A composition for treating cancer, including synergistic amounts of a primary cell-derived biologic having the cytokines IL-1, IL-2, IL-6, IL-8, TNF-α, and IFN-γ, and a cancer vaccine having at least one antigen. A composition comprising synergistic amounts of the primary cell-derived biologic in combination with at least one adjuvant. A method of treating cancer by administering the composition. A method of reversing immune suppression and gaining immunity to cancer. A method of producing an immune response to an exogenous antigen. A method of enhancing an immune response in a patient by administering the primary cell-derived biologic in combination with at least one adjuvant, and enhancing the immune response of the patient by a synergistic interaction of the primary cell-derived biologic and the adjuvant. A method of increasing function of an immune system.

1. Technical Field
The present invention relates to vaccine immunotherapy. More specifically, the present invention relates to compositions and methods for eliciting and potentiating an immune response to endogenous or exogenous antigens in patients having cancer or other antigen-producing disease states or lesions and for eliciting and potentiating an immune response to adjuvants.
2. Background Art
It has become increasingly apparent that human cancers possess antigens, which, if acted upon by the host's immune system, can result in tumor regression. These antigens have been defined by both serological and cellular immune approaches, which have lead to the definition of both B and T cell epitopes (Sahin, 1997; Van der Eynde, 1997; Wang, 1999). Based upon these results, it has become a goal of cancer immunotherapists to induce the regression of tumors. However, historically, successful efforts have been sporadic and generally minor in frequency and magnitude.
A fundamental problem in the effort to immunize cancer patients, i.e., against tumor antigens, is that the tumor-bearing state is associated with immunosuppressive mechanisms derived from both the tumor and the host's disturbed immune system (Kavanaugh, 1996), thereby making immunization difficult and until now impossible on a consistent basis. Immune suppression or depletion involves a reduced capacity of the immune system to respond. Such suppression can be drug-induced, i.e., by drug treatment, virus-induced, e.g., as in AIDS, or induced by a disease state such as cancer. The immune system in this condition is effectively turned off. In the case of a disease state such as cancer, the body is not able to protect itself against tumor antigens, thus allowing a tumor to grow and possibly metastasize.
A variety of tumor immunization strategies have been developed. All of these strategies are complex and deviate significantly from the conventional immunization strategies used for infectious diseases (see, e.g., Weber, 2000). One such tumor immunization strategy involves THERATOPE® (Biomira), a sialyl Tn polysaccharide mucin antigen conjugated with keyhole limpet hemocyanin (KLH) and administered with DETOX® mycobacterium adjuvant and low dose cyclophosphamide (Maclean, 1996). Use of this vaccine in patients with metastatic breast and ovarian cancer has yielded major clinical responses (i.e., greater than 50% tumor reduction) in only a low percentage of patients.
Gene therapy has also been attempted using viral constructs as expression vectors for genes expressing tumor antigens. For example, a recombinant vaccinia virus construct encoding modified forms of human papilloma virus (HPV) E6 and E7 protein sequences has been used for immunization of patients with cervical cancer. Vaccination with this construct yielded questionable clinical responses (Borysiewickz, 1996). See also, Sanda, 1999 wherein a recombinant vaccinia-PSA (prostate-specific antigen) construct was used as a vaccine in prostate cancer patients.
Another approach has been dendritic cell-mediated therapy, e.g., wherein dendritic cells were pulsed with oligopeptide fragments of prostate-specific membrane antigens (PSMA). The dendritic cells (with or without the priming PSMA antigens) were then administered to patients with metastatic prostate cancer. Major clinical responses were obtained in only a low percentage of patients (Murphy, 1999; see also, Tjoa, 2000).
Additionally, autologous tumors have been used with low dose cyclophosphamide and BCG (Bacillus Calmette-Guerin) to immunize cancer patients with malignant melanoma. However, few clinical responses were reported (Mastrangelo, 1996). Another strategy included using MAGE antigens with a variety of vaccine adjuvants. Again, this has yielded few, if any, responses in patients with malignant melanoma (personal communication, Thierry Boon).
Several patents to Doyle et al (U.S. Pat. Nos. 5,503,841; 5,800,810; 6,060,068; 5,643,565; and 5,100,664) disclose methods of enhancing the immune response in patients using interleukin 2 (IL-2). This method is disclosed for use in response to infectious diseases and primarily functions using antigens known to be immunogenic. Limited applicability was demonstrated. As disclosed above, the treatment of cancer is known to require different approaches. To date, treatment with IL-2 has shown minor effects in two cancers, renal cell and malignant melanoma (response rates less than 20%). It is generally considered ineffective in squamous cell head and neck and cervical cancer and in prostate cancer. Hence, it is not approved for these uses.
It is important to contrast prophylactic vaccines using known "classic" antigens of complex structure and high molecular weights in healthy patients vs. therapeutic vaccines (generally unsuccessful) with tumor antigens or peptides (general unsuccessful) in immunosuppressed patients (generally unsuccessful). The first is easy and our current viral vaccines attest to their efficacy. The latter is nearly impossible on a routine basis despite thirty years of intense effort.
Effective cancer vaccines require stimulation of cell-mediated immunity, perhaps even in preference to antibody production. As noted, despite numerous studies with various antigens, adjuvants and vaccine constructs, the clinical trial data to date have been disappointing. The critical events for a T cell mediated anti-cancer immune response are antigen presentation to T cells, primarily in the lymph nodes draining the site of the tumor or immunization, followed by T cell activation and migration to the peripheral sites. In fact, the uptake of the antigen by tissue macrophages, neutrophils and/or dendritic cells and presentation of processed peptides in combination with MHC class I and class II antigens to the T cells in the lymph node are crucial to a complete immune response. Key to a successful T cell immune activation is the generation of the appropriate cytokine environment to drive the immune response to a vaccine, at both the site of immunization and draining lymph nodes. The fact that the mechanism of action of the immune system has heretofore not been completely understood prevents the currently available cancer vaccines from achieving their full potential.
The kinetics of the immune response includes two phases. The first is the draining of the antigen and soluble proteins to the lymph nodes, where an initial immune activation occurs. Twenty four to forty eight hours later, antigen-presenting cells (APCs), most particularly dendritic cells, migrate from the site of immunization via the draining lymphatic ducts to the lymph node, where a second wave of presentation of antigen and activation occurs. More specifically, the APCs interact in the lymph node with precursor T helper cells via engagement of co-stimulatory receptors as well as T cell receptors to yield T helper 1 (Th1) cells and/or T helper 2 (Th2) cells. The ratio of these subsets controls subsequent development of either cell-mediated or humoral (antibody) immune responses (Th1 biasing towards DTH/cytotoxicity, whereas Th2 biases towards antibody production). Following the induction of these activated T cells, the immune response subsides, leaving predominately memory T cells, which are capable of responding upon re-exposure to antigen.
The critical events in this pathway are mediated by cytokines that bias the response in the direction of humoral or cellular immunity. Locally produced cytokines, such as IL-1, IL-2, IFN-γ, GM-CSF, IL-6, TNF-α, IL-12 and IL-8, are associated with the recruitment of immune system cells, antigen uptake, dendritic cell maturation, dampening of T regulatory cell activity, T cell education and proliferation, and the development of Th1 cells (Naylor, 2003). The interdependence of the response means that the activity of any given cytokine depends on the occurrence of precursor events such that the simultaneous presence of multiple cytokines can have different effects at both the injection site and the draining lymph nodes, depending on the kinetics of cell responses to different cytokines.
Failure to evoke a sufficient immune response with traditional vaccines has remained a challenge for vaccine development. Adjuvants have thus been developed to accelerate, enhance, and prolong the immune response to vaccination and reduce the amount of antigen needed per dose. Adjuvants have been used for almost 100 years. Le Moignic and Pinoy first recognized that Salmonella typhimurium suspended in mineral oil potentiated immune responses in 1916. In 1926, Ramon demonstrated that an antitoxin response could be augmented by a large range of substances such as agar, tapioca, lethicin, starch oil, saponin, and breadcrumbs, and Glenny used aluminum salt to precipitate diphtheria toxoid improving immunogenicity, leading to alums used today. Quil A was determined to have adjuvant properties in 1936 by Thibaud and Richou. Quil A is a triterpenoid saponin extracted from the bark of the South American Molina soap tree Quillaja saponaria. In 1937, Freund also developed adjuvants from emulsions. Little progress has been made since then. As we begin to understand the immune system as described above, more progress is being made with adjuvants. Several adjuvants have been developed for vaccines, including cancer vaccines, but still only alum has really had success worldwide. Alum is a Th2 adjuvant; however, adjuvants providing a Th1 response are also desired. Adjuvants are especially needed for population groups that do not sufficiently respond to conventional vaccines due to impaired immune response, such as elderly or immunosuppressed patients. Adjuvants have the potential to overcome immunotolerance; however, none have been very successful in doing so to date. Therefore, there remains a need for an effective adjuvant for various diseases including cancer.
The present invention utilizes the primary cell-derived biologic IRX-2, also previously known as a natural cytokine mixture (NCM), as disclosed in U.S. Pat. Nos. 5,632,983 and 5,698,194, issued to Applicant, to immunize patients and/or potentiate immunization, such as cancer patients or other patients with other antigen-producing lesions or disease states. More specifically, IRX-2 has been previously shown in U.S. Pat. No. 5,698,194 to be effective in promoting T cell development and function in aged, immunosuppressed mice. IRX-2 was shown to decrease the proportion of immature T cells and increase the proportion of mature T cells in the thymus. The IRX-2 included IL-1, IL-2, IL-6, IL-8, IL-12, IFN-γ, TNF-α, GM-CSF, G-CSF, and IL-3, IL-4, IL-7 in trace amounts.
It will be apparent from the disclosure detailed herein that the cytokine compositions of the invention and the methods that utilize them are applicable to the stimulation of an immune response to any antigen of interest, e.g., cancer or tumor antigens, as well as antigens produced by other persistent disease states or lesions. As detailed herein, the cytokine mixture of the invention acts as an adjuvant preferably to stimulate T cell immunity in vivo.
Moreover, the present invention relates to, but not exclusively to, eliciting an immune response to either endogenous antigens, i.e., proteins or peptides that are located in vivo and are processed and presented by APCs (such as dendritic cells) in vivo, or to exogenous antigens, i.e., proteins or peptides that have been isolated or generated in vitro and then administered in vivo to an environment (e.g., a lymph node) where dendritic cells are present and can effectively present the antigens, e.g., to T cells. In particular as it relates to peptide antigens, this goal is considered by many immunologists to be insurmountable. Peptides are generally considered to be much too small to be effective immunogens, their half-life is short, and they are often non-mutated self antigens to which the patient is immunologically tolerant. Thus, gaining an immune response to such antigens is tantamount to inducing auto-immunity.
As described herein, the present invention is useful to develop a consistent and effective method of vaccine immunotherapy, wherein immune responses are elicited in patients, such as cancer patients, using the cytokine compositions of the present invention in combination with endogenous and/or exogenous disease-associated antigens, including tumor antigens and peptides, as well as with other adjuvants.


