The present invention relates to HLA-A*02-restricted cellular epitopes within the VP1 polypeptide of human polyomaviruses, which are useful as diagnostic reagents for virus infection. Preferred peptides correspond to amino acids residues 107-116, 108-116 and 44-52 of BKV VP1, and are processed in vivo in natural infection with BKV. Effector T cell populations stimulated by the peptides represent functional CTLs as assessed by cytotoxicity and cytokine production, and are reactive against cells presenting both the BKV peptides above and the JC virus homolog sequences.

1. Technical Field
This invention relates to the field of medical sciences, in particular the field of immunology and viral immunity. Specifically, the invention relates to cellular epitopes of the VP1 polypeptide of polyomaviruses, for example BK virus, JC virus and SV40.
2. Description of the Background Art
Polyomavirus hominis 1, known as BK virus (BKV), is a ubiquitous human polyomavirus that causes asymptomatic primary infection and resides, latent, in several body sites, notably the kidney and genitourinary tract. See Stolt et al., J. Gen. Virol. 84:1499-1504, 2003. BKV, the related polyomavirus hominis 2 (also known as JC virus or JCV) and simian vacuolating virus 40 (SV40) are closely related species of the genus polyomavirus. The BKV genome is about 75% homologous overall to JCV and about 70% homologous overall to SV40.
Primary BKV infection during childhood is presumed to occur via the respiratory tract. Following infection, hematologous dissemination is postulated to occur. Persistence is preferentially within the genitourinary tract (renal epithelial cells and the lower genitourinary tract (bladder, ureters)). Chesters et al., J. Infect. Dis. 147:676-684, 1983. BKV reactivation often occurs in immunocompromised individuals such as hematopoietic stem cell transplant and kidney transplant recipients, causing clinical disease states which include hemorrhagic cystitis, ureteric stenosis and polyomavirus-associated nephropathy (PVAN, also referred to as BK virus-associated nephropathy (BKVN)). The incidence of polyomavirus-associated nephropathy, variously reported as between 1% and 8% of kidney transplant patients, has increased in recent years, concomitant with the use of newer and more potent immunosuppressive agents in transplant patients, suggesting that immune responses to BKV are important in control of the virus. Hirsch and Steiger, Lancet 3:611-623, 2003.
Polyomavirus associated nephropathy now is recognized as an important cause of allograft dysfunction in kidney transplant recipients. Binet et al., Transplantation 678:918-922, 1999; Hurault et al., Transplant Proc. 32:2760-2761, 2000; Randawa et al., Transplantation 67:103-109, 1999. With immunosuppression, viral reactivation can occur, presumably primarily from the lower genitourinary tract, and is detected as virus shed in the urine (viruria). With continued immunosuppression and other local injury within the kidney, such as rejection or calcineurin inhibitor toxicity, polyomavirus reactivation also can occur in the kidney itself, leading to viral replication, direct injury to the infected tubular epithelial cells and indirect injury manifested by inflammation and nephritis, ultimately leading to rejection of the kidney in some cases. In kidney transplant recipients, BKV reactivation is particularly associated with interstitial nephritis/nephropathy and ureteric stenosis. Nickeleit et al., J. Am. Soc. Nephrol. 10:1080-1089, 1999; Nickeleit et al., Nephrol. Dial. Transplant. 15:324-332, 2000.
Other than the antiviral agent, cidofovir, for treatment of PVAN, no other antiviral therapies are available for polyomavirus. Kadambi et al., Am. J. Transplant. 3:186-191, 2003; Scantlebury et al., Graft 5(supp):S82-S87, 2002; Vats et al., Transplantation 75:105-112, 2003. Cidofovir requires intravenous administration and is associated with considerable nephrotoxicity itself, particularly in patients with pre-existing nephrotoxicity. Based on a consensus opinion that PVAN may represent a state of relative over-immunosuppression, the current approach to managing patients with PVAN is reduction of immunosuppression. Even using this approach, however, up to 30-50% of patients with PVAN develop progressive polyomavirus infection and deterioration of kidney function, ultimately resulting in loss of the kidney allograft. Hirsch and Steiger, Lancet 3:611-623, 2004; Nickeleit et al., Nephrol. Dial. Transplant. 15:324-332, 2000; Randhawa et al., Transplantation 67:103-109, 1999. Given the limited treatment options, there is an urgent need for alternative approaches to protect against BKV reactivation and disease.
JCV also is prevalent worldwide, with about 80% of adults showing serological evidence of JCV infection. Stolt et al., J. Gen. Virol. 84:1499-1504, 2003. Most individuals are infected in childhood, without showing any symptoms. The virus remains latent in the lymphocytes, urogenital tract and brain and can reactivate in the immunocompromised, causing disease syndromes. JCV is the causative agent of progressive multifocal leukoencephalopathy (PML), a fatal degenerative disease affecting brain oligodendroglial cells seen in immunosuppressed AIDS, cancer and organ transplant recipient patients. JCV also is associated with hemorrhagic cystitis and nephritis in kidney transplant recipients.
SV40 is a closely related polyomavirus of simians which also widely infects humans and has been associated with some tumor types. This virus has a high degree of serological cross-reactivity with both BKV and JCV antigens. SV40 is believed to spread through a respiratory or fomite route and to be established as a human pathological agent. Its presumed site of persistence also is the kidney, and other tissues that give rise to SV40-associated tumors (e.g., mesothelioma, lymphoma, osteosarcoma, and certain brain tumors).
The capsid of polyomavirus is largely made up of VP1, VP2 and VP3, with each virion containing 360 copies of VP1. Two cellular epitopes of JCV VP1 have been identified, including the epitope sequences, ILMWEAVTL (JCV VP1p100-108; SEQ ID NO:3; referred to herein as "JC100") and SITEVECFL (JCV VP1p36-44; SEQ ID NO:6; referred to herein as "JC36"). Du Pasquier et al., J. Neurovirol. 7:318-322, 2001; Du Pasquier et al., J. Virol. 77:11918-11926, 2003; Du Pasquier et al., Brain 127(9):1970-1978, 2004; Du Pasquier et al., J. Virol. 78:10206-10, 2004; Koralnik et al., J. Immunol. 168:499-504, 2002; Koralnik et al., J. Virol. 75:3483-3487, 2001. CTL recognizing these epitopes have been associated with control of the virus; patients suffering from the JCV syndrome, progressive multifocal leukoencephalopathy, demonstrate a prolonged survival when they possess CTL responses to the JC100 epitope. Du Pasquier et al., Brain 127(9):1970-1978, 2004; Koralnik et al., J. Immunol. 168:499-504, 2002. BKV-specific cells also have been detected in samples from renal transplant patients. Comoli et al., Transplantation 78:1229-1232, 2004. These prior studies, which used BKV-infected cell lysates as antigens, did not identify any specific antigens or epitopes, however. BKV-specific T-cell lines have been developed from healthy seropositive individuals and kidney transplant recipients. Comoli et al., Transplantation 78:1229-1232, 2004; Comoli et al., J. Am. Soc. Nephrol. 14:3197-3204, 2003; Drummond et al., J. Med. Virol. 17:237-247, 1985; Drummond et al., J. Med. Virol. 23:331-344, 1987.
Several previous studies have shown that both JCV and BKV are common in most adult populations, but that JCV is less prevalent than BKV. Knowles et al., J. Med. Virol. 71:115-123, 2003; Padgett et al., J. Infect. Dis. 127:467-470, 1973; Taguchi et al., Microbiol. Immunol. 26:1057-1064, 1982. Knowles and colleagues reported 81% seropositivity for BKV and 35% for JCV in a survey of 2,435 sera from 1991. Knowles et al., J. Med. Virol. 71:115-123, 2003. These types of studies are complicated by substantial serological crossreactivities between antibodies to these two human polyomaviruses. Viscidi et al., Clin. Diagn. Lab Immunol. 10:278-285, 2003. However, antibody adsorption studies show that some individuals experience infection by both JCV and BKV. This is further supported by PCR studies of polyomavirus shedding in urine that indicate co-infection in a minority of patients. Bendiksen et al., J. Gen. Virol. 81:2625-2633, 2000; Hamilton et al., J. Clin. Microbiol. 38:105-109, 2000; Priftakis et al., J. Clin. Microbiol. 38:406-407, 2000; Shah et al., J. Infect. Dis. 176:1618-1621, 1997.
Knowledge of specific MHC—I restricted epitopes within BK virus antigens allows one to track virus-specific CTLs in at-risk patients and produce compositions to modify immunity to BK and related viruses such as JCV and SV40. Peptides identified as immunoreactive are useful for vaccines as well as diagnostic reagents. Vaccine peptides from viral proteins may be used for enhancing the immune system of mammals with respect to the virus in both seropositive and seronegative individuals. However, no such specific information concerning BKV epitopes has been available. There is a need in the art for compositions and methods which can be used to identify and diagnose polyomavirus-related conditions in patients and patient-derived samples, and to modify the immune response of patients in need, such as immunosuppressed patients, or any person at risk for polyomavirus infection or reactivation.


A method of controlling a component within a lithographic apparatus is presented. The component is moved relative to a reference within the lithographic apparatus by a first actuator. A second actuator that exerts a force between the component and a reaction mass is used to adjust at least one of a position, velocity and acceleration of the component relative to the reference within the lithographic apparatus.

