Abstract: In a general aspect, an apparatus can include a first carbon nanotube array that is patterned to define a first electrode having a first plurality of electrode segments. The apparatus can also include a second carbon nanotube array that is patterned to define a second electrode having a second plurality of electrode segments. The second plurality of electrode segments can be interdigitated with the first plurality of electrode segments. The apparatus can further include a biorecognition agent disposed on a surface of the first electrode and disposed on a surface of the second electrode. The first plurality of electrode segments can each have a height-to-width aspect ratio of at least 1 to 1.

Abstract: The present invention generally relates to microfluidics and/or epigenetic sequencing. In one set of embodiments, cells contained within a plurality of microfluidic droplets are lysed and the DNA (e.g., from nucleosomes) within the droplets are labeled, e.g., with adapters containing an identification sequence. The adapters may also contain other sequences, e.g., restriction sites, primer sites, etc., to assist with later analysis. After labeling with adapters, the DNA from the different cells may be combined and analyzed, e.g., to determine epigenetic information about the cells. For example, the DNA may be separated on the basis of certain modifications (e.g., methylation), and the DNA from the separated nucleosomes may be sequenced using techniques such as chromatin immunoprecipitation (“ChIP”). In some cases, the DNA sequences may also be aligned with genomes, e.g., to determine which portions of the genome were epigenetically modified, e.g., via methylation.

Abstract: The present invention relates to a method to cleave target nucleic acid sequence by the catalytic domain of a GIY-YIG homing endonucleases I-TevI. More precisely, the invention relates to the deciphering of new preferential I-TevI cleavage sites for efficient and specific cleavage activity. The invention concerns a method for the generation of TevI specific chimeric endonucleases to target nucleic acid sequence including such cleavage sites and methods of using same for gene editing.

Abstract: The present invention relates to a method for in vitro determining generation of a haemostatis factor such as thrombin and/or plasmin in a test sample using a chemiluminescent substrate specific for said blood clotting factor. Upon cleavage of the substrate, a luminescent signal is generated via aminoluceferin with the aid of a luciferase. The invention also relates to a kit for in vitro determining generation of a haemostasis factor in a test sample, and to novel chemiluminescent substrates for the determination of thrombin and plasmin.

Abstract: Medulloblastoma (MB) is the most common malignant brain tumor of children. To identify the genetic alterations in this tumor type, we searched for copy number alterations using high density microarrays and sequenced all known protein-coding genes and miRNA genes using Sanger sequencing. We found that, on average, each tumor had 11 gene alterations, markedly fewer than in common adult cancers. In addition to alterations in the Hedgehog and Wnt pathways, our analysis led to the discovery of genes not previously known to be altered in MBs. Most notably, inactivating mutations of the histone H3K4 trimethylase genes MLL2 or MLL3 were identified in 16% of MB patients. These results demonstrate key differences between the genetic landscapes of adult and childhood cancers, highlight dysregulation of developmental pathways as an important mechanism underlying MBs, and identify a role for a specific type of histone methylation in human tumorigenesis.

Abstract: Described embodiments provide devices, systems and methods for sequencing liquid flow in response to a driving force by entrapping and releasing gas between volumes of liquid in a controlled manner. In one particular form, a centrifugal “lab on a disk” device is provided to drive liquid flow and sequencing by virtue of the centrifugal force and in one particular form a radially inward bend conduit is used in connection with controllably trapping and releasing gas between liquid volumes.

Abstract: A polypeptide comprising a chromogenic amino acid. The chromogenic amino acid is flanked by at least one amino acid to the N and C termini thereof. The amine group of the chromogenic amino acid has a pKa of less than 5. The chromogenic amino acid is capable of reacting with a conjugated aldehyde. The polypeptide comprises a target sequence for a target protease which is capable of cleaving the peptide bond comprising the amino group of the chromogenic amino acid.

Abstract: A sample acquiring device, an apparatus and a method for spectrophotometric measurement of high density lipoprotein (HDL) and at least one of total cholesterol (TC), triglycerides (TG) and glucose (FPG).

