This invention relates to compounds that inhibit protein tyrosine kinase activity. In particular the invention relates to compounds that inhibit the protein tyrosine kinase activity of growth factor receptors, resulting in the inhibition of receptor signaling, for example, the inhibition of VEGF receptor signaling and HGF receptor signaling. More particularly, the invention relates to compounds, compositions and methods for the inhibition of VEGF receptor signaling and HGF receptor signaling. The invention also provides compositions and methods for treating cell proliferative diseases and conditions.

The present invention provides a method for treating tumors or tumor metastases in a patient, comprising administering to said patient simultaneously or sequentially a therapeutically effective amount of a combination of an anti-cancer agent or treatment that elevates pAkt levels in tumor cells and an IGF-1R kinase inhibitor of Formula (I) (e.g. OSI-906). Examples of such anti-cancer agents or treatments include doxorubicin, cisplatin, and ionizing radiation. The present invention also provides a pharmaceutical composition comprising an anti-cancer agent that elevates pAkt levels in tumor cells and an IGF-1R kinase inhibitor of Formula (I), in a pharmaceutically acceptable carrier. The present invention also provides a method of identifying tumor cells that will respond most favorably to treatment with a combination of an anti-cancer agent or treatment that elevates pAkt levels in tumor cells and an IGF-1R kinase inhibitor.

Extracts from plant material, or semi-purified/purified molecules or compounds prepared from the extracts that demonstrate the ability to modulate one or more cellular activities are provided. The extracts are capable of slowing down, inhibiting or preventing cell migration, for example, the migration of endothelial cells or neoplastic cells and thus, the use of the extracts to slow down, inhibit or prevent abnormal cell migration in an animal is also provided. Methods of selecting and preparing the plant extracts and methods of screening the extracts to determine their ability to modulate one or more cellular activity are described. The purification or semi-purification of one or more molecules from the described extracts is also contemplated as well as the use of these molecules, alone or in combination with an extract, to slow down, inhibit or prevent abnormal cell migration in an animal.

Provided are novel nanostructures comprising hollow nanospheres and nanotubes for use as chemical sensors and molecular specific photothermal coupling agents. The nanostructures can be used in laser-induced phototherapy for treatment of cancer and other disorders. The nanostructures can also be used as a sensor that detects molecules. The nanostructures are of particular use in the fields of clinical diagnosis, clinical therapy, clinical treatment, and clinical evaluation of various diseases and disorders, manufacture of compositions for use in the treatment of various diseases and disorders, for use in molecular biology, structural biology, cell biology, molecular switches, molecular circuits, and molecular computational devices, and the manufacture thereof. The hollow gold nanospheres have a unique combination of spherical shape, small size, and strong, tunable, and narrow surface plasmon resonance absorption covering the entire visible to near IR region.

The present invention relates to antibodies specific for glycosylated mammalian NGAL, and to methods of making and using such antibodies.

A soybean cultivar designated 7524005 is disclosed. The invention relates to the seeds of soybean cultivar 7524005, to the plants of soybean 7524005, to plant parts of soybean cultivar 7524005 and to methods for producing a soybean plant produced by crossing soybean cultivar 7524005 with itself or with another soybean variety. The invention also relates to methods for producing a soybean plant containing in its genetic material one or more transgenes and to the transgenic soybean plants and plant parts produced by those methods. This invention also relates to soybean cultivars or breeding cultivars and plant parts derived from soybean variety 7524005, to methods for producing other soybean cultivars, lines or plant parts derived from soybean cultivar 7524005 and to the soybean plants, varieties, and their parts derived from use of those methods. The invention further relates to hybrid soybean seeds, plants and plant parts produced by crossing the cultivar 7524005 with another soybean cultivar.

A soybean cultivar designated S070149 is disclosed. The invention relates to the seeds of soybean cultivar S070149, to the plants of soybean S070149, to plant parts of soybean cultivar S070149 and to methods for producing a soybean plant produced by crossing soybean cultivar S070149 with itself or with another soybean variety. The invention also relates to methods for producing a soybean plant containing in its genetic material one or more transgenes and to the transgenic soybean plants and plant parts produced by those methods. This invention also relates to soybean cultivars or breeding cultivars and plant parts derived from soybean variety S070149, to methods for producing other soybean cultivars, lines or plant parts derived from soybean cultivar S070149 and to the soybean plants, varieties, and their parts derived from use of those methods. The invention further relates to hybrid soybean seeds, plants and plant parts produced by crossing the cultivar S070149 with another soybean cultivar.

