Compositions, and products comprising a MutS homolog which binds to a mismatched region of a duplex DNA molecule in the presence of ADP are provided, as are methods of binding MutS homologs to mismatched DNA in the presence of ADP. The use of MutL homolog derivatives in combination with MutS homologs is also included. Nonhuman mammals which are nullizygous for both Msh2 and p53 are also provided, as are methods of making and using the same.

DNA Mismatch Repair
The most widely accepted model for DNA post-replication mismatch repair is based largely on the model of the DNA adenine methylation (Dam)-Instructed pathway of Escherichia coli proposed by Modrich (1986, Basic Life Sci. 38:303-310; Modrich, 1987, Ann. Rev. Biochem. 56:435-466; Modrich, 1989, J. Biol. Chem. 264:6597-6600; Modrich, 1991, Annu. Rev. Genet. 25:229-253; Modrich et al., 1996, Annu. Rev. Biochem. 65:101-133). According to this model, the MutS protein recognizes and binds mismatched nucleotides resulting from polymerase misincorporation errors to form a MutS-DNA product (Su et al., 1986, Proc. Natl. Acad. Sci., USA 83:5057-5061; Su et al., 1988, J. Biol. Chem. 263:6829-6835). MutS mismatch binding is followed by the interaction of MutL protein with the MutS-DNA product (Grilley et al., 1990, Mutat. Res. 236:253-267), which accelerates ATP-dependent translocation of the MutS-MutL complex (Allen et al., 1997, EMBO J. 16:4467-4476) to a hemimethylated GATC Dam site to which MutH protein is bound (Welsh et al., 1987, J. Biol. Chem. 262:15624-15629; Au et al., 1992, J. Biol. Chem. 267:12142-12148). The MutS-MutL complex stimulates an intrinsic endonuclease activity of MutH protein, which cleaves the non-methylated (i.e. more recently replicated) DNA strand (Welsh et al., 1987, J. Biol. Chem. 262:15624-15629; Lahue et al., 1987, Proc. Natl. Acad. Sci. USA 84:1482-1486; Su et al., 1989, Genome 31:104-111; Cooper et al., 1993, J. Biol. Chem. 268:11823-11829; Grilley et al., 1993, J. Biol. Chem. 268:11830-11837). Strand cleavage enables one of three single-stranded exonucleases of E. coli (RecJ, Exol, ExoVII) to degrade the non-methylated strand, which can then be re-synthesized by the E. coli PolIII holoenzyme complex (Lahue et al., 1989, Science 245:160-164). The net result is a strand-specific mismatch repair event.
Many genetic studies performed using E. coli support this interpretation. For example bacteria having a mutated mutH, mutL, or mutS gene exhibit a mutator phenotype that is presumed to be the result of the increased probability of misincorporation errors leading to mutations (Demerec et al., 1957, Bact. Genet., Carnegie Inst. Wash. Yearbook 370:390-406; Miyake, 1960, Genetics 45:755-762; Siegel et al., 1967, J. Bacteriol. 94:38-47; Hill, 1970, Mutat. Res. 9:341-344). However, not all predictions arising from the E. coli Dam-instructed model agree with experimental results. For example, bacteria having a mutation in each of the recJ, exol, and exo VII genes do not exhibit a mutator phenotype, suggesting that other exonuclease(s) or mechanism(s) are involved in the mismatch repair process.
Homologs of the procaryotic MutS and MutL proteins have been identified in eukaryotes (Fishel et al., 1993, Cell 75:1027-1038; Prolla et al., 1994, Science 265:1091-1093; Bronner et al., 1994, Nature 368:258-261). MutH analogs appear to exist only in gram-negative bacteria.
Multiple MutS and MutL homologs have been identified in yeast and human cells which individually participate in such diverse activities as nuclear and organelle mismatch repair as well as distinct meiotic functions (Fishel et al., 1997, Curr. Opin. Genet. Dev. 7:105-113). Germ-line mutations of the human MutS and MutL Homologs, hMSH2, hMLH1, and hPMS2, have been found to be associated with the common cancer predisposition syndrome, hereditary non-polyposis colorectal cancer (HNPCC; Bronner et al., 1994, Nature 368:258-261; Fishel et al., 1993, Cell 75:1027-1038). Yeast and human MutS and MutL homologs exist primarily as heterodimeric proteins. Yeast MSH2 protein has been found to be associated with MSH3 or MSH6, and yeast MLH1 has been found to be associated with PMS1. Human hMSH2 protein has been found to be associated with hMSH3 or hMSH6 (also designated GTBP or p160 by some authors), and human hMLH1 has been found to be associated with hPMS2 (Li et al., 1995, Proc. Natl. Acad., Sci. USA 92:1950-1954; Prolla et al., 1994, Science 265:1091-1093; Drummond et al., 1995, Science 268:1909-1912; Marsischky et al., 1996, Gen. Dev. 10:407-420; Acharya et al., 1996, Proc. Natl. Acad. Sci. USA 93:13629-13634). Furthermore, MSH2/MSH3 and MSH2/MSH6 protein complexes appear to possess overlapping and redundant mismatch binding activities (Acharya et al., 1996, Proc. Natl. Acad. Sci. USA 93:13629-13634; Risinger et al., 1996, Nature Genet. 14:102-105).
Classification of MutS and MutL homologs is based on the presence in the proteins of highly conserved regions of amino acid identity. The most highly conserved region among MutS homologs includes approximately 150 amino acids which comprise a helix-turn-helix domain associated with a Walker A adenine-nucleotide and magnesium binding motif (Walker et al., 1982, EMBO J. 1:945-951). This adenine nucleotide binding domain constitutes more than 80% of the identifiable homology between MutS homologs (Fishel et al., 1997, Curr. Opin. Genet. Dev. 7:105-113). Both purified bacterial MutS homologs and purified yeast MutS homologs possess an intrinsic low-level ATPase activity (Haber et al., 1991, EMBO. J. 10:2707-2715; Chi et al., 1994, J. Biol. Chem. 269: 29993-29997; Chi et al., 1994, J. Biol. Chem. 269:29984-29992; Alani et al., 1997, Mol. Cell Biol. 17: 2436-2447). This ATPase activity is likely to be important for the function of MutS homologs, as indicated by the fact that mutation of conserved amino acid residues in the adenine nucleotide binding domain results in a dominant mutator phenotype in both bacteria and yeast (Haber et al., 1991, EMBO. J. 10:2707-2715; Wu et al., 1994, J. Bacteriol 176:5393-5400; Alani et al., 1997, Mol. Cell Biol. 17: 2436-2447). A central role for the adenine nucleotide binding domain is consistent with the ATP-dependent translocation model of mismatch repair proposed by Modrich and colleagues (Allen et al., 1997, EMBO J. 16:4467-4476).
Genetic and biochemical studies of the human mismatch repair process indicate that it is similar to bacterial mismatch repair, except that the physiologically relevant mechanism for directing strand specificity is unknown (Miller et al., 1976, Proc. Natl. Acad. Sci. USA 73:3073-3077; Glazer et al., 1987, Mol. Cell. Biol., 7:218-224; Holmes et al., 1990, Proc. Natl. Acad. Sci. USA 87:5837-5841; Thomas et al., 1991, J. Biol. Chem. 266:3744-3751; Fang et al., 1993, J. Biol. Chem. 268:11838-11844; Longley et al., 1997, J. Biol. Chem. 272:10917-10921). Purified hMSH2 protein binds mismatched nucleotides and DNA lesions (Fishel et al., 1994, Science 266:1403-1405; Fishel et al., 1994, Cancer Res. 54:5539-5542; Mello et al., 1996, Chemistry & Biology 3:579-589), and the specificity and affinity of that recognition is enhanced by association of hMSH2 with hMSH3 or hMSH6 (Drummond et al., 1995; Acharya et al., 1996, Proc. Natl. Acad. Sci. USA 93:13629-13634; Palombo et al., 1996, Curr. Biol. 6:1181-1184).
Although the ability of MutS homologs to bind to mismatched duplex DNA has been recognized (e.g. U.S. Pat. No. 5,556,750), methods of using MutS homologs in vitro have been limited by a lack of understanding regarding the properties of such homologs. A need remains for methods of binding MutS homologs and mismatched duplex DNA, which methods take advantages of the biochemical properties of such homologs.
Transgenic and Nullizygous Animals
The development of transgenic animals and nullizygous animal models has provided important new avenues for the study of specific gene functions in differentiation, embryogenesis and neoplastic development (Palmiter et al., 1986, Ann. Rev. Genet. 20:465-499). Transgenic animals frequently serve as model systems for the study of various disease states and also provide an experimental system in which to test compounds for their ability to regulate disease. Nullizygous animals are similarly useful as experimental systems for the testing of compounds useful for diagnosis, treatment, or both, of disease.
Lukkarinen et al. (1997, Stroke 28:639-645) teaches that gene constructs which enable the generation of transgenic mice also enable the generation of other transgenic rodents, including rats. Similarly, nullizygous mutations in a genetic locus of an animal of one species can be replicated in an animal of another species having a genetic locus highly homologous to the first species. For example, many genetic loci are highly homologous among mammals, and even more highly homologous among subgroups of mammals, such as among rodents.
The mutator hypothesis of tumorigenesis suggests that loss in an organism of a chromosomal stability function, a chromosomal maintenance function, or both, results in an elevated mutation rate in the organism. An elevated mutation rate hastens accumulation of the numerous mutations required for multistep carcinogenesis (Loeb, 1991, Cancer Res. 51:3075-3079).
Loss of the function of p53 protein has been proposed to increase cellular hypermutability in an organism, thereby accelerating tumorigenesis, although a clear role for p53 protein in genomic instability remains controversial (Kastan et al., 1992, Cell 71:587-597; Fishel et al., 1997, Curr. Opin. Genet. Dev. 7:105-113). p53, the gene encoding p53 protein, is frequently mutated in a wide range of human cancers including, but not limited to, colonic tumors (Fearon et al., 1990, Cell 61:759-767). Transgenic mice nullizygous for p53 are viable and susceptible to tumorigenesis (de Wind et al., 1995, Cell 82:321-330; Reitmair et al., 1995, Nature Genet. 11:64-70; Donehower et al., 1992, Nature 356:215-221; Jacks et al., 1994, Curr. Biol. 4:1-7; Purdie et al., 1994, Oncogene 9:603-609).
Although nullizygous p53 mice can be used as models of carcinogenesis, the rates at which such mice develop tumors can be slower than what is desirable, particularly for large-scale screening studies involving numerous potential anti-cancer therapeutic or prophylactic compositions. What is needed is a transgenic mouse which, when exposed to a carcinogen, succumbs to tumorigenesis caused by the carcinogen more readily than does a nullizygous p53 mouse and which, even when not exposed to an identifiable carcinogen, succumbs to tumors more readily than does a nullizygous p53 mouse.
Critical unmet needs also exist for animal models of programmed cell death (apoptosis) and of aging.
The present invention satisfies the needs identified above.

