A head suspension includes a planar load beam, and a gimbal extending from, and formed integrally with the load beam. The gimbal has a slider loader on which a head slider is adapted to be attached. Also included in the head suspension is a reinforcing plate cooperatively attached to the load beam.

The present invention relates to a magnetic disk apparatus, and particularly to a head suspension and a head assembly used therein.
Recently, to reduce the size and increase the recording density of magnetic disk apparatus, the xe2x80x9cflying heightxe2x80x9d of a head slider over a recording medium has been decreased to an extremely low height, or contact recording and reproduction have been implemented so that the slider remains in contact with the recording medium. The head assembly used in the magnetic disk apparatus requires a gimbal having low rigidity to enable the magnetic head slider to track even in the presence of installation errors of the head assembly or undulations of the magnetic disk, and a suspension or load beam having high resonant frequency in the seek direction, i.e., in the radial direction of the disk, for highly accurate positioning.
Portable personal computers such as notebook computers must have strong shock resistance because they are often carried. Thus, the magnetic disk apparatus for these computers are equipped with a loading and unloading scheme to unload the head slider from the disk surface when the power is off or when the computers go into a sleep mode, and to load the head slider onto the disk surface when in use. Typically, a magnetic disk apparatus equipped with the loading/unloading scheme raises a rectangular tip installed on the front end of the magnetic head assembly onto the ramp inclined portion of a ramp component provided on the outer periphery of the disk medium when the computer power is off or the computer is in a sleep mode, thereby separating the magnetic head slider from the magnetic disk. In this manner, the magnetic head slider can be prevented from hitting and damaging the magnetic disk when the computer receives a shock.
A known gimbal structure which satisfies the demand for low gimbal rigidity and high resonant frequency in the seek direction, supports a head slider on a pivot point. The gimbal is fixed by spot welding to the tip of a load beam, and the magnetic head slider is loaded onto the gimbal. A pair of ribs are formed integrally on both sides of the load beam to increase rigidity. A rectangular tip to be raised onto the ramp component and unload the magnetic head slider from the magnetic disk is formed integrally at the tip of the load beam. The known load beam and gimbal are generally formed from stainless steel. The plate thickness of the load beam is about 43 xcexcm, and that of the gimbal is about 20 xcexcm.
To achieve higher recording density, faster speed, and higher reliability for magnetic disk apparatus, gimbal rigidity must be reduced to stabilize the flying of the magnetic head slider in the magnetic head assembly, and the load beam must have high resonant frequency in the seek direction, i.e., in the radial direction of the magnetic disk. Furthermore, the resilient part of the load beam must have a low spring constant to reduce load fluctuations. There must be at least four printed wires for signal lines when a magnetoresistance effect head (MR head) and a loading/unloading scheme are adopted.
Resonance in the seek direction is normally accompanied by torsion. Thus, at the same time the rigidity in the seek direction is increased, the torsional rigidity must also be increased. A conventional load beam having ribs formed on the rigid part of the load beam has increased flexural rigidity, but the torsional rigidity is not sufficiently high and no different from a flat plate. When the plate thickness of the entire load beam is increased to raise the torsional rigidity, the accompanying increase in mass does not result in an equivalent contribution to an increase in the resonant frequency of the load beam. The increase in the mass of the head assembly also induces a drop in the reliability of the shock resistance.
To stably fly the magnetic head slider over a disk, the gimbal rigidity and the spring constant of the resilient part of the load beam must be decreased and the variations in the load must be minimized. If a load beam has the same thickness as the gimbal, the load beam can be made more rigid by a strategy such as thickening the plate of the load beam. However, lowering the spring constant requires opening a hole in the resilient part of the load beam. If a hole is opened in the resilient part of the load beam, the torsional rigidity of the resilient part is lost, and the resonant frequency drops. The spring constant of the load beam can also be lowered by thinning the resilient part by half etching, but obtaining the desired thickness is difficult.
Low flying sliders used recently in some computers are mostly negative pressure sliders. Therefore, when the slider is unloaded from the top of the magnetic disk, the slider tends to stick to the surface of the magnetic disk. Forcibly pulling offthe slider deforms the gimbal.
Accordingly, one object of this invention is to provide an improved head assembly which enables high recording density at faster speeds.
Another object of this invention is to provide an improved head assembly having a gimbal with low rigidity and a load beam having high resonant frequency in the radial direction of a magnetic disk.
Still another object of this invention is to provide an improved head assembly having a reinforcing plate attached to the load beam.
Yet another object of this invention is to provide an improved head assembly having a gimbal which is not prone to deformation when a slider is unloaded from a disk surface.
Further object of this invention is to provide an improved head assembly having a hook formed on a gimbal to prevent the gimbal from deforming when the slider is unloaded from a disk surface.
In keeping with one aspect of this invention, a head suspension includes a substantially planar load beam, a gimbal extending from and formed integrally with the load beam. The gimbal has a slider loader on which a head slider is adapted to be attached. Also included in the head suspension is a substantially rigid reinforcing plate cooperatively attached to the load beam.
A head assembly of this invention includes a substantially planar load beam, a gimbal extending from and formed integrally with the load beam. The gimbal has a slider loader. A reinforcing plate is cooperatively attached to the load beam and a head slider is fixedly attached to the slider loader.
A disk apparatus of this invention includes a housing, a head assembly provided in the housing and having a head element for reading and writing data on a disk having a plurality of tracks, and an actuator for moving the head assembly over the tracks. The head assembly further includes a substantially planar load beam, and a gimbal extending from and formed integrally with the load beam and having a slider loader. A reinforcing plate is cooperatively attached to the load beam, and a head slider having the head element is fixedly attached to the slider loader.
Another aspect of a disk apparatus of this invention includes a housing with a base, a head slider having a head element for reading and writing data on a disk having a plurality of tracks, and an actuator having an actuator arm rotatably fixed on the base for moving the head slider over the tracks of the disk. A controller moves the actuator for loading and unloading the head slider on and from the disk. A ramp component is fixed to the base for slidably receiving the head slider when the head slider is unloaded from the disk. Also, a head assembly is mounted on a tip of the actuator arm. The head assembly includes a substantially planar load beam, a gimbal extending from and formed integrally with the load beam and having a slider loader on which the head slider is fixedly attached, and a reinforcing plate cooperatively attached to the load beam.

Head assembly having an apertured reinforcing plate cooperatively attached to a load beam to prevent excessive movement of components of the head assembly


Desugared carob pod is treated with superheated steam to pasteurize and dry the carob.

This invention relates to a process for the production of an anti-diarrhoeic product based on carob.
The anti-diarrhoeic properties of carob are well known. Thus, a composition containing 60 to 80% by weight roasted carob bean flour marketed under the name AROBON is known. However, this composition, which gives good results in the treatment of diarrhoea with no side effects, has the disadvantage of necessitating daily doses on the order of 20 g to 40 g which can give rise to problems of administration, particularly in young children.
Thus, European Patent Application Publication No. 214 317 describes an anti-diarrhoeic dietetic product containing a carob bean flour as active principle.
In this process, carob pods which have been shelled and crushed are ground in a mill and introduced into water. The sugars present in the carob and the tannins soluble in water at ambient temperatures are thus dissolved. After preparation of the liquid phase, a sugar-free product is collected.
To obtain a product freed from its microorganisms, the desugared carob is then introduced into a further quantity of water and pasteurized.
After pasteurization, the carob is reground so that it can be reduced to powder and spray-dried before being finally ground to a particle size enabling it to be suspended in a liquid.
Although the product obtained has all the characteristics of an effective anti-diarrhoeic agent coupled with considerable ease of administration by comparison with the prior art, it has several disadvantages in regard to the process used for its production.
In the first place and as explained in European Patent Application Publication No. 214 317, the anti-diarrhoeic effect is obtained through the presence of tannins in condensed forms which are insoluble in cold or tepid water and, more particularly, are insoluble at body temperature. Thus, these tannins enter the intestine without being degraded by gastric acid or inactivated by proteins. Accordingly, they perform a depurative and antiseptic function without intervening in the physiological processes.
Accordingly, in order to obtain an effective anti-diarrhoeic product, it is crucial to avoid solubilization of the tannins present in the desugared carob. Now, this solubilization process begins at temperatures of the order of 90.degree. C. and is considered to be complete at temperatures of the order of 120.degree. C.
Accordingly, this limits the pasteurizing treatment which is carried out at around 95.degree. C.
Accordingly, the end product obtained contains at least 20% by weight native tannins (expressed as total polyphenols) with a ratio by weight of soluble tannins to insoluble tannins of less than 0.37 for solubility measurement at 37.degree. C.
In the second place, the drying process is uneconomical because it follows a considerable addition of water required for pasteurization, the product having a dry matter content before drying of 20% to 25% by weight.
Accordingly, the problem addressed by the present invention was to provide a process for the production of an anti-diarrhoeic product of the type described in European Patent Application Publication No. 214 317 in which the pasteurization step could be carried out at much higher temperatures without solubilization of the tannins and which, in addition, would enable the pasteurization and drying steps to be carried out in a single stage.
The use of superheated steam for pasteurizing food products has been known for some time, cf. for example French Patent No. 1 020 798.
In addition, European Patent No. 58 651 describes a process and an apparatus for treating animal foods with superheated steam.
By means of this process and apparatus for treatment with superheated steam, it is possible to dry the product to be treated in proportions dependent on the treatment parameters of pressure and temperature of the superheated steam and treatment time.

