Human immunodeficiency virus (HIV) comprising reverse transcriptase inactivated by photoinactivation. The inactivated virus may be more safely handled, stored, and analyzed, used in diagnostic procedures and kits, and may be used as an immunogen to evoke an immune response. The immune response may protect an individual from challenges with live virus. Alternatively, the inactivated HIV particles may be used to augment the immune response to HIV in an infected individual.

1.1 Field of the Invention
The present invention relates generally to the fields of virology, immunology, disease treatment and prevention. More particularly, it concerns HIV particles with inactivated reverse transcriptase, methods of inactivation, and the use of such particles to prepare components of HIV and to elicit effective immunological responses to HIV. These immune responses are useful in producing diagnostic reagents, assays, and kits for the diagnosis of HIV and related retroviral disease, providing protection from an HIV challenge, and assisting an HIV-infected individual in controlling the replication of the virus. Methods of inactivation are useful for preventing disease through decreasing the risk of infection associated with exposure to HIV infected tissues and materials.
1.2 Description of Related Art
1.2.1 Human Immunodeficiency Virus
Human Immunodeficiency Virus-1 (HIV-1) infection has been reported throughout the world in both developed and developing countries. HIV-2 infection is found predominately in West Africa, Portugal, and Brazil. It is estimated that as of 1990 there were between 800,000 and 1.3 million individuals in the United States that were infected with HIV. An important obstacle to developing a vaccine against HIV is that the mechanism of immunity to HIV infection is ill-understood. Not all of those infected individuals will develop acquired immunodeficiency syndrome (AIDS). Indeed recent reports have suggested that there may be certain individuals that are resistant to HIV-1 infection.
The HIV viruses are members of the Retroviridae family and, more particularly, are classified within the Lentivirinae subfamily. Like nearly all other viruses, the replication cycles of members of the Retroviridae family, commonly known as the retroviruses, include attachment to specific cell receptors, entry into cells, synthesis of proteins and nucleic acids, assembly of progeny virus particles (virions), and release of progeny viruses from the cells. A unique aspect of retrovirus replication is the conversion of the single-stranded RNA genome into a double-stranded DNA molecule that must integrate into the genome of the host cell prior to the synthesis of viral proteins and nucleic acids.
Retrovirus virions are enveloped and contain two copies of the genome. The conversion of the genomic RNA into DNA is provided by the viral protein reverse transcriptase (RT). This protein is bound to the RNA genome within the virion, and its enzymatic conversion of the genome to DNA is believed to take place after viral entry into the host cell. However, recent evidence suggests that the conversion process may initiate in the virion particles themselves, known as endogenous reverse transcription (ER), and that ERT may be important in increasing the infectivity of the virus in sexual transmission (Zhang et al., 1993, 1996).
Because of the requirement for reverse transcription in the viral replication cycle, compounds that interfere with RT activity have been utilized as anti-HIV therapeutic agents. Many of these compounds, including 3′-azido-2′, 3′-dideoxythymidine (AZT), are nucleoside analogs that, upon activation by host cell kinases, are competitive inhibitors of reverse transcriptase (Furman et al., 1986). Other anti-RT compounds are nonnucleoside inhibitors (NNI), hydrophobic compounds that do not require cellular modification for antiviral activity. Examples of such compounds include nevirapine (Grob et al., 1992; Merluzzi et al., 1990), the pyridinones (Carroll et al., 1993; Goldman et al., 1991), and the carboxanilides (Bader et al., 1991; Balzarini et al., 1995, 1996). The nevirapine analog 9-azido-5,6-dihydro-11-ethyl-6-methyl-11H-pyrido[2,3-b][1,5]benzodiazepin-5-one (9-AN) and the carboxanilide analog N-[4-chloro-3-(3-methyl-2-butenyloxy)phenyl]-2-methyl-3-furanocarbothiamide (UC781™) have been shown to be potent inhibitors of RT. In respect of the 9-AN, the exposure of a mixture of this compound and RT to UV-irradiation has been particularly effective in inhibiting RT. From the series of carboxanilides compounds, UC781™ has been found to be particularly effective (Barnard et al., 1997). The addition of a photoreactive label to UC781™ should increase further its ability to inactivate HIV RT, when a mixture of UC781™ and RT is exposed to UV-irradiation. The irradiation of a mixture of a photolabeled NNI of RT and RT is a type of photoinactivation.
The binding affinity and inhibitory effect of UC781™ is so high that the compound was able to eliminate HIV infectivity following short exposure of the isolated virus to UC781™ without the need for photoinactivation (Borkow et al., 1997). Further, this compound was shown to inhibit ERT in HIV virions and, when provided to HIV infected cells, caused the production of noninfectious nascent virus (Borkow et al., 1997). Therefore, it appears that UC781™ is a particularly powerful inactivator of HIV. Although UC781 has been proposed for use in retrovirucidal formulations (Borkow et al., 1997), use as a photoinactivator of HIV for the purpose of producing an non-infectious virus particle useful as an immunogen is absent from the prior art.
Non-infectious, virus-like particles have previously been produced via manipulations of the viral genome. For example, U.S. Pat. No. 6,080,408, incorporated herein by reference, discloses non-infectious virus-like particles wherein RT has been made inactive by virtue of deletions and sequence changes in the viral genome. Rovinski also discloses other methods of making non-infectious, virus-like particles, (or pseudovirions), that involve alterations to other genes of the HIV genome, expression of a subset of HIV virion components, and heat-inactivation of sera from HIV infected individuals. U.S. Pat. No. 6,017,543 discloses methods using formalin, psoralen, beta-propriolactone, alone and in combination, as well as exposure to gamma radiation.
1.2.2 Immune Response to HIV
The immune response to HIV is composed of an initial cell mediated immune response followed by the subsequent development of neutralizing antibodies. Within weeks of infection, virus titers in the blood fall coincident with the induction of anti-HIV cellular and humoral immune responses. The fall in viremia correlates well with the appearance of anti-HIV major histocompatibility complex (MHC) class I-restricted CD8+ cytotoxic T cells (Haynes et al., 1996). Recent evidence has shown a strong correlation of anti-HIV CD4+ T cell responses and reduced viral loads (Rosenberg et al., 1997). Therefore, the presentation of HIV antigens in the context of MHC class II molecules to CD4+ T cells may be the key aspect of the control of the HIV infection.
Rosenberg et al. (1997) suggest that in HIV-1 infection, HIV-specific CD4+ cells may be selectively eliminated. This may be due to the activation of these cells during high-level viremia, increasing their susceptibility to infection (Weissman et al., 1996; Stanley et al., 1996), or may be due to activation induced cell death during primary infection (Abbas, 1996). Nonetheless, increasing the virus-specific CD4+ T cell response without infecting, or destroying, the responding cells may be an effective means of controlling viral loads. Therefore, some existing HIV vaccines may be ineffective because they do not provide presentation of HIV peptides in the context of MHC class II by antigen presenting cells.
1.2.3 HIV Vaccines
Historically, viral vaccines have been enormously successful in the prevention of infection by a particular virus. Therefore, when HIV was first isolated, there was a great amount of optimism that an HIV vaccine would be developed quickly. However, this optimism quickly faded because a number of unforeseen problems emerged. A discussion of the problems that an HIV vaccine must overcome is provided within Stott and Schild (1996) and is incorporated herein by reference.
First, HIV is a retrovirus, thus, during its growth cycle, proviral DNA is integrated in the host genome. In this form the virus is effectively protected from the immune response of the host and this feature of the virus suggests that effective vaccination must ideally prevent the initial virus-cell interaction following transmission. Few, if any, of the currently available successful viral vaccines against other infections achieve this level of protection. Secondly, HIV specifically targets and destroys T-helper lymphocytes, which form an essential component of the immune response. Thirdly, the virus is capable of extremely rapid antigenic variation which permits escape of the virus from immune responses. Fourthly, the majority of infections are acquired sexually via the genital or rectal mucosae, and infections of this route are generally considered difficult to prevent by vaccination. Finally, infection may be transmitted by virus-infected cells in which the proviral DNA is integrated and viral antigens are not expressed. Such a cell would not be recognized by immune responses to viral proteins and would therefore pass undetected. Few data are available to indicate how significant this mode of transmission is in the overall epidemiology of HIV-1. Nevertheless, it represents a potential route and one which some authorities believe cannot be blocked by vaccination (Sabin, 1992).
Types of HIV vaccines include inactivated virus vaccines, live attenuated virus vaccines, virus subunit vaccines, synthetic particle vaccines, and naked DNA vaccines and are reviewed in Stott and Schild (1996), Schultz (1996), and Johnston (1997). Several of these vaccines are already in human trials.
The first evidence that vaccination against immunodeficiency viruses was feasible came from early experiments using simple inactivated virus prevented the onset of disease when vaccinated animals were subsequently challenged (Desrosiers et al., 1989; Sutjipto et al., 1990). These results were confirmed and extended by Murphey-Corb et al. (1989) who showed that most animals immunized with formalin-inactivated virus were protected against infection with SIV. Similar results were subsequently obtained by several laboratories using virus-infected cells (Stott et al., 1990) or partially purified virus, inactivated by aldehydes (Putkonen et al., 1991, 1992; Johnson et al., 1992a; Le Grand et al., 1992), β-propiolactone (Stott et al., 1990) detergent (Osterhaus et al., 1992) or psoralin and UV light (Carlson et al., 1990). Several different isolates of SIV or infectious molecular clones derived from them were used to prepare the vaccine and challenge viruses. A wide variety of adjuvants were also employed. On every occasion vaccinated macaques were protected against infection by intravenous challenge of between 10-50 MID50 (50% monkey infectious doses). Infections virus could not be recovered from the blood or tissues of the protected animals even when they were followed for prolonged periods of over 1 year. Even more impressive was the failure to detect proviral DNA in the lymphocytes of protected animals, indicating that there had been no integration of the challenge virus (Stott et al., 1990; Johnson et al., 1992a). It was thus clear that inactivated virus vaccines induced a powerful protective response in macaques. Unfortunately, the protection induced by inactivated SIV in macaques was not reproduced in chimpanzees vaccinated with inactivated HIV and challenged with HIV-1 (Warren and Doltshahi, 1993).
1.2.4 Photoinactivation of HIV
Methods of photoinactivation of HIV are known in the art and have been the subject of at least three patents. U.S. Pat. No. 5,041,078 describes the use of sapphyrins in the photodynamic inactivation of viruses, including HIV. U.S. Pat. Nos. 5,516,629 and 5,593,823 describe the use of psoralens and ultra violet light to inactivate HIV. U.S. Pat. No. 5,516,629 is incorporated herein by reference. Psoralens are naturally occurring compounds which have been used therapeutically for millennia in Asia and Africa A psoralen binds to nucleic acid double helices by intercalation between base pairs. Upon absorption of UVA photons, the psoralen excited state has been shown to react with a thymine or uracil double bond and covalently attach to both strands of a nucleic acid helix. The crosslinking reaction is specific for a thymine (DNA) or uracil (RNA) base and will proceed only if the psoralen is intercalated in a site containing thymine or uracil. The initial photoadduct can absorb a second UVA photon and react with a second thymine or uracil on the opposing strand of the double helix to crosslink the two strands of the double helix.
Lethal damage to a cell or virus occurs when a psoralen intercalated into a nucleic acid duplex in sites containing two thymines (or uracils) on opposing strands sequentially absorb 2 UVA photons. This is an inefficient process because two low probability events are required, the localization of the psoralen into sites with two thymines (or uracils) present and its sequential absorption of 2 UVA photons.
Attempts to inactivate viruses using photosensitizers and light have also been developed using some non-psoralen photosensitizers. The photosensitizers that have been employed are typically dyes. Examples include dihematoporphyrin ether (DHE), Merocyanine 540 (MC540) and methylene blue.
Carlson et al. (1990) has shown that a psoralen-inactivated whole SIV (the Simian counterpart of HIV) vaccine can protect against low challenge doses of SIV and prevent early death in those monkeys that do become infected, suggesting that inactivated HIV may be an effective vaccine in humans. However, because photoinactivation using psoralens is dependent on two rare events, a more efficient method of inactivation is preferable to decrease the likelihood of live virus within a sample. Furthermore, these methods alter the antigenic conformation of HIV affecting the production of an effective immunological response.
1.3 Deficiencies in the Prior Art
Due to previous successes in preventing viral diseases using subunit, live-attenuated viral, and inactivated viral vaccines, the scientific community was initially optimistic that a vaccine would be developed to prevent the spread of HIV. However, early optimism soon diminished because of repeated failures in the development of an effective vaccine.
Vaccines based on subunit immunogens, although extremely safe, are limited in the breadth of antigens that are presented to the immune system because only one or a few of the viral proteins are utilized as immunogens. This may limit the likelihood of cross protection between clades of HIV. Also, the production of vaccines based upon subunit immunogens requires the molecular manipulation of the viral proteins into cloning or expression vectors, perhaps leading to increased production time and costs.
Live-attenuated HIV vaccines typically utilize whole, or nearly whole virions as immunogens. Production of these vaccines may require molecular manipulations of the HIV genome in their production, although spontaneous attenuated viruses may occur naturally. Attenuated HIV vaccines have included deletions in the nef region of the virus. Mutant-nef SIV vaccines showed initial promise in primates, however, it was quickly shown that these vaccines were capable of causing disease in newborn animals. Furthermore, recent evidence suggests that these vaccines are capable of causing full-blown AIDS in adult monkeys (Cohen, 1997). Therefore, the lack of an efficient understanding of HIV and its pathogenesis makes the use of attenuated viruses a risky endeavor.
Inactivated viral vaccines provide a larger compliment of immunogens presented to the immune system, and, therefore, provide a greater amount of protection from HIV and are more likely to provide protection across HIV clades. Furthermore, the inactivated viral vaccines do not require molecular manipulation of HIV and can be made to essentially any strain. Because inactivation of the virus is readily shown in in vitro and animal models, the inactivated HIV vaccines are able to be tested in a timely manner to determine the effectiveness of inactivation. Attenuated viruses may take years to determine the effectiveness of the vaccine.
To be safe to administer to humans, efficient methods of inactivation of HIV are required for vaccine production. Methods known for the inactivation include the use of aldehydes, β-propiolactone, psoralin and UV light, and others including detergents. Many of these methods alter the conformation of the virus thereby altering the specificity of the immune response to the virus. Even gamma radiation may require the additional use of protective compounds to help preserve viral protein integrity, as disclosed in U.S. Pat. No. 6,017,543. Photoinactivation of HIV using psoralin and UV light does not alter the conformation of the virus, but it is an inefficient method of inactivation. Therefore, more efficient methods of inactivation that do not affect the conformation of the viral immunogen would be ideal for use in the production of an HIV vaccine.