Compositions, kits, and methods for effecting adenine nucleotide modulation of DNA mismatch recognition proteins


Non-Small Cell Lung Carcinomas (NSCLCs) are treated with Gel Micro-Particles (GMPs) that passively accumulate in the lungs and contain Nano-Particles (NPs) combining one or more therapeutic agents that are cytotoxic to the NSCLC with one or more NSCLC active targeting ligands, as well as one or more other optional agents that increase cellular uptake, enhance the pro-apoptotic effect of the chemotherapeutic agent(s), and the like. NPs targeting other cancer cells are also disclosed, as well as NP-containing GMPs that reduce the occurrence of tumor metastasis.

A central issue in cancer chemotherapy is the severe toxic side effects of anticancer agents on healthy tissues, which invariably imposes dose reduction, treatment delay or even discontinuance of therapy (Fennelly (1995) Clin. Cancer Res. 1:575-582; Hanjani, et al. (2002) Gynecol. Oncol. 85:278-284; Kobayashi, et al. (2002) Chronobiol. Int. 19:237-251; Ross and Small (2002) J. Urol. 167:1952-1956; Markman, et al. (2002) J. Clin. Oncol. 20:2365-2369; Sehouli, et al. (2002) Gynecol. Oncol. 85:321-326). Cytotoxicity for healthy organs can be significantly diminished by employing a drug delivery system which targets cancer cells (Alvarez, et al. (2002) Expert. Opin. Biol. Ther. 2:409-417; Dass and Su (2001) Drug Deliv. 8:191-213; Kopecek, et al. (2001) J. Controlled Rel. 74:147-158; Kunath, et al. (2000) Eur. J. Pharm. Biopharm. 49:11-15; Minko, et al. (2001) Dis. Manag. Clin. Outcomes 3:48-54; Vasey, et al. (2002) J. Clin. Oncol. 20:1562-1569). The usage of these drug delivery systems prevents, in most cases, the uptake of the drug by normal cells and enhances the influx and retention of the drug in cancer cells.
NSCLC remains one of the leading causes of cancer-related mortality worldwide. NSCLC represents a heterogeneous group of diseases that are often classified together due to similarities in diagnosis, prognosis and treatment. The standard-of-care with an anticancer agent paclitaxel and a platinum drug extends life only minimally due to drug-related toxicities, poor treatment/prevention of metastases, and resistance. Increasing drug doses in order to boost tissue concentrations is not feasible due to cytotoxic effects and low solubility.
The lung is the only organ in the body that accepts the entire venous blood output from the heart. Since it is the first capillary bed encountered by the venous blood, it is in a singular position to entrap a wide variety of particles. "Passive" drug targeting to the lung (i.e., accumulation) can be achieved by taking advantage of this natural flow-filtration phenomenon. In 1964, human serum albumin "macroaggregates" ("MAA") exhibiting suitable size and degradation properties became the first MPs approved for IV injection and lung targeting. Two approved products remain on the market today as pulmonary perfusion diagnostic agents, Pulmolite® (CIS-US) and Draximage® (Draxis). There are not any products for delivering drugs to the lung that exploit this established and safe pathway. The rationale for passive lung accumulation is compelling—MAA product and MPs are efficiently entrapped (>90%) after a single injection as compared to only 5-20% of an inhaled dose. In addition, inhalers must be used multiple times daily but a single IV injection may provide effective treatment for up to one week. Size and deformability are the two major determinants of the passive accumulation and retention of MPs in the lung.
In addition to these factors, toxicity is also influenced by the total particle dose. Presently, approved human MAA dosages are much lower (<0.2 mg or ˜350,000 MPs) than the corresponding LD50 in animals (43.8 mg/kg to 82.6 mg/kg) suggesting that tolerable human MP doses may be significantly higher than what is currently used in the diagnostic product. It has been estimated that only ˜0.6% of available (i.e., opened) capillary vessels are occluded immediately following administration of 1×106 albumin aggregates (4 times the current human MAA dose). About 33% of all pulmonary capillaries are normally collapsed and not available (the main reason for this is that lung blood pressure is about ⅙ of systemic blood pressure). When micro-occlusions occur, collapsed capillaries are recruited in order to maintain normal physiological perfusion conditions. Therefore, the maximum tolerated dose of MPs in humans is higher than current MAA doses and in the milligram range.
While targeted drug delivery is an effective approach for improving drug concentrations, the options for lung targeting are narrow. The inherently low absorption and poor lung distribution associated with inhalation are further diminished as a result of reduced lung function in NSCLC patients. Despite recent advances in molecular characterization and targeted and adjuvant therapies, surgical resection remains the mainstay of curative treatment. Unfortunately, less than one third of NSCLC patients present with resectable disease. Neoadjuvant chemotherapy alone or with concurrent radiation is often used for stage IIIA NSCLC but is often tried in patients with stage IIIB and at times in patients with stage I or II disease. The general prognosis of NSCLC patients remains poor and unpredictable due to the high invasiveness potential of the disease. However, after the initial diagnosis, more than half of the patients with localized lung cancer survive at least 5 years. Therefore, an alternative delivery approach that targets primary lung tumors and controls metastasis is urgently needed.

Synergistic combinations to reduce particle dose for targeted treatment of cancer and its metastases

RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY


A motor vehicle device has a device interior in which a water-containing lubricant is held in order to lubricate at least one component arranged in the device interior. The device interior is fluidically connected to a venting apparatus for pressure equalization with the environment surrounding the motor vehicle device. The venting apparatus has a semipermeable membrane, which is water-impermeable in a first direction, i.e. from a first surface of the membrane to a second surface. The first surface of the semipermeable membrane faces the device interior and therefore the semipermeable membrane seals off the device interior from the environment surrounding the motor vehicle device in such a way that water and water vapor cannot permeate.

The invention relates to a liquid-lubricated motor vehicle device having a ventilation installation.
A motor vehicle device having a device interior space in which a water-containing lubricant is received for lubricating at least one component disposed in this device interior space is known from DE 10 2010 025980 A1.
The invention is described hereunder in the context of a water-containing lubricant; this description is not to be understood as a limitation of the invention. Water-containing lubricants in comparison to conventional lubricants offer advantages in particular with a view to efficiency and in particular also in terms of thermal behavior. The lubricating properties of such a water-containing lubricant depend inter alia on the water content in this lubricant. In the operation of a motor vehicle device, temperatures in the lubricant can be reached such that water is converted to water vapor and escapes from the motor vehicle device.
It is the object of the invention to provide a motor vehicle device having a water-containing lubricant, wherein the variability of the water content in this water-containing lubricant is improved in comparison to a conventional motor vehicle device, that is to say that the variability of the water content is kept almost constant during the operation of the motor vehicle device. This object is achieved by a motor vehicle device as claimed in the independent claim; preferred embodiments of the invention are the subject matter of the dependent claims.
In the context of the invention, a motor vehicle device is to be understood to be a device in a motor vehicle, and preferably a transmission installation, and particularly preferably a transmission installation in the drivetrain for transmitting the drive forces for overcoming rolling resistances. This motor vehicle device has a device interior space in which at least one and preferably a multiplicity of components, which in the operation of the motor vehicle device is/are at least temporarily lubricated by a lubricant, is/are disposed.
Such a component is preferably understood to be a gear wheel, a bearing, a shifting element, or a shaft, in particular a transmission shaft. This lubricant is furthermore received in this device interior space or for lubricating the at least one component is incorporated into this device interior space. This lubricant is furthermore configured as a water-containing lubricant. A water-containing lubricant in the context of the invention is to be understood to be a lubricant which comprises at least 5% or more by volume of water, the remaining components of this lubricant potentially being solids, preferably so-called nanoparticles, or water-soluble substances. Water-containing lubricants per se are known from the prior art and are in some instances also referred to as water-based lubricants. The operating properties of the motor vehicle device can in particular be improved by using water-containing lubricants.
The motor vehicle device preferably has a ventilation installation for pressure equalization with the environment surrounding the motor vehicle device during the operation of the motor vehicle device; in other words, the device interior space, by means of the ventilation installation, is in particular fluidically connected to this environment. This ventilation installation furthermore has a semi-permeable membrane.
A semi-permeable membrane in the context of the invention is to be understood to be a membrane which is impermeable to water and/or water vapor in a first direction, from a first surface toward a second surface, and this membrane is furthermore preferably permeable to water and/or water vapor in a second direction, from the second surface toward the first surface. Membranes of this type in a similar form are also known under various trade names from their use in breathable sportswear.
The semi-permeable membrane by way of the first surface thereof faces the device interior space such that an imaginary fluid flow from the device interior space into the environment surrounding the motor vehicle device would have to flow through this membrane from the first surface to the second surface of the membrane; however, this direction of flow is specifically blocked by the installed position of the semi-permeable membrane and an escape, in particular of water vapor, from the device interior space into the environment is thus able to be prevented.
The device interior space, in particular by a membrane disposed in such a manner, is closed off so as to be impermeable to water and water vapor in relation to the environment surrounding the motor vehicle device such that no moisture, or only minor quantities of moisture, can escape from the device interior space. By way of such a semi-permeable membrane it is thus furthermore possible for the exit of water or water vapor to at least be minimized, and the water content in the water-containing lubricant can thus be kept constant or almost constant.
In one preferred embodiment of the invention, a further membrane is provided in the ventilation installation. This further membrane in terms of a flow direction from the device interior space into the environment surrounding the motor vehicle device is preferably disposed downstream of the semi-permeable membrane. This further membrane is preferably configured as a semi-permeable membrane and is thus to be understood as a further semi-permeable membrane. This further semi-permeable membrane is furthermore preferably disposed in such a manner that this further semi-permeable membrane closes off this device interior space so as to be impermeable to water and water vapor in an imaginary flow direction from the environment surrounding the motor vehicle device into the device interior space. Figuratively speaking, the further semi-permeable membrane in such a case is disposed counter to the semi-permeable membrane. On account of a disposal of this type, it is in particular possible for the uncontrolled ingress of water and/or water vapor into the device interior space to be prevented or at least to be minimized.
In one preferred embodiment, the motor vehicle device is designed as a motor vehicle transmission, in particular as a motor vehicle transmission in the drivetrain of a motor vehicle that is designed for providing drive forces for overcoming rolling resistances (air drag, frictional resistance, incline resistance, etc.). The at least one component disposed in the device interior space is in particular configured as a gear wheel, or as a multiplicity of gear wheels, respectively.
Individual features of the invention are explained in more detail hereunder by means of a FIGURE.

