Abstract: The present invention relates to modified serpins for use in the treatment of bradykinin-mediated diseases. The modified serine protease inhibitors (serpins) have mutations in one or more of the P4, P3, P2, P1 and P1? residues of their reactive center loop, which mutations increase the serpin's inhibition of plasma kallikrein (PK) as compared to the corresponding unmodified serpin. The mutations in the modified serpins of the invention further ensure that serpins display substantially no inhibition of at least thrombin and activated protein C. A modified serpin of the invention further preferably shows increased inhibition of at least one of an active form of Factor XII (FXII) and plasmin as compared to the corresponding unmodified serpin, and, preferably, the serpin inhibits at least one of an active form of FXII and PK stronger than they are inhibited by C1 esterase inhibitor. Preferably the modified serpin is a modified ?1-antitrypsin.

Abstract: The invention relates to highly luminescent nanostructures, particularly highly luminescent nanostructures comprising a ZnSe1-xTex core and ZnS and/or ZnSe shell layers. The invention also relates to methods of producing such nanostructures.

Abstract: A nanoscale drug carrier capable of crossing the blood-brain barrier. Said carrier can target brain lesions (brain tumors or other neurodegenerative diseases). The targeting drug carrier capable of crossing the blood-brain barrier comprises all-heavy-chain human ferritin or a functional fragments reconstituted structure or a mutant thereof. The manner for crossing the blood-brain barrier of the drug carrier is receptor-mediated transcytosis. The drug carrier provides an effective nanoscale drug carrier for the treatment of brain tumors or other neurodegenerative diseases.

Abstract: A method for analyzing planar sample is provided. In some cases the method comprises: (a) labelling the planar sample with a capture agent that is linked to a nucleic acid, wherein the capture agent specifically binds to complementary sites in the planar sample; (b) reading a fluorescent signal caused by extension of a primer that is hybridized to the nucleic acid, using fluorescence microscopy. Several implementations of the method, and multiplexed versions of the same, are also provided.

Abstract: Provided is a composition by which glycated hemoglobin can be measured even in the presence of a stronger surfactant than a conventional case. Also provided is a buffer and/or stabilizer which maintains the residual activity of an amadoriase or lowers a reduction of residual activity. The present invention provides a composition for use in measuring glycated hemoglobin containing an amadoriase having substitution of one or more amino acid residues at a position(s) corresponding to an amino acid(s) selected from the group consisting of position 262, position 257, position 249, position 253, position 337, position 340, position 232, position 129, position 132, position 133, position 44, position 256, position 231 and position 81 of an amadoriase derived from the genus Coniochaeta and represented by SEQ ID No: 1 or 3, and having residual activity even in the presence of a surfactant.

Abstract: Method, apparatus, and computer-readable media providing medical personnel artificial intelligence (AI)-derived data regarding a patient presenting neurological indications includes a guidance server. Preferably, the guidance server receives three or more of: (i) natural language input from medical personnel, (ii) real-time vital signs telemetry data, (iii) neurosurgical treatment database information, (iv) neurosurgical treatment guideline information, (v) clinical laboratory testing results, (vi) patient historical data, and (vii) patient imaging information. An imaging post-processor receives (i) patient imaging history information, (ii) and real-time patient imaging data, and provides to the guidance server the patient imaging information. The guidance server then provides one or more alerts (or other guidance) to the medical personnel.

Abstract: The method according to the present invention includes: a training sample measurement process (S1, S2) in which, for a food product belonging to the same kind as a determination target, a plurality of training samples individually labeled with a known state of quality are subjected to a measurement using a chromatograph mass spectrometer under the same analysis condition; a training sample data collection process (S3, S4) in which an index value related to the magnitude of a peak observed on an extracted ion chromatogram obtained by the measurement is acquired for each training sample, and the index value of the peak at each retention time common to the training samples is extracted; and a discrimination model creation process (S5-S7) in which a supervised training is performed to create a discrimination model, using, as the training data, the index value of the peak at each retention time common to the training samples acquired for each of the labeled training samples.

Abstract: The present invention relates to cell-penetrating effector proteins of type III secretion system (T3SS)-containing bacteria of the genus Salmonella or Shigella and variants, fragments and immunomodulatory domains thereof, for use in immunotherapy. The present invention further relates to cell-penetrating effector proteins of type III secretion system (T3SS)-containing bacteria of the genus Salmonella or Shigella and variants, fragments and immunomodulatory domains thereof, for delivering cargo molecules into eukaryotic cells.

