A lighting optical machine and defect inspection system having high reliability and safety when a laser beam is used as a light source. The lighting optical machine comprises: a housing, which accommodates a laser source, a beam deflection mechanism having first and second plane mirrors enabling a beam emitted from the laser source to be reflected so that the beam travels in the direction almost parallel to the beam emitted from the laser source, a beam expander for converting the beam to a parallel beam having a larger cross-sectional area, an objective lens, through which the parallel beam is reduced and applied to the surface of a sample; a first control mechanism for controlling the directions of the two plane mirrors of the beam deflection mechanism with an electric signal; and a second control mechanism for controlling the focus position of the beam expander with an electric signal.

1. Technical Field
The present invention relates to a lighting optical machine and a defect inspection system used for the inspection or observation of critical dimensional pattern defects and foreign matters typically found in manufacturing processes of semiconductor devices or flat panel displays.
2. Background Art
As semiconductors are highly integrated, circuit patterns tend to be finer than ever. Under these circumstances, higher and higher resolution is required for detecting defects of circuit patterns on wafers, which are lithographed through exposure from circuit patterns formed on masks or reticles for use in photolithography processes for manufacturing semiconductors. In order to enhance the resolution, a lighting beam may be changed from visible light to ultraviolet light so that the beam has a shorter wavelength. Conventionally, an Hg lamp has been used as a light source, and among various emission lines generated from an Hg lamp, those with required wavelengths have been optically selected for use. However, the emission lines of the Hg lamp have a broader emission spectrum and it is difficult to correct optical color aberrations thereof. Further, in order to obtain sufficient illuminance, a large light source is necessary, resulting in decreased efficiency.
In recent years, an exposure device carrying a KrF excimer laser with a wavelength of 248 nm as a light source therefor in the semiconductor manufacturing processes has been developed. However, the excimer laser light source is large and predetermined safety measures must be taken due to the use of fluorine gas.
Examples of ultraviolet laser light sources include a laser device wherein the wavelength of a solid-state YAG laser light is converted with a nonlinear optical crystal and an Ar—Kr laser device, and a laser beam with the wavelength of 266 or 355 nm can be obtained thereby. It is advantageous that these laser devices have a larger output power in comparison with lamps conventionally used as light sources, and generate a parallel pencil, the beam passage of which can freely be routed. On the other hand, due to the coherence properties of lasers, laser speckle occurs, and causing adverse influences such as uneven brightness in detecting the circuit patterns formed on a sample. Incidentally, JP Patent Publication (Kokai) No. 2001-141428 A discloses a solution to this problem as a conventional technology. However, the technology of the above publication is not directed at reliability regarding the detection accuracy, such as optical axis adjustment and luminous energy adjustment, or at safety during the use of a laser.

Lighting optical machine and defect inspection system


A rest room shelf for use in a public rest room includes a base for storage of a person's personal items and adjustable brackets which fit over a rest room stall wall for supporting the base. The brackets include first and second bracket members which when slidably secured together form a U-shape. The U-shaped bracket fits on top of the stall wall in the rest room and the U-shaped portion of the bracket may be widened or narrowed depending on the width of the stall wall for providing a secure fit of the bracket onto the stall wall. An alternative bracket may be used for installing the rest room shelf directly onto a wall in the rest room. At least one hook is attached to the base for providing additional storage space for a person using the shelf.

The invention relates to shelves for storage of items and, more particularly, to a shelf which can be hung in a public rest room.
In public rest rooms, often there are no shelves or hooks for storage of a person's personal items, such as shopping bags, coats, umbrellas, diaper bags, etc. A person must put these items on the floor, which is usually dirty and also makes the items accessible for someone to steal.
There are several kinds of shelves and brackets available for different purposes. One such device is disclosed in U.S. Pat. No. 4,059,248 issued Nov. 22, 1977 to Kuntz and entitled "Shelf Support Bracket for Mounting on Railings and the like". The shelf bracket includes a U-shaped mounting bracket which may be mounted on a railing. A thumbscrew is installed in one of the legs of the bracket for engaging the railing support and enabling leveling of the shelf. However, the U-shaped bracket does not have means for adjusting the size of the U-shaped bracket for accommodating various sized railings or the like.
Another type of shelf is disclosed in U.S. Pat. No. 5,505,318 issued Apr. 9, 1996 to Goff and entitled "Collapsible Rack". The collapsible rack includes shelves which are mounted by brackets directly to a wall. However, the shelves are attached to support rods which extend vertically along the wall, and the front edge of the shelf is not supported by a bracket.
Therefore, what is needed is an apparatus for storing items in a public rest room which utilizes brackets which may be adjusted for positioning the brackets over various sized rest room stall walls.


A soluble coffee is prepared from ground green coffee which is extracted with water, the green extract obtained is dried and green powder obtained by drying is passed into and through a twin-screw extruder, and while the powder is passed through the extruder, the powder is heated in the extruder at a temperature of from 130.degree. C. to 240.degree. C. for up to 5 minutes to obtain a heat-caramelized extrudate product from the extruder, and that product is cooled and thereafter dried and ground to provide a powder-form product. Additionally, obtaining green extracts from low temperature and high temperature split extraction enables separate processing of low and high temperature extracted extracts, and low temperature extracted extracts may be heated in an extruder at a temperature of from 180.degree. C. to 240.degree. C. and high temperature extracted extracts may be heated in an extruder at a temperature of from 130.degree. C. to 180.degree. C. which enables obtaining a balanced product. Further, in the context of use of low and high temperature extraction, an extract may be obtained from roast and ground coffee by low temperature extraction and then the spent grounds and green coffee may be extracted by high temperature extraction, and the extracts may be treated as set forth above.

The invention relates to a soluble instant coffee and a process for its preparation.
Soluble coffee has been available on the market for over half a century. The production of such a soluble (instant) coffee has been known in the prior art. The green coffee was roasted and finely ground. Water was used to extract the soluble solid from roasted and ground coffee in a train of percolators. The extract was concentrated by evaporation or freeze concentration to a high concentration and was then spray dried or freeze-dried into powder form. During this operation, aroma flavor-components loss occurred in every step starting at the roasting process. This is due to the fact that the aroma is very volatile and is extremely unstable to heat, oxygen and light, which has been known in the prior art which provides disclosure of efforts and technologies employed in the soluble coffee industry to reduce aroma loss and to recover the aroma during soluble coffee manufacture to improve and to produce a better instant coffee quality. However, to date, there still is a great quality gap between coffee brew from roast and ground and instant coffee.
In the context of the present invention, a technique wherein green coffee first is extracted and a green powder obtained therefrom is heat treated is known from the disclosures of U.S. Pat. Nos. 2,758,927 and 1,932,769 already known in FR 52 337, FR 864 412, U.S. Pat. No. 2,872,323, FR 460 949, U.S. Pat. No. 2,758,927, U.S. Pat. No. 1,932,769 and GB 630 153.

Soluble instant coffee prepared from extract obtained from green coffee


The present invention relates to a radiation-sensitive composition containing a resinous binder which is insoluble in water, but soluble or at least swellable in aqueous alkaline solutions, at least one radiation-sensitive compound and optionally a crosslinking agent. The radiation-sensitive compound is an ester composed of a) a compound containing 2 to 6 aromatic hydroxyl groups, b) a ring-substituted (o-naphthoquinone 2-diazide)-4-sulfonic acid (diazo compound D.sub.1) and c) an (o-naphthoquinone 2-diazide)-4- or -5-sulfonic acid which is not further substituted (diazo compound D.sub.2) and/or a non-radiation-sensitive organic acid (compound D.sub.0) , where the D.sub.1 :(D.sub.2 and/or D.sub.0) molar ratio is between about 0.1:1 and 30:1.

