An insert for cell cultures has a hollow housing (1) of a cylinder-like shape, with an upper, in particular circular, opening (2) and a membrane-like base located opposite the opening (2). On the peripheral opening edge (6) outward protruding support arms (5) are spaced apart from one another. The housing (1) has on its outer peripheral surface (12), between at least two support arms (5), a flattened region (11) extending from the opening edge (6) in the direction of the base (3), so that in a plane perpendicular to the central longitudinal axis (Y) of the housing (1) in the region of the flattened region (11) there is a radial clearance of the peripheral surface (12) relative to the longitudinal axis (Y) which is smaller than the radial clearance and/or outer radius of the peripheral surface (12) in the non-flattened region of the peripheral surface (12).

A cell culture insert of the above-mentioned kind is known from DE 102 40 787 A1. In the cell culture insert according to that reference, the support arms and spacers dedicated to the support arms are distributed along the perimeter of the cell culture insert and configured with different lengths on the sides. The eccentric mounting owing to the differently configured support arms and spacers thus increases the size of a feeding window located between the cell culture insert and a surrounding wall of a multiwell plate into which a pipette can be inserted. This design of the cell culture insert has disadvantages in that these inserts are not located in the center of a receptacle for a multiwell plate. Consequently, positioning difficulties arise during automatic filling of the inserts.


An image recording apparatus records an image of an original on a photosensitive recording medium using a plurality of intermediate sheets. The image of the original includes a fine line image, such as character, symbol, and a half-tone image, such as picture. To form a latent image of the fine line image on the recording medium, a light sheilding image corresponding exactly to the fine line image is printed on one of the intermediate sheets while completely masking an area where the half-tone image exists. On the other hand, to form a latent image of the half-tone image of a particular color, a light shielding image corresponding to the half-tone image of such a color is printed on another intermediate sheet, and another light sheilding image is printed thereon with a thicker line than the original fine line image. Accordingly, toner powder or ink needed for producing the intermediate sheets can be saved and thus cost for producing the same is reduced.

The present invention relates to an image recording apparatus for recording an image on a recording medium using intermediate image sheets each carrying a light shielding image on a light transmissive sheet (hereinafter referred to as "mask members"). More particularly, the invention relates to an image recording apparatus in which the mask member is interposed between a light source and a positive type photosensitive recording medium and light from the light source is irradiated onto the recording medium through the mask member to form thereon a latent image corresponding to the light shielding image of the mask member.
There is a co-pending U.S. patent application Ser. No. 07/175,392 filed by Masashi UEDA et al on Mar. 30, 1988, in which disclosed is an image recording method upon which the present invention is based. In the co-pending application, it is proposed that a color image and a monochromatic image (black image on white background) both provided on an original are recorded on a recording medium so that color displacement of the monochromatic image is obviated. More specifically, as shown in FIGS. 5A through 5D, four mask members 330R, 330G, 330B and 330L are used to record black character images (ABCDEFGH) together with color images as shown in FIG. 5E. In FIGS. 5A through 5D, those designated by 330R, 330G and 330B are half-tope mask members used for reproducing a half-tone image and the one designated by 330L is a fine line mask member used for reproducing fine line images. The half-tone image is reproduced according to a gradation reproducing method, but such a method is not employed when reproducing the fine line image.
Three kinds of half-tone mask members 330R, 330G and 330B are needed, since the image on a half-tone area is recorded by way of color resolution. Light of a wavelength causing to reproduce red color is irradiated onto the recording medium through the mask member 330R. Similarly, lights of wavelengths causing to reproduce green and blue colors are successively irradiated thereonto through the mask members 330G and 330B, respectively. By such a multiplexed exposure, the full-color image is reproduced according to a quasi-gradation method. On the other hand, in order to reproduce the fine line image, the fine line mask member 330L is used in which the half-tone area is wholly masked to prevent light from reaching the recording medium and the lights corresponding to red, green and blue are successively or simultaneously irradiated onto the fine line area to thus expose the recording medium to light through the mask member 330L. By the exposure performed in such a way, a highly resolutive monochromatic image is reproduced without incurring color displacement in the fine line image.
However, the fine line mask member 330L includes a light shielding area covering entirely the half-tone area, while each of the half-tone mask members includes a light shielding area covering entirely the fine line area. Therefore, in the case of reproducing an original in which the fine line area occupies a larger part, a large amount of light shielding material is required to shield the fine line area. When the four mask members are produced by an electrophotographic printer or an ink jet printer, a large amount of toner or ink is used and thus cost for producing one sheet of the mask member becomes costly.

Apparatus for recording color image using mask members


Techniques are disclosed for customization of fin-based transistor devices to provide a diverse range of channel configurations and/or material systems, and within the same integrated circuit die. Sacrificial fins are removed via wet and/or dry etch chemistries configured to provide trench bottoms that are non-faceted and have no or otherwise low-ion damage. The trench is then filled with desired semiconductor material. A trench bottom having low-ion damage and non-faceted morphology encourages a defect-free or low defect interface between the substrate and the replacement material. In an embodiment, each of a first set of the sacrificial silicon fins is recessed and replaced with a p-type material, and each of a second set of the sacrificial fins is recessed and replaced with an n-type material. Another embodiment may include a combination of native fins (e.g., Si) and replacement fins (e.g., SiGe). Another embodiment may include replacement fins all of the same configuration.

Maintaining mobility improvement and short channel control as microelectronic device dimensions continue to scale provides a challenge in device fabrication. In particular, during design and manufacture of metal-oxide-semiconductor (MOS) transistor semiconductor devices, such as those used in complementary metal-oxide-semiconductor (CMOS) devices, it is often desired to increase movement of electrons (carriers) in n-type MOS device (NMOS) channels and to increase movement of holes (carriers) in p-type MOS device (PMOS) channels. Fin-based transistor devices can be used to provide improved short channel control. Typical CMOS transistor devices utilize silicon as the channel material for both hole and electron majority carrier MOS channels. Switching to other channel materials can improve mobility. For example, silicon germanium (SixGe1-x, where x<0.2) fin-based channel structures provide mobility enhancement, which is suitable for use in many applications.
As will be appreciated, the figures are not necessarily drawn to scale or intended to limit the present disclosure to the specific configurations shown. For instance, while some figures generally indicate perfectly straight lines, right angles, and smooth surfaces, an actual implementation of an integrated circuit structure may have less than perfect straight lines, right angles, and some features may have surface topology or otherwise be non-smooth, given real world limitations of the processing equipment and techniques used. To this end, the X-SEM image figures have been provided in conjunction with man-made figures to demonstrate examples of actual real world shapes and features, including trench bottoms having low-ion damage and non-faceted morphology according to an embodiment as well as trench bottoms having ion damaged irregular morphology and faceted morphology.

Replacement channel etch for high quality interface


A heat exchanger (120) includes a core (130) containing inlet manifold (140), outlet manifold (126), interconnecting channels (144) and a heat-transfer surface (128). Each interconnecting channel fluidly communicates at one end with a corresponding inlet manifold and at the other end with the two outlet manifolds located adjacent that inlet manifold. The inlet manifolds are located distal from the heat-transfer surface. The interconnecting channels are configured such that substantially all of the heat collected by a working fluid is collected as the working fluid flows from the inlet manifolds away from the heat-transfer surface in a direction substantially normal to the heat-transfer surface.

Heat exchangers that utilize a single-phase working fluid to transfer heat from a heat source or to a heat sink are known as single-phase heat exchangers. Single-phase heat exchangers are used in a variety of applications ranging from radiators of conventional automobiles to more exotic water-to-ammonia heat exchangers for sustaining life in outer space, e.g., aboard a space shuttle or a space station. Single-phase heat exchangers are also used in other diverse applications, such as removing waste heat from electronic devices, e.g., microprocessors, cooling fusion reactor diverters and producing slush hydrogen.
Compact single-phase heat exchangers are particularly desirable in applications having relatively high heat fluxes. For example, the continually increasing speeds and complexity of microprocessors cause these microprocessors to generate commensurately increasing amounts of heat. Present generation microprocessors typically have heat fluxes in the range of 5 watts/cm2 to 15 watts/cm2 The next several generations of microprocessors are predicted to have much greater heat fluxes, e.g., on the order of 50 watts/cm2 to 200 watts/cm2 or more. One type of compact heat exchanger contemplated for high flux heat transfer applications is what has become known as a normal-flow heat exchanger (NFHX). Specific embodiments of NFHXs have been previously disclosed by the present inventor, e.g., in U.S. Pat. Nos. 5,029,638 and 5,145,001. An NFHX is desirable for applications such as microprocessor cooling because it provides: (1) a single phase heat exchanger having a high surface heat flux capability; (2) a compact heat exchanger in which the working fluid experiences a generally small pressure drop as it passes through the heat exchanger; and (3) a small and lightweight heat exchanger having a high thermal transfer efficiency.
FIG. 1 shows one embodiment of an NFHX 20 as taught in the aforementioned patents. NFHX 20 includes a heat-transfer surface 22 for thermally communicating with a heat source or sink (not shown). For example, heat-transfer surface 22 may be thermally coupled to a microprocessor for removing waste heat from the microprocessor. NFHX 20 further includes a heat-transfer element 24 comprising an inlet end 26 located opposite heat-transfer surface 22 and a plurality of closely spaced plates 28. The spaces between plates 28 define a plurality of passageways 30 that are substantially normal to heat-transfer surface 22. A plurality of outlet manifolds 32 are located adjacent, and parallel, to heat-transfer surface 22. Outlet manifolds 32 are spaced from one another and each intersects each passageway 30 to permit a working fluid 34 to flow from the passageways into the outlet manifolds.
During use, working fluid 34 flows from a source (not shown) into passageways 30 via inlet end 26, and then through passageways 30 to outlet manifolds 32 in a direction substantially normal to heat-transfer surface 22, and out of heat-transfer element 24 through the outlet manifolds in a direction substantially parallel to the heat-transfer surface. As working fluid 34 flows through heat-transfer element 24, it gains, or loses, most of its heat while flowing through passageways 30. The heat is transferred to, or from, working fluid 34 via plates 28, which are in thermal communication with heat-transfer surface 22. It is the fact that the majority of heat transfer to or from working fluid 34 occurs in passageways 30 that are normal to heat-transfer surface 22 that NFHX 20 gets its name.
Unfortunately, conventional NFHXs have a number of shortcomings. For example, for NFHX 20 to provide highly efficient heat removal, the spacing between plates 28, and, hence the depth of normal-flow passageways 30, must be very small, preferably less than 0.10 mm. Relatedly, to increase the heat transfer efficiency of NFHX 20, it is desirable to make plates 28 relatively thin, e.g., on the order of 0.25 mm or less. Accordingly, the dimensions of plates 28, passageways 30 and outlet manifolds 32 must be precisely controlled. Typically, the elements of an NFHX are fabricated using techniques such as traveling-wire EDM and traditional machining. However, these techniques are typically not capable of, or are impractical for, forming elements having the small dimensions necessary for producing NFHXs capable of handling the high heat fluxes of the next generation of microprocessors.
In addition, the configuration of passageway 30 and outlet manifolds 32 produces performance limitations that limit conventional NFHX 20 from achieving the needed high flux heat transfer capacity. For example, the location of outlet manifolds 32 proximate to heat-transfer surface 22 interferes with the direct conduction of heat between the heat-transfer surface and plates 28. Outlet manifolds 32 extend the length of NFHX 20 and, therefore, interrupt thermal conduction from heat-transfer surface 22 to plates 28 along the entire length of the NFHX. This interruption increases the thermal resistance between heat-transfer surface 22 and working fluid 34 in passageways 30, For this reason, it is desired to make the outlet manifolds 32 as small as possible in cross-sectional dimension, but this has the detrimental effect of increasing the pressure drop therewithin. In addition, pressure drop within outlet manifolds 32 creates non-uniform flow distribution of working fluid 34 over the cooling area of plates 28, thereby reducing the heat transfer efficiency of NFHX 20.
The normal-flow heat exchanger of the present invention, however, overcomes these and other shortcomings of conventional normal-flow heat exchangers.

