A dog clutch control apparatus for an automated transmission includes a rotary shaft, plural dog clutch mechanisms, each of the dog clutch mechanisms including a clutch ring, a clutch hub arranged next to the clutch ring, a sleeve fitted with the clutch hub, a dog clutch portion which is provided at the clutch ring and selectively meshes with a spline formed at the sleeve, an axial driving device for moving the sleeve, the dog clutch control apparatus includes a disengagement detecting portion for detecting disengagement before the sleeve reaches a neutral position and a control apparatus for controlling operation of the axial driving device, wherein in a case where the disengagement is detected at a time of shifting operation, the control apparatus starts a shift-related control.

A battery charge/discharge control device which performs battery charge/discharge control in a working machine with a battery capable of storing electric energy generated by a generator motor coupled to an engine and driving the generator motor or at least one of other electric actuators by the stored electric energy and a controller which controls a distribution of the electric energy among the battery, the generator motor, and the electric actuator, wherein the controller performs the charge/discharge control in which the electric energy of the battery is discharged when the engine is driven and recharging to the battery is permitted on a condition that a state in which an engine speed is equal to or lower than a predetermined engine speed is maintained for a predetermined time after the battery is completely discharged.

Disclosed are a method, a composition, a microarray, an antibody and a kit for diagnosis and prognosis of cancer, based on detection of deletion of the exon 3 region of G-CSF gene or levels of a mutated G-CSF protein having a deletion of an amino acid sequence corresponding to the exon 3 region, wherein the deletion of the exon 3 region of the G-CSF gene is used as a cancer biomarker.

The invention discloses a combined preparation containing IL-10 and rapamycin, able to induce immunosuppression and antigen-specific immune tolerance, and the use thereof in the treatment of diseases involving an excessive, dysfunctional or uncontrolled immune responses mediated by T cells.

The invention relates to the use of NF-κB inducing kinase (NIK) and related molecules for the modulation of signal activities controlled by cytokines, and some new such molecules.

The present invention is directed to the use of the peptide compound Ac-Arg-Phe-Met-Trp-Met-Arg-NH2 as a therapeutic agent for the prophylaxis and/or treatment of cancer, autoimmune diseases, fibrotic diseases, inflammatory diseases, neurodegenerative diseases, infectious diseases, lung diseases, heart and vascular diseases and metabolic diseases. Moreover the present invention relates to pharmaceutical compositions preferably in form of a lyophilisate or liquid buffer solution or artificial mother milk formulation or mother milk substitute containing the peptide Ac-Arg-Phe-Met-Trp-Met-Arg-NH2 optionally together with at least one pharmaceutically acceptable carrier, cryoprotectant, lyoprotectant, excipient and/or diluent.

The present invention is directed to the use of the peptide compound Pyr-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2 as a therapeutic agent for the prophylaxis and/or treatment of cancer, autoimmune diseases, fibrotic diseases, inflammatory diseases, neurodegenerative diseases, infectious diseases, lung diseases, heart and vascular diseases and metabolic diseases. Moreover the present invention relates to pharmaceutical compositions preferably in form of a lyophilizate or liquid buffer solution or artificial mother milk formulation or mother milk substitute containing the peptide Pyr-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2 optionally together with at least one pharmaceutically acceptable carrier, cryoprotectant, lyoprotectant, excipient and/or diluent.

A chimeric protein containing neutrophil inhibitory factor and hirugen, the chimeric protein having an amino acid sequence that includes FPRPGSGG (SEQ ID NO:21) Also provided is a pharmaceutical composition comprising the chimeric protein, which can be used for treating or preventing cerebral injury and cerebral edema, or for inhibiting platelet aggregation.

The present invention relates to fusion proteins comprising an antibody, functional fragment or functional derivative thereof having specific binding affinity to either the extracellular domain of oncofetal fibronectin (ED-B) or at least one of the extracellular domains of oncofetal tenascin fused to a cytokine selected from the group consisting of IL-10, IL15, IL-24 and GM-CSF, functional fragments and functional derivatives thereof. The invention is also directed to the use of at least one of said fusion proteins for the manufacture of a medicament. In particular, the invention concerns the use of said medicament for the treatment of tumors or chronic inflammatory diseases such as atherosclerosis, arthritis and psoriasis.

