The present invention provides novel benzimidazole derivatives or salts thereof represented by the general formula, ##STR1## wherein R.sup.1 is a hydrogen atom or a halogen atom; R.sup.2 is a phenyl-lower alkyl group; R.sup.3 is a heterocyclic group selected from the group consisting of an indolyl group, indolinyl group, 1H-indazolyl group, 2(1H)-quinolinonyl group, 3,4-dihydro-2(1H)-quinolinonyl group and 1,4-benzoxazinyl group; A is a lower alkylene group; n is 0 or 1.. The benzimidazole derivatives or salts of the present invention are effective agents for treating various arteriosclerotic diseases.

Proliferation of the smooth muscle cells of the blood vessel induces hypertrophy of the intima of the blood vessel and, from a long-term view point, it causes, arteriosclelerotic diseases such as myocardial infarction, cerebral infarction and the like. Moreover, from a short-term view point, it induces reobstruction of the blood vessel after treatments of percutaneous transluminal coronary angioplasty (PTCA), stent and/or aterectomy. In consideration of the present situation, the therapeutic effects of conventional medicines used therefor are thought of as within certain limits, because they are classified as agents of indirectly effective for curing the diseases induced by the promotion factors of hypertrophy of the interim, for example hyperlipidemia, hypertension and the like. Therefore, development of essentially effective medicines therefor have been eagerly expected.
Generally, it is known that proliferation of the smooth muscle cells is related to the influence of cyclic guanosine 3',5'-monophosphate (cGMP). In this connection, pharmaceutical preparations of nitro group-containing compound known as coronary vasodilators activate the enzymatic activity of guanylate cyclase, and accentuate the production of cGMP, and also inhibit the proliferation of the cells. However, the pharmaceutical preparations of nitro group-containing compound are scarecely used for treatment of arteriosclerotic diseases which need to be administered for a long period of time, because the effect of the pharmaceutical preparations of nitro group-containing compound can be sustained only for a quite short time, and when they are administered repeatedly, then the tolerance against said pharmaceutical preparations may be occurred. On the other hand, in recent years, there have been reported several pharmaceutical preparations which can increase the concentration of cGMP by inhibiting the enzymatic activity of the enzyme [i.e., cGMP-PDE (cGMP-phosphodiesterase)] for decomposition of cGMP. However, there have not been suggested the activity for inhibiting proliferation of the smooth muscle cells performed by pharmaceutical preparations. The guanine derivative which was reported recently in an academic conference (IBC's International Conference on RESTENOSIS, 1994, U. S. A.) is the only known compound having both effects for inhibiting the enzymatic activity of cGMP-PDE and for inhibiting proliferation of the smooth muscle cells.
In consideration of the present status of such pharmacotherapy, and referring to the fact that cGMP relates to proliferation of the smooth muscle cells of the blood vessel, the present inventors have made an extensive research work regarding pharmaceutical preparations having the activity for inhibiting proliferation of the smooth muscle cells of the blood vessel which acts directly to the cells thereof, and can be used as the essential agent for treating arteriosclerotic diseases.
As the results, the present inventors have found the fact that the objective compounds, having the activity for inhibiting proliferation of the smooth muscle cells of the blood vessel, are existed among benzimidazole derivatives having property for inhibiting the enzymatic activity of cGMP PDE, thus the present invention has been completed.
Related art references which disclose compounds having chemical structural formulas similar to those disclose in the present invention are JP-A-2-306916, U.S. Pat. No. 4,886,803, U.S. Pat. No. 4,551,421, JP-A-62-246546, JP-A-4-346974, JP-A-61-167952, U.S. Pat. No. 4,994,477, U.S. Pat. No. 5,098,924, EP-A1-0560407, EP-A1-0407217, JP-A-64-65551, JP-A-1-96645, and JP-A-7-133224, however, those references neither disclose nor suggest benzimidazole derivatives of the present invention, and do not touch on inhibition of the enzymatic activity of cGMP PDE at all which benzimidazole derivatives of the present invention possess.
Furthermore, references JP-A-5-222000, WO-A-93-07124, and WO-A-94-22855 disclose structural similar compounds having inhibition of the enzymatic activity of cGMP PDE, however, those references neither disclose nor suggest benzimidazole derivatives of the present invention.


Ball grid array packages that can be stacked to form highly dense components and the method for stacking ball grid arrays are disclosed. The ball grid array packages comprise flexible or rigid substrates. The ball grid array packages additionally comprise an arrangement for the substantial matching of impedance for the circuits connected to the semiconductor devices.

