An apparatus and method for immunomagnetic separation and concentration of target biological materials is disclosed. The immunomagnetic separation is performed by a magnetic flow cell, or filter block, as part of an automated mostly continuous immunomagnetic assay system. The magnetic flow cell has two bundles of ferromagnetic rods or pins positioned inside an internal chamber so that a fluid sample flowing through the flow cell passes through the pins. A pair of cobalt magnets flank the flow cell so that the pins concentrate and sufficiently increase the magnetic fields so that even nanometer size magnetic beads can be captured. The overall system combines a reaction subsystem for reacting coated magnetic beads with a sample, a collection subsystem for capturing magnetic beads, a rinsing subsystem for removing debris and a filtering subsystem for removing captured magnetic beads from the collection subsystem. The new magnetic flow filter is the key component for the collection and filtering subsystems.

The present invention relates generally to apparatus and methods for immunomagnetic separation and concentration of target biological materials, and more specifically to an automated flow-through immunomagnetic assay system that rapidly and efficiently captures all types of immunomagnetic beads from fluid samples.
Immunomagnetic separation and concentration of specific target ligands or particles, such as bacteria or leukocytes, from complex mixtures, such as bone marrow, blood and other body fluids, is an increasingly popular technique for identifying biological pathogens. In this technique, antibodies to the bacteria or other pathogen of interest are immobilized on magnetic beads. The beads, with the attached antibodies, are mixed with the media being investigated so that molecules of any target organisms present in the media attach to the antibodies, and thus to the magnetic beads. The beads are then separated from the mix by a magnetic field and the now more concentrated mix of captured target organisms (if the target organisms were present in the original mix) tested by a variety of detection methods, such as ELISA, flow cytometry, automated microscopy and electrochemiluminescence (ECL) assay, for the presence of the target organism. To the extent that immunomagnetic assay systems can be made more effective and more rapid, they can be used for rapid clinical diagnosis of pathogens, toxins and other analytes in body fluids, rapid environmental detection of harmful bacteria, viruses and other substances in water and in industrial monitoring system for detection of harmful materials in foods and other substances.
A key element of any immunomagnetic assay system is a system for capturing the magnetic beads. Magnetic beads are, or typically contain, paramagnetic (that is, magnetizable in the presence of an external magnetic field, but nonmagnetic on removal of the field) magnetite (Fe.sub.3 O.sub.4). Magnetic beads may range in diameter from 50 nm (colloidal "ferrofluids") to several microns. Ferrofluids are so small that they require magnetic fields greater than 4 Tesla per cm to capture them.
The prior art has shown that such relatively large field strengths may be generated by a small diameter wire that creates a high field gradient when placed in an external magnetic field. The small diameter wire acts as an antenna to concentrate the magnetic fields near it. The prior art has utilized this property in a number of existing immunomagnetic separation and detection methods and apparatus. One method has been to place steel wool inside a collecting vessel and then place the vessel inside a strong magnetic field. Another method has been to place paperclip-shaped bent metal pins inside microtitre wells and then move the holder for the microtitre wells inside a strong magnetic field. In the presence of the enhanced magnetic gradients, magnetic beads can be captured from any fluid samples inside the vessel or microtitre wells onto the steel wool or the bent metal pins. After the magnetic fields are removed, the captured magnetic beads can be removed from the steel wool or bent pins by various techniques. A third method described in the prior art for concentrating magnetic fields is a quadrupole magnetic arrangement which concentrates a magnetic field near the intersection of two north and two south poles of four bar magnets brought in close proximity.
The bent metal pins inside microtitre wells technique is primarily a batch process suitable for laboratory use. This technique can only process small batches of samples at one time.
The steel wool technique suffers from a number of disadvantages, a primary example of which is that steel wool-based systems are very difficult to clean completely and generally exhibit unacceptable levels of hysteresis, the tendency for later tests to show false results from contamination by leftover captured magnetic beads from previous tests.
In a quadrupole magnetic arrangement, the magnetic field strength is zero at the center of the arrangement, which requires designing a chamber to either eliminate cells in that area or depend on the magnetic beads sufficiently mixing to somewhat alleviate the problem.
Existing prior art techniques are not designed to accommodate all types of magnetic beads or are not fully automated. In particular, while suitable for laboratory work on small batches, they are not easily adaptable for continuous (or virtually continuous) monitoring for pathogens.
Thus it is seen that there is a need for an immunomagnetic assay system that can rapidly and efficiently capture all types of magnetic beads from milliliter quantities of fluid samples, and which can be used as part of a continuous process. The ability to run an immunomagnetic assay system on a continuous, or nearly continuous, basis is needed for immunomagnetic systems to find use in industry.
It is, therefore, a principal object of the present invention to provide an immunomagnetic assay system utilizing a flow cell for capturing magnetic beads that can rapidly and efficiently capture all types of magnetic beads from milliliter quantities of fluid samples.
It is a feature of the present invention that it works very rapidly.
It is another feature of the present invention that it will work will all sizes of magnetic beads.
It is an advantage of the present invention that it can be easily automated to provide a nearly continuous immunomagnetic assay system.
These and other objects, features and advantages of the present invention will become apparent as the description of certain representative embodiments proceeds.

Immunomagnetic assay system for clinical diagnosis and other purposes

The United States of America as represented by the Secretary of the Air Force


A unitary swirler assembly that provides improved service life, having a ferrule body and a unitary swirler body. The unitary swirler body has oppositely-directed primary swirler passages and secondary swirler passages. A pair of rails formed on the unitary swirler body engage the ferrule body to limit relative movement, and prevent relative rotation, of the ferrule body and the unitary swirler body.

The invention relates to swirler assemblies for supplying compressed air to the combustor of gas turbine engines.
A gas turbine engine includes a compressor that provides pressurized air to a combustor wherein the air is mixed with fuel and ignited for generating hot combustion gases. These gases flow downstream to one or more turbines that extract energy therefrom to power the compressor and provide useful work such as powering an aircraft in flight. In combustors used with aircraft engines, the fuel is typically supplied to the combustor through a plurality of fuel nozzles positioned at one end of the combustion zone. The air is supplied through surrounding assemblies, known as swirler assemblies, which impart a swirling motion to the air so as to cause the air and fuel to be thoroughly mixed. The swirler assemblies are mounted in a dome plate that is joined to the upstream ends of the combustor's inner and outer liners, and each fuel nozzle tip is received in a corresponding one of the swirler assemblies.
One conventional swirler assembly is a three part assembly comprising a primary swirler, a secondary swirler and a retainer. The primary swirler has a plurality of circumferentially spaced swirl vanes or air passages. The vanes or passages are angled with respect to the axial centerline of the swirler assembly so as to impart a swirling motion to the air flow. The secondary swirler, also having a plurality of circumferentially spaced swirl vanes or air passages, is disposed immediately downstream of the primary swirler. The vanes or passages of the secondary swirler are angled so as to produce a swirl of air swirling in the opposite direction as the primary swirler to further promote fuel-air mixing. The retainer fits over the primary swirler and is welded to the secondary swirler to retain the two swirlers in engagement with one another.
The air flow through the vanes or passages of the primary swirler creates a reaction force that tends to cause the primary swirler to rotate with respect to the secondary swirler and the fuel nozzle. However, if allowed to rotate, the primary swirler would fail to impart the necessary level of swirling to the air, and effective mixing of the air and fuel would not be achieved. Furthermore, rotation of the primary swirler would cause excessive wear to the fuel nozzle tip. Primary swirler rotation is thus prevented in conventional swirler assemblies by providing an outwardly extending tab on the primary swirler and a post on the secondary swirler, wherein the tab engages the post so as to limit relative rotation of the swirlers.
However, the combustor structure is vibrationally active and there is substantial thermal expansion of components during operation of a gas turbine engine. As a result, there is relative movement between the tab and the post resulting in significant wear that eventually requires repair and increases maintenance costs. The repair process is relatively difficult because it requires removal of the permanently welded retainer. It is also possible that a worn tab and/or post could break off and cause damage to the turbine downstream. Furthermore, the retainer is susceptible to cracking during operation and often needs to be replaced.
Accordingly, there is a need for an improved swirler assembly that can prevent and preferably prevent rotation of the primary swirler relative to the secondary swirler, to eliminate frequent repairs, and which is easy to field assemble and disassemble.


A method for etching a high-k dielectric layer on a substrate in a plasma processing system is described. The high-k dielectric layer can, for example, comprise HfO2. The method comprises elevating the temperature of the substrate above 200° C. (i.e., typically of order 400° C.), introducing a process gas comprising a halogen-containing gas, igniting a plasma from the process gas, and exposing the substrate to the plasma. The process gas can further include a reduction gas in order to improve the etch rate of HfO2 relative to Si and SiO2.

In the semiconductor industry, the minimum feature sizes of microelectronic devices are approaching the deep sub-micron regime to meet the demand for faster, lower power microprocessors and digital circuits. Process development and integration issues are key challenges for new gate stack materials and silicide processing, with the imminent replacement of SiO2 and Si-oxynitride (SiNxOy) with high-permittivity dielectric materials (also referred to herein as "high-k" materials), and the use of alternative gate electrode materials to replace doped poly-Si in sub-0.1 μm complementary metal-oxide semiconductor (CMOS) technology.
Dielectric materials featuring a dielectric constant greater than that of SiO2 (k˜3.9) are commonly referred to as high-k materials. In addition, high-k materials may refer to dielectric materials that are deposited onto substrates (e.g., HfO2, ZrO2) rather than grown on the surface of the substrate (e.g., SiO2, SiNxOy). High-k materials may incorporate metallic silicates or oxides (e.g., Ta2O5 (k˜26), TiO2 (k˜80), ZrO2 (k˜25), Al2O3 (k˜9), HfSiO, HfO2 (k˜25)). During the manufacturing of semiconductor devices, the high-k layers must be etched and removed in order to allow silicidation for the source/drain regions, and to reduce the risk of metallic impurities being implanted into the source/drain regions during ion implantation.

