Herein is provided a method for identifying extreme stressors which may become causative agents responsible for syndromes characterized by premature progressive cell loss or cell over growth in an individual. A sample of cells obtained from an individual is subjected to stressor in vitro to form a stressed cell sample. At least one stress criteria is measured for the stressed cell sample and the steps are repeated for a plurality of stressors. The measured stress criteria are then compared to norms derived from such measurements on cell samples obtained from third parties and a plurality of extreme stressors to which the sample of cells taken from the individual are unusually sensitive are identified. The procedure can be used to identify an effective bypass agent or needed alteration in lifestyle to prevent or delay clinical signs of disease, and/or to identify an effective bypass agent or needed alteration in lifestyle to better manage or reverse the course of the disease process.

Cell growth and cell death are programmed and the precise timing of each of the programs is a critical factor in the life or death of the cells of our body. Each of these life/death programs for each person is unique. This uniqueness is due, largely, in the way in which each of our genes; with their multiple mutations break and recombines together. It is the interaction of these genomes (genes) and our changing environments that will inevitably lead to the dysregulation of these multiple timing devices of all our cell types which must be maintained to protect the very delicate balance between cell growth and cell death. All of the cell types in our body grow and die at very different rates and therefore a huge number of timing devices are required to maintain homeostasis (life/death balance) between all of these different cell types. Moreover, some individual cell types survive only for a few hours while other cell types survive for years. The maintenance and regulation of this delicate balance is most difficult for the immune system (cell survival measured in hours and the nervous system (cell survival measured in years). The immune system must rapidly mobilize and proliferate in response to inflammation but it just as rapidly must demobilize and the cells must die once the crisis is past, the invaders destroyed, digested and their foreign residues are excreted or properly stored. Similarly, while the nervous system must rapidly process all incoming information and store this information or relay it to other cell in the organism. It is precisely the storage and retrieval process of the nervous system that mandates that the cells survive for years. When any toxic or metabolic mishap appears in the immune system or nervous system, then one or more programmed death programs becomes dominant.
In this age of increased communication and heightened changing environmental perturbations, these two critical systems are overworked and apt to either misread the incoming information or fail to respond to the information properly. The result is the development of symptomatic disease of multiple types and this is dependent upon the type of stress and the individual; genetic weak points that are present in our unique genomes. In most cases, death occurs, with the resultant swelling of their membrane-bound cytoplasmic granules, mitochondria and fragmentation and condensation of the nucleus. This is called apoptosis. However, occasionally, a rare over stressed cell learns how to suppress or knock out their programmed cell death, survive and amplify their own growth programs. The end result is an immortal cell, cancer.
Thus, it appears that stress induced changes in the delicate balance between cell life and cell death appears to be responsible for the chronic conditions in which the timing for cell proliferation vs. cell death becomes imbalanced and either the chronic loss or excessive accumulation of uncontrolled cells is the end result. Therefore, there are two major factors in the development of chronic diseases.
1. Stressors. These include food, especially calories or oxidants and various poisons (physical, immunologic, psychic, chemical, bacteriologic, parasitic or viral, and behavioral). The specific amount (dose) of stress that is intolerable for each specific individual must be identified.
2. Genetic weak links. These genetic factors which are responsible for the development of chronic disease are biologically trivial and, therefore, usually bypassable. Since, our over-stressed genomes have developed many routes or devices which can wither repair or develop alternate routes that bypass for the minor damages. However, in order for these alternative pathways to operate, different signals must be obtained from the living cell.
Syndromes Associated With Stressors
1. Caloric Imbalance. Calories, like all growth factors for cells, are potent activators if cell death when they are deficient (too little) or in excess (too much). When calories in excess are provided, the over worked adipocytes (fat cells), pancreatic insulin secreting cells and vascular epithelium (blood vessel lining cells) die while conversely, the cells of the colon, breast, vascular phagocytes are forced to grow excessively. The delayed symptoms that may appear include those of diabetes, fat cell death, vascular obstructions (heart and brain), immune or cerebral dysfunction and excessive cellular proliferation (cancer). The constellation of genetic weak links in each unique individual determine both the specific breaking point and the target organ system.
In the experimental model, when rodents who are deprived of motivation and supplied with an excess of food, their normal pathways that are responsible for controlling energy intake, energy usage and energy storage rapidly falter. These rodents soon degenerate. Obesity, diabetes, occluded blood vessels and excretory ducts and dysregulated cells growth disease and senility soon emerge. Not surprisingly, removal of the excess food (calories) stress prevents all of these random losses of cellular functions, including the late developing cancers. These murine experiments in caloric glut teach us that a global stress, such as energy excess, which in time results in multiple breakdowns in most of the control pathways, can be prevented by simply removing the causative energy stress plus adding a motivational component, hunger.
Undoubtably, the removal of the caloric glut along with application of living motivations in humans will slow the loss of many of our degenerating cells, especially of those cells which control our energy metabolism. However, in long lived humans, successful prevention of chronic slowly progressive cell loss/overproductive syndromes, such as atherosclerosis and cancer is difficult because it is not currently detectable at the early dpe-dysfunctional stages of the disease. Thus, to prevent these later cell losses, early detection methods are required. To perfect and quantitate such detection methods is our initial objective. Quantification is essential since each individual is unique and his response to his individual stress is also unique.
2. Oxygen. Oxygen, like calories is a potent and essential growth factor, which when taken in excess or is deficient , is rapidly fatal. When totally deficient, neurons die in 3-5 minutes and when in excess, the lining cells of the lung die within a few hours. In the metabolic consumption of calories, electrons are liberated and are capable of destroying cellular enzymes, cellular membranes (lipids and lipoproteins) as well as cellular genome (nuclear DNA). Oxygen or other electron acceptors must be available intracellularly in the appropriate amounts and the appropriate time. Furthermore, enzymes which allow oxygen to accept two electrons rather than only one must always be present and capable of functioning rapidly, especially when calories are in excess. Because superoxide and peroxide act as potential growth factors as well as potential poisons, the end result of their excess is a dysregulated oxygen metabolism which may lead to either a degenerative or proliferative disease, depending upon the genetic constitution of the individual.
3. Drugs and Addiction. Drugs, notably tobacco and alcohol damage the cellular life/death regulating systems. Some cells proliferate excessively while the cells die and disappear. The extent of the changes in the life/death homeostatic cellular programs depends upon the individual weak links that are present in the specific cell type of each individual as well as the dose (potency) and timing of the dysregulating drug. Tobacco smoke affects the lining cells of the lungs that are necessary for the transport of oxygen and carbon dioxide into and out of the blood. Alcohol may poison the liver and a protective overgrowth of fibroblasts follow hepatocyte death.
4. Environmental Toxins. Solvents, gases, hydrocarbons, oxidants, heavy metals and many others, all effect the genetically weak link and thus are related to a dysfunction in the life/death cycle.
5. Viruses
A. The herpes virus group (herpes, Epstein Barr and other DNA viruses) lives in human cells. The prostate is commonly infected and the virus is present in the semen. The virus may cause cellar overgrowth by inhibiting one of our natural protective growth inhibitors (tumor suppressor gene, called P53) which normally inhibits cellular overgrowth. Without this effective inhibitor, the deficient cells rapidly out grow its neighboring cells and ultimately kill the surrounding cells by usurping the neighboring cells nutrition.
B. Murine retroviral model of neuro-immuno-degeneration. Injections of a murine virus, Ts1, into newborn mice results in a loss of specific immune cells and neurons with an overgrowth of astocytes in the brain in 3-5 weeks. If the animals survives the early immune and nerve cell loss, tumors of the immune system and the nervous system develop. The Ts1 virus enters its target cell by binding with the surface receptor that normally transports basic amino acids into the cell. The infected cell either multiply and produce defensive molecules or die. If the viral load is large and completely occupies all of the amino acid transporter sites on the cell membrane, the cell will either starve to death due to lack of the essential basic amino acids, especially arginine, or it will activate one of its death programs. Arginine is one of the essential amino acids that is required to produce polyamines, e.g., spermine, which amines are essential for structural integrity of the nucleus. In this murine model, the ensuing amino acid deficiencies are the crucial death factor and the predicted death may be prevented by supplying the deficient amino acids in amounts large enough to compete with the virus for transport into the cell. Furthermore, the excess amino acids that bind to the transporter will deny entrance of the virus into the cells and are potent protector agents. Moreover, in this model with imbalanced cell growth/death programs, then immune and nervous system modulators, nutritionals, anti-oxidative preventive therapies have proved to be a successful combination therapy.
Genetic Imbalance: Syndromes in which the Weak Links are Known
It is because each of us possesses unique gene pools which harbor multiple mutations that each, under stress, may activate signals which program cellular death. Therefore, we are all vulnerable to life's many stresses, especially stresses that may perturb electron flow, such as Down's Syndrome or amyotrophic lateral sclerosis syndromes (ALS). In Down's Syndrome trisomy 21, in which genes that control oxidative metabolism are imbalanced, the cell death programs, especially in the brain, are very labile and easily perturbated by most stresses. In ALS syndrome in which a major gene involved in the electron transfer (superoxide dismutase) is mutated, electron flow becomes dysregulated, especially in the very active RNA rich motor neurons. The result is that the cell death pathways are again activated and these neurons slowly degenerate.
In syndromes in which the genes that control the timing for the major activities of cells, i.e., cellular growth, death, differentiation and repair, mutagens which disrupt or imbalance these carefuilly orchestrated timing genes lead to the production of ill-formed cells with defective parts and limited survival. This fate leading to premature death is especially prominate in cells which must rapidly reproduce under stress and also must as rapidly die, such as most cells of the immune system. This type of premature death also awaits those neurons which must continuously produce and maintain cell parts, i.e., synapses and dendrites, and are, therefore, more susceptible to oxidative or metabolic stresses.
1. Ataxia Telangiectasia (AT)
AT is a syndrome in which certain cells in the immune and nervous system fail to mature properly and are eventually lost. A defective gene has been identified and it appears to function as a modulator or switching box for directing the cellular life/death process in the thymus derived T and B cells, cerebellar neurons and in some vascular cells. The result is immune deficiency, ataxia and deformed dilated blood vessels. AT is a recessive genetic disorder of childhood that occurs in one in 40,000 to 100,000 persons worldwide. At least 10% of AT patients develop cancer of the lymphoid tissues, stomach, brain, breast, skin, parotid gland, liver, larynx and ovaries. The location of the ATM gene on Chromosome 11q22-23. AT cells show increased chromosomal breakage, telomere shortening and elevated intrachromosomal recombination and are hypersensitive to ionizing radiation and radiomimetic chemicals. In ataxia telangiectasia, in which the ATN gene is mutated and fails to efficiently upregulate the major timing gene, p53, the premature death of immune cells and susceptible neurons is the end result. In those few immature cells in the thymus gland which manage to adapt to their missing timing gene (ATM), and continue to grow uncontrollably, thymic cancer in the absence of any other cancer is the end result. Furthermore, in mice, in which the ATM gene is completely knocked out, all homogenous mice, which are normal at birth, die of the thymic cancer by 4 months of age.
Since mice lacking the ATM gene from conception grow and develop normally until the thymic tumor intervenes, and since no cells other than the immature lymphocytes in the thymus either die or become cancerous, it is clear that the timing function of the ATM gene product is critical only in cells which must respond defensively to environmental stresses induced by living, i.e., cells involved in postnatal learning, immune defense and postnatal reproduction. The rapidly dividing living cells in the intestines do not degenerate but do lose their ability to defend themselves against radiant energies.
Other gene products which may disrupt the delicate balance in the cell growth and cell death pathways are abundant in man and include the presenilin genes in Alzheimer's Syndrome, the telomere genes in Huntington's Disease or AIDs, or the Fas, Fas ligands genes in murine autoimmune syndrome. In all of these syndromes, the dysregulation in the cell growth/cell death pathways leads to either excessive cell growth or to accelerated cell death, depending upon the presence of alternate or bypass pathways in the specific cell. For example, when various stresses are directed toward the central nervous system, neurons will degenerate while their more numerous support or helper cells will adapt and finally proliferate.
Progressive cerebellar ataxia and progressive oculocutaneous telangiectases appear at the ages of 2-6 in the affected children. Elevated serum alphafetoprotein and plasma carcinoembryonic antigen combined with low levels of IgA and/or IgE provide the laboratory basis for the clinical picture of AT.
2. Down's Syndrome (Trisomy 21)
One extra chromosome is present and too much DNA is present in each cell and the resultant dysregulated signaling also leads to either cell death or uncontrolled cell growth. The premature neuronal cell death in Down's Syndrome can be completely prevented, in vitro, by supplying the cells with extra reductants and/or antioxidants. Thus, although the precise function of all the excess normal genetic material is not known, it is clear that the loss of neurons is due at least in part either to a deficiency in reductive energy or to an excess of oxidizing power. The extra copy of chromosome 21 may lead to the development of Alzheimer's/Parkinson's Disease pathology is that the gene leads to the over production of amyloid and the accumulation of senile plaques,
3. Cancer
Cancer is an imbalance of Life/Death programs:
a. Life/death balancing factors in which stimulators such as c-mye, cyclin, D1, AP-1, Il-2, and E1A, TGFa are opposed by P21, p53, Rb, Fas, Stromelysin and TGFb. PA1 b. Energy Homeostasis (calories, fatty acids, etc.) PA1 c. Redox Homeostasis (cysteine, NO) PA1 d. Proteolysis Homeostasis (Ice, CPP32, Stromelysin) PA1 e. Nutrient Homeostasis(choline, arginine) PA1 f. Transport Homeostasis PA1 g. Nuclear Structure Homeostasis PA1 h. Basal Membrane Homeostasis (differentiation, apoptosis) PA1 i. Plasma Membrane Homeostasis (ligands, matrix, signal transduction) PA1 j. Cell Cycling Homeostasis (Cyclin, p21, c-myc, WAF1, ICE) PA1 k. Basement Membrane (Matrix) Homeostasis.
The C-myc primary gene which is responsible for maintaining the cellular life/death balance, while Cyclin-D1 is an enzyme that is required during mitosis. E1, AP1, TGFs, IL-2 and the basement membrane are some of the known growth factors which are required for cells to grow and differentiate into mature cells. P21, p53, Rb, Fas, TGFb are factors that stop cellular growth and cellular cycling. Stromelysin is a proteolytic enzyme that destroys the basement membrane and thus removes the major required for cell differentiation. Spermine is a highly charged growth factor which is used to stabilize the ever changing structure of DNA and various other structural proteins and lipids. p34 is a factor required to stabilize the nuclear components to be reproduced during cell cycling (mitosis).
Signal Transduction Imbalances
Viruses, which must bind to specific receptors or transporters on the surface of cells for entry and exit from specific cells and they also must usurp the cell's growth machinery for its own parasitic reproduction and will eventually perturb the cell's growth/death pathways with subsequent uncontrolled cell growth and/or cell death.
Viruses also disrupt cellular growth/death pathways by inserting their own promotional genes into inappropriate locals in the host DNA. This insert, like other agents which may oxidize or change or damage host DNA, may activate the cell death pathways. Such activated pathways may be beneficial in the sense that unwonted viruses or cancerous cells or overactive destructible inflammatory cells can be eliminated. But perturbation of this cell destruction process will in time result in the cell loss syndromes as seen in neuro-immuno-degenerative disorders or aging.
There examples suggest that most of our current chronic ills result form aberrant signals induced by mutated genes or destructive environmental cues which perturb timing of the cell growth/cell death pathways. These examples also suggest that if counter signals which can rebalance these uncontrolled pathways were available, most of our degenerative and neoplastic illnesses could be avoided.