Abstract: The present invention provides a method for preparing nicotinamide mononucleotide (NMN) by bioanalysis. The method includes a step of catalytically reacting a plurality of raw materials including nicotinamide, ATP, and ribose in the presence of nicotinamide phosphoribosyltransferase (Nampt), ribose phosphate pyrophosphokinase, and ribokinase, to prepare the NMN.

Abstract: The methods and configurations herein provide for analysis of microplate based assays. Certain aspects include: an optical illumination panel; a plurality of sample wells configured to receive light from the optical illumination panel, and wherein the plurality of sample wells is configured with a first field of view; at least one aperture array configured to isolate directed light therethrough the plurality of sample wells; at least one optical array configured to receive optical information from the plurality of sample platforms, wherein the at least optical array comprises an array of individual microprisms configured with equal apex angles at distal equidistances along a row, wherein the individual microprism apex angles decrease toward the center of the row culminating in at least one flat surface along a center portion of the row; and a detector configured to capture the optical information with a second field of view as provided by the at least one optical array.

Abstract: Described herein are compositions and methods for inhibiting an inflammatory or autoimmune response and for inducing immune tolerance in a subject in need thereof comprising administering to the subject a therapeutically effective amount of an antigen presenting cell (APC)-targeted antibody operatively linked to IL-10 or a fragment thereof. The compositions and methods described herein are useful for treating inflammatory and autoimmune disorders.

Abstract: The present invention relates to therapeutic and prophylactic methods based on inhibition of CIS in NK cells. In particular, the present invention relates to treating or preventing a NK-responsive condition by administering to a subject a CIS inhibitor, or administering CIS-inhibited NK cells. The invention further relates to methods for identifying a CIS inhibitor, and for determining a likelihood of cancer response to treatment with CIS inhibition.

Abstract: The present invention provides reagents and methods for breast cancer detection.

Abstract: Described are dual mass-spectrometry-cleavable cross-linkers that can be cleaved selectively using two differential tandem mass-spectrometric techniques such as collision induced dissociation (CID) or electron transfer dissociation (ETD), i.e., a dual cleavable crosslinking technology (DUCCT) cross-linker. When used to cross-link a macromolecule, such as a peptide, MS/MS fragmentation produces two signature complementary mass spectra of same cross-linked peptides, the analysis of which gives rise to high confidence in characterizing the structures of the cross-linked macromolecules as well as sites of interactions. Also described, are methods of making and using DUCCT cross-linkers.

Abstract: Compositions and methods relating to potentially pathogenic mutations in the nucleotide sequence of a human NAGLU gene. Some NAGLU gene variants have been discovered to be associated with reduced N-acetyl-?-D-glucosaminidase (NAGLU) activity.

Abstract: The invention provides an assay for assessing the conformational stability of a membrane protein, comprising: (a) providing a sample comprising a first population and a second population of a membrane protein; wherein the membrane protein in the first population is labelled with a donor label and the membrane protein in the second population is labelled with an acceptor label, or the membrane protein in the first population is labelled with an acceptor label and the membrane protein in the second population is labelled with a donor label, (b) exposing the first and second populations of the membrane protein to a stability modulating agent and/or condition, (c) and assessing aggregation between membrane proteins of the first and second populations by activating the donor label to permit a distance-dependent interaction with the acceptor label, which interaction produces a detectable signal.

Abstract: The present invention relates to cell-penetrating effector proteins of type III secretion system (T3SS)-containing bacteria of the genus Salmonella or Shigella and variants, fragments and immunomodulatory domains thereof, for use in immunotherapy. The present invention further relates to cell-penetrating effector proteins of type III secretion system (T3SS)-containing bacteria of the genus Salmonella or Shigella and variants, fragments and immunomodulatory domains thereof, for delivering cargo molecules into eukaryotic cells.

Abstract: A method is taught for the accurate determination of the premature rupture of membranes (PROM), defined as spontaneous rupture of membranes before the onset of uterine contractions. More specifically, a lateral flow assay strip tests for at least two antigens to greatly limit or eliminate the possibility of false negatives. A built-in timer in the cassette holding the lateral flow assay further increases the accuracy of the test. A collection buffer vial with self-contained shipping and dropper caps and built-in stand is also taught.

Abstract: The present invention includes compositions and methods for making and using anti DC-ASGPR antibodies that can, e.g., activate DCs and other cells.