This patent is subject to a terminal disclaimer.


A method for the production of phenol and acetone from a cumene hydroperoxide mixture comprises a first stage and a second stage and at least two serially connected reactors, wherein the first stage comprises decomposition of a cumene hydroperoxide mixture in the presence of a catalyst mixture to form a dicumyl peroxide mixture, and the second stage comprises formation of a phenol and acetone mixture from decomposition of the dicumyl peroxide mixture formed in the first stage, wherein, the first stage further comprises: a) forming a catalyst mixture by combining sulfuric acid and phenol in a weight ratio of from 2:1 to 1:1000 in a catalyst formation reactor, b) holding the catalyst mixture in the catalyst formation reactor at a temperature of about 20 to 80° C. for about 1 to 600 minutes; and, c) adding the catalyst mixture to the cumene hydroperoxide mixture to form the phenol and acetone mixture. The proposed method permits a significant reduction in the yield of hydroxyacetone that causes deterioration in the quality of commercial phenol.

The present invention relates to industrial organic synthesis, specifically to production of phenol and acetone by the cumene method.
A well-known method for the production of phenol and acetone by oxidation of cumene with atmospheric oxygen, followed by the acid-catalytic decomposition of cumene hydroperoxide permits both end products to be produced with high yield (see, for example, Kruzhalov B. D., Golovanenko B. N., Combined Production of Phenol and Acetone, Moscow, Goskhimizdat, 1964, or Kirk-Othmer Encyclopedia of Industrial Chemistry). The method is widely used to produce these products, and is the principal technique used in world practice.
Methods are known for producing phenol and acetone in which, to reduce the yield of phenol tar, cumene oxidation products containing cumene hydroperoxide (CHP), cumene, and dimethylphenylcarbinol (DMPC) cleavage process in the presence of sulfuric acid. In the first stage, at a temperature of 55 to 80° C., most of the CHP (97 to 99%) is decomposed and dicumyl peroxide (DCP) is synthesized from DMPC and CHP. In the second stage, acetone is added at a temperature from 80 to 146° C. to the obtained reaction mixture containing phenol, acetone, dimethylphenylcarbinol (DMPC) and dicumyl peroxide (DCP). The addition is made in an amount of 1.5 to 1.8 times the original concentration of acetone. Water is also added. In some cases the acid is partially neutralized with ammonia before the second separation stage in order to ensure optimal acidity of the catalyst. Breakdown of DCP formed in the first stage, decomposition of the remaining CHP and dehydration of the remaining DMPC occur here at a temperature from 80 to 146° C. (See, for example, Russian Patent Nos. 2068404, 2121477, 2142932.)
These methods significantly reduce the amount of formed byproducts in comparison with decomposition in one stage (the yield of tar is 25 kg/t of phenol), whereas the amount of formed byproduct (hydroxyacetone) remains at a high level (and sometimes increases).
Hydroxyacetone is a precursor to 2-methylbenzofuran, which is difficult to separate from phenol and which causes a deterioration in the color indices of the commercial phenol. Elimination of hydroxyacetone from phenol by alkaline treatment complicates the process (Vasil'eva I. I., Zakoshanski V. M., Petroleum Processing and Petrochemistry, St. Petersburg, "Giord", 2005, page 344).
The yield of hydroxyacetone during decomposition of CHP to phenol and acetone is reduced by running the reaction in excess phenol. (See, for example, Russian Patent No. 2291852 and U.S. Pat. No. 7,109,385.) However, these methods propose that part of the commercial product (phenol) that has already passed through all separation stages be returned to the CHP decomposition stage, which undoubtedly leads to a reduction in the output of the unit because of an increase in the load on the phenol separation and purification system.
The method closest to the proposed method for the decomposition of CHP is a decomposition method that is accomplished in two stages. (See, for example, Russian Patent No. 2142932.) The prior art process is run in three serially connected mixing reactors in the first stage and in a displacement reactor in the second stage. In the first stage, CHP decomposition is carried out under conditions that are close to isothermal at a temperature of 47 to 50° C. and a catalyst concentration (sulfuric acid) of 0.018 to 0.20 wt. % by additional dilution of the reaction mass with acetone in an amount equal to 5 to 8 wt. % relative to the amount of supplied CHP. Almost all the CHP reacts, and DCP is formed from part of the CHP and DMPC.
In the second stage, the process is run while sulfuric acid is partially neutralized with ammonia to form ammonium hydrosulfate at a temperature of 120 to 146° C. A certain amount of water is added, as needed. The concentration of sulfuric acid is 0.09 to 0.10 wt. %. Decomposition of CHP and DCP occurs in a reaction medium containing phenol and acetone. These are formed from CHP and the additionally introduced acetone.
Shortcomings of the prior art method include the significant amount of hydroxyacetone in the obtained phenol. According to the inventors, this amount constitutes 1300 ppm in the reaction mass resulting from the decomposition of CHP, which significantly reduces the quality of the compound (as described in a report of the inventor of the prior art method at the conference "Outlook for Development of Chemical Processing of Fossil Fuels", KHPGI-2006, 12-15 Sep. 2006, Saint Petersburg; "Khimizdat", Saint Petersburg, 2006, page 130). Another shortcoming is the need for the partial neutralization of sulfuric acid with ammonia, which complicates the process and process control.

Method for the production of phenol and acetone


A method for specifically quantifying HDL cholesterol in which cholesterol in lipoproteins other than HDL is erased in the first step, and HDL cholesterol is specifically quantified in the second step, by which accurate values can be obtained even in measurements of abnormal samples such as disorder of lipid metabolism and lipoprotein abnormality, is disclosed. The method for quantifying cholesterol in high density lipoprotein according to the present invention comprises a first step of erasing cholesterol in lipoproteins other than high density lipoprotein by treating a test sample with cholesterol esterase and cholesterol oxidase in the absence of a surfactant which acts on high density lipoprotein and removing generated hydrogen peroxide; and a second step of adding a surfactant which specifically acts on high density lipoprotein to the product of said first step and quantifying hydrogen peroxide generated from cholesterol in high density lipoprotein by actions of cholesterol esterase and cholesterol oxidase. As the cholesterol oxidase used in the first step, one having a molecular weight of not more than 60 kilodaltons is used.

