Reagents and methods for whitening and remineralizing teeth using biomineralizing peptides are described.

Accumulation of various chromogens/discolorants, for example, food and tobacco that come into contact daily onto tooth surfaces and their subsequent penetration into deeper regions (dentin), cause tooth discoloration. Furthermore, the process of aging, disease, trauma, certain medications, certain congenital conditions, and environmental effects can also cause teeth to become discolored. Although discolored teeth do not cause health problems, since bright white teeth are usually considered to be cosmetically desirable, there is a great deal of interest in developing compositions and methods for whitening teeth.
There are several techniques for whitening or bleaching of teeth. Professional whitening methods, also known as "in-clinic" whitening strategies, are considered presently as the most effective methods. These in-clinic whitening strategies typically involve the application of high-concentration peroxide products (up to 35%) and other abrasive chemicals to the discolored area. These peroxide species penetrate the stained area (up to underlying dentin layer) and dissolve the accumulated discoloring agents through an oxidation process. To achieve desired effects more quickly, such oxidation reactions on teeth are often assisted with external laser light application, which heats up the reaction site and thereby increases the rate oxidation reaction. Furthermore, utilization of titanium dioxide up to 10% is often preferred to facilitate these photo-catalytic reactions. Other in-clinic whitening techniques involve superficially removing the enamel layer with abrasive instruments or pumice followed by treatment with additional caustic agents.
There are several drawbacks of these in-clinic techniques. First of all, the abrasive chemicals and peroxide agents causes enamel demineralization and results with teeth sensitivity. In most cases sore/injured gums as well as bad taste of the product itself cause much discomfort to the patients. Further, patients are required to make a clinic appointment to get this medical service.
Other existing products for at-home use contain considerably lower concentrations of active oxidizing agents and, thus, are generally less effective than in-clinic whitening strategies and products. Therefore, dramatic whitening effect can only be achieved by the repeated applications of these reagents for several weeks. These treatments often assisted with bleaching trays (night-guard) in order to better localize bleaching products and, thereby, maximize the whitening effect. However, even though these at home products contain active whitening agents in lower concentrations, similar side effects as those associated with professional treatments are very common. In addition, there are paint-on, at-home whitening products, also known as "tooth varnishes", as well as whitening strips intended to eliminate the need for dental trays. However, these products require more frequent applications, usually 3-times in a day, to complete whitening procedure. Finally, among the variety of at-home use products, whitening toothpastes and gels are the least effective form of whitening products due to their short contact time with the tooth surfaces. Although bleaching agent additives augment the effectiveness, the whitening effect is primarily as a result of removal of surface stains via mechanical action of brushing and other polishing ingredients (for example, silica particles).
Dental caries is one of the major public health problems and it is a highly prevalent disease among the global population. Incipient caries and white spot lesions (WSL) as well as hypersensitivity, are the earliest clinical evidence of enamel demineralization and dental caries. Dental caries occurs when tooth enamel is exposed to acid produced by cariogenic bacteria. As a result, acid diffuses into surface enamel and dissolves hydroxyapatite (HAp) mineral. Due to its non-regenerative nature, enamel is unable to heal and repair itself post-demineralization. Traditionally, fluoride (F) has been used as the key agent in prevention of caries. Fluoride functions primarily via topical mechanisms. It is believed that fluoride forms a thin layer of new but harder mineral, namely fluorapatite (FAp) which is incorporated into the existing HAp mineral on the tooth surface. There is a trend of enhancing the remineralization effect of fluoride with calcium and phosphate supplementation in high risk individuals. Although controversial, the use of fluoride products remains the primary treatment modality for caries prevention and remineralization, with major limitations regarding the efficacy of these products for the reversal or prevention of dental caries. Fluoride delivery systems, therefore, are not sufficient to overcome the high caries risk especially in younger and elderly population.
There is presently an unmet need for tooth whitening and mineralization methods and products that reduce or eliminate the need for concentrated, abrasive oxidizing agents and attendant side effects such as demineralization-associated tooth sensitivity and gum line injuries.

Reagents and methods for mineralization of tooth enamel


A wing-to-body fairing for reducing noise due to wing-to-body fairing vibrations in an aircraft, spacecraft, or vehicle may include a honeycomb center having a cavity which is at least partially filled with particle material.

Spacecraft, aircraft, and other vehicles often experience substantial vibrations, noise, and fatigue in fairings and in particularly wing-to-body fairings which are attached between the wings and body of the spacecraft, aircraft, or vehicle. Some of the previous prior art devices may have involved heavy, complex, excessive part, and/or expensive noise and vibration dampening devices in an effort to attempt to reduce vibrations, noise, and fatigue. However, many of these prior art devices do not sufficiently reduce noise, vibration, and/or fatigue, and/or may lead to increased weight, increased complexity, an increased number of parts, an increased cost, and/or experience other types of issues.
A wing-to-body fairing, and a method of use thereof, is needed to decrease one or more problems associated with one or more of the existing wing-to-body fairings and/or methods of use thereof.

Particle-filled wing-to-body fairing and method for reducing fairing vibrations


A fructose transferring enzyme is immobilized by adsorption on a granular carrier having a primary to quaternary amine. The carrier is preferably an epoxy polymer, a vinyl polymer or a chitosan derivative having a primary, secondary or tertiary amine. Immobilization can be performed without or with a crosslinking agent. The immobilized enzyme is used for producing fructooligosaccharides by passing a sucrose solution through a column containing the immobilized enzyme.

It is known that when sucrose is contacted with an enzyme having fructose transferring activity (hereinafter referred to generally as fructose transferring enzyme), there is obtained a sweetener containing products of fructose transfer reaction, such as glucose as a byproduct, fructooligosaccharides which are mostly the trisaccharide (GF.sub.2), tetrasaccharide (GF.sub.3), pentasaccharide (GF.sub.4) and hexasaccharide (GF.sub.5) corresponding to sucrose coupled with 1 to 4 moles of fructose, respectively, and as a minor component, unreacted sucrose. It is further known that these fructooligosaccharides are not-substrates for the dextran sucrase produced by Streptococcus mutans, the cariogenic bacterium, and that a low-cariogenic sweetener can be produced by permitting a fructose enzyme to act on sucrose (JP-A-56-154967; the term "JP-A" used herein means "an unexamined published Japanese patent application"). It is also known that fructooligosaccharides are low-calorie sweeteners which are not digested in the living body (JP-A-58-40065) and are selectively utilized by bifidobacteria forming main part of the inetestinal bacterial flora, they can be accordingly used as selective growth factors for intestinal bifidobacteria (JP-B-59-53834; the term "JP-B" used herein means "an examined published Japanese patent application").
As the fructose transferring enzyme which can be used in the production of fructooligosaccharides, there can be mentioned the enzymes derived from strains of the genus Aspergillus such as A. niger etc., those of the genus Penicillium such as P. nigricans etc., those of the genus Fusarium such as F. lini IAM 5008 etc., those of the genus Gloeosporium such as G. kaki IAM 5011 etc., and those of the genus Aureobasidium such as A. pullulans var. melanigenum A-8 ATCC 20612 and so on. Aside from the above-mentioned microorganisms, the enzymes derived from yeasts and other microorganisms, for example strains of the genus Saccharomyces such as S. cerevisiae etc., those of the genus Rhodotorula such as R. glutinis etc., those of the genus Pichia such as P. miso etc., those of the genus Hansenula such as H. miso etc., and those of the genus Candida such as C. tropicalis etc., as well as the enzymes derived from certain plants such as asparagus, Jerusalem artichoke and so on (JP-A-56-154967 and JP-B-59-53834) can be utilized.
As an industrial process for production of fructooligosaccharides using a native fructose transferring enzyme, there is known a batch process in which a culture broth of such microorganism or the cells, disrupted cells, extract or enzyme harvested or purified therefrom is stirred together with sucrose at suitable sucrose concentration, pH and temperature (JP-A-56-154967 and 61-268190).
From the standpoint of production cost, a continuous process using an immobilized enzyme or an immobilized microorganism is preferred to a batch process with native enzyme and for this purpose, it has been proposed to immobilize microbial cells with an alginate gel by entrapping immobilization (JP-A-58-162292) or with .beta.-1,3-1,6-glucan and aluminum sulfate (JP-A-60-41497).
In order to produce fructooligosaccharides using an immobilized enzyme or an immobilized microorganism continuously on an industrial scale, it is necessary to pack the immobilized enzyme or the like into a column and pass a highly concentrated sucrose solution through the column. However, in order that this process may be successfully carried out, the immobilized enzyme or the like must have a fairly high mechanical strength. Generally speaking, an immobilized enzyme or the like obtained by gel entrapment is comparatively low in mechanical strength so that in industrial production using a highly concentrated sucrose solution as the substrate, the gel tends to be compacted to cause a progressive decrease in flow rate.
To obviate this disadvantage, entrapping immobilized microbial cells (JP-A-62-40289) and entrapping immobilized enzymes (JP-A-62-278983), having improved mechanical strength characteristics have been developed.
However, when such an immobilized preparation is packed into a column and a substrate solution is passed under industrial conditions, for example at a temperature of 50.degree. C. and a sucrose concentration of 50%, there are encountered difficulties such that the half-life of the enzyme activity is as short as about 20 days, the output and composition of the desired product vary considerably, and the withdrawal and repacking of the immobilized cells or enzyme must be carried out frequently.

Fructose transferring enzyme absorbed on a granular carrier for production of fructooligosaccharides


The human immunodeficiency virus (HIV) contains, in addition to the canonical genes gag, pol, and env, an open reading frame in the 3' region of the genome that overlaps with the 3' long terminal repeat (LTR). Initial studies on the protein encoded by this ORF revealed a negative effect on HIV replication in vitro and this gene product was subsequently designated the negative factor, or Nef. The nef gene product is 25-29 kDa protein that localizes primarily to the cytoplasm of HIV-infected cells. The subject of this invention pertains to the discovery of a superantigen activity associated with this peptide and peptidic fragments derived therefrom. Superantigens are powerful T-cell mitogens that bind directly to major histocompatibility complex (MHC) class II molecules and form a binary complex with the variable .beta. (V.sub..beta.) region of the T-cell antigen receptor (TCR). It was demonstrated that Nef induces the rapid proliferation of human peripheral mononuclear cells and T-lymphocyte cytokine production. Nef peptidic fragments were also identified that display major histocompatibility complex (MHC) class II binding activity. These peptides can be utilized to generate suitable immune responses in the desired host.