Provided herein are novel compounds and novel protected compounds that can be derived from polymyxin, including, e.g., polymyxin A. The novel compounds have antibacterial properties against a diverse range of Gram negative bacteria and reduced toxicity compared to polymyxins such as polymyxin A. Also provided are antibacterial pharmaceutical compositions containing the novel compounds and novel protected compounds, as well as methods for preparing the antibacterial compounds and protected compounds.

The invention relates to indolesulfonyl halogenides which are useful for the protection of organic compounds comprising at least one guanidino moiety and/or at least one amino group. The invention further relates to a process for their preparation and their use as protecting reagents. The invention also relates to the process for the protecting reaction and to the protected compounds thereof.

This invention relates to compositions and methods comprising “lymphotoxin-β-receptor blocking agents”, which block lymphotoxin-β receptor signalling. Lymphotoxin-β receptor blocking agents are useful for treating lymphocyte-mediated immunological diseases, and more particularly, for inhibiting Th1 cell-mediated immune responses. This invention relates to soluble forms of the lymphotoxin-β receptor extracellular domain that act as lymphotoxin-β receptor blocking agents. This invention also relates to the use of antibodies directed against either the lymphotoxin-β receptor or its ligand, surface lymphotoxin, that act as lymphotoxin-β receptor blocking agents. A novel screening method for selecting soluble receptors, antibodies and other agents that block LT-β receptor signalling is provided.

Peptides having a structure characterized by the presence of two loops constrained in cyclic structure by the presence of covalent bonds between amino acid side chains, the amino acid sequences of the first and the second loop being substantially homologues to that of loop 1 (residues 29-38) and of loop 4 (residues 92-97) of NGF, respectively, displaying nerve growth factor (NGF) agonist or partial agonist activity.

The present invention relates to the identification and selection of attachment molecules that attach/immobilize an entity having a detectable activity or property on a support in an orientation that provides a detectable activity or property, and to surfaces made of the attachment molecules.

The present invention provides a method for enhancing an immune response in a mammal to facilitate the elimination of a chronic pathology. The method involves the removal of immune system inhibitors such as soluble TNF receptor from the circulation of the mammal, thus, enabling a more vigorous immune response to the pathogenic agent. The removal of immune system inhibitors is accomplished by contacting biological fluids of a mammal with one or more binding partner(s) such as TNFα muteins capable of binding to and, thus, depleting the targeted immune system inhibitor(s) from the biological fluids. Particularly useful in the invention is an absorbent matrix composed of an inert, biocompatible substrate joined covalently to a binding partner, such as a TNFα mutein, capable of specifically binding to a targeted immune system inhibitor such as soluble TNF receptor.

Mono-pegylated arginase conjugate and method producing thereof. The mono-pegylated arginase is homogeneous in molecular weight and shows therapeutic effect for treating cancers and viral infections. The method of producing such arginase conjugate has a main step of genetically modifying the gene encoding an arginase so that the PEG moiety can attach to the enzyme at a predetermined, specific intended site. This is achieved by removing the PEG attaching amino acid residues at undesirable sites while keeping (or adding, if necessary) the one at the desirable site of the enzyme. Two exemplary mono-pegylated arginase conjugates so produced are human arginase I (HAI) where a polyethylene glycol (PEG) moiety is site-specific covalently bonded to Cys45 of the enzyme and Bacillus caldovelox arginase (BCA) where a polyethylene glycol (PEG) moiety is site-specific covalently bonded to Cys161 of the enzyme.