A review facility and review method for interactively reviewing an item, such as a block of code, by a group of reviewers and collecting comments from the reviewers. An author provides the item as text for preparation for interactive review. The text is prepared, tagging each line and making the tagged text available to reviewers, e.g., as links on a web page. Reviewers interactively comment on individual lines and review previously entered comments. An abbreviated formal review may follow the interactive review.

1. Field of the Invention
The present invention is related to software package development and more particularly to reviewing and approving software products at various stages of development.
2. Background of the Invention
Most large development projects such as developing a consumer software package are collaborative efforts. Typically, these are modular projects where individuals or small groups are each assigned a specific development task. Such a task may be to write a specific piece of code for large software package, e.g., a subroutine, a macro, etc. Normally, after each participant develops his or her particular code to a point where it may be complete or close to completion, the code is reviewed for approval.
Prior to the review, the author or a moderator creates a static packet of the code for review and distributes the packet to all reviewers. After a suitable period of time, the author or moderator holds the packet review meeting wherein one person, e.g., the author or developer, reads the code aloud and reviewers are allowed to comment and identify errors or problems with the code. Comments are recorded and the author may take whatever action he or she feels is necessary such as, for example, correcting errors or rewriting portions of code. These code inspection or review meetings are integral parts of software development processes.
Generally, these code inspections are done manually, providing each reviewer with a paper copy of the code and, review/inspection meetings generally take a great deal of time. A typical code inspection/review meeting may cover 100 to 125 lines of code per hour. For a large software module, e.g., a couple of thousand lines long, this review can be a long tedious process.

Interactive collaborative facility for inspection and review of software products


The present invention provides a process for preparing a carbohydrate-binding lectin derivative for use as immune modulators or immunoconjugates. The polymer-lectin conjugate produced in accordance with the process is polyethylene glycol Ricinus communis agglutinin I (PEG-RCAI). The lectin is coupled to the polymer by activating the polymer with a coupling agent such as 1,1-carbonyldiimidazole. The polymer-lectin conjugate is biologically active, biocompatible and is expected to be substantially non-immunogenic.

Lectins are proteins derived from plant, animal, or microbial sources which have specific carbohydrate-binding activity. Because of their binding specificity for sugars and oligosaccharides, lectins have become useful reagents in the study of the biology and biochemistry of glycoconjugates in vitro (Rhodes et al., 1988, Digest. Dis. Sci., 33:1359-1363; and Green and Baenziger, 1989, Trends Biochem Sci., 14:168-171), and for the analysis of cellular components of the mammalian immune system (Smith, 1972, Transplant Rev., 11:179-216; and MacDonald and Natoholz, 1986, Ann. Rev. Cell. Biol., 2:231-254). The interaction of lectins with surface g1Ycoproteins of various cells of the immune system induce or inhibit a variety of responses in vitro which are indicative of cellular functions in vivo. For example, lectins can induce mitogenesis of T-lymphocytes (Favero et al., 1988, Cell. Immunol., 142:4401-4406) and induce synthesis and secretion of a variety of cytokines which are proteins involved in the regulation of immune responses (Miyajima et al., 1988, FASEB J., 2:2462-2473; and Taniguchi, 1988, Ann. Rev. Immunol. 6:439-464).
Many lectins have the potential for being powerful therapeutic and diagnostic reagents in vivo due to their carbohydrate-binding activity and specificity. Numerous lectins have been identified which could be screened for these purposes (Sharon and Lis, 1987, Tends Biochem. Sci. 12:488-491). However, principal factors which limit the development of lectins for in vivo use include their inherent toxicity, their potential to elicit an immunogenic response, and the short half-life of these substances in the circulatory system. In particular, an immune response against the lectins would enhance the destruction and clearance of subsequent introductions of the lectin, in addition to the possibility of causing an allergic reaction.
An inert water-soluble polymer may be conjugated to proteins to alter their properties (Inada et al. 1988, Trends Biotech. 6:131-134). The reduction in toxicity, immunogenicity, and clearance rate of certain polymer-protein conjugates has led to using polymer conjugation as a drug delivery system (Krieger, 1990, Chem. Eng. News, 68:38-40). For example, U.S. Pat. No. 4,179,337, discloses a process for coupling polypeptides, including enzymes and hormones, to polymers such as PEG. The resulting PEG-polypeptide conjugates are substantially non-immunogenic and retain some of the desired physiological activity of the base polypeptide when injected into the mammalian circulatory system.
U.S. Pat. No. 4,791,192 discloses a chemically modified protein which comprises an islet-activating protein produced by bacteria belonging to the genus Bordetella and a polyethylene glycol moiety bound with a primary amino group of the islet-activating protein.
U.S. Pat. No. 4,496,689, discloses a process for producing covalent conjugates formed by the chemical coupling reaction of the blood plasma glycoprotein, alpha-1-proteinase inhibitor, with an "activated" water soluble polymer, such as PEG. The conjugates are used in a method for treating pulmonary emphysema and respiratory distress syndrome.
Although conjugation of proteins to water-soluble polymers has been described in the prior art, it cannot be expected that the carbohydrate-binding activity of lectins can be retained after coupling because of potential steric hindrances involved in conjugation. Typically modification, such as by conjugation, of lectins involves covalent coupling between constituents of one or more functional groups of the modifying agent and one or more amino acids of the particular lectin. Thus, modification of lectins can result in concomitant loss of bioactivity, i.e. carbohydrate-binding activity, when amino acid residues of the lectin affected by the modification are amino acids which are necessary for bioactivity. The prior art fails to disclose a method which overcomes the problem of loss of carbohydrate-binding activity from modification of the lectin. Therefore, there exists a need for a method for predictably producing a water-soluble polymer-lectin conjugate that retains carbohydrate-binding activity subsequent to conjugation.
Additionally, lectins have been unable to achieve their potential for being biological response modifier in vivo because of their toxicity, immunogenicity and rapid clearance. Therefore, a need exists for carbohydrate-binding lectin derivatives which may be useful as therapeutic and diagnostic reagents in vivo and have reduced toxicity and immunogenicity with extended biologically active lifetime in vivo.

Synthesis and utilization of carbohydrate-binding polymer-lectin conjugates


A solid phase magnetic support having a hydrophilic surface, a method of making the support, and a method of using the support for peptide synthesis are provided. The solid phase magnetic support is synthesized from a starting material which is a magnetic polystyrene polymer bead which has a plurality of polystyrene coated metal oxide particles randomly distributed in a polystyrene matrix having chloromethyl groups. Hydrophilic long chain hydrocarbon spacer arms, such as polyalkylene diamine molecules are coupled with sonication to the chloromethyl groups. Each spacer arm is provided with a terminal amine for linking to a first amino acid. Preferably, the terminal amine on the spacer arm is provided by a low molecular weight linker molecule which can be acid cleaved from the spacer arm. However, the spacer arm may be derivatized and linked to a first amino acid which cannot be acid cleaved from the spacer arm. The inventive support can be used for automated peptide synthesis or as a support for a bound ligand in bioassays. The support is held in place magnetically while the surrounding solution is siphoned off allowing simultaneous separation of the support bound component from the reactants in solution and washing.