(3R,3′R,6′R)-Lutein and (3R,3′R)-zeaxanthin are two dietary carotenoids that are present in most fruits and vegetables commonly consumed in the US. These carotenoids accumulate in the human plasma, major organs, and ocular tissues. In the past decade, numerous epidemiological and experimental studies have shown that lutein and zeaxanthin play an important role in the prevention of age-related macular degeneration (AMD) that is the leading cause of blindness in the U.S. and Western World. The invention provides a process for the synthesis of (3R,3′R,6′R)-lutein and its stereoisomers from commercially available (rac)-α-ionone by a C 15 +C 10 +C 15 coupling strategy. In addition, the present invention also provides access to the precursors of optically active carotenoids with 3-hydroxy-ε-end group that are otherwise difficult to synthesize. The process developed for the synthesis of lutein and its stereoisomers is straightforward and has potential for commercialization.

Isolated nucleic acids and polypeptides associated with lipid and sugar metabolism regulation are provided. In particular, lipid metabolism proteins (LMP) and encoding nucleic acids originating from Arabidopsis thaliana are provided. The nucleic acids and polypeptides are used in methods of producing transgenic plants and modulating levels of seed storage compounds in a plant. Preferably, the seed storage compounds are lipids, fatty acids, starches, or seed storage proteins.

The present invention comprises methods and compositions for producing and/or enhancing an immunological response in a subject against a target moiety such as a disease-related moiety by administration of an antigenic version of the target moiety having one or more unnatural amino acid and/or by administration of an antibody against a version of a target moiety having one or more unnatural amino acid which antibody is cross reactive with the natural target moiety.

The invention provides a method for treating an autoimmune disease in a subject by administering an interferon antagonist and a Flt3 ligand (Flt3L) antagonist. The invention also provides compositions containing one or more interferon antagonists, and one or more Flt3L antagonists, an in vitro assay for determining a subject's risk for developing an autoimmune disease, and kits for use, inter alia, with the assay.

A soybean cultivar designated 7643392 is disclosed. The invention relates to the seeds of soybean cultivar 7643392, to the plants of soybean 7643392, to plant parts of soybean cultivar 7643392 and to methods for producing a soybean plant produced by crossing soybean cultivar 7643392 with itself or with another soybean variety. The invention also relates to methods for producing a soybean plant containing in its genetic material one or more transgenes and to the transgenic soybean plants and plant parts produced by those methods. This invention also relates to soybean cultivars or breeding cultivars and plant parts derived from soybean variety 7643392, to methods for producing other soybean cultivars, lines or plant parts derived from soybean cultivar 7643392 and to the soybean plants, varieties, and their parts derived from use of those methods. The invention further relates to hybrid soybean seeds, plants and plant parts produced by crossing the cultivar 7643392 with another soybean cultivar.

This invention pertains to a method for detecting a compound in the presence of other compounds that are substantially similar in structure and metabolically related to the analyte. The invention is particularly suited for the detection of S-adenosylmethionine in the presence of S-adenosylhomocysteine, other nucleosides and derivatives in a biological sample. The methods of this invention involve an antibody produced specifically against S-adenosylmethionine; particularly, analogs modified strategically at the sulfonium position. An assay protocol comprises chemically modified analyte analog linked to an enzymatic reporter and the aforementioned antibody was used to demonstrate the assay specificity and sensitivity. Additional assay method with immobilized immunogen, the specific antibody, and an enzyme labeled secondary antibody was also described for illustration. The invention also features hapten design and novel compounds used as haptens to prepare immunogen and for the specific antibody production.

The invention relates in part to molecules having certain biological activities that include, but are not limited to, inhibiting cell proliferation, modulating protein kinase activity and modulating polymerase activity. Molecules of the invention can modulate casein kinase (CK) activity and/or poly(ADP-ribose)polymerase (PARP) activity. The invention also relates in part to methods for using such molecules.