Abstract: Disclosed herein are compositions and methods for eliciting immune responses against HCV antigens. In particular embodiments, the compounds and methods elicit immune responses against all or a segment of HCV glycoprotein E1 and/or HCV glycoprotein E2.

Abstract: Provided herein are compositions and methods including the step of thermally scanning a sample that can be used and implemented to detect the presence of and/or concentration of a molecule in a sample.

Abstract: Lipidated peptides, analogs of both forms of the prolactin-releasing peptide, PrRP31 and PrRP20, represent anorexigenic compounds that lower food intake and function in the brain after peripheral administration. The analogs PrRP31 and PrRP20 lipidated at the N-terminus by myristic or palmitic acids bind with high affinity to the endogenous receptor GPR10 in the rat pituitary cell line RC-4B/C and CHO cell line with transfected human receptor. These lipidated peptides also significantly decrease, in a dose-dependent manner, the food intake in fasted mice and have similar effects in comparable doses as centrally administered natural PrRP31, these effects are, however, stronger and longer lasting. Lipidation of an effective anorexigenic neuropeptide PrRP induces a central effect after peripheral administration and thus makes the lipidated analogs of PrRP a promising anti-obesity drug.

Abstract: The present invention concerns methods and compositions for treating or preventing a bacterial infection, particularly infection by a Staphylococcus bacterium. The invention provides methods and compositions for stimulating an immune response against the bacteria. In certain embodiments, the methods and compositions involve a non-toxigenic Protein A (SpA) variant or an antibody directed thereto.

Abstract: Provided are a method of analyzing ubiquitin-proteasome activity with respect to a target polypeptide and a method of screening a ubiquitin-proteasome inhibitor. According to the provided methods, the pattern of lysis of a target polypeptide by a ubiquitin-proteasome in target cells may be quantitatively analyzed in a rapid and highly sensitive way, a ubiquitin-proteasome inhibitor may be screened in a rapid and highly sensitive way, and an anticancer agent and the activity thereof may be rapidly screened.

Abstract: The present invention includes compositions and methods for making and using anti DC-ASGPR antibodies that can, e.g., activate DCs and other cells.

Abstract: Methods and compositions for measuring the amount of vitamin D derivatives are disclosed. Fluorescence Resonance Energy Transfer (FRET) in combination with a modified ligand-binding domain of the vitamin D receptor (LBD-VDR) to measure vitamin D derivatives are also disclosed.

Abstract: Methods for determining the presence of heparin/platelet factor 4 antibodies in a sample suspected to contain heparin/platelet factor 4 antibodies are provided, along with apparatus suitable for performing the methods. The method depends upon a color visualization indicating the presence or absence of heparin/platelet factor 4 antibodies in the sample. Preferred methods comprise contacting the sample with particles being complexed to platelet factor 4 (PF4) and which particle-complexed PF4 reacts specifically with heparin/platelet factor 4 antibodies, passing the sample/particle mixture through a filter, and then analyzing the color of the filtrate. The presence of heparin/platelet factor 4 antibodies in the sample is established where the color of the filtrate is substantially different from the color of the receptor-bearing particles.

Abstract: The present invention provides, among other things, methods for the characterization of recombinant Heparan N-Sulfatase (HNS) during manufacture. The present invention uses capillary zone electrophoresis to determine the charge profile, isoform distribution, and/or glycan profile of recombinant HNS; and represents a quality feature for the batch consistency, storage stability, biological half-life, pharmacokinetic, pharmacodynamic and biological activity of the enzyme. In particular, such characterization methods may be beneficial to optimize conditions and ensure consistency for the manufacture of HNS for the treatment of a patient diagnosed with Sanfilippo syndrome using enzyme replacement therapy.

Abstract: The present invention includes compositions and methods for increasing the effectiveness of antigen presentation using a DCIR-specific antibody or fragment thereof to which an antigen is attached that forms an antibody-antigen complex, wherein the antigen is processed and presented by a dendritic cell that has been contacted with the antibody-antigen complex.

Abstract: The present invention concerns methods and compositions for treating or preventing a bacterial infection, particularly infection by a Staphylococcus bacterium. The invention provides methods and compositions for stimulating an immune response against the bacteria. In certain embodiments, the methods and compositions involve a non-toxigenic Protein A (SpA) variant or an antibody directed thereto.