Process for the production of an anti-diarrheic product based on carob


A computer system including a group of CPUs, each having a private cache which communicates with its CPU to receive requests for information blocks and for servicing such requests includes a CPU bus coupled to all the private caches and to a shared cache. Each private cache includes a cache memory and a cache controller including pairs of half-block operand buffers, each divided into quarter block segments. The operand buffer set is coupled to selectively receive, under control of an input multiplexer, requested information blocks from the CPU bus in quarter-block segments and is further coupled to selectively send, under control of an output multiplexer, received quarter-block segments to the CPU and received full blocks to the cache memory.

In the generation-to-generation development of mainframe computer systems, increased speed of operation is sought for a give class of system, and it is therefor useful to minimize the time required to carry out operations which are performed often. This is particularly the case in multiprocessor systems because frequent operations which cause interaction between the processors, or in which one processor briefly takes over a common facility, affects the performance of the entire system.
Some modern computer systems employ multiple processors, each of which has its own private cache memory. As is well known in the art, if a given processor asks its cache for a block of information which is not currently resident, the cache requests the block from one or more additional units in the system, at least one of which should be able to fill the request. The other units may include the private caches of the other processors and a main memory. Other systems, such as that contemplated, interpose a secondary, shared cache between the several private caches and a main memory (and possibly other information sources). In this configuration, a private cache miss in a given processor results in an request to at least the shared cache and, as in the present system, to all the private caches in a group of processors. If none of these units have a valid copy of the requested block, the shared cache seeks it in main memory or elsewhere.
When a processor requests a block which is not in the private cache, it is known that the missed block will be promptly brought into the private cache such that room must be made for the incoming block. This requirement causes a decision algorithm(usually, least recently used) to select the block to be moved out of the private cache to a larger memory such as main memory or, as in the present system, to the shared cache (which is typically much larger than the private caches). This is called a "swap" operation.
It often happens, in a multiprocessor system employing private caches for each processor and a shared cache, that a request, resulting from a cache miss, originating in a given processor has been recently preceded by a request from another processor of the block which the given processor has decided to swap out to the shared cache. The block being swapped is therefore temporarily unavailable to the other processor which has a detrimental effect on system performance.
In another aspect of multiprocessor systems employing private caches for each processor, a private cache must know what blocks are currently resident, a task performed by a cache directory which usually includes an appropriate associative memory. As blocks are siphoned from private cache as a result of serviced misses from other processors, the cache directory must be accordingly updated, but the updating process may interfere with its ongoing task of checking processor requests against the current contents of the private cache. This is another load on system performance.
Another limitation on system performance in such multiprocessor systems relates to the handling of information blocks brought into a given private cache as a result of a request to the other units in the system Typically, a given private cache must receive a block identified in a first request issued to the other units before a second request for another block can be fully undertaken. If the requested block is transferred in block segments, such as quarter blocks, all the blocks of a first request must be received and handled before any of the blocks in a second request can be received. A still further advantage could be realized if a received block, or even a block segment, could be immediately made available to the requesting CPU before storage into its private cache.
Thus, it will be clear to those skilled in the art of multiprocessing that if a plurality of block requests from a given CPU could be performed concurrently and if incoming block segments from such a plurality of concurrent requests could be received and handled intermixed and also made available to the given CPU before storage in its private cache, a significant improvement in system speed could be achieved, and it to these ends that the present invention is directed.

Information block transfer management in a multiprocessor computer system employing private caches for individual center processor units and a shared cache


A preparation method of rare earth ions doped alkaline earth metal silicate luminescent glass is provided. The steps involve: step 1, mixing the source compounds of cerium, terbium and alkaline earth metals and putting the mixture into solvent to get a mixed solution; step 2, impregnating the nanometer pores glass with the mixed solution obtained in step 1; step 3: calcining the impregnated nanometer pores glass obtained in step 2 in a reducing atmosphere, cooling to room temperature, then obtaining the cerium and terbium co-doped alkaline earth metal silicate luminescent glass. Besides, the rare earth ions doped alkaline earth metal silicate luminescent glass prepared with aforesaid method is also provided. In the prepared luminescent glass, cerium ions can transmit absorbed energy to terbium ions under the excitation of UV light due to the co-doping of cerium ions. As a result, the said luminescent glass has higher luminous intensity than the glass only doped with terbium.

Currently, there are many methods for preparation of luminescent glass, wherein one method is to introduce rare earth ion into the pores of the nano-porous glass, then the pores of the nano-porous glass are shrinked by high-temperature solid phase sintering to obtain a compact transparent rare earth ion doped high silicate luminescent glass. The luminescent glass prepared by this method has many advantages, such as: excellent chemical stability, high mechanical strength, good thermal shock resistance, and high-energy ion irradiation resistance, high UV and visible light transmittance and good machinability and the like. However, the luminous intensity of this material is not high, thus the application thereof in the field of lighting and display is greatly limited, and a lot of researches about how to enhance the luminous intensity of the rare earth ion doped high silicate glass are actively carried out at home and abroad.
In 2005 Japan's National Institute of Advanced Industrial Science and Technology reported the preparation of terbium-doped green luminescent high silicate glass by using nano-porous glass. The terbium ion was introduced into the nano-porous glass by soaking, then the nano-porous glass was sintered at 1100° C. in the air or in reductive atmosphere to give a colorless transparent quartz-liked green luminescent glass. In some research methods both alkali metal ion and terbium ion are introduced simultaneously to the pores of the nano-porous glass, after high temperature sintering and heat treatment, terbium-doped alkali metal silicate nanocrystallite will grow in the pores of the nano-porous glass, and the green luminescence of the glass is enhanced. However, the continuous enhancement of the luminescence properties of the luminescent glass is still a potential demand in the practical application. Therefore, the development of a luminescent material which may enhance the luminescence properties of the luminescent glass continuously has become an inevitable trend for the researchers.

Rare earth ions doped alkali metal silicate luminescent glass and the preparation method thereof

OCEAN'S KING LIGHTING SCIENCE & TECHNOLOGY CO., LTD.


An electronic lock is provided with an emergency technique by which the lock may be possibly opened in the event that the electronic memory used to store the authorized combinations for operation in unlocking of the lock becomes corrupted, damaged or is unable to provide a valid read of storage locations containing combinations. Upon the determination that an invalid read has occurred and that the invalid read has been verified for at least a plurality of additional read cycles, the lock is conditioned to accept an otherwise inoperable master combination for purposes of opening the lock. Under the prescribed conditions, the master combination is capable of opening the lock and providing access to the interior of the container carrying the lock, thus permitting either replacement or repair of the lock and also simultaneously eliminating the need for drilling or other destructive access to the interior of the container.

Electronic locks typically have more than one memory. The typical electronic lock has a microprocessor which either has an incorporated or an associated read-only memory as well as at least one other memory, which is a non-volatile type memory for storage of data necessary to the operation of the lock. Combinations are written to or stored in and further read from the non-volatile memory, typically an Electrically Erasable Programmable Read-Only Memory (EEPROM), during lock operations. The stored data may be properly written to the memory; and, due to some subsequent event, one or more of the data bytes may become corrupted or damage may occur to the memory at the location of such stored data.
If, during the normal operation of the electronic lock, a combination is not readable from the memory or corrupted data representing an incorrect combination is read from the memory, then the lock is unopenable. Whenever the lock does not respond to a combination, the lock and/or safe typically must be drilled to gain access to the locking mechanism of the lock in order to open the container. Drilling a container and the lock thereon not only is expensive but damages the container door and the lock, thereby requiring repair or replacement of the container door and replacement of the lock at considerable inconvenience and expense.
Corrupted data may result from such events as electrostatic discharge (ESD), memory failure or any other damage which may render a particular memory location incapable of retaining the data stored therein.
Anytime data is stored in the memory of the electronic lock, the data is read from a buffer, internal to the microprocessor controlling the operations of the lock, and then under the control of the microprocessor, written into the memory along with a Cyclic Redundancy Check (CRC) byte. There is a CRC byte associated with each of the buffer entries recorded into memory.
Immediately after the data is recorded into the memory, a confirmation read operation is initiated in which the data just recorded is reread from the memory for purposes of confirming the accuracy of the information stored. The CRC byte is calculated based upon the data which is read from the memory, compared with the CRC byte stored in the previous storage cycle, and reread from the memory. If the CRC bytes and the data both compare, at this point the data is assumed to be written in correct form and further actions of the microprocessor proceed from that point. In the event that there is a discrepancy, there is an immediate rewriting of the information from the buffer into the lock microprocessor control memory and that rewritten information then is read for confirmation, as previously described.
At a later time when the lock is being operated to open the lock and the related container upon which it is installed, the data may be read from the memory. The data, typically under these circumstances, would be the stored combination which is the authorized combination. Any combination entered into the lock must compare equal to the stored or authorized combination and, therefore, the combination must be retrieved accurately from the memory.
If the calculated CRC byte and the retrieved CRC byte associated with the data read from the memory compare favorably, then the data bytes associated with the retrieved CRC byte are assumed to be correct and the electronic controls of the lock then further process that information and compare the retrieved combination with the combination entered into the lock. However, if the retrieved CRC byte and the calculated CRC byte do not compare, this no-compare condition serves as an indicator that there has been a failed read operation and the lock is incapable of proper operation. Accordingly, the lock will not open unless there is another combination for another user properly programmed into the lock. In the event that either there is no other combination which may be tried or the memory has been so thoroughly corrupted that any other combinations similarly are detected as errors, then the alternative is to drill the container and the lock to gain access to the lock mechanism and manipulate the lock mechanism in such a way as to open the container. Other data reading and writing validity checking techniques may be used. Alternative techniques include Longitudinal Redundancy Check (LRC), check sum, parity and Brown Peterson codes. Other techniques may be used if desired to verify the accuracy of data read or written from or to a memory.


