The present invention includes an image acquisition device configured to acquiring multiple viewpoint images that are generated by pupil-division imaging and that are different in viewpoint, a parallax calculation device 40a for calculating a first parallax amount between viewpoint images for the multiple viewpoint images, a memory 48 in which parallax correction information indicating the relationship between the first parallax amount and the deviation amount in the parallax direction for the corresponding object images, which is a deviation amount between viewpoint images for the multiple viewpoint images and is caused by the pupil-division imaging, is stored, and a parallax correction device 40b for calculating a second parallax amount, which is an amount resulting from correcting the first parallax amount to the deviation amount in the parallax direction for the object images, based on the first parallax amount and the parallax correction information stored in the memory 48.

1. Field of the Invention
The present invention relates to an image processing device, an imaging device and an image processing method, and particularly relates to an image processing device, an imaging device and an image processing method that make it possible to obtain a parallax resistant to noise and equivalent to a parallax to be perceived by humans, in the case of detecting a parallax for multiple viewpoint images that are imaged by pupil division.
2. Description of the Related Art
A stereoscopic imaging device including an imaging element that performs imaging by a pupil-division scheme is known. In the case of using such an imaging element with a pupil-division scheme, as a method for calculating a parallax by performing matching between left and right images, a method in which the positional deviation amount between blocks to minimize the sum of squares of the pixel value differences is regarded as a right solution and is output is well known. Thus, typically, the calculation of the parallax is performed using a method (correlation method) in which the parallax is calculated by the correlation based on the pixel values of the left-eye image and right-eye image.
For example, PTL 1 (Japanese Patent Application Laid-Open No. 2002-191060) discloses a phase difference type image sensor that includes a micro-lens whose upper part is opened and a micro-lens whose lower part is opened, and thereby, makes it possible to obtain a left-eye image and a right-eye image. Further, it is disclosed to perform the matching between the left-eye image and the right-eye image by a correlation method and determine the distance information.
Further, PTL 2 (National Publication of International Patent Application No. 2011-515045) discloses a phase difference type image sensor that disposes photoelectric conversion elements at the left side and the right side for one cylindrical micro-lens, and thereby, makes it possible to obtain a left-eye image and a right-eye image.
Further, PTL 3 (WO 2011/118089) discloses that a pupil-division imaging is performed so that multiple viewpoint images (a first image and a second image) are acquired, and when different image processes are respectively performed for the multiple viewpoint images, the image processes are performed such that the image quality difference between the multiple viewpoint images after the image processes is reduced.
Further, PTL 4 (WO 2011/118077) discloses that a pupil-division imaging is performed so that multiple viewpoint images (a first parallax image and a second parallax image) are acquired, a restoration filter corresponding to the defocus amount and image height for each position in the multiple viewpoint images is selected for each position, and the deconvolution is performed for each position in the multiple viewpoint images based on the selected restoration filter, so that the multiple viewpoint images are restored.

Image processing device, imaging device, and image processing method


A method and an apparatus for repairing a system file are provided. The computer-implemented method for repairing a system file, comprises: detecting, by a processor, a corrupted system file in an operating system; sending identification information of the operating system and an identifier of the corrupted system file to a server; receiving an integrity identifier of an intact system file to be used in repairing the corrupted system file, wherein the intact system file is determined by the server according to the identification information of the operating system and the identifier of the corrupted system file; verifying, by the processor, the received integrity identifier with a locally stored integrity identifier of the corrupted system file; and if the received integrity identifier passes the verification, obtaining, from the server, the intact system file corresponding to the verified integrity identifier and repairing the corrupted system file with the obtained intact system file.

In the case that a corrupted system file in an operating system is detected, according to a version number and a patch number of the operating system, an identifier of the system file such as the name of the system file, and version information of the corrupted system file, a corresponding system file is downloaded from a file library to replace the corrupted system file, thus the system file is repaired.

Tencent Technology (Shenzhen) Company Limited


A powered slide rail device including an electrode element extending along the lower rail thereof and a contact brush element provided in the upper runner rail element thereof which is slidably engaged with the lower rail. The electrode element is so arranged as to provide a sloped surface. The contact brush element, with which an output connector is electrically connected, projects from the upper runner rail element and contacts such sloped surface of electrode element. A biasing element may be provided to retain the contact brush element in contact with the sloped surface of electrode element.

1. Field of the Invention
The present invention relates to a powered slide rail device for adjustably moving a vehicle seat in forward and backward directions under the drive force of an electric motor and associated electric element.
2. Description of Prior Art
FIG. 1 shows a conventional powered slide rail device (102) on which a front seat (100) and a rear seat (101) are slidably mounted. This kind of slide rail device is frequently used in a vehicle having a long and wide cabin, such as a minivan, and typically comprised of a long lower rail, an upper rail slildably engaged with the long lower rail, a lead screw disposed in and along the long lower rail in the longitudinal direction thereof, a nut member rotatably disposed in the upper rail, the nut member being threadedly engaged about a part of such long lead screw, and a motor connected with the nut member. Normal and reverse operation of the motor causes forward and backward movement of the upper rail along the lower rail to adjustingly position a seat on the slide rail device at a desired point.
In most cases, such powered slide rail device is one mechanical part of a powered vehicle seat which includes a plurality of electric motors associated with a seat cushion tip-up mechanism, reclining device and so forth. Hence, as shown in FIG. 1, a long electric cable (103), which is electrically connected between the seat and a power source, extends along the long lower rail or a floor of vehicle, so that the seat can smoothly move on and along the long lower rail.
But, the long electric cable stands in the way of a passenger who sits on the seat, or narrows the floor area on which the passenger can rest his or her feet. It is therefore frequently the case that the wire cable is cut off by the passenger's feet, or partly broken to cause a short circuit therein.
Solution to such problem has been found for example in the Japanese Laid-Open Patent Publication No. 8-332906 which discloses a powered slide rail device wherein an electrode plate, electrically connected with a power supply, is fixed to and along the inner wall of a lower rail of the slide rail device, and a contact brush, electrically connected with a motor, is provided on an upper rail slidably engaged with the lower rail. The contact brush is kept in contact with the electrode plate, so that an electric current flows from the power supply side (e.g. an electric connector for powered seat, which is provided on a control box) to the motor. With that structure, the electric current path is not exposed outwardly like the afore-said electric cable.
Nonetheless, in the foregoing prior art, the electrode plate extending along the lower rail inner wall is perpendicular with the flat plane of floor, and the contact brush is provided on a movable connector so as to project horizontally and slidably contact such perpendicular electrode plate. This conventional arrangement is found defective in that a slidable contact between the contact brush and electrode plate is not complete, and thus, it is highly possible that a loose connection will occur between those contact brush and electrode plate due to a vibration of a vehicle body or a deformation of the upper and lower rails in a collision case or the like.

Powered slide rail device for vehicle seat


A unitary support bracket facilitates secure and efficient support of an electrical box, and one or more associated conduits. The support bracket includes a central portion, and a plurality of leg portions which extend integrally therefrom. Each of the leg portions includes a downwardly deformable distal portion, which in turn each include at least one resiliently deformable tab engageable with a respective one of the conduits. By this arrangement, the efficient support of an electrical box, and one or more associated conduits, can be provided, with minimal assembly of various components required, thus facilitating convenient and efficient installation of the associated electrical system.

In the typical construction of a building structure, electrical wiring for the structure is typically routed through various conduits, with the conduits commonly joined to an electrical box, within which suitable electrical connections or the like are provided. As will be recognized by those familiar with the art, typical building codes require that such conduits and electrical boxes meet certain structural requirements, including spacing, support, and like requirements.
Heretofore, support of an electrical box, and one or more associated conduits, has typically required that a suitable arrangement of support brackets, clamps, fasteners, and the like be employed to ensure that the electrical components meet the applicable building codes. As such, installation of typical electrical boxes and conduits can be relatively time-consuming, as workers must fit and assemble the various brackets, clamps, and like components to ensure that the resultant structure is in accordance with industry standards.
The present invention is directed to an improved, unitary, one-piece support bracket for an electrical box, and one or more associated conduits, which particularly facilitates efficient installation of such components, while at the same time, permitting the arrangement to be customized, as may be required, for use with a wide variety of different configurations of an electrical box and conduit elements.


A method of operating a modem generally comprising the steps of (A) transmitting an invalid signal from the modem at each of a plurality of settings for an echo cancelling hybrid of the modem, (B) calculating a plurality of merit values each in response to an echo signal received by the modem in response to the invalid signal, and (C) adjusting the echo cancelling hybrid to a particular setting of the settings determined from the merit values.

A frequency duplexed Asymmetric Digital Subscriber Line (ADSL) modem transmits in one frequency band and receives in a second, disjoint frequency band. In an "Annex A" mode, a Customer Premises Equipment (CPE) modem transmits from about 26 kilohertz (KHz) to 138 KHz in an upstream direction to a Central Office (CO) mode. The CO modem transmits from 138 KHz to 1104 KHz in a downstream direction to the CPE modem. Since the CPE transmits in a lower frequency band than the CPE receives, the CPE transmit circuit non-linearity and modulation of an upstream data signal on transmit carriers causes some frequency content of the CPE transmit signal to appear in the CPE receive band as echo signals. The echo signals acts as noise and an impediment to downstream data transmission.
Echo signals are conventionally reduced in several ways. First, the transmitted signal from the CPE modem is filtered to reduce energy in the frequencies that cause echo. Second, an analog circuit called an "echo cancelling hybrid", or "hybrid" for short, is used to measure and cancel the transmitted signal from the received signal. Finally, complicated adaptive techniques called echo cancellation can be used to suppress the echo further.
Some filtering will always be done. However, increasing the filtering degrades the upstream data rate because the filter will increase the phase loss in the pass band, making the upstream channel more difficult for the CO modem to equalize. Additional filtering also requires more electronic components, which can increase the manufacturing cost of the modems. Likewise, the hybrid circuit will always be used. However, because of the variation of phone lines, a non-programmable hybrid circuit design must sacrifice echo signal attenuation for robustness. Conversely, a hybrid optimized for a particular phone line without bridged taps may perform unacceptably for phone lines with moderate length bridged taps. Furthermore, required digital and analog hardware support used to implement the echo cancellation functions add to an expense and design complication for the modems.

