Disclosed is a composition of matter comprising a defined dispersion of lactoferria immobilized on a naturally occuring substrate via the N-terminus region of the lactoferrin. Compositions comprising immobilized lactoferrin (Im-LF) are used in a method for reducing the microbial contamination of a composition subject to microbial contamination, which is also disclosed, and which encompasses a method for reducing the microbial contamination of a foodstuff, such as a meat product. Foodstuffs treated by the method are disclosed, including meat products. A method of inhibiting the growth and/or adhesion of a microbial species on a food-contacting surface f a material for food packaging or food handling with Im-LF is also disclosed. Food containers and food-handling implements so treated are also disclosed, as are antimicrobial cleansers, polishes, paints, sprays, soaps, or detergents containing Im-LF for applying to an inanimate surface.

1. Field of the Invention
This invention relates to antimicrobial agents and their use.
2. Discussion of the Related Art
Antimicrobial agents are used in the treatment of infections, particularly of the gastrointestinal tract. Gastrointestinal infections affect millions of people world-wide, especially children. Infantile gastroenteritis affects more than 20 million children below twelve months age worldwide annually and considered a leading cause of mortality. Intestinal infections in children, unassociated with antibiotic use or hospital stays, can cause chronic diarrhea and failure to grow. (E.g., T. E. Liston, Clostridium difficile toxin associated with chronic diarrhea and failure to gain weight, Clin. Pediatr. (Phila.) 22(6):458-60 [1983]). Toxic shock, or bacteraemia and subsequent sepsis are other possible complications of intestinal infection. (See, e.g., P. Naaber et al., Bacterial translocation, intestinal microflora and morphological changes of intestinal mucosa in experimental models of Clostridium difficile infection, J. Med. Microbiol. 47(7):591-98 [1998]). Enterotoxigenic bacterial strains are linked with a significant number of cases of antibiotic-associated diarrhea, especially among the elderly, children, and infants. Gastrointestinal infections also pose an increasing health hazard in hospital settings.
Of course, bacteria inhabit healthy intestines to the benefit of their human and animal hosts. But pathogenic bacterial strains and opportunistic pathogens that can infect immunocompromised hosts have an adverse disease-causing effect.
Prominent agents of microbial disease include Clostridium species, especially C. difficile and C. perfringens. Clostridium species are gram-positive, spore-forming anaerobes; some strains that colonize the human intestines can, under certain circumstances, release potent protein exotoxins that induce inflammation of the intestinal mucosa. (M. L. Job and N. F. Jacobs, Jr., Drug-induced Clostridium difficile-associated disease, Drug Saf.17(1):3746 [1997]). For example, antibiotics and other chemotherapeutic agents can induce the expression of Toxins A and B from Clostridium difficile. (B. A. Cunha [1998]). Agents known to have a high potential to induce C. difficile-associated disease are aminopenicillins, cephalosporins and clindamycin. (M. L. Job and N. F. Jacobs, Jr., Drug-induced Clostridium difficile-associated disease, Drug. Saf. 17(1):37-46 [1997]; Y. Hutin et al., Prevalence of and risk factors for Clostridium difficile colonization at admission to an infectious diseases ward, Clin. Infect. Dis. 24(5):920-24 [1997]; C. D. Settle and M. H. Wilcox [1996]).
In developed countries, the great majority of cases of C. difficile infection are hospital-acquired, and the number of nosocomial clostridial infections is reported to be rising. (C. D. Settle and M. H. Wilcox, Review article: antibiotic-induced Clostridium difficile infection, Aliment. Pharmacol. Ther. 10(6): 83541[1996]; J. S. Brazier, The epidemiology and typing of Clostridium difficile, J. Antimicrob. Chemother. 41 Suppl. C: 47-57 [1998]; S. Tabaqchali and M. Wilks, Epidemiological aspects of infections caused by Bacteroides fragilis and Clostridium difficile, Eur. J. Clin. Microbiol. Infect. Dis. 11(11): 1049-57 [1992]; C. R. Clabots et al., Acquisition of Clostridium difficile by hospitalized patients: evidence for colonized new admissions as a source of infection, J. Infect. Dis. 166(3):561-67 [1992]).
A nosocomial pleural infection with C. difficile, following surgical insertion of a chest drain has also been reported (A. J. Simpson et al., Nosocomial empyema caused by Clostridium difficile, J. Clin. Pathol. 49(2):172-73 [1996]), but intestinal infections are the greatest problem.
Nosocomial diarrhea due to gastrointestinal infection with C. difficile has become a major health care problem, causing 20-30% of all nosocomial diarrheas and affecting up to 8% of hospitalized patients. (L. R. Peterson and P. J. Kelly, The role of the clinical microbiology laboratory in the management of Clostridia difficile-associated diarrhea, Infect. Dis. Clin. North Am. 7(2):277-93 [1993]). Clostridium difficile is considered to be the premier cause of diarrhea among hospitalized patients. (M. Delmee et al., Treatment of Clostridium difficile colitis. Summary of a round table held in Brussels on Mar. 3, 1994, Acta Clin. Belg. 50(2):114-116 [1995]).
In developing countries, C. difficile is also thought to be a causal agent of wide-spread acute diarrheal disease. (S. K. Niyogi et al., Prevalence of Clostridium difficile in hospitalized patients with acute diarrhea in Calcutta, J. Diarrhoeal Dis. Res. 9(1):16-19 [1991]; S. Q. Akhtar, Isolation of Clostridium difficile from diarrhea patients in Bangladesh, J. Trop. Med. Hyg. 90(4):189-92 [1987]).
Enterotoxigenic strains of C. perfringens are linked with a significant number of cases of antibiotic-associated diarrhea, especially among elderly hospitalized patients, children, and infants. (A. Wada et al., Nosocomial diarrhea in the elderly due to enterotoxigenic Clostridium perfringens, Microbiol. Immunol. 40(10):767-71 [1996]; M. M. Brett et al., Detection of Clostridium perfringens and its enterotoxin in cases of sporadic diarrhea, J. Clin. Pathol. 45(7):609-11 [1992]; S. C. Samuel et al., An investigation into Clostridium perfringens enterotoxin-associated diarrhea, J. Hosp. Infect. 18(3):219-30 [1991]; S. P. Boriello et al., Epidemiology of diarrhea caused by enterotoxigenic Clostridium perfringens, J. Med. Microbiol. 20(3):363-72 [1985]; R. Willliams et al., Diarrhoea due to entertoxigenic Clostridium perfringens: clinical features and management of a cluster of 10 cases, Age Ageing 14(5):296-302 [1985]). Clostridium perfringens has been implicated as a possible contributor to sudden infant death syndrome (SIDS) in susceptible infants. (R. R. Meer et al., Human disease associated with Clostridium perfringens enterotoxin, Rev. Environ. Contam. Toxicol. 150:75-94 [1997]).
Clostridium perfringens is well known as a causative agent of non-gastrointestinal gangrene, a special problem for many elderly and diabetic patients with poor blood circulation. But also in more extreme cases of gastrointestinal infection, C. perfringens can cause enteritis necroticans, a gangrene of the bowel resulting in necrosis, sepsis, and hemolysis, in humans and domesticated animals. (L. E. Clarke et al., Enteritis necroticans with midgut necrosis caused by Clostridium perfringens, Arch. Surg. 129(5):557-60 [1994]; D. Bueschel et al., Enterotoxigenic Clostridium perfringens type A necrotic enteritis in a foal, J. Am. Vet. Med. Assoc. 213(9):1305-07 [1998]; E. G. Pearson et al., Hemorrhagic enteritis caused by Clostridium perfringens type C in a foal, J. Am. Vet. Med. 188(11): 1309-10 [1986]; F. Al-Sheikhy and R. B. Truscott, The interaction of clostridium perfringens and its toxins in the production of necrotic enteritis of chickens, Avian Dis. 21(2):256-63 [1977]).
Although rare in developed countries, clostridial enteritis necroticans in humans is more common in some developing countries. (D. A. Watson et al., Pig-bel but no pig: enteritis necroticans acquired in Australia, Med. J. Aust. 155(1):47-50 [1991]). In New Guinea, enteritis necroticans, known locally as pigbel, has been a major cause of illness and death among children. (G. W. Lawrence et al., Impact of active immunisation against enteritis necroticans in Papua New Guinea, Lancet 336(8724):1165-67 [1990]). Clostridium perfringens type C, the etiologic agent of enteritis necroticans, was also isolated from Bangladeshis with bloody or watery diarrheal illness. (F. P. van Loon et al., Clostridium perfringens type C in bloody and watery diarrhea in Bangladesh, Trop. Geogr. Med. 42(2):123-27 [1990]).
Entertoxigenic strains of C. perfringens have also been linked to nosocomial and non-nosocomial outbreaks of food poisoning, due to heat-resistant spores and a rapid growth rate in warm food. (A. M. Pollack and P. M. Whitty, Outbreak of Clostridium perfringens food poisoning, J. Hosp. Infect. 17(3):179-86 [1991]; M. Van Darnme-Jongsten et al., Synthetic DNA probes for detection of enterotoxigenic Clostridium perfringens strains isolated from outbreaks of food poisoning, J. Clin. Microbiol. 28(1):131-33 [1990]).
Spores of Clostridium botulinum germinating in warm food can cause another form of food poisoning called botulism. Growing particularly in non-acidic foods lacking nitrites, and protected from oxygen, the vegetative cells of C. botulinum release an exotoxin that when consumed with the food is activated by trypsin in the stomach, and is absorbed intact by the blood stream. The exotoxin binds to nerve cells, preventing the release of the neurotransmitter acetylcholine. Resulting symptoms of botulism include blurred vision, difficulty in swallowing and speaking, and increasing muscular weakness, and usually nausea and vomiting. Death often results from paralysis of the muscles required for breathing. (R. Y. Stanier et al., The Microbial World, 5th ed., Prentice Hall, Englewood Cliffs, N.J., pp. 626-27 [1986]). Clostridium botulinum sometimes colonizes the intestines of infants and can cause infantile botulism, which can lead to respiratory paralysis and sudden infant death.
Botulism is a problem for the food packaging industry. Spores of C. botulinum may not be killed if canning is done at too low a temperature. High temperature autoclave treatment may be unsuitable for some foods Mayonnaise and other non-acidic foods are particularly prone to foster the growth of C. botulinum. Now with increasing health concerns about the use of nitrite as a food preservative, alternative antimicrobial agents are needed against the growth of C. botulinum and other food poisoning bacterial pathogens.
