A diversity receiver estimates a reception weight sing signals received at a plurality of antennas, a target pattern former forms a target radiation pattern based on the estimated reception weight, a transmission pattern former forms a transmission radiation pattern with a transmission weight using an arbitrary transmission weight as an initial value, a controller limits an angle range in which formation of the target radiation pattern and formation of the transmission radiation pattern are executed, an error detector detects an error between the target radiation pattern and the transmission radiation pattern, and subjects the detected error to logarithmic transformation, an updator updates the transmission weight so as to reduce the error subjected to logarithmic transformation, and a directivity former provides a transmission signal with a directivity according to the transmission radiation pattern formed using an updated transmission weight.

The present invention relates to an adaptive-directivity transmission apparatus and adaptive-directivity transmission method that are applied to, for example, a base station apparatus in a mobile communication system.
An example of conventional adaptive-directivity transmission techniques is explained. The adaptive-directivity transmission is a technique that is studied on the premise that mainly a base station apparatus transmits a signal to a mobile station such as a portable telephone in a mobile communication system. Specifically, the base station first estimates a direction of a place where the mobile station is present based on reception weight information obtained in a reception circuit such as an adaptive array antenna provided in the base station. Then, the base station generates a directivity toward the estimated direction, and transmits a signal to the mobile station. Since the base station thus performs the adaptive-directivity transmission, it is possible to improve a reception gain in the mobile station, andfurthertoreduce interference to other mobile stations.
When this technique is used, in the case of a Time Division Duplex (hereinafter referred to as TDD) system in which transmission and reception carrier frequencies used in communications are same, it is possible to use a reception weight as a transmission weight without modifying the reception weight.
However, in the case of a Frequency Division Duplex (hereinafter referred to as FDD) system in which transmission and reception carrier frequencies used in communications are different, antenna intervals defined by a wavelength are different between a reception carrier frequency and a transmission carrier frequency. Therefore, it is not possible to obtain a directivity to be needed using the reception weight as the transmission with no modification performed. Accordingly, it is necessary to perform a correction on the reception weight due to a difference between the reception and transmission frequencies.
As methods for correcting the difference between the reception and transmission frequencies, there are following methods:
{circle around (1)} Convert reception weights into transmission weights collectively using a predetermined conversion equation in the case where an arrival direction of a received signal is recognized in advance, or where an arrival direction of a received signal is estimated;
{circle around (2)} obtain a transmission weight for forming a transmission radiation pattern (hereinafter referred to as xe2x80x9ctransmission patternxe2x80x9d) with a directivity pointing only to an arrival direction of a desired signal, using a reception radiation pattern(hereinafter referred to as xe2x80x9creception patternxe2x80x9d) ; and
{circle around (3)} obtain a transmission weight for minimizing an error between a reception pattern and a transmission pattern using a predetermined calculation equation with a negative feedback control. Thus, in the adaptive-directivity transmission in a conventional FDD system, the transmission weight is obtained from the reception weight with the predetermined equation, and then the appropriate transmission pattern is achieved.
However, in the above-described method {circle around (3)} of collectively converting, in the case where the transmission pattern obtained with the transmission weights that are collectively converted is compared to the reception pattern, the patterns of a portion around a signal arrival direction are approximate in both radiation patterns, but a difference between the transmission pattern and the reception pattern becomes large in the portion away from the signal arrival direction as the portion goes away therefrom.
Further, in the above-described method {circle around (3)} of obtaining a transmission weight for minimizing an error between a reception pattern and a transmission pattern using a predetermined calculation equation, the approximation is poor in a direction where an antenna directive gain is extremely suppressed, called null point. Furthermore, since it is necessary to examine a pattern error for all directions (0xc2x0 to 360xc2x0) on the two-dimensional plane, this method requires a lot of time and calculation amounts by the time a value of the obtained transmission weight converges.
The null point is generated to suppress the interference signal, for example, when a base station receives the interference signal against a desired signal at the time the desired signal is received from mobile station A. Therefore, since it is considered that another base station B is present at the direction of the null point, in the case where the base station performs the adaptive-directivity transmission to mobile station A, if the base station suppresses a signal transmission level to the direction of the null point, the interference in mobile station B is thereby reduced. Accordingly, it is important, for the improvement of the system performance, to obtain the transmission pattern of which the null point is approximated to that in the reception pattern.
An object of the present invention is to provide an adaptive-directivity transmission apparatus and adaptive-directivity transmission method which can improve the approximation of a transmission pattern and reception pattern at a directive antenna gain suppressed direction, while being capable of reducing a time and calculation amount required by the time a value of transmission weight converges, in the case of using the method for obtaining a transmission weight that minimizes an error between the transmission pattern and reception pattern with a predetermined calculation equation.
To achieve the above object, the adaptive-directivity transmission apparatus according to the present invention subjects the error between the transmission pattern and reception pattern to logarithmic transformation, and obtains a transmission weight that minimizes the error subjected to the logarithmic transformation. The directive antenna gain is generally represented using dB as a unit. The directive antenna gain at a null point is normally smaller than the maximum value of the directive antenna gain by 30 dB to 40 dB. Otherwise, the gain at the null point is {fraction (1/1,000)} to {fraction (1/10,000)} the maximum value in the true value. Accordingly, since the error between the transmission pattern and reception pattern around the null point becomes an extremely small value,in the adaptive-directivity transmission apparatus according to the present invention the error is calculated using dB, not the true value. In the adaptive-directivity transmission apparatus according to the present invention it is thus possible to improve the approximation of the transmission pattern and reception pattern at the directive antenna gain suppressed direction.
Further, to achieve the above object, the adaptive-directivity transmission apparatus of the present invention limits a range in which the error between the transmission pattern and reception pattern is searched to a predetermined range. In the adaptive-directivity transmission apparatus according to the present invention it is thereby possible to reduce the time and calculation amount required by the time the value of transmission weight converges.

Adaptive directivity transmission device and method

Matsushita Electric Industrial Co., Ltd.


A hearing device is configured to be worn in an ear of a user, and is configured to provide an audio signal to the user. The hearing device comprises a circuit assembly. The circuit assembly comprises a printed circuit board assembly. The printed circuit board assembly comprises a first circuit board, a second circuit board, and a third circuit board between the first and second circuit boards. The circuit assembly comprises a battery, wherein the printed circuit board assembly is folded about the battery; and an antenna comprising an antenna element, the antenna being configured for emission and reception of electromagnetic radiation at a wavelength (λ); wherein the antenna element has a first end connected to a feed, wherein the feed is provided in a portion of the first or third circuit board which is adjacent an interconnection between the first and third circuit boards.

Hearing devices are used more and more by all kinds of people. Hearing devices may be used for listening to music, having phone calls etc. Hearing devices may be hearing aids used for compensating a hearing loss of the user.
Small and compact wireless hearing devices are gaining popularity as they are easy to bring along in a bag or pocket, comfortable to wear and visually appealing.
US2016050474A discloses a circuit assembly including a printed circuit board assembly. The printed circuit board assembly includes a first circuit board, a second circuit board, and a first flexible substrate interposed between, and continuous with, the first circuit board and the second circuit board. A second flexible substrate extends from, and is continuous with, the second circuit board. One or more electronic circuits comprising electronic components are disposed along one or more of the first circuit board or the second circuit board. The printed circuit board assembly is folded about a battery, with the first circuit board adjacent to the first major face, the second circuit board adjacent to the second major face, and the first flexible substrate spanning the one or more side faces.
Hearing devices have over the later years been increasingly able to communicate wirelessly with the surroundings, including communicating with other hearing devices, remote controls and other external electronic devices, including smart phones.
To fulfil the above requirements, the hearing device need to comprise many electronic and metallic components contained in a housing small enough to fit in an ear of a user.
The many electronic and metallic components in combination with the small size of hearing device housing impose high design constraints on the radio frequency antennas to be used in hearing devices with wireless communication capabilities.
Thus, there is a need for an improved small and compact hearing device with an antenna, typically radio frequency antenna, designed to achieve connectivity with a wide range of devices to obtain good communication for all sizes and shapes of heads, ears and hair, in all environments and with as large frequency bandwidth as possible despite the space limitation and other design constraints imposed by the size requirements of the hearing device.


Techniques for multiple access differential M-ary coding applications that can be optionally aided by multiuser detection (MUD) are disclosed. An initial hopped feature decoding is performed to provide data estimates for each user represented in a received co-channel signal. Interference cancellation can then be performed using MUD, thereby providing an interference-cancelled signal. Data estimates remaining are then re-decoded. Iteration on the interference cancellation and re-decoding can be carried out to satisfy a particular rule of iteration, although iteration is not always necessary. The final decoded signal can then be provided to its destination.

Spread spectrum is a communications technique where the baseband signal bandwidth is intentionally spread over a larger bandwidth by modulating the signal with a higher-frequency "spreading" code prior to transmission. As a result, energy used in transmitting the baseband signal is spread over a wider bandwidth, and appears noiselike. The ratio between the spread baseband and the original signal is called processing gain. Typical Spread spectrum processing gains vary between 10 dB and 60 dB. A complementary de-spreading operation is performed at the receiver. Example spread spectrum techniques include frequency hopping spread spectrum (FHSS) and direct sequence spread spectrum (DSSS), each of which provide a reliable communications method for users.
In the presence of many users, however, co-channel interference degrades the performance of existing spread spectrum techniques. Media access control (MAC) must be implemented to reduce co-channel interference and to coordinate access to the channel by all interested, cooperating parties. In addition, it is desirable in some applications that the transmitted waveform has a low probability of detection (LPD) by unintended receivers, and that the transmitted waveform is resilient in the presence of jamming signals (i.e., AJ).
None of the known existing spread-spectrum techniques provide a signal that has suitable LPD and AJ performance, while simultaneously allowing for conferencing without a MAC, and easy implementation. In addition, each known technique is associated with one or more disadvantages, such as wasteful use of bandwidth in DSSS, performance degradation in the presence of burst errors, and performance degradation in the presence of interference, both hostile and non-hostile.
What is needed, therefore, is an improved differential M-ary coding scheme having one or more hopped features, where the coding scheme can optionally be combined with an iterative or non-iterative form of multiuser detection (MUD).