Adaptable hybrid and selection method for ADSL modem data rate improvement


An instantaneous hot water device comprises a gate valve means connected to a hot water line and having a gate valve and a gate valve seat providing a controlled flow of hot water from the hot water line into a ball valve means having a ball check and a first ball valve seat having slot cooperating with the ball check to provide a small, controlled flow of hot water into a cold water line and a second ball valve seat cooperating with the ball check to prevent flow of cold water into the gate valve means and the hot water line.

1. Field of the Invention
This invention relates to a device for providing instant hot water at a hot water outlet in a home water plumbing system.
2. Description of Related Prior Art
A great deal of water and heating energy are wasted in waiting, after a hot water faucet or other tap is turned on, for the temperature of the water to rise to the temperature provided by a hot water heater. It has been estimated that about 5000 gallons of water per year are so wasted in the average home. When cold water is drained from hot water pipes, additional cold water enters the hot water heater and must be heated. The energy required for heating such wasted water is considerable.
Numerous prior art devices have been developed for providing instantaneous hot water at a hot water tap, for example in residential plumbing systems. In general, such prior art devices comprise expensive and complicated equipment for such purpose.
For example, Peters, U.S. Pat. No. 2,842,155 discloses a device for providing instantaneous hot water at a hot water faucet by interconnecting the hot and cold water lines and permitting a thermally-induced circulation of hot water into the cold water line. The Peters device comprises a control means 25 interconnecting the hot and cold water lines below the faucets. Means 25 comprises a pipe-like housing 27 which is attached at either end to the hot and cold water lines, and a bypass valve 35 which is seatable against and movable away from valve seat 37 under the action of a thermostatic element 31 responsive to water temperature, thus permitting or preventing the flow of hot water through an orifice 39. Cold water is prevented from entering the hot water line by pressure of cold water exerted on a ball valve 43 positioned in a cage 44 and forcing valve 43 against a valve seat 41 formed on cage 44. Thus Peters requires a thermostatically controlled Bourdon tube 80 that depends on the temperature of the hot water to expand and close a plunger 70. Hot water is maintained at a given point by using a pressure and temperature differential. The Peters device will function only as long as hot water is being purged through the hot water side of the faucet. After hot water has been purged, and the faucet is closed, a cooling effect takes place. The Bourdon tube contracts and closes plunger 70. The cross connection is sealed, and thus there is no convection and the hot water line will cool back to the hot water heater. The only time that the Peters device delivers hot water is after the first purge of hot water (approximately 3-5 gallons). It will maintain hot water for approximately 30 minutes only.
Chubb U.S. Pat. No. 1,108,550 has, as a primary use, the warming of waste water in traps under sinks and bath tubs. Such use no longer applies in modern home construction and plumbing systems.
Chubb U.S. Pat. No. 1,247,374 also discloses a device for preventing freezing of a water distribution system, wherein the hot and cold water lines are interconnected by means of an automatic valve 36 or 36a. Valve 36 is connected at either end to the hot and cold water lines. Mounted within the valve 36 are valve elements 50 and 51, connected by a rod 52 extending through a restricted passageway 48, and biased by springs 56 and 57. In the closed position of the faucets, springs 56 and 57 are so biased that they keep the elements 50 and 51 spaced from the openings to passageway 48 so that hot water can pass into the cold water line. If a faucet is opened, the flow of water is such as to cause element 50 or 51 to compress the respective biasing springs and to close the passageway 48, preventing water from passing therethrough. The Chubb device is designed to work on relatively low temperatures and pressures. Modern high technology, high efficiency water heaters would damage the Chubb device and render it inoperable.
Paulson U.S. Pat. No. 3,543,836 discloses a device for providing instantaneous hot water comprising a pipe 10 interconnecting the hot and cold water lines and forming a closed loop which contains a pump 9 which, on activation, circulates cooled hot water from the hot water line to the cold water lines. The pump is activated by a thermostat 16 positioned in the pipe 10 upstream of the pump and downstream of the connection to the hot water supply line. A signal, equal to the temperature sensed by the thermostat, is transmitted to a temperature controller 17 via a capillary tube 18. Thus Paulson requires a temperature controller to operate a pump on a temperature drop creating a part time delivery of hot water. The device depends on a fan blowing air over a coil to reduce temperature of hot water being moved to the cold water source. The Paulson device is designed for trapped plumbing systems only, so its application is limited. Moreover, the Paulson device in very expensive and is not practical in today's modern systems; it would not be allowed under the plumbing codes of many areas of the United States which prohibit a 110 volt controlling device to be installed under sinks in bathrooms because of the danger of electrical shorts causing injury.
Zimmer U.S. Pat. No. 4,331,292 relates to an instantaneous hot water supply system and comprises a pipe 20 interconnecting the hot and cold water lines. Mounted in pipe 20 is a temperature sensor 15 comprising a U-shaped bimetallic element 17, the free end of which carries a seal 20. Depending upon the temperature in the hot leg of the pipe 20, seal 20 moves into or out of sealing engagement with an orifice 19, permitting or preventing flow of hot water into the cold leg of the pipe 20. A check valve 21 prevents cold water from flowing from the cold leg into the hot leg of pipe 20. Thus, Zimmer requires a thermostatic control device to open or close a seated ball. This device is limited in use and would not apply in a trapped system. A build up of lime deposits on the U-shaped bimetallic member would render it inoperable.
Robillard U.S. Pat. No. 4,672,990 discloses another device for freeze protection of water lines exposed to extreme cold temperatures. This devices requires a mixing tank to receive hot water pumped through a hot water plumbing system through a cross connection. It also requires a thermostatic controller and a remote valve. This system is costly and would waste energy. Lime deposits inside the mixing tank would cause the device to be inaccurate and cause the pump to run longer and waste energy.
Britt U.S. Pat. No. 5,105,846 is directed to an instant hot water system comprising a purge line 25 connected to the hot and cold water lines in which there is provided a pump 28 which can be periodically actuated, e.g. by a timer, to discharge a slug of cool water in the hot water line into the cold water line. A check valve 29 prevents cold water from flowing into the hot water line while allowing water from the hot water line to pass into the cold water line. Thus, Britt requires the use of a third, purge, line to be installed at the back fixture, and a pump. Such an installation is expensive and, practically, Britt is limited to new, modern slab type plumbing systems.
Pegg U.S. Pat. No. 5,135,021 discloses an instantaneous hot water device having a body which is cast in bronze, using a sand core and molding plate. This requires several matching processes to manufacture and is very costly. The device uses a mixing chamber to cross connect the hot and cold water lines through a conduit. In this device it is imperative that the mixing chamber be purged of air or the device will not work. This is done through an air bleed screw. The chamber also becomes a shock absorber and transmits a loud thump when a cold water faucet is opened, causing a pressure drop. Construction is such that installation in close spaces is a problem.
There is a need for an instantaneous hot water device of simple construction, easy to install and of low cost.


Current imbalance may be detected in a 3-phase power system by monitoring current output between two points of a phase signal provided along wire pairs from an inverter to a motor. In some embodiments, each wire of a wire pair leading to the motor from the inverter may be provided with a line current sensor. A comparison of current output from each wire in the wire pair may be performed to determine if a current imbalance is present. In some embodiments, a phase current sensor may be coupled to a phase input of the inverter. Failures in the 3-phase system may be detected by measuring the output from each phase current sensor for imbalanced distribution of power output. In some embodiments, the output from the phase current sensors may be compared to an output of a line current sensor along the same phase for current imbalances or harness failures.

The present invention generally relates to power detection systems and more particularly to parallel harness current imbalance and failure detection.
High-power electronics play a significant role in the modern aircraft and automotive industry. This is particularly true in the area of traction drive applications for aircraft and ground vehicles. The commercial aircraft business is moving toward more fuel efficient and environmental friendly traction drive operations. One example from this latest trend is the electrical taxi application for the Airbus A320 NEO airplane. In the Airbus A320 NEO, the airplane will be using an auxiliary power unit (APU) to power the electric drive system to taxi into and/or out from a runway. All or part of the airplane's engines will be turned off during taxiing to save fuel. The electric drive system contains an autotransformer rectifier unit (ATRU), a motor controller/inverter, a gearbox, and a traction motor. The benefits of an electrical taxi system include reduction of fuel consumption, brake wear, and ground tug operation.
Military ground vehicles have migrated toward hybrid electric technology where some vehicles employ main propulsion from electric drives. Substantial demand for power utilization increases when using more electric technology to propel the vehicle. Thus, a significant increased usage in high-power harnesses for the electric drive system results from the demand for more power. In some applications, a set of 3-phase high-power harnesses may be used to bring 3-phase 115-VAC at 400 Hz from the APU to the ATRU to generate a high-voltage DC source for the motor controller/inverter. A power distribution harness may be used to deliver a high-voltage DC source from the ATRU to the motor controller/Inverter. A set of 3-phase cables may connect the motor controller/inverter outputs to drive the traction motor with AC voltage/current generated from the motor controller. The harness may carry the high load current that is necessary to deliver high torque (such as breakaway torque) and acceleration for vehicles/airplanes to reach a desired taxi speed.
In conventional power systems for taxi systems, for example hydraulic brakes, 1 kilowatt was adequate to power the system. Thus smaller radius wires are sufficient for routing in the system. However, for the increased power requirements of the power aforementioned distribution harnesses, routing constraints of the vehicle as well as the current carrying capacity may require thicker wiring. For example, some electric applications may use 50-kW-60 kW to the taxi system fed from the fuselage. Due to additional environmental and space constraints (such as routing and bending of cables for retrofitting an existing system), there may be a need to parallel the harness with smaller wires to meet the power and current rating of the system. The parallelization creates new challenges. The paralleled wires may be difficult to impedance match and result in imbalanced currents to circulate in the taxi system that may create power losses and heat.
As can be seen, there is a need for detection that monitors for imbalanced current in 3-phase power systems in vehicles.

Parallel harness current imbalance and failure detection


According to one embodiment, a nonvolatile semiconductor memory device includes a first memory portion. The first memory portion includes a first base semiconductor layer, a first electrode, a first channel semiconductor layer, a first base tunnel insulating film, a first channel tunnel insulating, a first charge retention layer and a first block insulating film. The first channel semiconductor layer is provided between the first base semiconductor layer and the first electrode, and includes a first channel portion. The first base tunnel insulating film is provided between the first base semiconductor layer and the first channel semiconductor layer. The first channel tunnel insulating film is provided between the first electrode and the first channel portion. The first charge retention layer is provided between the first electrode and the first channel tunnel insulating film. The first block insulating film is provided between the first electrode and the first charge retention layer.

