SUBSTITUTED N-ARYLSULFONYLHETEROCYCLI AMINES AS GAMMA SEKRETASE HEMMER

Verfahren zum Ausführen einer Vorschub-Dicken-Regelung in einem Tandemkaltwalzwerk

The present invention relates to the field of strip cold rolling, and in particular to a thickness control method for strips in a tandem cold mill. A performance feed-forward thickness control method in a tandem cold mill comprises selecting one or more frames as virtual indirect measuring instruments for the strip performance, in which the frame S1 must be used as a virtual indirect measuring instrument for the strip performance; calculating the deformation resistance fluctuation of supplied materials, providing a load cell on the frames that are selected as the indirect measuring instruments for the strip performance, and obtaining the deformation resistance fluctuation of the supplied materials of the frame Si by calculation; finally, calculating the feed-forward adjustment amount of each frame. The present invention performs the feed-forward thickness control through the deformation resistance force of the supplied materials measured indirectly, and by measuring the deformation resistance ...

Verfahren zum Ausführen einer Vorschub-Dicken-Regelung in einem Tandemkaltwalzwerk

A feedforward thickness control method for the performance of a cold rolling mill. One or more frames are selected as virtual indirect measuring instruments for the strip performance, and frame S1 must be used as a virtual indirect measuring instrument for the strip performance. The deformation resistance fluctuation of supplied materials is calculated, a pressure measuring head is disposed on the frames that are selected as the indirect measuring instruments for the strip performance, the deformation resistance fluctuation of supplied materials of frame S1 is obtained through calculation, and finally the amount of the feedforward adjustment for each frame is calculated. By performing feedforward thickness control through the indirectly measured deformation resistance of the supplied materials, and by measuring the deformation resistance of each section of the strip of the supplied materials through the selected frame, the influence of the performance fluctuation of hot-rolled finished ...

Gamma secretase modulators

In its many embodiments, the present invention provides a novel class of heterocyclic compounds as modulators of gamma secretase, methods of preparing such compounds, pharmaceutical compositions containing one or more such compounds, methods of preparing pharmaceutical formulations comprising one or more such compounds, and methods of treatment, prevention, inhibition, or amelioration of one or more diseases associated with the central nervous system using such compounds or pharmaceutical compositions.

Gamma secretase modulators

In its many embodiments, the present invention provides a novel class of heterocyclic compounds as modulators of gamma secretase, methods of preparing such compounds, pharmaceutical compositions containing one or more such compounds, methods of preparing pharmaceutical formulations comprising one or more such compounds, and methods of treatment, prevention, inhibition, or amelioration of one or more diseases associated with the central nervous system using such compounds or pharmaceutical compositions.

Tetrahydropyranochromene gamma secretase inhibitors

GAMMA SECRETASE MODULATORS

In its many embodiments, the present invention provides a novel class of heterocyclic compounds as modulators of gamma secretase, methods of preparin g such compounds, pharmaceutical compositions containing one or more such co mpounds, methods of preparing pharmaceutical formulations comprising one or more such compounds, and methods of treatment, prevention, inhibition, or am elioration of one or more diseases associated with the central nervous syste m using such compounds or pharmaceutical compositions.

Multi -functional sensor measurements support of jumbo size

The utility model discloses a multi -functional sensor measurements support of jumbo size, base on horizontal guide rail supports including setting up, peripheral frame and be used for stationary sensor's test frame, peripheral frame is fixed on the base supports, and it is embedded in peripheral frame that the test frame passes through tilting mechanism, the sensor is fixed on the survey point that test frame interior iron wire was shaped, the bottom of peripheral frame be provided with the horizontal running gear that the level of support motion was measured in the drive, be provided with the elevating system of drive test frame elevating movement on the lateral wall, tilting mechanism, horizontal running gear and elevating system are connected with control system. The utility model provides a multi -functional sensor measurements support of jumbo size should test the stationary sensor that the portal not only can not damage, can conveniently measure level or vertical plane's air current ...

Process for preparing titanium and titanium alloy from titanium hydride powder

The invention discloses a process for preparing a metallurgical powder product from titanium hydride powder preparedmade by hydrogenating sponge titanium instead of titanium powder. The process comprises the following steps of: firstly, hydrogenating sponge titanium, crushing and, rating and mixing brittle titanium hydride, and mixing the titanium hydride with an alloy element; and then, carryingout near-net shape pressing to finish dehydrogenation in a vacuum sintering process. In the process of directly forming the titanium hydride powder, because of the secondary crushing of the brittle titanium hydride powder, the pressed green density is higher than that obtainedan occasion when titanium or titanium alloy powder is used, and the titanium is prevented from being oxidized. In the sintering process, the density of a sintering blank can rapidly rise (to be higher than 99 percent) because of the decomposition of the titanium hydride. The method has the characteristics short process flows ...

Method for distributing code stream encrypting and decrypting keys in SIP video monitoring system

Manufacturing process for metal felt sealing member and dedicated press forming die

The invention relates to a manufacturing process for a metal felt sealing member, which comprises the following steps: metal wires are closely wound to form spiral spring rolls, the spiral spring rolls are stretched to form spiral springs with equal pitch, the spiral springs are cross-woven to form a metal felt sealing member blank, and the metal felt sealing member blank is molded by press forming process in a dedicated forming die. The invention also relates to a dedicated press forming die for manufacturing the metal felt sealing member, which comprises a lower die right base, a lower die left base, a lower die left/right base splint, a spacer plate, an upper die cutter blade, an upper die left base, an upper die right base, short bolts, a short cylindrical pin, a long bolt and a long cylindrical pin, wherein the lower die right base and the lower die left base are fixedly connected through the short cylindrical pin, the long bolt and the long cylindrical pin; the lower die left/right ...

Formation pore pressure field establishing method based on well-seismic data fusion

The invention provides a formation pore pressure field establishing method based on well-seismic data fusion. The formation pore pressure field establishing method comprises the steps that 1, well-seismic data are obtained and preprocessed; 2, converting the seismic stacking velocity or the root-mean-square velocity field into a seismic horizon velocity field; 3, comparing, correcting and fusing all the preprocessed well data acoustic logging information of the work area and a seismic horizon velocity field; 4, establishing a formation pore pressure prediction model of the area according to the well logging data of the drilled well in the area; 5, combining the fused interval velocity field with a formation pore pressure model, and preliminarily calculating a work area formation pore pressure field; step 6, calculating a formation pore pressure curve of all drilled wells in the work area by using well logging sound wave data, and carrying out constraint correction by using actual drilling ...

Oligopeptide POP1 as well as preparation method and application thereof

The invention relates to the field of biological medicine, in particular to oligopeptide POP1 as well as a preparation method and application thereof. The amino acid sequence of the primary structure of the oligopeptide POP1 is as shown in SEQ ID NO. 1; the polypeptide comprises oligopeptide POP1 or a pharmaceutically acceptable salt of the oligopeptide POP1; the preparation method comprises the following steps: crushing periplaneta americana, extracting with an organic solvent, and decolorizing to obtain a concentrated solution; performing chromatography, separation and purification on the concentrated solution for multiple times to obtain a compound; performing vacuum freeze drying on the compound to obtain the oligopeptide POP1; according to the application, the oligopeptide POP1 is used for preparing the medicine for treating wounds, scalds and ulcers; the short peptide only containing five amino acids in length is screened and separated from periplaneta americana, and the structure ...

PROCESS FOR PREPARING BETA 3 AGONISTS AND INTERMEDIATES

The application is directed to efficient and economical processes as described in more detail below for the preparation of the beta 3 agonists of the formula of 1-7 and intermediate compounds that can be used for making these agonists. The present disclosure relates to a process for making beta-3 agonists and intermediates using ketoreductase (KRED) biocatalyst enzymes and methods of using the biocatalysts.

Verfahren zum Ausführen einer Vorschub-Dicken-Regelung in einem Tandemkaltwalzwerk

Die vorliegende Erfindung betrifft das Gebiet des Bandkaltwalzens und insbesondere ein Verfahren zur Dickenregelung für Bänder in einem Tandemkaltwalzwerk. Ein Verfahren zum Ausführen einer Vorschub-Dicken­ Regelung in einem Tandemkaltwalzwerk umfasst ein Auswählen eines oder mehrerer Gerüste als virtuelle, indirekte Messinstrumente für die Bandgüte, wobei das Gerüst S1 als ein virtuelles, indirektes Messinstrument für die Bandgüte verwendet werden muss, Berechnen der Schwankung des Verformungswiderstands der zugeführten Materialien, Bereitstellen einer Wägezelle an den Gerüsten, die als die indirekten Messinstrumente für die Bandgüte ausgewählt sind, und Erhalten der Schwankung des Verformungswiderstands der zugeführten Materialien des Gerüsts S; mittels Berechnung, schließlich Berechnen des Vorschubeinsteilwerts für jedes Gerüst. Die vorliegende Erfindung führt die Vorschub-Dicken-Regelung durch den indirekt gemessenen Verformungswiderstand der zugeführten Materialien aus und mittels Messen des Verformungswiderstands jedes Bandabschnitts der zugeführten Materialien durch die ausgewählten Gerüste, wobei der Einfluss der Güteschwankung von warmgewalzten Enderzeugnissen der zugeführten Materialien auf die Genauigkeit der Dickenregelung beim Kaltwalzens vermieden wird und wobei die Genauigkeit der Dickenregelung verbessert wird, was sich vorteilhaft auf das Sicherstellen der Genauigkeit der Dicke der Enderzeugnisse aus den Bänder in der Längsrichtung der gesamten Stahlcoil auswirkt, wobei die Schwankung der Dicke der Enderzeugnisse aus den Bänder verringert und ein stabiles Walzen sichergestellt wird. The present invention relates to the field of strip cold rolling, and more particularly to a method for controlling the thickness of strips in a tandem cold rolling mill. A method of performing feed-to-thickness control in a tandem cold rolling mill includes selecting one or more stands as virtual, indirect, strip grade meters, wherein the stand S1 must be used as a ...

PROCEDURE FOR the PRODUCTION OF SUBSTITUTED NARYL N' Ä3 (1H-PYRAZOL-5-YL) PHENYLÜ UREA AND INTERMEDIATE OF it.

Gamma secretase modulators

Gamma secretase modulators

Evaluation data processing system and data processing method for municipal company teams

The invention discloses an evaluation data processing system and a data processing method for municipal company teams. The data processing system comprises a system basic data maintenance module, an evaluation rule establishment module, a report setting, evaluation authority set and data input module, a data collection, data statistics, data analysis, data analysis result display and statement output module and a benchmarking team and advanced team matching module, wherein the report setting, evaluation authority set and data input module is used for setting the report authority and the evaluation authority, and inputting report data; the data collection, data statistics, data analysis, data analysis result display and statement output module is used for summary statistics of the input evaluation scores of the teams, calculation of the corresponding team evaluation detailed rules and regulations according to the set statistics template, concrete analysis of the team evaluation, display ...

Graphene field effect transistors for detection of ions

A graphene-based ion sensitive field effect transistor (GISFET) with high sensitivity and selectivity for ions is provided. For example, the GISFET of the present invention can exhibit high sensitivity and selectivity for K+ ions has been demonstrated utilizing a valinomycin-based ion selective membrane. The sensitivity of the GISFET can be at least about 50 millivolts/decade and can be stable for a time period of about two months, indicating the GISFET's reliability and effectiveness for physiological monitoring.

DIARYL AND ARYL HETERO ARYL UREA DERIVATIVES AS MODULATORS of the 5-HT2A-SEROTONINREZEPTORS, ITSELF TO the PROPHYLAXIS AND TREATMENT OF ILLNESSES BEING SUITABLE STANDING THEREBY IN the CONNECTION

Gamma secretase modulators

Diaryl and arylheteroaryl urea derivatives as modulators of the 5-HT2a serotonin receptor useful for the prophylaxis and treatment of disorders related therto

AUTOMATIC DROOP CONTROL METHOD FOR MICROGRIP INVERTERS BASES ON SMALL-SIGNAL STABILITY ANALYSIS

Disclosed is a microgrid inverter sagging automatic control method based on small-signal stability analysis. According to the control method, on the basis that the slope of a P-f sagging curve and the slope of the Q-V sagging curve are actively regulated, small-signal stability analysis is introduced, the feasibility of the slopes after the active regulation is verified, and no-deviating regulation of voltages and frequencies is implemented on the premise that the stability of a system is ensured. According to the present invention, for distributed generation under sagging control in an islanding state, the requirement of load changes is met by automatically regulating the slopes of the sagging curves and changing a reference active power value corresponding to a rated frequency in the sagging curves and a reference reactive power value corresponding to a rated voltage, and no-deviating frequency regulation and voltage regulation are implemented; the range of the slopes of the sagging curves ...

AUTOMATIC DROOP CONTROL METHOD FOR MICROGRID INVERTERS BASED ON SMALL-SIGNAL STABILITY ANALYSIS

The invention discloses an automatic droop control method for microgrid inverters based on small-signal stability analysis. On the basis of actively adjusting the slopes of P-f and Q-V droop curves, the control method introduces small-signal stability analysis to verify the feasibility of the actively adjusted slopes, thereby realizing no-deviating adjustment of voltage and frequency on the premise of guaranteeing system stability. For distributed power sources under droop control in an islanding status, the automatic droop control method for microgrid inverters based on small-signal stability analysis involves varying an active power reference value corresponding to a rated frequency and a reactive power reference value corresponding to a rated voltage in the droop curves by automatically adjusting the slopes of the droop curves, thus meeting the requirements of load changes and realizing no-deviating adjustment of frequency and voltage; besides, the slope ranges of the droop curves allowed ...

BENZENESULFONYL-CHROMANE, THIOCHROMANE, TETRAHYDRONAPHTHALENE AND RELATED GAMMA SECRETASE INHIBITORS

Disclosed are novel gamma secretase inhibitors of the formula (I): or a pharmaceutically acceptable salt, solvate, or ester thereof, wherein L1' n, X, Ar, Y, Z, Q, and Q1 are as defined herein. Also disclosed are methods for inhibiting gamma secretase, methods for treating Azheimer's disease, methods of treating one or more neurodegenerative diseases, and methods of inhibiting the deposition of amyloid protein (e.g., amyloid beta protein) in, on or around neurological tissue (e.g., the brain) using the compounds of formula 1Ø ...

Honokiol derivative and preparation method and application thereof in preparation of antitumor drugs

The invention provides a honokiol derivative and a preparation method and the application thereof in preparation of antitumor drugs. According to the invention, a new-skeleton honokiol derivative is extracted and separated from ripe fruits of magnolia gradiflora by using an active track separation method. The honokiol derivative or a salt thereof can be prepared into preparation forms of intestinal or parenteral assembled drugs according to known methods in the preparation field, the preparation forms mainly include liquid preparation, granule, tablet, infusion, gelatin pearl, slow-release preparation, dripping pill or orally disintegrating preparation, and the administration manners of preparations mainly include oral medication or injection. Compared with effective component honokiol of traditional Chinese medicine mangnolia officinalis, the honokiol derivative provided by the invention has better antitumor activity and a better effect of inducing tumor cell apoptosis; therefore the honokiol ...

Construction methods and application of fusion protein and vector thereof

The invention discloses construction methods and application of a fusion protein and a vector thereof and aims to provide a method for constructing a fusion protein scientifically and effectively by taking TALEN (transcription activator-like effector nuclease) as a cell strain. The method is technically characterized in that the fusion protein has a structure of EGFP-_mODC_NLS, and an expression vector of the fusion protein comprises the fusion protein with the structure of EGFP-_mODC_NLS and an NLS cutting TALEN plasmid pair of the fusion protein. The fusion protein is used for the NLS cutting TALEN plasmid pair and a prokaryotic expression protein with the structure of EGFP_mODC_NLS_TALEN_R and a protein with the structure of EGFP_mODC_NLS_TALEN_R, and the fusion protein can be used for verifying the transfection efficiency of the TALEN plasmid pair and the activity of the TALEN plasmid pair in cells. The invention belongs to the field of biotechnology.

Ceftizoxime sodium compound preparation

An antibacterial compound ceftizoxime sodium is prepared from the ceftizoxime or its physiologically acceptable salt and a beta-lectamase depressant in weight ratio of (2-8):1.

SULFUR-SUBSTITUTED PODOPHYLLOTOXIN DERIVATIVE, SYNTHESIS METHOD THEREOF, AND USE THEREOF

The present invention discloses a sulfur-substituted podophyllotoxin derivative, synthesis method thereof, and use thereof. The present invention introduces a rigid aromatic heterocyclic compound, as well as a further sulfonamidated product of 3-amino-5-mercapto-1,2,4-triazole, 2-amino-5-mercapto-1,3,4-thiadiazole, 4-methylbenzenesulfonyl chloride, or 4-methoxybenzenesulfonyl chloride as a substituent group, into position 4 of the C-ring of podophyllotoxin or 4′-demethylepipodophyllotoxin to obtain the podophyllotoxin derivative shown in formula (V), said derivative having significantly increased antitumor activity and reduced toxic side effects. Experiments on in vitro tumor cell inhibition indicate that the antitumor activity of the compound of formula (V) of the present invention is significantly higher than the antitumor activity of podophyllotoxin or 4′-demethylepipodophyllotoxin. 2. A method for preparing the sulfur-substituted podophyllotoxin-type derivative as claimed in claim 1 , comprising the steps of:by nucleophilic substitution reaction, 3-amino-5-mercapto-1,2,4-triazole, 3-mercapto-5-methyl-1,2,4-triazole, 2-amino-5-mercapto-1,3,4-thiadiazole, 2-mercapto-5-methyl-1,3,4-thiadiazole, 2-mercaptopyridine, 2-mercapto nicotinic acid, 2-mercapto-6-methylpyridine, 4-mercaptopyridine, 2-mercaptopyrimidine, 4-amino-2-mercaptopyrimidine, 4,6-dimethyl-2-mercaptopyrimidine, 2-mercaptobenzothiazole, 2-mercaptobenzimidazole or 2-mercaptobenzoxazole being introduced into position 4 of the C-ring of podophyllotoxin,or, by nucleophilic substitution reaction, 3-amino-5-mercapto-1,2,4-triazole, 3-mercapto-5-methyl-1,2,4-triazole, 2-mercapto-5-mercapto-1,3,4-thiadiazole, 2-mercaptopyridine, 2-mercapto nicotinic acid, 2-mercapto-6-methylpyridine, 4-mercaptopyridine, 2-mercaptopyrimidine, 4-amino-2-mercaptopyrimidine, 4,6-dimethyl-2-mercaptopyrimidine, 2-mercaptobenzothiazole, 2-mercaptobenzimidazole or 2-mercaptobenzoxazole being introduced into position 4 of the C-ring of ...