A lithographic apparatus is a machine that applies a desired pattern onto a substrate, usually onto a target portion of the substrate. A lithographic apparatus can be used, for example, in the manufacture of integrated circuits (ICs). In that instance, a patterning device, which is alternatively referred to as a mask or a reticle, may be used to generate a circuit pattern to be formed on an individual layer of the IC. This pattern can be transferred onto a target portion (e.g., comprising part of, one, or several dies) on a substrate (e.g., a silicon wafer). Transfer of the pattern is typically via imaging onto a layer of radiation-sensitive material (resist) provided on the substrate. In general, a single substrate will contain a network of adjacent target portions that are successively patterned. Known lithographic apparatus include so-called steppers, in which each target portion is irradiated by exposing an entire pattern onto the target portion at one time, and so-called scanners, in which each target portion is irradiated by scanning the pattern through a radiation beam in a given direction (the "scanning"-direction) while synchronously scanning the substrate parallel or anti-parallel to this direction. It is also possible to transfer the pattern from the patterning device to the substrate by imprinting the pattern onto the substrate.
Within a lithographic apparatus, many moving components are controlled with extremely high accuracy. For example, it is desirable in a scanner to control the position, velocity and acceleration of the support that supports the patterning device and the support that supports the substrate. The accuracy requirements are all the more stringent because the velocities and the accelerations required may be relatively high. Combined with the relatively large mass of such structures, which is desired in order to provide sufficient stiffness, the forces involved are high, with a result that it is difficult to provide an actuation system with the required accuracy. Therefore, in the presently known systems, a long-stroke stage is provided that may be moved relative to the base frame of the lithographic apparatus with the required velocity and acceleration. A short-stroke stage is mounted to the long-stroke stage and supports the substrate support or the support for the patterning device. The short-stroke stage, as its name suggests, has a limited range of movement. However, it is possible to control the accuracy of the position, velocity and/or acceleration of the substrate support or support for the patterning device to the required level of accuracy. Accordingly, the short-stroke stage is used to correct the inaccuracies that may be introduced by the long-stroke stage. These may be caused by, for example, cogging, motor force factor variations and external disturbance forces, for example caused by the vibration of other components within the lithographic apparatus and/or the connection of cables or conduits for gas supplies to the support for the substrate or patterning device.
However, in order to provide the desired accuracy, it is desirable that the short-stroke stage be able to provide relatively high accelerations. For example, a short-stroke actuator for a substrate support may need to accelerate a 20 kg substrate support up to an acceleration of 20 m/s2, requiring about 400 N of force. Consequently, the short-stroke actuator is relatively bulky and requires considerable thermal conditioning in order to avoid distortion of the substrate support and other temperature sensitive components due to heating.

Lithographic apparatus, method of controlling a component of a lithographic apparatus and device manufacturing method


A substrate including a first patterned metallic layer, a second patterned metallic layer and an insulator is provided. One side of the first patterned metallic layer is connected to a corresponding side of the second patterned metallic layer. The first patterned metallic layer and the second patterned metallic layer are formed as a whole. The insulator fills the gaps in the first patterned metallic layer and the gaps in the second patterned metallic layer.

1. Field of the Invention
The present invention relates to a substrate core and method for fabricating the same. More particularly, the present invention relates to a substrate core having high thermal conductivity and high electrical conductivity and a method of fabricating the same.
2. Description of the Related Art
The information technology products in this business world have becoming increasingly important. As new models continue to be introduced, current electronic products not only offer diversifying functions but have developed to be more miniaturized, with the operating performance upgraded to be more stable. As the electronic products become miniaturized, heat dissipation has become a major issue in high power chips, such as microprocessors or light-emitting diodes, because a stable operation depends on the rapid heat dissipation from the heat generating sources. For a chip packaging structure having a chip on a substrate, the substrate is one of the principal channels for dissipating heat from the chip. Therefore, the thermal properties of the substrate will directly affect the reliability of the chip operation.
FIG. 1 is a schematic cross-sectional view of a conventional substrate. To fabricate the substrate shown in FIG. 1, a core layer 110 is provided and then a plurality of holes 112 passing through the core layer 110 are formed. Thereafter, a reverse oxidation reaction and an electroplating process are performed to form metallic layers 122, 124, 126 on the top/bottom surface of the core layer 110 as well as the inner wall of the hole 112. After that, photolithography and etching processes are performed to pattern the metallic layers 122 and 124. Then, insulation layers 132, 134, 136, 138 and patterned metallic layers 142, 144 are separately formed on each side of the core layer 110. Through the metallic layers 122, 124 and 126, the patterned metallic layers 142 and 144 on each side of the core layer 110 can be electrically connected.
In the aforementioned substrate 100, the metallic layer 126 with good thermal conductivity is formed only on the inner wall of the hole 112 in the core layer 110 without filling the entire hole 112. When heat is transferred from one side of the core layer 110 to the other, the amount of heat conducted through the metallic layer 126 is quite limited because the cross-sectional area of the metallic layer 126 perpendicular to the thermal path is relatively small. In other words, the metallic layer 126 inside the hole 112 can not provide optimal heat dissipation effect and electrical performance.


A prompt translation application for use in a telecommunications messaging system provides an administrator with a plurality of messaging prompts in a base language for revising, translating, and editing. The administrator can nearly simultaneously revise both a visual component of a prompt and an audio component of the prompt, and save the revisions for use on any number of associated endpoints. In the preferred embodiments, revisions to the visual component are made by user input, such as keystrokes, and to the audio component by selection of audio segments to be played in a particular order.

Language translation presents particular problems to the software industry. Developers must be aware of cultural nuances for multiple countries at the time of a program release. Additionally, how well the developer internationalizes and localizes the software application often determines how successful the product will be in other countries. Regardless of how close the developer translates and customizes the software product to match a particular locale, errors often remain in the translated version due to regional dialects and the like.
Commercially available translation products attempt to minimize the number of remaining errors in a translated product by using an automated or rule-based translation system. For example, translation on a concatenated word-by-word basis may help to improve the accuracy of the material. These translation products are costly and often require an expert to launch. Once the translation is complete, edits often require a total system reboot and the return of the expert.
Other message-translation systems attempt to localize the software product by identifying portions of the data that require translation. These types of systems use various techniques to localize the software, such as message translations using keyword lookups, applying language-specific data looked up from message files, and database tables pre-loaded with translated information associated with a base language to use as a reference when translating to language-specific messages. These systems generally permit software created for a single market to be revised for multiple languages by a systematic substitution of message references within the software code. Revisions can be made quickly and the translation table references are relatively easy to implement. However, these types of translations are limited to simple sub-sentence displayed messages and provide no means for end users to make adjustments for longer message prompts that often contain dynamic variables (e.g., time of day, day of week, etc.).
Another problem with translation applications is the inability to make on-the-fly local translation adjustments to the software. Typically, any adjustments made to the system require a complete shut down or restart of the programs. In a telecommunications application, even a short shut down interval results in missed telephone calls and voice messages.
Modern telecom products provide integration between the endpoint (e.g., desktop telephone or keyset), personal computer, and PBX. For example, Unified Communicator®, an integration product from Inter-Tel, Inc., permits the user to control and manage telephony functions using a personal computer or an endpoint. In this manner, the user is able to view control functions and messages on either the display of the endpoint or the computer. Thus, these types of modern telephony products must be able to support language translation in both audio (e.g., voice messages) and visual (e.g., text messages on the endpoint and/or computer displays), and preferably simultaneously.
Moreover, advanced programming systems, such as in the telecommunications industry, undergo constant updating and revisions. Language translation systems must be able to accommodate these software updates on a regular basis without requiring a complete re-translation of the program.
It is also desirable to allow multiple translations of the same program to coexist on one system. For example, the program may be available in a base language, such as English, and have multiple languages available, such as French, Spanish, Japanese and Chinese, for selection at individual endpoints.
Accordingly, an improved system and method for language translation is needed. In particular, a translation system providing an easy-to-use prompt selection that is locally customizable and available across a network is needed. Additionally, a prompt language translation system for simultaneous visual and audio translations in a telecommunications application is desired. Moreover, a language translation system that is conducive to a dynamic system, such as in a telephony messaging system with variable data and reoccurring updates, is needed.

Prompt language translation for a telecommunications system


An image forming apparatus includes a subunit. The subunit includes a non-volatile RAM which previously stores data items corresponding to ID information used in the manufacturing process of parts constructing the image forming apparatus, ID information of the main body of the image forming apparatus, history information of the parts used at the time of service operation and maintenance information. A support tool is connected to a communication I/F in the manufacturing process and at the time of service operation, and necessary information stored in the non-volatile RAM is read out in response to a readout instruction from the support tool and displayed on the display screen of the support tool. Data corresponding to ID information of the part incorporated in the manufacturing process and data corresponding to service information in the service operation are stored in a preset storage area of the non-volatile RAM.

This invention relates to an image forming apparatus for forming an image on a photosensitive body by the electrostatographic process, and more particularly to an image forming apparatus having a communication device for receiving and transmitting information such as service information of the apparatus and ID information of parts thereof, a method for manufacturing the same, and a method for maintaining the same.
An image forming apparatus utilizing the electrostatographic process, for example, an electrophotographic copying machine includes an original holding section for holding an original to be copied, an image reading section for reading image information of the original held by the original holding section as information of brightness, and an image forming section for forming a copying image based on the image information read by the image reading section and printing the copying image on a recording material such as paper.
In the process of assembling the image forming apparatus such as the above electrophotographic copying machine, for example, information items of the lot number, the assembling method of the apparatus in the production line and the like are identified by the operator by visually observing a number ticket. Selection of parts and assembling of the apparatus are effected based on the judgment of the operator.
Further, service operations such as investigation on defective portions of the apparatuses manufactured and put on the market, preparation of parts and repair are performed based on the judgment of the serviceman according to the manufacture's serial number attached to the apparatus.
In the above apparatus, since parts are mounted according to the judgment of the operator based on the visual observation and the apparatus is assembled, occurrence of erroneous mounting of parts of a lot cannot be checked at the assembling time even if such erroneous mounting of parts occurs at the assembling time. Therefore, defective portions will be detected after the apparatuses are put on the market.
In order to cope with the above defective portion, a skilled serviceman is required to disassemble the apparatus to search for the cause of the defective portion, order a corresponding part and replace the defective part by the new part, and as a result, the service efficiency is lowered.
Further, in the process of manufacturing the above apparatus, one type of apparatus is manufactured in one production line to prevent the operator's work from becoming complicated, thereby making it difficult to mass-produce various types of apparatuses by occupying the production line. Therefore, there occurs a possibility that quick response to the market needs becomes difficult and the manufacturing cost will rise accordingly.
Thus, in the conventional apparatus, a lowering in the reliability due to frequent occurrence of erroneous operations in the simple operation at the manufacturing time, a lowering in the service quality at the time of maintenance after the apparatus is put on the market, and a rise in the manufacturing cost because of difficulty in the mass production of various types of apparatuses may occur.