Of course, a wide variety of microbes, beside pathogenic Clostridium spp., poses problems of contamination and infection. These include bacteria such as enterotoxigenic Escherichia coli, enteropathogenic Escherichia coli, verotoxic Escherichia coli, including serotype O157:H7, Shigella dysenteriae, Shigella flexneri, Salmonella typhimurium, Salmonella abony, Salmonella dublin, Salmonella hartford, Salmonella kentucky, Salmonella panama, Salmonella pullorum, Salmonella rostock, Salmonella thompson, Salmonella virschow, Campylobacter jejuni, Aeromonas hydrophila, Staphylococcus aureus, Staphylococcus hyicus, Staphylococcus epidermidis, Staphylococcus hominis, Staphylococcus warneri, Staphylococcus xylosus, Staphylococcus chromogenes, Bacillus cereus, Bacillus subtilis, Candida albicans, and such radiation-resistant bacteria as: Brochothrix thermospacta, Bacillus pumilus, Enterococcus faecium, Deinococcus radiopugnans, Deinococcus radiodurans, Deinobacter grandis, Acinetobacter radioresistens, Methylobacterium radiotolerans, as well as other kinds of bacteria. Various pathogenic fungi, protozoa and viruses are also microbes that are often difficult to treat with known antimicrobial agents.
Antimicrobial agents with selective toxicity for a specific spectrum or range of pathogenic microorganisms are well known in the art. One class of antimicrobial agents is the antibiotics, which are compounds, synthesized and excreted by various microorganisms, that are selectively toxic to other microorganisms, specifically bacteria. In addition, some antibiotics can be artificially modified to produce antimicrobial agents that are more effective and/or more able to overcome antibiotic resistance.
Antimicrobial agents with selective toxicity for a specific spectrum or range of pathogenic microorganisms are well known in the art. One class of antimicrobial agents is the antibiotics, which are compounds, synthesized and excreted by various microorganisms, that are selectively toxic to other microorganisms, specifically bacteria. In addition, some antibiotics can be artificially modified to produce antimicrobial agents that are more effective and/or more able to overcome antibiotic resistance.
One of the most commonly used antibiotics for the treatment of gastrointestinal infections or bacterial overgrowths is vancomycin. Like many antimicrobial agents, vancomycin is prohibitively expensive, especially for developing countries, and there are concerns about the rapid development of vancomycin-resistance among pathogenic Clostridium, Enterococcus, Pediococcus, Citrobacter, Klebsiella, Enterobacter, and Staphylococcus species, because the plasmid-borne vancomycin resistance gene (VanR) is readily transmissible. (ASHP therapeutic position statement on the preferential use of metronidazole for the treatment of Clostridium difficile-associated disease, Am. J. Health Syst. Pharm. 55(13): 1407-1 [1998]; S. H. Cohen et al., Isolation of a toxin B-deficient mutant strain of Clostridium difficile in a case of recurrent C. difficile-associated diarrhea, Clin. Infect. Dis. 26(2): 1250 [1998]; C. Edlund et al., Effect of vancomycin on intestinal flora of patients who previously received antimicrobial therapy, Clin. Infect. Dis. 25(3):729-32 [1997]; C. A. O'Donovan et al., Enteric eradication of vancomycin-resistant Enterococcus faecium with oral bacitracin, Diagn. Microbiol. Infect. Dis. 18(2):105-09 [1994]; E. Yamaguchi et al., Colonization pattern of vancomycin-resistant Enterococcus faecium, Am. J. Infect. Control 22(4):202-06 [1994]; C. P. Kelly and J. T. LaMont [1998]). The phenomenon of antibiotic resistance, by no means limited to vancomycin-resistance, is an increasing public health problem.
Accordingly, there remains a definite need for a modestly priced antimicrobial agent for treating gastrointestinal and other infections, without the commonly unpleasant side effects and bacterial resistance often associated with vancomycin and other antibiotics.
Meat animals and egg laying hens often carry, among their native gastrointestinal microflora and/or within their lymph nodes, bacteria associated with food-poisoning and gastrointestinal disease in humans, for example various Salmonella species. (E.g., Letellier, A. et al., Assessment of various treatments to reduce carriage of Salmonella in swine, Can. J. Vet. Res. 64(1):27-31 [2000]). Some pathogenic bacteria, such as Salmonella enteritidis, can invade the reproductive organs of egg layers and ultimately contaminate egg contents. (E.g., Seo, K. H. et al., Combined effect of antibiotic and competitive exclusion treatment on Salmonella enteritidis fecal shedding in molted laying hens, J. Food Prot. 63(4):545-48 [2000]).
With respect to the meat, the edible tissues of a healthy meat animal are essentially sterile prior to slaughter. Various innate host defense mechanisms at the external and internal organ surfaces create an effective barrier and prevent microorganisms from invading the tissues of a live animal. As soon as the animal is slaughtered, however, the natural defenses against invading microbes virtually disappear, and the exposed tissues become highly susceptible to microbial colonization and proliferation. Meat of the freshly slaughtered animal is prone to contamination with a variety of bacterial species, influenced by the degree of sanitation practiced during the meat processing and packing operations.
The economic impact of food-borne pathogenic outbreaks and the shorter than desired shelf life of refrigerated products, even vacuum packaged refrigerated products, has necessitated the search for an effective antimicrobial system for the meat industry. The recent occurrence of verotoxic Escherichia coli (E. coli) serotype O157:H7 in ground beef causing hemolytic uremic syndrome highlighted this longstanding problem, in foods and, especially, meats. It has prompted a major review of safety issues in the food industry and a call for improved methods for preventing microbial contamination. Various methods are currently in practice to control E. coli and other microbial contamination in foods, but, unfortunately, they suffer from a variety of drawbacks.
For example, in the meat industry, acid washing of beef carcasses is currently being employed as a microbial intervention. However, recent studies have shown that certain types of E. coli, such as the verotoxic strains of serotype O157:H7 and vancomycin-resistant strains of Enterococcus faecium, can survive acid conditions, while at the same time produce harmful toxins. The meat industry is also irradiating meat in an attempt to control pathogens and food spoilage organisms. However, studies have shown that although irradiation appears to be effective at killing some types of Escherichia coli, there are still various other microorganisms, including strains of Brochothrix thermospacta and Bacillus pumilus, known to be radiation resistant and thus are able to survive such processes. Irradiation also can produce undesirable changes in the texture and/or organoleptic quality of beef. Further, both of these methods are cidal processes that kill microorganisms leaving endotoxins, microbial debris and other proinflammatory substances which can cause undesirable immunological reactions in the host. Finally, neither of these methods excludes the possibility of post-processing contamination once the beef is treated for microbial contaminants.
In addition to food-borne pathogens, microbial spoilage of packaged foods, including fresh meats and vegetable foods, is a significant concern to the food industry. Under certain conditions, it is possible to control microbes, including enteric pathogens, using such well known antimicrobial agents as acids, salts, oxidative agents, antibiotics, bacteriocins, and the like. Typically, the mode of action of these agents is "cidal"—the direct killing of the microbes, or "stasis"—the inhibition of microbial growth/multiplication. Another mode of action for conventional antimicrobial agents is opsonization. The agents intervene by promoting microbial phagocytosis by macrophages.
Certain cellular research relating to the mechanisms of microbial biosurface interactions has led to the identification of another mode of action, microbial blocking, and a new class of antimicrobial agents, microbial blocking agents (MBAs). MBAs are naturally occurring biological substances that block microbial adhesion-colonization, retard growth-multiplication, and neutralize the adverse effects of proinflammatory cell debris.
It has not proved possible to apply such microbial blocking agents during meat packing or other food processing conditions, because of the difficulty of delivering a biofunctionally active and structurally stable MBA to the food product to be treated. The difficulty is compounded when the food product is a meat product, because a controlled milieu is required for a broad-spectrum activity of MBA to block various microorganisms on a chemically complex and heterogenous meat tissue.
Breast-fed infants are better protected against various gastrointestinal infections than the formula-fed infants. Lactoferrin is one of the major antimicrobial systems in milk and colostrum and has been credited for protection of newborns against gastrointestinal illness. However, deficiency or dysfunction of lactoferrin and/or other antimicrobial systems may exist in certain breast milks depending on the nutritional and health status of feeding mothers.
Lactoferrin (LF) is an iron-binding glycoprotein present in milk and various mammalian secretions (e.g. saliva, tears, mucus, and seminal fluids). Crystallographic studies of LF indicate a bilobate structure (N-terminus and C-terminus lobes) with one iron-binding site in each lobe. LF has ability to reversibly bind two Fe3+ ions per lobe in coordination with two CO32− ions. LF can release the bound iron in a fully reversible manner, either on exposure to lowered pH (below 4.0) or on receptor binding. This high affinity for iron is linked to many of its biological functions including antimicrobial effects. Various laboratory studies have reported that the structural integrity of LF is critical for its antimicrobial effects against bacteria, fungi, protozoa, and viruses.
However, the activity of LF, like the activity of most proteins, is highly dependent on the three-dimensional or tertiary structure of the protein. If the protein does not have the proper conformation its activity is diminished or lost. LF's instability limits it usefulness. Milieu conditions such as metals (iron in particular), carbonic ions, salts, pH and conductivity affect the antimicrobial properties of LF. In addition, protein isolation procedures, storage, freezing-thawing, can adversely affect the biofunctionality of LF. Consequently, before LF can be used for commercial application, it would be expected to become denatured or inactivated, and lose its antimicrobial properties.
In fact, under certain conditions, when the LF molecule is degraded or denatured, cationic peptide fragments are generated. These cationic peptide fragments exhibit a non-specific antimicrobial activity, making them absolutely unsuitable as an ingredient in a food product. The consumer of a food product does not want to ingest a non-specific antimicrobial agent, because of the agent's adverse affect on the desirable microbes always present in a human body, particularly within the gastrointestinal tract.
Thus, an antimicrobial agent is needed for blocking microbial contamination in foods, meats and seafood in particular, on non-biological surfaces, on biological surfaces, and in biological fluids, whether in vivo or in vitro, that does not pose the undesired affects of cidal antimicrobial systems but that also exhibits carry through properties for the prevention of post-processing contamination.

