The procedure and the apparatus serve for the control of a respirator device which is used for the supply of breathable gas to a patient. At least one sensor for the capture of the time-wise evolution of at least one respirator-treatment parameter is provided. The sensor can be arranged in the area of an air delivery which encompasses a respirator device as well as a connecting installation. The sensor is connected to an analyzer which carries out a pattern recognition and which is connected to a control for the modification of at least one respirator-treatment parameter. In order to implement the pattern recognition, one captures—at least at intervals—the time-wise evolution of at least one of the respirator-treatment parameters.

The invention concerns a procedure for the control of a respirator device, in which one can set at least two different pressure levels of a breathable-gas supply and in which at least one respirator-treatment parameter is captured by a measurement technique and is evaluated for the purpose of controlling the respirator-treatment pressure.
In addition to the above, the Invention concerns an apparatus for monitoring at least one respirator-treatment parameter when a patient is supplied with the breathable gas. The apparatus features a sensor for capturing the time-wise evolution of the respirator-treatment parameter, the sensor being arranged in an air-delivery area which encompasses a respirator device as well as a connecting installation.
A not inconsiderable number of people suffer from sleep disturbances which affect the daytime well-being of these individuals and which [disturbances] may impair their social and professional capacity as well as quality of their life, to an occasionally considerable extent. One of these sleep disturbances is sleep apnea which is treated primarily with the so-called CPAP therapy (CPAP=Continuous Positive Airway Pressure). In this therapy an airstream consisting of a breathable gas is continuously supplied to the sleeping patient via a nose mask. By means of a hose the mask is connected to a respirator device which encompasses an aerator that produces a gas stream with a gauge pressure of 5 to 20 mbar.
The gas stream is supplied to the patient either under constant pressure or else—in order to facilitate the breathing work—at a lower pressure during the expiration stage. Even though sleep apneas occur only for short periods and make up a minor portion of sleep, in both cases the aerator operates during the entire sleep period (night), a fact which detracts from the acceptability of this sleep apnea treatment.
U.S. Pat. No. 5,245,995 teaches a CPAP respirator device which can be used on patients with sleep apnea. The breathable gas is supplied to the patient via a breathing mask, a source of compressed gas being provided in the area of the device. The source of compressed gas can be controlled as a function of airway resistance.
European Patent No. 0,373,585 describes a method for capturing the breathing resistance of a patient by means of ORM measurements. Here, the volumetric breathing stream is overlaid at a predetermined frequency with an oscillating volumetric stream featuring a low volumetric rise. Because of the periodic pressure variation occurring at the same frequency, one can generate a reading which is a function of the actual airway resistance.
From U.S. Pat. No. 5,318,038 one knows a respiratory measurement which involves the use of a pneumotachygraph in the gas delivery line. European Patent No. 0,705,615 describes a high-quality implementation of control for a respirator device based on the application of ORM measurements.
The procedures and apparatus in the prior art already provide greatly reliable means for preventing the occurrence of conditions threatening the patient's life. However so far it has not been possible to eliminate all impairments of the patient's quality of life. A special goal is to leave intact as much as possible the patient's own breathing activity, providing equipment-based support solely when the latter is indeed needed. This objective requires the optimization of the respirator device's control and regulation, as well as the use of appropriate regulating-technology components. In particular one must recognize at the earliest possible moment the occurrence of deviations from the patient's normal breathing activity, and react to them by means of the appropriate control and regulation of the respirator device.
Consequently it is the task of the present Invention to improve a procedure of the type described at the outset, in a manner such as to promote a prompt adjustment of the device's operation to the respective breathing condition.
This task is achieved by means of the Invention in that at least one respirator-treatment parameter is modified as a function of a pattern recognition. To carry out this pattern recognition, one captures—at least at intervals—the time-wise evolution of at least one respirator-treatment parameter and one analyzes it with respect to a typical individual pattern and/or with respect to an evolution pattern.
It is a further task of the present Invention to design an apparatus of the type described at the outset, in a manner such that, using a simple device structure, early changes in the respective respirator-treatment situation are recognized.
This task is achieved by the Invention in a manner such that the sensor is connected with an analyzer which carries out a pattern recognition, the analyzer being connected to a control installation for modifying at least one respirator-treatment parameter.
Carrying out a pattern recognition makes it possible to detect early changes in an existing breathing condition and thus permits a timely modification in the respirator device's controls. Here, advantage is taken of the fact that a plurality of respirator-treatment conditions are characterized by typical evolution patterns—for instance, of the respirator-treatment pressure or the respirator-treatment flow, or of variables proportional to them. In addition there is also the factor of the relatively early appearance, in the transition from one respirator-treatment condition to another, of typical evolution patterns.
The use of pattern recognition and the prompt introduction of modifications in the device's controls make it possible—even before a change in the respirator-treatment condition, noticeable by the patient, actually occurs—to counteract this change by adjusting the device's controls. The result is that, on one hand, no respirator-treatment conditions negatively affecting the patient's health are reached. On the other hand, the countermeasures are initiated at such an early point that relatively small changes in respirator-treatment parameters suffice to return to the desired normal condition. At the very least, the deviations from such normal conditions are kept within a narrow interval. The early triggering of the measures makes it possible to keep the intensity of those counteracting steps at a very low level which, as a rule, cannot even be noticed by the patient.
For greater ease of detection of significant patterns, it is proposed that the prevailing pressure level for breathing support be temporarily overlaid with a stimulating stream which oscillates at a specific frequency. In particular, this also comprises a change in the respective frequency during the application of the therapy.
A factor which contributes to the patient perception of the device's control setting as being pleasant is that—after the selective evaluation of an oscillatory pressure amplitude at the frequency of the stimulating stream, in the air supply to the patient (corresponding to a specific breathing resistance of the patient)—one carries out a selection of the respective pressure amplitude.
A typical application consists in the implementation of a CPAP respirator treatment.
A class of signals capable of evaluation is defined by the fact that at least one electric signal is evaluated during the pattern recognition.
Consideration is also given to evaluating a physical signal during the pattern recognition. The physical signal can be transformed into an electrical signal for further processing.
In order to support a systematic evaluation of the pattern recognition, it is proposed that in the context of the pattern recognition one carry out a derivation of error classes.
A typical signal evolution to be evaluated is defined in that an OPS signal is evaluated. By OPS signal we refer to an Oscillating Pressure Signal which corresponds to the numerical value of the impedance.
It is also possible that a pressure signal and/or a sound pressure and/or a pressure variation will be evaluated.
Because of the retro-acting effect, exerted by the production of a respirator treatment situation upon the electrical drive conditions of the compressed-air supply, consideration has also been given to evaluating an electrical drive parameter of the compressed-gas supply. This proves particularly practical if the regulation is carried out via an electric drive. Alternatively, however, the regulation can also be carried out independently of the pressure-building drive—e.g., via a valve.
In accordance with a typical evaluation run it is envisaged that, in the pattern recognition, it is distinctive form features that will be evaluated.
Consideration is also given to the possibility that, in the pattern recognition, distinctive time features and/or distinctive amplitude features will be evaluated.
The activation of predefined control runs, as a function of a pattern-recognition result, is promoted by the fact that an assignment to a class is carried out subsequent to the pattern recognition.
In order to increase the evaluation speed it is provided that the analyzer be coupled with a storage for supplying the comparative patterns.
Another contributory factor to a high processing speed is that the analyzer is coupled with a classifier.
A prompt evaluation of the time-wise evolution characteristics of the pattern that is to be evaluated is facilitated by the fact that the analyzer features a time-wise evolution analyzer and/or an amplitude-wise evolution analyzer.
A prompt evaluation of the form-wise evolution characteristics of the pattern that is to be evaluated is facilitated by the fact that the analyzer features a form-wise evolution analyzer.

Procedure for the control of a respirator device as well as apparatus for monitoring

Gottlieb Weinmann Gerate fur Medizin und Arbeitsschutz GmbH & Co.


An ignition plug (1) includes a center electrode (5) extending in the direction of an axis (CL1), an insulator (2) having an axial hole (4) into which the center electrode (5) is inserted, a tip (31) joined to a forward end portion of the center electrode (5) by a fusion portion (35), and a ground electrode (27) forming a gap (33) in cooperation with the tip (31). The ignition plug generates high-frequency plasma at the gap (33) when high-frequency electric power is supplied to the gap (33). The forward end of the tip (31) is located forward of the forward end of the insulator (2) with respect to the direction of the axis (CL1). Also, at least a portion of the outer surface of the fusion portion (35) is located within the axial hole (4), and, the distance between a forward-end-side opening of the axial hole (4) and the rearmost end of the outer surface of the fusion portion (35), measured along the axis (CL1), is equal to or greater than 0.1 mm. Thus, in the ignition plug (1) which generates high-frequency plasma, corrosion of the fusion portion can be suppressed effectively, whereby durability is improved.

An ignition plug used for a combustion apparatus such as an internal combustion engine includes, for example, a center electrode extending in the axial direction, an insulator provided around the center electrode, a tubular metallic shell provided around the insulator, and a ground electrode having a base end portion joined to a forward end portion of the metallic shell. Through application of high voltage to the center electrode, spark discharge is produced at a gap formed between the center electrode and the ground electrode, whereby a fuel-air mixture is ignited.
In recent years, a technique for improving ignition performance has been proposed (see, for example, Patent Document 1, etc.). In the proposed technique, high-frequency electric power is supplied to the gap in place of high voltage so as to produce high-frequency plasma to thereby ignite a fuel-air mixture. Also, there has been proposed a technique of producing high-frequency plasma by supplying high-frequency electric power to spark generated through application of high voltage.
In addition, in order to enhance durability and/or ignition performance, a tip formed of a noble metal alloy or the like may be joined to a forward end portion of the center electrode. In general, such a tip is joined to the center electrode via a fusion portion which is formed by laser welding from the metal which forms the center electrode and the metal which forms the tip (see, for example, Patent Document 2, etc.).


A working vehicle, such as an agricultural combine, includes a vehicle body and an internal combustion engine carried by the vehicle body. The internal combustion engine includes a heat exchanger. An air scoop has an inlet positioned near a top of the vehicle body and facing in an upward direction, and an outlet positioned in association with the heat exchanger.