1. Field of the Invention
The present invention relates to ball grid array packages that can be stacked to form highly dense components and the method for stacking ball grid arrays. The ball grid array packages may be stacked on flexible or rigid substrates.
2. State of the Art
Chip-on-board technology generally consists of three types of techniques for attaching a semiconductor device to a printed circuit board, such as flip-chip attachment, wire bonding, and tape automated bonding techniques.
Flip-chip attachment consists of attaching a semiconductor device, generally having a ball grid array (BGA), a slightly larger than integrated circuit carrier (SLICC), or a pin grid array (PGA) to a printed circuit board. With the BGA or SLICC, the solder ball arrangement on the semiconductor device must be a mirror-image of the connecting bond pads on the printed circuit board such that precise connections are made. The semiconductor device is bonded to the printed circuit board by refluxing the solder balls. With the PGA, the pin arrangement of the semiconductor device must be a mirror-image of the pin recesses on the printed circuit board. After insertion, the semiconductor device is generally bonded by soldering the pins into place. An underfill encapsulant is generally disposed between the semiconductor device and the printed circuit board to prevent contamination. A variation of the pin-in-recess PGA is a J-lead PGA, wherein the loops of the J-leads are soldered to pads on the surface of the circuit board. However, the lead and pad locations must coincide, as with the other types of flip-chip techniques.
Wire bonding and tape automated bonding (TAB) attachment generally begin with attaching a semiconductor device to the surface of a printed circuit board with an appropriate adhesive. In wire bonding, a plurality of bond wires is attached, one at a time, from each bond pad of the semiconductor device to a corresponding lead on the printed circuit board. The bond wires are generally attached through one of three industry-standard wire bonding techniques, such as ultrasonic bonding—using a combination of pressure and ultrasonic vibration bursts to form a metallurgical cold weld, thermocompression bonding—using a combination of pressure and elevated temperature to form a weld, and thermosonic bonding—using a combination of pressure, elevated temperature, and ultrasonic vibration bursts. The semiconductor device may be oriented having either the active surface up or the active surface down (with the bond pads thereon either up or down with respect to the printed circuit board) for wire bonding, although active surface up is the most common. With TAB, metal tape leads are attached between the bond pads on the semiconductor device and the leads on the printed circuit board. An encapsulant is generally used to cover the bond wires and metal tape leads to prevent contamination.
Although such methods are effective for bonding semiconductor devices to printed circuit boards, the terminal arrangements of the devices and the connection arrangements of the boards must be designed to accommodate one another. Thus, it may be impossible to electrically connect a particular semiconductor device to a printed circuit board for which the semiconductor device terminal arrangements were not designed to match the board's connection arrangement. With either wire bond or TAB attachment, the semiconductor device bond pad arrangement may not correspond to the lead ends on the circuit board, making attachment difficult due to the need for overlong wires and the potential for inter-wire contact and shorting. With flip-chip attachment, if the printed circuit board connection arrangement is not a mirror-image of the solder ball or pin arrangement of the semiconductor device, electrically connecting the flip-chip to the printed circuit board is impossible.
Ball grid array (BGA) semiconductor device packages are well known in the art. A BGA package typically comprises a substrate, such as a printed circuit board, with a semiconductor device, such as a dynamic random access memory device, mounted on the top side of the substrate. The semiconductor device has a plurality of bond pads on the active surface thereof electrically connected to a series of metal traces on the top surface or top side of the printed circuit board. The connection between the bond pads and the metal traces is provided by wire bonds electrically and mechanically connecting the semiconductor device and the printed circuit board. The series of metal traces on the printed circuit board is connected, in turn, to a second series of metal traces on the bottom surface or bottom side of the printed circuit board using a series of vias extending therethrough. The second series of metal traces each terminate with a connection contact pad where a conductive element is attached. The conductive elements can be solder balls or conductive filled epoxy. The conductive elements are arranged in an array pattern and the semiconductor device and wire bonds are encapsulated with a molding compound.
As semiconductor device and grid array densities increase, the desire in packaging semiconductor devices has been to reduce the overall height or profile of the semiconductor package. The use of BGAs has allowed for this reduction of profile, as well as increased package density. Density has been increased by using lead frames, such as lead-over-chip-type lead frames, in an effort to increase the semiconductor device density, as well as allow stacking of the semiconductor devices one on top another.
One example of a lead chip design in a BGA package is shown in U.S. Pat. No. 5,668,405. A semiconductor device is disclosed having a lead frame attached to the semiconductor device. Through holes are provided that allow for solder bumps to connect via the lead frame to the semiconductor device. Such a mounting arrangement requires several steps for attaching the semiconductor device to the lead frame, then providing sealing resin, and subsequently adding a base film and forming through holes in the base film. A cover resin is added before solder bumps are added in the through holes to connect to the lead frame. This particular structure lacks the ability to stack semiconductor devices one on top another.
U.S. Pat. No. 5,677,566, commonly assigned to the assignee of the present invention, illustrates a semiconductor device package that includes discrete conductive leads with electrical contact bond pads on a semiconductor device. The lead assembly is encapsulated with a typical encapsulating material and electrode bumps are formed through the encapsulating material to contact the conductive leads. The electrode bumps protrude from the encapsulating material for connection to an external circuit. The semiconductor device has the bond pads located in the center of the active surface of the device, thus allowing the conductive leads to be more readily protected once encapsulated in the encapsulating material. However, the assembly illustrated in the '566 patent lacks the ability to stack one semiconductor device on top another.
U.S. Pat. No. 5,625,221 illustrates a semiconductor device package assembly that has recessed edge portions that extend along at least one edge portion of the assembly in an attempt to form a stacked package of semiconductor devices. An upper surface lead is exposed therefrom and a top recess portion is disposed on a top surface of the assembly. A bottom recess portion is disposed on the bottom surface of the assembly such that when the assembly is used in fabricating a three-dimensional integrated circuit module, the recess edge portion accommodates leads belonging to an upper semiconductor assembly to provide electrical interconnection therebetween. However, the assembly requires long lead wires from the semiconductor chip to the outer edges. These lead wires add harmful inductance and unnecessary signal delay and can form a weak link in the electrical interconnection between the semiconductor device and the outer edges. Further, the assembly profile is a sum of the height of the semiconductor devices, the printed circuit boards to which they are bonded, the conductive elements, such as the solder balls, and the encapsulant that must cover the semiconductor devices and any wire bonds used to connect the devices to the printed circuit boards. Reducing such a package profile is difficult because of the geometries required in having the bond pads on the semiconductor device along the outer periphery with extended lead wires reaching from the semiconductor device to the outer edges.
U.S. Pat. Nos. 5,266,912 and 5,400,003 illustrate another stacked arrangement of semiconductor devices on a substrate interconnected by pins. However, the height of the stacked package is limited by the length of the pin connections between the individual multi-chip modules or printed circuit boards.
Another problem which arises in stacking semiconductor devices mounted on printed circuit boards is that it is difficult to provide a flat, smooth surface on which to mount the printed circuit board. Accordingly, flexible boards have been developed to allow both lighter-weight structures and greater adaptability at conforming to nonuniform surfaces. However, the use of such flexible circuit boards has resulted in other problems, such as the problem in joining several flexible boards while maintaining the proper interconnection between the respective boards. Further, in some applications, such as protecting semiconductor devices mounted on a bottom surface of a flexible substrate from touching the top of another flexible circuit board, the use of a rigid member or assembly is required to support the stacked flexible circuit boards. This sacrifices the flexibility that is present in the flexible circuit boards that allows their compliance with a non-planar surface.
U.S. Pat. No. 5,440,171 illustrates semiconductor devices mounted on flexible, stackable circuit boards to form semiconductor modules. A basic structure unit is illustrated comprising a flexible circuit board made from a polyamide film with circuit lines formed on both sides, typically using copper foil. A supporting frame is provided and bonded to the flexible circuit board with a heat-resistant resin, such as a polyamide resin. Electrical connections are possible between the flexible circuit board and the support frame. Conductive through holes are provided so that electrical continuity exists between a semiconductor device mounted upon the flexible circuit board and either at least one other semiconductor device mounted on another flexible circuit board stacked within the module assembly or an outside source upon which the entire basic structure unit is mounted. The semiconductor devices are electrically connected to electrodes on the support frame. Although the semiconductor device is mounted on a flexible circuit board that is stackable in an arrangement, the support frame attaching the stackable circuit boards one to another is made from a rigid material that does not allow for any bending. One type of frame material is ceramic, such as silicon nitride. Silicon nitride is used for its high thermal conductivity for heat radiation or dissipation when the semiconductor device has a high power consumption. Since the support frame is made from rigid and non-flexible material, the semiconductor device package assembly needs to be mounted on a substantially planar surface, thereby preventing the assembly from being molded on surfaces that are not uniformly planar or smooth.
Additionally, when stacking semiconductor devices using flexible or rigid substrates, as the operation speed of the semiconductor device increases it is desirable to match the impedance of the various circuits to which the semiconductor devices are connected, to try to keep the circuit response time the same for each circuit. Since in stacked arrangements the circuit length for each semiconductor device will vary, attention must be given to keeping the circuit impedance substantially the same.
Accordingly, what is needed is a ball grid array package that allows for the stacking of packages where printed circuit board substrates or flexible substrates may be used as desired and which allows for the matching of the impedance for the different circuits as required.

This patent is subject to a terminal disclaimer.


A method of minimizing car bunching at any traffic flow level allocates closely adjacent stops to a given car which is favored by a variable, readjustable distributor bonus. The estimated lost time costs of all passengers are computed for each elevator and for each hall call, these costs are reduced by a variable distributor bonus concentrating adjacent stops in one car, and a hall call is then allocated for service to that elevator which displays the lowest, reduced estimated lost time costs. In order to assure the function of this method equally at high and low traffic levels, the variable distributor bonus (Bvn) is readjusted to the traffic flow level (Va) which serves as a tracking parameter by means of a tracking function according to the relationship Bvn=Bv.F(Va) and the readjusted variable distributor bonus is defined thereby. The tracking function F(Va) is determined by one of artificial intelligence methods and expert programs. By the dependence of the distributor bonus on traffic flow, the desired small local bunching of elevator cars is an optimum for every traffic level. This method is applicable to a plurality of different allocation criteria, service requests and tracking parameters.