Immobilized lactoferrin (Im-LF) antimicrobial agents and uses thereof


A system, method and software product for prescribing rigid body in finite element analysis is described. According to one aspect, user defines a rigid body orientation time history based on a variety of schemes including, but not limited to, direction cosine, orientation angles, Euler parameters, Rodriguez parameters, and Caley-Klein parameters. The unique combination in one of the schemes is converted to direction cosine time histories first. The direction cosine matrix can then be interpolated from either the defined or the converted direction cosine time history at each solution cycle. The time derivative of the direction cosine matrix and the resulting angular velocity matrix are calculated. The solution for the equation of motions is obtained using calculated angular velocity for each solution cycle until the simulation ends. According to another aspect, the present invention interpolates user specified rigid body orientations time history in several schemes including, piecewise linear, cubic spline.

1. Field of the Invention
The present invention generally relates to a method, system and software product used in the area of mechanical computer-aided engineering design and analysis, more particularly to method and system for prescribing rigid body orientations in finite element analysis.
2. Description of the Related Art
Finite element analysis (FEA) is a computerized method widely used in industry to model and solve engineering problems relating to complex systems such as three-dimensional non-linear structural design and analysis. FEA derives its name from the manner in which the geometry of the object under consideration is specified. With the advent of the modern digital computer, FEA has been implemented as FEA software. Basically, the FEA software is provided with a model of the geometric description and the associated material properties at each point within the model. In this model, the geometry of the system under analysis is represented by solids, shells and beams of various sizes, which are called elements. The vertices of the elements are referred to as nodes. The model is comprised of a finite number of elements, which are assigned a material name to associate with material properties. The model thus represents the physical space occupied by the object under analysis along with its immediate surroundings. The FEA software then refers to a table in which the properties (e.g., stress-strain constitutive equation, Young's modulus, Poisson's ratio, thermo-conductivity) of each material type are tabulated. Additionally, the conditions at the boundary of the object (i.e., loadings, physical constraints, etc.) are specified. In this fashion a model of the object and its environment is created.
Rigid body is defined as a body whose parts all have a fixed relationship to each other. Rigid bodies have been included in the finite element analysis software to model mechanical parts that is rigid or at least relatively rigid compared to other parts to be analyzed. However, main features of finite element analysis software have been focused on various elements (e.g., solids, shells, beams). Rigid bodies are added to complement the main features. As a result, many of the operations on the rigid bodies are approximations with assumption of small displacements. For example, to prescribe the orientation of a rigid body, the calculations are incremental based, thereby the results are incorrect for arbitrary orientations.
It is therefore desirable to have a new improved method and system for prescribing rigid body orientations in a finite element analysis.

Method and system for prescribing rigid body orientations in finite element analysis

Livermore Software Technology Corporation


Improved process for the purification and formulation of o-phthalaldehyde in which crude o-phthalaldehyde, obtained by cleavage of an acetal of o-phthalaldehyde by means of acidic hydrolysis, is, optionally by adding an aqueous basic solution, adjusted to a pH of from 1 to 8, and then, after phase separation has taken place, water is distilled off from the phase which contains the aldehyde with very short thermal stress of less than 1 minute at a pressure of between 100 mbar and atmospheric pressure and a temperature of from room temperature to 180xc2x0 C. on a thin-layer overhead evaporator and o-phthalaldehyde is then stripped off from the distillation bottom which remains with very short thermal stress of less than 1 minute at a pressure of from 0.5 to 50 mbar and a jacket temperature of from 80 to 80xc2x0 C. via a thin-layer evaporator and the resulting o-phthalaldehyde melt is pelleted at atmospheric pressure and a temperature of from 60 to 80xc2x0 C., giving pale yellow o-phthalaldehyde in high purity and storage-stable form.

Phthalaldehydes, such as o-phthalaldehyde (OPA), are used in many fields, for example as intermediates for the preparation of dyes, optical brighteners or special polymers, in the biocide or photo industry, and for the synthesis of pharmachemicals. For this reason, a number of preparation variants have already been described. Thus, o-phthalaldehyde (OPA) can, for example, be obtained according to EP-B-0 147 593 by ozonolysis of naphthalene in methanol and catalytic reduction of the resulting peroxides with subsequent extraction or crystallization. The disadvantage of this process is that the ester which forms as byproduct can only be separated off from the OPA with difficulty and inadequately.
In addition, OPA is a reactive compound which is not thermally and oxidatively stable and which, upon prolonged storage has a tendancy to block, as a result of which lengthy detachment processes are required, which may lead to discoloration of the OPA.
In order to protect the aldehyde against undesired reactions, EP-A1-0522 312 has described the option of using o-phthalaldehyde tetraalkyl acetals, prepared by electrochemical oxidation, as donor compounds.
Furthermore, EP-B-0 839 789 discloses the conversion of OPA by acid-catalyzed acetal formation with subsequent distillation into a suitable donor compound, such as, for example, into a dialkoxyphthalan or tetraalkyl acetal, from which, if necessary after complete acetal cleavage by acidic hydrolysis, crude OPA is obtained with purities of greater than 99.5%.
Since crude OPA, for example prepared in accordance with EP-B-0 839 789, however, has a red-orange color, it must then still be recrystallized following decoloration with, for example, activated carbon or tonsil.
The fine OPA powder having a melting point of 57xc2x0 C. which is obtained by crystallization likewise has a tendency to block. In addition, the different batches do not have constant color and quality.
An object of the present invention was therefore to find an improved process for the isolation and formulation of OPA, by which crude OPA can be purified in a simple and safe manner and virtually quantitatively and be converted into a storable form which does not block even after years.
Surprisingly, this object was achieved by a distillation of the crude thermally unstable o-phthalaldehyde obtained from the acetal cleavage on a thin-layer evaporator with subsequent pelleting.
Accordingly, the invention provides an improved process for the purification and formulation of o-phthalaldehyde wherein crude o-phthalaldehyde, obtained by cleavage of an acetal of o-phthalaldehyde by means of acidic hydrolysis,
a) is, optionally by adding an aqueous basic solution, adjusted to a pH of from 1 to 8, and then, after phase separation has taken place,
b) water is distilled off from the phase which contains the aldehyde with very short thermal stress of less than 1 minute at a pressure between 100 mbar and atmospheric pressure and a temperature of from room temperature to 180xc2x0 C. on a thin-layer evaporator and
c) o-phthalaldehyde is then stripped off overhead from the distillation bottom which remains with very short thermal stress of less than 1 minute at a pressure of from 0.5 to 50 mbar and a jacket temperature of from 80 to 180xc2x0 C. via a thin-layer evaporator and
d) the resulting o-phthalaldehyde melt is pelleted at atmospheric pressure and a temperature of from 60 to 80xc2x0 C.,
giving pale yellow o-phthalaldehyde in high purity and storage-stable form.
In the novel process, crude o-phthalaldehyde (OPA) is purified and converted into a storage-stable form.
The starting material used is crude OPA which is obtained by cleavage of an OPA acetal. OPA acetals, such as, for example, dialkoxyphthalans or tetraalkyl acetals, can be prepared, for example, analogously to EP-A1-0522 312 or EP-B-0 839 789. ; The cleavage of the acetals likewise takes place by the customary route, analogously to the prior art, for example by acidic hydrolysis at a pH between 0 and 7, preferably between 0 and 3 by means of mineral acids such as HCl, H2SO4, H3PO4, or organic acids, such as acetic acid, formic acid and p-toluenesulfonic or methanesulfonic acid. The reaction temperature is preferably between room temperature and 100xc2x0 C. The alcohol which is eliminated and optionally the acid is then distilled off under reduced pressure.
The resulting crude OPA to be purified has a content of more than 99.5%. According to the invention, an aqueous basic solution is then optionally added so that a pH between 1 and 8, preferably between 2 and 7, is established. Suitable bases are carbonates, such as, for example, bicarbonates or dilute hydroxide solutions, such as, for example, NaOH, KOH etc.
The aqueous basic solution is added at atmospheric pressure and at a temperature of from 40 to 95xc2x0 C., preferably from 50 to 70xc2x0 C. Phase separation then takes place, the OPA being present in the lower heavy phase which has a water content of from 0.5% to 3%, preferably 1.0 to 2%. Water is removed from the OPA-containing phase by distillation on a thin-layer evaporator with very short thermal stress by distilling off water or aqueous OPA.
Suitable thin-layer evaporators are falling-film evaporators, short-path evaporators etc. Preference is given here to using a falling-film evaporator.
The first distillation step takes place at a pressure of 100 mbar to atmospheric pressure, preferably at a pressure of from 100 to 250 mbar and particularly preferably at a pressure of from 150 to 200 mbar.
The reaction temperature here is a jacket temperature between room temperature and 180xc2x0 C., preferably between 100xc2x0 C. and 180xc2x0 C.
The residence time in the thin-layer evaporator is very short and is between 10 seconds and  less than 1 minute.
In this distillation step, water is distilled off, but in most cases some OPA is also codistilled. This aqueous OPA can be introduced in a next batch, again with pH adjustment using aqueous basic solution, so that a loss in the yield of OPA is prevented.
The material which remains is the distillation bottom which comprises the majority of brown colored OPA, with a water content of now only 0.01 to 0.4%, preferably up to 0.1%, and a content of more than 99.5%.
This distillation bottom is then subjected again to distillation with very short thermal stress on a thin-layer evaporator, OPA this time being drawn off overhead.
Suitable thin-layer evaporators here are likewise falling-film evaporators, short-path evaporators etc. Preference is given here to using a short-path evaporator. The residence time in the thin-layer evaporator is very short and is between 10 sec and  less than 1 minute.
The second distillation step takes place at a pressure of from 0.5 to 50 mbar, preferably at a pressure of from 3 to 15 mbar, and particularly preferably at a pressure of from 5 to 10 mbar.
The temperature here is a jacket temperature between 80xc2x0 C. and 180xc2x0 C.
The distillate comprises the purified, now pale yellow OPA with a content of more than 99.5%. The bottom in which, however, still relatively large amounts of OPA are also present, can be metered in in a subsequent batch to avoid losses in yield.
The distillation is then followed by pelleting at a temperature of from 60xc2x0 C. to 80xc2x0 C., preferably between 60 and 70xc2x0 C. and atmospheric pressure.
During pellet bottling, the temperature is cooled to below 30xc2x0 C.
The purification process according to the invention produces OPA in a storage-stable form which does not form clumps even after several months. In addition, OPA purified in accordance with the invention has a uniform color, while a different coloration arises in the case of OPA which is purified by crystallization. Furthermore the purification process according to the invention prevents losses in the yield of OPA.