This patent is subject to a terminal disclaimer.

Methods of eliciting antiviral immune responses utilizing viral particles comprising photoinactivated reverse transcriptase


An AC/DC converting circuit, has a full-bridge rectifier having two input terminals and two output terminals, a first capacitor, a second capacitor, an electronic switch having a control terminal, a trigger circuit having an input terminal and an output terminal, and a detecting circuit having an input terminal and an output terminal. The first capacitor and the second capacitor are serially connected between the output terminals of the full-bridge rectifier, the input terminals of the full-bridge rectifier are connected to an AC input, one end of the electronic switch is connected between the first capacitor and the second capacitor, the other end of the electronic switch is connected to one of the output terminals of the full-bridge rectifier, the input terminal and the output terminal of the detecting circuit are connected to the output terminals of the full-bridge rectifier, the output terminal of the detecting circuit is connected to an input terminal of the trigger circuit, and the output terminal of the trigger circuit is connected to the control terminal of the electronic switch.

1. Field of the Invention
The invention relates to an AC/DC converting circuit and a motor controller using the same.
2. Description of the Related Art
AC/DC converting circuits are widely used in current motor controllers. However, there are several problems with the conventional AC/DC converting circuits: 1) the circuit is complex and expensive and comprises large components; 2) manual switching between a full-bridge rectifier and a full-bridge double-voltage circuit makes use of the circuit inconvenient; and 3) erroneous switching may increase an output voltage and thus bringing damage to the motor controller and the motor, which affects safety and reliability of the circuit.
For motor controllers using the conventional AC/DC converting circuits, the same problems as above exist.

AC/DC converting circuit and motor controller using the same


D- and L-.alpha.-amino acids and D- and L-.alpha.-amino aldehydes are synthesized from olefin substrates in two steps. The first step is a catalyzed asymmetric aminohydroxylation addition reaction to the olefin substrate. The addition reaction is catalyzed by osmium and is co-catalyzed by chiral ligands. The chiral ligands, in addition to being co-catalysts with the osmium, also serve to direct the addition reaction regioselectively and enantioselectively. Divalent ligands are preferred over monovalent ligands because of their enhance regio- and enantio-selectivity. As an oxidant nitrogen source for the addition reaction, either a carbamate or sulfonamide may be employed. If carbamate is employed as an oxidant nitrogen source, the resultant .beta.-hydroxycarbamate is deprotected to yield the corresponding .beta.-hydroxyamine. If sulfonamide is employed as an oxidant nitrogen source, the resultant .beta.-hydroxysulfonamide is deprotected to yield the corresponding .beta.-hydroxyamine. The resultant .beta.-hydroxyamine is then selectively oxidized in a second synthetic step to produce the desired D- and L-.alpha.-amino acid or D- and L-.alpha.-amino aldehyde.