Solid-supported organic synthesis has recently entered a renaissance due to the emergence of the field of combinatorial chemistry, aimed at rapidly synthesizing vast libraries of compounds for biological testing (Moos, W. H.; et al., Annual Reports in Medicinal Chemistry (Bristol, J. A. editor), 28:315 (1993)). Most of these libraries are produced through solid-supported organic synthesis and consist of peptides or peptide-like compounds (Zuckermann, R. N.; et al., J. Am. Chem. Soc., 114:10646 (1992); Houghten, R. A.; et al., Nature, 354:84 (1991)). Some groups have begun to produce chemical libraries that do not rely on the peptide backbone (Lebl, M.; et al., Int. J. Pept. Protein Res., 41:201 (1993); Dewitt, S. H.; et al., Proc. Natl. Acad. Sci. USA, 90:6909 (1993)). The major advantage in producing chemical libraries by solid-supported synthesis over traditional solution synthesis is the relative ease in separating starting material from product. This rapid ability to separate staring material from product can also make the library's production through automation that much easier.
However, in the field of solid-supported peptide synthesis, the methods of separation have been filtration and centrifugation. The physical separation of the support from the solubilized components of the reaction mixture has primarily been accomplished by filtration through a glass or polymer filter (Wolfe, H. R.; Wilk R. R., Peptide Research, 2:352 (1989); Knapp, D. R.; et al., Int. J. Peptide Protein Res., 42:259 (1993)). Centrifugation has also been used as a means of separation (Anderson, N. G.; et al., J. In Innovation and Perspectives in Solid Phase Synthesis, Oxford, In Press (1993); Lebl. M., et al., U.S. Pat. No. 5,202,418). Although filtration has been the method of choice in both solid-phase peptide and nucleotide synthesis, it does have limitations that warrant the development of new approaches. One such limitation is the difficulty of automating the simultaneous washing and filtration of hundreds of small scale solid-phase reactions. Another problem is the tendency for a percentage of the filters to get clogged over time with precipitated reagent which makes the use of filtration in automated procedures less reliable.
Automation of bioassays and organic syntheses is desirable to improve quality control in order to insure uniformity of results. A field that has had some success in automating some of its techniques is immunodiagnostics. Antibody-bound paramagnetic beads can be exposed to a magnetic field to separate antibody-bound antigen from unbound antigen in immunoassays (Okada, M., et al., U.S. Pat. No. 5,320,944; Ugelstad, J., et al., WO 83/03920; Fjeld, J. G., et al., J. Immunol. Methods, 109:1 (1988)), each of which is incorporated herein by reference. Assays directly measuring the radiolabeled ligand-protein complex after it has been separate from unbound material are termed radioimmunoassays. Alternatively, in a method termed scintillation proximity assay, the extent of binding is determined by measuring the intensity of fluorescence released when the radiolabel affects a fluorescent molecule bound to another particle (H. Hat; U.S. Pat. No. 4,271,139) incorporated herein by reference. However, the loading capacity of the support systems currently used is limited. Further, non-specific binding of unbound reactants to the support can yield incorrectly elevated values.
Magnetic separation methods have also been applied successfully in cell sorting (Treleaven, J. G.; Lancet, 14:70 (1984); Miltenyi, S.; et al.; Cytometry, 11:231 (1990); Padmanabhan, R., et al., Analytical Biochem., 170:341 (1988)). A definite advantage that magnetic separation has over simple filtration is the ability to separate out particles in small reaction volumes. As with immunoassays, the loading capacity of the support systems currently used is limited.
Unlike immunodiagnostic and cell sorting technologies, the use of magnetic separation in the field of solid-supported organic chemistry has been slow in coming due to the instability in organic solvents such as dimethylformamide and methylene chloride exhibited by the currently available supports. Upon exposure to these solvents, typical polymer coated magnetic beads dissolve. Silica coated magnetic beads are more stable to these solvents but lack the loading capacity (typically<0.2 mmoles/gram) and acid stability that make them practical for organic synthesis (Benner S. A., U.S. Pat. No. 4,638,032).
One way to increase paramagnetic polymer beds stability in organic solvent is to enhance the levels of cross-linking of the polymer around the magnetite core to make macroporous polymer particles (Ugelstad, J., et al., U.S. Pat. No. 4,774,265; Wang, C. H. J., and Shah, D. O., U.S. Pat. No. 5,283,079), each of which is incorporated herein by reference. A major problem with this approach is that higher levels of cross-linking reduce the extent to which the support expands and contracts and also affects the level of reactivity. Work by Regen using electron spin resonance (ESR) spectroscopy of nitroxide radical probes showed that the bound substrate was more restricted than a substrate dissolved in the swollen particle (Regen, S. L. J. Am. Chem. Soc., 96:5275 (1974); Regen, S. L., Macromolecules, 8: 689 (1975)). In addition, Regen provided evidence that with greater cross-linking, which translates to less expansion of the support, the internal viscosity of the solvent increased.
Again looking to the non-magnetic solid-phase support field, one can dramatically enhance the mobility of the bound substrate even with high levels of cross-linking of the support by attaching a long polyethylene glycol (MW=2000-3000 daltons) spacer arm which acts as a linker between the bound molecule and the support (Bayer, E., and Rapp, W., U.S. Pat. No. 4,908,405; Barany, G., et al., WO 92/04384), each of which is incorporated herein by reference. However, previous methods required multiple, complex reactions to achieve coupling of the spacer arm to the support.
Clearly, what is needed is an organic solvent stable support which can achieve high loading capacities, which is easily manufactured, and which is useful in automated assays and solid phase organic syntheses.

Method of making and using derivatized paramagnetic polymer beads


A method for reducing the incidence of Salmonella in harvested meat comprising treating the meat with an effective electrostatically charged antimicrobial solution comprising a blend of lactic and citric acids in proportions containing a predominance of lactic acid from 65:5 wt./wt. to 77:3 wt./wt. lactic acid to citric acid; and the pH of the solution is less than about 3.2.

The United States poultry industry processes approximately nine billion chickens, turkeys, and other fowl (collectively, "poultry") annually with a sales value in excess of $20 billion. In recent years, chicken and turkey, for example, have been perceived by some consumers as being healthier and/or less expensive than certain other protein options, such as, red-meat. For these and other reasons, the U.S. poultry industry has been expanding at a rate of 3 to 6 percent annually.
Food safety is the most important issue in the poultry industry. Consumers are constantly reminded that chicken and turkey must be cooked thoroughly and that cooked meat should not contact un-cleaned surfaces, such as cutting boards and countertops, on which the uncooked meat was processed. The reason for this is to avoid Salmonella contamination in the chicken or turkey that is consumed.
The majority of live chickens and turkeys carry Salmonella, and at least two-thirds of live poultry carry Campylobacter. Salmonella and Campylobacter are the two leading bacterial causes of food poisoning in the United States. According to the Center for Disease Control, there are 40,000 reported cases of Salmonella poisoning and 600 deaths annually. The CDC estimates that the actual number of Salmonella cases is approximately 30 times the number of reported events. Obviously, it is highly desirable for producers to deliver processed poultry with minimal incidence of these bacteria. For a number of reasons, however, government regulations allow up to a 50% incidence of Salmonella on uncooked poultry sold for consumption. Assuming that the poultry is properly prepared for eating, there should be minimal risk of illness from bacterial poisoning. Obviously, from the statistics quoted previously, reliance on proper cooking and preparation by consumers is not dependable. In February 2006, the USDA announced an initiative to further reduce the incidence of Salmonella in meat and poultry.
While it is possible to promulgate regulations mandating a zero percent tolerance, i.e., incidence, for Salmonella in poultry leaving a production plant, no known process exists at the present time for achieving that lofty and desirable goal.
Various chemical treatments have been tried. A survey of the poultry industry in March 2006 revealed the use of a number of chemicals in "online processing" to reduce Salmonella. In the order of most to least used, those chemicals included: acidified sodium chlorite; trisodium phosphate; chlorine dioxide; hypochlorous acid; organic acids, peracetic acid; cetylpyridinium chloride; citric acid and HCL; bromine; sodium metasilicate; and electrolyzed oxidative brine. Organic acids approved for use include lactic; acetic and citric acids. Acetic acid, however, has a flavor/taste issue. To mitigate that problem and issues of poultry discoloration, acetic acid must be used at low concentrations that significantly diminish the antimicrobial efficacy. Also, acetic acid is flammable. Citric acid, on the other hand, is generally believed not to be a particularly good antimicrobial. Also, it is normally available in a crystalline form, is difficult to deal with and involves more handling for the user. To the extent that citric acid is available in solution, it is not at the correct concentration level and would still involve additional handling. Thus, lactic acid, which is a good antimicrobial, is currently the most frequently employed of the organic acids.
However, none of the various chemicals listed above and others have been able to achieve a zero tolerance efficacy level for Salmonella. Efforts to improve efficacy levels through the application of larger doses of chemical have been accompanied by discoloration of the meat and "off-smells" or tastes that are offensive or objectionable to potential purchasers and consumers. Many of the chemical treatments are quite expensive even at dosage levels that barely meet the 50% incidence level.
Accordingly, there has been a significant industry and public need for improved processes that can inexpensively and effectively reduce the incidence of Salmonella and other pathogens in poultry products leaving the production plant and that can do so without adversely affecting the color, smell or taste of the poultry.

This patent is subject to a terminal disclaimer.

Method of processing poultry and other meat to reduce or eliminate


This invention relates to a vaccine and a method for immune activation which is effective for eliciting both a systemic, non-antigen specific immune response and a strong antigen-specific immune response in a mammal. The method is particularly effective for protecting a mammal from a disease including cancer, a disease associated with allergic inflammation, an infectious disease, or a condition associated with a deleterious activity of a self-antigen. Also disclosed are therapeutic compositions useful in such a method.