Work vehicles such as off road construction and agricultural vehicles are usually powered by combustion engines and operate in dirty environments. Often, an engine compartment is used to isolate the engine and cooling system from the dirty ambient air, which contains dust and other particulate matter. A work vehicle such as an agricultural harvester (e.g., combine) is also exposed to chaff (crop residue ) from the crop being harvested. The crop harvesting process creates dust, dirt, and chaff that surrounds the vehicle. Hot engine exhaust is also discharged from the vehicle.
During operation, clean air is needed for efficient combustion in the internal combustion (IC) engine and cool air is needed for efficient engine and vehicle cooling system operation. More particularly, the air supply must be free of debris and dust so as to mix with the fuel to provide combustion in the IC engine. The combustion air intake usually includes an air pre-filter and a separate air cleaner. Further, the air supply must be free of debris and dust for use as cooling air to cool the combustion engine, hydraulic system and cab air conditioning system of the work vehicle.
The air management system on some current combines involves drawing air through a louvered side panel into the cooling package. A rotating rotary screen with a vacuum cleaning system is used to pre-clean the dirty air before it passes through the heat exchangers of the cooling package. A combustion air inlet is located downstream of the rotary filter and has a separate pre-cleaner and air filter for the combustion air supplied to the engine.
However, prolonged use during harvesting operations can result in plugging of the rotary screen, plugging of the cooling package cores, plugging of the pre-cleaner, short air filter life, and excess debris accumulation on the engine deck. These affects of dirty air often require the operator to stop the vehicle and clean the air management system. Structural changes to the vehicle have reduced debris accumulation on the engine deck. However, the root cause of the dust and chaff in the intake air remains a problem.

Agricultural working vehicle with air scoop for air intake system


A low-cost microelectromechanical system (MEMS) device has a mass-produced carrier fabricated as a pre-molded leadframe so that the space of the leadframe center is filled with compound and a two-tier stepped recess is created in the center. The first tier is filled by an inset with a first perforation and a second perforation. An integrated circuit chip with an opening and a membrane at the end of the opening, operable as a pressure sensor, microphone, speaker, etc, is assembled on the inset so that the chip opening is aligned with the first perforation. The chip is protected by a cover transected by a vent aligned with the second inset perforation. An air channel extends from the ambient exterior through the vent and the second perforation to the second tier recess, which acts as a channel and connects to the first perforation and the chip opening to the membrane.

This relates generally to the field of semiconductor devices and processes, and more specifically to the structure and fabrication method of microelectromechanical system (MEMS) devices in leadframe-based pre-molded packages with acoustic channel suitable for microphones, speakers, and pressure gauges.
The wide variety of products collectively called microelectromechanical system (MEMS) devices are small, low weight devices on the micrometer scale, which may have mechanically moving parts, including transducers and actuators, and may have parts sensitive to thermal, acoustic, or optical energy. Because of the moving and sensitive parts, MEMS devices have a need for physical and atmospheric protection. Consequently, MEMS devices are typically placed on a substrate and surrounded by a housing or package, which shields the MEMS device against ambient and electrical disturbances, and against stress.
A MEMS device integrates mechanical elements, sensors, actuators, and electronics on a common substrate. MEMS device manufacturing aims at using batch fabrication techniques similar to those used for non-MEMS microelectronics devices. MEMS devices can thus benefit from mass production and minimized material consumption to lower the manufacturing cost, while trying to exploit the well-controlled integrated circuit technology, although today the production of MEMS devices is still far from the level of maturity that manufacturing and packaging of microelectronics have reached.
MEMS devices may be mechanical sensors, both pressure sensors such as microphone membranes, and inertial sensors such as accelerometers, either of which may be coupled with the integrated electronic circuit of the chip. Mechanical sensors react to and measure pressure, force, torque, flow displacement, velocity, acceleration, level, position, tilt, and acoustic wavelength and amplitude. Among the general requirements for pressure sensors are long term stability, small temperature sensitivity, low pressure and temperature hysteresis, resistance to corrosive ambients, and often hermeticity. Two specific bulk micromachining processes employed in MEMS sensor production to create in bulk semiconductor crystals the movable elements and the cavities for their movements are anisotropic wet etching and deep reactive ion etching (DRIE).
The semiconductor MEMS pressure sensors and microphones are assembled on insulating substrates, which include multi-level metallizations patterned for horizontal and vertical connections. As an example, the substrate may have four metallization levels. The assembly typically involves adhesive chip attachment and metal wire bonding to the terminals. In many products, the terminals are positioned similar to the compact Small Outline No-Lead (SON) or Quad Flat No-Lead (QFN) type semiconductor devices, since they show the compact outline of chip-size packages. The substrates also include the air channels needed to expose the membranes to the ambient pressure and acoustic signals to be monitored by the MEMS devices. For protection and robustness reasons, the chip, wires, and portions of the substrate are packaged in a metal can or molded in a plastic encapsulation. As an example, the dimensions of a MEMS cuboid analog-output microphone with four terminals for mobile phones may be about 4.8 mm by 3.8 mm by 1.25 mm, or even as small as 2 mm by 2 mm by 1.25 mm (resulting in a 4 mm2 footprint).

Leadframe-based premolded package having air channel for microelectromechanical system (MEMS) device


Methods and systems are disclosed for processing stereoscopic video data for transmission into a single frame or field, including multiplexing color data for left-eye and right-eye image into a single frame or field in a spatially incongruous manner. Embodiments of the invention also relate to methods and systems for processing such a single frame or field and displaying the corresponding stereoscopic video data either on a passive monitor or on an active monitor, to render three-dimensional (3D) video content. The invention also relates to corresponding computer programs and signals.

In the context of display technologies, stereoscopic 3D television (3DTV) monitors and display devices exist and are continuing to be developed for viewing stereoscopic video data: whether the stereoscopic video data has been produced directly from a scene, using for instance two cameras, or by conversion of pre-existing two-dimensional video content. Two stereoscopic 3D monitor technologies are available; namely, passive monitor technology and active monitor technology. Both create an illusion of depth using a two-dimensional (2D) screen and special wearable glasses.
The passive monitor technology displays left-eye and right-eye images simultaneously on alternating lines of a monitor, and polarizes these alternating lines differently. Therefore the left-eye and right-eye images are polarized differently. Passive glasses, worn by the users, allow images polarized in a first manner to be viewed by the user's left eye and images polarized in a second manner to be viewed by the user's right eye. Thus, only the left-eye images reach the user's left eye and only the right-eye images reach the user's right eye. In other words, the passive glasses filter the light so that the left-eye images are not viewed by the user's right eye and, conversely, the right-eye images are not viewed by the user's left eye.
The active monitor technology alternates left-eye and right-eye images sequentially in time. The active glasses, worn by the users, alternately allow images to be viewed by the user's left eye and images to be viewed by the user's right eye, using a shuttering mechanism synchronized with the monitor. Thus, when a left-eye image is displayed at a first instant on the active monitor, only the user's left eye can see it and when a right-eye image is displayed at a second instant on the active monitor, only the user's right eye can see it. The shuttering mechanism synchronized with the monitor may be based on the use of liquid-crystal-shutter (LCS) 3D glasses. The synchronization between the active glasses and the monitor may be based on an infrared link. The active monitor technology is therefore said to be "active" compared to the passive monitor technology not because the monitor itself would be more "active" but because the active monitor technology is based on the use of active glasses including a shuttering mechanism.
It is desirable to provide methods and systems to improve the quality of the stereoscopic video content viewed on stereoscopic 3D televisions and other display devices, and it is desirable to do so while efficiently using the storage and network resources necessary to store and transfer stereoscopic video data.

Methods and systems for processing stereoscopic video data


The present invention provides hepatoprotectant acetaminophen mutual prodrugs, which have an acetaminophen moiety covalently linked to a second moiety that may act as a hepatoprotectant against acetaminophen hepatotoxicity. Additionally, acetaminophen mutual prodrugs may have improved water solubility which may provide better suitability for parenteral and other dosage forms relative to administration of acetaminophen. Also provided are methods of treating a disease or condition that is responsive to acetaminophen (such as fever, pain and ischemic injury) using hepatoprotectant acetaminophen mutual prodrugs, as well as kits and unit dosages.

