The present invention is based on the discovery of genetic polymorphisms that are associated with coronary stenosis. In particular, the present invention relates to nucleic acid molecules containing the polymorphisms, variant proteins encoded by such nucleic acid molecules, reagents for detecting the polymorphic nucleic acid molecules and proteins, and methods of using the nucleic acid and proteins as well as methods of using reagents for their detection.

Stenosis
Coronary stenosis is the narrowing of coronary arteries by obstructive atherosclerotic plaques. The coronary arteries supply oxygenated blood flow to the myocardium. Although mild and moderate coronary stenosis do not impede resting coronary flow, stenosis >30-45% starts to restrict maximal coronary flow. Severe coronary stenosis (>70% reduction in luminal diameter) causes stable angina (ischemic chest pain upon exertion). Significant stenosis contributes, along with plaque rupture and thrombus formation, coronary spasm, or inflammation/infection, to unstable angina as well as myocardial infarction. Together with arrhythmia, coronary stenosis is a major factor of sudden cardiac deaths, as evidenced by its presence in two or more major coronary arteries in 90% of adult sudden cardiac death victims.
Coronary stenosis is a prevalent disease. Each year in the United States, 440,000 new cases of stable angina and 150,000 new cases of unstable angina occur. This year, an estimated 1.1 million Americans will have a new or recurrent heart attack. These incidences result in over six million individuals in the U.S. living with stable or unstable angina pectoris, a debilitating condition, and over seven million individuals in the U.S. living with a history of myocardial infarction. Coronary stenosis is frequently a deadly disease. It is a major underlying cause of coronary heart disease (CHD), which is the single largest cause of death in the U.S. Over half a million coronary deaths, including 250,000 sudden cardiac deaths, occur each year in U.S. Coronary stenosis is also a costly disease. It is the major reason for 1.2 million cardiac catheterizations, 0.4 million angioplasties, and 0.6 million bypass surgeries, contributing to the estimated 110 billion dollar total costs of CHD in the U.S. for the year 2002. Still, these statistics underestimate the true prevalence of the disease since coronary stenosis often remains clinically asymptomatic for decades, and only becomes symptomatic when the disease has progressed to a severe, and sometime fatal, state.
There is therefore an unmet need in early diagnosis and prognosis of asymptomatic coronary stenosis. This need is particularly significant given that early diagnosis or prognosis results can significantly influence the course of disease by influencing treatment choices (for example, those with genetic risks can be treated to modify risk factors such as hypertension, diabetes, inactivity, dyslipidemia, etc.), thresholds (e.g., lipid levels used to trigger the use of lipid-lowering drugs), and goals (e.g., target blood pressure or lipid levels), and possibly enhance compliance.
Diagnosis of coronary stenosis currently starts by assessing if the risk profiles (e.g., hypertension, dyslipidemia, family history, diabetes, etc.) and symptoms (e.g., angina) of patients are consistent with coronary heart disease, followed most commonly by resting and exercise EKGs. However, risk assessments and EKGs are imperfect diagnostic tests for stenosis since they can be both insensitive (giving false negatives) and non-specific (giving false positives). Coronary arteriography is the definitive test for assessing the severity of coronary stenosis, however, it is not very sensitive in early detection of mild stenosis. It is also an invasive procedure with a small risk of death due to the catheterization procedure and the contrast dye. Because of this risk, it is typically only used at a time when coronary stenosis is considered likely from symptoms or other tests, which is hardly an ideal time to start intervention.
Coronary stenosis risk is presumed to have a strong genetic component. It is well known that several major risk factors of coronary disease are heritable, e.g. serum lipid levels (Perusse L. et. al., Arterioscler Thromb Vasc Biol (1997): 17(11) 3263-9) and obesity (Rice T. et. al., Int J Obes Relat Metab Disord (1997):21(11) 1024-31). Indeed, several known genetic defects are individually sufficient to cause elevated serum LDL-cholesterol (e.g., familial hypercholesterolemia) leading to premature coronary disease (Goldstein and Brown, Science 292 (2001): 1310-12). In addition, linkage studies in humans have replicated the findings of the link of several chromosomal regions (quantitative trait loci) to coronary heart disease and related diseases and risk factors (Pajukanta P. et. al., Am J Hum Genet 67 (2000):1481-93, Francke S. et. al., Human Molecular Genetics (2001): 10 (24) 2751-65). Finally, a family history of premature coronary disease is a significant factor in the risk assessment and diagnosis of coronary disease (Braunwald E., Zipes D. and Libby P., Heart Disease, 6th ed. W. B. Saunders Company, 2001, 28).
Although many risk factors for coronary stenosis have been identified, including age, diabetes, hypertension, high serum cholesterol, smoking, etc., and genetic factors play significant roles in several of these risk factors, significant genetic risk factors are likely to exist which have not been identified to date. In addition to the anecdotal coronary disease patients that exhibit few traditional risk factors, a study of multiple existing risk factors showed that only half of the "population-attributable risk" was attributable to known risk factors (Change M. et. al., J Clin Epidemiol (2001) 54 (6) 634-44). Therefore, the presently known risk factors are inadequate for predicting coronary stenosis risk in individuals. Given the magnitude of the disease, there is an urgent need for genetic markers that are predictive of coronary stenosis risk. Such genetic markers could increase the prognostic ability of existing risk assessment methods and complement current diagnostic methods such as exercise EKG, especially in early detection of disease when intervention is most effective and should ideally start.
SNPs
The genomes of all organisms undergo spontaneous mutation in the course of their continuing evolution, generating variant forms of progenitor genetic sequences (Gusella, Ann. Rev. Biochem. 55, 831-854 (1986)). A variant form may confer an evolutionary advantage or disadvantage relative to a progenitor form or may be neutral. In some instances, a variant form confers an evolutionary advantage to the species and is eventually incorporated into the DNA of many or most members of the species and effectively becomes the progenitor form. Additionally, the effects of a variant form may be both beneficial and detrimental, depending on the circumstances. For example, a heterozygous sickle cell mutation confers resistance to malaria, but a homozygous sickle cell mutation is usually lethal. In many cases, both progenitor and variant forms survive and co-exist in a species population. The coexistence of multiple forms of a genetic sequence gives rise to genetic polymorphisms, including SNPs.
Approximately 90% of all polymorphisms in the human genome are SNPs. SNPs are single base positions in DNA at which different alleles, or alternative nucleotides, exist in a population. The SNP position (interchangeably referred to herein as SNP, SNP site, or SNP locus) is usually preceded by and followed by highly conserved sequences of the allele (e.g., sequences that vary in less than 1/100 or 1/1000 members of the populations). An individual may be homozygous or heterozygous for an allele at each SNP position. A SNP can, in some instances, be referred to as a "cSNP" to denote that the nucleotide sequence containing the SNP is an amino acid coding sequence.
A SNP may arise from a substitution of one nucleotide for another at the polymorphic site. Substitutions can be transitions or transversions. A transition is the replacement of one purine nucleotide by another purine nucleotide, or one pyrimidine by another pyrimidine. A transversion is the replacement of a purine by a pyrimidine, or vice versa. A SNP may also be a single base insertion or deletion variant referred to as an "indel" (Weber et al., "Human diallelic insertion/deletion polymorphisms", Am J Hum Genet 2002 October; 71(4):854-62).
A synonymous codon change, or silent mutation/SNP (terms such as "SNP", "polymorphism", "mutation", "mutant", "variation", and "variant" are used herein interchangeably), is one that does not result in a change of amino acid due to the degeneracy of the genetic code. A substitution that changes a codon coding for one amino acid to a codon coding for a different amino acid (i.e., a non-synonymous codon change) is referred to as a missense mutation. A nonsense mutation results in a type of non-synonymous codon change in which a stop codon is formed, thereby leading to premature termination of a polypeptide chain and a truncated protein. A read-through mutation is another type of non-synonymous codon change that causes the destruction of a stop codon, thereby resulting in an extended polypeptide product. While SNPs can be bi-, tri-, or tetra-allelic, the vast majority of the SNPs are bi-allelic, and are thus often referred to as "bi-allelic markers", or "di-allelic markers".
As used herein, references to SNPs and SNP genotypes include individual SNPs and/or haplotypes, which are groups of SNPs that are generally inherited together. Haplotypes can have stronger correlations with diseases or other phenotypic effects compared with individual SNPs, and therefore may provide increased diagnostic accuracy in some cases (Stephens et al. Science 293, 489-493, 20 July 2001).
Causative SNPs are those SNPs that produce alterations in gene expression or in the expression, structure, and/or function of a gene product, and therefore are most predictive of a possible clinical phenotype. One such class includes SNPs falling within regions of genes encoding a polypeptide product, i.e. cSNPs. These SNPs may result in an alteration of the amino acid sequence of the polypeptide product (i.e., non-synonymous codon changes) and give rise to the expression of a defective or other variant protein. Furthermore, in the case of nonsense mutations, a SNP may lead to premature termination of a polypeptide product. Such variant products can result in a pathological condition, e.g., genetic disease. Examples of genes in which a SNP within a coding sequence causes a genetic disease include sickle cell anemia and cystic fibrosis.
Causative SNPs do not necessarily have to occur in coding regions; causative SNPs can occur in, for example, any genetic region that can ultimately affect the expression, structure, and/or activity of the protein encoded by a nucleic acid. Such genetic regions include, for example, those involved in transcription, such as SNPs in transcription factor binding domains, SNPs in promoter regions, in areas involved in transcript processing, such as SNPs at intron-exon boundaries that may cause defective splicing, or SNPs in mRNA processing signal sequences such as polyadenylation signal regions. Some SNPs that are not causative SNPs nevertheless are in close association with, and therefore segregate with, a disease-causing sequence. In this situation, the presence of a SNP correlates with the presence of, or predisposition to, or an increased risk in developing the disease. These SNPs, although not causative, are nonetheless also useful for diagnostics, disease predisposition screening, and other uses.
An association study of a SNP and a specific disorder involves determining the presence or frequency of the SNP allele in biological samples from individuals with the disorder of interest, such as stenosis, and comparing the information to that of controls (i.e., individuals who do not have the disorder; controls may be also referred to as "healthy" or "normal" individuals) who are preferably of similar age and race. The appropriate selection of patients and controls is important to the success of SNP association studies. Therefore, a pool of individuals with well-characterized phenotypes is extremely desirable.
A SNP may be screened in diseased tissue samples or any biological sample obtained from a diseased individual, and compared to control samples, and selected for its increased (or decreased) occurrence in a specific pathological condition, such as pathologies related to stenosis. Once a statistically significant association is established between one or more SNP(s) and a pathological condition (or other phenotype) of interest, then the region around the SNP can optionally be thoroughly screened to identify the causative genetic locus/sequence(s) (e.g., causative SNP/mutation, gene, regulatory, region, etc.) that influences the pathological condition or phenotype. Association studies may be conducted within the general population and are not limited to studies performed on related individuals in affected families (linkage studies).
Clinical trials have shown that patient response to treatment with pharmaceuticals is often heterogeneous. There is a continuing need to improve pharmaceutical agent design and therapy. In that regard, SNPs can be used to identify patients most suited to therapy with particular pharmaceutical agents (this is often termed "pharmacogenomics"). Similarly, SNPs can be used to exclude patients from certain treatment due to the patient's increased likelihood of developing toxic side effects or their likelihood of not responding to the treatment. Pharmacogenomics can also be used in pharmaceutical research to assist the drug development and selection process. (Linder et al. (1997), Clinical Chemistry, 43, 254; Marshall (1997), Nature Biotechnology, 15, 1249; International Patent Application WO 97/40462, Spectra Biomedical; and Schafer et al. (1998), Nature Biotechnology, 16, 3).

