Abstract: The present invention relates to a method of determining if a patient is likely to respond to a treatment with a targeted therapy compound selected from protein kinase inhibitors, small molecule inhibitors, and monoclonal antibody-based compounds. The present invention further relates to a method of identifying a targeted therapy compound selected from protein kinase inhibitors, small molecule inhibitors, and monoclonal antibody-based compounds for personalized medicine. The present invention also relates to a method of treatment of cancer in a patient. The present invention also relates to a targeted therapy compound selected from protein kinase inhibitors, small molecule inhibitors, and monoclonal antibody-based compounds for use in a method of treatment of cancer in a patient.

Abstract: The invention relates to the ADH3 promoter; polynucleotide sequences, vectors and expression cassettes including DNA regions responsible for the regulation of the ADH3 promoter; the host cells, including these vectors and expression cassettes, and, the recombinant proteins performed with the developed cells. In the scope of the invention, deletion analyzes in the ADH3 promoter were performed to identify regions that affect promoter strength and significant data was obtained in the formation of mutant ADH3 promoters. Deletion of the nucleotides between 539 and 638 (?361 to ?262) in SEQ ID NO: 1 resulted in a 63% increase in ADH3 promoter activity. Five different synthetic promoters were created using positive regulatory regions identified and approximately 165% to 200% promoter activities were achieved with these promoters.

Abstract: Provided herein are methods and compositions for batch production of producer cells using fluorescence activated cell sorting (FACS). In some aspects, the disclosure provides a drug-selection-free method for batch production of producer cells using FACS. Such batch production methods and compositions can be further utilized to generate clonal populations of producer cells, e.g., for large-scale manufacturing of a polypeptide of interest.

Abstract: Some aspects of this disclosure relate to systems, apparatuses, compositions (e.g., isolated nucleic acids and vectors), and methods for improving the stability and/or solubility of proteins evolved using phage-assisted continuous evolution (PACE). In some embodiments, vectors described herein comprise nucleic acids encoding selection systems (e.g., positive and/or negative selection systems) that link expression of genes required for production of infectious phage particles to a desirable physiochemical (e.g., stability or solubility) and/or desired function of an evolved protein.

Abstract: A method of characterizing a glioblastoma multiforme (GBM) stem cell (GSC), comprising culturing the GSC to provide a culture, contacting a first set of aliquots of the culture with individual compounds selected from a panel of compounds, identifying two or more of the selected compounds that cause more than a threshold level of cell death in the first set of aliquots, and characterizing the GSC as suitable for treatment with one or more combinations comprising the two or more identified compounds. A panel of chemical compounds, the compounds selected by a method comprising surgically resecting the tumor, culturing a GSC derived from GBM tissue derived from a GBM tumor, contacting aliquots thereof with individual compounds selected from a panel of compounds, and identifying two or more of the selected compounds that cause more than a threshold level of cell death in the aliquots, thereby identifying the compounds.

Abstract: Kits and methods are provided for performing multiplex LAMP reactions. These kits and methods are directed to specific and sensitive methods of target nucleic acid detection and more specifically pathogen diagnostics such as detection of Coronavirus. The kits and methods utilize a plurality of sets of oligonucleotide primers for targeting the viral nucleic acid target.

Abstract: Provided are epithelial cell spheroids including spheroids that have apical membranes and cilia that face towards the interior core of the spheroid and spheroids that have apical membranes and cilia that face away from the interior core of the spheroid. Also provided methods of making and using such spheroids.

Abstract: Provided are methods of producing nucleic acid libraries. In certain aspects, the methods include combining target nucleic acids (e.g., 5? phosphorylated nucleic acids) and an oligonucleotide pool. Oligonucleotides of the oligonucleotide pool may include complementarity regions of varying length and nucleotide sequence, and a complementarity region identification sequence. In such aspects, the combining is under conditions in which oligonucleotides of the oligonucleotide pool hybridize to nucleic acids of the target nucleic acids (e.g., 5? phosphorylated nucleic acids) having overhang regions that are complementary in sequence and have corresponding lengths with respect to the complementarity regions of the oligonucleotides. Compositions and kits that find use, e.g., in practicing the methods of the present disclosure are also provided.

Abstract: The invention relates to microbial host cells engineered to produce glycoconjugate vaccines by stable integration of an acceptor protein and an oligosaccharyltransferase into the host's genome, wherein expression of the oligosaccharyltransferase is regulated.