A flow restrictor includes a first disc and a second disc. A rod extends between the first disc and the second disc and spaces the first disc from the second disc. A first hole is formed in the first disc.

The present invention is generally related to flow restrictors.
Fuel metering units, pneumatic systems, and lubrication systems in gas turbine engines commonly use a flow restrictor to restrict and regulate the flow of fluids through fluid passages. A flow restrictor is generally a cylindrical tube disposed inside a fluid passage and includes an internal profile that reduces the diameter of the flow area in the fluid passage, similar to a venturi tube. Some flow restrictors are installed inside the fluid passage through an interference fit while others are installed through intricate retaining systems.
If the flow restrictor and retaining system are misassembled inside the fluid passage, the retaining system may fail and permit the flow restrictor to shift and move inside the fluid passage. Engine vibrations, over time, may also loosen the interference fit or retaining system between the flow restrictor and the fluid passage, thereby allowing the flow restrictor to shift and move within the fluid passage. If the flow restrictor shifts or moves inside the fluid passage, the flow restrictor could undesirably block inlet and outlet orifices connected to the fluid passage. The flow restrictor could also move to a position inside the fluid passage where the flow restrictor is no longer operable in restricting or regulating the flow of fluid inside the fluid passage. This problem has been overcome in the past by permanently fixing the flow restrictor inside the fluid line through the use of an adhesive or braze. However, permanently fixing the flow restrictor inside the fluid passage prevents an operator from easily replacing the restrictor in the future should the operator wish to subsequently adjust the flow in the fluid passage by installing a flow restrictor with a larger or smaller interior profile.


The present invention provides a novel ruthenium complex which has an excellent catalytic activity in terms of reactivity for an asymmetric reduction of a carbonyl compound and enantioselectivity, a catalyst using the ruthenium complex, and a method for preparing optically active alcohol compounds using the ruthenium complex. The present invention relates to a ruthenium complex having a ruthenacycle structure, a catalyst for an asymmetric reduction consisting of the ruthenium complex, and a method for preparing optically active alcohol compounds using the ruthenium complex.

A transition metal complex which has an optically active diphosphine compound as a ligand is very useful as a catalyst for an asymmetric reaction, and until now many catalysts have been developed.
Among the catalysts, in combination of a base compound, a ruthenium-diphosphine-diamine complex is known as a highly active catalyst for an asymmetric hydrogenation (for example, Patent Literature 1). As a method for synthesizing the complex, [RuCl2(p-cymene)]2 as a precursor of the complex reacted with an optically active diphosphine and an optically active diamine in order in a specific solvent is known (Patent Literature 2), as an example. In addition, as a complex having an optically active diphosphine and a tridentate amine ligand, the compound represented by the following formula is known (Patent Literature 3).

A ruthenium-diphosphine-diamine complex having a counter anion is also known (Patent Literature 4).
The ruthenium metal complex having an optically active diphosphine compound and a diamine compound as a ligand is highly useful because of the use for an asymmetric hydrogenation of various carbonyl compounds, showing a high activity and a high enantioselectivity, and giving an optically active alcohol compound with high optical purity. However, such catalyst shows a high performance but not for every carbonyl compound, then the development of a catalyst with higher activity is needed.

This patent is subject to a terminal disclaimer.

Ruthenium complex and method for preparing optically active alcohol compounds using the same as a catalyst


A method and system dynamically calculates confidence levels associated with accuracy of Z depth information obtained by a phase-shift time-of-flight (TOF) system that acquires consecutive images during an image frame. Knowledge of photodetector response to maximum and minimum detectable signals in active brightness and total brightness conditions is known a priori and stored. During system operation brightness threshold filtering and comparing with the a priori data permits identifying those photodetectors whose current output signals are of questionable confidence. A confidence map is dynamically generated and used to advise a user of the system that low confidence data is currently being generated. Parameter(s) other than brightness may also or instead be used.

