Abstract: The present invention provides compounds that are surrogates of post-translationally modified proteins and uses thereof. Numerous diseases are associated with post-translationally modified proteins that are difficult to obtain in homogenous form and in quantities needed for immunization and use as convenient standards, calibrators, and/or reference compounds that facilitate the detection and analysis of endogenous post-translationally modified proteins. The surrogate compounds of the invention typically comprise antigenic epitopes (one of which carries a post-translational modification) that are tethered by a flexible and hydrophilic linker. The resulting compound behaves like a surrogate of the post-translationally modified protein because it preserves the character of the included antigens and allows recognition by specific antibodies targeting the individual antigens.

Abstract: A method of sample analysis is provided. In certain embodiments, the method comprises: a) labeling cells of a blood sample using an antibody that specifically binds to phospho-AMPK or a phosphorylated target thereof, to produce a labeled sample; and b) measuring antibody binding by a population of blood cells of the labeled sample using flow cytometry. In particular embodiments, the method may further comprise, prior to the labeling step: contacting blood with a test agent ex vivo or in vivo; and comparing the evaluation to results obtained from a reference sample of blood cells.

Abstract: Apparatus and methods for mechanical cell lysis with single cell resolution which requires very low applied pressure. The device can be handheld, simple to operate, requires no external power except for hand-applied pressure via a syringe, and is applicable to all cell types including yeast and bacterial cells. The device is also capable of mechanically lysing a single cell. A single cell is selected from a biological sample of interest. The single cell is lysed by application of mechanical stress in a single cell lysing apparatus having a trap structure for deterministically capturing the cell and a stress raiser that cooperates with a source of mechanical stress so as to apply sufficient force to rupture a cell. The stress raiser can be a properly designed edge of the trap or it can be a lithographically produced structure such as a nanoblade or a nanopillar.

Abstract: Delayed release of a drug to the colon is achieved from a delayed release formulation comprising a core and a coating for the core. The core comprises a drug and the coating comprises an outer layer and at least one layer between the core and the outer layer selected from the group consisting of an isolation layer and an inner layer. The outer layer comprises a mixture of a first polymeric material which is susceptible to attack by colonic bacteria, and a second polymeric material which has a pH threshold at about pH 5 or above. The inner layer comprises a third polymeric material which is soluble in intestinal fluid or gastrointestinal fluid, said third polymeric material being selected from an at least partially neutralised polycarboxylic acid and a non-ionic polymer. In embodiments in which the third polymeric material is a non-ionic polymer, the inner layer comprises at least one of a buffer agent and a base.

Abstract: The present invention provides matriptase inhibitors and compositions for treating and preventing orthomyxovirus infections such as flu infections. The present invention also provides novel compounds, compositions, methods of use, uses and kits thereof for inhibiting matriptase. Such compounds are useful for treating and preventing orthomyxovirus infections, such as flu infections, and for inhibiting tumor growth, progression and/or metastasis.

Abstract: A breast cancer pathological image diagnosis support system for supporting a diagnosis of breast cancer based on a pathological image is provided. The breast cancer pathological image diagnosis support system includes an image obtaining unit which obtains an HE-stained image and an IHC image as pathological images to be diagnosed; an information obtaining unit which obtains information of a tumor area in the HE-stained image; a matching unit which calculates a matching position of the HE-stained image and the IHC image obtained by the image obtaining unit; a specifying unit which specifies a tumor area in the IHC image based on the information of the tumor area in the HE-stained image obtained by the information obtaining unit and information of the matching position calculated by the matching unit; and a calculating unit which calculates a staining positive cell content rate in the tumor area based on information of the tumor area in the IHC image specified by the specifying unit.

