Sample records for autoantibody-based immunotoxin specific

  1. A Human Recombinant Autoantibody-Based Immunotoxin Specific for the Fetal Acetylcholine Receptor Inhibits Rhabdomyosarcoma Growth In Vitro and in a Murine Transplantation Model

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    A. Marx


    Full Text Available Rhabdomyosarcoma (RMS is the most common malignant soft tissue tumor in children and is highly resistant to all forms of treatment currently available once metastasis or relapse has commenced. As it has recently been determined that the acetylcholine receptor (AChR γ-subunit, which defines the fetal AChR (fAChR isoform, is almost exclusively expressed in RMS post partum, we recombinantly fused a single chain variable fragment (scFv derived from a fully human anti-fAChR Fab-fragment to Pseudomonas exotoxin A to generate an anti-fAChR immunotoxin (scFv35-ETA. While scFv35-ETA had no damaging effect on fAChR-negative control cell lines, it killed human embryonic and alveolar RMS cell lines in vitro and delayed RMS development in a murine transplantation model. These results indicate that scFv35-ETA may be a valuable new therapeutic tool as well as a relevant step towards the development of a fully human immunotoxin directed against RMS. Moreover, as approximately 20% of metastatic malignant melanomas (MMs display rhabdoid features including the expression of fAChR, the immunotoxin we developed may also prove to be of significant use in the treatment of these more common and most often fatal neoplasms.

  2. Novel CD7-specific nanobody-based immunotoxins potently enhanced apoptosis of CD7-positive malignant cells (United States)

    Tang, Jinle; Li, Jialu; Zhu, Xuejun; Yu, Yuan; Chen, Dan; Yuan, Lei; Gu, Zhenyang; Zhang, Xingding; Qi, Lin; Gong, Zhishu; Jiang, Pengjun; Yu, Juhua; Meng, Huimin; An, Gangli


    Various CD7-targeting immunotoxins have been tested for its potential in treating CD7+ malignant patients but none of those immunotoxins was approved clinically because of lacking enough efficacy and safety. Here we successfully constructed the monovalent and bivalent CD7 nanobody-based immunotoxins PG001 and PG002, both conjugated with a truncated derivative of Pseudomonas exotoxin A respectively. The prokaryotic system expressed immunotoxins not only maintained their binding specificity for CD7-positive cells with a Kd of 16.74 nM and 3.6 nM for PG001 and PG002 respectively, but also efficiently promoted antigen-restricted apoptosis of the CD7-positive leukemia cell lines Jurkat and CEM, and primary T-cell acute lymphoblastic leukemia (T-ALL) and acute myeloid leukemia (AML) cells with an in vitro cytotoxic activity (EC50) in the range of 23-30 pM for PG002. In NOD/SCID mice transplanted with CEM cells, PG001 and PG002 prevented engraftment of the cells and markedly prolonged mouse survival. Owing to the efficient antigen-restricted anti-leukemic activity of PG002, this CD7 nanobody-based immunotoxin exhibited a superior anti-CD7 positive malignancies activity than previously reported immunotoxins, and may represent a promising therapeutic strategy in treating CD7-positive leukemia and lymphoma, which still remain a significant clinical challenge. PMID:27083001

  3. A CSPG4-specific immunotoxin kills rhabdomyosarcoma cells and binds to primary tumor tissues. (United States)

    Brehm, Hannes; Niesen, Judith; Mladenov, Radoslav; Stein, Christoph; Pardo, Alessa; Fey, Georg; Helfrich, Wijnand; Fischer, Rainer; Gattenlöhner, Stefan; Barth, Stefan


    The treatment of rhabdomyosarcoma (RMS) remains challenging, with metastatic and alveolar RMS offering a particularly poor prognosis. Therefore, the identification and evaluation of novel antigens, which are suitable targets for immunotherapy, is one attractive possibility to improve the treatment of this disease. Here we show that chondroitin sulfate proteoglycan 4 (CSPG4) is expressed on RMS cell lines and RMS patient material. We evaluated the immunotoxin (IT) αMCSP-ETA', which specifically recognizes CSPG4 on the RMS cell lines RD, FL-OH1, TE-671 and Rh30. It is internalized rapidly, induces apoptosis and thus kills RMS cells selectively. We also demonstrate the specific binding of this IT to RMS primary tumor material from three different patients.

  4. Immunotoxins and Cancer Therapy

    Institute of Scientific and Technical Information of China (English)

    ZhengLi; TaoYu; PingZhao; JieMa


    In the past decade, an increased amount of clinically-oriented research involving immunotoxins has been published. Immunotoxins are a group of artificially-made cytotoxic molecules targeting cancer cells. These molecules composed of a targeting moiety, such as a ligand or an antibody, linked to toxin moiety, which is a toxin with either truncated or deleted cell-binding domain that prevents it from binding to normal cells. Immunotoxins can be divided into two categories: chemically conjugated immunotoxins and recombinant ones. The immunotoxins of the first category have shown limited efficacy in clinical trials in patients with hematologic malignancies and solid tumors. Within the last few years, single-chain immunotoxins provide enhanced therapeutic efficacy over conjugated forms and result in improved antitumor activity. In this review, we briefly illustrate the design of the immunotoxins and their applications in clinical trials. Cellular & Molecular Immunology. 2005;2(2):106-112.

  5. Immunotoxins and Cancer Therapy

    Institute of Scientific and Technical Information of China (English)

    Zheng Li; Tao Yu; Ping Zhao; Jie Ma


    In the past decade, an increased amount of clinically-oriented research involving immunotoxins has been published.Immunotoxins are a group of artificially-made cytotoxic molecules targeting cancer cells. These molecules composed of a targeting moiety, such as a ligand or an antibody, linked to toxin moiety, which is a toxin with either truncated or deleted cell-binding domain that prevents it from binding to normal cells. Immunotoxins can be divided into two categories: chemically conjugated immunotoxins and recombinant ones. The immunotoxins of the first category have shown limited efficacy in clinical trials in patients with hematologic malignancies and solid tumors. Within the last few years, single-chain immunotoxins provide enhanced therapeutic efficacy over conjugated forms and result in improved antitumor activity. In this review, we briefly illustrate the design of the immunotoxins and their applications in clinical trials. Cellular & Molecular Immunology. 2005;2(2):106-112.

  6. Immunotoxins: The Role of the Toxin

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    David FitzGerald


    Full Text Available Immunotoxins are antibody-toxin bifunctional molecules that rely on intracellular toxin action to kill target cells. Target specificity is determined via the binding attributes of the chosen antibody. Mostly, but not exclusively, immunotoxins are purpose-built to kill cancer cells as part of novel treatment approaches. Other applications for immunotoxins include immune regulation and the treatment of viral or parasitic diseases. Here we discuss the utility of protein toxins, of both bacterial and plant origin, joined to antibodies for targeting cancer cells. Finally, while clinical goals are focused on the development of novel cancer treatments, much has been learned about toxin action and intracellular pathways. Thus toxins are considered both medicines for treating human disease and probes of cellular function.

  7. The future of antiviral immunotoxins

    DEFF Research Database (Denmark)

    Spiess, K.; Høy Jakobsen, Mette; Kledal, Thomas N;


    There is a constant need for new therapeutic interventions in a wide range of infectious diseases. Over the past few years, the immunotoxins have entered the stage as promising antiviral treatments. Immunotoxins have been extensively explored in cancer treatment and have achieved FDA approval...

  8. Attempts to express the A1-GMCSF immunotoxin in the baculovirus expression vector system.


    Jahanian-Najafabadi, Ali; Bouzari, Saeid; Oloomi, Mana; Roudkenar, Mehryar Habibi; Mayr, Lorenz M


    International audience; Immunotoxins are fusion proteins consisting of two elements, a targeting and a toxin moiety, and are designed for specific elimination of tumor cells. Previously we expressed a recombinant fusion protein consisting of the toxic fragment of Shiga toxin (A1) and GMCSF (A1-GMCSF) in Escherichia coli, and evaluated its cytotoxic properties in acute myeloid leukemia and colon carcinoma cell lines. In view of the specific cytotoxic effects of this immunotoxin, further detail...

  9. Immunotoxin BAC5-CT treated nasopharyngeal carcinoma

    Institute of Scientific and Technical Information of China (English)


    In this study, immunotoxin (IT) was prepared by conjugating BAC5 and CT with SPDP. The effects of IT on NPC and its mechanisms were explored using double labeled with radioactive nuclides, immunography and electron microscope technique in vivo and in vitro. The specific concentration of BAC5 in the tumor area showed. The radioactivity rate of tumor/nontumor (T/NT) was up to 10.26. IT had cytotoxic effects both on the cultured CNE-2 cell line and tumor multicell spheroides. In vivo, the preliminary result indicated that IT also had a inhibitory action on the nude mice models bearing human NPC (Reported in another article). Under electron microscope, the necrosis and apoptosis of tumor cells were found. The membranes of most tumor cells were found intacted not or corrosined, some of them had the character of apoptosis, including reduce of tumor cells membrane villi, condensation of cytoplasm and pyknosis or cleavage of nuclear. There were many of apoptosis bodies, which were occasionally phagocytosed by tumor cells. The infiltration of immunocytoes in tumor tissue could be seen. The results indicated that BAC5 can specifically combine with NPC cells and BAC5-CT has the inhibitory effect on NPC in vitro and in vivo, mechanism of which may be related to the effects that ‘warhead' CT dissolute the membrane of tumor cells directly, or/and IT promote the infiltration of immunocytoes so as to induce the apoptosis of tumor cell.

  10. Abrin immunotoxin: targeted cytotoxicity and intracellular trafficking pathway.

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    Sudarshan Gadadhar

    Full Text Available BACKGROUND: Immunotherapy is fast emerging as one of the leading modes of treatment of cancer, in combination with chemotherapy and radiation. Use of immunotoxins, proteins bearing a cell-surface receptor-specific antibody conjugated to a toxin, enhances the efficacy of cancer treatment. The toxin Abrin, isolated from the Abrus precatorius plant, is a type II ribosome inactivating protein, has a catalytic efficiency higher than any other toxin belonging to this class of proteins but has not been exploited much for use in targeted therapy. METHODS: Protein synthesis assay using (3[H] L-leucine incorporation; construction and purification of immunotoxin; study of cell death using flow cytometry; confocal scanning microscopy and sub-cellular fractionation with immunoblot analysis of localization of proteins. RESULTS: We used the recombinant A chain of abrin to conjugate to antibodies raised against the human gonadotropin releasing hormone receptor. The conjugate inhibited protein synthesis and also induced cell death specifically in cells expressing the receptor. The conjugate exhibited differences in the kinetics of inhibition of protein synthesis, in comparison to abrin, and this was attributed to differences in internalization and trafficking of the conjugate within the cells. Moreover, observations of sequestration of the A chain into the nucleus of cells treated with abrin but not in cells treated with the conjugate reveal a novel pathway for the movement of the conjugate in the cells. CONCLUSIONS: This is one of the first reports on nuclear localization of abrin, a type II RIP. The immunotoxin mAb F1G4-rABRa-A, generated in our laboratory, inhibits protein synthesis specifically on cells expressing the gonadotropin releasing hormone receptor and the pathway of internalization of the protein is distinct from that seen for abrin.

