Abstract: The present invention provides methods of treating a subject diagnosed with, or at risk for developing, pathogenic fibrosis, particularly pulmonary fibrosis. The method of the invention comprises administering to the subject a compound or composition which inhibits semaphorin (SEMA) 7A, SEMA 7A receptors, or downstream effectors. A SEMA 7A inhibitor comprises an antibody, a soluble SEMA 7A receptor, an siRNA, a ribozyme, an antisense, an aptamer, a peptidomimetic, a small molecule, a soluble receptor, or any combinations thereof.

Abstract: The invention relates to a method for optimizing the automatic fluorescence pattern recognition in immunodiagnosis. In this method, in addition to or together with the fluorescence dye, one or more other indicator dyes for the identification of relevant structures are incubated before an image is taken with a camera.

Abstract: This invention relates to methods for evaluating or inhibiting the aggregation of a protein in an aqueous suspension including organopolysiloxane and medical articles coated with organopolysiloxane containing a protein solution including sugar and a non-ionic surfactant.

Abstract: The present invention generally relates to organic polymers able to participate in an analyte-recognition process, where an analyte facilitates an energy transfer between an energy donor and an energy acceptor. Certain embodiments of the invention make use of fluorescent conjugated polymers, such as poly(phenylene ethynylene)s and other polymers comprising pi-conjugated backbones. For example, one aspect of the invention provides a fluorescent conjugated polymer and an indicator that can interact with each other in the presence of an analyte to produce an emissive signal. In some cases, the interaction may include energy exchange mechanisms, such as Dexter energy transfer or the strong coupling effect. The interaction of the conjugated polymer and the indicator, in some instances, may be facilitated through specific interactions, such as a protein/carbohydrate interaction, a ligand/receptor interaction, etc.

Abstract: The present invention relates to compositions and methods for prevention and treatment of diseases and conditions, particularly ocular diseases and conditions, characterized by aberrant fibrogenesis or scarring, inflammation, and/or aberrant neovascularization or angiogenesis. The compositions and methods of the invention utilize immune-derived moieties that are specifically reactive against the bioactive lipid, sphingosine-1-phosphate, and its variants, which moieties are capable of decreasing the effective concentration of bioactive lipid being targeted. In one embodiment, the immune-derived moiety is a humanized monoclonal antibody that is reactive against sphingosine-1-phosphate.

Abstract: The invention relates to novel and improved photostable rhodamine dyes of the general structural formulae I or II and their uses as fluorescent markers, e.g. for immunostainings and spectroscopic and microscopic applications, in particular in conventional and stimulated emission depletion (STED) microscopy and fluorescence correlation spectroscopy.

Abstract: An object of this invention is to provide a fluorescence analysis method that enables analysis (including imaging) of in vivo substances, etc., using antigen-antibody reactions to be carried out simply, at high sensitivity, and yet continuously and in real time.

Abstract: Methods comprising the use of photoactivated chemical bleaching for detecting multiple targets in a biological sample are provided. The methods include the steps of providing a biological sample containing multiple targets, binding at least one probe to one or more target present in the sample, and observing a signal from the probe. The method further includes the steps of contacting the sample comprising the bound probe with an electron transfer reagent and irradiating the sample, thereby initiating a photoreaction that substantially inactivates the probe by photoactivated chemical bleaching. The method further includes the steps of binding at least one probe to one or more target present in the sample, and observing a signal from the probe. The process of binding, observing and bleaching may be iteratively repeated.

Abstract: A enhancing reagent for enhancing chemiluminescence of 1,2-dioxetane compounds and a method for using the enhancing reagent to enhance the chemiluminescence are provided, in which the enhancing reagent contains an alkyl bis-quaternary ammonium salt of Formula I. A chemiluminescent composition with a 1,2-dioxetane compound as a substrate and a kit thereof are further provided, which contain a 1,2-dioxetane compound and an alkyl bis-quaternary ammonium salt of Formula I.