Abstract: The present invention provides transgenic non-human animals and non-human mammalian somatic and germ cells harboring a human DNA sequence encoding Alzheimer's Disease (AD) derived tau protein, capable of inducing AD pathology in transgenic animals. Alzheimer's tau protein is expressed on specific genetic backgrounds allowing also simulation of different human diseases including hypertension, diabetes, hyper-cholesterolemia, which are associated with neurodegeneration and are considerable risk factors for AD development. Transgenic animals and cells of the invention exhibit neurofibrillary pathology and may serve as in vivo and in vitro assay systems for screening and developing therapeutic and preventive substances and also diagnostic markers and probes for tauopathies and AD.

Abstract: Methods of determining levels of unbound metabolites are disclosed. Probes derived from fatty acid binding protein muteins are described that bind preferentially to a number of unbound metabolites including oleate, stearate, linoleate, palmitate, arachidonate and unconjugated bilirubin. A profile for a patient is determined using one or more of the described probes. The profile is useful in diagnosis of disease, particularly myocardial infarction, non-alcoholic fatty liver disease (NAFLD), diabetes, stroke, sepsis and neonatal jaundice. The responses of multiple probes to a test sample are used to classify the degree of acute coronary syndrome by comparison to multi-probe profiles generated from unstable angina, non ST elevation myocardial infarction, and ST elevation myocardial infarction.

Abstract: The present invention concerns methods and compositions for treating or preventing a bacterial infection, particularly infection by a Staphylococcus bacterium. The invention provides methods and compositions for stimulating an immune response against the bacteria. In certain embodiments, the methods and compositions involve a non-toxigenic Protein A (SpA) variant. In some embodiments, the methods and compositions involve SdrD, ClfA, and/or FnbpB polypeptides.

Abstract: The present invention relates to novel iridium-based Ir(III) luminescent complexes, conjugates comprising these complexes as a label and their application, e.g. in the electrochemiluminescence based detection of an analyte.

Abstract: The present invention relates to methods for diagnosing and treating focal segmental glomerulosclerosis. More particularly, the present invention relates to a method for determining whether a subject is at risk of having or developing a focal segmental glomerulosclerosis (FSGS) comprising the step consisting of determining the level of calcium/calmodulin-dependent serine protein kinase (CASK) in a blood sample obtained from the subject. The present invention also relates to an agent effective to inhibit the binding of CASK to hCD98 present on the surface of podocytes for use in the prevention or treatment of focal segmental glomerulosclerosis (FSGS) in a subject in need thereof.

Abstract: The invention is directed to a method of determining whether a non-purified sample contains a target protein bound to a ligand of interest comprising the steps of: a) exposing said non-purified sample to a temperature which is capable of causing or enhancing precipitation of the unbound target protein to a greater extent than it is capable of causing or enhancing precipitation of the target protein bound to said ligand; b) processing the product of step a) in order to separate soluble from insoluble protein; and c) analysing either or both the soluble and insoluble protein fractions of step b) for the presence of target protein, wherein said target protein is not detected on the basis of enzymatic activity of a tag, peptide, polypeptide or protein fused thereto. Particularly, the invention may be used to determine whether drugs can bind to their protein targets in samples derived from patients to ascertain whether a certain drug can be used in a therapy for that patient.

Abstract: A modified polynucleotide has a different base sequence in at least one codon from a wild-type base sequence encoding a horseradish peroxidase polypeptide. The usage frequency of the modified codon of the polynucleotide corresponds to the codon usage frequencies of three filamentous fungal species in Humicola, Aspergillus, and Trichoderma. The polynucleotide is capable of expressing the polypeptide to be encoded in a filamentous fungus.

Abstract: This invention provides novel compounds and methods for promoting cell survival and/or plasticity, especially in neuronal cells, by targeting the microtubule End Binding (EB) proteins and other associated proteins (e.g., drebrin). Methods for identifying potential modulators of cell death/plasticity are also described.

Abstract: Disclosed is an antibacterial composition comprising titanium oxide particles immobilized with an antibody having affinity and cognitive power to a microorganism of interest, and a method for sterilizing the microorganism by using the same. In particular, the present invention relates to a method for preparing functional titanium oxide particles capable of recognizing a microorganism or a virus of interest, and a method for selectively and efficiently sterilizing the same by using the functional titanium oxide particles, and not for randomly sterilizing microorganisms or viruses by using conventional titanium oxide particles having no recognition power to a microorganism or a virus of interest.