Genetic polymorphisms associated with coronary stenosis, methods of detection and uses thereof


According to the invention, the position sensor is characterized in that the correction means (3) are achieved by at least one saturated magnetic pole, a so-called stabilization pole (Ps), having a sign opposite to the sign of the irregular pole (Pi) which is also saturated, each stabilization pole (Ps) extending from one to the other edge of the magnetic ring, by being inserted in the irregular pole, so as to stabilize the magnetic signal delivered by the passage of the poles adjacent to the irregular pole, said magnetic signal delivered between the passage of the adjacent poles not passing through the zero value.

The object of the invention relates to the technical field of magnetic sensors including an encoder component moving close to a detection cell, and broadly speaking, adapted for locating at least one angular position.
The object of the invention more particularly relates to making a sensor, the encoder of which is equipped with a series of North poles and South poles mounted in an alternating way.
The object of the invention finds a particularly advantageous application in the automotive field where this sensor may for example be used within the framework of ignition functions.
In the preferred field above, it is known how to apply an adapted magnetic sensor for measuring the intensity change of a magnetic induction field when a ferromagnetic encoder provided with field perturbation units, moves past a detection cell. The detection cell such as a Hall effect or magneto-resistive probe, for example, delivers a periodic sinusoidal signal. The detection cell is associated with a level comparator with hysteresis, such as a Schmitt trigger, in order to obtain clear-cut transitions of the output voltage for distinct values of the magnetic induction according to whether it changes by increasing or by decreasing.
In order to form a velocity detection sensor, it is known how to make an encoder provided with teeth laid out in a regular way and in high numbers for improving the resolution of such a sensor. An enhancement to this sensor is known which consists of making an encoder formed by a multipolar magnetic ring provided on its circumference with alternating North poles and South poles, regularly spaced out according to a given pitch.
In order to allow at least one position to be determined, which for example corresponds to the ignition top dead centre of a cylinder, it is known how to make a mark on the magnetic encoder. Thus, it is for example known how to suppress two teeth on the cog wheel. In the solution applying an encoder with alternating North and South poles, either suppressing several magnetic poles by leaving an empty space, or replacing one or more poles of a given sign with one or more poles of an opposite sign, may be contemplated. A so-called irregular or singular pole having a magnetization with a sign opposite to the sign of both of its adjacent poles on the one hand, and a different spacing relatively to the spacing pitch of the other poles on the other hand are thereby achieved.
In order to achieve good accuracy in measurement, notably as regards the detection of the irregular pole, French Patent FR 2 757 943 teaches how to make an encoder comprising, for each irregular pole, means for correcting the value of the magnetic field generated by the irregular pole, so that the signal delivered by the passage of the poles neighboring said irregular pole, is symmetrical relatively to the zero value of the magnetic field.
By applying such an encoder, it is possible to obtain at the output of the detection cell of the sensor, a magnetic signal with constant period, as regards the regular poles. As a result of this, good accuracy of the thereby conducted measurements notably for locating the irregular pole, is achieved.
If the technical solution described in this patent gives satisfaction in practice, under certain operating conditions, a, large range variation of the width of the delimited gap between the encoder and the measurement cell was seen on the one hand, and a not insignificant side shift was seen on the other hand between the plane of rotation of the encoder and the axis of the measurement cell, which is detrimental to the accuracy of the measurements.
Also, U.S. Pat. No. 4,866,381 describes a position sensor including an encoder provided on its circumference with alternating North poles and South poles and mounted in order to move past a measurement cell. Such an encoder includes a magnetic singularity formed by a series of North and South poles having a determined pitch adapted for stabilizing the magnetic signal delivered by the passage of the poles adjacent to this singularity and inside this singularity. The ideal signal of this position sensor includes, upon passing the singularity, a succession of high and low states, consecutive to the passages through zero of the corresponding magnetic signal at different poles of the singularity.

Irregular saturated pole position sensor


According to one embodiment, a recognition device includes a hardware processor. The hardware processor is configured to identify presence or absence of composition elements of a target from input observation data, acquire setting information indicative of a relationship between a type and composition elements, and identify a type of the target based on the setting information acquired and the presence or absence of the composition elements.

For example, in the case of recognizing a traffic sign from an image, a neural network is generally used. When the image of a traffic sign targeted for recognition is input to the neural network, the type of the traffic sign corresponding to the image is output as a recognition result.
The neural network requires a large amount of information to recognize various targets, and an amount of calculation is also large. Further, to make the neural network additionally learn a new target, various parameters related to the target have to be input to the neural network.

Recognition device, vehicle system and storage medium

Toshiba Electronic Devices & Storage Corporation


The invention is a device that modifies the target aperture for the standard game board for the traditional lawn game known as cornhole or bean bag toss. The device, when inserted into the game board's target aperture, replaces the open hole with a circular shaped “trapdoor” that opens only when directly struck by a tossed game bag. When opened, the trapdoor allows the passage of the game bag through the game boards target aperture. The device includes a spring hinge mechanism that returns the trapdoor to the closed position after the bag has passed through the opening. The device is designed so that it can be quickly and easily inserted into and removed from the target aperture of the game board without moving or damaging the game board.

Whether it is called corn toss, soft horseshoes, bean bag toss or tailgate toss, the lawn game cornhole is increasing in popularity across the United States. There are numerous associations and clubs for the game including the American Cornhole Association (www.playcornhole.org), the American Cornhole Organization (www.americancornhole.com), the Central Alabama Cornhole Club (www.alabamacornhole.com), and the Maryland Cornhole Organization, Inc. (www.marylandcornhole.org). The exact origins of the game are unknown. One version of its history says the game originated in Germany during the fourteenth century and reemerged in Kentucky approximately one hundred years ago. Another version has the game originating in Ohio during the last century. Regardless of its origins, the game appeals to people of all ages.
The game consists of two elevated platforms, typically made of wood, located several feet apart in a level area. The platforms are elevated on an angle with the lower end located typically two to four inches above the ground and the higher end approximately twelve inches above the ground. A standard platform generally measures two feet wide by four feet long with a six inch circular aperture centered horizontally on the board approximately nine inches from the edge of the higher end. In a standard game, the platforms are placed facing each other approximately twenty-seven feet apart. Players take turns tossing a small bag filled with dried beans, corn or other pellets at the platform the farthest from them. Points are awarded for landing the bag on the platform or sending the bag through the target aperture, with a greater number of points awarded for sending the bag through the target aperture. The bag can go through the target aperture by either hitting the target aperture directly or sliding the bag across the board into the aperture. The invention described in this application is intended to provide the players the option of changing the target aperture through which the players desire to send their bag so that the bag can go through the target aperture only by hitting the target aperture directly.