Motor vehicle device lubricated with a water-containing lubricant

Bayerische Motoren Werke Aktiengesellschaft


Gravity measurements from a borehole gravity survey are obtained by continuously moving the gravity meter within the borehole. Movement-induced acceleration errors are quantified and subtracted from the gross measurements from the gravity meter to obtain actual gravity values at a multitude of measurement points within the borehole. Acceleration errors are calculated from the second differential of the true vertical depth of the gravity meter, which is computed measured length and weight and elongation characteristics of a cable which suspends the gravity meter in the borehole, upper and lower tension measurements in the cable, and the topography of the borehole.

A borehole is typically used to access subterranean areas of interest beneath the surface. In many cases, data recording devices are lowered into the borehole to gather additional information about the subterranean structure and composition of subterranean material surrounding the borehole but not directly accessed by the borehole, at certain preselected depths. The measurements are then used to model the subterranean area of interest.
Of particular interest to geologists, geophysicists, civil and petroleum engineers, and others, is the density of material within certain subterranean areas. The density of a particular subterranean area can often be related to the presence of hydrocarbon (oil and gas) deposits. The density of a particular subterranean area can also be indicative of the ability of the subterranean area to support heavy structures, such as buildings and bridges.
One way to determine the density of a subterranean area is to measure gravity within the subterranean area. Gravity has a well known relationship with material density, so the density of a particular subterranean area can be evaluated from gravity measurements of that subterranean area. Gravity meters are commonly used to derive density information. Gravity meters offer certain advantages when measuring gravity compared to other types of density-related measurement devices, because gravity meters are not as affected by near-hole anomalies, such as washouts, borehole casing variations or fluid invasion, as are other measurement devices. Gravity meters also have a superior range of measurement compared to other measurement devices. The range of measurement of a typical gravity meter extends outward over one hundred feet from the borehole.
Gravity measurements are taken from a borehole as part of a borehole gravity survey. The gravity survey usually extends over a significant length or depth of the borehole. The gravity survey typically starts by lowering a pressure housing containing the gravity meter, known as a sonde, to a preselected starting depth within the borehole. The sonde is connected to a cable which is wound around a motorized take-up spool at the earth surface. The motorized spool is rotated to raise and lower the sonde within the borehole. An odometer is connected with the cable or spool to measure the length of cable inserted into the borehole and determine subsequent depth of the gravity meter within the borehole. After the sonde has been lowered to the preselected starting depth or measurement point, a gravity measurement is obtained from the gravity meter. The sonde is then raised a predetermined interval or distance, for example 10-30 feet, to another predetermined measurement point, where another gravity measurement is taken after sufficient time has elapsed to allow the sonde to stabilize in position and all extraneous movements of the sonde and the cable have dampened out. Additional gravity measurements are taken in this same manner at the other measurement points until the entire borehole gravity survey is completed.
Gravity meters determine the value of gravity by measuring the effect of gravity on a test mass within the gravity meter. Different types of gravity meters measure the effect of gravity on the test mass in different ways, but all gravity meters measure a force (gravity) acting on the test mass. For example, some relative gravity meters suspend the test mass from a spring and measure the displacement of the test mass as the spring stretches. The displacement of the test mass is proportional to the force of gravity acting on the test mass. Other relative gravity meters maintain the test mass stationary and measure an electric or magnetic force required to maintain the test mass in a stationary position. The amount of electric or magnetic force is proportional to gravity. Absolute gravity meters typically measure the acceleration of the test mass as it is released into a free fall. The acceleration of the test mass is directly related to the force of gravity acting on the test mass.
Movement of a gravity meter during measurement can create an inaccurate gravity measurement. Changes in movement of the gravity meter result in acceleration which itself causes a force on the test mass. In such circumstances, the force acting on the test mass results both from movement-induced acceleration and from gravity. A movement-induced acceleration therefore causes an acceleration error in the gravity meter measurement. By stopping the sonde and allowing the gravity meter to stabilize, movement-induced acceleration errors on the gravity meter measurements are eliminated. The stopped and stabilized gravity meter measures only gravity, because there are no movement-induced acceleration errors.
Movement-induced acceleration errors in the gravity meter measurements are unavoidable when the measurements are taken as the gravity meter is moving in the borehole. Movement-induced acceleration errors are due to changes in movement of the sonde and the cable which suspends it in the borehole. The diameter of the sonde is smaller than the inside diameter of a casing which typically lines the borehole, and the sonde and the cable occasionally contact the casing as they move up or down in the borehole. Additionally, the sonde and cable may encounter debris or fluid within the borehole. Under these circumstances, the sonde may occasionally experience momentary resistances to movement as the cable is moved in the borehole due to frictional contact of the sonde or the cable with the casing or due to the sonde encountering the debris or fluid within the borehole. These disturbances of the sonde create erratic forces which create acceleration of the sonde. The cable is made of material which has a natural elasticity characteristic, such as steel, causing the cable to behave as a spring in accordance with Hooke's law. Hooke's law states that the amount of stretch of a spring is proportional to the amount of force applied to the spring. The intermittent changes in tension or force in the cable caused by disturbances and perturbations cause slight spring-like oscillations in the cable, and these oscillations also engender movement-induced acceleration on the test mass of the gravity meter. Other factors may also cause acceleration of the sonde and cable in the borehole.
The prior art technique of moving the sonde from one preselected stationary measurement point to the next preselected stationary measurement point is accomplished by raising or lowering the cable within the borehole a predetermined distance. Raising and lowering the cable causes the cable to transition between stationary and moving states, which in turn changes the tension within the cable. Due to the spring-like characteristics of the cable, the length of the cable changes during the transition between stationary and moving states, which results in the sonde oscillating or bouncing slightly at the end of the cable for a period of time after each movement point transition. Similar to the oscillations of the sonde at the end of the cable, moving the sonde from one stationary position to another causes the test mass to oscillate slightly at the end of the spring which suspends the test mass. It is for these reasons that a considerable waiting time is required at each measurement point to allow movement of the test mass and the sonde to dampen out and stabilize before the gravity measurement is made. The cumulative amount of time elapsed during these wait periods at each preselected measurement depth constitutes a large portion of the overall time to conduct the borehole gravity survey, typically in excess of 50% of the total time required to complete the entire survey.
Conducting a borehole gravity survey may take up to three or four days depending on the depth of the borehole and the interval of the gravity measurement points. Production of oil and gas and/or drilling in the borehole must be halted when conducting a borehole gravity survey of a producing well, because the movement of fluids around the sonde also perturbs the sonde and introduces acceleration errors into the gravity measurements. Halting the production of a producing well can cost up to $20,000 per hour for high capacity wells. Reducing the time required to conduct a gravity survey of a borehole has the potential for significant cost savings.
It has previously been recognized that it would be desirable to make continuous gravity measurements in a borehole. However, such continuous gravity measurements were recognized as unreliable since there was no known accurate way to quantify and eliminate the effects of movement-induced acceleration on the gravity meter. Consequently, it was previously considered impractical to obtain accurate gravity measurements from a continuously moving gravity meter in a borehole.


A user interface enables the input of text and other complicated inputs by identifying entities having an increased likelihood of being selected and decreasing the precision needed to select these entities. The user interface displays a set of entities in a radial pattern. The user manipulates a pointer with a joystick or other input device to select entities. The entities having a higher selection probabilities are allocated more space in the pattern than the other entities. The entities having a higher selection probabilities may also be emphasized with visual cues. Selection probabilities may be determined by comparing a sequence of entities previously selected, such as a partially input word, with a set of commonly selected sequences of entities, such as a set of words commonly used by users. The user interface can display a list of words corresponding with a sequence of selected entities, including characters from different writing systems.