Abstract: The methods of the disclosure provide fluorescence-based assays for calcineurin activity, especially in isolated T cells. The methods include the stimulation of the T cells with agents that specifically target the TCR with or without influencing co-stimulatory pathways. One TCR agonist is monoclonal antibodies specific for CD3, which more precisely distinguish the inducible activity of calcineurin than does an alternative method targeting the T cell receptor (CD3) combined with CD28 costimulation. This method more accurately distinguishes between the measured level of calcineurin activity of T cells from immunosuppressed transplant recipients and normal individuals, and thus has improved diagnostic accuracy with respect to the response of an individual to immunosuppressant therapy following an organ transplant.

Abstract: New chemiluminescent compounds, stable in aqueous buffers, for use in biological assaying include acridane-based compounds and 1,2-dioxetanes. Among the new acridane-based compounds are water-soluble acridanes, enhancer coupled acridanes, bis and tris-acridanes as well as acridane-1,2-dioxetanes. Among the new 1,2-dioxetanes are electron deficient group-containing dioxetanes and tethered bis-1,2-dioxetanes. The 1,2-dioxetanes are useful as substrates for various enzymes. The acridanes can be admixed with an oxidizing agent an aqueous buffer and, optionally, a stabilizer to form a substrate or reagent formulation useful for assaying, inter alia, HRP.

Abstract: The present invention provides a blood analyzer and a blood analyzing method capable of obtaining information regarding B lymphocytes and T lymphocytes without using a fluorescence-labeled antibody. The blood analyzer of the present invention includes a blood specimen supplying portion, a sample preparation portion that prepares a measurement sample without using a fluorescence-labeled antibody by mixing a blood specimen supplied from the blood specimen supplying portion, a hemolyzing agent, and a fluorescent dye that stains nucleic acid, a light source, a first detector that detects fluorescence, a second detector that detects scattered light, and information processing portion that classifies lymphocytes based on the intensity of fluorescence and scattered light, and based on the fluorescence intensity of the classified lymphocytes, obtains information regarding B-lymphocytes and T-lymphocytes.

Abstract: The present invention provides for methods and materials for diagnosing and treating neuromyelitis optica (NMO).

Abstract: The present invention provides a method for reducing undesirable light emission from a sample using at least one photon producing agent and at least one photon reducing agent (e.g. dye-based photon reducing agents). The present invention further provides a method for reducing undesirable light emission from a sample (e.g., a biochemical or cellular sample) with at least one photon producing agent and at least one collisional quencher. The present invention also provides a method for reducing undesirable light emission from a sample (e.g., a biochemical or cellular sample) with at least one photon producing agent and at least one quencher, such as an electronic quencher. The present invention also provides a system and method of screening test chemicals in fluorescent assays using photon reducing agents. The present invention also provides compositions, pharmaceutical compositions, and kits for practicing these methods.

Abstract: This invention pertains to methods, mixtures, kits and/or compositions for the determination of analytes by mass analysis using unique labeling reagents or sets of unique labeling reagents. The labeling reagents can be isomeric or isobaric and can be used to produce mixtures suitable for multiplex analysis of the labeled analytes.

Abstract: Monoclonal antibodies, synthetic and biotechnological derivatives thereof (ScFv or others) are able to recognise the NGF high affinity receptor, TrkA, and act as NGF-antagonist molecules. Pharmacological compositions for therapy, gene therapy, diagnostics of neurological pathologies are also described. Transgenic animal models to study such pathologies are also described.

Abstract: The present invention relates to a technique of measuring a protein based on a degree of coloring in a liquid sample mixed with a protein measurement indicator. In the present invention, information reflecting creatinine concentration in the liquid sample is obtained, and then an influence quantity caused by creatinine to the protein concentration measurement is eliminated based on the information.

Abstract: Chemically-reactive, water-soluble, heterocycle-substituted 7-hydroxycoumarin dyes, their bioconjugates and uses are described. The conjugates derived from reactive heterocycle-substituted 7-hydroxycoumarin dyes are used for analyzing biological compounds. These heterocycle-substituted 7-hydroxycoumarin dyes are particularly useful as fluorescent labels for biopolymer detection reagents, such as antibodies or nucleic acid probes. The dye-antibody conjugates of the invention are particularly useful for analyzing analytes using a flow cytometer equipped with a violet laser as an excitation source due to their strong absorption at 405 nm and high fluorescence quantum yield.