Method and system for etching a high-k dielectric material


An exhaust-gas filter, for example a soot-particle filter, has a filter element which has inlet passages for the raw gas and outlet passages for the clean gas. In order as far as possible to prevent clogging of the filter over the running time caused by deposits on the filter walls, the raw-gas passages are configured with a larger cross-section than the clean-gas passages.

The present invention relates to an exhaust-gas filter, and, more particularly, a soot-particle exhaust gas filter, comprising a filter element constructed in layers of filter plates configured in wave form transversely to a flow direction of exhaust gas and, in a continuous layer sequence, are arranged alternately to form with one another inlet passages for raw gas and outlet passages for clean gas.
An exhaust-gas filter shown in DE-OS 33 30 020 Al is configured as a right parallelepiped. Its the filter element comprises a plurality of filter plates arranged in layers one on top of the other. The filter plates have a waved or flat structure transversely to the direction of flow of the exhaust gas, wherein a waved layer alternates layer by layer with a flat layer. For conducting the exhaust gas through the passage side walls, the filter passages formed between the filter plates are closed on alternate sides and thereby form raw-gas and clean-gas passages. The exhaust-gas filter described has, however, the disadvantage that, as the running time of the motor vehicle increases, the volume of the filter and the entry area of the filter are reduced by deposition of combustion residues such as, for example, soot particles, oil ash and fuel additives on the filter wall. As a result, the counterpressure to the exhaust gas increases greatly. This results in a reduction in the engine power and an increase in consumption.
An object of the present invention is to provide an exhaust-gas filter such that clogging of the filter owing to deposition of combustion residues on the filter walls over the running time of the motor vehicle is prevented.
The object is achieved according to the present invention by configured the filter such that the inlet passages have a larger cross-section than a cross-section of the outlet passages, the inlet passages and the outlet being formed by a sinusoidal configuration of the filter plates and respective pairs of mutually neighboring filter plates having an identical phase and periodically, but different amplitude and forming a plate group with a layer structure arranged phase-shifted by 180.degree. with respect to neighboring plate groups.
In the present invention, the raw-gas passages are thus provided with a larger cross-section than the clean-gas passages. Because of the enlargement of the wall area of the raw-gas passages, a significantly higher accumulating capacity of the filter results, which at least delays clogging of the filter to a later time. Furthermore, the raw-gas passages covered by the deposits lie closer together, whereby an improved heat transfer between passages carrying the raw gas is achieved and consequently more favorable thermal preconditions for soot burn-off are created. Altogether, due to the increased storage capacity of the filter and the improved thermal conditions for burning off the soot particles over the running time, clogging of the filter is prevented. In addition, the susceptibility of the filter to burning through of the filter walls during soot burn-off is reduced, since the soot filtered out over the running time is distributed over a larger filter surface.
In a constructionally advantageous development of the present invention, the filter plates are sinusoidally waved transversely to the direction of flow of the exhaust gas. Respective pairs of mutually neighboring filter plates have the same phase and the same period but different amplitude and forming a plate group which in the layer structure is arranged phase shifted by 180.degree. with respect to neighboring plate groups. Raw-gas passages of large cross section or clean-gas passages of smaller cross-section are bounded alternately in continuous layer sequence by mutually neighboring filter plates. As a result, the configuration of an exhaust-gas filter having an enlarged filter area for the raw gas with the same external dimensions as in the case of a conventional exhaust-gas filter is made possible.
According to another advantageous embodiment of the present invention, the waving of a filter plate is formed by wave crest groups of the same amplitude which are connected by deep wave troughs and are for their part in each case composed of wave crests connected to one another by flat wave troughs. In this instance, the layer structure of the filter is made up by a continuous reflection of a filter plate at an imaginary plane which forms a tangent to the vertices of the deepest wave troughs of the respective filter plate. Filter passages of various cross-sections are formed between the filter plates. The filter passages of largest cross-section are assigned to the conducting of raw gas. Apart from the constructional advantage of the external dimensions of the filter element remaining the same with regard to conventional exhaust-gas filters, with at the same time an enlargement of the filter area for raw gas, this embodiment of the invention has the technical advantage in terms of production that only one filter plate form is required for the construction of the exhaust-gas filter.


A non-steroid containing anabolic nutrient formulation for the building and sustaining of muscle mass in humans or other warm-blooded animals, that enables the body to synthesize and maintain muscle at a mass and in a manner optimally suited to the genetic makeup of that person or animal. The formulation comprises effective amounts of a chromium salt, complex or chelate and a magnesium glycyl glutaminate chelate. Optionally, one or more additional nutrients selected from the group consisting of a magnesium amino acid chelate or proteinate, an .alpha.-glutaric acid salt of ornithine, creatine or a salt thereof, and a branched chain amino acid selected from the group consisting of leucine, isoleucine and valine and mixtures thereof may be included.