The invention relates to field of user interfaces for computers and electronic devices. Keyboards are the most common input devices for computers. Keyboards enable computers to receive text and other complicated inputs. However, portable electronic devices, including handheld computers, electronic organizers, personal digital assistants, portable game systems, wireless phones, are often too small to include a standard size keyboard. As a result, they require alternative input devices for receiving text and other complicated inputs.
One user interface displays a virtual keyboard on a screen and allows users to manipulate a cursor, using a joystick, directional pad, or other input device, to select letters on the virtual keyboard. This approach is time-consuming, often requiring many button presses to select each letter.
One user interface includes a small keyboard designed to be operated by a user's thumbs. Unfortunately, the thumb keyboard requires two hands to operate, is too large for many portable electronic devices, and has a steep learning curve.
Another user interface input device maps letters of the alphabet to the keys of a standard telephone keypad. A set of multiple letters is mapped to each of at least a portion of the keys. To enter text, the user presses each key one or more times to select one of the set of letters associated with that key. A selection is completed by waiting for a predetermined period of time or by pressing another button. One disadvantage of this approach is that text entry is very slow, often requiring multiple button presses and long pauses for each letter.
A variation of this user interface is referred to as T9. T9 is a predictive text input system that attempts to reduce the number of button presses required for each letter. Like standard telephone keypad-based text input, a set of multiple letters is mapped to each of at least a portion of the keys. To enter words, the user only needs to press each key associated with a letter once. Because there are multiple letters associated with each key, an input sequence can correspond to many different combinations of letters. As the user enters a word, the system accesses a dictionary or other database to identify the word or words likely to correspond with a given input sequence. If there are multiple words associated with a sequence of inputs, the user interface allows the user to select the desired word. Although telephone keypads take less space than a thumb keyboard, few devices besides wireless phones have telephone keypads. Additionally, these user interfaces are limited to text input and are difficult or impossible to use with languages having a large number of characters, such as Chinese and Japanese.
It is therefore desirable for a user interface of an electronic device to enable quick and efficient entry of text and other complicated inputs. It is further desirable for the user interface to use minimal space for input devices and to be easily integrated with a wide variety of types of electronic devices. It is also desirable for the user interface to enable users to enter text for languages having a large number of characters. It is desirable for the user interface to handle non-text input. It is desirable that the user interface can be operated with only one hand.


A device to fix a smaller object (a book, rolled up articles of clothing, a fabric bag, newspaper, lunch box or the like) to be transported securely on the handlebar and or the handlebar support of a vehicle, in particular a two-wheeled vehicle and more particularly a bicycle. The transport device has three fixing elements (3) which are fixedly attached to the handlebar (1) and/or the handlebar support (2). Each of the fixing elements (3) is provided with a retaining device (4) (ring, figure-of-eight ring, eye, tab or the like), through which a securing element (5) is movably fed. The fixing element (5) can be elastic (e.g. rubber or the like), or inelastic (e.g. cable, belt, tie-down strap, chain or the like). The fixing element (5) is fed twice through the retaining devices (4) such that an object can be fixed easily and then transported by being gripped between the at least two layers of the fixing element (5). The fixing element (5) can be fed through a cord stopper (6) and securely tied off with a knot or the like (7). The fixing element (4) can be tightened by the cord stopper (6), thus assisting, if necessary, in securing the object. The transport device has an extremely economical use of materials and is extremely low weight. The device does not significantly alter the appearance of the vehicle and can be fastened to the vehicle without drilling or adhesive bonding.

In principle, various transport devices for two-wheeled vehicles and in particular bicycles are known:                racks, which are usually manufactured from wire or tubing and are generally fixedly mounted over the rear wheel and allow the transported material to be fixed to the supporting surface of the rack by spring flaps or bungee cords.        bicycle baskets, which are usually manufactured from wire or tubing and are mounted on a rack or directly on the handlebar by way of a mount.        panniers, which are usually manufactured from textile and are generally attached laterally to a rack.        saddlebags, which are usually manufactured from textile and are generally attached under the saddle of a two-wheeled vehicle.
A drawback of fixedly mounted transport devices, such as racks or bicycle baskets, is that they generally have a relatively large dead weight that has to be carried along even when nothing is being transported during a journey.
A drawback of transport devices that are removable in a relatively problem-free manner, such as panniers or saddlebags, is that it is always necessary to decide, before starting a journey, whether something will need to be transported, and that it is frequently necessary to repeat the attaching or removing operation.
A drawback of all the abovementioned and other previously known transport devices is that they have a relatively large impact on the appearance of the vehicle. In particular in the case of vehicles that are equipped in a very minimalistic manner for esthetic reasons, the abovementioned and other previously known transport devices can be considered very disruptive.


A headrest for an office chair includes a headrest body, two connecting blocks, a support frame and a hook. The support frame has two L-shaped hooks in an intermediate portion, and the headrest can be assembled with a backrest of an office chair by a hook and L-shaped hooks of the support frame to enable the headrest being assembled with any office chair easily. Moreover, the headrest body can be adjusted in its height and angle to be usable by users of different physical heights.

1. Field of the Invention
This invention relates to a headrest for an office chair, particularly to one easily adjustable in its angle and height, and conveniently assembled and disassembled.
2. Description of the Prior Art
A conventional headrest of an office chair is generally made stationary, impossible to be assembled with any office chairs or to be adjusted in its angle and height, so users of different physical height cannot sit comfortably, obliged to change its sitting posture to conform to the height of the headrest. Therefore, users may suffer from a sour head and back owing to a long period of use.


An electronic apparatus is provided. The electronic apparatus includes a memory storing a program including a plurality of program codes and performing a predetermined function; a communicator configured to receive policy information including target information and determination information from an external server; and a processor configured to perform the predetermined function using the program and, when a program code corresponding to the target information is executed while performing the predetermined function, compare an execution result of the program code with the determination information and determine whether the program code normally operates.

Owing to development of technology, functions of digital devices have become more complex and diverse. Since manufacturers provide open application platforms, many companies are striving to participate in development and provide their own services.
As a result of these changes, unpredictable behaviors occurred at the initial development stage of digital devices and these operations became the cause of problems. When problems were reported at the development stage of a digital device in the prior art, the same problem was reproduced and the problem was solved by using real-time debugging information through a console. However, when the problem was not reproduced or the reproduction method was not accurate, the problem could not be solved.
Also, problems that arise after a product is supplied to a consumer are not easy to reproduce the problem because an external environment is different from the development stage. Even if developers visited a relevant place to identify the problem that occurs, it is impossible to obtain debugging information in real time in a problem that occurs at a specific time. Debugging information that has been obtained took a long time because the developer had to check the information manually. Also, even if the problem is reproduced, it takes a lot of time to reproduce, and a lot of cost for the developer to visit a specific place.
As described above, obtaining the debugging information using the existing method is limited and a lot of cost is required, and a new method of recording the debugging information is needed.

Server, electronic device, and control method thereof


In a tag device wherein a wire 2 has a base end 21 fixed to a tag body 10 and a forward end 23 connected to the tag body 10 as releasably locked thereto, the wire 2 is provided at its forward end 23 with a lock pin 22. The tag body 10 comprises a case 1 having a pin insertion hole 13, and a latch member 3 engageable with the lock pin 22. The latch member 3 comprises a main body 31 supported inside the case 1 and a spring piece 32 provided on the main body 31. The latch member 3 prevents the thick rod portion 26 from slipping off when moved in one direction to a limit position, and allows the thick rod portion 26 to slip off when moved in the other direction to a limit position.