Abstract: The present invention provides a method to quantitatively measure the response of a patient to an immune-modulator drug that will aid clinicians in the determination of the optimal combination/posology of immunosuppressant/immune-modulator drugs. In addition, this method will open the possibility for clinicians to make the necessary adjustments in immunosuppressive therapy, as a way to avoid organ rejection to actually take place. Furthermore, this method will significantly reduce side effects of immunosuppressant drugs, optimizing therapeutic scheme and dosages, enabling the determination of the most effective immunosuppression regimen at the lower dosages for each patient individually and monitoring of treatment efficiency along time, thus opening the door to treatment personalization.

Abstract: A kit includes a microfabricated device having a top surface defining an array of microwells for receiving a sample comprising at least one cell, and a membrane for applying on the top surface of the microfabricated device to retain the at least one cell in at least one microwell of the array of microwells after the sample is loaded on the microfabricated device.

Abstract: The present disclosure relates to biofragment compositions that comprise bioparticle fragments and at least one heterologous antigen-binding molecule. In some embodiments, the biofragment is typically derived from a larger, intact bioparticle that express the at least one heterologous antigen-binding molecule at the surface, and the biofragment has increased solubility to facilitate assays for antigen detection. The disclosure also relates the related methods of using and making the biofragment compositions, as well as systems and devices implementing the biofragment compositions. In some embodiments, the related methods, systems and devices do not require additional detection reagents, such as animal derived detection antibodies.

Abstract: Apparatus and methods for determining whether a test compound induces cell activity, changes cell activity, prevents cell activity, or inhibits cell activity. An embodiment comprises placing a test compound solution in contact with a cell suspension media containing cells, diffusing the test compound solution into the cell suspension from one or more sides, and detecting activity in the cells with respect to their distance from the side from which the test compound is diffusing. Embodiments may provide an apparatus that allows a side source, a point source, or both, from which a test compound solution diffuses into a cell suspension media and contacts cells. Detecting cell activity may involve detecting activity in a first cell group proximate to the side from which the test compound is diffusing, and detecting activity in a second cell group farther than the first cell group from the side from which the test compound is diffusing.

Abstract: Yeast having modified chromosomes are provided. The chromosomes are modified such that at least one of yeast histones H3, H4, H2A or H2B are fully or partially replaced by their human histone counterparts H3, H4, H2A or H2B, respectively. Histone amino acid substitutions are included. Cell fusions with the yeast having the modified chromosomes and non-yeast cells are provided. Methods for screening test agents using the yeast are also provided. Yeast with a mutated yeast DAD1 gene, the mutated DAD1 gene encoding an E50D mutation in yeast DAD1 protein, are provided, and provide a useful genetic background for making the yeast with partially or fully replaced histone(s).

Abstract: The present invention relates to production of renewable fuels and fuel components from plant oil originating from at least one Brassica species, where said Brassica species, doped with at least one nitrogen-fixing bacteria, is cultivated to obtain Brassica seed oil, and feedstock comprising the Brassica seed oil is converted in a converting step, whereby renewable fuel or renewable fuel components are obtained. The invention also relates to a method for reducing nitrate release in renewable fuel production. Further, the invention relates to a method for reducing greenhouse gases in renewable fuel production.

Abstract: A method of detecting cells is provided. The method includes the following steps. A sensor device including a base and at least one response electrode is provided, wherein the response electrode is spaced apart from the base with respect to a gate end of the base. A test solution containing a target cell is placed on the response electrode, a first pulse voltage is applied to the response electrode, and a first detection current generated from the base is measured. A membrane potential of the target cell is changed, a second pulse voltage is applied to the response electrode, and a second detection current generated from the base is measured, wherein a sign of the first detection current and a sign of the second detection current are opposite.

Abstract: The present invention provides assays and compositions to identify the risk of toxicity in a patient population with genotypic variations in specific proteins and/or protein complexes within the patient population.

Abstract: The majority of clinically used antibiotics and anticancer agents are derived from bacterial small molecules. These molecules are produced by dedicated biosynthetic gene clusters, sets of genes that are responsible for the step-wise generation of the target small molecule. Recent investigations have indicated, to the surprise of many experts, that the majority of these biosynthetic genes are inactive or ‘silent’ for unknown reasons. Thus under typical bacterial culturing conditions, these genes are not expressed and consequently the bioactive small molecule products are not synthesized. Disclosed is a method for high throughput screening of elicitors of cryptic metabolites, a method for producing cryptic metabolites, and a new family of cryptic metabolites, the acybolins, as well as their complete structural elucidation.

Abstract: Compositions and methods related to anucelate cells (e.g., bacterial minicells) for pesticide degradation applications including related cells, polypeptides, and vectors.