D- and L-.alpha.-amino acids are key building blocks for peptides, proteins, pharmaceuticals, and other important biomolecules. Naturally occurring L-.alpha.-amino acids are readily available from biological sources. However,enantiomerically pure D-.alpha.-amino acids and unnatural L-.alpha.-amino acids are more difficult to obtain. Due to their chirality, these compounds can be difficult to synthesize in an enantiomerically pure form. Several compounds within this class have significant economic value. Similarly, and D- and L-.alpha.-amino aldehydes are a re-occurring motif in biologically and pharmaceutically important molecules but are difficult to obtain in enantiomerically pure form.
Over the past 20 years, separate and distinct synthetic methodologies have been developed by Sharpless et al. for the vicinal hydroxyamination of olefins. There are three major groups of oxyamination procedures which produce aminoalcohols (Sharpless et al. J. Am. Chem. Soc. 1975, 97, 2305; Sharpless et al. J. Org. Chem. 1978, 43, 2628; Sharpless et al. J. Org. Chem. 1980, 45, 2257), hydroxysulfonamides (Sharpless et al. J. Org. Chem. 1976, 41, 177; Sharpless et al. J. Org. Chem. 1978, 43, 2544; Sharpless et al. J. Org. Chem. 1979, 44, 1953; Sharpless et al. Org. Syn. 1980, 61, 85) or hydroxycarbamates (Sharpless et al. J. Am. Chem. Soc. 1978, 100, 3596; Sharpless et al. J. Org. Chem. 1980, 45, 2710; Sharpless et al. U.S. Pat. Nos. 4,871,855; 4,965,364; 5,126,494; EP 0 395 729). Each oxyamination procedure has unique reaction conditions and includes variations in solvents, auxiliary salts, nucleophiles, temperature, stoichiometric v. catalytic amounts of osmium species and stoichiometric v. catalytic amounts of ligand. Each procedure is highly dependant on the nature of the substrate and possesses unique properties which afford different yields, chemoselectivities, stereoselectivities, regioselectivities and enantioselectivitive outcomes.
1. Aminoalcohols
The first reported oxyamination procedure (Sharpless et al. J. Am. Chem. Soc. 1975, 97, 2305) generated aminoalcohols from mono and di substituted olefins, using stoichiometric quantities of a tri-oxo(tert-butylimido)osmium species. The procedure required reductive cleavage of the osmate ester which was performed with lithium aluminum hydride and afforded tertiary vicinal aminoalcohols. Yields were good to excellent, but in some cases, the side product vicinal diol was formed as an undesired by-product. The stereochemistry of addition, in methylene chloride or pyridine, was exclusively cis (Sharpless et al. J. Org. Chem. 1978, 43, 2628). In addition, the carbon-nitrogen bond formed was, in every case, at the least substituted olefinic carbon atom. Di and tri-substituted olefins reacted much slower with the generated imido reagent than with monosubstituted alkenes; tetrasubstituted alkenes yielded only the corresponding diol. However, by using a coordinating solvent such as pyridine, higher yields and higher ratios of aminoalcohol to diol were reported. Sharpless et al. J. Org. Chem. 1980, 45, 2257; Sharpless et al. J. Org. Chem. 1976, 41, 177; Sharpless et al. J. Org. Chem. 1978, 43, 2544.
2. Hydroxysulfonamides
Sharpless et al. first demonstrated that hydroxysulfonamides could be obtained using either stoichiometric or catalytic amounts of 1% osmium tetraoxide in the presence of 1.5-5 equivalents of Chloramine-T trihydrate (TsSO.sub.2 NClNa.3H.sub.2 O, Ts=tosylate; commercially obtained) to effect cis addition of a hydroxyl (OH) and an arylsulfonamide moiety (Ar--SO.sub.2 NH) across a mono or disubstituted olefinic linkages (Sharpless et. al. J. Org. Chemistry 1976, 41, 177).
Two procedures were developed to effect hydroxyamination of olefins using sulfonamides. (Sharpless et al. Org. Syn. 1980, 61, 85). The first procedure used phase transfer catalysis conditions at 55-60.degree. C. with 1% OSO.sub.4, 1:1 v/v, 0.20 Molar CHCl.sub.3 /H.sub.2 O, and benzyltriethylammonium chloride as the phase transfer catalyst. The chloramine T-trihydrate (TsSO.sub.2 NClNa.3H.sub.2 O) was either added directly or formed in situ in water; this solution was then directly used in the phase transfer mixture. The in situ procedure, for generating the chloramine salts, involved stirring a suspension of the arylsulfonamide with an equivalent of sodium hypochlorite (Clorox) until a homogenous solution was obtained. The yields were comparable with those obtained with isolated chloramine salts and the procedure was found most effective for monosubstituted and 1,2 disubstituted olefins. The phase transfer method, however, gave poor results with trisubstituted and 1,1-disubstituted olefins and the procedure did not succeed with diethyl fumarate and 2-cyclohexen-1-one. Sharpless et al. J. Org. Chem.1978, 43, 2544.
A second procedure was carried out in tert-butyl alcohol at 55-60.degree. C. with 1% OSO.sub.4, silver nitrate (with or without) and commercially obtained chloramine T-trihydrate (TsSO.sub.2 NClNa.3H.sub.2 O) which provided the only source of water. The procedure did not succeed with tetramethylethylene and cholesterol, and negative results were found with most hindered tri- and tetrasubstituted olefins. Sharpless et. al. J. Org. Chemistry 1976, 41, 177; Sharpless et al. Org. Syn. 1980, 61, 85. The addition of divalent metal salts such as AgNO.sub.3 and Hg(NO.sub.3).sub.2 improved some reactions, however, other reactions suffered deleterious effects from the addition of the metal salts. Sharpless et al. J. Org Chem. 1978, 43, 2544; Sharpless et. al. J. Org. Chemistry 1976, 41, 177.
Further elaboration on either procedure showed that other sulfonamide derivatives (ArSO.sub.2 NClNa) could be successfully employed in addition to chioramine T, where Ar=phenyl, o-tolyl, p-chlorophenyl, p-nitrophenyl, and o-carboalkoxyphenyl. Sharpless et al. J. Org. Chem.1978, 43, 2546.
Neither the phase transfer catalyst or tert-butyl alcohol procedures succeeded with tetramethyl ethylene, 2,3-dimethyl-2-octene, diethyl fumarate, or 2-cyclohexen-1-one. Negative results were also obtained with most hindered tri- and tetrasubstituted olefins. Herranz E., MIT Ph.D. Thesis, 1979, 33.
Solvent conditions for the synthesis of the hydroxysulfonamides included organic solvents such as acetonitrile, tert-butyl alcohol, isopropyl alcohol and chloroform which was in contact with the aqueous phase in the phase transfer catalyst procedure.
The tert-butyl alcohol procedure (including other solvents used) was not run with added water; the phase transfer catalyst (PTC) procedure required a biphasic mixture of 1:1 v/v chloroform/water. Recently, however, an improvement was reported which used a 1:1 ratio of organic solvent to water in a homogeneous, rather than a biphasic solution or organic solvent with small amounts of water. These conditions were found to provide optimum enantioselectivity, regioselectivity and improved yields from either the previously described t-butyl alcohol or PTC conditions. Sharpless et al. Angew. Chemie Intl Ed. 1996, 35, 451.
The use of chiral ligands with sulfonamides provides enantioselectivity and has been observed to both accelerate and decelerate the rate of catalysis. The hydroxysulfonamide process is a stereoselective cis process. The presence of ligands also has a dramatic effect on the regioselectivity. In a study with no ligand present with methyl cinnamate, the two regioisomers were present in a 2:1 ratio. With the addition of ligand, the ratio was improved to 5:1 or greater. Another positive effect of the ligand was its ability to suppress formation of diol by-product. Angew. Chemie Intl Ed. 1996, 35, 451.
Preferred ligands for use with sulfonamides have included the use of monovalent cinchona alkaloids or the bivalent phthalazine based, commercially available (DHQ).sub.2 PHAL and (DHQD).sub.2 PHAL alkaloids. Sharpless et al. Angew. Chemie Intl Ed. 1996, 35, 451.
Temperature conditions for the hydroxysulfonamide asymmetric aminohydroxylations have varied from 60.degree. C. to 25.degree. C. for reactions including sulfonamides, auxiliary salts, ligands, phase transfer catalysts and stoichiometric or catalytic osmium species, primarily in organic solvents with small amounts of water. Recently, it has been shown that temperature can been lowered to 0.degree. C. while running the reaction, to obtain product by filtration; many hydroxysulfonamides tend to be highly crystalline. Sharpless et al. Acta Chemica Scandinavica 1996 in press.
Cleavage of the sulfonamides, to free aminoalcohols, have been accomplished via standard deprotection conditions including dissolving metals (Na, NH.sub.3 ; Sharpless et al J. Org. Chem 1976, 41, 177) and HBr, acetic acid and phenol (Fukuyama et al. Tetrahedron Lett. in press).
3. Hydroxycarbamates
A drawback with the hydroxysulfonamide procedure was that cleavage conditions were too strong for some substrates. The use of carbamates to protect the nitrogen, however, provided a methodology which avoided the use of harsh acids or reducing deprotection problems found with hydroxysulfonamides (Sharpless et al. J. Am. Chem. Soc. 1978, 100, 3596; Sharpless et al. J. Org. Chem. 1980, 45, 2710; Sharpless et al. Org. Syn. 1981, 61, 93; Sharpless et al. U.S. Pat. Nos. 4,871,855; 4,965,364; 5,126,494; EP 0 395 729).
Sharpless first demonstrated the synthesis of hydroxycarbamates with the use of N-chloro-N-argentocarbamates (Sharpless et al J. Am. Chem. Soc. 1978 100, 3596). The N-chloro-N-argentocarbamates were generated in situ via the addition of N-chlorosodiocarbamates and silver nitrate to a solution of the olefin in acetonitrile or tert-butanol with trace amounts of water (4.5 molar equivalents based on olefin) and 1% of osmium tetroxide catalyst to generate vicinal hydroxycarbamates in generally good yields. The methodology was reported to be more effective with electron deficient olefins such as dimethyl fumarate and trisubstituted olefins were reported to be less readily oxyaminated with N-chloro-N-argentocarbamates than with the chloramine-T procedures (Sharpless et. al. J. Org. Chem. 1976, 41, 177).
Sodio-N-chlorocarbamates were always first converted to either argento or mercurio salt analogs. The addition of the AgNO.sub.3 or Hg(NO.sub.3).sub.2 salts, to make N-chloro-N-argentocarbamates or mercurio salt analogs, was crucial for the reaction to retain its desired properties. (Sharpless et al J. Org. Chem., 1980, 45, 2711). This was in contrast to the sulfonamide conditions, where the sodio-N-chloro-sulfonamide salts could be used directly with either the t-butanol or chloroform/water--phase transfer catalyst procedures (Sharpless et al. J. Org. Chem. 1978, 43, 2544).
The addition of nucleophiles such as tetraethylammonium acetate were also proven to be beneficial to the reaction in the procedures using the silver and mercury salts of the chloramines from carbonates. Alternatively, the reactivity and yields were enhanced by addition of excess AgNO.sub.3 and Hg(NO.sub.3).sub.2 (over that needed to react with the NaClNCOOR salt) Sharpless et al. J. Org Chem. 1980, 45, 2710.
Preferred conditions included employment of ROCONClNa+Hg(NO.sub.3).sub.2 +Et.sub.4 NOAc with N-chloro-N-sodiocarbamates; these conditions were recommended as the best procedure for mono, di and tri substituted olefins even including some olefins unreactive in all of the various chloramine T based processes. (Sharpless et al. Org. Syn. 1981, 61, 93).
Among the carbamates tried, it was found that both benzyl N-chloro-N-argentocarbamate and tert-butyl N-chloro-N-argentocarbamates (or mercurio analogs) were among the most effective oxidants, especially with addition of nucleophiles such as tetraethylammonium acetate. Other carbamates such as isopropyl, ethyl, menthyl and bornyl derivatives were also used, however, chemo, regio and stereoselectivities were lower. Virtually no asymmetric induction was observed when chiral menthyl or bornyl derived carbamates were employed for hydroxyaminations. (Sharpless et al J. Am. Chem. Soc. 1978, 100, 3596).
Sharpless disclosed the use of stoiciometric amounts of a first generation monovalent alkaloid ligand with a tert-butyl derived N-chloro-N-argentocarbamate for hydroxyamination in a series of patent applications directed to ligand accelerated catalytic asymmetric dihydroxylation. These disclosures illustrated an hydroxyamination on trans-stilbene with the use of 1.0 equivalent (stoichiometric to olefin) of monovalent DHQD-p-chlorobenzoate (DHQD=hydroquinidine) ligand, 1 mol % osmium tetroxide, silver nitrate (figure) or mercuric chloride (0.80 equivalents; in protocal), 0.09 Molar acetonitrile (93.11 volume % acetonitrile)/water mix (6.89 volume % water) and tertbutyl derived N-chloro-N-argentocarbamate (1.45 equivalents) at 20.degree. C. (figure) or 60.degree. C. (protocal) for 1 hour. The disclosure reported a 51% ee with a 93% yield of aminoalcohol. (Sharpless et al. U.S. Pat. Nos. 4,871,855; 4,965,364; 5,126,494; EP 0 395 729).
In a review on ligand accelerated catalysis, Sharpless et al. noted that a 92% ee had been achieved in a stoichiometric reaction of trioxo-(tert-butylimido) osmium with stilbene in the presence of DHQD-CLB at ambient temperatures (Sharpless et al. Angew. Chem. Int. Ed. Engl. 1995, 34, 1059, ref. 80 "unpublished results"); this mention did not disclose reaction conditions.
Recently, an oxyamination reaction for the hemisynthesis of taxol and analogs was reported using a tertbutyl derived N-chloro-N-argentocarba-mate, excess silver nitrate or other metallic salts, with the use of either catalytic or stoichiometric amounts of osmium and the addition of stoichiometric amounts of monovalent DHQD (hydroquinidine), DHQ (hydroquinine) ligands in an unsuccessful attempt to influence the diastereoselectivity and the regioselectivity of the aminohydroxylation process. Solvent conditions varied from acetonitrile, toluene or pyridine, and the reactions were carried out at 4.degree. C. to room temperature, in the dark. The study reported that quinuclidine ligands had no effect on the amino alcohol yields but found that the addition of chiral tertiary amines had some beneficial effect on the yields of the various amino alcohol isomers formed. (Mangatal et al. Tetrahedron 1989 45, 4177). However, the two pseudoenantiomeric alkaloid ligands (i.e. DHQ-OAc and DHQD-OAc; OAc=acetate) gave a mixture of stereo and regioisomeric products. The result indicates that this particular hydroxyamination process (be it stoichiometric or catalytic was unclear) had exhibited no "asymmetric" effects. The procedure can therefore not be regarded as an asymmetric aminohydroxylation.
As a whole, the prior art uses hydroxycarbamates which always run at room temperature with either argento or mercurio salt analogs, monovalent ligands, stoichiometric or catalytic osmium species and organic solvents with trace amounts of water. (Sharpless et al. J. Am. Chem. Soc. 1978, 100, 3596; Sharpless et al. J. Org. Chem. 1980, 45, 2710; Sharpless et al. U.S. Pat. Nos. 4,871,855; 4,965,364; 5,126,494; EP 0 395 729).
Cleavages of the hydroxycarbamates, to free aminoalcohols, are well known in the art and include mild acid or base hydrolysis and catalytic hydrogenolysis, depending on the attached functionality to the carbamate. (Greene, Protective Groups in Organic Synthesis, 1981, Wiley, 1st edn. pp. 223-249).
What is needed is an improved method for synthesizing D- and L-.alpha.-amino acids and D- and L-.alpha.-amino aldehydes using olefins as starting materials.

