98 results about "Cellular process" patented technology

A membrane for implantation in soft tissue comprising a first domain that supports tissue ingrowth, disrupts contractile forces typically found in a foreign body response, encourages vascularity, and interferes with barrier cell layer formation, and a second domain that is resistant to cellular attachment, is impermeable to cells and cell processes, and allows the passage of analytes. The membrane allows for long-term analyte transport in vivo and is suitable for use as a biointerface for implantable analyte sensors, cell transplantation devices, drug delivery devices, and / or electrical signal delivering or measuring devices. The membrane architecture, including cavity size, depth, and interconnectivity, provide long-term robust functionality of the membrane in vivo.

The invention provides a class of substituted quinazolinone compounds and methods of treating diseases mediated by PI3Kδ activity. The disclosed compounds are useful in treating diseases such as bone-resorption disorders; and cancer, especially hematopoietic cancers, lymphomas, multiple myelomas and leukemia. The compounds are also useful in disrupting or inhibiting cellular processes such as leukocyte function or accumulation, neutrophils function, lymphocyte proliferation, and endogenous immune responses.

The present invention concerns compounds, compositions, and methods for the study, diagnosis, and treatment of diseases and conditions associated with alpha-1 antitrypsin (AAT) allelic variants that respond to the modulation of gene expression and / or activity. The present invention also concerns compounds, compositions, and methods relating to diseases and conditions associated with alpha-1 antitrypsin (AAT) allelic variants that respond to the modulation of expression and / or activity of genes involved in alpha-1 antitrypsin (AAT) gene expression pathways or other cellular processes that mediate the maintenance or development of alpha-1 antitrypsin (AAT) diseases and conditions such as liver disease, lung disease, and any other diseases or conditions that are related to or will respond to the levels of an alpha-1 antitrypsin (AAT) variant protein in a cell or tissue, alone or in combination with other therapies. Specifically, the invention relates to small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (mRNA), and short hairpin RNA (shRNA) molecules capable of mediating RNA interference (RNAi) against the expression disease related genes or alleles having alpha-1 antitrypsin (AAT) sequences.

The present invention relates to compounds, compositions, and methods for the study, diagnosis, and treatment of traits, diseases and conditions that respond to the modulation of Proprotein Convertase Subtilisin Kexin 9 (PCSK9) gene expression and / or activity. The present invention is also directed to compounds, compositions, and methods relating to traits, diseases and conditions that respond to the modulation of expression and / or activity of genes involved in Proprotein Convertase Subtilisin Kexin 9 (PCSK9) gene expression pathways or other cellular processes that mediate the maintenance or development of such traits, diseases and conditions. Specifically, the invention relates to double stranded nucleic acid molecules including small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA) molecules capable of mediating RNA interference (RNAi) against Proprotein Convertase Subtilisin Kexin 9 (PCSK9) gene expression, including cocktails of such small nucleic acid molecules and lipid nanoparticle (LNP) formulations of such small nucleic acid molecules. The present invention also relates to small nucleic acid molecules, such as siNA, siRNA, and others that can inhibit the function of endogenous RNA molecules, such as endogenous micro-RNA (miRNA) (e.g, miRNA inhibitors) or endogenous short interfering RNA (siRNA), (e.g., siRNA inhibitors) or that can inhibit the function of RISC (e.g., RISC inhibitors), to modulate PCSK9 gene expression by interfering with the regulatory function of such endogenous RNAs or proteins associated with such endogenous RNAs (e.g., RISC), including cocktails of such small nucleic acid molecules and lipid nanoparticle (LNP) formulations of such small nucleic acid molecules. Such small nucleic acid molecules and are useful, for example, in providing compositions to prevent, inhibit, or reduce metabolic diseases traits and conditions, including but not limited to hyperlipidemia, hypercholesterolemia, cardiovascular disease, atherosclerosis, hypertension, diabetis (e.g., type I and / or type II diabetis), insulin resistance, obesity and / or other disease states, conditions, or traits associated with PCSK9 gene expression or activity in a subject or organism.