Abstract: A gel microdrop composition is provided. In certain embodiments, the gel microdrop composition contains a polymer matrix, an effector particle that releases an effector molecule into the polymer matrix, a first reporter particle that emits a first optically detectable signal and a second reporter particle that emits a second optically detectable signal that is distinguishable from the first optically detectable signal, where the effector particle and said first and second reporter particles are encapsulated by the polymer matrix. Methods of screening that employ the gel microdrop composition and methods of making the gel microdrop composition are also disclosed.

Abstract: Methods using chemiluminescent label compounds and chemiluminescent labeled conjugates are provided. The compounds comprise an acridan ring bearing an exocyclic ketene dithioacetal group and further contain a labeling substituent which permits attachment to compounds of interest. The novel chemiluminescent compounds and labeled conjugates are convenient to prepare, are highly stable, and generate chemiluminescence rapidly on demand. The compounds and conjugates are useful in assays of an analyte in a sample and in assays employing labeled specific binding pairs.

Abstract: The invention provides methods and compositions for the rapid and sensitive detection of post-translationally modified proteins, and particularly of those with post-translational glycosylations. The methods can be used to detect O-GlcNAc posttranslational modifications on proteins on which such modifications were undetectable using other techniques. In one embodiment, the method exploits the ability of an engineered mutant of ?-1,4-galactosyltransferase to selectively transfer an unnatural ketone functionality onto O-GlcNAc glycosylated proteins. Once transferred, the ketone moiety serves as a versatile handle for the attachment of biotin, thereby enabling detection of the modified protein. The approach permits the rapid visualization of proteins that are at the limits of detection using traditional methods. Further, the preferred embodiments can be used for detection of certain disease states, such as cancer, Alzheimer's disease, neurodegeneration, cardiovascular disease, and diabetes.

Abstract: A nanostructured particulate material, which includes a redox active luminescent organic and/or ionic compound, is provided herein. The nanostructured particulate material may be used for determining the presence of an analyte of interest in a sample by detecting the emitted electromagnetic radiation generated by exposing a reagent mixture, which includes the nanostructured material and the target analyte, to chemical or electrochemical energy.

Abstract: Methods and compositions are provided that include a multichromophore and/or multichromophore complex for identifying a target biomolecule. A sensor biomolecule, for example, an antibody can be covalently linked to the multichromophore. Additionally, a signaling chromophore can be covalently linked to the multichromophore. The arrangement is such that the signaling chromophore is capable of receiving energy from the multichromophore upon excitation of the multichromophore. Since the sensor biomolecule is capable of interacting with the target biomolecule, the multichromophore and/or multichromophore complex can provide enhanced detection signals for a target biomolecule.

Abstract: Methods and reagents are disclosed for pretreating a sample suspected of containing a hydrophobic drug for conducting an assay method for detecting the hydrophobic drug. A combination is provided in a medium that includes the sample, a releasing agent for releasing the hydrophobic drug and the metabolites from endogenous binding moieties, and a selective solubility agent that provides for substantially equal solubility of the hydrophobic drug and the metabolites in the medium. The selective solubility agent includes a water miscible, non-volatile organic solvent and is present in the medium in a concentration sufficient to provide for substantially equal solubility of the hydrophobic drug and the metabolites in the medium. The medium, which may further include a hemolytic agent, is incubated under conditions for releasing the hydrophobic drug and the metabolites from endogenous binding moieties. The pretreated sample may be subjected to an assay for determining the hydrophobic drug.

Abstract: The present invention relates to a labeling reagent of formula: in which: R1 represents at least one detectable label, L and A are each a linker arm, n is an integer equal to 1, and u is an integer between 0 and 2. The present invention also describes a method of synthesizing said markers and also applications for the labeling of biological molecules, more particularly nucleic acids, with a labeling reagent bearing diazo and nitro functions. The invention is particularly suitable for use in the diagnostics field.