This patent is subject to a terminal disclaimer.

Multiuser detection aided multiple access differential M-ary coding applications

BAE Systems Information and Electronic Systems Integration Inc.


Disclosed is a hip joint socket for insertion into bone tissue, having an outer metal shell and an inner antifriction liner. The antifriction liner is fixed in the metal shell by means of a taper lock. To safeguard the socket insert and antifriction liner against misalignment and separation, and enable a non-destructive removal of the liner and replacement thereof, the angle (.alpha.) of the taper lock of the liner in the shell is between 10.degree. and 25.degree..

The invention relates to a hip joint socket for insertion into bone tissue.
Hip joint endoprostheses consist of a hip joint socket which is anchored in the pelvic bone and a ball, which is inserted into the socket for rotation therein, and is anchored to a shaft in the femur.
Hip joint sockets consist of an outer metal shell which constitutes the external shape of the implant, and an inner antifriction liner which is made of ceramic or of plastic such as an ultra-high molecular weight polyethylene (UHMWPE).
It is state of the art to fix the antifriction liner in the metal shell by means of a taper lock having an angle of about 5.degree. 43', i.e., an angle ratio of 1:10. A disadvantage of this socket is that the antifriction liner easily becomes canted when inserted into the metal shell resulting in an unequal distribution of forces which, under some circumstances, can result in a fracture of the internal antifriction liner especially if it is made of ceramic. Another important disadvantage is that after the antifriction liner or socket has been installed, the antifriction liner can no longer be removed nondestructively due to the high seizing forces. However removeability without destruction is extremely important for the surgeon. A further disadvantage is that due to the configuration of the antifriction liner and socket insert the overall size of the implant has to be made relatively large. This is a disadvantage from the medical viewpoint because either it entails significant bone loss or, if the bone wall is thin, may prevent installation of such an implant.

Cerasiv, GmbH Innovative Keramik Engineers


An anonymous information system is capable of maintaining anonymity of data while improving safety with regard to loss of anonymity caused by hacking of secret information, or the like. Conversion processing for converting from individual specifying information to anonymous individual information is split between an information providing device and an anonymity server device. Further, the manner in which the conversion processing is split is varied for each information providing device. A parameter generating device calculates Xinv to satisfy Xi×Xinv=1 mod q, a first characteristic parameter KAi=G^Xinv mod q, and a second characteristic parameter KBi=Xi. The information providing device generates a semi-anonymous individual identifier C=(KAi)^D mod P. The anonymity server device calculates an anonymous individual identifier E=(C)^KBi mod P.

(1) Field of the Invention
The present invention relates to a technology for converting information of a highly private nature into an anonymous form such that it is impossible to specify to whom the information relates, and for storing and supplying the converted information.
(2) Description of the Related Art
Medical information such as the results from diagnoses and medical examinations which have taken place in hospitals is commonly recorded together with personal information capable of specifying the patient to whom the results belong, such as a name, a date of birth, and an address, and the like. Further, grade data from examinations and the like in schools or other institutions and personal assessment data in industry are commonly stored together with students' and employees' personal information respectively. Moreover, in the case of data resulting from various types of survey, respondents' survey responses are commonly stored together with personal information.
Since this information reveals information such as who has which medical history, who obtained which grade or personal assessment, and who gave which survey response, it bears strongly upon privacy, and from the point of view of privacy protection, strict confidentiality management is required.
On the other hand, in the case of medical information, for instance, in order that statistical information, such as the number of patients afflicted with particular disease in a given year, or the like, may be acquired, and that the medical histories of particular patients may be traced and put to use in establishing new medical treatments and in preventative medicine, it is desirable to enter the medical information into a database and thereby make it available to a large number of researchers. Similarly, in the case that the information is grades and results, it is desirable that it can be used for finding statistical information such as grade distributions and the like, and thereby be of use in providing students with academic guidance, and the like.
Thus, it is desirable that information of the type described above is disclosed in the kind database that enables statistical enquiries, tracing, and the like, while protecting the privacy of the patients, the students, or the like.
Here, protecting the privacy of the patients or students is used to mean disclosing the results of medical examinations or diagnoses, or the grades, but making it impossible to specify the patients or students to whom the data belong.
In one general method conceivable as a method to fulfill the type of demands described above, data is stored in the public database only after the personal information section specifying the individual patients, individual students, or the like has been removed. In the case of medical information, for instance, each hospital removes the section containing personal information from the examination data (medical records) of patients who have been examined, and stores the remaining information in the public database. The information in the public database is disclosed to researchers, but since data specifying the origins of the patients is not included, patient privacy is protected.
However, there is a problem with this method in that if the same patient is examined at different hospitals for each of a series of medical problems, it is impossible to tell from the public database that the various clinical information belongs to the same patient since it is stored in the database with the patient's personal information removed.
One method disclosed as a method to solve this problem is capable of distinguishing clinical information belonging to the same patient while protecting patient privacy (see Japanese Laid-open Application No. 2002-312361, for instance). According to this method, the patient information is converted into an anonymous patient ID and stored in a data base, and a code table showing correspondences between the patient information and anonymous patient IDs is stored and managed. Using this method, it is possible to distinguish whether clinical information belongs to the same patient by making reference to the anonymous patient ID attached to the clinical information.
However, with this prior art, a code table showing the correspondences between the patient information and the anonymous patient IDs must be stored at the apparatus recording onto the public database. Consequently, the prior art has the problem that, if in a worst case scenario the code table were stolen from the apparatus in which it had been stored, the original patient information would be exposed by way of the anonymous patient IDs, and the anonymity of the clinical information on the data base would be completely lost.

Anonymous information system, information registering device and information storing device


A system and method for managing life cycle of a batch in a production control system in real time. The system comprises of an enterprise management system, manufacturing execution system (MES), task execution assistance (TEA) system and a production control system. The TEA system is interfaced between the MES and the production control system for executing the production request. The batch production request generated by the enterprise management system is received by the MES wherein the MES forwards the batch production request to the TEA system. The TEA system obtains information required to execute the batch production request from the production control system. Upon obtaining the information the TEA system instructs an operator to create the batch in the production control system. The production control system confirms the creation of the batch and updates real time status of the batch to the TEA system.

Batch production is a technique used in manufacturing industries, in which the object is created stage by stage over a series of workstations in a production control system. An enterprise application used in a manufacturing organization generates a production request for each of the object to be created. The manufacturing execution system (MES) manages execution of each of the production request by coordinating with the production control system.
At present lot of initiatives is happening towards integrating all the applications from enterprise applications to MES and from MES to the production control system. However, in the batch production scenario, though ERP-MES integration is realized, MES to real-time batch production control system is a challenge. So far efforts are made to integrate the real-time production control system through Object Linking and Embedding for Process Control (OPC) interface. Still integrating the batch production control system to manage overall life cycle of the batch is not achieved.
Hence, there exists a need for bridging the gap between the MES layer and the batch production control system layer to manage overall life cycle of the batch in the production control system in real time and to increase the flexibility, efficiency and transparency of the industrial production.

System and method for managing life-cycle of batch in production control system in real time


A working position measuring system, comprising a rotary laser device for irradiating and rotating a laser beam and a photodetection sensor device for receiving the laser beam and for detecting a working position, wherein the rotary laser device comprises a laser projector for projecting at least two fan-shaped beams with at least one beam tilted, and the photodetection sensor device comprises at least one photodetection unit for receiving the fan-shaped beams and an arithmetic unit for calculating an elevation angle relative to the rotary laser device based on photodetection signals produced when the photodetection unit receives the light beam.