A method of using resorbable waxes for coagulation of blood on endogenous hard tissue, especially bone, which waxes consist of waxy polyester-oligomers of hydroxybarboxylic acids which are viscous to solid at body temperature. On the basis of their structure, these waxes are degradable by endogenous metabolic mechanism, wherein the rate of degradation can be adjusted.

For mechanical blood coagulation on endogenous hard tissues, for example bone, it is customary to treat resected bone parts with bone wax. For the same reason, blocks of bone wax are also used to cover spaces filled with spongiosa.
The waxy masses used up to the present time were made, for example, of beeswax, almond oil and salicyclic acid, or beeswax and isopropyl palmitate. Relevant literature includes, for example:
Douglas, B. L.: Oral Surg., Vol. 6, p. 1195, 1953;
Selden, H. S.: Oral Surg., Vol. 29, p. 262, 1970;
Shields, T. W.: General Thoracic Surgery, Lea and Febiger, Philadelphia, 1972; and
Wolter, D. et al.: Chirug., Vol. 46, p. 459, 1975.
In general, postoperative healing proceeds without disturbance; bacterial contamination is rare.
Commonly, however, in the case of the bone waxes used for coagulation during surgery up to the present time, coverage of the implant by granulation tissue containing abundant macrophages and giant cells is observed, see D. Wolter et al., op cit. The granulation tissue becomes fibrotic within the body with the passage of time.
Direct contact between the bone and the wax does not occur. Nonspecific foreign body reactions often takes place at the spongiosa/bone wax contact zones. This inhibits the new formation of bone and promotes the development of pseudoarthroses, see Geary, I. R. et al.: Ann. Surg., Vol. 132, p. 1128, 1950 and Howard, C. C. et al.: Clin. Orthop., Vol. 63, p. 226, 1969.

Method for blood coagulation on hard tissues


A method of mounting electronic parts on a surface mounting substrate includes a step of forming a film resist layer by applying a resist with a film coating device to amounting surface of a surface mounting substrate formed with a wiring pattern including a pair of lands to mount an electronic part; precuring the formed film resist layer; exposing, by using a mask, inner side regions of the film resist layer, the inner side regions defining the exposure regions and another region defining non-exposure region; etching away the film resist layer in the non-exposure regions and forming film resist layers in the inner side regions; post curing the film resist layers; printing solder pastes in regions on the lands excluding the inner side regions; and placing the electronic part on the solder pastes and reflow-soldering thereon.

With this kind of surface mounting substrate, when reflow-soldering a chip part such as a capacitor, which has no lead wire portion, to the surface mounting substrate, the solder height to the bottom of the chip, that is, stand-off height is increased in order to relax the displacement gap between the surface mounting substrate and the chip part due to thermal strain of the surface mounting substrate.
In order to secure the stand-off height, it is heretofore known to provide a solder wetting-up suppression structure configured so that in order to prevent solder from wetting up along the end face electrodes of a substrate surface mount part such as a chip part having end face electrodes, all or one portion of the end face electrodes is covered with a material which is not wetted with the solder (refer to PTL 1).

Method of mounting electronic parts on surface mounting substrate using a film resist standoff

FUJI ELECTRIC FA COMPONENTS & SYSTEMS CO., LTD.


A sample removing tool comprises two partly spherical blades which are rotatably mounted on a carrier member about parallel axes. The cutting edges of the blades face each other and a portion of the cutting edges are arranged to lie in a nominal circle. The carrier member is rotatably mounted on a support member about an axis, the axis is perpendicular to a plane containing the nominal circle and passes through the center of the nominal circle. The axes of the blades are inclined to the axis of rotation of the carrier member. The blades are rotated about their axes and the carrier member is rotated about its axis such that the cutting edges of the blades move along the circumference of the nominal circle to cut a sample from a surface of a component arranged perpendicular to and intersecting the nominal circle.

It is known from published International Patent application WO8806722A, to use a half spherical blade which rotates about an axis to provide a cutting action and the half spherical blade is articulated about an axis such that the blade follows an arcuate path to cut and separate a sample from the surface of a component.
It is also known from our prior UK Patent application GB2282778A to use a part spherical blade which reciprocates about an axis to provide a cutting action and the part spherical blade is moved through an arcuate path to cut a sample from the surface of a component.


A cell composition composed of spermatogonial stem cells, Sertoli cells, Leydig cells and optionally peritubular cells, is provided, as is a culture composition, artificial testicular construct, hydrogel composition, and device containing the same. A method for using the device as a physiologically relevant in vitro model of human testicular function to screen compounds for pharmacological or toxicological activity is also provided.

The mammalian testis maintains an elaborate communication network between several cell types and subpopulations that cooperatively drive differentiation of male germ cells to haploid gametes, and the production of androgens via the process of steroidogenesis. This dual functionality reflects activities of two distinct testicular regions, the seminiferous tubules and interstitial tissue of the testis. Primitive spermatogonia confined to the basement membrane of the seminiferous epithelium develop in close contact with Sertoli cells. As spermatogonia progress from the basement membrane into the intermediate and adluminal compartments, they differentiate into spermatocytes and spermatids, eventually giving rise to mature sperm. Steroidogenesis is the biological process of steroid hormone synthesis from cholesterol precursors. Leydig cells are located in the testicular interstitium and secrete testosterone initiating the masculinization of the fetal gonad and maintaining post-pubertal spermatogenesis/spermatogenesis. The overall efficiency and success of spermatogenesis relies on the presence of the Sertoli cell-spermatogonial stem cell niche. This relationship between the developing germ cells and the surrounding testicular environment allows for the correct spatial arrangement of cells and enables them to receive and interpret the various signals and factors necessary for spermatogonial stem cell self-renewal and germ cell differentiation.
The isolation, characterization, and culture of testicular cells from rodents have been studied (de Rooij, D. G., Proliferation and differentiation of spermatogonial stem cells. Reproduction 121:347-354 (March 2001)). Culture systems composed of two-dimensional (2D) Sertoli-germ cell co-cultures incorporating extracellular matrix components have also been described (Hofmann, M. C., et al., Immortalized germ cells undergo meiosis in vitro. Proc. Natl. Acad. Sci. USA 91:5533-5537 (1994); Wu, N. & Murono, E. A Sertoli cell-secreted paracrine factor(s) stimulates proliferation and inhibits steroidogenesis of rat Leydig cells. Molecular and Cellular Endocrinology 106:99-109 (1994); Benton, L., et al., Differentiation of Adult Leydig Cells. J. Steroid Biochem. Molec. Biol. 53:61-68 (1995)). However, in these systems, the enzymatic digestion and mechanical disruption of native tissue required to isolate, characterize, and expand the various cell types often resulted in a loss of functionality and cell-type-specific gene expression. It also produced cells with markedly divergent phenotypes when compared to the defining in vivo characteristics of the tissue from which these cells are isolated (Huh, D., et al., From 3D cell culture to organ-on-chips. Trends in Cell Biology 21745-754 (2011); Sasai, Y., Next-generation regenerative medicine: organogenesis from stem cells in 3D culture. Cell Stem Cell 12:520-530 (2013)). Complete spermatogenesis in vitro has been reported in mice using decapsulated mouse testis in a soft-agar organ-culture method (Sato, T., et al., In vitro production of fertile sperm from murine spermatogonial stem cell lines. Nat. Commun. 2:472 (2011); Sato, T., et al., In vitro production of functional sperm in cultured neonatal mouse testes. Nature 471:504-507 (2011)). However, existing in vitro models are predominately inadequate for maintaining the highly complex signaling interactions of the mammalian testis. Currently, no human in vitro system exists that is able to support the paired functionality of both spermatogenesis and steroidogenesis within the same model system. There is recognizable need for such an in vitro system particularly for use in high-throughput and first-tier drug screening applications, as the number of potential human reproductive toxicants exceed current investigative capacities. See generally Saldutti, L., et al., In Vitro Testicular Toxicity Models: Opportunities for Advancement via Biomedical Engineering Techniques. ALTEX 30(3):353-377 (2013).

Method of producing in vitro testicular constructs and uses thereof


A two part device is used in leveling and spacing tiles. The device includes two parts, a rotatable portion called a knob-cam and a fixed portion called hook-base. The hook-base includes ribs for spacing and separating tiles, and a neck portion extending through a slot opening in the knob-cam. In use, the hook-base portion is set down and tiles are laid down and spaced by the ribs of the base portion. The neck portion extends upwardly above the tiles, and is adapted to be broken away upon application of sufficient upward force or sideways force. The knob-cam includes two diametral opposed frontal action cam surfaces that engage portions of the hook when the knob-cam is rotated. The knob-cam is rotated until the tiles are secured between the knob-cam and the hook-base. This clamps the corners or edges of the tiles, making coplanar upper surfaces.

It is a problem in the art, when laying tiles on a surface, to equally level the tiles to be coplanar and space the tiles. This is applicable to laying tiles on surfaces in general, including floors, walls, ceilings, and on other surfaces which can support tiles. The term tiles should be understood as including panels, sheets, boards, paving stones, and other materials capable of being laid out in a pattern.


A circulation type media agitator mill includes a cylindrical vessel, and an agitating member arranged rotatably in the cylindrical vessel. A grinding media is contained in a grinding chamber defined between a cylindrical wall of the agitating member and a surrounding cylindrical wall of the vessel. A media-separating member is arranged coaxial with the agitating member in the inner space of the agitating member. An inlet is provided for leading material to be ground to the grinding chamber, and an outlet leads the material separated from the grinding media to the outside of the mill via the media separating member. The vessel may have a length to diameter ratio smaller than one. The cylindrical wall and hub of the agitatihg member have openings to allow the grinding chamber to communicate with the media separating chamber.