Abstract: The present invention concerns a method for specifically detecting and identifying Streptococcus agalactiae, using a reaction medium comprising at least one esterase enzymatic substrate.

Abstract: The present invention is directed to peptide sequences that were identified from combinatorial libraries and could serve as substrates of plague plasminogen activator (Pla). Another aspect of the present invention is drawn to peptides derived from the substrates for Pla as a result of chemical modifications leading to specific inactivation of the proteolytic activity of Pla. Additionally, the present invention is directed to the use of the substrates identified herein in the detection of bacteria expressing omptin family of proteases which includes Y. pestis. Furthermore, the present invention is also directed to the use of the inhibitors identified herein in the prevention and treatment of infection caused by these bacteria.

Abstract: A biochip includes: a first chamber; a second chamber filled with a wax, a melting point of the wax being 25° C. or more and 63° C. or less; an injection path between the first chamber and the second chamber; and a sub-chamber that includes a wall at least partially made of the wax, the sub-chamber is formed inside the second chamber and communicates with the first chamber via the injection path.

Abstract: A method for determining disease severity in a subject afflicted with a tauopathy-related neurodegenerative disease comprises detecting the level of a PINCH protein or isoform thereof in a test sample comprising brain tissue or cerebrospinal fluid. The PINCH protein level in the test sample indicates the relative severity of the tauopathy-related neurodegenerative disease afflicting the subject.

Abstract: The present invention relates to the use of matrix metalloproteinase-2 (MMP2) as a predictive biomarker of response to antiangiogenic therapy and survival after antiangiogenic therapy in cancer patients, and to related methods for predicting or monitoring the response to an antiangiogenic treatment and the survival after said treatment of a cancer patient.

Abstract: The disclosure provides a label-free viscosity-based analyte detection system using paramagnetic beads as an asynchronous magnetic bead rotation (AMBR) microviscometer. It is disclosed herein that the bead rotation period is linearly proportional to the viscosity of a solution comprising analytes surrounding the paramagnetic bead. Optical measurement of asynchronous microbead motion determines solution viscosity precisely in microscale volumes, thus allowing an estimate of analyte concentration. The results demonstrate the feasibility of viscosity-based analyte detection using AMBR in microscale aqueous volumes.

Abstract: The invention provides a method for screening for colorectal cancer, the method comprising: screening a biological sample from an individual for one or more biomarkers selected from the group defined in Table 1 and/or Table 6, wherein the presence of or increased expression of the one or more biomarkers relative to a control sample is indicative that the individual is at risk of suffering from or is suffering from colorectal cancer. The invention also provides an array and kit suitable for use in the methods of the invention, methods of treating colorectal cancer and therapeutic agents for use in methods of treating cancer.

Abstract: Described is a method for accurately and highly sensitively measuring glycated hemoglobin in a hemoglobin-containing sample without being influenced by hemoglobin. It is related to a method for measuring glycated hemoglobin in a hemoglobin-containing sample, comprising: reacting hemoglobin-containing sample with a protease in the presence of a surfactant; and then reacting the obtained reaction product with fructosyl peptide oxidase, wherein the latter reaction or both of the former reaction and the latter reaction are performed in the presence of a halogen oxide, and measuring the generated hydrogen peroxide. The method for measuring glycated hemoglobin in a hemoglobin-containing sample provided by the present invention is useful in, for example, the measurement of glycated hemoglobin useful in the diagnosis of diabetes mellitus.

Abstract: The invention describes methods that are useful for treating cancer by administering a Chk1 inhibitor which can induce apoptosis in p53-defective cells when combined with a chemotherapy and/or radiotherapy. Methods for screening candidates for a Chk1 inhibitor-based cancer treatment regimen are also described.

Abstract: The present disclosure provides peptide amino acid sequencing and identification methods and kits for performing such methods. For example, single-molecule detection of fluorophore-labeled peptides is disclosed using multiple rounds of standard Edman degradation or using digestion by chemicals or enzymes. Different fluorophores covalently attached to each of a specific type of amino acid side chain of a peptide provide for the derivation of the peptide's encoded amino acid sequence following image alignments of multiple Edman cycles or following digestion by chemicals or enzymes. The amino acid sequence of a peptide and/or the identity of the peptide can be determined by bioinformatic analysis based on the encoded amino acid sequence. The present disclosure further provides peptide derivatization and immobilization strategies to enable the sequencing and identification of a single peptide or a plurality of peptides.