The present invention relates to a working position measuring system for projecting a laser beam by rotary irradiation and for measuring a working position from photodetecting condition of the laser beam.
In the past, as a typical device for forming a reference plane by projecting a laser beam by rotary irradiation, a rotary laser device and a photodetection device for receiving the laser beam have been known.
The rotary laser device forms a reference plane by irradiating and rotating a laser beam with a spot-like luminous flux. For instance, by irradiating and rotating the laser beam within a horizontal plane, a horizontal reference plane can be formed. By irradiating and rotating the laser beam within a vertical plane, a vertical reference plane can be formed. By irradiating and rotating the laser beam within a tilted plane, a tilted reference plane can be formed.
The photodetection device comprises a photodetection unit for receiving and detecting the laser beam. Based on the laser beam detected by the photodetection unit, measurement is made to determine a horizontal reference position, a vertical reference position, etc.
When a conventional type working position measuring system is used in a relatively narrow space such as in a room, the photodetection device with the smaller photodetection unit is used. In order that the photodetection unit can receive the laser beam, an operator must move the photodetection device in an upward or downward direction, for instance, and a position of the photodetection device must be aligned so that the photodetection unit can receive the laser beam.
When the working position measuring system is used in a wide outdoor space for civil engineering work by using a construction machine, a range for positioning of the photodetection device with respect to the reference plane is also widened. If the photodetection unit is small, it is difficult to operate manually by the operator, and the photodetection unit is designed in larger size. For instance, when the reference plane to be formed is a horizontal reference plane, the photodetection device is equipped with a photodetection unit of several tens of cm in length in an up-to-bottom direction, and, in some cases, of more than 1 m in length.
In the construction machine represented by a bulldozer, operation control in a plane is performed by a combination operation of the rotary laser device and the photodetection device installed on the construction machine. When the operating condition of the construction machine is to be controlled, a GPS position measuring device is added in some cases, and 3 dimensional operation control is carried out using three from ground positions and elevation. By the GPS position measuring device, a position in a horizontal direction on the ground surface is detected. To detect the direction of elevation, the stable rotary laser device and the photodetection device are used.
FIG. 16 shows a rotary laser device 1 used mostly in indoor operation and a photodetection device 2 for detecting a laser beam 3 projected from the rotary laser device 1.
The photodetection device 2 is arranged, for instance, on a wall (not shown) in an area where the laser beam 3 can reach. Reference numeral 4 denotes a reference line formed by the laser beam 3, and 5 represents a setting reference line to be set at a position deviated from the reference line 4 by a predetermined distance.
FIG. 17 shows the photodetection device 2 to be used in indoor operation. The photodetection device 2 comprises a photodetection unit 6, a display unit 7 with an index for indicating whether a scanning position is at the center or above or under the center when the laser beam 3 passes through the photodetection unit 6, a buzzer 8 for issuing an alarm when the laser beam 3 concurs with the center of the photodetection unit 6, and switches 9 and 10 for switching over the setting of the display unit 7 and the buzzer 8. An index line 12 for indication is marked at a position corresponding to the height at the center of the photodetection unit 6 on the photodetection device 2.
The photodetection unit 6 is designed in rectangular shape with longer side in a vertical direction. The photodetection unit 6 has a pair of photodetection elements 13 and 14 each in form of a right-angle triangle and these two elements are divided by a diagonal line, and the index line 12 is set so as to pass through the center of the photodetection unit 6. A photodetection area of each of the photodetection elements 13 and 14 varies according to the change of the scanning position of the laser beam 3. When the laser beam 3 to form the reference plane passes through the two photodetection elements 13 and 14, each of the photodetection elements 13 and 14 produces an output, which is proportional to a ratio between the areas where the laser beam 3 is projected. A position of the reference line 4 is obtained based on this output, and the setting reference line 5 is marked at a position deviated from the reference line 4 by a predetermined distance.
Next, FIG. 18 shows the rotary laser device 1 and a photodetection device 15 when these are used on a construction machine.
The rotary laser device 1 is fixed on a tripod 16 installed at a predetermined position K, and a reference plane is formed by the laser beam 3 projected from the rotary laser device 1. The photodetection device 15 is fixed on a mounting pole 19 erected on a working tool of the construction machine, e.g. on a blade 18 of a bulldozer 17. When a distance from a ground surface at the predetermined position K to the reference plane is already known and a distance from a reference position of a photodetection unit (not shown) of the photodetection device 15 to a position of an edge 18a of the blade 18 is also already known, ground leveling operation can be carried out as per a planned plane if the development operation is performed in such manner that a photodetection position (light receiving position) of the laser beam 3 on the photodetection unit is maintained at a predetermined position.
FIG. 19 represents the photodetection device 15 to be used primarily on a construction machine.
The photodetection device 15 is fixed on the mounting pole 19 by means of pole clamps 21. A pair of photodetection units 23 (only one of them is shown) is installed on both sides of a main unit 22 of the photodetection device 15. A storage battery receiving unit 24 is arranged at a bottom of the main unit 22. The photodetection unit 23 comprises a multiple of photodetection sensors 25 arranged in a longitudinal direction. By identifying the photodetection sensor 25 receiving the laser beam 3 among the photodetection sensors 25, a photodetecting position of the laser beam 3 can be detected.
Although not shown in the figure particularly, a GPS position measuring device is installed on the construction machine, e.g. the bulldozer 17. An absolute position of the working point can be detected by the GPS position measuring device. By combining the operating position with the operating information at the operating position, 3-dimensional operation can be carried out.
In the photodetection device 2 used in indoor operation, the photodetection unit 6 is very small and of several cm in length. Unless the laser beam 3 is projected within the photodetection range of the photodetection unit 6, the reference position cannot be detected.
When a ground surface is excavated or the ground is filled with soil at a working place in accordance with the reference plane by using a construction machine, e.g. a bulldozer, ground leveling operation must be carried out in many cases on the topographical condition beyond the photodetection range of the photodetection unit 23. In the photodetection device with photodetection range of several tens of cm, photodetection or light receiving is difficult to achieve.
Further, when the GPS position measuring device is used and 3-dimensional operation with difference in height is controlled corresponding to operation zones, the photodetection range of the photodetection unit 23 must cover the changes in height of the working plane in addition to the topographical change. In this type of work, the vertical change of the reference plane crossing the photodetection unit 23 of the photodetection device 15 results in the change of excavating operation in the range of several tens of cm to nearly 1 m.
The blade 18 is moved up and down to cope with the topography, and the photodetection device 15 installed on the blade 18 may not be adequate even when the photodetection device 15 has the photodetection unit 23 of 300 mm in length, for instance. Therefore, in order to widen the photodetection range of the photodetection unit 23, it is designed sometimes in such manner that the mounting pole 19 is made longer or shorter to move the photodetection device 15 itself up or down.
However, problem arises in that the photodetection unit 23 with long length must have a multiple of the short photodetection elements 25 and is very expensive. Also, the device to move the photodetection unit 23 up and down must be designed in complicated structure including a driving unit and a control unit for the driving unit, and the device is very costly.


In an output method and output apparatus, one page of text data is divided into portions corresponding to bands of the print image of the page. Each portion of data is serially developed as a high-density image (600 dpi) on a bit map memory, and then is serially printed. One page of graphic data is, as a whole, developed as a low-density image (300 dpi) on the bit map memory. The low-density image is smoothed before output.

1. Field of the Invention
The present invention relates to an output method and an apparatus employing such a method which requires a relatively small memory capacity in order to output information received from a host computer as high-density data.
2. Description of the Related Art
Output apparatuses such as laser beam printers are generally used to output data from computers. Laser beam printers of low density, e.g. 300 dpi, have been increasingly employed because of their quiet operation, reasonable price and compact size.
Recently, the development of a higher-density printer engine unit has been undertaken in order to further upgrade the print quality. A high-density printer engine of 600 dpi has now been developed. A printer controller for such a printer engine analyzes printing information sent to it and, according to the analysis, develops the printing information over the bit map memory, at a designated density. In the known art, it is required for the printer controller to have a bit map memory capacity corresponding to the print density of the printer engine connected thereto. For example, the memory of the controller connected to a printer engine of 600 dpi is required to be four times as large as that of the controller connected to a printer engine of 300 dpi.
Since a controller for high-density printing (600 dpi) must employ a bit map memory four times as large as that employed by a controller for low-density printing (300 dpi), a high-density (600 dpi) laser beam printer employing such a controller and engine becomes rather large and expensive, especially in a situation where color or half-tone images are to be formed.


There is provided a diffraction grid which is easily produced without reducing a grid size. There is provided an optical scanning device having effects such as a chromatic aberration correction and a temperature compensation even when a short wavelength light source having a wavelength of 500 nm or less is used, and an image forming apparatus using the optical scanning device. In the optical scanning device having the diffraction grid, for which the short wavelength light source having a wavelength of 500 nm or less is used, a design order of the diffraction grid is set to a diffraction order equal to or larger than a second order to obtain a grid shape which is easily formed.