Normally, when a person's immune system encounters a protein made by a virus or other microbe, fewer than one in 10,000 of the white blood cells known as T lymphocytes react. Although their number is small, these T lymphocytes orchestrate an attack that specifically targets the alien protein, or antigen, without harming healthy tissue. In contrast, proteins called superantigens highly activate the immune system and can cause an unproductive, even destructive, immune response.
Superantigens are the most powerful T cell mitogens known (Johnson, H. M., H. I. Magazine [1988] Int. Arch Allergy Appl. Immunol. 87:87-90). As explained below, these unique antigens stimulate T cells by first binding to class II major histocompatibility (MHC) molecules (Carlsson, R., H. Fischer, H. O. Sjogren [1988] J. Immunol. 140:2484-2488; Fleischer, B., H. Schrezenmeier [1988] J. Exp. Med. 167:1697-1707; Mollick, J. A., R. G. Cook, R. R. Rich [1989] Science 244:817-820) forming a binary complex which binds in a V.sub..beta. -specific manner to the T cell antigen receptor (TCR) (Janeway, C. A., J. Yagi, P. J. Conrad, M. E. Katz, B. Jones, S. Vroegop, S. Buxser [1989] Immunol. Rev. 107:61-88; White, J., A. Herman, A. M. Pullen, R. Kubo, J. W. Kappler, P. Marrack [1989] Cell 56:27-35).
Superantigens can arouse as many as one in five T cells, most of which are useless for fighting a current infection. What is worse, certain of the activated cells may unleash an autoimmune attack which targets tissues of the host organism. At times, superantigens may even have the opposite effect: they somehow trigger the death of the cells they excite.
Scientists have gleaned much of what they understand about superantigens from studying the earliest known examples: a group of structurally related proteins called staphylococcal enterotoxins (SEs). Staphylococcal enterotoxins account for as much as 45 percent of all cases of food poisoning. It is well established that when strains of the bacterium Staphylococcus aureus colonize food, they secrete one or more enterotoxins, which are now named alphabetically as A, B, C, D, and E. Within hours after people ingest badly contaminated, toxin-laden food, they begin to feel weak, feverish, and nauseated. Interestingly, intestinal tissue of affected patients looks virtually normal under the microscope. The only obvious abnormality is the presence of white cells in the tissue. It has now also been found that introduction of an enterotoxin to blood triggers the proliferation of lymphocytes. Just a few hundred molecules of toxin triggers a degree of replication that surpasses what could be achieved by a billion copies of a conventional antigen--for example, a protein on the influenza virus.
Further research has documented that a small amount of an enterotoxin can yield extraordinarily high production of chemical signals known as cytolines, which are produced by the subset of T lymphocytes called helper cells. These helper T cells direct much of the immune response. The helper T cells do not attack microbes themselves; instead they rely on the cytokines to activate both cytotoxic T lymphocytes, which kill infected cells, and B lymphocytes, which secrete antibodies against antigens.
By the mid-1980s it was recognized that when a tiny amount of enterotoxin A was mixed with T lymphocytes, the collection of cells produced a huge quantity of the cytokine known as interleukin-2 (IL-2). It has also been determined that infusion of high doses of IL-2 into the circulation of cancer patients (as part of an experimental therapy) causes the very symptoms associated with food poisoning. These data indicate that enterotoxins make people ill by stimulating production of high levels of interleukin-2.
Before helper T cells can recognize conventional protein antigens, the proteins must first undergo processing by macrophages or other antigen-presenting cells (APC). These cells engulf the antigens and process them into peptides. The presenters then display the peptide antigens at the cell surface in combination with major histocompatibility complex (MHC) class II molecules. A peptide fits in a cleft on an MHC molecule. Once an antigen is displayed, the few helper cells in the body that bear receptors for the particular peptide link up with it. Each T cell is specific for one kind of peptide antigen.
Like conventional toxins, enterotoxin superantigens can arouse helper T cells only if antigen-presenting cells display the proteins to the T cells. Moreover, it is MHC class II molecules that do the presenting. Yet, unlike typical antigens, the enterotoxins bind to MHC molecules directly; they do not require uptake and processing by APC. Also, enterotoxins do not bind to the inner surface of the peptide-recognizing pocket of the MHC molecule, attaching instead to its outer surface. Then the MHC-superantigen unit contacts the T cell receptor at a site distinct from the surface that envelops conventional antigens. To be more precise, T cell receptors consist of two protein chains, alpha and beta. Both chains include structurally invariant and variable regions that participate in the binding of conventional peptide antigens. The enterotoxins are thought to link up with the beta-chain variable--or V-beta (V.sub..beta.)--region, at a part not involved in the binding of typical antigens.
Each enterotoxin interacts with particular V.beta. types. For instance, one enterotoxin may be recognized by the variable types numbered 5 and 12, whereas another might be recognized by types 12, 15, and 18. For example, SEB has been shown to be specific for T cells bearing V.sub..beta. elements such as 7 and 8.1-8.3 in mice (Herman, A., J. W. Kappler, P. Marrack, A. M. Pullen [1991] Ann. Rev. Immunol. 9:745-772). Investigators estimate that every human has fewer than 30 V.sub..beta. types, although the fraction of helper T cells carrying any given type can differ from person to person. A conventional antigen can activate only the relatively few helper cells specific for that antigen. A given enterotoxin, however, can activate many times that number of helpers (having a huge variety of peptide-antigen specificities) as long as the T cells bear selected V.sub..beta. types.
Although superantigens are suspected of, at times, causing over-activation of the immune system, some evidence suggests that superantigens may also depress the immune system. T cell clones aroused by superantigens often disappear (depletion) or become inactive (anergy) after being stimulated. Staphylococcal enterotoxdns, the prototype superantigens, activate T cells bearing specific T cell antigen receptor .beta.-chain variable region elements. Their V.sub..beta. specificity has profound implications with regard to expansion, anergy, and deletion of various T cell populations in terms of immunologic disease. It has been demonstrated that although an initial mitogenic effect is observed after in vivo administration of staphylococcal enterotoxin B (SEB), the lasting result appears to be both clonal anergy and deletion of V.sub..beta. specific peripheral T cells (Kawake, Y., A. Ochi [1991] Nature 349:245-248; Kawake, Y., A. Ochi [1990] J. Exp. Med. 172:1065-1070; Rellahan, B. L., L. A. Jones, A. M. Kruisbeek, A. M. Fry, L. A. Matis [1990] J. Exp. Med. 172:1092-1100).
Thus far, we have primarily focused on the interaction between superantigens and helper T cell activity; however, the possible deranging effects of superantigens on B cells should not be ignored. Staphylococcal enterotoxins sometimes enhance antibody production by B cells and sometimes inhibit it, depending on the initial state of immune arousal. Enhancement and suppression may each be destructive. Inhibition of antibody production can depress immune functioning. Overzealous production can lead to immune complex disorders, in which antibodies attract various components of the immune system to healthy tissue, clogging them and impeding normal function.
Interaction of the staphylococcal enterotoxins with class II molecules induces production of the cytokines tumor necrosis factor alpha (TNF.alpha.) and interleukin-1 (IL-1) by monocytes (Fischer, H., M. Dohlsten, U. Andersson, G. Hedlund, P. Ericsson, J. Hansson, H. O. Sjogren [1990] J. Immunol. 144:4663; Gjorloff, A., H. Fischer, G. Hedlund, J. Hansson, J. S. Kenney, A. C. Allison, H. O. Sjogren, M. Dohlsten [1991] Cell Immunol. 137:61). Both SEA and the related toxic shock syndrome toxin one (TSST-1) are potent inducers of TNF.alpha. and IL-1. Binding of these superantigens to MHC transduces a signal through the monocyte membrane which leads to tyrosine kinase activation and phosphorylation of multiple cytoplasmic proteins and monokine gene induction (Scholl, P. R., N. Trede, T. A. Chatila, R. S. Geha [1992] J. Immunol. 148:2237). Subsequently, monokines can have effects on T cells; for example, TNF.alpha. can further enhance human T cell proliferation (Yokota, S., T. D. Geppert, P. E. Lipsky [1988] J. Immunol. 140:531). IL-1 is an additional stimulator by increasing IL-2 secretion and IL-2 receptor expression. Both IL-1 and TNF.alpha. secretion may require the presence of T cells, particularly CD4.sup.+ 45RO.sup.+ memory T cells (Fischer et aL, supra; Gjorloff et al, supra). A variety of peptide sequences of the superantigen SEA that participate in binding to the class II MHC molecules have previously been studied (Pontzer, C. H., J. K. Russell, H. M. Johnson [1989] J. Immunol. 143:280; Pontzer, C., J. K. Russell, M. A. Jarpe, H. M. Johnson [1990] Int. Arch. Allergy Appl. Immunol. 93:107; Griggs, N. D., C. H. Pontzer, M. A. Jarpe, H. M. Johnson [1992] J. Immunol. 148:2516; Grossman, D., R. G. Cook, J. T. Sparrow, J. A. Mollick, R. R. Rich [1990] J. Exp. Med. 172:1831; Grossman, D., M. Van, J. A. Mollick, S. K. Highlander, R. R. Rich [1991] J. Immunol. 147:3274).
Superantigens have been hypothesized to be associated with a number of pathological conditions. For example, superantigen alteration of the T cell repertoire has import for immunodeficiency and autoimmunity. T cells bearing certain V.sub..beta. types have been implicated in various autoimmune conditions, including arthritis, lupus, and multiple sclerosis. It is conceivable, but not yet established, that over-activation of T cells by superantigens could play a role in certain autoimmune disorders.
Involvement of a predominant V.sub..beta. specific T cell population has been suggested for certain animal models of autoimmune disease. For example, experimental allergic encephalomyelitis (EAE) is an animal model for multiple sclerosis. Multiple sclerosis (MS) is a chronic, often disabling disease that attacks the central nervous system, damaging the protective coating that surrounds nerve fibers. EAE is mediated by V.sub..beta. 8.2.sup.+, CD4.sup.+ T cells in PL/J mice after injection with myelin basic protein (MBP). This limited heterogeneity of TCR usage has implicated the involvement of V.sub..beta. 8.2.sup.+, CD4.sup.+ T cells in EAE in PL/J mice immunized with rat myelin basic protein (Acha-Orbea, H., D. J. Mitchell, L. Timmerman, D. C. Wraith, G. S. Tausch, M. K Waldon, S. S. Zamvil, H. O. McDevitt, L. Steinman [1988] Cell54:263-273).
Recently, several novel immunological approaches have been explored relevant to autoimmune diseases such as EAE in mice and rats and lupus nephritis in MRL/1 pr mice. Many have been directed toward blocking the function of the effector CD4.sup.+ T cell which has been shown to exhibit V.sub..beta. isotype restriction in EAE. These approaches have included the use of anti-TCR antibodies (Acha-Orbea et al., supra), synthetic TCR peptides (Offner, H., G. A. Hashim, A. A. Vandenbark [1991] Science 251:430-432) and superantigen treatment (Kim, C., K. A. Siminovitch, A. Ochi [1991] J. Exp. Med. 174:1431-1437).
Superantigens are also associated with retroviruses such as mouse mammary tumor virus (MMTV), and possibly human immunodeficiency virus (HIV), the virus responsible for AIDS. It has recently been reported that two exogenous strains of MMTV encode retroviral superantigens in the open reading frames (ORFs) of the 3' Long Terminal Repeat (LTR) of the viral genome (Pullen, A. M., Y. Choi, E. Kushnir, J. Kappler, P. Marrack [1992] J. Exp. Med. 175:41-47; Choi, Y., P. Marrack, J. Kappler [1992] J. Exp. Med. 175:847-851). There is preliminary evidence that the HIV genome may also encode a superantigen. It has been suggested that an HIV superantigen may target a sub-population of CD4.sup.+ T cells for HIV viral replication (Laurence, J., A. S. Hodtsev, D. N. Posnett [1992] Nature 358:255-259). HIV infection also results in the programmed cell death of CD4.sup.+ T cells (apoptosis), both in vitro and in vivo, possibly as a result of an HIV protein with superantigen properties (Gougeon, M-L., L. Montagnier [1993] Science 260:1269-1270). Feline immunodeficiency virus (FIV) is a lentivirus which has been described extensively in the literature. See, for example, Kiyomasu, Takahiro, et al. (1991) "Identification of Feline Immunodeficiency Virus rev Gene Activity" Journal of Virology 65(8):4539-4542, and references cited therein. There has also been speculation that the human spumaretrovirus (HSRV) expresses a superantigen ("Molecular Biology of the Human Spumavirus," in Human Retroviruses, B. R. Cullen, ed., Oxford University Press, Oxford and New York, 1993, pp. 205-206).
Like many viruses, including MMTV and FIV, the HIV genome has a 3' Long Terminal Repeat. Initial studies indicated that a protein encoded by an ORF in the 3' LTR had negative effects on HIV replication in vitro, and hence was designated Negative Factor (Nef). Nef is a 25-29 kD protein that is mainly located in the cytoplasm of HIV-infected cells, but is also associated with the plasma membrane (Allan, J. S., J. E. Coligan, T-H. Lee, M. F. McLane, P. J. Kanki, J. E. Groopman, M. Essex [1985] Science 230:810-813). The role of NeF in retroviral pathogenesis has been studied (Laurent, A. G., A. G. Hovanessian, Y. Riviere, b. Krust, A. Regnault, L. Montagnier, A. Findeli, M. P. Kieny, B. Guy [1990] J. Gen. Virol. 71:2273-2281). There are no reports that suggest Nef as a superantigen.

