127 results about "Signaling transduction" patented technology

The present invention relates generally to methods for stimulating cells, and more particularly, to a novel method to concentrate and stimulate cells that maximizes stimulation and / or proliferation of such cells. In the various embodiments, cells are stimulated and concentrated with a surface yielding enhanced proliferation, cell signal transduction, and / or cell surface moiety aggregation. In certain aspects methods for stimulating a population of cells such as T-cells, by simultaneous concentration and cell surface moiety ligation are provided by contacting the population of cells with a surface, that has attached thereto one or more agents that ligate a cell surface moiety and applying a force that predominantly drives cell concentration and cell surface moiety ligation, thereby inducing cell stimulation, cell surface moiety aggregation, and / or receptor signaling enhancement. Also provided are methods for producing phenotypically tailored cells, including T-cells for the use in diagnostics, drug discovery, and the treatment of a variety of indications, including cancer, viral infection, and immune related disorders. Compositions of cells having specific phenotypic properties produced by these processes are further provided.

The present invention relates generally to methods for stimulating cells, and more particularly, to a novel method to concentrate and / or stimulate cells that maximizes stimulation and / or proliferation of such cells. In the various embodiments, cells are stimulated and concentrated with a surface yielding enhanced proliferation, cell signal transduction, and / or cell surface moiety aggregation. In certain aspects methods for stimulating a population of cells such as T-cells, by simultaneous concentration and cell surface moiety ligation are provided by contacting the population of cells with a surface, that has attached thereto one or more agents that ligate a cell surface moiety and applying a force that predominantly drives cell concentration and cell surface moiety ligation, thereby inducing cell stimulation, cell surface moiety aggregation, and / or receptor signaling enhancement. Also provided are methods for producing phenotypically tailored cells, including T-cells for the use in diagnostics, drug discovery, and the treatment of a variety of indications, including cancer, viral infection, and immune related disorders. Compositions of cells having specific phenotypic properties produced by these processes are further provided.

The invention relates to a modified antibody which contains two or more H chain V regions and two or more L chain V regions of monoclonal antibody and can transduce a signal into cells by crosslinking a cell surface molecule(s) to thereby serve as an agonist. The modified antibody can be used as a signal transduction agonist and, therefore, useful as a preventive and / or remedy for various diseases such as cancer, inflammation, hormone disorders and blood diseases.

Provided are electrokinetically-altered fluids (gas-enriched electrokinetic fluids) comprising an ionic aqueous solution of charge-stabilized oxygen-containing nanostructures in an amount sufficient to provide modulation of at least one of cellular membrane potential and cellular membrane conductivity, and therapeutic compositions and methods for use in treating diabetes and diabetes-associated conditions or disorders (e.g., insulin resistance), or symptoms thereof. Provided are electrokinetically-altered ioinic aqueous fluids optionally in combination with other therapeutic agents. Particular aspects provide for regulating or modulating intracellular signal transduction associated with said inflammatory responses by modulation of at least one of cellular membranes, membrane potential, membrane proteins such as membrane receptors, including but not limited to G-Protein Coupled Receptors (GPCR), and intercellular junctions (e.g., tight junctions, gap junctions, zona adherins and desmasomes). Other embodiments include particular routes of administration or formulations for the electrokinetically-altered fluids (e.g., electrokinetically-altered gas-enriched fluids and solutions) and therapeutic compositions.

The present invention relates to a new generation of chimeric antigen receptors (CAR) referred to as multi-chain CARs. Such CARs, which aim to redirect immune cell specificity and reactivity toward a selected target exploiting the ligand-binding domain properties, comprise separate extracellular ligand binding and signaling domains in different transmembrane polypeptides. The signaling domains are designed to assemble in juxtamembrane position, which forms flexible architecture closer to natural receptors, that confers optimal signal transduction. The invention encompasses the polynucleotides, vectors encoding said multi-chain CAR and the isolated cells expressing them at their surface, in particularly for their use in immunotherapy. The invention opens the way to efficient adoptive immunotherapy strategies for treating cancer and viral infections.

Provided are electrokinetically-altered fluids (gas-enriched (e.g., oxygen-enriched) electrokinetic fluids) comprising an ionic aqueous solution of charge-stabilized oxygen-containing nanostructures in an amount sufficient to provide, upon contact with a cell, modulation of at least one of cellular membrane potential and cellular membrane conductivity, and therapeutic compositions and methods for using same in treating cystic fibrosis or a symptom thereof. The electrokinetically-altered fluid compositions and methods include electrokinetically-altered fluids optionally in combination with other therapeutic agents (e.g., antibiotics, albuterol, budesonide, etc.). Particular embodiments comprise use and / or synergy with tobramycin for treating bacterial infection, and use and / or synergy with a bronchiodilator. In certain aspects, the methods comprise regulating intracellular signal transduction by modulation of at least one of cellular membranes, membrane potential, membrane proteins (like, membrane receptors, including but not limited to G protein coupled receptors, and intercellular junctions).