Process for the purification and formulation of o-phthalaldehyde

DSM Fine Chemicals Austria NFG GmbH and CO KG


An electric actuator comprises a rotary driving source, a timing belt which is circled or orbited under the driving action of the rotary driving source, a slider which is displaced by the timing belt in the axial direction, and a belt-adjusting mechanism which is connected to a side surface of the slider. Both ends of the timing belt are connected to the belt-adjusting mechanism respectively. The tension of the timing belt is adjusted by rotating an adjusting screw of the belt-adjusting mechanism.

1. Field of the Invention
The present invention relates to an electric actuator comprising a driving force-transmitting belt for transmitting the rotary driving force of a rotary driving source to a slider so that the slider is moved.
2. Description of the Related Art
An electric actuator has been hitherto widely used as a means for transporting a workpiece or the like, in which a timing belt is driven by the rotary driving force of a rotary driving source such as a motor to displace a slider for transporting the workpiece.
A tension-adjusting means is provided for the timing belt of a resin material in order to adjust the tension when the timing belt is loosened during the assembling or due to the use for many years.
As the tension-adjusting means for the timing belt, for example, a pair of pulleys are used. The timing belt runs over the pulleys. The pulleys are displaced in directions to approach or separate from each other so that the tension of the timing belt is adjusted.
Further, for example, a pair of connecting members, which are connected to both ends of the timing belt, are installed to a slider. The tension of the timing belt is adjusted by making the pair of connecting members approach or separate from one another.
As shown in FIG. 25, a conventional electric actuator 1 comprises a guide rail 3 which is provided along the axis of a rectangular housing 2, and a slide block 4 which transports the workpiece by sliding along the guide rail 3.
In the housing 2, there are a driving pulley 5a which is rotated by an unillustrated rotary driving source, and a plurality of driven pulleys 5b which are arranged in the four corners of the housing 2. The driving pulley 5a is rotated by the unillustrated rotary driving source, and a timing belt 6 running over the driving pulley 5a and the driven pulleys 5b is circled or orbited by a predetermined distance. Both ends of the timing belt 6 are connected to belt attachment fixtures 7a, 7b. The belt attachment fixtures 7a, 7b are installed to the upper surface of the slide block 4 by attachment screws 8. The belt attachment fixtures 7a, 7b and the timing belt 6 are integrally connected to one another by screw members 9.
Elongate holes 11a, 11b extend in the axial direction through fastening sections 10a, 10b which are provided at upper portions of the belt attachment fixtures 7a, 7b.
A groove 12 is formed on the upper surface of the slide block 4, and the belt attachment fixtures 7a, 7b are slidably engaged with the groove 12 in the axial direction. The groove 12 is recessed by a predetermined depth on the upper surface of the slide block 4.
When the tension is applied to the timing belt 6, the attachment screws 8 to fix the belt attachment fixtures 7a, 7b to the slide block 4 are loosened, and one belt attachment fixture 7a is displaced in the direction to approach the other belt attachment fixture 7b along the groove 12 of the slide block 4. In this case, the belt attachment fixture 7a, 7b is displaced in the groove 12 along the shape of the elongate hole 11a, because the attachment screws 8 are engaged with the elongate hole 11a which extends in the axial direction.
As a result, the ends of the timing belt 6 are pulled in the directions to approach one another. Therefore, the tension of the timing belt 6 is increased. When the attachment screws 8, which are temporarily tacked to the slide block 4, are tightened to completely fix the belt attachment fixtures 7a, 7b, the adjusted tension of the timing belt 6 is retained (see, for example, Japanese Laid-Open Patent Publication No. 9-89067).
In the case of the conventional electric actuator 1 shown in FIG. 25, if the driving pulley 5a or the driven pulley 5b, over which the timing belt 6 runs, is displaced to adjust the tension of the timing belt 6, it is necessary to secure the space for displacing the driving pulley 5a or the driven pulley 5b in the axial direction. Therefore, the size or dimension of the electric actuator 1 in the axial direction is increased, and the entire electric actuator 1 is large.
In relation to the method in which the tension of the timing belt 6 is adjusted by displacing the belt attachment fixtures 7a, 7b in the axial direction, the attachment positions of the fastening sections 10a, 10b of the belt attachment fixtures 7a, 7b to be attached to the slide block 4 are offset with respect to the attachment positions of the timing belt 6 in the X-Y plane as viewed in the direction of the arrow Z. Therefore, the moments are caused by the tension of the timing belt 6, and are exerted on the belt attachment fixtures 7a, 7b in the directions (directions of the arrows Q) to pull both ends of the timing belt 6 through the fastening sections 10a, 10b. As a result, it is difficult to correctly adjust the tension of the timing belt 6.
Another method is explained in FIG. 26, for example. In this case, end blocks 13a, 13b are arranged at both ends of an operation mechanism 19. A timing belt 16, which transmits the rotary driving force supplied from a driving mechanism 14 to an operating section 15, has its ends 16a, 16b which are fixed to the end blocks 13a, 13b by fixing pieces 17a, 17b, respectively.
The ends 16a, 16b of the timing belt 16 are inserted into attachment portions of the end blocks 13a, 13b while the fixing pieces 17a, 17b are engaged with teeth of the timing belt 16. When two screw members 18a, 18b, which are screwed with each of the fixing pieces 17a, 17b, are tightened, the ends 16a, 16b of the timing belt 16 are integrally fixed to the end blocks 13a, 13b (see, for example, Japanese Laid-Open Patent Publication No. 63-134191).
In the conventional operation mechanism 19 shown in FIG. 26, the ends 16a, 16b of the timing belt 16 are fixed to the end blocks 13a, 13b by screwing the two screw members 18a, 18b into each of the fixing pieces 17a, 17b and pressing the fixing pieces 17a, 17b toward the timing belt 16.
Therefore, when attachment operation is performed for the timing belt 16, the operation is complicated to fix the timing belt 16 with the fixing pieces 17a, 17b by screwing the plurality of screw members 18a, 18b. Further, the number of parts is increased, such as the plurality of fixing screw members 18a, 18b.
When the timing belt 16 is fixed by tightening the screw members 18a, 18b, the tightening force may be changed depending on the respective operators, and the screw members 18a, 18b may be excessively tightened. Therefore, excessive pressing force may be exerted on the timing belt 16 by the fixing pieces 17a, 17b, and the durability of the timing belt 16 may be deteriorated.
On the other hand, if the tightening force is changed depending on the respective operators, and the tightening force to tighten the screw members 18a, 18b is decreased, then the timing belt 16 may be loosened. As a result, the attachment of the timing belt 16 by the fixing pieces 17a, 17b is unstable due to the difference of the tightening force depending on the respective operators.


An improved solution for verifying access to a data object. In particular, the invention automatically determines when access to the data object requires verification and provides an owner of the data object a set of current users for verification. The set of current users can include all or a subset of the users/user groups that have access to the data object. Additionally, an indication of one or more attributes of each user can be provided to the owner to assist in verification. Access information can be updated based on a response from the owner.

1. Technical Field
The invention relates generally to verifying user access to a data object, and more particularly to a solution that automatically determines when access to the data object requires verification and assists an owner of the data object in verifying the access.
2. Background Art
Many companies limit the number of users that can access a certain data object (e.g., a database, directory, file, etc.). To this extent, some companies require that the access privileges of users be periodically reviewed in order to ensure that it remains current. For example, the data object can have an associated owner that is responsible for managing it. The owner may be required to periodically (e.g., annually) verify that access privileges to the data object are current. Further, the owner may be required to maintain a history of the verifications performed for the data object.
To date, a data object owner often must remember when the access is due to be verified, and maintain his/her own records of having performed these verifications. Further, the data object owner frequently must obtain information from various sources in order to perform the verification. For example, the data object owner may first need to determine all users that currently have access rights, and then determine which users, if any, have left the company, changed jobs/divisions, etc. In some cases, the data object owner may not have ready access to the necessary information, thereby requiring assistance from co-workers and delay in completing the verification. As a result, access verification is frequently a time consuming, tedious task that frequently fails to be consistently and reliably performed.
Some solutions have been proposed to automate this process. For example, user access rights can be compared to an employee directory, and those that do not appear in the employee directory can be automatically purged. However, these solutions often unintentionally remove the access rights for some users. For example, a user can be created that is shared by a group of people (e.g., "guest"), that is associated with a non-employee, etc. Therefore, it is often necessary to maintain some human oversight of the verification process.
As a result, a need exists for an improved solution for verifying access to a data object. In particular, a need exists for a method, system and program product that automatically determine whether access to the data object requires verification, and provides an owner of the data object with a set of current users that have access to the data object. The set of current users can include attribute information obtained from an employee database or the like to assist the owner in verifying the access rights.

Method, system and program product for verifying access to a data object

International Business Machines Corporation


A bottle fraud system and method encapsulates a wireless communication tag into a bottle to ensure the authenticity of the bottle. The tag stores information about the bottle. The tag is physically integrated into a bottle stopper through encapsulation by multiple layers of a polymer film and a wax composition. The physical condition to the bottle stopper or the layers serves as an indication of whether tampering has occurred. The information in the tag is accessible through a reading device. The reading device communicates with a database that stores information about the bottle and analyzes the probability of fraud with an algorithm. The algorithm analyzes the information about the bottle, such as shipping history, contents and location, to predict whether fraud is likely. Thus, both the physical condition of the bottle, and the predictive capacity of the algorithm help detect fraud on the bottle.