Methods for stimulating immune responses in a host through the administration of superantigen peptides derived from human immunodeficiency virus type 1 Nef


A golf ball having a spherical shell with a plurality of internal structures is disclosed herein. A fluid material is disposed within the spherical shell. The plurality of internal structures effect the spin decay of the golf ball.

1. Field of the Invention
The present invention relates to a golf ball. More specifically, the present invention relates to a golf ball with a liquid-filled core that includes internal structures.
2. Description of the Related Art
Fluid filled cores for golf balls have been practiced in the prior art.

Liquid-filled golf ball with preferential internal structures


Correlating activity events to identify a root cause of a process failure. Activity event data is received from a process executing on a computing device. The activity event data corresponds to a plurality of activity events. Each of the activity events has a correlation identifier, a resolution status, and an occurrence time value associated therewith. Each of the activity events are assigned to one of a plurality of event groups based on the correlation identifier of the activity event. Thereafter, at least one of the event groups is determined to have an activity event with a resolution status indicating failure of the process. One of the activity events within the determined event group is selected as a root cause activity event based on the occurrence time values. In some embodiments, the root cause activity event is identified to a user of the computing device.

Root cause identification is a class of methods in the problem-solving field that identify root causes of problems or events. Generally, problems can be solved by addressing the root causes of the problems, instead of addressing symptoms that are being continuously derived from the problem. Ideally, when the root cause has been addressed, the symptoms following the root cause will disappear. Traditional root cause analysis is performed in a systematic manner with conclusions and root causes supported by evidence and established causal relationships between the root cause(s) and problem(s). During root cause identification, however, it is difficult to differentiate between events that demand manual intervention of an operations team of a service/product from events that do not demand manual intervention. Such differentiation is important, for example, in software services and enterprise IT departments because an ongoing operation cost of a service is proportional with the number of support tickets that a system issues.
Some existing systems detect errors in a process by assuming that a first or last error event that occurs during analysis window execution of the process is the root cause. However, this approach lacks precision and may produce false alarms (e.g., if the error event is not severe, is only temporary, or if the event self-resolves). Further, it is difficult and time-consuming to trace code paths to understand the reason for each failure.

Root cause problem identification through event correlation


Corner mask portions are provided at four corners of an exposure opening. The corner mask portions are formed by rounding the corners into curves. The quantity of developing solution contained in a developing solution pod is reduced, consequently, it is possible to reduce the thickness of a solution pod section and a trap section.

1. Field of the Invention
The present invention relates to an instant film unit of a self-developing type.
2. Description Related to the Prior Art
An instant film unit (hereinafter referred to as a "film unit") has a peel-apart type and a monosheet type. Each of them maintains a characteristic of providing a printed photo soon after photography. In the peel-apart type, after the film unit is loaded into a printer or an instant camera and is recorded an image, a photosensitive sheet is overlaid on an image receiving sheet by an operation of pulling a tab. The peel-apart film unit needs a manual step of putting those overlaid sheets into between a spreading roller pair. On the other hand, the film unit of the monosheet type is in a sheet shape, and it is possible to eject the film unit outside automatically. Therefore, the monosheet film unit is widespread among the general public.
A printer using the film unit is assembled such that an exposure head in a line shape is moved on the photosensitive surface of the film unit and exposes three fields of red, green and blue sequentially, then the exposed film unit is ejected through the spreading roller pair while it is processed (JP-A 2002-023254).
The monosheet film unit includes a photosensitive surface on which a latent image is created by exposure, a photosensitive sheet having a image creating surface on which a positive image is created, a cover sheet overlaid on the photosensitive sheet, a developing solution pod for containing developing solution to be spread between these sheets, a trapping material for catching a surplus of the developing solution being spread. Furthermore, these components are integrated by a white mask sheet (U.S. Pat. No. 6,304,725).
The film unit described in U.S. Pat. No. 6,304,725 has the approximately same size as a business card or a credit card(hereinafter referred to as a card size). The film unit has such a size to fit into a widespread business card holder (54 mm width×86 mm length) that it may be easy to arrange a plurality of the exposed film units (photo prints). Moreover, by filing a plurality of the business card holders containing the photo prints, it is possible to make a photo album readily and to watch well-organized photo prints.
In the film unit described in U.S. Pat. No. 6,304,725, a photosensitive layer and a image receiving layer are formed on each face of one sheet. Accordingly, an exposing side is different from an observing side. The film unit described in U.S. Pat. No. 4,639,963 includes a transparent image receiving sheet and a photosensitive sheet. The exposing side is the same as the observing side. In either film unit, a positive image is in a rectangle. Further, for the purpose of providing a more decorative effect, there are the known instant films. One of which is pre-exposed a frame on the inside margin of the opening on the mask sheet (JP-U 63-73743), and another includes the opening for the exposure in a heart shape or a circle (JP-U 3048920).
However, the developing solution pod and the portion including the developing solution pod becomes thick to some extent, because the film unit generally includes a developing solution pod containing developing solution with a certain extent of extra, for spreading the developing solution on the whole exposure area. Also, due to an increased surplus of developing solution, a trapping material to be used for catching the surplus has necessarily to have a certain thickness, and the portion including the trapping material also becomes thick. Thus, when the film unit has a thickness, there is a problem that it is bulky in the card folder or the album.


The present invention relates to a gas intake device (1) for a cylinder of an internal-combustion engine. The gas intake device comprises two intake pipes (5a, 5b), two intake valves (4), two intake valve calibration parts (6a, 6b) and, in each intake pipe (5a, 5b), means for forming an aerodynamic gas motion of tumble type in the cylinder. Furthermore, for each intake pipe (5a, 5b), the intersection between intake pipe (5a, 5b) and calibration part (6a, 6b) occurs along a line non-parallel to the plane of the fire face. Besides, the inclination angle of this intersection is different for each pipe (5a, 5b).

