The present invention generally relates to use of compounds and compositions as a chemosensitizers and/or radiosensitizers and/or inhibitors of PNKP phosphatase activity. The present invention provides pharmaceutical combinations and/or a pharmaceutically acceptable salt thereof, kits containing such compounds and/composition and methods of using such compounds and/or compositions.

The present invention provides a process for the synthesis of substituted phenoxymethylpropionic acid and related compounds. The compounds are useful for inhibiting the formation of AGEs (Advanced Glycation End Products).

The present invention provides compounds having the general structural formula (I), and pharmaceutically acceptable derivatives thereof, as described generally and in classes and subclasses herein, and additionally provides pharmaceutical compositions thereof, and methods for the use thereof for the treatment of any of a number of conditions or diseases involving abnormal or excessive fibrosis.

Many GTPases such as Ras, Ral and Rho require post-translational farnestylation or geranylgeranylation for mediating malignant transformation. Dual farnesyltransferase (FT) (FTI) and geranylgeranyltransferase-I (GGT-1) inhibitors (GGTI) were developed as anticancer agents from based on an ethylenediamine scaffold. On the basis of a 4-fold substituted ethylenediamine scaffold, the inhibitors are structurally simple and readily derivatized, facilitating extensive structure-activity relationship studies. The most potent inhibitor is compound exhibited an in vitro hFTase IC50 value of 25 nM and a whole cell H-Ras processing IC50 value of 90 nM. Several of the inhibitors proved highly selective for hFTase over the related prenyltransferase enzyme geranylgeranyltransferase-I (GGTase-I). A crystal structure of an inhibitor cocrystallized with farnesyl pyrophosphate in the active site of rat FTase illustrates that the para-benzonitrile moiety is stabilized by a π-π stacking interaction with the Y361β residue, suggesting an importance of this component of the inhibitors.

The present invention relates to the use of selective adenosine A1 agonists, in particular the dicyanopyridines of formula (I), for the treatment and/or prophylaxis of glaucoma and ocular hypertension as well as the their use for the production of a medicament for the treatment and/or prophylaxis of glaucoma and ocular hypertension.

The disclosure relates to BAX activators and therapeutic uses relates thereto. In certain embodiments, the disclosure relates to methods of treating or preventing cancer, such as lung cancer, comprising administering a therapeutically effective amount of a pharmaceutical composition comprising a compound disclosed herein or pharmaceutically acceptable salt to a subject in need thereof.

The invention provides a chemical entity of Formula (I) wherein R1, R2, R3, R4, Y and Z have any of the values described herein, and compositions comprising such chemical entities; methods of making them; and their use in a wide range of methods, including metabolic and reaction kinetic studies, detection and imaging techniques, and radioactive treatments; and therapies, including inhibiting PDE4, enhancing neuronal plasticity, treating neurological disorders, providing neuroprotection, treating a cognitive impairment associated with a CNS disorder, enhancing the efficiency of cognitive and motor training, providing neurorecovery and neurorehabilitation, enhancing the efficiency of non-human animal training protocols, and treating peripheral disorders, including inflammatory and renal disorders.

Compounds according to Formula I and Formula II are potent inhibitors of Arginase I and II activity: where R1, R2, R3, R4, R5, R6, R7, R8, R9, D, M, X, and Y are defined as set forth in the specification. The invention also provides pharmaceutical compositions of the compounds and methods of their use for treating or preventing a disease or a condition associated with arginase activity.

The present invention relates to a novel method for producing a pyridazinone compound and an intermediate thereof as shown in the following scheme: wherein the symbols are as defined in the specification.

Disclosed are compounds which inhibit the activity of anti-apoptotic Bcl-2 or Bcl-xL proteins, compositions containing the compounds and methods of treating diseases during which are expressed anti-apoptotic Bcl-2 protein.

The invention provides a chemical entity of Formula (I) wherein R1, R2, R3, Y, and n have any of the values described herein and compositions comprising such chemical entities; methods of making them; and their use in a wide range of methods, including metabolic and reaction kinetic studies, detection and imaging techniques, and radioactive treatments; and therapies, including inhibiting MAO, and MAO-B selectively, enhancing neuronal plasticity, treating neurological disorders, providing neuroprotection, treating a cognitive impairment associated with a CNS disorder, enhancing the efficiency of cognitive and motor training, providing neurorecovery and neurorehabilitation, enhancing the efficiency of non-human animal training protocols, and treating treating peripheral disorders (including obesity, diabetes, and cardiometabolic disorders) and their associated co-morbidities.