Provided are compositions and methods for treating lung or respiratory disorders or conditions characterized by airflow obstruction or limitation, or a symptom thereof (e.g., asthma, rhinitis, allergic rhinitis, and chronic obstructive pulmonary disease (COPD) and COPD-associated conditions (e.g., bronchitis, emphysema, asthma), emphysema, pneumonia, bronchitis, influenza, SARS, tuberculosis, and whooping cough (pertussis), and the like) in a subject in need thereof by administering a therapeutic composition comprising at least one electrokinetically altered fluid (gas-enriched (e.g., oxygen-enriched) electrokinetic fluids) comprising an ionic aqueous solution of charge-stabilized oxygen-containing nanostructures as disclosed herein. In certain aspects, the methods comprise regulating intracellular signal transduction by modulation of at least one of cellular membranes, membrane potential, membrane proteins (e.g., membrane receptors, (e.g., to G protein coupled receptors, and intercellular junctions)). Additional aspects include therapeutic compositions, and combination treatment methods comprising administration of electrokinetically generated fluid in combination with at least one additional therapeutic agent.

Provided are compositions and methods for treating or preventing lung or respiratory disorders or conditions characterized by airflow obstruction or limitation, or a symptom thereof (e.g., asthma, rhinitis, allergic rhinitis (e.g. nose respiratory tract), and chronic obstructive pulmonary disease (COPD) and COPD-associated conditions (e.g., bronchitis, emphysema, asthma), emphysema, pneumonia, bronchitis, influenza, SARS, tuberculosis, and whooping cough (pertussis), and the like) in a subject in need thereof by administering a therapeutic composition comprising at least one electrokinetically generated fluid (including gas-enriched electrokinetically generated fluids) as disclosed herein, the electrokinetically altered aqueous fluid suitable to alter cellular membrane structure or function sufficient to provide for modulation of intracellular signal transduction, wherein treating a lung disorder or a symptom thereof is thereby afforded. Additional aspects relate to therapeutic compositions, and combination treatment methods comprising administration of at least one electrokinetically generated fluid in combination with at least one additional therapeutic agent.

Provided are compositions and methods for treating lung or respiratory disorders or conditions characterized by airflow obstruction or limitation, or a symptom thereof (e.g., asthma, rhinitis, allergic rhinitis, and chronic obstructive pulmonary disease (COPD) and COPD-associated conditions (e.g., bronchitis, emphysema, asthma), emphysema, pneumonia, bronchitis, influenza, SARS, tuberculosis, and whooping cough (pertussis), and the like) in a subject in need thereof by administering a therapeutic composition comprising at least one electrokinetically altered fluid (gas-enriched (e.g., oxygen-enriched) electrokinetic fluids) comprising an ionic aqueous solution of charge-stabilized oxygen-containing nanostructures as disclosed herein. In certain aspects, the methods comprise regulating intracellular signal transduction by modulation of at least one of cellular membranes, membrane potential and / or conductance, membrane proteins (e.g., membrane receptors, (e.g., to G protein coupled receptors, and intercellular junctions)). Additional aspects include therapeutic compositions, and combination therapies comprising administration of the electrokinetically generated fluids with at least one additional therapeutic agent.

Modified antibodies containing 2 or more H chain V domains and or more L chain V domains of a monoclonal antibody which can transduce a signal into cells by crosslinking a cell surface molecule, thereby serving as an agonist. Because of being usable as agonists for signal transduction, these modified antibodies are useful as, for example, preventives and / or remedies for various diseases such as cancer, inflammation, hormone disorders and blood diseases.

The present invention relates to compounds useful as inhibitors of ATR protein kinase. The invention also relates to pharmaceutically acceptable compositions comprising the compounds of this invention; methods of treating of various diseases, disorders, and conditions using the compounds of this invention; processes for preparing the compounds of this invention; intermediates for the preparation of the compounds of this invention; and methods of using the compounds in in vitro applications, such as the study of kinases in biological and pathological phenomena; the study of intracellular signal transduction pathways mediated by such kinases; and the comparative evaluation of new kinase inhibitors.The compounds of this invention are represented by formula I-A and formula I-B:or a pharmaceutically acceptable salt, wherein the variables are as defined herein.