The present invention relates to a circulation type media agitator mill. The circulation type media agitator mill in accordance with this invention is appropriate for grinding or dispersing into powder a variety of small pieces of material such as ink, paint, dying material, ceramic material, metal, inorganic material, ferrite, toner, glass or pigmented paper-coating material. These materials, however, should not be understood as restrictive.
Japanese Patent Publication No. H 02-10699 shows a conventional mill of the type which has being in practical use. It comprises: a mill body which includes a grinding chamber to be filled at least partly with grinding media and material to be ground and has an inlet for material to be ground and an outlet for crushed material, an agitator shaft having an inner shaft end inside the grinding chamber, and a separating means permitting finished pulverized material to flow out of the grinding chamber to the outlet yet retaining grinding media, wherein the agitator shaft has an end portion formed with a cavity therein which is open at the inner shaft end, the end portion of the agitator shaft includes recesses distributed around the cavity and spaced from the inner shaft end, through which said grinding media from said grinding chamber may axially flow into the cavity and through the inner shaft end to flow back into the grinding chamber, and the separating means is arranged at least substantially inside the cavity.
This type of mill is so designed that the material to be ground may remain an extended length of time in the mill, excluding any short cuts to the outlet. As a natural consequence, the quotient of the lateral length "L" divided by the diameter "D" of the vessel (L/D) is in the 3 to 4 range, as seen from FIG. 1 of the publication. This provides some disadvantages: if the material to be ground is high in viscosity, or if the bead-like grinding media is of relatively small sized pieces, the grinding media is apt to be driven toward the outlet, thereby preventing the even application of the crushing power to the "to be ground" material while being rubbed, and abnormal heat generation or wearing is caused. Sometimes, the mill may be overloaded in operation until it stalls. This problem grows noticeable more and more as the bead-like grinding media reduces less and less in particle size.
In the hope of preventing appearance of short cuts and making full use of the rotary energy it has been proposed that an annular space around the grinding vessel is used as the grinding chamber, but the problem of the grinding media being localized remains unsolved.


The present invention provides an effective method for the transfection of dendritic cells by non-viral methods. The present invention provides this benefit by incubating dendritic cells and a specified transfection agent. The transfection agent comprises a polynucleotide and microparticles, with the microparticles being comprised of biodegradable polymer and cationic detergent. The dendritic cells and transfection agent are incubated for a time sufficient to transfect the dendritic cells with the polynucleotide.

The generation of an immune response involves the sensitization of helper (CD4+)(TH) and cytotoxic (CD8+)(CTL) T cell subsets through their interaction with antigen presenting cells. Antigen presenting cells express major histocompatibility (MHC)-class I or class II molecules associated with antigenic fragments (i.e., specific amino acid sequences derived from an antigen which bind to MHC I and MHC II for presentation on the cell surface). The MHC in humans is also referred to as the HLA (human leukocyte antigen) complex. The sensitized CD4+ T cells produce lymphokines that participate in the activation of B cells as well as various T cell subsets. The sensitized CD8+ T cells increase in numbers in response to lymphokines and act to destroy cells that express the specific antigenic fragments associated with matching MHC-encoded class I molecules. In the course of a tumor or viral infection, cytotoxic T cells eradicate cells expressing tumor or virus associated antigens.
Dendritic cells (DCs) are thought to be the most potent antigen presenting cells of the immune system (reviewed in Steinman, R. M. 1991. The dendritic cells system and its role in immunogenicity. Ann. Rev. Immunol. 9:271; Banchereau, J. B. and R. M. Steinman. 1998. Dendritic cells and the control of immunity. Nature. 392:245). Given their broad spectrum of roles in initiating the immune response by internalizing and processing antigens, migrating to lymphoid organs, secreting cytokines, and expressing co-stimulatory molecules required for lymphocyte signaling, it is no surprise that dendritic cells are logical targets for clinical use (Banchereau, J. B. and R. M. Steinman. 1998. Dendritic cells and the control of immunity. Nature. 392:245). By targeting antigens into dendritic cells in vivo or exposing dendritic cells to antigen ex vivo, it may be possible to enhance the immunogenicity of vaccines by eliciting helper and cytotoxic T cells, antibodies, and IL-12 for prophylactic applications, or induce T cell mediated anti-tumor responses for cancer immunotherapy. Akbari, et al. have suggested that transfection and activation of dendritic cells are key events for immunity following DNA vaccination by scarification of the ear skin in mouse models (O. Akbari, N. P., S. Garcia, R. Tascon, D. Lowrie, and B. Stockinger. 1999. DNA vaccination: transfection and activation of dendritic cells as key events for immunity. J. Exp. Med. 189:169). Anti-tumor CTL activity and protection against lethal tumor challenge in mouse models have been demonstrated using cytokine-driven bone-marrow-derived dendritic cells (BMDCs) pulsed with tumor-associated peptides (J. I. Mayordomo, T. Z., W. J. Storkus. 1995. Bone marrow-derived dendritic cells pulsed with synthetic tumour peptides elicit protective and therapeutic antitumour immunity. Nature Med. 1:1297), and whole tumor lysates (R. C. Fields, K. S., and J. J. Mule'. 1998. Murine dendritic cells pulsed with whole tumor lysates mediate potent antitumor immune responses in vitro and in vivo. Proc. Natl. Acad. Sci. USA 95:9482) transferred by the subcutaneous route.
In vitro generation of dendritic cells has been optimized sufficiently so that genetic immunotherapy based on passive transfer of dendritic cells has become an attractive target for development (N. Romani, S. G., D. Brang. 1994. Proliferating dendritic cell progenitors in human blood. J. Exp. Med. 180:83). However, in vitro transfection efficiency of dendritic cells by non-viral methods has been extremely poor (J. F. Arthur, L. H. B., M. D. Roth, L. A. Bui, S. M. Kiertscher, R. Lau, S. Dubinett, J. Glaspy, W. H. McBride, and J. S. Economou. 1997. A comparison of gene transfer methods in human dendritic cells. Cancer Gene Ther. 4:17) and has limited progress toward effective dendritic-cell-based immunotherapy. While progress has been made by the use of electroporation, the efficiency of transfection is extremely low and results in substantial loss of cell viability (V. F. I. Van Tendeloo, H.-W. S., F. Lardon, GLEE Vanham, G. Nijs, M. Lenjou, L. Hendriks, C. Van Broeckhoven, A. Moulijn, I. Rodrigus, P. Verdonk, D. R. Van Bockstaele, and Z. N. Berneman. 1988. Nonviral transfection of distinct types of human dendritic cells: high efficiency gene transfer by electroporation into hematopoietic progenitor—but not monocyte-derived dendritic cells. Gene Ther. 5:700). To date, no purely chemical method has been shown to be effective.
Particulate carriers have been used in order to achieve controlled, parenteral delivery of therapeutic compounds. Such carriers are designed to maintain the active agent in the delivery system for an extended period of time. Examples of particulate carriers include those derived from polymethyl methacrylate polymers, as well as microparticles derived from poly(lactides) (see, e.g., U.S. Pat. No. 3,773,919), poly(lactide-co-glycolides), known as PLG (see, e.g., U.S. Pat. No. 4,767,628) and polyethylene glycol, known as PEG (see, e.g., U.S. Pat. No. 5,648,095). Polymethyl methacrylate polymers are nondegradable while PLG particles biodegrade by random nonenzymatic hydrolysis of ester bonds to lactic and glycolic acids, which are excreted along normal metabolic pathways.
For example, U.S. Pat. 5,648,095 describes the use of microspheres with encapsulated pharmaceuticals as drug delivery systems for nasal, oral, pulmonary and oral delivery. Slow-release formulations containing various polypeptide growth factors have also been described. See, e.g., International Publication WO 94/12158, U.S. Pat. 5,134,122 and International Publication WO 96/37216.
Particulate carriers have also been used with adsorbed or entrapped antigens in attempts to elicit adequate immune responses. Such carriers present multiple copies of a selected antigen to the immune system and promote trapping and retention of antigens in local lymph nodes. The particles can be phagocytosed by macrophages and can enhance antigen presentation through cytokine release. For example, commonly owned, co-pending application Ser. 09/015,652, filed Jan. 29, 1998, describes the use of antigen-adsorbed and antigen-encapsulated microparticles to stimulate cell-mediated immunological responses, as well as methods of making the microparticles.
In commonly owned provisional Patent Application 60/036,316, for example, a method of forming microparticles is disclosed which comprises combining a polymer with an organic solvent, then adding an emulsion stabilizer, such as polyvinyl alcohol (PVA), then evaporating the organic solvent, thereby forming microparticles. The surface of the microparticles comprises the polymer and the stabilizer. Polynucleotides such as DNA, polypeptides, and antigens may then be adsorbed on those surfaces. See also PCT US99/17308.
Commonly owned Provisional Application 60/146,391 discloses a method of forming microparticles with adsorbent surfaces that are capable of adsorbing a variety of macromolecules including polynucleotides. In one embodiment, the microparticles are comprised of both a polymer and a detergent. The microparticles are derived from a polymer, such as a poly(α-hydroxy acid), preferably, a poly(D,L-lactide-co-glycolide), a polyhydroxy butyric acid, a polycaprolactone, a polyorthoester, a polyanhydride, a polycyanoacrylate, and the like, and are formed with detergents, such as cationic, anionic, or nonionic detergents, which detergents may be used in combination. Cationic detergents disclosed are cetrimide (CTAB), benzalkonium chloride, DDA (dimethyl dioctodecyl ammonium bromide), DOTAP, and the like. It is noted that these microparticles yield improved adsorption of viral antigens, and provide for superior immune responses, as compared to microparticles formed by a process using only PVA.
Dendritic cells can capture antigen at peripheral sites via macropinocytosis using membrane ruffling, or may also internalize antigen by receptor-mediated processes involving FcγIII, the mannose receptor, or the C-type lectin DEC-205 (reviewed in Lanzavecchia, A. 1996. Mechanisms of antigen uptake for presentation. Curr. Op. Immunol. 8:348). Thus, dendritic cells may be targeted by the capture of larger (>250 nm) particulate antigens by phagocytosis. Biodegradable polymer microspheres such as poly-lactide-co-glycolide (PLG) are readily internalized by phagocytic cells up to a diameter of 5 μm (Ikada, Y. T. et al. 1990. Phagocytosis of polymer microspheres by macrophages. Adv. Polymer. Sci. 94:107) and have been utilized as carriers for drug delivery systems.
Recently, Newman, et al. reported cytoplasmic delivery of Texas red labeled dextran encapsulated in PLGA microspheres following phagocytosis in mouse peritoneal macrophages (K. D. Newman, G. K., J. Miller, V. Chlumecky, J. Samuel. 1999. Cytoplasmic delivery of a fluorescent probe by poly(D,L lactic-co-glycolic acid) microspheres. In 1999 AAPS Annual Meeting Abstracts Online, vol. 1).
The application of synthetic biopolymers for nucleic acid delivery has proven advantageous by protecting DNA against nuclease degradation and increasing cellular uptake (C. Chavany, T. S.-B., T. Le Doan, F. Puisieux, P. Couvreur, and C. Helene. 1994. Adsorption of oligonucleotides onto polyisohexylcyanoacrylate nanoparticles protects them against nucleases and increases their cellular uptake. Pharm. Res. 11:1370).
Evidence for direct transfection of non professional antigen presenting cells mediated by PLG was recently reported by Ciftci and Su who found PLG microparticles containing a DNA:polycation complex provided controlled release of DNA and surfactant-enhanced uptake and gene expression in 293 and MCF-7 cells (K. Ciftci, J. S. 1999. DNA-PLGA microparticles: a promising delivery system for cancer gene therapy. In 1999 AAPS Annual Meeting Abstracts Online, vol. 1).
While polyalkylcyanoacrylate nanoparticles have been used to bind CTAB-oligonucleotide complexes to deliver antisense oligonucleotides to macrophage cell lines in vitro (C. Chavany, T. S.-B., T. Le Doan, F. Puisieux, P. Couvreur, and C. Helene. 1994. Adsorption of oligonucleotides onto polyisohexylcyanoacrylate nanoparticles protects them against nucleases and increases their cellular uptake. Pharm. Res. 11:1370; E. Fattal, C. V., I. Aynie, Y. Nakada, G. Lambert, C. Malvy, and P. Couvreur. 1998. Biodegradable polyalkylcyanoacrylate nanoparticles for the delivery of oligonucleotides. J. Controlled Release 53:137), these vehicles have not been shown to transfect dendritic cells with plasmids carrying recombinant genes.
Hence, there is a need in the art for an effective non-viral technique for the transfection of dendritic cells. While microparticle technology has been heretofore used for introduction of polynucleotides into cells, applicants are aware of no such technology having been used for the transfection of dendritic cells, which are notoriously resistant to transfection.

