Abstract: Disclosed herein include systems, methods, compositions, and kits for associating single cell sequencing data with phenotypic data and/or agent exposure. In some embodiments, cell indexing oligonucleotides comprising cell indexing sequences are associated with cells. In some embodiments, synthetic particles are associated with stochastic labels comprising cell indexing sequences. Sequential hybridizing and imaging of probes annealing to a cell indexing sequence can generate a spatial index. The spatial index can be employed to identify of the partition from which a sequenced nucleic acid target molecule originated.

Abstract: The invention comprises a method of amplifying nucleic acids by primer extension with reduced formation of primer-primer byproducts.

Abstract: Present disclosure provides a method including isolating DNA from a source, thereby providing a composition including the isolated DNA. The isolated DNA has at least first and second target regions, where the length of the second target region is greater than the length of the first target region. The method further includes quantifying a total mass of the isolated DNA, quantifying a first quantification cycle (Cq) of the first target region and a second Cq of the second target region, and calculating a Q-ratio for the isolated DNA by dividing the second Cq by the first Cq. The method further includes determining a value for a quality-mass constant (kQm), estimating a required input mass by dividing kQm by the Q-ratio, and preparing the isolated DNA for sequencing if the total mass of the isolated DNA in the composition is equal or greater than the required input mass.

Abstract: Contemplated systems and methods use identification and classification of somatic single nucleotide variants found in a primary tumor and metastases to determine phylogeny of the metastases.

Abstract: Provided herein are methods for capturing a connected probe and/or a capture handle sequence to a capture domain of a capture probe.

Abstract: Arrays of single molecules and methods of producing an array of single molecules are described. Arrays with defined volumes between 10 attoliters and 50 picoliters enable single molecule detection and quantitation.

Abstract: System, including methods, apparatus, compositions, and kits, for making and using a stabilized emulsion. A method of generating a stabilized emulsion is provided. In the method, an aqueous phase may be provided. The aqueous phase may include an effective concentration of one or more skin-forming proteins. An emulsion may be formed. The emulsion may include droplets of a dispersed phase disposed in a continuous phase, with the aqueous phase being the continuous phase or the dispersed phase. The emulsion may be heated to create an interfacial skin between each droplet and the continuous phase, to transform the droplets into capsules.

Abstract: Provided herein is technology relating to detecting neoplasia and particularly, but not exclusively, to methods, compositions, and related uses for detecting premalignant and malignant neoplasms such as gastric cancer.

Abstract: A method of predicting cancer recurrence risk for an individual includes receiving patient spatial multi-parameter cellular and sub-cellular imaging data for a tumor of the individual, and analyzing the patient spatial multi-parameter cellular and sub-cellular imaging data using a prognostic model for predicting cancer recurrence risk to determine a predicted cancer recurrence risk for the individual, wherein the joint prognostic model is based on spatial correlation statistics among features derived for a plurality of intra-tumor spatial domains from spatial multi-parameter cellular and sub-cellular imaging data obtained from a plurality of cancer patients.

Abstract: Compositions, methods and systems are provided for isolating nucleic acids. A polymerase-nucleic acid complex can be formed by mixing a polymerase enzyme comprising strand displacement activity and a mixture of double stranded nucleic acids. Nucleic acid synthesis can then be initiated by the polymerase enzyme to produce a nascent strand complementary to the first strand, thereby displacing a portion of the second strand. After halting or reducing the rate of nucleic acid synthesis, a hybridizing a hook oligonucleotide can be used hybridize to the nucleic acid through a capture region on the hook oligonucleotide that is complementary to the displaced portion of the second strand. The nucleic acid can then be isolated from the mixture of nucleic acids using the hook oligonucleotide.