Abstract: In one aspect, the invention is directed to methods of expanding hematopoietic stem cells (HSCs) comprising culturing the HSCs with Wharton's Jelly mesenchymal stem cells (WJSCs), a cell culture medium that has been conditioned with WJSCs, or a combination thereof, thereby producing a HSC culture; and maintaining the HSC culture under conditions in which the HSCs expand in the culture, thereby expanding the HSCs. In another aspect, the invention is directed to a method of transplanting the expanded HSCs in an individual in need thereof. In yet another aspect, the invention is directed to compositions comprising HSCs and Wharton's Jelly mesenchymal stem cells (WJSCs). The composition can further comprise a cell culture medium that has been conditioned with WJSCs.

Abstract: Embodiments of the present invention are directed toward devices, system and method for conducting toxin activity assay using sedimentation. The toxin activity assay may include generating complexes which bind to a plurality of beads in a fluid sample. The complexes may include a target toxin and a labeling agent, or may be generated due to presence of active target toxin and/or labeling agent designed to be incorporated into complexes responsive to the presence of target active toxin. The plurality of beads including the complexes may be transported through a density media, wherein the density media has a lower density than a density of the beads and higher than a density of the fluid sample, and wherein the transporting occurs, at least in part, by sedimentation. Signal may be detected from the labeling agents of the complexes.

Abstract: Disclosed is a method of treating cancer, comprising administering to a mammal in need thereof a therapeutically effective amount of a compound that inhibits a plurality of mammalian dipeptidyl peptidase (DPP) IV activity and/or structural homologues thereof (DASH) serine proteases. Also disclosed is a method of (a) increasing antitumor immunity, (b) stimulating or enhancing an immune response, (c) treating a condition characterized by abnormal cell proliferation, (d) increasing cytokine and/or chemokine production, or (e) stimulating or enhancing production of T-cells, in a mammal, comprising administering to a mammal in need thereof an effective amount of a compound that inhibits a plurality of mammalian DASH serine proteases. For example, the compound that inhibits a plurality of mammalian DASH serine proteases may be t-butylGly-boroPro.

Abstract: The present invention relates to novel hydrogenases isolated from novel hyperthermophilic strains belonging to Thermococcus spp., genes encoding the hydrogenases, and methods of producing hydrogen using strains having the genes. According to the hydrogen production methods of the invention, a large amount of hydrogen can be produced merely by culturing the strains in specific culture conditions. Thus, the methods of the invention have advantages in that they are more economic and efficient than existing hydrogen production methods and can produce hydrogen even at high temperature.

Abstract: Compositions for targeting to a desired region of the brain or spinal cord include a therapeutic compound useful for the treatment of a neurodegenerative disease; a cell penetrating peptide (CPP); and a thermal targeting polypeptide (TTP).

Abstract: Specific peptides, and derived ionization characteristics of the peptides, from the Insulin Receptor protein (IR), and its isoforms IR-A and IR-B, that are particularly advantageous for quantifying the IR protein, IR-A isoform and/or IR-B isoform, directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring (SRM) mass spectrometry, or what can also be termed as Multiple Reaction Monitoring (MRM) mass spectrometry. Such biological samples are chemically preserved and fixed and are selected from tissues and cells treated with formaldehyde containing agents/fixatives including formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and tissue culture cells that have been formalin fixed and or paraffin embedded.

Abstract: Provided is a method for identifying a malodor inhibitor based on a response of an olfactory receptor. The present invention provides a method for identifying a malodor inhibitor including: adding a test substance and a malodor-causing substance to at least one olfactory receptor selected from the group consisting of OR5P3, OR5K1, OR2W1, OR8H1, and a polypeptide which has 80% or more identity in amino acid sequence to any one of the aforementioned polypeptides; measuring the response of the olfactory receptor to the malodor-causing substance; identifying the test substance which can suppress the response of the olfactory receptor based on the measured response; and selecting, as a malodor inhibitor, the test substance which can suppress the response of the olfactory receptor.

Abstract: The present invention relates to methods of suppressing the transcriptional expression of one or more genes by methylating the chromatin histone proteins of the one or more genes. Specifically, a viral SET domain histone lysine methyltransferase (vSET or vSET-like protein) methylates lysine 27 of a gene's histone protein 3 (H3-K27) thereby suppressing the transcription of the gene.