Microparticle-based transfection and activation of dendritic cells


A method implemented using a controller based device includes receiving a measured electrical signal from an electrical device of an electromechanical device and receiving a measured vibration signal from a mechanical device of the electromechanical device, coupled to the electrical device. The method further includes determining a first signal signature based on the measured electrical signal and determining a second signal signature based on the measured vibration signal. The method also includes determining a diagnostic parameter based on the first signal signature and the second signal signature and determining a fault in the mechanical device based on the diagnostic parameter.

The technology disclosed herein, generally relates to fault detection of electromechanical machines (EMM). More specifically, the subject matter relate to detection of faults in various components of a drivetrain in an electromechanical machine.
Electromechanical machines having electrical generators, motors and a drive train may generate torsional and radial vibrations due to presence of defective components such as bearings, gears, or the like. Conventionally, vibration analysis of electro mechanical machines may be performed to monitor operating conditions of the machine. Mechanical faults in electromechanical systems having a drive train may generate vibrations at the rotor rotating frequency. Analysis of rotor rotating frequency facilitates to detect mechanical faults associated with the drive train. Vibration signals may be used to effectively monitor radial vibrations. But, it has been found that vibration signals cannot detect all types of faults associated with the various components of the drive train.
Further, torsional vibrations generated by the defective drive-train components that are physically present outside of the machine may not be captured. Although, certain conventional techniques are available for determining faults in gears of the drivetrain, a bearing fault in the gearbox is not effectively determined by conventional techniques.
Therefore, there exists a need for an improved method and system for monitoring a fault condition of a mechanical device in an EMM.

Fault detection system and associated method


A surface electrode on a surface of a LED has a pad, and further, at least first-order branches linearly extending from the pad, second-order branches diverged and linearly extending from the first-order branches, and third-order branches diverged and linearly extending from the second-order branches. The pad out of the surface electrode is not in electrical contact with a underlying semiconductor layer, whereas the surface electrode and the semiconductor layer are in electrical contact with each other at ends of the highest-order branches. Also, the semiconductor layer is provided along a pattern of the surface electrode in a mesa shape. Thus, ineffective light emission underneath the surface electrode is relatively reduced so that external quantum efficiency can be improved, and moreover even shorter-wavelength light can be allowed to go out at high efficiency by omitting a current diffusion layer.

1. Field of the Invention
The present invention relates to a light-emitting diode (LED) for use of display or the like.
2. Description of the Prior Art
In recent years, there have been developed light-emitting diodes (LEDs) that emit yellow or green light using aluminium gallium indium phosphide (AlGaInP) series materials, besides those using gallium arsenide phosphide (GaAsP) series or gallium phosphide (GaP) series materials.
A prior-art AlGaInP series LED is fabricated in the following way. First, as shown in FIG. 1 which is a sectional view of the LED, on a surface of an n-type GaAs substrate 90 are stacked over all an n-type AlGaInP clad layer 91, an undoped AlGaInP light-emitting layer 92, a p-type AlGaInP clad layer 93, a p-type AlGaAs current diffusion layer 94, a p-type GaAs contact layer 95, and a p-side surface electrode 96. Next, as shown in FIG. 2 which is a plan view showing the LED, this surface electrode 96 and the p-type GaAs layer 95 are patterned by removing part of them. As a result, the surface electrode 96 is composed of a circular pad 98 for performing wire-bonding, and branches 99a, 99b, 99c, and 99d linearly extending from the pad 98 in four directions. By providing a plurality of branches 99a, 99b, 99c, and 99d in this way, it is arranged that electrical current is diffused within a LED chip as uniformly as possible. Thereafter, an n-side rear-face electrode 97 is formed on the rear face of the substrate 90. Light emitted from the light-emitting layer 92, being absorbed into the substrate 90 and the surface electrode 96, goes out of the chip through a region 100a of a chip surface 100 resulting from partially removing the surface electrode 96 and through a side face 101.
It should be noted that this LED is of double-hetero structure in which the light-emitting layer 92 is sandwiched by the two clad layers 91 and 93 greater in bandgap than the light-emitting layer 92. With this structure, to attain an effective confinement of electrons and holes into the light-emitting layer 92 by the clad layers 91 and 93, the Al composition ratio y is required to be increased to as much as 0.7 to 1 in the composition (Al.sub.y Ga.sub.1-y).sub.0.5 In.sub.0.5 P of the clad layers 91 and 93. However, if the Al composition ratio y is increased to such a value, doping a p-type or n-type element into the clad layers 91 and 93 becomes difficult so that the specific resistance of the clad layers 91 and 93 becomes difficult to lower. Therefore, in this LED, the current diffusion layer 94 is provided to prevent the current from concentrating underneath the surface electrode 96, thereby increasing the amount of light emitted in the region 100a that is not covered with the surface electrode 96.
However, the current diffusion layer 94 does not work to a sufficient extent, so that ineffective light emission underneath the surface electrode 96 is greater in amount relative to light emission in the region 100a that is not covered with the surface electrode 96. This accounts for the fact that the prior-art LED is worse in external quantum efficiency, as one problem.
Another problem is that since the wavelength of light emission is in the range of 590 nm (yellow) to 550 nm (green), there will occur light absorption in the AlGaAs current diffusion layer 94. This is attributed to the fact that even if Al.sub.x Ga.sub.1-x As was set to a composition ratio of x=1 that gives the widest bandgap, its absorption end would be 574 nm, not allowing the light of shorter wavelengths to pass through the layer. In addition, AlAs (corresponding to x=1) is susceptible to corrosion in air, unsuitable for use as the surface layer.
Another example of the prior-art AlGaInP series LEDs is such as shown in FIGS. 3 and 4. FIG. 3 shows the surface of the LED and FIG. 4 is a sectional view taken along the line IV--IV as indicated by arrows in FIG. 3. This LED is fabricated in the following way. First, as shown in FIG. 4, on a surface 180 of an n-type GaAs substrate 190 are stacked over all an n-type AlGaInP clad layer 191, an undoped AlGaInP light-emitting layer 192, a p-type AlGaInP clad layer 193, a p-type GaAs contact layer 194, and a surface electrode (e.g. AuZn) 195. Next, the stacked surface electrode 195 and the layers 194, 193, 192, and 191 are selectively removed until a substrate surface 190a is reached, leaving specified portions to provide mesa (trapezoidal) portions 200. The pattern of the mesa portions 200 (approximately identical to the pattern of the surface electrode 195) is, as shown in FIG. 3, provided in combination of a pad 198 for performing wire-bonding, lateral branches 199a and 199b extending from the pad 198, and longitudinal branches 200a, . . . , 200h crossing the lateral branches 199a and 199b. Thereafter, as shown in FIG. 4, a rear-face electrode 196 is formed on the rear face of the substrate 190.
Referring to the longitudinal branch 200h in FIG. 4 by way of example, light emitted from the light-emitting layer 192 goes out of the LED primarily through right and left side faces 201a and 201b of a mesa portion 200. This is attributed to the fact that the light beams traveling upward and downward will be absorbed into the surface electrode 195 and the substrate 190. As will be understood from this, the reason the mesa portions 200 are formed on the substrate surface 180 is to take light out of the LED efficiently by increasing the area of a light outgoing face (mesa slant face).
However, the construction of the mesa portions 200 is no more than such an arrangement that the lateral branches 199a and 199b and the longitudinal branches 200a, . . . , 200h merely cross each other, involving relatively long longitudinal lengths of the branches. On this account, most of the light emitted in the longitudinal direction (back and forth in FIG. 4) within each of the branches 200a, . . . , 200h will not reach the ends (e.g. an end 201c) of the branches, resulting in ineffective light emission. As a result, the above prior-art LED is not so good in external quantum efficiency, disadvantageously.