The present invention relates to a method for determining likelihood of an individual of developing a psychiatric disorder. More particularly, the method of the invention is based on the identification of genetic variations in genes involved in the modulation of melatonin and their consequences on such pathway for the determination of whether an individual is susceptible of being afflicted by a psychiatric disorder such as autism spectrum disorders (ASD), Deficits and Hyper Activity Disorder (ADHD) and anorexia.

This disclosure provides methods and compositions for the promotion of enzymatic activity of Target Enzymes, including but not limited to oligosaccharide/polysaccharide enzymes, protein enzymes, polynucleotide enzymes. The methods involve use of a non-naturally occurring polysaccharide (including but not limited HES) for promoting the enzymatic activity of an enzyme in liquid milieu, wherein the concentration of the polysaccharide in the composition comprising the Target Enzyme is from about 0.01% to about 55% w/v.

A novel gene 254P1D6B and its encoded protein, and variants thereof, are described wherein 254P1D6B exhibits tissue specific expression in normal adult tissue, and is aberrantly expressed in the cancers listed in Table I. Consequently, 254P1D6B provides a diagnostic, prognostic, prophylactic and/or therapeutic target for cancer. The 254P1D6B gene or fragment thereof, or its encoded protein, or variants thereof, or a fragment thereof, can be used to elicit a humoral or cellular immune response; antibodies or T cells reactive with 254P1D6B can be used in active or passive immunization.

The invention relates to crystals of the influenza virus neuraminidase protein, their structures and their use.

Retrocyclin peptides are small antimicrobial agents with potent activity against bacteria and viruses. The peptides are nonhemolytic, and exhibit minimal in vitro cytotoxicity. A pharmaceutical composition comprising retrocyclin as an active agent is administered therapeutically to a patient suffering from a bacterial and/or viral infection, or to an individual facing exposure to a bacterial and/or viral infection, especially one caused by the HIV-1 retrovirus or other sexually-transmitted pathogens.

The present invention is intended to clarify the relationship between PAR-2 and cerebral infarction and thereby provide an efficient method of preventing and treating cerebral infarction, as well as a pharmaceutical composition therefore. Namely, the present invention relates to a method of preventing and treating cerebral infarction by activating PAR-2 and/or promoting expression of PAR-2 gene. The present invention further relates to a pharmaceutical composition for preventing and treating cerebral infarction, comprising one, or two or more of the active ingredients selected from the group consisting of a PAR-2 activator and/or a PAR-2 gene expression promoter; as well as a pharmaceutically acceptable carrier. It further relates to a method of screening an active ingredient for preventing and treating cerebral infarction using as an indicator the PAR-2 activation promoted by a test substance.

A detection test assembly for detecting the presence of a substance preferably a blood substance in a feces sample comprising feces diluted in buffer solution or water is described. The blood substance is detected by acceptors having binding properties for the substance or that may be specifically bound by the substance. Said assembly comprises a reaction field having a mobile first acceptor with visualization properties and a detection field comprising a test field connected to and located downstream from the reaction field having an immobilized second acceptor. After direct application of a prepared feces sample to the assembly, first acceptor forms a complex with blood substance, flows to test field and binds to or is bound by immobilized second acceptor. Accumulation of first acceptor in the test field results in the formation of a visualizable line such as color different from the color of the test field itself. The detection test assembly includes at least two positive internal controls.

A transgenic non-human animal of the species selected from the group consisting of avian, bovine, ovine and porcine having a transgene which results in disrupting the production of and/or activity of growth differentiation factor-11 (GDF-11) chromosomally integrated into the germ cells of the animal is provided. Also provided are methods for making such animals, and methods of treating animals, including humans, with antibodies or antisense directed to GDF-11. The animals so treated are characterized by increased muscle tissue and bone tissue.

The present invention provides a method for producing a salt-free miso-like food having strong umami and rich flavor with strong taste. As a means to solve the problem, a liquid koji is prepared by culturing an aspergillus in a predetermined amount of lactic acid bacterium culture solution or a supernatant thereof. The thus-obtained liquid koji is added to a food material, and koji making is performed in a hermetically sealed koji-making machine while successively or intermittently supplying disinfected air thereto. Subsequently, a lactic acid bacterium culture solution or a supernatant thereof is mixed into the obtained koji, and optionally a food material is mixed therewith. The obtained mixture is provided as it is or in paste form to give moromi, and the moromi is hydrolyzed in the absence of salt.