Whether the growth hormone (GH)/Insulin-like growth factor 1(IGF-I) axis exerts cardioprotective effects remains controversial; and the underlying mechanism(s) for such actions are unclear. Here we tested the hypothesis that growth-hormone releasing hormone (GHRH) directly activates cellular reparative mechanisms within the injured heart, in a GH/IGF-I independent fashion. Following experimental myocardial infarction (MI), rats were randomly assigned to receive, during a 4 week period, either placebo (n=14), rat recombinant GH (rrGH, n=8) or JI-38 (n=8; 50 μg/Kg/day), a potent GHRH-agonist. JI-38 did not elevate serum levels of GH or IGF-I, but markedly attenuated the degree of cardiac functional decline and remodeling after injury. In contrast, GH administration markedly elevated body weight, heart weight, circulating GH and IGF-I, but did not offset the decline in cardiac structure and function. Whereas, both JI-38 and GH augmented levels of cardiac precursor cell proliferation, only JI-38 increased anti-apoptotic gene expression. The receptor for GHRH was detectable on myocytes supporting direct activation of cardiac signal transduction. Collectively, these findings demonstrate that within the heart GHRH-agonists can activate cardiac repair following MI, suggesting the existence of a potential signaling pathway based on GHRH in the heart. The phenotypic profile of the response to a potent GHRH agonist has therapeutic implications.

Plant viral vectors have great potential in rapid production of proteins, but no simple. Here a geminivirus-based system for high-yield and rapid production of oligomeric protein complexes, including virus-like particle (VLP) vaccines and monoclonal antibodies (mAbs) is described. In particular, a single vector that contains two non-competing replicons for transient expression in Nicotiana benthamiana leaves is described. The correct assembly of these subunit proteins into functional oligomeric structures (VLPs or full-size mAb) is also described. This system advances plant transient expression technology by eliminating the need for non-competing viruses, and thus, enhances the realistic commercial application of this technology for producing multiple-subunit protein complexes.

A method for reducing or substantially preventing formation of a trisulfide derivative of a polypeptide in a liquid medium containing the polypeptide ijn question comprises stripping the liquid medium with a gas, suitably a chemically unreactive gas such as nitrogen or argon.

The present invention provides methods and pharmaceutical formulations for treating diabetic foot ulcers.

Disclosed are compositions and methods related to the isolation and identification of the primate T-lymphotropic viruses, HTLV-3 and HTLV-4. The diversity of HTLVs was investigated among central Africans reporting contact with NHP blood and body fluids through hunting, butchering, and keeping primate pets. Herein it is shown that this population is infected with a variety of HTLVs, including two retroviruses; HTLV-4 is the first member of a novel phylogenetic lineage that is distinct from all known HTLVs and STLVs; HTLV-3 falls within the genetic diversity of STLV-3, a group that has not previously been seen in humans. The present disclosure also relates to vectors and vaccines for use in humans against infection and disease. The disclosure further relates to a variety of bioassays and kits for the detection and diagnosis of infection with and diseases caused by HTLV-3 and HTLV-4 and related viruses.

The present invention relates to compositions and methods for inhibiting the activity of an enzyme, for example, Protein Kinase B, p70S6K and/or Abl using the catalytic subunit of Protein Kinase A (PKAc), or at least one PKAc fragment or variant PKAc fragment thereof. In this regard, methods for preventing or treating cancer or a neurodegenerative disease or disorder are also provided.

Compositions and methods for the treatment of asthma and inflammatory ocular disorders are disclosed.

The invention relates to compositions comprising vasoactive intestinal peptide (VIP) or fragments thereof, and the use of such compositions in the treatment of kidney disease, in particular kidney fibrosis, and other associated conditions.

The present invention relates to methods for producing a polypeptide having biological activity, comprising: (a) cultivating a fungal host cell in a medium conducive for the production of the polypeptide, wherein the fungal host cell comprises a first polynucleotide encoding the polypeptide operably linked to a second polynucleotide encoding a variant signal peptide or a variant prepropeptide; and (b) isolating the secreted polypeptide having biological activity from the cultivation medium.

Disclosed herein are polypeptides, polynucleotides encoding, cells and organisms comprising novel DNA-binding domains, including TALE DNA-binding domains. Also disclosed are methods of using these novel DNA-binding domains for modulation of gene expression and/or genomic editing of endogenous cellular sequences.

The present invention relates to novel compounds having a function of a peptide in the amylin family, related nucleic acids, expression constructs, host cells, and processes production of the compounds. The compounds of the invention include one or more amino acid sequence modifications. In addition, methods and compositions are disclosed to treat and prevent metabolic disorders such as obesity, diabetes, and increased cardiovascular risk.