Abstract: The present invention provides compositions and methods for detecting the activation states of components of signal transduction pathways in tumor cells. Information on the activation states of components of signal transduction pathways derived from use of the invention can be used for cancer diagnosis, prognosis, and in the design of cancer treatments.

Abstract: The candidates are screened and then employed by administering to patients in need thereof of a drug candidate that affects heterotypic intercellular mechanotransduction. At least two types of cells are labeled with distinct intracellular fluorescent marker labels and combined to form a cell suspension and cultured to form a microtissue, such as spheroids. The cells or the spheroids are combined with a drug candidate, either before, during or after forming the spheroids. The distribution of the different cell types is compared to that of essentially the same suspension culture in the absence of the drug candidate. Alternatively, the cell power of cells cultured in a non-adherent mold that determines at least in part, the shape of microtissue formed is measured and compared with essentially the same cell suspension cultured in the same manner in the absence of a drug candidate. A patient in need thereof can be administered a drug identified as affecting heterotypic intercellular mechanotransduction.

Abstract: This application relates to a newly identified animal cell structure, the midbody scar. This structure is a remnant of the midbody that is retained by one daughter cell following cytokinesis and persists through multiple subsequent cell cycles. The midbody scar can be useful as a marker of dividing cells or of a cell's replicative age.

Abstract: There is provided a microbial culture medium and a microbial culture method for adequately growing a target bacterium contained in an antibacterial test sample. The microbial culture medium for growing a target bacterium contained in an antibacterial test sample is composed of a basal medium for microbial culture, and acid clay or activated clay contained in the basal medium. The microbial culture method for growing a target bacterium contained in an antibacterial test sample using a microbial culture medium includes adding acid clay or activated clay to a solution of the test sample. It is preferred that the acid clay or activated clay be combined with activated carbon.

Abstract: The present invention provides novel cycloalkyl-substituted pyrimidine dione compounds that are useful for the treatment of hypertrophic cardiomyopathy (HCM) and conditions associated with left ventricular hypertrophy or diastolic dysfunction. The synthesis and characterization of the compounds is described, as well as methods for treating HCM and other forms of heart disease.

Abstract: The invention relates to compositions and methods for the preparation, manufacture and therapeutic use of polynucleotides, primary transcripts and mmRNA molecules.

Abstract: The instant invention relates to the field of protein production and purification, and in particular to compositions and processes for controlling the amount of acidic species expressed by host cells, as well as to compositions and processes for controlling the amount of acidic species present in purified preparations.

Abstract: Systems and methods for the determination of a peptide receptor. Specifically to determine a receptor for any peptide provided that the receptor is a G protein coupled receptor (GPCR).

Abstract: A sample of blood containing CTCs, or other cells of interest, is stained with fluorescent markers for image analysis and scanned to identify the presence and location within the cartridge of target cells or subcellular elements. A sample containing desired target cells or subcellular elements is then further processed, in part by photobleaching the sample, so that those same targets may be re-analyzed with additional biomarkers conjugated to the same or different fluorochromes using the same imaging criteria that were used for the initial analysis. The present invention has applications with targets such as circulating epithelial, cells, circulating tumor cells, circulating endothelial cells, leukocytes, lymphocyte subsets, cells containing an organelle or receptor of interest, cellular debris, disrupted cells and their debris, or any other formed element that might be captured and imaged.

Abstract: The invention intends to provide a bioassay method using a simple in-vitro test for Daikinchuto, and further to provide a more highly accurate method for quality control of Daikenchuto using the same. These methods are a bioassay method for the pharmacological activity of Daikenchuto, characterized in that a test sample containing Daikenchuto is added to cultured serotonin-producing cells, and the serotonin content in the culture supernatant is subsequently measured; and a quality control method for Daikenchuto preparations in which the pharmacological activity of a test preparation and a reference preparation for which the pharmacological effect as Daikenchuto has been clinically confirmed are evaluated under the same conditions, and the equivalence of the reference preparation and testing preparation is evaluated.