Electronic camera and range sensor systems that provide a measure of distance from the system to a target object are known in the art. Many such systems approximate the range to the target object based upon luminosity or brightness information obtained from the target object. However such systems may erroneously yield the same measurement information for a distant target object that happens to have a shiny surface and is thus highly reflective, as for a target object that is closer to the system but has a dull surface that is less reflective.
A more accurate distance measuring system is a so-called time-of-flight (TOF) system. FIG. 1 depicts an exemplary TOF system, as described in U.S. Pat. No. 6,323,942 entitled CMOS-Compatible Three-Dimensional Image Sensor IC (2001), which patent is incorporated herein by reference as further background material. TOF system 100 can be implemented on a single IC 110, without moving parts and with relatively few off-chip components. System 100 includes a two-dimensional array 130 of pixel detectors 140, each of which has dedicated circuitry 150 for processing detection charge output by the associated detector. In a typical application, array 130 might include 100×100 pixels 230, and thus include 100×100 processing circuits 150. IC 110 also includes a microprocessor or microcontroller unit 160, memory 170 (which preferably includes random access memory or RAM and read-only memory or ROM), a high speed distributable clock 180, and various computing and input/output (I/O) circuitry 190. I/O circuitry can provide functions including analog-to-digital conversion of detection signals, video gain, etc. Among other functions, controller unit 160 may perform distance to object and object velocity calculations.
Under control of microprocessor 160, a source of optical energy 120 is periodically energized and emits optical energy via lens 125 toward an object target 20. Typically the optical energy is light, for example emitted by a laser diode or LED device 120. Some of the emitted optical energy will be reflected off the surface of target object 20, and will pass through an aperture field stop and lens, collectively 135, and will fall upon two-dimensional array 130 of pixel detectors 140 where an image is formed. In some implementations, each imaging pixel detector 140 captures time-of-flight (TOF) required for optical energy transmitted by emitter 120 to reach target object 20 and be reflected back for detection by two-dimensional sensor array 130. Using this TOF information, distances Z can be determined.
Emitted optical energy traversing to more distant surface regions of target object 20 before being reflected back toward system 100 will define a longer time-of-flight than radiation falling upon and being reflected from a nearer surface portion of the target object (or a closer target object). For example the time-of-flight for optical energy to traverse the roundtrip path noted at t1 is given by t1=2·Z1/C, where C is velocity of light. A TOF sensor system can acquire three-dimensional images of a target object in real time. Such systems advantageously can simultaneously acquire both luminosity data (e.g., signal amplitude) and true TOF distance measurements of a target object or scene.
As described in U.S. Pat. No. 6,323,942, in one embodiment of system 100 each pixel detector 140 has an associated high speed counter that accumulates clock pulses in a number directly proportional to TOF for a system-emitted pulse to reflect from an object point and be detected by a pixel detector focused upon that point. The TOF data provides a direct digital measure of distance from the particular pixel to a point on the object reflecting the emitted pulse of optical energy. In a second embodiment, in lieu of high speed clock circuits, each pixel detector 140 is provided with a charge accumulator and an electronic shutter. The shutters are opened when a pulse of optical energy is emitted, and closed thereafter such that each pixel detector accumulates charge as a function of return photon energy falling upon the associated pixel detector. The amount of accumulated charge provides a direct measure of round-trip TOF. In either embodiment, TOF data permits reconstruction of the three-dimensional topography of the light-reflecting surface of the object being imaged. While systems described in U.S. Pat. No. 6,323,942 can acquired Z information, the accuracy of such information is not known on a per frame of acquired data basis.
Some systems determine TOF by examining relative phase shift between the transmitted light signals and signals reflected from the target object. Detection of the reflected light signals over multiple locations in a pixel array results in measurement signals that are referred to as depth images. U.S. Pat. Nos. 6,515,740 (2003) and 6,580,496 (2003) disclose respectively Methods and Systems for CMOS-Compatible Three-Dimensional Imaging Sensing Using Quantum Efficiency Modulation. FIG. 2A depicts an exemplary phase-shift detection system 100′ according to U.S. Pat. No. 6,515,740 and U.S. Pat. No. 6,580,496. Unless otherwise stated, reference numerals in FIG. 2A may be understood to refer to elements identical to what has been described with respect to the TOF system of FIG. 1.
In FIG. 2A, an exciter 115 drives emitter 120 with a preferably low power (e.g., perhaps 50 mW peak) periodic waveform, producing optical energy emissions of known frequency (perhaps a few hundred MHz) for a time period known as the shutter time (perhaps 10 ms). Energy from emitter 120 and detected signals within pixel detectors 140 are synchronous to each other such that phase difference and thus distance Z can be measured for each pixel detector.
The optical energy detected by the two-dimensional imaging sensor array 130 will include amplitude or intensity information, denoted as "A", as well as phase shift information, denoted as φ. As depicted in exemplary waveforms in FIGS. 2B, 2C, 2D, the phase shift information varies with distance Z and can be processed to yield Z data. For each pulse or burst of optical energy transmitted by emitter 120, a three-dimensional image of the visible portion of target object 20 is acquired, from which intensity and Z data is obtained (DATA'). As described in U.S. Pat. Nos. 6,515,740 and 6,580,496 obtain depth information Z requires acquiring at least two samples of the target object (or scene) 20 with 90° phase shift between emitted optical energy and the pixel detected signals. While two samples is a minimum figures, preferably four samples, 90° apart in phase, are acquired to permit detection error reduction due to mismatches in pixel detector performance, mismatches in associated electronic implementations, and other errors. On a per pixel detector basis, the measured four sample data are combined to produce actual Z depth information data. Further details as to implementation of various embodiments of phase shift systems may be found in U.S. Pat. Nos. 6,515,740 and 6,580,496. However while the systems and methods described in these two patents can acquire Z information, accuracy of the acquired Z information is not known on a per frame basis.
Many factors, including ambient light, can affect reliability of data acquired by TOF systems. The depth accuracy of Z-data information acquired by pixel detectors 140 in array 130 will vary with the amount of optical energy incident on the pixel detector. In extreme cases there can be too little reflected optical energy, for example from dark target objects 20, perhaps black motor vehicle tires, dark clothing on a pedestrian, etc. On the other hand, an overly reflective target object 20 can reflect too much optical energy. An excess of incoming optical energy can saturate the pixel detector, with the result that the Z-data indicates that the target object 20 moved. However the data alone cannot be used to discern whether the target object 20 actually moved, or whether pixel detector saturation has produced erroneous Z-data indicative of movement, when in fact there was no movement. In these and other extreme cases, the Z-data provided by the TOF system can include incorrect depth information. But while the information is incorrect, the prior art provides no mechanism to so identify the questionable Z-data.
As a result, in an attempt to reduce errors, in some TOF systems the transmitted optical energy may be emitted multiple times using different systems settings to increase reliability of the acquired TOF measurements. For example, the initial phase of the emitted optical energy might be varied to cope with various ambient and reflectivity conditions. The amplitude of the emitted energy might be varied to increase system dynamic range. The exposure duration of the emitted optical energy may be varied to increase dynamic range of the system. Further, frequency of the emitted optical energy may be varied to improve the unambiguous range of the system measurements.
In practice, TOF systems may combine multiple measurements to arrive at a final depth image. But if there is relative motion between system 100 or 100′ and target object 20 while the measurements are being made, the TOF data and final depth image can be degraded by so-called motion blur. For example, while acquiring TOF measurements, system 100 may move, and/or target object 20 may move, or may comprise a scene that include motion. If shutter time is 10 ms (25 frames/second), relative motion occurring faster than about 1/40 ms (for a four-sample acquisition) will produce motion blur. As a result, the motion blur will cause erroneous distance Z data, and will yield a depth image with errors. Unfortunately prior art systems do not provide a mechanism to alert the end user of the Z data that the data being processed at any given time may be relatively low confidence data, e.g., data that perhaps should not be relied upon unduly.
Various other patents have provided methods and systems to improve performance of TOF systems. For example, U.S. Pat. No. 6,522,395 entitled Noise Reduction Techniques Suitable for Three-Dimensional Information Acquirable with CMOS-Compatible Image Sensor ICs (2003) is directed to improving noise reduction in time-of-flight systems by integrating the photodetected brightness signal until integration reaches a predetermined threshold level. The system provides a corrected TOF measurement equal to the round-trip time from system to target object plus an additional time needed for the integrated photodetector signal to cross the threshold value, less a constant times the ratio of photodetector signal amplitude after integration over time equal to pulse width of the emitted optical signal, divided by the pulse width duration. U.S. Pat. No. 6,674,895 entitled Methods for Enhancing Performance and Data Acquired from Three-Dimensional Image Systems (2004), and U.S. Pat. No. 6,512,838 entitled Methods for Enhancing Performance and Data Acquired from Three-Dimensional Image Systems (2003) are directed to a time-of-flight system in which accuracy and resolution are enhanced by various techniques including over-sampling the acquired photodetector data and forming running averages with the data. Acquired data may be rejected certain criteria are not met. However TOF systems according to these patents do not per se identify questionable or low confidence data to a user of the system.
Applications for TOF systems can vary, from systems used to implement virtual input devices such as a keyboard (e.g., see U.S. Pat. No. 6,614,422, U.S. Pat. No. 6,710,770), for which Z measurements are over a fairly small range of distance, to vehicular or security or robotic type systems for which the range of applicable Z measurements may be many meters. By way of example, FIG. 3A depicts a prior art system such as 100′ mounted so as to provide the operator of a motor vehicle 200 with information as to Z distance to objects 20 behind the vehicle. Assume that vehicle 200 is backing up, generally towards object 20. System 100′ can obtain Z data and can provide the processed information to an operator-viewable monitor 220. As shown in FIG. 3B, monitor 220 can provide a display 230 with a representation 240 as to Z distance to any proximate target objects. But assume that the target object 20 in FIG. 3A is surrounded by a highly reflective region 210, perhaps a puddle of water. Thus although the actual distance from the rear of vehicle 200 where system 100′ is located to the target object 20 is distance Z5, perhaps due to the reflectivity of the water, the displayed information 240 erroneously reports a smaller distance, here approximately Z1.
Unfortunately although the information being displayed in FIG. 3B is the result of low confidence data, the operator of vehicle 200 has no indication of this infirmity in the data. If system 100′ is allowed to automatically apply the brakes to vehicle 200 when distance Z to a perceived object is too short, perhaps Z<Z2, vehicle 200 will brake needlessly, since the true distance is Z5. A worse case would be where system 100′ erroneously reports the distance to a target object 20 as being greater than the true distance. In such case, since the vehicle operator has no knowledge that the data is questionable, vehicle 200 might continue to back-up until it collides with the target object.
While FIGS. 3A and 3B depict a rear-viewing application of a TOF system 100′, understandably there are other applications, for example robotic systems in a factor, where errors in Z data are very undesirable, especially where the users of the system do not know that erroneous data may be generated.
To recapitulate, prior art TOF systems can, for a variety of reasons, generate erroneous Z-data depth information. Regardless of the TOF application, the Z-data that is acquired cannot by itself be used to determine whether the data is worthy of full confidence. For example, Z data erroneously indicating target object movement from a saturated pixel detector is indistinguishable from Z-data properly indicating target object movement. TOF systems subject to such unidentified ambiguity in the Z-data are adversely affected. Further, in applications such as tracking a target object within a scene, the accuracy of the depth information of each pixel detector in each frame is to be known to identify which pixels to use in calculations.
Unfortunately prior art statistical methods such as spatial standard deviation, which use depth values in neighboring pixel detectors to estimate the depth accuracy, or prior art temporal standards, which use past depth measurements to estimate the depth accuracy, cannot be used to provide assistance. This is because these prior art methods assume that the mean value of the depth, i.e. position of the object(s), does not change. Unfortunately this unchanging positional requirement cannot be achieved in dynamic scenes.
There is a need for a method and system that take into account both accuracy-type positional errors and uncertainty-type positional errors that can exist in a TOF system. Such method and system should detect and identify erroneous or low confidence Z data generated by a TOF system, and quantify accuracy of the acquired depth values in terms of confidence. Preferably such method and system should require no further data than is already acquired by the TOF system.
The present invention provides such a method and system.