The following background information may present examples of specific aspects of the prior art (e.g., without limitation, approaches, facts, or common wisdom) that, while expected to be helpful to further educate the reader as to additional aspects of the prior art, is not to be construed as limiting the present invention, or any embodiments thereof, to anything stated or implied therein or inferred thereupon.
However, there are alternative wine closures are substitute closures used in the wine industry for sealing wine bottles in place of traditional cork closures. These synthetic corks are made from plastic compounds designed to look and "pop" like natural cork, but without the risk of TCA contamination The following is an example of a specific aspect in the prior art that, while expected to be helpful to further educate the reader as to additional aspects of the prior art, is not to be construed as limiting the present invention, or any embodiments thereof, to anything stated or implied therein or inferred thereupon.
By way of educational background, another aspect of the prior art generally useful to be aware of is that wine and related types of beverages are most often packaged in glass bottles and depending on the kind or quality of the wine, the bottles are sealed with a cork. Some wines, e.g. Champagnes, are corked with stoppers having enlarged heads and which can be grasped and twisted. However the majority of red, white and rose wines are "corked" with stoppers made out of cork which is recessed in the neck of the bottle requiring some implement such as a corkscrew to extract the cork. Though there are other wines that are bottle packaged with "screw tops" and movement in this direction is obviously predicated to some extent on meeting consumer's demands for packaging which is easily opened without the necessity of additional equipment.
In many instances, wine fraud is a form of fraud in which the wine bottle is molested to change either the wine, or the bottle itself. The wines can be adulterated, usually with the addition of cheaper products such as juices and sometimes with the addition of harmful chemicals and sweeteners to compensate in color or flavor. Another form, is the substitution of labels, with cheap poor quality products sold under the labels of more expensive better wines. It is known that Federal governments and individual producers have taken many efforts in order to curb the prevalence of wine fraud. Some examples include marking bottles with engraved serial numbers on the glass and taking more control of the distribution process of their wines. Better documentation of the wine bottles can also help reduce wine fraud. However, for older vintages, the threat of fraud persists.
It is well known that a bottle stopper, especially for wine, is generally made from cork, which is an impermeable, buoyant material. Because of its impermeability, buoyancy, elasticity and fire retardant, cork is used in a variety of products, the most common of which is for wine stoppers. It is significant to note that both types of bottle stoppers may have other components and materials integrated therein.
Near-field communication (NFC) is a type of radio frequency communication technology, operating at about 13.56 MHz and at bandwidth of about 2 MHz, which allows for read-only and read-write communications between a NFC-enabled RF tag reader and a NFC-enabled tag. NFC operation is based on inductive coupling between two loop antennas, which allows for sharing of power and data between NFC-enabled devices.
Even though the above cited methods for detecting wine fraud address some of the needs of the market, a bottle fraud detection system and method that integrates a wireless communication device tag into a bottle cork, and then tracks and analyzes information from the tag to predict fraud is still desired.

Bottle fraud detection system and method


Novel compounds useful in the treatment of, prevention of or protection against diseases and/or conditions related to metabolic syndrome and lipid metabolism, especially diseases of fatty acid and cholesterol metabolism, such as those mediated by stearoyl-CoA desaturase, are disclosed along with methods of employing said compounds for such uses.

Acyl desaturase enzymes catalyze the formation of double bonds in fatty acids derived from either dietary sources or de novo synthesis in the liver. Mammals synthesize at least three fatty acid desaturases of differing chain length specificity that catalyze the addition of double bonds at the Δ9, Δ6, and Δ5 positions. Stearoyl-CoA desaturases (SCDs) introduce a double bond in the Δ9-position of saturated fatty acids. The preferred substrates are palmitoyl-CoA (16:0) and stearoyl-CoA (18:0), which are converted to palmitoleoyl-CoA (16:1) and oleoyl-CoA (18:1), respectively. The resulting mono-unsaturated fatty acids are substrates for incorporation into phospholipids, triglycerides, and cholesteryl esters.
A number of mammalian SCD genes have been cloned. For example, two genes have been cloned from rat (SCD1, SCD2) and four SCD genes have been isolated from mouse (SCD1, 2, 3, and 4). A single SCD gene, SCD1, has been characterized in humans. A second human SCD isoform has recently been identified, and because it bears little sequence homology to alternate mouse or rat isoforms it has been named human SCD5 or hSCD5. (See WO 02/26944 of Brownlie).
While the basic biochemical role of SCD has been known in rats and mice since the 1970's (Jeffcoat R. and James, A T. Elsevier Science, 4: 85-112 (1984); de Antueno, R J. Lipids 28(4)285-290 (1993)), it has only recently been directly implicated in human disease processes. Thus, an SCD1 enzyme highly useful in such studies has been identified and is further described in Brownlie et al, WO 01/62954 (30 Aug. 2001), the disclosure of which is hereby incorporated by reference in its entirety.
A number of mechanisms for the inhibition or modulation of SCD activity are available to suggest a means of approaching the rational design of SCD-modulating agents. Among these are the following, each of which serves to identify a specific mechanistic class of compound. One class of compounds includes those inhibitors that effectively inhibit SCD1 expression. This are believed to include putative PPAR agonists, such as thiazolidinedione compounds, and certain polyunsaturated fatty acids. A leading thiazolidinedione, troglitazone, has recently been withdrawn from human clinical use having been found to have an undesirable toxicity profile.
A second class of SCD inhibitors includes those inhibitors that effectively inhibit SCD1 enzymatic activity directly. Known examples include thia-fatty acids, cyclopropenoid fatty acids, and certain conjugated linoleic acid isomers. Specifically, Cis-12, trans-10 conjugated linoleic acid is known to effectively inhibit SCD enzyme activity and reduce the abundance of SCD1 mRNA while Cis-9, trans-11 conjugated linoleic acid does not. Cyclopropenoid fatty acids, such as those found in stercula and cotton seeds, are also known to inhibit SCD activity. For example, sterculic acid (8-(2-octyl-cyclopropenyl)octanoic acid) and Malvalic acid (7-(2-octyl-cyclopropenyl)heptanoic acid) are C18 and C16 derivatives of sterculoyl- and malvaloyl fatty acids, respectively, having cyclopropene rings at their Δ9 position. These agents inhibit SCD activity by inhibiting Δ9 desaturation. Other agents include thia-fatty acids, such as 9-thiastearic acid (also called 8-nonylthiooctanoic acid) and other fatty acids with a sulfoxy moiety.
Finally, the third class of inhibitors includes those agents that are capable of interfering with the proteins essential to the desaturase system, such as those agents that interfere with cytochrome b5, NADH (P)-cytochrome b5 reductase, and terminal cyanide-sensitive desaturase. This latter group of compounds may well be toxic and therefore of little use.
The known modulators of delta-9 desaturase activity are either not useful for treating the diseases and disorders linked to SCD1 biological activity as claimed in this invention, or else they are otherwise unsatisfactory therapeutic agents. The thia-fatty acids, conjugated linoleic acids and cyclopropene fatty acids (malvalic acid and sterculic acid) are neither useful at reasonable physiological doses, nor are they specific inhibitors of SCD1 biological activity, rather they demonstrate cross inhibition of other desaturases, in particular the delta-5 and delta-6 desaturases by the cyclopropene fatty acids. In some cases, it is preferred to identify compounds which inhibit SCD specifically and do not cross inhibit delta-5 desaturase and/or delta-6 desaturase.
Using such methodology, new classes of compounds have been identified and disclosed herein that are useful in modulating SCD activity and thereby regulating lipid levels, especially plasma lipid levels.

This patent is subject to a terminal disclaimer.

Pyridylpiperazines and aminonicotinamides and their use as therapeutic agents


The present disclosure relates to systems, non-transitory computer-readable media, and methods for implementing asymmetric cryptography for digital rights licensing during system disruptions. In particular embodiments, the disclosed systems transmit, to a licensing device that issues digital licenses, a digital communication indicating a system outage of an identity server that verifies digital licenses of client devices. Based on the digital communication, the disclosed systems call a monitoring device using a licensing device identifier. In response to the call, one or more embodiments of the disclosed systems use the monitoring device to encrypt and transmit a verification token back to the licensing device. In certain implementations, the disclosed systems then verify the system outage by decrypting the encrypted verification token and validating a corresponding digital signature. Upon validation, the disclosed systems can trigger a failover mechanism for issuing a grace digital license to one or more client devices during the system outage.

Recent years have seen increased adoption of software applications that utilize security and authentication protocols implemented across computer networks. For example, conventional verification systems utilize remote servers to issue and authenticate digital licenses for user devices to access and run software applications. Although conventional systems can implement digital software licenses protocols across computer networks, a number of problems exist with conventional verification systems. For example, during system disruptions, conventional systems are prone to deceptive digital communications that lead to insecure digital rights licensing and/or limited flexibility that inhibits user devices from efficiently accessing software applications.

Utilizing encrypted digital communications to dynamically secure digital rights licensing during authentication system disruptions


Disclosed are a nicotinic acid or isonicotinic acid compound and a use thereof. The compound is the compound shown in Formula I, or a pharmaceutically acceptable salt, ester or solvate thereof. Efficacy tests demonstrate that the nicotinic acid compound can inhibit botulinum toxin endopeptidase activity in vitro, and has a significant protective effect on mice poisoned with botulinum toxin. On this basis, the compound may be used to prepare a drug preventing and/or treating botulinum toxin exposure and/or poisoning.