Abstract: An inventive method for treatment or prevention of vascular diseases of the retina is provided. A Norrin compound is optionally administered to a subject either directly and/or as expressed by a cell. The presence of the compound is either protective of or therapeutic for a pathological condition of the retina. Preferred pathological conditions are those linked to the absence of or mutation of norrin protein and are preferably Norrie disease, FEVR, or macular degeneration.

Abstract: The present invention relates to a gene expression and eradication system for Helicobacter pylori (H. pylori). In particular, the present invention relates to a genetic construct comprising, in the 5?-3? direction: (a) a promoter sequence and (b) a DNA sequence of interest, wherein the promoter sequence comprises a polynucleotide sequence capable of regulating expression of the DNA sequence of interest in Helicobacter pylori and wherein said promoter sequence is modified to comprise a tetracycline (tet) operator sequence.

Abstract: A microfluidic device adapted to perform many simultaneous binding assays including but not limited to immunological experiments, such as ELISA assays, with minimal cross-talk between primary and secondary antibodies.

Abstract: The subject invention pertains to the development of a novel human mast cell line, USF-MC1. USF-MC1 is a mast cell precursor present in human umbilical cord blood (HUCB) that may be sustained in culture in the absence of exogenous cytokines to serve as a convenient experimental model of human mast cell activation. The SCF-independent human mast cell line USF-MC1 responds to IgE-mediated and IgE-independent stimuli in a way comparable to that of LAD2. USF-MC1 cells are useful for investigation of IgE-mediated activation mechanisms of human mast cells, contributing to the development of effective treatments for allergic disorders and other disorders. The subject invention provides a ready source of human mast cells for research, including pharmacological studies for the screening of various agents, and toxicologic, e.g., for the cosmetic and pharmaceutical industries. The mast cells can also be used as biofactories, for the large-scale production of biomolecules.

Abstract: A method of analyzing an image of a cell in a laminated structure may include the steps of: (a) fluorescently labeling a cell nucleus in the laminated structure having at least one cell layer and one or more other types of biomolecules; (b) acquiring a plurality of planar tomographic fluorescent labeled images in different height directions from the laminated structure for each type of fluorescently labeled biomolecules after the step (a); (c) superimposing a planar tomographic fluorescent labeled image group acquired in the step (b) to construct a three-dimensional tomographic image; (d) dividing the three-dimensional tomographic image constructed in the step (c) into one or two or more cell regions; (e) producing one planar stacked image for each divided cell region after the step (d); and (f) performing image analysis on each planar stacked image produced in the step (e) to analyze cells in the laminated structure.

Abstract: A biosensor system for the detection of particles includes a biosensor cartridge having a sensor surface. A biosensor magnet assembly is disposed on one side of the cartridge for generating a magnetic field effective at the cartridge and the sensor surface. The biosensor magnet assembly includes at least two magnetic sub-units separated by a gap. A first optical detection system detects the particles arranged at the same side of the cartridge as the magnet assembly. The magnet assembly and the first optical sensor are disposed such that the optical detection is accomplished through the gap of the magnet assembly.

Abstract: A system and method of indirectly modifying an environmental condition at a test site in one embodiment includes providing a test site on a substrate, providing a hydrogel composition loaded with a chemical factor at the test site, providing an actuator configured to activate the hydrogel composition to release a chemical factor at the test site, controlling the actuator to activate the hydrogel composition to release a chemical factor at the test site, and modifying the local chemical environment at the test site with the chemical factor.

Abstract: In one aspect, the present invention relates to a system 100 for automated cellular assay data analysis. The system 100 comprises a virtual assay module (VAM) 115 operable to generate simulated images of cell responses to one or more stimuli. The system 100 also comprises a comparator module 116 operable to compare the actual and simulated images, and an analysis module 117 operable to quantify the differences between phenotypes represented by the actual and simulated images. Various aspects and embodiments of present invention may account for stochastic variations in the response of single cells, to provide additional useful information relating to, for example, toxological effects and/or for use as part of a feedback mechanism to refine dynamically a virtual assay model such that it is not limited by way of there being only inadequate static fitting expressions available.