The present invention relates to a radiation-sensitive composition containing a resinous binder which is insoluble in water, but is soluble or at least swellable in aqueous alkaline solutions and at least one radiation-sensitive compound.
The radiation-sensitive layer of standard copying materials is essentially composed of a mixture of an alkali-soluble cresol formaldehyde novolak with radiation-sensitive compounds, such as 1,2-benzo- or o-naphthoquinone 2-diazide derivatives. The novolak is soluble per se in aqueous alkaline solutions, but the radiation-sensitive o-quinone diazide compounds act as solution inhibitors. In the imagewise exposure of the layer to actinic radiation, the radiation-sensitive diazocarbonyl compound is converted into a carboxylic acid via a ketene intermediate. The carboxylic acid is readily soluble in aqueous alkaline solution and, consequently, also enhances the solubility of the novolak. The preparation of novolaks is described, for example, by A. Knop and W. Scheib in "Chemistry and Application of Phenol Resins," chapter 4, Springer, New York 1979.
The exposed regions of the copying layer dissolve in the alkaline developer solution, while the unexposed regions remain essentially unaltered and intact, with the result that a positive relief image of the master is produced on the layer support.
The solubility behavior described can, however, also be reversed. For this purpose, the recording layer is subjected to a heat treatment after imagewise irradiation. Under these circumstances, the resin molecules of the layer crosslink in the regions of the layer affected by the light. The process, referred to as "hardening", requires, as a rule, the presence of a "crosslinking agent" which brings about the crosslinking and, consequently, the hardening during the heat treatment, under the influence of the acid which has been produced from the o-quinone diazide during the exposure. During hardening, heating is carried out to temperatures below the decomposition temperature of the o-quinone diazide. Heating can be carried out by irradiation, placing into a stream of hot gas, contact with heated surfaces, for example with heated rollers, or by immersion in a heated bath of an inert liquid, for example water. The temperature is in general between 90.degree. and 150.degree. C., preferably between 100.degree. and 130.degree. C.
Efficient crosslinking agents are generally compounds which readily form a carbonium ion under the acid and temperature conditions described. Examples of these are the hexamethylolmelamine ethers in accordance with DE-A 33 25 022 (=U.S. Pat. No. 4,581,321) and also the compounds described in EP-A 0 212 482, such as 1,4-bishydroxymethylbenzene and 4,4'-bismethoxymethyl diphenyl ether, which contain two or more aromatically bound hydroxymethyl or alkoxymethyl groups. 2,6-Bishydroxymethyl-4-methylphenol in accordance with U.S. Pat. No. 4,404,272 is also known as a crosslinking agent.
After the heat treatment, the photoresist layer is, as a rule, subjected to a whole-surface exposure ("flood exposure") in order to render the still radiation-sensitive layer regions completely alkali-soluble. The flood exposure is in general carried out with the same light source which was also used for the image exposure.
The development following the flood exposure is in general carried out with one of the aqueous alkaline solutions which are also used to develop a positive-working photoresist. These are, for example, aqueous solutions of sodium hydroxide, tetramethylammonium hydroxide, trimethyl(hydroxyethyl)ammonium hydroxide, alkali-metal phosphates, alkali-metal silicates or alkali-metal carbonates, which solutions may contain wetting agents or fairly small amounts of organic solvents. During the development, the layer regions not affected by light in the original image exposure are washed out, with the result that a negative resist image of the master is obtained.
In most cases, the exposed and developed resist material is then treated with an etchant, in which process the etchant is only able to act on the layer support in the non-image regions. In this way, a negative etching image is produced on the layer support in the case of a positive-working copying layer and a positive etching image in the case of a negative-working copying layer.
The positive or negative relief image of the copying layer produced on the layer support by the processes described is suitable for various application purposes, inter alia as exposure mask or as image in the production of semiconductor components in microelectronics, as printing forms for letterpress, gravure or lithographic printing, and also for the production of nickel rotation cylinders in an electroplating process.
The commercial suitability of a copying layer, for example a photoresist layer, is assessed, inter alia, on the basis of the radiation-sensitivity, the development and image contrast, the resolution and the adhesion to the layer support.
A high radiation sensitivity of the composition is an important factor in the manufacture of microelectronic circuits or components, especially in the so-called "in-line" processing of wafers, in which the throughput of wafers is determined by the longest lasting process step. With the relatively long exposure times hitherto necessary, the exposure equipment throughput is the limiting factor. The exposure equipment cycle times are too long, especially with monochromatic irradiation and with irradiation using shorter-wave actinic light, and this results in an unduly low production rate.
The resist resolution relates to the capability of a photoresist system to reproduce even the finest lines and gaps of a mask used for the exposure, the exposed and developed regions being required to exhibit a high degree of edge steepness and sharpness.
In many technical application fields, in particular in the production of semiconductor components in microelectronics, the photoresist has to achieve a particularly high resolution as very small line and gap widths (<1 .mu.m) have to be reproduced. The ability to reproduce smallest details in the order of magnitude of 1 .mu.m and less is of the greatest importance for the large-scale production of integrated circuits on silicon chips and similar components. If photographic processes are used, the integration density on such a chip can be increased by increasing the resolving power of the photoresist.
It is known that the resolution of a photoresist increases if photoactive compounds containing a plurality of radiation-sensitive radicals in one molecule are present in it, since the radiation-sensitive component in the mixture is then increased. [P. Trefonas III and B. K. Daniels, "New Principle for Image Enhancement in Single Layer Positive Photoresists", SPIE Advances in Resist Technology and Processing IV, 771 (1987), 194-210; P. Trefonas III, B. K. Daniels and R. L. Fischer, "Photoresist Design for Submicron Optical Lithography: Application of Polyphotolysis", Solid State Technology 30 (1987), 131-137].
If the mixed esters mentioned in EP-A 0 244 762 and 0 244 763 are used, an improved resolution can already be observed. DE-A 38 37 500 reveals the superior properties of ring-substituted naphthoquinone diazide derivatives in lithographic applications. Esters of optionally substituted (o-naphthoquinone 2-diazide)-4- or -5-sulfonic acids with compounds which possess three or more aromatic hydroxyl groups often have, however, an unduly low solubility in the standard solvents, and this has the result that the resists prepared with these esters do not yet achieve an adequate resolution.

Composition containing naphthoquinone diazide sulfonic acid mixed esters and radiation-sensitive recording material prepared therewith


Embodiments of the present invention provide an apparatus that reduces an audible noise produced in a power supply. The apparatus includes: (1) a housing; (2) an inductor coil formed from a coil of wire enclosed in the housing; (3) a set of wires that are coupled from the inductor coil to the outside of the housing through corresponding apertures in the housing, comprising electrical leads for the inductor coil; and (4) a predetermined amount of adhesive in the apertures that bonds the wires to the housing to reduce an audible noise produced when the current through the inductor coil is cycled quickly.

1. Field of the Invention
Embodiments of the present invention relate to electronic circuits and power supplies. More specifically, embodiments of the present invention relate to techniques for reducing acoustic noise from power supply inductors.
2. Related Art
Many modern computer systems operate under strict power consumption limitations. In order to meet these limitations, some computer systems support one or more low-power modes in which some of the computer's components operate using less power or are disabled. For example, during a low-power mode, the computer system's hard drives can be stopped, the display can be deactivated, and/or the CPU clock can be slowed down.
When operating in full-power mode, the computer system draws current from a power supply according to the load on the computer system. For example, FIG. 1A presents a graph illustrating a current-flow pattern during full-power mode. As can be seen from FIG. 1A, the computer system draws different levels of power for different loads. For example, when a user loads a program from disk into memory, the disk, the memory, and the CPU are all activated. Hence, power usage increases, which increases the current drawn from the power supply. When the computer system subsequently finishes loading the program from disk, there is a corresponding decrease in the current drawn from the power supply.
When operating in low-power mode, the computer system can disable all but a minimal subset of computer system components. For example, the low-power mode may be a "sleep mode," wherein all components are deactivated except a hardware monitor that is designed to wake the computer system upon receiving a communication from a peripheral (e.g., a keystroke or mouse movement). During the low-power mode, the computer system draws a small fraction of the power drawn during full-power mode. For example, FIG. 1B presents a graph illustrating a current-flow pattern during a low-power mode.
Some computer systems support a hybrid mode, which limits power consumption by dynamically disabling and re-enabling computer system components and features as they are used. Although the components and features are sometimes disabled in the hybrid mode, the computer system appears to be fully functional. For example, in some hybrid modes, the computer system may slow down the CPU clock when a user is not performing operations that require the full CPU power. In some systems, during the hybrid mode the computer system cycles between a specialized low-power mode and full-power mode at every opportunity (e.g., between keystrokes). For example, FIG. 1C presents a graph illustrating a current-flow pattern during a hybrid low-power/full-power mode. As shown in FIG. 1C, the computer system is subject to significant current swings during the hybrid mode (i.e., high di/dt).
Unfortunately, some computer systems include parts in the power supply that perform inadequately during such hybrid modes. For example, in some power supplies, an inductor will produce a clearly audible whine caused by the high di/dt when cycling back and forth between low-power mode and full-power mode. Because there are often limitations on the noise that computer systems (particularly laptops) may emit, an audible whine from the power supply may be unacceptable.
Hence, what is needed is a power supply for a computer system without the above-described problem.

Acoustic noise reduction in power supply inductors


Methods are disclosed herein for increasing survival of transplanted cells, either in vitro or in vivo. In additional embodiments, methods are disclosed for treating a subject with a spinal cord injury or a neurodegenerative disorder. The methods include administering to a subject a therapeutically effective amount of cells, such as bone marrow stromal cells, and a therapeutically effective amount of a reverse thermal gel composition. The reverse thermal gel compositing includes a triblock copolymer, or pharmaceutically acceptable salt thereof, having the structure B-A-B in which A is one of a polyurethane or poly(ester urethane) group that comprises one or more pendant active groups, blocked active groups or active agents and B is a hydrophilic block, wherein the composition is a gel at 25° C.-40° C. and a liquid solution at a lower temperature.

Cell transplantation is considered for treatment of a myriad range of ailments including nervous tissue injury, cardiomyopathy, wound healing, and muscle dystrophy. Transplanted cells are chosen because of their reparative proficiency and accessibility. However, transplanted cell survival is often compromised. For instance, bone marrow-derived stromal cells (BMSCs) are often used in tissue repair approaches but they survive poorly in an injury site. In a model of spinal cord injury most BMSCs are lost during the first week post-transplantation. This early loss of BMSC transplants may limit their repair efficacy.
Reactive oxygen species (ROS) present in damaged tissue (Deng et al., Exp. Neurol. 205, 154-165 (2007); Bains and Hall, Biochim. Biophys. Acta 1822(5), 675-684 (2012); Facchinetti et al., Cell Mol. Neurobiol. 18(6), 667-682 (1998); Hamann, K. et al. J. Neurochem. 107(3), 712-721 (2008)) cause oxidative stress/damage which contributes to the loss of transplanted cells (Nandoe Tewarie, R. D. et al. J. Neurotrauma 26(12), 2313-2322 (2009); Swanger et al., Cell Transplant. 14(10), 775-786 (2005); Parr et al., Surg. Neurol. 70 (6): 600-607 (2008); Liu, D. et al. Superoxide production after spinal injury detected by microperfusion of cytochrome c. Free Radic. Biol. Med. 25, 298-304 (1998); Bao and Liu. Neurosci. 126, 285-295 (2004)). Methods that lead to ROS scavenging is a possible therapy to protect transplants from oxidative stress-related loss.
A need remains for methods to increase survival of stem cells, such as bone marrow stem cells.

Reverse thermal gels and their use in cell therapy

University of Pittsburgh—Of the Commonwealth System of Higher Education


A method and system for processing instructions in a floating point unit for executing denormalized numbers in floating point pipeline via serializing uses an instruction unit and having a control unit and a pipelined data flow unit, a shifter and a rounding unit. The floating point unit has an external feedback path for providing intermediate result data from said rounding unit to an input of the pipelined data flow unit to reuse the pipeline for denormalization by passing intermediate results in the pipeline which have a denormalized condition computed after the exponent calculation of the shifting circuit directly from the rounding unit to the top of the dataflow in the pipeline via an external feedback path. The pipelined has two paths which are selected based on the presence of other instructions in the pipeline. If no other instructions are in the pipeline a first path is taken which uses the external feedback path from the rounding unit back into the top of the dataflow. When there are instructions in the pipeline a shifter unit performing normalization of the fraction indicates possible underflow of the exponent, and prepares to hold the exponent and the fraction in a floating point data flow register; and upon detection of exponent underflow during the rounder stage and detection of any other instructions in pipeline; then the control unit forces an interrupt for serialization, and cancels execution of this instruction and other instructions in pipeline.

The IEEE standard for floating point execution is IEEE standard 754 adopted in the mid 1980s and used since that time. However, for floating point units (which may be part of a chip or a separate chip or other functional module of the computer system) which desirably would pipeline execution of the IEEE 754's standard denormalized numbers there has been a problem all this time.
There are several methods for handling an intermediate result which needs to be denormalized. There are methods for software handling, hardware handling with an auxiliary unit, or hardware handling with expensive logic devoted to early detection. A lower cost method is needed with better performance than we think obtainable by software handling. The problem is that the detection of exponent underflow which could result in a denormalized number is not determined until late in the pipeline. To date there has been no satisfactory solution.