Three major types of disease in mammals which are amenable to elicitation and/or modulation of an immune response include infectious diseases, allergic inflammatory diseases and cancer. Infectious diseases are caused by infectious agents (i.e., infectious disease pathogens), examples of which include viruses, bacteria, parasites, prions, yeast and other fungi. In allergic inflammatory diseases, allergens cause the release of inflammatory mediators that recruit cells involved in inflammation in allergic or sensitized animals, the presence of which can lead to tissue damage and sometimes death. Cancer can result from an inherited inability to repair DNA, to prevent DNA damage or to prevent propagation of cells with damaged DNA, and/or from a biochemical dysfunction or genetic mutation which leads to uncontrolled cell proliferation and DNA synthesis.
Traditional reagents that are used in an attempt to protect a mammal from such diseases include reagents that destroy infectious agents or the cells involved in deregulated biological functions, or that modify the activity of such cells. Such reagents, however, can result in unwanted side effects. For example, anti-viral drugs that disrupt the replication of viral DNA also often disrupt DNA replication in normal cells in the treated patient. The use of anti-inflammatory and symptomatic relief reagents in allergic inflammation is a serious problem because of their side effects or their failure to attack the underlying cause of an inflammatory response. Other treatments with chemotherapeutic reagents to destroy cancer cells typically leads to side effects, such as bleeding, vomiting, diarrhea, ulcers, hair loss and increased susceptibility to secondary cancers and infections.
An alternative method of disease treatment includes modulating the immune system of a patient to assist the patient's natural defense mechanisms. Traditional reagents and methods used to attempt to regulate an immune response in a patient also result in unwanted side effects and have limited effectiveness. For example, immunopharmacological reagents used to treat cancer (e.g., interleukins) are short-lived in the circulation of a patient and are ineffective except in large doses. Due to the medical importance of immune regulation and to the inadequacies of existing immunopharmacological reagents, reagents and methods to regulate specific parts of the immune system have been the subject of study for many years. Vaccines can be used not only to prevent disease (prophylactic vaccines), but can also be used to treat established diseases (i.e., therapeutic vaccines). For example, a number of tumor antigens which are recognized by T lymphocytes of the immune system have been recently identified and are being considered as potential vaccine candidates.
Conventional vaccines generally include either (1) purified antigens, or (2) an attenuated form of a pathogen that can be administered to a patient to generate an immune response, but not cause serious disease or illness. Genetic vaccines contain a DNA sequence that encodes an antigen(s) against which the immune response is to be generated. For genetic vaccines to generate an antigen-specific immune response, the gene of interest must be expressed in the mammalian host. Gene expression has been accomplished by use of viral vectors (e.g., adenovirus, poxvirus) that express the foreign gene of interest in the vaccinated patient and induce an immune response against the encoded protein. Alternatively, plasmid DNA encoding a foreign gene has been used to induce an immune response. The primary routes of administration of these so-called "naked" DNA vaccines are intramuscular or percutaneous. It is generally accepted that viral vector systems induce better immune responses than naked DNA systems, probably because the viral delivery systems induce more inflammation and immune activation than naked DNA vaccines. The propensity of viral vaccines to induce non-specific immune responses, primarily as a result of viral component recognition by the complement cascade and by the elicitation of antigen-specific immune responses against specific components of the viral vector, also represents a potential drawback, however, since such immune responses often prevent readministration of the vaccine.
Therefore, there is need to provide better vaccines which can produce an immune response which is safe, antigen-specific, can be repeatedly administered, and which is effective to prevent and/or treat diseases amenable to treatment by elicitation of an immune response, such as infectious disease, allergy and cancer.

Methods of using nucleic acid vector-lipid complexes

National Jewish Medical and Research Center


Provided is a method of manufacturing a crystalline semiconductor thin film formed on an amorphous or poly-crystalline substrate such as a glass substrate, a ceramic substrate, and a plastic substrate through induction heating using photo-charges. The method of manufacturing a crystalline semiconductor thin film includes a process of forming a low-concentration semiconductor layer on an inexpensive amorphous or poly-crystalline substrate such as a glass substrate, a ceramic substrate, and a plastic substrate and a process of crystallizing the low-concentration semiconductor layer through an induction heating manner using photo-charges. Accordingly, a low-concentration crystalline semiconductor thin film having characteristics better than those of general amorphous or poly-crystalline semiconductor thin film can be obtained by using simple processes at low production cost.

1. Field of the Invention
The present invention relates to a method of manufacturing a crystalline semiconductor thin film, and more particularly, to a method of forming a low-concentration crystalline semiconductor thin film on an amorphous substrate or a poly-crystalline substrate.
2. Description of the Related Art
In general, a MOSFET adapted to a switching device includes a channel region which is converted into a conductor by controlling a gate, high-concentration electrodes (drain and source electrodes) at two sides of the switching device, a gate oxide layer, and the gate, which are formed by performing an implant process and other general semiconductor processes. The channel region is made of a low-concentration semiconductor thin film having an impurity concentration of about 1019/Cm3 or less. The low-concentration semiconductor thin film used for forming the channel region becomes an important factor for determining switching characteristics and needs to be crystallized.
As conventional low-concentration semiconductor thin films that are made of silicon (Si), a hydrogenated amorphous silicon thin film (a-Si:H), a microcrystal silicon thin film (uc-Si), and a crystal-grown silicon thin film are mainly used.
The hydrogenated amorphous silicon thin film or the microcrystal silicon thin film (uc-Si) that are used for manufacturing a large-sized LCD has an advantage in that the thin films can be manufactured with a simple manufacturing method. However, since many defects are included in the thin film, a mobility of charges is low and a life cycle is short, so that switching characteristics of the switching device are not good. On the other hand, the crystal-grown silicon thin film that is used for manufacturing a small-sized high-image-quality LCD has an advantage in that the switching characteristics of the switching device are good due to a good mobility of charges and a long life cycle. However, the thin film has disadvantages in that the process of crystallizing silicon is complicated and a long time is taken to manufacture the crystal-grown silicon thin film.
As an example of taking all the advantages of these methods, there have been proposed methods of crystallizing a low-concentration semiconductor thin film. Various methods of crystallizing the low-concentration semiconductor thin film have been researched. As the most general method, there is a method of depositing an amorphous semiconductor thin film and performing thermal treatment. However, the method has a disadvantage in that a time for the crystallization process is too long. For example, a process of crystallizing a silicon thin film deposited on a Corning glass requires for the thermal treatment at a temperature of about 700□ for 4 or more hours. Therefore, a productivity of the low-concentration crystalline silicon thin film is very lowered.
As another example, there is an MIC (metal induced crystallization) method. In the MIC method, silicon is deposited on a thin metal layer made of aluminum (Al), nickel (Ni), or the like, and after that, thermal treatment is performed at a temperature of 450□ or less, so that the metal elements and the silicon are dislocated and the silicon is crystallized. Since the method utilizes low-temperature thermal treatment, the method has an advantage in that limitation to a material for an underlying substrate is alleviated. However, since many metal impurities are included in the crystallized silicon thin film, the method has a disadvantage in that characteristics of devices deteriorate.
As still another example, there is a method of crystallizing an amorphous silicon layer through an induction heating process.
FIG. 1 illustrates a general method for manufacturing a crystalline semiconductor thin film through an induction heating process. Now, the method of crystallizing an amorphous silicon layer through the induction heating process will be described in brief with reference to FIG. 1.
Firstly, a diffusion barrier 120 and an amorphous silicon layer 130 are formed on an upper portion of a substrate 110. The amorphous silicon 130 is disposed under an induction coil 152. Next, an alternating current generated by a current generator 151 is applied to flow through the induction coil 152, so that an alternating magnetic field affects the amorphous silicon layer 130.
Carriers in a portion (b) of the amorphous silicon layer 130 under the induction coil are rotated by the alternating magnetic field, so that Ohmic Heating occurs. Therefore, the portion (b) is changed into a fluid state, and the fluid-state portion is crystallized in an interface (d) between the portion (b) and solid-state portions (a) and (c) by using the solid-state portions (a) and (c) as a seed. Next, the amorphous silicon layer 130 is moved in a specific direction (e), and thus, the other portion (c) is crystallized.
Since the heat generated in the inductively heated portion depends on the number of carriers such as free electrons, the method can be adapted to a silicon thin film having a high impurity concentration. However, since a low-concentration semiconductor thin film used for manufacturing a switching device has a relatively small number of carriers, the method has a disadvantage in that the method cannot be adapted to the low-concentration semiconductor thin film. Therefore, in order to form a low-concentration crystalline semiconductor thin film by using the method, a separate process of reducing the impurity concentration is needed after the high-concentration semiconductor thin film is crystallized.
In order to crystallize the low-concentration semiconductor thin film through the induction heating, there is needed a pre-heating process for increasing a temperature of the low-concentration semiconductor thin film up to a high temperature so as to generate a sufficient number of thermal electrons. The generated thermal electrons are used as carriers for the induction heating. However, since the temperature of the pre-heating is increased as the impurity concentration of the semiconductor thin film is decreased. Therefore, there is a limitation to a type of material for the underlying substrate used for the serialization of the low-concentration semiconductor thin film.

Method of manufacturing crystalline semiconductor thin film


For several years, there has been interest in obtaining fast-rising, high-voltage pulses to drive particle-beam diodes and antennas in mobile situations. The Magnetic Voltage-Pulser (MVP) is a new device to satisfy this interest. The regime of operation of the basic unit comprises--output voltage=0.2 to 1.0 MV, pulse duration=1 microsec, and load impedance=1 to 10 ohms. For higher voltage and higher impedance needs, a plurality of pulsers can be used in a series-parallel arrangement. Typical dimensions for the basic pulser are: length=20 cm, and diameter=15 cm. The weight of the system will vary with the details of the technical approach selected for each application. Also, the basic arrangement can be used for single-shot or repetitive operation by selecting options in the technical details. The repetition rate can exceed 10 kHz. Typical applications include high-power microwave and other electronic warfare devices.