Abstract: Methods are provided for diagnosing the risk of a cardiovascular event in a patient. In some embodiments, the method includes measuring the level of proprotein convertase subtilisin kexin type 9 (PCSK9) in a sample obtained from a patient and comparing the measured level of PCSK9 to a control. Also provided are methods of selecting a therapy for a patient prior to administration of the therapy. In some embodiments, the method includes measuring a PCSK9 blood concentration in a sample from a patient to determine the presence or absence of a PCSK9 blood concentration indicative of responsiveness to an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase. Further provided are methods for assessing the efficacy of a therapy being administered to a patient. In certain embodiments, the method includes detecting a change in a PCSK9 blood concentration in a sample from a patient, wherein a change in detected levels is indicative of whether the therapy is efficacious.

Abstract: The present invention provides a diagnostic reagent or assay for assessing the activity of a protease in vivo or in vitro and methods of detecting the presence of a cancerous or precancerous cell. The assays are comprised of two particles linked via an oligopeptide linkage that comprises a consensus sequence specific for the target protease. Cleavage of the sequence by the target protease can be detected visually or using various sensors, and the diagnostic results can be correlated with cancer prognosis.

Abstract: Provided is an activatable probe that undergoes intramolecular cyclization and subsequent aggregation in apoptotic tumor cells upon peptidase-initiated, and most advantageously caspase-3, activation. These caspase-sensitive nano-aggregation probes (C-SNAFs) are generally biocompatible, possess NIR spectral properties or may serve as PET or MRI imaging agents, and have a mechanism of target-mediated nanostructure self-assembly amenable to in vivo use. The probes encompass biocompatible condensation chemistry products that comprise D-cysteine and 2-cyano-6-hydroxyquinoline (CHQ) moieties linked to an amino-luciferin scaffold, and which can be activated by a two-step reaction requiring caspase-3/7-mediated cleavage of an aspartate-glutamate-valine-aspartate (L-DEVD) capping peptide and the free intracellular thiol-mediated reduction of the disulfide bond.

Abstract: The invention provides agents and vaccines for treating and diagnosing celiac disease. In particular, the present invention provides a combination of three peptides that are useful for treating and diagnosing celiac disease in a large proportion of patients.

Abstract: Embodiments of the present invention provide methods, microfluidic devices, and systems for the detection of an active target agent in a fluid sample. A substrate molecule is used that contains a sequence which may cleave in the presence of an active target agent. A SNAP25 sequence is described, for example, that may be cleaved in the presence of Botulinum Neurotoxin. The substrate molecule includes a reporter moiety. The substrate molecule is exposed to the sample, and resulting reaction products separated using electrophoretic separation. The elution time of the reporter moiety may be utilized to identify the presence or absence of the active target agent.

Abstract: A method of selecting a subject for administration of an anti-c-Met antibody, comprising (i) determining the presence or the amount of a ubiquitin peptidase, (ii) determining the presence or expression level of a ubiquitin peptidase coding gene, or (iii) measuring the activity of a ubiquitin peptidase, in a biological sample; as well as related methods.

Abstract: Provided herein are compositions comprising native and denatured human leukocyte antigens (HLA) and methods of making said compositions. Also provided herein are methods and kits for the detection of antibodies to native HLAs.

Abstract: Rational design of immunotherapeutics relies on clear knowledge of the immunodominant epitopes of antigens. Current methods for identifying kinetically stable peptide-MHC complexes are in many cases inadequate for a number of reasons. Disclosed herein is a reductionistic system incorporating known participants of MHC class II antigen processing in solution to generate peptide pools from antigens, including those for which no immunodominant epitope has yet been identified, that are highly enriched for proteolytic fragments containing their immunodominant epitopes. HLA-DM-mediated editing contributes significantly to immunodominance and is exploited in discovering immunodominant epitopes from novel or previously uncharacterized antigens, particularly antigens associated with pathogens, tumors or autoimmune diseases.