The present invention relates to compounds, compositions, and methods for the study, diagnosis, and treatment of traits, diseases and conditions that respond to the modulation of gene expression and / or activity. The present invention is also directed to compounds, compositions, and methods relating to traits, diseases and conditions that respond to the modulation of expression and / or activity of genes involved in gene expression pathways or other cellular processes that mediate the maintenance or development of such traits, diseases and conditions. Specifically, the invention relates to double stranded nucleic acid molecules including small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA) molecules capable of mediating RNA interference (RNAi) against gene expression, including cocktails of such small nucleic acid molecules and lipid nanoparticle (LNP) formulations of such small nucleic acid molecules. The present invention also relates to small nucleic acid molecules, such as siNA, siRNA, and others that can inhibit the function of endogenous RNA molecules, such as endogenous micro-RNA (miRNA) (e.g., miRNA inhibitors) or endogenous short interfering RNA (siRNA), (e.g., siRNA inhibitors) or that can inhibit the function of RISC (e.g., RISC inhibitors), to modulate gene expression by interfering with the regulatory function of such endogenous RNAs or proteins associated with such endogenous RNAs (e.g., RISC), including cocktails of such small nucleic acid molecules and lipid nanoparticle (LNP) formulations of such small nucleic acid molecules. Such small nucleic acid molecules and are useful, for example, in providing compositions to prevent, inhibit, or reduce diseases, traits and conditions that are associated with gene expression or activity in a subject or organism.

This invention provides an advanced platform for the analysis of biological data that emphasizes pathway mapping and relationship inference based upon data acquired from multiple diverse sources. The platform employs a bioinformatic system that integrates data from the diverse sources, connecting related genes and proteins and inferring biological functions in the context of global cellular processes.

The invention provides a method detecting and quantifying proteins by mass spectrophotometric analysis using peptide internal standards and provides a highly sensitive way of detecting protein modifications. In one aspect, the invention provides a method for determining a site of ubiquitination in a polypeptide and for evaluating ubiquitination targets in a population of polypeptides. In this way, a proteome ubiquitination map can be obtained which comprises information relating to the ubiquitination states of a plurality of cellular polypeptides. Maps can be obtained for a variety of different types of cells and cell states. For example, ubiquitination targets in normal and diseased cells can be evaluated. Preferably, the map is stored as data files in a database. Individual ubiquitinated polypeptides identified can be used to generate molecular probes diagnostic of a cell state and / or can serve as targets for agents that modulate one or more cellular processes.

The invention herein comprises antibodies that bind to amyloid beta-derived diffusible ligands (ADDLs). ADDLs comprise amyloid β protein assembled into soluble, globular, non-fibrillar, oligomeric structures capable of activating specific cellular processes.

The present invention relates to compounds, compositions, and methods for the study, diagnosis, and treatment of traits, diseases and conditions that respond to the modulation of stromal cell-derived factor-1 (SDF-1) gene expression and / or activity. The present invention is also directed to compounds, compositions, and methods relating to traits, diseases and conditions that respond to the modulation of expression and / or activity of genes involved in SDF-1 gene expression pathways or other cellular processes that mediate the maintenance or development of such traits, diseases and conditions. Specifically, the invention relates to small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA) molecules capable of mediating or that mediate RNA interference (RNAi) against SDF-1 gene expression. Such small nucleic acid molecules are useful, for example, in providing compositions for treatment of traits, diseases and conditions that can respond to modulation of SDF-1 expression in a subject, such as ocular disease, cancer and proliferative diseases and any other disease, condition, trait or indication that can respond to the level of SDF-1 in a cell or tissue.

The invention described in this disclosure involves a new composition of matter, amyloid beta-derived dementing ligands (ADDL's). ADDLs consist of amyloid β peptide assembled into soluble globular non-fibrillar oligomeric structures that are capable of activating specific cellular processes. The invention further encompasses methods for assaying the formation, presence, receptor protein binding and cellular activities of ADDLs. The invention further encompasses assay methods and inhibitor molecules for cellular signaling molecules activated by ADDLs. Also described are molecules that block proteins that promote the formation of ADDLs.

The invention provides amyloid beta-derived dementing ligands (ADDLs) that comprise amyloid β protein assembled into globular non-fibrillar oligomeric structures capable of activating specific cellular processes. The invention also provides methods for assaying the formation, presence, receptor protein binding and cellular activity of ADDLs, as well as compounds that block the formation or activity of ADDLs, and methods of identifying such compounds. The invention further provides methods of using ADDLs, and modulating ADDL formation and / or activity, inter alia in the treatment of learning and / or memory disorders.

The invention is used as an additive to a culture medium to maintain and grow various cells including stem cells and support their manufactured and secreted products including cytokines, chemokines and growth factors in an environment which provides:a) metabolic enabling or enhancement of measurable parameters within the cellular populationb) availability and usage of nutrients to cellsc) distinct and positive effect on cellular dynamics (i.e. cellular proliferation and secretion of manufactured products by the cells)d) stabilized environment for maintaining conditions for growth and other cellular and metabolic processes including secretion of manufactured products including signaling factorse) enhanced biological cellular function of inherent cellular processesf) non-interference with normal cellular metabolics (i.e. signaling)g) increased protection from toxic effects to the cellh) additional benefits to the cellular population which in absence of the additive would be lacking.