Abstract: The present invention provides an approach for the simultaneous determination of the activation states of a plurality of proteins in single cells. This approach permits the rapid detection of heterogeneity in a complex cell population based on activation states, and the identification of cellular subsets that exhibit correlated changes in activation within the cell population. Moreover, this approach allows the correlation of cellular activities or properties. In addition, the use of potentiators of cellular activation allows for characterization of such pathways and cell populations.

Abstract: Provided is a method of detecting the presence and quantitating the amount of glycogen from a biological sample. This method employs PAS staining with detection in the infrared range.

Abstract: The present invention provides: a method of changing the fluorescence wavelength of a GFP-like fluorescent protein from copepod while maintaining recombinant expression efficiency, which comprises identifying a structural factor for determining the fluorescence wavelength thereof in the three-dimensional structure of the protein and modifying amino acid residues associated with the structural factor; and a modified fluorescent protein obtained by applying said method. For example, with regard to a GFP-like fluorescent protein from Chiridius poppei, His52 in an ? helix-like secondary structure: PFLLSHCMGYGFYHF (?1 47-61) comprising a fluorescent moiety site GYG is replaced with an aromatic amino acid selected from Phe, Tyr and Trp, so as to cause a red shift of the fluorescent peak wavelength; or it is replaced with Ala, Val, Ile, Leu, Gly, Cys, Met, Ser, Thr, or Asp, Asn, Glu or Gln, so as to cause a blue shift of the fluorescence peak wavelength.

Abstract: Tyrosine kinase substrates are described herein that are phosphorylated by many and diverse tyrosine kinases, and are chemically stable relative to co-polymers of poly-EY or poly-EAY having random molecular weights in the range of 20-50 kDa. Tyrosine kinase substrate peptides are provided according to embodiments described herein which include an isolated tyrosine kinase substrate peptide having molecular weight in the range of about 0.5 kD-10 kD. Tyrosine kinase substrate peptides are provided according to embodiments described herein having no more than 50 amino acids. The peptides include 2-25 phosphorylation modules and each phosphorylation module has 2-3 amino acid residues.

Abstract: A method, composition and system respond to ionizing radiation to adjust biological activity. In some approaches the ionizing radiation is X-ray or extreme ultraviolet radiation that produces luminescent responses that induce biologically active responses.

Abstract: The invention relates to a detectable molecule comprising a biospecific binding reactant attached to a luminescent lanthanide chelate comprising a lanthanide ion and a chelating ligand of the formula (I) wherein, R1A R1B are independently of each other selected from the group consisting of hydrogen, methyl, ethyl, —COOH, —COO—, —CH2COOH, —CH2COO—, hydroxyl or OR2; R2 is selected from the group consisting of —CH3, —C(CH3)3, —C(CR4)3, wherein R4 is an alkyl with 1 to 6 carbon atoms, —CH2COOH, —CH2COO?, and appropriate hexose residues; R3 is a linker for coupling to a biospecific binding reactant selected from the group consisting of thiourea (—NH—CS—NH—), aminoacetamide (—NH—CO—CH2—NH—), amide (—NH—CO— and —CO—NH—), aliphatic thioether (—S—), disulfide (—S—S—) and 6-substituted-1,3,5-triazine-2,4-diamine; and the lanthanide ion is selected from the group consisting of europium(III), terbium(III), dysprosium(III) and samarium(III). The invention also relates to corresponding lanthanide chelates.

Abstract: The present invention provides methods and systems for performing in vivo flow cytometry. In one embodiments, selected circulating cells of interest of a subject are labeled with fluorescent probe molecules. The labeled cells are irradiated in-vivo so as to excite the fluorescent probes, and the radiation emitted by the excited probes is detected, preferably confocally. The detected radiation is then analyzed to derive desired information, such as relative cell count, of the cells of interest. In some embodiments, the circulating cells comprise apoptotic cells whose detection can allow, e.g., non-invasive monitoring of the efficacy of a cancer treatment, such as an anti-tumor or an anti-angiogenic therapy.