Methods and system to quantify depth data accuracy in three-dimensional sensors using single frame capture


An electrochemical cell is provided that includes a current collector plate and a pellet. The current collector plate includes a circumferential outer peripheral wall and an inner wall coupled thereto, where the circumferential outer peripheral wall defines a cavity and has a height, and the inner wall extends across and physically separates the cavity into at least two regions and has a height that is less than the height of the circumferential outer peripheral wall. The pellet comprises active powder material and is disposed in the cavity and circumferentially surrounded by and in contact with the circumferential outer peripheral wall of the current collector plate. The pellet includes a first portion and second portion, where the first portion is disposed in a first region of the at least two regions and the second portion is disposed in a second region of the at least two regions.

Implantable medical devices (IMDs) are well known for providing a variety of treatments. For example, implantable cardiac defibrillators are used to monitor cardiac activity, detect ventricular fibrillation, and in response to that detection, deliver appropriate therapy pulses to restore a normal heart rhythm. Implantable neurostimulators have been used to stimulate the spinal cord and brain for, for example, the treatment of chronic pain and peripheral vascular disease. Implantable pacemakers generate and apply electric stimuli in the form of pulses to heart tissue to control the timing of heart contractions.
IMDs, and other similar devices, utilize an internal power source (i.e. an electrochemical cell) to provide the power required for operation. The electrochemical cell typically includes at least an anode and a cathode. In some embodiments, the electrochemical cell includes a cathode assembly having a powdered cathode material compressed into a disk-shaped pellet and a circumferential current collector disposed therearound. The circumferential current collector increases conductivity of current to the cathode material by maintaining low resistance and exerts a sufficient hoop force magnitude on the pellet to maintain its disk shape and allow for pellet growth during discharge.
Although the above-described cathode assembly performs well when implemented in an electrochemical cell, it has certain drawbacks. For example, in some instances, the hoop forces exerted by the circumferential current collector may be too high and may cause the disk-shaped pellet to dome. As a result, the overall thickness of the cathode assembly may undesirably increase. Consequently, it may become difficult, or even impossible, to insert the cathode assembly into the electrochemical cell. Additionally, the disk-shaped pellet typically expands as the cathode assembly is discharged. This expansion may cause degradation of contact between the cathode material and the circumferential current collector and may undesirably change the overall impedance of the cell as it discharges over time. Eventually, the change in cell impedance may cause a decrease in cell capacity. As IMDs and electrochemical cells become thinner, these issues may become more pronounced.
Accordingly, it is desirable to have a cathode assembly that can maintain its original configuration over time so that it may be easily assembled into an electrochemical cell. Furthermore, other desirable features and characteristics of the present invention will become apparent from the subsequent detailed description of the invention and the appended claims, taken in conjunction with the accompanying drawings and this background of the invention.

Electrode including a multi-region current collector


A non-single-crystal semiconductor layer is formed over a substrate, and then a single crystal semiconductor layer is formed over part of the non-single-crystal semiconductor layer. Thus, a semiconductor element of a region which requires a large area (e.g. a pixel region in a display device) can be formed using the non-single-crystal semiconductor layer, and a semiconductor element of a region which requires high speed operation (e.g. a driver circuit region in a display device) can be formed using the single crystal semiconductor layer.

1. Field of the Invention
The present invention relates to a method for manufacturing a semiconductor device, a semiconductor device and an electronic appliance.
2. Description of the Related Art
In recent years, flat panel displays such as liquid crystal display devices and electroluminescence (EL) display devices have attracted attention.
Driving methods of the flat panel displays include a passive matrix method and an active matrix method. An active matrix method has advantages over a passive matrix method in low power consumption, high definition, a large-sized substrate, and the like.
Here, a structural example of an active matrix panel is briefly described with reference to FIGS. 21A and 21B. FIG. 21A illustrates an example of a structure in which a driver circuit is provided using a tape automated bonding (TAB) method.
In FIG. 21A, a pixel portion 2101 in which pixels 2102 are arranged in matrix is formed over a substrate 2100 having an insulating surface. The pixels 2102 are arranged in matrix at intersections of scan lines extending from a scan line side input terminal 2103 and signal lines extending from a signal line side input terminal 2104. Each of the pixels in the pixel portion 2101 is provided with a switching element and a pixel electrode layer connected to the switching element. A typical example of the switching element is a TFT. A gate electrode layer side of the TFT is connected to a scan line, and a source or drain side of the TFT is connected to a signal line. In addition, an IC 2151 included in a driver circuit is connected to a flexible printed circuit (FPC) 2150.
In a structure where a driver circuit is provided outside a panel as in FIG. 21A, it is possible to use a driver circuit formed using a single crystal silicon substrate. However, when a driver circuit is provided in this manner, a manufacturing cost cannot be reduced sufficiently because of necessity of preparing a panel and a driver circuit separately, necessity of a step of connecting the panel and the driver circuit, and the like.
In terms of reduction in cost or the like, a method in which a pixel region and a driver circuit region are formed over the same substrate has been employed (e.g., see Patent Document 1: Japanese Published Patent Application No. H8-6053). FIG. 21B illustrates an example of a structure in which a pixel region and a driver circuit region are formed over the same substrate.

Method for manufacturing semiconductor device, semiconductor device and electronic appliance

Semiconductor Energy Laboratory Co., Ltd.


An apparatus and method for reproducing multi-angle data in a seamless manner, even during a change of angle, and an information storage medium on which the multi-angle data is recorded. AV data divided into clips, which are recording units, is recorded on the information storage medium. Additional information regarding jump points is recorded on a space of the information storage medium other than where the clips are recorded. The apparatus for reproducing the multi-angle data includes a reading unit which reads data from the information storage medium, and a reproducing unit which reproduces the data read by the reading unit by searching for and reproducing clips corresponding to the read data when the read data is multi-angle data, and, if there is an angle change command, reproducing clips for a new angle from a jump point of the clip for the new angle.

1. Field of the Invention
The present invention relates to seamless reproduction of multi-angle data, and more particularly, to an apparatus and method for guaranteeing seamless reproduction of multi-angle data, even during a change of angle, and an information storage medium on which the multi-angle data is recorded.
2. Description of the Related Art
Data obtained by photographing a scene at various angles and encoding the result is called multi-angle data. While a viewer watches a scene by reproducing contents containing the multi-angle data, if the viewer wants to see the scene photographed at a different angle, the viewer inputs an angle change command to a reproducing apparatus. After receiving the command, the reproducing apparatus reproduces data for a new angle. To guarantee seamless reproduction during angle change, the multi-angle data is stored using an interleaving method in which the multi-angle data is divided into units having a specified size and the units are recorded in an alternating fashion. To search for and reproduce data blocks for one angle in the interleaved multi-angle data, additional information for tracing data blocks by angles is recorded within a video bit stream.
Arrival time information, such as an arrival time stamp (ATS), is added to each angle data of the multi-angle data. When an angle data is reproduced, it is output and reproduced according to the ATS. In general, since an independent ATS is added to the angle data, seamless reproduction (i.e., without pause), cannot be ensured during change of angle.

Information storage medium storing multi-angle data and method and apparatus for reproducing the multi-angle data


A jig for aligning door hinges into a position at a predetermined mounting angle in an automatic system that automatically mounts door hinges to upper and lower seats on pillars of a vehicle body conveyed by a conveying unit. The jig may include a support frame, a first support part fixed to the support frame and supporting a hinge bracket of the door hinge, a pair of second support parts movably disposed at both sides of the first support part and respectively supporting both sides of a door bracket of the door hinge, and an actuating cylinder fixed to the support frame and connected with the second support parts.