Method and system for executing denormalized numbers

International Business Machines Corporation


A plug-type heat flux gauge can simultaneously measure heat flux on two opposite surfaces of thick or very thin convection or impingement cooled metal walls. The gauge is capable of continuously measuring transient and steady heat flux under transient and steady state gauge temperature operating conditions. The length of the gauge extends through the entire thickness of the material. A non-linear temperature gradient through the gauge can be measured by attaching 3-5 thermocouples along the length of the gauge.

Epstein et al U.S. Pat. Nos. 4,722,609 and 4,812,050 disclose a heat flux gauge which facilitates simultaneous measurement of both steady state and time resolved heat flux distributions. The configuration comprises a double-sided, high frequency response heat flux gauge comprising a metal film which is applied to both sides of a thin polyimide sheet. At low frequencies, the temperature difference between the polyimide sheet is a direct measure of the heat flux. At higher frequency, a quasi-one-dimensional assumption is used to infer the heat flux.
Japanese publication No. 60-201224 to Hayashi describes a heat conduction gauge which employs heat flux sensors. These sensors comprise heat resistance thin film and resistance thermometer element metallic thin films adhered to the top and reverse surfaces to calculate heat flux directly.

Dual active surface, miniature, plug-type heat flux gauge

The United States of America as represented by the Administrator of the National Aeronautics & Space Administration


The compound represented by formula (I), in which the substitutes are defined as in the specification and the claims, or their stereoisomers, the process for preparing them, pharmaceutical composition containing them and their use as medicine.