The present relates generally to magnetic flux compression generators, and more specifically the invention pertains to a magnetic voltage purser design.
MCG's also known as Flux Compression Generators, are usually explosively driven devices capable of generating tens of kilovolts at millions of amperes on a time scale of tens of microseconds. These performance figures are typical and particular designs may vary considerably from the numbers quoted. Other similar sources include capacitive energy storage banks. The simple generic consists of an inductor or coil through which a priming current is circulated by means of a low power source. The priming current establishes a seed magnetic field in the coil. A specially shaped explosive charge is arranged about the coil in such a manner as to compress the coil upon detonation. The seed flux is trapped in the coil and is thus compressed with the coil. The work done by the explosive in compressing the seed flux and the coil corresponds to a conversion of the explosive energy into electrical energy in the circuit.
Conventional techniques for generating fast-rising, high-voltage pulses generally involve high-voltage capacitors and a plurality of high-voltage, closing-switches in arrangements such as Marx generators. High voltages are also generated from lower voltage pulses by means of transformers. In this case, the output pulse generally follows the risetime and duration of the input pulse.
The task of providing a magnetic pulse generator for generating fast-rising, high-voltage pulses for high impedance loads is alleviated, to some extent by the systems disclosed in the following U.S. patents, the disclosures of which are incorporated herein by reference:
U.S. Pat. No. 4,484,090 issued to Wiegand et al; PA1 U.S. Pat. No. 3,636,313 issued to Markowitz; PA1 U.S. Pat. No. 4,229,700 issued to Greene; PA1 U.S. Pat. No. 5,526,213 issued to MacLauchian et al.
The above cited patents disclose magnetic pulse generators, electromagnetic pulse generators, explosive pulse generators and neutron pulse generators that may be used as elements of the present invention. A need remains for providing a magnetic pulse generator for generating fast-rising, high-voltage pulses for high impedance loads to drive particle beam diodes and antennas in mobile situations. The present invention is intended to satisfy that need.

The United States of America as represented by the Secretary of the Air Force


The present invention provides a propylene polymer molded article being high in tensile elongation and scratch resistance and a propylene polymer composition capable of affording such a molded article. Specifically, the present invention provides, in one embodiment thereof, a propylene polymer composition comprising a propylene polymer (A-1) that is a polymer having an intrinsic viscosity, as measured in tetralin at 135° C., of from 1.2 dl/g, inclusive, to 1.7 dl/g, exclusive, or a propylene polymer (A-2) that is a polymer having an intrinsic viscosity, as measured in tetralin at 135° C., of from 1.7 dl/g, inclusive, to 2.9 dl/g, inclusive, a propylene polymer (B) that is a polymer having an intrinsic viscosity, as measured in tetralin at 135° C., of from 0.5 dl/g, inclusive, to 1.1 dl/g, exclusive, and a nucleating agent.

Molded articles obtained by molding propylene polymer compositions are used for automotive materials or household appliance materials.
For example, Patent Document 1 discloses a polypropylene-based resin composition for foam applications comprising a resin composition comprising at least one propylene polymer selected from the group consisting of a propylene homopolymer and a propylene-ethylene copolymer and an ethylene-α-olefin copolymer, and a β crystal nucleating agent.
Patent Document 2 discloses a polyolefin resin molded article characterized in that the crystal conformation in a propylene-based polymer phase in a polyolefin resin molded article is one formed of crystal lamella layers piled in layer and that the direction in which the long period regularity of the crystal lamella layers is formed is almost perpendicular to the direction in which the resin flows during the formation of the molded article.

Propylene polymer composition and molded article thereof


A system and method for notification management includes collecting information for a number of objects within a management tool for security assets. The display of the information is displayed on a window of a graphical user interface of the management tool. In response to user interaction with the graphical user interface, a notification tool window of a notification tool is displayed. The notification tool window is layered over at least a portion of the window of the graphical user interface. In response to user interaction with the notification tool window, notification instructions are created for at least one of the number of objects based on a portion of the information of the window of the graphical user interface. The notification instructions are operable to cause the notification tool to communicate at least one notification communication to at least one recipient concerning at least one object.

Network administrators may manage large numbers of secure communication protocols, for example Secure Sockets Layer ("SSL") certificates. Sometimes administration is relatively simple. For example, in some cases, administrators may be limited to sending emails regarding certificate renewals and processing new identification requests.
One method of managing certificates provides a tool for administrators to control reminders. For example, an administrator uses the tool to set a 90 day, 60 day, 30 day, or 7 day reminder. The reminder then sends an automated email reminder to, for example, the certificate owner.
The tool is a useful way for administrators to set reminders, however it removes administrators from the context of the page within which they were working to establish the reminder. For example, an administrator may be viewing a page showing a number of certificates with corresponding owners, expiration dates, IP addresses, security ratings, etc. The administrator might then want to make a change to a particular certificate. In order to make the change, the administrator needs go to a separate page, thus removing the administrator from the original page. After making the change, the administrator then needs to navigate back to the original page. Another problem is that the administrator may need access to information that was on the original page in order to set the reminder—another inconvenience if the administrator needs to navigate away from the page to establish a reminder.
Even for relatively simple administrative tasks, the back and forth navigation between pages adds considerable time to an administrator's work. In addition, many administrators have increased responsibilities. For example, administrators need to know if sensors are up or down, the progress of scans, the completion of scans, etc. Again, moving between pages that an administrator is working on, and additional pages needed to make changes, increases the time required to complete jobs. As administrative tasks become more complex, providing administrators with quicker access to tools, more control, and new flexibility can increase efficiency.


A method, computer program product and computer system are provided. A processor receives a plurality of pointers corresponding to a plurality of electronic files. A processor determines at least one affinity score for the plurality of electronic files based, at least in part, on one or more usage patterns of a user. A processor generates a geometric diagram including a plurality of regions, wherein the geometric diagram is represented by a matrix. A processor assigns the plurality of pointers to the plurality of regions based, at least in part, on the at least one affinity score. A processor selects at least one pointer of the plurality of pointers based, at least in part, on a selection area of the geometric area, where the at least one pointer is located within the selection area. A processor generates a list including the at least one pointer of the plurality of pointers.

The present invention relates generally to the field of randomization, and more particularly to generating a pseudorandom list of electronic files based on a user affinity.
Pseudo-randomization is the process of generating an outcome that appears random but is not. Pseudorandom outcomes typically exhibit some statistical randomness while being generated by an entirely set of deterministic rules or procedures. A pseudorandom list is a series of pseudorandom outcomes. Particularly, a pseudorandom list provides an order of items that appear random, however the list is driven by an underlying set of procedures. Affinity is a liking or inclination towards something. A user's affinity indicates how much a user prefers a particular item.

Electronic file management based on user affinity

International Business Machines Corporation


An improved method and vaccine is provided for the immunization of swine against infectious diseases caused by RTX toxin-secreting bacteria (e.g., porcine pleuropneumonia) which comprises administering to swine an effective amount of a live, immunizing, RTX toxin-secreting organism which induces in the swine a sufficiently high RTX toxin-neutralizing antibody titer to at least prevent clinical symptoms of the disease in the swine. For example, an intranasally administered, live, low virulence strain of A. suis (EM1) confers immunity upon swine against challenge with a virulent, disease-causing strain of A. pleuropneunmoniae.

1. Field of the Invention
The present invention is broadly concerned with an improved method and vaccine for the immunization of swine against infectious diseases caused by bacteria which secrete RTX toxins, such as pleuropneumonia, pneumonia, enteritis, septicemia and rhinitis sore particularly, the invention pertains to such a method and vaccine which includes an effective amount of a live, immunizing, RTX toxin-secreting organism which induces in the swine a sufficiently high RTX toxin-neutralizing antibody titer to at least prevent clinical symptoms of the diseases.
2. Description of the Prior Art
A number of gram-negative bacteria are known to secrete RTX toxins in swine. Such bacteria are generally selected from the group consisting of the genera Actinobacillus, Pasteurella, Haemophilus, Escherichia and Salmonella. The RTX toxins are a family of calcium-dependent, pore-forming, secreted toxins.
Organisms which secrete RTX toxins are known to cause a variety of debilitating swine diseases such as pleuropneumoniae pneumonia, enteritise septicemia and rhinitis. These diseases, and particularly porcine pleuropneumonia, have very serious economic consequences for pig farmers. Susceptible pigs exposed to aerosolized A. pleuropneumoniae develop acute necrotic bronchopneumonia following inhalation of a threshold number of organisms. The toxins produced by A. pleuropneumoniae and the associated inflammatory response rapidly induce focal vascular necrosis leading to localized thrombosis, edema, ischemic necrosis, and fibrinous pleuritis. The severity of the diseases following exposure to A. pleuropneumoniae is dependent on the relative virulence of the strain involved and the number of organisms inhaled. In a typical pleuropneumonia outbreak caused by a virulent strain of A. pleuropneumoniae, morbidity may be in excess of 50% with mortality being quite variable, from 1-10%. Growing pigs are often most severely affected, although immunologically susceptible sows, boars and piglets may also develop severe disease. A full discussion of the causes, epidemiology and treatment of pleuropneumonia is set forth in Fenwick et al., Porcine Pleuropneumonia: An Update, J. Am. Vet. Ned. Assoc., 1994; 204:334, which is incorporated by reference herein.
While the impact of porcine pleuropneumonia and other diseases caused by bacteria which secrete RTX toxins is well known, there have heretofore been no commercially available vaccines with the ability to reliably induce protective immunity against these diseases. Some vaccines reduce mortality rates, but none are effective in preventing infections of A. pleuropneumoniae or apparently the development of carrier pigs capable of shedding the organism. Additionally, difficulties with antigens and adjuvants have led to injection site lesions. As far as is known, none of the prior vaccines induce significant neutralizing antibody titers in swine against the exotoxins such as the RTX toxins secreted by the etiologic organisms.
There is accordingly a real and unsatisfied need in the art for an improved vaccine and method whereby swine may be immunized against infectious diseases caused by bacteria which secrete RTX toxins.

