Abstract: The present disclosure provides engineered ketoreductase enzymes having improved properties as compared to a naturally occurring wild-type ketoreductase enzyme. Also provided are polynucleotides encoding the engineered ketoreductase enzymes, host cells capable of expressing the engineered ketoreductase enzymes, and methods of using the engineered ketoreductase enzymes to synthesize a variety of chiral compounds.

Abstract: The crystal structure of ligand-bound EGLN1 catalytic domain of prolyl hydroxylase is disclosed. These coordinates are useful in computer aided drug design for identifying compounds that regulate EGLN1 prolyl hydroxylase and thereby regulate HIF-regulated disorders.

Abstract: Methods of screening, identifying and isolating HMG-CoAR inhibitors are disclosed herein. In particular, said method is useful for screening natural raw products. The present invention also provides potent HMG-CoAR inhibitors for treatment and prevention of diseases and conditions associated with elevated cholesterol and/or blood lipid levels.

Abstract: A soluble and stable form of 5-lipoxygenase (5-LOX) has been made, 5-Lox is the enzyme which initiates leukotriene biosynthesis by catalyzing the two-step transformation of arachidomc acid to leukotriene A4 (LTA4). The soluble and stable 5-LOX is suitable for a number of applications, including, but not limited to, high throughput screening of 5-LOX inhibitors, structural analysis of the enzyme's active site, designing inhibitors based on the three-dimensional structure of the enzyme's active site, and synthesis of LTA4. Using Stable-5-LOX, the crystal structure for 5-LOX has been resolved and the amino acids defining the active site determined.

Abstract: LSD1, a homolog of nuclear amine oxidases, functions as a histone demethylase and transcriptional co-repressor. LSD1 specifically demethylates histone H3 lysine 4, which is linked to active transcription. Lysine demethylation occurs via an oxidation reaction that generates formaldehyde. Importantly, RNAi inhibition of LSD1 causes an increase in H3 lysine 4 methylation and concomitant de-repression of target genes, suggesting that LSD1 represses transcription via histone demethylation. The results thus identify a histone demethylase conserved from S. pombe to human and reveal dynamic regulation of histone methylation by both histone methylases and demethylases.

Abstract: The current invention discloses novel methods for the inhibition of inducible nitric oxide synthesis (iNOS) and the production of NO. Methods of inhibiting the induction of proinflammatory cytokines are also described. Methods of treating various disease states, such as X-linked adrenoleukodystrophy, multiple sclerosis, Alzheimer's and septic shock using inhibitors of iNOS and cytokine induction are disclosed. The inhibitors include the exemplary compounds lovastatin, a sodium salt of phenylacetic acid (NaPA), FPT inhibitor II, N-acetyl cysteine (NAC), and cAMP.

Abstract: A device and method are disclosed for use in the conduct of a non-invasive analysis of a bodily fluid to determine the presence and level of a certain constituent carried by the bodily fluid, which analysis utilizes an indicator formulation that changes color in response to exposure to the constituent to provide a visible indication of the presence and level of the constituent carried by the bodily fluid. A stabilizing formulation is carried in a vessel for mixing with a sample of the bodily fluid to be analyzed. The stabilizing formulation includes a first component for promoting formation of a film, a second component for adjusting the pH of the sample and inhibiting microbial digestion of the certain constituent carried by the bodily fluid, and a third component for reducing interference of ascorbic acid present in the bodily fluid. Where the certain constituent is glucose, the stabilizing formulation includes a microbial digestion inhibitor.

Abstract: The present invention relates to a method of screening placental proteins responsible for pathophysiology of preeclampsia, and a marker for early diagnosis and prediction of preeclampsia. In accordance with one aspect of the present invention, there is provided a method of screening placental proteins responsible for pathophysiology of preeclampsia by 2D E-proteomics analysis, comprising: isolating placental proteins from a placental tissue; separating the isolated proteins two-dimensionally through 2D electrophoresis; and comparing and analyzing the separated proteins based on scanned gel images and differences in the images between normal placental proteins and preeclamptic placental proteins, wherein the comparison and analysis of the placental proteins based on the scanned gel images and differences in the images are accomplished by selecting proteins with differences of 140% or more between two placentas.

Abstract: Disclosed is a method for the preparation of carbamic acid (R)-1-aryl-2-tetrazolyl-ethyl ester, comprising the asymmetric reduction of arylketone and the carbamation of alcohol.