Microfluidic systems and methods are disclosed which are adapted to transport and lyse cellular components of a test sample for analysis. The disclosed microfluidic systems and methods, which employ an electric field to rupture the cell membrane, cause unusually rapid lysis, thereby minimizing continued cellular activity and resulting in greater accuracy of analysis of cell processes.

The present invention relates to compounds, compositions, and methods for the study, diagnosis, and treatment of traits, diseases and conditions that respond to the modulation of Sterol Regulatory Element-Binding Protein 1 (SREBP1) gene expression and / or activity. The present invention is also directed to compounds, compositions, and methods relating to traits, diseases and conditions that respond to the modulation of expression and / or activity of genes involved in Sterol Regulatory Element-Binding Protein 1 (SREBP1) gene expression pathways or other cellular processes that mediate the maintenance or development of such traits, diseases and conditions. Specifically, the invention relates to double stranded nucleic acid molecules including small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA) molecules capable of mediating RNA interference (RNAi) against Sterol Regulatory Element-Binding Protein 1 (SREBP1) gene expression, including cocktails of such small nucleic acid molecules and lipid nanoparticle (LNP) formulations of such small nucleic acid molecules. The present invention also relates to small nucleic acid molecules, such as siNA, siRNA, and others that can inhibit the function of endogenous RNA molecules, such as endogenous micro-RNA (miRNA) (e.g, miRNA inhibitors) or endogenous short interfering RNA (siRNA), (e.g., siRNA inhibitors) or that can inhibit the function of RISC (e.g., RISC inhibitors), to modulate SREBP1 gene expression by interfering with the regulatory function of such endogenous RNAs or proteins associated with such endogenous RNAs (e.g., RISC), including cocktails of such small nucleic acid molecules and lipid nanoparticle (LNP) formulations of such small nucleic acid molecules. Such small nucleic acid molecules and are useful, for example, in providing compositions to prevent, inhibit, or reduce metabolic diseases traits and conditions, including but not limited to hyperlipidemia, hypercholesterolemia, cardiovascular disease, atherosclerosis, hypertension, diabetis (e.g., type I and / or type II diabetis), insulin resistance, obesity and / or other disease states, conditions, or traits associated with SREBP1 gene expression or activity in a subject or organism.

The present invention relates to compounds, compositions, and methods for the study, diagnosis, and treatment of traits, diseases and conditions that respond to the modulation of gene expression and / or activity. The present invention is also directed to compounds, compositions, and methods relating to traits, diseases and conditions that respond to the modulation of expression and / or activity of genes involved in gene expression pathways or other cellular processes that mediate the maintenance or development of such traits, diseases and conditions. Specifically, the invention relates to double stranded nucleic acid molecules including small nucleic acid molecules, such as short interfering nucleic acid (siN A), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA) molecules capable of mediating RNA interference (RNAi) against gene expression, including cocktails of such small nucleic acid molecules and lipid nanoparticle (LNP) formulations of such small nucleic acid molecules. The present invention also relates to small nucleic acid molecules, such as siNA, siRNA, and others that can inhibit the function of endogenous RNA molecules, such as endogenous micro-RNA (miRNA) (e.g, miRNA inhibitors) or endogenous short interfering RNA (siRNA), (e.g., siRNA inhibitors) or that can inhibit the function of RISC (e.g., RISC inhibitors), to modulate gene expression by interfering with the regulatory function of such endogenous RNAs or proteins associated with such endogenous RNAs (e.g., RISC), including cocktails of such small nucleic acid molecules and lipid nanoparticle (LNP) formulations of such small nucleic acid molecules. Such small nucleic acid molecules and are useful, for example, in providing compositions to prevent, inhibit, or reduce diseases, traits and conditions that are associated with gene expression or activity in a subject or organism.

The invention provides isolated nucleic acids encoding a variety of proteins and nucleic acids having diagnostic, preventive, therapeutic, and other uses. These nucleic acids and proteins are useful for diagnosis, prevention, and therapy of a number of human and other animal disorders. The invention also provides antisense nucleic acid molecules, expression vectors containing the nucleic acid molecules of the invention, host cells into which the expression vectors have been introduced, and non-human transgenic animals in which a nucleic acid molecule of the invention has been introduced or disrupted. The invention still further provides isolated polypeptides, fusion polypeptides, antigenic peptides and antibodies. Diagnostic, screening, and therapeutic methods utilizing compositions of the invention are also provided. The nucleic acids and polypeptides of the present invention are useful as modulating agents in regulating a variety of cellular processes.