Rotation sand control oil and gas separator

The utility model discloses a rotation sand control oil and gas separator, hang urceolus, oil -gas separation device, lower clutch on including, wherein, the position difference of oil -gas separationdevice divide into outer sand control and interior sand control again, the utility model discloses a sand control not problem of sand control that does not outgas, does not outgas has been solved inthe past to the oil -gas separation device. Through the effect of exhaust with oil pumping oil feed drive and high -efficient oil and gas separator inner tube helical blade and bearing, when making the oil pump oil pumping, the separation inner tube can the free rotation, and oil and gas fully separates in more effective messenger's well, makes the oil -well pump alleviate airlock when pumping. Through oil reservoir in the effective separation well of sand control protection when the play is taken out with fracturing sand and sand powder china ink, reduce oil -well pump sand card, the industrytime ...

Anti-interference LED pilot lamp drive circuit

The invention belongs to the field of drive circuit, discloses an anti-interference LED pilot lamp drive circuit and solves the problem that the LED pilot lamp is easily accidentally lighted or in dark light state under action of the drive circuit. The drive circuit comprises a resistor R1, an MOSFET (metal-oxide semiconductor field effect transistor), a capacitor C1, a resistor R2 and a resistor R3. One end of the resistor R1 is connected with a positive electrode of a power supply of a vehicle battery, and the other end of the resistor R1 is connected with an anode of the LED pilot lamp. A drain of the MOSFET is connected with a cathode of the LED pilot lamp, and a source of the MOSFET is connected with a negative electrode of the power supply of the vehicle battery. A grid of the MOSFET is simultaneously connected with one end of the capacitor C1, one end of the resistor R3 and one end of the resistor R2. The other end of the capacitor C1 and the other end of the resistor R3 are simultaneously ...

Method and system for displaying reported data on basis of Gis (geographic information system) maps of power grid

The invention discloses a method and a system for displaying reported data on the basis of Gis (geographic information system) maps of a power grid. The method includes steps of (1), acquiring the data, to be more specific, acquiring administrative region dividing units with data reporting requirements and storing information of the administrative region dividing units in first buffer areas; (2), receiving region coordinate information of the administrative region dividing units which are marked on the Gis maps of the power grid by users, creating second buffer areas in corresponding relations with the first buffer areas and storing the received region coordinate information in the second data buffer areas one by one; (3), dividing data submission ranges by the aid of classifiers, to be more specific, dividing data submission conditions into unreported conditions, reported and unchecked conditions and reported and checked conditions by the aid of the classifiers, defining data reporting ...

Chemical scrubbing method for boiler

The invention relates to a method of cleaning a boiler, in particular to a method of chemically cleaning a boiler, which comprises the following steps: caustic cleaning, acid cleaning, rinsing, passivating and liquid waste processing. The invention has the advantages that: 1. raw material adopted in the whole cleaning process has little toxic side effect and is environment-friendly. 2. Technological mistaken ideas on cleaning various prior boilers are overcome. 3. Sequential processing is easy according to cleaning solutions.

Tartary buckwheat oxidation resistance health care wine

The invention relates to a duck wheat anti- oxidizing health- care wine, which is prepared by adding flavone extract in duck wheat- based wine. The detail process is as follows: extracting brewer's by-products with edible alcohol, condensing filterate and recovering solvent; absorbing condensed liquid with large- porous resin, washing with water and edible alcohol, collecting washing liquid, condensing and drying and getting brewer's by-products flavone extract; adding brewer's by-products flavone extract into wheat- based wine, heating for dissolution, blending and getting duck wheat anti- oxidant health- care wine. The ability to remove DPPH free residue and anti- oxidizing are increased by more than 8.1 and 33.3 times compared with original wheat- based wine, and the anti- oxidizing performance is distinctive.

Method for predicting photovoltaic power generation load by using improved long short-term memory neural network

The invention discloses a method for predicting a photovoltaic power generation load by using an improved long-short-term memory neural network, and the method comprises the steps: 1, obtaining photovoltaic power generation historical data, carrying out the dimension reduction preprocessing through a principal component analysis method, carrying out the range standardization processing to obtain training data, and dividing the training data into a training set and a test set; and step 2, constructing a long short-term memory neural network, inputting the training set to train parameters, inputting the test set to the trained neural network to obtain a photovoltaic power generation load prediction value, and evaluating the photovoltaic power generation load prediction value. The photovoltaic power generation load is predicted by constructing the long-short-term memory neural network, the function of effectively extracting time sequence features of the long-short-term memory network is fully ...

Molecular marker related to slaughter performance of yellow feather broilers and application of molecular marker

The invention discloses a molecular marker related to slaughter performance of yellow feather broilers and application of the molecular marker, and belongs to the technical field of poultry genetic breeding. The molecular marker is located on a chicken CYP4B7 gene, the nucleotide sequence of the molecular marker is shown as SEQ ID NO: 1, and the nucleotide sequence comprises a mutation site SNP1; the SNP1 is CM000100.5: g. 22244031Tgt, and the SNP1 is CM000100.5: g. And C. The SNP1 has genotypes TT, TC and CC, and the slaughter performance of an individual with the genotype TC is obviously higher than that of an individual with the genotype CC. The molecular marker provided by the invention can accurately identify carcass traits of spotted-brown chickens, is beneficial to breeding yellow-feather broilers with better slaughter performance, rejects individuals with poorer slaughter performance, and improves the slaughter performance of the yellow-feather broilers, thereby providing a scientific ...

BIOMARQUEUR DE LA PNEUMOCONIOSE DE TRAVAILLEURS CHARBONNIERS ET SON APPLICATION

L'invention concerne la détection d'un biomarqueur biologiquement associé de la pneumoconiose de travailleurs charbonniers. En outre, la présente invention divulgue un biomarqueur de la pneumoconiose de travailleurs charbonniers et son application, et en particulier, une application d'un article pour détecter un niveau d'expression d'un biomarqueur dans la préparation d'un réactif pour indiquer la pneumoconiose de travailleurs charbonniers dans un objet, le biomarqueur étant un miR-138 et le réactif étant utilisé dans un procédé comprenant les étapes suivantes consistant à : détecter un niveau d'expression du miR-138 dans l'objet, comparer le niveau d'expression du miR-138 dans l'objet à un niveau d'expression de référence du miR-138, et indiquer la pneumoconiose de travailleurs charbonniers dans l'objet sur la base de la comparaison, le niveau d'expression du miR-138 dans l'objet étant inférieur au niveau d'expression de référence du miR-138 pour indiquer la pneumoconiose de travailleurs ...

Substituted n-arylsulfonylheterocyclic amines as gamma-secretase inhibitors

Tetrahydropyranochromene gamma secretase inhibitors

Disclosed are novel gamma secretase inhibitors of the formula. Also disclosed are methods of inhibiting gamma-secretase, methods of treating neurodegenerative diseases, and methods of treating Alzheimer's Disease. Also disclosed are processes for preparing alkenes in one reaction step using a mixture of an aldehyde (or ketone) and an alkyl substituted with two electron withdrawing groups, and reacting the mixture with: (a) a sulfonyl halide (e.g., a sulfonyl chloride) and a basic tertiary amine, or, (b) a sulfonyl anhydride and a basic amine, or (c) an aryl-C(O)-halide and a basic tertiary amine, or (d) an aryl-C(O)-O-C(O)-aryl and a basic tertiary amine, or (e) an heteroaryl-C(O)-halide and a basic tertiary amine, or (f) a heteroaryl-C(O)-O-C(O)-heteroaryl and a basic tertiary amine.

CONSTRUCTING GEOLOGIC MODELS FROM GEOLOGIC CONCEPTS

Method for constructing a geologic model of a subsurface region. A concept region and a geologic concept is selected (300). A design region is created corresponding to the concept region (310). A conceptual model is generated compatible to data in the design legion (320). The conceptual model is mapped from the design legion concept region (330). The conceptual interfaces and region properties may be adjusted to match data in the concept region (340).

Novel electronic gate valve of parallel double -gate board

The utility model relates to a novel electronic gate valve of parallel double -gate board belongs to valve fields such as thermoelectricity, nuclear power, chemical industry. This practical novel electronic gate valve of parallel double -gate board installs on the ultra -supercritical thermal power generating unit pipeline, is used for cutting off (switch -on) pipeline steam or water. The utility model discloses comprise parts such as valve body, disk seat, support, valve rod, filler rooms, locking mechanism adopts valve clack, band, spring to form, and the valve body lumen adopts pressure self -energized seal, and pressure high leakproofness more can be good more, is equipped with the spring between two valve clacks, with the help of spring tension auxiliary seal. The valve clack is fixed in the band by baffle, screw, nut, the opening of valve, closes and drives band, valve clack by the valve rod and do the elevating movement with the aid of the guide of disk seat, and valve rod upper ...

Adriamycin sustained-release medicinal rod for treating Cerebral gliomas disease and preparation method thereof

The invention relates to an Adriamycin sustained-release medicinal rod for treating Cerebral gliomas disease and a preparation method thereof. The medicinal rod is a cylindrical solid body or a flaky solid body. The raw materials of the medicinal rod comprise Adriamycin and a sustained-release substrate in a weight ratio of (10-20):(80-90), wherein the sustained-release substrate is made of a lactic acid-glycollic acid-trimethylene carbonate terpolymer, and the weight ratio of lactic acid to glycollic acid to trimethylene carbonate terpolymer is (45-49):(45-49):(2-10). The preparation method comprises the following preparation steps: (1) preparing the sustained-release substrate; (2) placing a cylindrical or square mold on a worktable for later use; (3) dissolving the sustained-release substrate into an acetone solvent according to a required ratio; and (4) adding Adriamycin into the sustained-release substrate according to the weight ratio of the Adriamycin to the sustained-release substrate ...

Power-grid-GIS-based real-time early warning method and apparatus of satellite cloud picture

The invention discloses a power-grid-GIS-based real-time early warning method and apparatus of a satellite cloud picture. The method comprises: a power grid equipment coordinate at an early warning area is localized; a power grid equipment graph layer is determined according to the coordinate of the power grid equipment; the power grid equipment at the specific longitude and latitude is monitored in real time and meteorological data in meteorological cloud picture information of the power grid equipment coverage area are obtained; matching of the monitored meteorological data in meteorological cloud picture information and a disaster weather early warning model is carried out to determine a disaster weather type; a disaster weather chart layer is established on the power grid GIS according to the longitude and latitude positioning information; and the data association processing is carried out to realize regional refined power grid meteorological disaster early warning at different time ...

Overhead transmission line cleaning robot

The invention discloses an overhead transmission line cleaning robot. The overhead transmission line cleaning robot is composed of a plurality of module structures. Each module structure comprises a movable trolley, a power source module, a cleaning motor, a servo driver, a compressing device and a cleaning device, wherein the movable trolley is hung on an overhead transmission line and can move back and forth along the overhead transmission line; the power source module, the cleaning motor, the servo driver and the compressing device are installed on an upper cover board of the movable trolley; the lower portion of the upper cover board is connected with the cleaning device. The overhead transmission line cleaning robot can be independently used and can also be used in cooperation with a spraying robot. The modular structure and design are adopted, so that the design cost is effectively lowered, the universality is improved, and the overhead transmission line in the exposed mode is cleaned ...

Nourishing type traditional Chinese herbal plant edible food raw juice

A Chinese medicinal plant edible primary syrup ready to be blended into carbonated beverage is prepd. from aborvitae seed, ginseng, Poria with hostwood, Chinese angelica root, malt, cinnamon, radix polygalae, etc through maceration, separation, filtration, and sterilization to obtain the edible primary syrup which can also be used as additive in soymilk, candy, pastry, noodles, fruit jelly, puffed snack, etc. It contains no caffeine and is not habituative.

Automatic clothing modeling method for multiplexing sewing information

The invention discloses an automatic clothing modeling method for multiplexing sewing information. And extracting sewing relationship information of the 2D model from the modeled garment model, and multiplexing the information to a new 3D model to realize automatic modeling. Constructing a clothing model library containing sewing information and clothing pattern contour information; a user inputs a 2D version DXF file, contour information of all cut pieces in the file is extracted, and a closed polygon is constructed; representing pattern contour information of the garment model by using a multi-scale non-rigid closed polygon shape descriptor MCC, matching each garment piece with the garment pieces in the library, and determining a corresponding relationship between gap lines of the garment pieces and the garment pieces in the library; under boundary constraint, using an SLIM method to migrate UV coordinates of the library model to a 2D version closed polygon; and recombining the original ...

Diaryl and arylheteroaryl urea derivatives as modulators of the 5-HT2A serotonin receptor useful for the prophylaxis and treatment of disorders related thereto

Constructing geologic models from geologic concepts

Method for constructing a geologic model of a subsurface region. A concept region and a geologic concept is selected (300). A design region is created corresponding to the concept region (310). A conceptual model is generated compatible to data in the design legion (320). The conceptual model is mapped from the design legion concept region (330). The conceptual interfaces and region properties may be adjusted to match data in the concept region (340).

PROCESS AND INTERMEDIATES FOR PREPARING MACROLACTAMS

GAMMA SECRETASE MODULATORS

This invention provides novel compounds that are modulators of gamma secretase. The compounds have the formula (Chemical formula should be inserted here as it appears on abstract in paper form). Also disclosed are methods of modulating gamma secretase activity and methods of treating Alzheimer's Disease using the compounds of formula (I).

GAMMA SECRETASE MODULATORS

In its many embodiments, the present invention provides a novel class of heterocyclic compounds of Group A or Group, as defined herein, as modulators of gamma secretase, methods of preparing such compounds, pharmaceutical compositions containing one or more such compounds, methods of preparing pharmaceutical formulations comprising one or more such compounds, and methods of treatment, prevention, inhibition, or amelioration of one or more diseases associated with the central nervous system using such compounds or pharmaceutical compositions.

Extraction and separation method of extracellular scleroglucan

The invention discloses an extraction and separation method of extracellular scleroglucan, belonging to the technical field of polysaccharide extraction and separation. The extraction and separation method comprises the steps of firstly, enabling a fermentation liquid to penetrate into a microfiltration membrane to remove mycelium, then, adding ammonium sulfate into the filtered clear liquid, magnetically stirring the liquid, standing and salting out, next, adding distilled water to enable polysaccharide to be suspended, dissolved and diluted, and transferring a dissolving liquid into a dialysis bag with the molecular weight of 100-200KDa to dialyze; then, collecting a polysaccharide liquid in the dialysis bag, regulating the pH value of the polysaccharide liquid to 7-9 by using a NaOH liquid, adding absolute ethyl alcohol, standing and carrying out alcohol precipitation to obtain extracellular scleroglucan; and finally, cleaning the extracellular scleroglucan by using a small deal of diethyl ...

Aging effect technique for Al-Mg-Si-0.3Mn-0.2Er

The invention is an aging process for Al-Mg-Si-0.3Mn-0.2Er, belonging to the field of metal alloy technology. The invention improves the alloy strength by mill scraping the Al-Mg-Si-0.3Mn-0.2Er alloy cast ingot after 460/12h+ 550 DEG/12h double-layer homogenization treatment, 540 DEG C/0.5h+ water quenching solution processing the plate manufactured by hot rolling and cold rolling after milling, aging heat processing for 0.5 to 24 hours under a simulating stoving varnish temperature of 175 DEG C or aging heat processing for 0.5 hours under a simulating stoving varnish temperature of 175 DEG C to 250 DEG C. The alloy can acquire the highest strength when aging for 24 hours under 175 DEG C or aging heat processing for 0.5 hours under 225 DEG C. The invention provides an aging system for Er-containing Al-Mg-Si-Mn, and improves its feasibility by examples.

Method for extracting D-chiro-inositol from buckwheat husks

The process of extracting D-chiral inositol from buckwheat bran includes: extracting D-chiral inositol and its derivative from buckwheat bran with water or water solution of alcohol in the concentration up to 60 %, filtering the extracted liquid and concentrating, hydrolyzing to convert the D-chiral inositol derivative into D-chiral inositol, decolorizing with active carbon, separating and refining in ion exchange resin, and concentrating to obtain D-chiral inositol product. The present invention extracts D-chiral inositol from buckwheat bran as the side product of buckwheat powder and has high resource utilizing rate, and the extract has D-chiral inositol content as high as 40 %.

Digital control gear-brushing machine

The invention relates to a digital control gear-brushing machine which comprises a rotary worktable, a first brushing frame and a second brushing frame respectively arranged at both ends of the worktable. The first brushing frame is provided with a wheel brush which is used for processing a gear cogging, has a rotary axis perpendicular to a rotary axis of the worktable and can lift along the first brushing frame, the second brushing frame is provided with a disk brush which is used for processing the end part of a gear and has a rotary axis parallel to a rotary axis of the worktable, and the worktable, the wheel brush and the disk brush are controlled by a digital control system. The invention adopts the wheel brush to process the cogging, adopts the disk brush to process the end surface of the gear, removes metal edge blur while obtaining a trace element R and has the advantages of high degree of automation and high processing efficiency.

Method for preparing ergothioneine by biosynthesis of cordyceps sinensis fungus

The invention relates to the technical field of microbial fermentation, and particularly discloses a method for preparing ergothioneine by biosynthesis of cordyceps sinensis fungus, which comprises the following steps: performing slant culture, shake-flask culture, liquid strain seed amplification culture and submerged fermentation culture on cordyceps sinensis fungus strains until the fermentation end point is reached, thereby obtaining the ergothioneine. And collecting fermentation liquor, carrying out homogenate treatment, carrying out enzymolysis, carrying out solid-liquid separation, collecting filtrate, decoloring, filtering, collecting filtrate, concentrating and drying to obtain an ergothioneine product. The method has the advantages of low cost and large-scale production.