It is known that HDL relates to removal of cholesterol accumulated in cells because it receives cholesterol from various tissues including walls of blood vessels with arterial sclerosis, so that HDL is useful for estimating the risk for various arterial sclerosises including coronary artery sclerosis, and that its blood level is an indicator for the risk of onset of arterial sclerosis.
Methods for measuring cholesterol in HDL include a method in which HDL is separated from other lipoproteins by ultracentrifugation and then the HDL is measured; and a method in which the cholesterol in HDL is separated by electrophoresis, then the lipid is stained, and the intensity of the generated color is measured. However, these methods are complex or a number of samples cannot be assayed, so that they are not commonly used.
The method for measuring the cholesterol in HDL, which is generally used in the field of clinical test is the method in which a precipitating agent is added to the sample so as to coagulate the lipoproteins other than HDL, removing the coagulated lipoproteins by centrifugation, and the cholesterol in the resulting supernatant containing HDL alone is measured. Although this method is simpler than the ultracentrifugation method and the electrophoresis method, it is not satisfactorily simple because it comprises addition of the precipitating agent and subsequent separation, and a comparative large amount of sample is needed.
On the other hand, methods in which the cholesterol in HDL is separately quantified by using enzymes have been proposed. For example, a method is known, which comprises the steps of preliminarily coagulating the lipoproteins other than HDL by an antibody and polyanion, enzymatically reacting the cholesterol in HDL alone, inactivating the enzyme and simultaneously re-dissolving the coagulated mass, and measuring the absorbance of the resulting solution (Japanese Laid-open Patent Application (Kokai) No. 6-242110). However, this method has a problem in that it is necessary to add reagents at least three times, so that this method can be practiced only by the limited analyzing apparatuses. Therefore, this method is not widely used.
Other methods include a method in which an enzyme reaction is carried out in the presence of a bile salt or a nonionic surfactant (Japanese Laid-open Patent Application (Kokai) No. 63-126498); a more recently developed method in which the cholesterol in HDL is specifically trapped by chemically modified cholesterol esterase and/or cholesterol oxidase in the presence of a clathrate compound such as cyclodextrin (Japanese Laid-open Patent Application (Kokai) No. 7-301636); and a method in which the lipoproteins other than HDL are made into aggregates or complexes and then the cholesterol in HDL is trapped by an enzyme reaction (Japanese Laid-open Patent Application (Kokai) Nos. 8-131197 and 8-201393). However, with these methods, the results for certain samples are different from the results by the precipitation method, so that their specificities are problematic.
The present applicant previously developed a method for quantifying HDL cholesterol which does not necessitate a fractionating operation (International Publication No. WO98/26090), and the reagent therefor is now being generally used in the actual clinical tests. In this method, cholesterol in lipoproteins other than HDL in a sample is erased (the term "erase" herein means to decompose ester type cholesterol and free cholesterol, and to make the decomposed products undetectable in the second step), and HDL cholesterol is specifically quantified in the second step.
However, this method has a problem in that the measured amount of HDL is larger than the actual amount of HDL for abnormal clinical samples such as disorder of lipid metabolism and lipoprotein abnormality. Abnormal samples often indicate abnormal triglyceride (TG) values, bilirubin values and the like in biochemical tests, so that overcoming the above-mentioned problem will increase the usefulness of the measuring method, and so the solution of the problem is demanded.

Method of quantifying cholesterol in high density lipoprotein and reagent compositions


Heat dissipation device for an electronic board comprising a support body connected to the electronic board, said electronic board being provided with an electric connection interface which can be inserted into/extracted from an electric connector provided in a direction orthogonal with respect to the lying plane of a support plate, having a heat dissipation surface configured to dissipate the heat transmitted to it by thermal conduction, wherein said heat dissipation device comprises at least one holding element and a leveling member, coordinated with respect to each other in order to position a surface of the support body in contact with the heat dissipation surface of the support plate.

High performance processing units, for example in the field of supercomputers, typically provide a support plate provided with a plurality of electric connectors, where electronic boards are installed.
The electronic boards in question are the "card edge" type, that is, they have a series of electric contacts, also called "gold fingers", and can be removably inserted into electric connectors, also known as sockets, present on the support plate of the processing unit.
By way of non-restrictive example, by removable electronic boards we also mean node cards of a server system, electronic expansion cards, Line Replaceable Units (LRU), Field Replaceable Units (FRU), or other similar or comparable electronic boards that can be installed without needing to be disassembled, also the customized type. Other electronic boards to which this description refers are those with an electric interface connection of the "board to board" type.
The present disclosure does not refer to systems based on a blade architecture, connectable through a rear backplane, which make the connection in the same direction of insertion/extraction into/from the system.
For these electronic boards, connection and heat dissipation devices are known that are very complex and cannot be generalized to different electronic boards, such as for example PCIe electronic boards.
In this context, it is required to achieve a high degree of electronic integration and therefore high power densities, which means that the electronic boards have to be highly compact.
In order to avoid exceeding the temperature limit values, the electronic boards need to be greatly cooled, so as not to cause malfunctions and/or irreversible damage.
Various types of cooling techniques are known, such as for example forced air cooling, heat-carrier fluid cooling, or techniques that use passive heat dissipation devices.
Cooling obtained by means of forced air, or with heat-carrier fluid, passing between the electronic boards, normally have volumes that limit the power density obtainable, and require complex assemblies with numerous additional elements, such as for example the conduits where the heat-carrier fluid flows.
In this context, the cooling obtained by means of passive heat dissipation devices is preferable, since it is simple to obtain and, in the event of a malfunction, the probability of damage to the various components is lower than other types of cooling.
One of the preferred solutions, using passive heat dissipation devices, provides to use a cooling plate, also known as a "cold plate", which comprises integrated conduits in which a cooling fluid flows.
To guarantee maximum heat dissipation efficiency, the cooling plates require a reliable and extensive heat coupling between the cooling plates and the electronic boards installed on them.
Two main types of insertion/extraction of electronic boards into/from electric connectors are known, but they do not always guarantee a reliable and extensive thermal and mechanical coupling with the cooling plate for any type of electronic board.
Blade-type electronic boards are known, in which the electric and mechanical connection is obtained by inserting the electronic boards in a longitudinal insertion direction, until they are connected to an electric connector located at the end-of-travel, perpendicular to the insertion direction. In this case, the electric connector is on a "backplane".
Electronic boards inserted orthogonally are also known which, once positioned above the electric connectors, are inserted/extracted orthogonally to the longitudinal extension of the electric connectors.
When it is possible to access the electric connectors exclusively in a direction parallel to the longitudinal extension of the electric connectors, the orthogonally inserted electronic boards are not easy to use in the processing units of the invention because they are difficult to position, but above all, even if installed, do not guarantee a reliable and extensive mechanical, heat and electric coupling.
Document U.S. 2004/0022045 describes a rack for mounting electronic boards, which uses a forced air cooling system with fans provided on the internal faces of the panels that contain the rack. The electronic boards are mounted on the top and bottom faces of a motherboard using connectors provided on these faces.
This document also provides a guide system to guide into position the single electronic board with respect to its position associated with the motherboard. This document does not show solutions to obtain dissipation of the heat produced by thermal conduction functioning between a cooling plate and a surface suitable for the reciprocal contact heat transmission.
In this case, the only contact with the motherboard is given by the electric connectors that are not configured to dissipate the heat, but to connect the electronic board electrically to the motherboard itself, which in turn is distanced from the electronic board, being itself a source of heat.
U.S. Pat. No. 5,966,289 (U.S.' 289) describes a system for mounting an electronic component, such as a CPU, in which a support and a clamping element coupled to the support are provided.
The support comprises a finned heat dissipater that develops substantially parallel to an electronic board. The heat dissipater is mounted on a face of the housing where the electronic board is installed and, thanks to its finned configuration, has the function of dissipating the heat generated by the electronic board during functioning.
This document also does not show solutions to obtain a dissipation of the heat produced by thermal conduction functioning between a cooling plate and a surface suitable for reciprocal contact heat transmission.
In this case too, the system board is distanced from the housing of the electronic board, since the system board is a source of heat.
Document U.S.' 289 shows a fin in contact with a reference surface of a mechanical support so as to keep the housing distanced from the system board.
There is therefore a need to perfect the state of the art and make available a heat dissipation device for an electronic board that overcomes at least one of the disadvantages of the state of the art.
The purpose of the present invention is to obtain a heat dissipation device for electronic boards that can be installed orthogonally with respect to the direction defined by the longitudinal extension of the electric connector which allows to obtain a reliable mechanical and electric coupling, as well as a reliable and extensive heat coupling, so as to guarantee effective heat dissipation between the electronic board installed and the support plate, possibly provided with a cooling plate.
Another purpose of the present invention is to perfect the installation of orthogonally inserted electronic boards, even if only one access is available in a direction parallel to the longitudinal extension of the electric connector, so as to obtain a reliable and extensive heat coupling with the support plate.
The Applicant has devised, tested and embodied the present invention to overcome the shortcomings of the state of the art and to obtain these and other purposes and advantages.

Heat dissipation device for an electronic card


A method for verifying instructions of diagnostic equipment is used to solve a technical problem that a lower computer of the diagnostic equipment is prone to be cheated by an upper computer, this method comprises: obtaining first verification data sent from the upper computer of the diagnostic equipment, wherein the diagnostic equipment carries the first verification data when a software version of the diagnostic equipment is updated, the first verification data is encrypted and comprises a set of instructions sent from the upper computer to the lower computer in a corresponding software version; decrypting the first verification data to obtain the set of instructions; comparing instruction data received from the upper computer with the set of instructions, and judging whether the instruction data comply with the set of instructions; if the instruction data comply with the set of instructions, executing the instruction data; and if the instruction data doesn't comply with the set of instructions, refusing to execute the instruction data.

With a rapid development of vehicle electronics technology, functionalities of vehicles are becoming more and more complicated, and vehicle diagnosis is becoming more and more important, vehicle diagnostic equipments play a very important role in people's daily lives. As for the diagnostic equipment, lower computer programs of the diagnostic equipment are core programs that serve to communicate with an ECU (Electronic Control Unit) of vehicle. Due to development of vehicles, the lower computer programs of the diagnostic equipment need to be updated to be supportive of diagnosis of new types of vehicles, diagnostic software and the lower computer programs work as a whole by combination and coexistence.
However, a lawbreaker may operate an upper computer reversely so as to use data of a certain type of vehicle to cheat the lower computer of the diagnostic equipment, thereby evading a validity check of the lower computer programs, and achieving a purpose of illegally communicating with the ECU of the vehicle.

Method and device for verifying instructions of diagnostic equipment, and lower computer


A method and apparatus is provided for the continuous microwave depolymerization of high molecular weight organic feedstock material, such as waste plastics and includes intermittent or continuous feeding of the processing material on the surface or into the bulk of the sensitized hot bed located under microwave irradiation. As a result of the interaction of electromagnetic field with processed materials, sensitizer is heated by microwave energy and feedstock material undergoes the depolymerization reactions. The reaction zone can be localized on the surface of the hot bed or distributed in the bulk of the reaction mass depending on the agitation conditions of the reaction mass, such as stirring, or other agitation means, for example by re-circulated gas. Products of the reactions are vaporized and transported to the collection system, which may include a combination of a scrubber, a condenser and a settler.