A nonvolatile semiconductor memory device uses the charge storage state in a charge storage layer to store information. There is a demand for increasing a program speed in this type of nonvolatile semiconductor memory device.
Since a conventional nonvolatile semiconductor memory device exhibits a low charge trapping efficiency in a charge storage layer, it is an impediment to increase the program speed. When the charge trapping efficiency is low, the time required for programming is increased, and there is a tendency for deterioration in memory cells due to the program operation.


The present invention provides sputtering targets which are useful for depositing ferroelectric films and are resistant to crack generation during sputtering. The sputtering targets comprise a disk target which is formed using a sintered material including a compound oxide of Ba and Ti, Sr and Ti, or Ba, Sr and Ti, and which has a surface which has been subjected to grinding, wherein the scratches 4 formed on the surface of the disk target due to grinding have a pattern radiating from an arbitrary point on the plane of the surface of said disk target.

1. Field of the Invention
The present invention relates to sputtering targets which are useful for depositing ferroelectric films and which are free of crack generation even when used to deposit a thin film for a DRAM or the like containing a ferroelectric oxide having the perovskite structure.
2. Discussion of the Background
As is well-known, a sputtering target composed of a sintered material including a compound oxide of Ba and Ti (hereinafter referred to as BaTi compound oxide), a compound oxide of Sr and Ti (hereinafter referred to as SrTi compound oxide), or a compound oxide of Ba, Sr and Ti (hereinafter referred to as BaSrTi compound oxide) is generally used to form a memory-retaining capacitor thin film for a dynamic random access memory (DRAM). Further, it is also well-known that any ferroelectric film which is formed of a BaTi, SrTi, or BaSrTi compound oxide by sputtering such a target has the perovskite structure, and that particularly a sputtering target composed of a BaSrTi compound oxide is most widely used to form a memory-retaining capacitor thin film for a DRAM.
A sputtering target composed of a sintered material including such a BaTi, SrTi, or BaSrTi compound oxide is manufactured as follows. Initially, a BaCO.sub.3 powder, a SrCO.sub.3 powder, and/or a TiO.sub.2 powder are prepared as raw-material powders, and then blended in a predetermined ratio and mixed in a ball mill. Next, the obtained powder mixture is placed in a MgO pot and burned in air at 1200 to 1350.degree. C. for 3 to 10 hours. Subsequently, the burned material is crushed using a ball mill to form a BaTi, SrTi, or BaSrTi compound oxide powder. Here, such a compound oxide powder can also be prepared according to hydrothermal synthesis, or can be commercially obtained.
Next, the obtained BaTi, SrTi, or BaSrTi compound oxide powder is subjected to burning and crushing under the same conditions as above further two times or more, and then hot-pressed in a vacuum of 1.times.10.sup.-4 to 5.times.10.sup.-2 Torr under a load of 50 to 200 kg/cm.sup.2 at 900 to 1300.degree. C. for 0.5 to 3 hours. The thus-prepared sintered material of the BaTi, SrTi, or BaSrTi compound oxide is then processed by grinding into a target having a predetermined size.
As shown in FIG. 12, such a process for grinding a sintered material of a BaTi, SrTi, or BaSrTi compound oxide is usually carried out by placing a rotating straight grinding wheel 2' into perpendicular contact with the surface of the sintered material which is horizontally rotated on a grinding table 3, and moving the rotating straight grinding wheel 2' in the direction of the radius of the grinding table. Scratches 4' due to grinding (grinding scratches) are formed in concentric circles on the surface of the thus-obtained conventional target 1' by such grinding.
As shown in FIG. 10, the obtained target is set in a sputtering system 6 by being soldered onto a water-cooled copper plate 5 and subjected to sputtering under the condition that the region of the system for the target is adjusted to a vacuum atmosphere, thus depositing a ferroelectric film.
Recently, for mass production of DRAMs or the like and for saving the costs of producing the same, a larger target is used and sputtered with a greater power under a high-vacuum atmosphere thereby achieving a high deposition rate, and thus depositing a ferroelectric film in a shorter time. Such a target may, however, suffer damage such as peeling of the surface or cracking when subjected to sputtering with a greater power under a high-vacuum atmosphere. If the target is thus damaged, particles are generated on the obtained thin film, seriously affecting the yield of DRAMs. Thus, there remains a need for a sputtering target which is useful for depositing a ferroelectric film and does not suffer from cracking during sputtering. There also remains a need for a method for preparing such a sputtering target and a method for preparing a DRAM using such a target.

Sputtering target for depositing ferroelectric film, method for preparing the same, and method for preparing a DRAM using the same


An air compressor having a pen-type pressure gauge is disclosed and provided for measuring the pressure of the compressed air produced by air compressor as well as releasing air into an ambient environment when the pressure is greater than a predetermined maximum safety value, so as to achieve the operational safety without installing a separate safety valve and prevent an inflated object from damages.

A conventional air compressor simply has two air outlet ducts on the gas storage unit, and one duct is used for installing a circular-box pressure display meter and the other duct is connected with a hose having an air nozzle (wherein the air nozzle may be connected to an object to be inflated). Since there are only two air outlet ducts and thus the air compressor is incapable of being installed with a protection or safety device, the inventor of the present invention has developed an air compressor as disclosed in U.S. Pat. No. 7,462,018, wherein the air compressor comes with a structure comprising more than two ducts, wherein a safety valve is provided for relieving the pressure when an over-pressure condition of the air compressor occurs, so as to protect the object to be inflated. Since the conventional circular-box pressure meter is fixed to an external end of the duct directly by screwing means or bolts, and such connection method is undesirable, the inventor of the present invention has developed a pressure meter structure that can be assembled or removed quickly as disclosed in U.S. Pat. No. 8,297,944, and such patented invention allows users to install and remove various devices such as pressure meters, hoses, relief valves, etc, so as to provide a convenient and practical assembling process. However, the conventional air compressor still has a safety valve installed at one of the ducts to prevent the over-pressure issue, thus incurring a higher manufacturing cost for providing the protection effect. On the other hand, the conventional air compressor adopts a pointer-type pressure meter which is a circular-box device, and simply provides the functions of measuring the pressure of the compressed air and displaying the current pressure value. The conventional mechanical circular-box pressure meter does not have other new functions. FIGS. 7 to 9 show a conventional air compressor 7, which is equipped with a safety valve 77 and a circular-box pointer-type pressure meter 76. In operation, after the air compressor is started, a motor 70 drives a transmission mechanism 79 to have a piston conduct reciprocating motion in a cylinder 71 so to produce compressed air in an air reservoir 72 which includes a plurality of air outlet ducts 73, 74, 75, wherein the duct 73 is used for installing an inflating hose (not shown in the figure), the duct 74 is coupled to the circular-box pointer-type pressure meter 76, and the duct 75 is installed with a safety valve 77. Although the functional accessories including the hoses, pressure meter 76 and safety valve 77 can be assembled to the air reservoir 72 of the air compressor 7 directly and conveniently, yet when the compressed air produced in the air compressor 7 is greater than a predetermined safety tire-pressure of a car tire, the safety valve 77 is started to relieve the pressure. If the safety valve 77 fails to work properly, the car tire will be over-inflated or even has a blow-out, and furthermore, the manufacturing cost cannot be lowered.


A heart rate module, comprising a housing structure composed of a rear housing (2) and a light-transmitting cover plate (3), the housing structure being internally provided with a PCB assembly (1); the PCB assembly (1) comprises a PCB, PDs (6, 7) and an LED (5), the PDs (6, 7) and the LED (5) being fixed on the PCB according to a preset distance; a hot melt positioning column (21) is provided on the rear housing (2), and the PCB assembly (1) is fixed, by means of the hot melt positioning column (21), on the rear housing (2). Use of the heart rate module can solve the problems of the assembly method of the available heart rate meter being complicated and the requirement for a terminal product being high.

Most of the heart rate meters currently on the market come in two forms: one is a small heart rate device only with integrated PD (photodiode) and LED (light emitting diode); and the other form is to mount the PD and the LED onto a FPC soft board and a PCB hard board of a product separately, adjust the left-right spacing of the PD and LED, and the up-down spacing of the PD and LED from the LENS. Such two assembly manners are complicated, terminal products are required to make fine structural spacing to match the adjustment, and at the same time, terminal customers are required to separately develop algorithm writing, which has higher requirements for the terminal customers.
To solve the above problems, the present application provides a heart rate module.

WEIFANG GOERTEK MICROELECTRONICS CO., LTD.


Medicament for the treatment or the prevention of a bacterial infection, characterized in that it contains at least one polypeptide selected from the group of SEQ ID NO: 1 to SEQ ID NO: 9, and contiguous fragments thereof, wherein said at least one polypeptide or contiguous fragment thereof induces opsonic antibodies in a patient in need thereof. The polypeptides or the contiguous fragments thereof according to the present invention can be used for the preparation of a vaccine against an infection against Enterococcus.

