contacting at least a first and second samples derived from different groups of a cohort with a first plurality of peptides. The first plurality of peptides includes a first subset of peptides defining at least one naturally occurring amino acid sequence, and a second subset of peptides defining a plurality of variants of the first subset of peptides. The plurality of variants includes, for each one of the first subset of peptides, a variant peptide having at least one of a substitution, a deletion, an insertion, an extension, and a modification. The method further includes selecting at least one of the plurality of variants from the second subset of peptides, and defining a synthetic classifier including the at least one of the plurality of variants that distinguishes between samples derived from the first and second cohorts.

Abstract: The present disclosure relates to antisense oligonucleotides, which target CAMK2D mRNA in a cell, leading to reduced expression of CAMK2D protein. Reduction of CAMK2D protein expression is beneficial for the treatment of certain medical disorders, e.g., cardiovascular-related diseases or disorders.

Abstract: Techniques for forming a nanopore in a lipid bilayer are described herein. In one example, an agitation stimulus level such as an electrical agitation stimulus is applied to a lipid bilayer wherein the agitation stimulus level tends to facilitate the formation of nanopores in the lipid bilayer. In some embodiments, a change in an electrical property of the lipid bilayer resulting from the formation of the nanopore in the lipid bilayer is detected, and a nanopore has formed in the lipid bilayer is determined based on the detected change in the lipid bilayer electrical property.

Abstract: The present invention provides a Cas9 platform to facilitate single-site nuclease gene editing precision within a human genome. For example, a Cas9 nuclease/DNA-targeting unit (Cas9-DTU) fusion protein precisely delivers a Cas9/sgRNA complex to a specific target site within the genome for subsequent sgRNA-dependent cleavage of an adjacent target sequence. Alternatively, attenuating Cas9 binding using mutations to the a protospacer adjacent motif (PAM) recognition domain makes Cas9 target site recognition dependent on the associated DTU, all while retaining Cas9's sgRNA-mediated DNA cleavage fidelity. Cas9-DTU fusion proteins have improved target site binding precision, greater nuclease activity, and a broader sequence targeting range than standard Cas9 systems. Existing Cas9 or sgRNA variants (e.g., truncated sgRNAs (tru-gRNAs), nickases and FokI fusions) are compatible with these improvements to further reduce off-target cleavage.

Abstract: The invention provides a nucleotide or nucleoside having a base attached to a detectable label via a cleavable linker, characterised in that the cleavable linker contains a moiety selected from the group comprising: Formula (I) (wherein X is selected from the group comprising O, S, NH and NQ wherein Q is a C1-10 substituted or unsubstituted alkyl group, Y is selected from the group comprising O, S, NH and N(allyl), T is hydrogen or a C1-10 substituted or unsubstituted alkyl group and * indicates where the moiety is connected to the remainder of the nucleotide or nucleoside).

Abstract: This invention relates to the delivery of heterologous peptides or proteins such as therapeutic peptides, therapeutic proteins or antigens to mucosal sites using vesicles derived from the outer membrane of commensal bacteria, recombinant bacteria capable of producing such vesicles, and methods for the production of such vesicles. The invention further relates to an inducible expression system for use in recombinant bacteria.

Abstract: Methods are disclosed for detecting peripheral mitochondrial DNA damage and dysfunction. Methods are also disclosed that utilize blood samples to detect a neurodegenerative disease, such as Parkinson's disease, and determine the efficacy of therapy.

Abstract: The present disclosure provides compositions and methods for regulating gene expression via RNA-mediated silencing. The present disclosure also provides compositions and methods to optimize the processing of a dsRNA molecule into small RNA duplexes. The present disclosure further provides compositions and methods to improve the efficiency of a dsRNA molecule in producing desired small RNAs and promoting the silencing of a gene of interest.

Abstract: Disclosed is a method for detecting and quantifying gut flora derived from human faeces, comprising acquiring a solid support containing human faeces; optionally amplifying nucleic acid from the human faeces; and detecting and quantifying the presence of gut flora of interest. Also disclosed is a method for assessing whether a person has type-2 diabetes as well as a kit for detecting and quantifying gut flora from human faeces, comprising a solid support for collecting human faeces; and primer pairs for amplifying 16S rRNA sequence from bacteria of interest.