Abstract: In one form, a mutant fructosyl amino acid oxidase modified at an amino acid residue involved in a proton relay system is provided. The mutant fructosyl amino acid oxidase has reduced oxidase activity while substantially maintaining its dehydrogenase activity. Other forms include an assay device and assay method for measuring glycated protein. Still, other forms include unique methods, techniques, systems and devices involving a mutant fructosyl amino acid oxidase.

Abstract: Enzyme based analyte sensors having radiation stabilizing agents are disclosed and described. More particularly, devices comprising a radiation stabilizing agent and methods for stabilizing sensors to high energy radiation sterilization are disclosed and described.

Abstract: This invention pertains to methods, mixtures, kits and compositions pertaining to analyte determination by mass spectrometry using labeling reagents that comprise a nucleophilic reactive group that reacts with a functional group of an analyte to produce a labeled analyte. The labeling reagents can be used as isobaric sets, mass differential labeling sets or in a combination of isobaric and mass differential labeling sets.

Abstract: This invention relates generally to the field of homocysteine detection. In particular, the invention provides a method for determining homocysteine presence or concentration in samples, which method comprises: contacting a sample containing or suspected of containing Hcy with a Hcy co-substrate and a Hcy converting enzyme in a Hcy conversion reaction to form a Hcy conversion product and a Hcy co-substrate conversion product; and assessing the Hcy co-substrate conversion product to determine the presence, absence and/or amount of the Hcy in the sample. The Hcy co-substrate conversion product may be assessed directly, or it may be assessed by further conversion of the Hcy co-substrate conversion product into another material by the action of one or more additional enzymes. A kit for assaying homocysteine based on the same principle is also provided.

Abstract: The measuring device of the invention includes: a first container and a second container for holding a sample; and an optical measurement part for carrying out an optical measurement. The first container has a first sample supply inlet for supplying a sample containing an analyte to the first container and at least one electrode. The second container has a second sample supply inlet for supplying the sample to the second container and a reagent holding part for holding a reagent for the optical measurement.

Abstract: The present invention provides: a reagent composition having higher storage stability; a sensor involving the reagent composition; and others. According to the present invention, a specific heterocyclic compound is added to a reagent composition to improve the storage stability of the reagent composition and reduce the degree of fluctuation in current values in a sensor that utilizes reagent composition.

Abstract: The present invention pertains to a method for in vitro diagnosing a bacterial infection in a biological fluid selected amongst cerebrospinal fluid, ascitic fluid, pericardial fluid, pleural fluid, urine and synovial fluid, based on the measure, in a sample of said fluid, of the production of reactive oxygen species (ROS); a high level of ROS production is indicative of the presence of activated polymorphonuclear neutrophils (PMNs) in said fluid, which in turn is a hallmark of bacterial infection.

Abstract: By a method for measuring 1,5-anhydroglucitol, comprising the steps of: eliminating or converting glucose interfering with the measurement of 1,5-anhydroglucitol and/or a derivative thereof beforehand; and measuring 1,5-anhydroglucitol performed thereafter, wherein such glucose and/or a derivative thereof are/is eliminated or converted in whole blood as such without performing blood cell separation, an enzyme for measuring 1,5-anhydroglucitol is allowed to act on without performing blood cell separation, and 1,5-anhydroglucitol is electrochemically measured, it becomes possible to measure 1,5-anhydroglucitol using a small amount of whole blood without resort to a centrifuge or the like. Accordingly, this measurement method can be applied to rapid measurement of 1,5-anhydroglucitol at bedside or in a medical examination room or to home self-measurement thereof by a patient.

Abstract: An electrochemical device for determining the percentage of glycated hemoglobin in a blood sample is provided. The device includes a cathode and anode and one or more cells. The device may include an enzyme capable of reducing oxygen to water for determining the total amount of hemoglobin in a sample by electrochemically measuring, in an oxygen electroreduction reaction at a cathode, the amount of oxygen in the sample. The device may also be used to determine the amount of glycated hemoglobin in the sample (e.g., spectrometrically or electrochemically). Also provided are devices that include glycated hemoglobin hydrolysis agents or glycated hemoglobin separating agents.

Abstract: The present invention provides a method for measuring the gastric acidity of a mammal using a 13C-labeled carbonate compound. Specifically, the present invention relates to a method for measuring the gastric acidity of a mammal including the following steps: (1) using, as a test sample, expired air of a mammalian subject excreted at any point in time within 30 minutes after oral administration of a predetermined amount of a 13C-labeled carbonate compound, measuring behavior of 13CO2 in the expired air; (2) comparing the behavior of 13CO2 (measured 13CO2 behavior) obtained in step (1) with the behavior of corresponding 13CO2 (reference 13CO2 behavior) that has been obtained beforehand in a control mammal; and (3) determining the gastric acidity of the mammalian subject based on a difference between the reference 13CO2 behavior and the measured 13CO2 behavior obtained above.