Abstract: A honeycomb tube with a planar frame defining a fluidic path between a first planar surface and a second planar surface. A fluidic interface is located at one end of the planar frame. The fluidic interface has a fluidic inlet and fluidic outlet. The fluidic path further includes a well chamber having an well-substrate with a plurality of wells. The well chamber is arranged in the planar frame between the first or second surface and the well-substrate. The well chamber is in fluidic communication between the pre-amplification chamber and the fluidic outlet.

Abstract: A system and method for processing long scan data from a mass spectrometer is described. The long scan data is broken into multiple discrete subsets and each of the multiple subsets are padded by adding additional strings of data on either end of the subset. Each of the multiple subsets is deconvolved and overhang errors are corrected for on each deconvolved subset. A deconvolved full data set is then assembled from the deconvolved subsets.

Abstract: Disclosed are methods for cell transfection and regulating cellular behavior. More particularly, the present disclosure relates to methods of non-viral cell transfection and regulating cellular behavior using mineral coatings that allow for the enhanced transfection of cells. The mineral coatings bind polynucleotides and provide a source of calcium and phosphate ions to enhance transfection. The present disclosure also provides a high throughput platform for screening non-viral transfection of cells. The methods of the present disclosure also provide an advantageous polynucleotide delivery platform because the mineral coatings may be deposited on various medical device materials after being specifically developed using the high throughput screening platform.

Abstract: The present invention relates to a method for determining a decrease in the functions of the hippocampus by using the correlation between a micro RNA (miRNA) and an N-methyl-D-aspartate receptor (NMDAR), a method for inhibiting the decrease in the functions, and a method for screening for inhibitors of the decrease in the functions.

Abstract: The present invention relates to purified and isolated DNA sequences having protein production increasing activity and more specifically to the use of matrix attachment regions (MARs) for increasing protein production activity in a eukaryotic cell. Also disclosed is a method for the identification of said active regions, in particular MAR nucleotide sequences, and the use of these characterized active MAR sequences in a new multiple transfection method.

Abstract: The present invention provides methods for the identification, isolation and/or enrichment of human corneal endothelial cells (HCECs). In some embodiments, the method comprises a positive selection process in which a cell population containing human corneal cells is contacted with a positive affinity reagent that selectively binds to HCECs relative to cells other than HCECs (e.g., corneal keratocytes, etc.) in the population and/or a negative selection process in which a cell population containing HCECs is contacted with a negative affinity reagent that selectively binds to cells other than HCECs in the population relative to HCECs. The present invention also provides reagents and kits for the identification, isolation and/or enrichment of HCECs as well as compositions that are enriched in HCECs.

Abstract: A method for evaluating in vitro the effect of a xenobiotic (e.g., a drug) on drug metabolism in hepatocytes. The kit comprises a first culture of hepatocytes, a portion of in vitro xenobiotic-stimulated biological sample, and instructions for incubating the first culture of hepatocytes with the portion of in vitro xenobiotic-stimulated biological sample, and analyzing the activity, expression, or a combination thereof of a biomarker in the hepatocytes to evaluate the effect of the xenobiotic on drug metabolism in the hepatocytes.

Abstract: The present invention provides for a system comprising (a) a first nucleic acid comprising a nucleotide sequence encoding a nucleotide sequence of interest operatively linked to a promoter comprising a repressor polypeptide binding site, and (b) a second nucleic acid comprising a nucleotide sequence encoding a repressor polypeptide having at least 70% amino acid identity with EilR, SmvR, KmrR, RcdA, or QacR; wherein expression of the nucleotide sequence of interest from the promoter is induced by the presence of a hydrophobic inducer, such as a hydrophobic cation inducer, such as a triarylmethane, acridine, phenazine, phenothiazine, or xanthene.

Abstract: Biomarkers are not as commonly used in ALS drug development as in the drug development process for oncology. Biomarkers are important component of the ALS drug development pathway to demonstrate drug effect and target engagement. In a recent Phase 2A double-blind, randomized, placebo controlled clinical trial with GM604 (AKA MNTF, GM6), where ALS patients were treated with six doses of GM604 for two weeks and then continued to be evaluated for disease progression until 10 weeks after cessation of GM604 treatment, it was demonstrated that GM604 can modulate expression of ALS disease related genes, through pathways that bring about homeostasis of pertinent ALS biomarkers. The statistical significance in biomarker changes also correlate with treatment effects in clinical observations.