The present invention relates to tag devices to be attached to articles such as bags for preventing the article from being stolen or unlawfully brought out of a predetermined monitoring area.
Tag devices of the type mentioned already known comprise a tag body and a wire having a base end fixed to the tag body and a forward end provided with a lock pin which is connected to the tag body as releasably locked thereto. The tag device is attached to an article by unlocking the lock pin from the tag body, winding the wire around the article and thereafter locking the lock pin to the tag body.
When an attempt is made to bring out the article having the tag device thus attached thereto from a predetermined monitoring area (for example, from a store), the tag device receives radio waves (alarm actuating signal) emitted from an entrance-exit gate, whereupon a buzzer in the tag body goes on, giving notice of the occurrence of theft. Alternatively if it is attempted to cut the wire of the tag device attached to the article and bring out the article only from the monitoring area, the break in the wire is detected by the tag body, whereupon the buzzer in the tag body goes on, giving notice of the occurrence of theft.
With the conventional tag device, the lock pin attached to the forward end of the wire is locked to the tag body by pushing the lock pin into a metal latch member to thereby engage the latch member with the lock pin, and is released from the tag body by elastically deforming the latch member with use of an unlocking member and thereby disengaging the latch member from the lock pin. In order to lock the lock pin to the tag body by the latch member reliably, therefore, the portion of the latch member to be engaged with the lock pin needs to be as high as possible in rigidity (difficulty of elastic deformation) so as not to elastically deform easily under the action of an impact or the like.
Nevertheless, giving high rigidity to the portion of the latch member to be engaged with the lock pin requires a great force for unlocking the lock pin with use of the unlocking member, entailing the problem of making the unlocking member difficult to use. Even if the unlocking member is driven by a solenoid or the like, there arises the problem of necessitating a great electric power. Additionally, the higher the rigidity of the engagement portion of the latch member for the lock pin, the greater is the elastic repulsive force involved in the engagement. Since the elastic repulsive force acts toward the direction unlocking, there is a likelihood that the lock pin will be unlocked when subjected to a small impact.
Accordingly, an object of the present invention is to provide a tag device which is adapted to realize a reliable locked state and yet which ensures facilitated unlocking.
The present invention provides a tag device comprising a tag body 10 and a wire 2 fixed at a base end 21 thereof to the tag body 10 and having a lock pin 22 attached to a forward end 23 thereof. The lock pin 22 has a thick rod portion 26 at an outer end of a thin rod portion 25. The tag body 10 comprises a case 1 having a pin insertion hole 13 permitting the lock pin 22 to pass therethrough, and a latch member 3 disposed inside the case 1 and engageable with the lock pin 22 as inserted through the hole 13.
The latch member 3 comprises a main body 31 supported inside the case 1 and reciprocatingly movable in directions orthogonal to the direction of insertion of the lock pin 22, and a spring piece 32 provided on the main body 31 and elastically shiftable in a direction intersecting the direction of insertion of the lock pin 22. The latch member 3 permits the spring piece 32 to be opposed to the thin rod portion 25 of the lock pin 22 in an inserted position to prevent the thick rod portion 26 from moving in a slipping-off direction when moved in one direction to a limit position, and permits the spring piece 32 to be positioned away from the thin rod portion 25 of the lock pin 22 in the inserted position to allow the thick rod portion 26 to move in the slipping-off direction when moved in the other direction to a limit position.
According to the tag device of the invention, with the latch member 3 moved in the above-mentioned one direction to the limit position, the lock pin 22 is pushed into the latch member 3 through the pin insertion hole 13 in the tag body 10, whereby the thick rod portion 26 of the lock pin 22 is moved past the spring piece 32 of the latch member 3, positioning the thin rod portion 25 as opposed to the spring piece 32. In this process, the spring piece 32 of the latch member 3 is elastically deformed by sliding contact with the outer peripheral surface of the thick rod portion 26 and is thereafter opposed to the outer peripheral surface of the thin rod portion 25 to elastically restore itself. As positioned in proximity to the outer peripheral surface of the thin rod portion 25, the spring piece 32 prevents the thick rod portion 26 from moving in the slipping-off direction (locked state). Accordingly, even if an external force acts in a direction to withdraw the lock pin 22 from the tag body 10, the thick rod portion 26 bears on the spring piece 32 of the latch member 3, whereby the lock pin 22 is prevented from slipping out of the tag body.
When the lock pin 22 is to be lawfully handled for removal from the tag body 10, the latch member 3 is moved in the other direction to the corresponding limit position, and the lock pin 22 is thereafter pulled out from the tag body 10. The movement of the latch member 3 moves the spring piece 32 away from the thin rod portion 25 of the lock pin 22, permitting the thick rod portion 26 to move in the slipping-off direction, so that the lock pin thick rod portion 26 moves without being restrained by the spring piece 32, slipping out of the pin insertion hole 13 of the tag body 10.
The movement of the latch member 3 between the locking position and the unlocking position merely involves slight frictional resistance offered to the latch member 3 by the neighboring members. The latch member 3 can therefore be driven reciprocatingly without requiring any great force.
Stated more specifically, the thick rod portion 26 of the lock pin 22 is provided at an outer end thereof with a tapered face 27 for elastically shifting the spring piece 32 of the latch member 3 by pushing with the insertion of the lock pin 22. Accordingly, while the lock pin 22 is being pushed into the latch member 3, the tapered face 27 of the lock pin 22 comes into pressing contact with the spring piece 32 of the latch member 3 and elastically shifts the spring piece. Thus, the thick rod portion 26 of the lock pin 22 is brought into sliding contact with the latch member spring piece 32.
Further stated more specifically, the tag body 10 has incorporated therein a solenoid 5 for reciprocatingly driving the latch member 3 by an attracting/releasing movement of a rod 51, and a control circuit for controlling the operation of the solenoid 5. The latch member 3 can then be reciprocatingly moved between a locking position and an unlocking position by the rod 51 attracting/releasing movement of the solenoid 5.
The solenoid 5 as unenergized retains a locking operative state, for example by virtue of the magnetic force of a permanent magnet incorporated therein, to hold the latch member 3 moved to a lock pin 22 locking position. Accordingly, no electric power is required for holding the latch member 3 in the locking position, hence a reduction in power consumption.
The solenoid 5 is provided with a spring 53 for biasing the rod 51 from the locking operative state toward an unlocking operative state. Accordingly, the force required for moving the latch member 3 from the locking position to the unlocking position is partly provided by the elastic restoring force of the spring 53.
Further stated more specifically, the tag body 10 has a switch 6 for detecting the movement of the latch member 3 from the lock pin locking position to the unlocking position where the lock pin 22 is unlocked, and the control circuit commands the solenoid 5 to perform a locking operation upon detecting the unlocking operative state based on a detection signal from the switch 6. Accordingly, even when the latch member 3 or the solenoid 5 in the locking position or state is subjected, for example, to a great impact to bring the rod 51 of the solenoid 5 into the unlocking operative state and release the lock pin, this situation is detected by the switch 6, whereupon the solenoid 5 is given a command to perform a locking operation. The latch member 3 is therefore driven to the locking position immediately after unlocking to resume the locking state.
Further stated more specifically, the control circuit holds the solenoid 5 in an unlocking operative state only for a specified period of time in response to an unlocking signal. Accordingly, when the lock pin 22 is to be removed from the tag body 10 by a lawful procedure, an unlocking signal is sent to the tag body 10, and the lock pin 22 is thereafter pulled out of the tag body 10 before the lapse of the specified period of time.
Further stated more specifically, the tag body 10 has a buzzer 8 incorporated therein, and the control circuit gives an alarm command to the buzzer 8 upon receiving an alarm actuating signal or upon detecting a break in the wire 2, with the lock pin 22 locked by the latch member 3. The buzzer 8 actuated then gives notice of a wrongful act.
Further stated more specifically, the control circuit gives an alarm stop command to the buzzer 8 upon receiving an alarm cancel signal during alarming or when alarming continues for a predetermined period of time. The buzzer 8 is then brought out of operation by sending the alarm cancel signal to the tag body 10 during alarming or by allowing the alarming operation to continue only for the predetermined period of time.
Further stated more specifically, upon the control circuit receiving an alarm actuating signal or detecting a break in the wire 2, with the lock pin 22 locked by the latch member 3, the control circuit wirelessly emits an alarm information signal giving notice of the situation. An unlawful act can then be found by monitoring the reception of an alarm information signal, for example, in a monitoring room.
The tag device embodying the invention as described above is adapted to realize a reliable locking state by using a locking mechanism wherein the spring piece 32 of the latch member 3 is deeply engaged with the lock pin 22, also realizing a facilitated unlocking procedure by using an unlocking mechanism wherein the latch member 3 is moved away from the lock pin 22.


A control apparatus for carrying out a spot welding operation using a robot comprises a spot welding gun having a spot welding tip, an electric drive mechanism for driving the tip, and a control unit for controlling the electric drive mechanism, in which the operation of the spot welding gun is synchronously controlled with that of the robot. The electric drive mechanism is composed of an electric drive servo mechanism comprising a servo amplifier, an electric drive servo-motor and a spot welding tip driving unit. The control unit comprises a central processing unit, a random access memory, a read only memory, a timer and an input/output interface which is operatively connected to the servo mechanism and the spot welding gun. The control apparatus further comprises an input unit, a tip position detector, a robot driving unit and a robot position detector, all of which are connected to the control unit.

The present invention relates to a control apparatus for a spot welding robot particularly capable of controlling opening/closing operations of tips of a direct spot welding gun without utilizing a hydraulic or pneumatic controlling device.
In a conventional art of an automobile manufacturing line, for example, spot welding robots R have been utilized. Such a spot welding robot utilizes a spot welding gun operated by hydraulic or pneumatic means as shown in FIG. 7, which is a schematic diagram of a conventional spot welding robot controlling system. The system of FIG. 7 comprises a hydraulic or pneumatic tip elevating unit 101, a tip elevating member 102, a pneumatic or hydraulic control unit 103, called fluid control unit hereinafter and a robot control unit 104. The hydraulic control unit 103 has a construction basically different from a robot control unit 104 which is mainly composed of electric elements or parts. Therefore, the hydraulic control unit 103 cannot be integrally combined with the robot control unit 104, and hence, these control units 103 and 104 are independently installed. In an operation of welding a workpiece W, the robot control unit 104 controls a control element of the hydraulic control unit 103 thereby indirectly controlling the operation of a spot welding gun G having a tip G1 which opens and closes in both the directions shown by an arrow onto tip 621, thus making the control system more complex, resulting in increased cost of manufacture and maintenance of the entire apparatus.
Furthermore, the hydraulic control unit 103 of the conventional apparatus includes piping means, cylinder means and valve means, each of which has a certain capacity or volume, resulting in that time delay in operation may be likely caused. Accordingly, it is difficult to synchronously control the hydraulic control unit with the robot control unit mainly composed of electric elements having less time delay in operation. For this reason, in the prior art, as shown in FIG. 8, because it is difficult to perform synchronous control it is not possible to perform opening, closing and welding operation of the spot welding gun G while the robot is moving. Therefore, the robot has to be first moved without operating the gun at this time and moved to the position for welding. Then, only the gun has to be moved and the series of operations of closing.fwdarw.welding.fwdarw.opening are then performed. In particular, the following steps are performed:
Step 1: The robot is at standby at the original point. PA0 Step 2: Axis 1 and axis 2 are started and the robot is moved to the escape point close to the welding point, then to the welding point. PA0 Step 3: The gun is closed after the robot has arrived at the welding point, and the operation commences. PA0 Step 4: The gun is closed, and the welding starts after the work is held at a required pressure. PA0 Step 5: The welding finishes. PA0 Step 6: The gun opening work starts, and after the gun has opened to a certain extent, the robot operation for moving to the escape point close to the welding point and to the origin starts. PA0 Step 7: The robot returns to the origin, and axis 1 and axis 2 stop. PA0 a spot welding gun having a spot welding tip; PA0 an electric drive means for driving the tip; and PA0 a control means for controlling the electric drive servo mechanism, PA0 wherein the operation of the spot welding gun is synchronously controlled with that of the robot as one axis means of the robot.
Thus this requires much time for the spot welding, resulting in a significant problem in an automobile industry in which an improved production efficiency on the production line is increasingly required.
In order to obviate such defects of a spot welding gun G utilizing the fluid control unit 103 of the prior art, there is provided a spot welding gun utilizing an induction motor as disclosed in the Japanese Patent Publication (KOKOKU) No. 3-50631 (50631/1991).
However, a spot welding gun utilizing the induction motor includes a servo mechanism, which differs from that of the robot control unit, and accordingly, in order to synchronously operate such a spot welding gun utilizing the induction motor with the robot control unit, another independent control unit is required between this spot welding gun and the robot control unit, thus increasing the cost and making the apparatus itself complicated. Thus, synchronous operation cannot be easily achieved and the entire welding time cannot be remarkably shortened. Therefore, it is difficult to directly or easily apply conventional spot welding guns to spot welding robots.