1. Field of the Invention
The present invention relates to an optical scanning device and an image forming apparatus using the same. In particular, the present invention relates to an optical scanning device that is suitably used for an apparatus such as a laser beam printer or a digital copying machine having an electrophotographic process, in which a light flux optically modulated and emitted from light source means is reflected and deflected on a polygon mirror serving as optical deflection means and then a surface to be scanned is scanned with the light flux through a scanning optical system to record image information. The present invention relates to an optical scanning device capable of providing a satisfactory image by adopting a diffraction grid for correction of chromatic aberration of magnification or temperature compensation and to an image forming apparatus using the same. In addition, the present invention relates to a color image forming apparatus which uses a plurality of optical scanning devices and is composed of a plurality of image bearing members corresponding to respective colors.
2. Related Background Art
Up to now, in an optical scanning device used for a laser beam printer (LBP) or the like, a light flux optically modulated according to an image signal and emitted from light source means is periodically deflected by, for example, an optical deflector composed of a rotating polygonal mirror (polygon mirror). The deflected light flux is converged to form a spot shape on a photosensitive recording medium (photosensitive drum) by a scanning optical system having an fθ characteristic. The surface of the recording medium is scanned with the light flux to perform image recording.
FIG. 13 is a schematic view showing a main part of a conventional optical scanning device.
In FIG. 13, a divergent light flux emitted from a light source means 1 is converted into a substantially parallel light flux by a collimator lens 3. The substantially parallel light flux is limited by a diaphragm 2 and incident into a cylindrical lens 4 having predetermined refractive power only in the sub scanning direction. Of the substantially parallel light fluxes incident into the cylindrical lens 4, the light flux within a main scanning section outgoes therefrom without changing an optical state. The light flux within a sub scanning section is converged and imaged as a substantial linear image onto a deflection surface (reflection surface) 5a of a deflecting means 5 composed of a polygon mirror.
The light flux which is deflected on the deflection surface 5a of the deflecting means 5 is guided onto a photosensitive drum surface 8 serving as a surface to be scanned through a scanning optical system 6 having an fθ characteristic. By rotating the deflecting means 5 in a direction indicated by an arrow "A", the photosensitive drum surface 8 is scanned with the light flux in a direction indicated by an arrow "B" to record image information.
Further, in order to achieve high speed scanning, a multi-beam optical scanning device that simultaneously forms a plurality of scanning lines by light fluxes from a plurality of light sources has been proposed and commercially available from various companies. FIG. 14 is a schematic view showing a main part of a multi-beam optical scanning device. Two light fluxes emitted from light sources 81 and 82 are converted into parallel light fluxes by collimator lenses 83 and 84 and then synthesized into one by a synthesizing optical element 85. The synthesized light flux forms a linear image extended in the main scanning direction near a deflection surface of a polygon mirror 87 by the action of a cylindrical lens 86 and then forms a light spot on a photosensitive drum 89 by a scanning optical system 88. Therefore, the two scanning lines can be formed by performing optical scanning once, so that extremely high speed scanning can be achieved as compared with a conventional optical scanning device. With respect to a multi-beam light source other than one using the above-mentioned synthesizing optical element, a monolithic multi-beam laser in which a large number of light emitting points exist has been produced. In the case where the monolithic multi-beam laser is used, it is unnecessary to use the synthesizing optical element. Thus, it is possible to simplify the optical system and the optical adjustment.
In an optical scanning device using a multi-beam light source, in order to eliminate a jitter caused by a wavelength difference between a plurality of light sources (variation in interval between scanning lines on the photosensitive drum surface in the main scanning direction), any countermeasure such as the appropriate selection of the light sources has been taken so as to minimize the wavelength difference between the light sources. When the jitter caused by the wavelength difference between the light sources (chromatic aberration of magnification) is corrected by the scanning optical system, a plurality of lenses having different dispersion characteristics are required. As compared with a scanning optical system that does not correct the chromatic aberration of magnification, the number of lenses generally increases to cause an increase in cost. There is a limitation with respect to the range of selection of the wavelengths of the light sources. Therefore, it is difficult that the wavelengths are made completely equal to one another. There is a problem with respect to a cost for the selection of the wavelengths. When a semiconductor laser is activated, an image quality is deteriorated by a variation in wavelength, which is called mode hopping. Thus, even in an optical scanning device other than the optical scanning device using the multi-beam light source, in order to improve the stability of the image quality, it is necessary to minimize the jitter caused by the variation in wavelength.
A semiconductor laser used as a conventional light source (as disclosed in, for example, Japanese Patent Application Laid-Open No. H10-197820 and Japanese Patent Application Laid-Open No. H10-068903) is an infrared laser (780 nm) or a visible laser (675 nm). However, in order to realize a high resolution, the development of an optical scanning device in which a minute spot shape is obtained by using a short wavelength laser having an oscillating wavelength of 500 nm or less is under way. The advantage of the use of the short wavelength laser is that a minute spot size which is about half of a conventional spot size can be achieved while an exit F number of the scanning optical system is kept equal to a conventional one. In the case where a spot size is reduced to half of the conventional spot size while using the infrared laser, it is necessary to increase the intensity of the scanning optical system to an intensity about two times larger than that in a conventional case. A focal depth is proportional to a wavelength of a used light source and to the square of the exit F number of the scanning optical system. Therefore, to obtain the same spot size, the focal depth in the infrared laser becomes equal to or smaller than about ½ of the focal depth in the short wavelength laser.
In such an optical scanning device, in order to record image information with high precision, it is necessary to preferably correct a curvature of field over the entire surface to be scanned, to have a distortion characteristic (fθ characteristic) with a constant speed, between an angle of view θ and an image height Y, and to make spot sizes on the image plane uniform at respective image heights. Various optical scanning devices or various scanning optical systems that satisfy the optical characteristics like those have been proposed up to now.
According to Japanese Patent Application Laid-Open No. H10-197820 and Japanese Patent Application Laid-Open No. H10-068903 as described above, a (temperature compensation) optical scanning device using a diffraction optical element for a scanning optical system has been proposed to reduce a focal variation on a surface to be scanned due to the correction of the chromatic aberration of magnification and an environmental variation.
In particular, in an optical scanning device using a short wavelength light source having a wavelength of 500 nm or less, a dispersion characteristic of a material used for a scanning lens is large. Therefore, the chromatic aberration of magnification becomes six times or seven times larger than that in a conventional infrared laser. Thus, in the optical scanning device using the multi-beam laser, the jitter is significantly caused in the main scanning direction to reduce the image quality.
When a blue-violet laser which is made of a material such as gallium nitride and oscillated at the wavelength of 405 nm is used to obtain a spot size which is about half of a spot size of the infrared laser, as described above, the focal depth is proportional to the wavelength. Therefore, only a depth about half the conventional depth can be allowed. Thus, along with the improvement of precision of respective parts composing the optical scanning device, a (temperature compensation) optical scanning device in which the focal variation is not caused even in the case of the environmental variation is desired.
As described below, a phase function φ for determining a grid shape is inversely proportional to the wavelength. Therefore, when a diffraction grid having the same power is designed, a grid pitch of the short wavelength laser having 500 nm or less becomes smaller than that of the conventional infrared laser.
For the above-mentioned reason, when a light flux having a short wavelength of 500 nm or less is imaged on the surface to be scanned in the optical scanning device using the short wavelength light source having a wavelength of 500 nm or less, there is a problem in that a grid size becomes smaller.
In general, as shown in FIG. 15A, a grid shape formed on a mold by mold forming is transferred to an optical resin member or an optical glass member. After that, as shown in FIG. 15B, the transferred grid shape is separated from the mold to produce the diffraction optical element. Alternatively, a method of dropping a small amount of ultraviolet curable resin on a glass substrate (lens can be also used) serving as a base and curing the grid shape similarly formed on the mold by ultraviolet light is used.
However, as the grid size becomes smaller, the following problems are caused:
it is hard to produce the mold by a cutting tool;
transfer property of the grid shape formed on the mold deteriorates; and
along with the deterioration of the transfer property, an imaging performance deteriorates and a diffraction efficiency reduces.

Optical scanning device and image forming apparatus using the same


An inhaler which comprises a base having a plurality of consecutive sealed cavities containing medicament. Foil portions are on one side attached to the base for sealing the medicament within respective associated cavities. A plurality of separating elements are attached to the other side of the foil portions, each separating element being associated with a respective cavity for separating a foil portion from that cavity. Each separating element can be moved-away from its associated cavity so that the sealing foil portion is separated from the cavity which is thereby uncovered so that medicament contained therein is enabled to become entrained in a fluid flow, and then returned with the attached foil portion to cover its associated cavity. A method of operating an inhaler is also disclosed.

There are different types of inhalers on the market. A pressurized Metered Dose Inhaler (pMDI) releases a fixed dose of substance in aerosol form. A powder inhaler generally releases a dose of powdered substance entrained in an air stream. In a powder inhaler the powder may be provided in a bulk container of the inhaler from which doses of powder are metered for dispensing. As an alternative to a bulk container, powder inhalers may comprise a single compartment or a plurality of compartments for containing discrete doses of powdered substance. Such compartments may take the form of sealed blisters in a blister pack, a cavities-containing strip joined to a sealing strip or other suitable forms.
There are different solutions to opening compartments containing discrete doses of powder. WO 01/72605 discloses different embodiments of a dose strip for use with a powder inhaler. Various opening mechanisms are disclosed. For instance, in FIG. 4 a lid strip covers spaced apart blisters. Lid tabs are attached to the lid strip over each blister. A peel strip is joined to each lid tab. Pulling of the peel strip opens the blisters. In FIG. 22 of WO 01/72605 a dose strip comprises a number of blisters containing pharmaceutical powder. Each blister is connected to a respective plunger. A blister is opened by a slider having a wedge that engages a slot on the plunger. The wedge pulls the plunger down, breaking the seal and releasing pharmaceutical powder into a flow path, for inhalation.

Inhaler comprising a base having a plurality of medicament containing sealed cavities


A semiconductor assembly which includes a carrier and a semiconductor die is mounted on a printed wiring board. The die includes a top active surface and a bottom active surface. The two active surfaces are non-coplanar. The carrier is made from layers of a ceramic material. Holes are formed through all but one of the layers. The layers are laminated into an integral substrate, and the substrate is fired. The holes form a cavity into but not through the substrate. The number of layers, lamination pressures, and firing parameters are all adjusted in response to the thickness of the die to insure that the height of cavity walls approximately equals the thickness of the die. Continuous metallization is applied in the cavity and on a top surface of the substrate. The die is bonded in the cavity, and conductive bumps are formed on the die and the metallization.

Electrical circuit designers often face the problem of needing to implement electrical circuits using as little space as is practical. Circuit space is often a valuable asset which needs to be conserved, and the miniaturization of electrical circuits often improves speed, reduces noise, and leads to other performance advantages. The packages within which semiconductors are housed play a large role in determining the space needed for implementing an electrical circuit because larger packages require more space.
Traditionally, semiconductors have been housed in packages which consume an order of magnitude or more area than the actual semiconductor die which represents the electrical component. When an electrical circuit requires several semiconductor components, the circuit requires an amount of space dictated by the components' packages and interconnections between the packages.
"Flip chip" or direct chip attachment mounting techniques are used to increase the density of electrical circuits. Flip chip mounting techniques relate to "flipping" an integrated circuit semiconductor die over and directly attaching a single active or top surface of the die to a printed wiring board. The attachment conventionally occurs through solder bumps formed on the metalized pads or contacts of the die. Since the actual semiconductor die size is so much smaller than a typical semiconductor package, tremendous improvements in electrical circuit space requirements can result.
However, various types of semiconductors have two active surfaces rather than just one. In the case of a transistor, a collector contact usually resides on one surface of the die while emitter and base contacts reside on an opposing surface of the die. In the case of a diode, an anode contact usually resides on one surface of the die while a cathode contact resides on an opposing surface of the die. Such components cannot simply be flipped over and attached to a printed wiring board because electrical coupling will not be made between the printed wiring board and one of the active surfaces.
Moreover, when electrical circuits include both planar contact devices and non-coplanar contact devices, flip chip manufacturing processes become more complicated. Such processes must be able to attach planar contact semiconductor dice to printed wiring boards using flip chip techniques and attach semiconductor packages to the printed wiring boards using conventional semiconductor package handling techniques. These complicated manufacturing processes are more expensive and more prone to errors than would be the case were the manufacturing processes required to accommodate only flip chip attachment techniques.