Abstract: Methods of profiling the nucleic acid composition of single cells and tools for same. The methods can include isolating a single cell in a liquid droplet, lysing the single cell in the liquid droplet to release template nucleic acid from the cell, amplifying the template nucleic acid in the liquid droplet to generate amplified nucleic acid, and detecting the amplified nucleic acid in the liquid droplet. The methods can be useful for profiling expression patterns and/or detecting genetic characteristics such as single nucleotide polymorphisms. The tools include nucleic acid logic gates, including polymerase-dependent logic gates. The logic gates can perform logical operations such as YES, NOT, AND, OR, AND-NOT, NOT-AND, NOT-OR, EXCLUSIVE-OR, EXCLUSIVE-NOR, and IMPLY. The tools also include microfluidic systems for performing the methods.

Abstract: The present invention corresponds to the field of cancer and is related to predicting cancer detection, diagnosis, monitoring and prediction of response to treatment, in particular platelet derived-endothelial cell growth factor (PD-ECGF) levels for their use as a potential value in monitoring disease evolution and predicting response to anti-angiogenic treatment.

Abstract: The present invention provides an improved method of quantitative and/or qualitative analysis of a target molecule using nitrocellulose membrane (NCM). In particular, the present invention provides a porous nitrocellulose membrane that includes a surface and an organic nanostructured molecule that is non-covalently attached to the surface of NCM. The organic nanostructured molecule has a branched region that includes a plurality of terminal region (e.g., terminal end) moieties that are non-covalently attached or bound to a surface of the porous NCM. The organic nanostructured molecule also comprises a linear region that includes a covalently attached capture molecule that is adapted to selectively bind to a target molecule. The NCM of the invention provides an improved reproducibility, reliability, and selectivity compared an NCM in the absence of the organic nanostructured molecule.

Abstract: The present technology is directed to the nanoparticles for use as molecular environmental sensors. The nanoparticles comprise a photoluminescence core and a plurality of ligands bound to the core and forming a quencher permeable ligand shell. The ligands comprise a reactive or charged moiety capable of being modulated between a first stand and a second state, and the proportion of ligands in each state determine the permeability of the ligand shell to a photoluminescence quencher.

Abstract: Compositions and methods for displaying antibodies in the periplasmic space of yeast cells are disclosed. In particular, antibodies are linked to a cell membrane-spanning transmembrane domain, a cell-membrane associated protein domain that is on the external face of the yeast cell membrane, a protein that binds to the inner face of the yeast cell wall, or a periplasmic protein in order to display the antibodies in the yeast periplasmic space. In addition, a target protein of interest can be coexpressed in yeast such that it is localized to the plasma membrane or periplasmic space and accessible to binding by displayed antibodies. The disclosure further relates to high-throughput screening of antibody libraries using yeast cell periplasmic display.

Abstract: An example of a flow cell includes a substrate, a plurality of chambers defined on or in the substrate, and a plurality of depressions defined in the substrate and within a perimeter of each of the plurality of chambers. The depressions are separated by interstitial regions. Primers are attached within each of the plurality of depressions, and a capture site is located within each of the plurality of chambers.

Abstract: Provided herein are methods, assays and devices for the detection and diagnosis of autoimmune diseases, including systemic lupus erythematosus. The methods, assays and devices provided herein analyzes binding patterns of peripheral-blood antibodies on peptide array that correlates well with current systemic lupus erythematosus clinical assessment standards.

Abstract: Protein biomarkers may be used to rapidly and accurately diagnose stroke. Biomarkers may be utilized in a rapid and inexpensive test that could be used at the bedside or ambulatory setting to definitively indicate the presence or absence of stroke and its severity. Such a test would quickly stratify patients in need of immediate stroke treatment from those who are not having a stroke. The test may aid emergency personnel in the decision for the most appropriate treatment plan and treatment location, thereby minimizing morbidity and mortality of stroke patients.