Various technical solutions have been developed to achieve these turbulent flows in the cylinder.
A first solution is notably described in U.S. Pat. No. 6,606,975. This solution consists in controlling a flap arranged in the intake pipe so as to generate turbulence. This patent further mentions the notion of low load swumble. Such a solution is complex and penalizing as regards cylinder filling.
A second solution is notably described in U.S. Pat. No. 5,056,486. This solution provides a definition of asymmetrical intake pipes allowing complex aerodynamics to be generated. However, this solution requires phase shift of the intake valves opening, which is penalizing at high loads.
A third solution is notably described in patent applications DE-10,128,500 and EP-1,783,341. This solution allows complex aerodynamics to be generated by means of passive or active appendages in the intake pipe. In both cases, these appendages limit cylinder filing with gas. Furthermore, active appendages require a control system making the solution more complex.
A fourth solution is notably described in patent applications US-2008/0,149,063, JP-2010/261,314 and US-2012/160,198. This solution consists in generating aerodynamic motions of the gas in the cylinder by means of masks arranged at the end of the intake pipe. However, to obtain an aerodynamic gas motion of swumble type, it appears necessary to use two masks per intake pipe or to use specific valve lift laws, which makes this solution complex. Furthermore, the masks used limit filing of the cylinder with gas.
Furthermore, internal-combustion engines whose cylinders are provided with two intake pipes or siamese pipes are common (in other words, cylinders with two intake valves). Conventionally, these cylinders can also be provided with two exhaust pipes and two exhaust valves, they are then referred to as four-valve engines. In relation to the configuration with two valves per cylinder, the slightest mechanical inertia of a four-valve engine resulting from the lightening of the moving parts enables higher engine speeds, thus providing higher efficiency and power of the internal-combustion engine.

Gas intake device having two asymmetrical intake ducts


A method of operating an Uninterruptible Power Supply (UPS) system can be provided by activating an idle state for a UPS module included in the UPS system and providing a UPS module test input to the UPS module in the idle state. A UPS module test response can be provided from the UPS module in the idle state, to the UPS module test input. The UPS module test response can be compared to a predetermined UPS module test response and the UPS module can be identified as a potentially faulty UPS module responsive to determining that the UPS module test response varies from the predetermined UPS module test response by more than a threshold value.

The present invention relates to uninterruptible power supply systems (UPS), and more particularly, to testing UPS systems.
UPS systems are commonly used in installations such as data centers, medical centers and industrial facilities to provide backup power to maintain operation in event of failure of the primary utility supply. These UPS systems often have an "on-line" configuration including components, such as, a rectifier and inverter coupled by a DC link that is also coupled to an auxiliary power source, such as a battery, fuel cell or other energy storage device. UPS systems may include two or more UPS modules, each of which may include the components described above. The UPS modules commonly are designed to operate in parallel to provide scalable power capacity, e.g., the UPS modules may be coupled in common to an AC source, a DC source (e.g., a battery) and to a load.
UPS systems typically may be configured for testing when, for example, a diagnostic is run, which may result in the UPS systems being brought off-line. Various UPS arrangements are discussed further in, for example, U.S. Pat. No. 7,265,458 to Edelen et al., U.S. Pat. No. 7,403,364 to Anderson et al., U.S. Pat. No. 7,583,109 to Oughton Jr. et al., and U.S. Pat. No. 7,948,778 to Pfitzer et al., the disclosures of each of which are incorporated herein in their entireties.

Methods of testing unInterruptible power supply (UPS) systems with multiple UPS modules


An apparatus (10) for use in turning steerable vehicle wheels (12, 14) includes first and second piston and cylinder type hydraulic motors (32, 34) which are connected with a central portion of a vehicle. A steering control valve (24) is operable in response to manual rotation of a steering wheel (18) to effect extension and contraction of the first and second hydraulic motors. A rack and pinion steering gear (110, 114) may be connected with a piston rod (86) of one of the hydraulic motors (32). A secondary control valve (200) may be provided to effect operation of one of the hydraulic motors to a greater extent than the other hydraulic motor.

The present invention is directed to a new and improved apparatus for use in turning steerable vehicle wheels in response to rotation of a steering wheel. The apparatus includes first and second hydraulic motors which are connected with the steerable vehicle wheels.
Steerable vehicle wheels have previously been turned by a rack and pinion steering system. The rack and pinion steering system may include a hydraulic motor which is connected with the steerable vehicle wheels in the manner disclosed in U.S. Pat. No. 3,709,099. Other known rack and pinion steering systems are disclosed in U.S. Pat. Nos. 4,887,683 and 5,851,015.
Steerable vehicle wheels have also been turned by steer-by-wire steering systems. In a known steer-by-wire steering system, there has been no mechanical connection between a steering wheel and a steering apparatus connected with steerable vehicle wheels. In at least one known steer-by-wire steering system, a transmitter assembly associated with a steering wheel sends a signal to a receiver assembly associated with a steering apparatus connected with the steerable vehicle wheels. This steering apparatus is actuated in accordance with the signal received by the receiver assembly. Known steer-by-wire steering systems are disclosed in U.S. Pat. Nos. 6,546,322 and 6,655,709.


A fuel injector for a machine is disclosed. The fuel injector has a nozzle member with a first end and a second end. The first end of the fuel injector has at least one orifice. The fuel injector also has a control chamber located at the second end of the nozzle member with an end wall portion approximately orthogonal to an axial direction of the nozzle member. The fuel injector further has a port disposed in the end wall portion of the control chamber and at least one passageway in fluid communication with the control chamber via the port. The fuel injector additionally has a needle valve element with a tip end and a base end. The tip end is configured to selectively block fuel flow through the at least one orifice. The base end has a recess configured to cap off the port.

Common rail fuel systems typically employ multiple closed-nozzle fuel injectors to inject high pressure fuel into combustion chambers of an engine. Each of these fuel injectors may include a nozzle assembly having a cylindrical bore with a nozzle supply passageway and a nozzle outlet. A needle check valve may be reciprocatingly disposed within the cylindrical bore and biased toward a closed position where the nozzle outlet is blocked. To inject fuel, the needle check valve may be selectively moved to open the nozzle outlet, thereby allowing high pressure fuel to spray from the nozzle supply passageway into the associated combustion chamber.
One way to move the needle check valve between the open and closed positions includes draining and filling a control chamber associated with a base of the needle check valve. In particular, the control chamber may be filled with pressurized fluid to retain the needle check valve in a closed position and selectively drained of the pressurized fluid to bias the needle check valve toward the open position. When in the open position, the flow of pressurized fuel to the control chamber may be restricted by the base of the needle check valve, thereby minimizing losses associated with pressurized fuel draining to a low pressure reservoir.
One problem associated with this fuel injector arrangement involves efficiency. In particular, although the flow of pressurized fuel to the control chamber may be restricted to minimize losses, some fuel may still be allowed to drain to the low pressure reservoir because the base of the needle check valve does not completely block the flow of pressurized fuel into the control chamber. A method implemented by engine manufacturers to reduce this loss of pressurized fuel and improve efficiency of the affected engine includes changing the shape of the needle check valve base to provide better sealing of the control chamber. One example of changing the needle check valve base is described in U.S. Pat. No. 5,487,508 (the '508 patent) issued to Zuo on Jan. 30, 1996. The '508 patent describes a fuel injector nozzle and tip assembly comprising a check housing defining a cavity with a spray orifice at one end and a control port at the other end. A needle check valve is disposed in the cavity and has a tip at one end for blocking the orifice, and a control port check at the other end for blocking the control port. The control port check is conical in shape for seating against a complementarily shaped seat of the control port.
Although the fuel injector nozzle of the '508 patent may reduce the loss of pressurized fuel and improve efficiency of an associated engine by changing the geometry of the control port check, it may be problematic and expensive. For example, because the seating surfaces of the control port check and control port are conical and designed to engage each other, even slight misalignment between the two surfaces could result in leakage of the pressurized fuel. In addition, the two conical seating surfaces may be difficult and expensive to fabricate.
The fuel injector of the present disclosure solves one or more of the problems set forth above.


A method is provided for identifying an event of network activity associated with a network where the network includes a plurality of interfaces and the method includes providing a first data structure comprising a node, partitioning the plurality of interfaces into a plurality of groups, associating the plurality of groups with the node, providing a vector corresponding to a group of the plurality of groups for representing a summary of the network activity, and identifying an event of network activity according to the vector. Experimental results are shown to demonstrate the effectiveness and robustness of the invention.

1. Field
The present invention relates to computers and computer networks. More particularly, the present invention relates to keeping and searching network history for corrective and preventive measures.
2. Description of Related Art
Many events happen in networks, such as an IP network at all times. Techniques in the prior art for network event detection is based on the independent signals, for example, a network event may be detected by comparing current levels of independent signals to a threshold. Network events such as attacks, anomalies, and/or overloads may be identified based on catastrophic impact, customer call-in, etc., or they may be discovered by chance. Put together over time, network managers may develop a fairly extensive list of network event profiles, from a history of the network activity, they have identified as being anomalies, attacks, overloads or other events. In the prior art, network operation specialists, such as a network manager, use this experience in history of network activity accumulated from the past to address network problems in a manual fashion. The manual process may be tedious, inaccurate, and not effective. Accordingly, an automated method for keeping and searching network history for corrective and preventive measures is desirable.

Method for keeping and searching network history for corrective and preventive measures


A method and system for generating modulated optical vortices. Optical vortices can be used for a variety of applications, such as applying controlled torque or controlled force patterns to objects from a few nanometers to hundreds of micrometers in size. Numerous optical modes of optical vortices can be created to meet virtually any desired need in manipulating of objects. Furthermore, one can modify the wavefront of a beam of light in a specific way to create a new type of optical trap useful for manipulating mesoscopic materials. When the modified beam is brought to a focus, the resulting optical trap exerts forces transverse to the optical axis that can be used to transport mesoscopic matter such as nanoclusters, colloidal particles, and biological cells.