  11. Efficiency of immunotoxin cytotoxicity is modulated by the intracellular itinerary.

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    Lori L Tortorella

    Full Text Available Pseudomonas exotoxin-based immunotoxins, including LMB-2 (antiTac(F(v-PE38, are proposed to traffic to the trans-Golgi network (TGN and move by a retrograde pathway to the endoplasmic reticulum, where they undergo translocation to the cytoplasm, a step that is essential for cytotoxicity. The retrograde transport pathways used by LMB-2 are not completely understood, so it is unclear if transit through specific organelles is critical for maximal cytotoxic activity. In this study, we used Chinese hamster ovary (CHO cell lines that express chimeric constructs of CD25, the Tac antigen, attached to the cytoplasmic domain of the TGN-targeted transmembrane proteins, TGN38 and furin. These chimeras are both targeted to the TGN, but the itineraries they follow are quite different. LMB-2 was incubated with the two cell lines, and the efficiency of cell killing was determined using cell viability and cytotoxicity assays. LMB-2 that is targeted through the endocytic recycling compartment to the TGN via Tac-TGN38 kills the cells more efficiently than immunotoxins delivered through the late endosomes by Tac-furin. Although the processing to the 37 kDa active fragment was more efficient in Tac-furin cells than in Tac-TGN38 cells, this was not associated with enhanced cytotoxicity - presumably because the toxin was also degraded more rapidly in these cells. These data indicate that trafficking through specific organelles is an important factor modulating toxicity by LMB-2.

  12. Immunotoxin Therapies for the Treatment of Epidermal Growth Factor Receptor-Dependent Cancers

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    Nathan Simon


    Full Text Available Many epithelial cancers rely on enhanced expression of the epidermal growth factor receptor (EGFR to drive proliferation and survival pathways. Development of therapeutics to target EGFR signaling has been of high importance, and multiple examples have been approved for human use. However, many of the current small molecule or antibody-based therapeutics are of limited effectiveness due to the inevitable development of resistance and toxicity to normal tissues. Recombinant immunotoxins are therapeutic molecules consisting of an antibody or receptor ligand joined to a protein cytotoxin, combining the specific targeting of a cancer-expressed receptor with the potent cell killing of cytotoxic enzymes. Over the decades, many bacterial- or plant-based immunotoxins have been developed with the goal of targeting the broad range of cancers reliant upon EGFR overexpression. Many examples demonstrate excellent anti-cancer properties in preclinical development, and several EGFR-targeted immunotoxins have progressed to human trials. This review summarizes much of the past and current work in the development of immunotoxins for targeting EGFR-driven cancers.

  13. Preliminary study on immunotoxin for the prevention of Schistosomiasis japonica

    Institute of Scientific and Technical Information of China (English)


    @@To investigate the effects of immunotoxin (bio-missile) on the prevention of schistosomiasis. The monoclonal antibody NP11-4, located in out-layer membrane of adult worm, membrane of cercariae, membrane of schistosomula, shell of egg and membrane of miracidium in egg, was combined with artesunate (produced by Guilin Pharmaceutical Factory of China) by chemical method to fabricate immunotoxin.

  14. Glypican-3 Targeting Immunotoxins for the Treatment of Liver Cancer (United States)

    Fleming, Bryan D.; Ho, Mitchell


    Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer, yet no effective therapeutics exist. This review provides an overview of the recent development of recombinant immunotoxins for the treatment of glypican-3 (GPC3) expressing HCC. GPC3 is a cell surface heparan sulfate proteoglycan that is overexpressed in HCC, but is absent from normal adult human tissues. Treatment of HCC with anti-GPC3 immunotoxins represents a new therapeutic option. Using phage display and hybridoma technologies, three high affinity antibodies (HN3, HS20 and YP7) have been generated against GPC3. Two of these antibodies (HN3 and HS20) have demonstrated the ability to inhibit Wnt/Yap signaling, leading to a reduction in liver cancer cell proliferation. By combining the HN3 antibody capable of inhibiting Wnt/Yap signaling with the protein synthesis inhibitory domain of the Pseudomonas exotoxin, a recombinant immunotoxin that exhibits a dual inhibitory mechanism was generated. This immunotoxin was found to be highly effective in the treatment of human HCCs in mouse xenograft models. Engineering of the toxin fragment to reduce the level of immunogenicity is currently being explored. The development of immunotoxins provides opportunities for novel liver cancer therapies. PMID:27669301

  15. Glypican-3 Targeting Immunotoxins for the Treatment of Liver Cancer

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    Bryan D. Fleming


    Full Text Available Hepatocellular carcinoma (HCC is the most common form of primary liver cancer, yet no effective therapeutics exist. This review provides an overview of the recent development of recombinant immunotoxins for the treatment of glypican-3 (GPC3 expressing HCC. GPC3 is a cell surface heparan sulfate proteoglycan that is overexpressed in HCC, but is absent from normal adult human tissues. Treatment of HCC with anti-GPC3 immunotoxins represents a new therapeutic option. Using phage display and hybridoma technologies, three high affinity antibodies (HN3, HS20 and YP7 have been generated against GPC3. Two of these antibodies (HN3 and HS20 have demonstrated the ability to inhibit Wnt/Yap signaling, leading to a reduction in liver cancer cell proliferation. By combining the HN3 antibody capable of inhibiting Wnt/Yap signaling with the protein synthesis inhibitory domain of the Pseudomonas exotoxin, a recombinant immunotoxin that exhibits a dual inhibitory mechanism was generated. This immunotoxin was found to be highly effective in the treatment of human HCCs in mouse xenograft models. Engineering of the toxin fragment to reduce the level of immunogenicity is currently being explored. The development of immunotoxins provides opportunities for novel liver cancer therapies.

  16. The current status of immunotoxins: an overview of experimental and clinical studies as presented at the Third International Symposium on Immunotoxins. (United States)

    Uckun, F M; Frankel, A


    The Third International Symposium on Immunotoxins was held on June 19-21, 1992 in Orlando, Florida. This symposium was sponsored by NATO, NIH, Pierce Chemical Company, Walt Disney Cancer Institute at Florida Hospital, Duke Comprehensive Cancer Center, Xoma, Immunogen, Seragen, Bristol-Myers Squibb, Chiron, Ortho Biotech, Upjohn, Merck Sharp & Dohme Research Laboratories, Abbot Laboratories, Lilly Research Laboratories, and Evans & Sutherland. The Pierce Immunotoxin Award which recognizes outstanding contributions to immunotoxin research and development, was presented to Drs David FitzGerald, Fatih Uckun, David Eisenberg, and Ira Wool, for their contributions to the immunotoxin field.

  17. Cloning and Expression of Ontak Immunotoxin Using Intein Tag

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    SA Moosavizadeh


    Full Text Available Introduction: Inteins (INT are internal parts of a number of proteins in yeast and some other unicellular eukaryotes, which can be separated from the immature protein during protein splicing process. After identifying the mechanism of intein action, applications of these sequences are be considered in the single- step purification of recombinant proteins and different intein tags were developed. The most important advantage of using intein tags in purification of recombinant proteins than other affinity tags is no requirement of expensive protease enzymes and following additional steps to remove protease that make intein tags economically are considered more important. In the present study, denileukin diftitox immunotoxin (brand name Ontak, be fused with an intein tag and it was inserted in pTXB1 plasmid. Methods: In this study, with respect to multiple cloning sites (MCS of pTXB1, specific primers were designed. Polymerase Chain Reaction (PCR was performed and encoding sequence of ONTAK was cloned using restriction sites of NdeI and SapI. Recombinant vector (PTX-IDZ was transformed into E. coli strain ER2566 and expression of gene was studied. Results: The accuracy of recombinant construct was confirmed by PCR and enzymatic digestion. The produced recombinant proteins were confirmed by SDS-PAGE and Western blotting. Conclusion: Restriction site of SapI guarantees no additional residues incorporate in primary protein sequence. Also, the expression of this construct was analyzed in compare with fused protein to poly-His tag. According to the appropriate expression of fused protein in both constructs it was expected that one step- purification of considered drug protein will be success in the following steps.

  18. Initial characterization of an immunotoxin constructed from domains II and III of cholera exotoxin. (United States)

    Sarnovsky, Robert; Tendler, Tara; Makowski, Matheusz; Kiley, Maureen; Antignani, Antonella; Traini, Roberta; Zhang, Jingli; Hassan, Raffit; FitzGerald, David J


    Immunotoxins are antibody-toxin fusion proteins under development as cancer therapeutics. In early clinical trials, immunotoxins constructed with domains II and III of Pseudomonas exotoxin (termed PE38), have produced a high rate of complete remissions in Hairy Cell Leukemia and objective responses in other malignancies. Cholera exotoxin (also known as cholix toxin) has a very similar three-dimensional structure to Pseudomonas exotoxin (PE) and when domains II and III of each are compared at the primary sequence level, they are 36% identical and 50% similar. Here we report on the construction and activity of an immunotoxin made with domains II and III of cholera exotoxin (here termed CET40). In cell viability assays, the CET40 immunotoxin was equipotent to tenfold less active compared to a PE-based immunotoxin made with the same single-chain Fv. A major limitation of toxin-based immunotoxins is the development of neutralizing antibodies to the toxin portion of the immunotoxin. Because of structure and sequence similarities, we evaluated a CET40 immunotoxin for the presence of PE-related epitopes. In western blots, three-of-three anti-PE antibody preparations failed to react with the CET40 immunotoxin. More importantly, in neutralization studies neither these antibodies nor those from patients with neutralizing titers to PE38, neutralized the CET40-immunotoxin. We propose that the use of modular components such as antibody Fvs and toxin domains will allow a greater flexibility in how these agents are designed and deployed including the sequential administration of a second immunotoxin after patients have developed neutralizing antibodies to the first.