It is well known that both negative energy balance and muscle catabolism are consequences of physiological stress that often accompanies protein calorie malnutrition, strenuous physical exercise, physical trauma, burn injury, surgical trauma, malnutrition, maldigestion, malabsorption, hyperthyroidism, chemotherapy, radiation therapy, anorexia, cachexia, short bowel syndrome, old age, sepsis and other conditions. It is also known that maintaining a positive metabolic energy balance can help to alleviate such problems and also has a sparing effect on muscle catabolism that occurs during strenuous physical exertion causing fatigue.
Athletes, in particular, have needs for maintaining and/or building muscle mass compatible with their genetic makeup to optimize their strength, body tone and physical abilities. Ideally, this would be accomplished using the body's own resources without being subjected to the administration of anabolic steroids and the associated negative side effects.
It is well known that anabolic steroids, such as testosterone and natural and synthetic derivatives and substitutes, affect many metabolic activities such as muscular development and fat distribution. Administration of anabolic steroids tend to take users past their natural or genetic limits to create body size and muscle mass beyond that which is optimal to the genetic makeup of the individual and past that which can be effectively supported by the various organs of the body.
Excess anabolic steroids tend to suppress or dam up other natural, yet essential, hormones in the body such as the andrenocorticosteroids. The glucocorticoids, and cortisol (hydrocortisone) in particular, are necessary in the metabolism of carbohydrates and fats. Cortisol promotes gluconeogenesis by peripheral and hepatic actions. It acts to mobilize proteins and amino acids from skeletal muscle. Proteins and amino acids funnel into the liver, where they engage the enzyme systems involved in the production of glucose and glycogen. In quantitative terms, the peripheral action of cortisol accounts in large measure for its gluconeogenic effect. In the liver, especially on a long term basis, cortisol induces the synthesis of a number of enzymes intimately involved in gluconeogenesis.
However, release or administration of large doses of cortisol can produce changes in carbohydrate, protein and fat metabolism. Blood sugar tends to be high, liver glycogen is increased and there is increased resistance to insulin. The catabolic action of cortisol is reflected in the wasting of tissues, reduced mass of muscle, osteoporosis and thinning of the skin. In certain instances, a diabetic-like state may be produced.
Excess amounts of cortisol also causes an alteration in fat distribution. There is a gain of fat in depots in the neck, supraclavicular area and cheeks and a loss of fat from the extremities.
Elevated cortisol levels are also known to suppress the immune system. Cortisol prevents glucose entry into muscle and adipose tissue and decreases activity of insulin. Moreover, cortisol has been shown to inhibit LH release in the bovine species and therefore has an effect on reproduction. Insulin availability may limit the onset of ovarian activity in the female leading to ovulation. Insulin is also known to reduce concentration of blood ketone bodies. Sartin et al., Plasma Concentrations of Metabolic Hormones in High and Low Producing Dairy Cows, J. Dairy. Sci. 71:650-657, 1988 reports that cortisol is antagonistic to milk production.
Chromium has been shown to suppress the production of glucocorticoids. Chromium functions as a potentiator of insulin. Chromium is a trivalent mineral which has been found in recent years to be more bioavailable when administered as an organic complex. The most common organic complex is a low-molecular weight organic complex termed "glucose tolerance factor" (GTF) obtained primarily from Brewer's yeast. Recent research has shown that various stressors such as infection, strenuous exercise, pregnancy, change of environment, etc, increase urinary excretion of chromium. Sub-optimal levels of chromium may be a factor in several stress related diseases. Schnauzer et al., Effects of Chromium Supplementation in Food Energy Utilization and the Trace-element Composition in the Liver and Heart of Glucose-exposed Young Mice, Biol. Trace Element Res. 9:79 1986, have shown that chromium supplementation protects against stress-induced losses of trace minerals such as zinc, copper, iron and manganese. Polansky et al., Beneficial Effects of Supplemental Chromium on Glucose, Insulin and Glucagon of Subjects Consuming Controlled Low Chromium Diets, FASEB J. A2964. 1990, report that human dietary chromium intakes is suboptimal with diets of approximately twenty-five percent of the U.S. population containing forty percent or less of the recommended daily chromium intake. There is also evidence that chromium in the human body decreases with age. In the animal kingdom, it has been found that steers, subjected to conditions of stress, have increased serum cortisol levels which can be lowered by administration of supplemental chromium.
Moreover, chromium is an essential trace element as a cofactor in several enzyme systems. As mentioned above, it is associated with a low-molecular weight organic complex termed "glucose tolerance factor" (GTF) that acts with insulin in promoting normal glucose utilization. Brewer's yeast, which is rich in GTF, has been shown to improve glucose tolerance, lower serum cholesterol and triglycerides in some subjects and to reduce insulin requirements in some diabetics. Glucose tolerance is usually impaired in protein-calorie malnutrition and some cases have shown a dramatic response to administration of trivalent chromium. Deficiency has been reported in patients on prolonged parenteral feeding. Additionally, GTF is not only a co-factor of insulin thus influencing glucose, but protein and lipid metabolism as well. GTF is not as effective, if not ineffective, in the absence of insulin. The exact mechanism by which GTF improves glucose tolerance is not known. However, it is thought that GTF enhances the binding of insulin to its specific receptors.
Another part of the beneficial effects of chromium on the immune system may be related to vitamin C metabolism. It is known that cattle arriving at a feedlot in a chronically stressed condition show evidence of hyperglycemia and are at greater risk of disease as vitamin C entry into neutrophils is most likely reduced. Vitamin C is needed for neutrophil function, decreases circulating corticoid levels and ameliorates immunosuppression in stress. Nockels, Effect of Stress on Mineral Requirements, Western Nutritional Conference, 1990 and Satterlee et al., Vitamin C Amelioration of the Adrenal Stress Response in Broiler Chickens Being Prepared for Slaughter, Comp. Biochem. Physiol., 94A:569-574, 1989 have shown that vitamin C ameliorates the negative effect of stress in broiler chickens being prepared for slaughter which is possibly due to suppression of adrenocortical steroidogenesis. Synthesis of ascorbate from glucose may be reduced when glucose is deficient as in earlier fasting during transport. Calves may also have a low glucose synthesis when fed forage diets so vitamin C synthesis may be low.
Glucocorticoids are known to suppress the immune system according to Munck et al, Physiological Functions of Glucocorticoids in Stress and Their Relation to Pharmacological Actions, Endoc. Rev. 5:25, 1984. Therefore, another beneficial effect of chromium supplementation during periods of stress in suppressing cortisol serum levels could conceivably result in improving effectiveness of certain vaccines. Carlson et al., The Bovine Proceedings, 15:84 1990, measured antibody response to IBR vaccination in feedlot cattle found cattle to be poorly responsive to immunization upon arrival in the feedlot. These results were attributed to the stresses of shipping and respiratory infection drawing the conclusion that such factors may render an animal immunoincompetent.
Supplemental chromium, administered to bovine species, has been shown to decrease serum cortisol and may increase milk production. Supplemental chromium has also has been found to be associated with weight gain in stressed animals. Part of the improvement in gain with administering supplemental chromium may be due to decreasing cortisol production. It has been shown by Southorn et al., The Effect of Corticosterone Treatment of the Response of Muscle Protein Synthesis to Insulin Infusion in the Rat, J. Endocrin. 23: abst. #127, 1989, that rats treated with corticosterone developed insulin resistance with respect to muscle protein synthesis. Clinical evidence supports the immunosuppressive activity of glucocorticoids through impairment of neutrophil function and suppression of lymphocyte blastogenesis.
However, once chromium is mobilized in the body in response to increased glucose metabolism, elevated insulin response, stress, elevated cortisol levels, etc., it is not reabsorbed in the tissues but is excreted in the urine. Therefore, diets and/or conditions that lead to chromium utilization also lead to chromium depletion. Sufficient chromium supplementation, in a bioavailable form, is therefore essential to the proper functioning of the metabolic system.
Magnesium is the fourth most abundant cation in the body. Almost half of the magnesium in the body is located in the bone. Of the non-osseous tissues, liver and striated muscle have the highest magnesium concentrations. Magnesium is an activator of a host of enzyme systems that are critical to cellular metabolism. Prominent among these are the enzymes that hydrolyze and transfer the phosphate groups, e.g. the phosphatases and those concerned in the reactions involving adenosine triphosphate (ATP). Since ATP is required for glucose utilization, fat, protein, nucleic acid and coenzyme synthesis, muscle contraction, methyl group transfer, sulfate, acetate and formate activation, by inference the activating effect of magnesium extends to all these functions. One means by which magnesium is involved in protein synthesis is by contributing to the binding of messenger RNA to the 70S ribosome. Magnesium is also required for the synthesis and degradation of DNA and has also been included in all the amino acid activating systems.
By means of one or more of the above mechanisms, magnesium is essential to the building of maximum muscle mass and endurance. Strenuous physical activity and associated mental and physical stress can cause a decline in tissue magnesium levels as a result of hypermetabolic compensation and the increased elaboration of catecholamines, glucagon, and mineral corticoids. Magnesium administered in the form of inorganic salts to replenish reduced levels in the body, can cause serious side effects such as intestinal irritability, loose stools, or diarrhea. Because of this, many body builders or other athletes are magnesium deficient and sufficient levels of magnesium are not included in many prior art anabolic formulas. It is therefore essential that any magnesium administered is in a safe but effective bioavailable form. One such form which has been shown to be superior to all others is as an amino acid chelate.
There are certain amino acids that affect the positive balance of nitrogen in the building or synthesis of skeletal or muscular proteins. These function in the presence or absence of insulin but have a greater response in the presence of insulin. Glutamine, glycine and arginine are all anabolic and also all have well-defined metabolic behaviors that are distinct from their participation in protein synthesis and breakdown. According to Rennie et al., J Nutr. 124: 1503S-1508S (1994) it has been found that there is a strong relationship between the rate of muscle protein synthesis and intramuscular glutamine concentration. Rennie et al. state that there is little doubt that the phenomenon of an anabolic effect of glutamine in human and animal muscle exists, however, the nature of the mechanism is not evident. Glutamine or L-glutamine, not only has a positive effect on the nitrogen balance in protein, i.e. is anabolic, but also stimulates the accumulation of muscle glycogen in rats. It is suggested that any processes that interfere with the ability of muscle to accumulate glutamine will result in muscle wasting and therefore, the effects of disease and injury causing muscle wasting may include interference with the muscle glutamine transporter.
Young et al, J. Parenteral and Enteral Nutrition, 17: 422-427 (1993) states that glutamine has been shown to be clinically safe when administered as a supplemental nutrient and improves nitrogen balance. It is also known that glutamine is a precursor of the neurotransmitter .tau.-aminobutyric acid and can cross the blood-brain barrier. Glutamate, which is a product of glutamine metabolism, and vice versa, is the most abundant single amino acid within the central nervous system and also functions as a neurotransmitter. Because of this property, Young et al., have found that glutamine also possesses antidepressive properties.
According to Gore, et al., Arch. Surg. 129:1318-1323 (1994) catabolic hormones, such as cortisol, increases the efflux of glutamine resulting from an accelerated release of glutamine from the free intracellular glutamine pool that is then replenished from either increased endogenous protein breakdown or from de novo glutamine synthesis. This is further indication that increased cortisol has an adverse or catabolic affect on the nitrogen balance of muscle tissues and also of the need for a source of bioavailable glutamine.
To permit optimal muscle growth and maintenance, it is essential that a proper balance be maintained between endogenous anabolic steroids and cortisol such that these hormones are present in amounts sufficient to enable the various body processes to function normally while, at the same time, minimizing the adverse side effects caused by these same hormones. It is also necessary that adequate amounts of chromium and magnesium, in a bioavailable form, are present to regulate enzyme functions, cortisol levels, and optimize synthesis of proteins, glucose, and fat distribution.
Ashmead et al., U.S. Pat. No. 4,020,158; Ashmead, U.S. Pat. No. 4,076,803; Jensen U.S. Pat. No. 4,167,564; Ashmead, U.S. Pat. No. 4,774,089 and Ashmead, U.S. Pat. No. 4,863,898 all disclose metal amino acid chelates and various uses for these chelates in reference to increasing absorption of essential minerals into biological tissues. Some of these patents suggest that certain mineral and ligand combinations can enhance metal uptake in specific organs or tissues where specific biological functions are enhanced, i.e. minerals crossing the placental membranes into foeti, estrus or spermatogenesis, etc.
However, although amino acid chelates and some of the uses to which they are applicable are documented in the art, there is no teaching or suggestion that proper formulations and administration of a chromium salt, complex or chelate, in combination with a specific magnesium amino acid chelate (magnesium glycyl glutaminate) can have an anabolic effect in the building and maintaining of muscle mass in a manner which equals or is superior to the administration of anabolic steroids but without having the negative side effect.
It would be desirable to enable the building of muscle mass and strength in a manner consistent with the genetic makeup of an individual without resorting to the use of substances, natural or synthetic, which have a negative physiological impact. It would also be desirable to optimize such building of muscle mass using nutritional supplements which awaken the inherent processes of the body to function at peak natural performance for that particular individual.


The present disclosure provides a process for synthesis of 3-aryl-2-hydroxy propanoic acid derivatives of formula (S)-1. wherein R1 represents H or (C1-C5) alkyl groups and R2 represents (C1-C5) alkyl groups.

3-Aryl-2-hydroxy propanoic acid derivatives serve as a key intermediate for the synthesis of many pharmaceutically important compounds especially, peroxime proliferator activated receptor (PPAR) agonist. Optically active 3-aryl-2-alkoxy propanoic acid and its esters, particularly, ethyl (2S)-2-ethoxy-3-(4-hydroxyphenyl)propanoate (EEHP) and isopropyl (2S)-2-ethoxy-3-(4-hydroxyphenyl)propanoate (IEHP) are versatile chiral pharmacophores present in many pharmaceutically important compounds, especially in peroxisome proliferator activated receptor (PPAR) agonists that have beneficial effects in treating Type 2 diabetes. Several PPAR agonists, in particular PPAR α/γ dual agonists, commonly termed as glitazars (Ragaglitazar, Tesaglitazar, Navaglitazar etc.), as shown in the FIGURE below were developed by many pharmaceutical companies that have a potential application in the treatment of Type 2 diabetes and dyslipidemia. However, many of these drugs were discontinued due to their undesirable side effects, but some of them still have great potential [For example, Saraglitazar (Lipaglyn™) developed by Zydus Cadila got approval in India for the treatment of diabetic dyslipidemia or hypertriglyceridemia]. Several PPAR α/γ agonists possessing chiral (S)-1 moieties are shown below.