A micro flow control capillary electrophoresis liquid core waveguide fluorescence detector includes a liquid core waveguide capillary, a laser light source, a photodetector, a high-voltage power supply, an electrode, a liquid storage container, a sample tube, a pinhole diaphragm, a filter and a shadow shield; the device makes use of a liquid core waveguide phenomenon and uses the same liquid core waveguide capillary as a capillary electrophoresis separation channel and for fluorescence signal transduction. In the invention, the light given out by the laser light source can be not focused by a lens but directly radiates on the liquid core waveguide capillary through the pinhole diaphragm; the fluorescence led out by the outlet port of the liquid core waveguide capillary can not be collected by the lens but directly enters into the photodetector through the filter. The liquid core waveguide capillary is taken as a micro flow control capillary electrophoresis separation channel and an optical conduction channel, so as to furthest reduce optical elements, simplify an optical system, make the structure more compact, so as to provide a feasible technical route for developing miniature micro flow control analytical instruments.

The present invention relates to compounds useful as inhibitors of ATR protein kinase. The invention also relates to pharmaceutically acceptable compositions comprising the compounds of this invention; methods of treating of various diseases, disorders, and conditions using the compounds of this invention; processes for preparing the compounds of this invention; intermediates for the preparation of the compounds of this invention; and methods of using the compounds in in vitro applications, such as the study of kinases in biological and pathological phenomena; the study of intracellular signal transduction pathways mediated by such kinases; and the comparative evaluation of new kinase inhibitors.The compounds of this invention have formula I:or a pharmaceutically acceptable salt, wherein the variables are as defined herein.

The application relates to the technical field of the display, and in particular relates to an organic light-emitting display panel and a display device; the organic light-emitting display panel comprises a substrate and multiple pixel units arranged on the substrate; each pixel unit comprises a drain electrode, a pixel electrode and a light-emitting layer orderly arranged on the substrate; the organic light-emitting display panel further comprises multiple power signal transduction lines on the substrate; a conducting layer which comprises at least one first conducting part and multiple second conducting parts, wherein the first conducting part and the second conducting parts are insulated from each other, the multiple second conducting parts are insulated from each other, the first conducting part is electrically connected with multiple power signal transduction lines, and multiple second conducting parts are in one-to-one corresponding and electric connection with the drain electrode; a first insulating layer located between the conducting layer and the pixel electrode, wherein an electrode via hole is formed on the first insulating layer, and the pixel electrode is electrically connected with each second conducting part through the electrode via hole. The organic light-emitting display panel can enable the display brightness of the display device to be more uniform.

Modified antibodies containing 2 or more H chain V domains and or more L chain V domains of a monoclonal antibody which can transduce a signal into cells by crosslinking a cell surface molecule, thereby serving as an agonist. Because of being usable as agonists for signal transduction, these modified antibodies are useful as, for example, preventives and / or remedies for various diseases such as cancer, inflammation, hormone disorders and blood diseases.

The present invention relates to a benzothiadiazole compound represented by the following formula I, and a preparation method and use thereof, the benzothiadiazole compound has the biological activityof inhibiting protein-tyrosine-phosphatase SHP2, can be used as a tool compound to study the biological functional relevance of the protein-tyrosine-phosphatase SHP2 in a cell signal transduction process, and provides a new means for prevention and treatment of cancer and metabolic and immune diseases.

The invention discloses novel phosphorylation sites identified in signal transduction proteins and pathways, and provides phosphorylation-site specific antibodies and heavy-isotope labeled peptides (AQUA peptides) for the selective detection and quantification of these phosphorylated sites / proteins, as well as methods of using the reagents for such purpose. Among the phosphorylation sites identified are sites occurring in the following protein types: adaptor / scaffold proteins, adhesion / extracellular matrix protein, apoptosis proteins, calcium binding proteins, cell cycle regulation proteins, chaperone proteins, chromatin, DNA binding / repair / replication proteins, cytoskeletal proteins, endoplasmic reticulum or golgi proteins, enzyme proteins, G / regulator proteins, inhibitor proteins, motor / contractile proteins, phosphatase, protease, Ser / Thr protein kinases, Protein kinase (Tyr)s, receptor / channel / cell surface proteins, RNA binding proteins, transcriptional regulators, tumor suppressor proteins, ubiquitan conjugating system proteins and proteins of unknown function.

The present invention relates to organic molecules capable of modulating tyrosine kinase signal transduction in order to regulate, modulate and / or inhibit abnormal cell proliferation.