Two step synthesis of D- and L- .alpha.-amino acids and D- and L- .alpha.-amino-aldehydes


The present invention relates to a hypertension treatment. More particularly, the present invention relates to combination of four herbs' extract including 95% ethanolic extract of U. rhynchophylla (UR95), 95% ethanolic extract of P. thomsonii (PT95), 95% ethanolic extract of P. notoginseng (PN95), and 50% ethanolic extract of A. orientale (AO50) in particular range of ratio (known as F1 ratio), and all the raw herbs were then extracted in total by using 50% ethanol (known as F1-2) for use in a medicament for treating hypertension and hypertension-related complications and a composition thereof.

Hypertension is the persistently high blood pressure (BP) exerted against the walls of arteries. The force exerted by the blood is strictly dependent on the resistance of the blood vessels and the cardiac output. There were at least 32.7% of Malaysian aged 18 years old, and 43.5% of the Malaysian aged 30 years old were suffering from hypertension in 2011. Furthermore, there is approximately 1.56 billion of human worldwide are predicted to have hypertension by the year of 2025. According to American Heart Association (AHA), the ranges of the human BP can be classified as five different stages as such, normal BP is ≤120 mmHg systolic and ≤80 mmHg diastolic, pre-hypertension BP is ranged between 120-139 mmHg systolic or 80-89 mmHg diastolic, stage 1 high BP (hypertension) is 140-159 mmHg systolic or 90-99 mmHg diastolic, and stage 2 high BP (hypertension) is ≥160 mmHg systolic or ≥100 mmHg diastolic. The classification as stated by AHA is exactly the same as stated in Joint National Committee 7 (JNC 7). However, there is a critical stage of hypertension when the BP has reached ≥180 mmHg systolic or ≥110 mmHg diastolic, where the patient should be immediately treated as medical emergency. Hypertension is a silent killer, it can possess on anyone of us for years without causing any symptoms, whilst damaging our vasculatures and cardiovascular systems. In case of remaining undiagnosed, concomitant diseases including stroke, dementia, kidney diseases could be happened, and eventually causes death. Upon aging, there could be plenty of plaques building-up on the wall of the blood vessel which causing the lumen of the arteries becomes narrower, hence higher BP is required to pump the blood throughout the whole body.
There is plenty of anti-hypertensive drugs available in market. According to the clinical practice guideline in management of hypertension (4th edition) in Malaysia, there are five groups of antihypertensive drugs used as first line mono-therapy for newly diagnosed patient with no compelling indication which including angiotensin receptor blockers (ARBs), angiotensin-converting-enzyme inhibitors (ACEIs), thiazide-type diuretics, calcium channel blockers (CCBs), and beta blockers. However, reports showed that only around 35% of the blood pressure for hypertension patients were successfully under controlled, thus combination therapy often preferred and is necessary for those with stage 1 hypertension and above. Apparently, combination therapy is more effective then mono-therapy. At this point, we can deduce that blocking the multiple signaling mechanism pathways that causing the hypertension could be the key for treating hypertension instead of solely blocking anyone of that. Moreover, there are various chronic adverse effects reported due to the long-term consumption of anti-hypertensive drugs. For these, traditional Chinese medicine (TCM) could serve as alternative.
TCM herbs have been used to treat different kind of diseases on human since 2000 years ago. Their holistic therapeutic effects and rarely been reported to cause significant adverse effects when used in clinical have drawn the attention of scientists in latest era. There were many clinical evidences showed that the TCM physicians had treated the hypertension's patient effectively by using the TCM principles, even it is not a term in TCM. According to TCM principles, diseases will be treated according to their symptoms appeared on patient's body, while hypertension is a multi-syndromic disease that would causes "fire", phlegm-fluid retention, and deficiency syndromes. Four TCM herbs that most frequently used to treat hypertension and could counteract on its syndromes as aforementioned were selected which includes Uncaria rhynchophylla, Pueraria thomsonii, Panax notoginseng, and Alisma orientale. The most optimum ratio for four TCM herbs combination was determined by using the scientific-based formula which is orthogonal stimulus-response compatibility group studies with L25 (55) formulation. Subsequently, the most effective solvent used to extract the combined herbs which prepared in optimum ratio was investigated as well.
CN104645091 A discloses a capsule in the treatment of hypertension, the patient can make in a short time by taking the drug after symptoms have been alleviated, with lower blood pressure and lipids easy rebound, low cost. The technical solution of the present invention is a capsule in the treatment of hypertension, characterized in that it is formulated from the following parts by weight of the drug from traditional Chinese medicine raw materials: Astragalus 2 parts, 20 parts of Salvia, Pueraria 6 parts, yam 8 parts of Ginkgo biloba 10 parts, 16 parts of corn, 16 parts Gynostemma, March 7 parts, 35 parts of hawthorn, basil 3 parts, apocynum 2 parts, 5 parts of wild chrysanthemum, Prunella 2 parts, 17 parts of Uncaria, medlar 16 parts, abalone 3 parts, gutta 6 parts, raw oysters 10 parts, 15 parts of white peony root, Achyranthes 15 parts, lotus heart 3 parts, 10 parts of Poria, Alisma 10 parts and 10 parts Tianma.
In light of the above, there appears a need for developing a medicament with fewer herb ingredients that is capable of treating hypertension and hypertension-related complications.

Optimum ratio for herbs combination obtained by using scientific-based formula for hypertension treatment and a composition thereof


A hemostatic device including a band that is wrapped around a limb of a living body at a site of the living body where bleeding is to be stopped and an inflatable portion which is inflated by injection of gas to cause the inflatable portion to press the site where bleeding is to be stopped. The hemostatic device includes an injection part that injects gas into the interior of the inflatable portion. The injection part includes a hole penetrating the injection part and communicating the housing space with outside environment. The hemostatic device includes a first support plate and a second support plate positioned adjacent one another along the longitudinal direction of the band. The second support plate is movably connected to the first support plate. The inflatable portion is on the first support plate and the injection part is on the second support plate.

Percutaneous treatment/examination, etc. has recently been performed by puncturing a blood vessel of an arm, a leg, etc. of a living body, introducing an introducer sheath into the living body through a puncture site, and delivering a medical instrument such as a catheter to a lesion through a lumen of the introducer sheath. When such treatment/examination, etc. is performed, an operator needs to perform hemostasis in the puncture site after withdrawing the introducer sheath. One known hemostatic device for performing hemostasis includes means for securing a band wrapped around a limb such as an arm or a leg (i.e., securing the band in a state in which the band is wrapped around the limb), and an inflatable portion that is disposed between the band and the limb and is inflated by injection of a fluid to press a puncture site.
When such a hemostatic device is used, in general, a doctor or a nurse connects a dedicated instrument such as a syringe separate from the hemostatic device to a port communicating with an inflatable portion of the hemostatic device and injects a fluid into the inflatable portion using the dedicated instrument, thereby inflating the inflatable portion of the hemostatic device.
Japanese Patent Application Publication No. 2014-521368 discloses a hemostatic device that includes an injection part (pressure pump) capable of injecting gas to an inflatable portion (by being attached to the inflatable portion). Specifically, the injection part is provided with a housing space capable of housing gas and a gas intake hole portion communicating with the housing space. When the injection part is deformed (contracted) in a state in which the hole portion is blocked with a finger, gas housed in the injection part is injected into the inflatable portion. Since the inflatable portion can be inflated by the injection part attached to the inflatable portion, it is possible to eliminate an effort of the doctor or the nurse to carry a separate dedicated instrument or an effort to connect the separate dedicated instrument to the hemostatic device. In addition, it is possible to prevent a situation in which the dedicated instrument is lost and a fluid may not be injected into the inflatable portion.