Toxins of Clostridium species comprise botulinum neurotoxins and tetanus toxins. The tetanus toxins are produced by Clostridium tetani under an anaerobic environment and can clinically cause tetanus. Clostridium botulinum neurotoxins (referred to as botulinum toxins for short) is a group of known proteins (including types A-G) which have strongest toxicity and are mainly produced by Clostridium botulinum under an anaerobic environment, with a median lethal dose of about 1 ng/kg for intravenous injection and a median lethal dose of about 3 ng/kg for inhalation. Common poisoning by botulinum toxins is mainly caused by consumption of contaminated food, introduction of toxins produced by infected wound into the body, and production of active toxins from toxin precursors through digestion in baby's intestinal tract. In addition, botulinum toxin type A has been widely used in the clinical treatment of dysfunction of cholinergic nerves and muscles, as well as in cosmetic wrinkle removal, which may cause the occurrence of systemic botulism symptoms due to overdose, misuse, and/or adverse reactions during the treatment. The incubation period of botulism is short, the course of disease is developing rapidly, the condition is serious, and the mortality rate is high. Human botulism is mainly caused by types A, B, E, and F, while type A has the strongest neurotoxicity to humans. The drugs currently used for prevention and treatment of botulism and tetanus are (type) specific anti-toxin horse serum, which can be effective for more than 80% of poisoned patients. However, these drugs have evident side effects, and it is reported clinically that serum sickness and allergic reactions occur in about 9% of clinical cases (Black R E, et al. Am J Med, 1980, 69: 567-570), which severely limits the use of horse serum antitoxins. There is an urgent need to find novel drugs which are safer and more effective.
Tetanus and botulism have a similar pathogenic process, in which C-terminus of the heavy chain of the toxin binds to ganglioside on the membrane of nerve cells, and the structure of the toxin is rearranged under the acidic environment to promote entrance of N-terminus of the heavy chain into the membrane and the unfolding of the light chain which, after the disulfide bond is reduced, is introduced into the cell as a zinc ion metalloenzyme to catalyze the cleavage of a class of intracellular substrate proteins (botulinum neurotoxins types A and E act on the synaptosome-associated protein SNAP-25, botulinum neurotoxins types B, D, F, G and tetanus toxin act on synaptic vesicle-associated membrane protein VAMP), thereby affecting the transfer of acetylcholine, interfering with the transmission of nerve impulses, and thus causing paralysis or excitation of motor nerves. If one or more of the 3 aspects including binding, introduction and catalysis are inhibited or hindered, the neurotoxicity of the toxin can be effectively inhibited. The design and development of catalytic inhibitors targeting the light chain of the toxin that has an enzymatic activity have become a research hotspot in recent years. Harry B et al. found 30 non-subtype inhibitors by in vitro high-throughput screening of natural extracts of plants, marine tissues, and fungi that can inhibit the toxins of Clostridium species, of which 5 extracts can inhibit both Botulinum toxins types B and E. Smith L A et al. found in 2009 that quinolinol derivative CB7969312 is a potential inhibitor that effectively neutralizes the toxicity of botulinum toxin type A to N2a cells by binding to the Zn catalytic region in the large hydrophobic pocket of the active site in light chain of the botulinum toxin type A (Roxas-Duncan, V, et al. Agents Chemother. 2009, 53:3478-3486; Pang, Y.-P. et al. PLos One 2009, 4, e7730). Janda K D et al. found in 2010 that lomofungin is able to inhibit the light chain of the botulinum toxin type A (Ki value of 6.7±0.7 uM), showing a typical non-competitive kinetics (Eubanks, L. M., et al. ACS Med. Chem. Lett. 2010, 1:268-272). These natural products or compounds reported have an inhibitory effect on the light chain of the toxin in vitro, and some natural products or compounds also have an inhibitory effect at the level of overall toxins and animal models, but there is still possibility for improvement in activity. In addition, most of the compounds reported so far have a type-specific toxin-inhibiting activity, and the cross-inhibition effect needs to be improved. Therefore, it is necessary to study and develop novel natural products or active compounds, which can have a wider range of in vitro inhibition and antagonism against Clostridium neurotoxins (multiple types of botulinum toxin and tetanus toxin), and can show a high anti-toxic activity at the level of overall animals, and from which to develop new therapeutic drugs.

Nicotinic acid or isonicotinic acid compound and use thereof


An intake apparatus of an internal combustion engine for a vehicle comprises a duct for taking into a wind during a running of a vehicle, an air cleaner operatively connected to the duct, a fuel supply device for injecting a fuel into an intake air coming from the air cleaner, a movable valve arranged between an outlet port of the duct and an inlet port of the air cleaner, a negative-pressure motor for driving the movable valve, and an electronic control unit for controlling the movable valve. The electronic control unit is connected to an ignition means, and the electronic control unit controls the opening and closing of the movable valve in accordance with a rotational speed of an internal combustion engine, an opening degree of a throttle of the engine and a gear position of the engine as control parameters and carries out a delay angular control of an ignition timing in response to the opening and closing control of the movable valve.

The present invention relates to an intake apparatus of an internal combustion engine for a vehicle such as motorcycle and, more particularly, to an intake apparatus having an opening and closing portion of the butterfly type structure arranged at a suction port of an air cleaner.
Conventionally, in an air cleaner arranged on the intake side of an internal combustion engine, there has been known a technology for controlling the opening and closing of a suction port of the air cleaner so as to change an air intake condition of the internal combustion engine.
First, such a technology is disclosed in the Japanese Utility Model Publication No. SHO 59-13333. In the technology of this publication, a movable member for opening and closing the suction port is actuated by means of a negative-pressure motor in accordance with an engine rotational speed to attain the improving of fuel consumption and the increasing of an output power of the internal combustion engine.
Further, in the above-mentioned technology, there have been also known a diaphragm type, a rod type and a valve type ones adapted to open and close an intake passage, which are disclosed in the Japanese Utility Model Publication No. SHO 58-51409. That is, in the technology of this publication, a diaphragm is moved in accordance with a change of a negative pressure on the downstream side of an engine throttle valve and a valve is opened and closed by means of a negative pressure motor through a rod in accordance with that movement to reduce a suction noise.
Furthermore, the above-mentioned technology is also disclosed in the Japanese Patent Laid-open Publication No. SHO 63-239350, in which a shutter is arranged at an opening portion of an air cleaner and the opening and closing of the shutter are controlled by an electronic control unit (ECU) depending on factors representing a running condition of an internal combustion engine so as to adequately control a fuel-air ratio.
In such prior arts, however, although an area of the suction port of the air cleaner is variable in accordance with the rotational speed of the engine, a variation of an output power of the internal combustion engine is large because the area of the suction port is controlled suddenly by the ON/OFF operations of the negative-pressure motor (i.e. diaphragm) due to the characteristics thereof.
Especially, when the suction port is changed over from a small opening area to a large opening area, an increase of the output power is so large that a riding feeling happens to be affected badly.
In the case of the ECU controlling like in the last mentioned prior art, since only the rotational speed of the engine is used as the control parameter and other informations are not employed, it is impossible to carry out fine control.

Intake apparatus of internal combustion engine


A method for executing a computer program on computing hardware, e.g., on a microprocessor, is provided, the computer program including multiple program objects and errors being detected in the method while running the computer program on the computing hardware. The program objects are subdivided into at least two classes, and multiple program objects are executed during one run, program objects of the first class being repeated when an error is detected and, when an error is detected in one program object of the first class, which has already been sent for execution, this program object of the first class is restarted instead of a program object of the second class after the other program objects of the first class of a run.

1. Field of the Invention
The present invention relates to a method for executing a computer program on computing hardware, e.g., on a microprocessor, which computer program includes multiple program objects, in which method errors are detected during the running of the computer program on the computing hardware. The present invention also relates to an operating system capable of running on computing hardware, e.g., on a microprocessor. The present invention also relates to a computing hardware for running a computer program including multiple program objects, which computing hardware has an error detection mechanism for detecting an error during the running of the computer program on the computing hardware.
2. Description of Related Art
So-called transient errors may occur in running a computer program on computing hardware. Since the structures on semiconductor modules (so-called chips) are becoming progressively smaller, but the clock rates of the signals are becoming progressively higher and the signal voltages are becoming progressively lower, there is an increased incidence of transient errors. Transient errors occur only temporarily, in contrast with permanent errors, and usually disappear spontaneously after a period of time. In transient errors, only individual bits are faulty and there is no permanent damage to the computing hardware. Transient errors may have various causes such as electromagnetic influences, alpha-particles or neutrons.
The emphasis in error handling in communications systems is even presently on transient errors. It is known that when an error is detected in communications systems (e.g., in a controller area network, CAN), the erroneously transmitted data are resent. Furthermore, the use of an error counter is known in communications systems, which is incremented on detection of an error, is decremented when there is a correct transmission, and prevents transmission of data as soon as it exceeds a certain value.
In the case of computing hardware for running computer programs, however, error handling is performed essentially only for permanent errors. Taking transient errors into account is limited to incrementing and, if necessary, decrementing an error counter. This counter reading is stored in a memory and may be read out off-line, i.e., as diagnostic or error information during a visit to a repair shop, e.g., in the case of computing hardware designed as a vehicle control unit. Only then is it possible to respond appropriately to the error.
Error handling via error counters thus, on the one hand, does not allow error handling within a short error tolerance time, which is necessary in particular for safety-relevant systems, and also, on the other hand, does not allow constructive error handling in the sense that the computer program is being run again properly within the error tolerance time. Instead, in the related art, the computer program is switched to emergency operation after exceeding a certain value on the error counter. This means that a different part of the computer program is run instead of the part containing the error, and the substitute values determined in this way are used for further computation. The substitute values may be modeled on the basis of other quantities, for example. Alternatively, the results calculated using the part of the computer program containing the error may be discarded as defective and replaced by standard values that are provided for emergency operation for further calculation. The known methods for handling a transient error of a computer program running on computing hardware thus do not allow any systematic constructive handling of the transient nature of most errors.
It is also known in the art that transient errors occurring in running a computer program on computing hardware may be eliminated by completely restarting the computing hardware. This approach is also not actually satisfactory, because quantities obtained in processing of the computer program to that point are lost and the computing hardware is unable to fulfill its intended function for the duration of the restart. This is unacceptable in the case of safety-relevant systems in particular.
Finally, it is also known that, for error handling for transient errors of a computer program run on computing hardware, the computer program may be set back by a few clock pulses and individual machine instructions of the computer program may be repeated. This method is also known as micro-rollback. With the known method, the system only returns by objects on a machine level (clock pulses, machine instructions). This requires appropriate hardware support on a machine level, which is associated with a considerable complexity in the area of the computing hardware. It is impossible for the known method to be executed exclusively under software control.
The error handling mechanisms known in the art are unable to respond in a suitable manner to transient errors occurring in running a computer program on computing hardware.
However, transient errors are especially frequent in future technologies. If they are detected, e.g., via dual core mechanisms, the question of error localization still remains to be answered in order to identify the correct result. This is true even more so if one has the goal that a transient error does not always result in restarting the computer. As described, error localization can typically only be achieved via comparatively complex methods.

Restarting an errored object of a first class


A method for delivery of a tool into a submerged bore includes controlling the movement of a tool delivery device in the pool by operating at least one propulsion drive located on the tool delivery device. The tool delivery device is coupled to an inlet to the bore and a tool is inserted from the tool delivery device through the inlet and into the bore.