A fastening assembly includes a connecting member, a mounting member mounted to the connecting member, and a sliding member. The mounting member includes a first fixing portion. The sliding member is slidably received in the mounting member and the connecting member. The sliding member includes a first end exposed out of the first fixing portion, and a second end slidably received in the connecting member. The second end of the sliding member is operable to be extended out of or substantially coplanar with an end of the connecting member. The fastening assembly can be utilized to mount a heat sink to a board.

An electronic device includes, a circuit board including a through hole, a member including a screw hole, a screw including a screw body having an outer diameter smaller than an inner diameter of the through hole and a screw head having an outer diameter larger than the inner diameter of the through hole, wherein the screw body penetrates through the through hole to engage with the screw hole and the screw head is disposed on an opposite side of the circuit board to the member, and a first washer provided between the screw head and the circuit board, the first washer including a first washer body and a plurality of first washer legs extending from the first washer body toward the circuit board, the first washer legs being in contact with the circuit board and having a characteristic of reducing stress on the circuit board upon being heated.

A method of manufacturing fastenings or fasteners with radial outer contours, especially screws or threaded bolts, made of solid metal is performed by a device. The method manufactures the fastenings or fasteners preferably on a multi-stage press. Several recesses running in an axial direction at a fixed radial distance are formed in the shank-shaped section of a blank. The prefabricated blank with the recesses is inserted into a multi-part split mold within a multi-stage press, whose die stocks have an inner profiling forming the outer contour, and are opened in the starting position, that at the places where the die stocks are opened, there are the recesses. During the closing movement of the die stocks, at least one radial outer contour is pressed on the shank-shaped section of the blank by radial action of forces, with the recesses preventing material from getting between the die stocks during the pressing process.

The present invention is premised upon method of manufacturing rolled pierce nuts having a predetermined profile from a metal rod, more particularly to a method and apparatus delivering greater manufacturing flexibility through the use of multiple stations with flexible inputs and outputs.

The present invention provides a method for manufacturing a fitting that has a configuration where a fitting plate and a blind nut are integrally formed and also provides a tap tool for use in this method. According to the present invention, performing tap processing to an internal diameter portion to integrally form a portion corresponding to the blind nut, when a tap tool having a protrusion at an end thereof is utilized to be inserted into the bag-like blind hole at a planned part of the blind nut and the tap processing is carried out, the protrusion provided at the end of the tap tool comes into contact with an inner wall at the end of the bag-like blind hole, and a pressed material thereby forms a convex shape on an outer side of the bag-like blind hole.

A magnetized nut for fastening a compressor wheel of an exhaust turbocharger to a turbo shaft. The nut has a base body made of a non-magnetic material forming a hollow space for accommodating a magnetic material, and a method for the production of the magnetized nut. In order to provide a magnetized nut that is produced in a simple and cost-effective manner and ensures as equal a distribution of mass as possible with regard to the rotational axis of the nut, the magnetic material is introduced into the hollow space using injection molding.

There is provided a nut having a thread portion having a female thread, a metallic plate portion having a base segment, and a hardness gradient portion provided between the thread portion and the metallic plate portion. The thread portion, metallic plate portion and the hardness gradient portion are monolithic each other, a metallographic structure of the metallic plate portion differs from a metallographic structure of the thread portion and a hardness of the hardness gradient portion is lower than a hardness of the thread portion and lowers from the thread portion toward the metallic plate portion.

A full-round head nail having an offset head is configured with a gusset formed integrally between an undersurface of the offset head and a superior portion of a shank. The head of the nail is relatively thin, and the shank is positioned radially off center of the round head such that no heel is formed at a point tangential to both the head and the shank. The gusset has a lofted surface tapering radially from a roundness at the zero heel to a taper at the toe. The gusset reinforces the junction of the shank with the head, supports the toe of the head, and distributes the force of a load on the head through a longitudinal axis of the shank, preventing the toe from bending or yielding and prevents the shank from yielding to the stresses of the load applied.