Lithium ion battery

In order to overcome the problems of battery impedance increase and high-temperature capacity attenuation caused by defects of a carbon material on the surface of existing lithium manganese iron phosphate, the invention provides a lithium ion battery which comprises a positive electrode, a negative electrode and a non-aqueous electrolyte, the positive electrode comprises a positive electrode material layer containing a positive electrode active material, and the negative electrode comprises a negative electrode material layer containing a negative electrode active material; the positive electrode active material comprises lithium manganese iron phosphate coated with a carbon coating layer, a Raman test shows that ID/IG is more than or equal to 0.5 and less than or equal to 1.1, ID is the peak intensity of a D peak in a Raman spectrum from 1300 cm <-1 > to 1400 cm <-1 >, IG is the peak intensity of a G peak in the Raman spectrum from 1530 cm <-1 > to 1630 cm <-1 >, the non-aqueous electrolyte ...

ATRAZINE-DEGRADING BACTERIUM AND METHOD OF UISNG THE SAME FOR SOIL AND PLANT REMEDIATION

The bacterium liulou 1 (CGMCC 9667) possesses a unique combination of high atrazine-degrading activity, a capability of colonizing plant roots after seed inoculation and traits of a plant growth promoting bacterium. Also disclosed is a method of liulou 1 (CGMCC 9667) application for remediation of the polluted soils and plant protection from atrazine. 1Arthrobacter ureafaciens. An atrazine-degrading bacterium having all identifying characteristics of the strain liulou 1 deposited in the China General Microbiological Culture Collection Center (CGMCC) , under the No. 9667 , on Sep. 10 , 2014.2. The bacterium of claim 1 , wherein said bacterium completely degrades atrazine in a solution with a concentration of 25 mg/L in a stationary state within 1 week.3. The bacterium of claim 1 , wherein said bacterium is motile and actively spread on soft agar surfaces.4. The bacterium of claim 1 , wherein said bacterium applied to plant seeds at an effective amount from 10to 10colony forming units per seed colonizes plant roots and produces populations sufficient to degrade soil atrazine.5. The bacterium of claim 1 , wherein said bacterium is capable of mobilizing insoluble phosphate.6. The bacterium of claim 1 , wherein said bacterium applied to the seeds of plants at an amount no less than 10colony forming units per seed promotes the growth of seedling roots.7. A method of remediation of liquids and soils contaminated with atrazine or related s-triazine compounds and for plant protection from atrazine or related s-triazine compounds claim 1 , wherein the related s-triazine compounds are desethyl atrazine claim 1 , desisopropyl atrazine claim 1 , simazine claim 1 , cyanazine claim 1 , propazine claim 1 , terbuthylazine claim 1 , prometryn claim 1 , ametryn claim 1 , terbutryn claim 1 , simetone claim 1 , the method comprising applying a biological agent comprising an effective amount of a biologically pure culture of the bacterium of .8. The method of claim 7 , for remediation of ...

Microbial fertilizer with double effects of fertilization and disease-resistance, and preparation method and use thereof

MICROBIAL FERTILIZER WITH DOUBLE EFFECTS OF FERTILIZATION AND DISEASE-RESISTANCE, AND PREPARATION METHOD AND USE THEREOF The present invention provides a microbial fertilizer, and a preparation method and use thereof, and belongs to the technical field of fertilizer production. The microbial fertilizer is prepared from the following raw materials: crop stalks, livestock and poultry manure, a first bacterial agent and a second bacterial agent, where the first bacterial agent includes Bacillus megaterium and Bacillus subtilis, and the second bacterial agent includes Pseudomonas fluorescens and Streptomyces jingyangensis. The microbial fertilizer of the present invention includes Bacillus megaterium, Bacillus subtilis, Pseudomonas fluorescens and Streptomyces jingyangensis, and this strain combination can achieve the nutrient, disease-resistance and stress-resistance efficacies. In addition, the present invention adopts an absorbent prepared from raw materials of crop stalks and livestock ...

Carbocyclic and heterocyclic arylsulfones as gamma secretase inhibitors

Gamma secretase modulators

In its many embodiments, the present invention provides a novel class of heterocyclic compounds of Group A or Group, as defined herein, as modulators of gamma secretase, methods of preparing such compounds, pharmaceutical compositions containing one or more such compounds, methods of preparing pharmaceutical formulations comprising one or more such compounds, and methods of treatment, prevention, inhibition, or amelioration of one or more diseases associated with the central nervous system using such compounds or pharmaceutical compositions.

GAMMA SECRETASE MODULATORS

In its many embodiments, the present invention provides novel heterocyclic compounds as modulators of gamma secretase, methods of preparing such compounds, pharmaceutical compositions containing one or more such compounds, methods of preparing pharmaceutical formulations comprising one or more such compounds, and methods of treatment, prevention, inhibition, or amelioration of one or more diseases associated with the central nervous system using such compounds or pharmaceutical compositions.

CARBOCYCLIC AND HETEROCYCLIC ARYLSULFONES AS GAMMA SECRETASEINHIBITORS

This invention discloses novel gamma secretase inhibitors of the formula: R2and R3, or R2 and R4, or R3 and R4, together with the atoms to which they are bound, can form a fused cycloalkyl or fused heterocycloalkyl ring. The cycloalkyl ring or the heterocycloalkyl ring can be optionally substituted with one or more substituents. One or more compounds of formula (I), or formulations comprising such compounds, may be useful, e.g. in treating Alzheimer's Disease.

Parabolic demonstration ware that teaching was used

The utility model provides a parabolic demonstration ware that teaching was used, includes the base, both ends on the base are equipped with the stand, the upper end of stand is equipped with the through -hole, be equipped with the axle sleeve in the through -hole, be equipped with the axostylus axostyle in the axle sleeve, the one end of axostylus axostyle is equipped with the external screw thread, still includes the carousel, the intermediate position of carousel is equipped with the screw hole that closes with outer thread to match, be equipped with the blind hole of four interior arriss on the lateral wall of carousel, still include hand handle, the hand crank is equipped with the four outer arriss with four interior arris matched with on hand, the other end of axostylus axostyle is equipped with parabola, the utility model discloses simple structure, it is with low costs, convenient operation, the practicality is strong, can the more easy students of letting know paraboloidal formation ...

High-throughput construction method for human type-3 adenovirus display vector

The invention discloses a high-throughput construction method for a human type-3 adenovirus display vector, and aims at providing a high-throughput construction method for a human type-3 adenovirus display vector based on a Goldgen gate technique. According to the technical scheme, the method comprises the following steps: 1) purifying a PCR segment or a synthetic nucleic acid segment, diluting and determining the concentration; 2) transferring to a 96-hole Golden gate reaction prefabricated slab, and carrying out Golden gate reaction together with the 96-hole Golden gate reaction prefabricated slab; (3) transferring a reaction product to a competent state cell plate, and transforming the Golden gate reaction product; (4) transferring the cell to a large LB solid culture medium, and separating a monoclonal antibody; (5) choosing the monoclonal antibody, culturing, transferring into the 96-hole Golden gate reaction prefabricated slab, and cloning and identifying a Golden gate reaction product ...

Method for controlling torque of salient pole type permanent magnet synchronous motor in weak magnetism area

The invention discloses a method for controlling the torque of a salient pole type permanent magnet synchronous motor in a weak magnetism area. The method is characterized by including the steps that the instruction torque and torque estimation are compared based on the torque estimation of the salient pole type permanent magnet synchronous motor, weak magnetism area phase angles of inverter reference voltage vectors are generated through a single-torque closed-loop PI adjuster, and as a monotonous relationship exists between the weak magnetism area phase angles of the inverter reference voltage vectors and the electromagnetic torque output by the motor, the weak magnetism area phase angles of the inverter reference voltage vectors are independently controlled for achieving dynamic control over the torque of a control system in the weak magnetism area. By means of the method, the fault that when a traditional control system, based on double-current PI adjuster closed-loop control, of the ...

Method for continuously deoxidizing deionized water

The invention relates to a method for continuously deoxidizing deionized water which is a raw material in a process for producing acrylamide by hydration of acrylonitrile in the presence of a copper catalyst. A filler is filled in a packed column of which the height-diameter ratio is 10 to 1 in one third volume, wherein the filler is an inwards bent arc rib flat and annular filler which is 4/3 centimeters long and is filled on the top part of the column; the deionized water is continuously filled from the top part of the packed column, is gathered at the bottom of the column after passing through a distributor and the packed column, and is continuously pumped to a storage tank by a centrifugal pump; and a vacuum pump continuously vacuumizes the column through a pipeline positioned at the place 20 centimeters below the filler so as to keep the vacuum degree of the packed column between 4 and 6KPa. By the method, oxygen content of the deionized water can be kept below 0.2ppm and production ...

Thin-walled corrugated sleeve centering device

The invention relates to a thin-walled corrugated sleeve centering device which comprises a mandrel, wherein a corrugated sleeve is sheathed on the mandrel, one end of the corrugated sleeve is fixedly connected with the mandrel by utilizing a fixing plate, and a pressure plate is arranged at the other end of the corrugated sleeve; and the pressure plate is mounted on the mandrel through a locking nut, and the other end of the pressure plate, which is correspondingly connected with the locking nut, is in contact with the corrugated sleeve. One end of the corrugated sleeve is fixedly mounted on the mandrel through the fixing plate, and the pressure plate is arranged at the other end of the corrugated sleeve; and a workpiece is sheathed on the corrugated sleeve. When the locking nut is screwed, the pressure plate can extrude the corrugated sleeve so as to enable the corrugated sleeve to generate extrusion deformation, enable the outer wall of the corrugated sleeve to be in close contact with ...

Simulating device for strip steel continuous annealing process

Apple yield prediction method based on meteorological main control factors

The invention discloses an apple yield prediction method based on a meteorological main control factor, and particularly relates to the technical field of fruit tree yield prediction. Apple base county per unit yield data are utilized, and base county apple trend yield is fitted through four methods of three-year moving average, two-year moving average, five-year moving average and quadratic polynomial fitting of per unit yield; the meteorological yield is separated from the per unit yield of the apples; secondly, taking the meteorological yield as a research object; a grey correlation analysis method is used for analyzing the correlation degree of 88 climate factors such as total solar radiation, evaporation capacity of an evaporation pan, accumulated temperature, precipitation, wind speed, highest temperature, lowest temperature, average temperature, high-temperature heat damage days, frost days in a flowering period, low-temperature freezing damage days in a dormancy period in winter ...

Bio-organic fertilizer and preparation method thereof

The invention relates to a bio-organic fertilizer and a preparation method thereof. The bio-organic fertilizer is used for soil testing and fertilizer recommendation of cotton, and comprises a nitrogen phosphorus and potassium compound fertilizer, zinc sulfate and wheat straw organic fertilizer. The bio-organic fertilizer is capable of comprehensively balancing the cotton nutrient so as to enable the nutrient supply to be lasting and harmonious, and is capable of remarkably improving the quality and the yield of the cotton, has remarkable economic benefit and is suitable for most soil of cotton planting areas in China.

Nutrient solution for breeding selenium rich snail, breeding method and selenium rich snail product

The invention discloses a nutrient solution for breeding a selenium rich snail, which can promote the growth of a snail and obviously improve the selenium content in snail meat, a breeding method and a selenium rich snail product. The nutrient solution for breeding a selenium rich snail is prepared by the following steps: mixing 1 percent of red nano-selenium aqueous solution, brown sugar, glucose, honey, lysine, methionine and EM origin liquid in percentage by weight and then fermenting the mixture at 20-30 DEG C for 2 days. The breeding method of the snail comprises the following steps: adding water into the nutrient solution for breeding the selenium rich snail for diluting in the diluting ratio of 1:4-40; spraying the diluting liquid of the nutrient solution for breeding the selenium rich snail on vegetable leave green feed and airing for 1-2 hours and then feeding the snail, wherein the weight ratio of the nutrient solution for breeding the selenium rich snail and the vegetable leave ...

Extension coefficient and plate shape integrated control method in steel strip flattening process

Preparation technique for Al-Mg-Si-0.3Mn-0.2Er

The invention is an aging process for Al-Mg-Si-0.3Mn-0.2Er, belonging to the field of metal alloy technology. The invention improves the alloy strength by mill scraping the Al-Mg-Si-0.3Mn-0.2Er alloycast ingot after 460/12h+ 550 DEG/12h double-layer homogenization treatment, 540 DEG C/0.5h+ water quenching solution processing the plate manufactured by hot rolling and cold rolling after milling, aging heat processing for 0.5 to 24 hours under a simulating stoving varnish temperature of 175 DEG C or aging heat processing for 0.5 hours under a simulating stoving varnish temperature of 175 DEG Cto 250 DEG C. The alloy can acquire the highest strength when aging for 24 hours under 175 DEG C or aging heat processing for 0.5 hours under 225 DEG C. The invention provides an aging system for Er-containing Al-Mg-Si-Mn, and improves its feasibility by examples.

DIARYL AND ARYLHETEROARYL UREA DERIVATIVE AS MODULATOR OF THE 5-HT2A SEROTONIN RECEPTOR USEFUL FOR THE PROPHYLAXIS AND TREATMENT OF DISORDERS RELATED THERETO

PROBLEM TO BE SOLVED: To provide a specific diaryl and arylheteroaryl urea derivative modulating activity of 5-HT2A serotonin receptor and to provide a pharmaceutical compositions thereof. SOLUTION: The invention relates to the diaryl urea derivative and arylheteroaryl urea derivative represented by formula (I), or a pharmaceutically acceptable salt thereof, a hydrate or a solvate thereof. COPYRIGHT: (C)2008,JPO&INPIT ...

Gamma secretase modulators

Diaryl and arylheteroaryl urea derivatives as modulators of the 5-HT2A serotonin receptor useful for the prophylaxis or treatment of progressive multifocal leukoencephalopathy

Benzenesulfonyl-chromane, thiochromane, tetrahydronaphthalene and related gamma secretase inhibitors

METHOD FOR INDUCING EXON SKIPPING BY GENOME EDITING

A method for skipping a target exon of a desired gene in a genome using CRISPR-Cas and a guide RNA, characterized in that the guide RNA has a spacer sequence wherein the CRISPR-Cas cleavage site is positioned within 80 bases apart from a splice donor site immediately before the target exon or a splice acceptor site immediately after the target exon.

TETRAHYDROPYRANOCHROMENE GAMMA SECRETASE INHIBITORS

Disclosed are novel gamma secretase inhibitors of the formula. Also disclosed are methods of inhibiting gamma-secretase, methods of treating neurodegenerative diseases, and methods of treating Alzheimer's Disease. Also disclosed are processes for preparing alkenes in one reaction step using a mixture of an aldehyde (or ketone) and an alkyl substituted with two electron withdrawing groups, and reacting the mixture with: (a) a sulfonyl halide (e.g., a sulfonyl chloride) and a basic tertiary amine, or, (b) a sulfonyl anhydride and a basic amine, or (c) an aryl-C(O)-halide and a basic tertiary amine, or (d) an aryl-C(O)-O-C(O)-aryl and a basic tertiary amine, or (e) an heteroaryl-C(O)-halide and a basic tertiary amine, or (f) a heteroaryl-C(O)-O-C(O)-heteroaryl and a basic tertiary amine.

GAMMA SECRETASE MODULATORS FOR THE TREATMENT OF ALZHEIMER'S DISEASE

This invention provides novel compounds that are modulators of gamma secretase. The compounds have the formula: Also disclosed are methods of modulating gamma secretase activity and methods of treating Alzheimer's disease using the compounds of formula (I).

High strength steel-aluminum alloy dissimilar metal connecting method

The invention relates to a high strength steel-aluminum alloy dissimilar metal connecting method in the technical field of metallurgy, material, machinery and automobile, railway vehicle and other mobile machines. The method, aiming at the welding problem of high strength steel-aluminum alloy dissimilar metal, utilizes an orthogonal design test method to optimize a resistance spot-welding parameter, based on thermal, electric and force coupling characteristics of the steel-aluminum alloy dissimilar metal in a spot-welding process and rule of influence of the spot-welding parameter on the diameter of an aluminum alloy nugget, thickness of an intermetallic compound layer on an aluminum/steel interface, joint pulling and shearing force, spot-welding defects and the like; so that, to a certain extent, the diameter of the aluminum alloy nugget is increased, the growth of intermetallic compound layer on the aluminum/steel interface is limited, splashing in spot-welding and defects of joint breaking ...

Preparation method of grade-A fireproof external thermal insulation material

The invention discloses a grade-A fireproof external thermal insulation material and a preparation method thereof. The preparation method is characterized by comprising the steps: adding 83.0-92.0wt% of fine plaster powder into 1.57-3.68wt% of solution A and uniformly stirring; then, adding 4.3-7.5wt% of additive B, 1.3-3.4wt% of anti-crack fiber, 0.13-0.33wt% of water reducing agent and 0.67-2.0wt% of stabilizer and stirring for 1min; and next, adding 0.03-0.09wt% of additive C, stirring, forming by pouring, standing at room temperature for 4h and demolding. The grade-A fireproof external thermal insulation material prepared by the invention has the characteristics of high volume increment speed, short setting time, high fireproof grade, low volume density, small main distribution range of aperture, uniform air hole distribution and low heat conductivity coefficient.

Blood purification equipment's A, B liquid blending tank

The utility model discloses a blood purification equipment's A, B liquid blending tank, fix the epitheca on the base including the base with sealing, the epitheca is the open cylinder of lower extreme the upper end tangential of epitheca lateral wall is connected with the feed liquor pipe the lower extreme tangential of epitheca lateral wall is connected with the drain pipe. The utility model discloses a be the cylinder with the epitheca setting, connect upper end and lower extreme at the epitheca lateral wall in the tangential respectively with feed liquor pipe and drain pipe to open the top cap that has the exhaust hole in epitheca upper end installation, thereby provide a simple structure, wash blood purification equipment A, B liquid blending tank convenient, can the degasification, have that the design is ingenious, simple structure, production is easy and characteristics such as low in production cost.

Welder fixing device

The utility model discloses a welder fixing device, welder fixing device include the base, be equipped with vertical rod on the base and connect through the connecting seat the last transverse bar of vertical rod, the one end of transverse bar is equipped with welder fixture, welder fixture including be used for adjusting welder for the every single move regulating arm of the angle of transverse bar. When using, this fixing device not only can adjust welder's upper and lower position and left and right sides position, can also adjust welder's angle through the every single move regulating arm, makes it can the every single move swing for the transverse bar. This fixing device can make welder be in best welding position when the welding to welder's the adjustment of carrying out arbitrary angle in the space, has improved the welding quality of welding seam.