Abstract: The present invention generally relates to a set of early developmental reference data or “lineage scorecard” for stem cells, and methods, systems and kits to generate a lineage scorecard for predicting the functionality and suitability of stem cell lines. In some aspects, methods for generating a scorecard comprises measuring the gene expression of a plurality of early developmental genes, such as pluripotent, early ectoderm, early mesoderm and early endoderm genes to predict the pluripotency and differentiation potential of the stem cell line and its functionality and/or suitability for a desired use. In some embodiments, a reference scorecard can be compared with the test stem cell line scorecard to accurately predict the utility and/or identify specific characteristics of the stem cell line, e.g., to determine its suitability for downstream applications, e.g., therapeutic use, drug screening, toxicity assays, differentiation into a desired cell lineage, etc.

Abstract: A method for detecting an interaction between one or more protein bait and one or more candidate prey in a eukaryotic cell, comprising the steps of: a) providing an eukaryotic cell expressing (i) one or more protein bait, and (ii) one or more candidate prey, wherein said protein bait comprises a bait moiety and a polymerized-tubulin binding moiety. b) determining the occurence of an interaction between said one or more protein bait and said one or more candidate prey in the eukaryotic cell, wherein said protein bait is bound to polymerized tubulin in the eukaryotic cell, thereby localizing said one or more candidate prey along said polymerized tubulin, thereby detecting said interaction.

Abstract: Embodiments described herein are directed to devices for supporting growth of anisotropic muscle tissue layers and in vitro readout and quantification of force generated by the tissue layers using one or more strain-sensing elements integrated into the device. Embodiments also include multiplexed apparatuses of multiple independent devices, methods of fabricating the devices and apparatuses, and methods of using the devices and apparatuses.

Abstract: The invention provides a method for determining the activity of an inhibitor of a target protein that has a deleterious effect on cell growth. The principle of the claimed method is that a compound that inhibits the function of an overexpressed protein will relieve the detrimental effect of such overexpression in a concentration-dependent manner, thereby allowing the determination of the activity of the compound in inhibiting its target protein in live cells.

Abstract: A library of cell strains is characterized by culturing cells at spatially defined and separated positions in a culturing device (1) and determining a phenotypic characteristic of each cell strain in the culturing device (1). The cells are fixated at the spatially defined and separated positions in the culturing device (1) followed by in situgenotyping a respective variable region (150) of each cell strain at the spatially defined and separated positions in the culturing device (1). Each respective phenotypic characteristic is connected to each respective genotype based on the spatially defined and separated positions in the culturing device (1).

Abstract: Example paper substrate diagnostic apparatus and related methods and systems are disclosed herein. An example apparatus includes a hydrophobic substrate having a first end and a second end opposite the first end. The apparatus includes a detection zone on a first surface of the substrate, the detection zone defining an area to sense an analyte in a sample, the detection zone comprising a first electrode and a second electrode disposed on the first surface of the substrate and a layer of hydrophilic ink disposed on the two electrodes and an area between the first and second electrodes. The apparatus also includes a channel comprising hydrophilic ink disposed on the first surface of the substrate, the channel having an inlet section adjacent the first end of the substrate, a middle section, and an outlet section in contact with the layer of hydrophilic ink. The channel is to transfer a fluid sample from the inlet section to the layer of hydrophilic ink.

Abstract: Described herein is a previously unknown function of XBP1 in controlling anti-tumor immunity. It is shown that inhibiting XBP1 in tumor-associated dendritic cells inhibits tumor growth and induces protective anti-tumor immune responses.

Abstract: Systems and methods for targeted therapy based on single-cell stimulus perturbation response. In one embodiment, a method for optimizing stimulus combinations for therapy includes receiving a cell sample, treating the cell sample with a plurality of stimuli by treating a different portion of the cell sample with one of the plurality of stimuli for each of the plurality of stimuli, labeling the cell sample with a plurality of metal-conjugated probes, analyzing the cell sample using a mass spectrometer, obtaining mass spectrometry data from the mass spectrometer, identifying subpopulations within the cell sample using the mass spectrometry data, computing stimulus effects, generating a nested-effects model using the mass spectrometry data, and scoring stimuli combinations using the computing device, wherein the stimulus combinations are combinations made from the plurality of stimuli.

Abstract: A polypeptide biosensor that detects free NAD+ is disclosed. The polypeptide comprises a first fragment from an NAD+ dependent DNA ligase acetylation domain, a second fragment from the NAD+ dependent DNA ligase acetylation domain, and a fluorescent protein, wherein the fluorescent protein is positioned between the two DNA ligase acetylation domain fragments. Also disclosed are expression vectors comprising the biosensor as well as methods of using the biosensor to detect NAD+.