Leveled non-coplanar semiconductor die contacts


A valve assembly is disclosed for modulating the flow of fuel to a fuel nozzle at a high frequency or in a stepped manner to actively control combustion in a gas turbine engine which includes a valve housing defining an inlet portion for receiving fuel from a fuel source at an initial flow rate and an outlet portion for delivering fuel to a fuel nozzle at the initial flow rate or a modulated flow rate depending upon a detected combustion condition, and a mechanism disposed within the valve housing for modulating the flow rate of fuel to the outlet portion in response to a detected combustion condition.

1. Field of the Invention
The subject invention is directed to gas turbine engines, and more particularly, to a valve assembly for modulating the flow of fuel to the combustor of a gas turbine engine for actively controlling the combustion process to maintain combustion stability and otherwise optimize engine performance.
2. Background of the Related Art
Combustion instability is a significant problem in the design of low-emission, high performing combustion chambers for gas turbines. Combustion instability is generally understood as high amplitude pressure oscillations that occur as a result of the turbulent nature of the combustion process and the large volumetric energy release within the combustion chamber. Combustion instability diminishes engine system performance, and the vibrations resulting from pressure oscillations can damage hardware components, including the combustion chamber itself. Moreover, when the combustion heat release becomes in phase with and reinforces acoustic pressure waves, a thermo-acoustic instability results.
In the past, passive control methods were employed to correct combustion instability, including, for example, modifying the fuel injection distribution pattern, or changing the shape or capacity of the combustion chamber. Passive controls are often costly and limit combustor performance. More recently, active control methods have been used to correct combustion instability by modifying the pressure within the system. One way this can be done is by sensing the amplitudes and frequencies of acoustic pressure waves, and then modulating fuel injection at frequencies out of phase with the instabilities.
Currently, fuel injector flow rates are controlled by changing the fuel pressure feeding a common fuel manifold, with no individual control to each of the fuel injectors. For example, U.S. Pat. No. 6,672,071 discloses a combustion control system that includes a fuel pulsator communicating with a plurality of fuel injectors through a manifold. Fuel is pulsed to the injectors through the manifold at a frequency that promotes stable combustion.
Combustion stability could be achieved more effectively with active controls, if fuel flow could be modulated or pulsed at each fuel injector individually. Furthermore, if fuel flow could be pulsed to each fuel injector at high frequencies, the droplet size of fuel could be dramatically reduced, which would improve ignition and optimize engine performance.
It would be beneficial therefore, to provide a valve assembly for an active combustion control system for gas turbine engines, that is designed to modulate or otherwise command pulsed fuel flow to individual fuel injectors at relatively high frequencies on the order of 1000 Hz or more, so as to effectively stabilize combustion and otherwise optimize engine performance.

Valve assembly for modulating fuel flow to a gas turbine engine


Hot flashes (intense heat sensation, flushing, profuse sweating, palpitations, and/or sense of anxiety) in a menopausal woman may be substantially eliminated or ameliorated by administering to a woman in need of treatment an effective amount of ingestible material which has as substantially the only active ingredient a herbal complex. These exemplary herbal complex formula utilize a number of different species of herbs using the unique properties found in different parts of the plant, the root, the leaves, the aerial parts, the bark and the rhizomes.

It is well recognized that women in many countries (the percentage often varying from country to country, however, due to dietary and lifestyle differences) experience what are commonly termed "hot flashes" at menopause. In fact more women seek medical treatment for hot flashes then for any other menopausal complaint. Hot flashes are defined in the literature as brief (often disabling) periods of intense heat sensation, flushing, profuse sweating, palpitations and/or sense of anxiety. Current therapy in the United States and some other countries for the treatment of hot flashes is estrogen replacement. However various estrogen treatment formulas have undesirable side effects (for example as described in U.S. Pat. No. 4,096,254), and usually estrogen replacement is not a practical or viable option for women who have had cancer or who are at high cancer risk levels for cancers that are affected by hormone levels. Also estrogen replacement is considered undesirable by some individuals, and a less extreme treatment medicine is desired by many.
According to the present invention, various herbal complexes are provided which can be administered to practice a method of substantially eliminating or ameliorating hot flashes. According to one aspect of the present invention this method comprises the step of administrating to a menopausal woman in need of treatment ingestible material that consists essentially of a complex herbal formulation in an amount effective to substantially eliminate or ameliorate brief periods of intense heat sensation, flushing, profuse sweating, palpitations, and for sense of anxiety (hot flashes). The complex herbal formulation is essentially free of human or animal origin estrogen or other female hormones. Substantially inert ingredients may also be added to the complexes to affect their taste, bulk, texture, or other attributes.
While a number of herbal complexes may achieve pharmacologically effective results according to the invention, three particular pharmacologically effective compositions have been identified. The first pharmacologically effective composition comprises a mixture of Curculigo orchioides, Epimedium grandiflorum, Angelica sinensis, Morinda officinalis, Anemarrhena asphodeloides, Phellodendron amurense, Leonurus heterophyllus and Millettia dielsiana, in a pharmacologically effective amount. The second formulation comprises a pharmacologically effective composition comprising a mixture of Glycyrrhizae uralensis, Glycyrrhizae glabra, Astragalus membraneaceus, Poria cocos, Atractylodes lancea, Saussurea lappa, Polygala tenuifolia, Gardenia jasminoides, Cinnamomum cassia, Ziziphus jujuba, Panax ginseng, and Angelica sinensis, in a pharmacologically effective amount. A third pharmacologically effective composition comprises a mixture of Paeonia suffruticosa, Lycium chinense, Paeonia lactiflora, Paeonia lactiflora, Rehmannia glutinosa, Artemisia apiacea, Poria cocos, Phellodendron amurense, Bupleurum scorzoneraefolium, Coptis chinensis, and Cinnamomum cassia, in a pharmacologically effective amount.
The formulations according to the invention may be administered in any conventional form including tablets, capsules, elixirs, as additives to food or beverages, or even can be made into a tea. The administered amount may vary widely depending upon the particular individual, but daily dosages of between 500-2000 mg are normally effective. Not all intensity, frequency, or both of most of the manifestations will be positively impacted.

Using complex herbal formulations to treat hot flashes


Amino terminus-blocked peptide boronate compounds of Formulas I and II are useful for inhibiting Fibroblast Activation Protein (FAP) and other proteases, and for treating disorders mediated by FAP. Methods of using the amino terminus blocked peptide boronate compounds, and stereoisomers, tautomers, solvates and pharmaceutically acceptable salts thereof, for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions are disclosed.