Bores such as pipes or cylindrically shaped equipment are often submerged in a pool of water or other liquid. There is often a need to have a maintenance tool or inspection probe delivered into the submerged bore. For example, a reactor pressure vessel (RPV) of a boiling water reactor (BWR) typically has submerged bores that need to be inspected during maintenance routines. Hollow tubular jet pumps having internal bores are positioned within an annulus to provide the required reactor core water flow. The jet pump includes an upper portion, known as the inlet mixer, and a lower portion, known as the diffuser. The inlet mixer and the diffuser, due to their large size, are formed by welding a plurality of cylindrical and conical sections together. Specifically, respective ends of adjacent cylindrical sections are joined with a circumferential weld. During operation of the reactor, the circumferential weld joints may experience inter-granular stress corrosion cracking (IGSCC) and irradiation assisted stress corrosion cracking (IASCC) in weld heat affected zones which can diminish the structural integrity of the jet pump.
It is important to examine the welds of the jet pump inlet mixer and diffuser periodically to determine whether any cracking has occurred. While examinations in the annulus or region between a shroud and a pressure vessel wall can be performed, these examinations are likely to be only partial inspections due to access limitations in the annular region of the reactor. As such, the examination of the jet pump welds are often examined by an inspection tool positioned inside of the jet pump inlet mixer and jet pump diffuser. Such inspection tool performs ultrasonic and/or eddy current examinations of jet pump welds from inside the jet pump inlet mixer and diffuser in a nuclear reactor.
Typically, operational personnel located on a refuel bridge above the surface of the pool manipulate poles and other mechanical suspension devices to position a funnel to the inlet mixer of each jet pump to be inspected. For a single BWR, there can be up to 20 jet pumps and therefore 20 funnels must be attached and/or relocated during the operation. Once a funnel is positioned at the inlet of a jet pump inlet, the funnel is clamped to the inlet using another handling pole. As the inlet to the jet pumps are submerged, often up to 50 feet under the surface of the pool, the manual manipulation of these poles and the funnel is difficult and time consuming. After a funnel is attached to a jet pump inlet, a mechanical tool delivery device is placed in the pool. Typically, the tool delivery system is placed into the pool using an overhead crane and is then transferred to a monorail hoist on the refuel bridge. The tool delivery system is then lowered onto a head stud or top flange at the top of the open reactor pressure vessel RPV. The tool delivery system is placed between two adjacent jet pumps such that the position can be used to inspect both without having to move the tool delivery system. The tool delivery system is connected to the funnel with a locating cone and requires that one of the operators mate the cone, which is attached to a flexible arm on the lower portion of the tool delivery system, with the funnel. The arm must be manually manipulated by the operator from the refuel bridge using a rope to lower the tool delivery system until the cone is mated with the funnel.
After the tool delivery system is mated with the funnel, the inspection tool or probe is inserted into each of the funnel and the jet pump inlets to perform the inspection of the inside of the jet pump assembly. Once the first adjacent jet pump is inspected, the tool delivery system is disconnected from the first funnel and moved to the second funnel and the attachment, insertion, and inspection operations are repeated. The tool delivery system must be detached from the head stud or top flange for the first two jet pumps and manually moved to a position that is between two other jet pumps to be inspected. This manual process is repeated until all jet pumps have been inspected. Often the operator will utilize at least one submerged camera to aid in the movement, manipulation, attachment, and detachment of the submerged components.
In other systems and methods, a probe driver assembly can be located at the upper-most level of the probe outside of the jet pump diffuser. Such a probe driver assembly provides for axial movement of the inserted probe by using a take-up reel and a set of pinch wheels to raise and lower the probe head. However, such systems are difficult to position and require considerable operator involvement and still require manual placement on each jet pump.
As such, all of the current systems and methods require manual manipulation by poles to attach, move and operate submerged tools. These processes often require more than one operator. As such, current systems and methods for inspecting the inside of a submerged bore such as a nuclear reactor jet pump that can be submerged 50 feet below the surface of a water pool are difficult, time consuming, and costly. Often such tasks become a critical path item during a nuclear reactor reloading process. As such, any opportunity for reducing the required time can decrease the amount of off-line or down-time of the reactor and therefore provide significant cost savings to the reactor operator.

Method of delivering a tool into a submerged bore


A coupling structure for grinding members adopts a removable structure to fasten a grinding member to a pneumatic tool. One or more grinding member may be mounted on the coupling structure according to requirements. The coupling structure may be used repeatedly to reduce costs.

The common pneumatic tool aims to provide a driving force through a pneumatic motor to rotate a spindle and drive a grinding member coupled on a distal end of the spindle to perform grinding operation. Refer to FIG. 1 for a conventional grinding member 10 which is coupled with a fastening element 11 in an integrated manner. The fastening element 11 has a screw thread 12 on a distal end to be fastened to a coupling head 22 of a pneumatic tool 20.
As the grinding member 10 and the fastening element 11 are fabricated in an integrated manner, when the grinding member 10 has been used for a period of time and has to be replaced, the fastening element 11 also is discarded. This results in an extra cost. Moreover, with the grinding member 10 and the fastening element 11 formed in an integrated manner, the number of the grinding member 10 is fixed and cannot be increased to meet the actual requirements. The overall practicality is lower.


The present invention relates to a semiconductor device; and, more particularly, to a power-on reset circuit to produce a stable reset signal irrespective of driving speed of a power-on signal which is applied thereto at the time of its initial chip operation. The power-on reset circuit according to the present invention comprises an input unit receiving the power-on signal from an external circuit; a schmitt trigger inverter including an output node, wherein a voltage level at the output node is toggled from a high voltage level signal to a low voltage level signal before an output signal from the input unit increases up to a desired voltage level; and an output unit coupled to the output node for generating the power-on reset signal in response to the voltage level at the output node.