In addition, these derivatives find an application in photosensitive materials, sweetening agents, treatment of certain eating disorders etc. Therefore, these compounds have attracted a great deal of attention of synthetic chemists and different methods of preparation of the compound of formula (S)-1 have been extensively studied. Generally, the reported protocols for the synthesis involve chiral pool approaches starting from L-tyrosine and its derivatives (Refer WO 02/24625, U.S. Pat. No. 6,559,335B2, WO 2003/027084), asymmetric synthesis (Org. Lett. 2005, 7, 1947, US 2007/0149804) and resolution processes using chiral amines or enzymes (WO 2000/026200, WO 2001/11073, Org. Process Res. Dev. 2003, 7, 82, Org. Process Res. Dev. 2004, 8, 838, Tetrahedron Asymmetry 2009, 20, 2594). Some of these methods have disadvantages such as expensive chiral starting materials and catalysts, low enantioselectivity and overall yields, problems associated with the O-alkylation step which often leads to the loss of optical purity, and many others.
The processes described in WO20026200 (Rao et. al.) uses benzyl bromide for benzylation, which is highly lachrymatory. Again, in the processes described, the debenzylation of the final intermediate was done by using Pd/C under pressure, which escalates the process economics.
WO2003024915 describes a process for the preparation 3-aryl-2-hydroxy propanoic acid derivatives from 3-(4-hydroxyphenyl)-2-oxopropanoic acid.
WO 2003008362 describes 3-Aryl-2-hydroxy propanoic acid derivatives of formula I and the preparation thereof.
wherein R1 and R2 may be same or different and represent hydrogen or (C1-C6) alkyl.The process includes i) reducing the compound of formula (III) where R represents hydrogen or alkyl group, R3 represents benzyl to a compound of formula (IV) where R3 represents benzyl, ii) etherifying the compound of formula (IV) using alkylating agent to a compound of formula (V) where R1, R2 and R3 are as defined above and iii) debenzylating the compound of formula (V) in the presence of metal catalysts to yield pure compound of formula (I).
The process is depicted in Scheme 1 below.

In another process variant as in Scheme 2, WO′362 discloses a process for the preparation of novel 3-aryl-2-hydroxy propanol and their derivatives of the formula (I)
wherein OR and OR together form a substituted or unsubstituted 5 membered cyclic structure containing carbon and oxygen atoms, which comprises: i) reducing the compound of formula (III) where R represents hydrogen or alkyl group, R3 represents benzyl to a compound of formula (IV) where R3 represents benzyl, ii) cyclizing the compound of formula (IV) to a compound of formula (V) where OR1 and OR2 together form a substituted or unsubstituted 5 membered cyclic structure containing carbon and oxygen atoms and R3 represents benzyl and iii) debenzylating the compound of formula (V) in the presence of metal catalysts to yield pure compound of formula (I).

Both the processes described in WO'362 result in poor overall yield and further fail to describe the preparation of compound of formula V using different alkylating agents. This document exemplifies the compound of formula V with similar ether groups as it fails to teach selective alkylation of formula IV.
WO2005019152 discloses an improved process for the preparation of compound of the general formula (1a) and (1b).
Wherein, R1 represent H or (C1-C6) alkyl group such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl and the like. R2 represents (Ci-Ce) alkyl group such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl and the like. R3 represents H, protecting groups such as benzyl, substituted benzyl, (C1-C3) alkyl and like.The compound of general formula (1a) is prepared according to the following schemes 3 and 4.

Both the processes start with selective O-alkylation or O-aralkylation of L-Tyrosine of formula (2a) using a base, a chelating agent, an alkyl or aralkyl halide in the presence of solvents to obtain the compound of formula (3a), which is diazotized to obtain formula (4a) which upon dialkylation using an excess of alkylating agent and excess base, in presence of suitable solvent to obtain optically pure compound of formula (1a). Alternatively, compound of formula (4a) may be selectively esterified to obtain compound of formula (5a), which is subsequently O-alkylated to obtain compound of formula (1a) (Scheme 2).
However, the above processes have many disadvantages such as multistep synthesis including protection & deprotection and low overall yield. Further, low temperature diazotization on industrial scale is not viable. Moreover, the starting material is very expensive and hence escalates the process.
In the light of the foregoing, development of a new, alternate enantio-selective synthetic route to these important chiral intermediates, which are simple and can preserve the optical purity at the C-2 carbon of 3-Aryl-2-hydroxy propanoic acid derivatives, is highly desirable. There is a need for an efficient process for synthesis of 3-Aryl-2-hydroxy propanoic acid derivatives of formula (S)-1 in high enantiopurity and good overall yield from commercially available starting material.

Process for the preparation of 3-aryl-2-hydroxy propanoic acid compounds

Council of Scientific and Industrial Research


The disclosure provides a current steering digital to analog converter (DAC) that includes a plurality of DAC elements. At least one DAC element of the plurality of DAC elements is coupled to a calibration circuit. The calibration circuit includes a fixed current source coupled to a primary node of the DAC element through a first estimation switch. A digital code generator is coupled to the primary node, and generates a first digital code corresponding to a primary voltage generated at the primary node. The digital code generator generates a second digital code. A correction DAC is coupled to the digital code generator and generates a bias voltage based on the second digital code. The bias voltage is provided to the DAC element such that a current flowing through each DAC element of the plurality of DAC elements is equal.

The digital to analog converter (DAC) is widely used for signal conversion in electronic devices. The DAC converts a digital signal to an analog signal such that the analog signal can be provided to an electronic device. A current steering DAC is a widely used DAC architecture. The current steering DAC finds application in communication systems such as cell phone or base station, image processing, wireless communications, and audio-visual systems. There is an increasing demand for high resolution and high speed current steering DAC.
The current steering DAC includes multiple independent current sources. The current steering DAC has limited linearity and resolution due to current mismatch across PVT (process voltage temperature). The existing calibration techniques include off-chip calibration and on-chip calibration. The off-chip calibration is used only once. The on-chip calibration is executed every time a chip with the current steering DAC is activated. These calibration techniques are helpful when operating conditions (PVT) does not change during real time operation.
Thus, another form of calibration technique referred to as background calibration technique is utilized. The background calibration technique is useful when the operating conditions are varying and the device with the current steering DAC is running. Thus, it is important in the background calibration technique, that the current steering DAC is calibrated independent of the operating conditions.

Calibration technique for current steering DAC


According to an example, a three-dimensional (3D) printed object may include a body formed of an electrically non-conductive material. In addition, an electrically conductive channel, a sensing device, and a signal emitter may be embedded within the body. The sensing device may be in electrical communication with the electrically conductive channel such that the sensing device is affected by a disruption in a current applied through the electrically conductive channel. In addition, the signal emitter may emit a wireless signal in response to the sensing device being affected by a disruption in the applied current.

3D manufacturing apparatuses that employ additive manufacturing techniques to build or print parts are gaining in popularity and use. Some additive manufacturing techniques employ a layering process in which particles of build material are spread into a layer and selectively fused together. Following that process, additional particles are spread into another layer and fused together. This process may be repeated for a number of times to build up a 3D part having a desired configuration.

3D printed object with embedded sensing device

Hewlett-Packard Development Company, L.P.


Presented is a method of displaying a newly requested channel in a mobile TV device prior to retuning the mobile TV device to the newly selected channel. The mobile TV device demodulator and tuner are cycled on for a short period of time at regular intervals to conserve battery power. Data is buffered from multiple channels in a buffer within the mobile TV device while the demodulator is cycled on. The mobile TV device displays data from one of the buffered channels upon a request to switch to the channel prior to retuning the mobile TV device to the newly selected channel. The mobile TV device is then retuned to the newly selected channel at the next instance the demodulator and tuner are cycled on.

The present invention relates to portable mobile communications devices and systems, and more particularly to a portable mobile communications device, system and method that can receive television broadcast signals.
Portable mobile communications devices such as mobile phones are becoming more sophisticated and include many new features and capabilities. One such feature is the capability to receive mobile broadcast television signals or mobile television or the like, such as digital video broadcast-handheld (DVB-H), digital media broadcast (DMB), integrated services digital broadcast-terrestrial (ISDB-T) or similar technologies.
The DVB-H standard reduces power consumption and extends battery life by using a time sliced format to transfer one of many data channels to a mobile device. For instance, the radio and demodulator associated with the television portion of the mobile device are only powered on for relatively short periods of time (i.e., 0.1 seconds) while they remain powered off for longer periods of time (i.e. 1 to 5 seconds). Thus, the ratio between on/off of the radio and demodulator can range from 10:1 to 50:1 while the interval between on cycles can vary from 1.0 to 5.0 seconds.
The drawback to this power save method is that the time required to switch from one channel to another channel is noticeably and annoyingly long for the user/viewer. Conversely, leaving the radio and demodulator powered on all the time to capture and buffer all available channels will drastically affect the battery life of the device.
Currently, there are no provisions addressing the user's dilemma described above. What is needed is a mechanism that allows the user to shorten the time it takes to change channels without overly affecting the battery life of the mobile device.

Mobile television channel switching system and method


A thermally conductive interface material formed of a polymeric binder and one or more thermally fillers is disclosed. One or both of the major surfaces of the interface material has a means for removing air from between that surface and the surface to which it is attached, such as a heat sinker an electronic component. Alternatively, the heat sink or component may have the air removal means instead of or in addition to the interface material. The air removal means may be a series of embossments, channels or grooves or throughholes. Preferably, the interface is a pressure sensitive acrylic adhesive material and more preferably, it is in the form of a tape.