Acetaminophen (also known as paracetamol, and chemically known as N-(4-hydroxyphenyl)acetamide)) is a widely-used analgesic for the treatment of a variety of conditions related to pain. For example, acetaminophen is used to manage pain from surgery or traumatic injury, and pain produced by chronic inflammatory conditions such as osteoarthritis, rheumatoid arthritis, and lower back pain. In some cases acetaminophen is used to treat pain from mixed nociceptive/neuropathic etiologies, such as cancer or fibromyalgia. Acetaminophen also may have utility in management of other conditions, such as myocardial injury (Spiler N M, Rork T H, Merrill G F; Curr Drug Targets Cardiovasc Haematol Disord. 2005; 5(5):419-29) and nerve injury (Bisaglia M, Venezia V. Piccioli P, Stanzione S, Porcile C, Russo C, Mancini F, Milanese C, Schettini G. Neurochem 2002; 41(1):43-54).
Large quantities of acetaminophen (alone or in combination with other therapeutic agents, such as opioids) are manufactured, prescribed, and distributed throughout the world. With increasing concerns about the cardiovascular and gastrointestinal safety of conventional NSAIDs (such as ibuprofen and naproxen) and selective cyclooxygenase-2 inhibitors such as Vioxx®), patients and physicians have turned to acetaminophen for its seemingly lower safety risks.
However, it is well known that under certain conditions acetaminophen may be toxic to the liver (known as hepatotoxicity). It is estimated that most liver transplants in the United States are caused by acetaminophen toxicity, and 49% of all acute liver failure cases in 2004 were the result of acetaminophen overdose. Each year, overdoses of acetaminophen (sold as Tylenol® and other brands) account for more than 56,000 emergency room visits and an estimated 458 deaths from acute liver failure (Harvard Women's Health Watch, March, 2006). According to a recent study from the U.S. Acute Liver Failure Study Group (Lee W M. Hepatology 2004; 40(1):6-9), acetaminophen-related liver failure appears to be on the rise. Researchers at the University of Washington Medical Center in Seattle found that between 1998 and 2003, the percentage of acute liver failure cases attributed to acetaminophen nearly doubled, rising from 28% to 51%, Acetaminophen toxicity may go beyond liver and may involve kidneys and/or myocardium (J T DiPiro, R L Talbert, G C Yee, G R Matzke, B G Wells, L M Posey (eds) Pharmacotherapy: A Physiological Approach 6th ed McGraw Hill (New York 2005) pp. 133).
Acetaminophen's daily dose limit of 4 grams reduces its therapeutic utility as 4 grains can be consumed in 16 hours (1 gram every 4 hours) leaving the remaining 8 hours of the day to seek alternative analgesics. Further, ethnic and intersubject variability in acetaminophen metabolism have been reported to be as high as 60-fold (S. Bridger, et al. BMJ 1998; 316:1724-1725), which complicates the acetaminophen safety profile as it imparts a high degree of uncertainty in the toxic dose for a given patient. By attenuating toxicity, improved compounds may provide greater utility by allowing doses higher than 4 grams and/or provide a larger safety margin for patients of any ethnic background.
Acetaminophen induced hepatic toxicity has been found to be dependent on both acetaminophen blood level concentration and length of exposure. Consequently, acetaminophen package labels instruct patients to not use the maximum dosage (4000 mg per day) for more than 10 days, and to not take the product for pain for more than 10 days, or for fever for more than 3 days unless directed by a physician. Even healthy adults receiving 4000 mg of acetaminophen per day for 14 days show elevated levels of enzymes indicative of liver toxicity (Journal Amer. Med. Assoc. 296, 87-93, 2006).
It is known that after administration, about 90% of acetaminophen is conjugated with glucuronide and sulphate, and less than 5% remains unmetabolized. The remaining ˜5% of acetaminophen is metabolized in the liver by cytochrome P450 mixed-function oxygenase system (mainly by CYP2E1), and is converted to N-acetyl-p-benzquinone imine (NAPQI) (J T DiPiro, R L Talbert, G C Yee, G R Matzke, B G Wells, L M Posey (eds) Pharmacotherapy: A Physiological Approach 6th ed McGraw Hill (New York 2005) pp. 133). NAPQI is capable of damaging proteins by covalently binding to nucleophilic residues (e.g., cysteine residues). Glutathione (GSH; a tripeptide of L-glutamate, L-cysteine and L-glycine) aids in detoxification by conjugating with NAPQI and may be depleted by as much as 90% following a toxic dose of acetaminophen. Low concentrations of GSH in centrilobular cells of liver can lead to centrilobular hepatic necrosis, which can be fatal (Drug Metabolism and Disposition 31: 1499-1506, 2003). The GSH adduct with NAPQI is either excreted into bile or further metabolized via the mercapturic acid pathway, which involves removal of glutamyl and glycine groups and conversion of cysteine to N-acetylcysteine conjugate. (The Journal of Pharmacology and Experimental Therapeutics 294: 735-745, 2000).
N-acetylcysteine (NAC) also called acetylcysteine (Acetadote®) is an FDA-approved antidote for acetaminophen toxicity available in both oral as well as intravenous dosage form. (Acetadote® package insert. Cumberland Pharmaceuticals, Nashville, Tenn. Issued March 2004.) NAC has been known to prevent or mitigate hepatic toxicity of acetaminophen by stimulating glutathione synthesis (by promoting metabolic pathways) which produces nontoxic metabolites of acetaminophen and/or by detoxifying toxic metabolites (In Goldfrank's Toxicologic Emergencies 7th Ed. New York: McGraw-Hill; 2002, 502-506). However, NAC only has been shown to be effective at minimizing hepatic toxicity when administered within 8-10 hours of acute exposure to toxic blood levels of acetaminophen. Anaphylactoid reactions to intravenously administered NAC have also been reported (Lynch R M, Robertson R. Accid Emerg Nurs. 2004; 12(1):10-5).
Cysteine and methionine (methionine can be converted to cysteine through the hepatic cystathionine pathway) can ensure the maintenance of normal hepatic GSH levels when supplied in adequate amounts. GSH can also be a transport and storage form of cysteine (Journal of Nutrition, 127: 2135-2141, 1997). Extracellular methionine has found to be as strong an antioxidant as cysteine against intracellular reactive oxygen species (Metabolic Bases of Inherited Disease 5th Ed, New York: McGraw-Hill; 1982, 522-559). Oral administration of methionine has been used to treat acetaminophen overdoses, as 30 patients at risk of hepatic damage from acetaminophen ingestion were given 2-5 g oral methionine every four hours up to a total dose of 10 g; where the first dose was given within ten hours of the overdose. There were no deaths and no reports of hepatic encephalopathy or other complications following administration of the methionine (Crome P, Vale J A, Volans G N, Widdop B, Goulding R. Lancet. 1976; 2(7990):829-30). A combination of acetaminophen (500 mg) and methionine (100 mg) is available in the United Kingdom (Paradote®) to prevent the onset of acetaminophen poisoning through the maintenance of high glutathione levels in the liver. The methionine in this formulation contains both the L-isomer (an essential amino acid in humans) and the D-isomer (unnatural). Cysteine and acetylmethionine coupled to acetaminophen have been described in DE 4327462A1 and Skoglund L A, Skjelbred P. Eur J Clin Pharmacol 1984; 26(5):573-7.
Administration of procysteine (L-2-oxothiazolidine-4-carboxylate), which is converted to L-cysteine by 5-oxo-L-prolinase, may result in an increase of intracellular cysteine levels and has been shown to increase GSH synthesis. This effect has been shown to be more pronounced when administered prior to acetaminophen than when administered after acetaminophen (e.g., administration of L-2-oxothiazolidine-4-carboxylate 30 minutes post-acetaminophen administration caused GSH tissue levels to reach 6.1 μmol/g, of tissue compared to 5.3 μmol/g of tissue when administered 120 minutes post-acetaminophen administration; Proceedings of The Natural Academy of Sciences, 79: 6246-6249, 1982).
Some patients (e.g., those with chronic pain) may seek acetaminophen treatment for extended periods to avoid the potentially adverse events of alternative analgesics, such as NSAIDs, selective COX-2 inhibitors, and opioids. Additionally, patients with higher risks for hepatotoxicity (e.g., those with pre-existing liver damage and/or other stressors on the liver, such as alcohol consumption), may still benefit by having access to acetaminophen to control pain and fever.
Accordingly, it would be desirable to provide improved formulations or prodrugs of acetaminophen which address the important problem of hepatotoxicity while maintaining its therapeutic properties and/or which could alter the physicochemical properties of the acetaminophen to allow the development of alternative dosage forms.
The disclosures of all publications, patents, patent applications and other references referred to herein are hereby incorporated herein by reference in their entireties.

Hepatoprotectant acetaminophen mutual prodrugs


A method of producing a sealed structural joint between two components (23, 24) and such a sealed joint are provided. The method includes the steps of applying a layer of sealant (27) to the first component (23), applying liquid shim (28) to the second component (24), inserting an intermediate layer (29) between the sealant (27) and the liquid shim (28), the intermediate layer (29) having a series of raised structural features (31) to engage the first component (23). The features (31) are positioned to allow the sealant (27) to extend across the joint between the raised features (31) to form a continuous seal. The joint is then closed and cure of the liquid shim (28) and sealant (27) takes place to solidify the shim (28) to the desired thickness within the joint.

The use of liquid shim in structural joints is commonplace in the aircraft industry. Liquid shim compensates for small tolerance mismatches between components prior to fastening and avoids build stresses that can lead to delamination of composite materials, stress corrosion cracking of metallic parts and premature fatigue cracking.
Liquid shim is generally a two-part epoxy paste. It may be applied by injection into the joint or by a "butter and paste" application. The liquid shim cures in place in the joint and the composition is optimised for compression and fatigue properties.
Current processes require joints to be disassembled several times during manufacture for cleaning, de-burring and application of liquid sealant. An example process which would require the joint to be assembled three times would be as follows:—
Step 1—Assemble joint and measure the gap or use a decision gauge
Step 2—Disassemble the joint and clean the faying surfaces
Step 3—Mix the liquid shim
Step 4—Apply liquid shim and assemble the joint
Step 5—Allow the shim to cure
Step 6—Disassemble joint for cleaning, preparation and drilling
Step 7—Inspect the joint
Step 8—Re-work the shim as necessary
Step 9—Apply sealant and final fasten joint together.

Sealing and shimming of structural joints


A master information carrier is made to overlap with a magnetic recording medium being a magnetic recording medium in an adhering state, and a pattern corresponding to information signals on the master information carrier is transferred to the magnetic recording medium, thereby magnetically transferring a magnetized pattern of information signals to the magnetic recording medium. Thereafter, an urging force to the magnetic recording medium side is applied to the master information carrier, and in the urging force applied state, a gas under pressure is supplied on the adhering/joining surfaces of the master information carrier and the magnetic recording medium, thereby releasing the adhering state of the master information carrier and the magnetic recording medium. Then, the application of the urging force is released to continue the supply of the gas under pressure, thereby pulling away the master information carrier from the magnetic recording medium and moving them.