Abstract: A method for screening a compound to determine whether the compound is a proteasome deubiquinating inhibitor of high specificity comprises contacting the compound with human 19S regulatory particles (19S RP) of 26S proteasome and determining whether the compound inhibits activity of deubiquinating (DUB) enzymes UCHL5 and USP14; inhibition of UCHL5 and USCP14 activities indicates that the compound is a proteasome deubiquinating inhibitor of high specificity.

Abstract: The development of a series of fluorescent materials including heterocycle-functionalized luminogens with aggregation-induced/enhanced emission (AIE/AEE), long wavelength emission, and high solid state fluorescence quantum efficiency is contemplated. The described fluorescent materials are promising candidates in selective luminescence-based chemosensor for Hg2+ or ATP, fluorescent staining for mitochondria in living cells with high photostability, stimuli-responsive luminescent materials, and materials for optical waveguides. In addition, these heterocycle-functionalized luminogens are particularly useful as fluorescent labels for biopolymers such as peptides, antibodies, or nucleic acids, making them useful as AIE-active biocompatible probes for clinical cancer imaging and diagnostics.

Abstract: The peptidoglycan layer is a vital component of the bacterial cell wall, which comprises 4?3 and 3?3 transpeptide cross-linkages, the formation of which are catalyzed by D,D- and L,D-transpeptidases, respectively. Methods for the treatment of bacterial infections with agents that inhibit L,D-transpeptidases, either alone or in combination with D,D-transpeptidase inhibitors, are provided herein. Also provided are methods for the treatment of chronic stage tuberculosis with agents that inhibit enzyme with L,D-transpeptidase activity.

Abstract: Methods and processes for conducting genetic analysis through protein polymorphisms, including identification of individuals, establishment of paternity and measurement of genetic diversity and distance. Some illustrative embodiments of methods of the present invention include the identification of peptide biomarkers using proteomic techniques, including liquid chromatography-tandem mass spectrometry from biological samples, using hair, dentin, or bone as a source of the protein to be analyzed. Other illustrative embodiments include the determination of allelic frequency and feasibility of protein polymorphism peptide biomarkers, and the application of these frequencies to allow statistical analysis and population genetics to be applied to collected biological samples.

Abstract: In accordance with the present invention, it has been discovered that compounds which modulate the ?-secretase enzyme to make more of the shorter, less toxic and less aggregation-prone A? peptides (such as A?37 and A?38), while making less of the longer and more toxic and aggregation-prone AB peptides (such as AB40 and AB42) are useful as gamma-secretase modulators. In addition, these GSM compounds have further been discovered to have the selective property of modulating the formation of various AB peptides, while not inhibiting the overall activity of the ?-secretase enzyme. Thus, such compounds do not impede other critical functions of the ?-secretase enzyme, such as generating fragments from Notch that appear to control gene expression and cell differentiation. Therefore, in accordance with the present invention, there are provided screening assays useful for determining whether test compounds have GSM activity; accordingly, invention assays facilitate the identification of new gamma-secretase modulators.

Abstract: This document relates to methods and materials involved in modulating deubiquitinases (e.g., USP10 polypeptides) and/or ubiquitinated polypeptides (e.g., tumor suppressor polypeptides or mutant versions of tumor suppressor polypeptides). For example, methods and materials for increasing deubiquitinase (e.g., a USP10 polypeptide) expression or activity, methods and materials for decreasing deubiquitinase (e.g., a USP10 polypeptide) expression or activity, methods and materials for stabilizing tumor suppressor polypeptides (e.g., wild-type p53 polypeptides), methods and materials for de-stabilizing mutant versions of tumor suppressor polypeptides (e.g., mutant p53 polypeptides), and methods and materials for reducing cancer cell proliferation, increasing cancer cell apoptosis, and/or treating cancer (e.g., cancers having reduced levels of wild-type p53 polypeptides or cancers having increased levels of mutant p53 polypeptides) are provided.