Swine immunization using live, RTX toxin-secreting organisms

Kansas State University Research Foundation


A magnetic cassette recorder is disclosed which has a microprocessor having stored therein a standard recording level. Inputting a signal representative of an actual amount of attenuation being offered by a level control rheostat to the input record signal, and a signal representative of the amplitude of the record signal that has traveled through the rheostat, the microprocessor computes the actual amplitude of the record signal before being attenuated by the rheostat. When the thus computed amplitude of the input record signal exceeds the stored standard amplitude, the microprocessor puts out a control signal for adjusting the rheostat to the standard amplitude. The standard recording level stored in the microprocessor is manually variable by switches to the liking of the particular user.

This invention relates generally to recording devices such as magnetic tape recorders and, particularly, those for use with tape cassettes. More particularly, the invention pertains to an automatic recording level control system for such recording devices featuring provisions for manual change of the standard level.
In tape recording, as is well known, the recording level or amplifier output level must be adjusted to secure a satisfactory recording, eliminating distortion due to too high a level and a decrease in signal to noise radio due to too low a level. Tape recorders are therefore usually equipped with a level control knob or knobs to be handled manually and a level indicator or indicators which show the voltage level or levels at which a recording is being made. The level control takes the form of a rheostat or adjustable attenuator.
The setting of the recording level by the manipulation of the level control knob can be troublesome to average users. A conventional solution to this problem has been a computer controlled, full automatic level control, as disclosed in Hasegawa et al. U.S. Pat. No. 4,352,130, which makes knob handling totally unnecessary. This seeming advantage of the prior art device, the complete exclusion of the user from the setting of the recording level, is its weakness at the same time. Just as an optimum setting to one user is not necessary so to another, so the setting made by the manufacturer for automatic level control may not be to the liking of the particular user of the recorder.

Automatic recording level control system providing for manual change of the standard level


The apparatus for the thermal spray delivery of a precursor solution comprises a first solution reservoir, a second solution reservoir, singular or multiple atomizing liquid injector(s) disposed in fluid communication with the reservoirs, a flame source configured to direct a spray from the atomizing liquid injector to a substrate, and a thermal control device disposed in thermal communication with the substrate. The method of depositing a precursor solution at a substrate to form a coating comprises maintaining a substrate at a pre-selected temperature, delivering the precursor solution from a reservoir bank, atomizing the precursor solution, injecting the atomized precursor solution into a flame, and directing the flame to the substrate.

This disclosure relates to an apparatus used during thermal spray operations, and, more particularly, to an apparatus for the continuous and stable delivery, atomization, and injection of solution for producing films, coatings, or bulk forms in a solution thermal spray process such that the desired microstructural features of the films, coatings, or bulk forms are obtained upon application. The invention also particularly relates to the control of the temperature of the substrate at which the films, coatings, or bulk forms are formed or deposited.
In thermal spray processes, particles of metallic, composite, or ceramic materials are at least partially melted, accelerated, and impinged onto a target substrate to produce a coating having anti-corrosion, anti-wear, thermal insulation or other functional properties. The coating is thickened and built up through the continuous overlaying of material in the form of droplets to produce a coating having splat/lamellar boundary features and partially melted and/or unmelted particle inclusions. The lamellar structure of such coatings, because of their low tolerance to thermal stress induced during thermal cycling in the service environment, may be considered a disadvantage for certain applications, particularly in thermal barrier coating (TBC) applications.
Although the deposited coatings typically derive from solid material, liquid precursors comprising aqueous solutions of metal salts, metal-organic salt solutions, or polymer-based solutions may also be utilized as feedstock sources to produce coatings, particularly when the thermal spray process is a plasma spray process.
The above discussed and other features will be appreciated and understood by those skilled in the art from the following detailed description and drawings.

Apparatus and method for solution plasma spraying


A processing unit for a substrate has a vertical thermal processing furnace 4 having a bottom and an opening 4a provided at the bottom. A boat 3 holding substrates W in vertical multistairs can be placed on a first lid 17, and the first lid 17 can open and close the opening 4a of the vertical thermal processing furnace 4 with the boat 3 placed thereon. The processing unit also has a boat-placing portion 19 on which the boat 3 and another boat 3 can be placed and a boat conveying mechanism 21 for conveying the two boats 3 alternatively between the boat-placing portion 19 and the first lid 17. A second lid 18 hermetically closes the opening 4a of the vertical thermal processing furnace 4 when the first lid 17 opens the opening 4a but no boat 3 passes through the opening 4a. The processing unit can effectively reduce the undesirable influence from the opening 4a when the first lid 17 is taken off from the opening 4a and the boat 3 is conveyed out, and can also reduce the wasted energy by preventing the fall of the temperature in the interior of the thermal processing furnace 4.

1. Field of the Invention
This invention relates to a processing unit for a substrate and a processing method for a substrate.
2. Disclosure of the prior art
Processes for manufacturing semiconductor devices include steps in which semiconductors as substrates undergo processes such as oxidation, diffusion, CVD (Chemical Vapor Deposition) or the like. Vertical thermal processing units are often used for conducting the various processes. A conventional vertical thermal processing unit comprises: a carrier-transferring area where an operator or an automatic conveying mechanism holds and conveys a carrier housing semiconductor wafers, and a loading area where semiconductor wafers in the carrier are transferred to a boat as a holder for a thermal processing which is then loaded into or unloaded from a thermal processing furnace.
In such vertical thermal processing units, it is preferable for a partition (bulkhead) to be provided between the carrier-transferring area which is exposed to the atmosphere and the loading area. The partition allows the loading area to remain clean and prevents a natural oxidation film from forming on the semiconductor wafers. The loading area should also be preferably filled with an inert gas such as nitrogen. A closed-type carrier, whose entrance for semiconductor wafers can be hermetically closed by a lid, should also be preferably used in the vertical thermal processing unit in order to prevent the semiconductor wafers from being contaminated with particles.
A carrier-placing portion having an opening is arranged at the partition between the carrier-transferring area and the loading area. The opening is adapted to become in contact with the carrier on the side of the carrier-transferring area. A door is provided at the opening on the side of the loading area to open and close it. When processing the semiconductor wafers, the lid of the carrier is aligned to be in contact with the carrier-placing portion, and the door and the lid are opened to communicate the interior of the carrier with the loading area. The semiconductor wafers are then conveyed from the interior of the carrier to the boat in the loading area via the opening. The boat is then loaded in the thermal processing furnace to perform the prescribed processes on the semiconductor wafers.
Furthermore, two boats are used as below. One boat of them is placed on the lid which can be vertically elevated to open and close the opening of the thermal processing furnace. The boat is conveyed into the thermal processing furnace. While the opening of the furnace is hermetically closed with the lid and the semiconductor wafers in the boat undergo the thermal processing, other the semiconductor wafers are transferred to the other boat. This improves the throughput of the vertical thermal processing unit.
Vertical thermal processing units for semiconductor wafers having large, for example 300 mm diameters need thermal processing furnaces having large capacities and large openings. Thus, after the thermal processing, considerable heat in the furnace may leak from the opening of the furnace into the loading area while the opening of the furnace is opened, the boat in the furnace is conveyed out, the next boat is conveyed into the furnace and the opening of the furnace is closed with the lid. This may raise the temperature of the loading area and influence instruments in the loading area. In addition, the wasted energy may be so much because the interior of the thermal processing furnace has to be maintained above the predetermined temperature.
The width, the depth and the height of the vertical thermal processing unit are increased accompanying the increase of the diameter of the semiconductor wafer, for example to 300 mm. The space of the floor and the height of the ceiling are also increased for arranging the vertical thermal processing unit. These lead to the increase of the costs for manufacturing and maintaining of the vertical thermal processing unit. Therefore, there is a requirement that the vertical thermal processing unit be miniaturized as much as possible.
In order to improve the ability to process the semiconductor wafers with the vertical thermal processing unit, it is desirable that the boat-placing portion is disposed in the loading area for placing one boat to which semiconductor wafers are transferred while the thermal processing is conducted to the other boat, that the transferring mechanism is disposed in the loading area for transferring the semiconductor wafers between the boat on the boat-placing portion and the carrier at the carrier-placing portion and that the boat-conveying mechanism is disposed in the loading area for conveying the boat between the boat-placing portion and the lid. Having the trace of the boat and the occupying space of the conveying mechanism overlap is effective in miniaturizing the vertical thermal processing unit. However, in that case, there is an undesirable possibility that the boat and the transferring mechanism interference with each other.
In addition, the boat before the thermal processing may be under the lee of the other boat after the thermal processing while the two boats are conveyed between the boat-placing portion and the lid respectively. In that case, the semiconductor wafers in the boat before the thermal processing may be contaminated with particles or gases coming from the other boat after the thermal processing.
Therefore, the object of this invention is to provide a vertical thermal processing unit, which can reduce the undesirable influence caused by the heat leaking from the opening of the furnaces when the lid is taken off from the opening and the boat after the thermal processing is conveyed out.
Another object of this invention is to improve the ability to process the substrates, by making the trace of the boat and the occupying space of the transferring mechanism of the substrates overlap and by laterally evacuating the transferring mechanism from the trace of the boat when the boat is conveyed, in order to prevent the interference of the boat and the transferring mechanism.
Another object of this invention is to achieve the miniaturization of the unit by arranging a notch aligning mechanism along a vertical central line of the carrier-placing portion and by reducing the width and the depth thereof without increasing the height thereof.
Another object of this invention is to provide a boat conveying method where the contamination of the substrates is restricted when the boat is conveyed.
To achieve the above objects, this invention is characterized by a feature wherein a processing unit for a substrate comprises: a vertical thermal processing furnace having a bottom and an opening provided at the bottom, a first lid on which a boat holding substrates in vertical multistairs can be placed and which can open and close the opening of the vertical thermal processing furnace with the boat placed thereon, a boat-placing portion on which the boat and another boat can be placed, a boat conveying mechanism for conveying the two boats alternatively between the boat-placing portion and the first lid, and a second lid for hermetically closing the opening of the vertical thermal processing furnace when the first lid opens the opening but no boat passes through the opening.
According to the feature, the processing unit can effectively reduce the undesirable influence from the opening when the first lid is taken off from the opening and the boat is conveyed out, and can also reduce the wasted energy by preventing the fall of the temperature in the interior of the thermal processing furnace.
Preferably, the second lid is a shutter which can be moved vertically and horizontally with respect to an outside surface of the opening of the vertical thermal processing furnace to open and close the opening.
Preferably, the processing unit further comprises: a carrier-placing portion on which a carrier housing the substrates can be placed, and a transferring mechanism for transferring the substrates between the carrier placed on the carrier-placing portion and the boat placed on the boat-placing portion. In that case, the transference mechanism is preferably retractable in such a manner that the transferring mechanism does not interfere with the boat when the boat is conveyed by the boat conveying mechanism. In that case, the processing unit can be suitably miniaturized.
Preferably, a notch aligning mechanism is arranged along a vertical central line of the carrier-placing portion for aligning notches provided at the substrates. In that case, the width, the depth and the height of the processing unit can be effectively reduced, so that the time for transferring the substrates can be substantially reduced.
Preferably, the boat conveying mechanism includes; a first arm which has a rotational axis and a distal end and which can be vertically elevated and horizontally rotated around the rotational axis, and a second arm which is supported at the distal end in such a manner that the second arm can horizontally rotate around the distal end and which can vertically hold the boat and convey the boat in such a manner that a center of the boat passes over the rotational axis of the first arm, and the boat conveying mechanism can convey the boat in a radial direction with respect to the rotational axis of the first arm by synchronously rotating the first arm and the second arm. In that case, the space for conveying the boat can be minimized, so that the width and the depth of the processing unit can be substantially reduced.
Preferably, the transferring mechanism is movable vertically above the boat conveying mechanism.
Preferably, a ventilating unit is disposed adjacent the boat-placing portion for making a clean gas flow. In that case, the boat-placing portion has preferably a first placing portion and a second placing portion arranged between the first placing portion and the first lid, and the boat conveying mechanism is also preferably operable to convey the boat from the first placing portion to the second placing portion, from the second placing portion to the first lid, and from the first lid to the first placing portion in such a manner that the boat passes under lee of the second placing portion with respect to the clean gas flow made by the ventilating unit.
In addition, this invention is characterized by a feature wherein a processing method for a substrate by using a processing unit for the substrate comprising: a vertical thermal processing furnace having a bottom and an opening provided at the bottom, a first lid on which a boat holding substrates in vertical multistairs can be placed and which can open and close the opening of the vertical thermal processing furnace with the boat placed thereon, a boat-placing portion having a first placing portion and a second placing portion arranged between the first placing portion and the first lid, a second lid for hermetically closing the opening of the vertical thermal processing furnace when the first lid opens the opening but no boat passes through the opening, a carrier-placing portion on which a carrier housing the substrates can be placed, a transferring mechanism for transferring the substrates between the carrier placed on the carrier-placing portion and the boat placed on the boat-placing portion, a ventilating unit disposed adjacent the boat-placing portion for making a clean gas flow, and a boat conveying mechanism for conveying the boat from the first placing portion to the second placing portion, from the second placing portion to the first lid, and from the first lid to the first placing portion in such a manner that the boat passes under lee of the second placing portion with respect to the clean gas flow made by the ventilating unit, said method comprises the steps of: conveying a first boat from the first portion to the second portion by the boat conveying mechanism, conveying a second boat from the first lid to the first portion by the boat conveying mechanism in such a manner that the second boat passes under the lee of the second placing portion with respect to the clean gas flow made by the ventilating unit, and conveying the first boat from the second portion to the first lid by the boat conveying mechanism.
According to the feature, the contamination of the substrates in the boat before the thermal processing is prevented when the boat is conveyed because the boat does not pass under the lee of the other boat after the thermal processing.