The present invention relates to a thermally conductive interface material that is interposed between a source of heat, such as an electronic component and a heat sink. The most common example of this invention is the use of a thermal material between a semiconductor device and a heat sink so that heat generated by the semiconductor can be removed.
Typically, silicone or urethane binders filled with one or more thermally conductive materials are used as the thermal interface. One such product is commercially known as CHO-THERM.RTM. thermally conductive materials, available from Chomerics, Inc.
In placing the thermally conductive material between the heatsource and the heatsink, care must be taken to ensure that no air becomes trapped between the thermally conductive material and the adjacent substrate. Air is a notoriously poor conductor of heat and its presence reduces the ability of the thermally conductive material to transport heat from its source to its sink. This can lead to an overheating of the heat source. Moreover, the overheating will be localized at the spot where the air is trapped, causing the overheating to be concentrated in a small area making it more intense and its effects more devastating, especially to electronic components.
Moreover to ensure that air is not trapped, such thermally conductive interface materials are applied individually by hand. This is a labor extensive, slow process. Additionally, the assembly can only be done with fairly large components which contain a measn for attaching them to the heat source, such as screws, rivets, etc.
Therefore, there is a need for a thermally conductive material that will eliminate the problem of air becoming trapped between the thermal material and the adjacent substrate and a method for forming a heat transferring assembly.
Moreover, there is a need for a process that will speed up the assembly of thermally conductive electroinc packages and for products that will provide thermal conductivity to smaller electronic assemblies.

Thermally conductive electrical assembly


A dual-mass flywheel has a first mass body and a second mass body which can rotate relative to one another by way of a damping device disposed between the first mass body and the second mass body. The damping device includes, running in the shape of an arc, at least one helical compression spring, which introduces spring force into the mass bodies via contact surfaces formed on the first mass body and the second mass body. The helical compression spring is guided in the radial direction by a wall formed by a mass body. At least one friction-reducing sliding component in the form of a wire cushion body is provided between the wall and the helical compression spring.

The present invention relates to a dual-mass flywheel having a first mass body and a second mass body which can rotate relative to one another by way of a damping device disposed between the first mass body and the second mass body. The damping device includes, running in the shape of an arc, at least one helical compression spring which introduces spring force into the mass bodies via contact surfaces formed on the first mass body and the second mass body. The helical compression spring is guided in the radial direction by a wall formed by a mass body. Between the wall and the helical compression spring at least one friction-reducing sliding component is provided.
A dual-mass flywheel according to this type can be used in the drive train of a motor vehicle. The drive train includes a motor, transmission, and vehicle so that the excitation of vibration by the motor also acts on the other components of the drive. In order to improve the vibration behavior and thus also the noise behavior of the drive train, dual-mass flywheels are used, which include a primary mass or a first mass body which, for example, can be rigidly connected to the crankshaft of the motor and a secondary mass or a second mass body which can rotate relative to the first mass body. The first and second mass bodies are connected to one another in a rotationally elastic manner via a damping device.
A dual-mass flywheel according to this type has been disclosed, e.g., based on DE 10 2007 003 047 A1. The mass body of this known dual-mass flywheel is supported via helical compression springs and, in fact, via contact surfaces provided on the mass bodies.
This known dual-mass flywheel is formed so that the sheet metal parts forming the receiving chamber for the helical compression springs are formed with low wall thicknesses to reduce weight and the helical compression springs are supported against the sheet metal parts via sliding shoes. The introduction of compressive forces into the sheet metal parts is done via impact components formed in the manner of a flange. Via the sliding shoes between the helical compression springs and the sheet metal parts, the result is supposed to be achieved that the spring ends do not dig through the sheet metal parts.
In other words, this means that additional parts are present in the form of the sliding shoes. The additional parts are intended to ensure that the friction between the helical compression spring and a wall guiding the helical compression spring is reduced. The helical compression springs are namely massive parts which at high angular speed of the dual-mass flywheel are pressed against the wall with great centrifugal force.
Due to the great centrifugal force, lubricants present in the channel guiding the helical compression spring are pressed out of the contact area between the helical compression spring and the wall, which leads to the result that the friction between the wall and the helical compression spring increases so much that the helical compression spring behaves as a rigid body element and thus the desired acoustic decoupling between the drive motor and the drive train of the vehicle is no longer present.
The sliding shoes present in the known dual-mass flywheel described above are made of a plastic material, which due to the relative movement between the helical compression spring and the wall is, so to speak, rubbed to pieces and thus can no longer exercise its function of reducing friction. The plurality of sliding shoes present in the known dual-mass flywheel also leads to a significant and undesirable increase in cost of the dual-mass flywheel.
In view of the above, there is therefore needed a dual-mass flywheel of the above type such that its function of reducing friction between the helical compression spring and the wall is maintained even for a longer operating period and thus the acoustic decoupling between the motor and the drive train is retained.
This need is met according to the invention by providing a dual-mass flywheel with a first mass body and a second mass body which can rotate relative to one another via a damping device disposed between the first mass body and the second mass body. The damping device includes, extending in the shape of an arc (curved), at least one helical compression spring which introduces spring force into the mass bodies via contact surfaces formed on the first mass body and the second mass body. The helical compression spring is guided in the radial direction by a wall formed by one mass body. Between the wall and the helical compression spring, at least one friction-reducing sliding component is provided, where a wire cushion body is provided as a sliding component.
With this dual-mass flywheel, a configuration is created which is substantially more stress-resistant than the plastic sliding shoes of the known dual-mass flywheels described above which are made of a plastic material. The helical compression spring under centrifugal force no longer directly abuts the wall but rather with the interposition of a wire cushion body, at least in sections along the longitudinal direction of the helical compression spring.
The wire cushion body has a spring action which, depending on in which direction it is packed more or less densely, can be configured differently. Thus, the wire cushion body can be formed to be elastic in the longitudinal direction and/or in the radial direction of the helical compression spring. The wire cushion body has cavities in which lubricants in the form of grease or the like can be embedded.
Due to the spring action of the wire cushion body it is, under the load of centrifugal force on the helical compression spring, in fact compressed in the radial direction relative to the longitudinal axis of the dual-mass flywheel but, with an appropriately chosen rigidity of the wire cushion body, the cavities are preserved in the radial direction and thus also the lubricants present between the wire cushion body and the wall of the dual-mass flywheel. Due to the laminar abutment of the wire cushion body against the wall, the contact pressure per unit area between the wire cushion body and the wall is significantly less than the contact pressure per unit area between the coils of the helical compression spring and the wall when the helical compression spring abuts the wall directly.
Care must also be taken when forming the wire cushion body that lubricants are embedded in the matrix of the wire cushion body which, even at a high angular speed of the dual-mass flywheel, remain present in the area of contact between the wire cushion body and the wall and thus retain their friction-reducing action even for longer periods of operation of the dual-mass flywheel according to the invention.
The wire cushion body can, for example, be a body formed of knitted wire fabric, where the body is compressed in a mold by a pressing process. Along with this, the wire cushion body can also be formed by a wound body which is wound in layers on a shaft or a spool. Before the wire in this case is subjected to the winding process, it is subjected, at least within partial segments or sections along its length, to a preliminary deformation, which leads to the result that the individual wire sections within the layers and also between the layers intertangle with one another significantly better and more intensively than is the case with wire which has not been deformed. This leads to a wire cushion body which is significantly more stress-resistant than a wire cushion body made of wire which has not been deformed.
In connection with this, it is provided according to an extension of the invention that the wire cushion body is formed to be elastic in the longitudinal direction and/or in the radial direction of the helical compression spring. Depending on how densely the wire cushion body is packed in the radial direction, it is possible to achieve rigidity of the wire cushion body in its radial direction. With this, for example, a configuration is possible in which the relative movement between the spring and the wire cushion body is greater than the relative movement between the wire cushion body and the wall of the dual-mass flywheel.
The wire cushion body can also be formed to be elastic in the longitudinal direction of the helical compression spring so that in a spring movement of the helical compression spring, e.g., in the radially inward-lying area of contact between the helical compression spring and the wire cushion body, the spring movement is reproduced, taken up so to speak, by the wire cushion body in the radially outward-lying area between the wire cushion body and the wall of the dual-mass flywheel, but a relative movement no longer takes place or takes place only to a slight degree.
In such a configuration, care is therefore taken that the helical compression springs can move almost freely and thus hardening of the helical compression springs is avoided and thus the desired acoustic decoupling is retained.
According to one embodiment of the present invention, it is provided that the wire cushion body is disposed as an elongated insert between at least one partial area of the length of the helical compression spring and the wall. In other words, this means that it can even be sufficient if the wire cushion body only separates partial areas of the length of the helical compression spring and the wall from one another. However, an arrangement of the wire cushion body as an insert between the helical compression spring and the wall and along the entire length of the helical compression spring running in the shape of an arc is provided according to the invention.
According to a different embodiment of the present invention, it is provided that the wire cushion body is formed as a mantle which envelopes the helical compression spring, at least along a partial area of its length. With this the helical compression spring, so to speak, plugs into the wire cushion body formed as a mantle and in fact at least at partial areas of its length. However, a complete envelopment of the helical compression spring along its entire length by the wire cushion body in the form of a mantle is also provided according to the present invention.
According to an extension of the invention, it is provided that the wire cushion body includes, in the area of one end facing a contact surface, a wire cushion counterbearing body formed as one piece with the wire cushion body or disposed thereon. The wire cushion counterbearing body is provided between one spring end of the helical compression spring and the contact surface. An introduction of spring force into the contact surface takes place via the wire cushion counterbearing body.
The wire cushion counterbearing body can therefore, for example, be inlaid at the end of the wire cushion body or also can be formed together with the wire cushion body during the manufacture of the wire cushion body. The wire cushion counterbearing body then leads to a reduction of wear of the contact surface on the dual-mass flywheel and thus to an extension of the service lifetime of the dual-mass flywheel.
It is also possible in this way to reduce the contact surface since the wire cushion body, unlike the spring end of the helical compression spring, lies over the surface of the contact surface and thus the contact pressure per unit area of the contact surface is reduced. This can also be utilized to reduce the contact surface, whereby a reduction of the dimensions of the components is made possible and thus an advantage in weight is achieved.
The wire cushion counterbearing body can also be provided at a distance from the spring end or from the contact surface so that initially a relatively free mobility of the helical compression springs is achieved and only after a predetermined excursion of the spring is contact between the spring end of the helical compression spring and the wire cushion counterbearing body reached. In general, an improved insulation against vibration can be achieved with the wire cushion counterbearing body between the spring end and the contact surface and thus an improvement of the acoustic behavior of the dual-mass flywheel according to the invention with respect to the known dual-mass flywheel.
According to an extension of the invention, it is provided that the wire cushion body is formed by at least two wire cushion segment bodies which are disposed functionally in a row or in parallel.
Through the connection in a row a soft configuration of the wire cushion body is achieved while through the connection in parallel a wire cushion body can be formed which has a spring characteristic with greater rigidity and thus a harder wire cushion body, depending on which configuration is desired for a given application.
According to an extension of the invention, it is also provided that the wire cushion body is formed along its direction of action with a linear or progressively or regressively variable spring rate. Such a configuration with a variable spring rate can, for example, be achieved in the manufacture of the wire cushion body by forming the wire cushion body with a predetermined number of cavities, which leads to the number of cavities corresponding to a softer or harder configuration. A progressive spring rate can, for example, be of advantage when, depending on the spring excursion of the wire cushion body, flexible behavior is desired initially in order to achieve, after a predetermined spring excursion, an increase of the spring characteristic and thus a harder behavior of the wire cushion body.
The wire cushion body can be formed of metallic, ceramic, or vitreous materials, of polymers, or of mixtures thereof. Also, the wire cushion body can be formed of metallic materials of different hardness. With this a configuration is made possible in which the wire cushion body has a first contact area of a soft metallic material which is then followed by a second contact area of a harder metallic material, whereby, for example, a configuration deviating from a linear spring rate is possible.
The wire cushion body provided according to the invention in the dual-mass flywheel can have cavities in which a lubricant is embedded. It can also have embedded solid lubricant parts, each of which provides that the friction between the wire cushion body and the wall of the dual-mass flywheel remains low and thus hardening of the helical compression springs is prevented.
Other objects, advantages and novel features of the present invention will become apparent from the following detailed description of one or more preferred embodiments when considered in conjunction with the accompanying drawing.