The invention relates generally to elevator controls and, in particular, to a method and an apparatus for preventing local bunching of elevator cars in an elevator group with variable traffic flow.
Hall calls have been allocated to the cars in a group of elevator cars by a large number of different known strategies. The strategy disclosed in the U.S. Pat. No. 4,790,412 determines the estimated time of arrival (ETA) of each elevator car for a specific hall call to be allocated. A count is computed for each car, which count represents the time estimated for the car in question to reach the call floor with the proper service direction to serve the hall call. The hall call assignment is given to the car in the elevator group having the lowest ETA count. This strategy is based on calculating the estimated time of arrival (ETA) to every hall call in the building for each elevator car and then allocating a specific hall call to the car with the lowest ETA.
The concept of car distribution in an elevator system is apparent when the constantly changing patterns of elevator traffic are considered. If the dispatching strategy keeps the elevators well distributed throughout the building, for conditions other than morning up-peak, the cars are in a better position to respond to future hall calls. To accomplish this, some group controls resort to schemes that will spot cars throughout the building when traffic flow has subsided. However, spotting is inefficient. The cars are doing no useful work as they travel to parking floors, therefore wasting energy. The unnecessary wear and tear on the cars increases the maintenance costs.
U.S. Pat. No. 4,790,412 presents a better method for minimizing the bunching of the elevator cars in an ETA dispatching strategy by incorporating a algorithm for solving the distribution problem as part of the assignment algorithm itself. This distribution algorithm improves the distribution by considering previous allocations of the cars when making new allocations.
In the allocation algorithm, the floors of the building are processed sequentially from bottom to top for upward hall calls and from top to bottom for downward hall calls. In the calculation of ETA times for the cars, consideration is given to allocations that have already been made behind the floor that is currently being processed, called the "scan-floor", which is a hall call floor at which the scan has stopped for the purpose of allocating or re-allocating a hall call. This includes stops that a car is committed to make behind the scan-floor due to a car call. If a car is already committed to stops behind the scan-floor, then this car is given a greater chance of getting the allocation for the floor of the hall call being processed by calculating a dynamic bias value Tx and subtracting this bias value from the calculated ETA of the car.
The same procedure applies when a car has an intervening stop between the "present position" and the scan-floor. The "present position" or advanced position floor (avp-floor) is the actual floor location of the car when it is stationary, or it is the floor at which the car can make a normal stop when moving. This calculated dynamic bias Tx will favor the clustering of closely adjacent stops for a given car and thus minimize car bunching. The dynamic bias Tx is inversely proportional to a predetermined travel distance of the elevator car. The predetermined travel distance may be the same regardless of whether the intervening stop is due to a car call or an allocated hall call by using the travel distance between the "present position" of the elevator car being considered for allocation and the scan-floor as shown in the following equation I where K is a selected constant: ##EQU1## The further in terms of travel distance that the scan-floor is from the avp-floor which the car is committed to make to serve its trip list, the smaller is the amount of time subtracted from the ETA of the car. Thus, if the car is a relatively long distance from the scan-floor, a bunching problem is less likely even when it has an intervening stop and the amount of bias reflects this by becoming insignificant.
As an alternative, the predetermined travel distance may depend on whether the intervening stop is due to an allocated hall call or due to a car call. An allocated hall call may be re-allocated, especially if the car is a relatively long way from the hall call floor. Thus, when the intervening stop is due to a hall call, the travel distance from the avp-floor to the scan-floor is used. However, if the intervening stop is due to a car call, which is a stop that the car will have to make, the bias in favor of giving the hall call allocation to the presently considered car may be increased by making the predetermined distance equal to the travel distance from the car call floor to the scan-floor.
The dynamic biasing according to the method shown in the U.S. Pat. No. 4,790,412 prevents a bunching of cars by clustering closely adjacent stops for a given car thereby maintaining a better car distribution throughout the building without placing "dummy" calls for parking floors. Due to this dynamic biasing, the chances are that the cars will already be suitably spaced one from the other as the cars become idle.
Although such a hall call allocation, which allocates closely adjacent stops to a single car, substantially reduces the local bunching of elevator cars, it does however entail a serious disadvantage. As can be seen from the equation I, the amount of biasing Tx is not sensitive to traffic flow levels. The same amount of bias is calculated regardless of the number of calls in the system, i.e. the measure against the local bunching of elevator cars is not re-adjusted to follow the traffic flow level. Although an assignment based on this strategy achieves good distributions with moderate traffic, it often leads to a poor distribution of elevators throughout the building at higher traffic levels. As the traffic flow increases, the elevators start bunching and rely on the randomness of the traffic patterns and the lowering of the traffic flow level to unbunch the cars. During times of high traffic flow level, the result is poor service and an increase in the average waiting time that a passenger has to wait for service. The average waiting time is an industry standard for the measuring of the efficiency of an elevator system.

Method and apparatus for preventing local bunching of cars in an elevator group with variable traffic flow


Heat-sealing polypropylene films having specific characteristics, and being well-balanced between a tensile modulus and a heat seal temperature, less tacky, and excellent in processability, transparency and impact resistance, as well as being excellent in resistance to whitening due to peeling, softness and impact resistance. A multilayered heat-sealing polyolefin resin laminate having at least one outermost layer produced from the above heat-sealing propylene polymers exhibits excellent low-temperature heat sealability and sufficient interlaminar strength without the use of an adhesive. The heat-sealing propylene polymers are produced by polymerizing propylene or polymerizing propylene with ethylene and/or C4-C20 α-olefin in the presence of a polymerization catalyst containing a transition metal compound represented by the following formula (I):

Vinyl chloride resins are widely used as soft resin. However, it is known that the vinyl chloride resins generate harmful substances upon burning. For this reason, it has been strongly required to develop a substitute resin. Recently, there have been used, as a substitute resin, olefin polymers produced by using a metallocene catalyst. Example of these olefin polymers include a copolymer of ethylene and α-olefin. However, such a copolymer poses a problem that it becomes too tacky when softened. Further, shaped articles, such as film, produced from the copolymer have poor surface properties because of deteriorated transparency, rigidity and low-temperature heat sealability, thereby rendering it unsatisfactory. The copolymer is also poor in processability.
Crystalline propylene polymer films are widely used as a packaging film owing to their excellent rigidity, transparency and moisture resistance. The crystalline propylene polymer films may be used alone as monolayered films, or in combination with films of ethylene-vinyl acetate copolymer, linear polyethylene or the like as multilayered laminate films. For their use, the packaging films are often processed into bags, regardless of whether the films are monolayered or multilayered. A series of processes for forming a film into a bag and closing the opening of the bag after putting contents therein is generally carried out by pressing the film edges with a heated rod and melt-welding the edges to each other (so called "heat sealing"). Recently, it has been required to speed up the bag-forming and packaging processes for increased productivity, which results in great demands for materials with good heat sealability. Also, it has been required for the film to inevitably have slipping and anti-blocking properties so that the above fabrication process can be efficiently made.
However, films of propylene homopolymers are defective in that, when heat sealed, the films need to be pressed at high temperature for a long time. To overcome such a drawback, there has been commonly used a technique of copolymerizing propylene with ethylene, 1-butene or any other α-olefin. However, in the conventional technique, it is necessary to copolymerize propylene with a large amount of comonomer including ethylene, 1-butene or other α-olefin so as to obtain copolymers having satisfactory heat sealability. Further, these comonomers often remain dominantly in the low-molecular fractions to form a tacky low-crystalline component that makes the copolymers tacky (such a component is hereinafter referred to as "tacky component"). As a result, films of the copolymers fails to show a good rigidity that is intrinsic to polypropylene films, and tend to cause blocking between films, thereby impeding the fabrication process. In addition, the whitening of films due to bleeding occurs to deteriorate the appearance of films. For these reasons, the copolymers are not applicable to practical use. Heretofore, it has been attempted to remove the tacky component by dissolving them in an inert solvent. It is however difficult to wash out the tacky component efficiently while preventing the low-temperature melting component that contribute to heat sealability from being lost by the washing, this making the washing method unsatisfactory for industrial use.
Recently, the film forming process has come to be conduced by using a large film forming machine to speed up the process for increased productivity, this changing the film-forming conditions. The quality of films needs to be maintained regardless the change in the film-forming conditions. On the other hand, there is a problem that multilayered laminates fails to show sufficient interlaminar strength when produced without using an adhesive and the like. It is therefore necessary to adhere films by using an adhesive in order to impart excellent properties of low-temperature heat sealability, rigidity, transparency, moisture resistance and the like to the multilayered laminates.
Thus, a first object of the present invention is to provide a polypropylene film that is less tacky, well-balanced between a tensile modulus and a heat seal temperature, and excellent in processability, transparency and impact resistance. A second object of the present invention is to provide a polypropylene film that is less tacky and excellent in resistance to whitening due to peeling, softness and impact resistance. A third object of the present invention is to provide a multilayered polyolefin resin laminate having an excellent low-temperature heat sealability and exhibiting a sufficient interlaminar strength without using an adhesive or the like.

Polypropylene films and multilayered laminate

Abstract: wherein A1, A2, E1, E2, M, X, Y, q and r are as defined in the specification.


When operational information from a key pad 13 is received from the transmission section 18 of a mobile telephone 11, the microprocessor 17 of a smart card 12 specifies a character or a character string corresponding to operational information of the key pad 13.