1. Field of Invention
The present invention relates to an automatic system for mounting a door hinge to a vehicle. More particularly, the present invention relates to a jig for aligning a door hinge or hinges at a predetermined mounting angle on a vehicle.
2. Description of Related Art
In general, the process of mounting a door to a vehicle body is implemented by mounting door hinges to the front and rear pillars of a side panel and then fastening a door to the door hinges.
The process of mounting door hinges is implemented by bringing door hinges in close contact with upper and lower seats of the front and rear pillars with a door hinge mounting jig and then bolting the door hinges to the door hinge seats, after a vehicle body is moved into a position for work by a conveyor system.
The door hinge mounting jig can move forward to the side panel of the vehicle body, with the door hinges loaded, insert a tooling pin into the vehicle body, clamp the vehicle body, and move a door into a position on the upper and lower door hinge seats of the front and rear pillars. In this status, a worker manually bolts the door hinges to the door hinge seats with an electric fastening device.
The process of mounting door hinges described above loads the door hinges on the mounting jig and then fastens the door hinges on the mounting jig to the hinge seats of a vehicle body. The process may cause an increase in manufacturing cost, because it depends on the manual work throughout the aligning and mounting of the door hinges to a vehicle body.
Further, since the door hinges are manually fastened in the process of mounting door hinges, it is difficult, if not impossible, to avoid assembly variation, which may deform a door or deteriorate the external appearance of the door. Consequently, it deteriorates productivity, because the work for maintaining the product quality takes long time, including mounting again the door hinges in the following processes.
Therefore, it is required to develop automated equipments that can automatically align door hinges, before loading the door hinges onto a mounting jig, in order to solve such problems or at least some of problems in the art.
The information disclosed in this Background section is only for enhancement of understanding of the general background of the invention and should not be taken as an acknowledgement or any form of suggestion that this information forms the prior art already known to a person skilled in the art.

Jig for aligning door hinge of automatic system for mounting door hinge to vehicle


The present invention includes novel ether-ketone hyperbranched polymers that are prepared from polymerizing trimesic acid and bifunctional phenylether-based liquid or low-melting monomers, which melt at or below polymerization temperature. The resulting copolymer has repeating units of the formula:

1. Field of the Invention
The present invention relates to ether-ketone polymers, particularly to hyperbranched ether-ketone polymers and a new technique to synthesize them from the mixtures of a trifunctional carboxylic acid (A3) and a difunctional bis(arylether) (B2) monomers in appropriate stoichiometric ratios.
2. Description of the Related Art
Non-traditional macromolecules such as dendrimers and hyperbranched polymers are attracting a considerable amount of attention primarily because of their distinctly different properties compared to their linear counterparts. For example, they have better solubility compared to their linear analogs. Although dendrimers have precisely controlled structure and unique properties, their preparations generally involve tedious, multi-step sequences that are not practical in mass production. Synthesis of a hyperbranched polymer, on the other hand, is a one-pot process. Large quantities of hyperbranched polymers can be easily produced from ABx (x≧2) monomers. In addition, there are important characteristics such as low viscosity and dependence of the physical properties on the nature and number of endgroups such as solubility, glass-transition etc. are quite similar between hyperbranched polymers and dendrimers. Therefore, hyperbranched polymers are better suited for many practical applications. Perhaps an important disadvantage associated with a particular hyperbranched polymer is that the synthesis of its ABx monomer often time still involves several reaction sequences from commercially available starting materials.
To be more cost-competitive, a promising approach entails direct syntheses of hyperbranched polymers for high temperature applications from commercially available A3 and B2 or A2 and B3. Although a number of hyperbranched polymers have been synthesized via either an A3+B2 or an A2+B3 polycondensation process, these processes did present some difficulty in controlling polycondensation reaction due to premature gelation. Thus, an important key to the success of such an approach is to be able to: (a) control the reaction conditions such as the monomer concentrations and their time-dependent reaction ratio; and (b) stop the reaction before the gelation starts.

Hyperbranched poly(ether-ketones) via an A3 + B2 polymerization method

Abstract: wherein m is the degree of polymerization; n has a value of 0-5; the ratio x:y corresponds to the molar ratio of trimesic acid and arylether monomer and may range from 1.0:1.0 to 1.0:1.5 (i.e. x=1, y=1.0, 1.1, 1.2 . . . 1.5); and the substitution pattern of the arylether segment may be para or meta. The endgroups may be carboxylic acid (—CO2H), oxyphenyl (—OPh), or mixture of both moieties, depending on the reaction ratio x:y used. The total number of endgroups is typically defined by m+1.

THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY OF THE AIR FORCE


The present disclosure relates to a 5G or pre-5G communication system for supporting a higher data transmission rate beyond a 4G communication system such as LTE. The present invention relates to a method for guaranteeing quality of service in a wireless communication system. More particularly, a method of a base station according to an embodiment of the present invention comprises the steps of: identifying at least one non-Guaranteed bit rate (GBR) bearer configured for an arbitrary communication device; determining whether to guarantee a specific bit rate to the non-GBR bearer, on the basis of at least one of QoS class identifier (QCI) information, allocation and retention priority (ARP) information, and subscriber profile identifier (SPID), which are received from a core network node for the non-GBR bearer; and performing scheduling for the non-GBR bearer on the basis of the determination.

To meet the demand for wireless data traffic having increased since deployment of 4G communication systems, efforts have been made to develop an improved 5G or pre-5G communication system. Therefore, the 5G or pre-5G communication system is also called a 'Beyond 4G Network' or a 'Post LTE System'. The 5G communication system is considered to be implemented in higher frequency (mmWave) bands, e.g., 60 GHz bands, so as to accomplish higher data rates. To decrease propagation loss of the radio waves and increase the transmission distance, the beamforming, massive multiple-input multiple-output (MIMO), Full Dimensional MIMO (FD-MIMO), array antenna, an analog beam forming, large scale antenna techniques are discussed in 5G communication systems. In addition, in 5G communication systems, development for system network improvement is under way based on advanced small cells, cloud Radio Access Networks (RANs), ultra-dense networks, device-to-device (D2D) communication, wireless backhaul, moving network, cooperative communication, Coordinated Multi-Points (CoMP), reception-end interference cancellation and the like. In the 5G system, Hybrid FSK and QAM Modulation (FQAM) and sliding window superposition coding (SWSC) as an advanced coding modulation (ACM), and filter bank multi carrier (FBMC), non-orthogonal multiple access (NOMA), and sparse code multiple access (SCMA) as an advanced access technology have been developed.
Meanwhile, although different in communication standards and modes (e.g., wireline Ethernet/IP and wireless LTE/WiBro/Wi-Fi), all of wireline and wireless communication networks provide quality of service (QoS) functions based on certain standards (IETF RFC, IEEE 802, 3GPP, etc.). For example, the QoS may vary according to the priority of service type supported by a device. As a detailed example, real time service traffic such as voice or video traffic may have a QoS higher than that of Internet traffic.
The QoS may be mapped to a bearer established between a device and a network node. Here, the bearer may be categorized into one of a guaranteed bit rate (GBR) bearer and a non-GBR bearer according to resource type. In detail, the GBR bearer may denote a bearer guaranteeing a predetermined bit rate. That is, to use a GBR bearer means to guarantee at least a predetermined bit rate for transmitting service data. Whereas, the non-GBR bearer may be regarded as a best effort type bearer that does not guarantee any predetermined bit rate.
Meanwhile, 5G systems may be designed to support a fixed wireless access (FWA) system that is capable of providing more homes and offices with high speed Internet services by replacing optical cable sections with wireless sections. Even to the FWA system, the above-described QoS may be applied likewise. For example, even in the FWA system, the GBR type QoS may be applied to the services necessary to guarantee a predetermined bit rate such as IPTV rather than the Internet service within the constrained physical resources.
However, in the case where a communication device communicating on a GBR bearer is located in a weak electric field area occupying a large amount of resources, other communication devices sharing the resources of the base station may experience difficulty in receiving services. Furthermore, if the non-GBR type QoS is applied to the services of which qualities are maintained at over a predetermined data rate so such resources are indiscriminately allocated, this may cause a situation unsatisfying a service quality standard. There is therefore a need of a method for efficiently utilizing the entire physical resources of the FWA base station system.

Method and apparatus for guaranteeing quality of service in wireless communication system


This application describes insulated casings with cores of insulating material, coated with or otherwise encapsulated in a shell material are disclosed. A hinge may be fixed to first and second encapsulated cores and couple the first and second encapsulated cores to allow the insulated casings to removably cover a conduit.

Insulation often covers pipes that transport a product in extreme temperatures, such as very low temperatures. Some insulation is formed of fiberglass, foam or wool. However, these types of insulations are often relatively absorbent, in the case of fiberglass, or relatively fragile, in the case of foam. Given the absorptive qualities of the fiberglass, in the event that a pipe leaks or breaks, the product inside the pipe (e.g., oil) may be leaking outside of the pipe and into the pipe insulation, after which the insulation is no longer usable. Because the soiled insulating material must be disposed of and new insulation must be obtained, the cost of repairing the leaking and/or broken pipe is increased. In addition, the disposal of the ruined insulation and the installation of the new insulation may be labor intensive, again driving up a cost of the broken pipe.
Thus, there remains a need to develop new pipe insulations formed of materials which are reusable in an event of a leak and/or a break, are much faster to install than existing pipe insulations, much more durable than existing protective coverings, and/or are more cost effective than existing pipe insulations.


An apparatus for coupling components in a fuel delivery system together is presented. The apparatus comprises a first member having a first end, a second end, and throughgoing passageway therebetween. The apparatus further comprises a second member having a throughgoing bore therein. The throughgoing bore is configured to receive the first end of the first member. The first and second members of the apparatus are configured to be affixed together to create a joint between the first end of the first member and the inner wall of the bore of the second member such that the passageway and the bore are in substantial alignment with each other.