Image forming apparatus method for manufacturing the same and method for maintaining the same


A method of driving a display apparatus includes the steps of (a) providing the display apparatus with a plurality of pixel circuits having an electroluminescence element, a driving transistor for providing driving current to drive the electroluminescence element and a capacitor connected to a gate of the driving transistor, and a column control circuit comprising a transistor, a first switch for providing a voltage signal to a gate of the transistor through a capacitor element, a switch circuit for connecting the gate of the transistor to a reference voltage source, and a second switch capable of providing a current signal to the plurality of pixel circuits from the transistor, and (b) inputting a voltage of blanking level to the capacitor element through the first switch while connecting the gate of the transistor to the reference voltage source by the switch circuit. Additional steps include (c) inputting a video voltage through the first switch value disconnecting the gate of the transistor from the reference voltage source by the switch circuit so that a voltage is held by a gate capacitance of the transistor, (d) providing the current signal to a corresponding pixel circuit through the second switch according to the held voltage, (e) holding the current signal provided to the pixel circuit from the column control circuit as a charging voltage in a capacitor of the pixel circuit, and (f) providing the driving current through the driving transistor to the electroluminescence element based on the charging voltage held by the capacitor.

1. Field of the Invention
The present invention relates to a current signal output circuit for outputting a current signal. Further, the invention relates to a display apparatus using the current signal output circuit.
2. Related Background Art
Various display apparatus have been known as background arts. As an example of the display apparatus, there is a display apparatus using an electroluminescence element. The example is described in U.S. Pat. No. 6,373,454.

Display apparatus driving method using a current signal


An image forming apparatus includes a first control circuit, a second control circuit, and a third control circuit. The first control circuit communicates with an information processing device. The second control circuit is configured to communicate with the first control circuit. The third control circuit is configured to communicate with the second control circuit and control a printer. The first control circuit is configured to receive print information from the information processing device during a power-saving mode and control the start of the second control circuit based on the print information. The second control circuit is configured to control a power supply to the third control circuit based on the start by the first control circuit and transmit, to the third control circuit, a warm-up start instruction for the printer based on the print information acquired from the first control circuit after communication with the third control circuit becomes possible.

When an image forming apparatus is in a power-saving mode (S3 state in the Advanced Configuration and Power Interface (ACPI) standard), the image forming apparatus cuts off the power supply to the printer unit or the like. The image forming apparatus mainly supplies power to a part of the main central processing unit (CPU), the main memory, and the Network Interface Card (NIC) to maintain the functions related to the network of the image forming apparatus.
In the related art, when the image forming apparatus receives a NW packet during the power-saving mode, the NIC determines whether or not the packet requires restoration processing of the image forming apparatus. When the NIC determines that the packet requires restoration of the image forming apparatus, the image forming apparatus resumes the power supply to the entire system board and communicates with the client. When the client requests printing to the image forming apparatus by communication and the image forming apparatus receives the print data, the image forming apparatus resumes the power supply to the printer unit. The image forming apparatus enters the print-ready state based on the initialization of the printer unit and the completion of the warm-up operation and then performs the printing process based on the data received from the client.
The Energy Star, which is an international energy conservation system for office equipment, and the Blue Angel Mark, which is a German environmental label, set standards for the time required to complete the NW printing process from the power-saving mode. In order to obtain the certification, the print return time is shortened by various methods.


A push rod operating system for an AR-15/M-16 rifle includes an AR-15/M-16 rifle having a barrel coupled to an upper receiver, a bolt carrier carried by the upper receiver, and a mechanical key coupled to the bolt carrier. A gas block is coupled to the barrel, the gas block having a bore therethough. A rod tube extends from the gas block in communication with the bore, toward the upper receiver. A gas plug has a gas chamber closing the bore of the gas block opposite the rod tube. A discharge gas pathway permits discharge gasses to enter the gas chamber from the barrel. A piston rod element is carried in the rod tube with a piston portion thereof reciprocally received within the bore of the gas block and movable between a first position abutting the gas plug to define an operating volume, and a second position. A push rod element is carried by the rod tube and engages the mechanical key and the piston rod element.

Several problems are prevalent in a conventional AR-15/M-16 gas operated operating system. Chief among these are deposits of residues from discharge gasses, decreasing reliability and usability of the rifle. Deposits inhibit the proper operation of the firearm, requiring frequent cleaning of the gas operating system. Additionally, performing the cleaning in field conditions is difficult and requires specialized tools which may not be present.
It would be highly advantageous, therefore, to remedy the foregoing and other deficiencies inherent in the prior art.
Accordingly, it is an object the present invention to provide a new and improved operating system for an AR-15/M-16 rifle.
Another object of the present invention is to provide a push rod operating system for an AR-15/M-16 rifle.
And another object of the present invention is to provide a method of converting an AR-15/M-16 rifle to a push rod operating system.

M16 modified with pushrod operating system and conversion method


An NMR system comprises an NMR probe comprising multiple NMR detection sites. Each of the multiple NMR detection sites comprises a sample holding void and an associated NMR microcoil. The NMR system further comprises a controllable fluid router operative to direct fluid sample to the multiple NMR detection sites.