Abstract: Novel phenyl-glyoxal based anti-citrulline probes and methods of synthesis are provided. Methods of use, such as, the development of methods for monitoring substrate citrullination over time; for identifying citrullinated proteins from cells are described.

Abstract: Methods, devices, kits and compositions for detecting the presence or absence of one or more helminthic coproantigens in a sample are disclosed herein. The methods, devices, kits and compositions of the present invention may be used to confirm the presence or absence of roundworm, whipworm and/or hookworm in a fecal sample from a mammal and may also be able to distinguish between one or more helminth infections. Confirmation of the presence or absence of roundworm, whipworm and/or hookworm in the mammal may be made, for example, for the purpose of selecting an optimal course of treating the mammal and/or for the purpose of determining whether the mammal has been rid of the infection after treatment has been initiated.

Abstract: The present invention provides molecular biosensors capable of signal amplification, and methods of using the molecular biosensors to detect the presence of a target molecule.

Abstract: The present invention provides a FCCS method for determining the concentration and/or the diffusion coefficient of at least a first labeled species, a second labeled species and/or a complex between said first and second labeled species, in a system, wherein the method comprises the steps of determining a cross-talk parameter K, wherein K is the ratio between the brightness of the first labeled species and the second labeled species at the centre of each focus, as detected for both species in the channel for detecting the second labeled species; using the cross talk parameter K for determining a displacement parameter ro and using K, ro, or both K and ro for determining the concentration and/or the diffusion coefficient of said first and/or a second labeled species and/or a complex between said first and second labeled species.

Abstract: The present invention relates to the field of Serum Bactericidal Activity (SBA) assays for Gram negative bacteria, in particular N. meningitidis. The SBA assay is the most important method for measuring functional activity of serum antibodies against meningococcus. In order to determine whether a subject or a population is seropositive against invasive meningococcus the SBA test should ideally be both sensitive and specific. The inventors have found the standard N. meningitidis serotype A and W SBAs can be significantly improved in this regard.

Abstract: Arrays and methods for detecting one or more biological molecules, where the methods generally comprise the steps of: providing a first support structure fixed with one or more reagents; providing a second support structure fixed with a plurality of ligands; contacting the reagents fixed to the first support structure with the ligands fixed to the second support structure whereby a plurality of the reagents bind to one or more of the ligands; and separating the first support structure from the second support structure so that the plurality of the bound reagents remain bound to a plurality of ligands on the second support after separation. In one preferred method, proteins are immobilized on a support with adequate strength so that the proteins can be dissociated from the support under certain conditions, such as after binding with other proteins immobilized on another support.

Abstract: A phosphine derivative of DyLight dyes modified with ethylene glycol or (poly)ethylene glycol groups. In one embodiment, the compounds are useful in chemoselective ligation reactions.

Abstract: The present invention provides compositions and methods for the genetic manipulation of Algal cells. The compositions and methods allow enhanced transfer of genetic material into Algal cells and the cloning and selection of genetically modified cells. Expression of proteins encoded by the genetic material will be enhanced by the methods and compositions of the invention.

Abstract: The purpose of the present invention is to elucidate a relationship between deregulation of signaling by CD22 and a rapid response of B cells by IgG-BCR and the like, and to provide a method capable of inducing a rapid immune response and defending against infection instead of vaccine. The present invention relates to a method for promoting an immune response causing such a strong proliferation of clones and production of a large amount of antibody-producing cells as those seen in the memory immune response even in the naive B cells expressing IgM-BCR and IgD-BCR by inhibiting the CD22 function in B cells; and to a method for screening a substance capable of promoting the immune response based on a change in the CD22 function in B cells.