Dual-mass flywheel having radially arranged wire cushion bodies

Bayerische Motoren Werke Aktiengesellschaft


A video decoding system examines a block of DCT coefficients prior to computation of an inverse discrete cosine transform (IDCT) to determine the number of nonzero coefficients. A plurality of IDCT engines are available in the video system including an IDCT engine utilizing fewer computations for a sparse picture and an IDCT engine utilizing fewer computations for a nonsparse picture. The video decoding system selects an IDCT engine to minimize the number of computations performed and to thereby reduce the computational burden of IDCT transformation.

Video information requires a large amount of storage space, therefore video information is generally compressed before it is stored. Accordingly, to display compressed video information which is stored, for example, on a compact disk read only memory (CD ROM), the compressed video information is decompressed to furnish decompressed video information. The decompressed video information is then communicated in a bit stream to a display. The bit stream of video information is generally stored in a plurality of memory storage locations corresponding to pixel locations on a display. The stored video information is generally referred to as a bit map. The video information representing a single screen of information on a display is called a picture. A goal of many video systems is to quickly and efficiently decode compressed video information to enable a motion video capability.
Standardization of recording media, devices and various aspects of data handling, such as video compression, is highly desirable for continued growth of this technology and its applications. One compression standard which has attained wide spread use for compressing and decompressing video information is the moving pictures expert group (MPEG) standard for video encoding and decoding. The MPEG standard is defined in International Standard ISO/IEC 11172-1, "Information Technology--Coding of moving pictures and associated audio for digital storage media at up to about 1.5 Mbit/s", Parts 1, 2 and 3, First edition Aug. 1, 1993 which is hereby incorporated by reference in its entirety.
Pictures within the MPEG standard are divided into 16.times.16 pixel macroblocks. Each macroblock includes six 8.times.8 blocks: four luminance (Y) blocks, one chrominance red (Cr) block and one chrominance blue (Cb) block. The luminance blocks correspond to sets of 8.times.8 pixels on a display and control the brightness of respective pixels. The chrominance blocks to a large extent control the colors for sets of four pixels. For each set of four pixels on the display, there is a single Cr characteristic and a single Cb characteristic.
For example, referring to FIG. 1, labeled prior art, a picture presented by a typical display includes 240 lines of video information in which each line has 352 pixels. Accordingly, a picture includes 240.times.352=84,480 pixel locations. Under the MPEG standard, this picture of video includes 44 by 30 luminance blocks or 1320 blocks of luminance video information. Additionally, because each macroblock of information also includes two corresponding chrominance blocks, each picture of video information also includes 330 Cr blocks and 330 Cb blocks. Accordingly, each picture of video information requires 126,720 pixels or a total of 1,013,760 bits of bit mapped storage space for presentation on a display.
There are three types of pictures of video information which are defined by the MPEG standard, intra-pictures (I picture), forward predicted pictures (P picture) and bi-predicted pictures (B picture).
An I picture is encoded as a single image having no reference to any past or future picture. Each block of an I picture is encoded independently. Accordingly, when decoding an I picture, no motion processing is necessary. However, for the reasons discussed below, it is necessary to store and access I pictures for use in decoding other types of pictures.
A P picture is encoded relative to a past reference picture. A reference picture is a P or I picture. The past reference picture is the closest preceding reference picture. Each macroblock in a P picture can be encoded either as an I macroblock or as a P macroblock. A P macroblock is stored as a translated 16.times.16 area of a past reference picture plus an error term. To specify the location of the P macroblock, a motion vector (i.e., an indication of the relative position of the macroblock in the current picture to the position of the translated area in the past reference picture) is also encoded. When decoding a P macroblock, the 16.times.16 area from the reference picture is offset according to a motion vector. The decoding function accordingly includes motion compensation, which is performed on a macroblock, in combination with error (IDCT) terms, which are defined on a block by block basis.
A B picture is encoded relative to the past reference picture and a future reference picture. The future reference picture is the closest proceeding reference picture. Accordingly, the decoding of a B picture is similar to that of an P picture with the exception that a B picture motion vector may refer to areas in the future of the reference picture. For macroblocks that use both past and future reference pictures, the two 16.times.16 areas are averaged. The macroblocks from the reference pictures are offset according to motion vectors.
Pictures are coded using a discrete cosine transform (DCT) coding scheme which transforms pixels (or error terms) into a set of coefficients corresponding to amplitudes of specific cosine basis functions. The discrete cosine transform is applied to image compression to decorrelate picture data prior to quantization. The DCT coefficients are further coded using variable length coding. Variable length coding (VLC) is a statistical coding technique that assigns codewords to values to be encoded. Values of high frequency of occurrence are assigned short codewords, and those of infrequent occurrence are assigned long codewords. On the average, the more frequent shorter codewords dominate so that the code string is shorter than the original data.
For a video system to provide a motion video capability, compressed video information must be quickly and efficiently decoded. One aspect of the decoding process is inverse discrete cosine transformation (IDCT). A second aspect is a motion compensation operation. Both the IDCT operation and the motion compensation operation are computationally intensive operations. Over a wide range of processor capabilities and image characteristics, a condition sometimes arises in which the picture decoding operation overburdens a video system. Under this condition, video frames are commonly dropped or a lag in motion video results. A technique for providing such highly efficient inverse discrete transformation and decoding is necessary.

Method and apparatus for improved video decompression by selection of IDCT method based on image characteristics


A novel protein tyrosine phosphatase designated PTP-S31 and its subfamily are identified, as are nucleic acid molecule coding therefor. Included in this;family are PTP-S31 proteins or glycoproteins having one, two, or three identified amino acid changes in previously defined consensus sequences in the catalytic phosphatase domains of known protein tyrosine phosphatases. The PTP-S31 proteins or glycoproteins may be produced by recombinant means. Antibodies to PTP-S31 proteins or glycoproteins and nucleic acid constructs coding therefor, and methods for screening molecules which can bind to PTP-S31 proteins or glycoproteins and inhibit or stimulate their enzymatic activity, are provided.