The present invention relates to a communication device which facilitates the input of characters, for example, when recording a telephone number in a communication terminal (mobile information terminal, a fixed line telephone or a mobile telephone).
FIG. 1 shows a conventional communication device. In the figure, reference numeral 1 denotes a mobile telephone which is the communication terminal of a communication device, 2 is an operation key which inputs characters or telephone numbers, 3 is a display which displays operational information of the operation key.
The operational of the invention will be described below.
First, when a telephone call is made using a mobile telephone 1, the operation of pushing in sequence those operation keys 2 that correspond to the desired telephone number is performed. However when the telephone number of a specified person is recorded in the mobile telephone 1, for example, in addition to inputting telephone numbers, it is necessary to input the characters of the name or of the specified person.
Although the types of characters which can be input differ. depending on the type of mobile telephone, generally it is possible to input Roman script, and the Japanese syllabary scripts of hiragana and katakana. (Some types of device allow the input of Chinese characters).
However as only somewhat more than ten operation keys 2 are provided on the mobile telephone 1 (in the example shown in FIG. 1, 12 keys are provided), each alphabet character is not assigned to keys 2 independently.
Thus generally a complicated method of inputting characters is involved.
Two general types of character input will now be described.
1. First Operational Method
For example, when inputting Roman script characters via operation keys 2, numeral keys on which corresponding alphabet characters are labeled are pushed the number of times corresponding to their labeled position.
Specifically, in order to input the letter xe2x80x9cAxe2x80x9d, the numeral key xe2x80x9c2xe2x80x9d is pushed once.
In order to input the letter xe2x80x9cBxe2x80x9d, the numeral key xe2x80x9c2xe2x80x9d is pushed twice.
In order to input the letter xe2x80x9cCxe2x80x9d, the numeral key xe2x80x9c2xe2x80x9d is pushed three times.
In order to input the letter xe2x80x9cKxe2x80x9d, the numeral key xe2x80x9c5xe2x80x9d is pushed twice.
2. Second Operational Method
For example, when inputting Roman script characters via operation keys 2, numeral keys on which corresponding alphabet characters are labeled are firstly pushed, and then the letter is input by depressing the numeral key corresponding to the letter""s labeled position.
Specifically, in order to input the letter xe2x80x9cAxe2x80x9d, the numeral; key xe2x80x9c2xe2x80x9d is pushed and then the numeral key xe2x80x9c1xe2x80x9d is depressed.
In order to input the letter xe2x80x9cBxe2x80x9d, the numeral key xe2x80x9c2xe2x80x9d is pushed and then the numeral key xe2x80x9c2xe2x80x9d is depressed.
In order to input the letter xe2x80x9cCxe2x80x9d, the numeral key xe2x80x9c2xe2x80x9d is pushed and then the numeral key xe2x80x9c3xe2x80x9d is depressed.
In order to input the letter xe2x80x9cKxe2x80x9d, the numeral key xe2x80x9c5xe2x80x9d is pushed and then the numeral key xe2x80x9c2xe2x80x9d is depressed.
The method of inputting Chinese characters will not be specifically described however it is noted that it is considerably more complicated than the method of inputting Roman characters.
Since a conventional communication device is constructed as above, although the operation keys 2 can be operated according to the operational method determined for a mobile telephone to input desired characters, the method of inputting characters is complicated. Furthermore the method of inputting characters changes with the type of mobile telephone. Therefore, for example, if a user purchases a new mobile telephone 1, it will be necessary for the user to master a new method of inputting characters for the new mobile telephone 1 when recording telephones numbers and the like. Thus the problem has arisen that user-friendly characteristics with respect to character input have not been developed.
The present invention is proposed to solve the above problem and has as its object the provision of a communication device which can input characters according to a common operational method even when the type of mobile telephone differs.
The communication device of the present invention is provided with a smart card which specifies a character or a string of characters which correspond to operational information on receipt of operational information from a transmission means of a communication terminal and which transmits that character or character string to the communication terminal.
In such a way, it is possible to input characters by a common operational method even when the type of communication terminal is different.
The communication device of the present invention is provided with a presentation means which presents operational information of the operation keys and presents a character or character string transmitted from the smart card.
In this way, the operational efficiency of the operation keys may be improved.
The communication device of the present invention is provided with a designating means which designates a desired character or character string when a plurality of a characters or character string are presented by the presentation means.
In this way, similar to inputting Chinese characters, the device can be adapted to designate a desired character or character string from a plurality of character candidates as required.
The communication device of the present invention is adapted to consult frequency information showing the designation frequency of a character or character string and to prioritize the transmission of characters or character string with a high designation frequency when a plurality of characters or character strings exist corresponding to operational information.
In this way, operational characteristics can be improved when designating a desired character or character string.
The communication device of the present invention is adapted to consult frequency information showing the designation frequency of a character or character string and to prioritize the display of characters or character string with a high designation frequency when displaying a plurality of characters or character string.
In this way, operational characteristics can be improved when designating a desired character or character string.
The communication device of the present invention is adapted to determine a transmission order of characters or character string by consulting information showing past designation results when a plurality of characters or character string exist corresponding to operational information.
In this way, operational characteristics can be improved when designating a desired character or character string.
The communication device of the present invention is adapted to determine a display order of characters or character string by consulting information showing past designation results when displaying a plurality of characters or character string.
In this way, operational characteristics can be improved when designating a desired character or character string.
The communication device of the present invention is provided with an updating means which updates designation information or frequency information depending on a designation result of the designation means.
In this way, operational characteristics can be further improved as prior use characteristics are applied when designating a desired character or character string.
The communication device of the present invention is provided with a forwarding means which mutually forwards designation information and frequency information stored in a memory of the communication terminal and designation information and frequency information stored in the memory of the smart card.
In this way, for example, when the used smart card is changed, it is possible to apply use characteristics of a user in the new smart card.
The communication device of the present invention is ;provided with an editing means which edits stored content in the memory of the communication terminal or the stored content in the memory of the smart card.
In this way, it is possible to maximize the application of designation information and frequency information.
The communication device of the present invention is adapted to form an editing means using an external computer which is capable of communicating data with a communication terminal.
In this way, it is possible to heighten the operational. characteristics of editing operations.
The communication device of the present invention is adapted to transmit operational information of the external computer which is capable of communicating data with a communication terminal.
In this way, it is possible to improve the operational characteristics of character input.
The communication device of the present invention is provided with a selection means which selects a processing device which designates a character or character string when a communication terminal has a function of designating a character or character string corresponding to operational information.
In this way, it is possible to input characters using a function of a communication terminal according to the desires of a user (for example, when continued use of a smart card is inconvenient).
The communication device of the present invention is provided with a specifying means in the communication terminal which specifies a character or character string which corresponds to operational information when a smart card which has the function of specifying a character or character string corresponding to operational information is not connected to a communication terminal.
In this way, it is possible to input characters even when a smart card having a specifying function is not at hand.
The communication device of the present invention is provided with an updating means in the communication terminal which updates a program which executes the function of specifying a character or character string corresponding to operational information.
In this way, it is possible to use another operational method without preparing another smart card when it is desired to use another operational method.
The communication device of the present invention is provided with an choice means which chooses a used program when a plurality of programs are stored in a smart card or a communication terminal.
In this way, it is possible for a user to select an easy operational method.
The communication device of the present invention is adapted to output externally operation key operational information and a character or character string transmitted from a smart card and.
In this way, even when the communication terminal does not have a display, it is possible to present operational information of the operation keys and the like.

Smart card with multi-character memory for various telephone devices


The present invention relates to methods for detecting, quantifying and high throughput screening of donor-products and the catalytic activities generating the donor-products in group-transfer reactions catalyzed by adenosine triphosphatase (ATPase) or guanine triphosphatase (GTPase). The invention further provides immunoassays, antibodies and kits that may be used to practice the methods of the invention.