Abstract: This invention describes a new analytical method to determine the quantity and distribution of fucose per Fc within an antibody preparation.

Abstract: Disclosed are a nanoparticle sensor for measuring protease activity, for protease imaging, and a method for preparing the same. More specifically, the present invention relates to a nanoparticle sensor for measuring protease activity in which a fluorophore- and a quencher-conjugated peptide substrate is conjugated to a biocompatible polymer nanoparticle. The peptide substrate is specifically lysed by a protease. The sensor according to the present invention is capable of inhibiting emission of fluorescence with high extinctive activity of the quencher on a fluorescent material. But strong fluorescence is specifically emitted only if the peptide substrate is lysed by a specific protease. Therefore, the sensor is especially useful as a method for screening a novel drug such as a protease overexpression inhibitor, and early diagnosis of incurable diseases and various diseases such as autoimmune diseases including cancer, osteoarthritis, rheumatoid arthritis and dementia.

Abstract: This invention provides methods of measuring the viability of cultured cells by detecting one or more cell death-stable proteins or enzyme activities. Methods provided by the invention correlate viability to relative levels of enzyme activity in cell-containing and non-cell-containing fractions of a cell culture.

Abstract: Disclosed are imaging agents having the following Formula I: (I); wherein F is a near infrared fluorophore, S is an enzymatically cleavable oligopeptide, Q is a fluorescence quencher molecule, and M is a moiety selected from the group consisting of PEG or derivative thereof and a targeting ligand, and wherein F, Q and M are linked to separate amino acids of the enzymatically cleavable oligopeptide. Compositions comprising such compounds, as well as methods of use, methods of identifying a cell or a population of cells in vivo expressing a protease of interest, and methods of treating a disease through imaging are also disclosed.

Abstract: A method of utilizing the chymotrypsin level of an individual as a measure of the success of secretin, other neuropeptides, and peptides or digestive enzyme administration to such individuals, and in particular, as a prognosticative of potential secretin, other neuropeptides, peptides, and digestive enzyme administration for persons having ADD, ADHD, Autism and other PDD related disorders.

Abstract: The present disclosure relates to an Extra Cellular Matrix composition specific for cancer type and a tumor microenvironment platform for long term culturing of tumor tissue, wherein said culturing provides human ligands and tumor tissue micro-environment to mimic physiologically relevant signalling systems. The present disclosure further relates to the development of a Clinical Response Predictor and its application in the prognostic field (selection of treatment option for the patient) and translational biology field (development of anticancer drugs). The disclosure further relates to a method of predicting clinical response of a tumor patient to drug(s). The disclosure further relates to a method for screening tumor cells for the presence of specific markers for determining the viability of said cells for indication of tumor status.

Abstract: A method for measuring an analyte is described that includes the steps of: i) preparing a reagent (D) in which an enzyme (A) and an enzyme (B) coexist in the absence of the analyte; ii) bringing the analyte into contact with the enzyme (A) and the enzyme (B) so that the enzyme (A) acts on the analyte to produce a product (E), on which the enzyme (B) does not substantially act, from the analyte; iii) producing a product (C) by allowing the enzyme (A) or an enzyme (F) that is different from the enzyme (A) that acts on the analyte to produce a product (C) to act on the analyte and/or the product (E); and iv) detecting the product (C) by the enzyme (B).

Abstract: There is described a method for analyzing ubiquitin polymers using linkage-specific deubiquitinase enzymes. Novel specificities of deubiquitinase enzymes are also provided.

Abstract: Administering an effective dose of glutenase to a Celiac or dermatitis herpetiformis patient reduces levels of toxic gluten oligopeptides, thereby attenuating or eliminating the damaging effects of gluten.

Abstract: Enzyme substrates and associated technology of the present invention are provided. An enzyme substrate of the invention may comprise a biologically functional fluorescent dye and an enzyme-specific substrate moiety attached in such a way that the functionality of the functional dye is diminished. An enzymatic reaction may cleave at least a portion of the substrate moiety from the enzyme substrate to provide a more functional product dye. This product dye may be nonfluorescent or weakly fluorescent, in general, and relatively fluorescent, in a particular condition, such as when bound to a partner biological molecule or an assembly of partner biological molecules. An enzyme substrate of the present invention may thus be useful in fluorescence detection, and/or in any of a variety of useful applications, such as the detection of enzymatic activity in a cell-free system or in a living cell, the screening of drugs, or the diagnosis of disease.