Abstract: The disclosed subject matter relates to a force-clamp spectrometer that enables operation in constant force mode and allows for automated data acquisition and analysis, using feedback electronics and software. The disclosed subject matter also relates to methods of using the force-clamp spectrometer for the measurement of the dynamics of chemical reactions. The methods may include, but are not limited to, the measurement of the dynamics of substrate folding and unfolding, as well as bond cleavage and bond formation.

Abstract: A method for detecting inflammation in the urinary tract or urethra of a patient, especially urethritis, comprises a) contacting leucocytes obtained from a urine sample provided by the patient with a luminescence reagent which emits light on reaction with an oxidant; b) adding an activator to the mixture of leucocytes and luminescence reagent; c) continuously monitoring and/or measuring light emitted by the luminescence reagent over a predetermined time period commencing before and ending after the addition of the activator. The light emission is indicative of the presence or absence of inflammation in the urinary tract or urethra of the patient. The urine sample is preferably a sample of first pass urine. The method makes possible a diagnosis especially of urethritis and, in particular, urethral infections selected from Chlamydia trachomatis and Neisseria gonorrhoeae, which can be carried out quickly without invasive procedures.

Abstract: The present specification discloses clonal cell lines susceptible to BoNT/A intoxication, methods of producing such clonal cell lines, and methods of detecting Botulinum toxin serotype A activity using such clonal cell lines.

Abstract: Methods of aging biological samples through the use of fluorescence lifetime are disclosed herein. These methods provide aging of samples such as bloodstains using endogenous fluorophores and conformational protein changes. Advantageously, the methods provide the average fluorescence lifetime across a region of interest in a biological sample, thereby minimizing problems with sampling and providing accurate results.

Abstract: A method of monitoring water-soluble treatment chemicals in a fluid that is immiscible with water and which may or may not contain some aqueous fluid, the method using at least one reagent that produces an optically detectable product, the detection step can take place without separation of the aqueous phase containing the treatment chemicals from the fluid immiscible with water.

Abstract: The invention relates to a colorimetric method for detecting bacterial or fungal pathogens by detecting peptidoglycan or (1-3)-?-D-glucan in a sample.

Abstract: The present disclosure relates to oxidative decarbonylase enzymes, methods of making hydrocarbons with such enzymes, hydrocarbons produced therefrom and uses thereof. More particularly, the present disclosure relates to isolated polypeptide sequences that are cytochrome P450 enzymes with oxidative decarbonylase activity and methods of their use to generate hydrocarbon products, such as biofuels.

Abstract: The present invention provides a method for assaying oxygenase activity, the method comprising monitoring oxygenase activity of FTO.

Abstract: A panel for monitoring levels of biomarkers, including an assay having at least one inflammation monitoring test, at least one oxidative stress monitoring test, and at least one antioxidant activity monitoring test. A method of monitoring an individual's health, by collecting a sample from the individual, applying the sample to an assay panel, performing at least one inflammation monitoring test, at least one oxidative stress monitoring test, and at least one antioxidant activity monitoring test in the panel, and determining levels of biomarkers related to inflammation, oxidative stress, and antioxidant activity and therefore providing information regarding the individual's relative health and/or risk of developing one or more diseases.

Abstract: The application discloses a new tool for predicting, diagnosing and prognosing hypertensive disorders of pregnancy and particularly preeclampsia; methods for the diagnosis, prediction, prognosis and/or monitoring said disorders; and kits and devices for measuring said biomarker and/or performing said methods.

Abstract: A chemical composite useful for preparing a bioelectronic device includes a biologically active compound, such as an enzyme, that is bound directly or indirectly to a polyelectrolyte, which can be reversibly coupled to a chemically treated electrically conductive substrate by electrostatic forces to provide biomimetic sensors, catalyst systems, and other devices having an electrode that can be regenerated and reused. Required or desired cofactors, mediators or the like may be incorporated into the devices, typically by bonding them to the treated substrate and/or the polyelectrolyte.

Abstract: An in vitro sensor for point-of-care detection of at least one analyte or reaction product includes an inert, impermeable substrate, a sensing system, and a reference system. The substrate includes a first transparent surface oppositely disposed from a second surface and first and second cavities. Each of the first and second cavities defines an opening at the second surface. The sensing system is disposed in at least a portion of the first cavity and includes an analyte-detection optode membrane, an analyte-permeable membrane, and a plurality of non-transparent microbeads associated with at least one of the analyte-detection optode membrane and the analyte-permeable membrane. The analyte-permeable membrane is layered upon the analyte-detection optode membrane and covers the opening of the first cavity. The reference system is disposed in at least a portion of the second cavity.