1. Field of the Invention
The present invention relates to a magnetic transferring method of magnetically transferring information signals from a master information carrier to a magnetic recording medium, and to a magnetic transferring apparatus used for the method. The magnetic recording medium includes all media the whole or part of which is magnetically recordable.
2. Description of the Related Art
Currently, hard disc drives and other magnetic recording/reproducing devices tend to achieve a higher storage density in order to realize a smaller size and larger capacity thereof. In such a higher storage density, the tracking servo technology of recording/reproducing magnetic heads plays an important role. In the current tracking servo technology, preformattedly recorded on a magnetic recording medium are information signals such as tracking servo signals, address signals and clock signals. A magnetic head reproduces these information signals and scans correctly the data on the track while checking and correcting the position itself.
These information signals become ones used for a reference in order that a magnetic head scans correctly the data on the track. Therefore, the information signals are required to be correctly positioned and provided with respect to a magnetic recording medium. Thus, a magnetic recording medium is required to have an excellent flatness or smoothness on the recording surface for information signals, and to have no micro-deposits at recording information signals.
As a method of preformattedly recording information signals on a magnetic recording medium, there is a magnetic transferring method in which information signals recorded on a master information carrier are collectively recorded by magnetic transfer on the magnetic recording medium. In such a magnetic transfer, the transfer from the master information carrier to the magnetic recording medium takes place in an adhering state. Thus, after magnetic transfer, it is necessary to separate the master information carrier and the magnetic recording medium which are in a state of adhering to each other.
In such a magnetic transfer, when the master information carrier and the magnetic recording medium have a smooth and flat adhering surface because of a higher storage density, the master information carrier and the magnetic recording medium are in a state of sticking strongly to each other, so that it is not easy to separate the master information carrier from the magnetic recording medium after magnetic transfer.
Therefore, a primary object of the present invention is to provide a magnetic transferring method capable of separating easily and reliably a master information carrier and a magnetic recording medium which are in a state of adhering to each other for magnetic transfer, after magnetic transfer, and provide a magnetic transferring apparatus used for the method.
Another object of the present invention is to provide a magnetic transferring method capable of separating easily a master information carrier and a magnetic recording medium after magnetic transfer and manufacturing stably and at a good productivity in a short time the magnetic recording medium onto which information signals are magnetically transferred from the master information carrier, and provide a magnetic transferring apparatus used for the method.
Still other objectives, features and advantages of the present invention will be apparent from the following description.
The present invention, when summarized, includes a first step at which a master information carrier is overlapped on a magnetic recording medium in an adhering state, a second step at which in the above-mentioned adhering state, a pattern corresponding to information signals on the above-mentioned master information carrier is magnetically transferred to the above-mentioned magnetic recording medium, a third step at which a urging force of urging the above-mentioned master information carrier and the above-mentioned magnetic recording medium against each other is applied, while a gas under pressure is supplied between both the adhering surfaces of the above-mentioned master information carrier and the above-mentioned magnetic recording medium, and a forth step at which the above-mentioned urging force is released, and the above-mentioned gas under pressure is continued.
The present invention is preferably configured such that in the above-mentioned first step, the above-mentioned master information carrier is made opposite to the above-mentioned magnetic recording medium, and after a gas at a first supplying pressure has been supplied between opposed surfaces of the above-mentioned master information carrier and the above-mentioned magnetic recording medium, the supplying pressure is made to be stopped to cause the above-mentioned master information carrier and the above-mentioned magnetic recording medium to adhere to each other.
The present invention is more preferably configured such that the above-mentioned first supplying pressure is 0.1 through 1 kg/mm2.
The present invention is more preferably configured such that in the above-mentioned first step, the above-mentioned master information carrier is sucked to and held by a sucking pad, and in this holding state, the above-mentioned master information carrier is made to be opposite and close to the above-mentioned magnetic recording medium, and after a gas at a first supplying pressure has been supplied through a central hole of the above-mentioned magnetic recording medium between opposed surfaces of the above-mentioned master information carrier and the above-mentioned magnetic recording medium, the supplying pressure is made to be stopped and at the same time, a gas at the same sucking pressure as that of the above-mentioned sucking pad is sucked from opposed surfaces of the above-mentioned master information carrier and the above-mentioned magnetic recording medium to cause the above-mentioned master information carrier and the above-mentioned magnetic recording medium to adhere to each other.
The present invention is more preferably configured such that in the above-mentioned third step, with the area of the central hole of the above-mentioned magnetic recording medium expressed as S, the urging force against the above-mentioned master information carrier as F, and an pressure of the gas mentioned above pressure for releasing the adhering as P4, there is set a relationship of Fxe2x89xa7P4xc3x97S.

Magnetic transferring method and magnetic transferring apparatus

Matsushita Electric Industrial Co., Ltd.


A device for reading and writing of information on a magnetic medium such as a disk or tape comprises at least one reading and writing head placed on a base having a catamaran type profile. The head is composed of a magnetic circuit (a winding on a medium) self-positioned and welded to the walls of a hole made in the base, a flow concentrator in contact with the extremities of the magnetic circuit and a pole piece made up of two magnetic parts separated by a magnetic spacer. The pole piece is positioned opposite to the track of the magnetic medium.

Currently, an elementary magnetic storage cell on a medium in the form of a disk or tape requires a superficial area of about 100 to 120 square micrometers. One cell is described by the width of the recording track (usually 20 micrometers) and by the number of bits per unit of length.
Elementary cells with, a superficial area of 0.5 to 25 square micrometers and a surface density almost equal to 1 bit per square micrometer are currently envisaged. The reading and writing of information on such cells necessitates new type of magnetic heads offering improved performances.
According to the prior Art, three different types of heads currently exist : the first type is the normal type relating to monolithic or solid-state heads, the second is formed by heads made up of thin layers and the third corresponds to hybrid or composite heads.
Owing to the magnetic volume involved, mono and mini-monolithic heads generate significant noise and possess poor resolution. Their method of production limits access to large densities and renders difficult passage to densities greater than 1200 TPI (tracks per inch).
Heads consisting of thin layers have many advantages, but they are costly and complex to produce and volume production remains quite small.
Only hybrid or composite heads allow access to large recording densities while keeping production costs relatively low. Their current performances fall between those of the other types of heads.

Device for reading and writing on a magnetic medium


A differential voltage controlled current source generating one or more output currents is based upon a single external resistor. The differential voltage controlled current source may generate an output current that is proportional to a received differential voltage and a bias current with the use of a single external resistor. The technique may be used to generate multiple accurate and process independent current sources. The current sources may be a zero temperature coefficient (ZTC) current, a proportional to absolute temperature (PTAT) current, or an inversely proportional to absolute temperature (NTAT) current. The output of the current sources may be inversely proportional to the resistance of the external resistor.

As the need to reduce current in transceivers, radio frequency amplifiers, and other integrated circuits increases, the need to more accurately control currents of the integrated circuits also increases. In addition, an integrated circuit may require multiple current sources that have different temperature coefficients. As an example, a zero temperature coefficient (ZTC) current source may be used to develop a bias current. In some applications, a proportional to absolute temperature (PTAT) current source or an inversely proportional to absolute temperature (NTAT) current source may be useful to compensate for temperature drift. Furthermore, as power consumption requirements become more restrictive, there may be times in which a particular application needs to accurately set a bias current based upon an external reference element. For example, there may be a desire to set a bias current based upon one or more precision resistors coupled to the integrated circuit.
Even so, process drift and batch-to-batch differences may reduce the accuracy of internally generated currents and thereby reduce the yield of these integrated circuits. Thus, there is a need for a circuit and technique to generate process independent and batch independent current sources for integrated circuit applications to improve manufacturing yields.

Method of generating multiple current sources from a single reference resistor


Compositions, medicaments, and methods for the promotion of hair growth are disclosed. These compositions and medicaments are comprised of either local anesthetics of the secondary or tertiary amino type or niacin. The preferred secondary and tertiary amino compounds include those which are esters of para-aminobenzoic acid, esters of benzoic acid, esters of meta-amino benzoic acid, amides, ethers, and ketones. The preferred compositions and medicaments include either procaine hydrochloride or niacin or procaine hydrochloride and niacin in a non-sulfur-containing carrier. The disclosed compositions and medicaments may be topically applied to a scalp in need thereof by an eyedropper or other suitable means. An improved embodiment of this application adds minoxidil.