Fuel delivery systems for direct injection applications, such as, for example, fuel-injected engines used in various types of on-road and off-road vehicles, typically include a fuel source, one or more fuel rails and a plurality of fuel injectors associated with the fuel rail(s). In such applications, the fuel rail may include a plurality of apertures in which injector sockets or cups are affixed. The fuel injectors are then inserted into and coupled with the injector cups so as to allow for the fuel flowing from the fuel source to the fuel rail to be communicated to the fuel injectors. The fuel communicated to the fuel injectors is then communicated to the combustion chamber of the engine.
One drawback of such direct injection systems, however, is the amount of pressure attendant in the system (i.e., on the order of 10 MPa or more). This pressure results in a relatively large amount of force and different twisting or bending moments being applied to the components of the system, and the connections or couplings therebetween. Consequently, various types of coupling arrangements designed to withstand the pressure/force of these systems have been utilized for coupling the system components together (e.g., coupling the fuel source to fuel rail, a fuel rail to another fuel rail, and/or a fuel injector to the fuel rail). However, while generally proving adequate with respect to withstanding the pressure/force in the system, these arrangements have not been without their respective disadvantages.
For instance, with respect to the coupling of a fuel injector with the fuel rail, in one arrangement, the fuel injector is coupled directly to the fuel rail and sandwiched between the fuel rail and the cylinder head of the engine. In this arrangement, undesirable noise can be generated. One prior attempt at eliminating or at least reducing this noise has included suspending the injector from the fuel rail. In one such arrangement an O-ring seal and a fuel injector clip are used to seal the connection between the fuel rail and fuel injector, and to hold and retain the injector in the correct position, respectively. Accordingly, the sealing and retention functions are performed separately. While such an arrangement may reduce the noise in the system, it requires additional components (e.g., the O-ring and the clip), which in turn increases the cost of the overall system and makes the corresponding manufacturing process more difficult.
With respect to the coupling of two fuel rails together, or coupling the inlet of a fuel rail with the outlet of a fuel source, metal-to-metal high pressure tube fittings have been utilized. These fittings generally include a tubular member having a spherical, cone, or ball shaped member (so-called male fitting) affixed to either one or both ends of the tube, and a threaded nut that circumscribes and slides along the length of the tubular member. The threaded nut is configured for mating with a complementary threaded portion disposed on either a fuel rail inlet or a fuel source outlet. One drawback of these conventional fittings is that the ball member typically requires a machined shank that results in a thin cross-section at the point of attachment between the tubular member and the ball member. While such an arrangement is generally able to withstand the pressure in the system, because the shank has been required, additional machining operations and material, and therefore, cost and difficulty have to be added to the manufacturing process. Additionally, the attachment point between the tubular member and the ball member may have a reduced strength due to the reduced cross-section of the shank.
Therefore, there is a need for a coupling apparatus for high pressure fuel delivery systems that will minimize and/or eliminate one or more of the above-identified deficiencies.

Apparatus for coupling components of a fuel delivery system


A switching circuit includes a semiconductor switching element having a control electrode and a source-drain current path, the source-drain current path being connected between a voltage source and a load circuit, a parallel circuit formed by first and second transistors having respective collector-emitter paths connected between the control electrode of the semiconductor switching element and a reference potential point, a first resistor connected to the second transistor in series, a differential circuit connected between a control signal terminal and the base of the first transistor and a second resistor connected between the control signal terminal and the base of the second transistor. The first transistor is made conductive by a signal obtained by differentiating a control signal and subsequently the second transistor is made conductive to control the semiconductor switching element for ON/OFF.

1. Field of the Invention
This invention relates to a switching circuit and, more particularly, it relates to a switching circuit using a semiconductor element as a switching element and adapted to drive and control the switching element by means of a pulse signal.
2. Description of the Related Art
Switching circuits comprising a semiconductor element that operates as a switching element and is designed to be driven by a pulse signal are known. The switching circuit may typically be an FET (field effect transistor). Then, the source electrode of the FET is connected to a power source and the drain electrode thereof is connected to a load circuit while a control signal is supplied to the gate electrode thereof so that the FET is controlled for ON/OFF by the control signal. When a pulse signal is supplied as control signal, the FET is held ON to supply a voltage to the load circuit only in a pulse period.
Meanwhile, such a switching circuit is required to have good switching characteristics when the switching element of the switching circuit is driven by a pulse. Particularly, when it is driven at high speed by a pulse signal, it is necessary to make the rise time and the fall time satisfactorily short.
FIGS. 6A and 6B of the accompanying drawings show waveforms of a known switching circuit, illustrating the switching characteristics thereof. FIG. 6A shows a control signal P0 that is supplied to the control electrode of the switching element. The switching element is turned from OFF to ON when the level of the control signal P0 is raised from level Low to level High. As the switching element is held ON, a voltage is supplied to the load circuit during the ON period.
FIG. 6B shows the voltage waveform+V1 of the voltage supplied to the load circuit. While the voltage waveform+V1 rises and falls to show a waveform same as that of the control signal P0, in reality, both the rise and the fall of the switching element show a time lag due to the characteristics of the switching element. Then, there arises a problem that the waveform of the output voltage+V1 becomes blunt at the rise time and also at the fall time.
Jpn. Pat. Appln. Laid-Open Publication No. 8-46502 describes a transistor circuit showing improved rising and falling characteristics of a switching element thereof. In an embodiment of transistor circuit described in the above-cited patent document, the rise time is reduced by supplying a pulse signal to the base of the switching circuit by way of a parallel circuit of a resistor and a capacitor. In this embodiment, when the level of the pulse signal is raised from level Low to level High to turn the switching element from OFF to ON, the transistor rises very rapidly under the effect of the capacitor so that it shows a short rise time.
However, a long fall time is required to the transistor to make the switching element show bad falling characteristics when the level of the pulse signal falls from level High to level Low to turn the switching element from ON to OFF because of the large discharge time constant of the capacitor. Additionally, the above-cited patent document describes an instance of connecting two switching elements in series and driving them alternately in order to improve the rising and falling characteristics of the transistor. However, such an arrangement makes the circuit configuration a complex one.
Jpn. Pat. Appln. Laid-Open Publication No. 2002-152034 describes a switching circuit with improved falling characteristics that is realized by connecting a P-channel FET and an N-channel FET in series and driving the two FETs by means of a bipolar transistor and a differential circuit. However, the above-cited patent document does not describe any means for improving the rising characteristics. Additionally, the use of two FETs also makes the circuit configuration a complex one.
Thus, the present invention provides a switching circuit comprising a semiconductor element that operates as a switching element and showing excellent switching characteristics when driving the switching element by a pulse signal.

Switching circuit using semiconductor switching element


Exogenous cDNA capable of expressing interferon α activity, exogenous interferon α protein, inducers of endogenous interferon α protein activity, inducers of endogenous interferon β protein activity, inducers of endogenous interfereon Γ activity, or inducers of other immune-enhancing activity can be combined with a vaccine to enhance an immune response. Specifically disclosed are adjuvant and vaccine combinations where the adjuvant comprises a cDNA capable of expressing interferon α activity, a complex comprising polyriboinosinic-polyribocytidilic acid, or a complex comprising polyriboinosinic-polyribocytidilic acid, poly-L-lysine, and carboxymethylcellulose and where the vaccine is a live vaccine virus derived from a virus causing porcine reproductive and respiratory syndrome disease.