Enterococci are among the three most common nosocomial pathogens and due to their multiple antibiotic resistances cause substantial morbidity and mortality, especially among intensive care patients and the immunocompromised. While several new antibiotics have been introduced in the last decade, resistance against these new drugs is developing and spreading rapidly. Life-threatening systemic disease such as endocarditis caused by resistant strains may at times be untreatable. Therefore, alternative treatment and prevention strategies are desperately needed to counter the rise of multiply resistant clones in hospitals and nursing homes worldwide. A better understanding of the different enterococcal cell surface structures will help to target new therapeutic and prophylactic approaches.
It is known that all gram-positive bacteria (also those belonging to the genus of Enterococcus) contain in the cell wall several specific carbohydrates and proteins. In the course of the present invention several proteins have been identified that play a possible role in the dynamic equilibrium of the outer cell wall.
The humoral immune response is mediated by antibody molecules secreted by plasma cells. Antigen that binds to the B-cell antigen receptor signals B-cells and is at the same time internalized and processed into peptides that activate armed helper T-cells. Signals from the bound antigen and from the helper T-cell induce the B-cell to proliferate and differentiate into plasma cells secreting specific antibody. These antibodies protect the host from infection in three main ways. First, said antibodies can inhibit the toxic effects or infectivity of pathogens by binding to them. Such antibodies are termed neutralizing antibodies. Second, by coating the pathogens, said antibodies can enable accessory cells that recognize the Fc portions of arrays of antibodies to ingest and kill the pathogen. This process is called opsonisation. Third, antibodies can trigger the activation of the complement system. Complement proteins can strongly enhance opsonisation or can directly kill certain bacterial cells.
Genomics is a recently introduced new discipline that studies the functioning of an organism through its genome and has greatly accelerated the identification of new candidates for vaccine development. More than fifty genomic sequences of enterococci are currently available in different data bases and this number is constantly growing. The analysis of all these genes and genomes is an extremely fast and efficient approach to predict the cellular localization and/or function of proteins synthesized in an organism. This in silico approach combined with functional genomics data will in future years help to identify new targets for vaccination tests (Sette and Rappuoli, 2010).
EP2248533 discloses a medicament for the treatment or the prevention of a bacterial infection is disclosed which contains a polypeptide having a contiguous sequence of at least six amino acids of SEQ ID NO:1 as disclosed therein. Said polypeptide can be used for the preparation of a vaccine against an Enterococcus infection.
Similarly, EP2450053 discloses another polypeptide used for the preparation of a vaccine against an Enterococcus infection.
WO 2010/089340 relates to a protective peptide of Enterococcus faecalis (E. faecalis) or a functional active variant thereof, optionally further consisting of additional amino acid residue(s); a nucleic acid coding for the same; a pharmaceutical composition comprising said peptide or said nucleic acid; an antibody or functional active fragment thereof specifically binding to the antigen; a hybridoma cell line which produces said antibody; a method for producing said antibody; a pharmaceutical composition comprising said antibody; the use of said peptide or said nucleic acid for the manufacture of a medicament for the immunization or treatment of a subject; the use of said antibody or functional fragment thereof for the manufacture of a medicament for the treatment of an infection; a method of diagnosing an E. faecalis infection; and the use of said peptide for the isolation and/or purification and/or identification of an interaction partner of the peptide.
WO2007141278 relates to human binding molecules (e.g. antibodies) having killing activity against enterococci and uses thereof.
For the production of vaccines it is important that the antigen elicits antibodies which inhibit the pathogenic activity of the pathogenic microorganism. The opsonophagocytic assay has been used to simulate the immune response in vitro and to identify enterococcal virulence factors (see, for example, Romero-Steiner et al., Use of opsonophagocytosis for serological evaluation of pneumococcal vaccines. Clin Vaccine Immunol. 2006 February; 13(2):165-9). Protective antibodies elicited by a vaccine have therefore the effect of neutralization, opsonisation and complement activation whereby antibodies induced by a specific antigen may also have two or even three of the protective activities. However, only few antigens have been identified so far that may offer the potential of inducing a protective immune response, and therefore would be promising vaccine targets.
It is therefore an object of the present invention to provide new polypeptides or parts thereof which can be used in order to produce protective antibodies, preferably IgG antibodies against said polypeptide or parts of said polypeptide. It is furthermore an object of the present invention, to provide vaccine compositions against gram-positive bacteria, and in particular Enterococci, based on said polypeptides or parts thereof.
Fang Teng et al. (in: Fang Teng et al. An Enterococcus faecium Secreted Antigen, SagA, Exhibits Broad-Spectrum Binding to Extracellular Matrix Proteins and Appears Essential for E. faecium Growth, Infection and Immunity, September 2003, p. 5033-5041, Vol. 71, No. 9) discloses the extracellular and secreted E. faecium SagA protein as apparently essential for growth, showing broad-spectrum binding to ECM proteins, forming oligomers, and antigenic during infection. Furthermore, antibodies produced against recombinant Sag A are described. Although the protein is described as secreted antigen, there is no disclosure of an actual antigenicity of Sag A in vivo, let alone the formation of opsonic and/or protective antibodies in a host. The publication merely describes a C-terminal domain of Sag A that is "similar to that found in various proteins", including P60 (52% similarity) of L. monocytogenes, which has cell wall hydrolase activity, and has also been shown to be involved in virulence. The publication is thus limited to the functional characterization of Sag A.
Furthermore, the presence of a surface-exposed proteins does not automatically result in the formation of opsonic and/or protective antibodies in the host. In fact, to the knowledge of the inventors, only two protein antigens have been confirmed so far in E. faecalis as being the target of protective antibodies: an ABC transporter described by Burnie and colleagues (Burnie et al. Identification of ABC transporters in vancomycin-resistant Enterococcus faecium as potential targets for antibody therapy. FEMS Immunol Med Microbiol (2002) vol. 33 (3) pp. 179-89) and, only recently, the collagen adhesin ACE (Singh et al. Importance of the collagen adhesin ace in pathogenesis and protection against Enterococcus faecalis experimental endocarditis. PLoS Pathog (2010) vol. 6(1) pp. e1000716). Two other surface proteins have been shown to be not protective, namely the enterococcal aggregation substance (McCormick et al. Antibodies to a surface-exposed, N-terminal domain of aggregation substance are not protective in the rabbit model of Enterococcus faecalis infective endocarditis. Infect Immun (2001) vol. 69 (5) pp. 3305-14) and the enterococcal surface protein Esp (Sava et al., Sava I G Enterococcal surface protein contributes to persistence in the host but is not a target of opsonic and protective antibodies in Enterococcus faecium infection. J Med Microbiol. 2010 September; 59(Pt 9):1001-4). Studies on several other protein antigens have been reported in the literature as being involved in virulence, while no protective effect of either passive or active immunization has been documented. Therefore, to date, only very few vaccine targets, either proteinaceous or carbohydrates, have been identified in E. faecium.
In one aspect thereof, the object of the present invention is solved by providing a medicament for the treatment or the prevention of a bacterial infection, characterized in that said medicament contains at least one polypeptide selected from the group of SEQ ID NO: 1 to SEQ ID NO: 9, and contiguous fragments (active variants) thereof, wherein said at least one polypeptide or contiguous fragment thereof induces antibodies in a patient in need thereof. The present invention is based on the surprising finding that the polypeptides of SEQ ID NO: 1 to 9 or active fragments thereof can be used to provide such a vaccine target, and/or can form the basis to provide effective and preferably therapeutically effective (e.g. opsonic) antibodies.
In the context of the present invention, the inventors identified nine proteins (polypeptides) of E. faecium E155 and their homologues in E. faecalis, respectively, at least parts of which function as effective antigens (epitopes), and thus can be used to provide an active polypeptide and/or peptide-based vaccine or a passive antibody-based medicament for a prevention and/or treatment of a bacterial infection, such as, for example, infection caused by gram-positive bacteria, and in particular by Enterococci.
The main protective defense mechanism of the human immune system against enterococci is phagocytosis, which occurs through direct recognition of certain enterococcal surface structures or through opsonisation by antibody and complement. Therefore, in another aspect of the invention, the active vaccine according to the present invention can be administered to patients (preferably before the infection), in order to stimulate their immune response and to avoid an infection in a hospital or a nursing home.
The amino acid sequences of the polypeptides SEQ ID NOs: 1 to 9 are both disclosed in the attached Sequence Listing and Table 1 (see below). The polypeptides of SEQ ID NOs: 1 to 9 have been shown to be effective in opsonophagocytotic assays (see examples), a clear indication for their protective effect also in vivo.
TABLE 1Polypeptides as identified according to the present invention.SEQProtein name andIDMethod forabbreviationNo.Locus Tag/Acc No.identificationlow affinity penicillin-1EFAU004_00870;Biotin, High pH,binding proteinAAD26697Trypsin5 (PBP5)Basic membrane2EFAU004_00080;Biotin, High pH,lipoprotein (BML)YP_005353284Trypsinpeptidoglycan-binding3EFAU004_01059;Biotin, High pH,protein LysM (LysM)WP_002337891TrypsinD-alanyl-D-alanine4EFAU004_01127;Biotin, High pH,carboxypeptidase (Dala)WP_016922432TrypsinPpiC-type peptidyl-5EFAU004_02526;Biotin, High pH,prolylcis-transWP_002291335Trypsinisomerase (PpiC)Enolase (Enol)6EFAU004_02073;Biotin, High pH,YP_005355275TrypsinSCP-like extracellular7WP_002353118.1Biotin, High pH,protein (serine protease)Trypsin(SCP)Adhesion lipoprotien8EFUG_02345;Biotin, High pH,(Adlip)EEV57494TranscriptomicdataPeriplasmic solute9EFAU004_00598Biotin, High pH,binding family (PSB)Transcriptomicdata
The nine polypeptides according to the invention were overexpressed and purified in order to inject said proteins into a rabbit. The animal then produced antibodies, based on the combination of proteins. The different sera as obtained showed a significant opsonic killing activity, confirmed by the stimulation of an in vitro immune response by opsonophagocytic assay. Moreover, the protein Sag A is used as a positive control in all the experiments, a promising vaccine target in E. faecium (EP 2 248 533 B1).
The person skilled in the art is aware that not necessarily the whole polypeptide has to be used for the production of a vaccine. Even shorter fragments based on contiguous amino acids of a polypeptide can be used. Such fragments are designated herein as "active variants" and comprise an (at least one) "epitope" that usually consist of at least six contiguous amino acids out of the SEQ ID NO: 1 to 9. Preferably, however, said polypeptides have at least 10, more preferably at least 15 and more preferred at least 20 contiguous amino acids of the SEQ ID NO: 1 to 9. In a particularly preferred embodiment, the polypeptide has at least 30, more preferred at least 50 and especially preferred at least 100 contiguous amino acids of SEQ ID NO: 1 to 9. Preferred fragments are disclosed in table 2 and SEQ ID Nos. 10 to 167.
Active variants may also be obtained by changing the sequence of the polypeptide as defined herein and are characterized by having a biological activity similar to that displayed by the protective peptide of the sequence of SEQ ID NOs: 1 to 9 from which the variant is derived, including the ability to induce protective immune responses and/or to show protection against E. faecium or E. faecalis e.g. in an animal model as disclosed herein, wherein any variant may be tested as described in the Examples. In another preferred embodiment of the invention the polypeptide of the invention or an active variant, can consist of 1 to 400 additional amino acid residue(s), preferably 1 to 350, 1 to 300, 1 to 250, 1 to 200, 1 to 150, more preferably 1 to 100, even more preferably at most 1 to 50, most preferably 1, 2, 3, 4, 5, 10, 20, 30 or 40 additional amino acids residue(s).