Abstract: A peptide aptamer for specific recognition of arginine and its application are provided. The sequence of the peptide aptamer is shown in SEQ ID No. 1. The peptide aptamer is modified by a group that improves stability, or by a fluorescent group, an isotope and an electrochemical group that provide a detection signal, or by an affinity ligand and a mercapto. According to the computer-aided molecular docking simulation prediction, the peptide aptamer that can specifically bind to L-arginine is screened, which is verified by an isothermal titration calorimeter. The peptide aptamer has the advantages of good stability, strong binding ability, high specificity and low production cost.

Abstract: Provided herein is a method of detecting or predicting a relapse of multiple sclerosis in an individual afflicted with a form of multiple sclerosis, comprising: (a) providing a blood sample of the individual; (b) testing the blood sample to determine a protein activity or protein level, wherein the protein is Factor VIII, von Willebrand factor, or Protein C; and (c) detecting or predicting a relapse of multiple sclerosis in the individual if the protein activity or protein level is elevated compared to the protein activity or protein level in an individual not afflicted with the form of multiple sclerosis and patients' own baseline values. Also provided herein is a method of treating an individual afflicted with multiple sclerosis, who is experiencing a relapse or predicted to experience a relapse, comprising treating the individual by administering a dose of a steroid or anti-coagulation compound effective to alleviate the symptom of multiple sclerosis.

Abstract: Provided herein are methods for detecting an antigen or for detecting expression of a chimeric antigen receptor (CAR). The methods include obtaining a sample from a subject, contacting the sample with a fusion protein comprising a reporter fused to a single chain antibody specific to the antigen or fused to an extracellular domain of an antigen targeted by the CAR or fused to Protein L and assaying the activity of the reporter, wherein presence of reporter activity or increase in reporter activity relative to a reference value is indicative of presence of the antigen or presence of the expression of the chimeric antigen receptor in the sample.

Abstract: Provided are suspension-based cell culture systems and media for the timely and efficient proliferation of human tumor cell clusters from a patient, and related methods of evaluating the potential responsiveness of the tumor cells and the patient to one or more therapeutic agents.

Abstract: Provided herein are methods, assays and devices for the differential diagnosis and detection of disease progression of autoimmune diseases. The methods, assays and devices provided herein produce and analyze binding patterns of peripheral-blood antibodies on mimetic peptide arrays that differentiate autoimmune diseases, and identify patients progressing to internal organ complications such as interstitial lung disease (ILD), and gastric antral vascular ectasia (GAVE), or renal involvement.

Abstract: Embodiments of the disclosure provide various nanogap sensor designs (e.g., horizontal nanogap sensors, vertical nanogap sensors, arrays of multiple nanogap sensors, various arrangements for making electrical connections to the electrodes of nanogap sensors, etc.), as well as various methods which may be used to fabricate at least some of the proposed sensors. The nanogap sensors proposed herein may operate as molecular sensors to help identify chemical species through electrical measurements using at least a pair of electrodes separated by a nanogap.

Abstract: A compound comprising at least one looped peptide structure attached via at least one alkylamino linkage to a scaffold. Preferably the looped peptide structure is a Bicycle structure comprising two peptide loops attached to the scaffold via two alkylamino linkages and one thioether linkage, one of the linkages being common to both loops.

Abstract: The present inventors identified for the first time a germline genomic alteration that accounts for familial myeloproliferative neoplasms (MPN) and myeloid malignancies. More precisely, they identified a 700 kb germline duplication that proposes patients to essential thrombocythemia (ET) with a high frequency of evolution to myelofibrosis (MF), secondary myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML). Two out of the 6 duplicated genes (namely ATG2B and GSKIP) have been shown to be overexpressed in hematopoietic progenitors, and this overexpression cooperates with classical mutations in JAK2, MPL, and CALR to generate the MPN phenotype. The presence of the 700 kb germline duplication is thus of poor prognosis for a MPN patient. The present invention discloses a method for detecting a predisposition of developing a MPN, as well as a prognostic method for assessing the probability that an ET-suffering patient will develop a myelofibrosis, a secondary MDS or an AML.