Control apparatus for spot welding robot


A two-for-one twisting spindle with a compressed air operated threading device is provided. The thread is feed via a jet of compressed air through a thread feeding channel of a thread storage disk. At the outer opening of the thread feeding channel a first deflecting surface is provided which is attached to the underside of the turntable. The first deflecting surface is provided with a upwardly curved second deflecting surface which is essentially convex. These constructive measures at the outer opening of the thread feeding channel ensure that the jet of compressed air exiting from the outer opening of the thread feeding channel has a certain vertical width h and that the radius of curvature R of the second deflecting surface is such that the ratio of the radius of curvature to the width h corresponds to R/h.gtoreq.3. This ensures that the jet of compressed air is deflected in an upward direction essentially vertically with the aid of the so-called Coanda effect.

The present invention relates to a two-for-one twisting spindle with a compressed air operated threading device with which a thread is fed through a thread feeding channel by a jet of compressed air, with a first deflecting surface arranged at an underside of a turntable, disposed above a thread storage disk, and extending radially outwardly from an opening of a radial portion of the thread feeding channel whereby the first deflecting surface has a transition into a second deflecting surface that extends in an upward direction and is convex.
Such a two-for-one twisting spindle is known from EP 00 26 159 B1. With this known device, the jet of compressed air which leaves the thread feeding channel and carries the end of the thread with it is guided against a deflector plate. This deflector is fixedly or adjustably arranged relative to the turntable of the spindle at a position between the outer curved opening of the thread feeding channel and the outer edge of the turntable. The deflector plate is embodied such that its upper end extends at least to the height of the center axis of the outer opening of the thread feeding channel and the extension of its front end surface is essentially tangential to a second deflecting surface which is upwardly curved and convex.
In the above cited publication it is mentioned that the aforementioned device presumably relies on the so-called Coanda effect according to which a jet of air which is guided along a convex curved surface is deflected such that it follows the curvature of the surface.
With the known device, however, the deflection of the air jet is essentially effected by the deflector plate.
The known device has the disadvantage that the deflector plate must be arranged over the entire circumference of the turntable, or an exact position of the outer opening of the thread feeding channel relative to the deflector plate during the threading step, or an adjustment of the deflector relative to the outer opening must be provided in order to be able to perform the threading step. This requires complicated measures and disadvantageous especially for automatic threading.
A further disadvantage of the known device is the soiling and contamination of the surface of the fixedly connected deflector which is not contacted by the thread during the twisting process. Due to fluctuations of the position of the thread balloon, portions of the thread may come into contact with the contaminated surfaces which will result in a reduced quality of the resulting twisted thread.
Another possibility of deflecting a thread without a fixedly arranged deflector is described in DE 29 39 593 C2. In this device a second jet of compressed air is used which deflects the jet of compressed air together with the thread essentially about an angle of 90.degree. in an upward direction. This solution is also rather complicated and requires an exact positioning of the outer opening of the thread feeding channel relative to the second jet of compressed air during the threading step.
It is therefore an object of the present invention to provide a two- for-one twisting spindle with the aforementioned features which provides for an automatic threading of the thread without providing a deflector plate that is fixedly connected relative to the rotatable components of the spindle.

Two-for-one-twisting spindle with a compressed air operated threading device


A method for aiding detection of infection of a terminal by malware. The method includes: reception of a current request originating from the terminal asking for access to a resource of a network; detection that the resource requested is malevolent; when the current request includes a reference to an initial resource, verification that access to the initial resource has been requested from the terminal in at least one earlier request, the initial resource having been detected legitimate during processing of the earlier request; and wherein the current request being then considered to be an attempt to infect the terminal.

The infection of data processing terminals by means of malware programs is intended to allow persons of malicious intent, or cybercriminals, to take control of terminals remotely and to extract sensitive data from them such as identifiers, passwords, banking data, etc. Such an infection may take place in several ways: downloading onto the terminal infected files via the Internet, opening email attachments, which in this case is referred to as "phishing". The malware program may also be transmitted by means of a removable medium such as a "USB" (for Universal Serial Bus) stick. The infection may also be as a consequence of the exploitation by the creator of the malware program of a vulnerability of the terminal, for example a flaw in the browser, etc.
Once the terminal is infected by the malware program, it connects to one or more malicious servers situated on the Internet in order to receive commands and/or send information contained in the infected terminal. The majority of the malware programs use the protocol "http" (for "hypertext transfer protocol") which constitutes the majority of the Internet traffic. The malware programs thus generate a malicious traffic which merges into a legitimate traffic and which is furthermore difficult to identify and to isolate.
The usual techniques for detection of a malicious traffic are essentially based on a search within a database of malicious "URL" (for "Uniform Resource Locator") signatures, or black list of malicious URLs. These databases list malicious resources and servers known on the Internet. An attempt to connect from a terminal to one of the resources whose signature is present in the database indicates either the effective presence of a malware program on the terminal or an attempt to infect said terminal.
In order to overcome this type of attack, it is usual to establish a system for monitoring the network traffic which analyzes all of the traffic coming from the terminal in order to identify communications which may be associated with a malware program. Thus, when the terminal generates an http request sent over the Internet, the latter is intercepted by the monitoring system which analyzes the content of the request. If the URL does not appear on the black list, the traffic is not blocked and the software having generated the http request receives in response the requested resource. If the URL included in the request is referenced in the black list of the malicious URLs, the request is blocked and an error message is sent to the terminal. In this case, and in order to combat infections, a warning is raised and sent to a security administrator in order to apply remedial solutions as quickly as possible, such as a targeted anti-virus, a quarantining of the terminal, etc., before the malware program has had the time to do serious damage.
However, such a solution generates many false positives which are detrimental to the administration of the system. A false positive is defined by the generation of an infection alarm for a terminal even though the latter is not infected. Indeed, a large number of accesses to malicious URLs are not linked to the presence of a malware program in the terminal in question, but to redirections and automatic accesses using functionalities of the http protocol and exploited by the attackers to try to infect the terminals in question. For example, an innocent request emanating from a terminal may lead to the uploading onto a server of a page by the browser which may include links or redirections to malicious resources. The addition of these malicious resources may be made by the attacker, for example by exploiting a vulnerability of the web server contacted by the terminal, by hijacked use of advertisements, etc. For example, a user connects to the site "http://downloadmusic1.com/" and their browser connects in an automatic and transparent manner to the malicious server "http://1shot.ru/" subsequent to a redirection by the server contacted. Such an access is seen as indirect because it is subsequent to an access to a legitimate resource of the network, in this case "http://downloadmusic1.com/". The monitoring system analyzes the two requests that emanate from the terminal and generates an alarm for the second request indicating that the terminal is infected. Thus, no distinction is made by the monitoring system between an infection attempt by indirect access and a true infection which involves a direct connection to a malicious site. A security administrator is then obliged to analyze each alarm in order to determine whether the terminal really is infected. This reduces the efficacy and the advantage of an automatic detection for infection of a terminal whenever the infection attempts also give rise to alarms of the same level of criticality as the alarms representative of real infections.

Method of aiding the detection of infection of a terminal by malware


The present invention is related to the field of CRISPR-Cas9 gene editing platforms. In particular, the present invention has identified Type II-C Cas9 anti-CRISPR (Acr) inhibitors that control Cas9 gene editing activity. Co-administration of such Acr inhibitors may provide an advantageous adjunct in permitting safe and practical biological therapeutics through spatial or temporal control of Cas9 activity; controlling Cas9-based gene drives in wild populations to reduce the ecological consequences of such forced inheritance schemes; and contributing to general research into various biotechnological, agricultural, and medical applications of gene editing technologies.

CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats; CRISPR-associated system) comprises a bacterial immune system that recognizes and destroys foreign nucleic acids. The development of Type II CRISPR-Cas9 systems as programmable nucleases for genome engineering has been beneficial in the biomedical sciences. For example, a Cas9 platform has enabled gene editing in a large variety of biological systems, where both gene knockouts and tailor-made alterations are possible within complex genomes with unprecedented accuracy and efficiency. The CRISPR-Cas9 system has the potential for application to gene therapy approaches for disease treatment, whether for the creation of custom, genome-edited cell-based therapies or for direct correction or ablation of aberrant genomic loci within patients. Mutant versions of Cas9 in which the DNA cleavage activity has been inactivated ["dead" Cas9 (dCas9)] have also been developed for RNA-guided genome binding, enabling further applications in gene expression control and genome structure visualization.
The safe application of CRISPR-Cas9 in gene therapy requires an ability to control the gene editing activity of a Cas9/sgRNA complex once the intended use has been realized. While several engineered systems allow for controlled activation of CRISPR-Cas9 to increase precision, all of these systems still lack the ability to provide predictable control and robust inhibition.
What is needed in the art is the ability to predictably control gene editing (Cas9) or genome binding (dCas9) activity to prevent unintended Cas9 cleavage or DNA binding activity once a specific goal has been attained. Additionally, the ability to restrict Cas9 cleavage activity to a particular site, tissue, or cell cycle stage would greatly improve the efficacy and safety of Cas9-based clinical treatments and research applications.