To increase the speed with which a Second Layer Address Table (SLAT) is traversed, memory having the same access permissions is contiguously arranged such that one or more hierarchical levels of the SLAT need not be referenced, thereby resulting in more efficient SLAT traversal. “Slabs” of memory are established whose memory range is sufficiently large that reference to a hierarchically lower level table can be skipped and a hierarchically higher level table's entries can directly identify relevant memory addresses. Such slabs are aligned to avoid smaller intermediate memory ranges. The loading of code or data into memory is performed based on a next available memory location within a slab having equivalent access permissions, or, if such a slab is not available, or if an existing slab does not have a sufficient quantity of available memory remaining, a new slab with the proper access permissions is established.

Modern computing devices operate by executing computer-executable instructions from high-speed volatile memory in the form of random access memory (RAM), and the execution of such computer executable instructions often entails the reading of data from RAM. Due to cost, physical size limitations, power requirements, and other like constraints, computing devices typically comprise less RAM than is required by the processes that are typically executed on such computing devices. To accommodate such constraints, virtual memory is utilized, whereby the memory that appears to be available to processes executing on a computing device is greater than the physical memory circuitry provides for. The relationship between virtual memory and physical memory is typically managed by one or more memory managers, which implement, maintain, and/or reference a "page table" whose information delineates the relationship between one or more virtual memory addresses and the locations of corresponding data, either in physical memory, or on some form of storage media. To accommodate the quantities of memory relevant to modern computing devices and the processes executed thereon, a modern page table is typically comprised of multiple hierarchical levels of tables, with a hierarchically higher level table having entries that each identify a different hierarchically lower level table, and with the hierarchically lowest level table comprising entries that do not identify a still further table, but rather identify the memory addresses themselves.
Among the processes that can be executed by computing devices are virtual machines, which can simulate underlying computing hardware to processes executed within the context of such virtual machines. The virtualization of host computing hardware is typically performed by a hypervisor, or similar set of computer-executable instructions. A hypervisor can maintain a Second Layer Address Table (SLAT) which can, in a manner analogous to the aforementioned page tables, maintain information that delineates the relationship between one or more memory addresses that appeared to be physical memory locations to processes executing within the context of a virtual machine, and the memory locations of actual physical memory itself.
When a process executing within the context of a virtual machine accesses memory, two different page table lookups can be performed. One page table lookup can be to identify a physical memory address, as perceived processes executing within the context of the virtual machine, which corresponds to the virtual memory address, within the context of the virtual machine, that was accessed by the process executing within the context of the virtual machine. Such a lookup can be performed by a memory manager executing within the context of the virtual machine and can be made with reference to a page table that exists within the context of the virtual machine. A second page table lookup can then identify an actual physical memory address that corresponds to the memory address that was perceived as a physical memory address by processes executing within the context of the virtual machine, and which was the result of the prior page table lookup. Such a second lookup can entail one or more processing units of the computing device referencing the SLAT.
Like the page table maintained by the memory manager within the context of the virtual machine, the SLAT can be a hierarchical arrangement of different hierarchical levels of tables. The performance of a page table lookup, whether performed by the memory manager, with reference to the page table, in the context of the virtual machine, or whether performed by the hypervisor, with reference to the SLAT, can entail determining an appropriate table entry within a highest hierarchical table level, referencing a hierarchically lower level table that is identified by that table entry, determining an appropriate table entry within that hierarchically lower level table, referencing a hierarchically still lower level table that is identified by that table entry, and so on, until a lowest hierarchical level table is reached, whereupon the individual entries of that table identify one or more specific addresses, or ranges of addresses, of memory itself, as supposed to identifying a still further table. Each reference to a hierarchically lower level table consumes processor cycles and increases the duration of a memory access.
In the case of a memory access from a process executing within the context of a virtual machine, the duration of such a memory access can include both the lookup performed by the memory manager, with reference to the page table, in the context of the virtual machine, and, in addition, the lookup performed by the hypervisor, with reference to the SLAT. The additional delay introduced by the lookup performed by the hypervisor, with reference to the SLAT, renders memory access from processes executing within the context of a virtual machine more inefficient as compared with processes executing outside the context of the virtual machine. Such inefficiencies can discourage users from utilizing virtual machines and achieving the security benefits, and other benefits conferred by executing within the context of a virtual machine.

Faster computer memory access by reducing SLAT fragmentation


A new variable burner orifice furnace manifold for reducing the amount of heating fuel used without reducing the heating ability of the furnace. The inventive device includes a manifold pipe with a plurality of spaced apart gas exit openings between its open supply end and its closed end. The gas exit openings are inserted into the burner assembly of a furnace and the supply end is attached to an external heating fuel supply. A valve permitting selective opening and closing is included on the manifold pipe. The valve is positioned on the manifold pipe so that no more than half the total number of gas exit openings are positioned between the valve and the manifold pipe closed end. When the valve is closed, gas flow through the gas exit openings between the valve and the closed end is shut off while gas flow through the gas exit openings between the valve and the open supply end is unaffected.

1. Field of the Invention
The present invention relates to manifold systems and more particularly pertains to a new variable burner orifice furnace manifold for reducing the amount of heating fuel used without reducing the heating ability of the furnace.
2. Description of the Prior Art
The use of manifold systems is known in the prior art. More specifically, manifold systems heretofore devised and utilized are known to consist basically of familiar, expected and obvious structural configurations, notwithstanding the myriad of designs encompassed by the crowded prior art which have been developed for the fulfillment of countless objectives and requirements.
Known prior art manifold systems include U.S. Pat. No. 4,570,908; U.S. Pat. No. 5,234,196; U.S. Pat. No. 4,174,948; U.S. Pat. No. 4,585,021; U.S. Pat. No. 4,302,178; U.S. Pat. No. 4,392,509; U.S. Pat. No. 4,869,284; U.S. Pat. No. 4,191,215; U.S. Pat. No. Des. 304,070; and U.S. Pat. No. Des. 352,094.
While these devices fulfill their respective, particular objectives and requirements, the aforementioned patents do not disclose a new variable burner orifice furnace manifold. The inventive device includes a manifold pipe with a plurality of spaced apart gas exit openings between its open supply end and its closed end. The gas exit openings are inserted into the burner assembly of a furnace and the supply end is attached to an external heating fuel supply. A valve permitting selective opening and closing is included on the manifold pipe. The valve is positioned on the manifold pipe so that no more than half the total number of gas exit openings are positioned between the valve and the manifold pipe closed end. When the valve is closed, gas flow through the gas exit openings between the valve and the closed end is shut off while gas flow through the gas exit openings between the valve and the open supply end is unaffected.
In these respects, the variable burner orifice furnace manifold according to the present invention substantially departs from the conventional concepts and designs of the prior art, and in so doing provides an apparatus primarily developed for the purpose of reducing the amount of heating fuel used without reducing the heating ability of the furnace.

Variable burner orifice furnace manifold


Systems, methods, and computer program products to detect a keyword in speech, by generating, from a sequence of spectral feature vectors generated from the speech, a plurality of blocked feature vector sequences, and analyzing, by a neural network, each of the plurality of blocked feature vector sequences to detect the presence of the keyword in the speech.

Field of the Disclosure
Embodiments disclosed provide techniques for detecting words in human speech. More specifically, embodiments disclosed herein relate to sectioned memory networks for online word-spotting in continuous speech.
Description of the Related Art
Software applications may be used to detect the presence of specific words in human speech, commonly referred to as "speech-recognition." Traditionally, however, computers have been programmed to detect phonemes (a perceptually distinct unit of sound) and not entire words. Doing so allows software to piece the phonemes together to determine if (and what) word was spoken. Furthermore, existing techniques use hidden Markov models to search for the words, while using neural networks only to compute features of the speech. Such techniques leave much to be desired in terms of the accuracy and speed of detecting words in speech.

Sectioned memory networks for online word-spotting in continuous speech


A system and method of automating the management of public and private key pairs of a sender and recipient of electronic messages over a network and for retrieving public keys of senders or recipients from secured servers, local key rings, PKI server, or Certificate Authority without requiring client-side software or user maintenance.