  19. Cerebellar Purkinje cells incorporate immunoglobulins and immunotoxins in vitro: implications for human neurological disease and immunotherapeutics

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    Rose John W


    Full Text Available Abstract Background Immunoglobulin G (IgG antibodies reactive with intracellular neuronal proteins have been described in paraneoplastic and other autoimmune disorders. Because neurons have been thought impermeable to immunoglobulins, however, such antibodies have been considered unable to enter neurons and bind to their specific antigens during life. Cerebellar Purkinje cells - an important target in paraneoplastic and other autoimmune diseases - have been shown in experimental animals to incorporate a number of molecules from cerebrospinal fluid. IgG has also been detected in Purkinje cells studied post mortem. Despite the possible significance of these findings for human disease, immunoglobulin uptake by Purkinje cells has not been demonstrated in living tissue or studied systematically. Methods To assess Purkinje cell uptake of immunoglobulins, organotypic cultures of rat cerebellum incubated with rat IgGs, human IgG, fluorescein-conjugated IgG, and rat IgM were studied by confocal microscopy in real time and following fixation. An IgG-daunorubicin immunotoxin was used to determine whether conjugation of pharmacological agents to IgG could be used to achieve Purkinje cell-specific drug delivery. Results IgG uptake was detected in Purkinje cell processes after 4 hours of incubation and in Purkinje cell cytoplasm and nuclei by 24-48 hours. Uptake could be followed in real time using IgG-fluorochrome conjugates. Purkinje cells also incorporated IgM. Intracellular immunoglobulin did not affect Purkinje cell viability, and Purkinje cells cleared intracellular IgG or IgM within 24-48 hours after transfer to media lacking immunoglobulins. The IgG-daunomycin immunotoxin was also rapidly incorporated into Purkinje cells and caused extensive, cell-specific death within 8 hours. Purkinje cell death was not produced by unconjugated daunorubicin or control IgG. Conclusion Purkinje cells in rat organotypic cultures incorporate and clear host (rat and non

  20. The development and characterization of a human mesothelioma in vitro 3D model to investigate immunotoxin therapy.

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    Xinran Xiang

    Full Text Available BACKGROUND: Tumor microenvironments present significant barriers to penetration by antibodies and immunoconjugates. Tumor microenvironments, however, are difficult to study in vitro. Cells cultured as monolayers exhibit less resistance to therapy than those grown in vivo and an alternative research model more representative of the in vivo tumor is more desirable. SS1P is an immunotoxin composed of the Fv portion of a mesothelin-specific antibody fused to a bacterial toxin that is presently undergoing clinical trials in mesothelioma. METHODOLOGY/PRINCIPAL FINDINGS: Here, we examined how the tumor microenvironment affects the penetration and killing activity of SS1P in a new three-dimensional (3D spheroid model cultured in vitro using the human mesothelioma cell line (NCI-H226 and two primary cell lines isolated from the ascites of malignant mesothelioma patients. Mesothelioma cells grown as monolayers or as spheroids expressed comparable levels of mesothelin; however, spheroids were at least 100 times less affected by SS1P. To understand this disparity in cytotoxicity, we made fluorescence-labeled SS1P molecules and used confocal microscopy to examine the time course of SS1P penetration within spheroids. The penetration was limited after 4 hours. Interestingly, we found a significant increase in the number of tight junctions in the core area of spheroids by electron microscopy. Expression of E-Cadherin, a protein involved in the assembly and sealing of tight junctions and highly expressed in malignant mesothelioma, was found significantly increased in spheroids as compared to monolayers. Moreover, we found that siRNA silencing and antibody inhibition targeting E-Cadherin could enhance SS1P immunotoxin therapy in vitro. CONCLUSION/SIGNIFICANCE: This work is one of the first to investigate immunotoxins in 3D tumor spheroids in vitro. This initial description of an in vitro tumor model may offer a simple and more representative model of in vivo

  1. Targeted Anticancer Immunotoxins and Cytotoxic Agents with Direct Killing Moieties

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    Koji Kawakami


    Full Text Available Despite the progress of the bioinformatics approach to characterize cell-surface antigens and receptors on tumor cells, it remains difficult to generate novel cancer vaccines or neutralizing monoclonal antibody therapeutics. Among targeted cancer therapeutics, biologicals with targetable antibodies or ligands conjugated or fused to toxins or chemicals for direct cell-killing ability have been developed over the last 2 decades. These conjugated or fused chimeric proteins are termed immunotoxins or cytotoxic agents. Two agents, DAB389IL-2 (ONTAKTM targeting the interleukin-2 receptor and CD33-calicheamicin (Mylotarg®, have been approved by the FDA for cutaneous T-cell lymphoma (CTCL and relapsed acute myeloid leukemia (AML, respectively. Such targetable agents, including RFB4(dsFv-PE38 (BL22, IL13-PE38QQR, and Tf-CRM107, are being tested in clinical trials. Several agents using unique technology such as a cleavable adapter or immunoliposomes with antibodies are also in the preclinical stage. This review summarizes the generation, mechanism, and development of these agents. In addition, possible future directions of this therapeutic approach are discussed.

  2. Immunotoxin targeting glypican-3 regresses liver cancer via dual inhibition of Wnt signalling and protein synthesis. (United States)

    Gao, Wei; Tang, Zhewei; Zhang, Yi-Fan; Feng, Mingqian; Qian, Min; Dimitrov, Dimiter S; Ho, Mitchell


    Glypican-3 is a cell surface glycoprotein that associates with Wnt in liver cancer. We develop two antibodies targeting glypican-3, HN3 and YP7. The first antibody recognizes a functional epitope and inhibits Wnt signalling, whereas the second antibody recognizes a C-terminal epitope but does not inhibit Wnt signalling. Both are fused to a fragment of Pseudomonas exotoxin A (PE38) to create immunotoxins. Interestingly, the immunotoxin based on HN3 (HN3-PE38) has superior antitumor activity as compared with YP7 (YP7-PE38) both in vitro and in vivo. Intravenous administration of HN3-PE38 alone, or in combination with chemotherapy, induces regression of Hep3B and HepG2 liver tumour xenografts in mice. This study establishes glypican-3 as a promising candidate for immunotoxin-based liver cancer therapy. Our results demonstrate immunotoxin-induced tumour regression via dual mechanisms: inactivation of cancer signalling via the antibody and inhibition of protein synthesis via the toxin.

  3. CD64-directed immunotoxin inhibits arthritis in a novel CD64 transgenic rat model

    NARCIS (Netherlands)

    van Vuuren, AJ; van Roon, JAG; Walraven, [No Value; Stuij, [No Value; Harmsen, MC; McLaughlin, PMJ; de Winkel, JGJV; Thepen, T


    Macrophages are known to play a key role during inflammation in rheumatoid arthritis (RA). Inflammatory macrophages have increased expression of CD64, the high-affinity receptor for IgG. Targeting this receptor through a CD64-directed immunotoxin, composed of an Ab against CD64 and Ricin A, results

  4. Combination treatments with the PKC inhibitor, enzastaurin, enhance the cytotoxicity of the anti-mesothelin immunotoxin, SS1P.

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    Abid R Mattoo

    Full Text Available Activated protein kinase C (PKC contributes to tumor survival and proliferation, provoking the development of inhibitory agents as potential cancer therapeutics. Immunotoxins are antibody-based recombinant proteins that employ antibody fragments for cancer targeting and bacterial toxins as the cytotoxic agent. Pseudomonas exotoxin-based immunotoxins act via the ADP-ribosylation of EF2 leading to the enzymatic inhibition of protein synthesis. Combining PKC inhibitors with the immunotoxin SS1P, targeted to surface mesothelin, was undertaken to explore possible therapeutic strategies. Enzastaurin but not two other PKC inhibitors combined with SS1P to produce synergistic cell death via apoptosis. Mechanistic insights of the synergistic killing centered on the complete loss of the prosurvival Bcl2 protein, Mcl-1, the loss of AKT and the activation of caspase 3/7. Synergy was most evident when cells exhibited resistance to the immunotoxin alone. Further, because PKC inhibition by itself was not sufficient to enhance SS1P action, enzastaurin must target other kinases that are involved in the immunotoxin pathway.

  5. An anti-CD45RO immunotoxin eliminates T cells latently infected with HIV-1 in vitro


    McCoig, Cynthia; Dyke, Gregory; Chou, Chin-Sheng; Picker, Louis J.; Ramilo,Octavio; Vitetta, Ellen S.


    Despite the success of highly active antiretroviral therapy (HAART) in lowering circulating HIV-1 to undetectable levels in most infected individuals, several studies have documented the presence of a small reservoir of latently infected cells in HAART patients, the majority of which are CD45RO+ memory T cells. We previously have demonstrated that latently infected, replication-competent cells can be generated in vitro after eliminating CD25+ cells with an immunotoxin (IT). The present study ...

  6. A CSPG4-specific immunotoxin kills rhabdomyosarcoma cells and binds to primary tumor tissues

    NARCIS (Netherlands)

    Brehm, Hannes; Niesen, Judith; Mladenov, Radoslav; Stein, Christoph; Pardo, Alessa; Fey, Georg; Helfrich, Wijnand; Fischer, Rainer; Gattenloehner, Stefan; Barth, Stefan


    The treatment of rhabdomyosarcoma (RMS) remains challenging, with metastatic and alveolar RMS offering a particularly poor prognosis. Therefore, the identification and evaluation of novel antigens, which are suitable targets for immunotherapy, is one attractive possibility to improve the treatment o

  7. Cytotoxicity of an ebulin l-anti-human CD105 immunotoxin on mouse fibroblasts (L929) and rat myoblasts (L6E9) cells expressing human CD105. (United States)

    Benítez, Jorge; Ferreras, J Miguel; Muñoz, Raquel; Arias, Yolanda; Iglesias, Rosario; Córdoba-Díaz, Manuel; del Villar, Rosario; Girbés, Tomás


    Tumour growth is characterised by the formation of a fine vessel network or neovasculature which nourishes tumour cells. Two kinds of novel anti-angiogenic therapies are based on the prevention of vessels growth and on the destruction of those vessels already formed. We report here on the design and construction of a novel immunotoxin formed with the non-toxic type II ribosome-inactivating protein ebulin l and the mouse anti-human CD105 monoclonal antibody 44G4. The 44G4-ebulin immunotoxin was formed by covalent linking of both proteins with N-succinimidyl-3-(2-pyridyldithio)propionate (SPDP) and was purified by chromatography on Superdex 200 HiLoad. The analysis of the anti-ribosomal effects in a cell-free translation system indicated that conjugation does not affect the activity of ebulin l. The immunotoxin displays cytotoxicity with nanomolar IC50 values on human CD105+ cells like the mouse fibroblasts L929 cells transfected with the short form of human CD105 and the rat myoblasts L6E9 transfected with the long form of human CD105. In contrast, cells lacking human CD105 were 2-2.5 logs less sensitive to the immunotoxin. Free ebulin displays IC50 values in the range 10(-6) M. Since CD105 is being considered as a potential target for the anti-vascular therapy of tumours, the present immunotoxin could be a promising tool for the anticancer therapy, especially due to the very low in vivo toxicity of ebulin l as compared ricin and other toxins used for immunotoxins.