After the initial tumorigenic events triggered by genetic mutations of oncogenes and tumor suppressor genes occurring within tumor cells, tumor-host interactions remain as an intrinsic property for each of the critical steps leading to cancer disease progression. Growth and metastasis of solid neoplasms require the recruitment of a supporting tumor stroma, the connective tissue framework. The stromal compartment of a tumor comprises a variety of host cells, including endothelial cells, fibroblasts, and inflammatory cells. It is becoming increasingly appreciated that these host-derived cells infiltrate into tumor tissue, interact with tumor cells, and are subsequently conscripted by tumor cells to produce an array of soluble and insoluble factors that stimulate tumor angiogenesis, growth, and metastasis. These factors include integrins and cell adhesion molecules, extracellular matrix metalloproteinase inducer, as well as fibroblast activation protein (FAP, also known as seprase) that mediate the cross-talking between tumor cells and "hijacked" host stromal cells (Yan et al (2004) Preclinica 2(6):422-426). A highly consistent trait of tumor stromal fibroblasts in most epithelial cancers is the induction of FAP, a member of the serine protease family. Tumor-associated stromal cells can promote epithelial tumorigenesis, suggesting that stromal proteins may represent novel therapeutic targets (Bhowmick et al (2005) Current Opinion in. Genetics and Development 15:97-101; Joyce, J. A. (2005) Cancer Cell 7:513-520).
FAP is a cell surface serine protease expressed at sites of tissue remodeling in embryonic development. FAP is not expressed by mature somatic tissues except activated melanocytes and fibroblasts in wound healing or tumor stroma. FAP expression is specifically silenced in proliferating melanocytic cells during malignant transformation (Ramirez-Montagut et al (2004) Oncogene 23(32):5435-5446). FAP belongs to the prolyl peptidase family, which comprises serine proteases that cleave peptide substrates after a proline residue (Rosenblum et al (2003) Current Opinion in Chemical Biology 7(4):496-504; Sedo et al (2001) Biochimica et biophysica acta 1550(2):107-116; Busek et al (2004) Intl. Jour. of Biochem. & Cell Biol. 36:408-421). The prolyl peptidase family also includes dipeptidyl peptidase IV (DPP IV; also termed CD26), DPP7 (DPP II; quiescent cell proline dipeptidase), DPP8, DPP9, and prolyl carboxypeptidase (PCP; angiotensinase C). More distant members include prolyl oligopeptidase (POP or prolyl endopeptidase (PEP); post-proline cleaving enzyme; Ito, K. et al (2004) Editor(s): Barrett, Rawlings, Woessner, Handbook of Proteolytic Enzymes (2nd Edition) 2:1897-1900, Elsevier, London, UK; Polgar, L. (2002) Cellular and Molecular Life Sciences 59, 349-362) and acylaminoacylpeptidase (AAP; acylpeptide hydrolase (APH)). Proline peptidases and related proteins contain both membrane-bound and soluble members and span a broad range of expression patterns, tissue distributions and compartmentalization. These proteins have important roles in regulation of signaling by peptide hormones, and are emerging targets for diabetes, oncology, and other indications.
FAP (seprase) was isolated from bovine serum, purified to homogeneity, and sequenced (Collins et al (2004) Intl. Jour. of Biochem. & Cell Biol. 36(11):2320-2333). The protease activity of bovine FAP in cleaving synthetic peptide substrates suggests that: (i) multiple subsites in FAP are involved in enzyme-substrate binding, with the smallest peptide cleaved being a tetrapeptide; (ii) there is high primary substrate specificity for the Pro-X bond; and (iii) there is a preference for a hydrophobic residue at the C-terminal end of the scissile bond.
It was demonstrated that FAP has both dipeptidyl peptidase and collagenolytic activity capable of degrading gelatin and type I collagen. The expression and enzyme activity of FAP in benign and malignant melanocytic skin tumors has been established, indicating a possible role for FAP in the control of tumor cell growth and proliferation during melanoma carcinogenesis (Huber et al (2003) Jour. of Investigative Dermatology 120(2):182-188), colorectal cancer (Satoshi et al (2003) Cancer letters 199(1):91-98), and breast cancer (Goodman et al (2003) Clinical & Exp. Metastasis 20(5):459-470), as well as all of breast, colon, and lung cancer (Park et al (1999) J. Biol. Chem. 274:36505-36512). Furthermore, FAP seems to upregulated in cirrhosis (Levi, M T et al (1999) Hepatology 29:1768-1778), fibromatosis (Skubitz, K M et al J. Clin. Lab. Med. (2004) 143(2):89-98), and rheumatoid arthritis.
The fibroblast activation protein alpha (FAPα) was discovered with a monoclonal antibody, mAb F19, that was generated in the course of a serological survey of cell surface antigens expressed on cultured human fibroblasts, sarcomas and neuroectodermal tumor cells. This antibody was used to characterize the plasma membrane-associated 95 kDa FAPα glycoprotein, to isolate the FAP-encoding cDNA, and to examine FAPα expression in a broad range of normal and neoplastic human tissues (Park, John E.; Rettig, Wolfgang J., Editor(s): Barrett, Alan J.; Rawlings, Neil D.; Woessner, J. Fred, Handbook of Proteolytic Enzymes (2nd Edition) (2004) 2:1913-1917, Publisher: Elsevier, London, UK).
Maturation of blood cells via hematopoiesis involves cytokines and their regulation by the serine proteases CD26/dipeptidyl-peptidase IV (DPP-IV), as well as FAP (McIntyre et al (2004) Drugs of the Future 29(9):882-886; Ajami et al (2003) Biochemistry 42(3):694-701). The human fibroblast activation protein (FAPα) is a Mf 95,000 cell surface molecule originally identified with monoclonal antibody (mAb) F19 (Rettig et al. (1988) Proc. Natl. Acad. Sci. USA 85, 3110-3114; Rettig et al. (1993) Cancer Res. 53, 3327-3335; Rettig et al (1994) Intl. Jour. of Cancer 58(3):385-392). The FAP gene, localized to chromosome 2 in humans (Mathew et al (1995) Genomics 25(1):335-337) is a 2812 nt sequence with an open reading frame of 2277 bp conserved throughout a variety of species including mouse, hamster, and Xenopus laevis (Scanlan et al (1994) Proc. Natl. Acad. Sci. USA 91:5657-5661; Park et al (1999) J. Biol. Chem. 274:36505-36512; Niedermeyer et al (1998) Eur. J. Biochem. 254:650-654). The corresponding FAP protein product contains 759 or 760 amino acids and has a calculated molecular weight of about 88 kDa. The primary amino acid sequence is homologous to type II integral membrane proteins, which are characterized by a carboxy-terminal end that is large and corresponds to the extra-cellular domain (ECD), a hydrophobic transmembrane segment, and a short cytoplasmic tail. FAP is highly homologous to dipeptidyl peptidase IV (DDPIV) in various species, with 61% nucleotide sequence identity and 48% amino acid sequence identity to DPPIV. Although both FAP and DDPIV have peptidase (protease) activity, biochemical and serological studies show that these proteins are significantly different in their enzymatic activity with synthetic substrates as well as their functional activation of T lymphocytes (DDPIV induction) or reactive stromal fibroblasts (FAP induction (Mathew et al (1995) Genomics w5:335-337). The FAPα cDNA codes for a type II integral membrane protein with a large extracellular domain, trans-membrane segment, and short cytoplasmic tail (Scanlan et al. (1994) Proc. Natl. Acad. Sci. USA 91, 5657-5661; U.S. Pat. No. 6,846,910; WO 97/34927; U.S. Pat. No. 5,767,242; U.S. Pat. No. 5,587,299; U.S. Pat. No. 5,965,373). FAPα shows 48% amino acid sequence identity to the T-cell activation antigen CD26, also known as dipeptidyl peptidase IV (DPPIV; EC 22.214.171.124), a membrane-bound protein with dipeptidyl peptidase activity. FAPα has enzymatic activity and is a member of the serine protease family, with serine 624 being critical for enzymatic function WO 97/34927; U.S. Pat. No. 5,965,373). Seprase (FAPα) is a homodimeric 170 kDa integral membrane gelatinase whose expression correlates with the invasiveness of the human melanoma cell line LOX (Pineiro-Sanchez et al (1997) Jour. of Biol. Chem. 272(12):7595-7601), and which promotes rapid tumor growth in a mouse model of human breast cancer (Huang et al (2004) Cancer Res. 64:2712-2716). Molecular cloning of a cDNA encodes the 97 kDa subunit of seprase with a deduced amino acid sequence that predicts a type II integral membrane protein with a cytoplasmic tail of 6 amino acids, followed by a transmembrane domain of 20 amino acids and an extracellular domain of 734 amino acids. The carboxyl terminus contains a putative catalytic region (approximately 200 amino acids) which is homologous (68% identity) to that of the nonclassical serine protease dipeptidyl peptidase IV (DPPIV). The conserved serine protease motif G-X-S-X-G is present as G-W-S-Y-G. However, sequence analysis of seprase cDNA from LOX and other cell lines strongly suggests that seprase and human fibroblast activation protein α (FAPα) are products of the same gene and are essentially identical (Goldstein et al (1997) Biochimica et Biophysica Acta 1361(1):11-19).
FAPα is selectively expressed in reactive stromal fibroblasts of many histological types of human epithelial cancers, granulation tissue of healing wounds, and malignant cells of certain bone and soft tissue sarcomas. Normal adult tissues are generally devoid of detectable FAPα (Chen et al (2003) Adv. Exp. Med. Biol. 524:197-203), but some fetal mesenchymal tissues transiently express the molecule. In contrast, most of the common types of epithelial cancers, including >90% of breast, non-small-cell lung, and colorectal carcinomas, contain FAPα-reactive stromal fibroblasts. These FAPα+ fibroblasts accompany newly formed tumor blood vessels, forming a distinct cellular compartment interposed between the tumor capillary endothelium and the basal aspect of malignant epithelial cell clusters (Welt et al. (1994) J. Clin. Oncol. 12(6), 1193-1203). While FAPα+ stromal fibroblasts are found in both primary and metastatic carcinomas, the benign and premalignant epithelial lesions tested, such as fibroadenomas of the breast and colorectal adenomas, only rarely contain FAPα+ stromal cells. Based on the restricted distribution pattern of FAPα in normal tissues and its uniform expression in the supporting stroma of many malignant tumors, clinical trials with 131I-labelled mAb F19 have been initiated in patients with metastatic colon carcinomas (Tanswell et al (2001) British Jour. of Clin. Pharm. 51(2):177-180). Evidence for the promotion of tumor growth by murine FAP, and inhibition of tumor growth by antibody inhibitors of FAP was demonstrated by Cheng et al (2002) 62:4767-4772. Human FAP was expressed and targetted by 131I-labelled humanized anti-FAP mAb in a human skin/severe combined immunodeficient mouse breast cancer xenograft model (Tahtis et al (2003) Molecular Cancer Therapeutics 2(8):729-737).
A high-resolution X-ray crystal structure of the extracellular domain of FAPα revealed a difference from DPP-IV in their active sites. Kinetic analysis of an active site mutant of FAPα, A657D, with dipeptide substrates showed an increase in the rate of cleavage for a free amino terminus substrate but a decrease for the corresponding N-benzyloxycarbonyl substrate, relative to wild type FAPα (Aertgeerts et al (2005) J. Biol. Chem., April; 10. 1074/jbc.C500092200).
Four completely human antibody derivatives (single-chain-antibody fragments, scFvs) with specificity for FAP as a general tumor stroma marker were isolated by guided selection. Highly diverse IgG, IgM and IgD isotypes comprising heavy-chain variable domain libraries were generated using cDNAs derived from diverse lymphoid organs of a multitude of donors (Schmidt et al (2001) European Jour. of Biochemistry 268(6):1730-1738). Other recombinant FAP-binding proteins with framework modifications have been expressed (U.S. Pat. No. 6,455,677). Although attempts to fully block FAP activity with antibodies have not been successful (Cheng, et al (2004) Abrogation of Fibroblast Activation Protein Enzymatic Activity Attenuates Tumor Growth. In. American Association for Cancer Research, 95th Annual Meeting, Orlando, Fla.), Sibrotuzumab, a humanized monoclonal antibody directed against FAP, is in human clinical trials for cancer therapy (Kloft et al (2004) Investigational New Drugs 22(1):39-52; Scott et al (2003) Clinical Cancer Research 9(5): 1639-1647; Cheng et al (2003) Clinical Cancer Research 9(5):1590-1595; Hofheinz et al (2003 February) Onkologie 26(1):44-8).
The amino boronic dipeptide (talabostat, PT-100, Val-boro-Pro; Point Therapeutics), a dipeptidyl peptidase (DPP) inhibitor, has been shown to up-regulate gene expression of certain cytokines in hematopoietic tissue via a high-affinity interaction, which appears to involve fibroblast activation protein (US 2003/0158114; US 2004/0152192; Adams et al (2004) Cancer Research 64(15):5471-5480; Jones et al (2003) Blood 102(5):1641-1648). Because FAP is also expressed in stroma of lymphoid tissue and tumors, the effect of PT-100 on tumor growth was studied in mice in vivo although PT-100 has no direct cytotoxic effect on tumor cells in vitro. Oral administration of PT-100 to mice slowed growth of syngeneic tumors derived from fibrosarcoma, lymphoma, melanoma, and mastocytoma cell lines. Treatment of mice with PT-100 resulted in tumor growth attenuation in a tumor model characterized by murine FAP expression in the surrounding tumor stromal fibroblasts (Cheng et al (2005) Mol. Cancer Ther. 4(3):351-60). However, PT-100 is not FAP-specific because it also inhibits DPP-8 and DPP-9. In addition, PT-100 demonstrates a self-inactivation mechanism by intramolecular cyclization of the N-terminus amine and the boronate group. A phase I/II human clinical study has been initiated to test the safety and efficacy of talabostat in combination with RITUXAN® (Genentech, Inc.) in patients with hematologic malignancies, such as non-Hodgkin's lymphoma and chronic lymphocytic leukemia. Other inhibitors targeting prolyl peptidases, include: Val-BoroPro compounds (Flentke et al (1991) Proc. Natl. Acad. Sci. USA 88:1556-1559; Coutts et al (1996) J. Med. Chem. 39:2087-2094; Shreder et al. (2005) Bioorganic and Medicinal Chemistry Letters 15:4256-4260); N-acyl-Gly-BoroPro compounds (Edosada et al (2006) Jour. Biological Chem. 281(11):7437-7444); N-alkyl-Gly-BoroPro compounds (Hu, et al (2005) Bioorganic and Medicinal Chemistry Letters 15:4239-4242); 1-(2′-aminoacyl)-2-cyanopyrrolidine compounds (WO 2001/040180); and Boro-norleucine compounds (Shreder et al (2005) Bioorganic and Medicinal Chemistry Letters 15:4256-4260).
Peptidic prodrugs which are FAP cleavage substrates have been reported to be converted to cytotoxic or cytostatic metabolites by the sequence selective cleavage of FAP (U.S. Pat. No. 6,613,879; US 2003/021979; US 2003/0232742; US 2003/0055052; US 2002/0155565). Peptide proline-boronate protease inhibitors have been reported (Bachovchin et al (1990) Jour. Biol. Chem. 265(7):3738-3743; Flentke et al (1991) Proc. Natl. Acad. Sci. 88:1556-1559; Snow et al (1994) J. Amer. Chem. Soc. 116(24):10860-10869; Coutts et al (1996) J. Med. Chem. 39:2087-2094; U.S. Pat. No. 4,935,493; U.S. Pat. No. 5,288,707; U.S. Pat. No. 5,462,928; U.S. Pat. No. 6,825,169; WO 2003/092605; US 2004/0229820; WO 2005/047297). Cyclic boro-proline compounds are reported to be useful for oral administration (U.S. Pat. No. 6,355,614). An N-acetyl lysine proline boronate compound has been proposed as an antibacterial agent (U.S. Pat. No. 5,574,017).