Abstract: Provided are systems and methods for detecting and/or measuring in vivo interstitial biological activity, processes, and or compounds in human or animal subjects.

Abstract: A diagnostic test kit for detecting the presence or quantity of an enzyme or enzyme inhibitor is provided. The diagnostic kit utilizes substrate conjugates to facilitate the detection of the enzyme or enzyme inhibitor via direct detection of the substrate and/or a product formed in an enzyme-catalyzed reaction of the substrate. The substrate conjugates include a substrate joined (e.g., covalently bonded, physically adsorbed, etc.) to a reporter. In one embodiment, for example, a peptide, protein, or glycoprotein substrate is joined to a reporter (e.g., dyed latex particle). In this embodiment, the substrate provides a cleavage target for an enzyme. Specifically, upon contacting the substrate conjugate, the enzyme catalyzes a reaction with the substrate and forms a product conjugate that includes the product of the enzyme catalyzed reaction joined to the reporter. The signal exhibited by the reporters may then be used to indicate the presence or quantity of an enzyme or enzyme inhibitor within the test sample.

Abstract: The present invention relates to a method for determining the presence or absence of a microorganism, said method including the steps of: 1) providing an enclosure containing a liquid or semi-solid phase consisting of a biological medium capable of containing a living form of said microorganism, nutritional elements, and an enzymatic substrate which is specific to said microorganism and which can be metabolised into at least one VOC metabolite, and a gaseous phase adjacent to said liquid or semi-solid phase; 2) exposing at least said liquid or semi-solid phase to conditions that are propitious for said microorganism to metabolise said enzymatic substrate into a molecule of said VOC metabolite; and 3) determining, by optical transduction, the presence or absence of said VOC metabolite, characterised in that the latter interacts with a nanoporous matrix, said matrix being implemented in a form that is separate from said enzymatic substrate, and in that the detection, by optical transduction, of a change in the

Abstract: A reaction medium for detecting and/or identifying Staphylococcus aureus bacteria, comprising a combination of two enzymatic substrates for alpha-glucosidase.

Abstract: The present disclosure provides a method for assessing the environmental effects of alkylbenzenesulfonate (LAS). For example, the method includes contacting a population of cells with a sample, measuring an expression level of one or more LAS biomarkers in the cell population, comparing the level of expression of the one or more LAS biomarker to one or more reference values corresponding to the one or more LAS biomarkers, and determining an LAS risk associated with the sample.

Abstract: A Disease Severity Index (DSI) is provided for assessment of chronic liver disease in a patient using non-invasive liver function test results. A DSI was derived from non-invasive liver function test results based on hepatic blood flow. The DSI is used in methods for prediction of clinical outcomes, prediction of response to antiviral treatment, and assessment of progression of chronic liver diseases. Non-invasive methods to diagnose three distinct categories of patients with Primary Sclerosing Cholangitis (PSC) are provided. The methods can be used to diagnose PSC patients as Slow Progressors, Moderate Progressors and Rapid Progressors.

Abstract: The present invention provides a novel class of macrocyclic compounds as well as complexes formed between a metal (e.g., lanthanide) ion and the compounds of the invention. Preferred complexes exhibit high stability as well as high quantum yields of lanthanide ion luminescence in aqueous media without the need for secondary activating agents. Preferred compounds incorporate hydroxy-isophthalamide moieties within their macrocyclic structure and are characterized by surprisingly low, non-specific binding to a variety of polypeptides such as antibodies and proteins as well as high kinetic stability. These characteristics distinguish them from known, open-structured ligands.

Abstract: This invention provides methods of measuring the viability of cultured cells by detecting one or more cell death-stable proteins or enzyme activities. Methods provided by the invention correlate viability to relative levels of enzyme activity in cell-containing and non-cell-containing fractions of a cell culture.