Abstract: Methods and systems of performing an assay. A system for performing an assay includes an enclosure defining a temperature-controlled space. An imaging system, an actuator and a dispenser are disposed within the space. The actuator receives a well plate having wells. The actuator is to move the well plate relative to the imaging system to enable the imaging system to obtain image data of one of the wells. The dispenser includes a pump, an outlet and a reservoir holder to receive a reservoir containing a compound. The pump is to be fluidly coupled to the reservoir and an outlet. The pump is to pump the compound from the reservoir through the outlet into one of the wells. The system also includes a controller. The controller is to cause the dispenser to dispense the compound into the first one of the wells while the imaging system obtains the image data.

Abstract: A segmentation method for tumor regions in a pathological image of clear cell renal cell carcinoma based on deep learning includes data acquisition and pre-processing, building and training of a classification network SENet and prediction of tumor regions. The present invention studies clear cell renal cell carcinoma based on pathological images, yielding results with higher reliability than judgments made based on CT or MRI images. The present invention overcomes the drawback that the previous research on clear cell renal cell carcinoma is only limited to judgment on presence by being able to visually provide the position and size of tumor regions, which is convenient for the medical profession to better study the pathogenesis and directions to the treatment of clear cell renal cell carcinoma.

Abstract: A dual cavity, low power, outdoor combination line amplifier package for cable telecommunication systems is disclosed. It comprises: a dual-cavity main frame, cast in one piece and sectioned into an upper cavity and a lower cavity; a hardline entry cover, having a hardline receptacle PCB with a power supply fixed thereon, electrically and environmentally sealing on one side of the upper cavity; a tap plate cover, having a tap plate PCB fixed thereon and mounted with a plurality of taps, electrically and environmentally sealing on the other side of the upper cavity with the taps facing externally; a gain module heatsink cover, having a gain module PCB and a passive PCB fixed thereon, electrically and environmentally sealing on one side of the lower cavity; and a smart app accessories cover, having a smart access cover PCB fixed thereon, electrically and environmentally sealing on the other side of the lower cavity.

Abstract: The technology disclosed directly operates on sequencing data and derives its own feature filters. It processes a plurality of aligned reads that span a target base position. It combines elegant encoding of the reads with a lightweight analysis to produce good recall and precision using lightweight hardware. For instance, one million training examples of target base variant sites with 50 to 100 reads each can be trained on a single GPU card in less than 10 hours with good recall and precision. A single GPU card is desirable because it a computer with a single GPU is inexpensive, almost universally within reach for users looking at genetic data. It is readily available on could-based platforms.

Abstract: The present invention provides method essentially comprising the steps of (i) providing a DNA sample, (ii) providing at least a first pair of amplification primers which is capable of generating a first amplicon from a LINE sequence that has a size of less than 80 bp, (iii) providing at least a second pair of amplification primers which is capable of generating a second amplicon from a LINE sequence that has a size of more than 160 bp, (iv) performing a qPCR and determining cq values for each of the generated amplicons, and (v) determining the relative concentrations of said amplicons.

Abstract: A method and system for storing user application programs and micro-service programs, for each of multiple patients that have cancerous cells and receive treatment, includes obtaining clinical records data in original forms, storing it in a semi-structured first database, generating sequencing data for the patient's cancerous and normal cells using a next generation genomic sequencer, storing the sequencing data in the first database, shaping at least some of the first database data to generate system structured data optimized for searching and including clinical record data, storing the structured data in a second database, for each user application program, selecting an application-specific subset of data from the second database and storing it in a structure optimized for application program interfacing in a third database, wherein an orchestration manager operatively connected to one or more micro-service programs receives status messages and initiates a respective micro-service program when program prere

Abstract: Applicants have identified that three critical phenotypic/genetic measures are highly correlated with transition period health and may be used in selection and breeding protocols and/or in combination with traditional breeding and marker assisted selection methods to improve predictability of transition period health. According to the invention genetic evaluations for mastitis, ketosis, and metritis have been found to be highly predictive of overall transition health. The genetic evaluations are produced by directly measuring thousands of clinical cases of mastitis, ketosis, and metritis in ancestors of a particular animal and using this data in selection. Applicant's selection criteria and quickly impact a breeders population by reducing transition cow disease incidence in the initial population and in progeny.