Light-emitting diode having a surface electrode of a tree-like form


The invention provides a family of compounds useful as anti-infective agents and/or anti-proliferative agents, for example, chemotherapeutic agents, anti-fungal agents, anti-bacterial agents, anti-parasitic agents, anti-viral agents, and/or anti-inflammatory agents, and/or prokinetic (gastrointestinal modulatory) agents, having the formula:

The evolution of strains of cells or organisms resistant to currently effective therapeutic agents is an ongoing medical problem. For example, the development of cancerous cells resistant to chemotherapeutic drugs has long been recognized as a problem in the oncology field. Once resistant cells develop, the therapeutic regime, in order to remain effective, must be modified to introduce other chemotherapeutic agents. Another example of this resistance problem is the development of strains of microbial, fungal, parasitic and viral pathogens resistant to one or more anti-infective agents. As a result, there is still a need for new anti-proliferative and anti-infective agents that are effective against strains of cells or organisms that have developed resistance to currently available agents.
In the field of anti-infective agents, a variety of different antibiotics have been developed and approved for use in humans over the years. An oxazolidinone ring containing antibiotic known as linezolid (see, compound 1), available under the trade name Zyvox®, has been approved for use as an anti-bacterial agent active against Gram-positive organisms. Unfortunately, linezolid resistant strains of organisms are already being reported (Tsiodras et al. (2001) LANCET 358: 207; Gonzales et al. (2001) LANCET 357: 1179; Zurenko et al. (1999) PROCEEDINGS OF THE 39TH ANNUAL INTERSCIENCE CONFERENCE ON ANTIBACTERIAL AGENTS AND CHEMOTHERAPY (ICAAC); San Francisco, Calif., USA, September 26–29).

Because linezolid is both a clinically effective and commercially significant anti-microbial agent, investigators have been working to develop other effective linezolid derivatives. Research has indicated that the oxazolidinone ring is important for linezolid activity. The literature commonly describes molecules having small groups substituted at the C-5 of the oxazolidinone ring, and early structure-activity relationships suggested that compounds with larger groups at the C-5 position were less active as anti-bacterial agents. As a consequence, it is believed that, in general, investigators have been reluctant to place large substituents at the C-5 position of oxazolidinone rings in anti-microbial agents.
International patent publication no. WO 01/81350 discloses a series of C-5 substituted oxazolidinones (s, general structure 2) where the acetamido group of linezolid was replaced, for example, with an optionally substituted N-linked 5-membered heteroaryl ring or an N-linked 6-membered heteroaryl ring. The 5-membered heteroaryl ring may contain either (i) one to three further nitrogen heteroatoms, or (ii) a further heteroatom selected from O and S together with an optional further nitrogen heteroatom; wherein the ring is optionally substituted on a C-atom by an oxo or thioxo group; and/or is optionally substituted on a C-atom by one or two C1-4 alkyl groups; and/or on an available nitrogen atom (provided that the ring is not thereby quaternized) by C1-4 groups. The N-linked 6-membered heteroaryl ring may contain up to three nitrogen heteroatoms in total, wherein the ring is substituted on a suitable C-atom by oxo or thioxo groups, and optionally substituted on any available C-atom by one or two C1-4 alkyl groups.

In addition, International patent publication nos. WO 99/64416 and WO 00/21960 also disclose a series of 5-substituted oxazolidinones (see, general structure 3). In particular, WO 99/64416 discloses compounds having the general structure 3, where X is —O— or —S— and HET is a C-linked 6-membered heteroaryl ring containing 1 or 2 nitrogen atoms. WO 00/21960 discloses compounds having the general structure 3, where X is —N(H)— and HET is a C-linked 5-membered heteroaryl ring containing 2 to 4 heteroatoms independently selected from N, O and S.

European Patent no. 0 097 469 B1 discloses intermediates of compound 4 which are useful in the synthesis of triazole anti-fungal agents of general structure 5. The intermediates may contain a disubstituted C-5 atom in the oxazolidinone ring, and the nitrogen atom of the oxazolidinone ring is a secondary amine.

Gregory and coworkers disclose the synthesis of a variety of oxazolidinone containing antibacterial agents (Gregory et al. (1989) J. MED. CHEM. 32: 1673–1681). Compound 6, a C-5 substituted five-membered heteroaryl derivative, was inactive as an antibacterial agent. This observation appears to be consistent with other oxazolidinone containing compounds that have the opposite stereochemical configuration at C-5 relative to that found in linezolid.

Oxazolidinone compounds similar to those of compound 8 have been formed via decomposition of substituted nitrosoureas 7 and have been useful as anticancer agents (Mulcahy et al. (1989) EUR J. CLIN. ONCOL. 5: 1099–1104; Carmiati et al. (1989) BIOCHEM. PHARMACOL. 38: 2253–2258).

U.S. Pat. No. 6,034,069 discloses a series of 3′-N-modified 6-O-substituted erythromycin ketolide derivatives similar to compound 9. The aryl group attached to the aminosaccharide moiety (represented by a 3-pyridyl group in 9) was variable, and non-aryl substituents were synthesized as well.

Published German patent application DE 196 04 223 A1 discloses oxazolidinone ring-containing compounds of the general structure 10, where R1 can be, in addition to other structures, a substituted or unsubstituted five-membered ring chosen from thienyl, furyl, pyrrolyl, pyrazolyl, thiazolyl, oxazolyl, imidazolyl and pyrrolidinyl.

U.S. Pat. No. 6,362,189 discloses antibiotic compounds having the general formula 11. To the extent that the chemical moiety denoted by the symbol "G" may be an oxazolidinone ring, the ring may be substituted with a thiocarbonyl functionality, namely a —CH2NHC(S)R1.

International patent publication no. WO 99/63937 proposes the synthesis of multivalent macrolide antibiotics comprising a portion of a macrolide antibiotic linked via a linker to a portion of another known antibacterial agent. Two of the compounds proposed, although apparently not made or tested, include those shown below having the formulas 13a and 13b.

Notwithstanding the foregoing, there is still an ongoing need for new anti-infective and anti-proliferative agents. There is also an ongoing need for new anti-inflammatory agents, and new agents to treat gastrointestinal motility disorders.

Bifunctional heterocyclic compounds and methods of making and using same

Abstract: or pharmaceutically acceptable salts, esters, or prodrugs thereof.


A method and device for enhancing the run of a web in a paper machine in which water is removed from the web by pressing the web in at least one press nip and after pressing, the web is dried in at least one dryer group applying impingement drying. The web is guided along a substantially linear path or by using a large curve radius in the dryer group applying impingement drying. In the drying stage, after the impingement drying, the web is dried in at least one dryer group having normal single-wire draw. The web is passed from the pressing stage to the drying stage as a closed draw and more particularly, from the pressing stage to the area with single-wire draw in the drying stage so that the web is constantly supported against at least one support face.