Nuclear magnetic resonance spectroscopy, or NMR, is a powerful and commonly used method for analysis of the chemical structure of molecules. NMR provides spectral information as a function of the electronic environment of the molecule and is nondestructive to the sample. In addition, reaction rates, coupling constants, bond-lengths, and two- and three-dimensional structure can be obtained with this technique.
Systems for biochemical, chemical, and molecular analysis can be miniaturized as capillary-based systems or substrate-based, i.e., micro-scale, systems with multifunctional capabilities including, for example, chemical, optical, fluidic, electronic, acoustic, and/or mechanical functionality. Miniaturization of these systems offers several advantages, including increased complexity, functionality, and efficiency. Devices can be fabricated from diverse materials including, for example, plastics, polymers, metals, silicon, ceramics, paper, and composites of these and other materials. Mesoscale sample preparation devices for providing microscale test samples are described in U.S. Pat. No. 5,928,880 to Wilding et al. Devices for analyzing a fluid sample, comprising a solid substrate microfabricated to define at least one sample inlet port and a mesoscale flow channel extending from the inlet port within the substrate for transport of a fluid sample are described in U.S. Pat. No. 5,304,487. Currently known miniaturized fluid-handling and detection devices have not met all of the needs of industry.
NMR is one of the most information-rich forms of biochemical, chemical, and molecular detection and analysis, and remains highly utilized in a wide range of health-related industries, including pharmaceutical research and drug discovery. One of the fundamental limitations of NMR for these and other applications involves sample throughput. When compared to other forms of detection (e.g., mass spectrometry), the amount of sample required by NMR is generally orders of magnitude greater, and correspondingly the mass limits of detection are generally orders of magnitude poorer. Conventional NMR spectrometers typically use relatively large RF coils (mm to cm size) and samples in the ml volume range, and significant performance advantages are achieved using NMR microcoils when examining very small samples. Prior to such development of microcoil NMR and NMR flowprobes, NMR remained a test tube-based analytical technique requiring milliliters of sample and often requiring data acquisition times ranging from 10 min. to several hours for informative spectra with sufficient signal to noise ratio ("S/N"). NMR microcoils are known to those skilled in the art and are shown, for example, in U.S. Pat. No. 5,654,636 to Sweedler et al., and in U.S. Pat. No. 5,684,401 to Peck et al., and in U.S. Pat. No. 6,097,188 to Sweedler et al., all three of which patents are incorporated herein by reference in their entireties for all purposes. A solenoid microcoil detection cell formed from a fused silica capillary wrapped with copper wire has been used for static measurements of sucrose, arginine and other simple compounds. Wu et al. (1994a), J. Am. Chem. Soc. 116:7929–7930; Olson et al. (1995), Science 270:1967–1970, Peck (1995) J. Magn. Reson. 108(B) 114–124. Coil diameter has been further reduced by the use of conventional micro-electronic techniques in which planar gold or aluminum R.F. coils having a diameter ranging from 10–200 .mu.m were etched in silicon dioxide using standard photolithography. Peck 1994 IEEE Trans Biomed Eng 41(7) 706–709, Stocker 1997 IEEE Trans Biomed Eng 44(11) 1122–1127, Magin 1997 IEEE Spectrum 34 51–61.
Miniature total analysis systems (μ-TAS) are discussed in Integrating Microfluidic Systems And NMR Spectroscopy—Preliminary Results, Trumbull et al, Solid-State Sensor and Actuator Workshop, pp. 101–05 (1998), Magin 1997 IEEE Spectrum 34 51–61, and Trumbull 2000 47(1) 1–6. The Trumbull et al. device integrated multiple chemical processing steps and the means of analyzing their results on the same miniaturized system. Specifically, Trumbull et al. coupled chip-based capillary electrophoresis (CE) with nuclear magnetic resonance spectroscopy (NMR) in a μ-TAS system.
Capillary-based liquid chromatography and microcoil NMR have compatible flow rates and sample volume requirements. Thus, for example, the combination of the Waters CapLC™ available from Waters Corporation (Milford, Mass., USA) and the MRM CapNMR™ flow probe available from MRM Corporation (Savoy, Ill.), a division of Protasis Corporation (Marlborough, Mass., USA) provides excellent separation capability in addition to UV-VIS and NMR detection for mass-limited samples. The Waters CapLC™ has published flow rates from 0.02 μL/minute to 40 μL/minute. A typical CapLC on-column flow rate is 5 μL/min, the autosampler-injected analyte volume is 0.1 μL or more, and accurate flow rates are achieved through capillary of typically 50 μm inner diameter. The NMR flow cell has a typical total volume of 5 μL with a microcoil observe volume of 1 μL. A typical injected sample amount for CapLC-μNMR analysis is a few μg (nmol) or less.
Capillary scale systems also are shown in U.S. Pat. No. 6,194,900, the entire disclosure of which is incorporated herein by reference for all purposes. In such systems, a capillary-based analyte extraction chamber is connected to an NMR flow site, such as by being positioned as an operation site along a capillary channel extending to the NMR flow cell.
Small volume flow probes are shown, for example, by Haner et al. in Small Volume Flow Probe for Automated Direct-Injection NMR Analysis: Design and Performance, J. Magn. Reson., 143, 69–78 (2000). Specifically, Haner et al show a tubeless NMR probe employing an enlarged sample chamber or flowcell. Microcoil-based micro-NMR spectroscopy is disclosed in U.S. Pat. Nos. 5,654,636, 5,684,401, and 6,097,188, the entire disclosures of all of which are incorporated herein by reference for all purposes. Sample amounts can now range as small as several hundred microliters for conventional flowprobes to smaller than 1 uL for microcoil-based capillary-scale flowprobes. Acquisition times typically range from minutes to hours. The most expensive and technologically limiting component of the NMR system is the superconducting magnet. Although significant financial and technical investment has been made in the development of elaborate mechanical (robotic-controlled) sample changers and, more recently, automated flow injection systems for repetitive and continuous sample throughput, the magnet remains today a dedicated component in which only sequential, one-at-a-time analysis of samples is carried out.
NMR is one of the few analytical methods in which parallel data acquisition has not been applied to increase sample processing functionality, such as the number of samples that can be tested in a given time. At least some of the difficulties in accomplishing this objective are intrinsically related to the hardware involved in NMR data acquisition.
Recent academic results have shown that some of the limitations of NMR processing can be overcome by the use of multiple microcoil detectors in a wide-bore magnet. Proposed designs for incorporating multiple solonoidal microcoils into a single probe head are presented by Li et al. in Multiple Solenoidal Microcoil Probes for High-Sensitivity, High-Throughput Nuclear Magnetic Resonance Spectroscopy, Anal. Chem., 71, 4815–4820, 1999. A dual channel probe for simultaneous acquisition of NMR data from multiple samples is shown by Fisher et al. in NMR Probe for the Simultaneous Acquisition of Multiple Samples, J. Magn. Reson., 138, 160–163 (1999). Such devices, however, have not been commercially implemented and have not been shown to be commercially viable. In addition, higher numbers of multiple microcoil detectors are needed that are compatible also with narrow bore magnets, since narrow bore magnets are predominant in industrial settings. There is also both need for and benefit of microcoil NMR probes having enhanced sample processing functionality.
Accordingly, it is an object of the present invention to provide multi-microcoil NMR microfluidic devices having enhanced sample processing functionality. It is a particular object of the invention to provide improved microcoil NMR detectors for capillary-scale, high resolution NMR spectroscopy probes that can be adapted in accordance with certain preferred embodiments for use in large or small bore magnets and that are capable of enhanced sample processing functionality. Given the benefit of this disclosure, additional objects and features of the invention, or of certain preferred embodiments of the invention, will be apparent to those skilled in the art, that is, those skilled in this area of technology.

Microfluidic device with multiple microcoil NMR detectors enabling fluidic series communication


An elapsed time clock is incorporated into a part call tag for requesting replenishment of components used by workstations of a manufacturing facility. One or more transmission readers spatially distributed around the manufacturing facility detect a part call signal transmitted from the part call tag. A reader output processing subsystem processes part call signals detected by at least one of the tag transmission readers to recover information contained in the part call signal. A management processor associates the recovered information with a respective workstation, and what component is to be replenished. The elapsed time clock is reset when the part call tag is operated to transmit a part call signal, and thereby serves as a call tag xe2x80x98stop watchxe2x80x99xe2x80x94informing workstation personnel of the length of time that has elapsed since the last part call transmission from that tag.

The present invention relates in general to part/material replenishment for product manufacture and/or assembly systems and the like, and is particularly directed the use of an elapsed time clock in conjunction with the call tag employed in the wireless call tag-based material replenishment system described in the above-referenced co-pending Bacon et al application. The elapsed time clock serves essentially as a call tag xe2x80x98stop watchxe2x80x99, that is reset whenever a part replenishment call is made, and thereby functions to inform workstation personnel of the length of time that has elapsed since the last part call from that tag.
As described in the above-referenced co-pending application, product manufacturers widely employ a technique, referred to as xe2x80x98pull manufacturingxe2x80x99, to replenish components or material required by an assembly line-side workstation in the course of its participation in the production of an item. In accordance with this resupply scheme, parts or material required by a line-side workstation are resupplied in response to a request or xe2x80x98callxe2x80x99 from the workstation to a remote storage management and distribution subsystem, which then retrieves some number of the requested part from a storage facility and delivers them to the requesting site.
Unfortunately, within most manufacturing environments, options for communicating material replenishment requests to those responsible for delivering the parts are considerably limited. A significant number of production facilities continue to employ traditional manual, labor-intensive routines, such as card-based methods. Others, which have attempted to incorporate upgraded communication methods, use hardwired subsystems, that are not only costly to install but, due to their inherent inflexibility, are expensive, time consuming, and labor intensive to retrofit or modify, as the needs and/or retooling of the plant are continually being updated and reconfigured. Although some wireless forms of call systems have been proposed, they are complexxe2x80x94requiring two-way communications with a line-side locationxe2x80x94and are therefore very expensive to install and operate.
Pursuant to the invention described in the above-referenced co-pending application, shortcomings of conventional pull manufacturing replenishment systems are obviated by a wireless xe2x80x98call tagxe2x80x99 based system. In accordance with this call tag based scheme, diagrammatically shown in FIG. 1, advantage of the detection and signal processing infrastructure of the tagged object radio location system described in the U.S. Pat. No. 5,920,287, to D. Belcher et al (hereinafter referred to as the ""287 patent), by installing one or more xe2x80x98call tagsxe2x80x99 16 at or in proximity of each plant workstation 13 of one or more assembly lines 15 within a manufacturing plant 12. If a workstation employs different components, it is equipped with multiple call tagsxe2x80x94one for each different part.
A respective call tag 16 may have a physical configuration, shown in FIG. 2 as including a housing 30, that contains various input/output (I/O) units associated with the use of the call tag, such as a xe2x80x98part callxe2x80x99 push-button 32, and an optical indicator 36. The push-button 32 is employed by a (line-side) operator to trigger the operation (part call transmission) of the call tag. The optical indicator 36 may comprise a light emitting diode (LED), or the like, that is illuminated or flashed when a part replenishment call signal is transmitted by the call tag.
To initiate part replenishment, a line-side workstation operator simply pushes the tag""s xe2x80x98callxe2x80x99 button 32. This causes the call tag""s internal RF transmitter to transmit a spread spectrum RF transmitter to transmit a spread spectrum RF signal burst that is encoded with the identification (e.g., serial number) of the call tag. At the same time, the call tag""s optical indicator 36 (e.g., LED) is flashed to provide a visual indication that the xe2x80x98part callxe2x80x99 was transmitted. The transmitted RF burst is detected by one or more transmission readers 10 of a spatially distributed transmission burst detection and processing subsystem 24. In addition to having the ability to perform tag geolocation processing of the type described in the ""287 patent, the signal processing subsystem 24 reads identification and other data conveyed in each call tag transmission. The call tag identification data is used by a resource management operator to access an asset management database 20, which associates each call tag""s identity with a part employed by the site where the call tag is located. This enables the resource management operator to specify what component is to be accessed from storage, so that the part may be delivered to the identified call tag""s workstation.
Because of the effectively continuously dynamic character of assembly line production, including differences among production shifts and operator assignments, coupled with the ease with which the call tag system described above enables workstation personnel to request material replenishment (simply by pushing a button), system operators may not be particularly diligent in keeping track of replenishment orders. This can lead to duplicate and triplicate orders, as well as out of stock conditions. Moreover, a subsystem failure or an anomaly in the replenishment path, which could lead to assembly line slow down or interruption, may not be immediately noticed. It would be desirable, therefore, to know how recently a parts call has been made. Not only would this advise lineside personnel of the time of the call, but it would aid in determining maximum and minimum inventory levels to be stored lineside.
In accordance with the invention this objective is fulfilled by an enhancement to the call tag-based replenishment system described in the above-referenced copending application, which is effective to continuously inform workstation personnel of the length of time that has elapsed since the last part call was made from a respective call tag. In particular, the present invention includes the incorporation into the call tag of an elapsed time clock, that is automatically reset in response to the call button being pushed, and thereby essentially operates as a part replenishment xe2x80x98stop watchxe2x80x99.
Even though experience of normal assembly line operation will customarily enable a workstation operator to anticipate when to expect parts delivery once a parts call has been made, the incorporation of a part call xe2x80x98stopwatchxe2x80x99 or elapsed time device into the call tag not only allows the lineside operator to determine if an expected delivery is late, but to confirm whether a call was actually made within a given time reference (e.g., an assembly line shift). While the elapsed time clock may be installed and operate as a stand-alone item, it is preferred that it be integrated with other components of the call tag, to facilitate ease of use. In accordance with a non-limiting embodiment of the invention, the call tag timer is arranged to be reset by the operation of the call tag""s pushbutton. As a non-limiting example, the elapsed time may be displayed by way of a dedicated clock display on the call tag housing.