A process for production of cyclopropyl-fused pyrrolidine-based inhibitors of dipeptidyl peptidase IV is provided which employs a BOC-protected amine of the structure

Dipeptidyl peptidase IV is a membrane bound non-classical serine aminopeptidase which is located in a variety of tissues including, but not limited to, intestine, liver, lung, and kidney. This enzyme is also located on circulating T-lymphocytes wherein it is referred to as CD-26. Dipeptidyl peptidase IV is responsible for the metabolic cleavage of the endogenous peptides GLP-1(7-36) and glucagons in vivo and has demonstrated proteolytic activity against other peptides such as GHRH, NPY, GLP-2 and VIP in vitro.
GLP-1(7-36) is a 29 amino acid peptide derived from post-translational processing of proglucagon in the small intestine. This peptide has multiple actions in vivo. For example, GLP-1(7-36) stimulates insulin secretion and inhibits glucagon secretion. This peptide promotes satiety and slows gastric emptying. Exogenous administration of GLP-1(7-36) via continuous infusion has been shown to be efficacious in diabetic patients. However, the exogenous peptide is degraded too rapidly for continual therapeutic use.
Inhibitors of dipeptidyl peptidase IV have been developed to potentiate endogenous levels of GLP-1(7,36). U.S. Pat. No. 6,395,767 to Hamann et al. discloses cyclopropyl-fused pyrrolidine-based inhibitors of dipeptidyl peptidase IV. Methods for chemically synthesizing these inhibitors are disclosed in U.S. Pat. No. 6,395,767 as well as in the literature. For example, see Sagnard et al. Tet-Lett. 1995 36:3148-3152; Tverezovsky et al. Tetrahedron 1997 53:14773-14792; and Hanessian et al. Bioorg. Med. Chem. Lett. 1998 8:2123-2128. A preferred inhibitor disclosed in U.S. Pat. No. 6,395,767 is (1S,3S,5S)-2-[(2S)-2-amino-2-(3-hydroxytricyclo[126.96.36.199,7]dec-1-yl)-1-oxoethyl]-2-azabicyclo[3.1.0]hexane-3-carbonitrile, as depicted in Formula M′.
and the corresponding monohydrate of (1S,3S,5S)-2-[(2S)-2-amino-2-(3-hydroxy-tricyclo[22.214.171.124,7]dec-1-yl)-1-oxoethyl]-2-azabicyclo-[3.1.0]hexane-3-carbonitrile (M″)
Methods adapted for preparing intermediates used in the production of this dipeptidyl peptidase IV inhibitor are disclosed in EP 0 808 824 A2. Also see, Imashiro and Kuroda Tetrahedron Letters 2001 42:1313-1315, Reetz et al. Chem. Int. Ed. Engl. 1979 18:72, Reetz and Heimbach Chem. Ber. 1983 116:3702-3707, Reetz et al. Chem. Ber. 1983 116:3708-3724.
The present invention provides new production methods and compounds for use in the production of cyclopropyl-fused pyrrolidine-based inhibitors of dipeptidyl peptidase IV.
U.S. Pat. No. 6,395,767 to Hamann et al. describes procedures for the synthesis of (αS)-α-[[(1,1-dimethylethoxy)carbonyl]-amino]-3-hydroxytricyclo[18.104.22.168,7]decane-1-acetic acid, an intermediate for use in preparing the free base M′ or salt thereof, which involves an eight-step synthesis from adamantane carboxylic acid.
U.S. application Ser. No. 10/716,012 filed Nov. 18, 2003 discloses a method for preparing (αS)-α-[[(1,1-dimethylethoxy)carbonyl]-amino]-3-hydroxytricyclo[22.214.171.124,7]decane-1-acetic acid which utilizes 3-hydroxy-α-oxotricyclo[18.104.22.168,7]-decane-1-acetic acid as a starting material and wherein an enzymatic reductive amination is used to prepare and isolate (αS)-α-amino-3-hydroxytricyclo[220.127.116.11,7]decane-1-acetic acid which is converted to the desired product in a separate step.
The enzymatic reductive amination step involves use of various forms of the enzyme phenylalanine dehydrogenase (PDH) in combination with the enzyme formate dehydrogenase enzyme (FDH) in the presence of ammonium formate, DTT and NAD using ammonium hydroxide for pH adjustment. Where excess ammonium ions are present, it may be necessary to remove ammonia before further downstream processing to avoid possible interference with the introduction of a BOC group.
The cells from which the PDH and/or FDH enzymes are produced are isolated from fermentation broth, stored until ready for use. Before using, the cells are microfluidized to release enzyme from the cells together with the cell debris which must be removed before the enzymes are ready for use in reductive amination.

Process for preparing dipeptidyl peptidase IV inhibitors and intermediates therefor

Abstract: prepared by subjecting an acid of the structure

Abstract: to reduce amination by treating the acid with ammonium formate, nicotinamide adenine dinucleotide, dithiothreitol and partially purified phenylalanine dehydrogenase/formate dehydrogenase enzyme concentrate (PDH/FDH) and without isolating treating the resulting amine of the structure 2

Abstract: with di-tert-butyl dicarbonate to form the BOC-protected amine.


A process for the conversion of synthesis gas to higher hydrocarbons by synthesis gas, at an elevated temperature and pressure, with a suspension of a particulate Fischer-Tropsch catalyst, in a system comprising at least one high shear mixing zone and a reactor vessel wherein the process comprises: (a) passing the suspension and the gaseous stream through the high shear mixing zone wherein the gaseous stream is broken down into gas bubbles and/or irregularly shaped gas voids; (b) discharging suspension having gas bubbles and/or irregularly shaped gas voids dispersed therein from the high shear mixing zone into the reactor vessel; and (c) maintaining the temperature of the suspension discharged into the reactor vessel at the desired reaction temperature by means of an internal heat exchanger positioned within the suspension in the reactor vessel. At least 5% of the exothermic heat of reaction is removed from the system by means of the internal heat exchanger. The remainder of the exothermic heat of reaction may be removed from the system by means of an external heat exchanger and/or through the introduction of a liquid coolant.

The present invention relates to a process for the conversion of carbon monoxide and hydrogen (synthesis gas) to liquid hydrocarbon products in the presence of a Fischer-Tropsch catalyst.
In the Fischer-Tropsch synthesis reaction a gaseous mixture of carbon monoxide and hydrogen is reacted in the presence of a catalyst to give a hydrocarbon mixture having a relatively broad molecular weight distribution. This product is predominantly straight chain, saturated hydrocarbons which typically have a chain length of more than 2 carbon atoms, for example, more than 5 carbon atoms. The reaction is highly exothermic and therefore heat removal is one of the primary constraints of all Fischer-Tropsch processes. This has directed commercial processes away from fixed bed operation to slurry systems. Such slurry systems employ a suspension of catalyst particles in a liquid medium thereby allowing both the gross temperature control and the local temperature control (in the vicinity of individual catalyst particles) to be significantly improved compared with fixed bed operation.
Fischer-Tropsch processes are known which employ slurry bubble columns in which the catalyst is primarily distributed and suspended in the slurry by the energy imparted from the synthesis gas rising from the gas distribution means at the bottom of the slurry bubble column as described in, for example, U.S. Pat. No. 5,252,613.
The Fischer-Tropsch process may also be operated by passing a stream of the liquid medium through a catalyst bed to support and disperse the catalyst, as described in U.S. Pat. No. 5,776,988. In this approach the catalyst is more uniformly dispersed throughout the liquid medium allowing improvements in the operability and productivity of the process to be obtained.
GB 728543 relates to a process for the production of hydrocarbons by the reaction of synthesis gas in the presence of a catalyst which may be suspended in finely divided form within the hydrocarbon oil (contact oil). A mechanically moved stream of contact oil circulating after the separation of the gas, and the synthesis gas is introduced into the reaction chamber below a cooling arrangement disposed therein, suitably by means of one or a series of nozzles. Cooling of the contact oil or mixture of contact oil and gas in the reaction chamber is effected in a number of stages in such manner that the mixture of synthesis gas and contact oil successively flows through cooling stages at increasing temperature. Owing to the fact that the individual cooling stages have a temperature increasing from the bottom upwards, the reaction can be retarded in places where the concentration of carbon monoxide and hydrogen is highest, namely in the lower part of the reaction tower, by the application of low temperatures. In accordance with the reduction of the concentration of the reaction substances, the temperature is then increased in the higher zones of the reaction tower, so that the complete reaction between the carbon monoxide and the hydrogen, corresponding substantially to equilibrium, is obtained in the neighborhood of the top of the reaction tower. Thus, GB 728,543 relates to a plug flow reactor vessel where the reaction conditions vary in the individual cooling stages.

This patent is subject to a terminal disclaimer.

BP Exploration Operating Company Limited


A semiconductor apparatus is disclosed, including: multiple parallel monitor circuits each configured to control charge to a capacitor by controlling a transistor that bypasses, if the voltage of the capacitor exceeds a predetermined reference voltage, charge current provided to the capacitor. The semiconductor apparatus further includes high voltage side IC connection output terminals each connected to an open drain of N channel transistor; high voltage side IC connection input terminals each connected to a terminal of a high resistance component and to an inverter input terminal; low voltage side IC connection output terminal each connected to an open drain of P channel transistor; and low voltage side IC connection input terminal each connected to a terminal of a high resistance component and to an inverter input terminal.