Abstract: Gene expression signatures and pathways associated with tuberculosis are identified. The invention provides for diagnostic assays based on gene markers and cell composition, as well as therapeutic targets for modulating tuberculosis infection. In addition, tuberculosis copy number contained in cells and methods of detecting high and low copy number are disclosed.

Abstract: The present invention discloses a mouse-human chimeric antibody preferably recognizes the MUC1 glycopeptide epitope RPAPGS(GalNAc)TAPPAHG (SEQ ID NO.: 34) on the surface of cancer cells, and the encoding sequences, wherein the monoclonal antibody having a light chain and a heavy chain. Moreover, the present invention provides humanized light and heavy chains, and the encoding sequences. The results of paired expression show that humanized antibodies also recognize the MUC1 glycopeptide epitope RPAPGS(GalNAc)TAPPAHG (SEQ ID NO.: 34) on the surface of cancer cells, and show the same specificity as the parental antibody.

Abstract: The present invention provides MEL-18, which is a biomarker for human epidermal growth factor receptor2 (HER2)-positive cancer and anti-HER2 therapy, and a use thereof. According to the present invention, MEL-18 is a prognostic factor or predictor for a response of subjects to an anti-HER2-targeted drug in HER2-POSITIVE cancer and may be used in companion diagnostics for HER2-targeted drugs in subjects with HER2-positive cancer. Therefore, HER2-positive cancer may be more effectively treated by overcoming resistance to HER2 therapeutic agents and enhancing therapeutic efficacy by determining whether ADAM10/17 inhibitors are administered or co-administered with HER2-targeted drugs.

Abstract: Methods, systems, and apparatus, including computer programs encoded on computer storage media, for obtaining data defining a sequence for an aptamer, the aptamer comprising a string of nucleobases; encoding the data defining the sequence for the aptamer as a neural network input; and processing the neural network input using a neural network to generate an output that characterizes how strongly the aptamer binds to a particular target molecule, wherein the neural network has been configured through training to receive the data defining the sequence and to process the data to generate predicted outputs that characterize how strongly the aptamer binds to the particular target molecule.

Abstract: The present invention provides an apparatus of charged-particle beam e.g. an electron microscope comprising a plasma generator for selectively cleaning BSE detector. In various embodiments, the plasma generator is located between a sample stage and a sample table having one or more openings or holes. The plasma generator generates plasma and distributes or dissipates the plasma through the openings of the sample table toward and onto surface of the BSE detector. Cleaning contaminants on the surface of the BSE detector frequently and selectively with in-situ generated plasma can prevent the detectors from performance deterioration such as losing resolution and contrast in imaging at high levels of magnification.

Abstract: The present invention relates to the design of a customized therapy for a subject with breast cancer based on the c-MAF expression level and the menopausal status of the subject. In some embodiments, the customized therapy comprises an agent for avoiding, treating or preventing bone degradation. In some embodiments, the agent for avoiding, treating or preventing bone degradation is zoledronic acid. In other embodiments, the agent is clodronate or denosumab.

Abstract: A sequencing device is disclosed. The sequence device includes an array of conducting electrode pairs, each pair of electrodes comprising a source and a drain electrode arrangement separated by a nanogap, the electrode array deposited and patterned on a dielectric substrate; at least one transition metal dichalcogenide (TMD) layer disposed on each pair of electrodes, wherein the TMD layer connects each source and drain electrode within each pair, and bridges each nanogap of each pair of electrodes; and a dielectric masking layer disposed on the TMD layer and comprising at least one opening that defines an exposed TMD region, wherein the at least one opening is sized so as to allow a single biomolecule to fit therein and to attach on to the exposed TMD region. In embodiments of the disclosure, the TMD layer be a defective TMD layer.