Fibroblast activation protein inhibitor compounds and methods


A memory structure with a repair function and a repairing method thereof are provided. The memory structure has an independent main memory unit and register file design. It also incorporates a record control unit for storing the fault information of the main memory unit. Upon receiving an access command, the memory structure determines if the main memory space pointed by the access command is faulty according to the stored fault information. When the main memory space pointed by the access command is faulty, a backup memory space is selected from the register file to replace the faulty main memory space. Therefore, the present invention can provide the convenience of a modularized design and reduce the space occupation of the register file, and also improve the access efficiency of the memory.

1. Field of the Invention
The present invention relates to a memory. More particularly, the present invention relates to a memory structure with repairing function and a repairing method thereof.
2. Description of the Related Art
With rapid development in the electronic technology, information exchange has become a routine activity. Since information exchange relies heavily on media with a large storage capacity, fast-responding memories have become an indispensable storage media for all information systems. As the information flow continues to rise, the data transmission rate must also increase. Consequently, there is a constant need for an increase in the storage capacity of memory devices. In general, the yield of application specific integrated circuit (ASIC) is often affected by possible damages in the embedded memory. To increase the yield of the memory embedded ASIC and reduce the production cost, a memory with a repairing function has been developed. When a portion of the memory cells in a main memory is defective, the defective portion can be repaired using reserved memory.
In a conventional memory with repairing function, the locations of the defective bits are first recorded during a product trial period. Thereafter, a laser beam is applied to melt a fuse so that an entire row (or column) of backup memory can replace an entire row (or column) in the main memory containing faulty bits.
FIG. 1 is a block diagram of a conventional memory with repairing function. Aside from having a main memory circuit 110, the memory 100 also has a redundant memory circuit 120 for replacing an entire row or column of memory cells when some of the memory cells in a row or a column of the main memory circuit 110 are defective. Its method of operation is described in more details in the following.
First, the row (or column) address of the main memory circuit 110 containing the defective memory cells is recorded. Thereafter, a laser beam is applied to cut off the corresponding fuses inside a fuse box 130 so that the row (or column) address of the defective memory is recorded in the fuse box 130. To access this memory 100 with conventional repairing function, the access memory address A is compared with all the row (or column) addresses of the defective memory recorded in the fuse box 130 through a compare logic circuit. If the row (or column) address of the access memory is one of the row (or column) addresses of the defective memory, the compare logic circuit 140 outputs a repair signal R representing the row (or column) address of the defective memory to a routing logic circuit 150. Thereafter, the routing logic circuit 150 changes the access pathway from the defective main memory circuit 110 to a backup memory address in the redundant memory circuit 120 corresponding a the row (or column) address of the defective memory.
Obviously, the repairing function of the conventional memory 100 has the following disadvantages.
1. The compare logic circuit 140 changes the access pathway of the routing logic circuit 150 only after the compare logic circuit 140 has received the access memory address and compared with all the row (or column) addresses containing defective memory recorded in the fuse box 130. Hence, the access efficiency is very low.
2. Because the repair is achieved by replacing an entire row or column, the ratio of the redundant memory circuit 120 to main memory remains high despite of significant improvement in processing capability and reduction in defect density.
3. The memory 100 with repairing function designed according to ASIC principles normally adopts a full custom design rather than an independent and separate memory circuit module and backup memory module design. Hence, the development time is longer, the application is rather inflexible and the design cost is high.

Memory structure with repairing function and repairing method thereof


A modular storage and holder device for a plurality of flexible lines having a circular turntable arranged on a plane such as the deck of a ship and having reversibly attached thereto a central cylinder around which at least a first line is wound in carousel mode with a plurality of coaxial layers of helically superposed touching turns, internal posts serving as a winding support for at least one second flexible line itself retained by a series of second intermediate posts around which it is possible to wind at least one third flexible line, itself retained by peripheral retaining posts at the periphery of the turntable, the second and third lines being wound in rotary basket type mode having superposed pluralities of layers of juxtaposed concentric touching turns resting on a common plane.