Abstract: The invention relates to a method of fast identification and isolation of cells featuring a desired phenotype. The phenotype is coupled to the amount of gas-liberating enzymes or increased growth. The cells are encapsulated into microcapsules allowing exchange of solvents through the microcapsule wall, but retaining some or all of the gas formed by gas-liberating enzymes on contact with corresponding substrates. Microcapsules containing increased amounts of gas-liberating enzymes are starting to float and can be separated. The cells are then isolated from the microcapsules according to standard procedures.

Abstract: A reagent for detecting an analyte by a redox reaction and a fluorimetric determination is disclosed. The reagent comprises a compound of formula (I): wherein R1 and R2 are each independently selected from R, (CH2CH2O)mR, COR, COOR, and OCOR; each R3 is independently selected from NO2, CN, R, OR, OCOR, COOR, SR, and halogen; R is H or C1-C4 alkyl, where alkyl is optionally substituted with one or more functional group independently selected from the group consisting of halogen, OR, SR, NR2, COOR, CONR2, SO3R and salts thereof, and PO(OR)3 and salts thereof; m is an integer from 1 to 20; and n is 1, 2, or 3. The reagent may further comprise an enzyme or a coenzyme for reducing or oxidizing an analyte.

Abstract: The present invention can be described as an apparatus and cartridge for detecting the presence of an analyte in a fluid. The invention can also be described as a method of detecting the presence of an analyte in a fluid using the apparatus and cartridge. The method comprises the steps of clamping a sensor cartridge into a cartridge receiver of the apparatus, providing fluid to a fluid flow-path of the cartridge, illuminating at least a portion of a sensor, and using a photodetector to detect a change in the optical property of the sensor, wherein the change is caused by the presence or absence of an analyte in the fluid.

Abstract: The present invention relates to therapeutic targets for aging. In particular, the present invention relates to the inhibition of the kynurenine pathway of tryptophan metabolism to extend lifespan or provide anti-aging benefits.

Abstract: An electrochemical sensor system and membrane and method thereof for increased accuracy and effective life of electrochemical and enzyme sensors.

Abstract: The present invention relates to providing improved hydrogen peroxide assays, as well as droplet actuators for conducting such assays. The droplet actuators of the invention may be used to conduct droplet-based hydrogen peroxide assays. They may also be associated with detectors for analyzing the results of the hydrogen peroxide assays of the invention. They may be provided as components of systems which control droplet operations and/or detection for conducting the hydrogen peroxide assays. Measurement by the detector may be used to quantify the presence of an analyte in a sample.

Abstract: The present disclosure provides engineered ketoreductase enzymes having improved properties as compared to a naturally occurring wild-type ketoreductase enzyme. Also provided are polynucleotides encoding the engineered ketoreductase enzymes, host cells capable of expressing the engineered ketoreductase enzymes, and methods of using the engineered ketoreductase enzymes to synthesize a variety of chiral compounds. The engineered ketoreductase polypeptides are optimized for catalyzing the conversion of N,N-dimethyl-3-keto-3-(2-thienyl)-1-ketopropanamine to (S)—N,N-dimethyl-3-hydroxy-3-(2- thienyl)-1-propanamine.

Abstract: Methods, processes, systems, and apparatuses are disclosed for predicting anti-androgen therapy response in the treatment of androgenetic alopecia based on a fluorometric assay and proteomics.

Abstract: The present invention provides methods and kits for the diagnosis of schizophrenia, which employ mitochondrial complex I as a peripheral biological marker for schizophrenia. In an embodiment of the invention, the present invention provides a method for diagnosing schizophrenia in a subject by determining the level of m-RNA or protein mitochondrial complex I subunits and its activity by determining the cellular basal respiration through complex I enzyme.

Abstract: Chemiluminescent detection of metabolic by-products of inosine and hypoxanthine to diagnose ischemic events such as early acute cardiac ischemia.