There are many important biological reactions where the substrates are modified by chemical groups that are donated by other substrates, known as activated donor molecules. These biological reactions are broadly recognized as "group transfer reactions" and have the general reaction:donor-X+acceptor>donor-product+acceptor-X.Typically, donor-X, the activated donor molecule, is a nucleotide attached to a covalent adduct. The donor-X is activated by formation of a phosphoester bond in the nucleotide donor. Also the acceptor substrates can include small molecules such as steroid hormones or water, or macromolecules such as proteins or nucleic acids. Products of this reaction are the modified acceptor, acceptor-X and the donor-product molecule.
There are many enzymes that catalyze group transfer reactions such as for example kinases, which use ATP to donate a phosphate group; sulfotransferases (SULTs), which use phosphoadenosine-phosphosulfate (PAPS) to donate a sulfonate group; UDP-glucuronosyltransferases (UGTs), which use UDP-glucuronic acid to transfer a glucuronic acid group; methyltransferases, which use s-adenosyltransferase to donate a methyl group; acetyl transferase, which use acetyl coenzymeA to donate an acetyl group; and ADP-ribosyltransferases, which use nicotinamide adenine dinucleotide (NAD) to donate an ADP-ribose group. Enzymes such as the ones named above, which catalyze group transfer reactions in which the acceptor is a molecule other than water, are classified by the Enzyme Commission as "Transferases" (Transferases are classified as EC2 by the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology [IUBMB]). Enzymes that catalyze group transfer reactions in which water is the acceptor, also known as "hydrolysis" reactions are classified as "Hydrolases" (EC3), and include enzymes such as ATPases, GTPases, and nucleotidases. Many of the enzymes catalyzing group transfer reactions of both types are of interest to pharmaceutical companies.
Automated high throughput screening (HTS) assays are the paradigm for identifying interactions of potential drug molecules with proteins in a drug discovery setting, and this format requires simple, robust molecular assays, preferably with a fluorescent or chemiluminescent readout. The most suitable format for HTS is a homogenous assay, (e.g., "single addition" or "mix and read" assay), which does not require any manipulation after the reaction is initiated and the assay signal can be monitored continuously. Despite their importance from a drug discovery perspective, the incorporation of group transfer enzymes into pharmaceutical HTS programs is being slowed or prevented for a number of reasons: a) homogenous assay methods are not currently available, b) the detection methods used place serious limits on the utility of the assay, and c) the non-generic nature of the assay requires the development of many specific detection reagents to test diverse acceptor substrates.
The approach currently used to identify sulfotransferase substrates or inhibitors requires the use of radioactivity and involves cumbersome post-reaction separation steps, such as precipitation or chromatography. For instance, 35S-PAPS is used in a sulfotransferase reaction and the labeled product is quantified by scintillation counting after selective precipitation of unreacted 35S-PAPS (Foldes, A. and Meek, J. L., Biochim Biophys Acta, 1973, 327:365-74). This approach is not desirable in a high throughput screening (HTS) format because of the high radiation disposal costs and because the incorporation of separation steps complicates the automation process. Other SULT assays have been developed using colorimetric and fluorescent means, but they are dependent on the use of a specific acceptor substrate for detection, so their use is limited to a single SULT isoform, and they cannot be used to screen for diverse substrates (Burkart, M. D. and Wong, C. H., Anal Biochem, 1999, 274:131-7; Frame, L. T., Ozawa, S. et al., Drug Metab Dispos, 2000, 28:1063-8). As a result, SULT interaction studies are currently not included during the preclinical development of drugs. Also UGTs are currently assayed using radiolabeled donor molecules and require post-reaction separation steps such as thin layer chromatography (TLC) or high pressure liquid chromatography (HPLC) which seriously hampers preclinical HTS programs (Ethell, B. T., Anderson, G. D. et al., Anal Biochem, 1998,255:142-7). Likewise, traditionally, kinases have been assayed by filter capture or precipitation of radiolabeled polypeptide substrates produced using 32P-ATP or 33P-ATP as donor. However, since this method requires a separation step such as filtering or centrifugation, it cannot be easily adapted to an automated HTS format. Surface proximity assays (SPA) allow radioassays in a multiwell format with no separation (Mallari, R., Swearingen, E. et al., J Biomol Screen, 2003, 8:198-204) but their use by pharmaceutical companies is declining because of the disposal and regulatory costs of handling radioisotopes.
Because of the high level of interest in developing kinase inhibitor drugs, there has been a great deal of effort among scientists to develop improved assay methods for this enzyme family. Homogenous assay methods have been developed, in which highly specific reagents are used to detect the reaction products in the presence of the other components of the reaction using a light-based readout, such as fluorescence or chemiluminescence. The most common homogenous approach used for kinase assays is immunodetection of phosphopeptide products exhibiting different fluorescence properties (Zaman, G. J., Garritsen, A. et al., Comb Chem High Throughput Screen, 2003, 6:313-20). In this method, phosphorylation of substrate peptide leads to displacement of a fluorescent phosphopeptide tracer from an anti-phosphopeptide antibody and causes a change in its fluorescence properties. This basic approach has been adapted to several different readout modes used for competitive immunoassays including Fluorescence polarization (FP) (Parker, G. J., Law, T. L. et al., J Biomol Screen, 2000, 5:77-88); time resolved fluorescence (Xu, K., Stern, A. S. et al., J Biochem Mol Biol, 2003, 36:421-5); fluorescence lifetime discrimination (Fowler, A., Swift, D. et al., Anal Biochem, 2002, 308:223-31); and chemiluminescence (Eglen, R. M. and Singh, R., Comb Chem High Throughput Screen, 2003, 6:381-7).
The shortcoming with this approach is the requirement for phosphopeptide-specific antibodies. Though generic phosphotyrosine antibodies are common, phosphoserine and phosphothreonine antibodies are notoriously difficult to produce and only recognize phospho-serine or -threonine in the context of specific flanking amino acids (Eglen and Singh, 2003). There are over 400 kinases in humans and their specificity for phosphorylation sites vary widely. Thus, different antibodies are needed for assaying diverse kinases or profiling acceptor substrates. This greatly complicates the incorporation of new kinases into HTS, especially if their substrate specificity is not well defined. It also creates analysis problems in comparing data among kinases with different substrate selectivities, because the output of the assay depends on the particular antibody(Ab)-phosphopeptide pair used. Although efforts to develop generic phospho-serine antibodies and identify more generic kinase substrates continue (Sills, M. A., Weiss, D. et al., J Biomol Screen, 2002, 7:191-214), research in this direction has not been very successful to date.
A number of alternative approaches have been developed to circumvent the problem of context-specific Ab-phosphopeptide interactions, including use of metal complexes to bind phosphopeptides (Scott, J. E. and Carpenter, J. W., Anal Biochem, 2003, 316:82-91) and the use of modified ATP analogs that allow covalent tagging of phosphopeptide products (Allison Miller-Wing, E. G., Barbara Armstrong, Lindsey Yeats, Ram Bhatt, Frank Gonzales, and Steven Gessert., SBS 9th Annual Conference and Exhibition, Portland, Oreg., 2003). Chemical phosphate binding reagents suffer from background binding to nucleotide phosphates, requiring the use of very low, non-physiological levels of ATP and limiting assay flexibility. Modified nucleotides do not provide a generic format because the ability to use the ATP analogs as donors varies among kinases, requiring the development of a number of different analogs. Also competition of inhibitors with the modified nucleotides at the kinase ATP binding site—the most frequent site for kinase inhibitor binding—does not reflect the physiological situation. Differences in protease sensitivity caused by peptide phosphorylation have also been exploited in developing fluorescence based kinase assays (Kupcho, K., Somberg, R. et al., Anal Biochem, 2003, 317:210-7), but these assays are not truly homogenous; i.e. they require the post-reaction addition of developing protease reagents. In addition, the applicability of this method is limited to peptides where kinase and protease specificity overlap.
There are also a few methods that are dependent on interaction of reaction products with specific multiwell plate chemistries, but these are not truly homogenous in that they require post reaction reagent additions and/or processing. Also the requirement for specialized instrumentation for processing and/or detection does not fit with the open architecture desired by most pharmaceutical HTS platforms.
Furthermore, microfluidics-based kinase assays that rely on electrophoretic separation of reaction products have been developed (Xue, Q., Wainright, A. et al., Electrophoresis, 2001, 22:4000-7). In these assays, phosphorylated peptide products are electrophoretically separated from the non-phosphorylated acceptor substrates, thus eliminating the need for specialized detection reagents. However, in practice, the kinase assays are often run in multiwell plates and then the products are transferred to microfluidic devices for separation—a cumbersome process for an HTS format.
In summary, the non-generic nature of the current group transfer assays is resulting in significant expense and delays for drug discovery because of the need to develop assays for individual enzymes or small subgroups within a family. Also, because many of the current assays are based on modification and detection of specific tagged acceptors, there is limited ability for testing different acceptor substrates. Often the tagged acceptor substrates used are different from the substrates that are phosphorylated in vivo, thus the physiological relevance of the assay is questionable. In addition, a major concern in the pharmaceutical industry is that because of the non-generic nature of the current assays, investigators are sometimes forced to use different methods for different kinases. However, studies have shown that there are significant differences in the pharmaceutical targets identified using different assays methods (Sills, M. A. et al., J Biomol Screen, 2002, 7:191-214), which is a significant problem for profiling inhibitor selectivity across several kinases. These shortcomings of the existing HTS assay methods for group transfer reactions are hampering the rapid analysis of important enzyme families in pharmaceutical drug discovery programs.
Other existing approaches for assaying group transfer reactions have been to enable screening of diverse chemicals as substrates for group transfer reactions by detecting the donor molecule product, because it is the same regardless of the acceptor being modified. Detection of the donor product has been thought to provide the basis of a generic assay method, ADP is always a product of a kinase reaction and phosphoadenosine-phosphate (PAP) is always the product of a sulfotransferase reaction. Detection of these products, however, is complicated because the cleaved mono- and di-nucleotides cannot be differentiated from the activated donor molecules based on absorbance or fluorescence properties because for example ADP has the same fluorescence and absorbance properties as ATP. Separation of the donor product from the donor can be effected using chromatographic methods, such as thin layer chromatography or high pressure liquid chromatography, but incorporation of these methods into an HTS format is cumbersome.
To circumvent this difficulty, detection of the donor product has been achieved by using additional enzymes to generate a detectable product from the primary reaction product—the cleaved mono- or di-nucleotide; this is known as an enzyme coupled reaction. For instance, enzymes and other small molecules can be used for ADP-dependent generation of NADPH, which is detected by absorbance or fluorescence at 340 nm (Walters, W. P. and Namchuk, M., Nat Rev Drug Discov, 2003, 2:259-66). An enzyme coupled reaction has also been developed for UGTs, another type of group transfer enzyme (Mulder, G. J. and van Doorn, A. B., Biochem J, 1975, 151:131-40). However, the optical interference of drug compounds with absorbance assays, especially in the ultra violet, is a widely recognized problem with this approach. Another shortcoming of this approach is that all of the enzymes used to couple the detection are subject to potential inhibition from the chemicals being screened.
Another generic approach is to monitor ATP consumption using Luciferase as a reporter to detect protein kinase activity. An example of this method was disclosed by Crouch et al., in U.S. Pat. No. 6,599,711. Their method entailed determining the activity of a protein kinase to be tested by adding a substrate capable of being phosphorylated by the protein kinase to a solution having ATP and a protein kinase to be tested, and another solution having ATP in the absence of the kinase to be tested. The concentration or the rate of time change of ATP and/or ADP was then measured using bioluminescence. However this assay is not optimal because it relies on small decreases in a high initial signal. The need to keep ATP concentrations low to minimize background results in nonlinear reaction kinetics if assay conditions are not carefully controlled. In a related method, competition binding assays using fluorescent ATP analogs have also been developed, but these do not give a measure of enzyme catalytic activity, thus are of limited utility.
Enzymes that catalyze group transfer reactions where water is the acceptor, hydrolases, present an even more difficult assay challenge because generally the products are all small molecules, and thus more difficult to detect than a covalently adducted peptide or nucleic acid, which can be detected easily with an antibody. An example of such a reaction is that catalyzed by an ATPase: ATP+H2O→ADP+phosphate. Below we describe the HTS methods used to detect some types of hydrolases and their shortcomings.
A number of ATPases and GTPases are of significant interest for drug discovery because they are involved in cellular and subcellular movement (Pellegrini, F. and Budman, D. R., Cancer Invest, 2005, 23:264-73), ion transport or drug transport (Xie, Z. and Xie, J., Front Biosci, 2005, 10:3100-9), signal transduction (Kimple, R. J., Jones, M. B. et al., Comb Chem High Throughput Screen, 2003, 6:399-407), and the control of protein stability (Workman, P., Curr Cancer Drug Targets, 2003, 3:297-300).
The most common non-radioactive method used to detect ATPases and GTPases is colorimetric determination of inorganic phosphate using dyes like malachite green (Rowlands, M. G., Newbatt, Y. M. et al., Anal Biochem, 2004, 327:176-83). This method is problematic for HTS because the colorimetric readout is not very sensitive and is also subject to interference from colored test compounds. Other methods of phosphate detection have been developed more recently using fluorescently labeled phosphate binding proteins that undergo a change in fluorescence associated with conformational changes induced by phosphate binding (Brune, M., Hunter, J. L. et al., Biochemistry, 1994, 33:8262-71). Though fluorescence is preferable to absorbance as a detection mode for HTS, any method that relies upon phosphate detection is going to suffer from background signal because of the high phosphate concentrations found in biological samples and its use as a common biological buffer reagent. Detection of ADP using a coupled enzyme assay linked to NADPH formation is also used as an HTS assay approach for ATPases (DeBonis, S., Skoufias, D. A. et al., Mol Cancer Ther, 2004, 3:1079-90), but this method again relies on absorbance detection and so suffers from low sensitivity and interference from colored compounds. The coupled enzyme approach has also been adapted for fluorescence detection (Zhang, B., Senator, D. et al., Anal Biochem, 2005, 345:326-35), but the requirement for several enzymes for signal generation greatly increases the potential for assay interference from test compounds.
In general, the use of enzymes that catalyze group transfer reactions into HTS assays has been hampered by the lack of universal, homogenous assay methods that are not subject to interference from molecules in pharmaceutical drug libraries. Accordingly, it would generally be desirable to provide universal methods for assaying enzymes involved in group transfer reactions that are well suited for HTS drug discovery.