This application relates to a method and apparatus for the microwave depolymerization of hydrocarbon feedstocks, including plastic materials. An earlier effort is embodied in U.S. Pat. No. 6,184,427 entitled "Process and Reactor for Microwave Depolymerization of Plastic Materials", which is assigned to the assignee of the present invention. This patent discloses, among other things, using the interaction of microwave and sensitizers in order to provide heating and depolymerization of hydrocarbons. The present invention is an improvement upon such U.S. Patent.

Method and apparatus for microwave depolymerization of hydrocarbon feedstocks


A laminated ceramic electronic component has a variety of superior mechanical properties and electrical properties, including a high degree of freedom in the design for ceramic materials, and can be manufactured at low cost and with a low percentage of defective products. The laminated ceramic electronic component includes a laminate including a plurality of stacked ceramic layers and a plurality of internal electrodes containing Al as a main constituent, the internal electrodes being arranged along specific interfaces between the ceramic layers, and external electrodes located on an outer surface of the laminate, wherein surface layer sections of the internal electrodes include an Al2O3 layer.

1. Field of the Invention
The present invention relates to a laminated ceramic electronic component typified by a laminated ceramic capacitor, for example, and more particularly, relates to a laminated ceramic electronic component including an internal electrode containing Al as its main constituent.
2. Description of the Related Art
With reference to FIG. 1, a laminated ceramic capacitor 1 will be described first which is a typical example of a laminated ceramic electronic component.
The laminated ceramic capacitor 1 includes a laminate 2 composed of a plurality of stacked dielectric ceramic layers 3 and a plurality of internal electrodes 4 and 5 formed along specific interfaces between the dielectric ceramic layers 3.
First and second external electrodes 8 and 9 are formed in different positions from each other on the outer surface of the laminate 2. The laminated ceramic capacitor 1 shown in FIG. 1 has the first and second external electrodes 8 and 9 formed on respective end surfaces 6 and 7 of the laminate 2 opposed to each other, respectively. The internal electrodes 4 and 5 include a plurality of first internal electrodes 4 electrically connected to the first external electrode 8 and a plurality of second internal electrodes 5 electrically connected to the second external electrode 9, and these first and second internal electrodes 4 and 5 are alternately arranged with respect to the staking direction.
Since reduction in size is required, in particular, for laminated ceramic capacitors, an approach in which green sheets of a dielectric ceramic and internal electrode layers are stacked and then fired simultaneously is employed in the production process. In recent years, for the purpose of cost reduction, a base metal such as Ni has been used for internal electrodes of laminated ceramic capacitors.
However, since Ni is very likely to be oxidized in a co-firing process with the ceramic, it has been necessary to bring the atmosphere for firing into a reducing atmosphere and precisely control the temperature condition and the oxygen partial pressure. As a result, the material design is limited significantly. In addition, problems such as delamination and cracks have occurred and are caused by non-uniform stress associated with the co-firing.
Therefore, in order to increase the degree of freedom in the design of laminated ceramic electronic components, it is preferable to study internal electrodes made from a variety of metal materials.
For example, DE 19719174 A1 discloses a laminated ceramic body employing Al as an internal electrode material instead of Ni. However, since the melting point of Al is about 660° C., the ceramic has to be able to be sintered at about 660° C. in terms of the conventional rule of common sense. Thus, the laminated ceramic body has a problem in that the degree of freedom in the design of ceramic materials is limited significantly.
However, the laminated ceramic electronic component disclosed in DE 19719174 A1 has a problem in that the Al internal electrode is made into a spherical shape, resulting in an inability to secure sufficient conductivity, because the firing temperature is 1200° C. which is much higher than the melting point of Al at 660° C.
Furthermore, the laminated ceramic electronic component disclosed in DE 19719174 A1 has a problem in that the Al to define the internal electrodes is changed to an aluminum nitride (AIN), resulting in the inability to secure sufficient conductivity, because the firing atmosphere is a nitrogen atmosphere with an oxygen partial pressure of 10−5 atm.

Laminated ceramic electronic component and method for producing laminated ceramic electronic component


An optical disk player includes a main body, a cover engaging with the main body, a pivot module, and a deceleration module. The pivot module includes a torsion spring, two ends of the torsion spring being fixed on the main body and the cover respectively. The deceleration module includes a first deceleration portion arranged on the main body and a second deceleration portion arranged on the pivot module. The first deceleration portion contacts the second deceleration portion and frictional forces therebetween reduces the speed of opening the cover.

1. Technical Field
The present disclosure relates to optical disk players and, more particularly, to an optical disk player with a deceleration module.
2. Description of Related Art
Optical disk players, such as DVD (digital versatile disk) players etc., are widely used. An optical disk player includes a main body for receiving an optical disk, a cover pivotably connected to the main body, and a torsion spring arranged between the main body and the cover. The cover can automatically open because of the torsion spring. However, an opening speed of the cover may be too quick because of excessive force of the torsion spring; therefore, the cover is easily damaged over time, and a lifespan of the optical disk player will be reduced.
Therefore, there is room for improvement in the art.

Hong Fu Jin Precision Industry (ShenZhen) Co., Ltd.


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

Magnetic flux leakage testing (MFLT) has the advantages of strong in-field defect identification capability, no strict cleanliness requirements on a to-be-tested surface, great penetration depth, simple device design, convenient operation, quick testing, and flexible capability working under complex environments, etc. The MFLT is a common method of the current nondestructive testing, which is widely applied to nondestructive defects testing in key components, such as oil-and-gas pipelines, oil storage tanks, railway tracks. MFLT is also an important technology in maintaining equipment integrity, eliminating accidents, reducing loss of life and properties, and protecting environments.
However, the existing MFLT technology is only suitable for locating the defects, poor in accuracy when assessing the dimensions of a defect, i.e., unable to determine their geometric shape and size simultaneously, especially for those defects with complex and irregular shapes. Therefore, its application is limited to roughly estimating the defect size.


A system for adjusting control of an industrial vehicle comprises a badge communicator that communicates with electronic badges that are in short range proximity of the industrial vehicle; and a controller coupled to memory, wherein the controller executes program code stored in the memory to adjust control of operating parameters of the industrial vehicle. The controller executes the program code to receive a badge identifier wirelessly transmitted by a detected electronic badge and identify a role associated with the badge identifier. Based on the role associated with the badge identifier, the controller modifies a set point of the industrial vehicle from a first set point to a second set point by communicating information concerning the set point to a vehicle control module of the electronic vehicle.

The present disclosure relates to electronic systems that collect information related to the operation and movement of electronic badges in industrial applications, and in particular to the use of industrial vehicles in communication with electronic badges to control the operation of industrial vehicles and to track pedestrian movement, including the ability to authenticate and track the industrial vehicle operator.
Wireless strategies are deployed by business operations, including distributors, retail stores, manufacturers, etc., to improve the efficiency and accuracy of business operations. Wireless strategies may also be deployed by such business operations to avoid the insidious effects of constantly increasing labor and logistics costs.
For instance, in a typical warehouse implementation, a forklift truck is equipped with a communications device that links a corresponding forklift truck operator to a management system executing on an associated computer enterprise via a wireless transceiver. Essentially, the communications device is used as an interface to the management system to direct the tasks of the forklift truck operator, e.g., by instructing the forklift truck operator where and/or how to pick, pack, put away, move, stage, process or otherwise manipulate items within a facility.

Adjusting control of an industrial vehicle based on an electronic badge


An athletic cup that is convertible from a hard cup configuration to a soft cup configuration. The hard cup configuration can be used for contact sports or ball sports where maximum protection is needed. The cup can be converted to the soft cup configuration for non-contact sports where a lesser degree of protection is adequate. The cup comprises a hard cup and a soft cup that are detachably connected to each other to form the hard cup configuration. To convert to the soft cup configuration, the hard cup is detached and the soft cup is worn by itself.

The present invention relates to athletic protectors for protecting the genitals.
Athletic protectors for protecting the genitals during sporting activities generally fall into either the "hard cup" or the "soft cup" type. Hard cups are typically worn for contact sports or those involving high-speed projectiles (e.g., baseball, hockey, lacrosse, etc.), where there is a significant likelihood of being struck in the groin with a hard blow. The traditional type of hard cup includes a rigid plastic shell bonded to a softer material that forms a margin or edge region of the cup for contacting the wearer's body during use. Such hard cups are not particularly comfortable to wear.
Soft cups are much more pliable than hard cups, and are usually worn in non-contact sports or activities that do not involve a significant likelihood of receiving a hard, high-velocity blow to the groin. A soft cup offers more protection than a jock strap alone, but not nearly as much as a hard cup. The chief advantage of the soft cup is that it is much more comfortable to wear than a hard cup.
A particular individual who is involved in both contact sports and non-contact sports generally would have to own at least one hard cup and at least one soft cup.

Athletic protector convertible from hard-cup to soft-cup configuration


A method of fabricating a multi-compartment innerduct includes the steps of positioning a plurality of longitudinally extending, laterally spaced, strips of adhesive on a longitudinally extending sheet of fabric material, connecting adjacent of the strips together to form compartments, and attaching the compartments together.