The technical sector of the invention is more particularly the field of installing lines resting on the sea bottom, and in particular including risers having flexible pipes for extracting oil, gas, or other soluble or fusible material or a suspension of mineral material from under the sea via an underwater well head and up to a floating support, in order to develop production fields installed out at sea, off shore. The main and immediate application of the invention lies in the field of producing oil at sea.
The flexible pipes used as production or service lines for conveying liquid or gaseous hydrocarbons present great mechanical strength, in particular against internal pressure, against traction, and against flattening, and they are usually laid by means of winches or traction devices such as "caterpullers" (i.e. tensioners having crawler tracks fitted with shoes that clamp against the line and that move continuously in translation in order to entrain the line therewith), or indeed by combining both winches and caterpullers.
The traction forces applied by such caterpuller devices on a flexible pipe can be considerable when laying at great depth, and the compression forces exerted by the shoes on the line must be high enough to avoid any relative slip between the shoes and the line.
A control umbilical includes one or more hydraulic lines and/or electric cables for transmitting power and/or information.
The lines referred to as "flexible pipes" are well known in the art and they are described in standards documents published by the American Petroleum Institute (API), and more particularly under the references API 17J and API RP 17B. Such flexible pipes are manufactured and sold in particular by the supplier Coflexip France.
As a general rule, such flexible pipes comprise inner sealing layers of thermoplastic material associated with layers that withstand the pressure inside the line, generally made of steel or of composite materials. Such flexible pipes are constituted more particularly by assembling layers of tubular thermoplastic materials and strong layers of steel or of composite materials made in the form of spiral-wound strips with touching turns inside the thermoplastic pipe in order to withstand internal bursting pressure, and associated with external reinforcement over the thermoplastic tubular layer and likewise in the form of touching spiral-wound strips, but at a pitch that is longer, i.e. with a smaller helical slope angle, in particular lying in the range 15° to 55°.
In the present description, the term "undersea flexible line" is used more generally to designate a cable, an umbilical, or a pipe capable of accepting a large amount of deformation without giving rise to large return forces, and in particular a flexible pipe.
In the prior art, ships for laying flexible lines at sea are fitted with devices for storing and handling said lines as described below with reference to FIG. 4. Most conventionally, a series of winches or drums of horizontal axis have line portions wound thereon and are arranged adjacent to one another in the longitudinal direction of the ship. The various line portions are thus wound on a plurality of winches, each having a horizontal cylinder between two vertical side plates. In that type of prior art embodiment, the horizontal cylinder needs to present stiffness in bending because the weight of the wound line is taken up entirely by the cylinder.
Furthermore, the weight of the line and of the winch including its vertical side plates is transmitted in full to the motor drive for the drum. This results in the winches necessarily presenting a plate size and a windable capacity in terms of line length that are limited, particularly when the diameter of the line is larger.
With flexible lines of large diameter, such conventional storage on winches as shown in FIG. 4 is often not possible since the minimum radius of curvature of such a flexible line is very large, and in particular may be as much as 5 meters (m) or more, thereby requiring drums to be of very large size and therefore unsuitable for handling.
Thus, in practice, the diameter of the end plates does not exceed 5 m to 10 m for a drum weighing 400 (metric) tonnes (t) to 500 t corresponding to portions of line presenting lengths of less than 10 kilometers (km) and in particular lengths of 1 km to 10 km for line diameters of 50 millimeters (mm) to 300 mm, which is why it is necessary, when laying lines of great length and/or of large diameter, to make use of a large number of winches that are thus arranged adjacent to one another. Finally, connecting together the various line portions in order to constitute a complete line providing a bottom-to-surface connection represents handling operations that are relatively difficult and lengthy to perform and that require the laying ship to be out of operation for long periods of time, thus representing large costs.
Devices are also known for storing and handling flexible lines that involve using "winch" type winder devices having a cylinder on which the line is wound that is vertical, with that type of device either being placed on the deck of the ship or else installed inside the ship, generally at the bottom of a hold. Nevertheless, under such circumstances, the fact that the bottom plate of the winch is arranged horizontally over the deck of the ship means that that plate receives the load in full and needs to be supported by a support and rotation device that must present a very high degree of stiffness so as to be capable, on its own, of withstanding compression forces and also bending and/or twisting forces, since the plate constitutes a turntable that needs to be kept properly plane so that the winch can be rotated about its vertical axis in a manner that is stable and accurate; it is also necessary for said winch to be removable after it has been used in order to release the deck of the ship for other operations.
Installing such equipment is difficult, since it requires the use of powerful hoist means given that the structure carrying the turntable together with said turntable presents a weight in the range 250 t to 750 t, or even more under extreme circumstances. Thus, such equipment can be installed or removed only in a sheltered zone, generally in a port, thereby preventing the ship from being used for a period of four to five days, or even several weeks.
WO 2004/068012 describes devices for storing lines by winding them, such a device comprising a circular turntable mounted over a bottom supporting surface situated above the deck of the ship on which the line storage device is installed.
In WO 2004/068012, the line storage device operates by winding in a mixed carousel and rotary basket mode described in FIG. 4B, in which an umbilical 10422 of small diameter is wound in "basket" mode (in the meaning of the definition given in paragraph (e) below concerning a storage device of the invention), the umbilical being wound against a central cylinder of the storage device, while a line 1044 of larger diameter is wound in "carousel" mode (in the meaning of the definition given in paragraph (b) below in the definition of the modular storage device of the present invention) outside posts or other retaining means of the storage device.
Thus, given the fact that the line 10422 is wound in basket mode, the central cylinder is not covered by an end plate of diameter greater than the diameter of the cylinder. On the contrary, the top opening between the central cylinder and the peripheral means 10406 for retaining the line 10422 is empty.
In contrast, a top plate 10408 is added to the tops of the winding support elements 10406 outside which and against which the line 1044 is wound in carousel mode.
In document WO 2004/068012, by necessity, the umbilical or the line wound in basket mode around the central cylinder must accommodate a smaller minimum radius of curvature and the line must therefore present a smaller diameter.
The embodiment of the mixed storage device described in WO 2004/068012 presents the drawback of requiring a central cylinder of larger diameter when the lines stored in basket mode are of large diameter, thereby making the storage zone situated between said cylinder and the axis of the basket unusable, so the overall storage capacity is thus severely reduced compared with the storage mode of the present invention. In addition, it is more difficult to perform winding in basket mode with lines or umbilicals of small diameter since winding is not performed under tension and requires more accurate control that is therefore more difficult to perform in order to form concentric turns all lying on a common plane, particularly since the diameter of the line and the diameters of the turns are small.
EP 1 118 572 confirms the analysis given above about the difficulty of winding a multi-turn layer in basket mode, the layer comprising a plurality of concentric turns resting on a common plane and being constituted by a line of small diameter, as is required in basket mode.
In WO 2004/068012, EP 1 118 572, and WO 2009/129223 which describe devices for storing lines by winding on board a ship for laying the lines at sea and including a turntable or a bottom plate, said turntable or bottom plate of the device is situated over the deck of the ship.

Modular device for the storage and handling of a plurality of flexible pipes


Disclosed is a valve assembly in which a valve is actuated by a flexible high pressure hose in cooperation with a commonly attached linkage. The valve assembly is attachable between a fire hose and a source of high pressure fluid. The assembly allows a user to open the valve to the high pressure fluid source from a remote location.

1. Field of the Invention
The present invention relates to a valve assembly actuatable upon introducing a high pressure fluid flow into an attached flexible high pressure hose. The valve assembly is purposed for use in conjunction with fire emergency equipment.
2. Description of the Prior Art
In a fire emergency situation, there are usually few resources available for quickly controlling the spread of a fire hazard or for terminating the fire hazard at its source. Such shortage of resources relate to manpower and/or equipment combatting the fire emergency. A situation may arise where only one person is on hand to combat the fire, or if there are other people around, they may otherwise be occupied with more immediate on-site emergencies, such as rescuing human lives. In a situation where there is only a single individual and the immediate concern is to contain or put-out a fire, the individual must unreel a fire hose and transport the hose, including the fluid release nozzle, to a fire emergency site. This site is most likely at a distant location from where the fire hose originates, that is, where the fire hose was unreeled or the location of the source releasing water into the hose.
Time is also a resource to be used intelligently in an emergency situation. Having a remotely operable valve for releasing water into the fire hose would save time and allow that time to be delegated otherwise. A pressure assisted valve assembly, uncomplicated by electrical controls or compound mechanical parts, and which could be intuitively operated, would be invaluable to a user. Thus, an operation for opening the flow of water through a fire hose, while the user is at a remote location, would help facilitate the rapid and effective operation of extinguishing a fire.
In regard to the above, U.S. Pat. No. 1,255,364, issued to Henry Waibel on Feb. 5, 1918, discloses a water release valve structured and configured to be positively opened by a remote pulling action on a fire hose. Here, the end of the fire hose and its flexible collar are coupled to a valve outlet pipe. A chain is attached to the other end of the flexible collar. The length of the chain passes through a valve casing to a compound valve lever actuator. This compound valve actuator is a multi-membered actuator which opens a valve gate to allow water to flow to through the fire hose. U.S. Pat. No. 933,290, issued to William J. Clay on Sep. 7, 1909, describes a fire hose attached to a reel. The reel is axially mounted on a rotatable valve shaft. The valve connects to a hydrant. A pin associated with the reel is engageable with the valve shaft. With the pin in place, an unreeling of the fire hose would actuate the valve to an open position and allow water to flow to the fire hose.
None of the above inventions and patents, taken either singly or in combination, is seen to describe the instant invention as claimed.


The present invention relates to modified-release oral pharmaceutical compositions containing one or more active principles solubilized, suspended or embedded in a suitably formulated amphiphilicmatrix which, loaded in hydrophilic matrices, provides different release profiles.

A sustained-, delayed-, extended-, controlled- or anyway modified-release formulation can be prepared according to different known techniques:
Use of inert matrices, in which the main structural component is a highly lipophilic material having poor affinity to biological fluids, which affords some resistance to penetration of said fluids.
Use of hydrophilic matrices, in which the structural component affords a marked resistance to wetting and solubilization in biological fluids, as the system tends to form gels and to gradually swell in time.
Use of bioerodible and/or biodegradable matrices, in which the used polymers and materials gradually undergo metabolic and/or physiological degradation at certain biological sites.
Use of mixed matrices, which comprises the use of inert lipophilic matrices with hydrophilic systems or 3-matrix-systems, i.e. hydrophilic-amphiphilic-lipophilic matrices, where different interactions with different release kinetics take place.
All the above mentioned procedures suffer, however, from some drawbacks and disadvantages.
Inert matrices generally provide non-linear but exponential release kinetics of the active ingredient.
Hydrophilic matrices have at first a straight line dissolution profile then after a certain part of the active ingredient has been released, they deviate from release linearity.
Bioerodible and/or biodegradable matrices require the ideal enzyme and/or biological environment for the constant release of the drug.
Mixed matrices consist of suitably mixed lipophilic and hydrophilic matrices combined or by lipophilic, amphiphilic and hydrophilic matrices. Although being a progress as for modified release, they do not contain materials able to improve and guarantee restricted release of the drug as well as homogeneous absorption in the gastrointestinal tract, after the drug has been released.
When a modified-release formulation of a drug having either topical activity in the gastrointestinal tract or systemic activity is required, the controlled release has to be ensured from the very first moment after the administration. A somewhat homogeneous release range in time is also necessary, while ensuring, after an amount of the active ingredient has been released, the rapid activity of the drug both topically and systemically, thanks to it being present as microemulsion, solubilized or complexed.

Oral pharmaceutical compositions with modified release of the active ingredient