  8. Application of anti-CD103 immunotoxin for saving islet allograft in context of transplantation

    Institute of Scientific and Technical Information of China (English)

    ZHANG Lei; Gregg A. Hadley


    Background Previous studies using knockout mice document a key role for the integrin CD103 in promoting organ allograft rejection and graft-versus-host disease. However, a determination of whether blockade of the CD103 pathway represents a viable therapeutic strategy for intervention in these processes has proven problematic due to the lack of reagents that efficiently deplete CD103+ cells from wild type hosts. To circumvent this problem, in the present study, we invented an anti-CD103 immunotoxin (M290-SAP). We investigated whether M290-SAP has capacity to eliminate CD103-expressing cells in vivo and protect transplanted islets from destroying by host immune cells.Methods Flow cytometry was used to analyze the efficacy of M290-SAP in depleting CD103-expressing cells in vivo.Then using allogenic islet transplantation models as well as NOD mice with recent onset type 1 diabetes, the therapeutic efficacy of CD103-expressing cell depletion was addressed.Results M290-SAP dramatically reduces the frequency and absolute numbers of CD103-expressing leukocytes in peripheral lymphatic tissues of treated mice. Balb/c islets transplanted into streptozotocin-induced diabetic C57BL/6 mice under single M290-SAP treatment showed an indefinite survival time compared with untreated mice, M290-treated mice and IgG-SAP treated mice (mean survival time, >100 days vs. <20 days). C57BL/6 islets transplanted into hyperglycemic NOD mice under single M290-SAP treatment showed a pronounced delay in allograft rejection compared with untreated mice (mean survival time 12-13 days vs. <7 days). Immunological analysis of mice with long-term islet allograft survival revealed an obvious atrophy thymus and severe downregulation of alloimmunity of CD8 subpopulation response to allogenic stimulation.Conclusion Regardless of the underlying mechanisms, these data document that depletion of CD103-expressing cells represents a viable strategy for therapeutic intervention in islet allograft

  9. Cytotoxic effect of the immunotoxin constructed of the ribosome-inactivating protein curcin and the monoclonal antibody against Her2 receptor on tumor cells. (United States)

    Jaramillo-Quintero, Lidia Patricia; Contis Montes de Oca, Arturo; Romero Rojas, Andrés; Rojas-Hernández, Saúl; Campos-Rodríguez, Rafael; Martínez-Ayala, Alma Leticia


    The toxicity of the curcin on cancer cells allows to consider this protein as the toxic component of an immunotoxin directed to Her2, which is associated with cancer. Reductive amination was proposed to conjugate curcin and an anti-Her2; the binding was tested using Polyacrylamide gel electrophoresis, western blot, and immunocytochemistry. The in vitro cytotoxicity of curcin and the immunotoxin was assessed on breast cancer cell lines SK-BR-3 (Her2(+)) and MDA-MB-231 (Her2(-)). IC50 values for curcin were 15.5 ± 8.3 and 18.6 ± 2.4 μg/mL, respectively, statistically equivalent (p SK-BR-3 and 147.6 ± 2.5 μg/mL for MDA-MB-231. These values showed that the immunotoxin was seven times more toxic to the SK-BR-3 than curcin and eight times less toxic to the MDA-MB-231. The immunotoxin composed of curcin and an antibody against Her2 and constructed by reductive amination could be a therapeutic candidate against Her2(+) cancer.

  10. Enhanced Eradication of Lymphoma by Tumor-Specific Cytotoxic T-Cells Secreting an Engineered Tumor-Specific Immunotoxin (United States)


    5% CO2. The level of proliferation was then assessed using an ATP assay (CellTiter-Glo G7570; Promega, Madison, WI). Phenotyping. Cell-surface...trypan blue or an ATP assay (Promega). Cytotoxicity assay. T cell cytotoxic activity was evaluated in a flow cytometry based assay. Target PMA and 1µM ionomycin. Cells were collected and lysed, and the lysate analyzed for bioluminescent signal. This revealed that the promoter induced

  11. Validation of a mutant of the pore-forming toxin sticholysin-I for the construction of proteinase-activated immunotoxins. (United States)

    Pentón, David; Pérez-Barzaga, Victor; Díaz, Iscel; Reytor, Mey L; Campos, Javier; Fando, Rafael; Calvo, Loany; Cilli, Eduardo M; Morera, Vivian; Castellanos-Serra, Lila R; Pazos, Fabiola; Lanio, María E; Alvarez, Carlos; Pons, Tirso; Tejuca, Mayra


    The use of pore-forming toxins from sea anemones (actinoporins) in the construction of immunotoxins (ITs) against tumour cells is an alternative for cancer therapy. However, the main disadvantage of actinoporin-based ITs obtained so far has been the poor cellular specificity associated with the toxin's ability to bind and exert its activity in almost any cell membrane. Our final goal is the construction of tumour proteinase-activated ITs using a cysteine mutant at the membrane binding region of sticholysin-I (StI), a cytolysin isolated from the sea anemone Stichodactyla helianthus. The mutant and the ligand moiety would be linked by proteinase-sensitive peptides through the StI cysteine residue blocking the toxin binding region and hence the IT non-specific killing activity. To accomplish this objective the first step was to obtain the mutant StI W111C, and to evaluate the impact of mutating tryptophan 111 by cysteine on the toxin pore-forming capacity. After proteolysis of the cleavage sequence, a short peptide would remain attached to the toxin. The next step was to evaluate whether this mutant is able to form pores even with a residual peptide linked to cysteine 111. In this work we demonstrated that (i) StI W111C shows pore-forming capacity in a nanomolar range, although it is 8-fold less active than the wild-type recombinant StI, corroborating the previously reported importance of residue 111 for the binding of StI to membranes, and (ii) the mutant is able to form pores even with a residual seven-residue peptide linked to cysteine 111. In addition, it was demonstrated that binding of a large molecule to cysteine 111 renders an inactive toxin that is no longer able to bind to the membrane. These results validate the mutant StI W111C for its use in the construction of tumour proteinase-activated ITs.

  12. Construction, expression, purification and functional analysis of recombinant 6C6 immunotoxin to human breast-tumor cells

    Institute of Scientific and Technical Information of China (English)

    刘晖; 朱玉贤; 李■秋


    The 28 ku membrane protein is usually over-expressl m human bnasl bmast cancer and other tumor cells. licould be a larget for tumor therapy . By using genetie engineermg teehmgues.a 606 immunotoxin (sefv606-PE40) was construeted by joining the 606 single-chain antibdy (SeFv606) with the truncll Pseudonwnas exotoxin A (PE40), SeFv606 contains both the heavy and light-chnia variable domams of 606 monoelonal antibody. Which speeifieally ree-ognizes the 28 ku protein. The bacterial expression level og 606 imnmmotoxin is 3.3%. about 5.5 mg ml baeterial lysate.lsing singlc-step llisTrap (Nr2 chelating) column chronnetogaphy, the reeombinant peptide was obtained with a purit of 33.2%.This baeterial espressed 606 immunotosin binuls to MDA-231 human breast-tumer ccll surfaee and kill these cells with a median lethal dosage of 92 ngnd.

  13. 免疫毒素IL-18-PE38原核表达载体的构建及其鉴定%Genetic Construction and Characterization of Murine Interleukin-18 Immunotoxin with a Truncated Pseudomonas Exotoxin

    Institute of Scientific and Technical Information of China (English)

    李虹; 李明远; 吕梅励; 蒋忠华; 张林


    目的构建绿脓杆菌外毒素PE38融合鼠IL-18基因的原核表达载体,并鉴定其产物在大肠杆菌中的表达.方法首先经逆转录-聚合酶链反应(RT-PCR)获得小鼠IL-18基因,再通过酶切及连接反应,构建小鼠IL-18与PE38融合基因的原核表达载体PRKL-IL18-PE38,重组载体经PCR、限制性内切酶及DNA序列测定证实连接片段正确后,转染感受态大肠杆菌BL21,经IPTG诱导表达,表达产物用SDS-PAGE和蛋白免疫印迹法分别测定其相对分子质量及特异性.结果成功构建了IL-18-PE38免疫毒素的原核表达载体,重组载体在大肠杆菌中获得了稳定的表达,表达产物的相对分子质量与预期值一致,且所表达蛋白可被抗IL-18的特异性抗体所识别.结论获得了IL-18-PE38融合基因在原核系统的表达,为进一步研究其对Th1细胞的靶向细胞毒性及临床应用奠定了基础.%Objective To construct a new recombinant immunotoxin expression vector fused with a murine interleukin18(IL18) gene and a truncated pseudomonas exotoxin (PE38) gene, and examine the expression of IL-18-PE38 fusion protein in Escherichia coli (E. coli). Method Murine IL-18 (mIL-18) cDNA was cloned from murine liver tissue through reverse transcription-polymerase chain reaction (RT-PCR). The mIL-18 cDNA was ligased with a PE38 gene carried by PRKL expression vector through T4 DNA ligase and constructed into fusion protein expression plasmid PRKL-IL18-PE38. The recombinant vector was identified by restriction endonucleases digestion, PCR and DNA sequencing. After transformed into E.coli BL21 and induced by IPTG, the expressed product was obtained and the molecular weight and specificity were determined by SDS-PAGE and Western-blotting. Result The new recombinant immunotoxin expression vector was constructed successfully. DNA sequencing revealed that the mIL-18 and PE38 gene were consistent with NCBI Gene Bank. The IL-18-PE38 fusion protein was expressed in E.coli BL21, and

  14. A deimmunised form of the ribotoxin, α-sarcin, lacking CD4+ T cell epitopes and its use as an immunotoxin warhead (United States)

    Jones, Tim D.; Hearn, Arron R.; Holgate, Robert G.E.; Kozub, Dorota; Fogg, Mark H.; Carr, Francis J.; Baker, Matthew P.; Lacadena, Javier; Gehlsen, Kurt R.