There have been considerable efforts to identify substances that potentiate an immune response to a vaccine. For example, the cytokine interleukin-12 (IL-12) was reported to be useful as an adjuvant in U.S. Pat. No. 5,976,539, where the IL-12 was provided as a protein or nucleotide coding sequence. Interferon alpha is another cytokine reported to be useful as an oral vaccine adjuvant in, e.g., U.S. Pat. No. 4,820,514. In this patent only the protein form of the cytokine was used. Furthermore, oral administration of the protein resulted in a systemic effect, and too low or too high a dose of the protein was undesirable. It would be advantageous to generate a local adjuvant effect that does not require oral route administration of the protein and is not so dependent upon dose level.
An important aspect of the development of an adjuvant is the two-fold breadth potential for its application. Such breadth concerns both the underlying immune system and the target of the immune system's defense. An adjuvant can be useful in many mammalian species, if the adjuvant has the capacity to influence common attributes of the immune systems of those species. Further, if the targets of the immune system analogously have common attributes in how they are susceptible to immune responses, then an adjuvant stimulating an immune response should have broad applicability in defending against a variety of targets.
A need is recognized in the art for enhanced veterinary vaccines. An area of significant need for enhanced vaccines is manifested by outbreaks of porcine reproductive and respiratory syndrome (PRRS). PRRS has a severe impact on the health and reproductive ability of swine. To address this problem, vaccines were developed for the etiological agent of PRRS as reported in U.S. Pat. Nos. 5,989,563 and 6,042,830. In these patents, a viral agent capable of causing PRRS disease was isolated and used to develop a modified-live virus (MLV) vaccine. Classically, modified-live virus vaccines are derived from virulent strains that are modified by techniques such as growth in vitro, with or without alteration of conventional in vitro conditions, passage in non-natural host cells, or a combination of those techniques. In the U.S. Pat. Nos. 5,989,563 and 6,042,830 patents, the reported parental virulent porcine viral isolate is ATCC-VR2332. From this isolate, a modified vaccine virus was generated by attenuation through multiple passages of growth in vitro in simian cell culture. Thus ATCC-VR2495 was reported to be a suitable MLV for use in vaccine formulations for commercial purposes.
Currently the PRRS vaccines, even those that are of the MLV type, do not confer adequate protection from disease. In a study designed to test the efficacy of PRRS vaccines, currently available products failed to completely protect pigs from clinical disease caused by certain virulent strains of PRRS virus. Osorio et al., 1998. It was speculated that deficiencies in the pig's ability to mount cellular immune responses to PRRS virus may promote the evolution of more virulent strains in addition to predisposing the animal to virus infection. Alternatively, it was suggested that the PRRS virus itself may be responsible for altering the cellular immune response. Osorio et al., 1998.
Although the mechanisms that mediate protective immunity against PRRS virus are unknown, attempts have been made to study the characteristics of immunity induced by either infection with wild-type PRRS virus or vaccination with a commonly used PRRS modified live virus (MLV) vaccine. An example of PRRS MLV is described in U.S. Pat. Nos. 5,989,563 and 6,042,830. Exposure of an animal to either the wild-type virus or the MLV form of the PRRS virus does not stimulate a strong viral purging immunity. Virus-specific T cells secreting interferon gamma and virus neutralizing antibodies, both of which have the potential to mediate viral purging, are detected only several weeks after exposure of pigs to PRRS virus. One possible explanation for the failure of PRRS virus to stimulate the development of a strong viral purging immunity is that PRRS virus, in contrast to other viruses, is a poor stimulator of interferon alpha (abbreviated IFNalpha or IFNα) production in swine. Albina et al., 1998. Buddaert et al., 1998. Van Reeth et al., 1999. Consistent with this explanation is a reference indicating that IFNα can affect the development of anti-viral T cell interferon gamma (IFNgamma or IFNγ) responses and peak anti-viral immune defenses. Cousens et al., 1999.
There is considerable evidence in the art, however, that mere augmentation of IFNα in conjunction with wild-type PRRS virus infection or PRRS MLV exposure would be expected to have no significant positive effect on an immune response. For example, while the importance of IFNα on IFNγ response was shown in the mouse, it is unknown whether a similar response would occur in the pig. If the level of IFNα in the pig is indeed unnecessary for the induction of an adequate IFNγ response, then additional IFNα present in the pig would have no effect on immune response. Furthermore, while it is believed that PRRS virus can avoid the effects of the interferon system by blocking the production of IFN or by inhibiting its effects, it is not known which method of avoidance, blocking production or inhibition of effects, is significant or whether both methods function in a given organism. Albina, 1998. The lack of understanding about how PRRS directly or indirectly affects the innate IFNα response also makes it unclear that any attempts to further induce endogenous IFNα, to add IFNα (exogenous), or to add IFNα cDNA to express IFNα would enhance the immune response to PRRS. For example, if PRRS alters an IFNα response by inhibition of IFNα expressed protein, then it would be expected that no attempt to boost the level of IFNα would succeed in enhancing the immune response to PRRS. In fact, until now it has appeared unlikely that boosting the level of IFNα in combination with PRRS MLV exposure would have any clear effect on enhanced immunity. The present invention makes the unexpected discovery that boosting the level of IFNα in an animal can indeed yield enhanced immunity.
The fact that IFNα can enhance immunity coupled with any live virus vaccine is particularly surprising in light of the normal function of IFNα. Since IFNα is known to have a negative effect on the process of viral replication, one might reasonably expect that an immune response from exposure to a live vaccine virus would be negatively affected by a boosted level of IFNα.
Even more strikingly, evidence indicates that a heightened level of IFNα could in fact contribute to a disease state in an infected or exposed animal. For example, the proinflammatory cytokines IFNα, tumor necrosis factor alpha, and interleukin-1 have been shown to play key roles in several respiratory disease conditions. Van Reeth, 2000. From studies involving various porcine virus infections, it was proposed that the relatively low IFNα response following PRRS infection is related to the lack of acute respiratory disease, severe lung necrosis, and inflammation. Van Reeth, 1999. According to Van Reeth, the absence of a particular 'cytokine combination' such as IFNα, TNFa, and IL-1 during PRRS infection may in part explain the mild respiratory pathology and the absence of respiratory disease. As a corollary to this proposal, the augmentation of IFNα exogenously or endogenously, is predicted to contribute to a more severe disease state rather than to enhance immunity.
Prior research also reveals that at least three other cytokines, IFNγ, IL-12, and IL-18, share the capacity of type one interferons (including IFNalpha and IFNbeta) to augment immunity by inducing strong T cell proliferation under in vivo conditions. Sprent et al., 2000. Given that "the mechanisms involved here are still unknown," it is unexpected that a single cytokine such as IFNα serves to enhance an in vivo immune response, if there are multiple independent pathways for achieving a similar result. Currently, "the biological significance" of at least one type of immune enhancement, T-cell proliferation, "induced by type 1 interferons and other cytokines in vivo is still unclear." Sprent et al., 2000.
Non-human animal interferons are described in both protein form, U.S. Pat. No. 5,831,023, and in cDNA form (cDNA that expresses IFNα), U.S. Pat. No. 5,827,694. While these references disclose potential use of IFNα protein, including IFNα expressed from cDNA, in pharmaceutical compositions for prophylactic or therapeutic treatment of non-human animals, the particular use of IFNα in combination with a live virus vaccine is not disclosed and would be disfavored by those skilled in the art for the reasons discussed herein.
Substances capable of inducing endogenous interferon have been identified. Levine, 1970. These substances include live viruses with either DNA or RNA genomes, double stranded RNA, DNA from protozoan parasites, bacterial endotoxin, mannan, mitogens (phytohemagglutinin, streptolysin O, and poke-week mitogen), statolon, helenine, and synthetic polyribonucleotides.
Other inducers of interferon have been identified. In U.S. Pat. No. 5,730,971, the substances flavin adenine dinucleotide, flavin adenine mononucleotide, and riboflavin (vitamin B2) are disclosed as potential contributors to the potentiation of an interferon response.
More recently, an adjuvant role for certain short bacterial immunostimulatory DNA sequences was proposed due to their ability to stimulate T helper-1 responses in animals vaccinated with genetic versions of antigens. Roman M et al., 1997, Nature Med 3:849. These DNA sequences are known to contain CpG (Cytosine-Guanine) motifs that are believed to be significant in the immunostimulatory capacity. However, such sequences are suggested for use in vaccine compositions where the vaccine component or subunit thereof is inactivated and not for use with live organisms such as viruses or modified live viruses.
Inducers of interferon were reported as having potential for resisting viral infection and for treating viral diseases as disclosed in U.S. Pat. Nos. 4,124,702 and 4,389,395. In U.S. Pat. No. 4,124,702, complexes of polymers are reported for induction of interferon production. The polymers can be synthetic homopolynucleotides such as polyriboinosinic acid and polyribocytidylic acid mixed in a 1:1 molar ratio (polyIC). For example, a modified polyIC complex was reported to induce serum interferon in primates in a fashion superior to polyIC. Levy, 1975. In U.S. Pat. No. 4,389,395, complexes comprising polyIC, poly-L-lysine and carboxymethylcellulose are reported for use in the induction of endogenous interferon; these complexes are referred to as polyICLC. Both polyIC and polyICLC were assessed for their ability to induce interferon responses in pigs. Loewen, 1986; Loewen, 1988. Jordan, 1995. It is believed that the polyIC and polyICLC provide preferential enhancement of cell-mediated versus humoral immunity. Alternatively, the benefits of polyIC and polyICLC is believed to be the result of quantitative improvement, for example in increases of the numbers of activated cells or the amount of antibody produced. These and other possible non-exclusive mechanisms are ways that interferon inducers can aid in immunity.
The present invention provides methods and compositions that enhance the efficacy of vaccines, particularly modified live viruses (MLV). In particular, the invention enhances the immunity in pigs compared with the immunity achieved by vaccination with PRRS MLV alone. The ability to enhance immunity is shown by combining a vaccine with any of three adjuvants: IFNα protein, IFNα cDNA, and inducers of endogenous IFNα production.

Enhancement of immune response to vaccine by interferon alpha

The Board of Trustees of the University of Illinois


The invention relates to a method and a protection system for hindering the progress of avalanches that fall with high velocity and contain an enormous amount of energy. The method consists mainly in catching the avalanche in a special Avalanche Protection System (1)—the APS—where the protection system is placed in an oblong storage box (16) on a mountain slope, in a canyon, at the foot of a mountain or at other places, where the risk of falling avalanches exists. The APS can be put up in overlapping rows to form a continuous protective wall against a potential avalanche. The protective device (1) consisting mainly of a semi-circular net sack (9) with mesh and opening; a top rope (13); a foot rope (10); leading strings (12, 14, 15) and wing units (7) attached to the top rope (13) and the net sack (9); main strings (3, 11) which are fastened to ground anchors (2) at one end and at the other end to leading strings (12), foot rope (10) and the top rope (13) of the net sack (9); flat plates (8) that are attached to the main strings (3); storage platform (5) standing on poles (4) which are equipped with locking hinges (6); and a protective helmet (17).

Up until now, many methods of hindering avalanches have been used, but with rather bad results, though. Racks and cones have been raised, ditches and defense walls (embankments) have been built, but these protection systems have not been completely effective: Racks have (been swept away, avalanches have floated over the cones; embankments and ditches require a lot of land and can be dangerous. Embankments are also still at an experimental stage. Estimates show that the first avalanche to fall on a defense wall will almost fill up the slope in front of the wall putting at risk the village or town, that the wall is supposed to protect in the event of a secondary avalanche falling over the first one. In addition, the building of a defense wall or ditches can greatly damage the land, not to mention the view. Building a defense wall is also costly and time-consuming.