A set of tooling for making pointed headed bolts of a given diameter in numerous lengths with roll thread ready threaded to the head and partially threaded shanks in a four forming station forming machine, the tools being configured to work on wire stock as received at the first station of a diameter larger than or substantially the same as the roll diameter and not greater than the nominal diameter of the bolt, including at least two sequential head forming tools for mounting on the slide, an extrusion pointing tool for mounting on the die breast, a roll diameter extrusion tool for mounting on the die breast and a head support tool mountable in a station on the slide at multiple axial positions corresponding to standard lengths of the bolts being made, the head support tool being arranged to work at either the extrusion pointing station or the roll diameter extrusion station.

Provided is a method for manufacturing an FRP member with insert which enables to reduce a machining time to improve productivity. First, a threaded hole 11 is formed in an insert 3. An FRP member 2 where at least the threaded hole 11 of the insert 3 is covered with a coating 4 made of FRP is molded. A counter-bored hole 31 that penetrates the coating 4 of the FRP member 2 to communicate with the threaded hole 11 of the insert 3 is formed, to thereby obtain an FRP component 1 with insert. Accordingly, a machining step after molding the FRP member 2 in which dry machining is required includes only the boring step of forming the counter-bored hole 31 in the FRP member 2. Thus, the machining time can be reduced, and the productivity can be improved.

Embodiments of the present invention are directed to improved designs of railroad spikes and improved methods of manufacturing the same. According to one exemplary embodiment, a method for manufacturing a railroad spike may comprise the steps of: preparing a metal blank having a substantially circular cross-section; subjecting the metal blank to at least one cold heading process and at least one cold extrusion process to form a railroad spike having (a) a circular head with a fillet at its bottom side that is angled to engage a railroad tie plate or rail base and (b) a non-threaded shank with a substantially square cross-section and a chiseled tip; and coating the railroad spike with an anti-corrosion material.

A spiral fluted tap is provided which includes a threaded portion having an external thread corresponding to an internal thread to be cut and a cutting edge formed along a spiral flute formed to divide the external thread, and being screwed into a prepared hole that is provided on a workpiece to cut an internal thread by the cutting edge on an inner circumferential surface of the prepared hole with discharging chips toward a shank via the spiral flute, the spiral flute having a stepped portion at a rear end of a chamfer portion or in a portion on a shank side from the rear end of the chamfer portion in the threaded portion, and a flute bottom diameter on a distal end side of the spiral fluted tap from the stepped portion being smaller than a flute bottom diameter on a shank side from the stepped portion.

In various embodiments, a tapered thread roll, a set of tapered thread rolls, a thread rolling tool, and a thread rolling method are provided for rolling angled or tapered threads onto a workpiece to create a threaded workpiece. In at least one embodiment, the threaded workpiece may comprise a polished rod or a polished rod precursor as specified by the American Petroleum Institute for use in an oil-field sucker-type pump, for example.

A full-round head nail having an offset head is configured with a gusset formed integrally between an undersurface of the offset head and a superior portion of a shank. The head of the nail is relatively thin, and the shank is positioned radially off center of the round head such that no heel is formed at a point tangential to both the head and the shank. The gusset has a lofted surface tapering radially from a roundness at the zero heel to a taper at the toe. The gusset reinforces the junction of the shank with the head, supports the toe of the head, and distributes the force of a load on the head through a longitudinal axis of the shank, preventing the toe from bending or yielding and prevents the shank from yielding to the stresses of the load applied.

A slotted inverse tap, compressible for insertion past damaged entry threads in blind holes. (FIG. 1 thru FIG. 5) The tool can be made to smaller sizes than that of prior art. An elongate slot (23) proceeds through a first threaded end (21), then well into a reduced diameter cylindrical body (25). After insertion to the hole bottom, a tabbed shim (28) is inserted to the slot from its side, then pressed down until stopped. The shim (28) enforces mating engagement with undamaged internal threads. A second end of hex and/or squared or other configuration facilitates use of a tap wrench or other tool for rotational extraction. Damaged threads are reformed/re-cut upon rotational withdrawal.