This application is a 371 of PCT/CN99/00196 Nov. 19, 1999.
This invention relates to a series of new agarofuran derivatives, their preparation and pharmaceutical composition containing the same as well as pharmaceutical use thereof, particularly for the treatment of anxiety and/or depression.
Anxiety is a disease of human central nervous system (CNS) and its incidence is increasing in pace with the increasing competition of the society.
Anxiolytics were reported to be best sales among the CNS medication including benzadiazepine compounds (diazepam etc.), buspirone and fluoxetine. But,some of the side effects and defects have been observed such as resistance, addiction, relapse dr slow effect. So it is necessary to develop new anti-anxiety drugs which have better curative effect and lower unwanted effects.
Agarofuran compounds are contained in Aquillaria agallocha Roxb in which 9 compounds as follows have been reported in the following publications.
Tetrahedron 1963, 19, 1079 (M. L. Maheshwari); Tetrahedron 1963, 19, 1519 (M. L. Mheshwari); Tetrahedron 1965, 21, 115 (K. R. Varma); Phytochemistry 1984, 23, 2068 (K. Yoneda); Phytochemistry 1984, 23, 2066 (T. Nakamish); Acta Pharmaceutica Sinica 1986, 21, 516 (J-S, Yang); Acta Pharmaceutica Sinica 1989, 24,.264 (J-S, Yang); J. Am Chem. Soc. 1967, 89, 5665(H. C. Barret); J. Org. Chem. 1968, 33, 435 (J. A. Marshall); Tetrahedron, 1968, 24, 4917 (C. H. Heathcock); Can. J. Chem. 1968, 46, 2817 (A. Asselin); J. Org. Chem. 1979, 44, 546(G. Buchi); Chinese Chem. Lett. 1991, 2, 425(Q. Liu); Chinese Chem. Lett. 1992, 3, 495 (Q. Liu); J. Org. Chem. 1982, 47, 3254 (J. W. Huffman). All of the reports above were only concerned with chemistry of the compounds without teaching or mentioning their bioactivity.
The aim of this invention is to find new anxiolytics, which have better efficacy and lower toxicity.
This invention has made discovery of the following new agarofuran compounds, which have therapeutic effects, particularly anti-anxiety effect, with better safety profile.
The first aspect of the invention relates to compounds of the formula (I) and/or stereoisomers thereof
wherein
a double bond may or may not exist in A ring at position 2-3 or position 3-4; R1, R2 and R3 are respectively at position 2, 3 or 4. R1 and R2 or R2 and R3 are independently at position 2, 3, or 4.
R1 is H, C2-12 straight or branched alkyl chain, saturated or unsaturated, for unsaturated chain, it may include 1-3 double bonds; the above defined alkyl may be unsubstituted or substituted by one or more substituents such as hydroxyl or carbonyl, said alkyl may also be substituted with cycloalkyl, heterocycle containing one or more heteroatoms or aryl group in which aryl is unsubstituted or substituted by one or more substitutent such as straight or branched C1-C4 alkyl, alkoxyl, halogen, trihalomethyl, amino, hydroxyl, nitro or N,N-dialkylamino; in the above definition, heterocycle is saturated or unsaturated mono-ring or poly-ring containing at least one heteroatom selected from oxygen, sulfur or nitrogen; aryl includes phenyl and naphthyl; the substituent may be at any possible position of the alkyl.
R2 is H, oxo, hydroxyl, C1-C12 straight or branched alkyl chain, saturated or unsaturated, for unsaturated chain, it may include 1-3 double bonds, the above defined alkyl may be unsubstituted or substituted by one or more substituents such as hydroxyl or carbonyl, said alkyl may also be attached with cycloalkyl, heterocycle containing one or more heteroatoms or aryl group in which ary is unsubstituted or substituted by one or more substituent such as straight or branched C1-C4 alkyl, alkoxyl, halogen, trihalomethyl, amino, hydroxyl, nitro or N,N-dialkylamino; In the above definition, heterocycle is saturated or unsaturated mono-ring or poly-ring having at least one heteroatom selected from oxygen, sulfur or nitrogen; aryl includes phenyl and naphthyl; the substituent may be at any possible position of the alkyl.
R3 is H, oxo, hydroxyl or halogen.
Provided that, R1, R2, and R3 are not H at the same time.
According to the present invention, the compounds of the formula (I) exhibit prominent anti-anxiety activity which is characterized by its fast action, longer duration, lower dosage, higher safety coefficient and accompanied by anti-depression effect.
The another aspect of the invention provides a pharmaceutical composition comprising as active ingredient at least one compound of formula (I) or stereoisomer thereof and a pharmaceutical carrier or excipient.
The invention further includes the compound of formula (I) or composition containing it useful for prevention or treatment of anxiety and/or depression.
The invention further provides a method for prevention and/or treatment of anxietyxe2x80x94depression, which comprises administrating at least one compound of formula (I) or composition containing the same to host who needs prevention and/or treatment.
According to the present invention, compounds of formula (I) have exhibited anti-anxiety activity in elevated plus maze test and social interaction test on rat which are typical pharmacological model for axiolytics. Furthermore, a compound of formula (I) showed antidepressant activity in forced swimming test of mice which is typical pharmacological model for anti-depressants.
Specifically, the invention relates to agarofuran derivatives of formula (I) and their stereoisomers,
wherein
a double bond may or may not exist in A ring at position 2-3 or position 3-4; R1, R2 and R3 are respectively at position 2, 3 or 4. R1 and R2 or R2 and R3 are independently at position 2, 3, or 4.
R1 is H, C2-12 straight or branched alkyl chain, saturated or unsaturated, for unsaturated chain, it may include 1-3 double bonds; the above defined alkyl may be unsubstituted or substituted by one or more substituents such as hydroxyl or carbonyl, said alkyl may also be substituted with cycloalkyl, heterocycle containing one or more heteroatoms or aryl group in which aryl is unsubstituted or substituted by one or more substitutent such as straight or branched C1-C4 alkyl, alkoxyl, halogen, trihalomethyl, amino, hydroxyl, nitro or N,N-dialkylamino; in the above definition, heterocycle is saturated or unsaturated mono-ring or poly-ring containing at least one heteroatom selected from oxygen, sulfur or nitrogen; aryl includes phenyl and naphthyl; the substituent may be at any possible position of the alkyl.
R2 is H, oxo, hydroxyl, C1-C12 straight or branched alkyl chain, saturated or unsaturated, for unsaturated chain, it may include 1-3 double bonds, the above defined alkyl may be unsubstituted or substituted by one or more substituents such as hydroxyl or carbonyl, said alkyl may also be attached with cycloalkyl, heterocycle containing one or more heteroatoms or aryl group in which ary is unsubstituted or substituted by one or more substituent such as straight or branched C1-C4 alkyl, alkoxyl, halogen, trihalomethyl, amino, hydroxyl, nitro or N,N-dialkylamino; In the above definition, heterocycle is saturated or unsaturated mono-ring or poly-ring having at least one heteroatom selected from oxygen, sulfur or nitrogen; aryl includes phenyl and naphthyl; the substituent may be at any possible position of the alkyl.
R3 is H, oxo, hydroxyl or halogen.
Provided that, R1, R2, and R3 are not H at the same time.
According to the present invention, a preferred group of compounds of formula (I) is indicated as formula (Ia), wherein there is a double bond in A ring at position 2-3; R1 is defined as above and at position 2; R2 and R3 are H, provided that R1 is not H.
According to the present invention a preferred group of compound of formula (I) is indicated as formula (Ib), wherein there is no double bond in A ring; R1 and R2 are both at position 2, wherein R1 is as previously defined; R2 is H or OH, R3 is H, provided that R1 is not H.
According to the present invention, a preferred group of compounds of formula (I) is indieated as formula (Ic), wherein there is no double bond in A ring; R1 is at position 2; R2 and R3 are both at position 3 in A ring; R1, R2 and R3 are as previously defined, provided that R1 and R2 are not hydrogen at the same time.
According to the present invention, a preferred group of compounds of formula (I) is indicated as formula (Id) in which there is a double bond at position 3-4 in A ring; wherein R2 is at position 2, R2 is a C1-12 straight or branched alkyl chain, saturated or unsaturated, for unsaturated chain, it may include 1-3 double bonds; the above defined alkyl may be unsubstituted or substituted by one or more substituent such as substituents such as hydroxyl or carbonyl, it may also be attached with cycloalkyl, heterocycle containing one or more heteroatoms or aryl group in which aryl is unsubstituted or substituted by one or more substituent such as straight or branched C1-C4 alkyl, alkoxyl, halogen, trihalomethyl, amino, hydroxyl, nitro or N,N-dialkylamino; in the above definition, heterocycle is saturated or unsaturated mono-ring or poly-ring having at least one heteroatom selected from oxygen, sulfur or nitrogen; aryl includes phenyl and naphthyl; the substituent may be at any possible position of the alkyl
R1 and R3 are H.
According to the present invention, a preferred group of compounds of formula (I) is indicated as formula (Ie) in which there is a double bond at position 2-3 in A ring and R2 is at position 3 ; wherein R2 is a C2-12 straight or branched alkyl;, chain, saturated or unsaturated; for unsaturated chain, it may include 1-3 double bonds; the above defined alkyl may be unsubstituted or substituted by hydroxyl or carbonyl; it may also be attached with cycloalkyl, heterocycle containing one or more heteroatoms or aryl group in which aryl is unsubstituted or substituted by one or ore substitutent such as straight or branched C1-C4 alkyl, alkoxyl, halogen, trihalomethyl, amino, hydroxyl, nitro or N,N-dialkylamino; in the above definition, heterocycle is saturated or unsaturated mono-ring or poly-ring having at least one heteroatom selected from oxygen, sulfur or nitrogen; aryl includes phenyl and naphthyl; the substituent may be at any possible position of the alkyl.
R1 and R3 are H.
A particularly preferred group of compounds of formula (1) is as follows:
(1R,6S,9R)6,10,10-Trimethyl-2-propyl-11-oxatricyclo[7.2.1.01,6]dodec-2-ene;
(1R,6S,9R)6,10,10-Trimethyl-2-butyl-11-oxatricyclo[7.2.1.01,6]dodec-2-ene;
(1R,6S,9R)6,10,10-Trimethyl-2-pentyl-11-oxatricyclo[7.2.1.01,6]dodec-2-ene;
(1R,6S,9R)6,10,10-Trimethyl-2-hexyl-11-oxatricyclo[7.2.1.01,6]dodec-2-ene;
(1R,6S,9R)6,10,10-Trimethyl-2-isopentyl-11-oxatricyclo[7.2.1.01,6]dodec-2-ene;
(1R,6S,9R)6,10,10-Trimethyl-2-benzyl-11-oxatricyclo[7.2.1.01,6]dodec-2-ene;
(1R,6S,9R)6,10,10-Trimethyl-2-(4-fluorobenzyl)-11-oxatricyclo[7.2.1.01,6]dodec-2-ene;
(1R,6S,9R)6,10,10-Trimethyl-2-(3-hydroxypropyl)-11-oxatricyclo[7.2.1.01,6]dodec-2-ene;
(1S,2R,6S,9R)6,10,10-Trimethyl-2-butyl-11-oxatricyclo[7.2.1.01,6]dodecane;
(1S,2S,6S,9R)6,10,10-Trimethyl-2-butyl-11-oxatricyclo[7.2.1.01,6]dodecane;
(1R,2S,6S,9R)6,10,10-Trimethyl-2-butyl-2-hydroxy-11-oxatricyclo[7.2.1.01,6]dodecane;
(1R,2R,6S,9R)6,10,10-Trimethyl-2-butyl-11-oxatricyclo[7.2.1.01,6]dodecane;
(1R,6S,9R)6,10,10-Trimethyl-2-butylidene-11-oxatricyclo[7.2.1.01,6]dodecane;
(1S,2S,6S,9R)6,10,10-Trimethyl-2-(3-hydroxypropyl)-11-oxatricyclo[7.2.1.01,6]dodecane;
(1S,2R,6S,9R)6,10,10-Trimethyl-2-butyl-11-oxatricyclo[7.2.1.01,6]dodecane;
(1S,2S,3S,6R,9R)6,10,10-Trimethyl-2-butyl-3-hydroxy-11-oxatricyclo[7.2.1.01,6]dodecane;
(1S,2R,6R,9R)6,10,10-Trimethyl-2-butyl-11-oxatricyclo[7.2.1.01,6]dodec-3-one;
(1S,3S,6R,9R)6,10,10-Trimethyl-3-butyl-3-hydroxy-11-oxatricyclo[7.2.1.01,6]dodecane;
(1R,1xe2x80x2R,6S,9R)6,10,10-Trimethyl-2-(1-hydroxybutyl)-11-oxatricyclo[7.2.1.01,6]dodec-2-ene;
(1R,1xe2x80x2S,6S,9R)6,10,10-Trimethyl-2-(1-hydroxybutyl)-11-oxatricyclo[7.2.1.01,6]dodec-2-ene;
2-Butyryl(1R,6S,9R)6,10,10-Trimethyl-11-oxatricyclo[7.2.1.01,6]dodec-2-ene;
Methyl(1R,6S,9R)6,10,10-Trimethyl-11-oxatricyclo[7.2.1.01,6]dodec-2-ene-2-ethyl ketone;
(1S,6R,9R)6,10,10-Trimethyl-3-butyl-11-oxatricyclo[7.2.1.01,6]dodec-2-ene;
In the present invention, compounds of formula (Ia)-(Ie) may be prepared by reaction scheme I-V
Wherein R1 is as previously defined, X is halogen.
Where compound of formula (Ib-1) is a specific kind of formula (Ib) wherein R1 is as previously defined; R2 is xcex2-OH, or
Where compound of formula (Ib-2) is a specific kind of formula (Ib) wherein R1 is as previously defined, R2 is xcex1-OH, or
Where compound of formula (Ib-3) is a specific kind of formula (Ib) wherein R1 is as previously defined and at xcex1-position, R2 is H, or
Where compound of formula (Ib-4) is a specific kind of formula (Ib) wherein R1 is as previously defined and at xcex2-position, R2 is H.
Where compound of formula (Ic-1) is a specific kind of formula (Ic) wherein R1 is as previously defined, R2 is H, and R3 is OH, or
Where compound of formula (Ic-2) is a specific kind of formula (Ic) wherein R1 is as previously defined, R2 and R3 are oxygen, or
Where compound of formula (Ic-3) is a specific kind of formula (Ic) wherein R2 is as previously defined, R1 is H, and R3 is OH, or
Where compound of formula (Ic-4) is a specific kind of formula (Ic) wherein R1 and R2 are H, R3 is halogen.
where R2 is a C1-C12 straight or branched alkyl chain, saturated or unsaturated; for unsaturated chain, it may include 1-3 double bonds; the above defined alkyl may be unsubstituted or substituted by hydroxyl or carbonyl; it may also be attached with cycloalkyl, heterocycle containing one or more heteroatoms or aryl group in which aryl is unsubstituted or substituted by one or more substitutent such as straight or branched C1-C4 alkyl, alkoxyl, halogen, trihalomethyl, amino, hydroxyl, nitro or N,N-dialkylamino; in the above definition, heterocycle is saturated or unsaturated mono-ring or poly-ring having at least one heteroatom selected from oxygen, sulfur or nitrogen; aryl includes phenyl and naphthyl; the substituent may be at any possible position of the alkyl. R2 is at xcex1 position in formula (Id-1) and at xcex2-position in formula (Id-2).
Wherein R2 is a C1-12 straight or branched alkyl chain, saturated or unsaturated; for unsaturated chain, it may include 1-3 double bonds; the above defined alkyl may be unsubstituted or substituted by hydroxyl or carbonyl; it may also be attached with cycloalkyl, heterocycle containing one or more heteroatoms or aryl group in which aryl is unsubstituted or substituted by one or more substitutent such as straight or branched C1-C4 alkyl, alkoxyl or groups such as halogen, trihalomethyl, amino, hydroxyl, nitro or N,N-dialkylamino; in the above definition, heterocycle is saturated or unsaturated mono-ring or poly-ring having at least one heteroatom selected from oxygen, sulfur or nitrogen; aryl includes phenyl and naphthyl; the substituent may be at any possible position of the alkyl.