The invention belongs to the technical field of chemical printing ink, and specifically relates to an aqueous toughened glass printing ink dedicated for touch screen and a preparation method thereof. The aqueous toughened glass printing ink is prepared from the following raw materials in parts by weight: 6 to 28 parts of inorganic pigment, 20 to 50 parts of first glass powder frit, 10 to 40 parts of second glass powder frit, 10 to 60 parts of aqueous varnish, 0 to 2 parts of wetting dispersant, 0 to 1 part of antifoaming agent, and 0 to 2 parts of leveling agent. The printing ink can improve the surface acoustic wave signal transduction performance of touch screen glass, solves the problem that after surface acoustic waves go through tough screen glass, the signal attenuates, and has the advantages that the covering performance of the printing ink is good, the surface acoustic wave propagation speed is quick, the energy attenuation is little, no phase change happens, and the corrosion of the printing ink is weak.

The invention discloses a traditional Chinese medicine cancer toxin prescription for treating liver cancer and application thereof in the preparation of medicaments for resisting liver cancer. The cancer toxin prescription is prepared in accordance with the cancer toxin theory proposed by traditional Chinese medicine master Professor Zhou Zhongying, and is prepared from hedyotidis herba, muscardine silkworm, centipede, akebia fruit, pseudostellaria root, dwarf lilyturf root and rhizoma pleionis according to a certain weight ratio. The prescription has the main functions of eliminating pathogens, eliminating cancer and detoxicating and the auxiliary function of strengthening healthy qi. By using mice with liver cancer H22 transplantation tumor as materials, the pharmacological experiment result shows the cancer resistance effect of the cancer toxin prescription: the tumor inhibition rates of a low-dose group, an intermediate-dose group and a high-dose group are respectively 24.5%, 42.8% and 21.1%, thereby showing the effect of inhibiting the growth of H22 tumor mass; the tumor mass cell apoptosis rates of the low-dose group, the intermediate-dose group and the high-dose group are respectively 47.16%, 60.52% and 57.59%, thereby showing the effect of inducing tumor cells to die; and the cancer toxin prescription can block the high expression of TLR4, block the MyD88 dependent pathway of TLR4 intracellular signal transduction and inhibit the expression of downstream NF-kB proteins. Experiment shows that the cancer toxin prescription can be used for preparing medicaments for resisting liver cancer.

The invention discloses a radio-frequency electromagnetic impedance matching anti-electromagnetic interference composite coating, a preparation method and a spraying method thereof. The impedance matching coating consists of a resin solution, nano-beta silicon carbide, nano-nickel powder and polystyrene; the bottom black carbon coating consists of the resin solution and black carbon. The preparation method comprises solution preparation, resin dissolution, preparation of the impedance matching coating and preparation of the bottom black carbon coating. The spraying method is as follows: the bottom black carbon coating is first sprayed, and then the impedance matching coating is sprayed, both the coatings are dried at the temperature of 60-75 DEG C for 30min to obtain the radio-frequency electromagnetic impedance matching anti-electromagnetic interference composite coating. The coating obtained has the advantages of high electromagnetic impedance matching, strong anti-electromagnetic interference ability, wide absorption band, high absorptivity, little reflection, low RFID misreading rate, no secondary electromagnetic pollution, etc. The coating effectively solves the problem that signal transduction is interfered in and attenuated when electric waves meet metal or liquid in the RFID application, and further the reliability and accuracy of data reading are affected, thus the coating greatly expands the application field of the RFID, and can be widely used in various fields of radio frequency.

This invention is directed to a method for preparation of a biological sample for measurement of protein epitopes that allows for the preservation of intracellular protein epitopes and detection of signal transduction pathways based on the ability to capture transient activation states of the epitopes. The method provided by the invention allows for the rapid fixation of biological samples containing red blood cells, to ensure that epitopes of signal transduction molecules and other intracellular protein epitopes are preserved in the active state. The method of the invention further allows for lysis of red blood cells, thereby making it a useful method for cytometric analysis of biological samples, including, for example, whole blood, bone marrow aspirates, peritoneal fluids, and other red blood cell containing samples. The invention also provides a method to recover or “unmask” epitopes on intracellular antigens that have been made inaccessible by the cross linking fixative necessary to fix the sample. Significantly, the methods of the invention allow preservation and analysis of phospho-epitope levels in biological samples taken directly from patients to determine disease-specific characteristics.