At birth, the average human scalp has approximately 100,000-150,000 hair follicles. Initially, hair follicles normally exhibit fine lanugo hair shafts, which are commonly referred to as "baby hair". This lanugo hair "matures" eventually, into terminal hair shafts, which is the hair most often exhibited during adolescence and adulthood. Thereafter, this terminal hair may remain as such, or it may develop into non-terminal vellus hair, which is commonly referred to as a "thinning" of the hair and, in more advanced stages, baldness.
The precise mechanism that triggers the development of non-terminal vellus hair is not precisely understood or agreed upon. However, there have been numerous attempts to provide an effective safe prophylaxis to arrest development of non-terminal vellus hairs and even to stimulate the regeneration of these vellus hairs into terminal hair shafts. Unfortunately, none of these attempts have proven to be fully satisfactory.
Thus, it can be seen that there remains a need for compositions, medicaments, and methods for administering the same, which are effective in stimulating the development of terminal hairs from non-terminal vellus hairs, are safe for use with a human host, and which are easy to administer.
There are many causes of hair loss for which suitable treatments are well known. For example, if the hair loss is due to general poor health of the patient, then a program designed to improve overall health would be instituted. If the patient's dietary habits are the cause of hair loss, then the patient's diet should be changed. If the patient's medications have the side effect of hair loss, then the medications should possible be changed. If a patient's shampoo is the cause of the hair loss, then the shampoo should be changed. If the patient's hair loss can be attributed to certain types of stress, then those types of stress should be eliminated or reduced. A patient's hair loss may be attributable to certain underlying dermatological conditions such as psoriasis, seborrheic dermatitis, perifolliculitis capitis, pseudopelade of Brocq (alopecia cicatricata), lichenplanopilaris, fungal and bacterial infections, connective tissue diseases such as lupus erythematosus, scleroderma, sarcoidosis, genetic abnormalities (including ectodermal dysplasia) among others.
A patient's hair loss may be attributable to certain underlying symptomatic conditions or drug exposure, such as telogen effluvium and anagen effluvium. The compositions and methods of the invention may be employed to supplement or augment known treatments for such conditions.
Telogen effluvium is hair loss that often results in three to six months after a serious illness such as pneumonia, a life-threatening illness, a surgical intervention, or other illness that requires a person to spend an unusually large amount of time in bed rest. Telogen effluvium generally self corrects from three to six months after its onset.
Anagen effluvium is hair loss that results when patients are administered chemotherapeutic agents, or other toxic agents. It is theorized that anagen effluvium is caused by a sudden shock to hair generating tissues (hair bulbs) in the growing state that can result from the administration of chemotherapeutic agents. As a result of the shock, the growing hairs fall out of the hair follicles.
If the patient's hair loss is due to hypothyroidism, then increased thyroid hormones can be administered. If perceived hair loss is due to hyperthyroidism, then the patient's thyroid activity can be reduced by drug therapy. It is noted that hypothyroidism diminishes the amount of hair that will grow because of decreased metabolic rates. Hyperthyroidism causes hairs to become very fine, and the very fine hairs are perceived to be hair loss.
To determine specific known causes of hair loss, a history is taken, and a physical examination is conducted. Once a known cause of hair loss is diagnosed for which a known treatment is accepted, then the known treatment can be instituted.
However, even with types of hair loss whose cause is determined and whose treatment is known, the rate of return of the lost hair may often be undesirably slow. It would be desirable, therefore, to be able to treat the patient being treated for a known cause of hair loss to accelerate the return of hair to such patients.
There are other types of hair loss for which the causes are less well understood, and only a few and limited known effective treatments are accepted in medical practice, i.e., the use of topical minoxidil. For these types of hair loss, the need for alternate effective treatments is very strong. Some examples of hair loss for which satisfactory treatments are not currently available include: male androgenetic alopecia and female androgenetic alopecia (male and female pattern baldness).
Another form of alopecia, known as alopecia areata (including alopecia totalis and alopecia universalis), is a type of hair loss for which no single or multiple treatment modalities (even including minoxidil) are considered to be highly effective.
As further background, it is noted that some vasodilators have been tried topically to treat hair loss, and these vasodilators have not been effective. For example, diazoxide has been tried topically on the scalp to promote hair growth, but this was not deemed to be effective.
It would be desirable to provide effective topical treatments of the hair loss conditions for which satisfactory topical treatments are not currently available.
A number of patents and publications have been uncovered which may be relevant to the scalp treatment methods and compositions of the invention set forth hereinbelow. These patents and publication are as follows, in approximate chronological order:
1. French patent No. 336,814 of Ascoli (1904) PA1 2. New York State Journal of Medicine, Vol. 49, (1949), pages 1317-1318 PA1 3. Aslan A: Med. Klin.: 52, 1758, 1759, 1760 (1957) PA1 4. Scholzel, P.: Med. Klin.: 53, 2239 (1958) PA1 5. French patent No. 1439833 of Serviere (1966) PA1 6. U.S. Pat. No. 3,644,364 of Anthony (1972) PA1 7. Chemical Abstracts No. 79:23508s (1973) PA1 8. French patent No. 72.39675 of Indaly Oy (1973) PA1 9. UK patent No. 1 354 446 of Indal Oy (1974) PA1 10. U.S. Pat. No. 3,896,238 of Smith (1975) PA1 11. U.S. Pat. No. 3,903,256 of MacMillan et al (1975) PA1 12. U.S. Pat. No. 3,952,099 of Smith (1976) PA1 13. Merck Index of Chemicals and Drugs, hereinafter "Merck", 9th Edition, Merck & Co., Rahway, N.J., (1976), entries 6340 and 6343. PA1 14. U.S. Pat. No. 4,139,619 of Chidsey (1979) PA1 15. U.S. Pat. No. 4,150,114 of Smith (1979) PA1 16. UK patent no. 1 603 639 of Haggar (1981) PA1 17. Chemical Abstracts No. 96:74505x (1981) PA1 18. Current Therapy, (1981), page 662 PA1 19. U.S. Pat. No. 4,329,338 of Szego et al (1982) PA1 20. Japanese application no. 58-103310 of Yoshiya (1983) PA1 21. Conn's Current Therapy, 1984, entry on "Alopecia", by Gonzalez et al, pages 599-603. PA1 22. Chemical Abstracts No. 104:24067u (1985) PA1 23. EPO Patent No. 0 158 090 of Roshdy (1985) PA1 24. U.S. Pat. No. 4,596,812 of Chidsey et al (1986) PA1 25. EPO application No. 0 188 793 of Gans et al (1986) PA1 26. UK patent application No. 2 176 104A of Grollier (1986) PA1 27. UK patent application No. 2 177 919A of Salim (1987) PA1 1. French patent No. 336,814 of Ascoli (1904) appears to disclose a composition used to promote hair growth. The composition appears to disclose the active ingredient to be the chlorhydrate of cocaine. The carrier appears to be a grease, such as vaseline, to form a pomade. PA1 2. New York State Journal of Medicine, Vol. 49, (1949), pages 1317-1318, discloses a solution of niacin and procaine hydrochloride that is used for intravenous administration to treat a number of conditions listed in Table 1. The conditions listed include traumatic, degenerative, inflammatory, and miscellaneous conditions, none of which include hair loss. The composition was administered in an isotonic saline solution. There is a disclosure that niacin or nicotinic acid has a vasodilating effect, especially upon the capillary bed. PA1 3. Aslan A, in Med. Klin.: 52, 1758, 1759, 1760 (1957), appears to disclose, as indicated in the translation of the Scholzel article referred to below, that procaine has been used in injection or intravenous therapy of old people resulting in better mental and physical performance abilities, increase in muscle strength, improvement of rigidity, and stimulation of hair growth in many cases of baldness. PA1 4. Scholzel, P., in Med. Klin.: 53, 2239 (1958), in an English translation of the article in German, discloses the general content of the Aslan article mentioned above and goes on to disclose findings relating to a specific patient who, after 40 years of alopecia, showed hair growth after intravenous procaine therapy. There is also a disclosure that a person named Kohler, reported in 1957, the use of a combination of procaine with various vitamins in an apparently injectable composition ("Gerioptil pro injectione"). However, the specific use of effects of the Kohler compositions were not disclosed. PA1 5. French patent No. 1439833 of Serviere (1966) appears to disclose a composition which contains a synergistic combination of the following ingredients: malic acid, procaine, and a soluble derivative of sulfapyridine. The composition is apparently applied topically to improve hair characteristics, but not necessarily hair growth. PA1 6. U.S. Pat. No. 3,644,364 of Anthony (1972) discloses a process for preparing compounds which include minoxidil, an agent that may promote hair growth. PA1 7. Chemical Abstracts No. 79:23508s (1973) discloses an abstract of a German patent (to Indal Oy) that discloses hair growth promoting characteristics. The disclosures in the German patent of Indal Oy appear to be similar to the disclosures in French patent no. 72.39675 of Indal Oy (1973) and UK patent no. 1 354 446 of Indal Oy (1974) mentioned below. PA1 8. French patent No. 72.39675 of Indal Oy (1973) appears to disclose the compositions that are disclosed in UK patent no. 1 354 446 of Indal Oy (1974). PA1 9. UK patent No. 1 354 446 of Indal Oy (1974) discloses a composition for promoting the growth of hair. The composition contains nicotinic acid and salicylic and/or benzoic acid dissolved in a carrier containing ethanol, urea, polyoxyethylene sorbitan-monopalmitate or monostearate, with the remainder being isopropyl myristate. PA1 10. U.S. Pat. No. 3,896,238 of Smith (1975) discloses compositions for enhancing the penetration of pharmacologically active agents through skin comprising a sugar ester in combination with a sulfoxide or phosphine oxide. In Example VI, a topical anesthetic composition is disclosed for use in a spray can. The composition contains 1% benzocaine and 0.15% decyl methyl sulfoxide in a carrier comprised of approximately 50% ethanol and approximately 50% of a spray can propellant. There is a disclosure that the benzocaine can be replaced by an equivalent amount of procaine hydrochloride. PA1 11. U.S. Pat. No. 3,903,256 of MacMillan et al (1975) discloses compositions for topical application to skin comprising a sunscreen in certain aliphatic sulfoxides which enhance the penetration of the sunscreens through the skin. Example IV discloses a topical local anesthetic comprised of procaine hydrochloride, nonyl methyl sulfoxide, and the balance water. PA1 12. U.S. Pat. No. 3,952,099 of Smith (1976) is very similar in its disclosure to the above-mentioned U.S. Pat. No. 3,896,238 of Smith (1975). PA1 13. Merck Index of Chemicals and Drugs, hereinafter "Merck", 9th Edition, Merck & Co., Rahway, N.J., (1976), entries 6340 and 6343. PA1 14. U.S. Pat. No. 4,139,619 of Chidsey (1979) discloses compositions which employ minoxidil in carriers to be applied topically to a scalp to promote hair growth. PA1 15. U.S. Pat. No. 4,150,114 of Smith (1979) is very similar in its disclosure to the above-mentioned U.S. Pat. No. 3,896,238 of Smith (1975). PA1 16. UK patent No. 1 603 639 of Haggar (1981) discloses a composition for application to the hair and scalp for use in stimulating hair growth in treating alopecia and excessive hair loss. The composition includes a hair conditioner (lotion or cream) and a vitamin solution which contains vitamins B1, B2, B6, A, D, nicotinamide, and ascorbic acid. It has been found particularly advantageous to use Oil of Rosemary in the vitamin solution. More specifically, in one preferred embodiment, Oil of Rosemary is included. In another preferred embodiment, Oil of Balsam is included. In addition, the carrier can be the conditioner LIFE-TEX (T.M.) produced by Wella, which has been found satisfactory. The carrier desirably promotes absorption into the scalp and is preferably an antiseptic type spirit which may be alcohol, isophane insulin, or other biologically acceptable volatile liquid. However, white iodine is the preferred carrier. Petroleum jelly or liquid paraffin may also be included. There is a statement that the composition for application to the hair and scalp includes a commercial hair conditioner and a vitamin solution which contains one or more of the disclosed vitamins. PA1 17. Chemical Abstracts No. 96:74505x (1981) discloses an abstract of the UK Haggar patent discussed above. PA1 18. Current Therapy, (1981), page 662, discloses, that in the case of alopecia areata, single patches frequently regrow spontaneously within a few months although the course is unpredictable (including the rare extension to alopecia totalis or alopecia universalis), and recurrences are common. PA1 19. U.S. Pat. No. 4,329,338 of Szego et al (1982) discloses compositions for use as cosmetics. The compositions include a reaction product of nicotinic acid, a nicotinic acid salt, or a nicotinic acid halide and a polyhydroxy compound whose general formula is given in the Abstract. The active agents are disclosed as exerting beneficial effects for stimulating scalp or hair bulbs. PA1 20. Japanese application No. 58-103310 of Yoshiya (1983), in an English language Abstract, discloses a composition for accelerating hair growth that includes ginger in an alcoholic carrier which includes methyl alcohol, ethyl alcohol, and other lower alcohols. PA1 21. Conn's Current Therapy, 1984, entry on "Alopecia", by Gonzalez et al, pages 599-603, discloses a classification of causes of alopecia. Two main categories are nonscarring alopecia and scarring alopecia. Both the nonscarring alopecia and the scarring alopecia are subdivided into more specific conditions. See Table 1 on page 599. PA1 22. Chemical Abstracts No. 104:24067u (1985) discloses hair preparations for the promotion of hair growth which include extracts of the Acanthopanax root bark, with or without peripheral circulation promoting substances which include nicotinic acid. PA1 23. EPO Patent No. 0 158 090 of Roshdy (1985), written in the German language, appears to disclose compositions which contain vitamin C, vitamin A, vitamins of the B series, phospholipids, and unsaturated fatty acids. The compositions can be used in carriers that include alcohol or isopropyl alcohol. Other components of the compositions may include lecithin, amino acids, UV stabilizers, or antihistamines. PA1 24. U.S. Pat. No. 4,596,812 of Chidsey et al (1986) discloses methods and compositions for treating male pattern alopecia. The compositions include the substance known as minoxidil. Minoxidil is disclosed as a vasodilator that functions to dilate the peripheral vascular system. Minoxidil compositions are applied topically to the scalp and are used in a carrier system which can include equal parts of ethyl alcohol and propylene glycol. PA1 25. EPO application No. 0 188 793 of Gans et al (1986) discloses compositions containing minoxidil that include a carrier containing 70% alcohol, 20% water, and 10% propylene glycol. In this patent, an improvement comprises the inclusion of a hydroxy (lower alkyl) acrylate polymer to retard seepage of the minoxidil beyond the application site. PA1 26. UK patent application No. 2 176 104A of Grollier (1986) discloses compositions for the treatment of hair and of the scalp to promote fresh hair growth. It is disclosed that compositions containing nicotinic acid or its esters, when applied to the scalp, have rubefacient and vasodilant activity. The specific compositions disclosed in this patent include the combination of certain water-soluble polyamides of the poly-beta-alanine type with nicotinic acid or its esters. As shown in Examples 1 and 4, for a hair-care lotion, the carrier includes ethyl alcohol and water. PA1 27. UK patent application No. 2 177 919A of Salim (1987) discloses, in Example 9, a topical preparation to restore hair growth to areas of the human scalp suffering from hair loss. The preparation includes procaine, a physiologically acceptable, organic, in vivo sulphydryl group releasing agent, and castor oil.
More specifically, with respect to the references listed above, the following summaries of their disclosures are provided.
Entry 6340 is for nicotinamide. PA2 Entry 6343 is for nicotinic acid also known as niacin. Nicotinic acid is soluble in propylene glycol.
The following conclusions can be made from a consideration of the prior art discussed above. Procaine has been used topically, in the presence of other active ingredients and in the presence of complex carrier ingredients, often including sulfur-containing carriers, to treat the scalp for hair growth. It is also clear from the prior art that neither procaine nor niacin, either alone or in combination with one another, has been used topically without other active ingredients and without a complex carrier system which often includes sulfur-containing carriers and non-hydrophilic ingredients.
Carriers containing sulfur-containing ingredients have their problems. For example, the safety and efficacy of dimethylsulfoxide (DMSO) has not been sufficiently established to for the U.S. Food and Drug Administration to permit its use in the United States.
Carriers containing non-hydrophilic ingredients may have the undesirable property of impeding or preventing penetration of the active, hair-bulb treating agents into the hair bulb from the surface of the skin when the active ingredient is applied topically.