Hydraulic scaling mechanism of sealed cylinder body on basis of flexible element

The invention discloses a hydraulic scaling mechanism of sealed cylinder body on the basis of flexible element, which is composed of a piston connected with a movement input end, a piston connected with a movement output end and hydraulic cylinders with different calibres, wherein the hydraulic cylinder is filled with hydraulic fluid. The hydraulic scaling mechanism is characterized in that the outer surfaces of the piston connected with a movement input end and the piston connected with a movement output end are both covered by the flexible element which covers one side of the piston, which is provided with hydraulic fluid. The structure of the hydraulic scaling mechanism is the cylinder body based on cylindricity and adopts a flexible element to replace the traditional hydraulic piston to confine hydraulic fluid in a sealed space. The hydraulic scaling mechanism has simple structure, low cost and simple maintenance. Because the flexible element is adopted, the hydraulic scaling mechanism ...

Double-disk detonator automatic assembling machine buckling assembling pressing device

The invention discloses a double-disk detonator automatic assembling machine buckling assembling pressing device. The double-disk detonator automatic assembling machine buckling assembling pressing device is composed of two 24-position disk-type detonator automatic assembling machines and a buckling assembling pressing device. The buckling assembling pressing device is mainly assembled by a charging reinforcement cap ejecting device, a pair of a and b servo central rotating disks, two conveying devices, a overturn grabbing manipulator, three grabbing manipulators, a buckling assembling pressing device and a product turnover die which are joined and matched mutually. The buckling assembling pressing device is used for achieving ejection, grabbing, turnover, overturn and buckling with a discharging shell body of the charging reinforcement cap. The buckling assembling pressing device is arranged between the two 24-position disk-type detonator automatic assembling machines, and used for connection ...

Diagnosis method and system for short circuit fault of permanent magnet synchronous motor driving system of electric car

The invention discloses a diagnosis method and system for the short circuit fault of a permanent magnet synchronous motor driving system of an electric car. According to the diagnosis method, the current actual operation condition of a permanent magnet synchronous motor is simulated in a simulation mode, a short circuit fault threshold value corresponding to the occurrence time of the three-phase short circuit fault occurring when a simulation motor operates under the actual operation condition is obtained, and then whether the short circuit fault of the actual permanent magnet synchronous motor driving system occurs is judged according to the short circuit fault threshold value. Thus, whether the short circuit fault of the permanent magnet synchronous motor driving system occurs can be rapidly and accurately judged for different operation conditions under which the permanent magnet synchronous motor of the electric car operates. The diagnosis method and system have the advantages of being ...

Wind shielding structure of speed reducer

The invention relates to the technical field of speed reducers, in particular to a wind shielding structure of a speed reducer. The wind shielding structure of the speed reducer comprises a case, wherein a transmission gear is arranged on the side wall of one side of the case; the oil pumping port is formed in the bottom of the casing and is suitable for being connected with an oil well pump; the air blocking assembly is arranged on the side wall of the casing and located between the oil pumping port and the transmission gear, and the air blocking assembly and the casing are integrally formed; and the first oil inlet is formed in the air blocking assembly, and the first oil inlet and the oil pumping opening communicate and are arranged in a staggered mode. The wind shielding assembly and the case are integrally formed, the defect that welding seams crack due to the fact that the wind shielding assembly is fixed through welding is overcome, and meanwhile the wind shielding assembly further ...

Basalt fiber tensile test equipment and method

The invention relates to the technical field of tensile tests, and discloses basalt fiber tensile test equipment and method.The basalt fiber tensile test equipment comprises a base and two hydraulic lifting arms installed on the base, a connecting beam is installed at the top ends of the two hydraulic lifting arms, and a cross beam used for lifting is installed between the two hydraulic lifting arms; and a plurality of groups of clamps for clamping basalt fiber cloth are mounted at the top end of the base and the bottom end of the cross beam. According to the equipment, the two ends of basalt fiber cloth are wound on the roller bodies of the two clamps respectively, and when the two clamps stretch the basalt fiber cloth, the two ends of the basalt fiber cloth generate strong friction force with the two roller bodies respectively, so that the two ends of the basalt fiber cloth are fixed; in this way, a clamping mode is replaced to clamp the two ends of the basalt fiber cloth, and the situation ...

Steel wire rope core belt joint rubber removing device for mine engineering

The invention discloses a mine engineering steel wire rope core belt joint rubber removing device which comprises a base, a mounting plate is attached to one side of the top face of the base, the base is slidably connected with the mounting plate, a connecting plate is fixed to one side of the top face of the base, a C-shaped plate is fixed to the side wall of the connecting plate, and an n-shaped support is fixed to the top face of the mounting plate. A hydraulic cylinder is fixedly installed in the center of the top face of the n-shaped support. The device can simultaneously remove rubber wrapped outside all steel wire ropes in a steel wire rope core belt, and can effectively replace the traditional process of manually stripping the rubber with a knife, so that the working efficiency is effectively improved, and meanwhile, due to the arrangement of a semicircular blade of the scraper, the scraping efficiency is improved. The steel wire rope can be exactly wrapped between the two corresponding ...

Application of fountain pen extract in controlling snails and/or reducing methane emission of soil

The invention discloses an application of a fountain pen seed extract in controlling snails and/or reducing methane emission of soil, and belongs to the technical field of environment-friendly low-carbon agriculture of snail controlling plant resource utilization. The plant material fountain pen is a common plant in South China, and is easy to obtain, simple to operate, convenient for farmers to operate in the field, cost-saving and pollution-reducing. The method specifically comprises the following three aspects: 1, the fountain pen leaf extract can inhibit ampullaria gigas; 2, pomacea canaliculata can be killed; 3, methane emission of soil (especially rice field soil) can be reduced; the method has the effect of achieving three purposes (snail restraining, snail killing and emission reduction). Through the fountain pen leaf extract, in a certain concentration range (0.20-1.20 g/L), the pomacea canaliculata can be effectively prevented and controlled, the methane emission rate of rice ...

Glass kiln regenerative chamber bottom brick cleaning mechanism

The invention discloses a glass kiln regenerative chamber bottom brick cleaning mechanism which comprises a furnace body, a cleaning pipe and a spray head, the bottom of the furnace body is provided with a bottom layer formed by laying two layers of cross bricks, a through hole is formed between the two layers of cross bricks, and a sediment chamber is arranged below the bottom layer; one end of the cleaning pipe extends into the through hole, and the other end of the cleaning pipe is connected with a high-pressure air source; the nozzle is rotatably connected to one end, extending into the through hole, of the cleaning pipe, and the nozzle is communicated with the cleaning pipe; wherein the extending direction of the cleaning pipe is parallel to the horizontal plane, the rotating angle alpha of the spray head is larger than or equal to 90 degrees and smaller than 180 degrees, the spray head can swing in the vertical direction, and the symmetry axis of the swing range of the spray head ...

Diaryl and arylheteroaryl urea derivatives as modulators of the 5-HT2A serotonin receptor useful for the prophylaxis and treatment of disorders related thereto

The present invention relates to certain pyrazole derivatives of Formula (I) and pharmaceutical compositions thereof that modulate the activity of the 5-HT_2A serotonin receptor. Compounds and pharmaceutical compositions thereof are directed to methods useful in the prophylaxis or treatment of platelet aggreagation, coronary artery disease, myocardial infarction, transient ischemic attack, angina, stroke, atrial fibrillation, reducing the risk of blood clot formation, asthma or symptoms thereof, agitation or a symptom, behavioral disorders, drug induced psychosis, excitative psychosis, Gilles de la Tourette's syndrome, manic disorder, organic or NOS psychosis, psychotic disorder, psychosis, acute schizophrenia, chronic schizophrenia, NOS schizophrenia and related disorders, and sleep disorders, sleep disorders, diabetic-related disorders and the like. The present invention also relates to the method of prophylaxis or treatment of 5-HT_2A serotonin receptor mediated disorders ...

SUBSTITUIERTE N-ARYLSULFONYLHETEROCYCLISCHE AMINE ALS GAMMA-SEKRETASE-HEMMER

GAMMA SECRETASE MODULATORS

In its many embodiments, the present invention provides a novel class of heterocyclic compounds of the formula: as modulators of gamma secretase, methods of preparing such compounds, pharmaceutical compositions containing one or more such compounds, methods of preparing pharmaceutical formulations comprising one or more such compounds, and methods of treatment, prevention, inhibition, or amelioration of one or more diseases associated with the central nervous system using such compounds or pharmaceutical compositions.

Histone deacetylases inhibitor

The invention provides a histone deacetylases (HDACs) inhibitor compound N<1>-(6-(hydroxyamino)-6-oxohexyl)-N<4>-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)terephthalamide having an obvious inhibitory effect on both HDACs and human leukemia U937 cell growth and proliferation, wherein the inhibitory effect is significantly stronger than that of a common HDACs inhibitor trichostatin TSA. The invention also provides a preparation method and a process route of the compound.

Method for detecting depth of underground pipelines

The invention relates to a method of for detecting the depth of underground pipelines, which comprises the following steps: (1) connecting a probe with a hydraulic tank as well as a signal acquisition instrument by cables, connecting a rope to the probe; (2) threading a detecting rope in an empty sleeve of a to-be-detected well embedded with pipelines by a threading device; setting a bench mark near an end well on the ground; measuring the elevation of the bench mark by a geometric leveling method; (3) measuring the relative height of the bench mark bya hydraulic sensor and driving the probe to move in the empty sleeve, meanwhile, measuring the heights of the hydraulic sensor in different positions; (4) calculating horizontal shift distance L of a detected point according to the Pythagorean proposition; and (5) summarizing to obtain embedding depths of the pipelines embedded in different distances. The method effectively avoids the interference between to-be-built underground projects and ...

DIARYL AND ARYLHETEROARYL UREA DERIVATIVE AS MODULATOR OF THE 5-HT2A SEROTONIN RECEPTOR USEFUL FOR THE PROPHYLAXIS AND TREATMENT OF DISORDER RELATED THERETO

PROBLEM TO BE SOLVED: To provide specific diaryl and arylheteroaryl urea derivatives as modulators of the activity of the 5-HT2A serotonin receptor and to provide pharmaceutical compositions thereof. SOLUTION: The compounds which modulate the activity of the 5-HT2A serotonin receptor, are diaryl and arylheteroaryl urea derivatives represented by formula (I) or pharmaceutically acceptable salts, hydrate or solvate thereof. In the formula R1, R2, R3, R4, R5, R6a, R6b, R6c, R7, R8, Q and X are specially defined. COPYRIGHT: (C)2007,JPO&INPIT ...

Benzenesulfonyl-chromane, thiochromane, tetrahydronaphthalene and related gamma secretase inhibitors

This invention discloses novel gamma secretase inhibitors of the formula: R 2 and R 3 , or R 2 and R 4 , or R 3 and R 4 , together with the atoms to which they are bound, can form a fused cycloalkyl or fused heterocycloalkyl ring. The cycloalkyl ring or the heterocycloalkyl ring can be optionally substituted with one or more substituents. One or more compounds of formula (I), or formulations comprising such compounds, may be useful, e.g. in treating Alzheimer's Disease.

DIARYL AND ARYLHETEROARYL UREA DERIVATIVES AS MODULATORS OF THE 5-HT2A SEROTONIN RECEPTOR USEFUL FOR THE PROPHYLAXIS AND TREATMENT OF DISORDERS RELATED THERETO

The present invention relates to certain pyrazole derivatives of Formula (I) and pharmaceutical compositions thereof that modulate the activity of the 5-HTserotonin receptor. 232-. (canceled)34. The compound according to wherein the compound is selected from the group consisting of:1-[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenyl]-3-(4-chloro-phenyl)-urea;1-[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenyl]-3-(4-fluoro-phenyl)-urea;1-[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenyl]-3-(2,4-dichloro-phenyl)-urea;1-[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenyl]-3-(4-methoxy-phenyl)-urea;1-[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenyl]-3-(4-bromo-phenyl)-urea;1-[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenyl]-3-(4-chloro-3-trifluoromethyl-phenyl)-urea;1-[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenyl]-3-(3,5-difluoro-phenyl)-urea;1-[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenyl]-3-(2,4-difluoro-phenyl)-urea;1-[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenyl]-3-(4-chloro-2-trifluoromethyl-phenyl)-urea;1-[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenyl]-3-(3,4-difluoro-phenyl)-urea;1-[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenyl]-3-(3-trifluoromethyl-phenyl)-urea;1-[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenyl]-3-(4-trifluoromethyl-phenyl)-urea;1-(3,5-Bis-trifluoromethyl-phenyl)-3-[3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenyl]-urea;1-[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenyl]-3-naphthalen-2-yl-urea;1-[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenyl]-3-(3-nitro-phenyl)-urea;1-[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenyl]-3-(4-fluoro-3-nitro-phenyl)-urea;1-(3-Acetyl-phenyl)-3-[3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenyl]-urea;1-[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenyl]-3-(3-fluoro-phenyl)-urea;1-[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenyl]-3-(4-trifluoromethoxy-phenyl)-urea;1-[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)- ...

Constructing Geologic Models From Geologic Concepts

Method for constructing a geologic model of a subsurface region. A concept region and a geologic concept is selected (). A design region is created corresponding to the concept region (). A conceptual model is generated compatible to data in the design legion (). The conceptual model is mapped from the design legion concept region (). The conceptual interfaces and region properties may be adjusted to match data in the concept region (). 1. A computer implemented method for constructing a geologic model of a subsurface volume comprising:selecting a geological structural framework for the subsurface volume; andusing a computer to generate values of one or more physical properties for one or more regions within the geological structural framework using a conceptual model based on geologic concepts, said conceptual model comprising the one or more concept regions with one or more interfaces, wherein the interfaces are expressed in implicit functional form and the concept regions are expressed in explicit or implicit functional forms.2. The method of claim 1 , wherein the one or more physical properties are also expressed in implicit or explicit functional form.3. The method of claim 2 , wherein the geologic concepts and the physical properties are expressed exclusively in explicit or implicit functional form claim 2 , i.e. without use of a geo-cellular grid.4. The method of claim 1 , wherein the geologic concepts affect movement of fluids in the subsurface volume.5. The method of claim 1 , wherein the geologic concepts are represented at least partly by one or more conceptual surfaces and by the concept regions claim 1 , which are defined by the one or more conceptual surfaces.6. The method of claim 5 , wherein the one or more physical properties are represented claim 5 , within a concept region or on a conceptual surface claim 5 , using mathematical functions.7. The method of claim 6 , wherein the mathematical functions are parameterized relative to reference surfaces ...

PROCESS AND INTERMEDIATES FOR PREPARING MACROLACTAMS

The present invention relates to macrolactam compounds, intermediates useful in the preparation of macrolactams, methods for preparing the intermediates, and methods for preparing and modifying macrolactams. One use of the compounds and methods described herein is in the production of macrolactam compounds able to inhibit HCV NS3 protease activity. An example of an HCV inhibitory compound that can be synthesized using the procedures described herein is Compound A and derivative thereof. 7. The method of claim 6 , wherein Ris Calkyl and Ris a H or Calkyl.10. The method of claim 9 , wherein said Step C coupling is performed using EDC and pyridine or a pyridine derivative.13. The method of claim 8 , wherein Ris either H or Calkyl.17. The method of claim 13 , wherein Ris either H or Calkyl.19. The method of claim 8 , wherein said ring closure is performed by slow addition of catalyst and the compound of Formula IIa to a solvent at approximately the same time claim 8 , wherein:said solvent is provided at about 5-25 liters per Kg of substrate;said catalyst is provided at a concentration of about 250 ml to 3 L per Kg of catalyst;said compound is provided at a concentration of about 500 ml to 6 L per Kg of substrate; andsaid compound-solution, said catalyst-solution and said solvent are combined together over a period of 0.5-2.5 hrs.2122-. (canceled) The present invention relates to method and compounds that can be used to produce macrolactams, and modify macrolactams. One use of the methods and compounds described herein is in the production of macrolactam compounds able to inhibit HCV NS3 protease activity.Hepatitis C virus (HCV) infection is a major health problem that leads to chronic liver disease, such as cirrhosis and hepatocellular carcinoma, in a substantial number of infected individuals. Current treatments for HCV infection include immunotherapy with recombinant interferon-α alone or in combination with the nucleoside analog ribavirin. Several virally-encoded ...

FUSED BICYCLIC HETEROCYCLES USEFUL AS DIPEPTIDYL PEPTIDASE-IV INHIBITORS

The present invention is directed to novel bicyclic heterocycles of structural formula (I) which are inhibitors of the dipeptidyl peptidase-IV enzyme and which are useful in the treatment or prevention of diseases in which the dipeptidyl peptidase-IV enzyme is involved, such as diabetes and particularly Type 2 diabetes. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which the dipeptidyl peptidase-IV enzyme is involved. 2. The compounds of or pharmaceutically acceptable salts thereof wherein Xis —N— and Xis —CR—.3. The compounds of or pharmaceutically acceptable salts thereof wherein Xand Xare —N—.4. The compounds of or pharmaceutically acceptable salts thereof wherein Ris heterocycle.6. The compounds of or pharmaceutically acceptable salts thereof wherein Ris hydrogen.7. The compounds of or pharmaceutically acceptable salts thereof wherein Ris C-Calkyl.8. The compounds of or pharmaceutically acceptable salts thereof wherein n is 1.10. The compounds of or pharmaceutically acceptable salts thereof wherein Ris selected from the group consisting of C-Calkenyl claim 1 , C-Calkynyl and benzyl claim 1 , wherein C-Calkenyl claim 1 , C-Calkynyl and benzyl are unsubstituted or substituted with 1-3 substituents selected from R.11. The compounds of or pharmaceutically acceptable salts thereof wherein Ris selected from the group consisting of 2-butynyl claim 1 , 2 claim 1 ,5-difluorobenzyl claim 1 , 2 claim 1 ,4 claim 1 ,5-trifluorobenzyl claim 1 , 2-cyanobenzyl claim 1 , 2-cyano-5-fluorobenzyl claim 1 , 2-cyano-4 claim 1 ,5-difluorobenzyl claim 1 , 2 claim 1 ,4-dichlorobenzyl 2 claim 1 ,5-dichlorobenzyl claim 1 , and 2-bromo-5-fluorobenzyl.12. The compounds of or pharmaceutically acceptable salts thereof wherein Ris selected from the group consisting of hydrogen claim 1 , halogen claim 1 , and —CN.15. A pharmaceutical composition which ...