Assay method for group transfer reactions


An arrangement for step-by-step height adjustment of a holding or deflecting fitting of a seat belt on a hollow body part of a motor vehicle, particularly on a B-column or a C-column, includes a guide rail mounted on the body part, and a carriage which can be displaced along the guide rail, which can be fixed in defined adjusting positions, and which has a fastening device for the holding or deflecting fitting. The guide rail, which is arranged behind a column covering, is mountable on the vehicle body part by way of two mutually spaced fastenings. In the event of a vehicle collision, particularly a side impact, the forces acting upon a vehicle occupant's head are to be kept below a permissible limit value. Accordingly, it is provided that, in the event of a vehicle occupant's head impact onto the holding or deflecting fitting, starting from a defined force level, the guide rail and therefore the entire belt height adjusting arrangement, while absorbing energy, is laterally swivellable about an axis of rotation formed by one of two fastenings of the guide rails and extending in the transverse direction of the vehicle.

The present invention relates to an arrangement for the step-by-step height adjustment of a holding or deflecting fitting of a seat belt on a hollow body part of a motor vehicle, particularly on a B-column or C-column, having a guide rail mounted on the body part, and a carriage which can be displaced along the guide rail, can be fixed in defined adjusting positions and has a fastening device for the holding or deflecting fitting, and in which the guide rail, which is arranged behind a column covering, is mountable on the vehicle body part by means of two mutually spaced fastenings.
Arrangements of the initially mentioned type, which are usually called belt height adjusting devices, are used for adapting the height of the deflecting or fastening point of a seat belt to the body size of a vehicle occupant to be protected. In four-door passenger cars, the belt height adjusting arrangements are normally mounted in the upper part of the B- and C-columns. For adjusting the height of a fitting, usually by pressure onto a cover cap of a screw connecting the holding or deflecting fitting with the carriage, a carriage is pressed against the force of a spring in the direction of the column, in order to release the fixing caused by mutual detent engagement of detent elements of the carriage and of a guiding rail, so that the carriage can be moved along the guide rail into the desired adjusting position. When the cover cap is subsequently relieved from pressure, the detent elements again enter into a mutual detent engagement, so that the carriage is held in the selected adjusting position.
Many such arrangements are known from the prior art. Reference is made, for example, to German Patent Document DE 198 22 696 A1.
There is a risk that a motor vehicle occupant's head will carry out a transverse motion and impact on an area in which the deflecting fitting is arranged when lateral forces act upon a vehicle equipped with the deflecting fitting in the event of an accident, for example. In this case, loads which are above a permissible limit value may act upon the vehicle occupant's head.
It is known from German Patent Document DE 197 19 572 A1 to arrange a deformation element, which is designed for absorbing energy in the event of pressure admission to the seat belt linkage point, between the seat belt linkage point and the vehicle body part. Viewed in the transverse direction of the vehicle, such a deformation element requires a relatively large amount of additional space.
It is known from German Patent Document DE 196 15 804 C2 to arrange a damping device between the adjusting part holding the deflecting fitting and the vehicle body part at which a rail is fastened or can be fastened. When impact-caused forces act upon the deflecting fitting, the damping device is supported on the adjusting part and the vehicle body part and can be deformable during the process for damping impact energy. A corresponding space has to be provided for housing such a damping device.
It is an object of the invention to further develop a fastening for a belt height adjusting arrangement according to the above-mentioned type such that, in the event of a head impact onto the holding or deflecting fitting, loads acting upon the vehicle occupant's head are below the permissible limit value.
According to the invention, this object is achieved by having the guide rail and therefore an entire belt height adjusting arrangement, while absorbing energy, be laterally swivellable, starting from a defined force level, about an axis of rotation, formed by one of two fastenings of the guide rail and extending in the transverse direction of the vehicle, upon impact of a vehicle occupant's head with the holding or deflecting fitting. Additional characteristics advantageously further developing the invention are defined by the dependent claims.
Principal advantages achieved by the invention are that, in the event of a head impact onto the holding or deflecting fitting at a defined force level, the belt height adjusting arrangement, while absorbing energy, can be laterally swivelled about an axis of rotation formed by one of the two fastenings of the carrier rail and extending in the transverse direction of the vehicle. Energy is absorbed during swivelling of the belt height adjusting arrangement, and thus the head loads occurring are below the permissible limit value. Furthermore, an additional energy absorption can take place by deformation of the column covering disposed in front.
In one embodiment, the belt height adjusting arrangement swivels about the upper fastening, and specifically, viewed from the vehicle occupant compartment, against the driving direction toward the rear. Thus, while absorbing energy, the belt height adjusting arrangement yields laterally in the longitudinal direction of the vehicle. Energy absorption is formed by a bent-away column-side lug which bends or deforms during the swivelling of the guide rail of the belt height adjusting device. As a result of the geometry of the lug (length, width, thickness, set angle), the force level can be defined, starting from which the lug bends during the swivelling of the guide rail.
The invention will be explained in detail in the following by means of an embodiment illustrated in the drawing.