Methods and compositions for the promotion of hair growth


The present invention is concerned with linear double stranded DNA, which is coupled to a single support or a tag at the 3′ end of its non-coding strand and methods for producing said linear double stranded DNA. The present invention further relates to the use of said linear double stranded DNA in an RNA in vitro transcription reaction and also to a method for producing RNA in vitro. The present invention also relates to a bioreactor for RNA in vitro transcription.

RNA-based therapy is one of the most promising and quickly developing fields of modern medicine and ribonucleic acid molecules (RNA) therefore represent an emerging class of drugs. RNA-based therapeutics provide highly specific and individual treatment options for the therapy of various diseases and may for instance be used in immunotherapy, gene therapy and genetic vaccination. Therefore, there is a need for producing high-quality RNA in large amounts at a reasonable price.
Typically, RNA is produced by RNA in vitro transcription reactions using an appropriate DNA template. In order to obtain homogenous RNA suitable for RNA-based therapeutics, the RNA has to be of a distinct length, which is achieved by precise termination of the RNA in vitro transcription reaction. A common way of controlling RNA in vitro transcription termination is the linearization of the DNA template right after the RNA coding sequence. This way, a so called run-off RNA in vitro transcription is achieved.
For obtaining high-grade RNA suitable to be used in therapy, various quality control steps have to be performed such as ensuring proper linearization of the DNA template and also removal of the DNA template from the RNA product later on by DNA digestion and subsequent RNA purification.
Hence, one critical step in RNA production is the generation of a suitable DNA template, which at industrial scale is a major cost factor. However, currently, DNA templates can often only be used for a single RNA in vitro transcription reaction and need subsequently be destroyed by DNAse digestion and removed by RNA purification in order to ensure efficacy and safety of the RNA-based therapeutics. Residual amounts of DNA in the final RNA-based therapeutic may induce activation of the innate immune system and have the potential to act as an oncogene in a patient.
Thus, there is a need to provide a reusable DNA template which can easily and effectively be separated from the RNA in vitro transcription reaction without its destruction.
Marble and Davis describe the RNA in vitro transcription from DNA templates which are associated with agarose beads and can therefore be re-used by recovery of the beads using mild centrifugation. In particular, the DNA template to be used in an RNA in vitro transcription reaction is associated with streptavidin-coated agarose beads via a single biotin at the 5′ end of the non-template strand of the DNA template (Marble and Davis, Biotechnol. Prog. 1995, 11, 393-396). Furthermore, Liu and Price describe RNA in vitro transcription from DNA templates which are associated to streptavidin coated paramagnetic particles via 5′ bound biotin, which has been added to the DNA template via polymerase chain reaction (PCR) using a biotinylated primer (Liu and Price, Promega Notes, 64, 1997, 21-26). Fujita and Silver describe RNA in vitro transcription from linear double stranded DNA templates with a T7 or T3 RNA polymerase promoter at one end and a single biotin moiety at the other end attached to streptavidin-coated paramagnetic beads (Fujita and Silver, Biotechniques Rapid Dispatches, 14(4) 1993, 608-617). Fujita and Silver conclude that, when the DNA was oriented so that the transcription proceeded toward the bead and the DNA was attached by a biotin-dUTP or biotin-dATP moiety at the 3′ end of the non-template strand, the yield and quality of RNA synthesized was grossly equivalent to that made in solution.
PCR-based association of DNA templates (e.g. to agarose or to magnetic particles) as described above have the disadvantage that the association is sequence dependent (e.g. different primer pairs have to be designed for each individual DNA construct) and that PCR-based production of the DNA template is error-prone. Furthermore, the afore-described laboratory methods are not suitable for RNA production in large quantities on an industrial scale.
Although chemical, non-PCR-based DNA immobilization techniques are known, these do not provide for a directed coupling of DNA to a single support or tag. However, when coupling a DNA template to a support or tag for easy and effective separation of said template from an RNA in vitro transcription reaction, it is important that this coupling is done in a directed fashion e.g. not to impair efficient run-off of the RNA polymerase (RNAP) which ensures RNA products of homogenous length (see FIG. 1).
Thus, no methods are currently available which allow for a directed non-sequence, non-PCR-based coupling of a support or a tag to a linear DNA template after it is generated (e.g. after DNA preparation from an organism).
Accordingly, there is the need for providing high-quality linear DNA templates, which are associated with a support or a tag at the desired end of the linear DNA template and which can be produced at relatively low cost in large amounts so that RNA in vitro transcription on an industrial scale will become feasible.

Linear double stranded DNA coupled to a single support or a tag and methods for producing said linear double stranded DNA


An electron microscope equipped with a specimen positioning device for moving specimen holders within a place perpendicular to the optical axis of the electron beam between the upper and lower magnetic pole pieces of the objective lens and bringing the holders onto the optical axis. The microscope has a member extending through the side wall of the yoke of the objective lens, a preliminary chamber connected with the side wall of the yoke via a valve, and an exchange mechanism. The member can mount and dismount the specimen holders. The plural holders are placed in position within the chamber. The exchange mechanism can mount and dismount the specimen holder placed at a certain position within the chamber and can move this holder between the magnetic pole pieces of the objective lens from the chamber to the member or vice versa. Once the inside of the lens is evacuated to a high vacuum, a plurality of specimens can be observed successively.