In one preferred embodiment of the invention, the peptide and/or the antigens of the invention comprising additional amino acid residue(s) as defined herein is characterized in that it comprises at least 2, preferably at least 3, more preferably at least 4 epitopes as defined above. The antigenic peptide and/or the epitope may be flanked by the amino acid residue(s) C-terminally, N-terminally or C- and N-terminally.
The active variant of the polypeptide may have added at least one additional amino acid residue heterologous or homologous to the peptide of any of the SEQ ID NOs: 1 to 9. Homologous refers to any amino acid residue which is identical to the amino acid residue of the protein from E. faecium or E. faecalis from which the peptide is derived, wherein the peptide of any of the SEQ ID NO: 1 to 9 is derived from the polypeptide as listed in Table 1. Alternatively or additionally, the polypeptide may consist of the antigen, optionally the additional sequence as defined above and at least one amino acid residue heterologous to the antigen, preferably a marker protein.
The active variant of the polypeptide may be obtained by sequence alterations in the peptide, wherein the peptide with the sequence alterations retains a function of the unaltered peptide, e.g. having a biological activity similar to that displayed by the unaltered peptide. Such sequence alterations can include, but are not limited to, (conservative) amino acid substitutions, deletions, mutations and insertions. The additional sequence or amino acid residue(s) as defined above consists of (an) amino acid residue(s), which may be any amino acid, which may be either an L- and/or a D-amino acid, naturally occurring and otherwise. Preferably the amino acid is any naturally occurring amino acid such as alanine, cysteine, aspartic acid, glutamic acid, phenylalanine, glycine, histidine, isoleucine, lysine, leucine, methionine, asparagine, proline, glutamine, arginine, serine, threonine, valine, tryptophan or tyrosine. However, the amino acid may also be a modified or unusual amino acid. Examples of those are 2-aminoadipic acid, 3-aminoadipic acid, beta-alanine, 2-aminobutyric acid, 4-aminobutyric acid, 6-aminocaproic acid, 2-aminoheptanoic acid, 2-aminoisobutyric acid, 3-aminoisobutyric acid, 2-aminopimelic acid, 2,4-di aminobutyric acid, desmosine, 2,2′-diaminopimelic acid, 2,3-diaminopropionic acid, N-ethylglycine, N-ethylasparagine, hydroxylysine, allo-hydroxylysine, 3-hydroxyproloine, 4-hydroxyproloine, isodesmosine, allo-isoleucine, N-methylglycine, N-methylisoleucine, 6-N-Methyllysine, N-methylvaline, norvaline, norleucine or ornithine. Additionally, the amino acid may be subject to modifications such as posttranslational modifications. Examples of modifications include acetylation, amidation, blocking, formylation, γ-carboxyglutamic acid hydroxylation, glycosylation, methylation, phosphorylation and sulfatation. If more than one additional or heterologous amino acid residue is present in the peptide, the amino acid residues may be the same or different from one another.
Alternatively, the polypeptide of any of the SEQ ID NOs: 1 to 9 may be essentially identical to or even consists of the antigen, i.e. the full-length protein is used as the epitope and/or antigen.
The person skilled in the art is aware that with suitable computer programs the hydrophobicity and hydrophilicity of the areas of the polypeptide can be determined.
Therefore, the preferred fragments are mainly hydrophilic since the parts of the polypeptide which are located on the outer areas of the folded polypeptide are preferred for the preparation of a vaccine. Moreover, when longer parts of the polypeptide are used, it is more likely that not only linear epitopes are within the fragment but also conformational epitopes are present which occur in the course of three-dimensional folding of the polyprotein.
Preferred active peptides (active variants)—and thus epitopes—according to the present invention are listed in the following table 2, and are disclosed in SEQ ID Nos. 10 to 167.
TABLE 2Preferred peptides (epitopes)according to the present inventionPolypeptide/SEQ ID No./ReferenceAcc No./sizeofPosition/sequence of epitope polypeptide(residues) in decreasing likelihoodPBP5/1GTLVYPKLIAD (SEQ ID NO. 41);AAD26697;AYIAGAVILIAA (SEQ ID NO. 42);679 AALKQLGVVPSK (SEQ ID NO. 43);SYQVTRVSDVSQVDLKTALIYSDN(SEQ ID NO. 44);NQAISQSWVQPDYFVPLKII (SEQ ID NO. 45);EKKVLIEHE (SEQ ID NO. 46);GDLLALASSPS (SEQ ID NO. 47);IQEVDGRYYPLGEAAAQLIGYVGDI(SEQ ID NO. 48);GGYFYYQHYQETQAVEA (SEQ ID NO. 49);LQTIVPDLREVVQDV (SEQ ID NO. 50);VEQFVQAL (SEQ ID NO. 51);SELLQYLNQ (SEQ ID NO. 52);HSLSALGIPLAAK (SEQ ID NO. 53);GELLINPIQQAAMYSVF (SEQ ID NO. 54);PNLVFP (SEQ ID NO. 55);AADVKGLQISNLKVD (SEQ ID NO. 56);PNEVLTIN (SEQ ID NO. 57);ITAAIG (SEQ ID NO. 58);SDILLAD (SEQ ID NO. 59);IKAIASSF (SEQ ID NO. 60);YSFSYK (SEQ ID NO. 61);SFLFAF (SEQ ID NO. 62);KVSLTTQ (SEQ ID NO. 63);GELKDLSYKG (SEQ ID NO. 64);PELPAGA (SEQ ID NO. 65);QPFISR (SEQ ID NO. 66);GSTVATT (SEQ ID NO. 67);LDKYQNIY (SEQ ID NO. 68) BML/2KVWVIGVD (SEQ ID NO. 69);YP_005353284;NFVIIDDVIDGLDNVVSAT (SEQ ID NO. 70);360 AATSTLKAVGTVVEDL (SEQ ID NO. 71);SYLAGVAAAY (SEQ ID NO. 72);EIKVLNQY (SEQ ID NO. 73);TNVVGFIGG (SEQ ID NO. 74);EHTVYGL (SEQ ID NO. 75);SGDVKVPE (SEQ ID NO. 76);GIGYKLKPAIQE (SEQ ID NO. 77);NADIIFHA (SEQ ID NO. 78);KAGVDAG (SEQ ID NO. 79);EDGVGLTEG (SEQ ID NO. 80);KKAVDE (SEQ ID NO. 81) LysM/3EHTYVAPVETVEVAPAAPAAATAPWP_002337891;(SEQ ID NO. 82);197 AAVAEQYVTSR (SEQ ID NO. 83);RIYVGEQLTIP (SEQ ID NO. 84);GRYQLDASYLNGD (SEQ ID NO. 85);LSKISQK (SEQ ID NO. 86) Dala/4STVPVVLKSPVKVWVR (SEQ ID NO. 87);WP_016922432;SITKIIGLYIVLDQV (SEQ ID NO. 88);435 AAAGACFVGT (SEQ ID NO. 89); IITVVLNA (SEQ ID NO. 90);AQDVAIVARHLILDFPEILDVSST(SEQ ID NO. 91);NLSVTPDLSNVPLH (SEQ ID NO. 92);ASMVALAEK (SEQ ID NO. 93);KVNAKAAFAVDAQ (SEQ ID NO. 94);KVSISD (SEQ ID NO. 95);PGFVNYK (SEQ ID NO. 96);VKELFDSAIIQSA (SEQ ID NO. 97);MDYCYD (SEQ ID NO. 98);KANIFVIGWR (SEQ ID NO. 99);QSPVEM (SEQ ID NO. 100);ATIVNAS (SEQ ID NO. 101);ASIPSLKTID (SEQ ID NO. 102);GKILYD (SEQ ID NO. 103);TITLAED (SEQ ID NO. 104) PpiC/5YATEYYVVKMV (SEQ ID NO. 105);WP_002291335;FEAGLKAHVDI (SEQ ID NO. 106);336 AAQSLVQRMIIYKVFNN (SEQ ID NO. 107);ENVLSAF (SEQ ID NO. 108);KSFHPEVEAQIIKLS (SEQ ID NO. 109);TITVSDF (SEQ ID NO. 110);TTKVIGE (SEQ ID NO. 111);DKQVDAE (SEQ ID NO. 112);PAEVKEAAFKL (SEQ ID NO. 113);ESQLEAA (SEQ ID NO. 114);KDQLKDI (SEQ ID NO. 115);SKLAKD (SEQ ID NO. 116); Enol/6ANAILGVSIAVARAAADYLEVPLYHYLGYP_005355275;(SEQ ID NO. 117);432 AAGVYVLAD (SEQ ID NO. 118);YTAVVSHR (SEQ ID NO. 119);EVFHALASILKAR (SEQ ID NO. 120);YEELVSKYPIISIE (SEQ ID NO. 121);KAGYVPGKDVVLAMD (SEQ ID NO. 122);ITDVYAREI (SEQ ID NO. 123);LTDVLGDKVQLVGDDLFVTNT(SEQ ID NO. 124); SDIAVATN (SEQ ID NO. 125);EVEVYTE (SEQ ID NO. 126);NSILIKVNQI (SEQ ID NO. 127);AEAIIGYDV (SEQ ID NO. 128);FEVIIEAI (SEQ ID NO. 129);LGEVAEYKGLKSFY (SEQ ID NO. 130);TKVLPT (SEQ ID NO. 131);YNQLLRIE (SEQ ID NO. 132);TKAVDNV (SEQ ID NO. 133);IMPVGAP (SEQ ID NO. 134);YEAVEL (SEQ ID NO. 135) SCP/7GGHLVYRLYNK (SEQ ID NO. 136);WP_002353118;YNQVHQINLLCNN (SEQ ID NO. 137);685 AAQDLLESLGCYGA (SEQ ID NO. 138);KELQVSFSHY (SEQ ID NO. 139);ILGLGHNFVVDSA (SEQ ID NO. 140);GDSVTLTAPSIQGYVLDDR (SEQ ID NO. 141);IYRLFLPGVKSGSHHYTA (SEQ ID NO. 142);TGLYIDDL (SEQ ID NO. 143);VNILKEQIVNVT (SEQ ID NO. 144);NVTVNHV (SEQ ID NO. 145);LEALYTSV (SEQ ID NO. 146);VDNVFISANP (SEQ ID NO. 147);KKPVPTV (SEQ ID NO. 148);LQALYNRV (SEQ ID NO. 149);DHLVKI (SEQ ID NO. 150);NAVLSS (SEQ ID NO. 151);NYFLCRN (SEQ ID NO. 152);NDIVQQAADI (SEQ ID NO. 153);SQAQVN (SEQ ID NO. 154);GQVIATDQAKVTSG (SEQ ID NO. 155);EYTVTIN (SEQ ID NO. 156);NANLLYNNQ (SEQ ID NO. 157); TALSNAKKVLDDS (SEQ ID NO. 158);TFKYKKI (SEQ ID NO. 159);KPKVNKS (SEQ ID NO. 160);DAAFKGLQHK (SEQ ID NO. 161);QNGVAPM (SEQ ID NO. 162);QKQVDS (SEQ ID NO. 163);AKKVLND (SEQ ID NO. 164);RDHHYTA (SEQ ID NO. 165);KAKAFK (SEQ ID NO. 166);DSAYKGL (SEQ ID NO. 167) Adlip/8KLKVVVTNSILAD (SEQ ID NO. 10);KIDLHSIVPIGK (SEQ ID NO. 11);TTKVPSLFVESS (SEQ ID NO. 12);GIDVIYLEG (SEQ ID NO. 13);IVTSEGCFKYFSKAYNVPSAYIW(SEQ ID NO. 14);QIKHLVEKL (SEQ ID NO. 15);ADLIFYNGV (SEQ ID NO. 16);IPIYSTI (SEQ ID NO. 17);TKLVKN (SEQ ID NO. 18);YEPLPEDV (SEQ ID NO. 19);GIIYAK (SEQ ID NO. 20);YIEKLDSL (SEQ ID NO. 21) PSB/9QSVYPLLKDG (SEQ ID NO. 22);DADVFVYH (SEQ ID NO. 23);IKDQLVKLYPKKAKVFE (SEQ ID NO. 24);HQYTYKYVGYKILN (SEQ ID NO. 25);KSFVTQHAAFGYLALDYGLKQVPIAGL(SEQ ID NO. 26);NVDLMVPAGS (SEQ ID NO. 27);KLEVLNPLESL (SEQ ID NO. 28);GEEVVPEK (SEQ ID NO. 29);LEIVTTFYPMY (SEQ ID NO. 30);FYPASLSKHE (SEQ ID NO. 31);IDFVVNGE (SEQ ID NO. 32);FKYIQFSDHGIAPSKAEHFHIFF(SEQ ID NO. 33);LAELKEY (SEQ ID NO. 34);GPNVVEG (SEQ ID NO. 35);HTWVSPK (SEQ ID NO. 36);LDEVFDYK (SEQ ID NO. 37);MILLPG (SEQ ID NO. 38);NYIYFE (SEQ ID NO. 39);YLTKLKRLD (SEQ ID NO. 40)
Another aspect of the invention thus relates to the polypeptides of the invention or active fragments thereof as described herein, especially for use in medicine, and in particular for use in the prevention and/or treatment of bacterial infection, such as infection by Enterococci.
In a preferred embodiment the polypeptide according to the present invention (according to any of SEQ ID NO: 1 to 9) or the contiguous fragment thereof is used as conjugate, whereby the antigen is covalently bound to an immunocarrier. Such immunocarrier may be a polypeptide or a protein or a carbohydrate-containing molecule (such as for example a capsular polysaccharide or glycoconjugate) which improves the interaction between T- and B-cells for the induction of an immune response against the antigen. This may be preferred for vaccines intended for use in patients with reduced activity of the immune system. Since infections of Enterococci are frequently a problem in hospitals and nursing homes such conjugates are particularly preferred for such patients. Suitable immunocarriers according to the present invention comprise tetanus toxoid, diphtheria toxoid, Pseudomonas aeruginosa toxin A or its derivatives thereof. Carbohydrate-containing molecules such as capsular polysaccharides or teichoic acids may also serve as conjugation partner for the above-mentioned polypeptide or fragments thereof. In an especially preferred embodiment such fragments of the immunocarrier are used which stimulate the immune response in the patient to be treated without having, however, the undesired side effect which such proteins may elicit when used in an unmodified form.
The covalent bond between the antigen and the immunocarrier can be provided by a direct chemical bond or by a spacer. Sometimes short molecules having two reactive groups on both ends are reacted with the antigen and the immunocarrier in order to produce a covalently linked molecule.
In an alternative the molecule(s), preferably used as vaccine (antigen and immuno carrier), can be produced recombinantly wherein suitable gene fragments are linked together and inserted into an appropriate vector. The vector is introduced in a suitable host cell and the host cell (e.g. E. coli, bacillus, yeast, or insect cells) produces the polypeptide or fragment thereof as defined above together with the immunocarrier as one molecule.
The polypeptides or fragments thereof either alone or coupled to an immunocarrier may be used for the treatment or the prevention of bacterial infections. Another aspect of the present invention thus is a method for the treatment or the prevention of bacterial infections, in particular of Enterococci, more preferably Enterococcus faecium based on the medicament as described herein. Said medicament preferably is a vaccine which comprises preferably also a pharmaceutically acceptable adjuvant. The adjuvant promotes the protective IgG subtype antibodies. Typical adjuvants include complete Freund's adjuvant (CFA), incomplete Freund's adjuvant (IFA), alum and other adjuvants suitable for human use (e.g. virus-like particles). Polymers like dextran sulfate have been shown to be also a potent stimulator of IgG antibodies against bacterial cell surface antigen. Other adjuvants include incomplete adjuvants; salt i.e. AlK(SO4)2, AlNa(SO4)2, AlNH4(SO4)2, solica, kaolin, carbon polynucleotide, i.e. poly IC and poly AU. Preferred adjuvants include QuilA and Alhydrogel.
An active vaccine is administered to the patient preferably before an infection occurs. Such vaccination can therefore be applied regularly to patients at risk (e.g. elderly people, patients before solid organ or bone-marrow transplants) in order to stimulate their immune response and to avoid an infection in a hospital or a nursing home.