In Scheme 1, (6R/S,9R)6-methyl-9-(1-methylvinyl)-bicyclo[4.4.0]deca-1-ene-3-one (formula 1) reacts with alkyl halide R1X (R1 is as previously defined but not H, X is halogen) in the presence of alkaline medium in organic solvent, such as benzene, t-butanol of any other organic solvent that does not interfere with the reaction, to form (6R/S,9R)2-R1-6-methyl-9-(1-methylvinyl)bicyclo[4.4.0]dec-1-ene-3-one (formula 2). The reaction is generally conducted at reflux temperature of the solvent used and the preferable alkaline reagents are metallic alkoxide or hydride such as sodium hydride and potassium t-butoxide. Reaction of compound of formula (2) with organic peracid, preferably meta-chloro-perbenzoic acid, to form (6R/S,9R)2-R1-6-methyl-9-(1-methyl-epoxyethyl)bicyclo[4.4.0]-dec-1-ene-3-one (3). The reaction are conducted generally in organic solvents such as methylene chloride, chloroform, diethylether or any other solvent that does not interfere with the reaction, and at room temperature or lower temperature. Reduction of compound (3) with reducing agents such as metal hydride complex, preferably lithium aluminum hydride, to form compound of formula (4). The reactions are generally conducted at room temperature or lower temperature in organic solvent such as diethylether, tetrahydrofuran, methylene chloride, chloroform, benzene or any other solvent that does not interfere with the reaction. Compound (4) is converted to compound of formula (Ia) by treatment with acid, preferably inorganic acid, such as hydrochloric acid, sulfuric acid, or phosphoric acid and the reaction is generally conducted in solvents such as water, methanol, ethanol, diethylether, benzene, toluene, methylene chloride, chloroform, ethylacetate, tetrahydrofuran or a mixture thereof, preferably benzene-water, diethylether-water system at room temperature or lower temperature.
In Scheme II, compound of formula (Ia) is reacted with organic peracid, preferably meta-chloroperbenzoic acid, to form compound of formula (5) in organic solvent such as diethylether, methylene chloride, chloroform, benzene or any other solvent that does not interfere with the reaction at room temperature or lower temperature. The compound (5) thus formed is reduced by metal hydride complex or borane, such as LiAlH4/Lewis acid, preferably LiAlH4 or LiAlH4/AlCl3, to form compound of formula (Ib-1). The reaction is conducted in organic solvent such as diethylether, tetrahydrofuran or any other solvent that does not interfere with the reaction at room temperature or cooled with ice bath. (1R,6R,9R)6,10,10-trimethyl-11-oxatricyclo[126.96.36.199]dodecean-2-one (formula 6) reacts with organometallic reagent such as Grignard reagent or organolithium reagent to form compound of formula (Ib-2). The reaction can be conducted in organic solvent such as diethylether, tetrahydrofuran or any other solvent that does not interfere with the reaction at room temperature or cooled with ice bath or ice-salt mixture. Compound of formula (Ib-1) can be converted to compound of formula (7) when treated with thionyl chloride, phosphorus oxychloride, phosphorus pentoxide in 44 pyridine, or triethylamine at room temperature, or cooled with ice bath or ice-salt mixture. Catalytic hydrogenation of (7) to form compound of formula (Ib-3). The hydrogenation is catalyzed by generally used catalysts such as platinum oxide, Raney Ni, palladium on carbon, or rhodium on carbon etc. in organic solvent such as ethanol, methanol, acetic acid or any other solvent that does not. interfere with the reaction at room temperature. Similarly, catalytic hydrogenation of compound of formula (Ia) forms compound of formula (Ib-4) and the reaction is catalyzed by generally used catalysts such as platinum oxide, Raney Ni, palladium on carbon, or rhodium on carbon etc. in organic solvent such as ethanol, methanol, acetic acid or any other solvent that does not interfere with the reaction at room temperature.
In Scheme III, compound of formula (5) is reduced by metallic hydride complex, preferably LiAlH4, to form compound of formula (Ic-1) in organic solvent such as diethylether, tetrahydrofuran, 1,2-dimethoxyethane, or any other solvent that does not interfere with the reaction at room temperature. Oxidation of compound of formula (Ic-1) by CrO3/pyridine, pyridinum chlorochromate (PCC) or Jones reagent, preferably PCC, produces compound of formula (Ic-2) and the reaction is generally conducted in organic solvent such as methylene chloride, chloroform, benzene or any other solvent that does not interfere with the reaction at room temperature or heated. (1S,6S,9R)6,10,10-trimethyl-11-oxatricyclo[7.2.1.01,6]dodec-2-ene (formula 8) is oxidized by organic peracid, preferably meta-chloroperbenzoic acid, to form (1S,2S,6R,9R)6,10,10-trimethyl-2,3-epoxy-11-oxatricyclo[7.2.1.01,6]dodecane (formula 9) and the reaction is conducted in organic solvent such as diethylether, methylene chloride, chloroform, benzene or any other solvent that does not interfere with the reaction at room temperature or cooled. The thus produced compound (9) is reduced by metallic hydride complex, preferably LiAlH4 to form (1S,3S,6R,9R)6,10,10-trimethyl-11-oxatricyclo[7.2.1.01,6]dodecan-3-one (formula 10) and the reaction is conducted in organic solvent such as diethylether, tetrahydrofuran, 1,2-dimethoxyethane or any other solvent that does not interfere with the reaction at room temperature or cooled with ice bath. Compound of formula (10) is oxidized by CrO3/pyridine, PCC, or Jones reagent, preferably PCC to form (1S,6R,9R)6,10,10-trimethyl-11-oxatricyclo[7.2.1.01,6]dodecan-3-one (formula 11 ) and the reaction is conducted in organic solvent such as methylene chloride, chloroform, benzene or any other solvent that does not interfere with the reaction at room temperature or heated. Compound (11) is reacted with organometallic reagent such as Grignard reagent or organolithium reagent to form compound of formula (Ic-3) and the reaction is conducted in organic solvent such as diethylether, tetrahydrofuran or any other solvent that does not interfere with the reaction at room temperature or cooled with ice bath. Compound of formula (10) react with phosphorous trihalide in the presence of triphenylphosphine to form (1S,3R,6R,9R)6,10,10-trimethyl-3-halo-11-oxatricyclo[7.2.1.01,6]dodecane and the reaction is conducted in anhydrous diethylether and cooled with ice bath or ice-salt mixture.
In Scheme IV, compound (9) reacts with Grignard reagent to form compound of formula (12) and the reaction is usually carried out in diethylether, tetrahydrofuran or any other solvent that does not interfere with the reaction at room temperature or cooled with ice bath. Treatment of compound of formula (12) with pyridine/thionyl chloride to eliminate a molecule of water produces compounds of formula of (Id-1) and (Id-2) and the reaction is carried out at room temperature or cooled with ice bath or ice-salt mixture.
Compound of formula (13) may be prepared following the similar method for preparation of compound of formula (Ic-1).
In Scheme V, treatment of (6R/S,9R)-6-methyl-9-(1-methylvinyl)-bicyclo[4,4,0]dec-1-ene-3-one (1) with mixture of sulfuric acid and formic acid at room temperature produces (6R/S,9R)-6methyl-9-(1-hydroxyisopropyl)-bicyclo[4.4.0]-dec-1-ene-3-one (14). Compound (14) reacts with organometallic reagent such Grignard reagent or organolithium reagent to form compound of formula (15) and the reaction is conducted in diethylether, tetrahydrofuran or any other solvent that does not interfere with the reaction at room temperature or cooled with ice bath or ice-salt mixture. Cyclization of compound of formula (15) to form compound of formula (Ie) is carried out in acidic medium, optionally with inorganic acid such as hydrochloric acid, sulfuric acid, or phosphoric acid in any solvent that does not interfere with the reaction such as water, methanol, ethanol, diethylether, benzene, toluene, methylene chloride, chloroform, ethylacetate, tetrahydrofuran, or a mixture thereof, particularly benzene-water, diethylether-water mixture. The reaction temperature is usually room temperature or lower.
In this invention, the term xe2x80x9calkylxe2x80x9d, unless otherwise indicated, refers to straight or branched carbon chain with 2 to 12 carbon atoms, such as ethyl, propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, iso-pentyl, neo-pentyl, 1-methybutyl, n-hexyl, isohexyl, heptyl, octyl, nonyl, or decyl and sail alkyl may be unsubstituted or substituted by hydroxyl or carbonyl on the chain.
In this invention, the term xe2x80x9chalogenxe2x80x9d refers to as fluoro, chloro, bromo, or iodo.
The term xe2x80x9cunsaturated alkylxe2x80x9d, unless otherwise indicated, refers to straight or branched carbon chains which contain 2 to 12 carbon atoms and 1 to 3 double bond in it, for example vinyl, 2-propenyl, 3-butenyl, 2-butenyl, 2-pentenyl, 3-pentenyl. Said unsaturated alkyl may be unstubstituted or substituted by hydroxyl or oxo. Compound of formula (I) may contain chiral centers of S or R configuration., therefore may have stereoisomers. The invention includes all the possible enantiomers and diastereomers, both mixtures and separated individual isomers. The mixture of two enantiomers, that is levo and dextro, may exist in different ratio. If there is cis, trans isomer, the invention includes the cis, trans isomers or the mixture thereof. The individual stereoisomer may be prepared by conventional resolution method or by stereoselective synthesis. If there is active H, the invention may also include tautomers.
Compound of formula (I) and their stereoisomers have showed activity on experimental anti-anxiety tests, therefore may be used as anxiolytic for living creature, particularly for mammals, especially for human being.
This invention also provides pharmaceutical composition comprising at least one active compound of formula (I) and/or its stereoisomer, or a pharmaceutically acceptable salt thereof as well as conventional pharmaceutically excipient or adjuvant. The composition 0.1%xcx9c90% by weight a compound of formula (I) or a pharmaceutically salt thereof and is prepared by the known method in this field. For this purpose, it may combine compound of formula (I) with one or more solid of liquid excipient and/or adjuvant, to make proper administration or dosage form for use in medicine or veterinary medicine.
The compounds represented by the general formula (1) are administrated alone or in the form of a pharmaceutical composition containing the same, administration route may be intestinal or parenteral, such as oral, intramuscular, subcutaneous, transdermally, intransally, intraperitoneally, rectally, topically, and the like. Said pharmaceutical preparations are formulated. by using usually used diluents such as fillers, bulking fillers, binders, wetting agents, disintegrants, surface active agents, lubricants; or excipients. The pharmaceutical preparations can be selected from various administration forms in accordance with the therapeutic purposes. As to typical administration forms, there can be exemplified tablets, pills, powders, liquids, suspensions, emulsions, granules, capsules, suppositories, injection preparations (liquids, suspensions, etc.), slowly releasing preparation, preparation form controlling release and the like. For the purpose of shaping the administration unit form into the tables, various carriers which are well-known in this field can be widely used. As to the examples of carriers, excipients such as lactose, white sugar, sodium chloride, glucose, urea, starch, calcium carbonate, kaolin, crystal-line cellulose, aluminum silicate and the like; binders such as water, ethanol, propanol, simple syrup, glucose solution, starch solution, gelatin solution, carboxymethyl cellulose, shellac, methyl cellulose, potassium phosphate, polyvinylpyrrolidone and the like; disintegrants such as dry starch, sudium alginate, agar-agar powder, laminaran powder, sodium hydrogencarbonate, calcium carbonate, polyoxyethylene sorbitan fatty acid esters, sodium laurylsulfate, monoglyceride of stearic acid, starch, lactose and the like; disintegration inhibitors such as white sugar, stearin, cacao butter, hydrogenated oils and the like; absorption accelerators such as quaternary ammonium salts, sodium laurylsulfate and the like; wetting agents such as glycerin, starch and the like; adsorbents such as starch, lactose, kaolin, bentonite, colloidal silicic acid and the like; lubricants such as refined talc, strearates, boric acid powders, polyethylene glycols and the like can be mentioned. The tablets preparations can be further shaped into tablets coated with usual tablet coating, for example sugar coated tablets, gelatin film coated tablets, tablets coated with enteric coating, tablets coated with film coating, or double layer tablets and multiple layer tablets. For the purpose of shaping the administration unit into pills, various carriers which are well-known in this field can be widely used. As to the examples of carriers, excipients such as glucose, lactose, starch, cacao butter, hydrogenated vegetable oils, kaolin, talc and the like; binders such as powdered acacia, powdered tragacanth, gelatin, ethanol and the like can be exemplified. For the purpose or shaping the administration unit into suppositories, various carriers which are well-known in this field can be widely used. As to the examples of carries, polyethylene glycols, cacao butter, higher alcohols, esters of higher alcohols, gelatin, semi-synthesized glycerides and the like can be mentioned. For the purpose of shaping the administration unit form into capsules, the compounds of formula (I) as the effective ingredient is mixed with the above-mentioned various carriers and the mixture thus obtained is placed into rigid gelatin capsules or soft capsules. For the purpose of shaping the administration unit into injection preparations, liquid preparations, emulsion preparations and suspension preparations are sterilized, further these preparations are preferably isotonic to the blood, and the all diluents which are conventionally used in this field can also be used for example, water, ethyl alcohol, macrogols, propylene glycol, ethyoxylated isostearyl alcohol, polyoxylated isostearyl alcohol, polyoxyethylenesorbitan fatty acid esters can be used. Additionally, for the purpose to prepare isotonic injection solutions, an adequate amount of sodium chloride, glucose or glycerin may be added to the injection preparations, further, usual dissolving additives, buffering agents, local anesthetics and the like may be added. Moreover, if necessary, coloring agents, preservatives, spices, flavors, sweetening agents and others may be added to the pharmaceutical preparations.
Dose of pharmaceutical preparation of the present invention is suitably selected depend on the usage, age of the patient, distinguish of sex and other conditions, and degree of the symptom, and generally the daily amount of effective compound of formula (I) may be about 0.001 to 100 mg/about 75 kg of the body weight per day, preferably about 0.01 to 20 mg. The above preparation may be administrated in single dose or to be divided into several dose such two, three or four dose.