MULTI-GATE FIELD EFFECT TRANSISTOR (FET) INCLUDING ISOLATED FIN BODY

Aspects of the disclosure provide a multi-gate field effect transistor (FET) formed on a bulk substrate that includes an isolated fin and methods of forming the same. In one embodiment, the multi-gate FET includes: a plurality of silicon fin structures formed on the bulk substrate, each silicon fin structure including a body region, a source region, and a drain region; wherein a bottom portion the body region of each silicon fin structure includes a tipped shape to isolate the body region from the bulk substrate, and wherein the plurality of silicon fin structures are attached to the bulk substrate via at least a portion of the source region, or at least a portion of the drain region, or both. 1. A multi-gate field effect transistor (FET) formed on a bulk substrate , comprising:a plurality of silicon fin structures formed on the bulk substrate, each silicon fin structure including a body region, a source region, and a drain region;wherein a bottom portion the body region of each silicon fin structure includes a tipped shape to isolate the body region from the bulk substrate, andwherein the plurality of silicon fin structures are attached to the bulk substrate via at least a portion of the source region, or at least a portion of the drain region.2. The multi-gate FET of claim 1 , wherein a portion of the bulk substrate directly below the body region of each silicon fin structure includes a corresponding tipped shape.3. The multi-gate FET of claim 1 , wherein a portion of the bulk substrate between each silicon fin structure includes a tipped shape.4. The multi-gate FET of claim 1 , wherein the source region is partially isolated from the bulk substrate.5. The multi-gate FET of claim 1 , wherein the drain region is partially isolated from the bulk substrate.6. The multi-gate FET of claim 1 , wherein an oxide layer isolates the body region of each silicon fin structure from the bulk substrate.7. The multi-gate FET of claim 1 , further comprising a gate over each ...

IMMOBILIZED KETOREDUCTASES AND PROCESS FOR MAKING AND USING IMMOBILIZED KETOREDUCTASE

The invention is directed to immobilized ketoreductases and methods of making and using them. Enzymes are protein molecules which serve to accelerate the chemical reactions of living cells (often by several orders of magnitude). Without enzymes, most biochemical reactions would be too slow to even carry out life processes. Enzymes display great specificity and are not permanently modified by their participation in reactions. Since they are not changed during the reactions, enzymes can be cost effectively used as catalysts for a desired chemical transformation. 1. An immobilized ketoreductase comprising:a recombinant ketoreductase; anda resin, wherein the recombinant ketoreductase is attached to the resin and wherein the immobilized ketoreductase is stable in a solvent system that comprises at least 90% of organic solvents.2. An immobilized ketoreductase of wherein the immobilized ketoreductase is stable in a solvent system that comprises at least 95% of organic solvents.3. An immobilized ketoreductase of wherein the recombinant ketoreductase is attached to a resin by adsorption.4. An immobilized ketoreductase of wherein the recombinant ketoreductase is attached to a resin by covalent bonds.5. An immobilized ketoreductase of wherein the recombinant ketoreductase is attached to a resin by ionic bonds.6. An immobilized ketoreductase of wherein the resin comprises polymethacrylate with epoxide functional groups claim 1 , polymethacrylate with amino epoxide functional groups claim 1 , styrene/DVB copolymer or polymethacrylate with octadecyl functional groups claim 1 , silica claim 1 , carboxylic group or quaternary ammonia.7. An immobilized ketoreductase of wherein the resin comprises styrene/DVB copolymer claim 3 , silica or polymethacrylate with octadecyl functional groups.8. An immobilized ketoreductase of wherein the resin is selected from the group consisting of: LEWATIT VPOC 1600 claim 3 , SEPABEAD EXE120 claim 3 , DIAION HP2MG claim 3 , IMMOBEAD-EC1 claim 3 , ...

PROCESS FOR PREPARING BETA 3 AGONISTS AND INTERMEDIATES

The application is directed to efficient and economical processes as described in more detail below for the preparation of the beta 3 agonists of the formula of I-7 and intermediate compounds that can be used for making these agonists. The present disclosure relates to a process for making beta-3 agonists and intermediates using ketoreductase (KRED) biocatalyst enzymes and methods of using the biocatalysts. 118.-. (canceled)20. The process of claim 19 , wherein Catalyst D in step (a) is selected from the group consisting of Pd(PPh) claim 19 , PdCl claim 19 , (PPh)PdCl claim 19 , Pd(dppe)Cl claim 19 , Pd(dppp)Cl claim 19 , Pd(dppf)Cl claim 19 , and Pd(OAc)/PhP claim 19 , in the presence or absence of a catalytic amount of material selected from the group consisting of CuI claim 19 , CuBr claim 19 , and CuCl.21. The process of claim 19 , wherein the reaction in step (a) is carried out in the presence of a solvent selected from the group consisting of THF claim 19 , IPA claim 19 , MeOH claim 19 , EtOH claim 19 , n-PrOH claim 19 , NMP claim 19 , DMAc claim 19 , MTBE claim 19 , CHCl claim 19 , MeCN claim 19 , Me-THF claim 19 , methyl cyclopentyl ether claim 19 , toluene claim 19 , and combinations thereof.22. The process of claim 19 , wherein the reaction product in step (a) is isolated as an HCl salt.23. The process of claim 19 , wherein step (b) is conducted in the presence of a base selected from the group consisting of EtN claim 19 , i-PrNEt claim 19 , i-PrNH claim 19 , pyridine claim 19 , lutidine claim 19 , N-methyl morpholine claim 19 , t-BuOK claim 19 , t-BuONa claim 19 , t-BuOLi claim 19 , NaH claim 19 , NaHMDS claim 19 , LiHMDS claim 19 , and KHMDS.24. The process of claim 19 , wherein Compound I-6-1 is not isolated.25. The process of claim 19 , wherein step (c) is conducted in the presence of hydrogen gas.26. The process of claim 19 , wherein Catalyst E in step (c) is selected from the group consisting of Pt/AlO claim 19 , Pd/AlO claim 19 , Rh/AlO claim 19 , ...

DIARYL AND ARYLHETEROARYL UREA DERIVATIVES AS MODULATORS OF THE 5-HT2A SEROTONIN RECEPTOR USEFUL FOR THE PROPHYLAXIS AND TREATMENT OF DISORDERS RELATED THERETO

The present invention relates to certain pyrazole derivatives of Formula (I) and pharmaceutical compositions thereof that modulate the activity of the 5-HTserotonin receptor. 2. The process according to wherein Ris phenyl or naphthyl each optionally substituted with R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , and Reach selected independently from the group consisting of Cacyl claim 1 , Calkoxy claim 1 , Calkyl claim 1 , Calkylsulfonyl claim 1 , amino claim 1 , Calkylamino claim 1 , Cdialkylamino claim 1 , Calkylimino claim 1 , carbo-C-alkoxy claim 1 , carboxamide claim 1 , carboxy claim 1 , cyano claim 1 , Ccycloalkyl claim 1 , halogen claim 1 , Chaloalkoxy claim 1 , Chaloalkyl claim 1 , heterocyclic claim 1 , hydroxyl claim 1 , nitro claim 1 , and phenyl claim 1 , or two adjacent R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , and Rtogether with the atoms to which they are attached form a Ccycloalkyl group or heterocyclic group each optionally substituted with F; and wherein said Calkyl claim 1 , Calkylimino claim 1 , and heterocyclic are each optionally substituted with 1 to 5 substituents selected independently from the group consisting of Cacyl claim 1 , Calkoxy claim 1 , Calkyl claim 1 , Calkylsulfonyl claim 1 , amino claim 1 , Calkylamino claim 1 , Cdialkylamino claim 1 , carboxamide claim 1 , cyano claim 1 , Ccycloalkyl claim 1 , halogen claim 1 , Chaloalkoxy claim 1 , Chaloalkyl claim 1 , and hydroxyl.3. The process according to wherein Ris phenyl or naphthyl each optionally substituted with R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , and Reach selected independently from the group consisting of Cacyl claim 1 , Calkoxy claim 1 , Calkyl claim 1 , amino claim 1 , Calkylamino claim 1 , Cdialkylamino claim 1 , Calkylimino claim 1 , cyano claim 1 , halogen claim 1 , Chaloalkoxy claim 1 , Chaloalkyl claim 1 , heterocyclic claim 1 , hydroxyl claim 1 , nitro claim 1 , and phenyl claim 1 ...

NANOWIRE STRUCTURE WITH SELECTED STACK REMOVED FOR REDUCED GATE RESISTANCE AND METHOD OF FABRICATING SAME

Methods to fabricate a stacked nanowire field effect transistor (FET) with reduced gate resistance are provided. The nanowire stack in the stacked nanowire FET can be provided by first forming a material stack of alternating sacrificial material layers and nanowire material layer. The sacrificial material layers and selected nanowire material layers in the material stack are subsequently removed to increase a vertical distance between two active nanowire material layers. 1. A method of forming a semiconductor structure comprising:forming a material stack on a substrate, the material stack comprising, from bottom to top, at least a first nanowire material layer, a second nanowire material layer and a top nanowire material layer that are separated from each other by a respective sacrificial material layer;forming a hard mask layer on the top nanowire material layer of the material stack;patterning the hard mask layer and the top nanowire material layer to provide a vertical stack of a hard mask layer portion and a top nanowire material layer portion, each of the hard mask layer portion and the top nanowire material layer portion including a fin portion connected at each end to a respective supporting portion;forming a sacrificial spacer on each sidewall of the vertical stack;removing exposed portions of a sacrificial material layer located beneath the top nanowire material layer portion that are not covered by the sacrificial spacer or the vertical stack to expose portions of the second nanowire material layer;removing portions of the second nanowire material layer that are not covered by the supporting portions of the hard mask layer portion;removing the sacrificial spacer;patterning at least a remaining portion of the sacrificial material layer, the first nanowire material layer and another sacrificial material layer overlying the first nanowire material layer to provide a sacrificial material layer portion, a first nanowire material layer portion and another ...

METHOD FOR INDUCING EXON SKIPPING BY GENOME EDITING

A method of skipping a target exon of a gene of interest in a genome uses CRISPR-Cas and guide RNA. The guide RNA contains a spacer sequence such that the site of cleavage by the CRISPR-Cas is positioned within 80 bases from the splice donor site immediately before the target exon or the splice acceptor site immediately after the target exon. 1. A method of skipping a target exon of a gene of interest in a genome , comprising using CRISPR-Cas and guide RNA , wherein the guide RNA contains a spacer sequence such that the site of cleavage by the CRISPR-Cas is positioned within 80 bases from the splice donor site immediately before the target exon or the splice acceptor site immediately after the target exon.2. The method according to claim 1 , wherein two or more kinds of the guide RNA are used.3. The method according to claim 1 , wherein the CRISPR-Cas is a nickase-modified Cas containing a substitution in the nuclease activity residue in the RuvC domain claim 1 , and wherein a guide RNA for the sense strand and a guide RNA for the antisense strand of the gene of interest are used claim 1 , the guide RNAs containing spacer sequences such that the cleavage site in the sense strand of the gene of interest and the cleavage site in the antisense strand of the gene of interest are both positioned within 80 bases from the splice donor site immediately before the target exon or the splice acceptor site immediately after the target exon.4. The method according to claim 1 , wherein the CRISPR-Cas is Cas9.5Streptococcus pyogenesStaphylococcus aureus.. The method according to claim 4 , wherein the Cas9 is derived from claim 4 , or derived from6. The method according to claim 1 , wherein the CRISPR-Cas is Cpf1.7Acidaminococcus. The method according to claim 6 , wherein the Cpf1 is derived from sp. BV3L6 claim 6 , or derived from Lachnospiraceae.8. The method according to claim 1 , wherein the gene of interest is a human dystrophin gene.9. The method according to claim 8 , ...

PERFORMANCE FEED-FORWARD THICKNESS CONTROL METHOD IN TANDEM COLD MILL

The present invention relates to the field of strip cold rolling, and in particular to a thickness control method for strips in a tandem cold mill. A performance feed-forward thickness control method in a tandem cold mill comprises selecting one or more frames as virtual indirect measuring instruments for the strip performance, in which the frame Smust be used as a virtual indirect measuring instrument for the strip performance; calculating the deformation resistance fluctuation of supplied materials, providing a load cell on the frames that are selected as the indirect measuring instruments for the strip performance, and obtaining the deformation resistance fluctuation of the supplied materials of the frame Sby calculation; finally, calculating the feed-forward adjustment amount of each frame. The present invention performs the feed-forward thickness control through the deformation resistance force of the supplied materials measured indirectly, and by measuring the deformation resistance of each section of the strip of the supplied materials through the selected frame, the influence of the performance fluctuation of hot-rolled finished products of the supplied materials on the precision of the cold rolling thickness control is avoided, and improves the precision of thickness control, which is of positive significance for ensuring the precision of the thickness of finished products of the strip in the length direction of the entire steel coil, reducing the fluctuation of the thickness of the finished products of the strip and ensuring stable rolling. The present invention relates to the field of strip cold rolling, and in particular to a thickness control method of strips in tandem cold mill.Thickness precision is one of the most important quality indexes for cold rolled strips. With the rise and development of industries like automobiles, aviation, household appliances, precision instruments, civil architecture, food cans, there are strict requirements on the ...

MULTI-GATE FIELD EFFECT TRANSISTOR (FET) INCLUDING ISOLATED FIN BODY

Aspects of the disclosure provide a multi-gate field effect transistor (FET) formed on a bulk substrate that includes an isolated fin and methods of forming the same. In one embodiment, the multi-gate FET includes: a plurality of silicon fin structures formed on the bulk substrate, each silicon fin structure including a body region, a source region, and a drain region; wherein a bottom portion the body region of each silicon fin structure includes a tipped shape to isolate the body region from the bulk substrate, and wherein the plurality of silicon fin structures are attached to the bulk substrate via at least a portion of the source region, or at least a portion of the drain region, or both. 1. A multi-gate field effect transistor (FET) formed on a bulk substrate , comprising:a plurality of silicon fin structures formed on the bulk substrate, each silicon fin structure including a body region, a source region, and a drain region;wherein a bottom portion the body region of each silicon fin structure includes a tipped shape to isolate the body region from the bulk substrate, andwherein the plurality of silicon fin structures are attached to the bulk substrate via at least a portion of the source region, or at least a portion of the drain region.2. The multi-gate FET of claim 1 , wherein a portion of the bulk substrate directly below the body region of each silicon fin structure includes a corresponding tipped shape.3. The multi-gate FET of claim 1 , wherein a portion of the bulk substrate between each silicon fin structure includes a tipped shape.4. The multi-gate FET of claim 1 , wherein the source region is partially isolated from the bulk substrate.5. The multi-gate FET of claim 1 , wherein the drain region is partially isolated from the bulk substrate.6. The multi-gate FET of claim 1 , wherein an oxide layer isolates the body region of each silicon fin structure from the bulk substrate.7. The multi-gate FET of claim 1 , further comprising a gate over each ...

PREDICTION OF OUT OF SPECIFICATION BASED ON A SPATIAL CHARACTERISTIC OF PROCESS VARIABILITY

A method for determining a probabilistic model configured to predict a characteristic (e.g., defects, CD, etc.) of a pattern of a substrate subjected to a patterning process. The method includes obtaining a spatial map of a distribution of a residue corresponding to a characteristic of the pattern on the substrate, determining a zone of the spatial map based on a variation of the distribution of the residue within the spatial map, and determining the probabilistic model based on the zone and the distribution of the residue values or the values of the characteristic of the pattern on the substrate within the zone. 1. A method comprising:obtaining a spatial map of a distribution of a residue corresponding to a characteristic of a pattern on a substrate subjected to a patterning process;determining, by a hardware computing system, a zone of the spatial map based on a variation of the distribution of the residue within the spatial map; anddetermining, by the hardware computing system and based on the zone and the distribution of the residue values or the values of the characteristic of the pattern on the substrate within the zone, a probabilistic model configured to predict the characteristic.2. The method of claim 1 , wherein the determining the zone comprises:determining that the variation of the distribution of the residue exceeds a certain threshold; andresponsive to the variation of the distribution of the residue exceeding the threshold, defining a different zone.3. The method of claim 1 , wherein the determining the zone is an iterative process claim 1 , wherein a plurality of zones are obtained based on the variation of the distribution of the residue claim 1 , such that a first zone of the plurality of zones has a first variation of the distribution of the residue claim 1 , and a second zone of the plurality of zones has a second variation of the distribution of the residue.4. The method of claim 3 , wherein an iteration of the determining the zone comprises: ...

DIARYL AND ARYLHETEROARYL UREA DERIVATIVES AS MODULATORS OF THE 5-HT2A SEROTONIN RECEPTOR USEFUL FOR THE PROPHYLAXIS AND TREATMENT OF DISORDERS RELATED THERETO

The present invention relates to certain pyrazole derivatives of Formula (I) and pharmaceutical compositions thereof that modulate the activity of the 5-HTserotonin receptor. 154.-. (canceled)561. The pharmaceutical composition of claim , wherein the therapeutically effective amount is from about 0.001 milligram to about 5 ,000 milligrams.571. The pharmaceutical composition of claim , wherein the therapeutically effective amount is from about 0.001 milligrams to 100 milligrams.581. The pharmaceutical composition of claim , wherein the pharmaceutical composition is formulated for a mode of administration selected from the group consisting of oral , rectal , nasal , topical (including buccal and sub-lingual) , vaginal , parenteral (including intramuscular , sub-cutaneous and intravenous) , inhalation , insufflation , and transdermally.591. The pharmaceutical composition of claim , wherein the pharmaceutical composition is administered in a unit dose selected from the group consisting of tablets , capsules , solutions , suspensions , emulsions , elixirs , gels , suppositories , sterile injectable solutions , and transdermal patches.601. The pharmaceutical composition of claim , wherein the pharmaceutically acceptable salt is selected from the group of acid addition salts consisting of acetic , benzenesulfonic , benzoic , camphorsulfonic , citric , ethenesulfonic , dichloroacetic , formic , fumaric , gluconic , glutamic , hippuric , hydrobromic , hydrochloric , isethionic , lactic , maleic , malic , mandelic , methanesulfonic , mucic , nitric , oxalic , pamoic , pantothenic , phosphoric , succinic , sulfiric , tartaric , oxalic , and p-toluenesulfonic.611. The pharmaceutical composition of claim , wherein the compound of Formula I is administered in combination with a dopamine D2 receptor antagonist.62. The pharmaceutical composition of claim 61 , wherein the dopamine D2 receptor antagonist is Haloperidol.63. The pharmaceutical composition of claim 61 , wherein the ...