Arrangement for the step-by-step height adjustment of a holding or deflecting fitting of a seat belt on a hollow body part of a motor vehicle

Dr. Ing. h.c.f. Porsche Aktiengesellschaft


A cell sorter including a well that has a microspace filled with a liquid and having a typical length of 1 mm or less, and that has a bottom surface made of a light-permeable material allowing optical observation of an interior of the microspace; a matrix provided on the bottom surface in the well; a bone fragment placed on the matrix in the well; and osteoclasts placed between the matrix and the bone fragment.

In recent years, in vivo microenvironments have attracted attention. Among them, a system in which osteoclasts are present in a bone-marrow microenvironment is considered not only to be the front line of bone remodeling that is the original function of the system but also to provide a niche comfortable for other cells. Further, it is considered that cancer stem cells, which have drug resistance and interfere with the radical cure of cancer, are deeply involved with the presence of the niche.
It is considered that cancer stem cells are sources of many cancer cells and have drug resistance, and therefore, interfere with the eradication of cancer. Thus, drug discovery targeting cancer stem cells is considered to be important for the radical cure of cancer. In order to investigate the effect of a drug targeting cancer stem cells, it is necessary to sort out cancer stem cells from other cells. However, a method for sorting out cancer stem cells from other cells has not hitherto been established.


Disclosed is a polymer conjugate of folic acid or a folic acid derivative, wherein an amide bond is not used. The compound has chemical stability and adequate drug release rate in the living organism. Specifically disclosed is a polymer conjugate of folic acid or a folic acid derivative, wherein a substituent represented by formula (I) is bonded to a carboxy group of a block copolymer which is composed of a polyethylene glycol and a polymer having a carboxy group in a side chain, or a pharmacologically acceptable salt thereof.

Folic acid is one of water-soluble vitamins, and is a co-enzyme necessary in the synthesis of amino acids or nucleic acids. Folic acid is converted to tetrahydrofolic acid by a reductase in the body, and then is further converted to be used in the synthesis of dTMP (deoxythymidine-1-phosphate) or purine. Folic acid derivatives include compounds that have a function of inhibiting the in vivo conversion of folic acid and thereby terminating cell division. A group of these compounds are called as folic acid antimetabolites, and methotrexate, which is a representative compound of the group, has long been used in the treatment of leukemia, sarcoma, stomach cancer and the like. Furthermore, methotrexate also has an immunomodulating action and thus serves as an essential drug for the chemotherapy of rheumatoid arthritis.
In addition, folic acid itself or a folic acid derivative such as leucovorin is also used as a drug for treating folic acid deficiency or neutralizing the toxicity of methotrexate.
As such, folic acid, or a folic acid derivative, for example, a folic acid antimetabolite which is represented by methotrexate, is a compound useful as a pharmaceutical product, and research on various derivatives is in progress for the purpose of improving the drug efficacy. Examples of these derivatives include aminopterin, pralatrexate, plevitrexed, edatrexate, pemetrexed, raltitrexed, lometrexol and the like, as shown below. The mode of action of these folic acid antimetabolites is mainly a dihydrofolate reductase inhibitory activity, but among the drugs newly developed, some even have a thymidylate synthetase inhibitory activity. Thus, there is a demand for more effective drugs, and development of those drugs is under way. For example, pemetrexed is characterized by inhibiting multiple enzymes involved in the folic acid metabolic system, and has been approved as a therapeutic drug for malignant pleural mesothelioma.

On the other hand, an experiment intended for the reduction of toxicity and enhancement of effects of low molecular weight drugs has been made as a part of the research on drug delivery systems (DDS). Various methods are available to achieve the object, for example, a drug may be bound to a polymer or may encapsulated in a nano-sized carrier. Regarding methotrexate, which is a compound representing folic acid derivatives, systems utilizing microspheres, dendrimers and micelles have been reported. However, none of the reports can be sufficiently satisfy the final purposes of the DDS research, that is, enhanced effects and reduced adverse side effects.
Patent Document 1 and Patent Document 3 describe water-soluble macromolecular pharmaceutical preparations containing, as a carrier, micelles formed by an amphiphilic polymer. Patent Document 1 describes, as an example of a hydrophobic segment, a polymer carrier having methotrexate bound thereto, but in this case, methotrexate and the amphiphilic polymer are linked via an amide bond. Patent Document 3 does not describe a polymer conjugate having folic acid or a folic acid derivative bound thereto.
Patent Document 2 reports that chemical stability and in vivo drug release efficiency can be simultaneously achieved by linking a polymer compound and a camptothecin compound via a phenyl ester bond. However, this method cannot be directly used for a carboxy group of a folic acid derivative (including folic acid itself), which is represented by methotrexate.
Furthermore, Non-Patent Document 1 and Non-Patent Document 2 describe polymer conjugates, which use a carboxy group of methotrexate to link methotrexate to an amphiphilic polymer via an alkyl ester bond. However, in this case, the release rate of drug is slow, and there arises a question on whether the effects of the drug would be exhibited. Furthermore, when the release of a drug from a polymer conjugate is dependent on the enzymes in vivo, there is a fear that the enzymatic activity, which varies between individuals, may cause variability in the drug release rate, and may consequently cause variability in the efficacy.

Polymer conjugate of folic acid or folic acid derivative

Abstract: [In the formula, A represents a monocyclic or fused aromatic group; G represents an optionally substituted (C1-C6) alkylene group; Y represents a hydrogen atom or a substituent; and E represents a residue of folic acid or a folic acid derivative.]


A terminal which selects an access point (AP) and a method thereof are provided. The method for selecting the AP includes: receiving a plurality of packets from a plurality of APs which provide wireless communication services, analyzing the received plurality of packets and calculating reliability for security of the plurality of APs, and displaying the calculated reliability and identification information of the plurality of APs.

3rd Generation (3G) is a communication method that provides a wireless Internet service through a base station, and wireless fidelity (Wi-Fi) is a communication method that provides a wireless Internet service using an access point (hereinafter, referred to as an AP). Portable terminals such as smartphones and tablet PCs are able to use wireless Internet services using the 3G or Wi-Fi in any time and place. However, in the case of the 3G, users should pay for the use of the Internet, and, in the case of the Wi-Fi, users are free to use the Internet. In recent years, many open places such as public places are providing the Wi-Fi service.
However, the 3G provides a safe Internet service from the perspective of security, whereas the Wi-Fi uses the AP to provide the Internet service and thus does not guarantee high reliability about security of portable terminals.
For example, if an attacker such as a hacker disguises its terminal as an AP, it is difficult for a portable terminal to recognize that the AP is the attacker's terminal. Therefore, the portable terminal may access such an AP. In this case, the attacker may steal information stored in the portable terminal from the user of the portable terminal. Therefore, there is a need for a method for distinguishing between an attacker terminal which is disguised as an AP (hereinafter, referred to as a "fake AP"), and a real AP.