The present invention relates to the use of a peptide inhibiting TGF-β1 selected from: peptide p144 whose sequence corresponds to SEQ ID NO: 1, peptide p17 whose sequence corresponds to SEQ ID NO: 2, a peptide which has at least 90% homology therewith, or fragments of the above, in the preparation of an immune response modulating agent.

This invention provides analogs of hemiasterlin, methods of synthesis of the analogs and use of the analogs as a cytotoxic anti-mitotic agents.

Methods and compositions for using the MHC class II invariant chain polypeptide, Ii (also known as CD74), as a receptor for macrophage migration inhibitory factor (MIF), are disclosed. These include methods and compositions for using this receptor, as well as agonists and antagonists of MIF which bind to this receptor, or which otherwise modulate the interaction of MIF with CD74 or the consequences of such interaction, in treatment of conditions characterized by locally or systemically altered MIF levels, particularly inflammatory conditions and cancer.

The present invention is directed to methods and compositions methods and compositions for determining and inhibiting gene transcription in mammalian cells. The invention relates to novel inhibitors of rho-mediated gene transcription and to compounds that may be used as therapeutic agents.

The invention relates to a screening method for the Smoothened receptor for testing compositions as potential Smoothened receptor ligands, either agonist or antagonist activity, by use of an arrestin-reporter molecule conjugate. It also relates to testing cells and individuals by administering a smoothened receptor ligand-reporter molecule conjugate and observing locations where the ligand binds and then using an increased number of surface Smoothened receptors compared to a pre-established criteria as an indication of a cancerous growth or tumor.

The present invention provides a novel glyceroglycolipid produced by Mycoplasma pneumoniae . The glyceroglycolipid can be used as a diagnostic marker for a disease caused by Mycoplasma pneumoniae.

The invention relates to diagnostic methods to predict whether a subject is predisposed for acquiring a disease or to predict the therapy responsiveness of an individual patient. Provided is a method for determining whether a subject is predisposed for developing an autoimmune disease, comprising determining in a sample isolated from said subject the amount of intact genes, or gene products thereof, of the FcγRII/FcγRIII gene cluster, said gene cluster comprising the FCGR2C, FCGR3A, FCGR2A and FCGR3B genes encoding an activating FcγR, and FCGR2B encoding an inhibitory Fcγ R; and correlating said amount to the amount observed in a healthy population. Also provided is a method to predict the responsiveness of a subject to therapy with intravenous immunoglobulin (IVIg) therapy or a monospecific biological, such as a humanized or human monoclonal antibody or a chimeric molecule, comprising the C-terminal Fc-tail of IgG.

A method for constructing stable bioactive fusion proteins of the difficult to express turn or necrosis factor superfamily (TNFSF), and particularly members CD40L (CD 154) and RANKL/TRANCE, with collecting, particularly pulmonary surfactant protein D (SPD) is described. Single trimers of these proteins lack the full stimulatory efficacy of the natural membrane forms of these proteins in many cases. The multimeric nature of these soluble fusion proteins enables them to engage multiple receptors on the responding cells, thereby, mimicking the effects of the membrane forms of these ligands. For CD40L-SPD, the resulting protein stimulates B cells, macrophages, and dendritic cells, indicating its potential usefulness as a vaccine adjuvant. The large size of these fusion proteins makes them less likely to diffuse into the circulation, thereby limiting their potential systemic toxicity. This property may be especially useful when these proteins are injected locally as a vaccine adjuvant or tumor immunotherapy agent to prevent them from diffusing away. In addition, these and other TNFSF-collectin fusion proteins present new possibilities for the expression of highly active, multimeric, soluble TNFSF members.

The present invention provides methods for diagnosing and providing a prognosis for wound healing in a patient by characterizing and analyzing the single nucleotide polymorphism (SNP) of a wound healing associated gene wit3.0. In particular, the invention provides a method of diagnosis and prognosis of oral disease-wound healing, including gingival periodontitis and residual alveolar bone resorption, by characterizing and analyzing the wound inducible transcript-3.0 (wit3.0)SNP pattern in a sample of a patient with and without susceptibility for the disease.