Positioning cables in underground communication conduits which extend for several thousand feet has long been a problem. Such is particularly true when it is desired to position an additional cable or cables into a conduit that already has a cable in it. That cable, particularly because of its plastic jacket, provides a great deal of friction to the new cable as it is being inserted into the conduit. As a result, the new or the existing cable may be damaged due to that friction. Such is particularly true when the cable in the conduit is ungulating which causes the cable being introduced to take a sinuous, fraction-laden path.
An extremely successful solution to this problem is a fabric innerduct sold under the trademark MAXCELL® by TVC Communications, LLC and shown in U.S. Pat. No. 6,262,371 which is incorporated herein by reference for whatever details may be necessary to understand the present invention. This innerduct is first positioned in a conduit and divides the conduit into longitudinally extending compartments. A cable can be positioned in one of the compartments, and a pull tape or rope can be positioned in another compartment which can later be utilized to pull a second cable into that compartment. Because there is fabric between the cables, the friction is not on the cable jacket but on the fabric which makes installation easier.
The compartments of these innerducts are typically connected to each other to provide a multi-compartment innerduct by stitching them together. While such a connection is normally sufficient, at times the stitching could come loose resulting in a possible loss of integrity of the compartments of the innerduct.
Thus, the need exists for an alternative manner in which to connect and form the compartments of an innerduct.

Method of making an innerduct for a conduit


A flange 62 having motor mounting through holes 63 is provided on a motor 6, motor mounting holes 19 are provided on a base body 1, so that motor mounting screw 61 are passed through the motor mounting through hole 63 from a back surface 1b side so as to be screwed into the motor mounting holes 19 to fix the motor 6 to the base body 1. Housing mounting holes 83 are provided on a control housing 8, housing mounting through holes 17 are formed on the base body 1 so as to be offset from portions which are in abutment with the flange 62, so that housing mounting screws 81 are passed through the housing mounting through holes 17 from the back surface 1b side so as to be screwed into the housing mounting holes 83 to fix the control housing 8 to the base body 1.

1. Field of the Invention
The present invention relates to a vehicle brake hydraulic pressure control unit.
2. Description of Related Art
Various types of vehicle brake hydraulic pressure control units have been proposed, and among them, for example, there are vehicle brake hydraulic pressure control units which are described in Japanese Patent Unexamined Publication JP-A-07-47945 and U.S. Patent Examined Publication U.S. Pat. No. 6,260,582 B1.
In a vehicle brake hydraulic pressure control unit described in the JP-A-07-47945, a flange having through holes is provided on a motor, and by inserting screws from the motor side through the through holes so as to be screwed into a base body, the motor is fixed to the base body. On the other hand, a flange having through holes is also provided on a control housing, and by inserting screws from the control housing side through the through holes so as to be screwed into the base body, the control housing is fixed to the base body.
In a vehicle brake hydraulic pressure control unit described in the U.S. Pat. No. 6,260,582 B1, through holes are formed on a flange of a motor, and through holes are also formed on a base body coaxially with the through holes of the motor flange, and by inserting screws from the motor side through the through holes of the motor and the through holes of the base body so as to be screwed into a control housing, the motor, base body and control housing are fixed together.
In the vehicle brake hydraulic pressure control unit disclosed in JP-A-07-47945, however, the flanges are provided on both the motor and the control housing to prevent the interference of heads of the screws and a mounting tool (for example, a screw driver) with the motor main body or the housing main body, and due to the flange being provided on the control housing which is a relatively large constituent member, the control housing is made larger in size. Because of this, the base body is also made large in size in a portion which corresponds to the flange, these leading to a problem that an increase in overall size of the vehicle brake pressure control unit.
In contrast to this, in the vehicle brake hydraulic pressure control unit disclosed in U.S. Pat. No. 6,260,582 B1, since the screws are screwed into the base body from a back surface of the control housing, the flange of the control housing does not have to be formed large, and hence, a reduction in size of the control housing can be attained, whereby a reduction in size of the vehicle brake hydraulic pressure control unit has been attained.
In this vehicle brake hydraulic pressure control unit, however, since the configuration is adopted in which the common screws are used to fasten the base body and the control housing together, when considering tolerances of the respective constituent members, the inside diameters of the through holes of the flange of the motor and the through holes of the base body need to be set larger than the outside diameter of the screws in advance, to which extent the base body and the flange of the motor are enlarged in size.
In addition, in the event that the respective through holes are increased due to the tolerances, a certain length of time is necessary to position the respective members in a radial direction, this deteriorating the assembling efficiency, and furthermore, there has been caused a problem that looseness is generated between the respective constituent members after they have been assembled together.

Vehicle brake hydraulic pressure control unit


This invention relates to novel analogs of pituitary adenylate cyclase-activating polypeptide (PACAP), which are agonists for the PACAP/vasoactive intestinal peptide (VIP) receptors: PAC1, VPAC1 and VPAC2 receptors. These PACAP analogs can be used as prophylactic/therapeutic agents for a wide range of medical disorders, including (but not limited to) cancer and autoimmune disease. These PACAP analogs can be coupled to suitable radionuclides and used in the localization, diagnosis and treatment of disseminated cancers and metastatic tumors, or coupled to small molecule therapeutics and used as vectors for targeted drug delivery. This invention also provides pharmaceutical compositions of one or more PACAP-like compounds of the invention either alone or in combination with one or more other prophylactic/therapeutic agents.