It is conventionally known that holographic optical traps may be used for manipulating small objects dispersed in fluid. For example, material transport can result from a process resembling peristaltic pumping, with a sequence of holographically-defined manifolds of traps resembling the states of a physical peristaltic pump. In all such conventional approaches, transport transverse to the optical axis cannot be accomplished by a single optical intensity pattern, but rather requires three or more separate patterns of optical traps to be projected. Other approaches based on generalized optical traps (commonly known as optical vortices) trap small objects on rings of light transverse to the optical axis and drive them in circular orbits around these rings. The resulting motion can be used to drive fluid flow and thus transport other objects in the plane transverse to the optical axis. Such indirect optical driving requires conditions conducive to the operation of optical vortices, sufficiently open geometry and a sufficiently low flow rate.
In order to best understand the improvements of the invention, FIG. 1 illustrates prior art methods and systems which can be used to advantage in the invention features of characterizing and removing optical aberrations. In the prior art optical tweezer system 10 of FIG. 1, optical gradient forces exerted by a single beam of light 12 are used to controllably manipulate a small dielectric particle 14 dispersed in a medium 16 whose index of refraction, nm, is smaller than that of the particle 14 at optical frequencies. The nature of the optical gradient forces is well known, and also it is well understood that the principle has been generalized to allow manipulation of reflecting, absorbing and low dielectric constant particles as well. Any of these techniques can be implemented in the context of the invention described hereinafter and will be encompassed by use of the terminology optical tweezer, optical trap and optical gradient force trap hereinafter.
The optical tweezer system 10 is applied by using a light beam 12 (such as a laser beam) capable of applying the necessary forces needed to carry out the optical trapping effect needed to manipulate a particle. The object of a conventional form of the optical tweezer 10 is to project one or more beams of light into the center of a back aperture 24 of a converging optical element (such as an objective lens 20). As noted in FIG. 1, the light beam 12 has a width, w, and has an input angle φ relative to an optical axis 22. The light beam 12 is input to a back aperture 24 of the objective lens 20 and output from a front aperture 26 substantially converging to a focal point 28 in focal plane 30 of imaging volume 32 with the focal point 28 in near association with an optical trap 33. In general, any focusing optical system can form the basis for the optical tweezer system 10.
In the case of the light beam 12 being a collimated laser beam and having its axis coincident with the optical axis 22, the light beam 12 enters the back aperture 24 of the objective lens 20 and is brought to a focus in the imaging volume 32 at the center point c of the objective lens' focal plane 30. When the axis of the light beam 12 is displaced by the angle φ with respect to the optical axis 22, beam axis 31 and the optical axis 22 coincide at the center point B of the back aperture 12. This displacement enables translation of the optical trap across the field of view by an amount that depends on the angular magnification of the objective lens 20. The two variables, angular displacement φ and varying convergence of the light beam 12, can be used to form the optical trap at selected positions within the imaging volume 32. A plurality of the optical traps 33 can be arranged in different locations provided that multiple beams of light 12 are applied to the back aperture 24 at different angles φ and with differing degrees of collimation.
In order to carry out optical trapping in three dimensions, optical gradient forces created on the particle to be trapped must exceed other radiation pressures arising from light scattering and absorption. In general, this necessitates having the wave front of the light beam 12 to have an appropriate shape at the back aperture 24. For example, for a Gaussian TEMoo input laser beam, the beam diameter w should substantially coincide with the diameter of the back aperture 24. For more general beam profiles (such as Laguerre-Gaussian modes) comparable conditions can be formulated.
In another prior art system in FIG. 2, the optical tweezer system 10 can translate the optical trap 33 across the field of view of the objective lens 20. A telescope 34, or other relay optics, is constructed of lenses L1 and L2 which establishes a point A which is optically conjugate to the center point B in the prior art system of FIG. 1. In other forms of the invention the relay optics can include other conventional systems, such as multiple optical elements to minimize aberrations. In the system of FIG. 2 the light beam 12 passing through the point A also passes through the point B and thus meets the basic requirements for performing as the optical tweezer system 10. The degree of collimation is preserved by positioning the lenses L1 and L2 as shown in FIG. 2. The transfer properties of the telescope 34 can be chosen to optimize angular displacement of the light beam 12 and its width w in the plane of the back aperture 24 of the objective lens 20. As stated hereinbefore, in general several of the light beams 12 can be used to form several associated optical traps. Such multiple beams 12 can be created from multiple independent input beams or from a single beam manipulated by conventional reflective and/or refractive optical elements.
In another prior art system shown in FIG. 3, arbitrary arrays of optical traps can be formed. A diffractive optical element 40 is disposed substantially in a plane 42 conjugate to back aperture 24 of the objective lens 20. Note that only a single diffracted output beam 44 is shown for clarity, but it should be understood that a plurality of such beams 44 can be created by the diffractive optical element 40. The input light beam 12 incident on the diffractive optical element 40 is split into a pattern of the output beams 44 characteristic of the nature of the diffractive optical element 40, each of which emanates from the point A. Thus the output beams 44 also pass through the point B as a consequence of the downstream optical elements described herein before.
The prior art diffractive optical element 40 of FIG. 3 is shown as being normal to the input light beam 12, but many other arrangements are possible. For example, in the prior art system of FIG. 4 the light beam 12 arrives at an oblique angle β relative to the optic axis 22 and not at a normal to the diffractive optical element 40. In this embodiment, the diffracted beams 44 emanating from point A will form optical traps 50 in focal plane 52 of the imaging volume 32 (seen best in FIG. 1). In this arrangement of the optical tweezer system 10 an undiffracted portion 54 of the input light beam 12 can be removed from the optical tweezer system 10. This configuration thus enables processing less background light and improves efficiency and effectiveness of forming optical traps.
The diffractive optical element 40 can include computer generated holograms which split the input light beam 12 into a preselected desired pattern. Combining such holograms with the remainder of the optical elements in FIGS. 3 and 4 enables creation of arbitrary arrays in which the diffractive optical element 40 is used to shape the wavefront of each diffracted beam independently. Therefore, the optical traps 50 can be disposed not only in the focal plane 52 to form a three-dimensional arrangement of the optical traps 50.
In the optical tweezer system 10 of FIGS. 3 and 4, also included is a focusing optical element, such as the objective lens 20 (or other like functionally equivalent optical device, such as a Fresnel lens) to converge the diffracted beam 44 to form the optical traps 50. Further, the telescope 34, or other equivalent transfer optics, creates a point A conjugate to the center point B of the previous back aperture 24. The diffractive optical element 40 is placed in a plane containing point A.
In another form of prior art system, arbitrary arrays of the optical traps 50 can be created without use of the telescope 34. In such an embodiment the diffractive optical element 40 can be placed directly in the plane containing point B.
In the optical tweezer system 10, either static or time dependent diffractive optical elements 40 can be used. For a dynamic, or time dependent version, one can create time changing arrays of the optical traps 50 which can be part of a system utilizing such a feature. In addition, these dynamic optical elements 40 can be used to actively move particles and matrix media relative to one another. For example, the diffractive optical element 40 can be a liquid crystal phase modulating array that imprints computer generated holographic patterns onto incident light.
In another prior art system illustrated in FIG. 5, a system can be constructed to carry out continuous translation of the optical tweezer trap 50. A gimbal mounted mirror 60 is placed with its center of rotation at point A. The light beam 12 is incident on the surface of the mirror 60 and has its axis passing through point A and will be projected to the back aperture 24. Tilting of the mirror 60 causes a change of the angle of incidence of the light beam 12 relative to the mirror 60, and this feature can be used to translate the resulting optical trap 50. A second telescope 62 is formed from lenses L3 and L4 which creates a point A′ which is conjugate to point A. The diffractive optical element 40 placed at point A′ now creates a pattern of diffracted beams 64, each of which passes through point A to form one of the tweezer traps 50 in an array of the optical tweezers system 10.
In operation of the embodiment of FIG. 5, the mirror 60 translates the entire tweezer array as a unit. This methodology is useful for precisely aligning the optical tweezer array with a stationary substrate, for dynamically stiffening the optical trap 50 through small-amplitude rapid oscillatory displacements, as well as for any applications requiring a general translation capability.
The array of the optical traps 50 also can be translated vertically relative to the sample stage (not shown) by moving the sample stage or by adjusting the telescope 34. In addition, the optical tweezer array can also be translated laterally relative to the sample by moving the sample stage. This feature would be particularly useful for large scale movement beyond the range of the objective lens' field of view.
In another prior art system shown in FIG. 6, the optical system is arranged to permit viewing images of particles trapped by the optical tweezers 10. A dichroic beamsplitter 70, or other equivalent optical beamsplitter, is inserted between the objective lens 20 and the optical train of the optical tweezer system 10. In the illustrated embodiment the beamsplitter 70 selectively reflects the wavelength of light used to form the optical tweezer array and transmits other wavelengths. Thus, the light beam 12 used to form the optical traps 50 is transmitted to the back aperture 24 with high efficiency while light beam 66 used to form images can pass through to imaging optics (not shown).
A prior art application of optical traps is shown in FIGS. 7A and 7B. The diffractive optical element 40 is designed to interact with the single light beam 12 to create a 4×4 array of collimated beams. A 100 mW frequency doubled diode-pumped Nd:YAG laser operating at 532 nm provides a Gaussian TEM00 form for the light beam 12. In FIG. 7A the field of view is illuminated in part by laser light backscattered by sixteen silica spheres trapped in the array's sixteen primary optical tweezers 10. The 1 μm diameter spheres are dispersed in water and placed in a sample volume between a glass microscope slide and a 170 μm thick glass coverslip. The tweezer array is projected upward through the coverslip and is positioned in a plane 8 μm above the coverslip and more than 20 μm below the upper microscope slide. The silica spheres are stably trapped in three dimensions, each in one of the sixteen optical tweezers 10.
In FIG. 7B is shown the optically-organized arrangement of spheres 1/30 second after the optical tweezers 10 (traps) were extinguished but before the spheres had time to diffuse away from the trap site.
Consequently, optical tweezers and related optical traps use forces exerted by the intensity gradients in tightly focused beams of light to trap, move and otherwise modify small volumes of matter in three dimensions. Imprecise alignment and imperfect characteristics of the optical elements of an optical trapping system introduce aberrations into the trapping beam, diminish its intensity gradients, and thereby degrade its ability to manipulate matter. In common practice, the optical elements in optical trapping systems are aligned by systematically adjusting each element's position while observing the apparent quality of the focused optical trap using a optical imaging system. A well aligned optical tweezer comes to a tight and symmetric focus and spreads uniformly and symmetrically when defocused. While simple and reasonably effective, this approach does not generally achieve optimal performance, nor does it provide a quantitative assessment of the optical train's alignment.