LOW COST AND HIGH STRENGTH TITANIUM ALLOY AND HEAT TREATMENT PROCESS

Systems and methods of a low cost, high strength titanium alloy are disclosed. According to illustrative implementations, the weight percent of the alloy composition may be: Fe content 3%˜7%, Al content 3%˜5%, C content 0.01%˜0.02%, with the balance being Ti and unavoidable impurities. Industrial pure iron, carbon steel, and industrial pure aluminum etc. may be used as the raw materials. In one exemplary method, the raw materials are mixed before being pressed to a block. The block may be double-melted to an alloy cast ingot, forged by a conventional titanium alloy forging process, and subsequently undergo a solid solution treatment of (820° C.˜950° C.)/1 h+water quenching, and an ageing treatment of (450° C.˜550° C.)/4 h+air cooling, wherein the mechanical properties of the alloy are that σb=1000˜1250 MPa, δ=5%˜12%. 1. A low cost and high strength titanium alloy , characterized in that , alloy elements in the alloy and the weight percent thereof are that: the content of Fe is 3%˜7% , the content of Al is 3%˜5% , the content of C is 0.01%˜0.02% , the balance is Ti , and the unavoidable impurities.2. A heat treatment of solid solution and ageing process of the alloy according to , characterized in that , the alloy of undergoes the solid solution treatment of (820° C.˜950° C.)/1 h+water quenching , and the ageing treatment of (450° C.˜550° C.)/4 h+air cooling. The invention belongs to the technical field of metal alloys, and in particular, refers to a low cost and high strength titanium alloy that iron and aluminum can be used as the main alloying element, and the heat treatment process.The excellent comprehensive properties of the titanium and the titanium alloy can be widely applied in the aerospace field, etc., but as compared to the aluminum alloy and the ferrous materials, the high cost limits the broader use of the titanium alloy, particularly in the civil field, so in order to popularize the application of the titanium alloy, it is necessary to research and ...

SERVICE RESTORATION METHOD FOR MULTI-FAULTS IN DISTRIBUTION NETWORK

A multi-faults service restoration method for a power distribution network overcomes the defect that a traditional service restoration method for the power distribution network cannot solve multi-faults. The method includes the steps of performing multi-faults judgment on multi-faults with processing unfinished, to form many multi-faults and many single-faults; then performing unaided fault recovery area division on the multi-faults, and performing power restoration on unaided fault recovery areas one by one; and after the multi-faults are processed, performing power restoration on each single-fault. By adopting the method, the service restoration efficiency is greatly improved, thus contributing to the real-time of service restoration; the factor of load balance is considered when common power restoration lines are decoupled, so that the load rates of the power restoration lines participating in service restoration are more similar after service restoration, and therefore the power supply reliability of the power distribution network is improved. 1. A multi-faults service restoration method for a power distribution network , comprising the following several steps:(1) stopping executing an original fault processing strategy with executing unfinished;(2) turning on outlet circuit breakers for fault lines;(3) re-dividing unaided fault recovery areas: if some fault recovery areas subjected to single-fault are connected by a loop switch and these fault recovery areas subjected to single-fault are connected with the remaining fault recovery areas subjected to single-fault by at least one power restoration line, regarding these fault recovery areas subjected to single-fault as a whole, and calling them as unaided fault recovery areas;(4) determining common power restoration lines and unaided power restoration lines for the unaided fault recovery areas;(5) re-determining multi-faults;(6) performing multi-faults service restoration;(7) forming a service restoration scheme ...

Process for preparing beta 3 agonists and intermediates

The application is directed to efficient and economical processes as described in more detail below for the preparation of the beta 3 agonists of the formula of I-7 and intermediate compounds that can be used for making these agonists. The present disclosure relates to a process for making beta-3 agonists and intermediates using ketoreductase (KRED) biocatalyst enzymes and methods of using the biocatalysts.

Conditional Process-Aided Multiple-Points Statistics Modeling

A method of simulating a hydrocarbon reservoir is disclosed. A process-based model is generated that mimics a depositional process of the reservoir. The process-based model is analyzed to extract statistics of geometries of a body that forms part of the reservoir, and depositional rules of the body. An object-based modeling method is applied to construct multiple unconditional geologic models of the body using the statistics and the depositional rules. Training images are constructed using the multiple unconditional geologic models. Well data and gross thickness data are assigned into a simulation grid. A single multiple-point geostatistical simulation is performed using the training images. A three-dimensional (3D) reservoir model is constructed using results of the multiple-point geostatistical simulation. 1. A method comprising:generating, with a computer, a process-based model that mimics a depositional process of a hydrocarbon reservoir;analyzing, with the computer, the process-based model to extract statistics of geometries of a depositional or sedimentary body that forms part of the hydrocarbon reservoir, anddepositional rules of the depositional or sedimentary body;applying, with the computer, an object-based modeling method to construct multiple unconditional geologic models of the depositional or sedimentary body using the statistics and the depositional rules;constructing, with the computer, training images using the multiple unconditional geologic models;assigning, with the computer, well data and gross thickness data into a simulation grid; performing, with the computer, a single multiple-point geostatistical simulation using the training images; andconstructing, with the computer, a three-dimensional (3D) reservoir model using results of the multiple-point geostatistical simulation.2. The method of claim 1 , wherein performing the multiple-point geostatistical simulation comprises:defining a template vector to scan training images simultaneously; ...

STRESS-INDUCED MAGNETIC FIELD SIGNAL ACQUISITION METHOD AND STRESS MEASUREMENT METHOD BASED THEREON

A method for stress-induced magnetic field signal acquisition and stress measurement is disclosed. The method can include the following steps: a1, conducting AC magnetization on a to-be-tested structure by using an AC magnetic field with preset frequencies and strengths, and acquiring the excitation magnetic field signals in at least one cycle; a2, subtracting the excitation magnetic field signals in at least one cycle of a stress-free sample having the same material as the to-be-tested structure from the excitation magnetic field signals acquired in step a1 to obtain a stress-induced magnetic field signals of the to-be-tested structure; a3, quantitatively assessing the stresses in the to-be-tested structure by comparing the mean values of the stress-induced magnetic field signals acquired in step a2 with the pre-calibrated relationship of stresses and the mean values of the stress-induced magnetic field signals for the material of the to-be-tested structure. 1. A stress-induced magnetic field signal acquisition method , comprising the steps of:a1, conducting AC magnetization on a to-be-tested structure with preset frequency and strength, and acquiring excitation magnetic field signals in at least one cycle;a2, conducting the same AC magnetization as in step a1, on a stress-free sample of the same material as the to-be-tested structure, and extracting the excitation magnetic field signals in at least one cycle; anda3, subtracting the excitation magnetic field signals acquired in step a2 from the excitation magnetic field signals acquired in step al to obtain stress-induced magnetic field signals in at least one cycle of the to-be-tested structure.2. A stress measurement method based on claim 1 , comprising the steps of:b1, conducting AC magnetization on a to-be-tested structure with preset frequency and strength, acquiring the stress-induced magnetic field signals in at least one cycle of the to-be-tested structure, and calculating mean values of the stress-induced ...

Process for preparing tetracyclic heterocycle compounds

The present invention is directed to a process for preparing Tetracyclic Heterocycle Compounds of formula (I): which are useful as HCV NS5A inhibitors. The present invention is also directed to compounds that are useful as synthetic intermediates for making the compounds of formula (I).

METHIONINE LYASE, ENCODING GENE AND BIOSYNTHETIC METHOD THEREOF

Embodiment of the present invention discloses a kind of methionine lyase and its encoding gene and biosynthetic method. According to the present invention, the gene encoding methionine lyase as shown in SEQ ID No. 1 is separated from the genome of . Embodiment of the present invention further provides an efficient biosynthetic method of methionine lyase, comprising: (1) cloning gene (shown in SEQ ID No. 1) encoding methionine degradation enzyme into a yeast expression vector to construct recombinant yeast expression vector; (2) transforming the recombinant yeast expression vector into to obtain expression strain; (3) inducing the expression strain to express the methionine lyase, collecting induced strains, purifying expressed recombinant methionine lyase. Purity of recombinant methionine lyase prepared according to the present invention is above 90%, and its efficiency of degradating methionine can reach 0.53±0.0030 μM MTL·h·mg protein. 1. A gene encoding methionine lyase from the fungus , cDNA sequence of which is (a) , (b) or (c) as follows:(a) nucleotide as shown in SEQ ID No. 1;(b) nucleotide which is capable of being hybridized with complementary sequence of SEQ ID NO: 1 in strict hybridization condition;(c) nucleotide sequence with homology of at least 80% to the nucleotide sequence as shown in SEQ ID No. 1; preferably, nucleotide sequence with homology of at least 90% to the nucleotide sequence as shown in SEQ ID No. 1; more preferably, nucleotide sequence with homology of at least 95% to the nucleotide sequence as shown in SEQ ID No. 1; most preferably, nucleotide sequence with homology of at least 97% to the nucleotide sequence as shown in SEQ ID No. 1.2. A recombinant expression vector containing the encoding gene of claim 1 , wherein preferably claim 1 , the recombinant expression vector is a recombinant yeast expression vector.3Saccharomyces cerevisiae. A recombinant host cell containing the recombinant expression vector of ; wherein preferably claim 2 ...

ANILINO PODOPHYLLIN DERIVATIVE HAVING ANTITUMOR ACTIVITY, METHOD FOR PREPARATION THEREOF, AND USE THEREOF

The present invention discloses an anilino-substituted podophyllin derivative having antitumor activity, method for preparation thereof, and use thereof. By means of anilino reactions, the present invention introduces 4-chloro-3-methylaniline, 3-fluoro-4-methoxyaniline, 4,4′-diaminodiphenylmethane, o-anisidine, 4-chloro-2-aminoanisole, anthranilonitrile, 2,6-dichloro-4-aminophenol, N,N-dimethylamino meta-aniline, 2-ethyl-5-nitroaniline, 2 2′-diaminodiphenylsulfide, or 2-aminobenzotrifluoride into position 4 of the active C-ring of podophyllotoxin or 4′-demethylepipodophyllotoxin to obtain the aniline-substituted podophyllotoxin derivative shown in formula (V); by means of multi-pathway and multi-target effects on tumor cells, said derivative has significantly increased antitumor activity, and can be prepared as an antineoplastic drug and applied in clinical antitumor therapy. 110-. (canceled)12. A method for preparing the aniline-substituted podophyllotoxin-type derivatives as claimed in claim 11 , comprising the steps of: by aniline substitution reaction claim 11 , 4-chloro-3-methylaniline claim 11 , 3-fluoro-4-methoxyaniline claim 11 , 4 claim 11 ,4′-diaminodiphenylmethane claim 11 , o-anisidine claim 11 , 4-chloro-2-aminoanisole claim 11 , o-aminobenzonitrile claim 11 , 2 claim 11 ,6-dichloro-4-aminophenol claim 11 , N claim 11 ,N-dimethylamino metanil claim 11 , 2-ethyl-5-nitroaniline claim 11 , 2 2′-diaminodiphenylsulfide or 2-aminobenzotrifluoride is introduced into position 4 of C-ring of podophyllotoxin and 4′-demethylepipodophyllotoxin respectively claim 11 , to get crude product of aniline-substituted podophyllotoxin-type derivatives.13. The method as claimed in claim 12 , wherein claim 12 , the aniline reaction is comprising:(1) activating position 4 of C-ring of podophyllotoxin or 4′-demethylepipodophyllotoxin; (2) podophyllotoxin or 4′-demethylepipodophyllotoxin with activated position 4 of C-ring being dissolved in organic solvent, then adding 4-chloro ...

3d defect detection method with magnetic flux leakage testing

The present invention discloses a 3D defect detection method with magnetic flux leakage testing (MFLT). It has advantages of higher accuracy of 3D detection of defect and simpler testing device relative to the prior MFLT art. This method includes the following steps: S1: artificially magnetizing a to-be-tested structure, and measuring its MFLT signals {B}; S2: inverting magnetic charge distribution of the interior of the to-be-tested structure by using a magnetic charge distribution reconstruction algorithm to obtain the magnetic charge density of a non-defective region of the to-be-tested structure; and S3: using the magnetic charge density of the non-defective region of the to-be-tested structure as a known constant, and conducting inverse iteration to reconstruct defect depth of the defective region to obtain a 3D image of the defective region of the to-be-tested structure.

Graphene Field Effect Transistors for Detection of Ions

A graphene-based ion sensitive field effect transistor (GISFET) with high sensitivity and selectivity for ions is provided. For example, the GISFET of the present invention can exhibit high sensitivity and selectivity for Kions has been demonstrated utilizing a valinomycin-based ion selective membrane. The sensitivity of the GISFET can be at least about 50 millivolts/decade and can be stable for a time period of about two months, indicating the GISFET's reliability and effectiveness for physiological monitoring. 1. A graphene ion selective field effect transistor comprising:a substrate;a graphene film disposed on the substrate; andan ion selective membrane disposed on the graphene film, wherein the ion selective membrane comprises an ionophore, a lipophilic salt, and a polymer having a molecular weight ranging from about 100,000 Daltons to about 200,000 Daltons.2. The graphene ion selective field effect transistor of claim 1 , wherein the polymer has a glass transition temperature ranging from about −20° C. to about −60° C.3. The graphene ion selective field effect transistor of claim 1 , wherein the polymer is a block copolymer having a continuous amorphous phase and a discontinuous crystalline phase.4. The graphene ion selective field effect transistor of claim 3 , wherein the continuous amorphous phase comprises n-butyl acrylate and the discontinuous crystalline phase comprises methyl methacrylate.5. The graphene ion selective field effect transistor of claim 4 , wherein the n-butyl acrylate is present in the polymer in an amount ranging from about 82 wt. % to about 97.5 wt. % and the methyl methacrylate is present in the polymer in an amount ranging from about 2.5 wt. % to about 18 wt. %.6. The graphene ion selective field effect transistor of claim 1 , wherein the ion selective membrane is selective for potassium ions claim 1 , sodium ions claim 1 , calcium ions claim 1 , or cadmium ions.7. The graphene ion selective field effect transistor of claim 6 , wherein ...

DIARYL AND ARYLHETEROARYL UREA DERIVATIVES AS MODULATORS OF THE 5-HT2A SEROTONIN RECEPTOR USEFUL FOR THE PROPHYLAXIS AND TREATMENT OF DISORDERS RELATED THERETO

The present invention relates to certain pyrazole derivatives of Formula (I) and pharmaceutical compositions thereof that modulate the activity of the 5-HTserotonin receptor, 143.-. (canceled)46. The method according to wherein said sleep disorder comprises fragmented sleep architecture.47. The method according to wherein said effective amount of a compound Formula (I) promotes sleep consolidation.48. The method according to wherein said effective amount of a compound of Formula (I) increases delta power.49. The method according to wherein said sleep disorder is a dyssomnia.50. The method according to wherein said dyssomnia is selected from the group consisting of psychophysiological insomnia claim 49 , sleep state misperception claim 49 , idiopathic insomnia claim 49 , obstructive sleep apnea syndrome claim 49 , central sleep apnea syndrome claim 49 , central alveolar hypoventilation syndrome claim 49 , periodic limb movement disorder claim 49 , restless leg syndrome claim 49 , inadequate sleep hygiene claim 49 , environmental sleep disorder claim 49 , altitude insomnia claim 49 , adjustment sleep disorder claim 49 , insufficient sleep syndrome claim 49 , limit-setting sleep disorder claim 49 , sleep-onset association disorder claim 49 , nocturnal eating or drinking syndrome claim 49 , hypnotic dependent sleep disorder claim 49 , stimulant-dependent sleep disorder claim 49 , alcohol-dependent sleep disorder claim 49 , toxin-induced sleep disorder claim 49 , time zone change (jet lag) syndrome claim 49 , shift work sleep disorder claim 49 , irregular sleep-wake pattern claim 49 , delayed sleep phase syndrome claim 49 , advanced sleep phase syndrome and non-24-hour sleep-wake disorder.51. The method according to wherein said sleep disorder is a parasomnia.52. The method according to wherein said parasomnia is selected from the group consisting of confusional arousals claim 51 , sleepwalking and sleep terrors claim 51 , rhythmic movement disorder claim 51 , sleep ...

Process for preparing beta 3 agonists and intermediates

The application is directed to efficient and economical processes as described in more detail below for the preparation of the beta 3 agonists of the formula of I-7 and intermediate compounds that can be used for making these agonists. The present disclosure relates to a process for making beta-3 agonists and intermediates using ketoreductase (KRED) biocatalyst enzymes and methods of using the biocatalysts.

Diaryl and arylheteroaryl urea derivatives as modulators of the 5-ht2a serotonin receptor useful for the prophylaxis and treatment of disorders related thereto

The present invention also relates to the method of prophylaxis or treatment of 5-HT2A serotonin receptor mediated disorders in combination with a dopamine D2 receptor antagonist such as haloperidol, administered separately or together.

Device and method for detection of multiple analytes

Prediction of out of specification based on spatial characteristic of process variability

Described herein is a method for determining a probabilistic model configured to predict a characteristic (e.g., defects, CD, etc.) of a pattern of a substrate subjected to a patterning process. The method includes obtaining a spatial map of a distribution of a residue corresponding to a characteristic of the pattern on the substrate, determining a zone of the spatial map based on a variation of the distribution of the residue within the spatial map, and determining the probabilistic model based on the zone and the distribution of the residue values or the values of the characteristic of the pattern on the substrate within the zone.

Process for preparing tetracyclic heterocycle compounds

The present invention is directed to a process for preparing Tetracyclic Heterocycle Compounds of formula (I): which are useful as HCV NS5A inhibitors. The present invention is also directed to compounds that are useful as synthetic intermediates for making the compounds of formula (I).