Side-entry specimen positioning systems find extensive application in electron microscopy. Such specimen positioning systems are described in U.S. Pat. Nos. 3,745,341 and 3,778,621. FIG. 1(a) is a cross-sectional view of a conventional side-entry specimen positioning device. FIG. 1(b) is a cross-sectional view taken on line A--A' of FIG. 1(a). In these figures, an objective lens comprises a yoke 1, an excitation coil 2, an upper magnetic pole piece 3, and a lower magnetic pole piece. 4. The gap between the pole pieces 3 and 4 is maintained by a spacer 5. A stage 6 is installed in the yoke 1. A rotatable cylinder 7 is mounted to the stage 6 via a spacer 8 and a bearing 9. A specimen holder 11 extends through the cylinder 7. A specimen S is held to the front end of the holder 11 via a ball joint 10. A Z-axis adjusting screw 12 and a Y-axis adjusting screw 13 are mounted to the cylinder 7 to push that ball joint 10 in the Z and Y axes, respectively. Springs S.sub.1 and S.sub.2 are mounted between the cylinder 7 and the joint 10 and disposed opposite to the screws 12 and 13, respectively. The specimen holder 11 is capable of sliding inside the ball joint 10. The holder 11 is inserted between the pole pieces 3 and 4 from the X direction so as to cross the optical axis Z of the electron beam within the X-Y plane perpendicular to the optical axis Z. The specimen S can be rotated in the Z and Y directions about the ball joint 10 by rotating the Z-axis adjusting screw 12 and the Y-axis adjusting screw 13, respectively. Since the rotatable cylinder 7 is able to turn about the X axis perpendicular to the optical axis Z, the specimen S can be tilted to the optical axis Z by rotating the cylinder 7 in the direction indicated by the arrow C. The front end of the specimen holder 11 is retained by a pivot pin 14 and a pivot bearing 15. This bearing 15 is slidably fitted in a retainer 16 mounted to one side of the yoke 1. The bearing 15 is held by an X-axis adjusting screw 17 mounted to the retainer 16. The pivot pin 14 is supported by a spring (not shown) which is mounted to the pivot bearing 15. The specimen holder 11 can be moved in the X direction by rotating the X-axis adjusting screw 17.
It is well known that the resolution of an electron microscope is enhanced as the focal length of the objective lens is reduced. It is also well known that as the space between the upper pole piece 3 and the lower pole piece 4 is reduced, the focal length of the objective lens decreases, provided that the diameters of the pole pieces 3 and 4 of the objective lens are maintained constant. In the aforementioned specimen positioning device of the electron microscope, the front end of the specimen holder 11 is retained by the pivot pin 14 and the pivot bearing 15 and, therefore, the bearing 15 and the pin 14 are pressed against the front end cf the holder 11 when the X-axis adjusting screw 17 is rotated. Further, the atmospheric pressure acts on the specimen holder 11, because the inside of the yoke 1 is a vacuum. For this reasons, the front end of the holder is pressed against the pivot pin 14 with a greater force. In addition, a moment due to the weight of the pin 14 itself acts on the front end of the holder. In this way, a plurality of forces act on the front end of the specimen holder 11. Therefore, if the portion of the holder 11 which holds the specimen is thinned, then the specimen S bends. Accordingly, the front end of the specimen holder which grips the specimen must be thickened. Consequently, the space between the pole pieces 3 and 4 of the objective lens must be increased.
In recent years, a specimen positioning device which is free of the foregoing problems has been proposed. FIG. 2(a) is a cross-sectional view of this device. FIG. 2(b) is a cross-sectional view taken on line B--B' of FIG. 2(a). In these figures, an objective lens comprises a yoke 21, an excitation coil 22, an upper magnetic pole piece 23, and a lower magnetic pole piece 24. The gap between the pole pieces 23 and 24 are maintained by a spacer 25. A stage 26 is installed in the yoke 21. A rotatable cylinder 27 is mounted to the stage 26 via a spacer 28 and a bearing 29. A specimen holder 31 extends through the cylinder 27. A specimen S is held to the front end of the holder 31 via a ball joint 30. A Z-axis adjusting screw 32 and Y-axis adjusting screw 33 are mounted to the cylinder 27 to push the joint 10 in the Z and Y directions, respectively. Springs S.sub.1 and S.sub.2 are mounted between the cylinder 27 and the ball joint 30 and located opposite to the adjusting screws 32 and 33, respectively. A tapering insulator 34 is fixed to the outer periphery of the specimen holder 31 and protrudes from the front end of the cylinder 27 toward the optical axis Z of the electron beam. A spherical member 35 is fixed to the outer periphery of the insulator 34. A support 36 is fitted in the side wall of the yoke 21 perpendicularly to the X axis. An arm 37 is mounted inside the support 36 in such a way that the arm can be rotated about a pin 38 by rotating an X-axis adjusting screw 39. The front end cf the arm 37 is provided with a round hole through which the specimen holder 31 extends. Two bushings 40 and 41 are mounted around the hole. One of the bushings is located above the plane defined by the X axis and the optical axis, while the other is located below the plane. The central axis of the bushings 40 and 41 agrees with the central axis of the spherical member 35. The bushings 40 and 41 are fixed to the arm 37 such that they are in contact with the spherical member 35. A pivot bearing 42 is mounted between the arm 37 and the X-axis adjusting screw 39. A spring 43 is mounted between the arm 37 and the support 36.
In this specimen positioning device, the inside of the yoke 1 is a vacuum and so the atmospheric pressure acts on the specimen holder 31. This pressure is transmitted to the bushings 40 and 41 via the spherical member 35. When the arm 37 is rotated by rotating the x-axis adjusting screw 39, the bushings 40 and 41 are rotated about the pin 38. At this time, the spherical member 35 slides on the bushings 40 and 41. Then, the specimen holder 31, or the specimen S, is moved in the X direction by the sliding movement of the spherical member 35. The holder 31 can be rotated about the ball joint 31 in the Z and Y directions by rotating the Z- and Y-axis adjusting screws 32 and 33, respectively. Since the atmospheric pressure causes the spherical member 35 to press the specimen holder 31 against the bushings 40 and 41 and all times, the holder 31 rotates while sliding in the ball joint 30. Thus, the spherical member 35 rotates while sliding on the bushings. The specimen S moves in the Y or Z direction. Since the rotatable cylinder 27 can rotate about the X axis perpendicular to the optical axis Z of the electron beam, when the cylinder 27 is rotated in the direction indicated by the arrow C, the holder 31 turns about the X axis. Simultaneously, the spherical member 35 slides on the bushings 40 and 41. Consequently, the specimen S can be inclined to the optical axis Z.
In this manner, in the specimen positioning device shown in FIGS. 2(a) and 2(b), neither the atmospheric pressure nor the moment arising from the weight of the pivot pin itself is applied to the front end of the specimen holder 31 which grips the specimen and, therefore, the front end can be made thin. This enables the gap between the pole pieces 3 and 4 to be narrowed. Hence, the resolution of the electron microscope can be enhanced.
In this specimen positioning device of the electron microscope, after the specimen holder holding plural specimens is placed in position within the objective lens, the inside of the lens is evacuated to a high vacuum. Then, the specimens held by the holder are successively observed. If new specimens are to be observed, the inside of the objective lens is once returned to the atmospheric pressure. Subsequently, the new specimen holder is set in the lens. The inside of the lens is evacuated to a high vacuum. Thereafter, the specimens held by the holder are observed one after another. In this way, specimens which can be observed after the inside has been once evacuated are few in number, and it takes a long time to evacuate the inside to a high vacuum. Consequently, it is impossible to observe a number of specimens in a short time.
Where specimens are heated, cooled, subjected to an evaporation process, or otherwise processed before placed in position within the objective lens, a chamber is formed for the processing. However, in the specimen positioning device shown in FIGS. 2(a) and 2(b), the chamber for the processing must be located inside the specimen holder 31 which is opposite to the optical axis. Therefore, the holder 31 is long and susceptible to external vibration. This also hinders the observation of specimens.


A data writing method for writing data into a memory cell of a rewritable non-volatile memory module, and a memory controller and a memory storage apparatus using the same area provided. The method includes recording a wear degree of the memory cell and adjusting an initial write voltage and a write voltage pulse time corresponding to the memory cell based on the wear degree thereof. The method further includes programming the memory cell by applying the initial write voltage and the write voltage pulse time, thereby writing the data into the memory cell. Accordingly, data can be accurately stored into the rewritable non-volatile memory module by the method.

1. Technology Field
The present invention is directed to a data writing method for a rewritable non-volatile memory module, and a memory controller and a memory storage apparatus using the method.
2. Description of Related Art
Along with the widespread of digital cameras, cell phones, and MP3 in recently years, the consumers' demand for storage media has increased drastically. Since a rewritable non-volatile memory has the characteristics of non-volatility of data, low power consumption, small volume, non-mechanical structure, and fast reading and writing speed, the rewritable non-volatile memory is the most adaptable memory applied in a portable electronic product, e.g., a notebook computer. A solid state drive (SSD) is a storage apparatus which utilizes a flash memory as its storage medium. Therefore, the flash memory industry has become a very popular part of the electronic industry in recent years.
FIG. 1 is a schematic diagram illustrating a flash memory device according to the related art.
Referring to FIG. 1, a flash memory device 1 includes a charge-trapping layer 2 for storing electrons, a control gate 3 for applying a bias voltage, a tunnel oxide layer 4 and an interpoly dielectric layer 5. When data is about to be written to the flash memory device 1, a threshold voltage of the flash memory device 1 may be changed by injecting electrons into the charge-trapping layer 2. Accordingly, a digital level state of the flash memory device 1 is defined to implement a function of storing data. Here, the process of injecting the electrons to the charge-trapping layer 2 is referred to as programming. Otherwise, when the data is about to be removed, the flash memory device 1 is restored to the unprogrammed state by removing the injected electrons from the charge-trapping layer 2.
During operations of writing and erasing, the flash memory device 1 would be worn due to frequently injecting and removing the electrons, which leads to the increased speed of writing the electrons and wider distribution of the threshold voltage. As a result, after being programmed, the storage state of the flash memory device 1 can not be accurately identified, which results in the occurrence of error bits.
Nothing herein should be construed as an admission of knowledge in the prior art of any portion of the present invention. Furthermore, citation or identification of any document in this application is not an admission that such document is available as prior art to the present invention, or that any reference forms a part of the common general knowledge in the art.

Data writing method, and memory controller and memory storage apparatus using the same


In an element for a MOS type solid-state imaging device, a leakage current caused by a stress generated in a vicinity of an element isolation region having an STI structure is reduced. The element for the MOS type solid-state imaging device comprises: a signal accumulation region 102, of a second conductivity type, provided in an interior of a semiconductor substrate or well 101 of a first conductivity type, for accumulating a signal charge generated by performing photoelectric convention; a gate electrode 104 provided on the semiconductor substrate or well 101; a drain region 105, of a second conductivity type, provided on a surface portion, of the semiconductor substrate or well 101, on which the gate electrode is formed; and an element isolation region 201 provided on the surface portion, of the semiconductor substrate or well 101, on which the gate electrode is formed. The element isolation region 201 has the STI structure, and a cavity 202 is formed in an interior of the element isolation region 201.

