A method of controlling a multiple step downshift is disclosed. Two offgoing shift elements are released and two oncoming shift elements are engaged to complete the downshift. During a first phase of the downshift, one of the offgoing shift elements controls the rate of increase of input shaft speed. During a second phase of the downshift, one of the oncoming shift elements controls the rate of increase of the input shaft speed. The method computes target torque capacities such that output torque and input shaft acceleration are continuous during the transition between phases. Furthermore, the method computes target torque capacities such that both oncoming clutches reach zero relative speed simultaneously as the input shaft reaches the final speed ratio.

A hybrid vehicle in which at least two shift ranges can be selected for a single running direction includes an engine, a motor generator, an EHC raising the temperature of a catalyst for cleaning up an exhaust gas from the engine, and an ECU. While the vehicle is running, if the engine is stopped and, of the two shift ranges, a shift range where larger decelerating force is produced by regenerative braking of the motor generator has been selected, the ECU causes the EHC to raise the temperature of the catalyst using electric power generated by the motor generator.

A method for optimized launch of a vehicle is provided wherein a driveline of the vehicle at least includes an engine, an automatic transmission, a system for exhaust gas recirculation, which are controlled by a driveline management system, wherein the management system is able to determine the mass of the vehicle, and whereby a launching gear of the transmission is calculated dependent at least on the determined mass of the vehicle, whereby a launching gear is chosen dependent of the power loss caused by the EGR and wherein the power loss caused by the EGR is determined, the available power to launch the vehicle is determined, and the launching gear is recalculated dependent of the available power, and selecting said recalculated launching gear before launch of the vehicle, launch the vehicle with the recalculated launching gear.

A vehicle travel control apparatus that controls state of travel of a vehicle by adjusting force that acts on the vehicle includes: an acting force adjustment portion that adjusts the force that acts on the vehicle, according to the state of travel of the vehicle; an operating state detection portion that detects an operating state of an operation member that is operated to control the state of travel of the vehicle; and an adjustment degree alteration portion that alters degree of adjustment made by the acting force adjustment portion, according to the operating state of the operation member.

A device for controlling an automatic transmission including a lock-up clutch control portion and a zero slip control portion for bringing a lock-up clutch into a zero slip state immediately before slippage occurs in accordance with a zero slip request outputted during a non-gear shift, wherein in a case where a target slip amount is equal to or smaller than a slip amount threshold value upon transition to the zero slip state, the zero slip control portion fixes the target slip amount to the slip amount threshold value and retains the fixed target slip amount for a predetermined period of time, and after the predetermined period of time has elapsed, gradually decreases the target slip amount from the slip amount threshold value to a zero slip amount with a predetermined gradient with time.

A method of operating a drive-train of a vehicle that comprises a combustion engine whose torque for driving the vehicle can be transmitted to a drive output via a transmission, with a hydraulically actuated clutch when the clutch is engaged. An electric machine provides torque which can act upon the drive-train. The clutch is closed by filling the clutch with hydraulic fluid through a circuit by way of a pump which can be driven by the engine and the electric machine. The method is to engage the clutch when the combustion engine is initially off and/or when the electric machine is initially switched off, determining a driving dynamic based on the behavior of the driver and adjusting the speed of the electric machine based on the determined driving dynamic such that the greater the determined driving dynamic is, the more rapidly the clutch is filled by the pump.

In hydraulic control, an electronic control unit controls controlled hydraulic pressure of a control valve in order to control a hydraulic oil amount in a torque converter and a hydraulic oil pressure of a forward-reverse travel switching mechanism, and the electronic control unit increases the controlled hydraulic pressure when the hydraulic oil amount in the torque converter is insufficient at an engine start or immediately after the engine start in comparison with a case where the hydraulic oil amount in the torque converter is sufficient. The hydraulic control device includes: the torque converter; the forward-reverse travel switching mechanism; the control valve configured to change the hydraulic oil amount in the torque converter and the hydraulic oil pressure of the forward-reverse travel switching mechanism by changing the single controlled hydraulic pressure; and electronic control unit.

A two-wheeled inverted pendulum vehicle includes: single-winding first and second motors respectively rotating one of two wheels; first and second control systems respectively supplying drive currents to the first and second motors; a sensor detecting a physical quantity that varies with a turn of the vehicle; a dynamic brake unit being able to switch between active and inactive states of dynamic brake being applied to the first motor; and a control unit, when the control unit has determined that the vehicle is turning about the second motor side on the basis of the physical quantity while supply of drive current from the first control system to the first motor is inhibited, activating dynamic brake in the dynamic brake unit. The first control system, when an abnormality has been detected in the first control system, inhibits supply of drive current from the first control system to the first motor.