Medicaments and/or vaccines according to the present invention contain at least one polypeptide or active fragment thereof, but can contain 2 to up to 9 full length polypeptides according to the present invention. Preferred is a vaccine comprising at least one "set" of active fragments of at least one antigen according to the present invention, wherein said set is composed of 1, 2, 3 and up to 10 active fragments of said at least one antigen according to the present invention. The vaccine may also contain a mix of active fragments derived from antigens according to the present invention, i.e. SEQ ID Nos. 1 to 9. Preferred is a composition comprising at least one of the antigens (epitopes) as listed in table 2, above.
Under specific circumstances it may, however, also be possible to apply the vaccine at early stages of the infection in order to elicit protective antibodies which inactivate the bacteria belonging to the genus Enterococcus. In a preferred embodiment the vaccine of the present invention provides protection against different Enterococcus faecium and possibly also against Enterococcus faecalis strains since there is extensive sequence homology between these species.
Antibodies induced by the protein of SEQ ID NO: 1 to 9 or suitable fragments thereof are protective and facilitate phagocytosis. Since such protective, and in particular opsonic antibodies, are preferred, it is desired to use those parts of the polypeptide of SEQ ID NO:1 to 9 which elicit antibodies having opsonic properties.
As mentioned above, still another subject of the invention is a pharmaceutical composition, especially a vaccine, comprising the protective peptide or active fragments thereof or the antibody or functional fragments thereof as defined by the invention, useful for the immunization of a subject against an infection or the treatment of a subject having an infection, wherein the infection is preferably caused by E. faecium and/or E. faecalis. This pharmaceutical formulation of a medicament to be used as a vaccine is known to the person skilled in the art, and described in the respective literature. Usually, a solution of the antigen possibly coupled to an immunocarrier is dissolved in a physiologically acceptable solution like a buffer. The solution must be stabilized in order to avoid an undesired precipitation of the immunologically active compounds. The vaccine is preferably produced in the form of a solution adapted to injection, preferably intramuscular injection. Other forms of pharmaceutical formulations like plasters or sprays are also acceptable provided the antigen comes in sufficient contact with the immune system and the formation of specific antibodies is elicited.
Alternatively, the peptide or active fragments thereof of the invention are used in a method of immunizing or treating a subject in need thereof, wherein an effective amount of the peptide or the nucleic acid of the invention is administered to the subject. The subject may be immunized in order to prevent an infection, particularly an E. faecium and/or E. faecalis infection, or may be treated to ameliorate or cure an infection, particularly an E. faecium and/or E. faecalis infection. The determination of the effective amount to be administered is within the knowledge of the skilled practitioner.
The polypeptides or fragment thereof either alone or coupled to an immunocarrier may be used for the treatment or the prevention of bacterial infections. The prevention of bacterial infection achieved by regularly application of the vaccine to patients of risk such as elderly people, infants and patients before organ or bone-marrow transplantation so antibodies had been generated though the stimulation of the immune response.
The vaccine is preferably produced in the form of a solution adapted to injection, preferably intramuscular injection. Other forms of pharmaceutical formulations like plasters or sprays are also acceptable provided the antigen comes in sufficient contact with the immune system and the formation of specific antibodies are elicited.
On the other hand, it is sometimes not possible to treat patients with an active vaccine since the immune system is severely impaired. In those circumstances the polypeptide of SEQ ID NO: 1 to 9 or fragments thereof (epitopes) as defined above can be used to produce either polyclonal antibodies or monoclonal antibodies that bind to or opsonize Enterococcus. The person skilled in the art is well aware how such antibodies can be prepared.
The inoculum for polyclonal antibody production is typically prepared by dispersing the antigen or the antigen-immunocarrier conjugate in a physiologically tolerable diluent such as saline, to form an aqueous composition. An immunostimulatory amount of the inoculum preferably with adjuvant is administered to a mammal and the inoculated mammal is then maintained for a time period sufficient for the antigen to induce protective anti-Enterococcus antibodies. After suitable periods of time, two weeks until four months, boosting doses of the antigen-immunocarrier may be applied and the antigen titer is monitored. At a suitable point, when the titer of the neutralizing or opsonic antibodies is at its peak, the antibodies are collected. Such antibodies can include antibody preparations from a variety of commonly used animals (such as mice, goats, primates, donkeys, rabbits or horses) and humans, whereby the antibodies are isolated from blood donations.
The antibodies induced in the mammal are harvested, isolated and purified to the extent desired by well-known techniques such as by alcohol fractionation and column chromatography or preferably by immuno affinity chromatography whereby the antigen is bound to a chromatographic column. The antiserum passes the column whereby specific antibodies are retained and all other components of the serum are washed out. Then the purified antibodies are eluted with suitable gradients. A further purification may be required.
Alternatively, monoclonal antibodies can be prepared according to techniques well-known to the person skilled in the art. When a suitable monoclonal antibody is obtained, the binding regions can be identified and the whole antibody molecule as well as derivatives of the antibody like antibody fragments or subfragments can be provided. The general technique to produce monoclonal antibodies is amply described in textbooks. After having made the hybridomas or having selected the monoclonal antibody from libraries or genetically engineered animals it has to be determined to which part of the polypeptide of SEQ ID NO: 1 to 9 the mAb binds. Then, it has to be checked whether the antibody is opsonic and/or protective, preferably in vivo.
According to another preferred aspect of the present invention, it would be very beneficial to provide monoclonal or polyclonal antibody therapies which target antigenic polypeptides of E. faecium and/or E. faecalis as described herein and have the potential to support a therapy of an infection or eliminate the pathogen and the disease altogether. Therefore, another subject of the invention relates to an antibody or functional active fragment thereof which binds specifically to the antigens of the invention. In a preferred embodiment the antibody is a monoclonal, polyclonal, chimeric or humanized antibody or functional active variant thereof. In another preferred embodiment the functional active fragment comprises a Fab fragment. Antibodies generated against the antigens (polypeptides), fragments or variants thereof of the present invention can be obtained by direct injection of the antigens, fragments or variants thereof into an animal or by administering the antigens, fragments or variants thereof to an animal, preferably a non-human. The antibody so obtained will then bind the antigens, fragments or variants. Such antibodies can then be used to isolate reactive antigens, fragments or variants thereof from tissue expressing those.
For the preparation of monoclonal antibodies, any technique known in the art, which provides antibodies produced by continuous cell line cultures, e.g. a hybridoma cell line, can be used. Techniques described for the production of single chain antibodies (U.S. Pat. No. 4,946,778) can be adapted to produce single chain antibodies to the antigens, fragments or variants thereof according to this invention. Also, transgenic mice or other organisms such as other mammals may be used to express humanized antibodies to antigens, fragments or variants thereof according to this invention. Still another subject of the invention relates to a hybridoma cell line which produces the antibody of the invention. Hybridoma cell lines expressing desirable monoclonal antibodies are generated by well-known conventional techniques. Similarly, desirable high titer antibodies are generated by applying known recombinant techniques to the monoclonal or polyclonal antibodies developed to these antigens (see, e.g., PCT Patent Application No. PCT/GB85/00392; British Patent Application Publication No. GB2188638A; Amit et al., Science, 233:747-753 (1986); Queen et al., Proc. Natl. Acad. Sci. USA, 86: 10029-10033 (1989); WO 90/07861; Riechmann et al., Nature, 332:323-327 (1988); Huse et al., Science, 246:1275-1281 (1988)).
The present invention also provides a method for producing an antibody according to the invention, characterized by the following steps:
(a) administering an effective amount of the peptide according to the invention to an animal; and
(b) isolating the antibody produced by the animal in response to the administration of step (a) from the animal.
Another subject of the invention relates to a method for producing an antibody according to the invention, characterized by the following steps:
(a) contacting a B cell with an effective amount of the peptide according to the invention;
(b) fusing the B cell of step (a) with a myeloma cell to obtain a hybridoma cell; and
(c) isolating the antibody produced by the cultivated hybridoma cell. More particularly, the antibody may be produced by initiating an immune response in a non-human animal by administrating a peptide of the invention to an animal, removing an antibody containing body fluid from said animal, and producing the antibody by subjecting said antibody containing body fluid to further purification steps. Alternatively, the antibody may be produced by initiating an immune response in a non-human animal by administrating an antigen, fragment or variant thereof, as defined in the present invention, to said animal, removing the spleen or spleen cells from said animal and/or producing hybridoma cells of said spleen or spleen cells, selecting and cloning hybridoma cells specific for said antigen, fragment or variant thereof and producing the antibody by cultivation of said cloned hybridoma cells.
The antibody may be used in methods for treating an infection. Accordingly, still another subject of the invention relates to a pharmaceutical composition comprising the antibody of the invention. The pharmaceutical composition may encompass further components as detailed above for the vaccine. The composition may further encompass substances increasing their capacity to stimulate T cells. These include T helper cell epitopes, lipids or liposomes or preferred modifications as described in WO 01/78767. Another way to increase the T cell stimulating capacity of epitopes is their formulation with immune stimulating substances for instance cytokines or chemokines like interleukin-2, -7, -12, -18, class I and II interferons (IFN), especially IFN-gamma, GM-CSF, TNF-alpha, flt3-ligand and others.
Medicaments according to the present invention contain at least one antibody or active fragment thereof, but can contain 2 to up to 9 antibodies according to the present invention. Preferred is a medicament comprising at least one "set" of antibodies or active fragments thereof specifically directed against at least one antigen according to the present invention, wherein said set is composed of 1, 2, 3 and up to 10 antibodies or active fragments thereof specifically directed against said at least one antigen according to the present invention. Of course, also mixtures of antibodies or active fragments thereof specifically directed against 2, 3, and up to 9 of the antigens according to the present invention can be formulated into a medicament according to the present invention.
The polypeptides according to the present invention do not show significant differences in the percentage of killing, but preferred are the polypeptides according to the present invention showing a higher or equal activity at a higher dilution, namely Adlip (SEQ ID No. 8), PBP5 (SEQ ID No. 1), and PpiC (SEQ ID No. 5) (which are thus preferred). It is expected that a lower concentration of the antigen decreases and/or reduces the risk of prospective side effects.
The present invention will now be described further in the following examples with reference to the accompanying Figures and the Sequence Listing, nevertheless, without being limited thereto. For the purposes of the present invention, all references as cited herein are incorporated by reference in their entireties.
SEQ ID NOs: 1 to 9 show the amino acid sequence of the polypeptides according to the invention derived from strain Enterococcus faecium E155, and Enterococcus faecalis. SEQ ID NOs: 10 to 167 show the amino acid sequence of preferred peptide fragments (epitopes) as active fragments derived from the polypeptides according to the invention.