1. Field of the Invention
The present invention relates to an element for a solid-state imaging device, and more particularly to a structure, of an element isolation region, which solves a problem of the element being micromachined.
2. Description of the Background Art
In recent years, in the field of a solid-state imaging device, various techniques related to a structure of an amplified MOS image sensor have been proposed. It is advantageous that the amplified MOS image sensor consumes less power than a CCD image sensor. Furthermore, in the amplified MOS image sensor, it is also advantageous that a CMOS process is used for mounting both a sensor portion and a peripheral circuit thereof, thereby allowing the sensor portion and the peripheral circuit thereof to be easily integrated with each other.
Referring to FIGS. 4 and 5, an element for a solid-state imaging device, according to the conventional art, disclosed in Japanese Laid-Open Patent Publication No. 2000-150847 will be described. FIG. 4 is a plan view illustrating the element for the solid-state imaging device according to the conventional art. FIG. 4 shows a photoelectric conversion region and a signal read region, both of which are included in a pixel. FIG. 5 is a cross-sectional view illustrating the element for the solid-state imaging device along lines Y1-Y2 of FIG. 4.
As shown in FIG. 4, in the pixel, a signal accumulation region (photodiode) 102, a gate electrode 104 and a drain region 105 constitute a MOS transistor.
Furthermore, as shown in FIG. 5, the gate electrode 104 is provided on the P type well 101 with a gate oxide film 103 interposed therebetween. The drain region 105, made of an N type diffusion layer, is formed on a surface portion, of the P type well 101, on which the gate electrode 104 is formed. The signal accumulation region 102, made of the N type diffusion layer for converting light into electric charge and accumulating the converted electric charge, is formed in an interior of the P type well 101 which is formed in a semiconductor substrate (not shown) The drain region 105 is located on a side, of the gate electrode 104, opposite to that on which the signal accumulation region 102 is located.
A surface shield layer 106 is formed on the surface portion of the P type well 101. The surface shield layer 106 is located, such that at least a portion of the surface shield layer 106 is faced to the signal accumulation region 102 with the P type well 101 therebetween. The surface shield layer 106 is made of a P type diffusion layer.
An element isolation region 107 is provided on the surface portion of the P type well 101. The element isolation region 107 has an STI (shallow Trench Isolation) structure. The element isolation region 107 is operable to insulate the pixel from an adjacent pixel. Such an STI structure is formed by etching the P type well 101 to form a groove (trench), and then filling the groove with a silicon oxide 108.
In the element for the MOS type solid-state imaging device using the STI structure mentioned above, it is known that a crystal defect is generated in a vicinity of an interface between the element isolation region 107 and a peripheral portion thereof. Further, it is also known that when the element for the solid-state imaging device is thermally treated, a stress generated in the vicinity of the interface between the element isolation region 107 and the peripheral portion thereof is the largest among stresses generated in other areas of the element. Such a stress is caused by a difference between a thermal expansion coefficient of a material included in the element isolation region 107 (e.g., silicon oxide) and a thermal expansion coefficient of the P type well 101. Due to the crystal defect and the stress mentioned above, a leakage current flows from the element isolation region 107 into the signal accumulation region 102. When the leakage current flows into the signal accumulation region 102, a charge derived from the leakage current is added to a signal charge accumulated in the signal accumulation region 102, thereby causing white blemishes and minute unevenness to be generated on a screen when reproducing an image.
Nowadays, among the white blemishes and minute unevenness mentioned above, the white blemishes and minute unevenness caused by the crystal defect can be eliminated, by using an image correction technique developed along with the recent advancements in digital techniques, because the number of the white blemishes and minute unevenness caused by the crystal defect is relatively small. However, the stress is generated in almost all pixels. In other words, the stress is generated throughout an entirety of the screen. Thus, in order to eliminate, by using the image correction technique, the blemishes and minute unevenness caused by the stress, a memory having a large capacity is needed. As a result, it becomes difficult to miniaturize the imaging device, and to reduce electrical power consumed thereby, etc. Furthermore, steps and time required for fabricating the memory are caused to be increased, thereby resulting in an increased fabrication cost.
In order to solve the problems mentioned above, Japanese Laid-Open Patent Publication No. 2004-253729 proposes a technique, as shown in FIG. 6, in which a defect suppression layer 109, made of the P type diffusion layer, is provided along an entire exterior surface of the element isolation region 107. The defect suppression layer 109 is filled with a P type hole. By forming the defect suppression layer 109, it becomes possible to reduce the leakage current and a noise.
Furthermore, Japanese Laid-Open Patent Publication No. 2004-253729 discloses, as shown in FIG. 7, steps for forming the defect suppression layer 109. FIG. 7 is a schematic cross-sectional view illustrating steps, for implanting ions, performed when the defect suppression layer 109 is formed. As shown in FIG. 7, the P type well 101 is etched to form a groove (trench) 110. Thereafter, ions are implanted into an inner wall of the groove 110, thereby forming the defect suppression layer 109 along the entire exterior surface of the element isolation region 107. As shown by arrows in the FIG. 7, ions are implanted in diagonal directions with respect to the surface of the P type well 101.
However, the conventional art disclosed in Japanese Laid-Open Patent Publication No. 2004-253729 has the following problems. Specifically, along with the miniaturization of the element, a width of the groove 110, from which the element isolation region 107 is to be made, accordingly becomes narrower. In such a case, when ions are implanted in the diagonal directions with respect to the surface of the P type well 101, as shown in FIG. 8, there may be a case where the ions cannot be implanted directly into a surface of a deep portion of the groove 110. Therefore, the element for the solid-state imaging device, according to the conventional art, disclosed in Japanese Laid-Open Patent Publication No. 2004-253729, has a first problem in that there may be a case where the defect suppression layer 109 cannot be formed in an appropriate manner.
Furthermore, in the case where the defect suppression layer 109 is formed, as shown in FIG. 9, the defect suppression layer 109 causes a width of the signal accumulation region 102 to be reduced. Thus, a technique disclosed in Japanese Laid-Open Patent Publication No. 2004-253729 has a problem in that a capacity of the signal accumulation region 102 is caused be reduced when forming the defect suppression layer 109. Thus, a second problem of the element for the solid-state imaging device, according to the conventional art, is in that when a volume of the signal accumulation region 102 becomes reduced along with the miniaturization of the element, the capacity, of the signal accumulation region 102, which is reduced by forming the defect suppression layer 109, can be severe.


A method and apparatus for conveying workpiece is used for conveying a workpiece such as a semiconductor wafer, glass substrate or liquid crystal panel between processing apparatuses when the workpiece is processed in a plurality of processing apparatuses. The method includes adjusting the amount of liquid on a surface of a workpiece to a predetermined amount, and conveying the workpiece which retains the predetermined amount of liquid between processes. The surface of the workpiece is kept wet by the liquid on the workpiece. The adjusting includes supplying a sufficient amount of liquid onto the surface of the workpiece which is in a certain state, and removing a certain amount of liquid from the surface of the workpiece.

1. Field of the Invention
The present invention relates to a method and apparatus for conveying or transporting a workpiece such as a semiconductor wafer, glass substrate or liquid crystal panel, and more particularly to a method and apparatus for conveying a workpiece between processing apparatuses when the workpiece is processed in a plurality of processing apparatuses.
2. Description of the Related Art
Recent rapid progress in semiconductor device integration demands smaller and smaller wiring patterns or interconnections and also narrower spaces between interconnections which connect active areas. One of the processes available for forming such interconnection is photolithography. Though the photolithographic process can form interconnections that are at most 0.5 .mu.m wide, it requires that surfaces on which pattern images are to be focused by a stepper be as flat as possible because the depth of focus of the optical system is relatively small.
It is therefore necessary to make the surfaces of semiconductor wafers flat for photolithography. One customary way of flattening the surfaces of semiconductor wafers is to polish them with a polishing apparatus, and such a process is called Chemical Mechanical Polishing (CMP) in which the semiconductor wafers are chemically and mechanically polished while supplying an abrasive liquid comprising abrasive grains and chemical solution such as alkaline solution.
When semiconductor wafers are processed, small particles such as particles of semiconductor material, dust particles, crystalline protrusive particles, or the like often tend to be attached to the semiconductor wafers being processed. If a particle greater than the distance between interconnections exists on a semiconductor substrate, then the particle will short-circuit interconnections on the semiconductor substrate. Therefore, any undesirable particles on a semiconductor substrate have to be sufficiently smaller than the distance between interconnections on the semiconductor substrate. Such a problem and a requirement hold true for the processing of other workpieces including a glass substrate to be used as a mask, a liquid crystal display, and so on. To meet the above requirement, there have been practiced some cleaning procedures for removing fine particles or submicron particles from semiconductor wafers.
In this manner, the semiconductor wafers and the like are subjected to a plurality of processes. For example, after polishing, the semiconductor wafers are cleaned one by one and stored in a predetermined location. As a method of physically cleaning semiconductor wafers one by one, there have been scrubbing cleaning in which a surface of a semiconductor wafer is scrubbed by a brush of nylon or mohair or a sponge of polyvinyl alcohol (PVA), ultrasonic jet cleaning in which an ultrasonic jet is applied to the surface of the semiconductor wafer, and high pressure water cleaning in which high pressure water is applied to the surface of the semiconductor wafer. In cleaning the semiconductor wafer after polishing, a plurality of cleaning processes using the above two or three methods are applied to the semiconductor wafer. Therefore, it is necessary to convey or transfer the semiconductor wafer between cleaning processes. In this case, the semiconductor wafer is conveyed between cleaning processes in such a state that it is kept wet with liquid. This is because if the semiconductor wafer is not in a wet state before completing the cleaning processes, dust may be attached to the surface of the semiconductor wafer, and if the semiconductor wafer is half-dried, water marks may be formed on the surface of the semiconductor wafer. In particular, if the semiconductor wafer which has been subjected to the CMP process is once dried, the slurry attached to the polished surface of the semiconductor wafer is solidified thereon and is difficult to be removed therefrom, and hence the semiconductor wafer is kept wet with cleaning liquid between cleaning processes.
However, if the wet semiconductor wafer is conveyed at a high speed, as is the case in a recent high through-put-type apparatus, liquid on the surface of the semiconductor wafer may drop from the semiconductor wafer. The dropped liquid, when it is dried and solids contained in the liquid rise up, becomes a source of particles. Further, in the case where different cleaning liquids are used in the cleaning processes, an unexpected chemical reaction may occur upon contact of the different cleaning liquids.

Method and apparatus for conveying a workpiece