    Fungal ribotoxins that block protein synthesis can be useful warheads in the context of a targeted immunotoxin. α-Sarcin is a small (17 kDa) fungal ribonuclease produced by Aspergillus giganteus that functions by catalytically cleaving a single phosphodiester bond in the sarcin–ricin loop of the large ribosomal subunit, thus making the ribosome unrecognisable to elongation factors and leading to inhibition of protein synthesis. Peptide mapping using an ex vivo human T cell assay determined that α-sarcin contained two T cell epitopes; one in the N-terminal 20 amino acids and the other in the C-terminal 20 amino acids. Various mutations were tested individually within each epitope and then in combination to isolate deimmunised α-sarcin variants that had the desired properties of silencing T cell epitopes and retention of the ability to inhibit protein synthesis (equivalent to wild-type, WT α-sarcin). A deimmunised variant (D9T/Q142T) demonstrated a complete lack of T cell activation in in vitro whole protein human T cell assays using peripheral blood mononuclear cells from donors with diverse HLA allotypes. Generation of an immunotoxin by fusion of the D9T/Q142T variant to a single-chain Fv targeting Her2 demonstrated potent cell killing equivalent to a fusion protein comprising the WT α-sarcin. These results represent the first fungal ribotoxin to be deimmunised with the potential to construct a new generation of deimmunised immunotoxin therapeutics. PMID:27578884

  15. Affinity-matured recombinant immunotoxin targeting gangliosides 3'-isoLM1 and 3',6'-isoLD1 on malignant gliomas. (United States)

    Piao, Hailan; Kuan, Chien-Tsun; Chandramohan, Vidya; Keir, Stephen T; Pegram, Charles N; Bao, Xuhui; Månsson, Jan-Eric; Pastan, Ira H; Bigner, Darell D


    About 60 percent of glioblastomas highly express the gangliosides 3'-isoLM1 and 3',6'-isoLD1 on the cell surface, providing ideal targets for brain tumor immunotherapy. A novel recombinant immunotoxin, DmAb14m-(scFv)-PE38KDEL (DmAb14m-IT), specific for the gangliosides 3'-isoLM1 and 3',6'-isoLD1, was constructed with improved affinity and increased cytotoxicity for immunotherapeutic targeting of glioblastoma. We isolated an scFv parental clone from a previously established murine hybridoma, DmAb14, that is specific to both 3'-isoLM1 and 3',6'-isoLD1. We then performed in vitro affinity maturation by CDR hotspot random mutagenesis. The binding affinity and specificity of affinity-matured DmAb14m-IT were measured by surface-plasmon resonance, flow cytometry, and immunohistochemical analysis. In vitro cytotoxicity of DmAb14m-IT was measured by protein synthesis inhibition and cell death assays in human cell lines expressing gangliosides 3'-isoLM1 and 3',6'-isoLD1 (D54MG and D336MG) and xenograft-derived cells (D2224MG). As a result, the KD of DmAb14m-IT for gangliosides 3'-isoLM1 and 3',6'-isoLD1 was 2.6 × 10(-9)M. Also, DmAb14m-IT showed a significantly higher internalization rate in cells expressing 3'-isoLM1 and 3',6'-isoLD1. The DmAb14m-IT IC 50 was 80 ng/mL (1194 pM) on the D54MG cell line, 5 ng/ml (75 pM) on the D336MG cell line, and 0.5 ng/ml (7.5 pM) on the D2224MG xenograft-derived cells. There was no cytotoxicity on ganglioside-negative HEK293 cells. Immunohistochemical analysis confirmed the specific apparent affinity of DmAb14m-IT with 3'-isoLM1 and 3',6'-isoLD1. In conclusion, DmAb14m-IT showed specific binding affinity, a significantly high internalization rate, and selective cytotoxicity on glioma cell lines and xenograft-derived cells expressing 3'-isoLM1 and 3',6'-isoLD1, thereby displaying robust therapeutic potential for testing the antitumor efficacy of DmAb14m-IT at the preclinical level and eventually in the clinical setting.

  16. Augmenting the Efficacy of Immunotoxins and Other Targeted Protein Toxins by Endosomal Escape Enhancers

    Directory of Open Access Journals (Sweden)

    Hendrik Fuchs


    Full Text Available The toxic moiety of almost all protein-based targeted toxins must enter the cytosol of the target cell to mediate its fatal effect. Although more than 500 targeted toxins have been investigated in the past decades, no antibody-targeted protein toxin has been approved for tumor therapeutic applications by the authorities to date. Missing efficacy can be attributed in many cases to insufficient endosomal escape and therefore subsequent lysosomal degradation of the endocytosed toxins. To overcome this drawback, many strategies have been described to weaken the membrane integrity of endosomes. This comprises the use of lysosomotropic amines, carboxylic ionophores, calcium channel antagonists, various cell-penetrating peptides of viral, bacterial, plant, animal, human and synthetic origin, other organic molecules and light-induced techniques. Although the efficacy of the targeted toxins was typically augmented in cell culture hundred or thousand fold, in exceptional cases more than million fold, the combination of several substances harbors new problems including additional side effects, loss of target specificity, difficulties to determine the therapeutic window and cell type-dependent variations. This review critically scrutinizes the chances and challenges of endosomal escape enhancers and their potential role in future developments.

  17. Dissecting the Entry Route of Saporin-based a-CD7 Immunotoxins in Human T-Cell Acute Lymphoblastic Leukaemia Cells

    Directory of Open Access Journals (Sweden)

    Maria Serena Fabbrini


    Full Text Available Elucidating the intracellular fate(s of targeted toxins is of fundamental importance for their optimal use as anticancer drugs, since the biochemical targets of their enzymatic activity reside in the cell cytoplasm, as in the case of the plant ribosome inactivating proteins (RIP saporin, ricin and of bacterial toxins. In this paper, we compared the cell surface binding and cytotoxic properties of the model RIP ricin to an immunotoxin constructed with a monoclonal antibody directed against the human T-cell marker CD7 covalently linked to saporin (CD7-SAP. Our results indicate that, despite the fact that internalization takes place via an apparently common entry route leading to the Golgi complex, surprisingly, the addition of an endoplasmic reticulum retrieval C-terminal signal (KDEL to CD7-SAP does not potentiate its cytotoxicity. In addition, while ricin toxicity is clearly reduced by Brefeldin A under conditions where this fungal metabolite causes Golgi stack disruption, we paradoxically observed a potentiating effect by Brefeldin A on CD7-SAP cytotoxicity suggesting that this inhibitor interferes with retrograde route(s other than the well established Trans-Golgi Network-ER retrograde route.

  18. 抗胃癌单链抗体免疫毒素重组质粒的构建及表达%Construction of Anti-carcinoma ScFv Immunotoxin Recombina nt Plasmid and its Expression

    Institute of Scientific and Technical Information of China (English)

    韩梅; 戴寿芝; 靳更林; 寿成超


    Objectives To construct the recombinant plasm id that expresses anti-carcinoma ScF v immunotoxin.Methods By recombinant technique,the cDNA coding the anti-carcinoma ScFv antibody was recombined with the cDNA coding Pseudomonas areuginosa exotoxin to form the recombinanr plasmid.The E Coli.BL-21,after bein g transformed with the recombinant plasmid,was induced by IPTG to express the an ti-carcinoma ScFv immumotoxin.Results The recombinantion of pla smid was identifide to be correct by endonuclease restriction analysis and the B L-21 that contain the recombinant plasmid abundantly expressed the immunotoxin b y IPTG inducement.The size of the expressed protein is similar to that anticipat ed in MW. Conclusions The recombinant plasmid that can express the anti -carcinoma ScFv immunotoxin is successfully obtained.%目的 构建能表达抗胃癌单链抗体免疫毒素的重组质粒并进行表达。方法 应用基因工程方法,将抗胃癌的单链抗体基因与绿脓杆菌外毒素基因进行重组,得到的重组质粒转化大肠杆菌BL-21 ,鉴定后的阳性克隆经IPTG诱导表达。结果 重组质粒经酶切鉴定正确,IPTG诱导后可看到明显的表达带,分子大小与预计值相符。结论 得到了能表达抗胃癌单链抗体免疫毒素的重组质粒。

  19. Sortase-catalyzed in vitro functionalization of a HER2-specific recombinant Fab for tumor targeting of the plant cytotoxin gelonin. (United States)

    Kornberger, Petra; Skerra, Arne


    We report on the preparation of a new type of immunotoxin via in vitro ligation of the αHer2 antigen binding fragment (Fab) of the clinically-validated antibody trastuzumab to the plant toxin gelonin, employing catalysis by the bacterial enzyme sortase A (SrtA). The αHer2 Fab was fused with the extended SrtA recognition motif LPET↓GLEH 6 at the C-terminus of its heavy chain, thereby preventing interference with antigen binding, while the toxin was equipped with a Gly 2 sequence at its N-terminus, distant to the catalytically active site in the C-terminal region. Site-specific in vitro transpeptidation led to a novel antibody-toxin conjugate wherein gelonin had effectively replaced the Fc region of a conventional (monomerized) immunoglobulin. After optimization of reaction conditions and incubation time, the resulting Fab-Gelonin ligation product was purified to homogeneity in a two-step procedure by means of Strep-Tactin affinity chromatography--utilizing the Strep-tag II appended to gelonin--and size exclusion chromatography. Binding activity of the immunotoxin for the Her2 ectodomain was indistinguishable from the unligated Fab as measured by real-time surface plasmon resonance spectroscopy. Specific cytotoxic potency of Fab-Gelonin was demonstrated against two Her2-positive cell lines, resulting in EC 50 values of ~1 nM or lower, indicating a 1000-fold enhanced cell-killing activity compared with gelonin itself. Thus, our strategy provides a convenient route to the modular construction of functional immunotoxins from Fabs of established tumor-specific antibodies with gelonin or related proteotoxins, also avoiding the elevated biosafety levels that would be mandatory for the direct biotechnological preparation of corresponding fusion proteins.

  20. Purification and characterization of Moschatin, a novel type I ribosome-inactivating protein from the mature seeds of pumpkin (Cucurbita moschata), and preparation of its immunotoxin against human melanoma cells. (United States)

    Xia, Heng Chuan; Li, Feng; Li, Zhen; Zhang, Zu Chuan


    A novel ribosome-inactivating protein designated Moschatin from the mature seeds of pumpkin (Cucurbita moschata) has been successively purified to homogeneity, using ammonium sulfate precipitation, CM-cellulose 52 column chromatography, Blue Sepharose CL-6B Affinity column chromatography and FPLC size-exclusion column chromatography. Moschatin is a type 1 RIP with a pI of 9.4 and molecular weight of approximately 29 kD. It is a rRNA N-glycosidase and potently blocked the protein synthesis in the rabbit reticulocyte lysate with a IC50 of 0.26 nM. Using the anti-human melanoma McAb Ng76, a novel immunotoxin Moschatin-Ng76 was prepared successfully and it efficiently inhibited the growth of targeted melanoma cells M21 with a IC50 of 0.04 nM, 1500 times lower than that of free Moschatin. The results implied that Moschatin could be used as a new potential anticancer agent.

  1. Engineering and biological characterization of VB6-845, an anti-EpCAM immunotoxin containing a T-cell epitope-depleted variant of the plant toxin bouganin. (United States)

    Cizeau, Jeannick; Grenkow, Danielle M; Brown, Jennifer G; Entwistle, Joycelyn; MacDonald, Glen C


    The clinical development of immunotoxins in the treatment of solid tumors has been impeded in part, by the induction of an immune response directed primarily against the toxin moiety. Bouganin, a type I ribosome inactivating protein isolated from the leaf of Bougainvillea spectabilis Willd, was mutated to remove the T-cell epitopes while preserving the biological activity of the wild-type molecule. The T-cell epitope-depleted variant of bouganin (de-bouganin) was genetically linked to an anti-epithelial cell adhesion molecule (EpCAM) Fab moiety via a peptidic linker containing a furin proteolytic site to create the fusion construct VB6-845. To determine the optimal construct design for VB6-845, several dicistronic units where de-bouganin was genetically linked to either the N-terminal or C-terminal of either the heavy or light chain were engineered. Only the C-terminal variants expressed the full-length molecule. An in vitro assessment of the biological activity of VB6-845 showed that it bound and selectively killed EpCAM-positive cell lines with a greater potency than many commonly used chemotherapeutic agents. In vivo efficacy was demonstrated using an EpCAM-positive human tumor xenograft model in SCID mice with the majority of the mice treated being tumor free at the end of the study.