Elapsed time clock for part call tag-based replenishment system


Systems, methods, and computer-readable media for monitoring of equipment using a configurable rule base are disclosed. Configuration information associated with equipment may be identified, and a set of one or more configured rules may be generated from one or more configurable base rules based at least in part on the configuration information. One or more measured parameters associated with the equipment based at least in part on the set of one or more configured rules, and output information associated with the equipment may be generated based at least in part on the analysis.

Real-time monitoring of industrial equipment such as turbines, generators, and so forth may be performed to ensure that the equipment is operating properly. Operational data may be collected and analyzed to determine whether potential failure conditions are present. If such failure conditions are determined to be present, associated alarms may be generated. Real-time equipment monitoring may also be performed to determine performance trends, provide recommendations to an operator on improving equipment performance, and so forth.
Conventional equipment monitoring systems must be specifically tailored to each installation site where the equipment being monitored is deployed and to each particular deployment configuration. Further, extensive validation is often required to ensure that the monitoring system is capable of effectively monitoring equipment having a particular deployment configuration. Thus, conventional equipment monitoring systems entail significant maintenance and deployment costs and fail to provide for monitoring of equipment across a variety of deployment configurations.

Systems and methods for monitoring of equipment using a configurable rule base


A method for transferring a lens-shaped article from a first support to a centered position on a second support employs a transfer tool having a slideable plunger and plunger sleeve that cooperates with the first and second support to ensure that the article is oriented in a desired manner when transferred.

The present invention relates to a method and apparatus for transferring a lens-shaped article between different stages of a manufacturing process, while ensuring that the article remains centered during the transfer. The invention is especially useful for transferring contact lenses.
Small, delicate work pieces such as contact lenses are difficult to transfer through multiple stages of a manufacturing process. This is especially true if it is desired to maintain the contact lens in a desired orientation, such as in a centered position during the manufacturing process. Even though automated processes minimize human contact with the lenses thus reducing the chance of human error, the challenge is designing processes that ensure that the lens is properly oriented when transferred between stages.

Transfer and centering system for contact lenses


The present invention concerns composition, kits and methods for reducing the flushing effect (cutaneous erythema) of an antilipemic drug, for treating hyperlipemia, for improving the effectiveness of an anti-platelet aggregating drug (e.g., in nonresponders) and for treating thrombosis. The present compositions and kits for reducing the flushing effect and for treating hyperlipemia contain an antilipemic drug (such as niacin) and either a sustained release NSAID (such as aspirin) or an NSAID and a carboxylic acid compound other than the NSAID and antilipemic drug. The kits contain (a) pre-dosages of the NSAID and optional carboxylic acid compound and (b) an antilipemic dosage of the antilipemic drug, which optionally may be combined with NSAID and optional carboxylic acid compound in an amount effective to maintain the reduction of the flushing effect. The present method of treating hyperlipemia comprises predosing the patient with a sustained release NSAID or an NSAID and a carboxylic acid compound other than the NSAID and antilipemic drug at least 2 hours before administering the antilipemic drug. The present compositions and kits for increasing the effectiveness of an anti-platelet aggregating drug contain an NSAID such as aspirin, niacin or a congener thereof, and optionally, a carboxylic acid other than the NSAID, such as citric acid.

Abnormally high levels of circulating lipids (hyperlipidemias) are a major predisposing factor in development of atherosclerosis. Elevated levels of serum cholesterol and cholesteryl esters, which are carried by the beta-lipoprotein or low density lipoprotein (LDL) and lipoprotein (a) (Lp(a)) fractions of serum lipids, are known to be atherogenic. Also implicated in cardiovascular disease are elevated levels of triglycerides, carried mostly in the very low density lipoprotein (VLDL) fraction.
Drugs which lower serum lipids (i.e., hypolipemic drugs) frequently are prescribed to retard development of atherosclerotic lesions in individuals exhibiting hyperlipidemias. Many of these drugs are effective when taken regularly, but suffer from poor patient compliance due to unpleasant side effects. Examples of effective but underutilized hypolipemic drugs include the bile acid-binding resins, such as cholestyramine.
The ability of large doses of nicotinic acid (i.e., niacin) to lower serum lipid levels has been recognized for many years. This drug is unusually effective because it lowers the levels of several classes of morbidity-associated serum lipids, including LDL cholesterol (LDL-C), Lp(a), and triglycerides (Tg). In addition to its antilipemic activity, niacin is also an essential water-soluble vitamin. Nicotinic acid exhibits relatively low toxicity on a molar basis.
However, the doses required to lower atherogenic serum lipids are quite large, on the order of 1-8 grams per day. At these levels, adverse side effects are frequent, and may include gastrointestinal disturbances such as nausea, heartburn, and diarrhea. However, the most frequent and prominent side effect is intense flushing, often accompanied by cutaneous itching, tingling, or warmth, and occasionally by headache. Although the flushing side effect is in general harmless, it is sufficiently unpleasant that patient compliance is markedly reduced. Often, 30-40% of patients cease taking nicotinic acid within days after initiating therapy. Consequently, significant efforts have been exerted to develop niacin analogs, dosage forms, and treatment protocols which minimize the flush reaction.
Tolerance to the flush reaction develops after a few days or weeks of repeated administration of nicotinic acid. One strategy for administration is to begin with low doses, i.e., 125 mg twice daily, then to increase the daily dose by increments of 30-100% after 1-6 weeks at each dose level; see, e.g., McKenney et al., J. Am. Med. Assn. 271:672-710 (1994). This procedure reduces but does not eliminate the flush reaction. Ibid. A further difficulty with relying upon tolerance for suppression of the flush reaction is that tolerance is lost rapidly if the drug is discontinued for a day or two. Consequently, the dose must be reduced again when administration is resumed.
Another method of reducing flush is to administer a sustained release (SR) form of nicotinic acid. Sustained release preparations reportedly have a lower incidence of flushing and gastrointestinal side effects, and concomitantly greater patient compliance and tolerance; see King et al., Am. J. Med. 97:323-331, 329 (1994); Knopp et al., Metabolism 34:642-650 (1985); Alderman et al., Am. J. Cardiol. 64:725-729 (1989).
However, even sustained release preparations are not tolerated by a significant fraction of the patient population; see Luria et al., Arch. Into Med. 148:2493-2495 (1988). Moreover, sustained release dosage forms are prone to induce a much more severe side effect, hepatic toxicity; see, e.g., Rader et al., Am. J. Med. 92:77-81 (1992).
Recent studies have indicated that the flushing reaction is initiated by release of prostaglandin D. Prostaglandins are known to cause vasodilation, as well as a subjective experience of discomfort. Evidence supporting the role of prostaglandin D in mediating the niacin-induced flush includes the observation that a dramatic rise in the concentration of prostaglandin F2, a metabolite of D, occurs in the blood coming from the skin following administration of niacin. Furthermore, the level of prostaglandin F2 decreases markedly after 6 days of continuous, twice daily administration of nicotinic acid. This decrease in nicotinic acid-induced prostaglandin F2 correlates with the development of tolerance to the flush reaction which usually develops upon prolonged administration. Therefore, tolerance appears to reflect a decline in prostaglandin D release, rather than an increase in metabolic inactivation of nicotinic acid.
Several nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to inhibit the synthesis of one or more prostaglandins (PGs) by blocking the enzyme prostaglandin synthetase, also referred to as cyclooxygenase. Among the NSAIDs in clinical use are aspirin, ibuprofen, naproxen, phenylbutazone, indomethacin, and flufenamic acid and its congeners. These NSAIDs inhibit the synthesis of PGs such as E2 and F2, but typically at high micromolar (.mu.M) concentrations; see, e.g., Flower, Pharmacol. Rev. 26:33 (1974) (see Table 1 therein).
The prostaglandin synthetase inhibitors aspirin and indomethacin have been shown to reduce the cutaneous flush induced by nicotinic acid. Anderson et al., Acta Pharmacol. Toxicol. 41:1-10 (1977), demonstrated that nicotinic acid-induced flush in guinea pigs, as measured by an increase in ear temperature, was inhibited by pretreatment at 4.5 and 0.5 hr with indomethacin (25 or 50 mg/kg) or aspirin (50,100, or 200 mg/kg). An aspirin total dose of 975 mg, administered to human subjects in a divided dose of 650 mg at 1 hr and 325 mg at 0.5 hr prior to high dose nicotinic acid challenge, was shown to significantly reduce cutaneous flush; see Wilken et al. Clin. Pharmacol. Ther. 31:478-482 (1982).
A nicotinic acid ester derivative, methyl nicotinate, which causes local cutaneous erythema when administered topically, was used to study the flush-inhibiting effects of aspirin.
The effect of aspirin on niacin-induced cutaneous reactions has been studied clinically; see Whelan et al. J. Fam. Pract. 34:165-168 (1992). The authors of this study concluded that 325 mg of aspirin will decrease the warmth and flushing associated with niacin, but not the itching and tingling. In this study, either aspirin or a placebo was administered 30 minutes prior to niacin. As compared to the control group (to whom a placebo was administered prior to niacin), an 80 mg dose of aspirin appeared to have caused even more aggravated flushing, warmth, itching and tingling than pre-administration of the placebo. However, even a 325 mg dose of aspirin administered 30 minutes prior to niacin resulted in flushing and warmth in at least 72% of the patients.
NSAIDs such as aspirin inhibit cyclooxygenase and are therefore considered prostaglandin synthetase inhibitors. Thus, aspirin is considered to be the best NSAID for prevention of platelet aggregation (thrombosis) because it is a long-lasting inhibitor of platelet cyclooxygenase, and it irreversibly acetylates the enzyme. Platelet cyclooxygenase cannot by restored by protein biosynthesis because platelets lack a nucleus.
With regard to inhibiting platelet aggregation, the ex vivo effect of aspirin has been studied in patients taking aspirin for recurrent ischemic stroke prevention; see Helgason et al. Stroke 25:2331-2336 (1994). In this study, increasing doses of aspirin were administered to patients with previous ischemic stroke, and the extent of platelet aggregation inhibition was determined periodically. Over 33 months of initial testing, 288 out of 306 patients had complete inhibition, and 78 out of 306 had partial inhibition. However, at repeat testing, about 33% of the patients having complete inhibition at initial testing had lost part of the anti-platelet effect of aspirin and had converted from complete to partial inhibition without a change in aspirin dosage. Of 52 patients with partial inhibition at initial testing, 35 achieved complete inhibition either by dosage escalation or fluctuation of response at the same dosage, but 8 of the 35 reverted to partial inhibition on further testing. Thus, the anti-platelet (and presumably antithrombotic) effect of a fixed dose of aspirin was not constant over time in all individuals. Furthermore, the mechanisms by which the increased dosage requirement of aspirin resistance develop, and the clinical significance of this development, remained undefined.
Further, a method for reducing platelet aggregation in which patients having a predisposition for thrombus formation are treated with compositions of aspirin, citric acid, thiamine and/or a zinc salt is known (see U.S. Pat. No. 5,401,730; incorporated herein by reference in its entirety). The combination of aspirin and citric acid is believed to be more effective than aspirin alone. Further, thiamine is believed to contribute to the reduction in thrombotic potential by reducing plasma fibrinogen levels.