Method for selecting access point with reliability

KOREA UNIVERSITY RESEARCH AND BUSINESS FOUNDATION


An improved spray nozzle for use with air atomizable liquids wherein the spray pattern created by the atomizing nozzle may be adjusted from a circular pattern to a flat pattern or alternatively to an open oval. The open end faces in preselected directions. The adjustments are capable of occurring during the continuous operation of the nozzle.

Spray guns and nozzles, especially those used with spray painting systems, atomize the liquid paint by means of atomizing air which enters the nozzle area via a chamber which surrounds a fluid nozzle. The atomizing air is then impinged on the end of the chamber and exits via a central aperture located at the end of the chamber. The paint is atomized by the accelerating burst of forward motion of this air as it exits the nozzle via the aperture. The initial conventional pattern of the atomized liquid and air mixture in cross-section is a circle because the exit aperture is circular.
The term pattern as used herein describes a cross-section of the atomized cloud of paint droplets in a plane perpendicular to the direction of the spray from the fluid nozzle. When the compressed air source for a spray painting apparatus utilizes a high volume, low pressure compressor, it is conventional for the air exit nozzle on the spray painting gun to have a central aperture which is considerably larger than the circumscribed liquid nozzle. Therefore, the large amount of air utilized in a conventional nozzle is due to the relative size of the central aperture compared to that of the liquid nozzle. This excess air, air beyond that required to atomize the liquid properly, constitutes an energy waste as well as a pollution problem. The excess air is a pollution problem since the air in a paint system will tend to carry the paint solvent. The more air that is used, the more dilute the solvent, and the more air that must be processed for the removal of solvents.
Therefore, there is a need for an improved spray nozzle which more efficiently utilizes the air that it actually receives from the air source.
The pattern of a spray nozzle is conventionally adjusted by impinging additional air jets into the original circular pattern at a location beyond the outlet aperture. A standard design may include two oppositely directed jets which produce a flat or oval pattern, and if those jets are very powerful it produces a flat fan type spray pattern which is many times wider than it is high. However, in production line spraying, there are needs for other than such flat or oval patterns, especially when spray painting the reverse sides of objects or spray painting in an out-of-position way and also the traditional problem of painting the insides of angular surfaces.
Therefore, there is also a need for improved pattern control in spray nozzle systems and the ability to adjust the pattern to other than flat or oval pattern. It would additionally be desirable if such adjustments or modifications of the pattern could be achieved without the necessity of changing the nozzle in use.
Another problem with spray guns is that the air from the compressor is hot and tends to heat metal parts in the flow path to an extent that hand held spray guns may burn the operator or at least make his hand most uncomfortable.


An induction heating device having a control box, a magnetic core provided with at least one inductor fed with a current by a power electronics that is controlled by a control circuit, the power electronics and the control circuit being disposed in the control box, a removeable closing yoke for completing the magnetic circuit of the magnetic core, and a plurality of temperature sensors. A plurality of metal articles are simultaneously heated so as to each reach a target temperature and according to a heating cycle during which the temperatures sensors monitor the temperatures of the plurality of the metal articles so that each metal article is connected to a temperature sensor that is not connected to any other metal article.

EP 2728965A1 describes a known type of bearing induction heater for which two temperature probes are used during the heating of a bearing according to a heating cycle. One temperature probe monitors the temperature of the inner ring of the bearing and the other temperature probe monitors the temperature of the outer ring of the bearing. The difference between the two temperatures triggers a switchover between a first portion of the heating cycle and a second portion of the heating cycle.
Generally speaking, it is known to use induction heaters with a single induction coil or with several induction coils. Improvements are still possible.


A laser module has an optical amplifier, a first etalon and a wavelength selectable mirror. The first etalon has wavelength peaks at a given wavelength interval in transmission characteristics and transmits a light from the optical amplifier. The wavelength peaks are tunable. The wavelength selectable mirror acts as an external mirror of an external cavity laser including the optical amplifier, and has a relatively high reflection intensity at a part of wavelength range in an effective gain range of the optical amplifier. The effective gain range of the optical amplifier includes more than one wavelength peak of the first etalon. A reflection bandwidth where the wavelength selectable mirror has a relatively high reflection intensity is less than twice of the wavelength interval of the wavelength peaks of the first etalon.

1. Field of the Invention
This invention generally relates to a laser module and a method of controlling wavelength of an external cavity laser.
2. Description of the Related Art
Recently, an information-processing device and so on using a semiconductor laser have been developed. There is a demand for superior characteristics such as tunability or stability of wavelength. And so, Japanese Patent Application Publication No. 2003-152275 (hereinafter referred to as Document 1) discloses an art in which a wavelength selectable etalon whose inclination is tunable is provided between a semiconductor optical amplifier and an external mirror.
In accordance with the art, peak wavelengths of a light passing through an etalon change when the inclination of the etalon is changed. And, an effective gain range of the semiconductor optical amplifier includes one of the peak wavelengths. Therefore, an output wavelength of the semiconductor optical amplifier is selected to the peak wavelength of the light passing through the etalon.
However, the art disclosed in Document 1 has a problem that a full width of half maximum (FWHM) value of the peak of the light passing through the etalon is broadened when a Free Spectral Range (FSR) of the etalon is broadened so that the effective gain range of the semiconductor optical amplifier includes only one of the peak wavelengths of the light passing through the etalon. In contrast, the effective gain range of the semiconductor optical amplifier includes more than one peak of the light passing through the etalon when the FSR is reduced in order to reduce the half-value-width of the peak of the light passing through the etalon. Therefore, the selection accuracy of output wavelength of the external cavity laser is degraded.

Laser module and method of controlling wavelength of external cavity laser


Documents are automatically generated from data within a database. The look and feel of the document is defined externally from the data in the database such that a consistent look and feel is applied to the retrieved data. Templates are defined that specify the structure of the document including its look and feel for the documents created by using data from the database. When a document is requested to be generated for viewing and/or editing, the appropriate data from the database is retrieved and placed within the document according to the defined look and feel that is contained within the templates.

Many times data that is stored within a database system is better presented in the context of a word processing document for ease of readability by the intended audience. For example, data about an Application Programming Interface (API) may be stored within a database as items in a table (each method, property, and object in the API), but the documentation for the API is better presented as a word processing document. Similarly, product data may be stored within a database but the product descriptions are better viewed within a word processing document. Creating word processing documents comprised primarily from data within a database, however, is challenging.

Generating a word-processing document from database content


A conducting polymer composite is made by compounding a conducting polymer and an ionic polymer so as to achieve good conductivity. A high resistance material generated also has a high withstand voltage. A solid electrolytic capacitor using this conducting polymer composite as its solid electrolytic layer achieves low ESR and high withstand voltage.

Conducting polymers are increasingly being used in diverse fields. For example, in the field of electronic products, conducting polymers are typically used as antistatic films and conductive materials for organic transistors. With respect to commercialization, conducting polymers are extensively used as the solid electrolytic layer in solid electrolytic capacitors (SECs). These SECs are often used, in particular, in power circuits and CPU peripherals of personal computers, since SECs are smaller and have lower equivalent series resistance (ESR) at high frequencies.
One of the electrical characteristics of this SEC is withstand voltage, and this withstand voltage depends on the thickness of the dielectric film. In an aluminum SEC, for example, the dielectric film is formed by anodization, and thus the dielectric film becomes thicker in proportion to the anodization voltage. Accordingly, a higher anodization voltage results in a thicker dielectric film, and in turn a higher withstand voltage.
A basic structure of a conventional SEC as described above includes an anode made of a valve metal, the dielectric film formed on this valve metal and a solid electrolytic layer made of a conducting polymer formed on this dielectric film. In general, conducting polymer is used in unmodified form. Japanese Patent Laid-open Application No. 2003-158043 discloses an SEC with this structure.
In other cases, a conducting polymer is used with resin for the purpose of preventing any increase in leakage current resulting from mechanical stress sustained during assembly and thermal stress during packaging or mounting, and reducing shorting. This type of SEC is disclosed in Japanese Patent Laid-open Application No. H11-16783.
In the above conventional structure, however, it is also known that any leakage current in the SEC makes its solid electrolyte a high resistance material (HRM) due to the heat it generates. The HRM produced has a low withstand voltage, and thus the SEC becomes shorted in some cases. In particular, shorting is a serious problem in circuits running at high rated voltages.
In addition, the leakage current characteristic worsens if this conducting polymer is used as the solid electrolytic layer in an SEC.

Conducting polymer composite and solid electrolytic capacitor using the same

Matsushita Electric Industrial Co., Ltd.