  2. Purification and characterization of Moschatin, a novel type Ⅰ ribosome-inactivating protein from the mature seeds of pumpkin (Cucurbita moschata),and preparation of its immunotoxin against human melanoma cells

    Institute of Scientific and Technical Information of China (English)



    A novel ribosome-inactivating protein designated Moschatin from the mature seeds of pumpkin (Cucurbita moschata) has been successively purified to homogeneity, using ammonium sulfate precipitation, CM-cellulose 52 column chromatography, Blue Sepharose CL-6B Affinity column chromatography and FPLC size-exclusion column chromatography. Moschatin is a type 1 RIP with a pI of 9.4 and molecular weight of~29 kD. It is a rRNA Nglycosidase and potently blocked the protein synthesis in the rabbit reticulocyte lysate with a IC50 of 0.26 nM. Using the anti-human melanoma McAb Ng76, a novel immunotoxin Moschatin-Ng76 was prepared successfully and it efficiently inhibited the growth of targeted melanoma cells M21 with a IC50 of 0.04 nM, 1500 times lower than that of free Moschatin. The results implied that Moschatin could be used as a new potential anticancer agent.

  3. Specific Killing Effects of Immunotoxin BDI-1-PEA against Human Bladder Cancer Cells%抗膀胱癌免疫毒素BDI-1-PEA特异杀伤肿瘤细胞的研究

    Institute of Scientific and Technical Information of China (English)

    温儒民; 薛松; 孙晓青; 陈家存; 顾骧; 陈仁富; 郑骏年



  4. 重组免疫毒素GnRH-PTD-PE39KDEL的构建及表达%Construction and expression of a recombinant immunotoxin GnRH-PTD-PE39KDEL

    Institute of Scientific and Technical Information of China (English)

    扈进冬; 魏艳丽; 杨合同; 李纪顺; 张广志


    We improve killing activity to tumor cells of recombinant immunotoxin composed by a human gonadotropinreleasing hormone gene and Pseudomonas exotoxin a derivative (GnRH-PE39KDEL) by introducing the protein transduction domain (PTD).We design three primers,and then obtain the gene GnRH-PTD-PE39KDEL by two rounds PCR and PTD induced at the C end of gonadotropin-releasing hormone and the N end of Pseudomonas exotoxin a derivative.The gene is through endonucleases digestion,inserted into a pET-His carrier and then transformed into E.coli BL21 (DE3).We also purify resolvable protein by Ni-NTA,and determine biological activity.We successfully construct the expression carrier pET-His-GnRH-PTD-PE39KDEL.Fusion protein has good solubility.The quantity of expressed fusion protein is 20% of total bacterial proteins.IC50 of human breast cancer cell MCF-7 is 0.860 μg/mL.It indicates that GnRHPTD-PE39KDEL has stronger biological activity than GnRH-PE39KDEL.The GnRH-PTD-PE39KDEL is successfully expressed.It will lay the foundation for its further large-scale expression,purification and functionality research.%通过引入蛋白质转导域(PTD),提高免疫毒素人促黄体激素释放激素-绿脓杆菌外毒素A衍生物(GnRH-PE39KDEL)对肿瘤细胞的杀伤活性.设计了3条引物,通过2轮PCR在GnRH-PE39KDEL基因的人促黄体激素释放激素C端和绿脓杆菌外毒素A衍生物N端引入PTD,获得GnRH-PTD-PE39KDEL基因经酶切后插入pET-His载体,并转化至BL21(DE3)中.采用镍离子螯合层析法纯化诱导表达样品,并进行了生物活性测定.成功构建了免疫毒素表达载体pET-His-GnRH-PTD-PE39KDEL;诱导产物可以实现可溶性表达;表达产物占菌体总蛋白的20%,靶向融合蛋白引入PTD后对人乳腺癌MCF-7细胞的IC50为0.860μg/mL,表明较GnRH-PE39KDEL生物活性增强.成功地表达了融合蛋白GnRH-PTD-PE39KDEL,为其进一步大规模表达、纯化和功能研究奠定了基础.

  5. Specific Phobias (United States)

    ... Mental Health This information in Spanish ( en español ) Specific phobias Treatment More information on specific phobias A specific ... targeted psychotherapy. Return to top More information on Specific phobias Explore other publications and websites Phobias (Copyright © American ...

  6. Specificity of specific language impairment

    NARCIS (Netherlands)

    GoorhuisBrouwer, SM; WijnbergWilliams, BJ


    In children with specific language impairment (SLI) their problems are supposed to be specifically restricted to language. However, both on a theoretical basis as well as on a practical basis it is often difficult to make a sharp distinction between specific and nonspecific language disorders. In a

  7. Specific Dyslexia. (United States)

    Naidoo, Sandhya

    The investigation reported in this volume attempts to clarify some issues relating to the existence, nature, and causes of specific dyslexia. Based on an extended study of 98 boys of at least average intelligence with severe reading and spelling problems, the report provides detailed data relating to their developmental and perinatal histories,…

  8. HRT Specification

    CERN Document Server

    Möller, M


    In the context of the AIS Project (Advanced Informatics Systems for administration and management) a study has been conducted that resulted in the definition of a high level information systems model. Thirteen proposed systems were defined for detailed analysis. The Finance, Foundation, Human Resources, Logistics and Purchasing areas have been studied in detail. These studies have lead to the purchase and implementation of the ORIAC and SIRIAC packages, the Foundation database, the Oracle HR package, the Triton package and EDH and BHT. This specification describes the Human Resources Toolkit (HRT) intended to be used for accessing data in the HR and Foundation systems. This toolkit should help the divisions carry out their Human Resource management, planning and follow-up. It will have extensive report generation capabilities and offer a variety of standard graphs. It should have an easy-to-use graphical user interface and run on the CERN standard desktop platforms.

  9. Specific phobias. (United States)

    Hamm, Alfons O


    Exposure based treatments in which patients are systematically confronted with their feared objects of situations are highly effective in the treatment of specific phobias and produce stable improvement both in reported fear and behavioral avoidance. Exposure in reality is more effective in most cases than exposure in sensu. For situations that are difficult to realize, exposure in virtual environments has become increasingly valuable. Exposure in vivo is clearly superior to pharmacotherapy, although cognitive enhancers have been successfully used recently to increase the effect of exposure therapy. The induction of relaxation is not a necessary precondition for exposure therapy. Rather the current mechanisms of change focus on extinction learning as being the central mechanism both on a cognitive level namely that the feared object is no longer associated with severely threatening consequence but also on an affective level, meaning that feared cue is no longer capable to activate the fear circuit in the brain. Accordingly future diagnostic categorizations of phobic disorders in the DSM-V should rather focus on the pattern of the fear response that needs to be changed than on the eliciting cues or situations that are avoided.

  10. Myositis specific autoantibodies : specificity and clinical applications

    NARCIS (Netherlands)

    Hengstman, G.J.D.


    The sera of about half of the patients with myositis contain autoantibodies that are specific for this group of diseases compared to other inflammatory connective tissue disorders. In a recent study we showed that these myositis specific autoantibodies (MSAs) are also specific for myositis as compar

  11. Urine specific gravity test (United States)

    ... Urine specific gravity test To use the sharing features on this page, please enable JavaScript. Urine specific gravity is a laboratory test that shows the concentration ...

  12. Phobia - simple/specific (United States)

    Anxiety disorder - phobia ... Specific phobias are a type of anxiety disorder in which a person may feel extremely anxious or has a ... when exposed to the object of fear. Specific phobias are a common mental disorder. Common phobias include ...

  13. The SIFT Code Specification (United States)


    The specification of Software Implemented Fault Tolerance (SIFT) consists of two parts, the specifications of the SIFT models and the specifications of the SIFT PASCAL program which actually implements the SIFT system. The code specifications are the last of a hierarchy of models describing the operation of the SIFT system and are related to the SIFT models as well as the PASCAL program. These Specifications serve to link the SIFT models to the running program. The specifications are very large and detailed and closely follow the form and organization of the PASCAL code. In addition to describing each of the components of the SIFT code, the code specifications describe the assumptions of the upper SIFT models which are required to actually prove that the code will work as specified. These constraints are imposed primarily on the schedule tables.

  14. Screening for Specific Phobias (United States)

    ... Disorder Specific Phobias Obsessive-Compulsive Disorder (OCD) Posttraumatic Stress Disorder (PTSD) Depression Bipolar Disorder Suicide and Prevention Stress Related Illnesses Myth-Conceptions Find ...

  15. Experiences with effects specifications

    DEFF Research Database (Denmark)

    Simonsen, Jesper; Hertzum, Morten; Barlach, Anders


    We describe the effects-specification process from a project that was conducted during the fall 2010 and spring of 2011 in this chapter. The project configured and implemented an electronic patient record system at a maternity ward at a hospital located in a European region. The process comprised...... workshops with effects specification with management and end-users and an agile development process including prototypes configured from the effects specifications. We describe the project and the effects-specification process through which effects were related to the system design and instruments...... for measuring effects were designed. The project is analyzed and lessons learned are discussed....

  16. Lidar base specification (United States)

    Heidemann, Hans Karl.


    In late 2009, a $14.3 million allocation from the “American Recovery and Reinvestment Act” for new light detection and ranging (lidar) elevation data prompted the U.S. Geological Survey (USGS) National Geospatial Program (NGP) to develop a common base specification for all lidar data acquired for The National Map. Released as a draft in 2010 and formally published in 2012, the USGS–NGP “Lidar Base Specification Version 1.0” (now Lidar Base Specification) was quickly embraced as the foundation for numerous state, county, and foreign country lidar specifications.

  17. Improved technical specifications

    Energy Technology Data Exchange (ETDEWEB)

    Hoffman, D.R.


    Improved technical specifications for nuclear power plants are outlined. The objectives of this work are to improve safety, provide a clearer understanding of safety significance, and ease NRC and industry administrative burdens. Line item improvements, bases, and implementation of the specifications are discussed.

  18. Place-Specific Computing

    DEFF Research Database (Denmark)

    Messeter, Jörn


    An increased interest in the notion of place has evolved in interaction design based on the proliferation of wireless infrastructures, developments in digital media, and a ‘spatial turn’ in computing. In this article, place-specific computing is suggested as a genre of interaction design...... that addresses the shaping of interactions among people, place-specific resources and global socio-technical networks, mediated by digital technology, and influenced by the structuring conditions of place. The theoretical grounding for place-specific computing is located in the meeting between conceptions...... examples of place-specific computing are presented from a series of pilot studies, conducted in close collaboration with design students in Malmö, Berlin, Cape Town and Rome, that generated 36 design concepts in the genre. Reflecting on these examples, issues in the design of place-specific computing...