Pituitary adenylate cyclase-activating polypeptide (PACAP) was isolated from ovine (sheep) hypothalami based on its ability to stimulate adenylate cyclase activity in rat anterior pituitary cell cultures (Miyata et al., Biochem Biophys Res Commun 164:567-574, 1989). PACAP exists as two α-amidated peptides with 38 (PACAP38; SEQ ID NO:1) or 27 (PACAP27; SEQ ID NO:2) amino acids. Both peptides have the same N-terminal 27 amino acids and are synthesized from the same prohormone. The sequence of PACAP38 is identical in all mammals and differs from the avian and amphibian orthologs by only one amino acid (Vaudry et al., Pharmacol Rev 52:269-324, 2000). PACAP is a member of the secretin/vasoactive intestinal peptide (VIP)/growth hormone-releasing hormone (GHRH) family, and PACAP27 has 68% sequence identity with VIP (SEQ ID NO:3). PACAP is most abundant in the brain and testis, but there are significant levels in other organs, including the pancreas, adrenals, thymus, spleen, lymph nodes, and duodenal mucosa (Vaudry et al., Pharmacol Rev 52:269-324, 2000). PACAP is synthesized as a preprohormone and is processed mainly by prohormone convertase 1, prohormone convertase 2 and prohormone convertase 4 (Li et al., Neuroendocrinology 69:217-226, 1999; Li et al., Endocrinology 141:3723-3730, 2000). The half-life of [125I]-PACAP38 in the bloodstream of rats following intravenous injection is 5-6 minutes (Banks et al., J Pharmacol Exp Ther 267:690-696, 1993). Members of the secretin/VIP/GHRH family are degraded in plasma mainly by aminodipeptidases, especially dipeptidyl peptidase IV (Zhu et al., J Biol Chem 278:22418-2223, 2003).
A PACAP-specific receptor, designated as the PAC1 receptor, has been cloned from several vertebrate species (Arimura, Jpn J Physiol 48:301-331, 1998; Vaudry et al., Pharmacol Rev 52:269-324, 2000). It is a G-protein-coupled receptor with seven putative membrane-spanning domains and belongs to a family of glycoprotein receptors that are coupled to multiple signal transduction pathways (Segre and Goldring, Trends Endocrinol Metab 4:309-314, 1993). PACAP binds not only to the PAC1 receptor with a high affinity, but it also binds to the VIP1 (VPAC1) and VIP2 (VPAC2) receptors with an affinity comparable to or greater than VIP. On the other hand, VIP binds to the PAC1 receptor with an affinity 1,000 times less than PACAP (Arimura, Jpn J Physiol 48:301-331, 1998). At least 10 splice variants of the rat PAC1 receptor have been cloned and each variant is coupled to distinct combinations of signal transduction pathways (Vaudry et al., Pharmacol Rev 52:269-324, 2000). The "second" messengers include adenylate cyclase, phospholipase C, mitogen-activated protein (MAP) kinases, and calcium. PACAP/VIP receptor can be coupled to Gαs and/or Gαi in different types of cells. PACAP/VIP receptors are expressed in many different types of normal and cancer cells, including the catecholamine-containing cells in the adrenal medulla and the sympathetic ganglia; microglia, astrocytes and some types of neurons in the central nervous system; and T- and B-lymphocytes, macrophages, neutrophils, and dendritic cells in the immune system (Vaudry et al., Pharmacol Rev 52:269-324, 2000). PACAP is a potent stimulator of catecholamine secretion from the adrenal medulla (Watanabe et al., Am J Physiol 269:E903-E909, 1995), but a potent inhibitor of the secretion of tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-12 from activated macrophages (Ganea and Delgado, Crit. Rev Oral Biol Med 13:229-237, 2002). More pertinent to the present invention, PACAP stimulates the proliferation of C6 glioblastoma cells (Dufes et al., J Mol Neurosci 21:91-102, 2003), AR4-2J pancreatic carcinoma cells (Buscail et al., Gastroenterology 103:1002-1008, 1992) and MCF-7 breast cancer cells (Leyton et al., Breast Cancer Res Treat 56:177-186, 1999), but inhibits the proliferation of HEL myeloid leukemia cells (Hayez et al., J Neuroimmunol 149:167-181, 2004), SW403 colonic adenocarcinoma cells (Lelievre et al., Cell Signal 10:13-26, 1998) and multiple myeloma cells (Li et al., Regul Pept 145:24-32, 2008; see FIGS. 3 and 4).
Although PACAP was isolated during a screen for novel hypophysiotropic factors, it soon became apparent that it is a pleiotropic peptide (Arimura, Jpn J Physiol 48:301-331, 1998; Vaudry et al., Pharmacol Rev 52:269-324, 2000). The extraordinarily potent neuroprotective/neurotrophic properties of PACAP were investigated by several laboratories shortly after its isolation. The cytoprotective effects of PACAP and VIP have been studied much more extensively in the nervous system than in any other major organ of the body. The cell types that were protected by PACAP in various in vitro models include cerebellar granule cells, dorsal root ganglion cells, sympathetic ganglion cells, mesencephalic dopaminergic neurons, and basal forebrain cholinergic neurons (Arimura, Jpn J Physiol 48:301-331, 1998; Vaudry et al., Pharmacol Rev 52:269-324, 2000). PACAP also prevented the neuronal death induced by gp120, the envelope glycoprotein of the human immunodeficiency virus (HIV), in rat hippocampal neuron/glia co-cultures. The dose-response curve was bimodal, with peaks at 10−13 M and 10−10 M (Arimura et al., Ann NY Acad Sci739:228-243, 1994). The critical findings in this study have been confirmed by Kong et al. (Neuroscience 91:493-500, 1999), who used lipopolysaccharide as the neurotoxin in primary murine cortical neuron/glia co-cultures. The neuroprotective effect at 10−12 M was correlated with a significant reduction in the accumulation of nitrite in the culture medium. The neuroprotective effect of "low" (femtomolar) doses of PACAP in neuron/glia co-cultures was abolished by PD98059, a MAP kinase inhibitor, but the neuroprotective effect of "high" (nanomolar) doses of PACAP was not affected by PD98059 (Li et al., J Mol Neurosci 27:91-106, 2005). However, the neuroprotective effect of nanomolar doses of PACAP was abolished by Rp-cAMP, a protein kinase A inhibitor.
The drawbacks of using peptides for neuroprotection in the brain include their poor transport across the blood-brain barrier and their short half-life in the circulation after systematic administration. However, PACAP38 has been shown to be transported from the blood to the brain via a saturable mechanism (Banks et al., J Pharmacol Exp Ther 267:690-696, 1993). Therefore, PACAP38 was tested as a neuroprotectant in common in vivo preclinical models of heart attack and stroke. Four-vessel occlusion in the rat was used to model the consequences of a heart attack for the brain (transient global forebrain ischemia). Blood flow to the forebrain was interrupted for 15 minutes. Following the 15-minute occlusion, there was a significant reduction in the number of pyramidal cells in the CA1 field of the hippocampus after 7 days in vehicle-infused rats. The reduction in the number of pyramidal cells at day 7 post-occlusion was significantly reversed in the rats continuously infused intravenously with PACAP38 (Uchida et al., Brain Res 736:280-286, 1996). Middle cerebral artery occlusion (MCAO) in the rat was used to model a stroke (transient focal cerebral ischemia). The middle cerebral artery was occluded for 2 hours using the intraluminal filament technique. The continuous intravenous infusion of PACAP38 beginning at 4, 8 or 12 hours after the start of the transient MCAO resulted in a reduction of the infarct volume of approximately 51%, 22% or 12%, respectively, 48 hours after the start of the MCAO (Reglodi et al., Stroke 31:1411-1417, 2000). These observations suggest that small changes in the concentration of PACAP in the brain can alter the vulnerability of nerve cells to injury.
The neuroprotective effects of low concentrations of PACAP in the nervous system are indirect and are probably mediated by at least four distinct mechanisms. (1) PACAP is a potent anti-inflammatory peptide. It has been shown to inhibit the induction of inducible nitric oxide synthase (iNOS) in activated macrophages, to inhibit the production of the pro-inflammatory cytokines TNF-α, IL-6 and IL-12 in activated macrophages, and to stimulate the production of the anti-inflammatory cytokine IL-10 in activated macrophages (Ganea and Delgado, Crit Rev Oral Biol Med 13:229-237, 2002). PACAP probably inhibits inflammation at multiple steps in the inflammatory cascade because it is an endogenous counter-regulator of the inflammatory process. PACAP is also an extraordinarily potent "deactivator" of activated microglial cells (Kong et al., Neuroscience 91:493-500, 1999; Delgado et al., Glia 39:148-161, 2002), which are the resident macrophage-like cells in the nervous system. (2) Femtomolar (10−15 M) concentrations of PACAP increase the levels of the mRNA for activity-dependent neurotrophic factor in murine neuron/glia co-cultures (David et al., Society for Neuroscience [33rd Annual Meeting], New Orleans, La., #38.1 [Abstract], 2003). Furthermore, the number of PAC1 receptors on "reactive" glial cells is increased following injury (Uchida et al., Brain Res 736:280-286, 1996). Brenneman et al. (Neuropeptides 36:271-280, 2002) had previously shown that femtomolar concentrations of PACAP stimulate the release of RANTES in astrocyte cultures and that immunoneutralization of RANTES reduces the neuroprotective effect of PACAP in neuron/glia co-cultures. (3) Yang et al. (J Pharmacol Exp Ther 319:595-603, 2006) have shown that femtomolar concentrations of PACAP inhibit microglial NADPH oxidase activity and extracellular superoxide levels in mesencephalic neuron/glia co-cultures. (4) Figiel and Engele (J Neurosci 20:3596-3605, 2000) have reported that PACAP increased the expression of the glutamate transporters GLT-1 and GLAST and increased the activity of the glutamate metabolizing enzyme glutamine synthetase in astrocytes. These effects of PACAP would be expected to decrease glutamatergic neurotransmission. The extensive studies about the cytoprotective properties of PACAP in the nervous system have provided a solid framework for studying the cytoprotective properties of PACAP in other organs.
Native PACAP has already been administered to normal human volunteers by investigators in at least four different laboratories (Chiodera et al., Neuroendocrinology 64:242-246, 1996; Filipsson et al., J Clin Endocrinol Metab 82:3093-3098, 1997; Doberer et al., Eur J Clin Invest 37:665-672, 2007; Murck et al., Am J Physiol 292:E853-E857, 2007) and to a patient with multiple myeloma under a U.S. Food and Drug Administration (FDA)-approved protocol (Li et al., Peptides 28:1891-1895, 2007). The only untoward effect reported was a transient flushing.
PACAP is an extraordinarily potent peptide in vitro. However, the usefulness of PACAP as a drug is limited by its very short half-life in the circulation following systemic administration due to both rapid proteolysis and rapid filtration by the kidney. Therefore, there is a need for PACAP analogs that are resistant to proteolysis and/or have reduced rates of filtration by the kidney.
Citation or discussion of a reference herein shall not be construed as an admission that such reference is prior art to the present invention.

Analogs of pituitary adenylate cyclase-activating polypeptide (PACAP) and methods for their use

The Administrators of the Tulane Educational Fund


Provided are sulfide solid electrolyte particles which have sufficient ion conductivity and which are configured to suppress hydrogen sulfide generation, and an all-solid-state battery comprising the sulfide solid electrolyte particles. Disclosed are sulfide solid electrolyte particles comprising Li, P, S and a halogen as constituent elements and having a Li/P molar ratio of more than 3, wherein an oxygen/sulfur element ratio of a particle surface measured by XPS is 0.29 or more and 0.81 and less, and an oxygen/sulfur element ratio at a depth of 30 nm (in terms of a SiO2 sputter rate) from the particle surface measured by XPS, is 0.29 or less.

An all-solid-state battery such as an all-solid-state lithium secondary battery in which a solid electrolyte is used in place of a liquid electrolyte, does not use a combustible organic solvent inside the battery. Accordingly, such an all-solid-state battery is considered to be able to realize a simplified safety device and excellent in production cost and productivity.
The components of such an all-solid-state battery, that is, the cathode, the anode and the electrolytes of the battery, are all solid. Accordingly, the all-solid-state battery has a tendency to have large electrical resistance and provide small output current compared to, for example, a lithium secondary battery comprising an organic liquid electrolyte.
To increase the output current of the all-solid-state lithium secondary battery, therefore, an electrolyte with high ion conductivity may be used. A sulfide solid electrolyte is considered to show higher ion conductivity than an oxide solid electrolyte, since a sulfide ion has large polarizability compared to an oxide ion, and an electrostatic attraction force between a sulfide ion and a lithium ion is small.
Patent Literature 1 discloses a sulfide solid electrolyte material which comprises a sulfide layer containing a sulfide material and an oxide layer containing an oxide formed by the oxidation of the sulfide material, wherein the oxide layer is located on a surface of the sulfide layer, and the sulfide solid electrolyte material satisfies 1.28≤x≤4.06 and x/y≥2.60, where "x" is the oxygen/sulfur element ratio of the outermost surface of the oxide layer, which is measured by XPS depth profile analysis, and "y" is the oxygen/sulfur element ratio at a depth of 32 nm (in terms of a SiO2 sputtering rate) from the outermost surface of the oxide layer, which is measured by XPS depth profile analysis. Patent Literature 1 states as follows: by sufficiently increasing the ratio of oxygen binding in the outermost surface of the sulfide solid electrolyte material as in the specific range described above, the electrolysis of the sulfide solid electrolyte material in the outermost surface of the sulfide solid electrolyte material, which may be exposed to high potential by, for example, being in contact with an active material, can be sufficiently suppressed. Patent Literature 1 also states as follows: by reducing oxygen binding in the oxide layer in the vicinity of the boundary surface where the oxide layer is in contact with the sulfide layer as in the specific range described above, high ion conductivity can be maintained and, as a result, the charge/discharge characteristics of the battery can be further improved.
Patent Literature 2 discloses a sulfide solid electrolyte particle comprising an oxide layer on a surface thereof, the oxide layer resulting from the oxidation of the particle itself, and a sulfide solid electrolyte material. Patent Literature 2 states that the oxygen/sulfur element ratio of the surface of the sulfide solid electrolyte particle may be at least twice the oxygen/sulfur element ratio at a depth of 30 nm from the particle surface. As Example 1, Patent Literature 2 discloses a sulfide solid electrolyte particle such that the oxygen/sulfur element ratio of the particle surface is 1.54 and the oxygen/sulfur element ratio at a depth of 30 nm from the particle surface is 0.65. As Comparative Example, Patent Literature 2 discloses a sulfide solid electrolyte particle such that the oxygen/sulfur element ratio of the particle surface is 1.05 and the oxygen/sulfur element ratio at a depth of 30 nm from the particle surface is 0.54. Patent Literature 2 also states that the durability of an all-solid-state battery can be improved since the formation of a high resistance part in the interface between the sulfide solid electrolyte particle and an oxide active material, can be suppressed, and since the deterioration of the sulfide solid electrolyte particles can be suppressed.
Patent Literature 1: Japanese Patent Application Laid-Open (JP-A) No. 2018-26321
Patent Literature 2: JP-A No. 2012-94445
In practice, for the sulfide solid electrolyte material with high surface oxygen rate as disclosed in Patent Literature 1, the ion conductivity of the solid electrolyte rapidly decreases. In an all-solid-state battery comprising such a sulfide solid electrolyte material with low ion conductivity, the resistance of the interface between the sulfide solid electrolyte material and the oxide active material largely increases, and the initial resistance of the battery becomes very high. Accordingly, the all-solid-state battery can be only operated at the very low charge/discharge rate as disclosed in Patent Literature 1, and there is a problem with practical use of the all-solid-state battery.
Even for the sulfide solid electrolyte particles as disclosed in Patent Literature 2, it is still insufficient to have sufficient ion conductivity. Accordingly, further improvement is expected.
Meanwhile, a sulfide solid electrolyte is problematic in that sulfur atoms in the sulfide solid electrolyte react with the moisture in the air to generate hydrogen sulfide. A conventional sulfide solid electrolyte is problematic in that the effect of suppressing hydrogen sulfide generation, is not in sufficient. Especially in the case of a sulfide solid electrolyte having a Li/P molar ratio of more than 3 (for example, a Li2S/P2S5 molar ratio of more than 3), while the sulfide solid electrolyte has excellent ion conductivity, there is a tendency that the sulfur atoms in the sulfide solid electrolyte react with the moisture in the air, and hydrogen sulfide is likely to be generated.