Abstract: The present invention provides an approach for the simultaneous determination of the activation states of a plurality of proteins in single cells. This approach permits the rapid detection of heterogeneity in a complex cell population based on activation states, and the identification of cellular subsets that exhibit correlated changes in activation within the cell population. Moreover, this approach allows the correlation of cellular activities or properties. In addition, the use of potentiators of cellular activation allows for characterization of such pathways and cell populations.

Abstract: Methods are provided for detecting the formation of complexes of molecules, especially proteins, in a sample, such as a cell or tissue lysate. In one aspect, a cleaving probe specific for a first protein in a complex and one or more binding compounds specific for one or more second proteins in a complex are provided. Upon binding, the cleaving probe is induced to generate an active species, such as singlet oxygen, that cleaves molecular tags attached to the binding compounds only in the local region of the cleaving probe. The released molecular tags are separated from the assay mixture and from one another to provide a readout that is related to the number and types of proteins present in the complex.

Abstract: The ionic conjugates include an inorganic particle electrostatically associated with a macromolecule which can interact specifically with predetermined chemical species or biological targets.

Abstract: It is an object of the present invention to provide a luminescent polymer that is useful as a luminescent signal probe for labeling and detecting a target substance at high sensitivity in bioassay, and to provide the application of said luminescent polymer to bioassay. The luminescent polymer of the present invention comprises at least one biotin covalently attached to a polymer that includes monosaccharide or amino acid as a constituent monomer covalently attached to a luminescent substance. Preferably, two or more biotins are attached. Examples of the above-mentioned luminescent substance include cyanoisoindoles, luminols, and acridinium esters, and examples of the polymer include polysaccharides, polyamino acids, peptides, polypeptides, and proteins.

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: The present invention provides a method for reducing undesirable light emission from a sample using at least one photon producing agent and at least one photon reducing agent (e.g. dye-based photon reducing agents). The present invention further provides a method for reducing undesirable light emission from a sample (e.g., a biochemical or cellular sample) with at least one photon producing agent and at least one collisional quencher. The present invention also provides a method for reducing undesirable light emission from a sample (e.g., a biochemical or cellular sample) with at least one photon producing agent and at least one quencher, such as an electronic quencher. The present invention also provides a system and method of screening test chemicals in fluorescent assays using photon reducing agents. The present invention also provides compositions, pharmaceutical compositions, and kits for practicing these methods.

Abstract: The present invention provides multicolor reagent formulations containing in a single container both fluorescently labeled detection reagents and single-color compensation control reagents, wherein the compensation control reagents consist of reagent-capture particles bound to a fluorescently labeled detection reagent included in the multicolor reagent formulation. The multicolor reagent formulations of the present invention simplify manufacture and commercial distribution of multicolor reagent kits.

Abstract: The invention relates to a method for the determination of the concentration of a non-volatile analyte in an aqueous sample medium, with the use of an optical sensor which contains a luminescent dye and is calibrated at the user site by means of a single-point-calibration. To enable the user to completely dispense with all calibration media a luminescence measurement value is obtained at the user site with the sensor in contact with the aqueous or bloodlike sample medium, which value is referenced to the relative characteristic obtained at the factory site and to a measured dry calibration value obtained at the user site, the concentration of the non-volatile analyte being deduced from these data.

Abstract: Methods and compositions are provided that include a multichromophore and/or multichromophore complex for identifying a target biomolecule. A sensor biomolecule, for example, an antibody can be covalently linked to the multichromophore. Additionally, a signaling chromophore can be covalently linked to the multichromophore. The arrangement is such that the signaling chromophore is capable of receiving energy from the multichromophore upon excitation of the multichromophore. Since the sensor biomolecule is capable of interacting with the target biomolecule, the multichromophore and/or multichromophore complex can provide enhanced detection signals for a target biomolecule.

Abstract: The present invention provides dye compounds optimally excited at about 400 nm and have a Stokes shift of at least about 80 nm. These dyes find use in detection of analyte in a sample and the preparation of dye-conjugates.