  19. FOXP3-specific immunity

    DEFF Research Database (Denmark)

    Andersen, Mads Hald


    Forkhead box P3 (FOXP3)-specific cytotoxic CD8(+) T cells are present among human peripheral blood mononuclear cells (PBMCs), especially in cancer patients. Such T lymphocytes are able not only to specifically recognize dendritic cells (DCs) that have been exposed to recombinant FOXP3 and regulat......Forkhead box P3 (FOXP3)-specific cytotoxic CD8(+) T cells are present among human peripheral blood mononuclear cells (PBMCs), especially in cancer patients. Such T lymphocytes are able not only to specifically recognize dendritic cells (DCs) that have been exposed to recombinant FOXP3...... and regulatory T cells, but also to kill FOXP3(+) malignant T cells. The natural occurrence of FOXP3-specific cytotoxic T lymphocytes among human PBMCs suggests a general role for these cells in the complex network of immune regulation....


    Institute of Scientific and Technical Information of China (English)

    Boubacar KANE; Pierre Y.JULIEN


    An extensive database of reservoir sedimentation surveys throughout continental United States is compiled and analyzed to determine specific degradation SD relationships as function of mean annual rainfall R, drainage area A, and watershed slope S. The database contains 1463 field measurements and specific degradation relationships are defined as function of A, R and S. Weak trends and significant variability in the data are noticeable. Specific degradation measurements are log normally distributed with respect to R, A, and S and 95% confidence intervals are determined accordingly. The accuracy of the predictions does not significantly increase as more independent variables are added to the regression analyses.

  1. Place-Specific Computing

    DEFF Research Database (Denmark)

    Messeter, Jörn; Johansson, Michael

    An increased interest in the notion of place has evolved in interaction design. Proliferation of wireless infrastructure, developments in digital media, and a ‘spatial turn’ in computing provides the base for place-specific computing as a suggested new genre of interaction design. In the REcult...... project place- specific computing is explored through design oriented research. This article reports six pilot studies where design students have designed concepts for place-specific computing in Berlin (Germany), Cape Town (South Africa), Rome (Italy) and Malmö (Sweden). Background and arguments...... for place-specific computing as a genre of interaction design are described. A total number of 36 design concepts designed for 16 designated zones in the four cities are presented. An analysis of the design concepts is presented indicating potentials, possibilities and problems as directions for future...

  2. The Learning Design Specification

    NARCIS (Netherlands)

    Olivier, Bill; Tattersall, Colin


    Olivier, B. & Tattersall, C. (2005). The Learning Design Specification In: Koper, R. & Tattersall, C., Learning Design: A Handbook on Modelling and Delivering Networked Education and Training (pp. 21-40). Berlin-Heidelberg: Springer Verlag.

  3. Ontology Requirements Specification


    Suárez-Figueroa, Mari Carmen; Gómez-Pérez, A.


    The goal of the ontology requirements specification activity is to state why the ontology is being built, what its intended uses are, who the end users are, and which requirements the ontology should fulfill. This chapter presents detailed methodological guidelines for specifying ontology requirements efficiently. These guidelines will help ontology engineers to capture ontology requirements and produce the ontology requirements specification document (ORSD). The ORSD will play a key role dur...

  4. Comparative Test Case Specification

    DEFF Research Database (Denmark)

    Kalyanova, Olena; Heiselberg, Per

     This document includes a definition of the comparative test cases DSF200_3 and DSF200_4, which previously described in the comparative test case specification for the test cases DSF100_3 and DSF200_3 [Ref.1]....... This document includes a definition of the comparative test cases DSF200_3 and DSF200_4, which previously described in the comparative test case specification for the test cases DSF100_3 and DSF200_3 [Ref.1]....

  5. Acquiring specific interpreting competence

    Directory of Open Access Journals (Sweden)

    Jana Zidar Forte


    Full Text Available In postgraduate interpreter training, the main objective of the course is to help trainees develop various competences, from linguistic, textual and cultural competence, to professional and specific interpreting competence. For simultaneous interpreting (SI, the main focus is on mastering the SI technique and strategies as well as on developing and strengthening communicative skills, which is discussed and illustrated with examples in the present paper. First, a brief overview is given of all the necessary competences of a professional interpreter with greater emphasis on specific interpreting competence for SI. In the second part of the paper, various approaches are described in terms of acquiring specific skills and strategies, specifically through a range of exercises. Besides interpreting entire speeches, practical courses should also consist of targeted exercises, which help trainees develop suitable coping strategies and mechanisms (later on almost automatisms, while at the same time "force" them to reflect on their individual learning process and interpreting performance. This provides a solid base on which trained interpreters can progress and develop their skills also after joining the professional sphere.

  6. Site-Specific Innovation

    DEFF Research Database (Denmark)

    Reeh, Henrik; Hemmersam, Peter


    , but also places for emerging lifestyles and cultural processes. In this transformation process, harbours provide arenas for a new urban dynamics, involving multiple sectors and functions in society, as opposed to the monoculturalism prevailing in the ages of the industrial city. To us, the critical...... question is how innovation may contribute to urban life and site-specific qualities....

  7. IDC System Specification Document.

    Energy Technology Data Exchange (ETDEWEB)

    Clifford, David J.


    This document contains the system specifications derived to satisfy the system requirements found in the IDC System Requirements Document for the IDC Reengineering Phase 2 project. Revisions Version Date Author/Team Revision Description Authorized by V1.0 12/2014 IDC Reengineering Project Team Initial delivery M. Harris

  8. LOCKE Detailed Specification Tables

    CERN Document Server

    Menezo, Lucia G; Gregorio, Jose-Angel


    This document shows the detailed specification of LOCKE coherence protocol for each cache controller, using a table-based technique. This representation provides clear, concise visual information yet includes sufficient detail (e.g., transient states) arguably lacking in the traditional, graphical form of state diagrams.

  9. Specificity in LSP

    Directory of Open Access Journals (Sweden)

    Thomas N. Huckin


    Full Text Available The defining feature of our field is the teaching and use of language for specific purposes. Not surprisingly, this has led to a debate over just how specific those purposes should be. The debate is longstanding, stirred initially by Hutchinson and Waters' classic 1980 article, 'ESP at the Crossroads' and reinvigorated most recently by Hyland (2002, who argues that the field has drifted away from specificity, becoming too generalized and diffuse. This paper lays out the arguments on both sides and then stakes out a position that draws from each of them. While agreeing with some of Hyland's criticisms of the 'wide-angle' position (for example, that generalized LSP can fail to appreciate the distinct linguistic and rhetorical features of specialized discourses, the paper criticizes his 'narrow-angle' position as well by pointing out that it can easily lead to a teacher-centered prescriptivism and to an overly rigid focus on certain forms and tasks at the expense of others. Furthermore, such an approach fails to prepare students for the unpredictable new forms of communication that await them in their professional careers. In general, a teachercentered approach, no matter how specific, is unlikely to have the pedagogical effectiveness of a student-centered approach, especially in heterogeneous classes. Specificity, it is argued, must ultimately be supplied by the student, not by the teacher, for it is the student more than the LSP teacher who is in the process of becoming an insider and whose interests are best served by becoming an astute analyst of the specialist discourse. The teacher's role should be that of facilitator, instructing students in analytic strategies, both rhetorical and textual. The paper concludes with a number of illustrations in how this can be done, drawing especially on work in genre study.

  10. Allergen Specific Immunotherapy

    Directory of Open Access Journals (Sweden)

    Şükrü Çekiç


    Full Text Available Allergen specific immunotherapy (SIT is the only treatment that can provide a cure for allergic disorders. This treatment is based on development of immune tolerance by exposure to allergen in repetitive and increasing doses. It is tertiary to avoidance of allergen and pharmacotherapy. Allergens used for immunotherapy, must be confirmed by skin prick test or specific IgE and must be applied in supervision of allergy specialists. Studies show that immunotherapy, improve asthma symptoms, decreases drug consumption, prevent development of asthma in rhinitis patients and reduce new sensitizations. Common side effects diminished with the usage of standardized allergen solutions. It is contraindicated in severe asthma. Though it is recommended to avoid immunotherapy in patients using beta blockers and ACE inhibitors, immunotherapy can be considered in mandatory situations regarding possible benefits and harms. Most common ways of administration are subcutaneous and sublingual; new methods such as epicutaneous and intralymphatic injections are currently being studied.

  11. Empirical Test Case Specification

    DEFF Research Database (Denmark)

    Kalyanova, Olena; Heiselberg, Per

    This document includes the empirical specification on the IEA task of evaluation building energy simulation computer programs for the Double Skin Facades (DSF) constructions. There are two approaches involved into this procedure, one is the comparative approach and another is the empirical one. I....... In the comparative approach the outcomes of different software tools are compared, while in the empirical approach the modelling results are compared with the results of experimental test cases....

  12. Comparative Test Case Specification

    DEFF Research Database (Denmark)

    Kalyanova, Olena; Heiselberg, Per

    This document includes the specification on the IEA task of evaluation building energy simulation computer programs for the Double Skin Facades (DSF) constructions. There are two approaches involved into this procedure, one is the comparative approach and another is the empirical one. In the comp....... In the comparative approach the outcomes of different software tools are compared, while in the empirical approach the modelling results are compared with the results of experimental test cases. The comparative test cases include: ventilation, shading and geometry....

  13. Allergen-specific immunotherapy

    Directory of Open Access Journals (Sweden)

    Moote William


    Full Text Available Abstract Allergen-specific immunotherapy is a potentially disease-modifying therapy that is effective for the treatment of allergic rhinitis/conjunctivitis, allergic asthma and stinging insect hypersensitivity. However, despite its proven efficacy in these conditions, it is frequently underutilized in Canada. The decision to proceed with allergen-specific immunotherapy should be made on a case-by-case basis, taking into account individual patient factors such as the degree to which symptoms can be reduced by avoidance measures and pharmacological therapy, the amount and type of medication required to control symptoms, the adverse effects of pharmacological treatment, and patient preferences. Since this form of therapy carries the risk of anaphylactic reactions, it should only be prescribed by physicians who are adequately trained in the treatment of allergy. Furthermore, injections must be given under medical supervision in clinics that are equipped to manage anaphylaxis. In this article, the authors review the indications and contraindications, patient selection criteria, and the administration, safety and efficacy of allergen-specific immunotherapy.

  14. Specification of Concurrent Objects

    DEFF Research Database (Denmark)

    Sørensen, Morten U.

    Concurrent objects are named concurrent processes that interact by invoking each other's operations. We describe how such concurrent objects can be specified, how objects can be composed, and how it can be shown that one object refines another.First a model is defined, based on a transition...... relation over two objects and an event. In the model, objects can be composed by parallel composition, encapsulation, and hiding of operations. Refinement between objects is defined as fair trace inclusion.A specification language is presented where objects can be specified operationally by abstract...

  15. Disease specific protein corona (United States)

    Rahman, M.; Mahmoudi, M.