Abstract: Certain embodiments are directed to polypeptide sensors. Certain aspects of the invention are directed to polypeptides for sensing or detecting GTP and GTP concentrations. In further aspects, the polypeptide sensor can measure GTP concentrations, with high temporal and spatial resolution.

Abstract: This invention relates to agents that are inhibitors or activators of variant forms of endogenous proteins and novel methods of identifying such variants. Of particular interest are inhibitors and activators of endogenous protein variants, encoded by genes which have mutated, which variants often arise or are at least first identified as having arisen following exposure to a chemical agent which is known to be an inhibitor or activator of the corresponding unmutated endogenous protein.

Abstract: The present invention provides methods for analyzing a target compound from a biological sample. In one aspect, a method for analyzing a target compound in a biological sample can comprise delivering a biological sample through an affinity column, the affinity column having a binding ligand coupled to a stationary structural support, wherein the affinity column has a high density of the binding ligand per the stationary structural support and wherein the binding ligand has been preselected to cause weak affinity separation zonal retardation of the target compound from the biological sample forming a target compound fraction and a biological sample fraction and detecting the target compound by mass spectrometry.

Abstract: The invention concerns a peptide derived from intermediate filaments and an intermediate filament fragment capable of altering tubulin polymerization and used for inhibiting cell proliferation, and more particularly for obtaining medicines designed to prevent or treat diseases involving cell proliferation, such as cancers for example.

Abstract: The present invention discloses, inter alia, methods for labeling a target protein with an SHG-active probe for detection by second harmonic or sum-frequency generation in order to identify agents which bind to an allosteric site on the target protein thereby altering its structural conformation

Abstract: The present invention concerns methods and compositions related to type 3 phosphodiesterases (PDE3). Certain embodiments concern isolated peptides corresponding to various PDE3A isoforms and/or site-specific mutants of PDE3A isoforms, along with expression vectors encoding such isoforms or mutants. In specific embodiments, methods for identifying isoform-selective inhibitors or activators of PDE3 are provided, along with methods of use of such inhibitors or activators in the treatment of dilated cardiomyopathy, pulmonary hypertension and/or other medical conditions related to PDE3 effects on cAMP levels in different intracellular compartments.

Abstract: The use of Akt3 as a biomarker for detecting the occurrence of epithelial-to-mesenchymal transition (EMT) in a subject, and the use of Akt3 inhibitors to treat cancer is disclosed herein. Also disclosed are various methods for detecting the occurrence of epithelial-to-mesenchymal transition (EMT) in a subject by measuring Akt3 expression and/or activity.

Abstract: Methods of studying, interrogating, analyzing, and detecting particles, substances, and the like with near field light are described. Methods of identifying binding partners, modulators, inhibitors, and the like of particles, substances, and the like with near field light are described. In certain embodiments, the methods comprise immobilizing or trapping the particle, substance, and the like.

Abstract: The invention provides methods of treating a meiotic kinase-associated disease, preferably the meiotic kinase HSET, by administering an inhibitor of the meiotic kinase. Preferably, the disease is associated with the presence of supernumerary centrosomes, such as cancer. Methods of inhibiting the growth of a tumor cell by contacting the cell with an inhibitor of a meiotic kinase, preferably HSET, are also provided. Screening methods for identifying inhibitors of the meiotic Kinase HSET are also provided. Methods of selecting subjects for treatment with an inhibitor of a meiotic kinase, such as HSET, are also provides.

Abstract: The present invention provides methods for identifying a molecule that provides or enhances a sweet taste in the mouth and compositions containing such molecules. The methods involve determining the effect of a variety of known or new compounds on expression or functional activity of a glucose-transporter protein of the activity of an ATP-gated K+ channel (KATP) in a mammalian oral cell, taste cell, or heterologous cell that expresses the protein or channel.

Abstract: Cysteine engineered monospecific and bispecific EGFR and/or c-Met FN3 domain containing molecules comprising one or more free cysteine amino acids are prepared by mutagenizing a nucleic acid sequence of a parent molecule and replacing one or more amino acid residues by cysteine to encode the cysteine engineered FN3 domain containing monospecific or bispecific molecules; expressing the cysteine engineered FN3 domain containing molecules; and recovering the cysteine engineered FN3 domain containing molecule. Isolated cysteine engineered monospecific or bispecific FN3 domain containing molecules may be covalently attached to a detection label or a drug moiety and used therapeutically.