Abstract: Disclosed are compounds having the formula: wherein R1 is selected from the group consisting of hydrogen, C1-C6 alkyl, amino, N—C1-C6-alkylamino, and N,N—C1-C6-dialkylamino; and ring “A” is selected from the group consisting of unsubstituted or substituted C4-C8-cycloalkenyl, unsubstituted or substituted bicyclo[2,2,1]alkenyl, and unsubstituted or substituted bicyclo[2,2,2]alkenyl, unsubstituted phenyl, and phenyl substituted with a moiety selected from the group consisting of C3-C6-alkenyl, acryl, acryl-C1-C6 alkyl, acrylamido, and acrylamido-C1-C6 alkyl; polymers made from these compounds, and ELISAs that use the compounds and polymers as a chemiluminescent detection label.

Abstract: The invention provides methods and compositions for simultaneously detecting the activation state of a plurality of proteins in single cells using flow cytometry. The invention further provides methods and compositions of screening for bioactive agents capable of coordinately modulating the activity of a plurality of proteins in single cells. The methods and compositions can be used to determine the protein activation profile of a cell for predicting or diagnosing a disease state, and for monitoring treatment of a disease state.

Abstract: Methods and compound useful for detecting a source of hydrogen peroxide are disclosed wherein a signalling compound of the formula: is reacted with peroxide. Sig is a non-polymeric organic group, B is a boron atom, and each R is independently selected from hydrogen, alkyl and aryl groups and can be joined together as a straight or branched alkylene chain forming a ring or as an aromatic ring. A detectable product compound of the formula Sig-OH or Sig-O?is produced and detected by measuring color, absorbance, fluorescence, chemiluminescence, or bioluminescence. The signalling compound itself does not possess the detectable property or does so only to a very weak degree. The methods can be used as a detectable signal in assays for peroxide or peroxide-producing enzymes and in assays employing enzyme-labeled specific binding pairs.

Abstract: Disclosed are assays, methods, and kits for the screening of test compounds for their capability to induce cardiotoxicity in a subject. In particular, whether a test compound has the effect to prolong the Q-T interval as measured by an electrocardiogram in a human. The assays, methods, and kits disclosed herein make use of the binding interaction between novel fluorescent tracers and the hERG K+ channel, and the propensity of a test compound to influence that binding interaction.

Abstract: Chemiluminescent acridinium esters are provided which are fast light emitting and hydrolytically stable. The chemiluminescent acridinium esters are useful labels in assays for detecting or quantifying analytes.

Abstract: Assay systems and specialized antibodies for the detection and quantitation of troponin I and troponin T in body fluids as an indicator of myocardial infarction are disclosed. Troponin I and T exist in various conformations and the ratios of monomeric troponin I and T and the binary and ternary complexes, as well as which form of troponin present in the blood, may be related to the metabolic state of the heart. Disclosed are systems to determine the presence of a troponin form or a group of troponin forms in whole blood, serum or plasma samples. Disclosed is a method for improving the recovery of troponin I or T from a surface used in immunoassays. Also disclosed are antibodies which recognize unbound troponin forms, the forms of troponin in binary complexes, the ternary complex of troponin I, T and C, and the conformations of troponin I having intramolecularly oxidized and reduced cysteines.

Abstract: A generic structure for the peptides of the present invention includes A-X-B-C, where C is a cargo moiety, the B portion includes basic amino acids, X is a cleavable linker sequence, and the A portion includes acidic amino acids. The intact structure is not significantly taken up by cells; however, upon extracellular cleavage of X, the B-C portion is taken up, delivering the cargo to targeted cells. Cargo may be, for example, a contrast agent for diagnostic imaging, a chemotherapeutic drug, or a radiation-sensitizer for therapy. Cleavage of X allows separation of A from B, unmasking the normal ability of the basic amino acids in B to drag cargo C into cells near the cleavage event. X is cleaved extracellularly, preferably under physiological conditions. D-amino acids are preferred for the A and B portions, to minimize immunogenicity and nonspecific cleavage by background peptidases or proteases.

Abstract: A method for analyzing chemical and/or biological samples comprises the production of a particle image (42) of at least one particle included in the sample. Subsequently, a particle surface (10) of the at least one particle included in the particle image (42) is divided into particle zones (14,18). According to the invention, zone-dependent particle data are subsequently acquired in different states (z1, z2, z3), which then can be evaluated.