Transverse optical accelerator and generalized optical vortices


A process for the selective controlled reduction of the relative water permeability in high permeability, oil-bearing formations, with negligible reduction of the permeability to oil. The process comprises, for sandstone reservoir rocks, a first layer of cationic polymer, followed by a brine spacer slug and a second polymer layer made up of a suspension of anionic polymer and an anionic or non-ionic microgel, optionally this configuration being repeated. As a result the thickness of the polymer layer is considerably increased, which permits the process to be used in high permeability formations. For limestone rocks the first layer is made up of anionic polymer, while the second layer involves a suspension of cationic polymer/cationic or non-ionic microgel. The polymers are all injected as aqueous suspensions in brine or seawater.

One drawback of the oil companies over the world is the production of water associated to oil. Premature breakthrough of formation or injection water and the rise in water production from then on results in accelerated decline of oil production, with increased pumping operation costs, treatment and discarding of huge volumes of water.
Water production reaches such amounts that it can be said that actually oil companies are water companies, since for an oil production of 75 million barrels oil per day (BPD), 300-400 million barrels of water are produced. This means 5-6 barrels of water per barrel of oil, attaining 9 barrels of water per barrel of oil or even 50 barrels of water per barrel of oil.
Fluid properties required for the control of permeability and mobility of water flowing in a porous medium are the following: 1) be easily injected at a long distance from the treated well; 2) bear properties such that the fluid weakly interacts with the physical chemical conditions of the reservoir; 3) should contain colloids or polymer species that are able to be adsorbed on several kinds of reservoir rocks for the formation of layers of controlled thickness; such layers should be hydrated in the presence of water and dehydrated in the oil phase; 4) such layers should be kept stable for long periods under the physical chemical reservoir conditions.
As cited in the paper SPE 77963 "New Insights into Water Control—A Review of the State of the Art" by Gino di Lullo e Phil Rae, water production in an oil well brings a collection of problems such as scale in susceptible wells, induction of fines migration or sandface failure, increased corrosion in tubulars, and killing of wells by hydrostatic loading. Thus, in spite of the fact that water production is an unavoidable consequence of oil production, it is usually desirable to defer its onset, or its rise, for as long as possible.
Water cuts in oil producing wells increases as the oil fields become mature. The source of the water is either formation water (aquifers) or injected water used for reservoir pressure maintenance purposes. In addition, heterogeneities encountered in reservoir rocks can cause water channeling through higher permeability streaks/hairline fractures (natural or induced) and/or near wellbore water coning due to the proximity of the well with the water-bearing zone, high rock vertical permeability, or high pressure differentials between the well and the formation normally caused by a limited reservoir thickness or excessive pressure drawdowns.
No matter the context, the origin of the problem is nearly always associated to a higher mobility of water relative to that of oil. Normally the lower the API degree of oil, the higher the possibility of premature water production, since low gravity oils are typically much more viscous, and hence have lower mobility.
The control of water production has obtained a limited success through the use of several gel-forming systems.
Three main chemical-based treatments are known.                Permeability Blockers or gellants;        Disproportionate Permeability Reducers and/or Selective Permeability Blockers; and;        Relative Permeability Modifiers (RPM).Permeability Blockers:
As the name indicates, these products block or plug the pore spaces so as to hinder the movement of fluid, normally by means of a controlled, delayed chemical reaction that allows deep injection of the material before it reacts to form a three dimensional gel. Well-known examples of these processes are those involving sodium silicate solutions, internally activated with urea esters or aminoplast resins.
Other options include resins, latex or polymer solutions that gel up in response to temperature, salinity or pH to form coagulated precipitates or three dimensional gels, such as those created by latex or phenolic resins. The best-known systems are based on polyacrylamide crosslinked with chromium and PVA crosslinked with glutaraldehyde.
These products are not selective and they plug pores containing oil and/or water, thus requiring other procedures to avoid plugging off the oil-producing zone.
Selective Permeability Blockers
These products also plug the pore spaces, restricting fluid movement. However, due to their partial solubility in oil, precipitation, swelling or viscosifying is more reduced in the presence of hydrocarbons than in a water environment. The net effect is a reduction of water relative permeability by a larger factor than that to oil. Preferred products for use with water-based fluids (WBM) are rosin wood derivatives that form a colloidal precipitate that agglutinates, forming a gelatinous mass in the presence of water. Products for oil-based fluids (OBM) include tetramethyl orthosilicate (TMOS) and ethyl silicate that react in the presence of water to form a rigid silica gel.
There are also new systems based on viscoelastic anionic surfactant (VAS), designed for water control purposes. Such systems produce extremely shear thinning gels in the presence of cations. Such gels can easily permeate porous and permeable rocks, which allows to pump and inject them in the reservoir at full viscosity and higher matrix rates (below fracturing pressure). Once in the formation pores, the viscosity of such gels could increase as high as 100 times, thereby restricting fluid movement. The chemistry of such systems is such that hydrocarbons break them on contact and they revert to the base brine viscosity. This frees up only the pores with residual hydrocarbon saturation, leaving them clear and strongly water-wet. Highly water-saturated pores keep plugged with a high viscosity gel.
Relative Permeability Modifiers (RPM)
These are water-soluble, hydrophilic polymer systems that, when hydrated, produce long polymer chains that, in the rock, will loosely occupy the pore spaces. Being strongly hydrophilic, they attract water and repel oil and as a net result they exert a drag force on water flow in the pores, with a minimal and sometimes positive effect on oil flow.
Useful polymers for this purpose include high molecular weight polyacrylamides and more recently, scleroglucans. However, temperature limitations, shear sensitivity and poor tolerance to calcium and magnesium ions undermine their effectiveness, as they are produced back faster than expected by formation fluids.
Charged radicals have been added to polyacrylamides (poly-DMDAAC) improving their shear sensitivity, temperature and salt tolerance as well as their adhesion to rock.
Ideally, RPM systems should be aqueous solutions or suspensions, the features of which such as concentration and physical chemical properties should be adjusted to the formation permeability, among other parameters. RPMs provide a resistance (drag) to water flows in the order of 2 to 100 times and a detrimental drag to oil ideally lower than 2. Environmental changes such as pH, salinity or drawdown pressure will affect the effectiveness and durability of the treatment. Thus, post job interventions will most probably destroy, partially or completely, their water controlling properties.
SPE Paper 8228 "In-Depth Permeability Control by Adsorption of Soft Size-Controlled Microgels" by G. Chauveteau et al reports that the injection of stable, pre-formed microgels as relative permeability modifiers to reduce the permeability to water minimizes the risk of well plugging or the absence of efficiency inherent to a technology based on in-situ gelling. Recent investigations showed that microgels formed by crosslinking a polymer solution under shear are soft, size-controlled, and quasi-insensitive to reservoir conditions, stable over long periods of time and can control in-depth permeability by adsorbing onto all kinds of rock surface. The results shown in said paper are aimed at knowing how to control the kinetics of crosslink formation by ionic strength and at determining the role of the interactions between microgels on their propagation in porous media. Experiments include gelling tests at different ionic strengths, measurements of viscoelastic properties of solutions, determination of both microgel density and microgel-microgel interaction parameter for different stabilization conditions, and the relation between the interaction parameter and the mode of adsorption of microgels. Partly attractive microgels adsorb by forming multilayers and thus promote drastic permeability barriers. Fully repulsive microgels adsorb as monolayer and propagate easily in porous media at long distances, depending only on the quantity of microgel injected. Thus, by controlling both gelling and stabilization processes, microgels can be produced to be either diversion agents or disproportionate permeability reducers to control water permeability at long distances from the wells.
SPE paper 64988 "New Size-Controlled Microgels for Oil Production", by G. Chauveteau et al., reports that microgels formed by polymer crosslinking under shear flow are very promising for several applications in oil production. The proper polymer/crosslinker system and under the conditions needed to obtain the desired properties provides quasi-ideal products. Such products are expected to control water mobility at long distances from the wells to improve sweep efficiency and reduce selectively permeability to water for water production control. This paper reports experiments related to the theoretical understanding of the crosslinking process under shearing and tests the microgels in porous media. Several microgel positive properties are reported.
SPE paper 59317 "Controlling Gelation Time and Microgel Size for Water Shutoff", by G. Chauveteau et al., describes experiments designed to assess and control both size and conformation of microgels formed under constant shear flow. The reported studies indicate that the crosslinking species may be dimers, tetramers and associations of tetramers according to pH and Zr concentration in presence of lactate. Microgels formed in diffusion regime are isotropic and their size is significantly reduced as shear rate increases, while when formed in correction regime they are anisotropic and their size decreases negligibly with shear rate. Since experimental data are in agreement with such model, it is possible to design the microgel preparation as a function of its role in the aimed application, either relative permeability modifiers for water shut-off or viscosity enhancers for polymers flooding.
US Application 2004/0229756 relates to methods and solutions for treating water and hydrocarbon-producing formations for reducing the permeability to water thereof. The proposed solutions comprise a reactive hydrophilic polymer, a hydrophobic compound capable of reacting with the polymer in situ, and a surfactant. Solutions are prepared and injected in the formation followed by shutting-in the formation in order to permit reaction between the polymer and the hydrophobic compound. The reaction product attaches to adsorption sites on surfaces within the porosity of the formation and reduces the water permeability thereof without substantially reducing the hydrocarbon permeability thereof. The hydrophilic reactive polymer is selected among the group consisting of polyethylene imine, polyvinyl amine, poly(vinylamine/vinyl alcohol), chitosan, polysyline and alkyl acrylate polymers.
US Application 2004/0171495 teaches a method of reducing the water permeability of a well bore during the drilling phase, comprising: providing a polymer comprising: (i) a monomer selected from the group consisting of alkyl acrylates, alkyl methacrylates, alkyl acrylamides, alkyl methacrylamides, alkyl dimethylammoniumethyl methacrylate halides, and alkyl dimethylammonium propylmethacrylamide halides, wherein the alkyl groups have from about 4 to about 22 carbon atoms; and (ii) a monomer selected from the group consisting of acrylamide, 2-acrylamido-2-methyl propane sulfonic acid, N,N-dimethylacrylamide, vinyl pyrrolidone, dimethylaminoethyl methacrylate, acrylic acid, dimethylaminopropylmethacrylamide, trimethylammoniumethyl methacrylate chloride, methacrylamide and hydroxyethyl acrylate; and placing the polymer down hole, thereby reducing the water permeability of the well bore.
U.S. Pat. No. 6,579,909 relates to a method for preparing microgels of controlled size. According to the method, a gelling composition comprising a polymer and a crosslinking additive intended for the polymer is injected into a porous and permeable medium, and a monodisperse solution of microgels of substantially constant size is recovered at the outlet. The invention also relates to an application of the method for reducing the permeability of porous and permeable formations of reservoir rock type.
U.S. Pat. No. 6,516,885 describes that water shut-off is provided in a hydrocarbon well by injecting a first chemical composition, effective as a relative permeability modifier polymer, into the hydrocarbon and a water zone of the well followed immediately by the injection of a second chemical composition, which forms a flow blocking polymer composition, into the zones and, after a shut-in period for reaction of the relative permeability modifier polymer, back producing the polymer compositions from their hydrocarbon zones to provide a path for the hydrocarbons from the zones while allowing the flow blocking polymer compositions to form the water shut-off in the water zones. The hydrocarbon to which the process is applied is a gas. The first composition comprises a crosslinkable cationic polyacrylamide and the second chemical composition comprises a crosslinkable polyacrylamide-chromium acetate system.
U.S. Pat. No. 4,172,066 describes a composition, which comprises discrete, spheroidal microgels of a water-swellable polymer such as crosslinked polyacrylamide, useful for reducing the permeability of porous structures. Said microgels in the dry state have diameters less than about 20 micrometers, preferably lower than 4 micra, and still more preferably, lower than 1 micra, said polymer being sufficiently cross-linked to enable the microgels to remain as discrete spheroidal particles having diameters in the range from about 0.5 to about 200 micrometers, preferably between 1 and 10 micrometers when said microgels are dispersed in an aqueous fluid medium. In the partially water-swollen state the microgels contain at least 30% by weight of crosslinked polymer and up to 70% by weight of water. Useful monomers are the water-soluble ethylenically unsaturated amides such as acrylamide, methacrylamide and fumaramide, N-(diethylaminomethyl)methacrylamide and quaternized derivatives thereof, e.g., N-(trimethylammoniummethyl)acrylamide chloride; acrylic acid, methacrylic acid, itaconic acid, fumaric acid and the like; ethylenically unsaturated quaternary ammonium compounds such as vinylbenzyltrimethylammonium chloride.
U.S. Pat. No. 6,474,413, of the Applicant and hereby completely incorporated as reference teaches a process for the selective and controlled reduction of water permeability in oil-bearing formations made up of sandstone or limestone, the process comprising the injection of a slug of aqueous polymer solutions having a polarity opposite to the polarity of the rock, followed by the injection of a spacer slug of alkaline halide and then a fresh slug of polymer aqueous solution, the polarity of which is opposite to the polarity of the first polymer slug, and then a slug of aqueous solution of trivalent metal crosslinking agent to effect the partial crosslinking of the polymer charges, the polymer layers being successively added until the injection pressure of the polymer aqueous solutions show that the desired Residual Resistance Factor RRF has been attained, and well production may be resumed.
According to such process, spacer slugs consisting of an alkaline salt aqueous solution, such as a NaCl or KCl solution, always separate the polymer and crosslinking slugs. When the formation is rich in limestone rocks, initially an anionic polymer is injected, successively followed by cationic polymer slugs or multivalent crosslinking agent and anionic polymer slugs, the last layer being always made up of crosslinking agent. In this way the hydrophilic film formed bears an anionic character. All the polymer slugs are alternated with spacer slugs of an alkaline salt aqueous solution such as KCl. The process is useful for subterranean formations having permeability values of up to 3 Darcy.
The process described in said US patent is relatively cumbersome, since several polymer layers should be placed into the formation in order to reach the film thickness required for attaining the desired reduction in water permeability. On the contrary, in the present invention, the combined anionic polymer and controlled-particle size microgels used as second layer to be injected into the formation (in case of a sandstone formation) leads to the drastic reduction in the number of layers required for obtaining the desired RRF. This renders the present process more efficient, of lower cost and quicker to apply in the treatment of high permeability formations and high productivity wells. Besides, in the cited US reference the layered film forms a structure in the plane (two dimensional), while the present invention is directed to a structure forming a volume (three dimensional), where the microgel particles undergo hydration and dehydration according to their water or oil environment, in a reversible process.
Still, as cited on column 7, line 50 of the said U.S. Pat. No. 6,474,413, the process involves punctual crosslinking without gel formation, while in the present invention there is adsorption of the anionic polymer and also of the anionic microgel to the cationic layer, resulting in stronger/increased rigidity of the layer.
As compared to state-of-the-art processes using microgel only, an additional advantage of the invention results from combining anionic polymer and microgel besides the initial cationic polymer layer (for a sandstone formation), which provides better polymer adsorption to said initial layer. The net result is a rise in process efficiency due to lower polymer solution amounts to attain the desired effect of lower RRFw (Residual Resistance Factor) values.
Thus, when compared to state-of-the-art techniques—use of microgel only or the technique taught in U.S. Pat. No. 6,474,413—the process of the present invention provides potentialized results related to the FRRN ratio, those results not being described nor suggested in the cited known techniques.
Thus, in spite of the state-of-the-art developments, the technique is still in need of a selective process aimed at high productivity and high permeability fields using high molecular weight, seawater-soluble polymers combined to crosslinked acrylamide-based polymeric microgels, having a controlled particle size distribution for the reduction of relative water permeability in subterranean high permeability oil-bearing formations, while the permeability to oil is negligibly affected, such process being described and claimed in the present application.