Compositions, kits and methods for administration of antilipemic drugs


A main magnetic pole of a recording head is formed in an inverted trapezoidal shape by ion milling but, the long milling time poses a problem of variations in the inverted trapezoidal shape and the dimensional variations in track width. In one embodiment of the invention, a recording head is formed by first forming a lower magnetic pole, a gap layer, and conductor coils, forming an upper magnetic yoke over the gap layer at a position recessed from the air bearing surface, and forming an inorganic insulative layer in the recessed portion. A back magnetic pole connected with the upper magnetic yoke is formed on the back of the lower electrode. Successively, the upper surfaces of the inorganic insulative layer and the upper magnetic yoke are planarized, on which an underlayer film such as of Rh is formed. A magnetic layer is formed by stacking a plurality of thin magnetic films by sputtering over the underlayer film from the air bearing surface as far as the position overlapping the upper magnetic yoke. Successively, ion milling is applied to form a main magnetic pole of an inverted trapezoidal shape having a taper on the lateral surface as viewed from the air bearing surface.

The present invention relates to magnetic heads used for reading and writing data from and to a magnetic recording medium and manufacturing methods thereof and, more in particular, it relates to a magnetic head suitable for perpendicular magnetic recording and a manufacturing method thereof.
In magnetic disk apparatus, data on a recording medium is read and written by a magnetic head. To increase the recording capacity per unit area of the magnetic disk, it is necessary to increase the areal density. However, a current longitudinal recording system involves a problem in that the areal density cannot be increased because of thermal fluctuation over the magnetization of the medium as recordable bit length is smaller.
Methods capable of solving the problem include a perpendicular recording system of recording magnetization signals in the direction perpendicular to the medium. The perpendicular recording system can use a giant magnetoresistive head (GMR head), a tunneling magnetoresistive head (TMR head) with further higher reading output, or a CPP (current perpendicular to the plane) type GMR head, which allows a current to flow perpendicularly to the film surface. On the other hand, it is necessary to use a single magnetic pole head for recording. Also in order to increase areal density, the perpendicular recording requires improving the track density and the linear recording density. To increase the linear recording density, it is necessary to improve the gradient of recording magnetic fields of the recording head. For this purpose, the recording medium is constituted as a dual layer structure in which a soft underlayer is provided as a lower layer. To increase the track density, it is necessary to provide the magnetic head with a finer and higher-accurate track width.
Further, since the magnetic disc drive provides a skew angle adapted to access the inner circumference and outer circumference of a disc, a problem arises of side writing depending on the shape of a main magnetic pole particularly in the perpendicular recording. To eliminate this problem, it is necessary that the width of the track width direction of the main magnetic pole is wider on the trailing side and narrower on the magnetic head substrate side, that is, has an inverted trapezoidal shape with respect to the substrate direction. For example, Patent Document 1 (JP-A No. 2003-263705) discloses an example of a magnetic head for use in perpendicular recording in which the lateral surface of the main magnetic pole is formed, by ion milling, into an inverted tapered shape by etching the main pole formed by a frame plating method. Patent Document 2 (JP-A No. 2004-95006) discloses a method of manufacturing a magnetic head for use in perpendicular recording, in which the surface of a substrate is obliquely irradiated with ion beams by using, as a mask, a non-magnetic metal film comprising Ta, W, Ti or an alloy thereof in order to form a write pole in an inverted trapezoidal shape.

Hitachi Global Storage Technologies Netherlands B.V.


An average bidirectional flow tube, including a body having two side plates and upper and lower plates, a partition plate installed to be perpendicular to the side plates of the body so that front and rear ends of the tube are separated from each other, and two pairs of pressure impulse lines installed at front and rear positions of the partition plate. The upper and lower plates of the body each have a curvature to be in contact with an inner surface of a pipe in which the average bidirectional flow tube is installed, and each of the pressure impulse lines is installed to communicate with an interior of the pipe. Although a two-phase flow occurs in the pipe or the flow of the fluid flowing in the pipe is changed, an average flow rate of a fluid can be measured. Particularly, it is easy to measure an average flow rate of the fluid when the fluid flows at a low speed. Further, even when sudden pressure reduction occurs in the pipe, an additional cooling device is not required. When a two-phase flow occurs in the pipe, the fluid suffers a phase change due to the sudden pressure reduction of the pipe, or a stratified flow occurs due to the two-phase flow in a horizontal pipe, it is unnecessary to displace the average bidirectional flow tube.

1. Field of the Invention
The present invention relates generally to flow meters used to measure a flow rate of a fluid in a fluid system, and more particularly, to a flow meter capable of measuring a mass flow rate of a fluid, even if a single-phase or two-phase flow occurs in a vertical pipe or a stratified flow occurs in a horizontal pipe.
2. Description of the Related Art
FIG. 1 is a side sectional view of a pipe 1 equipped with a conventional pitot tube 10, with the pitot tube 10 comprising a double pipe (not shown). As shown in FIG. 1, the conventional pitot tube 10 is configured such that a total pressure hole 11 and a static pressure hole 13 are formed at predetermined positions in the double pipe. The pitot tube 10 is installed such that the total pressure hole 11 is opposite to the direction of fluid-stream movement. A total pressure acting on the total pressure hole 11 is a sum obtained by adding a static pressure to a dynamic pressure due to a fluid flowing in the pipe. Only the static pressure acts on the static pressure hole 13. Further, a pressure impulse line 15 extends from the double pipe having the total pressure hole 11 and the static pressure hole 13. As shown in FIG. 1, a differential pressure transmitter (not shown) connected to the pressure impulse line 15 measures the difference (ΔP) between a pressure acting on the total pressure hole 11 and a pressure acting on the static pressure hole 13. By the measured result, a flow velocity of the fluid is calculated. The flow velocity measured by the pitot tube 10 is a flow velocity at a position where the pitot tube 10 is located, but not an average flow velocity of the fluid flowing along the pipe 1. Thus, in order to find the average flow velocity of the fluid in the pipe 1, the flow velocity of the fluid must be measured at many positions several times while changing the insertion depth of the pitot tube 10, and then the mean flow velocity must be calculated.
FIG. 2 is a side sectional view to show a conventional average pitot tube 20, and FIG. 3 is a front sectional view of the conventional average pitot tube 20. In this case, the average pitot tube 20 comprises a double pipe (not shown). In the following description, those elements common to the pitot tube, of FIG. 1 and the pitot tube of FIGS. 2 and 3 will carry the same reference numerals.
As shown in FIGS. 2 and 3, a plurality of total pressure holes 21 and a plurality of static pressure holes 23 are formed on the double pipe of the conventional average pitot tube 20. A pressure impulse line 25 extends from the double pipe to be connected to a differential pressure transmitter (not shown). The principle of measuring the flow velocity of a fluid flowing in the pipe 1 remains the same as that of the pitot tube 10 of FIG. 1.
As described above, the pitot tube 10 is problematic in that the flow velocity of the fluid flowing in the pipe 1 must be repeatedly measured at many positions several times, so that it is complicated to measure the flow velocity and a longer time is required to measure the flow velocity. In order to solve the problems, the average pitot tube 20 has been proposed. The average pitot tube 20 is constructed so that total pressures are measured at a plurality of total pressure holes 21, and static pressures are measured at a plurality of static pressure holes 23. Thereby, the total pressures and the static pressures are simultaneously measured at several positions in the pipe 1, thus allowing an average flow rate of the fluid to be conveniently calculated.
FIGS. 4 and 5 show a local bidirectional flow tube 30. As shown in FIGS. 4 and 5, the local bidirectional flow tube 30 includes a cylindrical body 31, a partition plate 33, and a pressure impulse line 35. In the following description, those elements common to the pitot tubes of FIGS. 1 and 2 and the flow tube of FIGS. 4 and 5 will carry the same reference numerals.
The principle of measuring a flow velocity using the local bidirectional flow tube 30 is similar to the measuring principle using the pitot tube 10 of FIG. 1 and the average pitot tube 20 of FIG. 2. As for a fluid flowing forward, when the local bidirectional flow tube 30 is installed as shown in FIG. 4, the total pressure obtained by adding the static pressure to the dynamic pressure due to the fluid flowing in the pipe acts on the A part. On the other hand, a back pressure acts on the B part. At this time, the back pressure is slightly less than the static pressure due to a suction effect caused by a flow velocity of the fluid of the B part. The pressures acting on the A part and the B part are transmitted to the differential pressure transmitter through the pressure impulse line 35, so that the pressure difference between the A part and the B part is measured. Thereby, the average flow velocity of the fluid is calculated under any flow condition.
In the case of using the above-mentioned average pitot tube 20, when a two-phase flow may occur in the pipe 1, for example, when a liquid flows along the bottom of the pipe 1 and gas flows separately above the liquid, a pressure difference is generated between the total pressure holes 21, so that the liquid may escape from the average pitot tube 20 to the flow path in the pipe 1. Further, when a sudden pressure reduction occurs in the pipe 1 and then the pressure acting on the pressure impulse line 25 is abruptly reduced, a phase change may occur in the pressure impulse line 25. Thus, in order to solve the problem, an additional cooling device is required. Further, the local bidirectional flow tube 30 is problematic as follows. That is, the local bidirectional flow tube 30 is not capable of being used to measure the average flow rate of the fluid in the pipe 1.
Further, when two-phase flow occurs in the pipe 1, or the fluid suffers a phase change due to a the sudden pressure reduction in the pipe 1, or stratified flow of a two-phase fluid occurs in a horizontal pipe, the local bidirectional flow tube 30 must be displaced to another position to measure the average flow rate.