Abstract: The present disclosure relates to compositions and methods for generating capture probes on a substrate for identifying the location of analytes in a biological sample.

Abstract: Provided herein, among other aspects, are methods and apparatuses for analyzing particles in a sample. In some aspects, the particles can be analytes, cells, nucleic acids, or proteins and can be contacted with a tag, partitioned into aliquots, detected by a ranking device, and isolated. The methods and apparatuses provided herein may include a microfluidic chip. In some aspects, the methods and apparatuses may be used to quantify rare particles in a sample, such as cancer cells and other rare cells for disease diagnosis, prognosis, or treatment.

Abstract: The present disclosure provides methods of processing or analyzing a sample. A method for processing a sample may comprise hybridizing a probe molecule to a target region of a nucleic acid molecule (e.g., a ribonucleic acid (RNA) molecule), barcoding the probe-nucleic acid molecule complex, and performing extension, denaturation, and amplification processes. A method for processing a sample may comprise hybridizing first and second probes to adjacent or non-adjacent target regions of a nucleic acid molecule (e.g., an RNA molecule), linking the first and second probes to provide a probe-linked nucleic acid molecule, and barcoding the probe-linked nucleic acid molecule. One or more processes of the methods described herein may be performed within a partition, such as a droplet or well. One or more processes of the methods described herein may be performed on a cell, such as a permeabilized cell.

Abstract: The present invention relates to polypeptides which are covalently bound to aromatic molecular scaffolds such that two or more peptide loops are subtended between attachment points to the scaffold. In particular, the invention describes peptides which are high affinity binders of the Eph receptor tyrosine kinase A2 (EphA2). The invention also includes drug conjugates comprising said peptides, conjugated to one or more effector and/or functional groups, to pharmaceutical compositions comprising said peptide ligands and drug conjugates and to the use of said peptide ligands and dmg conjugates in preventing, suppressing or treating a disease or disorder characterised by overexpression of EphA2 in diseased tissue (such as a tumour).

Abstract: Diagnostic biomarkers for diagnosing immune suppression/dysfunction. The diagnostic biomarkers are genes and/or transcripts that are up or down regulated compared to normal expression when a subject has been stressed either mentally and/or physically. The invention also relates to a method of detecting comprised or suppressed immune response in a subject by comparing certain diagnostic biomarkers in the subject to a control set of diagnostic biomarkers.

Abstract: Described herein are systems relating to a continuous-flow instrument that includes all necessary components for digital droplet quantification without the need to introduce key reagents or collect and transfer droplets between stages of instrument operation. Digital quantification can proceed without any additional fluid or consumable handling and without exposing fluids to risk of external contamination.

Abstract: In various embodiments methods of determining methylation of DNA are provided.

Abstract: Provided is a method of predicting differentiation potential of undifferentiated iPS cells into cartilage cells. Provided is a genetic marker for predicting differentiation potential of undifferentiated iPS cells into cartilage cells. A method of predicting differentiation potential of undifferentiated iPS cells into cartilage cells based on gene expression data of the undifferentiated iPS cells. A method of predicting differentiation potential of undifferentiated iPS cells into cartilage cells by predicting differentiation potential of the iPS cells into neural crest cells (NC cells) based on gene expression data of the undifferentiated iPS cells.

Abstract: Disclosed are chiral phosphoramidite auxiliary compositions for diastereoselective synthesis of stereochemically enriched oligonucleotides, and nucleoside phosphoramidite compounds comprising the same. Exemplary structures of the chiral phosphoramidite auxiliary compositions include Formulas (IA) and (IB).

Abstract: The invention relates to methods for conducting solid-phase binding assays. One example is an assay method having improved analyte specificity where specificity is limited by the presence of non-specific binding interactions.