As the pace of electronic commerce and as online communications increase, the need for security and the ability to authenticate communications between parties has become critical. To meet this need, a public key infrastructure (PKI) has been developed to allow for encryption, decryption, digital signatures, and signature authentication. This encryption scheme involves public and private keys, used in conjunction, to encrypt and decrypt electronic messages. Such companies as IdCertity, Verisign, and Thawte are known as Certificate Authorities, who verify the identity of entities seeking digital certificates, issue digital certificates and make digital certificates available in public databases. The University of Southern California as well as another at Massachusetts Institute of Technology (MIT) provides such databases. Encryption schemes that rely upon these public databases are unmanageably complex to the average user. The user must know the public key of each recipient, know how to encrypt a message, maintain their own private key, and know how to decrypt messages. These solutions rely on distributed client software for performing encryption functions thereby creating another disadvantage. Each client must be able to manage the keys of senders and recipient. Distribution of public keys requires heavy investments in software and labor by the end user in order to correctly implement the client software. These solutions require that the client perform the function of encryption and decryption. Such placement of responsibility on the individual users significantly opens the door to user error as well as undermines the security of the entire system. Further, the centralizing management of public and private keys creates a bottleneck inhibiting the speed in which an encryption network can be maintained, as well as limiting its ability for expansion.
Therefore, there is a need for an encryption system with automated distributed key management that is implemented and operated with minimal interaction sender s and recipients. There is also a need for a system capable of querying and discovering public keys from many different Certificate Authorities or other remote databases having public keys.
In describing the current invention, the following terms are helpful:
Domain—a logical unit representing a collection of computers or a segment of computer network accessible by specific users who are members of the domain.
Secure Domain—a logical unit representing a collection of computers or a segment of a computer network utilizing encryption software of one or more secure servers.
Message Verification—the process of using the public key to determine whether a message was sent, in actuality, from the named sender.
Certification—the process of associating a public key with an individual, organization, or other entity to determine that a message was "certified" from that specific entity.
Digital Certificate—the mathematical parameters of a public key combined with identifying information regarding the owner or user of that public key. The contents of a digital certificate are cryptographically signed in order to protect its integrity. A Certification Authority issues digital Certificates.
Certification Authority—A person, organization, or other entity charged with the duty of Certification. It is the Certification Authority's responsibility to perform whatever identity verification is necessary to associate a real person with the Digital Certificate that will represent them.
Internet Message Access Protocol (IMAP)—a computer network protocol that allows computer software to manage the contents of electronic mailboxes that is stored on a remote computer. By sending IMAP messages, software can fetch, store, and delete messages, as well as create, delete, and rename mailboxes.
Multi-purpose Internet Mail Extensions (MIME)—Special encoding protocols used by electronic communications software (both the world wide web and e-mail, for instance). These encodings allow messages to identify and transmit various kinds of content and formats such as binary, audio, video, graphics, or other content types.
Post Office Protocol (POP)—a computer network protocol that allows computer software to manage the contents of a single electronic mailbox that is stored on a remote computer. POP is very similar to, but simpler than, IMAP. By sending POP messages software can retrieve and delete messages from a single mailbox stored on a remote computer.
Private key—one of a pair of mathematical parameters that are uniquely and tightly linked to a "public key." Encryption algorithms use these parameters to produce an encrypted version of information. The private key is mathematically linked to its unique public key so that only that public key can decrypt information encrypted by that private key.
Public key—the other of a linked pair of mathematical parameters. Only the corresponding private key can possibly decrypt any information encrypted by the public key.
Public key infrastructure (PKI)—a combination of software, hardware, encryption technologies, and services that enable the protection of electronic communications and business transactions over a computer network.
Public key publication—the process of making public keys available to individuals who wish to send encrypted messages to others able to receive and decrypt encrypted messages.
Simple mail transfer protocol (SMTP)—a server-to-server protocol for delivering electronic mail. SMTP is the standard protocol used presently on the Internet as well as other TCPIP networks.
In order for an encryption system to function, there must be controlled access to the public and private keys of the senders and recipients. The sender of a message requires access to the recipient's public key for encrypting a message. The sender needs access to his own private key for signing a message. The sender needs access to his private key for decrypting messages received. The recipient requires access to the sender's public key for signature authentication. Therefore, both the sender and recipient must have a system, process or method for discovering the respective public keys as well as a system, process or method for securely storing and accessing their respective private keys. Advantageously, access to the public and private keys, the related process for encryption, decryption, signing, and authentication should be automated so that intervention by the sender or recipient is not required.
Accordingly, it is an object of this invention to provide for an automated encryption system for encrypting, decrypting, signing, and authenticating electronic messages, attachments and documents without significant maintenance or user intervention.
It is another object of this invention to allow a system administrator to maintain public and private key pairs for senders and recipients so that the burden of maintenance of the encryption system is focused on the administrator rather than the sender and recipient.
It is another object of this invention to provide for access to the public keys of users located outside of the specific secure domain.

Automated electronic messaging encryption system


A compound is prepared, suitable for forming fluoroelastomers, having the unique features of a low glass transition temperature and desirable physical properties. The compound generally comprises an elastomeric copolymer, a curable component, and at least one mineral filler. The elastomeric copolymer includes interpolymerized monomeric units derived from vinylidene fluoride. Upon vulcanization the resulting elastomeric compound has desirable physical characteristics as indicated by the tensile strength, elongation and the retraction at lower temperatures (TR-10).

Increasingly stringent evaporative fuel standards for automobiles and trucks demand that the fuel system component minimize the emission of fuel vapors through automotive components such as the fuel tank, fuel filler lines, fuel injector seals, and fuel seals. Fluoroelastomers such as copolymer of vinylidene fluoride (VDF) and hexafluoropropylene (HFP), and terpolymers of tetrafluoroethylene (TFE), vinylidene fluoride (VDF) and hexafluoropropylene (HFP) have been used for reducing fuel permeation from the above-noted fuel seal applications. However, fluoroelastomers employed in fuel seal applications generally require low temperature properties to maintain sealing performance for cold weather.
Various types of fluoroelastomers for fuel seals have been proposed to address these concerns. In general, the most successful of the elastomers generally contain perfluoromethylvinylether (PMVE). PMVE effectively reduces the glass transition temperature of the resulting polymer. However, perfluoroalkylvinylether monomers are expensive and as such the resulting fluoroelastomers are relatively high priced.

Fluoroelastomers with improved low temperature property and method for making the same


This invention relates to certain phenylhetercyclic compounds, herbicidal compositions thereof and a method for their use as general and selective preemergent or postemergent herbicides or plant growth regulants.

This invention relates to certain substituted fused heterocyclic compounds which are useful as herbicides and their agriculturally suitable compositions as well as methods for their use as general or selective preemergent or postemergent herbicides or as plant growth regulants.
New compounds effective for controlling the growth of undesired vegetation are in constant demand. In the most common situation, such compounds are sought to selectively control the growth of weeds in useful crops such as cotton, rice, corn, wheat and soybeans, to name a few. Unchecked weed growth in such crops can cause significant losses, reducing profit to the farmer and increasing costs to the consumer. In other situations, herbicides are desired which will control all plant growth. Examples of areas in which complete control of all vegetation is desired are areas around railroad tracks, storage tanks and industrial storage areas. There are many products commercially available for these purposes, but the search continues for products which are more effective, less costly and environmentally safe.
U.S. Pat. No. 5,032,165 discloses herbicidal compounds of the formula ##STR1##


A computer-implemented method for multi-mode operation of a combustion system, a combustion system, and a heat engine are provided. The method includes initializing combustion of a fuel/oxidizer mixture, determining whether conditions at the combustion system meet or exceed a first threshold operating parameter, transitioning to detonation combustion of the fuel/oxidizer mixture if conditions at the combustion system meet or exceed the first threshold operating parameter, and maintaining or increasing fuel flow through a deflagrative fuel circuit if conditions at the combustion system do not meet or exceed the first threshold operating parameter.

Many propulsion systems, such as gas turbine engines, are based on the Brayton Cycle, where air is compressed adiabatically, heat is added at constant pressure, the resulting hot gas is expanded in a turbine, and heat is rejected at constant pressure. The energy above that required to drive the compression system is then available for propulsion or other work. Such propulsion systems generally rely upon deflagrative combustion to burn a fuel/air mixture and produce combustion gas products which travel at relatively slow rates and constant pressure within a combustion chamber. While engines based on the Brayton Cycle have reached a high level of thermodynamic efficiency by steady improvements in component efficiencies and increases in pressure ratio and peak temperature, further improvements are welcomed nonetheless.
Accordingly, improvements in engine efficiency have been sought by modifying the engine architecture such that the combustion occurs as a detonation in a continuous mode. High energy ignition detonates a fuel/air mixture that transitions into a detonation wave (i.e., a fast moving shock wave closely coupled to the reaction zone). The detonation wave travels in a Mach number range greater than the speed of sound with respect to the speed of sound of the reactants. The products of combustion follow the detonation wave at the speed of sound relative to the detonation wave and at significantly elevated pressure. Such combustion products may then exit through a nozzle to produce thrust or rotate a turbine.
However, although detonation combustion can increase engine efficiency, the range of operability of a combustion system and engine is limited by ranges at which detonation can be formed and sustained in a rotating detonation combustion system. As such, there is a need for systems and methods allowing for increased range of operability of a rotating detonation combustion system and engine.

Multi-mode combustion control for a rotating detonation combustion system


A tool joinable with a handle. The tool includes a body, the body includes a middle area configured to be joinable to the handle. The front end of the body includes a toe extending away from the middle area. The toe includes a first vertical thickness and a second vertical thickness less than the first vertical thickness for a length of the toe extending away from the middle area. The back end of the body can include a heal pad extending away from the middle area and to create a heal gap between a bottom surface of the heal pad and the second portion of the bottom edge defined by the middle area. The tool can include a fulcrum joined to the body and defining a fulcrum portion of the bottom edge with the fulcrum projecting away from the top edge.

There are at least three prior existing tools in the art to try and meet the need of moving a heavy object, like a manhole cover, in particular, removing and moving the manhole cover from its seated location over a manhole. However, each of these tools has limitations on its effectiveness, and none provide the various combination of benefits my tool can provide, especially when it comes to being able to more safely, and with less physical effort, and more ergonomically, remove the manhole cover from the manhole and then move it from over the manhole to adjacent to the manhole and not impeding access to the manhole. Thus, there is a need to address one or more of the deficiencies in the art to better aid in achieving more desirable requirements and avoiding negative ones, for a tool like mine, especially when used to remove a manhole cover, and preferably in a way that is more consistent and reliable for such a tool.


A top which can facilitate the coupling of a winder is provided. The toy top comprises: a blade; a shaft of which one end is fixed to a lower portion of the blade; a pinion to be inserted and coupled to the middle of the shaft; and a shaft holder capable of accommodating the pinion-coupled shaft in a rotating manner, wherein the shaft holder comprises winder connectors (for rotating the pinion. Particularly, the winder connectors comprise: a cut portion for contacting a part of a first portion of a winder on a lateral side; and a guide groove for allowing a second portion extended from the first portion of the winder to be stopped at stepped protrusions inside the cut portion so as to prevent the second portion from being separated from the lateral side when a part of the first portion of the winder is contacted to a lateral side and then the winder is moved to the lateral side.