Abstract: The present invention relates to a compound of Formula 1, wherein: (A) is heteroaryl or aryl; each (A?), if present, is independently chosen from aryl, arylalkoxy, arylalkyl, heterocyclyl, aryloxy, halo, alkoxy, haloalkyl, cycloalkyl, haloalkoxy, and cyano, wherein each (A?) is substituted with 0, 1, 2, or 3 substituents independently chosen from halo, haloalkyl, haloalkoxy, aryl, arylalkoxy, alkyl, alkoxy, amido, —CH2C(=0)NH2, heteroaryl, cyano, sulfonyl, and sulfinyl; X is 0, 1, 2, or 3; (B) is a cyclopropyl ring, wherein (A) and (Z) are covalently bonded to different carbon atoms of (B); (Z) is —NH—; (L) is chosen from a single bond, —CH2—, —CH2CH2—, —CH2CH2CH2—, and —CH2CH2CH2CH2—; and (D) is an aliphatic carbocyclic group or benzocycloalkyl, wherein said aliphatic carbocyclic group or said benzocycloalkyl has 0, 1, 2, or 3 substituents independently chosen from —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)(C1-C6 alkyl), alkyl, halo, amido, cyano, alkoxy, haloalkyl, and haloalkoxy.

Abstract: A small diameter flexible electrode designed for subcutaneous in vivo amperometric monitoring of glucose is described. The electrode is designed to allow “one-point” in vivo calibration, i.e., to have zero output current at zero glucose concentration, even in the presence of other electroreactive species of serum or blood. The electrode is preferably layered, with the layers serially deposited within a recess upon the tip of a polyamide insulated gold wire. A first glucose concentration-to-current transducing layer can be overcoated with an electrically insulating and glucose flux limiting layer (second layer) on which, optionally, an immobilized interference-eliminating horseradish peroxidase based film is deposited. An outer layer is preferably biocompatible.

Abstract: A small diameter flexible electrode designed for subcutaneous in vivo amperometric monitoring of glucose is described. The electrode is designed to allow “one-point” in vivo calibration, i.e., to have zero output current at zero glucose concentration, even in the presence of other electroreactive species of serum or blood. The electrode is preferably layered, with the layers serially deposited within a recess upon the tip of a polyamide insulated gold wire. A first glucose concentration-to-current transducing layer can be overcoated with an electrically insulating and glucose flux limiting layer (second layer) on which, optionally, an immobilized interference-eliminating horseradish peroxidase based film is deposited. An outer layer is preferably biocompatible.

Abstract: The present invention relates to a novel Bacillus pumilus bilirubin oxidase, to the method for preparing same and also to the use thereof in particular for assaying bilirubin and for using enzymatic biofuel cells.

Abstract: The present disclosure relates to a mutant lactate oxidase having increased stability, a nucleic acid encoding the mutant lactate oxidase, an expression vector comprising the nucleic acid, a host cell comprising the nucleic acid or the expression vector, a method of determining lactate in a sample, the use of the mutant lactate oxidase for determining lactate, a device for determining lactate in a sample using the mutant lactate oxidase and a kit for determining lactate comprising the mutant lactate oxidase.

Abstract: A biosensor system determines analyte concentration from an output signal generated from a light-identifiable species or a redox reaction of the analyte. The biosensor system compensates at least 50% of the total error in the output signal with a primary function and may compensate a portion of the residual error with at least one residual function. An SSP function may serve as the primary function, first residual function, or second residual function. Preferably, when the SSP function serves as the first residual function, the SSP function compensates at least 50% of the residual error remaining after primary compensation. Preferably, when the SSP function serves as the second residual function, the SSP function compensates at least 50% of the residual error remaining after primary and first residual compensation. The error compensation provided by the primary, first residual, and second residual functions may be adjusted with function weighing coefficients.

Abstract: The present invention provides methods for determining the stability of methyleneamine, methyleneamine-like compounds or compounds containing a methyleneamine moiety in the presence of semicarbazide-sensitive amine oxidase (SSAO) or a biological sample containing SSAO activity. The disclosed methods may be configured in an assay format for high throughput screening applications.

Abstract: The present invention relates to a biomarker and a method for determining an oxidative stress level in a biological sample, which employs co-factor-dependent oxidative stress parameters, as well as a kit adapted for carrying out such a method. In one aspect the co-factor is tetrahydrobiopterin.

Abstract: A method and device are disclosed for continuously detecting, classifying and identifying toxic particles, aerosols and/or vapor in an air sample, in near real time by directing an air sample containing an optional target analyte, in the form of particles, aerosols and/or vapors, enzyme(s), and enzyme substrate(s), to a surface of a collection matrix for forming a biocatalytic reaction product of a plurality of freely mobile optical reporters, and by using a light source with optical reader to interpret the signal from the optical reporter, enabling the detection, classification and identification of toxic particles, aerosols and/or vapor in the air sample.