Tetrahydropyranochromene gamma secretase inhibitors

Disclosed are novel gamma secretase inhibitors of the formula. Also disclosed are methods of inhibiting gamma-secretase, methods of treating neurodegenerative diseases, and methods of treating Alzheimer's Disease. Also disclosed are processes for preparing alkenes in one reaction step using a mixture of an aldehyde (or ketone) and an alkyl substituted with two electron withdrawing groups, and reacting the mixture with: (a) a sulfonyl halide (e.g., a sulfonyl chloride) and a basic tertiary amine, or, (b) a sulfonyl anhydride and a basic amine, or (c) an aryl-C(O)-halide and a basic tertiary amine, or (d) an aryl-C(O)—O—C(O)-aryl and a basic tertiary amine, or (e) an heteroaryl-C(O)-halide and a basic tertiary amine, or (f) a heteroaryl-C(O)—O—C(O)-heteroaryl and a basic tertiary amine.

Performance feed-forward thickness control method in tandem cold mill

The present invention relates to the field of strip cold rolling, and in particular to a thickness control method for strips in a tandem cold mill. Frame S 1 and one or more additional frames are selected as virtual indirect measuring instruments for the strip performance. A load cell is provided on the frames that are selected as the indirect measuring instruments for the strip performance, and deformation resistance fluctuation of the supplied materials of the frame S is calculated. Finally, the feed-forward adjustment amount of each frame is calculated. The present invention measures the deformation resistance of each section of the strip of the supplied materials through the selected frame, reducing the fluctuation of the thickness of the finished products of the strip and ensuring stable rolling.

Gamma secretase modulators for the treatment of alzheimer's disease

This invention provides novel compounds that are modulators of gamma secretase. The compounds have the formula: Also disclosed are methods of modulating gamma secretase activity and methods of treating Alzheimer's disease using the compounds of formula (I).

Gamma secretase modulators

This invention provides novel compounds that are modulators of gamma secretase. The compounds have the formula (Chemical formula should be inserted here as it appears on abstract in paper form). Also disclosed are methods of modulating gamma secretase activity and methods of treating Alzheimer's Disease using the compounds of formula (I).

Diaryl and Arylheteroaryl Urea Derivatives as Modulators of 5-Ht2a Serotonin Receptor Useful for the Prophylaxis or Treatment of Progressive Multifocal Leukoencephalopathy

The present invention relates to certain pyrazole derivatives of Formula (I) and pharmaceutical compositions thereof that modulate the activity of the 5-HT2A serotonin receptor. Compounds and pharmaceutical compositions thereof are directed to methods useful in the prophylaxis or treatment of progressive multifocal leukoencephalopathy.

Processes for preparing substituted n-aryl-n'-[3-(1h-pyrazol-5-yl) phenyl] ureas and intermediates thereof

The present invention is directed to processes for the preparation of substituted phenylpyrazole ureas of Formula (I), that are useful as 5-HT2A serotonin receptor modulators for the treatment of disease.

TETRAHYDROPYROCHYROMENE RANGE INHIBITORS SECRETASE

Gamma secretase modulators for the treatment of alzheimer ' s disease

This invention provides novel compounds that are modulators of gamma secretase. The compounds have the formula: Also disclosed are methods of modulating gamma secretase activity and methods of treating Alzheimer's disease using the compounds of formula (I).

Fused bicyclic heterocycles useful as dipeptidyl peptidase-iv inhibitors

The present invention is directed to novel bicyclic heterocycles of structural formula (I) which are inhibitors of the dipeptidyl peptidase-IV enzyme and which are useful in the treatment or prevention of diseases in which the dipeptidyl peptidase-IV enzyme is involved, such as diabetes and particularly Type 2 diabetes. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which the dipeptidyl peptidase-IV enzyme is involved.

Diaryl and arylheteroaryl urea derivatives as modulators of the 5-ht2a serotonin receptor useful for the prophylaxis and treatment of disorders related thereto

The present invention relates to certain pyrazole derivatives of Formula (I) and pharmaceutical compositions thereof that modulate the activity of the 5-HT2A serotonin receptor. Compounds and pharmaceutical compositions thereof are directed to methods useful in the prophylaxis or treatment of platelet aggreagation, coronary artery disease, myocardial infarction, transient ischemic attack, angina, stroke, atrial fibrillation, reducing the risk of blood clot formation, asthma or symptoms thereof, agitation or a symptom, behavioral disorders, drug induced psychosis, excitative psychosis, Gilles de la Tourette's syndrome, manic disorder, organic or NOS psychosis, psychotic disorder, psychosis, acute schizophrenia, chronic schizophrenia, NOS schizophrenia and related disorders, and sleep disorders, sleep disorders, diabetic-related disorders and the like. The present invention also relates to the method of prophylaxis or treatment of 5-HT2A serotonin receptor mediated disorders in combination with a dopamine D2 receptor antagonist such as haloperidol, administered separately or together.

Diaryl and arylheteroaryl urea derivatives as modulators of the 5-ht2a serotonin receptor useful for the prophylaxis and treatment of disorders related thereto

Processes for preparing substituted n-aryl-n'-[3-(1h-pyrazol-5-yl)phenyl] ureas and intermediates thereof

The present invention is directed to processes for the preparation of substituted phenylpyrazole ureas of Formula (I), that are useful as 5-HT2A serotonin receptor modulators for the treatment of disease.

Diaryl and aryl heteroaryl urea derivatives that adjust the 5-HT2A serotonin receptor useful for the prevention and treatment of diseases associated with it

Diaryl and arylheteroaryl urea derivatives as modulators of the 5-HT2A serotonin receptor useful for the prophylaxis and treatment of disorders related thereto

The present invention relates to certain pyrazole derivatives of Formula (I) and pharmaceutical compositions thereof that modulate the activity of the 5-HT 2A serotonin receptor. Compounds and pharmaceutical compositions thereof are directed to methods useful in the prophylaxis or treatment of platelet aggregation, coronary artery disease, myocardial infarction, transient ischemic attack, angina, stroke, atrial fibrillation, reducing the risk of blood clot formation, asthma or symptoms thereof, agitation or a symptom, behavioral disorders, drug induced psychosis, excitative psychosis, Gilles de la Tourette's syndrome, manic disorder, organic or NOS psychosis, psychotic disorder, psychosis, acute schizophrenia, chronic schizophrenia, NOS schizophrenia and related disorders, and sleep disorders, sleep disorders, diabetic-related disorders and the like. The present invention also relates to the method of prophylaxis or treatment of 5-HT 2A serotonin receptor mediated disorders in combination with a dopamine D2 receptor antagonist such as haloperidol, administered separately or together.

Processes for preparing substituted n-aryl-n’-[3-(1h-pyrazol-5-yl) phenyl] ureas and intermediates thereof

The present invention is directed to processes for the preparation of substituted phenylpyrazole ureas of Formula (I), that are useful as 5-HT2A serotonin receptor modulators for the treatment of disease.

Diaryl and arylheteroaryl urea derivatives as modulators of the 5-ht2a serotonin receptor useful for the prophylaxis and treatment of disorders related thereto

THE PRESENT INVENTION RELATES TO CERTAIN PYRAZOLE DERIVATIVES OF FORMULA (I) AND PHARMACEUTICAL COMPOSITIONS THEREOF THAT MODULATE THE ACTIVITY OF THE 5-HT 2A SEROTONIN RECEPTOR COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS THEREOF ARE DIRECTED TO METHODS USEFUL IN THE PROPHYLAXIS OR TREATMENT OF PLATELET AGGREAGATION, CORONARY ARTERY DISEASE, MYOCARDIAL INFARCTION, TRANSIENT ISCHEMIC ATTACK, ANGINA, STROKE, ATRIAL FIBRILLATION, REDUCING THE RISK OF BLOOD CLOT FORMATION, ASTHMA OR SYMPTOMS THEREOF, AGITATION OR A SYMPTOM,BEHAVIORAL DISORDERS, DRUG INDUCED PSYCHOSIS, EXCITATIVE PSYCHOSIS,GILLES DE LA TOURETTE'S SYNDROME, MANIC DISORDER, ORGANIC OR NOS PSYCHOSIS, PSYCHOTIC DISORDER, PSYCHOSIS, ACUTE SCHIZOPHRENIA, CHRONIC SCHIZOPHRENIA, NOS SCHIZOPHRENIA AND RELATED DISORDERS, AND SLEEP DISORDERS, SLEEP DISORDERS, DIABETIC-RELATED DISORDERS AND THE LIKE.THE PRESENT INVENTION ALSO RELATES TO THE METHOD OF PROPHYLAXIS OR TREATMENT OF 5-HT 2A SEROTONIN RECEPTOR MEDIATED DISORDERS IN COMBINATION WITH A DOPAMINE D2 RECEPTOR ANTAGONIST SUCH AS HALOPERIDOL, ADMINISTERED SEPARATELY OR TOGETHER.

Substituted n-arylsulfonylheterocyclic amines as gamma-secretase inhibitors

This invention discloses novel gamma secretase inhibitors of the formula I: wherein: L is -O- , -N(R6)-, -S-, -S(O)-, or -S(O2)-; R1 is selected from the group consisting of aryl and heteroaryl; R2 is selected from the group consisting of alkyl, -C(O)-Y, -X-C(O)-Y, -alkylene-X-C(O)-Y, -alkylene-C(O)-Y, -alkylene-cycloalkylene-X-C(O)-Y, -alkylene-cycloalkylene-C(O)-Y, -cycloalkylene-alkylene-X-C(O)-Y, -cycloalkylene-alkylene-C(O)-Y, -cycloalkylene-X-C(O)-Y, -cycloalkylene-C(O)-Y, -alkylene-cycloalkylene-alkylene-X-C(O)-Y, -alkylene-cycloalkylene-alkylene-C(O)-Y, aryl, and heteroaryl; R3 is selected from the group consisting of aryl, heteroaryl, alkyl, cycloalkyl, arylalkyl, arylcycloalkyl, heteroarylalkyl, heteroarylcycloalkyl, arylheterocycloalkyl, and alkoxyalkyl; each R4 and R5 is independently selected from the group consisting of H and alkyl; and Y is selected from the group consisting of -NR8R9, -N(R6)-(CH2)b-NR8R9, aryl, heteroaryl, alkyl, cycloalkyl, arylalkyl, arylcycloalkyl, heteroarylalkyl, heteroarylcycloalkyl, and arylheterocycloalkyl; or Y is selected from the group consisting of Formula II and Formula III: One or more compounds of formula I, or formulations comprising such compounds, may be useful, e.g. in treating Alzheimer's Disease.

N-ARYLSULFONYLAMINES SUBSTITUTE HETEROCYCLIC AS INHIBITORS OF GAMMA-SECRETASES

SE REFIERE A COMPUESTOS DE N-ARILSUFONILAMINAS HETEROCICLICAS DE FORMULA (I), EN DONDE L ES -O-, -N(R6)-, -S-, ENTRE OTROS; R1 ES ARILO O HETEROARILO SUSTITUIDO CON R7; R2 ES -(C0-C6)ALQUILEN-(C3-C6)CICLOALQUILEN-(C0-C6)ALQUILEN-X-C(O)-Y, -(C0-C6)ALQUILEN-(C3-C6)CICLOALQUILEN-(C0-C6)ALQUILEN-C(O)-Y, -(C3-C6)CICLOALQUILEN-(C1-C6)ALQUILEN-C(O)-Y, ENTRE OTROS, SUSTITUIDO EL ALQUILENO CON UNO O MAS HIDROXI; R3 ES ARILO, ALQUILO, CICLOALQUILO,HETEROARILO, ENTRE OTROS, OPCIONALMENTE SUSTITUIDOS CON R7; X ES -O-, -N(R6)-, ENTRE OTROS; Y ES -NR8R9, -N(R6)-(CH2)b-NR8R9-, ARILO, ENTRE OTROS; m Yn SON INDEPENDIENTEMENTE DE 0 A 2, SIEMPRE QUE m + n SEA 1 0 2. SON PREFERIDOS: ESTER 4-(4-CLORO-BENCENSULFONIL)-5-(3,5-DIFLUORO-FENIL)-MORFOLIN-3-IL-METILICO DEL ACIDO 4-(2-HIDROXI-ETIL)-PIPERAZIN-1-CARBOXILICO, ALFA-[1-[4-[(4-CLOROFENIL)SULFONIL]-5(r)-CICLOPROPIL-3(S)-MORFOLINIL]CICLOPROPIL]-BETA-OXO-3,8-DIAZABICICLO[3.2.1]OCTAN-3-ETANOL, ENTRE OTROS. TAMBIEN SE REFIERE A UNA COMPOSICION FARMACEUTICA. ESTOS COMPUESTOS SON INHIBIDORES DE LA GAMMA SECRETASA POR LO QUE SON UTILES EN EL TRATAMIENTO DEL ALZHEIMER REFERS TO HETEROCYCLIC N-ARYLSUFONYLAMINE COMPOUNDS OF FORMULA (I), WHERE L IS -O-, -N (R6) -, -S-, AMONG OTHERS; R1 IS ARYL OR HETEROARYL SUBSTITUTE WITH R7; R2 ES - (C0-C6) ALKYLEN- (C3-C6) CYCLOALKYLENE- (C0-C6) ALKYLEN-XC (O) -Y, - (C0-C6) ALKYLEN- (C3-C6) CYCLOALKYLEN- (C0-C6 ) ALKYLEN-C (O) -Y, - (C3-C6) CYCLOALKYLENE- (C1-C6) ALKYLEN-C (O) -Y, AMONG OTHERS, SUBSTITUTE THE ALKYLENE WITH ONE OR MORE HYDROXY; R3 IS ARYL, ALKYL, CYCLOALKYL, HETEROARYL, AMONG OTHERS, OPTIONALLY SUBSTITUTED WITH R7; X IS -O-, -N (R6) -, AMONG OTHERS; Y IS -NR8R9, -N (R6) - (CH2) b-NR8R9-, ARYL, AMONG OTHERS; m AND n ARE INDEPENDENTLY FROM 0 TO 2, PROVIDED THAT m + n IS 1 0 2. THEY ARE PREFERRED: ESTER 4- (4-CHLORO-BENCENSULFONIL) -5- (3,5-DIFLUORO-PHENYL) -MORFOLIN-3-IL -METHYL ACID 4- (2-HYDROXY-ETHYL) -PIPERAZIN-1-CARBOXYL, ALPHA- [1- [4 - [(4-CHLOROPHENYL) SULFONIL] -5 (r) -CYCLOPROPYL-3 (S) ...

Low cost and high strength titanium alloy and heat treatment process

Systems and methods of a low cost, high strength titanium alloy are disclosed. According to illustrative implementations, the weight percent of the alloy composition may be: Fe content 3%˜7%, Al content 3%˜5%, C content 0.01%˜0.02%, with the balance being Ti and unavoidable impurities. Industrial pure iron, carbon steel, and industrial pure aluminum etc. may be used as the raw materials. In one exemplary method, the raw materials are mixed before being pressed to a block. The block may be double-melted to an alloy cast ingot, forged by a conventional titanium alloy forging process, and subsequently undergo a solid solution treatment of (820° C.˜950° C.)/1 h+water quenching, and an ageing treatment of (450° C.˜550° C.)/4 h+air cooling, wherein the mechanical properties of the alloy are that σb=1000˜1250 MPa, δ=5%-12%.

Gamma secretase modulators

The present invention provides a novel class of heterocyclic compounds of Formula (I) as modulators of gamma secretase, wherein the definitions of the variables of Formula (I) are defined herein, methods of preparing such compounds, pharmaceutical compositions containing one or more such compounds, methods of preparing pharmaceutical formulations comprising one or more such compounds, and methods of treatment, prevention, inhibition, or amelioration of one or more diseases associated with the central nervous system using such compounds or pharmaceutical compositions.

Secondary battery

In order to overcome the problem of insufficient safety performance of existing secondary batteries, the present application provides a secondary battery, comprising a positive electrode, the positive electrode comprises a positive electrode material layer, and the positive electrode material layer comprises a positive electrode active material and a compound represented by structural formula 1: the positive electrode active material includes one or more of the compounds represented by formula (1) and formula (2);         Li 1+x Ni a Co b M' 1-a-b O 2-y A y      formula (1)         Li 1+z Mn c L 2-c O 4-d B d      formula (2) the positive electrode material layer meets the following requirements: 0.05 ≤ p ⋅ u/v ≤ 15 wherein, u is the percentage mass content of element phosphorus in the positive electrode material layer, and the unit is wt%; v is the percentage mass content of element M in the positive electrode material layer, element M is selected from one or two of Mn and Al, and the unit is wt%; p is the surface density of one single surface of the positive electrode material layer, and the unit is mg/cm 2 . The battery provided by the present application possesses higher safety performance.

Multi-gate field effect transistor (FET) including isolated fin body

Aspects of the disclosure provide a multi-gate field effect transistor (FET) formed on a bulk substrate that includes an isolated fin and methods of forming the same. In one embodiment, the multi-gate FET includes: a plurality of silicon fin structures formed on the bulk substrate, each silicon fin structure including a body region, a source region, and a drain region; wherein a bottom portion the body region of each silicon fin structure includes a tipped shape to isolate the body region from the bulk substrate, and wherein the plurality of silicon fin structures are attached to the bulk substrate via at least a portion of the source region, or at least a portion of the drain region, or both.

Diaryl and arylheteroaryl urea derivatives as modulators of the 5-ht2a serotonin receptor useful for the prophylaxis and treatment of disorders related thereto

Processes for preparing substituted N-aryl-N′-[3-(1H-pyrazol-5-YL) phenyl] ureas and intermediates thereof

The present invention is directed to processes for the preparation of substituted phenylpyrazole ureas of Formula (I), that are useful as 5-HT 2A serotonin receptor modulators for the treatment of disease.

System and method for de-embedding a device under test employing a parametrized netlist

S-parameter data is measured on an embedded device test structure, an open dummy, and a short dummy. A 4-port network of the pad set parasitics of the embedded device test structure is modeled by a parameterized netlist containing a lumped element network having at least one parameterized lumped element. The S-parameter data across a range of measurement frequencies is fitted with the parametrized netlist employing the at least one parameterized lumped element as at least one fitting parameter for the S-parameter data. Thus, the fitting method is a multi-frequency fitting for the at least one parameterized lumped element. A 4-port Y-parameter (admittance parameter) is obtained from the fitted parameterized netlist. The Y-parameter of the device under test is obtained from the measured admittance of the embedded device test structure and the calculated 4-port Y parameter.