Increased running speeds of paper machines provide new problems to be solved, which problems are mostly related to the runnability of the machine. Currently web running speeds of up to about 1600 meters per minute are employed in printing-paper machines. At these speeds, the so-called closed press sections, which comprise a compact combination of press rolls arranged around a smooth-faced center roll generally operate satisfactorily.
With increasing running speeds of paper machines, the problems of runnability of a paper machine are also manifested with higher emphasis, because a web with a high water content and low strength does not endure an excessively high and sudden compression pressure impulse or the dynamic forces produced by high speeds, but web breaks and other disturbances in operation arise and cause standstills. In a modem printing-paper machine, the cost of standstill time is today about: FIM 60,000 per hour ($13,200).
Further problems manifested with increased emphasis at high speeds of paper machines, for. which problems, at least for all of them in toto, satisfactory solutions have not been found as yet, include the problems of quality related to the requirements of uniformity of the profiles of properties of the paper web both in the machine direction and in the cross direction. Uniformity of the web produced by the paper machine also affects the runnability of the entire paper machine, and it is also an important quality factor of finished paper, which is emphasized in the case of copying and printing papers with increasing speeds of copiers and printing machines and with higher requirements imposed on the uniformity of the printing result.
Recently, even speeds as high as about 40 meters per second (2400 meters per minute) have been contemplated as running speeds of paper machines. Application of running speeds as high as these, in particular in wide machines, provides ever more difficult problems to be solved of which problems, the most important ones are runnability and adequate dewatering capacity of the machine at a high speed.
With respect to the prior art related to the press section of a paper machine, reference is made to U.S. Pat. No. 5,389,205 (Pajula et al.), which is hereby incorporated by reference herein, which describes a method and device for dewatering a paper web by pressing. In this patent, a method is suggested in the manufacture of paper or board for dewatering the paper web that is being manufactured and that has been drained in the web former of the paper machine. In the disclosed method, the dewatering takes place by passing the paper web on support of fabrics that receive water through a number of successive dewatering nips so that, by the effect of the compression pressure. water is transferred out of the fiber mesh of the paper web into the spaces in the fabric that receive water and into the spaces in the hollow faces of the mobile dewatering members, such as press rolls. Further, the paper web is transferred from the forming wire onto the wire of the dryer section while constantly on support of a fabric that receives water, a transfer fabric, or any other, corresponding transfer surface as a closed draw at a speed that is higher than about 25 to about 30 meters per second. It has been considered as one of the novel aspects of this prior art method that, in the method, dewatering of the paper web is carried out by means of at least two such successive press nips of which nips at least one press nip is a so-called extended-nip zone whose length in the. machine direction is larger than about 100 mm, and the extended-nip zone is formed in connection with a mobile flexible press-band loop. The distribution of the compression pressure employed within the extended-nip press zone is regulated and/or selected both in the cross direction of the web and in the machine direction so as to set or to control the different profiles of properties of the web. Also, as the first press stage, a dewatering pressing is carried out on the web forming wire by using a press zone and a water-receiving, relatively open fabric or fabrics running through that press zone.
As known from the prior art, in multi-cylinder dryers of paper machines, twin-wire draw and/or single-wire draw is/are employed. In twin-wire draw, the groups of drying cylinders comprise two wires which press the web, one from above and the other one from below, against the heated cylinder faces of drying cylinders situated in two separated rows. Between the rows of drying cylinders, which are usually horizontal rows, the web may have free and unsupported draws which are susceptible to fluttering, which may cause web breaks, in particular as the web is still relatively moist and, therefore, has a low strength. Therefore, in recent years, ever increasing use has been made of the single-wire draw in which each group of drying cylinders comprises only one drying wire on whose support the web runs through the entire group so that the drying wire presses the web against the heated cylinder faces of the drying cylinders and the web remains at the side of the outside curve of the reversing cylinders or rolls situated between the drying cylinders. Thus, in single-wire draw, the drying cylinders are arranged outside the wire loop, and the reversing cylinders or rolls are arranged inside the loop.
With increasing running speeds of paper machines, problems of runnability have also started occurring in the area of single-wire draw, in particular in the first groups in a dryer section. In a manner known from the prior art, attempts have been made to reduce these problems by using various components of runnability, such as the Uno Run Blow Box (the current assignee's trade mark) and by replacing the lower roll by a suction roll, for example a VAC-roll. However, so far, the running speeds are not yet known up to a level at which these prior art constructions are sufficient to support the web in the beginning of the dryer section when the speeds continue to become higher.
With increasing speeds of paper machines, the runnability of a paper machine is, of course, also affected by the dryer section, whose length with the prior art multi-cylinder dryers would, at high speeds, also become intolerably long. If it is imagined that a present-day multi-cylinder dryer were used at a web speed of about 40 meters per second, it would include about 70 drying cylinders, and its length in the machine direction would be about 180 meters. In such a case, the dryer would comprise about 15 separate wire groups and a corresponding number of draws over the group gaps. It is to be assumed that, in a speed range of from about 30 to about 40 meters per second, the runnability of the prior art multi-cylinder dryers would no longer be even nearly satisfactory, but web breaks would be frequent, which would lead to a deterioration in the efficiency of the paper machine.
In a speed range of from about 30 to about 40 meters per second and at higher speeds, the prior art multi-cylinder dryers would also become uneconomical because the cost of investment of an excessively long paper machine hall would be unduly high. It can be estimated that, at present, the cost of a paper machine ball is typically about one million FIM per meter in the machine direction (about $220,000).
It is known from the prior art to use various impingement drying/through drying units for evaporation drying of a paper web, which units have been used in particular for drying tissue paper. With respect to the prior art related to this, reference is made, e.g., to U.S. Pat. Nos. 3,874,997, 3,868,780, and 5,319,863.
With respect to the prior art related to the present invention, reference is made to an article entitled "Trends in high speed machines for newsprint and groundwood papers"Pulp & Paper, Apr. 1983, pages 100-103. In this paper, among other things, a newsprint machine is described which is operated at a speed of about 1000 meters per minute and in which, in the dryer section, a web support of full width is employed without draws between the dryers. In a pre-dryer in the dryer section, vacuum boxes and vacuum rolls are arranged inside the wire in order to keep the web in contact with the belt. The web is dried in the pre-dryer in the dryer section by means of hot air to a dry solids content of from about 45% to about 50%.
With further respect to the prior art, reference is made to U.S. Pat. No. 4,361,466 which describes a method and mechanism for removing water from a web in a paper machine in which there are press members and a first dryer unit based on heating in which there is a long, continuous, endless support belt which carries the web during the first drying cycle. In the first drying cycle, the rolls and the suction zones are placed below the web and there are members that blow hot air, as well as members by whose means the air blow is directed at the web, on the first heat-treatment run or which the web is received substantially at a dry solids content of about 40% and from which the web is removed substantially at a dry solids content of about 50%. In this prior art construction, the paper. web arrives and departs as an open draw into/from the pre-drying unit.
In addition, with respect to the prior art, reference is also made to the U.S. Pat. No. 5,256,257 which describes a construction in which a non-water-receivable transfer belt runs through two press nips and transfers the web to the dryer section as a supported draw so that the web can be. heated/dried by impingement drying between the press and a group with single-wire draw.
In a manner known from the prior art, the web is passed from the press section to the dryer section so that the web has been separated from the last smooth roll in the press section and passed by means of a guide roll to the dryer section, in which case the web has had a free draw directly after the press section. This passage has proved problematic, in particular because of the increased risk of web break in this connection. In order to amend this, a closed draw has been developed from the press section to the dryer section, such a closed draw being described, for example, in U.S. Pat. No. 5,389,205 mentioned above, in which the web is passed from the press section by means of a transfer belt to a group with single-wire draw in the dryer section. As is well known to those skilled in the art, a web tightness arising in connection with an open draw improves the running quality of the web, and in closed draws of the web, attempts have been made to produce a web tightness by using a difference in speed between the different support fabrics. This has, however, produced problems because in such a case, the support fabrics are subjected to rapid wear. In paper machines having very high web running speeds an adequate web tightness has not been achieved by means of a difference in speed, in which case the web has not followed the wire in the dryer section but rather. owing to its slackness, it has caused web breaks, fluttering, and similar problems.
The wet strength and the elastic properties of a paper web depend on the dry solids contents of the web, and directly after the press section, it has been problematic to make the web sufficiently tight because the web has not been sufficiently dry thereat. For this reason, in cylinder groups with single-wire draw, which are often placed in the beginning of the dryer section, i.e., in so-called slalom-draw groups, problems have been encountered in the runnability, in particular in high-speed paper machines. As one solution, short groups of just a few cylinders have been employed in the beginning of the dryer section, so that by means of a positive difference in speed between the groups, it has been possible to maintain web tightness. This solution, however, increases the costs of investment end operation because of the increased number of wire circulations.
Moreover, when tightening of the paper by means of differences in speed between support fabrics has been employed, the paper web may be constricted unevenly, and high differences in tension applied to the web may cause problems in achievement of a sufficiently uniform quality, in particular in relation to the cross-direction profile of the paper.

Method and device for enhancing the run of a paper web in a paper machine


A method of rapid prototyping a lighting system which is at least one of folded path and multifaceted includes determining output power of the lighting system by calculating phase space density. A method of rapid prototyping a lighting system comprises ray tracing the lighting system, determining photometric quantities which describe the lighting system based on the ray tracing step, and providing a stereoscopic three-dimensional rendering of the lighting system based on the determining step. The three-dimensional renderings reveal any hidden pseudo-image artifacts in a lighting system before the lighting system is actually fabricated. A computer system for rapid prototyping a lighting system comprises a plurality of slave processors networked to a host processor. The slave processor and the master processor cooperate to ray trace the lighting system, and the slave processors perform homogeneous independent tasks. The computer architecture allows the homogeneous independent tasks to be distributed to the plurality of slave computers, so that the overall amount of time required to perform the tasks is drastically reduced. The amount of computational time required to generate useful information about a prototype lighting system is thereby reduced.