1. Field of the Invention
The present invention generally relates to a semiconductor apparatus for charging a capacitor, and more particularly, to a semiconductor apparatus in which multiple parallel monitor circuits are integrated for evenly charging multiple electric double layer capacitors connected in series.
2. Description of the Related Art
An electric double layer capacitor can be charged more quickly than a secondary battery is. Additionally, an electric double layer capacitor can store more energy than a secondary battery can. Since the rated voltage of an electric double layer capacitor is about 2.7 V, if a higher voltage is required, multiple capacitors connected in series are used.
When multiple capacitors connected in series are charged, uneven charging of the capacitors may occur due to the diversity of capacitance of each capacitor, self-charging, and self-discharging.
A circuit called "parallel monitor" for evenly charging multiple capacitors is used to solve the above problem.
FIG. 4 is a circuit diagram showing a portion of a parallel monitor circuit disclosed in Japanese Patent Laid-Open Application No. 2000-050495.
The same parallel monitor as shown in FIG. 4 is provided to each one of multiple capacitors connected in series. The parallel monitor is described below with reference to FIG. 4.
The parallel monitor circuit shown in FIG. 4 includes reference voltages Vr1 and Vr2, a comparator circuit CMP for comparing the voltage of a capacitor C1 with the reference voltage Vr1 or Vr2, switches S1 and S2 for switching the reference voltages Vr1 and Vr2, a transistor Tr1 for bypassing the charge current that flows into the capacitor C1, and a switch control circuit for controlling the switches S1 and S2 in accordance with the output of the comparator circuit CMP.
The reference voltage Vr1 is set at 3 V which is the full charge voltage of the capacitor C1, and the reference voltage Vr2 is set at 0.8 V which is less than the full charge voltage of the capacitor C1. At the initial stage of charge, the switch S1 is connected to the reference voltage Vr2. When the voltage of the capacitor C1 increases up to 0.8 V, the output of the comparator circuit CMP is inverted, and turns on the transistor Tr1. When the transistor Tr1 is turned on, the capacitor C1 is discharged, and the time constant of the discharge is determined by the resistance component of the circuit including the transistor Tr1. The switch control circuit monitors the outputs of all comparator circuits CMP. While the capacitor C1 is discharged, if the charge voltage of another capacitor increases up to the reference voltage 0.8 V, the switch S1 is switched to the reference voltage Vr1, and bypass mode is discharged. The capacitors are charged up to the full charge voltage 3 V.
As described above, the quantity of the parallel monitor circuits required is equal to the number of capacitors that are connected in series. The scale of the entire parallel monitor circuits become large. However, the conventional parallel monitor circuits have not integrated in a semiconductor apparatus but assembled using discrete components. The scale of the conventional parallel monitor circuits are large, and their cost is high. The integration of the parallel monitor circuits are desired to solve the above problem.
However, the quantity of capacitors connected in series depends on their application. It is not practical to design and manufacture a semiconductor apparatus in which the suitable number of parallel monitor circuits are integrated for each application.
It is also not advantageous to make a semiconductor apparatus in which only one parallel monitor circuit is integrated.
To solve above problem, five through ten parallel monitor circuits are integrated in a semiconductor apparatus IC1 (five in the case of FIG. 1) as shown in FIG. 1. If there are capacitors more than the parallel monitor circuits integrated in one semiconductor apparatus that are to be charged, the semiconductor apparatuses are cascaded as many as necessary. According to the above arrangements, the reasonable number of parallel monitor circuits can be integrated in a semiconductor apparatus so as to increase the efficiency of integration and consequently to reduce the cost of the parallel monitor circuits.
Even in the case in which multiple parallel monitor circuits are integrated in one semiconductor apparatus (hereinafter referred to as a monitor IC), the control circuit for monitoring the output of the comparator circuit CMP and for switching the reference voltages is configured by a CPU, for example, and the control circuit is usually separate from the semiconductor apparatus as shown in FIG. 4.
In the case of multiple monitor ICs are cascaded (two in the case of FIG. 1), the voltage applied to the power supply voltages Vdd (plus) and Vss (minus) of each monitor IC may be different. As a result, the voltage level of signal lines for exchanging signals with the control circuit may differ for each monitor IC. It is impossible to directly connect the control circuit and all monitor ICs.
This problem can be solved by a technique in which wiring is made between the control circuit and the monitor IC1, the minus power supply voltage Vss of which is common to the minus power supply voltage Vss of the control circuit, and the monitor IC1 shifts the voltage level of the control signal, and the control signal line is connected from the terminal of the monitor IC1 to the terminal of the monitor IC2 as shown in FIG. 1. This connection technique is referred to as daisy chain.
However, as apparent from FIG. 1, since the plus power supply voltage Vdd of the monitor IC1 is the minus power supply voltage Vss of the monitor IC2, voltage between the minus power supply voltage Vss of the monitor IC1 and the plus power supply voltage Vdd of the monitor IC2 is applied to terminals CON1 through CON12 that connects the monitor IC1 and the monitor IC2. As a result, the monitor IC1 and monitor IC2 need to have withstanding voltage twice as high as the power supply voltage of the monitor IC in the case in which one monitor IC charges one capacitor. Since a high withstanding voltage transistor is larger than a low withstanding voltage transistor, the chip size and cost of the monitor IC is increased.

Semiconductor apparatus for charging capacitors


Protective flexible eyewear for, inter alia, providing for increased comfort and fit among a variety of users having different facial shapes.

The present invention relates generally to protective eyewear especially protective eyewear for protecting a user's eyes during a sporting event. More particularly, the present invention relates to protective sports eyewear having a flexible base in combination with a rigid protective element to protect the eyes of a wearer from contact while maintaining a secure fit.
The current improvement to the protective eyewear enhances the protection of the wearer's eyes and versatility of the eyewear itself while also being more comfortable to wear for extended periods of time. Specifically, the current invention protects a wearer's eyes while allowing the frame to fit more closely to the wearer's head while still maintaining a rigid protective element which may optionally be removed or replaced as desired by the wearer.
It will be appreciated by those skilled in the art that protective eyewear for sporting events has existed for years. However, most protective eyewear includes frames and/or lens elements which do not flex to fit a wide variety of different users' facial shapes, and thus, are not comfortable for a wide variety of users. Furthermore, many of these types of protective eyewear used in other fields, including contact sports, may become uncomfortable for a variety of different wearers as the eyewear does not fit closely to the user's face, and furthermore, may actually hamper the wearer's performance as the eyewear may be a source of irritation or distraction. For example, in Du Bois, U.S. Pat. No. 2,422,534 there is disclosed a protective eye shield which includes a curved frame and a flat lens piece used to protect the wearer's eyes.
In U.S. Pat. No. 3,530,506 Hoffmaster, there is disclosed a safety goggle having a readily attachable and replaceable lens and includes a fixed sized base for contact with the user's face.
In Hussey (U.S. Pat. No. 7,181,779) a sports goggle is disclosed with venting so as to provide for ventilation for the user. Allegedly, the goggle incorporates a system of high and low pressure areas external to the goggle to increase ventilation of the enclosed eye cavity to prevent fogging of the goggle lens.
Darnell et al., U.S. Pat. No. 7,127,747, discloses a protective eye mask for sports including a horizontal frame member forming an eye mask frame which defines a cage and a frame having at least an upper frame and lower frame segments. Furthermore, the protective eye mask of the '747 patent provides an improved eyewear device for addressing problems inherent from resulting impacts while also precluding fogging or otherwise impeding a user's vision during game play of a sport such as lacrosse.
Unfortunately, the conventional prior art eyewear does not have the structure to adequately fit a variety of faces of individuals of a participant of a sporting event and needs to be more comfortable to wear while also providing protection to the user's eyes. This prior art eyewear is composed of materials that would not adequately flex, bend, or shape to fit comfortably around the face of users and protect the eyes of participants in a sport such as lacrosse, hockey, football, or the like. For example, the conventional eyewear of the prior art lacks a multi-piece frame design while incorporating rigid protective elements which are necessary to protect the eyes of a participant from impact with solid objects at high speeds of which may occur during participation in a sporting event.
Accordingly, there is a need for protective eyewear which adequately protects a wearer's eyes while being comfortable to wear by a variety of users with different facial shapes. Furthermore, there is a need for protective eyewear which provides for an unimpeded vision while being comfortable to wear for the extended amount of time necessary for participation in a sport or the like.


A method of displaying traffic information, comprising: providing a graphical interface to display information related to traffic routes; displaying a first bar to represent a total distance of a first traffic route; and displaying segments of the first bar, each segment of the first bar representing a corresponding range of traffic speeds along the first traffic route, and each segment of the first bar located on the bar in rough proportion to where the corresponding range of traffic speeds occurs along the first traffic route.

Knowing traffic conditions can be very important to drivers, especially when traveling on roads with frequent congestion problems. Traffic information has traditionally been obtained through traffic reports on the television, radio, or telephone. Today, real-time traffic reports are also available through the Internet.
Systems have been implemented which monitor traffic conditions on well-traveled roadways using speed sensors. For instance, in California, loop detectors have been embedded in the pavement, as well as off the pavement, to provide traffic counts and speeds. Traffic services use these traffic counts and speeds to provide on-demand, up-to-the-minute traffic conditions and driving times.
FIG. 8a illustrates a prior art traffic report currently implemented by the Website at www traffic 511 org. Within the screenshot 800 is a graphical map 801, an information box 802, and legend 803. The graphical map 801 uses colors and symbols to represent various road conditions on the major highways in the area. The information box 802 provides information related to a selected symbol or segment of the highway. FIG. 8b illustrates the prior art traffic report after zooming into a portion of the graphical map 801.
Several additional Websites provide real-time traffic information on demand, either through a text-based interface or through a graphical map. A few websites allow a user to create custom routes. For example, the Website www traffic com allows a user to create a route by connecting roadways together and selecting the beginning and ending off-ramps. This Website provides real-time information on the defined route through symbols and colors on a graphical map.
There is an increasing demand for real-time traffic updates to be readily available to drivers at all times through the use of handheld devices (e.g., personal digital assistants ("PDAs") and cell phones. Once such device is the Hiptop™ communicator designed by Danger, Inc., and distributed by T-Mobile, Inc.
However, current techniques of conveying traffic information to computers are not necessarily practical for conveying traffic information on handheld devices. For example, handheld devices are generally connected over a more bandwidth-limited network and have significantly smaller display screens. Current techniques for viewing traffic information are not only impractical, they provide too much information that is irrelevant to the user's commute. For example, current traffic maps may display an entire region, 90% of which is not interesting to the user. Or conversely, the handheld programs provide text, which is not practical at a glance. Most users require traffic information in their automobiles and need a fast-to-process GUI to make a decision.