The invention, in the fields of biochemistry and cell and molecular biology, relates to a novel protein tyrosine phosphatase (PTPase or PTP) protein or glycoprotein, termed PTP-S31, the use of such molecule in pharmaceutical preparations, and pharmaceutical compositions comprising PTP-S31 or functional derivatives thereof. This invention is also directed to nucleic acid molecules encoding the PTP-S31 protein or functional derivative, recombinant expression vectors carrying the nucleic acid molecules, cells containing the recombinant expression vectors, methods for production and identification of PTP-S31 or the DNA coding therefor, antibodies specific for PTP-S31, and methods for screening compounds capable of binding to and inhibiting or stimulating protein tyrosine phosphatase enzymatic activity of PTP-S31.
Phosphorylation of proteins is a fundamental mechanism for regulating diverse cellular processes. While the majority of protein phosphorylation occurs at serine and threonine residues, phosphorylation at tyrosine residues is attracting a great deal of interest since the discovery that many oncogene products and growth factor receptors possess intrinsic protein tyrosine kinase activity. The importance of protein tyrosine phosphorylation in growth factor signal transduction, cell cycle progression and neoplastic transformation is now well established (Hunter et al., Ann. Rev. Biochem. 54:987-930 (1985), Ullrich et al., Cell 61 :203-212 (1990), Nurse, Nature 344:503-508 (1990), Cantley et al., Cell 64:281-302 (1991)).
Biochemical studies have shown that phosphorylation on tyrosine residues of a variety of cellular proteins is a dynamic process involving competing phosphorylation and dephosphorylation reactions. The regulation of protein tyrosine phosphorylation is mediated by the reciprocal actions of protein tyrosine kinases (PTKases or PTKS) and protein tyrosine phosphatases (PTPs). The tyrosine phosphorylation reactions are catalyzed by PTKs. Tyrosine phosphorylated proteins can be specifically is dephosphorylated through the action of PTPS. The level of protein tyrosine phosphorylation of intracellular substances is determined by the balance of PTK and PTP activities. (Hunter, T., Cell 58:1013-1016 (1989)).
2.1. PTKs
The protein tyrosine kinases (PTKs; ATP:protein-tyrosine O-phosphotransferase, EC 22.214.171.124) are a large family of proteins that includes many growth factor receptors and potential oncogenes. (Hanks et al., Science 241:42-52 (1988)). Many PTKs have been linked to initial signals required for induction or the cell cycle (Weaver et al., Mol. and Cell. Biol. 11(9):4415-4422 (1991)). PTKs comprise a discrete family of enzymes having common ancestry with, but major differences from, serine/threonine-specific protein kinases (Hanks et al., supra). The mechanisms leading to changes in activity of PTKs are best understood in the case of receptor-type PTKs having a transmembrane topology (Ullrich et al. (1990) supra). The binding of specific ligands to the extracellular domain of members of receptor-type PTKs is thought to induce their oligomerization leading to an increase in tyrosine kinase activity and activation of the signal transduction pathways (Ullrich et al., (1990) supra). Deregulation of kinase activity through mutation or overexpression is a well-established mechanism for cell transformation (Hunter et al., (1985) supra; Ullrich et al., (1990) supra).
2.2. PTPS
The protein phosphatases are composed of at least two separate and distinct families (Hunter, T.(1989) supra) the protein serine/threonine phosphatases and the protein tyrosine phosphatases (PTPs; protein-tyrosine-phosphate phosphohydrolase, EC 3.13.48)). The PTPs are a family of proteins that have been classified into two subgroups. The first subgroup is made up of the low molecular weight, intracellular enzymes that contain a single conserved catalytic phosphatase domain. All known intracellular type PTPS contain a single conserved catalytic phosphatase domain.; Examples of the first group of PTPs include (1) placental PTP 1B (Charbonneau et al., Proc. Natl. Acad. Sci. USA 86:5252-5256 (1989); Chernoff et al., Proc. Natl. Acad. Sci. USA 87:2735-2789 (1990)), (2) T-cell PTP (Cool et al. Proc. Natl. Acad. Sci. USA 86:5257-5261 (1989)), (3) rat brain PTP (Guan et al., Proc. Natl. Acad. Sci. USA 87:1501-1502 (1990)), (4) neuronal phosphatase (STEP) (Lombroso et al., Proc. Natl. Acad. Sci. USA 88:7242-7246 (1991)), and (5) cytoplasmic phosphatases that contain a region of homology to cytoskeletal proteins (Guet al., Proc. Natl. Acad. Sci. USA 88:5867-57871 (1991); Yang et al., Proc. Natl. Acad. Sci. USA 88:5949-5953 (1991)).
The second subgroup is made up of the high molecular weight, receptor-linked PTPs, termed RPTPs. RPTPs consist of (a) an intracellular catalytic region, (b) a single transmembrane segment, and (c) a putative ligand-binding extracellular domain. The structures and sizes of the putative ligand-binding extracellular xe2x80x9creqeptorxe2x80x9d domains of RPTPs are quite divergent. In contrast, the intracellular catalytic regions of RPTPs are highly homologous. All RPTPs have two tandemly duplicated catalytic phosphatase homology domains, with the prominent exception of an RPTP termed HPTPxcex2, which has only one catalytic phosphatase domain. (Tsai et al., J. Biol. Chem. 266:10534-10543 (1991)).
One example of RPTPs is a family of proteins termed leukocyte common antigens (LCA) (Ralph, S. J., EMBO J. 6:1251-1257 (1987)) which are high molecular weight glycoproteins expressed on the surface of all leukocytes and their hemopoietic progenitors (Thomas, Ann. Rev. Immunol. 7:339-369 (1989)). A remarkable degree of similarity exists in the sequences of LCA from several species (Charbonneau et al., Proc. Natl. Acad. Sci. USA 85:7182-7186 (1988)). LCA has been referred to in the literature by different names, including T200 (Trowbridge et al., Eur. J. Immunol. 6:557-562 (1962)), B220 for the B lymphocyte form (Coffman et al., Nature 289:681-683 (1981)), the mouse allotypic marker Ly-5 (Komuro et al., Immunogenetics 1:452-456 (1975)), and more recently CD45 (Cobbold et al., Leucocyte Typing III, A. J. McMichael et al., eds., pp. 788-803 (1987)).
CD45 appears to play a critical role in T cell activation (reviewed in Weiss A., Ann. Rev. Genet. 25:487-510 (1991)). For example, T-cell clones that were chemically mutagenized and selected for their failure to express CD45 had impaired responses to T-cell receptor stimuli (Weaver et al., supra). These T-cell clones were functionally defective in their responses to signals transmitted through the T cell antigen receptor, including cytolysis of appropriate targets, proliferation, and lymphokine production (Weaver et al., supra). Other studies indicate that the PTP activity of CD45 plays a role in the activation of pp 561ck, a lymphocyte-specific PTK (Mustelin et al., Proc. Natl. Acad. Sci. USA 86:6302-6306 (1989); ostergaard et al., Proc. Natl. Acad. Sci. USA 86:8959-8963 (1989)). These authors hypothesized that the phosphatase activity of CD45 activates pp56kk by dephosphorylation of a C-terminal tyrosine residue, which may, in turn, be related to T-cell activation.
Another other example of an RPTP is the leukocyte common antigen related molecule (LAR), initially identified as a homologue of LCA (Streuli et al., J. Exp. Med. 168:1523-1530 (1988)). Although the intracellular catalytic region of the LAR molecule contains two catalytic phosphatase homology domains (domain I and domain II), mutational analyses suggested that only domain I had catalytic phosphatase activity, whereas domain II was enzymatically inactive (Streuli et al., EMBO J. 9(8):2399-2407 (1990)). Chemically induced LAR mutants having tyrosine at amino acid position 1379 changed to a phenylalanine were temperature-sensitive (Tsai et al., J. Biol. Chem. 266(16):10534-10543 (1991)).
A recently cloned mouse RPTP, designated mRPTPxcexc, was found to have an extracellular domain that shared some structural motifs with LAR. (Gebbink, M. F. B. G. et al., FEBS Lett. 290:123-130 (1991). These authors also cloned a human homologue of RPTPxcexc and localized the gene on human chromosome 18.
Two Drosophila PTPs, termed DLAR and DPTP, have been predicted based on the sequences of cDNA clones (Streuli et al., Proc. Natl. Acad. Sci. USA 86:8698-8702 (1989)). cDNAs coding for another Drosophila RPTP, termed DPTP 99A, have been cloned and characterized (Hariharan et al., Proc. Natl. Acad. Sci. USA 88:11266-11270 (1991)).
Other examples of RPTPs include RPTP-xcex1, xcex2, xcex3, and xcex6 (Krueger et al., EMBO J. 9:3241-3252 (1990), Sap et al. Proc. Natl. Acad. Sci. USA 67;;6112-6116 (1990), Kaplan et al., Proc. Natl. Acad. Sci. USA 87:7000-7004 (1990), Jirik et al., FEBS Lett. 273:239-242 (1990), Mathews et al., Proc. Natl. Acad. sci. USA 87:4444-4448 (1990), Ohagi et al., Nucl. Acids Res. 18:7159 (1990)). Schlessinger, PCT Publication WO 92/01050 (Jan. 23, 1992) disclosed human RPTP-xcex1, xcex2 and xcex3, and described the nature of the structural homologies among the conserved domains of these three RPTPs and other members of this protein family. The murine RPTP-xcex1 has 794 amino acids, whereas the human RPTP-xcex1 has 802 amino acids. RPTP-xcex1 has an intracellular domain homologous to the catalytic domains of other tyrosine phosphatases. The 142 amino acid extracellular domain (including signal peptide of RPTP-xcex1) has a high serine and threonine content (32%) and 8 potential N-glycosylation sites. cDNA clones have been produced that code for the RPTP-xcex1, and RPTP-xcex1 has been expressed from eukaryotic hosts. Northern analysis was used to identify the natural expression of RPTP-xcex1 in various cells and tissues. A polyclonal antibody to RPTP-xcex1, produced by immunization with a synthetic peptide of RPTP-xcex1, identifies a 130 kDa protein in cells transfected with a cDNA clone encoding a portion of RPTP-xcex1.
Another RPTP, HePTP (Jirik et al., FASEB J. 4:82082 (1990) Abstract 2253) was discovered by screening a cDNA library derived from a hepatoblastoma cell line, HepG2, with a probe encoding the two PTP domains of LCA. The HePTP gene appeared to be expressed in a variety of human and murine cell lines and tissues.
Since the initial purification, sequencing, and cloning of a PTP, additional potential PTPs have been identified at a rapid pace. The number of different PTPs that have been identified is increasing steadily, leading to speculations that this family may be as large as the PTK family (Hunter (1989) supra).
Conserved amino acid sequences designated xe2x80x9cconsensus sequencesxe2x80x9d have been identified in the catalytic domains of known PTPS (Krueger et al., EMBO J. 9:3241-3252 (1990) and Yi et al., Mol. Cell. Biol. 12:836-846 (1992), which are incorporated herein by reference). Yi et al. aligned the catalytic phosphatase domain sequences of the following PTPs: LCA, PTP1B, TCPTP, LAR, DLAR, and HPTPxcex1, HPTPxcex2, and HPTPxcex3. This alignment includes the following xe2x80x9cconsensus sequencesxe2x80x9d (Yi et al., supra, FIG. 2(A)):
1. K C X X Y W P [SEQ ID NO:1]
2. H C S X G X G R X G [SEQ ID NO:2]
Krueger et al., aligned the catalytic phosphatase domain sequences of PTP1B, TCPTP, LAR, LCA, HPTPxcex1, xcex2, 8, xcex5 and xcex6, and DLAR and DPTP. This alignment includes the following xe2x80x9cconsensus sequences: (Krueger et al., supra, FIG. 7):
1. K C X X Y W P [SEQ ID NO:1]
2. H C S X G X G R X G [SEQ ID NO:2]
It is becoming clear that dephosphorylation of tyrosine residues can by itself function as an important regulatory mechanism. Dephosphorylation of a C-terminal tyrosine residue has been shown to activate tyrosine kinase activity in the src family of tyrosine kinases (Hunter, T. Cell 49:1-4 (1987)). Tyrosine dephosphorylation has been suggested to be an obligatory step in the mitotic activation of the maturation-promoting factor (MPF) kinase (Morla et al., Cell 58:193-203 (1989)). These observations point out the need in the art for understanding the mechanisms that regulate tyrosine phosphatase activity.
It is clear that further analysis of structure-function relationships among PTPs are needed to gain important understanding of the mechanisms of signal transduction, cell cycle progression and cell growth, and neoplastic transformation. Such understanding will also provide useful agents for regulating these processes and for treating diseases associated with their dysregulation.
The inventors describe herein the identification of a novel PTP, termed PTP S31. This novel PTP differs significantly in structure from previously reported PTPs. Further, several variants of this PTP have been identified. The present invention thus provides a PTP-S31 protein or glycoprotein which is a PTP or contains structural features known to be found in PTPs, as well as variants thereof.
When a PTP-S31 protein or glycoprotein of the present invention is one which occurs in nature, it is substantially free of other proteins or glycoproteins with which it is natively associated. A substantially pure PTP-S31 protein or glycoprotein of the invention may be produced by biochemical purification, by chemical means or by recombinant means in a prokaryotic or eukaryotic host, and is provided substantially free of other proteins with which it is natively associated. The PTP-S31 may have modified amino acids.
The invention is further directed to:
(1) a fragment of a PTP-S31 protein or glycoprotein;
(2) a PTP-S31 protein or glycoprotein having additional amino acids;
(3) a PTP-S31 protein or glycoprotein having substituted amino acids; and
(4) a PTP-S31 protein or glycoprotein having any combination of deleted, additional, or substituted amino acids.
In all cases the modified PTP-S31 protein or glycoprotein, or fragment thereof, possesses the desired biological activity.
The invention is further directed to a nucleic acid molecule comprising a nucleotide sequence encoding a PTP-S31 protein according to the invention. The nucleic acid molecule may be cDNA, genomic DNA or RNA. The invention is further directed to a nucleic acid construct in the form of an expression vehicle. Also provided are prokaryotic and eukaryotic host cells containing the expression vehicle.
Also included in the present invention is a process for preparing a PTP-S31 protein or glycoprotein of this invention, comprising:
(a) culturing a host capable of expressing a PTP-S31 protein or glycoprotein under culturing conditions,
(b) expressing the PTP-S31 protein or glycoprotein; and
(c) recovering the PTP-S31 protein or glycoprotein from the culture.
The invention is also directed to a polyclonal, monoclonal or chimeric antibody specific for a PTP-S31 protein or glycoprotein or for an epitope of a PTP-S31 protein or glycoprotein.
The invention is further directed to a method for detecting the presence, or measuring the quantity, of a PTP-S31 protein or glycoprotein in a sample, preferably a cell or a biological sample from a subject, comprising:
(a) contacting the sample, such as a preparation of cells or an extract thereof, with an antibody specific for an epitope of a PTP-S31 protein or glycoprotein; and
(b) detecting the binding of the antibody to sample material, or measuring the quantity of antibody bound,
thereby detecting the presence or measuring the quantity of the PTP-S31 protein or glycoprotein.
The invention is also directed to a method for detecting the presence of a nucleic acid encoding a normal or mutant PTP-S31 protein or glycoprotein in a sample, preferably a cell or biological sample of a subject, comprising:
(a) contacting the sample, such as a cell or an extract thereof, with an oligonucleotide probe encoding at least a portion of a normal or mutant PTP-S31 protein or glycoprotein under hybridizing conditions; and
(b) measuring the hybridization of the probe to nucleic acid of the cell,
thereby detecting the presence of the nucleic acid. The nucleic acid of the sample can be selectively amplified, for example, by using the polymerase chain reaction, prior to assay.
The present invention is also directed to a method for identifying or isolating in a sample, preferably a chemical or biological sample, a compound capable of binding to a PTP-S31 protein or glycoprotein, the method comprising:
(a) attaching a PTP-S31 protein or glycoprotein or the compound-binding portion thereof to a solid phase matrix or carrier;
(b) contacting the sample with the PTP-S31 bound to the solid phase matrix, allowing any compound to bind to said PTP-S31, and washing away any unbound material;
(c) detecting the presence of the compound bound to the solid phase.
For purposes of isolation, the bound compound is subjected to the additional step of (d) eluting the bound compound, thereby isolating the compound.
The invention includes a method for identifying an agent molecule capable of stimulating or inhibiting the enzymatic activity of PTP-S31, comprising:
(a) contacting the agent with a PTP-S31 protein or glycoprotein, or a fragment thereof, which PTP-S31 may be in pure form, in a membrane preparation, or in a whole live or fixed cell;
(b) incubating the mixture of step (a) for a sufficient interval;
(c) measuring the enzymatic activity of the PTP-S31;
(d) comparing the enzymatic activity to that of the PTP-S31 protein or glycoprotein incubated without the agent,
thereby determining whether the agent stimulates or inhibits the enzymatic activity.
In addition, the present invention provides methods for identifying agonists or antagonists of PTP-S31 action based on the ability of such agents to modulate interactions between (a) PTP-S31 and its target molecules or (b) PTP-S31 and molecules which regulate its enzymatic activity. Compounds identified by such methods may be useful to treat ,diseases associated with PTP-S31 dysfunction or with disordered signal transduction.