Process for the selective controlled reduction of the relative water permeability in high permeability oil-bearing subterranean formations


Embodiments of a method for examining shipments are disclosed herein. In the method, at least one shipment is arranged in an examination area. Radiation is emitted into the examination area for examining the at least one shipment by means of a radiation source. Radiation from the examination area is captured by means of a sensor device. The radiation source emits terahertz radiation, and the radiation source covers substantially the entire terahertz frequency spectrum from 1 terahertz to 6 terahertz.

When processing shipments, that is to say, for example, correspondence or small item shipments, for instance postcards, letters, packages or parcels, or else further cargo to be shipped such as pallets or containers, for instance Unit Load Devices (ULDs), it may be necessary to examine the respective shipment during processing. It may specifically be desirable or necessary to determine pieces of information relating to the respective shipment.
On the one hand, it may be necessary, for example, to determine particular printed pieces of information or pieces of geometrical information such as dimensions. However, printed pieces of information may be concealed under certain circumstances. Three-dimensional capture of the geometry for processing the shipment is desirable or necessary in the case of small item shipments, in particular. It is likewise desirable for not only externally visible pieces of information (for instance the dimensions of the shipment) but also pieces of information relating to the content of the shipment to be captured. This is the case, in particular, for shipments in the form of containers, pallets or small item shipments since very different contents may be shipped here, for instance perishable contents (for example food), sensitive contents (for example moisture-sensitive or temperature-sensitive contents) or else, under certain circumstances, hazardous or prohibited contents (for example chemicals, gases, explosives, weapons or the like). Information not only relating to the exterior of the shipment but also relating to the shipment content is therefore desirable when processing shipments.
The prior art, for example US 2002/0126008 A1, discloses detecting hazardous contents of shipments using sensors. The detection can be carried out using an olfactory sensor, a UV or infrared detector, an x-ray machine, a laser, a radio sensor or a heat sensor. The disadvantage of this is, on the one hand, that these detectors are very specific. For example, although particular contents of a shipment can be made visible by providing an x-ray machine, no spectroscopic analysis of substances or the establishment of a humidity level of an object can be determined, for example. A comprehensive image of the shipment or the shipment content would rather require a correspondingly large number of sensors, which would make the examination of the shipment very time-consuming and has a negative effect on the efficiency of the shipment processing, in particular if a very large number of shipments are to be examined. Opening of the shipment is generally neither economical nor allowed, apart from a few exceptions.

Method and apparatus for examining shipments


The present invention provides a gamma-correction circuit, which is capable to decrease the noise in graphic signal or make the noise not clearly sensible while carrying out gamma-correction on the graphic signals. In the circuit, a high-pass filter is used to decrease the noise in a graphic signal, a gamma-correction section is used for carrying out gamma-correction on the noise suppressed graphic signal, meanwhile a threshold handling section is used for threshold treatment on the high frequency component of the graphic signal to decrease noise, and then the output of the threshold handling section is combined with the gamma-corrected graphic signal through an adder.

In a graphic display device for TV receiver etc., gamma-correction is the kind of correction to make both the input signal and the illuminating output signal of a display device become linear. Moreover, gamma-correction can also be carried out automatically based on the histogram and average brightness level of the graphic signals.
While carrying out gamma-correction, if the slope of the gamma-correction characteristic curve of the darker portion of graphic signals increases, the contrast of the darker portion will increase, and the noise component of graphic signals will also increase, causing even greater noise. From visual aspect, noise in the darker portion of graphic is more significant, thus in this case, more serious problems exist for graphic of poor signal-to-noise ratio such as significant noises.
Prior arts deal with such problems by restricting the amount of gamma-correction not to exceed certain specified value, which, however, is not an effective solution as far as noise is concerned.