Cconveying traffic congestion data to a user


A method of monitoring a refrigeration unit including detecting premature return of air discharged into a conditioned space, and distinguishing this "short cycling" problem from a refrigeration capacity problem. The method includes determining the rates of change of the temperatures DA and RA of the discharge air and return air, respectively, during temperature pull down of the conditioned space, and comparing the rates of change with predetermined constants selected to detect a short cycling of the discharge air. When the rates of change do not fit a normal temperature pull down, the differential .DELTA.D between the temperatures DA and RA of the discharge air and return air is determined and compared with a third constant. Predetermined results of the comparisons of the rates of changes of DA and RA, and the temperature difference .DELTA.D with the first, second and third constants, respectively, are utilized to identify proper air flow in conditioned space, to indicate a problem with air flow in conditioned space, and to indicate that refrigeration capacity should be checked.

In order for a refrigeration unit, such as a transport refrigeration unit, to efficiently maintain a conditioned space and its associated load in a predetermined temperature range close to a selected set point temperature, it is important that air distribution throughout the conditioned space be proper. The refrigeration unit, via an evaporator fan or blower, discharges conditioned air into the conditioned space from a discharge air outlet associated with an evaporator plenum. Air is drawn from the conditioned space by the evaporator fan or blower back into the evaporator plenum via a return air inlet.
The discharge air should circulate throughout the conditioned space so that heat exchange between the conditioned air and load is as uniform as possible throughout the entire load, before the air is allowed to return to the air inlet. To insure uniform, highly efficient heat transfer between the conditioned air and load, chutes and/or bulkheads are often installed in the conditioned space. If conditioned air is allowed to return prematurely to the evaporator plenum, a condition which is called "short cycling", the heat transfer efficiency suffers, and the load in the conditioned space will not be uniformly conditioned. Short cycling may be caused, for example, by improper installation of air chutes and/or bulk heads in the conditioned space.
Refrigeration unit monitoring and diagnostic programs of the prior art may, upon encountering short cycling, incorrectly indicate a fault with the refrigeration unit, identifying low refrigeration capacity as the cause. It would be desirable, and it is an object of the present invention, to provide monitoring and diagnostic methods which differentiate between a short cycling air flow problem and a refrigeration capacity problem.

Method of detecting short cycling of air discharged by a refrigeration unit


This invention aims to provide a game machine which can offer exciting and varied game aspect. In the game machine, certain symbol combinations (group [C] and [E]) are set as a prize mode only when they occur in B.B (big bonus) game. The combinations in group [C] are not regarded as a prize mode when they occur during the ordinary regular game. These combinations are new to the player because the player encounters them only when the game shifts to the big bonus game. This gives a fresh impact to the player and the player can enjoy a variety in the big bonus game, which does not occur in the ordinary regular game.

1. Field of the Invention
This invention relates to a game machine having a controller, such as a microcomputer, to control the game aspect. More particularly, this invention relates to a game machine which has a variable display for displaying a plurality of symbols in a variable manner.
2. Related Art
In the game machine with such a variable display, prize is generally determined by a random sampling. Prizes given to a player based on the prize determination has various modes. For example, slot machine has a small hit mode, besides the regular game mode, which offers a small hit prize. Small hit occurs when a prescribed combination of symbols appears on the variable display during the regular game. With a small hit, a given number of coins are returned to the player.
There is also a medium hit mode to offer a medium hit prize. The game in this mode is called a normal bonus game (referred to as N.B game). Normal bonus (N.B) game takes place when a prescribed combination of symbols, which differ from the small hit symbol combination, appears on the display during the regular game. With a medium hit, the player can play an extra game called a "bonus game" once. The bonus game is composed of a set of several rounds of high bonus games.
There is also a big hit mode which offers a big hit prize. The game in this mode is called "big bonus game" (referred to as B.B game). This takes place when a prescribed combination of symbols, which is different from small or medium prize symbol combinations, appears on the variable display. With a B.B game, player can play several sets of regular games in which the small hit occurs with a high probability and the bonus game mentioned above.
The regular games in the B.B game are played several times before the game shifts to the bonus game. During the regular games in the B.B game, the small hit occurs with a high probability. A given number of coins are returned to the player every time the small hit symbol combination appears on the variable display. The player will finally win a number of coins with the B.B game. If none of these prize modes occurs during the game, the game is a non-prize mode and the player cannot win the game.
However, in the conventional game machine, the small hit, which occurs in the regular game of the B.B game with a high probability, is determined in the same combination of symbols as the small hit in the ordinary regular game. That is, even when the game shifts from the regular game to the B.B game, there is no variation in the prize composition using the same small hit mode until the game shifts to the bonus game. Variety and excitement were not satisfactory in the game flow of the conventional game machine.

Game machine in capable of controlling game aspect


According to one aspect of exemplary embodiments of the present invention, a method is provided for modeling a transition between adjoining surfaces. The method includes determining a curve of intersection of two adjoining surfaces, where the curve includes a plurality of points. For each of at least some of the points, the method includes selecting a point of the curve of intersection, and determining end points of a section of the transition located at the selected point, where each end point is located on a respective one of the adjoining surfaces. The method also includes determining a shape of the section of the transition, where the shape of the section for each of at least some of the points models the transition between the adjoining surfaces. The transition is curvature continuous with a first curvature at the end points and a second, different curvature at a portion therebetween.

In a number of different disciplines, such as computer-aided geometric design (CAGD), it is necessary to model a transition between two adjoining surfaces, where such modeling is often referred to as a filleting or rounding operation. Generally, the purpose of such filleting or rounding operations is to provide a gentle, continuous transition or fillet from one surface to an adjoining surface. Such fillets, in turn, can benefit the manufacturing process of structures including the fillet, as a number of manufacturing processes utilize rounded cutters. Additionally, such fillets can alleviate safety concerns for sharp corners on structures, can provide increased structural integrity due to smooth transitions, and improve engineering performance including, for example, aerodynamic drag and low radar cross sections.
Consider, for example, surfaces 10 and 12 illustrated in FIG. 1a. One technique for eliminating the corner or seam between the two surfaces is to replace a portion of each surface with a fillet or transition that smoothly joins the two surfaces. One conventional technique for modeling such a fillet utilizes a rolling ball or sphere 14, as shown in FIG. 1b. In this regard, imagine a sphere of some radius rolling along the intersection of two surfaces such that the sphere remains in contact with both surfaces at a point of tangency. As shown in FIG. 1b, as the sphere rolls along the intersection of the surfaces, the sphere can sweep out a tube along the seam, with the portion of the tube that lies between the two surfaces and tangent to each modeling the desired fillet.
Despite its conceptual appeal, the rolling ball fillet suffers from a number of drawbacks. In this regard, the rolling ball does not meet the edges of both surfaces simultaneously unless the four vectors given by the surface normals and surface edge tangents all lie in the same plane. And for the surfaces 10 and 12 of FIG. 1a, the four vectors given by the surface normals and surface edge tangents do not all lie in the same plane. Thus, as shown by region 16 in FIG. 1c, the fillet surface modeled by the rolling ball stops short of the edge of one of the surfaces.
A second drawback with the rolling ball fillet technique is that such a technique produces a surface whose curvature does not agree with the adjoining surfaces in directions transverse to the common edge, even in the simplest cases. For example, modeling a fillet in accordance with the rolling ball fillet technique may result in a cylindrical fillet when the two adjoining surfaces are planes. The curvature in the direction perpendicular to the axis of this cylinder is the reciprocal of the radius of the cylinder, whereas it is zero for the planes. Hence, the curvature is discontinuous across the seam where the cylinder and the planes meet.

System, method and computer program product for modeling a transition between adjoining surfaces


A stripper rubber for oil and gas wells, water and geo-thermal wells, having an interior surface design which includes a circular, convex knee portion in the throat area of the stripper rubber to provide additional support to the stripper rubber during insertion of a tubular member through the stripper rubber. The composition for the stripper rubber includes, in one embodiment, enhanced wear characteristics by the addition of milled fibers of Twaron.RTM. mixed homogeneously throughout the stripper rubber.