An apparatus is described for supporting and/or constricting a surface of a valve annulus. The apparatus includes a tubular member of dimensions suitable for insertion into a body vessel. The tubular member includes at least two first segments attachable to an interior wall of the body vessel. The tubular member further includes at least one second segment which is capable of decreasing its axial length to draw one of the first segments towards the other first segment.

1. Field
Stent like structures for insertion into body vessels, and the treatment of valve insufficiency.
2. Background
Generally speaking, oxygenated blood travels from the lungs to the left atrium by way of the pulmonary veins. The veins from the systemic circuit, the venae cavae and coronary sinus carry blood deficient in oxygen into the right atrium. The right ventricle takes blood received from the right atrium and sends it to the lungs, while the left ventricle takes blood received from the left atrium and sends it to the aorta.
The atrioventricular valves between respective ones of the atria and ventricles play important roles in the transport of blood through the body. The atrioventricular valves open during diastole, when the heart muscle relaxes, to allow blood to flow from the atria into the ventricles. The atrioventricular valves close during systole, when the heart muscle contracts, preventing the back flow of blood into the atria and allowing blood from the ventricles to be efficiently pumped into the lungs via the pulmonary tract and to the rest of the body via the aorta.
The mitral valve is the atrioventricular valve that controls blood flow from the left atrium into the left ventricle. The mitral valve is a bicuspid valve, describing the two cusps or leaflets that open and close the valve. The cusps or leaflets are attached to a muscular and fibrous ring around the orifice (mitral valve annulus) and their apices hang down into the left ventricle. When the ventricle fills with blood and begins to contract, the valve cusps or leaflets flow into position in the atrioventricular opening and are forced shut (coaptate) by the increasing pressure. To prevent the valve cusps or leaflets from turning into the left atrium and regurgitating blood, tendinous cords, the chordae tendineae, are attached to the free margins and ventricular surfaces of the cusps or leaflets. At the other ends, these cords attached to one of a respective pair of papillary muscles projecting from the ventricular wall. By contracting, these muscles maintain the integrity of the valve during ventricular contraction or systole.
When the two cusps or leaflets of the mitral valve do not completely close, there is backflow, or regurgitation of blood. The backflow increases the pressure in the left atrium which leads to pulmonary hypertension and dilation of the heart which are common symptoms of congestive heart failure. A heart then has to work harder pumping blood for the body which can lead to heart damage. Incomplete closing of the mitral valve cusps or leaflets is common, occurring generally in about seven percent of the population. Conditions contributing to incomplete closure of the mitral valve cusps or leaflets include genetic defects, infections, coronary artery disease, myocardial infarction, or congestive heart failure. These conditions contribute to mitral valve regurgitation resulting from enlargement of the mitral valve annulus and/or movement of the papillary muscles away from the valve as a result of ventricular enlargement. When the annulus enlarges, the cusps or leaflets of the valve are no longer able to close (coaptate), because the distance between the two cusps or leaflets has increased too much for the cusps or leaflets to touch each other and thus close off blood flow to the left atrium during, for example, systole. Mitral valve regurgitation can also result as a secondary etiology due to the remodeling of a distorted left ventricle in ischemic heart disease. It is known that as the ventricle is remodeled, the papillary muscles can be displaced away from their natural position. This displacement alters the natural tethering of the cusps or leaflets and restricts the ability of the cusps or leaflets to close properly at the level of the annulus.
In general, most cases of mitral valve regurgitation are mild and the symptoms may be controlled with drugs. In more serious cases, the mitral valve can be repaired through a procedure known as annuloplasty, a surgical procedure in which a synthetic ring is placed around the valve annulus. Annuloplasty encourages aptation of the mitral valve cusps or leaflets by shrinking the size of the valve opening. In other instances, a faulty mitral valve must be surgically replaced with a new valve. These surgical repairs require the opening of the chest by sternotomy or at best through small incisions in the chest wall, heart lung bypass and stopping the heart beat. In general, annuloplasty is an extremely invasive procedure, and, as such, a less invasive treatment for annular dilation is desirable.

Valve annulus constriction apparatus and method


An electronic torque wrench includes: a shank body, a drive head being connected with a front end of the shank body; a handle having a front handle section and a rear handle section, the front handle section being connected with a rear end of the shank body, a cell room being formed in the front handle section for placing cells therein, a front end of the rear handle section being detachably connected with the rear end of the front handle section; an electronic operation/control device disposed on the shank body; and at least one torque sensor mounted on the shank body. The front and rear handle sections together form the handle for a user to hold. The rear handle section of the handle serves as a cell cap for closing the cell room so as to shorten the length of the wrench.

1. Field of the Invention
The present invention relates generally to an electronic torque tool, and more particularly to an electronic torque wrench with improved handle.
2. Description of the Related Art
FIG. 1 is a side view of a conventional electronic torque wrench. The conventional electronic torque wrench includes a metal-made shank body 12, a drive head 14 mounted at one end of the shank body 12 for wrenching a threaded member, and a plastic-made housing 15 fitted on the shank body 12 with a rear end of the shank body 12 concealed in the housing 15. The electronic components of the torque wrench, such as the circuit board and the liquid crystal screen, are assembled in the housing. A rear half section of the housing 15 is integrally formed as a handle 16 for a user to hold. Several cells are mounted in the housing 15 to supply necessary power to the wrench. A plastic-made cell cap 18 is mounted at the rear end of the housing 15 to close the cell room in the housing.
According to the above arrangement, a user can hold the handle 16 to operate the conventional electronic torque wrench. The cell cap 18 is simply connected with the rear end of the housing 15 to close the cell room, not for holding. Moreover, the cell cap 18 itself is made of plastic material and unable to bear external force. Otherwise, the cell cap 18 will break and damage. According to such design, the cell cap 18 will lead to increase of the length and volume of the wrench. As a result, the space necessary for transfer and storage of the wrench is enlarged.
Besides, the handle 16 of the conventional electronic torque wrench is made of plastic material by molding. Therefore, the handle 16 has a fixed size without possibility of change. As a result, different users with different sizes of palms can hardly suitably use the conventional electronic torque wrench. Therefore, it has become a topic in this field how to selectively adjust the length of the handle 16 in adaptation to different users.

This patent is subject to a terminal disclaimer.

Electronic torque wrench with improved handle


An image capturing apparatus illuminate and captures an image of an object using reflected light from the object. In the apparatus, a plurality of light-emitting devices are mounted in the periphery of an image sensor, and the light of the plurality of light-emitting devices is guided to an image capturing region by a light guide member for illumination. On the image capturing apparatus having the image capturing system disposed close to the illumination system, a hood is provided for optically intercepting the image capturing system from the illumination system, with a flange disposed thereon. The light reflected on the upper face of a filter can be intercepted from being incident on an image capturing system unit. Accordingly, output light not irradiating the object and causing an image capturing noise can be intercepted, which is effective for a clear photographed image.