A formulation of human chorionic gonadotropin (HCG) for promoting weight loss comprising reconstituted HCG in an amount sufficient to promote weight loss; at least one vitamin selected from the group consisting of: vitamin B1, vitamin B2, vitamin B3, vitamin B5, vitamin B6, vitamin B7, vitamin B9, and vitamin B12; and at least one dietary supplement selected from the group consisting of: an amino acid, inositol, choline chloride, and L-carnitine.

Methods and systems for detecting azetidine-2-carboxylic acid (Aze) in food consumable by humans and animals are provided. Also provided are methods and systems for inactivating Aze in food and byproducts, as well as other methods for the diagnosis, prevention, and treatment of disorders associated with Aze.

The present invention relates to treating a tissue in a mammal from the effects of reperfusion using flagellin.

An insect-resistant protein exhibiting a sufficient resistance to insects; an insect-resistance gene encoding the insect-resistant protein; a recombinant vector containing the insect-resistance gene; a host cell and a plant cell having the recombinant vector transfected thereinto; a transformant transformed by the insect-resistance gene and a method for producing the same; a protein recovered thereby; and an insect-resistant agent comprising them as active ingredients. In accordance with the present invention, the insect-resistant protein is derived from a plant.

Methods, apparatus, systems, computer programs and computing devices related to biologically assembling and/or synthesizing peptides and/or proteins are disclosed.

The invention relates to human medicine and to the use of epidermal growth factor (EGF) for preparing a pharmaceutical composition which is administered by infiltration into the periphery of nerve ganglia and/or trunks for the morphofunctional restoration of peripheral nerves in painful sensory-motor neuropathy as well as manifestations of ischemic neuritis. The invention also includes a composition containing EGF which can be formulated together with anesthetics or analgesics or encapsulated in microspheres and to the use thereof for the morphofunctional restoration of peripheral nerves in painful sensitive-motor-type diabetic neuropathy and the manifestations of ischemic neuritis.

Disclosed are polypeptides, nucleic acids, and related compositions that render plants resistant to bacterial pathogens. Also disclosed are transgenic plants having the nucleic acids and resistant to bacterial pathogens.

Disclosed is a general methodology to create nano fibers of therapeutic molecules that have a dual role, as both the delivery vehicle and the drug itself. It is shown that with proper molecular design, the integration of enzymatic reaction and self-assembly provides a powerful method to create molecular hydrogels of clinically-used therapeutics without compromising their bioactivities. In addition, the results disclosed herein demonstrate enzyme-instructed self-assembly as a facile strategy for generating the supramolecular hydrogels of molecules that inherently have poor solubility in water. For example, by covalently connecting paclitaxel with a motif that is prone to self-assemble, a hydrogel of paclitaxel can be formed without compromising the activity of the paclitaxel.

The present invention provides spreading agents based on sequence-specific oligomers comprising a peptoid, a peptide-peptoid chimera, a retropeptoid or a retro(peptoid-peptide) chimera, and methods for using the same, including for the treatment of respiratory distress of the lungs. The spreading agents are sequence-specific oligomers, including retrosequence-specific oligomers, based on a peptide backbone, that are designed as analogs of surfactant protein-B or surfactant protein-C.

IL4/IL13-binding proteins comprise binding domains, which inhibit IL4/IL13 binding to IL4Ralpaha and common gamma chain complexes (Type 1) and inhibit IL4 binding to IL4Ralpha and IL13Ralpha1 complexes (Type 2), and IL13 binding to IL13Ralpha1 and/or IL13Ralpha2, are useful in the treatment of cancer, inflammatory, and other pathological conditions, such as allergic or fibrotic conditions, especially pulmonary conditions.

The present invention is related to the use of secretagogue peptides repeatedly administered as part of a pharmaceutical composition that prevent and eradicate the deposition of pathological fibrotic material in parenchymal tissues of internal organs like the liver, lungs, esophagus, small intestine, kidneys, blood vessels, joints, and other systemic forms of cutaneous fibrosis of any etiopathogenesis. Additionally, these peptides prevent and eradicate deposition of amiloid and hyaline materials in any of their correspondent chemical forms and tissue manifestations in the brain, cerebellum, blood vessels, liver, intestines, kidneys, spleen, pancreas, joints and the skin, among others. By this way, cellular, tissular and organ dysfunctions generated by these depositions are corrected. The peptides of the present invention are infiltrated or topically applied, contributing to prevent and eradicate keloids and hypertrophic scars in the skin, derived as sequelae of burns and other cutaneous trauma.