Abstract: The invention relates to a method and a device for determining the cell activation of a target cell by an activator, said method having the following steps: provision of a probe measuring device with a probe sample arrangement having a measuring probe and a sample holder; loading of the probe sample arrangement with a target cell and with an activator assigned to the target cell, the measuring probe being loaded with the activator, and the sample holder being loaded with the target cell, or vice versa; relative mutual displacement of the measuring probe and the sample holder until contact is made between the target cell and the activator by means of a displacement apparatus of the probe measuring device; recording of measurement values, indicating binding between the target cell and the activator, for the measuring probe with the probe measuring device during the relative displacement of the measuring probe and the sample holder; and determination of a dimension for the cell activation of the target cell from

Abstract: A microfluidic chip orients and isolates components in a sample fluid mixture by two-step focusing, where sheath fluids compress the sample fluid mixture in a sample input channel in one direction, such that the sample fluid mixture becomes a narrower stream bounded by the sheath fluids, and by having the sheath fluids compress the sample fluid mixture in a second direction further downstream, such that the components are compressed and oriented in a selected direction to pass through an interrogation chamber in single file formation for identification and separation by various methods. The isolation mechanism utilizes external, stacked piezoelectric actuator assemblies disposed on a microfluidic chip holder, or piezoelectric actuator assemblies on-chip, so that the actuator assemblies are triggered by an electronic signal to actuate jet chambers on either side of the sample input channel, to jet selected components in the sample input channel into one of the output channels.

Abstract: In some cases, the described systems and methods include obtaining a cell sample containing multiple antibody-producing cells. In such cases, the cells can be tagged with a cross-linking reagent having a first portion configured to bind to a marker on the antibody-producing cells and a second portion configured to bind to an antigen of interest. In some instances, the tagged antibody-producing cells are exposed to the antigen of interest such that the antigen becomes bound to the cells. In some such instances, the antibody-producing cells are also allowed to produce an antibody, such that a portion of the antibody-producing cells produce an antigen-specific antibody that binds to the antigen of interest. To identify cells that produce the antigen-specific antibody, the tagged cells can be exposed to a labeled secondary antibody that is configured to bind to the antigen-specific antibody. Other implementations are also described.

Abstract: The present disclosure provides, inter alia, genetically encoded recombinant peptide biosensors comprising analyte-binding framework portions and signaling portions, wherein the signaling portions are present within the framework portions at sites or amino acid positions that undergo a conformational change upon interaction of the framework portion with an analyte.

Abstract: Provided is a method for determining immunoglobulins in a neonatal ungulate. The method entails obtaining a sample of oral secretions from the neonatal ungulate and measuring an amount of immunoglobulins in the sample of oral secretions. The method is faster and more convenient than previously available methods for determining immunglobulins in neonatal ungulates, such as neonatal horses and cattle.

Abstract: The invention generally relates to the field of immunochemistry including antibody therapy, diagnostics, and basic research and specifically relates to the area of selecting affinity molecules such as natural antibodies, including artificial antibodies, antibody mimics, and aptamers. The invention relates particularly to a method of selecting affinity molecules using a homogeneous noncompetitive assay in a high throughput process.

Abstract: Provided are methods and compositions for determining whether an individual has Sjögren's disease (SD). The method entails determining in a biological sample from the individual the presence of antibodies directed to salivary gland protein 1 (SP-1), parotid secretory protein (PSP), carbonic anhydrase 6 (CA6), or determining a combination of the antibodies. Determining that the individual has SD is based on the presence of the antibodies. The method provides for detection of early SD. Kits for antibody detection containing the antigens to which the antibodies of SD patients are directed are also provided.

Abstract: The use of nanostructures to monitor or modulate changes in cellular membrane potentials is disclosed.

Abstract: The present invention relates to a method for selectively enriching and/or isolating microbial and optionally additionally viral nucleic acids from samples that contain a mixture of microbial cells, freely circulating nucleic acids and higher eukaryotic cells, and optionally additionally viruses, in a liquid, and to a kit for selectively enriching and/or isolating intracellular and extracellular microbial nucleic acids, and optionally additionally viral nucleic acids, from samples that contain a mixture of microbial and higher eukaryotic cells, freely circulating nucleic acids, in particular extracellular microbial nucleic acids, and optionally additionally viruses in a liquid.