A muffler for a two-stroke internal combustion engine includes an expansion chamber into which exhaust gas ejected from the exhaust port of the engine is introduced. An air-supplying device is adapted to supply outside air to the expansion chamber. The air-supplying device is actuated by taking advantage of the pressure pulsation in the crank case of the engine, and is constituted by a diaphragm pump.

1. Field of the Invention
This invention relates to a muffler for a small air-cooled two-stroke gasoline internal combustion engine which is suited for use in a portable small working machine such as a bush cutter or a chain saw. More particularly, the invention relates to an air-supplying device for a muffler in which an oxidation catalyst is accommodated in order to comply with exhaust gas regulations.
2. The Prior Art
In view of the recent increasing concerns over environmental issues, the reduction in the amounts of HC, CO, NOx, etc. in the exhaust gas discharged from an engine is now strongly required even for a small air-cooled two-stroke gasoline internal engine to be used in a portable small working machine such as a bush cutter or a chain saw. For example, according to the exhaust gas control bill in California known as CARB 1999, it is stipulated that CO should be reduced to 130 g/bhp-h or less, the total HC (THC) to 50 g/bhp-h or less, and NOx to 4 g/bhp-h or less, starting from 1999.
With a view to cope with such an exhaust gas regulation, there have been proposed various measures, such as improving the combustion chamber of internal combustion engines, modifying the shape of the suction/exhaust ports or of the scavenging port of cylinders of internal combustion engines, and providing an exhaust gas system with an exhaust gas-purifying means such as an oxidation catalyst. However, all of these attempts have failed to obtain a satisfactory result to date.
The present assignee of the present invention has already proposed, as a countermeasure to cope with the aforementioned exhaust gas regulation, a system wherein the exhaust gas discharged from the exhaust port of an engine is directly introduced into a muffler disposed in the engine body, and wherein the muffler is provided with an oxidation catalyst in a specific manner for purifying the exhaust gas. Specifically, the measures set forth in the Japanese Patent Application H7-272959 (U.S. patent application Ser. No. 08/733,299), now U.S. Pat. No. 5,722,237, are constituted such that an oxidation catalyst assembly is formed at first by superimposing a web-like oxidation catalyst on a spark arresting metal mesh having a peripheral folding portion to obtain a laminate. The peripheral folding portion of the metal mesh is then turned around the entire or most of the periphery of the laminate, thereby providing a U-shaped or V-shaped oxidation catalyst assembly, which is then disposed within the muffler (Prior Art No. 1). The measures set forth in the Japanese Patent Application H7-343092 are constituted such that an oxidation catalyst comprising an air-permeable metallic foamed body is disposed in an exhaust gas inlet portion of the muffler (Prior Art No. 2).
According to the muffler incorporated therein with an oxidation catalyst as proposed by the Prior Art No. 1 and 2, the structure of the muffler itself, the shape of the oxidation catalyst, and the layout of the catalyst are not yet optimized to sufficiently enhance the exhaust gas purifying property of the catalyst. Further, measures for improving the mounting property, assembling property and design freedom of the muffler in relation to the engine are not taken into account. Moreover, special consideration is not given to the problem resulting from the increase in temperature of the exhaust gas due to the reaction thereof with the oxidation catalyst (oxidative combustion).
Under the circumstances, the present applicant has proposed an improved muffler for a small air-cooled two-stroke gasoline internal combustion engine as set forth in the Japanese Patent Application H8-84260 and the Japanese Patent Application H8-84324 (U.S. patent application Ser. No. 08/773,978, now U.S. Pat. No. 5,738,184, which take into account the aforementioned problems. Namely, this improved muffler is provided with an expansion chamber to which an exhaust gas ejected from the exhaust port of an engine is introduced. The expansion chamber is perpendicularly separated by means of a partition plate into a first expansion chamber and a second expansion chamber. This partition plate is provided with an oxidation catalyst, which is composed of a metallic foamed body having gas-permeability. Accordingly, an exhaust gas is initially introduced into the first expansion chamber and then passed via the oxidation catalyst to the second expansion chamber. In the case of the Japanese Patent Application H8-84324 in particular, an outside air intake means is mounted near the exhaust gas inlet portion of the first expansion chamber. This outer air intake means is designed to introduce outside air into the expansion chamber by taking advantage of the jet flow of the exhaust gas into the expansion chamber.
Although this modified muffler is designed to introduce the outside air by taking advantage of the jet flow of the exhaust gas, it is difficult to introduce a sufficient quantity of air to sufficiently reduce the CO component even with the force of the jet flow of the exhaust gas. Namely, if the CO component in the exhaust gas is to be minimized, the CO component is required to be reacted with the O.sub.2 in the air so as to generate CO.sub.2. However, if the quantity of air introduced into the muffler by taking advantage of the jet flow of the exhaust gas is not sufficient, the quantity of O.sub.2 available for the reaction will also be insufficient, so that the reaction of CO to produce CO.sub.2 is limited, thus making it difficult to sufficiently reduce the CO component.
On the other hand, in the case of four-stroke engines employed in a motor car or a motor bicycle, there has been proposed to employ an air pump which is actuated by means of power for feeding outside air to the muffler. However, since the air pump itself is relatively expensive and heavy, requiring a special driving device, it is not suited for use with a muffler for a small air-cooled two-stroke gasoline internal combustion engine which is suited for use in portable small working machines.