PTP-S31: a novel protein tyrosine phosphatase

Max-Planck-Gesellschaft zur Forderung der Wissenschaften e.V.


The technology presented here reduces the number of audio ports associated with the mobile device by combining a plurality of audio ports into a single multipurpose audio apparatus. The multipurpose audio apparatus includes the functionality of multiple audio ports that have previously required separate audio ports, such as an external device audio port and an audio emitter audio port. When the external device is plugged in, the audio emitter powers off, and the sound is omitted through the external device. When the external device is not plugged in, the audio emitter emits the sound.

Mobile devices contain a plurality of different audio ports, which correspond to a plurality of devices, such as the audio emitter, the external device, etc. Each audio apparatus requires a dedicated opening formed in the mobile device casing, a dedicated circuit on the motherboard, a dedicated wiring between the hole in the mobile device casing and the circuit on the motherboard, etc. Each additional audio apparatus increases the cost of manufacturing the mobile device. Further, each additional audio apparatus increases the probability of a foreign substance, such as dust or water, getting inside the mobile device and disrupting the operation of the mobile device circuitry.


Pre-plating systems and related methods are disclosed. A pre-plating system includes a press, an infeed robot configured to deliver a structural member to the press, and an outfeed robot configured to remove the structural member from the press. The press is configured to secure a plate to the structural member while the structural member is held in position by at least one of the infeed robot or the outfeed robot. A pre-plating system includes a press, a transfer pedestal, a plate picking robot, and a press loading robot. The plate picking robot is configured to pick a plate from a container and position the plate on the transfer pedestal. The press loading robot is configured to transfer the plate to the press. The press is configured to press the plate into a structural member positioned within the press.

In constructing trusses, plates (e.g., nail plates) are used at joints between truss members to increase the strength of trusses. A plate may include teeth on a side of the plate that contacts the truss members to enable the plate to be coupled to the truss members by pressing the teeth into the truss members.

Systems and methods for pre-plating structural members


A one piece extruded differential side gear comprising internal splines which are used to connect to a drive shaft. The differential side gear includes outer circular gear teeth and defines a rectilinear blind hole in which an end portion of the drive shaft is received. The circular gear teeth and the blind hole are coaxially oriented along an axis of the differential side gear.

1. Field of the Invention
The present invention relates to a differential side gear, as well as to a method for producing such a side gear.
2. Brief Description of the Related Art
Within the meaning which is understood here, the shell of a differential is the rigid structure in which are mounted the side and pinion gears of this differential. In operation, it receives the movement that the differential has for its function to distribute between drive shafts, and it rotates on itself.
In the majority of automotive vehicles, the power of the drive motor is transmitted to the driving wheels via a gear box and a differential. It is known to mount the differential inside the gear box, and to ensure that the shell of this differential does not completely envelop the side and pinion gears, the expression "lantern wheel differential" being commonly employed to designate this type of differential. Consequently, like the gears of the gear box, the differential and its side and pinion gears dip in oil that is contained in the gear box.
In order to avoid the gear box losing oil, each side gear may be mounted, by means of a tight bearing, in a wall of the casing. In that case, it is important that the side gears are also tight. An axial passage for a drive shaft opens at the two ends of each of the side gears, so that these gears are able to be traversed on either side by a pin that is used to remove material so as to form internal splines for connection of the drive shaft. Consequently, a closure wall is mounted at one end of the passage of each side gear, whose tightness is thus ensured.
However, when side gears are produced in large quantities in this manner, there are always a few that are not sufficiently tight.

Differential side gear and the production method thereof

Ateliers Mecaniques et Industries Speciales