Agarofuan derivatives, their preparation, pharmaceutical composition containing them and their use as medicine

Institute of Materia Medica, Chinese Academy of Medical Science (CN)


The present invention relates to an information processing terminal that makes it possible to implement a more preferable user interface. A user can input various processes by inclining a PDA (Personal Digital Assistants) 1, while depressing a control button 14. For example, when a menu screen for selecting application programs is displayed on a display section, the user moves a cursor by inclining the PDA 1 to select an application program for execution. The PDA 1 generates a clicking feel (feedback) to the user every time it moves the cursor. The present invention is applicable to portable information terminals such as PDAs, and various remote controllers for televisions, game machines and the like.

The present invention relates to an information processing terminal and particularly to an information processing terminal that makes it possible to implement a more preferable user interface by generating vibrations according to a predetermined displacement being detected.
In recent years, it has been proposed to input various processes by rotating or inclining the terminals, as a user interface for information processing terminals such as portable phones and PDAs (Personal Digital Assistants).
For example, when a menu screen for application programs is displayed on a terminal, it is arranged such that a cursor on the screen moves according to the user inclining the terminal, to enable the user to select a desired application program.
However, when the user moves the cursor by, for example, inclining the terminal, there has been a problem that manipulation is difficult as a fine inclination adjustment is required.


An information processing device includes a plurality of arithmetic processing devices, a plurality of storage devices, a connection section that connects a first arithmetic processing device to a first storage device and a second storage device which are duplexed and a control section that causes, when the performance of the second storage device is reduced, the connection section to cut out the second storage device whose performance has been reduced from the first arithmetic processing device and the first storage device, causes to duplex a third storage device with the first storage device, causes the connection section to connect the first storage device and the third storage device which have been duplexed to the first arithmetic processing device and to connect a second arithmetic processing device to the second storage device that has been cut out, and causes the second arithmetic processing device to initialize the second storage device.

In recent years, a storage system including a nonvolatile memory has been proposed. In this type of storage system, a separate controller other than a controller that controls read and write of data copies data stored in a nonvolatile memory chip in which a failure has occurred to another nonvolatile memory chip (for example, Japanese Laid-open Patent Publication No. 2008-191966). Also, in this type of storage system, while the life of a nonvolatile memory is managed, data stored in a hard disk drive is moved to the nonvolatile memory, thereby reducing power consumption of the entire storage system (for example, Japanese Laid-open Patent Publication No. 2007-115232).
It has been known that, in a storage system, as the data write amount increases, the access efficiency reduces. For example, in a storage system including a hard disk drive, as a result of repeating of write and deletion of a file, fragmentation of a file occurs, and the access speed is reduced. On the other hand, in a nonvolatile memory, such as a flash memory and so forth, data is erased in a unit of block before data is rewritten. Thus, in a storage system including a nonvolatile memory, such as a flash memory and so forth, as the write data amount increases, the throughput of a write operation reduces.
However, there has not been any proposed method yet in which, while increase in load of a system is reduced, the performance of a storage system, which has been degraded by reduction in access efficiency and so forth, is recovered.

Information processing device, method for controlling information processing device


An image display device is capable of displaying an image, in which occurrence of color unevenness is suppressed. A method of driving the image display device is also disclosed. In an area above the dotted line, red light is transmitted in a first sub-frame period. In second and third sub-frame periods, light blocking data are respectively supplied as green data and blue data. Therefore, green light and blue light cannot be transmitted through the area. Hence, a red image with no color unevenness is displayed in the area. In contrast, in an area under the dotted line, the red light is transmitted in the first sub-frame period, and the green light is transmitted in the second sub-frame period. As a result, in a viewed image of the area, there is color unevenness where green is mixed to red.

In recent years, the field sequential system as one of driving systems of a liquid crystal, display device, which displays a color image, has been developed. In the field sequential system, by sequentially switching light emitting elements such as cathode fluorescent lamps (CCFL) and light emitting diodes (LED) of red (R) light, green (G) light, and blue (B) light as light of a backlight and by sequentially supplying color data corresponding to colors of light of the respective light emitting elements to a liquid crystal panel in synchronization with the switching, transmission states thereof are controlled, whereby additive color mixing is performed on the retinas of an observer. According to the field sequential system, colors can be displayed even when a plurality of sub-pixels are not formed on a single pixel. Therefore, it is possible to achieve high resolution. Further, since the light from each light emitting element is directly used, it is not necessary to form a color filter in each pixel (color-filterless), and usage efficiencies of light of the respective light emitting elements are improved.
When an image is displayed on the liquid crystal panel through the field sequential system, for each sub-frame period, the light emitting elements provided in a backlight unit are sequentially switched, and a scanning operation is performed from the upper end to the lower end (or from the lower end to the upper end) of the screen.
For example, a description will be given of a case of displaying a red image on the liquid crystal panel through field sequential driving disclosed in PTL 1. FIG. 29 is a diagram illustrating display states of an image in respective sub-frame periods when an image is displayed on the liquid crystal panel through a field sequential system in the related art. More specifically, FIG. 29(a) is a diagram illustrating timing of supplying data for red image display to each pixel of the liquid crystal panel, and FIG. 29(b) is a diagram illustrating lighting start times and lighting time periods of light emitting elements of respective colors.
As illustrated in FIG. 29(a), a red light emitting element is turned on from a start time to an end time in a first sub-frame period. Further, the scanning operation from the upper end to the lower end of a screen is started at the start time, and transmission data (an opening portion indicated in FIG. 29(a)), which is for maximizing an amount of transmitted red light, is supplied as red data to each pixel. Thereby, the red light is transmitted through an area to which the red transmission data is supplied.
The red light emitting element is turned on from the start time to the end time in a second sub-frame period. Further, the scanning operation from the upper end to the lower end of a screen is started at the start time, and light blocking data (a hatched portion indicated in FIG. 29(a)), which is for minimizing the amount of transmitted red light, is supplied as red data to each pixel. Thereby, the red light is transmitted through an area in which the red transmission data remains.
The green light emitting element is turned on from the start time to the end time in a third sub-frame period. Further, the scanning operation from the upper end to the lower end of a screen is started at the start time, and light blocking data, which is for minimizing the amount of transmitted green light, is supplied as green data to each pixel. Thereby, light blocking data is supplied to all the pixels, and thus the green light cannot be transmitted through the liquid crystal panel.
Likewise, also in a fourth sub-frame period, the green light cannot be transmitted through the liquid crystal panel. Further, also in a fifth sub-frame period and a sixth sub-frame period, the blue light cannot be transmitted through the liquid crystal panel. Thereby, as illustrated in FIG. 29(b), a red image with no color unevenness is displayed on the liquid crystal panel.
Further, there is a presentation box described in NPL 1 as an application example of the image display device that displays an image on the liquid crystal panel through the above-mentioned field sequential system. On the front surface of the presentation box, a color-filterless liquid crystal panel is provided. An illumination unit, which illuminates the inside of the presentation box, employs red, green, and blue LEDs or CCFLs. In a similar manner to the liquid crystal display device disclosed in PTL 1, by appropriately controlling the light emitting timing of the illumination unit and the timing of controlling the transmission state of the liquid crystal panel, red light, green light, and blue light emitted from the illumination unit are respectively transmitted through the liquid crystal panel in accordance with the transmission states of the liquid crystal panel. Thereby, an observer, who is observing the presentation box, is able to view not only a color image, which is displayed on the liquid crystal panel provided on the front surface of the presentation box, but also an exhibited object which is exhibited inside the presentation box.

Image display device, presentation box employing same, and method of driving image display device


The present invention provides microemulsifiable concentrates and microemulsions comprising azoxystrobin and propiconazole.