Phthalazine diones that function as intracellular redox modulators and buffers are used to treat stressed cells in various disease states in which the intracellular redox status is impaired. By optimal buffering of aberrant redox states, phthalazine diones enhance the cellular processes essential for survival and augment the conventional or other external therapies necessary for treatment. The phthalazine diones of the invention thus regulate cell growth, differentiation, or death to serve as essential adjunctive therapy for the stressed host in various disease states.

The present invention provides the use of Liver X Receptor (LXR) modulators that have been identified to downregulate 5-lipoxygenase gene expression in order to treat various diseases and disorders that involve the function of the 5-LO protein in intracellular signaling (or other cellular processes) or the function of protein products downstream of 5-LO in intracellular signaling (i.e., leukotrienes).

Phthalazinediones that function as intracellular redox modulators are useful in treating cells in various disease states where intracellular redox status is impaired. By buffering aberrant redox states, phthalazinediones enable cellular processes essential for survival and augment medical treatments. The phthalazinediones of the invention can modulate functions related to cell growth, differentiation, activity, or death, to correct aberrations and restore homeostasis, and can serve as adjunctive therapy in treating various disease conditions.

The invention provides a model for generating predicted action potentials of an electrically active cell. The disclosed model includes three operatively coupled submodels. A first submodel contains Hodgkin-Huxley elements generating action potentials based on electrical equivalent circuits. A second submodel is based on reaction kinetics of cell metabolism and is operatively coupled with the first submodel. A third submodel is based on Boolean dynamics representing signaling and associated cellular processes and is operatively coupled with the first and second submodels. The invention includes storing a library of calculated action potentials and associated cellular parameters generated by the model, applying a stimulus to the electrically active cell in vitro so that the cell generates an action potential; and comparing the cell-generated action potential with those stored in the library, wherein a match is predictive of the cellular point of action of the applied stimulus according to the parameters stored.

A test device applies a defined mechanical load to a soft biomaterial such as a cell culture and a microscope forms a volume image data set showing the strain field or displacement field occurring in the medium. The data set is processed to determine fundamental mechanical properties of the cell, its interaction with the surrounding medium, or its responses loading or deformation of its surrounding medium. The device may also be used to calibrate or determine fundamental mechanical properties of the medium. The device includes a linear actuator that bears against the specimen, and adapted for a volume imaging device such as a scanning laser confocal microscope that forms a volume image data set of the specimen. The specimen may be supported in a Petri dish and is preferably imaged from below by an inverted microscope. Preferably the actuator device attaches to or forms the specimen stage of microscope. Digital correlation of volumes in the data set allow computation of modulus, stress distribution and other mechanical characteristics of cell-matrix interactions, as well as mechanical properties of the cell and the matrix in response to changing loads, evolving chemical or ionic environment and growth phases. The test device may be operated to measure local mechanical parameters, to evaluate or design tissue-engineered implants, and to explore the mechanical properties of tissues, cells and cellular processes a micrometer scale with high accuracy.

Disclosed are products and methods to promote myoblast activation and cardiac and skeletal muscle growth or regeneration, and to treat heart and skeletal muscle diseases, based on the identification of cellular processes affected by prelamin A processing.

The present invention describes methods for carrying out experiments on living cells, including making measurements of the operation transcriptional regulatory processes and indicators of the kinds of processes operating in the cell in response to external stimuli. Image analysis allows for gathering data concerning the flow of information through a cell's genomic regulatory network as it is executing a programmatic change in its activities as a function of said stimuli. The method also allows collection of data of the results of the information-processing in the cell by observing the decisions the cell makes when modulating cellular process activities.

The present invention relates to compounds useful as inhibitors of protein kinase. The invention also provides pharmaceutically acceptable compositions comprising said compounds and methods of using the compositions in the treatment of various disease, conditions, or disorders. The invention also provides for methods and pharmaceutical agents to modulate the activity of Tousled-like kinase (TLK). The invention also provides for methods and pharmaceutical agents to inhibit the activity of Tousled-like kinase to provide increased sensitivity to irradiation (IR) and chemotherapeutic agents. The invention also provides for methods and pharmaceutical agents to increase the activity of Tousled-like kinase to provide increased protection against DNA damaging agents including to irradiation (IR) and chemotherapeutic agents.