Anti-CRISPR compounds and methods of use

THE GOVERNING COUNCIL OF THE UNIVERSITY OF TORONTO


Disclosed is an apparatus for applying a viscous liquid material and a method of controlling the discharge of the viscous liquid material. The apparatus has a movable nozzle having a port for discharging the viscous liquid material in a predetermined discharging direction. The nozzle is movably arranged to controllably trace a predetermined track. A shutter for controllably closing the port of the nozzle includes a shiftable member arranged on the port to move relative to the port between a first position and a second position along a plane which crosses the discharging direction of the nozzle so that the shiftable member release and covers the port of the nozzle. The present invention is suitable for application on a loop track or a closed path. In the method, it is preferred that the first position is located on the front side of the second position facing toward a direction in which the nozzle advances at termination of tracing with the viscous liquid material.

1. Field of the Invention
The present invention relates to an apparatus for applying a viscous liquid material, in particular, to an apparatus for injecting a viscous liquid material such as an adhesive with following a predetermined track on a surface of an object to be applied, and relates to a method of controlling application in an application apparatus.
2. Description of the Prior Art
Conventionally, work steps of applying a viscous liquid material such as an adhesive and the like have been utilized in various manufacturing processes in such a way to draw a line or a band with the viscous material on a surface to be applied, following a predetermined track. Specifically, in a process for assembling automobiles, a liquid rubber called a sealant is applied to the periphery of a sheet glass, and it is then pressed to a window panel at a normal temperature, thereby the sheet glass is adhered to the window. For another example, in assembly of picture tubes for a television set, a frit is applied to a joint surface at the brim of a coned funnel, and a front grass is then mounted on the brim of the coned funnel to be adhered by baking at a temperature of about 450.degree. C. As illustrated above, the apparatus for applying a viscous liquid material have been widely utilized in the industrial field.
The apparatuses which have been conventionally utilized for applying a viscous liquid material can be generally classified into three types, that is, a valved-tank type, a type of having a pressured tank and a separate valve, and a type of pumping to a separate valve.
FIG. 1 shows a construction of a valved-tank type frit application apparatus. In the frit application apparatus of FIG. 1, a large tank 1 containing a frit, whose capacity is rather large, for example, about 2 liters, is located with a robot hand (not shown) above a funnel 2 whose surface to be applied is faced upwards toward the tank 1. The tank 1 has a nozzle 3 at a bottom end thereof, and the tank 1 is moved by the robot hand so that the nozzle 3 traces on an application track, that is, the brim of the funnel. Inside the tank 1, a needle valve 4 is arranged to be axially moved downwards by a piston device 5, so that a tip end of the needle valve seats on a valve seat 4a to close the nozzle 3. Moreover, a blade 7 which is driven by an actuator 8 is provided inside the tank 1 in order to agitate the frit. On the other hand, a tube is provided on the tank 1 in order to apply an air pressure to inside of the tank 1 at a preset level of 0.2 to 0.5 kg/cm.sup.2. A sensor 9 is provided for detecting a initial point at which a band of the frit applied on the funnel begins on the surface.
According to the above construction, the needle valve 4 opens the nozzle 3 to apply the frit to the brim, while it travels along the brim of the funnel. Near the termination of the application along the brim, the initial portion of the frit band is detected by the sensor 9, and the needle valve 4 is then closed so that application of the frit is stopped at the initial point, thereby achieving a cycle of frit application.
However, in the apparatus described above, the tank 1 has large weight and high inertia. Therefore, correctness of the operation of the tank 1 by using the robot arm tends to decrease. Moreover, it is very difficult to control a volume of the injected frit by regulating the needle valve 4 which is moved downwards at the termination of the application in response to detection of the initial portion of the applied frit band. In particular, at closing of the needle valve 4, the frit between the needle valve 4 and the valve seat 6 is forced out of the nozzle 3 by the needle valve 4, so that the band drawn with the applied frit is suddenly swelled at a site A ahead the terminal point, which should meet the initial point, as shown in FIG. 2, and the band becomes extremely poor just behind the site A. Therefore, uniformity of the frit band deteriorates near the terminal point. Accordingly, it may cause incomplete adherence between the glass and the funnel assembled, which results in production of sub-standard articles, low reliability of the product and the like.
FIG. 3 shows a construction of a frit application apparatus of a type of having a pressured tank and a separate valve. In this apparatus, a frit which is enclosed in a main tank 10 and agitated with a blade 7 rotatively driven by an actuator 6 is pressed by an air pressure to be fed through a gate valve 11 and a flexible connecting tube 12 to a valve device 13 which is provided separately from the main tank 10. The valve device 13 is arranged to be moved by a robot arm (not shown) and the like above a surface to be applied of the funnel 2. In accordance with the above construction, the valve device 13 travels on an application track, while the valve is operated to open, thereby achieving frit application.
However, in this apparatus, since the frit is fed through the flexible connecting tube 12, the pressure applied on the frit decreases from a value Pt at the tank 10 down to a value Pi at an injection port of the valve device 13 according to the distance from the tank 10 as shown in FIG. 4. Therefore, it is rather difficult to control the injection pressure Pi. In addition, since the injection pressure Pi also easily changes in response to the travelling movement of the valve device 13, the frit applied to the funnel forms an uneven band 14 as shown in FIG. 5. Moreover, according to sudden pressure change at the gate valve 11, some component blended in the frit sometimes separates from the frit in the connecting tube 12, etc., the frit cannot be applied, accordingly, in a normal condition.
FIG. 6 shows a construction of a frit application apparatus of a type of pumping to a separate valve. In this apparatus, in place of a gate valve 12 of the apparatus shown in FIG. 3, a screw pump 15 is utilized for forcingly feeding the frit to the valve device 12. Therefore, this apparatus can avoid the frit separation caused by pressure decrease at the gate valve illustrated above. However, since the frit feeding method of this apparatus is basically the same as that of the apparatus shown in FIG. 3, the injection pressure at the valve device 13 cannot be controlled to fluctuate unstably. Therefore, the frit applied on the funnel 2 similarly draws a non-uniform band such as shown in FIG. 5.
Of course, in a process for applying a sealant to a sheet glass, the same problems as illustrated above similarly arises as frequently as in that for a frit application to a funnel described above.
Consequently, the conventional apparatuses for applying a viscous liquid material have various problems to be solved such as incorrect positioning due to weight and inertia of a large-volume tank, difficulty in control of an applied volume, unevenness of the band traced with the applied liquid material, component separation of the frit, etc. In other words, it is difficult to apply a viscous liquid material uniformly with high reliability.

Apparatus for applying a viscous liquid material and method of controlling application thereof


A predictive and self-tuning PI controller includes an apparatus for variably assigning gains thereto in accordance with specified time functions following a change in set-point. The control gains are computed in accordance with a plurality of input parameters and subsequently continuously adjusted to set-point errors based on a GPC approach thereby to optimize performance indices derived from simple and classical user specifications. Variation and tuning of control gains in accordance with set-point errors permits the PI controller to be useful in the general area of process control and applicable to a wider range of processes compared to traditional PI control, including time-delay processes, unstable processes and processes with time-varying dynamics.

This invention generally relates to the field of process control, and more particularly to a predictive and self-tuning PI (Proportional plus Integral) control design which enhances the performance achievable with conventional PI control while capitalizing on the strong user-support established and available for a simple PI control structure.
PI control has existed for more than fifty years. The current methodology in tuning a PI controller has been essentially to deduce and infer a set of fixed control gains from the characteristics of the process. Over the years, the control gains tuning process has evolved from simple and heuristic procedures to more elaborate and exact computations based on mathematical models of the process, resulting in increasing performance yields.
However, whichever inferencing procedure is used, the resultant control gains derived thereby are mostly fixed. As specifications on control performance are tightened by requirements for increased precision with greater complexity of processes being controlled, the fixed nature of the control gains has direct implications on the range of processes for which the known PI control structure continues to be applicable and useful. For example, the conventional fixed-gains PI controller is well-known to be inadequate for a number of classes of linear systems, including: time-delay processes, unstable processes, and processes with time-varying parameters.
Advanced and more complex control methods may be recommended for these systems. However, such methods require more structurally-elaborate devices which, in themselves, act as a dis-incentive to adoption and utilization. Moreover, there remains the decades-old dilemma that has been facing hordes of control engineers, in that under real working conditions (e.g., including model imperfections, modest process operators, limited availability of technical support, short breakdown recovery tolerance, etc), the benefits of advanced control over PI control have never been quite obtainable. This is one main reason as to why the traditional approach to PI control remains widely used despite the clear limitations associated therewith.
It is accordingly an object of the present invention to overcome the limitations of prior art PI controls.
It is a more specific object of the invention to provide improvements over traditional forms of PI control in a novel control apparatus which retains the conventional PI control structure, and thereby to capitalize on the massive user-support established for PI controllers over the decades.
It is still a more particular object of the invention to provide a novel method of and apparatus for control gains-tuning and continuous self re-tuning of control parameters of a process based on a GPC (Generalized Predictive Control) approach to optimize performance indices.
It is yet a more detailed object of the invention to provide a predictive and self-tuning PI controller.
It is still a more specific object of the invention to provide a predictive and self-tuning PI control apparatus which expands the domain of PI control applications to include time-delay processes, unstable processes, and time-varying processes.
It is thus an object of the invention to provide an improved PI controller which, by utilizing a predictive and self-tuning approach to control, is unified in design for different classes of processes, is applicable to a broader range of linear processes than the prior art, and yields performance improvements beyond traditional fixed-gains PI control.
In accordance with the foregoing objects, the present invention provides a novel predictive and self-tuning PI controller, which optimizes performance indices derived from simple and classical user specifications.
In accordance with another feature of the invention, there is provided a method for designing a predictive and self-tuning PI controller which is based on a GPC design approach.
In accordance with the invention, there is thus provided a control apparatus having a design which is naturally amenable to optimal control applications.
In accordance with another aspect of the invention, there is provided a control apparatus having inherent predictive and self-tuning capabilities which expand the PI control application domain to include time-delay processes, unstable processes, and time-varying processes.
In accordance with a more specific feature of the invention, there is provided a control apparatus comprising a novel combination of components, including a control structure similar to a conventional PI control, and a plurality of novel elements, including a gains design means, a gains scheduling means, and a gains self-tuning means.
In accordance with another aspect of the invention, there are provided novel design, scheduling and self-tuning algorithms for the gains of a PI controller, and apparatus for implementing the same.
In accordance with yet another feature of the invention, there is provided a control apparatus including a PI process controller and a gains design means for designing gains of the process controller, the gains design means being responsive to a user specified parameter set including parameters representing a first-order mathematical model of the process, a parameter representing an estimate of a time-delay of the process, parameters representing a desired closed-loop damping factor and natural frequency, and a sampling interval, and which, in response to the input parameters specified by the user, generates a plurality of time functions associating the PI control gains to the input parameters.
It is still another feature of the invention that the user specified parameter set which is input to the gains design means may include an optional prediction horizon and that, when the optional prediction horizon is unspecified, the gains design means recommends a default prediction horizon.
In accordance with a more detailed feature of the invention, the control apparatus also includes a gains scheduling means for assigning appropriate gains to the PI controller based on a schedule, the schedule depending on elapsed time following a set-point change according to the time functions generated by the gains design means. The gains scheduling means is further responsive to a set-point signal defining a desired process variable, and outputs are the actual time-scheduled gains to be assigned to and updated on the PI controller.
In accordance with still a more detailed feature of the invention, the control apparatus further includes a gains self-tuning means for continuously adjusting weighting parameters of the time functions generated by the gains design means to optimize performance of the PI process controller. The gains self-tuning means is further responsive to a set-point error which is the difference between the desired and actual process variables. The outputs from the self-tuning component are a set of replacement weighting parameters for the time functions generated by the gains design means.