Generally, a top is a kind of a rotation amusement mechanism using its inertia, and the configuration of the top is disclosed in Korean Patent No. 1051847 issued to this inventor.
As shown in FIGS. 1 and 2, the conventional toy top 100 includes a blade 110, a shaft 123 fixed to the lower portion of the blade 110 at one end thereof, a pinion 122 fitted to the intermediate portion of the shaft 123, and a shaft holder 120 adapted to allow the shaft 123 to which the pinion 122 is fitted to be rotatably accommodated thereinto.
The shaft holder 120 includes a pinion housing 124 adapted to surround the pinion 122, a handle 127 disposed on the underside of the pinion housing 124 to support the lower end periphery of the shaft 123, and a rotary tip 126 disposed on the underside of the handle 127.
Bearings 28a and 28b are disposed on the pinion housing 124 and the handle 127 to make the shaft 123 gently rotate.
The pinion housing 124 has winder insertion holes 124a formed symmetrically to each other on both sides thereof so as to rotate the pinion 122 fitted to the shaft 123 in a clockwise or counterclockwise direction.
In the state wherein the handle 127 of the shaft holder 120 is held by a user's one hand, a winder 16 on which a rack gear portion 16a adapted to be engaged with the pinion 122 is formed is inserted into one side winder insertion hole 124a, and if the winder 16 is pulled by the other hand of the user and drawn from the winder insertion hole 124a, the blade 110 rotates. If the handle 127 is put on the floor in the state where the rotary force is applied to the blade 110, the top 100 becomes spin.
Under the above mentioned configuration of the conventional top 100, the winder insertion holes 124a are formed to insert the winder 16 thereinto, thus making it inconvenient to insert the winder 16 thereinto, and the rotary force is unnecessarily applied to the blade 110 when the winder 16 pushes up to a position where the winder 16 can pull after the insertion of the winder 16.
Further, the time needed to insert the winder 16 into the selected winder insertion hole 124a becomes disadvantageously extended.


The present invention relates to a plastic substrate having a multi-layer structure and a method for preparing the same. The plastic substrate of the present invention comprises plastic films attached to each other, and a first buffering layer of an organic-inorganic hybrid, a layer of gas barrier, and a second buffering layer of an organic-inorganic hybrid which are stacked on both sides of the plastic films in an orderly manner, each layer forming a symmetrical arrangement centering around the plastic films.

(a) Field of the Invention
The present invention relates to a plastic substrate having a multi-layer structure with a small coefficient of thermal expansion, excellent dimensional stability, and superior gas barrier properties and a method for preparing the same.
(b) Description of the Related Art
Although glass plates used for display devices, picture frames, craftwork, containers, etc. are advantageous in that they have a small coefficient of linear expansion, superior gas barrier properties, high transparency, good surface flatness, excellent heat resistance and chemical resistance, etc., they tend to break easily and be heavy because of their high density.
Recently, as liquid crystal displays, organic light emitting devices, and electronic paper are arousing a growing interest, research on replacing the glass substrates used in such devices with plastic counterparts is gaining momentum. The plastic substrate is advantageous over the glass plate in terms of weight and ease of design. Also, because it is impact-resistant, an economic advantage may be attained from continuous manufacturing.
For a plastic substrate to be used in a display device, it should have a glass transition temperature high enough to endure the transistor processing temperature and the transparent electrode deposition temperature, oxygen and water vapor barrier properties so as to prevent aging of liquid crystals and organic light emitting materials, a small coefficient of thermal expansion and good dimensional stability so as to prevent deformation of the plate due to change of the processing temperature, mechanical strength comparable to that of the conventional glass plate, chemical resistance sufficient for enduring the etching process, high transparency, low birefringence, good surface scratch resistance, etc.
However, because a single polymer composite film (polymer film or polymer-inorganic material composite film) that satisfies all the requirements does not exist, several layers of functional coats are applied on a polymer film to fulfill them. Typical coating layers are an organic flattening layer for reducing surface defects and offering flatness, an inorganic barrier layer for blocking gaseous materials such as oxygen and water vapor, and an organic or organic-inorganic hard coating layer for offering surface scratch resistance. The conventional plastic substrates having a multi-layer structure are manufactured by coating an inorganic gas barrier layer on a plastic film and coating a hard coating layer on the gas barrier layer. In such a multi-layer structure, deformation of the plastic film or cracking or peeling of the inorganic layer may occur because of the difference of coefficients of linear expansion of the plastic film and the gas barrier layer. Accordingly, design of an appropriate multi-layer structure capable of minimizing stress at the interface of each layer and adhesion of each coating layer are very important.
Vitex Systems of the U.S. developed a substrate having a superior gas barrier property by obtaining an organic-inorganic multi-layer structure of several layers by forming a thin monomer film on a plastic film, polymerizing the monomer by illuminating UV (solidified organic layer), and forming a thin inorganic layer thereon by sputtering. Although a substrate having a superior gas barrier property can be obtained with this method, the requirement of a low coefficient of linear expansion, which is needed for a display, has not been satisfied, and a solution method for the problem has not yet been suggested.
U.S. Pat. No. 6,465,953 disclosed a method of dispersing getter particles capable of reacting with oxygen and water vapor on a plastic film to use for an organic light emitting device which is sensitive to oxygen and water vapor. The getter particles should have a particle size smaller than the characteristic wavelength of the emitted light, and should be dispersed uniformly so that the emitted light can transmit to the substrate without being scattered. This method is intended to minimize inflow of oxygen and water vapor by coating a gas barrier layer comprising an inorganic material on a plastic film. However, it is difficult to uniformly distribute nano particles having a particle size ranging from 100 to 200 nm, and the plastic film should be thick enough to comprise a lot of getter particles capable of reacting with oxygen and water vapor. Also, because the inorganic gas barrier layer is directly coated on the plastic film, the gas barrier layer tends to crack or peel off with changes in temperature.
U.S. Pat. No. 6,322,860 disclosed a plastic substrate for electronic display applications that was manufactured by coating a crosslinkable coating composition (comprising a polymer selected from the group consisting of polyfunctional acrylate monomers or oligomers, alkoxysilanes, etc. and a mixture thereof) on one or both sides of a polyglutarimide sheet having a thickness of no more than 1 mm, which has been prepared by extrusion, and photocuring or thermally curing it to form a crosslinked coating, and coating a gas barrier layer on the crosslinked coating and then coating another crosslinked coating on the barrier layer, if necessary. In specific cases, transmission rate of oxygen and water vapor was small enough to be used for a liquid crystal display. However, a small coefficient of thermal expansion and superior dimensional stability, which are required to replace the glass substrate, were not obtained.
U.S. Pat. No. 6,503,634 disclosed a multi-layer substrate manufactured by coating an organic-inorganic hybrid (ORMOCER) and silicon oxide on a plastic film or between two sheets of plastic films. The resultant film showed an oxygen transmission rate of no more than 1/30 and a water vapor transmission rate of no more than 1/40, compared with those before coating. Although this film can be used in packaging because of significantly reduced oxygen and water vapor transmission rate, there was no mention about improvement in the coefficient of thermal expansion or dimensional stability.

Plastic substrate having multi-layer structure and method for preparing the same

Abstract: Because the plastic substrate of the present invention has a small coefficient of thermal expansion, excellent dimensional stability, and superior gas barrier properties, it can replace the brittle and heavy glass substrate in display devices. Also, it can be used for a variety of packaging or container materials in applications requiring superior gas barrier properties.


In a misregister amount detection method, printed register marks of colors are sensed, and the inverted R, G, and B image data of R, G, and B image data respectively containing R, G, and B as red, green, and blue color components of the register marks are extracted. The minimum value of the pixel values of corresponding pixels of the generated inverted R, G, and B image data is extracted and converted into the pixel value of a corresponding pixel of K image data containing K as a black color component. Differential R, G, and B image data are obtained by subtracting the pixel value of each pixel of the K image data from the pixel values of corresponding pixels of the inverted R, G, and B image data. Enhanced R, G, and B image data are obtained by adding the pixel values of pixels of the differential R, G, and B image data or values corresponding to the pixel values to the pixel values of corresponding pixels of the inverted R, G, and B image data. The misregister amount between the colors is obtained on the basis of the pixel values of pixels of the enhanced R, G, and B image data. A misregister amount detection apparatus is also disclosed.