Abstract: Apparatus and methods for determining whether a test compound induces cell activity, changes cell activity, prevents cell activity, or inhibits cell activity. An embodiment comprises placing a test compound solution in contact with a cell suspension media containing cells, diffusing the test compound solution into the cell suspension from one or more sides, and detecting activity in the cells with respect to their distance from the side from which the test compound is diffusing. Embodiments may provide an apparatus that allows a side source, a point source, or both, from which a test compound solution diffuses into a cell suspension media and contacts cells. Detecting cell activity may involve detecting activity in a first cell group proximate to the side from which the test compound is diffusing, and detecting activity in a second cell group farther than the first cell group from the side from which the test compound is diffusing.

Abstract: The present invention relates to the field of pluripotent stem cell culture and methods facilitate pluripotent stem cell culture at industrial levels.

Abstract: The present invention provides compositions and methods for the culture and maintenance of pluripotent stem cells. More particularly, the present invention provides for compositions and methods for culturing, maintaining, growing and stabilizing primate pluripotent stem cells in a feeder-free defined media further comprising human serum, or a soluble attachment component of the human serum, for promoting cell attachment.

Abstract: The disclosure relates to a method for constructing a plasma Deoxyribonucleic acid (DNA) sequencing library. The method includes: extracting a plasma DNA; making the plasma DNA ligate to a sequencing linker, and purifying a ligation product; performing Polymerase Chain Reaction (PCR) amplification for the purified ligation product, purifying the PCR amplification product, and obtaining the plasma DNA sequencing library, wherein, the method does not include the step of performing 5?-terminus phosphorylation for the plasma DNA.

Abstract: Described herein are methods and assays relating to the presence and/or level of circulating tumor cells (CTCs). These CTC-Cs represent a highly metastatic subpopulation of CTCs. In some embodiments, the methods and assays described herein relate to the treatment of cancer.

Abstract: The disclosure describes the effects of transcription mediated from a promoter on the transcription mediated by divergently coupled supercoiling-sensitive promoter. Transcription initiated from a promoter inhibits transcription mediated by a specific supercoiling-sensitive promoter that is divergently coupled to the promoter. A gyrase inhibitor relieves this inhibition and substantially increases the transcription mediated by the specific supercoiling-sensitive promoter that is divergently coupled to another promoter. Accordingly, the invention pertains to a method for identifying a compound as a gyrase inhibitor or not a gyrase inhibitor based on differential expression of genes under the control of divergently coupled promoters in the presence of the compound. Another embodiment of the invention provides an assay for identifying one or more compounds from a library of compounds as a gyrase inhibitor.

Abstract: Described are three-dimensional, engineered, biological breast tissues, adipose tissues, and tumor models, including breast cancer models.

Abstract: Described herein is a previously unknown function of XBP1 in controlling anti-tumor immunity. It is shown that inhibiting XBP1 in tumor-associated dendritic cells inhibits tumor growth and induces protective anti-tumor immune responses.

Abstract: Methods are provided for diagnosis and prognosis of disease by analyzing expression of a set of genes obtained from single cell analysis. Classification allows optimization of treatment, and determination of whether on whether to proceed with a specific therapy, and how to optimize dose, choice of treatment, and the like. Single cell analysis also provides for the identification and development of therapies which target mutations and/or pathways in disease-state cells.

Abstract: Certain embodiments are directed to composition and methods related to DCLK1-S specific binding agents.

Abstract: This invention provides biosensors, cell models, and methods of their use for monitoring heme and oxygen. Biosensors can include targeting domains, sensing domains and reporting domains. Biosensors can be introduced into cells reprogrammed to represent experimental or pathologic cells of interest. Model cells expressing the biosensors can be contacted with putative bioactive agents to determine possible activities.

Abstract: The present disclosure relates to stretching apparatus and method for aligning microfibrils. Specifically, the present disclosure provides an apparatus for aligning microfibrils along a single direction, which includes: a first elastic substrate onto which a composition containing microfibrils is loaded; and a stretching module which stretches the width of the elastic substrate. In accordance with the apparatus the present disclosure, microfibrils or cells may be aligned along a particular direction simply by pulling and then releasing the elastic substrate. The present disclosure is also useful for culturing of the aligned cells because the physiological activity of the cells can be maintained and cytotoxicity can be prevented.

Abstract: The present invention relates to methods of detecting an increased likelihood of virus infection in a subject. In particular, the present invention relates to methods of detecting an increased likelihood of virus infection in a subject by detecting an altered level of at least one microRNA (miRNA), as well as methods of treating or preventing virus infection. The present invention also relates to nucleotide arrays, oligonucleotides and kits useful for the detection of miRNAs associated with an increased likelihood of virus infection in a subject.