Within this application, several publications are referenced by arabic numerals within parentheses. Full citations for these, and other, publications may be found at the end of the specification immediately preceding the claims. The disclosures of all these publications in their entireties are hereby incorporated by reference into the present application for the purposes of indicating the background of the present invention and illustrating the state of the art. Additionally, the disclosures of the following U.S. Patents and patent applications are hereby incorporated by reference for purposes of indicating the state of the art with respect to backlighting systems: U.S. Pat. No. 5,390,276, entitled "Backlighting Assembly Utilizing Microprisms and Especially Suitable for Use with a Liquid Crystal Display"; U.S. Pat. No. 5,359,691, entitled "Backlighting System with a Multi-Reflection Lighting Injection System and Using Microprisms"; U.S. Ser. No. 08/595,307, entitled "LCD with Light Source Destructuring and Shaping Device"; U.S. Ser. No. 08/601,133, entitled "Liquid Crystal Display System with Collimated Backlighting and Non-Lambertian Diffusing"; U.S. Ser. No. 08/618,539, entitled "Method of Making Liquid Crystal Display System"; and U.S. Ser. No. 08/782,962, entitled "Apparatus for LCD Backlighting." Finally, the disclosures of the following U.S. Patents are hereby incorporated by reference for purposes of indicating the state of the art with respect to diffuser systems: U.S. Pat. No. 5,534,386, entitled "Homogenizer Formed Using Coherent Light and a Holographic Diffuser" and U.S. Pat. No. 5,609,939, entitled "Viewing Screen Formed Using Coherent Light."
Generally speaking, multifaceted optical systems are systems in which there are a large number of small optical elements. Examples of multifaceted systems include composite mirrors and kaleidoscopes. Folded path systems are systems in which a light ray travels in multiple directions (or in a folded path), in contrast to single axis systems in which there is just one principal direction of the light beam. (The term "folded path" is used interchangeably with the term "multiaxial".) For example, a conventional periscope is multiaxial but is not multifaceted. Backlighting systems, such as those used with laptop computer screens, are both multifaceted and multiaxial.
Ray tracing is known for modeling lighting systems. A number of computer programs are available for performing such ray tracing, including Code V, OPTICAD, Radiance, and others.
Whenever performing ray tracing for lighting systems which are multiaxial or multifaceted or both, a large amount of rays is required to accurately trace the lighting system (at least 10,000 rays, and often 1,000,000 or more). The amount of computing time required by existing ray tracing programs to perform such complex ray tracing tasks is substantial. For example, in order to perform a ray tracing involving 100,000 rays, OPTICAD requires one to ten hours of computing time using a single computer.
The amount of computing time required to perform ray tracing is even greater for a substantial number of more complicated multiaxial and/or multifaceted lighting systems. Such systems include backlighting for laptop computer screens, dome lights in automobiles, and torus lighting structures used for ignition key lighting systems. All of these more complicated lighting systems require on the order of 1,000,000 rays in order to perform an accurate ray tracing. To perform such a ray tracing, about one day of computing time is required.
In nearly every industry, an emerging trend is the trend away from mass production and toward specialized product variations for individual customers. For example, in the context of backlighting systems for laptop computer-screens, each manufacturer of laptop computers is beginning to have slightly different backlighting specifications for each type of laptop computer manufactured. As a result, all types of laptop computers do not use exactly the same backlighting system. Rather, there are slight variations in terms of size and/or performance parameters of the backlighting systems. Thus, although mass production still exists, there is a move away from the "one size fits all" mentality which has characterized manufacturing and production in the past.
As a consequence of the trend towards greater product specialization, a subsidiary trend is the trend towards rapid prototyping. Prototyping is known in the context of product development for testing a product design before a product goes into mass production. Prototyping is done to ensure that the product is acceptable and will satisfactorily meet customer needs. Previously, a substantial amount of time could be devoted to the prototyping process. Once a product was developed, it was sold on a "one size fits all" basis to customers who did not ask to have products specially developed to optimally meet their special needs. With the trend toward product specialization, it is no longer acceptable to devote a substantial amount of time to the prototyping process. Product designs change rapidly and the "shelf life" of any given design tends to be shorter. From the customer's perspective, the benefits of purchasing a specially developed product as compared to an already existing product are lost if doing so results in a substantial delay due to prototyping times. Manufacturing customers have their own production schedules which must be met.
In the case of lighting systems, as is the case generally, it is necessary to prototype each product variation. This is because the product is sufficiently complex that slightly changing even just one parameter can drastically affect the overall performance of the product.
In view of the trend towards product specialization, it is apparent that the prototyping process should take as little time as possible. Consequently, for rapid prototyping, the use of ray tracing programs which take an entire day to ray trace a single lighting system prototype is unacceptable. It usually requires about one hundred separate iterations of the prototyping process to arrive at a lighting system prototype which in all respects satisfies customer needs. If it takes one day to ray trace one prototype, and if there are one hundred iterations of the prototyping process, then the resultant length of the prototyping process is at least one hundred days. This is in conflict with the basic concept of rapid prototyping, which is to provide a final design within days or weeks and not months.
Therefore, in order to make rapid prototyping possible in the context of multiaxial and/or multifaceted lighting systems, it is apparent that the amount of time required to perform one iteration of the prototyping process needs to be reduced dramatically, e.g., by a factor of one hundred. Indeed, since more than one hundred iterations are often required to produce an acceptable prototype, it is apparent that a reduction of greater than a factor of one hundred is even more desirable.
Moreover, it should also be the case that there is only one prototyping/design stage. In other words, once computer prototyping is complete, the prototype produced should satisfy customer needs in all respects. Thus, there should be only a single fabrication stage. It is undesirable to have to fabricate a physical prototype in order to learn of hidden defects, because the process of fabricating a physical prototype is time consuming and expensive as compared to computer prototyping.
Rapid prototyping thus far has not been applied to the development of lighting systems in general, and to ray tracing in particular. Existing ray tracing programs such as Code V implement very precise single ray tracing schemes. Other programs, such as Opticad and Radiance, apply conventional statistical methods (e.g., the Monte Carlo method) to implement a statistical multiray trace algorithm. All of these programs are slow and, moreover, none of these programs transfers the data which is produced into a convenient format. For example, although these programs generate ray coordinate, direction, and density information, these programs do not convert this information into photometric quantities so that the design engineer can easily assess the qualitative performance parameters of the final product. Also, there is no known method of transferring ray tracing information into three-dimensional visual imaging when the visual image surfaces are unknown. Also, there is no known method applying computer networks to ray tracing to reduce computation time.

Method of rapid prototyping for multifaceted and/or folded path lighting systems


An engine ECU executes a program including the steps of: detecting a fuel pressure in a high-pressure fuel system (S130) if a lock-up clutch is not in a released state (NO at S100) and if a tip end temperature of an in-cylinder injector is equal to or lower than a temperature threshold value (NO at S120); calculating fuel pressure lowering ΔP as a result of fuel injection from the in-cylinder injector (S140); calculating fuel shortage amount ΔQ corresponding to fuel pressure lowering shortage (S170) if ΔP is smaller than a fuel pressure threshold (YES at S150); and injecting fuel from an intake manifold injector in an amount obtained by adding ΔQ to an amount of fuel injection from the intake manifold injector of a cylinder (S180).

1. Field of the Invention
The present invention relates to an internal combustion engine for a vehicle, and more particularly to a control device for an internal combustion engine that includes a first fuel injection mechanism (in-cylinder injector) injecting fuel into a cylinder and a second fuel injection mechanism (intake manifold injector) injecting fuel into an intake manifold or an intake port.
2. Description of the Background Art
An internal combustion engine provided with an intake manifold injector for injecting fuel into an intake manifold and an in-cylinder injector for injecting fuel into a combustion chamber, in which fuel injection from the intake manifold injector is stopped when load of the engine is lower than preset load and fuel injection from the intake manifold injector is allowed when load of the engine is higher than the preset load, is known. Generally, such an internal combustion engine includes an intake manifold injector and an in-cylinder injector in each cylinder.
Though different from the internal combustion engine having such two types of injectors, there is an internal combustion engine in which fuel injection into each cylinder is performed twice prior to one expansion stroke. For example, there is a diesel engine in which a small amount of fuel is supplied to a combustion chamber in pilot injection prior to main fuel injection and the fuel injected in pilot injection is burnt prior to main fuel injection, so that ignition delay of the fuel injected in main fuel injection is decreased, thereby preventing increase in combustion noise (knocking noise) of the internal combustion engine. A control device for such a diesel engine is represented by a fuel injection control device disclosed in Japanese Patent Laying-Open No. 2004-27910. A fuel injection apparatus includes an accumulator for storing a high-pressure fuel and a fuel injection valve connected to the accumulator and injecting the fuel stored in the accumulator into the combustion chamber of the internal combustion engine, and pilot injection from the fuel injection valve is performed prior to main fuel injection. A fuel injection control device includes pulsation detection means for detecting fluctuation in a pressure of fuel supplied to the fuel injection valve that is caused by pilot injection and correction means for calculating variation in fuel injection performance of the fuel injection valve in pilot injection based on fluctuation in the pressure and correcting an amount of fuel injection in pilot injection based on variation in the fuel injection performance such that an actual fuel injection amount in next pilot injection attains a target pilot injection amount. The correction means corrects an amount of fuel injection in main fuel injection based on calculated variation in the pilot injection performance such that an actual fuel injection amount in main fuel injection attains a target main fuel injection amount.
According to the fuel injection control device, in what is called a common rail type fuel injection apparatus including an accumulator (common rail) storing high-pressure fuel, fluctuation in the fuel pressure involved in pilot injection is detected, and variation in the fuel injection performance of each fuel injection valve during pilot fuel injection is calculated based on detected pressure fluctuation. For example, when pilot injection is performed, the pressure of fuel within a system fluctuates depending on an amount of fuel injection. Accordingly, if the amount of pilot fuel injection is reduced due to wear of a valve seat or the like, magnitude of fuel pressure fluctuation within the system at the time of pilot fuel injection is also made smaller. Therefore, variation in the fuel injection performance such as the amount of fuel injection can thus be calculated based on fluctuation in the fuel pressure during pilot fuel injection, and an injection instruction signal is corrected so as to increase an actual fuel injection amount by that variation (lowered amount), whereby the actual pilot fuel injection amount can accurately attain the target value. In addition, the amount of fuel injection is corrected also in main fuel injection, so as to further ensure prevention of deterioration in exhaust performance or generation of smoke.
The fuel injection valve provided in each cylinder and injecting fuel into the cylinder, as disclosed in Japanese Patent Laying-Open No. 2004-27910, is used to perform pilot injection and main fuel injection. The fuel injection valve injecting fuel into the cylinder, however, is provided in such a manner that its tip end projects within the combustion chamber. Accordingly, deposits may adhere to an injection hole and the fuel may not properly be injected. In such a case, a desired amount of fuel can be injected neither in pilot injection nor in main fuel injection disclosed in Japanese Patent Laying-Open No. 2004-27910, and the internal combustion engine cannot exhibit desired performance.

Control device for internal combustion engine