The present invention relates to a misregister amount detection method and apparatus which sense printed register marks of colors and obtain the positional shift of the sensed mark of each color as a misregister amount.
In a conventional offset printing press, a printing plate with a printed image is attached to the outer surface of a plate cylinder. Ink stored in an ink fountain is supplied to the printing plate through ink rollers. The ink supplied to the printing plate is transferred to a blanket cylinder which rotates in press contact with the plate cylinder so that printing is executed for a printing paper sheet passing between the blanket cylinder and an impression cylinder. In multicolor printing, a plurality of printing units each having an ink fountain, ink rollers, plate cylinder, blanket cylinder, and impression cylinder are prepared for the respective colors. The printing units sequentially print the colors on a conveyed printing paper sheet.
As shown in FIG. 28, each printing unit comprises an inking device (inker) corresponding to each color. Referring to FIG. 28, reference numeral 1 denotes an ink fountain which stores ink 2; 3, an ink fountain roller; 4-1 to 4-n, a plurality of ink fountain keys which are juxtaposed in the axial direction of the ink fountain roller 3; 5, an ink ductor roller; 6, ink rollers; and 7, a plate cylinder to which a printing plate 8 is attached. An image is printed on the printing plate 8 mounted on the outer surface of the plate cylinder 7.
In each printing unit, the amount of ink supplied from the ink fountain 1 to the ink fountain roller 3 is adjusted by adjusting the opening ratios of the ink fountain keys 4-1 to 4-n. Simultaneously, the amount of ink supplied from the ink fountain roller 3 to the printing plate 8 through the ink rollers 6 is adjusted by adjusting the feed rate of the ink fountain roller 3. The ink supplied to the printing plate 8 is transferred to the blanket cylinder (not shown) and printed on a printing paper sheet.
In a multicolor printing press having a plurality of printing units, the printing plate 8 wound around the plate cylinder 7 of each color printing unit may be shifted from an appropriate position. In this case, color images of a finished printing product may have a positional shift (misregister) in the circumferential direction [the printing direction in the printing press (the direction of travel of a printing product)] or lateral direction (a direction perpendicular to the circumferential direction).
To solve this, in Japanese Patent Laid-Open No. 62-99149 (reference 1), a portion where cross-shaped register marks are printed as register marks of the respective colors is zoomed and sensed. The position of each color register mark contained in the sensed image is calculated. The misregister amount between the colors and the position correction amount of the plate cylinder are calculated from the calculated register mark positions. The position of the plate cylinder is automatically corrected on the basis of the calculation result.
FIG. 29 shows the schematic arrangement of the automatic registration apparatus of a printing press described in reference 1. Referring to FIG. 29, reference numeral 11 denotes a camera (color camera); 12, a processing unit; 13, an operation panel; 14, a motor driving circuit; 15, a plurality of motors to drive the register adjustment elements of the printing press; and 16, a plurality of potentiometers attached to the motors 15. The camera 11 zooms and senses an image portion X where four register marks TC, TM, TY, and TK of cyan (C), magenta (M), yellow (Y), and black (K) are printed. R image data with a red component R, G image data with a green component G, and B image data with a blue component B of the register marks TC, TM, TY, and TK are sent to the processing unit 12.
The processing unit 12 stores the R image data from the camera 11 in an R frame memory (not shown), the G image data in a G frame memory (not shown), and the B image data in a B frame memory (not shown). The R, G, and B image data stored in the R, G, and B frame memories are converted into C, M, Y, and K image data and stored in C, M, Y, and K frame memories. The R, G, and B image data are converted into C, M, Y, and K image data in the following way.
(1) The complement of the luminance level (pixel value) of each pixel of the R, G, and B image data is set to the density level (pixel value) of each pixel of the C, M, and Y image data and stored in the C, M, and Y frame memories.
(2) The density level of each pixel of the C, M, and Y image data is checked. For a pixel having a density of a predetermined level or more in all the C, M, and Y colors, the average density level of the C, M, and Y colors is obtained. The average density level is stored as the pixel value of a corresponding pixel in the K frame memory. In this case, the density levels of corresponding pixels in the C, M, and Y frame memories are rewritten to 0.
(3) The luminance level of each pixel of the R image data is checked. A pixel lower than a predetermined level (a pixel having a high C density level) is determined as a portion where C and K overlap. The complement of the luminance level is converted into a density level. The density level is multiplied by a predetermined constant to remove the increase in density by K. The density level of a corresponding pixel in the C frame memory is rewritten.
(4) The luminance level of each pixel of the G image data is checked. A pixel lower than a predetermined level (a pixel having a high M density level) is determined as a portion where M and K overlap. The complement of the luminance level is converted into a density level. The density level is multiplied by a predetermined constant to remove the increase in density by K. The density level of a corresponding pixel in the M frame memory is rewritten.
(5) The luminance level of each pixel of the B image data is checked. A pixel lower than a predetermined level (a pixel having a high Y density level) is determined as a portion where Y and K overlap. The complement of the luminance level is converted into a density level. The density level is multiplied by a predetermined constant to remove the increase in density by K. The density level of a corresponding pixel in the Y frame memory is rewritten.
With the above-described process, the R, G, and B image data are converted into C, M, Y, and K image data and stored in the C, M, Y, and K frame memories.
(6) To check which pixel of the C, M, Y, and K image data has an image portion, the density level of each pixel stored in the C, M, Y, and K frame memories is binarized with a predetermined slice level.
(7) In two directions (X and Y directions) perpendicular to each other in the C image data, the number of pixels determined to have an image is added. The sum of images in the Y direction is plotted for each pixel position in the X direction to obtain a first cumulative curve. The sum of images in the X direction is plotted for each pixel position in the Y direction to obtain a second cumulative curve. The center of the peak of the first cumulative curve is obtained as the X-coordinate of the center of the register mark TC. The center of the peak of the second cumulative curve is obtained as the Y-coordinate of the center of the register mark TC.
(8) In two directions (X and Y directions) perpendicular to each other in the M image data, the number of pixels determined to have an image is added. The sum of images in the Y direction is plotted for each pixel position in the X direction to obtain a first cumulative curve. The sum of images in the X direction is plotted for each pixel position in the Y direction to obtain a second cumulative curve. The center of the peak of the first cumulative curve is obtained as the X-coordinate of the center of the register mark TM. The center of the peak of the second cumulative curve is obtained as the Y-coordinate of the center of the register mark TM.
(9) In two directions (X and Y directions) perpendicular to each other in the Y image data, the number of pixels determined to have an image is added. The sum of images in the Y direction is plotted for each pixel position in the X direction to obtain a first cumulative curve. The sum of images in the X direction is plotted for each pixel position in the Y direction to obtain a second cumulative curve. The center of the peak of the first cumulative curve is obtained as the X-coordinate of the center of the register mark TY. The center of the peak of the second cumulative curve is obtained as the Y-coordinate of the center of the register mark TY.
(10) In two directions (X and Y directions) perpendicular to each other in the K image data, the number of pixels determined to have an image is added. The sum of images in the Y direction is plotted for each pixel position in the X direction to obtain a first cumulative curve. The sum of images in the X direction is plotted for each pixel position in the Y direction to obtain a second cumulative curve. The center of the peak of the first cumulative curve is obtained as the X-coordinate of the center of the register mark TK. The center of the peak of the second cumulative curve is obtained as the Y-coordinate of the center of the register mark TK.
(11) The misregister amounts in the circumferential and lateral directions between the colors are obtained from the obtained central coordinates of the register marks TC, TM, TY, and TK. The motors 15 are so driven as to nullify the misregister amounts while receiving feedback of position data from the potentiometers 16, thereby correcting the position of the plate cylinder 7 in each color printing unit.
However, in the conventional misregister amount detection method described in reference 1, in generating the K image data from the C, M, and Y image data in the step (2), a pixel having a density of a predetermined level or more in all the C, M, and Y colors is determined as K. However, the C, M, Y, and K densities change between actual printing products. Hence, if K pixels are determined in accordance with a threshold value of predetermined level, it makes a difference between printing products.
In the step (3), a pixel in the R image data whose luminance level is lower than a predetermined level is determined as a pixel where C and K overlap. In the step (4), a pixel in the G image data whose luminance level is lower than a predetermined level is determined as a pixel where M and K overlap. In the step (5), a pixel in the B image data whose luminance level is lower than a predetermined level is determined as a pixel where Y and K overlap. However, the C, M, Y, and K densities, i.e., the R, G, and B luminance levels change between actual printing products. Hence, if pixels overlapping K are determined in accordance with a threshold value of predetermined level, it makes a difference between printing products.
In the step (3), the complement of the luminance level of a pixel where C and K overlap is multiplied by a predetermined constant, thereby obtaining the C density level excluding the increase in density by K. In the step (4), the complement of the luminance level of a pixel where M and K overlap is multiplied by a predetermined constant, thereby obtaining the M density level excluding the increase in density by K. In the step (5), the complement of the luminance level of a pixel where Y and K overlap is multiplied by a predetermined constant, thereby obtaining the Y density level excluding the increase in density by K. However, the C, M, Y, and K densities change between actual printing products. Hence, if the density level excluding the increase in density by K is obtained by multiplication of a predetermined constant, it makes a difference between printing products.
In the step (6), to check which pixel has an image, the density level of each pixel stored in the C, M, Y, and K frame memories is binarized with a predetermined slice level. However, the C, M, Y, and K densities change between actual printing products. Hence, if the density level is binarized with a predetermined slice level, it makes a difference between printing products.
As described above, in the conventional misregister amount detection method of reference 1, K pixels are determined in accordance with a threshold value of predetermined level, or pixels overlapping K are determined in accordance with a threshold value of predetermined level, although the C, M, Y, and K densities change between actual printing products. In addition, the density level excluding the increase in density by K is obtained by multiplication of a predetermined constant, or the density level is binarized with a predetermined slice level. For this reason, a difference is generated between printing products. A detection error occurs in the central coordinates of the register marks of the respective colors. Hence, the misregister amount between the colors cannot accurately be obtained.

Misregister amount detection method and apparatus


A fitting for connecting first and second components arranged at right angles to each other that includes a flange part, which extends in a first direction and has a first connection surface in contact with the first component, and which has at least one first connection hole formed by a bore of a first insert; and a base part, which extends in a second direction, perpendicular to the first direction, and has a second connection surface in contact with the second component, and which has at least one second connection hole formed by a bore of a second insert. The first insert is joined to the second insert by at least one loop of continuous fiber tow wound around radially outer surfaces of the first insert second inserts.

Angled fittings or brackets for connecting two or more members are well known in the art. When intended to connect surfaces that are generally perpendicular to each other, such fittings/brackets often have a geometry that is essentially L-shaped or essentially T-shaped. In aerospace applications, where weight and strength are important considerations, composite materials are increasingly being used in the manufacture of fittings.
One example of a composite L-shaped fitting is known from U.S. Pat. No. 8,925,880. The fitting is made by placing pre-impregnated fibers in the form of fabrics or mats into a mold with a specific geometry. The fitting comprises two portions which are essentially perpendicular to each other in which connection holes are provided. One of the portions has at its inner side a concave curved profile, whereby the hole or holes provided in that portion have an axis radial to the curvature.
An example of a T-shaped fitting having three branches provided with connection holes is disclosed in U.S. Pat. No. 9,447,802. The branches are molded from a fiber-reinforced thermoplastic or thermoset matrix and extend radially from a joining zone. The joining zone has a cross-section in transverse direction in the shape of a polygon with concave sides.
There is still room for improvement.


A system and method for analyzing a chemical composition of a specimen are described. The system can include at least one pin; a sampling device configured to contact a liquid with a specimen on the at least one pin to form a testing solution; and a stepper mechanism configured to move the at least one pin and the sampling device relative to one another. The system can also include an analytical instrument for determining a chemical composition of the specimen from the testing solution. In particular, the systems and methods described herein enable chemical analysis of specimens, such as tissue, to be evaluated in a manner that the spatial-resolution is limited by the size of the pins used to obtain tissue samples, not the size of the sampling device used to solubilize the samples coupled to the pins.

Many types of surface sampling probes have been employed to deliver analytes to an analytic instrument, such as a mass spectrometer. Such surface sampling probes include probes employing thermal desorption, laser desorption and confined liquid extraction. Methods of liquid extraction surface sampling probes include those disclosed in Gary J. Van Berkel et al., "Thin-Layer Chromatography and Electrospray Mass Spectroscopy Coupled Using a Surface Sampling Probe," Anal. Chem. 2002, 74, pp. 6216-6223; Keiji G. Asano et al., "Self-aspirating atmospheric pressure chemical ionization source for direct sampling of analytes on surfaces and in liquid solutions," Rapid Commun. Mass Spectrom. 2005, 19, pp. 2305-2312; and U.S. Pat. No. 6,803,566 to Gary J. Van Berkel. Despite the existing liquid extraction probe technology, there is currently no efficient means of obtaining high resolution compositional analysis of a sample.

Device for high spatial resolution chemical analysis of a sample and method of high spatial resolution chemical analysis