The invention relates to compositions comprising vasoactive intestinal peptide (VIP) or fragments thereof, and the use of such compositions in the treatment of aortic fibrosis and other associated conditions.

Disclosed is a drug effective in the treatment of fibromyalgia. Basically, the disclosed therapeutic agent was created on the basis of experiments showing improvement in symptoms when etanercept was administered to patients suffering from fibromyalgia. Etanercept is known as a therapeutic agent for rheumatoid arthritis, and the JFIQ score of patients not suffering from fibromyalgia improved considerably in the preferred embodiment. In other words, a therapeutic agent for fibromyalgia is disclosed that contains etanercept as an active ingredient in an effective amount.

A method of treating cancer through use of guanosine 3',5'-cyclic monophosphate (cyclic GMP). Cyclic GMP decreases the number of human breast cancer and prostate adenocarcinoma as well as small-cell and squamous lung cells in culture by 30% (1 μM), 84% (1 mM), 31% (1 μM), and 30% (1 μM), respectively. Cyclic GMP decreases DNA synthesis in human pancreatic, breast, and prostate adenocarcinomas as well as small-cell and squamous cell carcinomas of the lung at its 1 μM concentration by 51%, 54%, 56%, 50% and 52%, respectively. Cyclic GMP when infused for one week decreases the tumor volume of human pancreatic adenocarcinomas in athymic mice 95% compared to untreated animals with human pancreatic adenocarcinomas.

A method of treating a disease or condition in which up-regulating GAGs is therapeutically beneficial is disclosed, in particular osteoarthritis and skin diseases. The method comprises locally administering to a subject a therapeutically effective amount of an agent capable of down-regulating activity or expression of a component of the renin-angiotensin system.

Disclosed are β-amino acid monomers containing cylcoalkyl, cycloalkenyl, and heterocylic substituents which encompass the α and β carbons of the peptide backbone and β-polypeptides made from such monomers. Method of generating combinatorial libraries of polypeptides containing the β-peptide residues and libraries formed thereby are disclosed.

The present invention relates to muscle repair promoters for local application that contain a colony-stimulating factor (CSF) as an active ingredient. The muscle repair promoters of the present invention exhibit their effect at low doses, particularly when they are administered intramuscularly.

Provided herein are novel compounds and novel protected compounds that can be derived from polymyxin, including, e.g., polymyxin A. The novel compounds have antibacterial properties against a diverse range of Gram negative bacteria and reduced toxicity compared to polymyxins such as polymyxin A. Also provided are antibacterial pharmaceutical compositions containing the novel compounds and novel protected compounds, as well as methods for preparing the antibacterial compounds and protected compounds.

The present inventors investigated the effects of anti-IL-6 receptor antibodies on improving the condition of infarcted areas in myocardial infarction, and on suppressing left ventricular remodeling after myocardial infarction. As a result, the administration of anti-IL-6 receptor antibodies significantly suppressed the increase of MPO activity in the infarcted area and suppressed myocardial MCP-1 expression in both the infarcted area and the non-infarcted area. Furthermore, echocardiography and histological examinations revealed that cardiac hypertrophy is also suppressed.

The present invention provides variable mass labeling reagents, a set of the variable mass labeling reagents, and a multiplexed set of variable mass labeling reagents.

The present invention provides for a bio-mimetic polymer capable of catalyzing CO2 into a carbonate.

The present invention provides processes for the manufacturing of polypeptide conjugates. In particular, the invention provides methods for the purification of polypeptide conjugates, which include at least one polymeric modifying groups, such as a poly(alkylene oxide) moiety. Exemplary poly(alkylene oxide) moieties include poly(ethylene glycol) (PEG) and poly(propylene glycol). In an exemplary process, hydrophobic interaction chromatography (HIC) is used to resolve different glycoforms of glycoPEGylated polypeptides.

The present invention relates to treating a tissue in a mammal from the effects of reperfusion using flagellin.