The present invention relates to a semiconductor device; and, more particularly, to a power-on reset circuit to produce a stable reset signal irrespective of driving speed of a power-on signal which is applied thereto at the time of its initial chip operation.
Generally, in case where a reset signal for initializing a chip is inputted through an external pin, an additional pin makes the chip go up in price. Accordingly, instead of using an additional reset pin, a circuit to generate a reset signal automatically, whenever the power is inputted into the chip, should be included in the chip itself. This circuit is called a power-on reset circuit.
FIG. 1 is a block diagram illustrating a conventional power-on reset circuit. As shown in FIG. 1, the conventional power-on reset circuit includes an input unit 110 receiving a power-on signal and outputting toggled pulse signals and a schmitt trigger 130 outputting a power-on reset signal in response to an output signal from the input unit 110.
The input unit 110 includes a capacitor C11 between an input pad of the power-on signal and node N11, an NMOS transistor NM11 which has a gate connected to node N11, a drain connected to node N11 and a source connected to a ground voltage level, a PMOS transistor PM11 which has a gate connected to node N11, a source connected to the input pad of the power-on signal and a drain connected to an output node N12, and a capacitor C12 coupled between the output node N12 and the ground voltage level.
The schmitt trigger 130 includes a schmitt trigger inverter 131 and an inverter INV11. Two PMOS transistors PM13 and PM14 are in series connected to each other and also two NMOS transistors NM13 and NM14 are in series connected to each other. Gates of these transistors PM13, PM14, NM13 and NM14 are coupled to the output node N12. A source of the PMOS transistor PM13 is connected to the input pad of the power-on signal and a drain of the PMOS transistor PM14 is connected to node N13. Accordingly, the power-on signal is transferred to node N13 in response to a voltage level at node N12. Also, a drain of the NMOS transistor NM13 is connected to the drain of the PMOS transistor PM14 and the source of the NMOS transistor NM14 is connected to the ground voltage level. A PMOS transistor PM15 in the schmitt trigger inverter 131 is coupled between the ground voltage level and a drain of the PMOS transistor PM13 and its gate is connected to node N13. Also, an NMOS transistor NM15 in the schmitt trigger inverter 131 is coupled between the source of the PMOS transistor PM13 and the source of the NMOS transistor NM13 and its gate is connected to node N13 which provides an input for the inverter INV11.
FIG. 3A is a voltage wave form of the conventional schmitt trigger in FIG. 1 and FIG. 3B is a hysteresis loop illustrating voltage transfer characteristics for the conventional schmitt trigger in FIG. 1.
Referring to FIG. 3A, the schmitt trigger inverter inverts the input signal VIN, by using a first voltage level VID as a reference voltage level for determining a high voltage level and a second voltage level VIU as a reference voltage level for determining a low voltage level. As a result, in case where the input signal VIN is larger than the first voltage level VID, the input signal VIN is considered as a high voltage level and, in case where the input signal VIN is smaller than the second voltage level VIU, the input signal VIN is considered as a low voltage level. Accordingly, when the input signal VIN is between the first voltage level VID and the second voltage level VIU, the schmitt trigger inverter may not positively work as an inverter. Accordingly, the schmitt trigger inverter doesn""t have an effect on its output in case where there is a voltage variation between the first voltage level VID and the second voltage level VIU based on a glitch which is caused by a sudden increases in the supply of electric power.
Also, as shown in FIG. 3B, in case where the input signal VIN is in the vicinity of the first voltage level VID and the second voltage level VIU, the schmitt trigger inverter produces a dramatically inverted output signal irrespective of transition time of the input signal VIN. As set forth above, the schmitt trigger inverter has been used in improving the transition of the slow signal and in removing an input noise. Referring again to FIG. 1, when the activated power-on signal is applied to the capacitor C11, a potential at node N11 rapidly increases in response to the power-on signal. Accordingly, the NMOS transistor NM11 is turned on, node N11 gradually goes into a pull-down mode, and then finally, the NMOS transistor NM11 may be turned off. When the PMOS transistor PM11 is turned on with the pull-down operation at node N11, the capacitor C12 is charged and the output node N12 of the input unit 110 is in a pull-up mode in such a way as to toggle the voltage level of the output node N12. After the output node N12 in the input unit 110 is toggled once, node N11 gradually goes into a pull-up mode and the PMOS transistor PM11 is turned on and the output node N12 goes into a pull-down mode. Namely, the output node N12 of the input unit 110, as an input signal of the schmitt trigger 130, gradually goes from xe2x80x9clow voltage levelxe2x80x9d to xe2x80x9chigh voltage levelxe2x80x9d or from xe2x80x9chigh voltage levelxe2x80x9d to xe2x80x9clow voltage levelxe2x80x9d.
If the output node N12 of the input unit 110 gradually goes from xe2x80x9clow voltage levelxe2x80x9d to xe2x80x9chigh voltage level,xe2x80x9d the schmitt trigger inverter 131 outputs an inverted low voltage level signal at the time when the input signal is higher than the first voltage level VID and, when the output node N12 of the input unit 110 gradually goes from xe2x80x9chigh voltage levelxe2x80x9d to xe2x80x9clow voltage levelxe2x80x9d and when the input signal is lower than the second voltage level VIU, the schmitt trigger inverter 131 outputs a toggled output signal from xe2x80x9chigh voltage levelxe2x80x9d to xe2x80x9clow voltage level.
FIG. 2 is a block diagram illustrating another conventional power-on reset circuit. The power-on reset circuit in FIG. 2 includes an input unit 210 to produce toggled signals in response to power-on signal, a schmitt trigger inverter 231 outputting a power-on reset signal in response to the toggled signals and a feed-back loop 270 feeding back an output signal of the schmitt trigger inverter 231 to the input unit 210.
The input unit 210 has a PMOS transistor PM21, an NMOS transistor NM21 and a capacitor C21. The PMOS transistor PM21 receives an voltage level at node N20 through its gate and transfers a power-on signal to a node 21. The NMOS transistor NM21 receives an voltage level at node N20 through its gate and transfers a ground voltage level to the node 21. Also, the capacitor C21, which is a MOS transistor having source and drain connected to a ground voltage level, is connected to the node 21. A schmitt trigger inverter 231 is the same as that (the reference numeral 131) in FIG. 1. An output unit 250 connected to an output terminal (node N23) of the schmitt trigger inverter 231 latches and buffers an output signal of the schmitt trigger inverter 231, having a plurality of inverters INV21 to INV25. Further, the feed-back loop 270 includes an inverter INV28 inverting a signal at node N20, an NAND gate ND27 receiving output signals from the inverter INV28 and the schmitt trigger inverter 231, and inverters INV26 and INV27 for buffering an output signal of the NAND gate ND27.
When the power-on signal is activated, the PMOS transistor PM21 is turned on by a low voltage level which is inputted into node N20 and the MOS capacitor C21 charges electric carriers. Accordingly, the output node N23 gradually goes from a low voltage level to a high voltage level and the output terminal of the schmitt trigger inverter 131 is toggled from a high voltage level to a low voltage level. Also, the output signal of schmitt trigger inverter 231 is latched and buffered at the output unit 250 and activates the power-on reset signal in a low voltage level.
The output signal of schmitt trigger inverter 231, which is in a high voltage level, is feed back to the input unit 210 through the feed back loop 270 so that such a feed-back signal makes the power-on reset signal (POR) in a high voltage level. The signal at node N20 is continuously inputted into the feed back loop 270 in a high voltage level and therefore the power-on reset signal is maintained in a high voltage level.
However, in case where it takes a long time (a few microsecondsxe2x80x94a few milliseconds) to turn on the power-on reset circuit after power is applied to it, the power-on reset circuit can not normally operate.
In case of the power-on reset circuit in FIG. 1, the power-on reset circuit does not work until the power-on signal goes up to the desired power within 10. If the power-on signal is slowly applied to the power-on reset circuit, charges are stored in the capacitor C11 and node N21 doesn""t comply with the power-on signal. As a result, the output node N23 is not toggled so that the reset signal may not be produced.
Also, in the power-on reset circuit of FIG. 2, if the input time of the power-on signal is long, the PMOS transistor PM21 is turned on in response to the signal at node N20 in the input unit 210 and, before the output node N21 is in a high voltage level, node N21 is continuously maintained in a high voltage level by the feed-back loop 270. After a predetermined time, node N21 is in a low voltage level and such a low voltage level is continuously maintained with the toggle of the power-on reset signal (POR).
However, since most of the expensive instruments is gradually turned on in order to prevent a damage, this long power-on time may interrupt a normal operation of the power-on reset circuit.
It is, therefore, an object of the present invention to provide power-on reset circuit producing stable reset signals irrespective of power-on time applied to it.
In accordance with an aspect of the present invention, there is provided a power-on reset circuit for producing a power-on reset signal in response to a power-on signal which is activated when power is applied to a chip in a semiconductor device, the power-on reset circuit comprising: an input means receiving the power-on signal from an external circuit; a first inverting means including an output node, wherein a voltage level at the output node is toggled from a high voltage level signal to a low voltage level signal before an output signal from the input means increases up to a desired voltage level; and a means coupled to the output node for generating the power-on reset signal in response to the voltage level at the output node.

Power-on reset circuit generating reset signal for different power-on signals

Hyundai Electronics Industries Co., Ltd.


A planetary transmission which has a drive shaft, an axial bearing, an internal gear, an axially displaceable sliding collar and a lubrication circuit and an output shaft which is mounted the transmission housing by an external bearing and an internal bearing. The housing is provided with an oil intake (13) which is connected to an oil line (16) with the external bearing (5) of the output shaft, which is linked by an oil feeding circuit with the axial bearing (9) of the output shaft. The axial bearing (9) is connected with an interior gear bearing by an interior gear (17), the interior gear (17) is encapsulated through a wall section (18). An oil discharge (14) is connected with an oil pump located outside the planetary transmission which, on the other hand, is connected with the oil intake (13).

Such planetary transmissions, mostly built from single- or multiple- stage planetary transmissions, are basically implemented in machine tools, as well as in lathes, milling machines and machining centers. The selectable planetary transmission increases the service scope of the main spindle motors, as well as the flexibility of the machine tool for processing the different work materials through increasing high torques or high speeds. For example, two transmission stages may be built in, while on one hand, the drive shaft which is connected to a sun gear with an internal gear and on the other, the internal gear can be coupled to the housing. A planetary carrier is connected to the output shaft.
In DE A 199 17 673 of the applicant, there is such a two-stage planetary transmission, with a drive shaft and an output shaft which are mounted in the housing over roller bearings. The drive shaft is connected to a sun gear which engages with the planetary gears, which are mounted over bearings on planetary bolts in a planetary carrier, which is connected over a positive-fit connection with the output shaft. The planetary gears are combed with an internal gear, which is mounted over the roller bearings in the housing or in the rotating planetary carrier and positively fit with a hub connection. The hub is torque-proof connected over an external gearing with the first part of the sliding collar.
A roller bearing is located over the sliding collar. The external part is axially displaceable in the housing, running over bearing bolts, whereby the axial displacement of the external part is carried over the roller bearings.
The sliding collar displacement takes place by means of a switching device, which is actuated by a solenoid or by a motorized switching unit whose armature is connected with the sliding collar.
This kind of planetary transmission has multiple rotating elements and, consequently, many bearings which are lubricated with the appropriate oil. Most of the traditional planetary transmissions for machine tools use splash lubrication, which has the disadvantage that it may be tainted with high mix losses and that the maximum possible rotational speed of the internal gear is limited by the internal gear bearings as they get warm, as the absorbed heating cannot be released. It is possible to cool the splash lubrication oil with circulatory lubrication, without avoiding the mix losses.
Further planetary transmissions are built with circulatory lubrication and oil cooling. High mix losses are shown also in these cases, on which the target maximum rotational speed of the interior gear is only possible conditionally. Under very high rotational speeds, the oil from the central part will be shot by the centrifugal force towards the housing, leaving the center of the transmission with a low oil level during the operation, generating frictional corrosion.
Operation of a planetary transmission with oil spray lubrication has also been tried. This is however not applicable for planetary transmissions, as the oil spray cannot reach the center of the transmission because of the strong ventilation effect caused by the high rotational speed of the interior gear, which means that the sun gear is not lubricated. Therefore the axial bearings will be insufficiently lubricated and frictional corrosion may even be generated.


A portable electronic device. A main body includes a first surface and a second surface opposite thereto. A display screen is disposed on the first surface and is electrically connected to the main body. A touchpad is disposed on the second surface and is electrically connected to the main body and display screen, providing a user to access or deal with data displayed on the display screen.

The invention relates to a portable electronic device, and in particular to a portable electronic device providing convenient and fast operation.
Referring to FIG. 1, a conventional PDA 1 comprises a main body 11 and a stylus 12. An LCD touch panel 13, a control button 14, and four directional buttons 15 are disposed on the front of the main body 11. Functions are selected and data is input on the LCD touch panel 13 using the stylus 12. In another aspect, function selection or data input can also be performed by pressing or operating the directional buttons 15 and control button 14. Accordingly, operation of the directional buttons 15 allows only four-directional movement on the LCD touch panel 13, thus limiting operational flexibility of the PDA 1.
Referring to FIG. 2, another PDA 2 comprises a main body 21 and a stylus 22. An LCD touch panel 23, a control button 24, and a joystick 25 are disposed on the front of the main body 21. Similarly, functions are selected and data is input on the LCD touch panel 23 using the stylus 22. The joystick 25 allows multidirectional movement, such as eight-directional movement, on the LCD touch panel 23, thereby enhancing operational flexibility of the PDA 2.
Nevertheless, the aforementioned PDAs 1 and 2 have many disadvantages. When operating the PDA 1 or 2 in a dynamic or unstable environment, for example in a moving car, the stylus 12 or 22 cannot precisely perform function selection or data input due to vibration. Additionally, when data is input by the stylus 12 or 22 with one hand, the PDA 1 or 2 must be held with the other hand. The aforementioned operation becomes impossible when a user stands in the moving car. Moreover, although the PDA 1 or 2 can be held with one hand and fingers thereof can be used to operate the directional buttons 15, joystick 25, control button 14, or control button 24 in a dynamic or unstable environment, the directional buttons 15 or joystick 25 can only perform step-by-step movement, making operation inconvenient. Further, since the front of the PDA 1 or 2 (main body 11 or 21) is provided with the directional buttons 15, joystick 25, control button 14, or control button 24, the disposed size of the LCD touch panel 13 or 23 is limited, adversely affecting display thereof.
Hence, there is a need for an improved portable electronic device that provides convenient and fast operation in a dynamic environment and a larger display screen to enhance display thereof.