Sulfide solid electrolyte particles, method for producing the same, and all-solid-state battery


The present invention relates to Chimeric Antigen Receptors (CAR) that are recombinant chimeric proteins able to redirect immune cell specificity and reactivity toward selected membrane antigens, and more particularly in which extracellular ligand binding is a scFV derived from a ROR1 monoclonal antibody, conferring specific immunity against ROR1 positive cells. The engineered immune cells endowed with such CARs are particularly suited for treating lymphomas and leukemia, and for solid tumors such as breast, colon, lung, and kidney tumors.

Adoptive immunotherapy, which involves the transfer of autologous antigen-specific T cells generated ex vivo, is a promising strategy to treat viral infections and cancer. The T cells used for adoptive immunotherapy can be generated either by expansion of antigen-specific T cells or redirection of T cells through genetic engineering (Park, Rosenberg et al. 2011). Transfer of viral antigen specific T cells is a well-established procedure used for the treatment of transplant associated viral infections and rare viral-related malignancies. Similarly, isolation and transfer of tumor specific T cells has been shown to be successful in treating melanoma.
Novel specificities in T cells have been successfully generated through the genetic transfer of transgenic T cell receptors or chimeric antigen receptors (CARs) (Jena, Dotti et al. 2010). A schematic representation for the 3 generations of CARs is presented in FIG. 1. CARs are synthetic receptors consisting of a targeting moiety that is associated with one or more signaling domains in a single fusion molecule. In general, the binding moiety of a CAR consists of an antigen-binding domain of a single-chain antibody (scFv), comprising the light and variable fragments of a monoclonal antibody joined by a flexible linker. Binding moieties based on receptor or ligand domains have also been used successfully. The signaling domains for first generation CARs are derived from the cytoplasmic region of the CD3zeta or the Fc receptor gamma chains. First generation CARs have been shown to successfully redirect T-cell cytotoxicity. However, they failed to provide prolonged expansion and anti-tumor activity in vivo. Signaling domains from co-stimulatory molecules, as well as transmembrane and hinge domains have been added to form CARs of second and third generations, leading to some successful therapeutic trials in humans, where T-cells could be redirected against malignant cells expressing CD19 (June et al., 2011). However, the particular combination of signaling domains, transmembrane and co-stimulatory domains used with respect to CD19 ScFv, was rather antigen-specific and cannot be expanded to any antigen markers.
Chronic lymphocytic leukemia (CLL) is one of the most commonly diagnosed leukemias managed by practicing hematologists. For many years patients with CLL have been viewed as similar, with a long natural history and only marginally effective therapies that rarely yielded complete responses. Recently, several important observations related to the biologic significance of VH mutational status and associated ZAP-70 overexpression, disrupted p53 function, and chromosomal aberrations have led to the ability to identify patients at high risk for early disease progression and inferior survival. Concurrent with these investigations, several treatments including the nucleoside analogues, monoclonal antibodies rituximab and alemtuzumab have been introduced. Combination of these therapies in clinical trials has led to high complete and overall response rates when applied as initial therapy for symptomatic CLL. Thus, the complexity of initial risk stratification of CLL and treatment has increased significantly. Furthermore, when these initial therapies do not work, approach of the CLL patient with fludarabine-refractory disease can be quite challenging (Byrd J. C et al, 2014).
One candidate antigen of immunotherapies for chronic lymphocytic leukemia (CLL) is Tyrosine-protein kinase transmembrane receptor ROR1 (also called NTRKR1; UniProtKB/TrEMBL) entries: Q01973). ROR1 (The receptor tyrosine kinase-like orphan receptor 1) is a 120-kDa glycoprotein containing an extracellular immunoglobulin (Ig)-like, Kringle, and Frizzled-like cysteine rich domain (FIG. 2). The protein encoded by this gene is a receptor tyrosine kinase that modulates neurite growth in the central nervous system. It is a type I membrane protein and belongs to the ROR subfamily of cell surface receptors (Reddy et al, 1997). Although ROR1 protein expression in patients with CLL with respect to normal leukocytes and its role in the pathobiology of CLL merits further studies. ROR1 may be an appropriate target for cancer immunotherapy (Daneshmanesh et al; 2008). ROR1 is indeed expressed on a variety of B-cell malignancies, but also on subsets of some solid tumors, including breast, colon, lung, and kidney tumors. It is believed that ROR1 functions in oncogenic signaling to promote tumor cell survival in epithelial tumors. Importantly, ROR1 is not expressed on vital organs, except adipose and pancreatic tissue, which reduces potential toxicities from killing of normal cells (Hudecek et al, 2013). ROR1 is expressed during embryogenesis but absent from normal adult tissues, apart from a subset of immature B-cell precursors, and low-level expression on adipocytes (Hudecek et al., 2010; Matsuda et al., 2001). ROR1 was first shown to be expressed in B-cell chronic lymphocytic leukemia (B-CLL) by transcriptional profiling (Klein et al., 2001; Rosenwald et al., 2001) and was subsequently identified on the surface of many cancers including mantle cell lymphoma (MCL), acute lymphoblastic leukemia (ALL) with a t(1;19) chromosome translocation, and a subset of lung, breast, colon, pancreas, renal, and ovarian cancers (Baskar et al., 2008; Bicocca et al., 2012; Daneshmanesh et al., 2008; Dave et al., 2012; Fukuda et al., 2008; Yamaguchi et al., 2012; Zhang et al., 2012a, 2012b). In both lung adenocarcinoma and t(1;19) ALL, ROR1 cooperates in oncogenic signaling and knockdown of ROR1 with siRNA exposed a critical role for this molecule in maintaining tumor cell survival (Bicocca et al., 2012; Choudhury et al., 2010; Gentile et al., 2011; Yamaguchi et al., 2012). Thus, ROR1 loss may not be readily tolerated by tumors making it an attractive candidate for CAR directed T-cell therapy that could be broadly applied. The present inventors have thus considered that ROR1 could be a valuable target antigen for treating CLL as well as solid tumors such as breast, colon, lung, ovarian and kidney tumors, by using CAR-expressing T cells.
The laboratories of Dr. Stanley Riddell and Dr. Laurence Cooper have previously engineered and validated anti-ROR1 scCARs containing the 4A5 and the 2A2 scFvs, respectively (Cooper et al 2010; Hudecek et al., 2013). In particular, Hudecek et al discloses anti-ROR1 scCARs which contain an IgG4 hinge of diverse length and a CD28 transmembrane domain.
There is still the need for the improvement of CAR functionality by designing CAR architecture and using suitable components since these parameters play a role important and a fine tuning is necessary.
Therefore, as an alternative to the previous strategies, the present invention provides with ROR1 specific CARs, which can be expressed in immune cells to target ROR1 malignant cells with significant clinical advantage. The inventors have found that, by combining CAR architecture to the choice of suitable components, they could obtain specific ROR1 single chain CARs with high cytotoxicity towards cancerous target cells,

ROR1 (NTRKR1) specific chimeric antigen receptors for cancer immunotherapy


A semiconductor device includes: a compound semiconductor substrate; an n-channel field-effect transistor region formed on the compound semiconductor substrate, and that includes a first channel layer; an n-type first barrier layer that forms a heterojunction with the first channel layer, and supplies an n-type charge to the first channel layer; and a p-type gate region that has a pn junction-type potential barrier against the n-type first barrier layer; and a p-channel field-effect transistor region formed on the compound semiconductor substrate, and that includes a p-type second channel layer, and an n-type gate region that has a pn junction-type potential barrier against the p-type second channel layer.