An imaging device comprises a photographing lens, a first imaging sensor for taking a subject image formed by the photographing lens, a second image sensor for taking a subject image formed by the photographing lens, an optical path switching section for selectively switching subject light that has passed through the photographing lens to either one of the first image sensor or the second image sensor, a display section for displaying an image taken by the second image sensor, and a display region storage section for storing information representing a region for display on the display section from a region where imaging by the second image sensor is possible. The display section controls the display region based on the information stored in the display region storage section.

1. Field of the Invention
The present invention relates to an imaging device having a plurality of image sensors, and in detail relates to an imaging device having a so-called Live View function for switching images acquired by the plurality of image sensors and displaying on a display device.
2. Description of the Related Art
In a conventional digital camera, observation of a photographic subject was performed using an optical viewfinder, but recently there has been proposed a digital camera that does not have an optical viewfinder, and also a camera that uses output of imaging elements provided for storage of photographic image data together with an optical viewfinder in live view display. For example, Japanese patent Laid open No. 2000-175100 discloses an imaging device having a main image sensor for storing a subject image and a sub image sensor for moving pictures, in which an image is displayed based on output of the sub image sensor.

Imaging device having a display to display images captured by a plurality of image sensors with different display regions


According to a first embodiment of the invention, a Land Grid Array (LGA) socket includes two sets of spring-loaded contacts, the contacts in the first set having an orientation opposite the contacts in the second set. Each set of contacts is positioned such that the total force and total moment of about the socket center by the wiping of the contacts is near zero. According to a second through fourth embodiment of the invention, a rectangular socket may be formed. According to these embodiments, the contacts are divided into four sets. Each set may have a different orientation, arranged so that the total force and moment are near zero.

Semiconductor devices, such as microprocessor dies, are typically mounted in a package and attached to a printed circuit board (PCB), such as a motherboard, through a socket. The socket interfaces with connections on the package to distribute power to and signals from the package (and the semiconductor device) to other devices. Several technologies exist for making connections between the socket and the package, including pin grid array (PGA), ball grid array (BGA), and land grid array (LGA).
LGA sockets include spring-loaded contacts to interface with conductive pads on a packaged semiconductor device. The socket may be soldered onto a motherboard with BGA contacts (e.g., solder balls) under the socket. The spring-loaded contacts create pressure against the pads of the package when the package is inserted into the socket. This pressure assures reliable electric connection between the motherboard and the package. When an LGA contact is pressed the package is inserted into the socket, the tip of the contact wipes a certain distance along the landing pad surface of the package.
FIG. 1 illustrates an LGA socket. The socket 100 includes several contacts divided into two L-shaped regions 102 and 104. The two regions 102 and 104 may include contacts having different orientations (relative to a socket sidewall 106) to obtain enough deflection working range and to avoid electrical shorting. The wiping angle of contacts in each of the two regions 102 and 104 may be represented by the two arrows 108 and 110, respectively. A package is inserted into the socket 100 and the contacts in the regions 102 and 104 make contact with pads on the package to create electrical connections with the semiconductor device encased in the package.
The wiping of the contacts onto the pads creates friction that may twist an installed package. Using some designs, the resulting torque could be as high as 6 lbs-in. This may result in a misalignment of the package during assembly or damage the solder balls under the socket 100. For example, the excessive torque can weaken solder joints connecting the contacts to the socket 100. Alignment pins 112, which attach to the installed package, may be used to reduce the force generated by the contacts, or the socket housing may be constructed from thicker and stronger material. However, these additions may significantly increase the cost of the package 100.


A yoke-trunnion universal joint has a plastic anti-wear coating disposed between the sleeve and trunnion for lubrication, anti wear and absorbing vibration. A combining means combines the plastic anti-wear coating with sleeve or trunnion tightly. The plastic anti-wear coating is made by nylon or polytetrafluoroethylene. The universal joint has a simple structure, long working life, low operating noise and cheap manufacture cost. The most advantage is that the universal joint needs not oil or grease for whole working life. It is an oil or grease free and maintenance free universal joint.

A conventional yoke-trunnion universal joint has a complicated structure between its trunnion ends and sleeves, leaving a large clearance there between. This, in turn, leads to loose construction and reduced strength. Moreover, needle bearings are rather complicated to manufacture, process and assemble and they easily wear out and run with a loud noise. For example, one kind of universal joint has been applied for patent (Chinese application No.: 87013541) that needs filling with lubricating oil to assure uniform and long-term lubrication at all four roller bearings. To meet these needs, two springs are installed in two vertical passages of the yoke-trunnion. Before installation, the length of the springs is greater than the axial size of the passage. After installation, both ends of each spring contact the inner end surface of the corresponding bearing housing. Such universal joint is quite complicated and the springs lead to a loose structure and high assembly difficulty, tend to wear out, run with loud noise and are hard to seal tightly. Oil leakage often occurs so that the universal joint has a shortened service life and is not economical.
U.S. Pat. No. 6,881,151 teaches a universal joint without needle bearings. Its center cub and rod ends are molded as one integral plastic unit, which make the universal joint weak, can not satisfy the requirements for transmission. Therefore, to date it is not popular in the market.
U.S. Pat. No. 6,881,151 teaches a yoke-trunnion universal joint without needle bearings. There is an anti-wear coating between the inner wall surface of a cup and the trunnion. The wear resistant materials include a material selected from the group consisting of chromium nitride, titanium nitride, titanium carbonitride, zirconium nitride, aluminum titanium nitride, titanium aluminum, zirconium nitride, and aluminum oxide. As the anti-wear coating is consisted of metallic compound, it still needs lubrication. Therefore, the yoke-trunnion universal joint without needle bearings still needs complex lubricant system. Further more, the process of making the metallic compound coating is quite complex. The anti-wear coating is easy to separate from the body. The cost for manufacture is high.