Predictive and self-tuning PI control apparatus for expanded process control applications


Apparatus for generating and delivering a pressurized hot water pulse to a brewing station comprises a water inlet adapted to close during delivering the pulse, an outlet for the pulse, a generator comprising a water heating chamber for receiving a amount of water via the inlet and for heating the water therein to produce sufficiently hot water for the brewing station, a pressurization chamber for vaporizing water to generate pressurized steam to deliver the hot water as a pressurized hot water pulse to the brewing station through the outlet, and a heating system for the heating and the vaporization of the water in said pulse generator. The chamber has a first end adapted to receive pressurized steam and a second end close to the hot water intake port of the inlet. The pressurization chamber is adapted to provide pressurized steam to the first end of the heating chamber in such a manner that substantially no interaction occurs between the pressurized steam and the hot water between the first and second ends of the heating chamber, thereby substantially preventing the overheating of the hot water by the pressurized steam. The pulse generator is adapted to cause water to flow into the pressurization chamber from the water heating chamber or inlet for the generation of the pressurized steam.

Extraction temperature and time are among the most critical considerations when brewing coffee. Automatic drip coffee makers (ADCs) brew better coffee than percolators by avoiding re-boiling coffee and reducing extraction time, thus preserving the aroma and reducing coffee bitterness. (The bitter, less soluble chemicals in the grounds require longer extraction time.) Shorter extraction time, however, normally causes incomplete extraction, which contributed to the weaker coffee made by single-cup ADCs and by displacement-type coffee makers (U.S. Pat. No. 5,200,221).
It is known that the best brewing temperature for coffee is 192° to 205° F. Such high temperature is easily achievable by boiling water in a percolator. But it is more difficult for ADCs, especially when a single cup of coffee is to be brewed, which also contributed to the weaker coffee made by single-cup ADCs.
In the applicant's earlier U.S. Pat. No. 5,267,506, apparatus is disclosed to brew coffee by extracting the grounds under elevated pressure to reduce the extraction time while achieving full flavor extraction. The apparatus has a cell in contact with a heater that draws an amount of water from a reservoir and subsequently heats the water and generates pressurized steam to deliver the hot water. In a first embodiment, the hot water in the cell is delivered to and through the flavor-containing materials under steam pressure and the steam is then released through a steam release valve. In a second embodiment, the hot water in the cell is first delivered and the steam is later delivered to the flavor-containing materials.
In the applicant's another earlier U.S. Pat. No. 6,405,637, apparatus and method are disclosed to brew coffee by generating and delivering a plurality of pressure pulses, each of which contains a pressurized hot water pulse and a pressurized steam pulse, to and through the flavor-containing materials to extract the useful compounds under the pressure of the pressure pulses.
Such apparatus have numerous advantages including higher brewing speed, less flavor loss and lower cost over known coffee makers and espresso machines. However, significant advancements can still be made with such apparatus to improve the taste and brewing time as well as the ease of use and cost of the apparatus.

Fluid delivery system for generating pressurized hot water pulses


An aqueous electrophoretic coating material, which can be deposited at the cathode and contains. (A) 90 to 50% by weight, based on the total portion of synthetic resin vehicle, of one or several polycondensation, polymerization and/or poly-addition resins, the resin or, in the event that several resins are present, their mixture PA1 (B) 10 to 50% by weight of one or several cross linking agents, which are compounds with methane tricarboxylic acid amide units of the formula ##STR1## which contain, on the average, at least 2 groups with reactive hydrogens per molecule and are derived from a reaction product of a monoisocyanate or polyisocyanate with a malonic acid derivative, and PA1 (C) 0 to 10% by weight of one or several capped diisocyanates and/or polyisocyanates, as well as its use.. (a) having a number average molecular weight (Mn) of 700 to 10,000 PA2 (b) having 1.2.times.10.sup.23 to 21.7.times.10.sup.23 lateral or terminal double bonds per 1,000 g, corresponding to a hydrogenation iodine number of 5 to 90, PA2 (c) optionally containing primary and/or secondary hydroxyl groups, corresponding to a hydroxyl number of 0 to 450 mg KOH/g of resin, and PA2 (d) tertiary amino groups corresponding to an amine number of 30 to 450 mg KOH/g of resin.

The advantages of cathodic electrophoretic enameling are described in the technical literature and in patents (Metalloberflache 31 (1977) 10, pages 455-459, EP-A-4 090, AT-C-3 46 989, U.S. Pat. No. 3,922,253, EP-B-66 859).
A disadvantage of the systems described is the use of relative high stoving temperatures of about 170.degree. C., as a result of which the expenditure of much heating energy is required. In the automobile industry, the main user of the cathodic electrophoretic enameling method, these high stoving temperatures prevent the inclusion of plastic parts in car bodies before priming and in some cases reach the melting temperatures of soldered connections.
The suppliers of cathodic electrophoretic enameling systems must therefore be able to produce these materials, with which the previously good properties of the primers are not adversely affected at low stoving temperatures (low bake).
In U.S. Pat. No. 4.443,559, .beta.-hydroxyurethanes are disclosed as cross-linking agents for cathodic electrophoretic enameling systems with a low stoving temperature. At 250.degree. F. (121.degree. C.), curing that is described as "appreciable" is achieved (column 6, lines 12-13). Only at 325.degree. F. (163.degree. C.) is the curing "excellent" and thus usable for car bodies. A further disadvantage is the handling of larger amounts of poisonous isocyanates during the production of this enamel system.
In EP-A-1 25 577, curing at low temperatures is achieved by the combination of onium group-containing polymers with special amino resins, however, at the expense of inferior corrosion protection properties.
The corrosion protection results, achieved at stoving temperatures below 160.degree. C. even with the systems from DE-A-32 46 812 and DE-A-33 28 455, are also inadequate for the demands of the automobile industry.
DE-A-33 46 812 discloses curable, cationic, modified products of epoxide resins, which contain .beta.-hydroxyalkylcarbamide ester groups, while DE-A-33 28 455 starts out from amino acid/salt adducts with urethanized amino groups.
In the DE-A-33 24 211 and DE-A-33 15 469, Michael addition products of monocarboxylate or dicarboxylate esters with compounds, which contain double bonds capable of reacting in a Michael addition reaction, are combined for cross linking with hydroxyl group-containing synthetic resins, for example, with cathodic electrophoretic enameling support resins.
As stoving conditions, a temperature of 130.degree. to 200.degree. C. over a period of 10 to 60 minutes and preferably a temperature of 150.degree. to 180.degree. C. over a period of 15 to 30 minutes are mentioned. In the examples, the stoving temperatures are between 150.degree. and 200.degree. C. Coatings, 16 to 18 .mu.m thick and stoved at temperatures below 150.degree. C., do not fulfill the requirements of the automobile industry, for example, with respect to good mechanical properties, sufficient resistance in the ASTM 117/6 or DIN 50 021 salt spray test or good outdoor exposure resistance.
DE-A-35 30 179 discloses the cross linking of cathodic electrophoretic enameling support resins, which have terminal or lateral double bonds, as well as reactive hydroxyl groups, with Michael addition products of monocarboxylic or dicarboxylic acids, which are capable of participating in a Michael addition reaction and suitable double bond-containing compounds. At stoving conditions of practically 60 minutes at 120.degree. C., corrosion-resistant and robust coatings are obtained.
The EP-A-208 867, in which the cross linking of cathodic electrophoretic enameling support resins, which have hydroxyl groups, with components of the reaction products of diisocyanate with CH-active alkyl esters and polyamines is regarded as a transesterification reaction, also discloses coatings, for which adequate properties can be anticipated only at stoving temperatures above 120.degree. C.

Aqueous electrophoretic enamel coating materials, which can be deposited at the cathode crosslinked with methane tricarboxylic acid amides of malonic acid derivatives