Gamma-correction circuit for graphic signals

InfoVision Optoelectronics Holdings Limited


The present invention encompasses compounds of Formula (I) or pharmaceutically acceptable salts or hydrates thereof, which are useful as novel non-steroidal selective glucocorticoid receptor modulators for treating a variety of autoimmune and inflammatory diseases or conditions, and possess advantages over steroidal glucocorticoid ligands with respect to undesireable side-effects, efficacy, toxicity and/or metabolism. Pharmaceutical compositions and methods of use are also included.

Intracellular receptors (IR's) are a class of structurally related proteins involved in the regulation of gene expression. The steroid hormone receptors are a subset of this superfamily whose natural ligands are typically comprised of endogenous steroids such as estradiol, progesterone, and cortisol. Man-made ligands to these receptors play an important role in human health and, of these receptors, the glucocorticoid receptor (GR) has an essential role in regulating human physiology and immune response. Steroids that interact with the glucocorticoid receptor have been shown to be potent anti-inflammatory agents, although cross-reactivity with other steroid hormone receptors such as the mineralocorticoid, progesterone and androgen receptors can lead to problematic ancillary pharmacology.
The dissociation of transactivation from transrepression at the glucocorticoid receptor is believed to be an approach toward improving the side-effect profile related to steroid therapy. The beneficial anti-inflammatory activity of GR modulators, such as steroids, is believed to occur through the transrepression of genes encoding for proinflammatory cytokines, adhesion molecules and enzymes. Many of the undesireable side-effects associated with such agents are believed to occur through the transactivation, or induction, of gene transcription leading to the downstream perturbation of homeostatic endocrine function. Some of these affected metabolic processes include induced gluconeogenesis, induced amino acid degradation, osteoporosis, suppression of HPA axis, induction of secondary adrenal suppression, changes in electrolyte concentration, changes in lipid metabolism, growth retardation, impaired wound healing and skin thinning. Weak, partial and full agonism of GR related to transrepression and transactivation, including potential antagonism of the receptor regarding transactivation, may be applied to the treatment of inflammatory and autoimmune diseases such as rheumatoid arthritis and asthma. For recent reviews see: (a) Recent Advances in Glucocorticoid Receptor Action; Cato, A. C. B., Schacke, H., Asadullah, K., Eds.; Springer-Verlag: Berlin-Heidelberg, Germany, 2002. (b) Coghlan, M. J.; Elmore, S. W.; Kym, P. R.; Kort, M. E. In Annual Reports in Medicinal Chemistry; Doherty, A. M., Hagmann, W. K., Eds.; Academic Press: San Diego, Calif., USA, 2002; Vol. 37, Ch. 17, pp 167-176.

Selective non-steroidal glucocorticoid receptor modulators


Disclosed is a method of analyzing mass of the phosphoproteins or phosphopeptides and of analyzing phosphorylated positions at a phosphoprotein or phosphopeptide, comprising the steps of: 1) dephosphorylating at least one Ser and/or Thr residue of the phosphoprotein or phosphopeptide; 2) tagging the dephosphorylated amino acid residues with a tag having a R-L-G moiety wherein R is a nucleophilic functional group that selectively bind with dephosphorylated amino acid residues, G is selected from the group consisting of guanidine moiety or protected guanidine moiety such as a mono-N-protected guanidino group, a di-N,N′-protected guanidino group and an N′-protected guanidino group, and L is a linker linking the R and the G; and 3) subjecting the tagged proteins or peptides to mass spectrometry. The method is capable of precisely analyzing mass of phosphoproteins of trace amounts as well as positions of phosphoryated amino acids.

Proteins play crucial roles in virtually every biological process. The analysis and identification of proteins at the molecular level is, therefore, very significant and necessary for understanding the versatile biological activities of cells and, further, for developing new therapies for diseases.
Most proteins undergo some form of modification following translation. Most representative of the post-translational modification is phosphorylation. Most commonly occurring on tyrosine, serine, threonine, histidine and lysine residues, phosphorylation plays critical roles in the regulation of many cellular processes.
Particularly, reversible phosphorylation is known to be closely related to intra- and inter-cellular signaling events. Many of the proteins involved in cell signaling pathways are phosphorylated by kinases and dephosphorylated by phosphotases. Many reported that abnormal phosphorylation/dephosphorylation of specific proteins is causative in many diseases.
Fast and accurate screening for the irregularity of proteins in phosphorylation state is very helpful for understanding intra- or inter-cellular signaling events as well as contributing to the development of effectively diagnosing methods for diseases.
Tandem mass (MS/MS) spectrometry, which is one of the most potent protein analysis methods in current use, requires the hydrolysis of proteins to smaller mass peptides for analysis. The tandem mass spectrometry suffers some disadvantages when analyzing phosphopeptides, unlike the case of non-phosphopeptides. First, protein phosphorylation is usually reversible so that the sites on which phosphorylation can occur may be partially phosphorylated. Thus, in many cases, the amount of phosphopeptides obtained after the hydrolysis of proteins is present substoichiometrically. Second, the phosphoric acid groups present in phosphopeptides give a significant ionization suppression effect in cation mass spectrometry, which is generally adopted in peptide analysis. As a result, the detection sensitivity of phosphopeptides is very poor in relation to that of non-phosphopeptides. Finally, as phosphoric acid groups are chemically unstable, phosphopeptides may be partially dephosphorylated during their mass analysis. If dephosphorylation occurs, not only reduce the detection sensibility but also complicate the spectrum interpretation, resulting in an incomplete MS/MS sequencing analysis of peptide.
To avoid these problems, β-elimination of phosphoric acid groups is used. When being subjected to β-elimination in a basic solvent, phosphoserine and phosphothreonine residues of peptides or proteins are converted into dehydroalanine and β-methyldehydroalanine residues, respectively. In advance of mass spectrometry, phosphoric acid groups are removed from sample peptides or proteins. The elimination of phosphoric acid groups from peptides or proteins is accompanied by the removal of the above-mentioned problems, such as the ionization suppression due to the presence of phosphoric acid groups, and the partial dephosphorylation attributed to the chemical instability of phosphoric acid groups. However, the residues resulting from the dephosphorylation, that is, dehydroalanine and β-methyldehydroalanine are unstable, as well. In order to make the dephosphorylated peptide stable, the residues are rendered to undergo Michael addition reactions with properly-designed, various nucleophiles. Consequently, the problems of phosphopeptides on mass spectrometry can be solved through dephosphorylation, and the analysis of phosphopeptides is facilitated by introducing tag with versatile information such as specific mass number into the dephosphorylated amino acid residues.
Tags, used in β-elmination/Michael addition reaction, generally contain sulfhydryl functionality. The tags can also have neutral functional groups or basic functional groups such as amine groups promoting the generation of cations in peptides. Thus the mass sensitivity of the tagged peptides is exceptionally improved. The tagged peptide derivatives are also so stable under general mass spectrometric conditions that accurate amino acid sequencing can be achieved using MS/MS spectrometry.
Another advantage of phosphospecific tagging method is that relative quantification between samples obtained from different sources can be achieved by using stable isotope-coded tag. When compared to intact tag, stable isotope-coded tag shows the same reactivity in the β-elimination/addition reaction and no different analysis sensitivity in mass spectrometry. Only difference between intact tag and stable isotope-coded tag in mass spectrometry is mass values read on mass spectra of each peptide derivatives. Thus the intact tag and the stable isotope-coded tag are used together but separately for tagging of each sample so that relative quantification can be achieved between samples obtained from different sources.
A further advantage provided by the β-elimination/addition reaction is that only tag derivatives of phosphopeptides can be selectively purified and concentrated by introducing an appropriate functional group having affinitive interactivity to tag. For example, a tag having biotin structure is used the purpose (Oda, Y. et al., 2001, Nature Biotechnology, 19, 379-382). When a biotin group is linked through ethanedithiol to a dephosphorylated residue, streptavidin which can affinitively interact with biotin can be used to selectively isolate and concentrate the tagged peptides formerly phosphopeptides from sample. Various neucleophiles containing a thiol group are used to label phosphopeptides and proteins.
None the less, there is a need of an improved mass spectrometry method for effectively analyzing phosphoproteins which are present in the body in trace amounts or in substoichiometric amounts due to partial phosphorylation as well as the phosphorylated sites of the proteins.

Selective labeling agent for phosphoproteome analysis and phosphorylated site analysis


A dental stone casting mold adapted to a single casting process for the preparation of a positive tooth replica, the mold having opposed side walls, end walls and a floor forming a cavity for containing fluid or set dental stone, a pair of cooperating interlocking mechanisms, one of the mechanisms being carried by the mold floor and the other being adapted for fixation to the dental stone, each mechanism being cooperatively configured with respect to the other such that when they are forced toward a mating position, vector forces are created tending to urge the set dental stone toward the mold floor.

In the field of dental care, replacement teeth are typically retained in place by means of bridge work or the like extending from the replacement tooth and anchored to adjacent healthy teeth. The manufacture of such replacement teeth and their mechanical bridge structure requires careful work to insure proper fitting thereof with respect to adjacent teeth. Also, restoration procedures such as the capping of decayed or broken teeth likewise requires close attention to the precise positions of proximate teeth.
To accurately form and position the replacement tooth or cap, a dentist usually makes a dental negative or impression of the relevant tooth or gap, typically including at least the adjacent teeth. This impression may be partial, unilateral or bilateral, depending upon the extent of the work to be done, and serves as a mold for eventually developing, e.g., a die of the patient's tooth to be replaced or restored. For example, when a tooth is to be crowned or otherwise rebuilt, it is conventional to make a negative casting or impression of the tooth using a rubber-like impression material, the impression then being used as a mold for preparing a positive replica of the tooth to be restored. The replica is then used to assist in forming a crown model of the tooth which, in turn, provides a form or die for making the crown. If needed, a full-bite positive replica of the teeth will be prepared for use in ensuring that the upper and lower teeth sets will close together properly.

Dental model preparation and apparatus therefor