1. Field of the Invention
The present invention relates to an image capturing apparatus for guiding light emitted from a light-emitting device to an object, irradiating the object and image capturing the object, and more particularly an image capturing apparatus cutting off the invasion of light to an image capturing unit outside an image capturing range even when disposing the light-emitting device close to the image capturing unit, and obtaining a clear image.
2. Description of the Related Art
An image capturing apparatus for image capturing a predetermined range of an object by irradiating the object with uniform light is widely used. In an image processing system using an image captured by such the image capturing apparatus, a clear image is particularly required.
For example, with the development of biometric technologies in recent years, there have been provided a variety of apparatuses for personal identification, which captures an image of a portion of a human body by which an individual can be distinguished and recognize a characteristic of a living body, for example, fingerprints of limbs, eye retinas, face and blood vessels.
In particular, blood vessels and skin patterns of a palm and a finger are suitable for reliable personal authentication, because a relatively large amount of personal feature data may be obtained therefrom. Further, it is believed that the patterns of blood vessels (veins) do not change from the time of an embryo throughout the lifetime of any person, and that no identical pattern exists among any persons without exception, which are therefore suitable for personal authentication.
For such the biometric authentication or the like, it is necessary to image an object (a portion of a human body in case of the biometric authentication) in a non-contact manner. For this purpose, image capturing apparatus emits light producing uniform light intensity in a certain image capturing range (distance and area), receives the reflected light of the above image capturing range by a sensor, and outputs a captured image signal as an electric signal.
FIGS. 22 and 23 show explanation diagrams of the conventional image capturing apparatus. As shown in FIGS. 22 and 23, image capturing apparatus 100 includes an image capturing (digital camera) unit 120 at the center, and in the periphery thereof, a plurality of light-emitting devices 130-1 to 130-8. The dotted lines shown in FIG. 22 represent the range of the light having uniform intensity emitted from an individual light-emitting device among the plurality of light-emitting devices 130-1 to 130-8.
As such, by disposing a plurality of (here, eight) point light sources in the periphery of image capturing unit 120, the image capturing range of image capturing unit 120 can be irradiated with the light of uniform intensity. Meanwhile, as shown in FIG. 23, the image capturing unit 120 includes a photoelectric conversion unit 122 such as a CMOS sensor, and an optical system 124 such as a lens. Since the photoelectric conversion device 122, which is a plane photodetector device, has a predetermined light receiving area, a predetermined optical distance is required to guide the reflected light of the image capturing range onto the light-receiving plane of the photoelectric conversion device 122. For this purpose, a lens 124 such as a fisheye lens is disposed between the photoelectric conversion unit 122 and the object, so that an image of the predetermined image capturing range is projected onto the light-receiving plane of the photoelectric conversion device 122.
Thus, conventionally, in order to irradiate the object with each point light source element 130-1 to 130-8 by sharing a predetermined image capturing range, the point light source elements 130-1 to 130-8 have been disposed apart from each other, as shown in FIG. 22. Also, in order to supply the light of predetermined uniform intensity to the image capturing range, the point light source elements 130-1 to 130-8 have been disposed closer to the object than the photoelectric conversion device 122, as shown in FIG. 23 (referring to the International Patent Publication No. WO 2004/088588, FIGS. 1 and 6).
In the above conventional image capturing apparatus, as described earlier, the point light source elements 130-1 to 130-8 are disposed apart from each other, and closer to the object than photoelectric conversion device 122, as shown in FIG. 23. Therefore, it is difficult to miniaturize the image capturing apparatus. Also, there is a restriction when incorporating the image capturing apparatus into equipment.
If light-emitting devices which generate high light intensity is used, it becomes possible to dispose the light-emitting device close to the image capturing unit 120. However, the light-emitting device generating high light intensity is expensive and has large power consumption, which is therefore not suitable for a small-sized low-cost image capturing apparatus.

Image capturing for capturing an image of an object by illuminating the object and receiving light from the object


A curtain type decorative light string set capable of connecting with several independent light strings is provided. The light strings are connected in parallel and use the main electrical wires as a support, to be hung on other objects to prevent the light strings from loosening and thereby ensure that all other bulbs stay lit.

A conventional curtain type decorative light string set is composed of a main electrical wire as a supporting means and a plurality of short light strings which are hung separately from the main wire as shown in FIG. 1, that arrangement forms a decorative light string set forming a curtain of lighting bulbs. The structure of this prior art includes several connecting bulb holders a1 on the main electrical wire to engage with the short light strings to be hung therefrom. Since the short light strings can possibly come loose because of the weight of the strings or can be pulled by accident, those light strings may become unlit. If the connecting bulb holder a1, located near to a plug of this light string set, is broken, it might cause the whole light string set to become unlit, as the bulb holder a1 is connected in series with the bulb holder a.

Decorative light string set of a curtained type


Methods and systems for managing bubbles in a micro electro mechanical systems device are described. One exemplary system includes a fluid-feed channel configured to supply fluid to a plurality of ejection chambers, individual ejection chambers comprising a resistor configured to eject fluid from the individual ejection chamber. The system further includes a processor configured to cause an individual resistor to be energized at a first intensity sufficient to eject fluid from a respective ejection chamber, the processor further configured to cause the resistor to be energized at a second lower intensity which heats the resistor but does not cause fluid to be ejected from the respective ejection chamber, and wherein the processor can energize, at the second lower intensity level, individual resistors in a pattern designed to detach a bubble from a surface defining a portion of the fluid-feed channel.

Contaminants, such as bubbles, can be present in various fluid-delivery or fluid-ejecting devices. In some fluid-delivery devices contaminants can reduce and/or occlude fluid flow and cause the device to malfunction. Management of the contaminants can enhance the performance and reliability of the fluid-delivery device. For these and other reasons, there is a need for the present invention.

Managing bubbles in a fluid-delivery device

Hewlett-Packard Development Company, L.P.


A light-emitting device is provided that is capable of being directly connected to an alternative current source, including at least one electronic element; at least one light-emitting diode array chip; at least one bonding pad, a conductive trace, and a submount for supporting the electronic element, the light-emitting diode array chip, the bonding pad, and the conductive trace. The conductive trace is electrically connected to the electronic element, the light-emitting diode array chip, and bonding pad.

Light-emitting diode (LEDs) can emit light energy in the presence of energy difference resulted from the movement of electrons between the n-type semiconductor and the p-type semiconductor. With this mechanism, the LEDs can generate cool light in contrary to incandescent bulbs. Besides, the LEDs are durable and compact, and have long lifespan and low energy-consumption. Accordingly, the LEDs become promising candidates in the market to be the next-generation lighting products in place of the conventional lighting sources, and are already applied to various fields such as traffic lights, backlight modules, street lights, and medical equipment.
As shown in FIG. 1, a light-emitting diode element 100, which can be adapted to an alternative current power source, includes a submount 10, a light-emitting diode array chip 12 on the submount 10, and at least one bonding pad 14 electrically connected to the light-emitting diode array chip 12. The light-emitting diode array chip 12 includes a substrate 120 and several light-emitting diode units 122 on the substrate 120.
To replace a conventional lighting device, the light-emitting diode element 100 must work on a high voltage condition of 100V˜240V, which may bring about a high temperature issue after long time operation. Under the high voltage and high temperature conditions, an electromigration effect, which is a result of a movement of metal ions caused by a mixed effect of the temperature and the electron wind, can be easily found in an electronic device. Generally, the electromigration of metal ions occurs easily at high temperature. In the light-emitting diode element, the metal ions may diffuse from the electrode to the active region by the effect of the electric current at high temperature. For example, the electromigration may occur easily in the electrode material such as indium tin oxide (ITO) and silver. Moreover, the element may fail due to voids caused by the electromigration in the solder or tiny metal connection.
As described above, the reliability of the light-emitting diode element for alternative current usage can be seriously deteriorated at high temperature and high voltage environment.


Dot characteristic points are first extracted from M-level image data by the dot characteristic point extracting device. A dot area identifying device subsequently identifies a dot area based on the results of the extraction carried out by the dot characteristic point extracting device. When the image attribute determination is completed, a parameter setting unit sets N-level conversion parameters based on the results of the determination carried out by the dot area identifying device. Consequently, N-level conversion takes place using the N-level conversion parameters appropriate for a dot area. Therefore, N-level conversion in which the occurrence of moire is prevented may be carried out regarding dot areas.

1. Field of the Invention
This invention relates to an image processing apparatus that processes images using digital image signals, and more particularly to an image processing apparatus capable of preventing the moire phenomenon that occurs when the number of gradations of the image data in dot areas is reduced.
2. Description of the Related Art
In a conventional image processing apparatus, the attribute of the image is first identified (i.e., character area or photograph area) to enable processing appropriate to such attribute to be carried out. Specifically, processing focusing on resolution is carried out regarding a character area, while processing focusing on gradation is performed regarding a photograph area. In such attribute determination, a process that uses the density difference in M-level image data is widely used. This technology uses the characteristic fact that a character area includes substantial edge components (i.e., that the density difference is large; see FIG. 12), and a photograph area has a flat density distribution (i.e., that the density difference is small; see FIG. 13).
However in a dot area, moire may occur due to interference between the resolution for image reading and the dot frequency of the original document. When moire occurs, the image quality deteriorates. Even if this moire is not conspicuous in an M-level image, when the image is converted into an N-level image (M>N), i.e., when the number of gradations of the image is reduced, it becomes markedly visible. Therefore, an N-level conversion process that prevents the occurrence of moire has been desired.
In the conventional image processing apparatus described above, however, the problem exists that moire becomes conspicuous in dot areas after N-level conversion (i.e., when the number of gradations is reduced), because, while it is desirable to preserve linear gradation in dot areas, such preservation is not possible when processing that uses the density difference is used. In other words, as shown in FIG. 14, a dot area is judged to be more character-like than a character area as the read resolution increases, and processing focusing on resolution is carried out on the dot area. In addition, because dot areas indicate various density patterns depending on such conditions as the screen angle, density and read resolution, it is difficult to accurately identify a dot area via processing using density difference. That is one of the reasons that appropriate processing cannot be performed on dot areas. Because N-level conversion that preserves linear gradation cannot be carried out regarding dot areas, as described above, moire visually stands out in such areas.