The subject invention provides a unique system and method that facilitates creating a summary page of content associated with disparate sources of data. For example, a user can select one or more regions of one or more disparate web pages for which he/she desires updated information over a length of time. The selected regions can be identified and then marked for monitoring via a web crawler. The web crawler can analyze the relevant web pages, and in particular, only the selected regions to determine if any of the corresponding content have changed. Changes to other non-selected content can be ignored. The desired changes can be extracted and included on the summary page to mitigate the number of times a user must revisit individual web pages to see what if any changes have occurred since the previous visit.

In the past several years, the Internet or World Wide Web ("the web") has become a relatively common source of various types of news, information, and entertainment. For many users, the Internet is frequently searched and referenced as a research tool; while for others, the Internet operates more as a link to the unreachable—whether it is a product or service—that is perhaps only available to the user via the Internet.
Admittedly, Internet users can spend hours browsing through pages and pages on the web. Unfortunately though, much of that time may be undesirably consumed by revisiting particular web pages to see if any content on the page has changed. This is because traditional browsing systems include a history display that may remind the user of the web pages that he/she has visited within a given period of time. However, no other useful information can be obtained or extracted. Newer systems employ techniques to modify visualizations of the respective hyperlinks to inform the user that the content on the hyperlink has changed in some way. These systems may have their own limitations as well. Although such techniques can assist the user in determining which pages to revisit, they still require the user to click on the hyperlink to see or obtain the changes.

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The present invention is to provide a method of producing multilayer laminates comprising a polyamide and a fluorine-containing ethylenic polymer laminated together and being excellent in interlayer adhesion strength by multilayer coextrusion in an easy and simple manner without need of any additional step or without being limited to some or other particular adhesive material.

Multilayer laminates formed by laminating a polyamide and a fluorine-containing resin are expected as composite materials having polyamide characteristics, such as high strength, high toughness, light weight, good processability and in particular, flexibility, as well as fluorine-containing resin characteristics, such as heat resistance, oil and chemical resistance, and low liquid agent permeability.
The successive lamination method and simultaneous lamination method are known for producing such multilayer laminates. Among them, the simultaneous lamination method, especially coextrusion method holds an important position because of its merit lying in that the number of steps required for obtaining the laminate can be lowered. The simultaneous multilayer coextrusion method is applied to multilayer molding or multilayer film formation using two or more extruders and, currently, films, sheets, extruded molded articles called profiles, pipes, hoses, tubes and other moldings varied in shape or form are being produced by the method. The method is applicable to various thermoplastic resins, such as polyamides, as well as to fluorine-containing resins.
However, fluorine-containing resins are characterized in that they are low in intermolecular cohesive force and very low in surface free energy because of the low polarizability of fluorine-containing molecules. Therefore, they can hardly be wet against solids higher in intermolecular cohesive force, hence they show low adhesive properties against most of other substances. They, as resins, are thus characteristically poor in adhesion properties and their interlayer adhesiveness with polyamides is low; it is therefore necessary to contrive to increase the interlayer adhesion strength. For example, methods are known which comprise subjecting the surface of the fluorine-containing resin to surface treatment such as corona discharge treatment or irradiation treatment. Japanese Kokai Publication Hei-05-8353, for instance, proposes a method of producing multilayer tubes comprising a polyamide resin as an outer layer and a fluorine-containing resin as an inner layer by irradiating the tubes to introduce intermolecular crosslinking structures among molecules in both layers and thereby secure the adhesion strength between the polyamide resin layer and the fluorine-containing resin layer. However, the method cannot be applied to the simultaneous lamination technique including coextrusion.
Also available is a technology according to which a polymer blend comprising a fluorine-containing resin is used for the resin layer to be adhered to a polyamide. As a production method using this technology, Japanese Kokai Publication Hei-07-53823 discloses a method of producing multilayer tubes comprising an outer layer comprising a polyamide and an inner layer comprising a fluorine-containing resin in which a resin composition comprising both a specific polyamide and a fluorine-containing resin is laminated to a polyamide layer so that it may serve as an adhesive layer with the inner layer. In this production method, however, the morphology of the adhesive layer changes according to the molding conditions due to the intrinsically poor compatibility between the constituent resins of the adhesive layer, namely the polyamide and fluorine-containing resin, and the morphology change influences on the cohesive force of the adhesive layer itself and the adhesion strength thereof with the other layers. Thus, such problems arise as a tendency toward variation in adhesion strength according to environmental factors such as molding conditions and temperature conditions during use and difficulty in securing a constant quality level. Furthermore, this technology does not intend to increase the adhesiveness of the polyamide and fluorine-containing resin themselves but merely utilizing the adhesiveness of the polymer blend. In addition, the use of such polymer blend in lieu of the fluorine-containing resin results in an impairment in those excellent characteristics of the fluorine-containing resin.
To solve this problem, attempts have been made to improve the fluorine-containing resin itself, and various fluorine-containing resin materials have been proposed. For example, in the WO 99/45044 pamphlet, there is disclosed a method of multilayer simultaneous extrusion of laminates which comprises polyamide 12 (nylon 12) as an outer layer and a fluorine-containing ethylenic polymer having carbonyl groups, such as carbonate groups and/or carbonyl halide groups, as an inner layer fluorine-containing resin to be laminated to the outer layer. In this method, the die temperature is set at 260° C., and an interlayer adhesion strength of ten and several of N/cm and a good appearance can be obtained. However, such a level of adhesion strength is not fully sufficient in some fields of application.
Thus, in the art, the efforts to develop production technologies of improving the performance characteristics of multilayer laminates comprising a polyamide and a fluorine-containing resin, in particular a fluorine-containing ethylenic polymer, can be said to have been principally directed to two aspects, namely investigations concerning the method of physical treatment of the adhesive surface and contrivances for adhesive materials, as mentioned above. There is no production method known, however, for attaining sufficiently high interlayer adhesion strength without requiring an additional step or steps and without being restricted to a specific adhesive material, in particular for attaining high productivity by applying the simultaneous multilayer coextrusion technique.

Process for producing multilayered product

Abstract: The present invention is a production method of a multilayer laminate which comprises laminating at least a polyamide (A) and a fluorine-containing ethylenic polymer (B) by simultaneous multilayer coextrusion using a coextrusion apparatus to obtain the laminate comprising said polyamide (A) and said fluorine-containing ethylenic polymer (B), said coextrusion apparatus comprising a die and a plurality of extruders for feeding resins to said die, and the temperature of said die being set within the range exceeding 260° C. but not higher than 310° C.


Methods and apparatus for merging critical sections are disclosed. An example disclosed system estimates the cost of merging a first critical section and a second critical section using a dataflow analysis on the first and second critical sections. In the example system, the first critical section and the second critical section are merged based on a least expensive cost of merging critical sections.

In a shared address space architecture, all parts of memory are accessible to all threads, processes, and/or processors. As a result, shared address space programming paradigms concentrate on methods for expressing concurrency and synchronization of data accesses. A significant aspect of creating correctly threaded programs involves synchronizing data accesses between concurrent threads and/or processes.
Most compilers provide explicit support for critical sections (e.g., a section of program instructions that must be executed atomically (i.e., as a whole) such as, for example, accessing a shared address space) using mutual exclusion locks (e.g., mutexes). A virtual mutex is a data structure within a program that is used to control access to shared data. Virtual mutexes are managed (e.g., locked, unlocked, etc.) using software instructions embedded within a program. During program execution, a thread must lock a virtual mutex before the thread can access shared data protected by the virtual mutex. If the virtual mutex is locked by a different thread, the thread is blocked from accessing the shared data and must wait for the virtual mutex to be unlocked before the thread can lock the mutex and enter the critical section. The virtual mutex must be unlocked when a thread leaves the critical section to enable other threads to access the shared data. As a result, critical sections have a serialization effect on threads that access the same shared data.
Parallel multi-threaded architectures provide resources to implement physical mutexes. Physical mutexes function in the same manner as virtual mutexes but are associated with hardware to implement the synchronization of data accesses rather than using a software data structure. For example, the Intel® Internet Exchange Architecture (IXA) family of network processors provides 15 signals for synchronizing of data accesses within one microengine (e.g., a form of microprocessor in the Intel® IXA family of network processors) and/or between two different microengines. These 15 signals may be used as physical mutexes.
A compiler that is configured to generate programs for these parallel multi-threaded processors must be configured to allocate these physical mutexes to the virtual mutexes used in the program. Due to the limited number of physical mutexes and potentially larger number of virtual mutexes used in the program, the compiler may attempt to merge critical sections until the number of physical mutexes equals the number of critical sections. However, it is important to minimize the size of the merged critical sections to prevent significant performance degradation.