When agriculturally active chemicals (agrochemicals) are relatively water soluble, preparing, storing, and shipping the same in a commercially acceptable form can be relatively clear-cut. However, many agrochemicals are hydrophobic and formulators are often confronted with difficulties in finding a suitable means for preparing these materials in stable formulations that deliver maximum loading of active ingredient per unit volume to the end-user.
A straight-forward approach to preparing concentrated liquid formulations with agrochemicals having limited aqueous solubility has been through the use of aromatic organic solvent systems. In such systems, aromatic organic solvents such as xylene or kerosene are used to solubilize the agrochemical compound of interest.
Commonly, surfactants are added to the agrochemical-solvent compositions to form emulsifiable concentrates. The surfactant-emulsifiers interact with the agrochemicals in a number of ways both before and during actual use, i.e., application to the site. The surfactants can initially disperse and/or emulsify the agrochemical in the solvent or in an inert carrier media and, for example, with herbicides, the surfactant composition may also act as a penetrant, spreader, sticker, stabilizer, and wetting agent. The surfactant composition may affect the rate of drying of a droplet on a plant and the nature of a residue liquid, or crystal. The surfactants may also influence the weathering characteristics of an agrochemical, including its rewetting characteristics and rainfastness.
Microemulsions are a subclass of emulsions and are typically clear solutions. In general, microemulsions are characterized by emulsion droplets having average particle sizes between 0.01 and 0.1 micron. The small particle size allows for the emulsion to be more stable than an emulsifiable concentrate formulation.
There is a need for microemulsifiable agrochemical concentrates that have a high biological activity in the target application, have good chemical and physical stability under a severe range of conditions that can be experienced in the marketplace, have good ecological and toxicological properties and can be readily water-dilutable to form a microemulsion.
Azoxystrobin, a strobilurin, is a fungicidal compound with a broad spectrum of disease control. Azoxystrobin inhibits mitochondrial respiration by blocking electron transfer between cytochrome b and cytochrome c1, at the ubiquinol oxidising site. Azoxystrobin is a fungicide with protectant, curative, eradicant, translaminar and systemic properties and inhibits spore germination and mycelial growth, and also shows antisporulant activity. At labelled application rates, azoxystrobin controls the numerous pathogens including Erysiphe graminis, Puccinia spp., Lepiosphaeria nodorum, Septoria tritici and Pyrenophora teres on temperate cereals; Pyricularia oryzae and Rhizoctonia solani on rice; Plasmopara viticola and Uncinula necator on vines; Sphaerotheca fuliginea and Pseudoperonospora cubensis on cucurbitaceae; Phytophthora infestans and Alternaria solani on potato and tomato; Mycosphaerella arachidis, Rhizoctonia solani and Sclerotium rolfsii on peanut; Monilinia spp, and Cladosporium carpophilum on peach; Pythium spp. and Rhizoctonia solani on turf; Mycosphaerella spp. on banana; Cladosporium caryigenum on pecan; Elsinoë fawcetii, Colletotrichum spp. and Guignardia citricarpa on citrus; Colletotrichum spp. and Hemileia vastatrix on coffee. Azoxystrobin is a solid material having low solubility in water.
Propiconazole is a steroid demethylation (ergosterol biosynthesis) inhibitor. Propiconazole is a systemic foliar fungicide with protective and curative action, with translocation acropetally in the xylem. At labelled application rates, propiconazole controls numerous diseases caused by, for example, Cochliobolus sativus, Erysiphe graminis, Leptosphaeria nodorum, Puccinia spp., Pyrenophora teres, Pyrenophora tritici-repentis, Rhynchosporium secalis and Septoria spp. on cereals; Mycosphaerella musicola and Mycosphaerella fijienis var. difformis in bananas; Sclerotinia homoeocarpa, Rhizoctonia solani, Puccinia spp., Erysiphe graminis in turf; Rhizoctonia solani, Helminthosporium oryzae and dirty panicle complex in rice; Hemileia vastatrix in coffee; Cercospora spp. in peanuts; Monilinia spp., Podosphaera spp., Sphaerotheca spp. and Tranzschelia spp. in stone fruit; and Helminthosporium spp in maize. Propiconazole is a substantially water-insoluble liquid at 20° C.
Water-dispersible granular formulations of azoxystrobin are currently known for use on turf grass, Microemulsifiable concentrates of azoxystrobin have been prepared and are commercially available under the name of, for example, HERITAGE® TL fungicide available from Syngenta Crop Protection, Inc. (Greensboro, N.C., USA). HERITAGE® TL fungicide is a liquid formulation having many properties characteristic of a microemulsifiable concentrate. Upon dilution, while not truly thermodynamically stable, HERITAGE® TL forms an optically transparent emulsion having average emulsion droplet sizes in the range of 0.01 to 0.1 microns and is stable for extended periods of time, Microemulsifiable concentrates of other fungicides are known as well including microemulsifiable concentrates of propiconazole commercially available under the name of, for example. Banner MAXX® fungicide available from Syngenta Crop Protection, Inc. (Greensboro, N.C., USA). As described above, the microemulsifiable concentrates do provide a number of advantages upon dilution, for example, they mix very easily with water and require minimal agitation. The microemulsions formed are quite stable, the emulsion droplet average particle size is smaller than that of an emulsifiable concentrate and biological activity may be superior.
It is often desirable to use mixtures of fungicides having different modes of action in order to increase the spectrum of fungal disease control as well as a means for resistance management. Mixtures of azoxystrobin and propiconazole are known and include QUILT™ fungicide, a suspoemulsion formulation commercially available from Syngenta Crop Protection, Inc. (Greensboro, N.C., USA). In this suspoemulsion, the azoxystrobin is present as a dispersed solid, while the propiconazole is in a dispersed liquid state.
While microemulsions prepared by diluting microemulsifiable concentrates are relatively stable compared to other formulation types, when the active ingredient starting materials are high melting solids, there is the possibility that these materials can crystallize and fall out of solution over time. This has been observed in microemulsions of azoxystrobin. When initially formed the formulations have an average emulsion droplet size of between 0.01 and 0.1 microns, however, over time the azoxystrobin can re-crystallize and settle. It is one object of the present invention to prepare microemulsifiable concentrates which, upon dilution, form liquid azoxystrobin microemulsion formulations having prolonged physical stability.


The present invention relates to a composite comprising a structural part, a porous part, and at least two interconnecting parts arranged at a distance from each other and extending from the structural part to the porous part, thus connecting them to each other. The implant is characterized in that each interconnecting part is in the form of a band having a length, a width and a height, the width and the height both being independently at most 20% of the length of the band, and in that at least one of the interconnecting parts is at least partially embedded into the structural and porous parts.

The use of reinforced composites made of particulate fillers or reinforcing fibres has been gaining popularity in dental and medical fields. Several fibre reinforced composites are already known. The state-of-the-art fibre reinforced composites yield high strength properties and by selecting the multiphase resin matrix for the composite, the handling characteristics of the composite can be considerably improved. These have been described, for example, in the patent applications WO 96/25911 and WO 99/45890.
On the other hand, a lot of development has occurred with bioactive materials, namely bioactive ceramics and glass and sol-gel processed silica. These materials can be used to achieve attachment of e.g. bone to a biomaterial surface after the material has been put in contact with tissue. An additional advantage of bioactive glass is its antimicrobial effect on the microbes existing for instance in sinuses of a bone. These properties have been described in several articles and patent applications, such as WO 96/21628 and Zehnder et al., J Endod 2004 April; 30(4):220-4.
From a surgical perspective individual replacement of bone, cartilage and soft tissues are insufficient in tumour, traumatologic and tissue reconstruction surgery despite the increasing advances in biomaterials research and their clinical application methods and tissue engineering. The need and indications for development of new kinds of materials result from disadvantages of the use of allografts. Risks for transmittable diseases (HIV, Creutzfeld-Jacob's disease, etc.) are related to allografting. Metals are not bioactive or osteoconductive, and their use results in stress shielding phenomena and bone atrophy of the adjacent bone. Metal implants cause also severe problems in magnetic resonance imaging (MRI) when diagnosing diseases of patients. These main disadvantages are well documented in large clinical series. On the other hand, medical treatments based on stem cells are becoming an option for treating tissue damages. Stem cell treatment in large reconstruction cases requires use of scaffolds with certain porosity. Currently, the scaffolds are made of biodegradable polymers and non-resorbable porous fibre reinforced composites have not been used for combining regenerative treatment stem cells and reconstructive treatment by fibre composite implants.
Document US 2007/0061015 discloses a biocompatible implement for bone and tissue regeneration having a layered structure. The layered structure can be reinforced by adding strips on the outer surface of the implement. In document US 2004/0258732 an implant material is made by combining a porous article and a pin penetrating through the porous article.
Several different composites comprising bioactive material and imitating bone structure have been presented, for example in applications WO 2004/103319 and WO2005/118744. A problem encountered with these materials is their insufficient mechanical strength. Another problem with these materials is the weak attachment of the porous material (having a low degree of impregnation with the matrix resin) to the load bearing material. A yet further problem is that the particles that are added to the material to enhance the osteoconductivity tend to get loose and disappear from the material before it is placed into the final position.


A mesoporous carbon composite includes mesoporous carbon having mesopores; a conductive polymer coated on only an outer surface of the mesoporous carbon; and an organic electrolyte. The mesoporous carbon composite may be prepared by impregnating an ordered mesoporous silica (OMS) with a mixture comprising a carbon precursor, an acid, and a solvent; heat-treating and carbonizing the impregnated OMS to form an OMS-carbon composite; mixing the OMS-carbon composite with a monomer that forms a conductive polymer and a solvent to provide a surface of the OMS-carbon composite with the monomer; polymerizing the monomer to obtain a conductive polymer-coated OMS-carbon composite; removing the OMS from the composite to obtain a conductive polymer-coated mesoporous carbon; and doping the conductive polymer-coated mesoporous carbon with an organic electrolyte. A supported catalyst and a fuel cell include the mesoporous carbon composite.

1. Field of the Invention
Aspects of the present invention relate to a mesoporous carbon composite, a method of preparing the same and a fuel cell using the carbon composite, and more particularly, to a mesoporous carbon composite that is coated with a conductive polymer to reduce a resistance between carbon particles, thereby reducing electrode resistance, a method of preparing the same, and a fuel cell using the mesoporous carbon composite as a catalyst support.
2. Description of the Related Art
Catalysts contained in electrodes for fuel cells play an important role in facilitating electrochemical reactions, and thus, it is beneficial to increase the activity of these catalysts. Since catalyst activity increases as the reaction surface area of the catalyst increases, catalyst particles should be reduced in diameter to increase the reaction surface area and should be uniformly distributed. To meet these requirements, a catalyst support should also have a large surface area, and thus much research on these requirements has been conducted. Meanwhile, in addition to a large surface area, which may be obtained through high porosity, a fuel cell catalyst support must have sufficient electrical conductivity to act as a path for the flow of electrons. A conventional example of a catalyst support is an amorphous microporous carbon powder, such as activated carbon or carbon black.
However, it is known that micropores of such amorphous microporous carbon particles are poorly connected. Therefore, in a conventional direct methanol fuel cell (DMFC), a supported catalyst that is prepared using an amorphous microporous carbon powder as a support exhibits much lower reactivity than do metal particles used by themselves as a catalyst. However, when metal particles are used as a catalyst, the amount of the catalyst required is greater, and thus, the manufacturing costs of a DMFC increase. Accordingly, the development of a supported catalyst that can improve catalyst activity is urgently required.

Mesoporous carbon composite, method of preparing the same, and fuel cell using the mesoporous carbon composite


An apparatus for connecting to an update server includes an update unit configured to connect to the update server over a network using a pre-stored domain name address of the update server and an IP address acquisition unit configured to acquire an IP address of the connected update server. The IP address acquired by the IP address acquisition unit is stored as a trusted IP address in a storage unit. The apparatus further includes a reconnection processing unit configured to fetch the trusted IP address of the update server and try connecting to the update server using the trusted IP address in the case of failure to connect to the update server using the pre-stored domain name address.