The present invention provides methods for detecting, measuring and quantitating the expression and activation states of signal transduction analytes in cells such as tumor cells. The invention also provides methods for selecting therapy, optimizing therapy, monitoring therapeutic efficacy, and / or detecting therapeutic resistance. Accordingly, the methods are useful for improving cancer therapy selection and disease monitoring.

The invention discloses a photo-induced dimer type chimeric antigen receptor. The photo-induced dimer type chimeric antigen receptor is composed of two monomers, wherein a first monomer is sequentially composed of a signal peptide, an extracellular antigen binding area, an extracellular hinge area, a transmembrane area, a costimulatory signal transduction area and an optically-controlled element and polymerization element 1 functional structure domain; a second monomer is sequentially composed of a signal peptide, an extracellular affine area, a transmembrane area, a costimulatory signal transduction area and a polymerization element 2 and T cell signal transduction area functional structure domain. The photo-induced dimer type chimeric antigen receptor is applied to mediating immune response of T cells; either monomer has no activity when not in a coupled mode, so that polymerization and depolymerization of the photo-induced dimer type chimeric antigen receptor can be controlled through blue light irradiation.

The invention discloses an application of CD200 in psoriasis, and belongs to the field of biological medicines. The invention specifically relates to an application of CD200 protein or CD200 fusion protein in treatment of psoriasis. Through the research, when an effective amount of exogenous CD200 protein or CD200 fusion protein is given in vitro, NF-kappa B signal transduction can be inhibited, the activation of inflammatory macrophages is inhibited, the secretion of IL-1beta, IL-6 and TNF-alpha inflammatory factors and the excessive proliferation of keratinocytes can be reduced, so that theprotein can be applied to psoriasis treatment.

The invention discloses novel phosphorylation sites identified in signal transduction proteins and pathways, and provides phosphorylation-site specific antibodies and heavy-isotope labeled peptides (AQUA peptides) for the selective detection and quantification of these phosphorylated sites / proteins, as well as methods of using the reagents for such purpose. Among the phosphorylation sites identified are sites occurring in the following protein types: adaptor / scaffold proteins, adhesion / extracellular matrix protein, apoptosis proteins, calcium binding proteins, cell cycle regulation proteins, chaperone proteins, chromatin, DNA binding / repair / replication proteins, cytoskeletal proteins, endoplasmic reticulum or golgi proteins, enzyme proteins, G / regulator proteins, inhibitor proteins, motor / contractile proteins, phosphatase, protease, Ser / Thr protein kinases, Protein kinase (Tyr)s, receptor / channel / cell suface proteins, RNA binding proteins, transcriptional regulators, tumor suppressor proteins, ubiquitan conjugating system proteins and proteins of unknown function.

The present invention provides a cell which comprises; (i) a chimeric antigen receptor (CAR) which comprises an antigen binding domain and an intracellular signalling domain; (ii) a membrane tethering component (MTC) which comprises a first dimerization domain; and (Hi) a signal-dampening component (SDC) comprising a signal-dampening domain (SDD) and a second dimerization domain which specifically binds the first dimerisation domain of the membrane-tethering component. Dimerisation between the MTC and SDC may be controllable with an agent, meaning that the agent can be used to control CAR-mediated cell signalling.

The invention provides a chimeric antigen receptor T cell targeting BCMA and application of the chimeric antigen receptor T cell. A chimeric antigen receptor comprises a signal peptide, an antigen binding structural domain, a transmembrane structural domain and a signal transduction structural domain, Wherein the antigen binding domain comprises an anti-BCMA single-chain antibody; and the signal transduction structural domain comprises 4-1BB, CD3 [zeta] and TLR2. According to the chimeric antigen receptor T cell, 4-1BB, CD3[zeta] and TLR2 which are connected in series are used as signal transduction structural domains of the chimeric antigen receptor, and are matched with a specific antigen binding structural domain anti-BCMA single-chain antibody, so that the constructed chimeric antigenreceptor T cell has remarkably enhanced capability of specifically recognizing and killing BCMA positive tumor cells, and is high in safety, and bright clinical application prospects are realized in the field of B cell malignant tumor treatment.

The invention relates to a phenyl ring-aromatic ring cascaded micro-molecular organic compound which can be used as a protein-tyrosine-phosphatase subtype inhibitor and is shown in a general formula I as described in the specification. The compound can be used as a tool compound for research on the biological functions of a variety of subtypes of a protein-tyrosine-phosphatase family in cell signal transduction, so novel means is provided for prevention and treatment of cancers, metabolism and immunological diseases, cardiovascular diseases and nervous diseases. The invention also relates to a preparation method and medicinal application of the compound.