Methods of using mass spectrometry and in particular matrix assisted laser Ligand-Complex from Target and desorption-ionization (MALDI) mass spectrometry to analyze, or otherwise detect the presence of or determine the identity of intact ions of undigested, unfragmented covalently stabilized supramolecular target-ligand-complexes, as well as the use of these methods in various biological application such as characterization of antibodies, drug discovery, and complexomics including automated or higher throughput applications.

A first aspect of the invention provides a method of screening cholesterol absorption inhibitors, including: administering to a mammal a biologically effective amount of a candidate SPT inhibitor; and determining whether an amount at least one cholesterol absorption indicator protein in the intestine has changed after the administering step.

The present invention include providing a therapeutically effective amount of a 3-substituted indolin-2-one compositions to protect against neurodegeneration including diseases such as Alzheimer's disease, Parkinson's disease, or Huntington's disease, and conditions such as ischemic stroke

This invention relates to a method of identifying a modulator of an NADPH oxidase, whereby said modulator is suitable as a lead compound and/or as a medicament for the treatment and/or prevention of hearing loss and/or phantom hearing, the method comprising the steps of (a) contacting a test compound with a protein, wherein said protein (i) comprises or consists of the amino acid sequence of any one of SEQ ID NO: 1, 3 or 5, or (ii) is encoded by a nucleic acid comprising or consisting of the sequence of any one of SEQ ID NO: 2, 4, 6, 23 or 24, or (iii) is a fragment of the protein according to (i) or (ii) and exhibits NADPH oxidase activity, or (iv) has a sequence at least 75% identical with the protein according to (i) or (ii) or with the fragment according to (iii) and exhibits NADPH oxidase activity, and optionally with one or more NADPH oxidase subunits, under conditions allowing binding of said test compound to said protein or, if present, said subunit(s); (b) optionally determining whether said test compound binds to said protein or, if present, said subunit(s); and (c) determining whether (ca) said test compound, upon contacting in step (a); or (cb) said test compound, upon binding in step (b) modulates the expression and/or activity of said protein or, if present, said subunit(s). Also provided are pharmaceutical compositions, medical uses and diagnostic uses of compounds of the invention.

The present application provides novel human genes B1194, A2282V1, A2282V2, and A2282V3 whose expression is markedly elevated in breast cancer. These genes and polypeptides encoded thereby can be used, for example, in the diagnosis of breast cancer, and as target molecules for developing drugs against breast cancer.

Disclosed are methods for identifying individuals suffering from a CNS disorder (including Alzheimer's Disease, behavioral disorders, and the like) that could be treated with a CNS drug with greater therapeutic efficacy and lower side effects and the compounds useful for such treatment. Also disclosed are methods for predicting the efficacy of a drug candidate for the treatment of a CNS disorder. The technology is also applicable to drug discovery for use in animal models of neurodegenerative diseases.

The present invention provides a translational product encoded by the nucleotide sequence of SEQ ID NO: 2, which corresponds to the gag gene of an endogenous human retrovirus named HERV-7q. The present invention also provides methods for diagnosing a neurological or autoimmune disease in a patient.

A process of producing transgenic plants or plant cells stably transformed on a chromosome with a DNA sequence of interest and capable of expressing a function of interest from said DNA sequence of interest, said process comprising (a) providing plant cells or plants with at least two different vectors, whereby (i) said at least two different vectors are adapted to recombine with each other by site-specific recombination in said plant cells for producing a non-replicating recombination product containing said DNA sequence of interest, (ii) said at least two different vectors are adapted for integrating said DNA sequence of interest into said chromosome, (iii) said DNA sequence of interest contains sequence portions from at least two of said at least two different vectors, said sequence portions being necessary for expressing said function of interest from said DNA sequence of interest; and (b) selecting plants or plant cells expressing said function of interest.