In general, in line with the recent rapid development and spread of the Internet, the value of information properties is increasing more and more, and various attempts have been made to protect the value of information properties. From a technical point of view, technologies for diagnosing or eliminating vulnerability to various threats such as hacking, viruses, worms, Trojans, phishing, pharming, or the like have been developing.
Phishing attacks refer to using spoofed emails and fraudulent websites designed to fool recipients into entering and transmitting personal information or financial information such as credit card number, account names and passwords, social security numbers, etc. Pharming attacks refer to a technique that fools a PC user into connecting to an internet protocol (IP) address designated by an attacker and divulging important information even when the user correctly enters a domain name address of website to be connected by exploiting hosts files referred to when performing a query from a PC to a domain name system (DNS) server and illegally modifying them.
In other words, a phishing attack is to put a link in emails that appear to be sent by websites of financial institutions, and steal personal authorization number, credit card number, account information or the like, while a pharming attack is a type of Internet fraud that occurs when a hijacker hijacks a legitimately owned website or fake domain name addresses to lure users to mistake fake sites as actual sites. The official domain of a website itself is hijacked in the middle of a transmission, and users believe without any suspicion that a fake site is the site they always use, and thus expose their personal ID, password, account information, and the like.
Moreover, the pharming attack increases the possibility of fooling a user more easily than the phishing attack because it directly or indirectly modifies the address of a DNS or proxy server. Methods for pharming attacks include modifying a DNS address, modifying a client hosts file, modifying an address established to a client's DNS server, modifying registered domain information, and using a proxy server.
In other words, the pharming attack infects a user terminal device with a malicious code or the like to change a hosts file in a user terminal device into that of a fake web server or information on a DNS server into that of a fake DNS server. Thereafter, if the user connects to a specific web server, the user uses the hosts file in the user terminal device or the fake DNS server in order to get the IP address of the web server. However, since the hosts file or DNS information has already been changed by infection with the malicious code, the user terminal device designates a web server with a fake IP address. As a result, the connection is made to the fake web server, and the user mistakes the fake site as a normal site and reveals his/her personal information.
In this way, pharming attacks are based on changing addresses to easily lure users to make connections without any suspicion, and generally take the form of 'modifying DNS information'. A DNS has the function of translating a frequently used domain name address, which is usually entered, into an IP address to connect to a site, or vise versa. The reason why this function is required is to use a domain name address to easily remember a desired site for visiting the site because it is not possible to remember all IP addresses enabling actual communication on a network.
But then, as mentioned above, while phishing attacks entice users to fake phishing sites by using similar domain name addresses, redirection via normal sites, and sophisticated fake pages or the like, the users themselves can recognize the phishing sites if they check them carefully. However, if DNS information is changed as is done in pharming attacks, this makes it more difficult for the users to recognize phishing sites and increases the possibility of luring the users to mistake these sites as actual sites, rather than fake sites. For this reason, large-scale damages due to pharming attacks can be expected to happen in some cases.
Further, although a technology for countering pharming attacks is employed, which requires user confirmation when setting a hosts file or DNS information or sets the hosts file or DNS information to be not changeable, it is difficult to determine whether any change in the hosts file or DNS information is a change due to a malicious code or a change made by the user. Thus, it is difficult to detect and counter pharming attacks in real situations.
Particularly, in case where information in the hosts file for update is modified due to a malicious code caused by a pharming attack, a new update cannot be performed and therefore information loss resulting from the pharming attack cannot be avoided.

Method and apparatus for connecting to server using trusted IP address of domain


System, device, and method of provisioning cryptographic assets to electronic devices. A delegation message is generated at a first provisioning server. The delegation message indicates provisioning rights that are delegated by the first provisioning server to a second provisioning server with regard to subsequent provisioning of cryptographic assets to an electronic device. The delegation message includes an association key unknown to the first provisioning server, encrypted using a public key of the electronic device. The delegation message further includes a public key of the second provisioning server. The electronic device locally generates the association key, which is unknown to the first provisioning server. The delegation message is delivered to the electronic device. Based on the delegation message, cryptographic assets are provisioned by the second provisioning server to the electronic device, using the association key.

Key Provisioning is a problem common to many cryptographic modules. Whenever a cryptographic device is designed to perform operations using internally-stored key material, this key material needs to be available to the cryptographic device.
For most key material, provisioning may be performed by means defined at the application level. Most applications may support methods to securely communicate keys to the participants of their security protocols. Provisioning methods specified by applications may usually rely on pre-existing key material, which may be used to secure a subsequent provisioning process. Other applications may perform provisioning without pre-existing key material, for example, if their threat models allow that.

System, device, and method of provisioning cryptographic data to electronic devices


A process for preparing a refrigerated prepared meal that includes includes selecting food components from the group consisting essentially of a starch component, a meat component, a vegetable component, a sauce component, and a spice component. The food components are cooked and then mixed to produce a food mixture. The food mixture is packaged in a hermetically sealed container to form a packaged prepared meal. The packaged prepared meal is heated to a temperature of greater than 165.degree. F. The packaged prepared meal is cooled to a temperature of less than about 41.degree. F. The packaged prepared meal produced according to the present invention has a shelf life of at least 90 days when the packaged prepared meal is maintained at a temperature of less than about 41.degree. F.

The present invention relates generally to a process for producing prepared foods. More particularly, the present invention relates to a process for preparing refrigerated meals.
Meals that reduce the preparation time prior to consumption are becoming increasingly popular with consumers. While consumers desire the convenience of prepared meals, consumers also desire prepared meals to exhibit taste and appearance characteristics that are similar to homemade meals.
Prepared meals typically contain one or more of the following food components: meat, vegetables, starches, and sauces. For example, consumers expect meat to be tender, vegetables to be crisp, and starches to be firm and flaky and not clumpy.
To maintain the prepared meals with a desired quality until the prepared meals are consumed, prepared meals are typically frozen during the manufacturing process. The prepared meals are then maintained frozen until it is desired to heat the prepared meal for consumption.
Frozen prepared meals are typically thawed and heated using a microwave oven. The frozen prepared meals thereby provide consumers with the ability to quickly prepare meals while minimizing the effort that must be expended to prepare the meals.
In spite of the fact that frozen prepared meals can be stored for extended periods of time without experiencing a decrease in taste and appearance characteristics, frozen prepared meals are typically believed to have inferior taste and appearance characteristics to prepared meals that are distributed and displayed in a refrigerated state.
Various types of pasta and meat prepared meals have been developed to be marketed in a refrigerated state. For example, "fresh" pasta typically exhibits superior taste and appearance characteristics to dried pasta. Similarly, rotisserie-style chicken, which is commonly prepared in a store where the rotisserie-style chicken is sold, has superior taste and appearance characteristics to chicken in frozen prepared meals. Additionally, both "fresh" pasta and rotisserie-style chicken allow consumers to reduce the time needed to prepare the meals when compared to the other listed alternatives.
One common drawback of prior art refrigerated prepared meals is that these prepared meals have a limited shelf life that is considerably less than 90 days. Consumers are reluctant to purchase refrigerated prepared meals where a longer shelf life is obtained through the addition of preservatives to the prepared meals because of potential health risks of consuming large amounts of preservatives over extended time periods.
One way to enhance the shelf life of prepared meals that are distributed and displayed in a refrigerated state is to process the prepared meals to reduce the amount of oxygen within the package. One common way of reducing the oxygen with the package is to purge with an inert gas, such as nitrogen.

Process for preparing refrigerated meals


A hybrid pepper designated ‘E20S1012777’ is disclosed. The invention relates to the seeds of hybrid pepper ‘E20S1012777’ to the plants of hybrid pepper ‘E20S1012777’ and to methods for producing a hybrid plant, and to methods for producing other pepper lines, cultivars or hybrids derived from the hybrid pepper ‘E20S1012777’.

The bell pepper (Capsicum annuum) originated in Mexico and the neighboring areas of Central America. Soon after Columbus' discovery of this plant, it was grown worldwide and used as a spice and a medicine. Today, pepper plants can be found growing wild in tropical areas around the world. Many countries grow it as a crop. Many of the hot peppers can be found in Latin America and China, but the United States prefers bell peppers. Peppers are used for fresh consumption, and they are processed into powders, sauces, and salsas. Many of the new cultivars grown today can be traced back to the early plants.
The genus Capsicum and species annuum includes most of the peppers grown in the United States. These can be further grouped into two broad categories: chile peppers which are pungent (hot) and sweet peppers which are non-pungent (mild). The United States produces four percent of the world's capsicum peppers (sweet and hot), ranking sixth behind China, Mexico, Turkey, Spain and Nigeria. Bell peppers are the most common sweet pepper and are found in virtually every retail produce department. Grown commercially in most states, the U.S. industry is largely concentrated in California and Florida, which together accounted for 78% of output in 2000. New Jersey, Georgia, and North Carolina round out the top five producing states (Economic Research Service, USDA, Vegetables and Melons Outlook/VGS-288/Dec. 14, 2001).
Bell peppers are eaten raw, cooked, immature and mature. Often nutritional content is altered by the changes in the way they are consumed. Per capita consumption of bell peppers in 1995 was 6.2 pounds. They are an excellent source of Vitamin C, Vitamin A, and Calcium. Red peppers have more of these qualities than the immature green peppers.
Peppers grown in temperate regions are herbaceous annuals, but are herbaceous perennials where temperatures do not drop below freezing. Pepper plants' growth habit may be prostrate, compact, or erect, but it is determinate in that after it produces nine to eleven leaves a single stem terminates in flowers. These plants are grown for the edible fleshy fruit produced by this dichotomous growth. Peppers are non-climacteric which means they do not produce ethylene. They need to stay on the vine to continue the ripening process. A deep taproot will form if the plant root system is uninjured during transplanting. The spindle root will develop fibrous secondary root systems spreading laterally and downward. On the soil surface the stem will produce adventitious roots, but not as easily as tomatoes. The leaves of the pepper plant arise singly and are simple, entire, and asymmetrical. Typical of all Solanaceous plants, the leaves are arranged alternately on the stem. They are shiny and glabrous and vary in shape from broadly ovate to ovate lanceolate. The flowers develop singly or in twos or threes continuously as the upper structure of the plant proliferates. The corolla is white and five lobed while the anthers are bluish or yellowish in color. The flowers have an open anther formation and will indefinitely self-pollinate. They are also pollinated by insects, which increases the chances of cross-pollination. Unlike tomatoes, whose pollen becomes nonviable in high temperatures, the pepper flowers' pollen is not extremely heat sensitive and it remains viable up to 100° Fahrenheit producing fruit throughout the season.
The fruit of a pepper plant is classified as a berry with colors from green, yellow, red, purple, black, brown, white, and orange. Green is an immature fruit, yet commonly eaten this way, and as the fruit matures it changes color. In most commercial cultivars color changes are from green to red, green to yellow or green to orange. Usually, fruits of the purple and white varieties have these colors as they develop, and therefore do not have a green stage. For fruit to set, the ovaries need to be fertilized. Auxin is then produced by the seeds, which determine fruit cell elongation. The number of seeds fertilized will determine the size and shape of the fruit. The seed develop on the interior and attach to the veins. Fully developed seed is kidney shaped. There are about 4,500 seeds per ounce.
Pepper is an important and valuable field crop. Thus, there is a continued need for new hybrid peppers.