Process for preparing beta 3 agonists and intermediates

Processes for preparing substituted n-aryl-n'-[3-(1h-pyrazol-5-yl) phenyl] ureas and intermediates thereof

The present invention is directed to processes for the preparation of substituted phenylpyrazole ureas of Formula (I), that are useful as 5-HT2A serotonin receptor modulators for the treatment of disease.

System and method for de-embedding a device under test employing a parametrized netlist

S-parameter data is measured on an embedded device test structure, an open dummy, and a short dummy. A 4-port network of the pad set parasitics of the embedded device test structure is modeled by a parameterized netlist containing a lumped element network having at least one parameterized lumped element. The S-parameter data across a range of measurement frequencies is fitted with the parameterized netlist employing the at least one parameterized lumped element as at least one fitting parameter for the S-parameter data. Thus, the fitting method is a multi-frequency fitting for the at least one parameterized lumped element. A 4-port Y-parameter (admittance parameter) is obtained from the fitted parameterized netlist. The Y-parameter of the device under test is obtained from the measured admittance of the embedded device test structure and the calculated 4-port Y parameter.

Compounds derived from tetrahydropyranochroman, preparation procedure, pharmaceutical composition, useful for inhibiting gamma-secretase, intended for the treatment of neurodegenerative diseases, Alzheimer's disease and inhibiting the deposit of amyloid protein.

Compuestos derivados de tetrahidropiranocromano, procedimiento de preparación, composición farmacéutica, útil para inhibir gamma-secretasa, destinados al tratamiento de enfermedades neurodegenerativas, enfermedad de Alzheimer e inhibir el depósito de proteína amiloide. Compounds derived from tetrahydropyranochroman, preparation method, pharmaceutical composition, useful for inhibiting gamma-secretase, intended for the treatment of neurodegenerative diseases, Alzheimer's disease and inhibiting the deposit of amyloid protein.

Carbocyclic and heterocyclic arylsulfones as gamma secretase inhibitors

This invention discloses novel gamma secretase inhibitors of the formula: R2 and R3, or R2 and R4, or R3 and R4, together with the atoms to which they are bound, can form a fused cycloalkyl or fused heterocycloalkyl ring. The cycloalkyl ring or the heterocycloalkyl ring can be optionally substituted with one or more substituents. One or more compounds of formula (I), or formulations comprising such compounds, may be useful, e.g. in treating Alzheimer's Disease.

Dianyl and aryl heteroarlurea derivatives as modulators of 5-HT 2A serotonin receptors useful for the prophylaxis and treatment of disorders associated with this

Foreliggende oppfirmelse angår spesielle pyrazolderivater med formel (I), og farmasøytiske sammensetninger derav som modulerer 5-HT2A- serotonin reseptoraktiviteten. Forbindelser og farmasøytiske sammensetninger derav er rettet mot fremgangsmåter som er nyttige i profylakse eller behandling av blodplateaggregering, hjertekarsykdom, hjerteinfarkt, forbigående iskemisk attakk, angina, slag, atrial fibrillering, reduksjon av risiko for blodproppdannelse, astma eller symptomer derav, agitasjon eller et symptom, atferdsforstyrrelser, medikamentindusert psykose, utagerende psykose. Grilles de la Tourettes syndrom, manisk forstyrrelse, organisk eller NOS-psykose, psykotisk forstyrrelse, psykose, akutt schizofreni, kronisk schizofreni, NOS schizofreni og henhørende forstyrrelser, søvnforstyrrelser, diabetesrelaterte forstyrrelser, og liknende. Foreliggende oppfirmelse angår også fremgangsmåter av profylakse eller behandling av 5-HT2A serotonin formidlete forstyrrelser i kombinasjon med en dopamin-D2-reseptorantagonist, slik som et haloperidol, tilført separat eller samtidig.

Conditional process-aided multiple-points statistics modeling

A method of simulating a hydrocarbon reservoir is disclosed. A process-based model is generated that mimics a depositional process of the reservoir. The process-based model is analyzed to extract statistics of geometries of a body that forms part of the reservoir, and depositional rules of the body. An object-based modeling method is applied to construct multiple unconditional geologic models of the body using the statistics and the depositional rules. Training images are constructed using the multiple unconditional geologic models. Well data and gross thickness data are assigned into a simulation grid. A single multiple-point geostatistical simulation is performed using the training images. A three-dimensional (3D) reservoir model is constructed using results of the multiple-point geostatistical simulation.

Solvent-free moisture curing silicone conformal coating and preparation method thereof

The present disclosure relates to a solvent-free moisture curing silicone conformal coating used for the surface protection of circuit boards in the electrical and electronic industries and a preparation method thereof. The solvent-free moisture curing silicone conformal coating comprises (A) a hydrolyzable functional group-terminated linear polysiloxane (I); (B) a hydrolyzable functional group-containing silicone resin with a three-dimensional structure (II); (C) a hydrolyzable functional group-containing crosslinking agent; (D) a catalyst; (E) an adhesion promoter. The solvent-free conformal coating of the present disclosure has low viscosity, high strength and good toughness, and can meet the traditional coating process such as spraying, brushing, dipping, etc., while satisfying the surface protection of the circuit board. Compared with the traditional solvent-based silicon conformal coating, the solvent-free silicon conformal coating can be cured by moisture, the VOC content released during the curing process is low, and the harm to the environment and occupational health is small.

Phenyl -o-quinoline, quinazoline, thienopyridine, thienopyrimidine, pyrrolopyridine, pyrrolopyrimidine compounds having anticancer activity

The present disclose includes, among other things, compounds that treat or lessen the severity of a disorder, pharmaceutical compositions and methods of making and using the same.

Verfahren zur herstellung von substituierte n- aryl-n'-ä3-(1h-pyrazol-5-yl)phenylü-harnstoffe and intermediate davon.

Phenyl -o-quinoline, quinazoline, thienopyridine, thienopyrimidine, pyrrolopyridine, pyrrolopyrimidine compounds having anticancer activity

The present disclose includes, among other things, compounds that treat or lessen the severity of a disorder, pharmaceutical compositions and methods of making and using the same.

Method for inhibiting bitter taste of tartary buckwheat seeds and its application

Disclosed is a method for inhibiting bitter taste of Tartary buckwheat seeds and its application, belonging to the field of whole grain food processing technology. The specific method includes: freezing the Tartary buckwheat seeds, then drying them to a moisture content of 10- 12% to obtain pretreated Tartary buckwheat seeds; placing the pretreated buckwheat seeds in a closed container for depressurization and exhaust; injecting steam into the material after depressurization and exhaust for heating treatment; cooling and drying the material for later use. The present invention focuses on the characteristic that rutinase in Tartary buckwheat is mainly concentrated in the grain bran layer, and after freezing treatment and air removal, the Tartary buckwheat seeds are subjected to steam heating treatment, which not only inactivates the rutinase in the Tartary buckwheat in a short period of time, inhibits the generation of quercetin, but also reverses hydrolysis of quercetin, which has already been enzymatically hydrolysed, and reduces it to rutin, increases the content of rutin in Tartary buckwheat and achieves the goal of inhibiting the bitterness of Tartary buckwheat grains at the same time.

Lithium-ion battery

The application relates to the technical field of lithium ion batteries and discloses a lithium ion battery. The lithium ion battery comprises a positive electrode, a negative electrode, a separator arranged between the positive electrode and negative electrode, and a non-aqueous electrolyte; an active material of the positive electrode comprises LiFePO₄, the non-aqueous electrolyte comprises an organic solvent, a lithium salt, vinylene carbonate and a compound represented by Formula (1), wherein R₁ is one or more of chain, cyclic and aromatic group with 2-20 carbon atoms, and a compacted density of the positive electrode material is more than 2g/cm³. The lithium ion battery provided by the application may obviously improve the cycle and storage performances at high temperature, greatly improve the capacity retention rate and capacity recovery rate of battery, obviously reduce the thickness expansion rate after high-temperature storage, and meanwhile, greatly reduce the precipitation of iron ions.

Integrated circuit development using density-aware border fill

Aspects of the invention include setting a fill mode for a border region of a layer of a macro of an integrated circuit. The border region has a depth defined by a multiple of the size of a tile used to select an area of the integrated circuit for implementation of a design rule check, and the fill mode indicates a fill percentage value or level of fill to be implemented in the border region of the layer of the macro. A fill of the border region of the layer of the macro is performed based on the fill mode. The integrated circuit is finalized and fabricated based on the performing of the fill and passing the design rule check.

Substituierte n-arylsulfonylheterocyclische amine als gamma-sekretase-hemmer

Phenyl -o-quinoline, quinazoline, thienopyridine, thienopyrimidine, pyrrolopyridine, pyrrolopyrimidine compounds having anticancer activity

The present disclose includes, among other things, compounds that treat or lessen the severity of a disorder, pharmaceutical compositions and methods of making and using the same.

Secondary Battery

In order to solve the problem that the existing manganese-based positive electrode material battery has insufficient high-temperature cycle and high-temperature storage performances due to the dissolution of manganese ions, the present application provides a secondary battery, comprising a positive electrode, a negative electrode and a non-aqueous electrolyte, the positive electrode comprises a positive electrode material layer containing a positive electrode active material, the positive electrode active material comprises a manganese-based material, and the non-aqueous electrolyte comprises a solvent, an electrolyte salt and an additive, and the additive comprises a compound represented by structural formula 1:the secondary battery meets the following requirements:0.05≤100×W×u/(q×s)≤5;and 2.0 g/Ah≤W≤4.5 g/Ah, 0.05%≤u≤3.5%, 5%≤q≤65%, 10 mg/cm2≤s≤30 mg/cm2.The secondary battery has a high capacity retention rate in the cycle and high-temperature storage processes, and has good cycle and storage performances.

Iron phosphate lithium battery

In order to overcome the problems of lithium dendrite and iron ion dissolution in the existing high-compacted-density lithium iron phosphate battery, the application provides a lithium iron phosphate battery, comprising a positive electrode, a negative electrode and a non-aqueous electrolyte, wherein the positive electrode comprises a positive electrode material layer with a compacted density of 2.3-2.8g/cc, and the positive electrode material layer comprises a positive electrode active material, the positive electrode active material comprises LiFePO 4 ; the non-aqueous electrolyte comprises a solvent, an electrolyte salt, vinylene carbonate and a compound represented by Structural formula 1; an addition amount of the compound represented by Structural formula 1 is 0.01-5% based on a total mass of the non-aqueous electrolyte being 100%. The lithium iron phosphate battery provided by the application adopts the combination of vinylene carbonate and the compound represented by Structural formula 1, which can inhibit the generation of lithium dendrites at the negative electrode interface and the dissolution of Fe at the positive electrode, and ultimately improve the high-temperature and safety performance of the High-compacted-density lithium iron phosphate battery.         A-D-B-E-C     Structural formula 1

Sulfur-substituted podophyllotoxin derivative, synthesis method thereof, and use thereof

The present invention discloses a sulfur-substituted podophyllotoxin derivative, synthesis method thereof, and use thereof. The present invention introduces a rigid aromatic heterocyclic compound, as well as a further sulfonamidated product of 3-amino-5-mercapto-1,2,4-triazole, 2-amino-5-mercapto-1,3,4-thiadiazole, 4-methylbenzenesulfonyl chloride, or 4-methoxybenzenesulfonyl chloride as a substituent group, into position 4 of the C-ring of podophyllotoxin or 4′-demethylepipodophyllotoxin to obtain the podophyllotoxin derivative shown in formula (V), said derivative having significantly increased antitumor activity and reduced toxic side effects. Experiments on in vitro tumor cell inhibition indicate that the antitumor activity of the compound of formula (V) of the present invention is significantly higher than the antitumor activity of podophyllotoxin or 4′-demethylepipodophyllotoxin.

Benzenesulfonyl-chromane, thiochromane, tetrahydronaphthalene and related gamma secretase inhibitors

Diaryl- und arylheteroarylharnstoffderivate als modulatoren des 5-ht2a-serotoninrezeptors, die sich zur prophylaxe und behandlung von damit im zusammenhang stehenden erkrankungen eignen

Positive electrode sheet and lithium ion battery

A positive electrode sheet includes a positive electrode current collector and a positive electrode material layer formed on the positive electrode current collector. The positive electrode material layer includes a high-nickel positive electrode material represented by formula I and a compound represented by formula II: Li a Ni q Co y M z O 2 , Formula 1, where 0.9 ≤ a ≤ 1.2, 0.7 ≤ q ≤ 1, y ≥ 0, z ≥ 0, and q + y + z = 1, in which M is selected from one or both of Mn and Al. R 1 , R 2 , and R 3 are each independently selected from an alkyl group of 1 to 5 carbon atoms, a fluoroalkyl group of 1 to 5 carbon atoms, an ether group of 1 to 5 carbon atoms, a fluoroether group of 1 to 5 carbon atoms, an unsaturated hydrocarbonyl group of 2 to 5 carbon atoms, and at least one of R 1 , R 2 , and R 3 is the unsaturated hydrocarbonyl group of 2 to 5 carbon atoms. The positive electrode sheet satisfies following conditions: 0.05 ≤ (b/10)*(h/x) ≤ 15; and 0.005 ≤ b ≤ 1, 0.7 ≤ x ≤ 1, 80 ≤ h ≤ 140; where b is a mass percent content of the compound represented by the formula 11 in the positive electrode material layer; x is a molar ratio of Ni element: (Ni element + Co element + M element) in the high-nickel positive electrode material; and h is a thickness of the positive electrode material layer on one side of the positive electrode current collector.

Monitor stand

Condensed azines for treating cancer

The present disclose includes, among other things, compounds that treat or lessen the severity of a disorder, pharmaceutical compositions and methods of making and using the same.

1h-benzo[b]azepin-2(3h)-one compounds, compositions and methods of treating cancer

The present disclose includes, among other things, compounds that treat or lessen the severity of cancer, pharmaceutical compositions and methods of making and using the same.

Kluyvera ascorbata and application thereof

Process for preparing ((1s,2s)-2-(5-methylpyridin-2-yl)cyclopropyl)methanol

Described is an efficient, scalable synthesis of compounds such as ((1 S ,2 S )-2-(5-methylpyridin-2-yl)cyclo-propyl)methanol, which contains a disubstituted cyclopropane with two stereogenic centers and represents a significant challenging synthetic target.

Lithium iron phosphate battery

Provided is a lithium iron phosphate battery, comprising a positive electrode, a negative electrode and a non-aqueous electrolyte, wherein the positive electrode comprises a positive electrode material layer with a compacted density of 2.3-2.8 g/cc, and the positive electrode material layer comprises a positive electrode active material, the positive electrode active material comprises LiFePO 4 ; the non-aqueous electrolyte comprises a solvent, an electrolyte salt, vinylene carbonate and a compound represented by Structural formula 1; an addition amount of the compound represented by Structural formula 1 is 0.01-5% based on a total mass of the non-aqueous electrolyte being 100%. The lithium iron phosphate battery provided by the application adopts the combination of vinylene carbonate and the compound represented by Structural formula 1, which can inhibit the generation of lithium dendrites and dissolution of Fe, and ultimately improve the high-temperature and safety performance of the High-compacted-density lithium iron phosphate battery. A-D-B-E-C  Structural formula 1

Constructing geologic models from geologic concepts

Method for constructing a geologic model of a subsurface region. A concept region and a geologic concept is selected (300). A design region is created corresponding to the concept region (310). A conceptual model is generated compatible to data in the design legion (320). The conceptual model is mapped from the design legion concept region (330). The conceptual interfaces and region properties may be adjusted to match data in the concept region (340).

Method for inducing exon skipping by genome editing

A method for skipping a target exon of a desired gene in a genome using CRISPR-Cas and a guide RNA, characterized in that the guide RNA has a spacer sequence wherein the CRISPR-Cas cleavage site is positioned within 80 bases apart from a splice donor site immediately before the target exon or a splice acceptor site immediately after the target exon.

Automated Personalized Electronic Communication Assistant

Mechanisms are provided which generate an action recommendation for a received electronic communication. A machine learning (ML) computer model is trained at least by executing a ML training operation based on electronic communication features extracted from a plurality of historical electronic communications and actions taken by a user in response to each historical electronic communication. The ML computer model is trained to predict an action classification that specifies a predicted action that the user will take in response to receiving electronic communications. A new electronic communication is received and electronic communication features are extracted from the new electronic communication. The extracted features are processed by the trained ML computer model to generate a predicted action classification and an action recommendation output specifying a recommended action to take corresponding to the predicted action classification for the new electronic communication.

3D defect detection method with magnetic flux leakage testing

The present invention discloses a 3D defect detection method with magnetic flux leakage testing (MFLT). It has advantages of higher accuracy of 3D detection of defect and simpler testing device relative to the prior MFLT art. This method includes the following steps: S 1 : artificially magnetizing a to-be-tested structure, and measuring its MFLT signals {B}; S 2 : inverting magnetic charge distribution of the interior of the to-be-tested structure by using a magnetic charge distribution reconstruction algorithm to obtain the magnetic charge density of a non-defective region of the to-be-tested structure; and S 3 : using the magnetic charge density of the non-defective region of the to-be-tested structure as a known constant, and conducting inverse iteration to reconstruct defect depth of the defective region to obtain a 3D image of the defective region of the to-be-tested structure.

1h-benzo[b]azepin-2(3h)-one compounds, compositions and methods of treating cancer

The present disclose includes, among other things, compounds that treat or lessen the severity of cancer, pharmaceutical compositions and methods of making and using the same.

均勻觸發具可調性觸發電壓之多指狀半導體裝置的結構與電路技術

Benzenesulfonyl-chromane, thiochromane, tetrahydronaphthalene and related gamma secretase inhibitors

Disclosed are novel gamma secretase inhibitors of the formula (I): or a pharmaceutically acceptable salt, solvate, or ester thereof, wherein L1, n, X, Ar, Y, Z, Q, and Q1 are as defined herein. Also disclosed are methods for inhibiting gamma secretase, methods for treating Azheimer's disease, methods of treating one or more neurodegenerative diseases, and methods of inhibiting the deposition of amyloid protein (e.g., amyloid beta protein) in, on or around neurological tissue (e.g., the brain) using the compounds of formula 1.0.