A faceted bone screw and a method for manufacturing the same includes a screw thread configuration having facets that are substantially transverse to the thread. The facets are generally made up of a plurality of transitioning peaks and valleys which vary the depth of the thread and are disposed in one or more locations throughout the threaded portion of the bone screw. The facets operate to reduce the torque required to drive the bone screw into bone, while at the same time operate to assist in anchoring the bone screw within the bone once inserted therein, and thereby reduce the possibility for the screw backing out after insertion.

An apparatus to produce a self-piercing and clinch nut includes a first forging die assembly, a second forging die assembly, a third forging die assembly, a transfer mechanism, and a controller. The first forging die assembly is configured to subject a blank to first processing. The second forging die assembly is adjacent to the first forging die assembly and configured to subject the blank to second processing after the blank has undergone the first processing in the first forging die assembly. The third forging die assembly is adjacent to the second forging die assembly and configured to subject the blank to third processing after the blank has undergone the second processing in the second forging die assembly. The controller is configured to control the first forging die assembly, the second forging die assembly, the third forging die assembly, and the transfer mechanism to operate.

A releasable lock nut assembly for securing a bearing on a threaded hub may include a thrust washer including a disk portion and a peripheral skirt extending axially away from the disk portion, the peripheral skirt having a plurality of openings and a characteristic diameter measured at an axial location of the openings, and a protuberance proximate to at least one of the openings. The assembly may also include a lock ring inserted into the thrust washer, where the lock ring includes a plurality of tangs that extend beyond a lock ring major diameter such that the tangs fit within the openings of the thrust washer. The protuberance may be deformed such that all of the peripheral skirt is within the characteristic diameter, and the protuberance may define an internal envelope of the thrust washer where the internal envelope is larger than the major diameter of the lock ring.

Tap and die devices are provided to repair internal and external threads, respectively. The tap and die devices are provided with components that coaxially align the tap and die to the nut or fitting being repaired. The tap and die devices are easily portable, compact tools that can be used in tight places.

A nail-forming apparatus and method to rapidly form nails typically with circular heads is provided. One aspect relates to a sequential wire piece positioner configured for sequentially positioning wire pieces respectively adjacent a plurality of nail head formers. The wire piece positioner may include several carriages related to moving and forming the wire pieces.

Disclosed herein is a method for manufacturing a screw comprising a continuous thread with a variable thread pitch, in which method a blank is rolled between two rolling dies, wherein in each rolling die a rolling profile is formed that comprises a host of curved non-parallel depressions. The depressions are designed and arranged in such a manner that during rolling no volume transport, or as little volume transport as possible, in the axial direction takes place, or a volume transport from a region of the blank where a thread section with a larger thread pitch is to be formed, to a region in which a thread section with a smaller thread pitch is to be formed takes place.

A method for manufacturing a bolting part, such as a screw or a nut. The bolting part having a head with a periphery having at least one shoulder extending in a radial plane. The method includes at least the following forming steps: shearing of a wire of material so as to obtain a part of determined length, calibration of the part so as to correct the geometry of the part, rough machining of the calibrated part so as to obtain the head of the bolting part, and finishing of the rough-machined part by means of a third punch so as to form a head having at least one shoulder. The calibration, rough machining and finishing steps being carried out only by cold heading.

A polishing pad, having a polishing layer comprising a thermoset polyurethane foam, wherein the polishing layer has an in-plane variation of 12 or less in microrubber A hardness, the variation being obtained by measuring the polishing layer from a polishing surface side of the layer, the thermoset polyurethane foam contains, as raw material components, an isocyanate component and active-hydrogen-containing compounds, and the active-hydrogen-containing compounds comprise a trifunctional polyol having at least one terminated hydroxyl group that is a secondary hydroxyl group, and having a hydroxyl group value of 150 to 1,000 mg KOH/g in an amount of 10 to 50 parts by weight for 100 parts by weight of the active-hydrogen-containing compounds.