1. Field of the Invention
This invention relates to a long-lasting, generally tubular, rubber or elastomer-based seal having a configuration for sealing against tubular members or drillstring components movable longitudinally through the seal, such as stripper rubber seals for rotating control heads, rotating blowout preventers, diverter/preventers and the like, used in oil, gas, coal-bed methane, water or geothermal wells.
2. Description of the Related Art
In the drilling industry, seals are used in various applications including rotating blowout preventers, swab cups, pipe and Kelly wipers, sucker rod guides, tubing protectors, stuffing box rubbers, stripper rubbers for coiled tubing applications, snubbing stripper rubbers, and stripper rubbers for rotating control heads or diverter/preventers. Stripper rubbers, for example, are utilized in rotating control heads to seal around the rough and irregular outside diameter of a drillstring of a drilling rig. Stripper rubbers are currently made so that the inside diameter of the stripper rubber is considerably smaller (usually about one inch) than the smallest outside diameter of any component of a drillstring. As the components move longitudinally through the interior of the stripper rubber, a seal is continuously effected. Stripper rubbers are self-actuating in that as pressure builds in the annulus of a well, and in the bowl of the rotating control head, the vector forces of that pressure bear against the outside surface or profile of the stripper rubbers and compress the stripper rubber against the outside surface of the drillstring, thus complementing resilient stretch fit forces already present in the stripper rubber. The result is an active mechanical seal which increases sealability as well bore pressure increases.
Stripper rubbers seal around rough and irregular surfaces such as those found a drill pipe, tool joints, and a Kelly, and are operated under well drilling conditions where strength and resistance to wear are very important attributes. In utilizing stripper rubbers in rotating control heads, the longitudinal location of the rotating control head is fixed due to the mounting of stripper rubbers onto bearing assemblies which allow the stripper rubbers to rotate with the Kelly or drillstring but restrain the stripper rubbers from longitudinal movement. Thus, relative longitudinal movement of the drillstring including the end to end coupling areas of larger diameter joints and the larger diameter of tools that bear against a stripper rubber thereby causing wear of the interior surface of the stripper rubbers.
The wear upon stripper rubbers will, over a period of time, cause a thinning of the stripper rubber to the point that the stripper rubber will fail. Such wear is enhanced or increased when multiple lengths of a drillstring are moved through the stripper rubbers, such as when a drillstring is "tripped" into or out of the well. Longer wear of stripper rubbers has been a long felt need in the industry. The advantage of a longer lasting stripper rubber is not only one of safety, but also one of expense since a longer lasting stripper rubber will reduce the number of occasions when the stripper rubbers must be replaced, an expensive and time consuming undertaking.
It is generally known that the mechanical properties of rubber-based products may be enhanced through the addition of para aramid fibrillated short fibers (pulp) and para aramid dipped chopped fibers (DCF) in applications such as hoses, V-belts and tires. Akzo Noble Fibers, Inc. of Conyers, Ga. through its European operation is one manufacturer of such reinforcing products, selling a product under the trademark Twaron.RTM.. A similar product is available from another manufacturer under the trademark Kevlar.RTM.. Twaron.RTM. is Akzo's organic manmade high performance para aramid fiber. Its chemical designation is poly (para-phenylen terephthalamid).
Twaron.RTM. fibers have been used in transmission belts where short fiber reinforced rubber is located under the cord layer, the short fibers being oriented perpendicular to the surface that transfers power. The increased hardness of the rubber in the fiber direction gives the transmission belt a lower friction coefficient, a reduced noise level when in service, a lower heat build up during cyclic compression and an increase in transmission capability. Twaron.RTM. fibers have also been used in the manufacture of hoses such as an automotive heater hose which is reinforced with a knitted (para aramid) continuous filament yarn construction. Para aramid pulp has also been used in the inner liner of grated high pressure hoses to provide an increased green strength of the liner and an improved production stability, coupling retention and better fatigue resistance.
Twaron.RTM. fibers are also utilized in tires. In the bead area, aramid short fibers give fewer mixing problems than high levels of high surface area carbon blacks. Advantages are offered by the high anisotropy and the increased dynamic modulus leading to a lower heat build-up which extends the life of the bead compound and preserves the adhesion between bead wire and bead compound. When short fibers are used in a tire tread compound, advantages include a lower rolling resistance of the tire, better water drainage, more uniform wear and possibly less noise.
In an article entitled Short Para Aramid Fiber Reinforcement published in Rubber World in June, 1994, van der Pol and de Vos of Akzo Nobel Fibers disclosed that para aramid pulp or DCF may provide certain advantages for rubber seals and oilwell packings including better mechanical properties at elevated temperatures, less creep, higher abrasion resistance and less swelling by solvents. Van der Pol and de Vos taught that short fibers provide abrasion resistance to rubber and suggested using Akzo's Twaron.RTM. fibers in applications such as V-belts, footwear, seals, rolls, tank-pads, gaskets, automotive hoses, conveyor belts, pneumatic tires, protection of mines and dams and roofing. This article is incorporated by reference.
In spite of the general knowledge pertaining to enhancing properties of rubber, there remains a long-standing problem of wear in seals and wipers used for drilling components. Wear is caused by relative movement of a drillstring or production well component against the rubber seal or wiper. Wear is present in all drilling and production applications where a rubber seal or wiper is subjected to the relative movement of a component such as drillstring tools, Kelly, pipe, or rod for the purpose of sealing, wiping, stripping, snubbing and/or packing off well fluids when drilling or producing oil or gas from a well. There remains a long-felt need for a rubber seal or wiper that is resistant to wear and capable of a longer service life than has been heretofore possible.

Seal for a longitudinally movable drillstring component


It is intended to provide a transgenic nonhuman mammal well representing the pathologic conditions of human rheumatoid arthritis. A transgenic nonhuman mammal is obtained by transferring a foreign DNA, wherein a DNA selected from the group consisting of an MHC class II transcriptional activator gene, the activity domain of an MHC class II transcriptional activator gene and a variant of an MHC class II transcriptional activator gene is provided under the control of a type II collagen promoter, into a cell at the early stage of development.

Conventionally, in the development of drugs (antirheumatic drugs) for human rheumatoid arthritis (human articular rheumatism), type II collagen arthritis model mice and the like have been used. In H-2q or H-2r haplotype mice, by administering 0.1 to 0.2 mg of type II collagen by subcutaneous injection, symptoms of rheumatoid arthritis are induced (collagen-induced arthritis, CIA). In frequently used H-2q haplotype mice, arthritis is usually observed by conducting secondary immunization after primary immunization. In several days after the secondary immunization, rheumatoid symptoms are presented including that acute phase inflammation occurs in a local region of the joint and then a series of chronic inflammation is elicited. Human rheumatoid arthritis is a disease whose main symptoms include inflammation in the joints, bone destruction, ankylosis and deformity of bones, and the like. In general, the disease tends to show a high chronicity. Furthermore, since human rheumatoid arthritis is often complicated with angiitis, it may induce myocarditis, interstitial pneumonia, peripheral angiitis, and the like. These complications are refractory. Therefore, development of specific treatment methods has been demanded.

Transgenic nonhuman mammal representing the pathologic conditions of human rheumatoid arthritis

Nagoya Industrial Science Research Institute


‘TWD01’ is a distinctive variety of Grevillea hybrid which is characterized by a short plant height, a denser plant habit, larger leaves, and a compact red flower.

The present invention relates to a new and distinct perennial variety of Grevillea hybrid, which has been given the variety denomination of 'TWD01'. Its market class is that of an ornamental plant. 'TWD01' is intended for use in landscaping and as a decorative plant.
Parentage: In 2004 a seedling occurred from open pollination between two parents, red-form Grevillea rhyolitica (unpatented) and Grevillea juniperina 'Molonglo' (unpatented). The seedling exhibited a shorter plant height, a denser habit and larger leaves when compared to either parent plant. Upon flowering, the new seedling, which was named 'TWD01', exhibited a red flower like that of parent plant Grevillea rhyolitica. By comparison, 'TWD01' has a shorter plant height, more compact overall habit, larger leaves and a more compact flower.
Asexual Reproduction: 'TWD01' was first propagated asexually by vegetative cuttings in the state of New South Wales, Australia in 2005 and has since been asexually propagated by micropropagation. The distinctive characteristics of the inventive 'TWD01' variety are stable from generation to generation; clones of the variety produced by asexual reproduction maintain the distinguishing characteristics of the original plant.
An application for plant breeders' rights for variety 'TWD01' has been lodged with the Australian Plant Breeders' Rights Office, and was first gazetted in 22 Dec. 2010 under Application No. 2010/281.


The present invention describes a novel method for crosslinking polysilazane polymers having Si--H or N--H bonds. The method comprises mixing the polysilazane with a silazane crosslinker having at least 2 boron functional groups which can react with the Si--H or N--H bonds of the polysilazane and then facilitating crosslinking.

The present invention relates to a method of crosslinking polysilazane polymers in which boron modified silazanes are used as crosslinkers. The invention also relates to a novel crosslinker comprising boron modified tris(trimethylsilylamino)silane and a method for it manufacture.
A variety of polysilazane oligomers, cyclics, resins and linear polymers are known in the art. Such polysilazanes are characterized as having backbones with alternating silicon and nitrogen atoms. These polymers have found broad utility as precursors to a variety of ceramic materials such as ceramic monoliths, ceramic fibers and matrices for ceramic matrix composites.
To be truly useful as ceramic precursors, however, the polysilazanes must be curable (infusible) to prevent deformation of the ceramic upon heating. Various approaches to providing curability have been suggested. For instance, Mahone in U.S. Pat. No. 5,086,126 discloses a process for adding vinyl groups to a polysilazane such that upon addition of a free radical precursor the polymer would rapidly cure.
Similarly, various references disclose the addition of boron compounds to polysilazanes to provide curability. For instance, Zank in U.S. Pat. No. 5,169,908 discloses the addition of borane to a hydridopolysilazane polymer to render the polymer curable. Funayama et al. in U.S. Pat. No. 5,030,744 discloses the addition of a boron compound to a polysilazane to increase its molecular weight. U.S. Pat. No. 4,910,173 granted to Niebylski discloses the formation of an organoborosilazane by the reaction of a boroxine with a polysilazane. Seyferth et al. in J. Am. Ceram. Soc. 73, 2131-2133 (1990) teaches the reaction of a silazane oligomer with borane to form a higher molecular weight borazine. Finally, Noth in Z. Naturforsch. B. Anorg. Chem., Org. Chem., 16 [9] 618-621 (1961) teaches the reaction of hexamethyldisilazane with diborane to form a higher molecular weight borazine.
As is readily apparent, each of the above references teaches the addition of boron to a polysilazane to render it infusible or to increase the molecular weight of the resultant polymer. By contrast, the present inventors have now discovered that boron-modified silazane crosslinkers can be utilized to render nearly any polysilazane having Si--H or N--H bonds infusible.