A process for preparing crystalline, anhydrous podophyllotoxin from a podophyllotoxin product comprises dissolving the product in a non-aromatic and non-halogenated solvent which has a boiling point at atmospheric pressure not exceeding 130.degree. C., and which contains at the most about 1% v/v of water, cooling the solution to precipitate crystals of podophyllotoxin, isolating the crystals and drying them at a temperature which during the drying procedure is increased but is always such that it is below the temperature at which the crystals sinter or melt, the drying being continued until the melting point is in a range of 183.degree.-184.degree. C. and the residual amount of solvent is at the most 500 ppm. When the starting material contains complexed or adsorbed organic solvent, an initial azeotropic evaporation treatment is performed to remove this solvent. The yield of pure podophyllotoxin is greatly increased by adding water to the crystallization mixture.

Podophyllotoxin is a well-known lignan which has been isolated from plant extracts, particularly from so-called Podophyllum resins obtained by solvent extraction of various parts--notably the roots and rhizomes--of plants of the genus Podophyllum, e.g. the North American species Podophyllum peltatum and the Indian species Podophyllum emodi.
Podophyllotoxin has proved to be a highly effective chemotherapeutic agent for the treatment of venereal warts (condylomata acuminata; also known as genital warts) [see, e.g., R. K. Beutner and G. von Krog, Seminars in Dermatol. 9 (1990) 148]. Another important current use of podophyllotoxin is as a starting material for the synthesis of the anti-cancer drugs known as VP 16-213 ("etoposide") and VM 26 ("teniposide") [see, e.g., B. F. Issell, Cancer Chemother. Pharmacol. 7 (1982) 73].
The use of podophyllotoxin as a drug in its own right, and as a starting material for the preparation of other important drugs, has led to considerable interest in the preparation of podophyllotoxin in pure form, and the patent literature contains a number of references, e.g. U.S. Pat. No. 4,680,399 (to Buchardt) and U.S. Pat. No. 5,057,616 (to Jennings et al.), relating hereto.
Podophyllotoxin has been reported to occur in a variety of polymorphic forms having different melting points, and in the form of various solvates [see, e.g., A. W. Schrecker et al., J. Org. Chem. 21 (1956) 288]. Thus, Schrecker et al. (in the latter reference) recognized at least four crystalline modifications of podophyllotoxin, viz.: A, with water (m.p. 161.degree.-162.degree. C.); B, unsolvated (m.p. 183.degree.-184.degree. C.); C, with water and benzene of crystallization (m.p. 114.degree.-118.degree. C. "foaming"); and D, unsolvated (m.p. 188.degree.-189.degree. C.).
Podophyllotoxin has also been found to retain not only water alone, but also water together with certain organic solvents--notably simple aromatic and heteroaromatic molecules, e.g. benzene, toluene, nitrobenzene, chlorobenzene, phenol and pyridine--in the crystal structure as so-called complexes (also known as "host-guest complexes" or "inclusion complexes") or solvates see, e.g., U.S. Pat. No. 4,680,399 and K. V. Andersen et al., J. Chem. Soc. Perkin Trans. 2 (1990) 1871. The ratio between podophyllotoxin, organic solvent and water in such complexes is frequently 2:1:2; thus, for example and by way of illustration, the crystalline toluene complex (which has the latter composition) contains approximately 100,000 ppm of toluene.
Andersen et al. (in the latter reference) have demonstrated by X-ray diffraction that unsolvated podophyllotoxin (C.sub.22 H.sub.22 O.sub.8) has a melting point in the range of 182.degree.-184.degree. C., and that podophyllotoxin semihydrate (C.sub.22 H.sub.22 O.sub.8.0.5H.sub.2 O) melts in the range of 162.degree.-164.degree. C.
Furthermore, and of particular significance in relation to the present invention (vide infra), a number of organic solvents become tenaciously adsorbed to or occluded on the surface of crystals of podophyllotoxin, and this has been confirmed by the present inventors for, for example, halogenated lower alkanes such as dichloromethane and chloroform. Moreover, this tenacity is often such that simple recrystallisation of such podophyllotoxin products having adsorbed solvent molecules using other solvents, e.g. alcohols, generally does not lead to satisfactory removal of the adsorbed solvent. The present inventors have found that the mere fact that a particular product exhibits a melting point in the correct range for pure, crystalline, anhydrous, solvent-free podophyllotoxin is no guarantee for the absence of adsorbed or occluded solvent, since a number of podophyllotoxin products with significant contents of absorbed halocarbon solvent have been found to exhibit the correct melting point interval for completely pure podophyllotoxin.
Failure on the part of various past investigators to recognize the occurrence of these various forms, solvates and "solvent adsorbates" has resulted in considerable confusion, as well as misinterpretation of results. Furthermore, and rather significantly from a pharmaceutical viewpoint, important patent literature methods for the preparation of podophyllotoxin, such as those described in U.S. Pat. No. 4,680,399 and U.S. Pat. No. 5,057,616, disclose the use of, inter alia, halocarbon solvents at a late stage in the isolation procedure, there being no disclosure in these documents to indicate any awareness of the fact that (as mentioned above) such solvents are tanaciously retained by crystals of (otherwise pure) podophyllotoxin.
U.S. Pat. No. 5,057,616 discloses (see column 5, lines 62-65) that the allegedly pure product produced by precipitation from a halocarbon solvent (such as dichloromethane) and subsequent recrystallization from, typically, a ketone/ether mixture "may have a somewhat low melting point", necessitating the use of a rather elaborate and time-consuming further crystallization and vacuum-drying procedure to arrive at a product displaying the correct melting point. In U.S. Pat. No. 4,680,399, which initially exploits the crystallization properties of podophyllotoxin complexes with simple aromatic and heteroaromatic molecules (yide supra) in a first stage of isolation of podophyllotoxin from Podophyllum resin, podophyllotoxin of "especially high purity" is isolated by simple recrystallization (from a solvent such as ethyl acetate or aqueous ethanol) of a product obtained, for example, from a chloroform solution of such a complex.
What appears to be the first reported attempt to prepare pure, anhydrous podophyllotoxin was made by W. R. Dunstan and T. A. Henry [J. Chem. Soc. (1898) 209] by recrystallization of a podophyllotoxin hydrate from "absolute ethanol". However, the crystals obtained by allowing the solvent to evaporate in "a vacuous desiccator" melted at 157.degree. C., and recrystallization of these crystals from alcohol by adding water resulted in podophyllotoxin in hydrated form. These authors go on to describe the preparation of "anhydrous podophyllotoxin" by heating the "hydrated substance" at its melting point (117.degree. C.) for a few minutes, dissolving the resulting product in dry chloroform, and adding light petroleum until the mixture became slightly turbid. Upon standing, the "anhydrous podophyllotoxin" crystallized.
Schrecker et al. [J. Org. Chem. 21 (1956) 288] describe the preparation of "unsolvated" (unhydrated) podophyllotoxin by a procedure involving heating hydrated podophyllotoxin at 137.degree. C. in a vacuum. However, not only is this method impracticable for the large scale preparation of anhydrous podophyllotoxin, but based on present knowledge it is apparent that prolonged treatment of podophyllotoxin at the elevated temperature in question will, owing to the thermolability of podophyllotoxin at such temperatures, at least lead to significant epimerisation [see, e.g., O. Buchardt et al., J. Pharm. Sci. 75 (1986) 1076].
On the basis of the above discussion, it is clear that there is a need for a straightforward method for the preparation--from any readily available intermediate podophyllotoxin product, such as a hydrate, an inclusion complex with an organic solvent, or another solvent-containing podophyllotoxin phase--of anhydrous podophyllotoxin which is of high and reproducible purity, and which is free of pharmaceutically unacceptable organic solvents. The present invention fulfils this need.

Process for preparing pure podophyllotoxin


A light-emitting diode or laser diode is provided which uses a Group III nitride compound semiconductor satisfying the formula (Al.sub.x Ga.sub.1-x).sub.y In.sub.1-y N, inclusive of 0.ltoreq.x.ltoreq.1, and 0.ltoreq.y.ltoreq.1. A double hetero-junction structure is provided which sandwiches an active layer between layers having wider band gaps than the active layer. The diode has a multi-layer structure which has either a reflecting layer to reflect emission light or a reflection inhibiting layer. The emission light of the diode exits the diode in a direction perpendicular to the double hetero-junction structure. Light emitted in a direction opposite to the light outlet is reflected by the reflecting film toward the direction of the light outlet. Further, the reflection inhibiting film, disposed at or near the light outlet, helps the release of exiting light by minimizing or preventing reflection. As a result, light can be efficiently emitted by the light-generating diode.

1. Field of the Invention
The present invention relates to a light-emitting semiconductor diode (LED) and a semiconductor laser diode which use gallium nitride (GaN) compound with a double hetero-junction structure, and which emit visible short wave rays in the blue to violet region and also in the ultraviolet region of the optical spectrum.
2. Description of Background Information
A conventional LED using a GaN compound semiconductor has been known to have a structure similar to that shown in FIG. 1. It has a sapphire substrate on which GaN compound semiconductor layers are epitaxially grown. Since the light from the emission layer of the LED is emitted equally in all directions, only a fraction of the emitted light, which is taken out through an outlet port, has been utilized. Most of the emission light has been wasted, resulting in low luminous intensity.
A conventional laser diode disclosed in U.S. Pat. No. 5,247,533 utilizes a sapphire substrate on which a double hetero-junction structure is epitaxially grown.
The double hetero-junction structure comprises indium gallium aluminum (InGaAlN) compound semiconductor layers, satisfying the formula (Al.sub.x Ga.sub.1-x).sub.y In.sub.1-y N inclusive of 0.ltoreq.x.ltoreq.1 and 0.ltoreq.y.ltoreq.1, and an active layer not doped with any impurities which are epitaxially grown. Since the laser diode utilizes a sapphire substrate whose crystalline characteristic is different from that of the active layer, it is difficult to obtain cleavage sufficient to function as an effective mirror for the edge surface of the active layer. Consequently, the conventional GaN laser diode has a low oscillation efficiency.

Light-emitting semiconductor device using gallium nitride compound

Research Development Corporation of Japan