A method for control of a gearbox installed in a motor vehicle (1), which method effects a downshift of the gearbox (20) from a first gear (G1), for which the acceleration a of the vehicle (1) is negative, to a second gear (G2), for which the acceleration a is positive or substantially equal to nil. The downshift involves at least one intermediate gear step between the first gear (G1) and second gear (G2), with a maximum engine speed at each intermediate gear step which is as high as, or higher than, a highest engine speed at a preceding intermediate gear step. Also, a system, a motor vehicle, a computer program and a computer program product for performing the method are disclosed.

A system and method of controlling a fail-safe for a vehicle is provided. The method includes determining, by a controller, that remaining hydraulic pressure exists in the clutch when the clutch is not opened and a target value of oil pressure for opening the clutch is maintained for a predetermined time period. In addition, whether a vehicle is stopped is confirmed in response to determining that remaining hydraulic pressure exists in the engine clutch. The controller is further configured to transmit a signal to shift to the vehicle to a neutral (N) stage to a transmission controller and shift to the vehicle to the N-stage in response to determining that the vehicle is stopped. Then, the engine is driven by the controller in response to determining that the vehicle is shifted to the N-stage.

Systems and methods for improving operation of a hybrid vehicle are presented. In one example, an electrical load may be automatically activated to consume electrical energy produced during driveline braking so that driveline braking may be extended. The electrical load may be a windscreen heater or other device.

A method of controlling an automated transmission for motor vehicles with one or several pressure activated positioning cylinders (6, 8, 20), via the assigned shift valves (10, 12), at least one main cut-off valve (4) which is positioned prior to the shift valves, and a control device for controlling the shift and main cut-off valves. The pressure requests, for the shifting, are determined and the respective main cut-off valves are triggered depending on the determined pressure requests. To enable a variable match of the supply pressure during transmission shifts, respective optimized pressures or pressure patterns are determined for certain shift scenarios which, for instance, consider a mass to be synchronized, the existence of a tooth-on-tooth position, or the like. Through this method, for instance, the load on shift elements, the shift timing, and the shift noise can be positively influenced.

Systems and methods for improving operation of a hybrid vehicle are presented. In one example, torque transferred via a driveline disconnect clutch is estimated based on characteristics of a torque converter to improve driveline operation.

Methods and systems are provided for controlling an engine system with a variable cam timing device. In one example, the variable cam timing device is operated to adjust engine valve timing differently at engine stop based on whether the engine stop is in response to an operator request or in response to an automatic controller initiated engine stop without an operator request.

A motor controlling apparatus includes a first target torque value calculator, a frequency detector, a second target torque value calculator, a torque command value calculator, a torque limiter, and a controller. The first target torque value calculator calculates a first target torque value, which is a target value of an output torque of a motor. The frequency detector detects a motor rotational frequency. The second target torque value calculator calculates a second target torque value based on the rotational frequency. The torque command value calculator mathematically combines (e.g., adds) the first and target torque values to calculate a torque command value. The torque limiter sets the signs of the first target torque value and the torque command value to be equal to limit the torque command value according to the first target torque value. The controller controls the motor based on the limited torque command value.

When a vehicle speed of a wheel loader (1) is determined to be not higher than a reference value (Yes) in step S4 and a forward/reverse command switch (40) is determined to have been switchingly operated (Yes) in step S5, the routine advances to step S6 where an increment ΔN of engine speed according to an engine load factor is determined. In step S7, the increment ΔN of engine speed is then added to a target engine speed Na corresponding to a depression stroke of an accelerator pedal (38), the thus-determined Na=Na+ΔN is set as a new target engine speed Na, and a target engine speed command i1 is sent to an engine controller (37).

The present invention provides for a transmission shift assembly for a vehicle and methods of monitoring and controlling the same. The transmission shift assembly includes a transmission having a shift position member movable between a plurality of gear positions, an actuator configured to move the shift position between the gear positions, and a linkage coupled to the actuator and movable between a plurality of positions in response to movement of the actuator. The assembly further includes a controller to control the actuator, an ignition to receive a key, and at least one key sensor positioned within the ignition and configured to transmit a signal to the controller upon sensing removal of the key, the controller controlling the actuator to move the shift position member to a predetermined gear position upon receiving the signal from the key sensor that the key has been removed from the ignition.

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.

A protein which is composed N-terminally of one or several C-terminal parts of the amino acid sequence of the mature tumor necrosis factor and C-terminally of one or several N-terminal parts of the amino acid sequence of the mature tumor necrosis factor, which activates epithelial ion channels and improves the lung function and which can be used for the manufacture of medicaments for the treatment of diseases associated with the lung function, such as oedemas.

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.

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.