The present invention describes rapid methods to screen for biomolecular interactions in vivo based on protein fragment complementation assays (PCA). We have demonstrated an in vivo library-versus-library screening strategy that has numerous applications in the identification of novel protein-protein interactions and in directed evolution. Also we demonstrate the detection of protein-protein interactions starting with defined (full-length) cDNAs, and the concomitant generation of functional assays that provide initial validation of the cDNA products as being biologically relevant. Also, we screened a large cDNA collection using automated PCA, combined with quantitative detection of protein-protein complexes. The invention enables bait-vs.-library, library-vs.-library and defined gene screening in any type of cell or cellular context, and using a wide range of reporters and detection methods. The invention allows for identifying and validating genes involved in any cellular process and also provide assays to study effects of potential drugs, or gene knockouts on specific pathways.

The present invention relates to compounds, compositions, and methods for the study, diagnosis, and treatment of traits, diseases and conditions that respond to the modulation of cyclic nucleotide type 4 phosphodiesterase (PDE4B) gene expression and / or activity, including PDE4B1, PDE4B2, and PDE4B3 gene expression and / or activity. The present invention is also directed to compounds, compositions, and methods relating to traits, diseases and conditions that respond to the modulation of expression and / or activity of genes involved in cyclic nucleotide type 4 phosphodiesterase (PDE4B) gene expression pathways or other cellular processes that mediate the maintenance or development of such traits, diseases and conditions, including but not limited to IL-6, IL-I, IL-8, IL-15, TNF-alpha and matrix metalloproteinases (MMPs), such as MMP-I, MMP-2, MMP-3, MMP-9 and MMP-12. Specifically, the invention relates to double stranded nucleic acid molecules including small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA), and multifunctional siNA molecules capable of mediating RNA interference (RNAi) against cyclic nucleotide type 4 phosphodiesterase (PDE4B) gene expression, including cocktails of such small nucleic acid molecules and lipid nanoparticle (LNP) formulations of such small nucleic acid molecules. The present invention also relates to small nucleic acid molecules, such as siNA, siRNA, antisense and others that can inhibit the function of endogenous RNA molecules or RNAi pathway components (RNAi inhibitors), such as endogenous micro-RNA (miRNA) (e.g, miRNA inhibitors) or endogenous short interfering RNA (siRNA), (e.g., siRNA inhibitors) or that can inhibit the function of RISC (e.g., RISC inhibitors), to modulate PDE4B gene expression by interfering with the regulatory function of such endogenous RNAs or proteins associated with such endogenous RNAs (e.g., RISC) including cocktails of such small nucleic acid molecules and lipid nanoparticle (LNP) formulations of such small nucleic acid molecules. Such small nucleic acid molecules are useful, for example, in providing compositions to prevent, inhibit, or reduce inflammatory, respiratory, and autoimmune diseases, traits, and conditions, and / or other disease states associated with PDE4B gene expression or activity in a subject or organism.

The invention described in this disclosure involves a new composition of matter, amyloid beta-derived dementing ligands (ADDL's). ADDLs consist of amyloid β peptide assembled into soluble globular non-fibrillar oligomeric structures that are capable of activating specific cellular processes. The invention further encompasses methods for assaying the formation, presence, receptor protein binding and cellular activities of ADDLs. The invention further encompasses assay methods and inhibitor molecules for cellular signaling molecules activated by ADDLs. Also described are molecules that block proteins that promote the formation of ADDLs.

Intradermal needles are commonly used in cosmetic procedure to improve the skin, for example to activate cellular processes such as induction and regeneration of some of the superficial levels of skin, such as collagen. The present invention discloses an intradermal needle comprising: a shaft, an insertion tip and a handle wherein handle depth is greater than shaft gauge so that the handle is spaced apart from skin when inserted allowing the intradermal needle to be easily inserted and removed.

A system and method for reversibly controlling clustering of proteins around an engineered multivalent nucleus is disclosed. The system and method utilize clustering, which may be controlled by light activation or deactivation. The system and method enable the spatiotemporal control of protein supramolecular assemblies, including liquid-like droplets under some conditions, and solid-like gels under other conditions. The system and method can be utilized for segregating or locally concentrating desired proteins and / or RNA in cells or cell lysate, which may be useful for protein purification purposes, or for assembling single or multiple membraneless bodies within specific sub-regions of the cells. These synthetically assembled bodies may recruit both transgenic and endogenic proteins and other biomolecules, thus can be linked to affect and even trigger a plethora of cellular processes.

Phthalazinediones that function as intracellular redox modulators in the redox therapy of certain stressed cells are provided. By buffering aberrant redox states, phthalazinediones enable cellular processes essential for survival and augment medical treatments. The phthalazinediones of the invention can modulate functions related to cell growth, differentiation, activity, or death, to correct aberrations and restore homeostasis, and can serve as adjunctive therapy in treating various disease conditions.