A fiber optic connector fiber stub remover and method for automated fiber stub removal. The device has a top plate with a platen opening, and a platen with a well that carries a polishing film over the well. An air pocket is formed between the polishing film and the well. The platen is positioned with a top surface of the polishing film accessible via the platen opening. A fixture holds connector ends of fiber optic cables with fiber stubs extending therefrom, and a weight biases the fiber stubs into contact with the polishing film. A motor is controlled by a motor control unit to control a ramp up time and final speed of movement of the platen over a timespan. Each connector ends moves independently relative to the polishing film. The air pocket provides shock absorption of the polishing film so that an ideal pressure is exerted on each fiber stub during stub removal.

The polishing solution for CMP according to the invention comprises abrasive grains, an additive and water, and the polishing solution comprises an organic compound satisfying specified conditions as the additive. The polishing method of the invention is for polishing of a substrate having a silicon oxide film on the surface, and the polishing method comprises a step of polishing the silicon oxide film with a polishing pad while supplying the polishing solution for CMP between the silicon oxide film and the polishing pad.

The process and apparatus for mobile separation and recovery of used contaminants abrasive blasting material from a work site. Entrained contaminants within used blast material are removed by a self-contained mobile platform process using multiple stage cleaning system including dual cyclonic separation, multiple stage dust filters with large debris magnetic drum, airwash and vibratory separation in a flow through containment and blast media separation process.

A honing machine has at least one clamping unit that clamps a workpiece and has a rotary drive for the workpiece. A spindle unit has a stroke drive for an inner honing tool for inner honing of the workpiece. An outer honing device that is movable relative to the workpiece in an axial direction of the workpiece is provided. The outer honing device has several honing stones and an advancing device acting on the honing stones. The honing stones each are advanced in a radial direction relative to the workpiece. The advancing device has at least one linear drive for each one of the honing stones and a common drive motor for all of the linear drives.

Disclosed are an apparatus and a method for monitoring a glass plate polishing state. The apparatus may include a location measuring unit for measuring a location on a glass plate being polished by a polishing machine, a current measuring unit for measuring an electric current flowing into the polishing machine, a memory unit for storing a reference value of the electric current flowing into the polishing machine for each polishing location of the glass plate, and a control unit for determining whether a polishing state is faulty, by comparing a value of the electric current measured by the current measuring unit for each polishing location measured by the location measuring unit with a corresponding reference value of the electric current stored in the memory unit for each polishing location.

Methods of shaping a glass sheet each include a step of removing a first portion of the glass sheet to form a first beveled surface. The methods further include the step of removing a second portion of the glass sheet to form a second beveled surface. The methods still further include the step of removing a third portion of the glass sheet comprising a remainder of an end surface of an edge portion of the glass sheet. In further examples, glass sheets are also provided with a first bevel surface intersecting a first glass-sheet surface and an apex surface, and a second bevel surface intersecting a second glass-sheet surface and the apex surface. The glass sheet exhibits a probability of failure of less than 5% at an edge stress of 135 MPa.

A fully symmetric cutter grinding machine with 5-axis includes a grinding machine base and a pillar, sliding rails are vertically arranged on an inside of the pillar, the sliding rails are provided with a grinding wheel head bracket, the grinding wheel head bracket comprises torque motors vertically provided, a lower part of the torque motor is connected to a horizontally provided spindle by means of a bearing of a rotation table, grinding wheels rotating around an axis of the spindle are symmetrically provided at two sides of the spindle, the grinding wheel head bracket further comprises a big rotatable pulley provided at an upper part of the grinding wheel head bracket and driven to rotate by spindle motors, the big pulley is connected to a spindle pulley by a wide synchronous belt.

A holding body includes a fastening layer which has a fastening surface configured to fasten a flexible grinding device. The fastening layer includes an air- and dust-permeable material and is substantially full-surface. The fastening layer includes a textile material. The holding body also includes a supporting body which has a supporting surface configured to support a holding surface of the fastening layer. The supporting body is air- and dust-permeable and includes an open-cell foam. A grinding system includes such a holding body and such a flexible grinding device.

A coated abrasive article comprises an abrasive layer secured to a backing. The abrasive layer comprises abrasive particles secured by at least one binder to a first major surface of the backing. A supersize is disposed on at least a portion of the abrasive layer. The coated abrasive article has a melt flow zone adjacent to an edge of the coated abrasive article, wherein the melt flow zone has a maximum width of less than 100 micrometers, and the melt flow zone has a maximum height of less than 40 micrometers. Methods of using infrared lasers to ablate coated abrasive articles are also disclosed, wherein a laser wavelength is matched to a component of the coated abrasive article.