Method of crosslinking polysilazane polymers


An objective lens driving apparatus for an optical pickup includes a blade on which an objective lens can be mounted, a plurality of elastic support members supporting the blade and capable of elastically moving with respect to the blade, and a servo mechanism driving the blade up and down, left and right, and in a rotational direction. The elastic support members are grouped into pairs arranged to face each other with respect to a center of rotation of the blade, and distances between the elastic support members in the respective pairs are substantially identical. By lessening the difference in the amount of deformation between the elastic support members supporting the blade during tilt control, the elastic support members are less likely to move in undesired directions when vibration is applied.

1. Field of the Invention
The present invention relates to an objective lens driving apparatus used with an optical pickup, and according to one aspect of the invention, to an objective lens driving apparatus used with an optical pickup having an improved arrangement structure including an elastic support member supporting a blade on which an objective lens is mounted to be capable of elastically moving.
2. Description of the Related Art
In general, optical pickups record or reproduce information on or from a disk, a recording medium, by emitting light thereon. The light emitted from the optical pickup must be perpendicularly incident on a recording surface of a disk to form a light spot with the most accurate focus. If a light incident direction is inclined, an accurate light spot cannot be formed on the disk so that an error may occur during recording and reproduction of data. Thus, to form a light spot accurately on a desired track, the light must be perpendicularly incident on the recording surface of the disk. The adjustment of the light to be perpendicularly incident on the recording surface of the disk is referred to as tilt adjustment or skew adjustment. Typically, an optical pickup apparatus includes a servo-mechanism controlling the position of the objective lens in a focusing direction and a tracking direction so that the focus of light can be accurately formed on a desired track of a recording surface of a disk. However, while the servo-mechanism controls the focus of a light spot by maintaining a predetermined distance between the objective lens and the recording surface of the disk and the light spot to trace a desired track, it does not directly control the incident angle between the light and the recording surface of the disk. Thus, for more accurate recording and reproduction, a way to dynamically control the tilt is needed.
To meet the above demand, one type of objective lens driving apparatus for an optical pickup, as shown in FIG. 1, has been suggested. The optical pickup is a servo-mechanism to control the position of an objective lens 1 and includes a focus control mechanism 100 driving a blade 2. The objective lens 1 is mounted in a focus direction A, a tracking control mechanism driving the blade 2 is mounted in a tracking direction B, and a tilt control mechanism driving the blade 2 is mounted in a tilt direction C.
The focus and tracking control mechanisms are formed by a pair of focus coils 3a and 3b, a tracking coil 4, and a magnet 6. Thus, during control, an electromagnetic force driving the blade 2 in a corresponding direction is generated by applying current to the focus coils 3a and 3b and the tracking coil 4.
The tilt control mechanism can be formed separately from the focus and tracking control mechanisms. However, as shown in FIG. 1, the tilt control mechanism can be formed to be also used as the focus control mechanism. That is, during tilt control, an electromagnetic force to drive the blade 2 in the tilt direction C can be generated by applying current in a different way from the current applied during control to the focus coils 3a and 3b symmetrically arranged, for example along the tracking direction B. In other words, during focus control, currents are identically applied to the left and right focus coils 3a and 3b to drive the blade 2 in the focus direction A. During tilt control, currents are applied in different directions to the focus coils 3a and 3b to drive the blade 2 in the tilt direction C.
A plurality of wires W, elastically supporting movement of the blade 2 with respect to a holder 5 are typically arranged as shown in FIGS. 2A and 2B. FIG. 2A shows part of the structure of FIG. 1 in a simple form for the convenience of explanation. However, in this wire arrangement, a possibility exists that the position of the blade 2 becomes unstable during driving of the blade when the tilt is high. That is, as shown in FIG. 2B, three pairs of wires W1 and W6, W2 and W5, and W3 and W4 are arranged to face each other with respect to a point P which is the center of rotation when the blade 2 is being driven in a tilt direction C. Among these wire pairs, two pairs i.e. W1 and W6, and W3 and W4, have the same distance therebetween (d1=d3), while the other pair i.e. W2 and W5 has a different distance therebetween (d2≠d1=d3).
In this structure, it is assumed that the blade 2 can be moved by an angle θ by the operation of the tilt control mechanism as shown in FIG. 3A. In this case, comparing the amounts of deformation between the first and second wires W1 and W2, as shown in FIG. 3B, the amount of deformation of the first wire W1 is that r1×θ (r1=d1/2) and the amount of deformation of the second wire W2 is that r2×θ (r2=d2/2) which is less than the amount of deformation of the first wire W1. Likewise, the amounts of deformation of the third, fourth, and sixth wires W3, W4, and W6 are the same as that of the first wire W1 while the amount of deformation of the fifth wire W5 is the same as that of the second wire W2. That is, the first, third, fourth, and sixth wires W1, W3, W4, and W6 are bent to a relatively greater degree than the second and fifth wires W2 and W5 are bent.
A compression force acts on the second and fifth wires W2 and W5 so that the second and fifth wires W2 and W5 can be buckled as shown in FIGS. 4A and 4B. This is a very unstable configuration and, even if a slight vibration or impact is applied, the buckled wires can be elastically expanded so that the blade 2 may be moved in an undesired direction. Therefore, the entire system controlling the position of the objective lens 1 can become unstable. Thus, an improved structure to solve the above problem is demanded.

Objective lens driving apparatus for optical pickup


The flexible sheet-like material comprises a textile layer, which is coated at least on one side with a functional layer which is permeable to gas but impermeable to the matrix material, acting as a barrier layer for the matrix material, and is produced by coating the textile layer directly with a foam or a paste.

The invention relates to a flexible sheet-like material for defining a matrix material feed space in the production of fibre-reinforced plastics material components from composite fibre semi-finished products. The invention also relates to a process for the production of a flexible sheet-like material of this type.
In the production of fibre-reinforced plastics material components, it is known that dry composite fibre semi-finished products, so-called preforms, are initially used which are impregnated with flowable, curable matrix material in the form of resin. The dry composite fibre semi-finished product can be present as woven fabric, as multi-axial non-crimp fabric or as chain-reinforced unidirectional semi-finished product and consists in particular of carbon fibres, glass fibres, aramid fibres, boron fibres or hybrid materials.
A process for the production of fibre-reinforced plastics material components is known as the resin-film-infusion (RFI) process. In this process, a dry carbon fibre woven fabric or non-crimp fabric is deposited in a curing device and covered from outside with a defined amount of resin film. Thereafter, the plastics material component consisting of the carbon fibres and resin is cured under pressure and heat in an autoclave or in another pressure vessel. However, the use of pressure vessels and the complex moulds required for this purpose are very expensive. Furthermore, it is difficult to manage a process of this type in respect of temperature and pressure. Moreover, the available autoclaves restrict the size of the plastics material components to be produced.
To avoid these disadvantages, a process has been developed which is described in DE 100 13 409 C1 and is called "VAP" (Vacuum Assisted Process). This process uses a multi-layer, flexible sheet-like material which defines a matrix feed space in which the semi-finished product is arranged. The sheet-like material consists of a plurality of separate layers which are to be handled independently of one another, namely a membrane which is permeable to gas but impermeable to matrix material, a highly gas-permeable spacer layer and a gas-impermeable film. These layers are successively positioned individually over a flow-promoting layer which is applied onto the semi-finished product. When the region between the film and the membrane is evacuated, thereby causing the build-up of a vacuum, the pressure is also reduced accordingly in the inner matrix feed space through the membrane, as a result of which liquid resin (matrix material) is drawn by suction from an external resin container into the matrix material feed space. In this respect, although the membrane allows gases to escape out of the matrix feed space into the spacer layer and from there to the outside, at the same time it holds back the resin in the matrix material feed space, so that the resin can infiltrate into the semi-finished product.
Although VAP affords considerable advantages over processes which use autoclaves, it suffers from the particular problem that the individual layers of the sheet-like material, namely the membrane, the spacer layer and the gas-impermeable film have to be positioned very precisely and without tension in succession over the semi-finished product. Accordingly, this is time-consuming and, if not performed accurately, can adversely affect the process reliability and can result in non-uniform accumulations in the matrix material.
These problems are avoided by a multi-functional laminate which is described in DE 10 2008 006 261 B3. In this case, a textile layer is laminated onto the membrane, which is permeable to gas but impermeable to matrix material, and furthermore the spacer layer is fixed to the textile layer. The gas-permeable film can either be positioned separately over the spacer layer or firmly joined to the spacer layer and, in the latter case, the film is also a fixed component of the multi-functional laminate. This multi-functional laminate provides significant advantages in respect of management, process accuracy and process reliability. However, with a multi-layer laminate of this type, the desired mechanical material characteristics and the characteristics in respect of gas permeability, matrix material impermeability and temperature resistance of the membrane and of the textile layer often cannot be accurately adjusted in the desired simple manner. The reasons for this are, inter alia, that the characteristics, present before the lamination process, of the membrane on the one hand and of the textile layer on the other can change significantly due to the lamination process and depending on the type, application method and amount of adhesive used between membrane and textile layer during lamination. A further disadvantage is that in these known configurations, the flow front of the resin cannot be observed, because the above-mentioned sheet-like materials are non-transparent.