Yoke-trunnion universal joint without needle bearings


A method for skin treatment consists of the steps of applying a moisturizing cream to the face, covering the face from the scalp to the neck with a soft light weight moist towel, covering this towel with a plastic sheet, and applying towels soaked in very hot water to the plastic sheet slowly bringing the temperature up to a level comfortable to the client and maintaining this temperature by continuously replacing the hot towels for a period sufficient to perform the skin treatment. The towels and plastic sheet are then removed and the face cleansed of the material drawn from the pores.

1. The Field of the Invention
This invention relates to a method for treating skin to both cleanse and revitalize the skin and, in particular, to a method for treating skin through the use of hot moisture.
2. Background of the Invention
It has long been known that warm moisture is good for the skin and improves the complexion. However, heretofore the methods and apparatus for applying warm moisture to skin have ranged from being uncomfortable to being dangerous. For example, U.S. Pat. No. 686,670 to Fitzgerald shows a device in which live steam is applied directly to the face, head and scalp. Clearly misuse of such a device could cause serious injuries. U.S. Pat. Nos. 1,758,286 to Larson and 2,252,423 to Baddour both show electrically heated masks which are to be placed over the face to supply heat thereto. These devices do not provide the necessary moisture to the skin and could become dangerous if used in conjunction with moisture. U.S. Pat. Nos. 4,614,189 to MacKenzie and 5,879,379 to Mason et al both show facial packs which can be used to apply either heat of cold to facial areas. However, both devices lack the capacity to provide moisture to the treated areas of the skin.


Intelligent monitoring systems and methods for virtual environments are disclosed that understand various components of a virtual infrastructure and how the components interact to provide improved performance analysis to users. In certain examples, a monitoring system assesses the performance of virtual machine(s) in the context of the overall performance of the physical server(s) and the environment in which the virtual machine(s) are running. For instance, the monitoring system can track performance metrics over a determined period of time to view changes to the allocation of resources to virtual machines and their location(s) on physical platforms. Moreover, monitoring systems can utilize past performance information from separate virtual environments to project a performance impact resulting from the migration of a virtual machine from one physical platform to another.

1. Field
Embodiments of the invention relate to monitoring virtual infrastructures and, in particular, to systems and methods for analyzing performance of interrelated objects in a virtual computing environment.
2. Description of the Related Art
Information technology specialists, or system administrators, are responsible for maintaining, managing, protecting and configuring computer systems and their resources. More and more, such maintenance includes ensuring multiple users local and remote access to vast resources of data over a great number of computer applications and systems, including the Internet. Moreover, system administrators are asked to provide access to these highly reliable systems at practically any time of day while ensuring the system's integrity is not threatened by dataflow bottlenecks or excessive overhead.
In addition, many companies now take advantage of virtualization solutions to consolidate several specialized physical servers and workstations into fewer servers running virtual machines. Understanding the performance of a virtual infrastructure, however, is a complex challenge. Performance issues with virtual machines can be based on a variety of factors, including what is occurring within the virtual machine itself, problems with the underlying platform, problems caused by consumption of resource(s) by other virtual servers running on the same underlying platform, and/or problems of priority and allocation of resource(s) to the virtual machine(s). When seeking to ensure performance and maximize uptime, administrators often struggle to understand and monitor the virtual infrastructure, and also to quickly diagnose and resolve problems. Additionally, being able to perform capacity planning and analysis, and in many cases, better understand utilization and costs associated with the virtual infrastructure compounds the challenge.
Moreover, performance statistics captured inside virtual machines for rates (e.g., bytes per second) and resource utilization (e.g., CPU utilization) can often be unreliable. For instance, problems with rate determinations can occur because a clock second inside a virtual image varies in duration and does not match a clock second in the physical or real world. In addition, many conventional monitoring systems are designed to operate strictly on a threshold approach, in which once a predetermined value is reached by a particular measurement, an alarm is triggered. Such monitoring systems oftentimes do not allow for flexibility in analyzing data in a virtual environment and/or do not provide the user with useful information to prevent, or correct, the underlying problem(s) prior to, or after, the alarm is triggered.

Systems and methods for analyzing performance of virtual environments


A suspension assembly transport device is configured for transporting a suspension assembly having hubs on both sides, wherein the device includes attachments for being attached to the hubs, receiving members that support the attachments so that the attachments do not move horizontally, left and right arm members on the bottom of which the receiving members are provided, and that are configured to move the receiving members in the width direction of the vehicle, and a transport mechanism that transports the attachments, the receiving members, and the left and right arm members together.

In vehicle assembly factories, suspension assemblies are preliminarily provided and subsequently assembled to vehicle bodies, in order to improve the work efficiency.
Such suspension assemblies are formed in a work process and conveyed to another process where the assemblies are incorporated into the vehicle bodies. The conveyance of the suspension assemblies requires a suspension assembly carrying apparatus. A know type of the suspension assembly carrying apparatus hangs and carries the suspension assembly (patent literature 1 below).
Patent literature 1 teaches three horizontally extending support shafts for supporting a hub. The hub may be horizontally displaced as the hub is carried. Such horizontal displacement of the hub occurs due to the hub being merely placed on the support shafts, and hence it is necessary to take measures to prevent the horizontal displacement.
However, if the suspension assembly carrying apparatus takes account of the measures to prevent the horizontal displacement, the apparatus may be structurally complicated and hence become heavier.
While meeting the need for lightening the apparatus, a structurally simple, lightweight suspension assembly carrying apparatus is desired.


A porous composite comprising a porous layer containing a calcium phosphate ceramic, and a dense layer formed on part of the porous layer and having a smaller average pore size than that of the porous layer. The porous composite can be produced by (1) introducing a slurry containing a calcium phosphate ceramic/collagen composite and collagen into a molding die having a high thermal conductivity, (2) rapidly freezing and drying the slurry in the molding die, to form a porous body comprising a porous layer and a dense layer formed on the porous layer, (3) cross-linking collagen in the porous body, and (4) removing the dense layer except for a portion thereof on a surface coming into contact with a soft tissue when implanted in a human body, so that the porous layer is exposed.

Because of excellent compatibility with human bone, artificial bone made of apatite can be directly connected to human bone. Accordingly, artificial bone made of apatite has recently been appreciated for effectiveness, finding clinical applications in cosmetic surgery, neurosurgery, plastic surgery, oral surgery, etc. However, apatite is not necessarily completely identical with human bone in terms of mechanical properties and physiological properties. For instance, an artificial bone made of calcium triphosphate, apatite, etc. is harder and more brittle than human bone. Accordingly, it is difficult to form an artificial bone adapted to an implant site, and the artificial bone is easily detached from the implant site. In addition, while human bone repeatedly undergoes metabolism of absorption and regeneration, artificial bone made of apatite is not substantially dissolved or absorbed in a human body, so that the artificial bone remains in a human body semi-permanently, and that human bone does not grow uniformly in the implanted artificial bone. Accordingly, the remaining artificial bone breaks human bone at an interface with the human bone, making it likely to cause bone fracture.
Research has recently become active on artificial bone decomposable in the human body, which is closer in composition to human bone than the artificial apatite bone, and various proposals have been made. For instance, porous bodies having networks comprising hydroxyapatite, to which collagen and other binders, if necessary, are bonded, were proposed (Japanese Patent 3048289 and JP 11-513590A which is a family member of U.S. Pat. No. 5,776,193). Because these porous bodies are decomposable in a human body, human bone is formed in the porous bodies, and the porous bodies per se are absorbed in a human body. Accordingly, these porous bodies can be used for fixation of vertebra, filling of bone defects, repair of fractured bone, and grafting to jaw bone defects, etc.
The use of a porous body containing a calcium phosphate ceramic, particularly porous apatite having properties close to those of human bone, as a material to be implanted in a living body, provides little likelihood of being rejected by the host, and enjoys a short recuperation period because of high bone-forming capability. Cells participating in the formation of bone are induced in an artificial bone implanted in a bone defect portion, so that human bone grows while the implanted artificial bone is absorbed by the host, resulting in the replacement of the artificial bone by the grown bone tissue.
It has been found, however, that when the implanted artificial bone comes into contact with a soft tissue such as a gum, a subcutaneous tissue, muscle, an internal organ, etc., cells, fibroblasts, etc. in the soft tissue enter into the porous artificial bone, hindering the growth of a bone tissue.

Porous composite containing calcium phosphate and process for producing the same

National Institute for Materials Science


A method for checking heat exchanger tubes of metallic material includes drying inner surfaces of the heat exchanger tubes. A compressed air-abrasive mixture is then led through the heat exchanger tubes. An eddy-current integrity test of the heat exchanger tubes is then performed.

FIELD OF THE INVENTION
The invention relates to a method for checking heat exchanger tubes made of metallic material.
Heat exchangers and especially heat exchanger tubes disposed in the heat exchanger are regularly checked with nondestructive test methods as to their condition. One of those test methods is the eddy-current integrity test which is known as such. That test makes it possible to recognize even very minor defects or damages in a tube, for example cracks, which penetrate only slightly into the tube wall and which cannot yet cause a leak. It is necessary to recognize such small cracks at an early stage, especially for heat exchangers which are part of a nuclear power plant, in order to prevent a leak.
It was found that the accuracy of the defect detection in the eddy-current integrity test decreases during the course of the operating time. Furthermore, it was found that in the course of the operating time the heat exchange also decreases.

Checking heat exchanger tubes with an eddy-current integrity test