1. Field of the Invention
The present invention relates to compound semiconductor field-effect transistors, particularly to semiconductor devices that include an n-type high electron mobility transistor and p-type field-effect transistor formed on the same compound semiconductor substrate.
2. Description of the Related Art
Field-effect transistors with a compound semiconductor layer of a material such as GaAs have high electron mobility and desirable frequency characteristics, and for this reason have been widely used with an n-channel for high-frequency region applications such as in cellular phones. The n-channel FET (Field Effect Transistor) currently in use for the high frequency band is the high electron mobility transistor (HEMT). Its variant pseudomorphic high electron mobility transistor (PHEMT; Pseudomorphic HEMT) is also known that tolerates certain degrees of lattice mismatch in epitaxial growth, and thus realizes even higher electron mobility. JPHEMTs (Junction Pseudomorphic HEMTs) that form a PN junction at a gate portion are also known (see, for example, JP-A-11-150264). In JPHEMTs, a large positive voltage is applied to the gate to reduce the carrier depleted region formed in a channel layer, and thereby reduce the parasitic resistance component of the channel layer.
With the movement toward high performance n-channel FETs, there is an increasing demand for higher integration, which requires the development of complementary elements using a compound semiconductor. Ion implantation is a common technique to simultaneously form n-channel and p-channel FETs on a compound semiconductor. In this technique, an n-channel forming region and a p-channel forming region are formed by selectively injecting a p-type dopant and an n-type dopant into the same substrate. However, the ion implantation technique requires high-temperature annealing of at least 800° C. after the ion implantation, in order to activate the injected dopants.
JP-A-61-67275 describes a method of simultaneously forming an n-channel FET and a p-channel FET on a compound semiconductor. According to this publication, an n-channel-type heterojunction field-effect transistor using a two-dimensional electron gas as the carrier, and a p-channel-type heterojunction field-effect transistor using a two-dimensional hole gas as the carrier are formed on a compound semiconductor substrate of GaAs. The n-channel-type heterojunction field-effect transistor includes a non-doped GaAs layer, a non-doped AlGaAs layer, an n-type impurity doped AlGaAs layer, and an n-type impurity doped GaAs layer. Each layer is laminated using an epitaxial growth method. The n-type impurity doped AlGaAs layer has a gate electrode of aluminum or titanium/platinum/gold. The n-type impurity doped GaAs layer has source and drain electrodes of gold-germanium/gold. The p-channel-type heterojunction field-effect transistor includes a non-doped GaAs layer, a non-doped AlGaAs layer, a p-type impurity doped AlGaAs layer, and a p-type impurity doped GaAs layer laminated on the laminate structure using an epitaxial growth method. The p-type impurity doped AlGaAs layer has a gate electrode of Al or titanium/platinum/gold. Source and drain electrodes of gold/zinc/gold are formed on the p-type impurity doped GaAs layer.

Semiconductor device and method for manufacturing same


A film comprising as a film-forming agent an alginate salt of monovalent cation or a mixture of alginate salts containing at least one alginate salt of monovalent cation, the film-forming agent being such that a 10% aqueous solution thereof at a temperature of 20° C. has a viscosity of 100-1000 mPas, as measured at a shear rate of 20 rpm by use of a Brookfield viscometer with a spindle No. 2. A method of preparing the film. The film is useful for delivery of active ingredients to a mammal.

Alginate, the salt of alginic acid, is a linear polysaccharide naturally produced by brown seaweeds (Phaeophyceae, mainly Laminaria). It is composed of typically 100-3000 monomer residues linked together in a flexible chain. These residues are of two types, namely β-(1→4)-linked D-mannuronic acid (M) residues and α-(1→4)-linked L-guluronic acid (G) residues, respectively. The residues are epimers (D-mannuronic acid residues being enzymatically converted to L-guluronic acid residues after polymerization) and only differ at C5. However, in the polymer chain they give rise to very different conformations; any two D-mannuronic acid residues are 4C1-diequatorially linked while the link connecting any two L-guluronic acid residues is a 1C4-diaxial link, as illustrated in Formula I, herein below.

The residues are organised in blocks of identical or strictly alternating residues (e.g. MMMMMM . . . GGGGGG . . . or GMGMGMGM . . . ).
Different monovalent and polyvalent cations, e.g. Na+, K+, NH4+, Mg2+ and Ca2+, are present as counter-ions to the negatively charged groups of the alginates.
Depending on factors such as mean polymer chain length, polymer composition and the cations present the flow characteristics of alginates vary widely, from free-flowing (low viscosity) to drip-free (high viscosity).
Alginates find uses in various fields, e.g. in pharmaceutical and food products where they are applied e.g. as thickeners, stabilizers and gelling agents. Their use in pharmaceutical compositions is mentioned in a number of patents and patent applications. Thus, U.S. Pat. No. 6,923,988 assigned to Lipocine, Inc. discloses a solid pharmaceutical composition for improved delivery of active ingredients. It is mentioned that the pharmaceutical composition may comprise alginate as a disintegrant.
U.S. Pat. No. 6,923,981 assigned to Warner-Lambert Company discloses fast dissolving orally consumable films for mouth hygiene. A listing of film forming agents is given and while sodium alginate is mentioned therein, pullulan is stated to be preferred and no example of an alginate film is given.
U.S. Pat. Nos. 6,656,493 and 6,740,332, both assigned to Wm. Wrigley Jr. Company disclose edible film formulations for mouth hygiene. The film formulations contain at least three types of film forming agents, viz. a maltodextrin, a hydrocolloid and a filler. The aim of the hydrocolloid is to provide thickness and decrease brittleness and alginates are mentioned as examples of a hydrocolloid.
US patent application No. 20050013847, assigned to FMC Corporation, relates to delivery systems comprising a homogenous, thermoreversible gel film, wherein the gel film comprises: a film forming amount of a water soluble thermoreversible alginate and optionally at least one of a plasticizer, a second film former, a bulking agent, and a pH controlling agent; and an active substance. The second film former is said to be optional but all examples show films comprising at least two film formers. The exemplified process for preparing the gel film comprises heating the alginate-containing mixture to an elevated temperature to form a homogeneous molten composition. The active substance is added either prior to or after formation of the molten composition and the molten composition containing the active substance then is cooled and further processed. It is mentioned that to modify the dissolution profile of the dosage forms the films can contain added components that can create solid dosage forms having immediate, enteric or delayed release capabilities.
U.S. Pat. No. 6,709,671, assigned to LTS Lohmann Therapie-Systeme AG discloses a monolayer film formed from a mucoadhesive composition which comprises at least one water-soluble polymer; a surfactant alone or in combination with at least one member selected from the group consisting of a polyalcohol and a plasticizer, or a polyalcohol and a plasticizer; and at least one cosmetic or pharmaceutical ingredient, for application into the mouth.
There are many ways of delivering active pharmaceutical ingredients (drugs) to the body (collectively termed formulations) depending on the type of drug and the disorder to be treated. For example, oral formulations such as tablets, capsules and lozenges; solutions of drugs in vials and pre-filled syringes for injection; topical formulations such as patches and ointments as well as nasal sprays. Other ways of delivering drugs, such as implanted pumps and slow-release depot formulations to be placed in the body, also exist. The formulation selected will typically have a marked influence on the therapeutic result of the drug, its side effects and the ease by which the patient can use the medication.
The most widely used drug formulation is the tablet that shall be swallowed for release of drug in the intestine. Tablets consist of a drug that is mechanically compressed together with a number of additional substances providing the structure and delivery properties of the tablet. Tablets need to be swallowed with a liquid such as water and some patients, e.g. children and elderly patients, may have difficulties in swallowing them.
A problem associated with oral tablets is that many drugs may be degraded during the passage through the acid environment of the stomach. When the drug has entered the intestine, drug is taken up into the blood stream via the portal vein into the liver where a large portion of the active pharmaceutical ingredients typically is metabolised to inactive chemicals by enzymes that normally take care of foreign substances in food, viz. the so-called first-pass metabolism.
These factors result in a significant delay before a positive therapeutic effect can be noted, leading to a risk of gastro-intestinal side effects augmented by the need of administering considerably higher amounts of drug than would be needed by, for example, a direct injection of a drug solution into a vein.
Although injections provide a rapid pharmacological effect and reduce the risk of side effects, injections usually must be carried out by medically qualified staff at a medical centre or hospital, thus limiting the convenience of this administration form.
Nasal sprays may produce a rapid onset of action but is usually limited to local treatment of the respiratory tract. Other forms of formulations such as depots, patches or infusion devices are usually applied to address conditions where a sustained level of drug is required over longer time periods.

Water-soluble films comprising low-viscosity alginates


According to one aspect, the subject matter described herein includes a method for validating a long term evolution (LTE) transport data block and code blocks within the data block. The method includes steps occurring at an LTE traffic simulator configured to simulate plural user equipment (UE) devices. The steps include receiving, from an evolved nodeB under test, an LTE transport block including a plurality of code blocks. The steps also include decoding the code blocks and verifying a cyclic redundancy check (CRC) code for each of the code blocks. The steps further include while decoding the code blocks and verifying the CRC codes for the code blocks, verifying a CRC code for the transport block.

As cellular communication technology evolves, providers are able to more effectively utilize their allocated spectrum. Enhanced protocols such as those specified by the 3rd generation partnership project's (3GPP) long term evolution (LTE) standards are enabling providers to increase the speed and capacity of their wireless networks. These enhanced protocols, however, are significantly more complex than their predecessors and require the design, integration, and support of new hardware, such as mobile base stations, within a provider's network. The successful implementation of such hardware often requires multiple iterations of testing and refinements in order to meet the specified performance requirements. Testing such hardware, however, is also becoming an increasingly complex task. As the number of user equipment (UE) nodes supported by a base station and the individual resource utilization of such UEs increases, testing hardware must be optimized to effectively simulate such demands.
Accordingly, a need exists for methods, traffic simulators, and computer readable media for validating LTE code blocks and transport blocks.

Methods, traffic simulators, and computer readable media for validating long term evolution (LTE) code blocks and transport blocks