The present invention relates to novel antibodies capable of binding specifically to the human insulin-like growth factor I receptor (IGF-IR). The invention likewise comprises the use of these antibodies as a medicament for the prophylactic and/or therapeutic treatment of cancers overexpressing IGF-IR, stimulated either by IGF1 and/or IGF2, or any pathology connected with the overexpression of said receptor as well as in processes or kits for diagnosis of illnesses connected with the overexpression of the IGF-IR and/or the IGF-I/Insulin hybrid receptor.

Vascular endothelial growth factor (VEGF) receptor fusion protein comprising Ig domain 2 of Flt-1 and Ig domains 3, or Ig domain 2 of Flt-1 and Ig domain 3 and 4 of KDR, the gene encoding the fusion protein, the pharmaceutical composition containing the fusion protein and the pharmaceutical use of the fusion protein are provided. The fusion protein can be used for treatment of eye disorders involving angiogenesis such as diabetic retinopathy.

The present invention relates to methods that may be used to improve or modify nutrient sensing, absorption, metabolism, root growth, stomatal conductance, N use efficiency, C and N metabolism, plant biomass production and seed yield. More specifically, this invention is related to the glutamate receptors (GLRs) and their role(s) in nutrient sensing, metabolism, regulation of growth, development, and yield.

The invention is directed to systems and methods for transferring nano-quantities of fluid samples using a high throughput or ultra high throughput dispenser. Such samples may be transferred from a first location and reformatted for being transferred to a second location. The invention may transfer a predetermined volume of sample quickly and accurately.

Disclosed herein are linear donor molecules comprising homology arms of 50-750 base pairs (e.g., 50-100 base pairs) flanking one or more sequences of interest. The donor molecules and/or compositions comprising these molecules can be used in methods for targeted integration of an exogenous sequence into a specified region of interest in the genome of a cell.

Disclosed herein is a system useful for detecting sequence differences (e.g., single-nucleotide polymorphisms) between genomes using data from a single hybridization with a genomic DNA microarray, such as a whole-genome array. The methods described herein can be used to detect, simply and inexpensively, differences in sequence among the genomes of individual members of a species, for example. In examples described herein, the system and methods were used to detect a variety of spontaneous single base-pair substitutions, insertions and deletions, and most (>90%) of the approximately 30,000 known single-nucleotide polymorphisms between two Saccharomyces cerevisiae strains. The system and methods were also used to elucidate the genetic basis of phenotypic variants and identify the small number of single base-pair changes accumulated during experimental evolution of yeast.

The present invention relates to newly identified nucleic acid molecules and polypeptides present in normal and neoplastic ovarian cells, including fragments, variants and derivatives of the nucleic acids and polypeptides. The present invention also relates to antibodies to the polypeptides of the invention, as well as agonists and antagonists of the polypeptides of the invention. The invention also relates to compositions containing the nucleic acid molecules, polypeptides, antibodies, agonists and antagonists of the invention and methods for the use of these compositions. These uses include identifying, diagnosing, monitoring, staging, imaging and treating ovarian cancer and non-cancerous disease states in ovarian, identifying ovarian tissue, monitoring and identifying and/or designing agonists and antagonists of polypeptides of the invention. The uses also include gene therapy, production of transgenic animals and cells, and production of engineered ovarian tissue for treatment and research.

Disclosed are methods of identifying subjects with osteoporosis or osteopenia, subjects at risk for developing osteoporosis, osteopenia, and bone fractures, methods of evaluating the effectiveness of osteoporosis treatments in subjects with osteoporosis or osteopenia, and methods of selecting therapies for treating osteoporosis or osteopenia, using biomarkers.

The present invention relates to compositions and methods for treating a disease in an animal, which disease is responsive to inhibiting of functional cystic fibrosis transmembrane conductance regulator (CFTR) polypeptide by administering to a mammal in need thereof an effective amount of a compound defined herein (including those compounds set forth in Tables 1-2 or encompassed by formulas I-II) or compositions thereof, thereby treating the disease. The present invention particularly, relates to a method of treating diarrhea and polycystic kidney disease.

Provided are methods of assessing the absence or presence of a neurodegenerative disease in a subject comprising characterizing TDP-43 in a tissue sample of the subject. Also disclosed are methods for diagnosing a neurodegenerative disease in a subject, and methods for determining the efficacy of a drug against a neurodegenerative disease. Novel antibodies that bind to TDP-43 are also provided.