The invention relates to a device (1) for machining a stepped shaft (2), having a workpiece rest (6); having a disk arrangement (3) which has a grinding disk (4) and a control disk (5); and having an axial stop arrangement (7), wherein the axial stop arrangement (7) has a contact adapter (8) which can be temporarily placed in contact with an end surface portion (9) of the shaft (2) and which has a punctiform contact surface (10) for contact against a stop part (11) of the stop arrangement (7).

A dust collecting attachment that is mounted on a sander includes a suction portion mounted on a portion of a front housing where an output shaft projects, a flexible hose having a front end of the flexible hose connected to the suction portion, a discharge portion connected to a rear end of the flexible hose and a changeable member placed on both a motor housing and the discharge portion. The changeable member allows the discharge portion to be mounted at any position around an axis of the motor housing.

Particularly, a thin-film solar cell panel or the like is processed without necessity of attaching and detaching of mask and washing steps with respect to a workpiece in a fine blasting employing a fine abrasive. A negative pressure space (20) and an opposing negative pressure space (40) having openings (22, 42) are opposed by being spaced at a movement allowable interval of the workpiece such as a thin-film solar cell panel or the like and so as to face one side edge in the same direction as a moving direction of the workpiece. Further, a fine abrasive is injected while relatively moving the workpiece in a moving direction (T) with respect to a blast gun (30) in which an injection hole (31) is disposed within the negative pressure space (20), and the fine abrasive injected into the negative pressure space (20) and/or the opposing negative pressure space (40) and a cut and removed cut scrap such as a thin film layer or the like are sucked and recovered through the intermediary of suction devices (21a, 21b) and/or an opposing suction device (41) respectively communicating with the spaces (20) and/or (40).

An automated method for reconditioning a plurality of digital discs within a reconditioning apparatus is disclosed. The method comprises holding the digital discs in a load area, and then transferring each of the digital discs from the load area to at least one workstation with a disc transfer mechanism. The method also comprises reconditioning each of the digital discs transferred to the workstation with at least one worktool operable to remove a portion of the protective coating of each of the digital discs without removal of the data underlying the protective coating. The method further comprises transferring each of the digital discs from the workstation to an unload area with the disc transfer mechanism, and then holding the digital discs in the unload area for manual retrieval. Advantageously, the digital discs may be automatically reconditioned within the reconditioning apparatus without manual manipulation of the digital discs during the reconditioning process. Various exemplary embodiments of the reconditioning apparatus and associated method are provided.

Methods and apparatus for making and using tools, for example concrete cutting blades. The tool includes a first layer and second layer that are oppositely disposed. The first and second layers include working surfaces that support at least one working element when the working element is applied to a work piece. Additionally, an intermediate structure is included between the first and second layers. The intermediate structure can include a plurality of components extending in the area between the structural surfaces and the working surfaces.

A carboxylate detergent prepared by the process comprising (a) alkylating a hydroxyaromatic compound with at least one normal alpha olefin having from about 12 to about 30 carbon atoms per molecule that has been isomerized to obtain an isomerized alpha olefin having 15-98 wt % branching and a residual alpha olefin content of between from about 0.1 to about 30 wt %, thereby producing an alkylated hydroxyaromatic compound; (b) neutralizing the resulting alkylated hydroxyaromatic compound with an alkali metal base; (c) carbonating the alkali metal salt from step (b) with carbon dioxide; (d) acidifying the salt produced in step (c); and (e) overbasing the resulting alkylated hydroxyaromatic carboxylic acid.

The present invention provides transgenic soybean event MON87769, and cells, seeds, and plants comprising DNA diagnostic for the soybean event. The invention also provides compositions comprising nucleotide sequences that are diagnostic for said soybean event in a sample, methods for detecting the presence of said soybean event nucleotide sequences in a sample, probes and primers for use in detecting nucleotide sequences that are diagnostic for the presence of said soybean event in a sample, growing the seeds of such soybean event into soybean plants, and breeding to produce soybean plants comprising DNA diagnostic for the soybean event.