Flexible sheet-like material for bounding a matrix material feed space and method for the production thereof


A method for preventing heartburn episodes in a patient at risk to development of heartburn, comprising administering to the patient, following the heartburn inducing event but prior to development of heartburn, a composition comprising a pharmaceutically effective amount of an H.sub.2 antagonist and an amount of antacid having between about 15 mEq and 46 mEq acid neutralizing capacity.

Heartburn, or pyrosis, is a sensation of pain or burning located substernally or high in the epigastrium with radiation into the neck and occasionally to the arms, associated with regurgitation of acid-peptic gastric juice into the esophagus. Occasional heartburn is common in normal persons, but frequent and severe heartburn is generally a manifestation of esophageal dysfunction. Heartburn may result from abnormal motor activity or distention of the esophagus reflux of acid or bile into the esophagus, or direct esophageal mucosa irritation (esophagitis).
Heartburn is most often associated with gastroesophageal reflux. In this setting, heartburn typically occurs after a meal, with stooping or bending, or when the patient is supine. It may be accompanied by the spontaneous appearance in the mouth of fluid which may be salty, sour, or bitter and green or yellow. Heartburn may arise following the ingestion of certain foods (e.g. citrus fruit juices) or drugs (e.g. alcohol or aspirin).
Reflux esophagitis consists of esophageal mucosal damage resulting from reflux of gastric or intestinal contents into the esophagus. Esophagitis, an inflammation of the esophagus from regurgitation of acid gastric contents, producing substernal pain, develops when the mucosal defenses that normally counteract the effect of injurious agents on the esophageal mucosa succumb to the onslaught of the refluxed acid pepsin or bile. Mild esophagitis shows microscopic changes of mucosal infiltration with granulocytes or eosinophils, hyperplasia of basal cells, and elongation of dermal pegs. Erosive esophagitis shows endoscopically visible damage to the mucosa in the form of marked redness, friability, bleeding, superficial linear ulcers, and exudates.
Known antagonists of the histamine H.sub.2 receptor include cimetidine, ranitidine, nizatidine, and famotidine. Famotidine (available from Merck & Co., Inc., Whitehouse Station, N.J., under the name PEPCID.RTM.), is 3-{{{2-[(aminoiminomethyl)amino]-4-thiazolyl]methyl]thio]-N-4-(aminosulfon yl)propanimidamide, having the structural formula: ##STR1## The primary clinically important pharmacologic activity of famotidine is inhibition of gastric secretion. Both acid concentration and volume of gastric secretion are reduced by famotidine. Famotidine is used to treat acid-related disorders such as gastric and duodenal ulcer, gastroesophageal reflux disease and Zollinger Ellison syndrome. Its safety and efficacy have been well established in controlled clinical studies. It is used by over 31 million patients worldwide.
Gitlin et al., Amer. Journal of Gastroenterology (1985) vol. 80 pp. 840 examines famotidine efficacy in the treatment of active duodenal ulcers. 20 mg twice daily, 40 mg twice daily and 40 mg at bedtime were administered over a four week period. Healing rates of 67, 75, 70% , respectively, were seen.
Similarly, Miyoshi et al., Naika Hokan (1987) vol. 34 pp. 442-457 demonstrates the efficacy of famotidine as a gastritis therapy. Miyoshi et al. evaluated dosage regimens of 5, 10, or 20 mg twice daily in the treatment of gastritis symptom relief. Patients treated with 10 to 20 mg of famotidine had fewer erosions and mucosal haemorrhages than those treated with 5 mg famotidine.
McCallum et al., Dig. Dis. Sci. (1985) vol. 30 pp. 1139-1144 describes a study of healthy patients demonstrating that 5 mg of famotidine produces has an effect on gastric acid secretion. Laskin et al., J. Clin. Pharmacol. (1993) vol. 33 pp. 636-639 describes a study demonstrating that single doses of 5 and 10 mg of famotidine produces statistically significant decreases in intragastric acidity, beginning at 90-100 minutes and persisting for approximately 9 hours.
Administration of H.sub.2 antagonists before ingestion of a heartburn inducing meal may reduce the amount of gastric acid produced and prevent heartburn symptoms. However, H.sub.2 antagonists do not neutralize gastric acid, and the onset of the antisecretory effect of H.sub.2 antagonists is not instantaneous. Therefore, administration of an H.sub.2 antagonist following a meal will not substantially prevent heartburn and related symptoms. Antacids are known to neutralize acid in the stomach and may also act locally in the distal esophagus. Antacids are not known to prevent heartburn when taken before food or beverages which may provoke symptoms.
Wolfe, U.S. Pat. No. 5,229,137, describes compositions and methods which require the simultaneous administration of an H.sub.2 antagonist with an antacid to provide relief from pain, discomfort and symptoms associated with episodic heartburn EP 138 540 describes oral compositions containing cimetidine and aluminum hydroxide-magnesium carbonate co-dried gel for treating duodenal, gastric, recurrent and stomal ulceration, and reflux esophagitis. EP 233 853 describes effervescent compositions containing cimetidine and sodium bicarbonate for treating duodenal and gastric ulcers. EP 290 229 describes compositions containing cimetidine, aluminum hydroxide gel, and magnesium hydroxide, for treating duodenal, gastric, recurrent and stomal ulceration, and reflux esophagitis. EP 294 933 describes compositions containing cimetidine, aluminum hydroxide gel and magnesium hydroxide, for treating duodenal, gastric, recurrent and stomal ulceration, and reflux esophagitis. The antacid is described as providing rapid relief from the symptoms of excess stomach acidity by neutralizing acid and the cimetidine is described as bringing about more sustained relief by inhibiting secretion of acid. WO 92/00102 describes coadministration of H.sub.2 antagonists with antacids for treating gastric disorders such as hyperacidity. WO 93/12779 describes compositions of H.sub.2 antagonists with antacids for treating gastric disorders such as hyperacidity. EP 600 725 describes compositions of famotidine with antacids for treating gastrointestinal distress.
Applicants have now found that administration to a patient of a composition comprising an H.sub.2 antagonist and antacid, following a heartburn inducing event such as consumption by the patient of heartburn-inducing food or beverage, but prior to development of heartburn, is an effective means for preventing heartburn or reducing the frequency and severity of postprandial heartburn.
Applicants have also found that compositions comprising about 10 mg famotidine and between about 15 and 46 mEq acid neutralizing capacity of antacid are effective for preventing and treating heartburn symptoms.

Methods and compositions for preventing and treating heartburn


Compositions are provided comprising a balance between lysine and essential amino acids and metabolizable energy. The compositions are useful in methods to prevent or treat obesity in an animal without concomitant loss of lean muscle mass. The compositions may also be used in methods to preserve or to cause a gain in lean muscle mass in an animal in need thereof.

Animals, particularly companion animals (e.g., dogs and eats), may weigh more than their ideal body weight. Having an excess of adipose tissue, these animals may be clinically diagnosed as, e.g., "fat", "overweight", or "obese" and, as such, are more likely to suffer from associated physical disorders such as arthritis, heart disease, respiratory disease, diabetes, bladder cancer, hypothyroidism, joint disease and/or pancreatitis.
Attempts to prevent or reduce the amount of excess adipose tissue on companion animals typically include dietary restriction and exercise. Indeed, many "low" or "reduced" calorie foods for overweight companion animals have been developed and are commercially available for the control of calorie intake, prevention of weight gain or for the promotion of weight loss. One strategy in weight loss involves high protein diets with high protein to calorie ratios in order to reduce the amount of body fat in humans. A similar approach has been used in companion animal products (e.g. PRESCRIPTION DIET® FELINE M/D®, Hill's Pet Nutrition, Topeka, Kans.). High protein diets have proven to be effective in weight loss in cats; however high protein foods have had mixed results when applied to canine weight management programs. Treatment strategies also include increasing the fiber and/or protein content while reducing the fat in the food. Depending on the fiber source, the fiber can induce satiety via gut distention or through feedback mechanisms GLP-1). Fiber can be effective in reducing the digestibility of food resulting in a lower availability of high calorie nutrient components (i.e. fat and carbohydrates).
Despite the availability of such pet food formulations, however, the need remains for the development of additional formulations comprising innovative ingredients and nutrients for preventing or treating obesity in companion animals. For example, one problem with weight loss is that lean muscle mass is commonly lost as a component of total body weight loss even though it is not the target tissue. Thus, there is a need for compositions which can cause weight loss in animals without causing loss of lean muscle mass.
We have now surprisingly discovered that a weight loss composition formulated to include a specific balance of essential and limiting amino acids can cause weight loss that is characterized by a preservation or gain of lean muscle. Thus, as contemplated herein, the compositions of the present invention may be useful to prevent or treat obesity in an animal without the concomitant loss of lean muscle in the animal.
Essential amino acids are amino acids that cannot be synthesized de novo, or in sufficient quantities by an organism and thus must be supplied in the diet. Essential amino acids vary from species to species, depending upon the organism's metabolism. For example, it is generally understood that the essential amino acids for dogs and cats (and humans) are phenylalanine, leucine, methionine, lysine, isoleucine, valine, threonine, tryptophan, histidine and arginine, in addition, taurine, while technically not an amino acid but a derivative of cysteine, is an essential nutrient for cats. A balanced diet can provide all the essential amino acids, however, there are certain essential amino acids that are more critical, as a diet deficient in one of them will limit the usefulness of the others, even if the other essential amino acids are present in sufficient quantities. Generally, these limiting amino acids are methionine, cysteine, tryptophan, and lysine.

Compositions and methods for controlling the weight of animals