    It is now well accepted that upon their entrance into the biological environments, the surface of nanomaterials would be covered by various biomacromolecules (e.g., proteins and lipids). The absorption of these biomolecules, so called `protein corona', onto the surface of (nano)biomaterials confers them a new `biological identity'. Although the formation of protein coronas on the surface of nanoparticles has been widely investigated, there are few reports on the effect of various diseases on the biological identity of nanoparticles. As the type of diseases may tremendously changes the composition of the protein source (e.g., human plasma/serum), one can expect that amount and composition of associated proteins in the corona composition may be varied, in disease type manner. Here, we show that corona coated silica and polystyrene nanoparticles (after interaction with in the plasma of the healthy individuals) could induce unfolding of fibrinogen, which promotes release of the inflammatory cytokines. However, no considerable releases of inflammatory cytokines were observed for corona coated graphene sheets. In contrast, the obtained corona coated silica and polystyrene nanoparticles from the hypofibrinogenemia patients could not induce inflammatory cytokine release where graphene sheets do. Therefore, one can expect that disease-specific protein coronas can provide a novel approach for applying nanomedicine to personalized medicine, improving diagnosis and treatment of different diseases tailored to the specific conditions and circumstances.

  16. ADANS database specification

    Energy Technology Data Exchange (ETDEWEB)



    The purpose of the Air Mobility Command (AMC) Deployment Analysis System (ADANS) Database Specification (DS) is to describe the database organization and storage allocation and to provide the detailed data model of the physical design and information necessary for the construction of the parts of the database (e.g., tables, indexes, rules, defaults). The DS includes entity relationship diagrams, table and field definitions, reports on other database objects, and a description of the ADANS data dictionary. ADANS is the automated system used by Headquarters AMC and the Tanker Airlift Control Center (TACC) for airlift planning and scheduling of peacetime and contingency operations as well as for deliberate planning. ADANS also supports planning and scheduling of Air Refueling Events by the TACC and the unit-level tanker schedulers. ADANS receives input in the form of movement requirements and air refueling requests. It provides a suite of tools for planners to manipulate these requirements/requests against mobility assets and to develop, analyze, and distribute schedules. Analysis tools are provided for assessing the products of the scheduling subsystems, and editing capabilities support the refinement of schedules. A reporting capability provides formatted screen, print, and/or file outputs of various standard reports. An interface subsystem handles message traffic to and from external systems. The database is an integral part of the functionality summarized above.

  17. Tissue specific electrochemical fingerprinting.

    Directory of Open Access Journals (Sweden)

    Pavlina Sobrova

    Full Text Available BACKGROUND: Proteomics and metalloproteomics are rapidly developing interdisciplinary fields providing enormous amounts of data to be classified, evaluated and interpreted. Approaches offered by bioinformatics and also by biostatistical data analysis and treatment are therefore of extreme interest. Numerous methods are now available as commercial or open source tools for data processing and modelling ready to support the analysis of various datasets. The analysis of scientific data remains a big challenge, because each new task sets its specific requirements and constraints that call for the design of a targeted data pre-processing approach. METHODOLOGY/PRINCIPAL FINDINGS: This study proposes a mathematical approach for evaluating and classifying datasets obtained by electrochemical analysis of metallothionein in rat 9 tissues (brain, heart, kidney, eye, spleen, gonad, blood, liver and femoral muscle. Tissue extracts were heated and then analysed using the differential pulse voltammetry Brdicka reaction. The voltammograms were subsequently processed. Classification models were designed making separate use of two groups of attributes, namely attributes describing local extremes, and derived attributes resulting from the level=5 wavelet transform. CONCLUSIONS/SIGNIFICANCE: On the basis of our results, we were able to construct a decision tree that makes it possible to distinguish among electrochemical analysis data resulting from measurements of all the considered tissues. In other words, we found a way to classify an unknown rat tissue based on electrochemical analysis of the metallothionein in this tissue.

  18. Use of colloidal gold cytochemistry in the study of the basic cell biology of cancer. (United States)

    Willingham, M C


    We are currently investigating the morphologic aspects of two areas of the basic cell biology of cancer: tumor-specific surface antigens as targets for immunotoxins, and the phenomenon of multidrug resistance in chemotherapy of human tumors. Colloidal gold cytochemistry has provided a useful method for the electron-microscopic cytochemical detection of materials endocytosed by cells in culture. This technique has been used to study the internalization pathway of ligands bound to the surface of cancer cells, particularly antibodies for use as immunologic targeting reagents for the construction of immunotoxins. These colloidal gold conjugates with monoclonal antibodies have demonstrated the internalization of these immunologic reagents through coated pits and receptosomes, which is a necessary step in the delivery of immunotoxins into the cell where they can mediate their cell-killing functions. Morphologic methods have been employed for the screening and selection of monoclonal antibodies reactive with the surface of human ovarian cancer cells for use as immunotoxins and have demonstrated the in vivo activity of immunotoxins made with these antibodies and Pseudomonas exotoxin in a nude mouse model system. In other studies, we have employed such reagents for the immunocytochemical detection of the surface expression of P170, the cell-surface efflux pump protein responsible for the phenotype of multidrug resistance in tumor cells, and to investigate the distribution of this protein by using immunocytochemistry in normal human tissues. These results have suggested a role for P170 in normal cell membrane transport of metabolites in various organ systems.

  19. Teaching English for Specific Purposes

    Directory of Open Access Journals (Sweden)

    Nijolė Netikšienė


    Full Text Available Teaching English for Specific Purposes and General English is analysed in the article. The scientific approach of a scientist M. Rosenberg is presented. The experience of teaching English for Specific Purposesat VGTU is alsopresented. The ideas and teaching methods from the classes of general English can be transferred to the classes of English for Specific Purposes.

  20. 77 FR 8263 - Prospective Grant of Exclusive License: The Development of Anti-mesothelin Targeted Immunotoxins... (United States)


    ... exotoxin A (``PE'') toxin domain that is (a) lysosomal protease resistant (PE-LR) and (b) lacks at least... is resistant to lysosomal proteases due to the deletion of a large portion of the exotoxin, and which... therapeutic strategy with fewer side effects. The prospective exclusive license will be royalty bearing...

  1. Specification-Based Testing Via Domain Specific Language

    Directory of Open Access Journals (Sweden)

    Sroka Michal


    Full Text Available The article presents tCF (testCaseFramework - a domain specific language with corresponding toolchain for specification-based software testing of embedded software. tCF is designed for efficient preparation of maintainable and intelligible test cases and for testing process automation, as it allows to generate platform specific test cases for various testing levels. The article describes the essential parts of the tCF meta-model and the applied concept of platform specific test cases generators.

  2. Anti-Human Endoglin (hCD105 Immunotoxin—Containing Recombinant Single Chain Ribosome-Inactivating Protein Musarmin 1

    Directory of Open Access Journals (Sweden)

    Begoña Barriuso


    Full Text Available Endoglin (CD105 is an accessory component of the TGF-β receptor complex, which is expressed in a number of tissues and over-expressed in the endothelial cells of tumor neovasculature. Targeting endoglin with immunotoxins containing type 2 ribosome-inactivating proteins has proved an effective tool to reduce blood supply to B16 mice tumor xenografts. We prepared anti-endoglin immunotoxin (IT—containing recombinant musarmin 1 (single chain ribosome-inactivating proteins linked to the mouse anti-human CD105 44G4 mouse monoclonal antibody via N-succinimidyl 3-(2-pyridyldithio propionate (SPDP. The immunotoxin specifically killed L929 fibroblast mouse cells transfected with the short form of human endoglin with IC50 values in the range of 5 × 10−10 to 10−9 M.

  3. Action-Specific Effects Underwater


    Witt, Jessica; Schuck, Donald M; Taylor, J. Eric T.


    Action-specific effects on perception are apparent in terrestrial environments. For example, targets that require more effort to walk, jump, or throw to look farther away than when the targets require less effort. Here, we examined whether action-specific effects would generalize to an underwater environment. Instead, perception might be geometrically precise, rather than action-specific, in an environment that is novel from an evolutionary perspective. We manipulated ease to swim by giving p...

  4. [Multilingualism and specific language impairment]. (United States)

    Arkkila, Eva; Smolander, Sini; Laasonen, Marja


    Specific language impairment is one of the most common developmental disturbances in childhood. With the increase of the foreign language population group an increasing number of children assimilating several languages and causing concern in language development attend clinical examinations. Knowledge of factors underlying the specific language impairment and the specific impairment in general, special features of language development of those learning several languages, as well as the assessment and support of the linguistic skills of a multilingual child is essential. The risk of long-term problems and marginalization is high for children having specific language impairment.

  5. Response to "Transfer or Specificity?" (United States)

    Miller, Judith


    This article presents the author's response to "Transfer or Specificity?" and reports a research that supports a strong case for a fundamental motor skill as a precursor to two sport specific skills as in Gallahue and Ozmun's (2002) theoretical model of motor development. Reported changes in performance of the overarm throw are…

  6. Performance Specifications for Occupational Programs. (United States)

    Maryland State Dept. of Education, Baltimore. Div. of Career Technology and Adult Learning.

    This document lists and discusses the development of Maryland's performance specifications for occupational programs. The introduction explains the process used to develop performance standards and specifications for 10 career cluster majors that were identified by a task force of educators and employers as high-demand occupational areas in…

  7. Hanford Site environmental management specification

    Energy Technology Data Exchange (ETDEWEB)

    Grygiel, M.L.


    The US Department of Energy, Richland Operations Office (RL) uses this Hanford Site Environmental Management Specification (Specification) to document top-level mission requirements and planning assumptions for the prime contractors involved in Hanford Site cleanup and infrastructure activities under the responsibility of the US Department of Energy, Office of Environmental Management. This Specification describes at a top level the activities, facilities, and infrastructure necessary to accomplish the cleanup of the Hanford Site and assigns this scope to Site contractors and their respective projects. This Specification also references the key National Environmental Policy Act of 1969 (NEPA), Comprehensive Environmental Response, Compensation, and Liability Act of 1980 (CERCLA), and safety documentation necessary to accurately describe the cleanup at a summary level. The information contained in this document reflects RL`s application of values, priorities, and critical success factors expressed by those involved with and affected by the Hanford Site project. The prime contractors and their projects develop complete baselines and work plans to implement this Specification. These lower-level documents and the data that support them, together with this Specification, represent the full set of requirements applicable to the contractors and their projects. Figure 1-1 shows the relationship of this Specification to the other basic Site documents. Similarly, the documents, orders, and laws referenced in this specification represent only the most salient sources of requirements. Current and contractual reference data contain a complete set of source documents.

  8. Patient-Specific Computational Modeling

    CERN Document Server

    Peña, Estefanía


    This book addresses patient-specific modeling. It integrates computational modeling, experimental procedures, imagine clinical segmentation and mesh generation with the finite element method (FEM) to solve problems in computational biomedicine and bioengineering. Specific areas of interest include cardiovascular problems, ocular and muscular systems and soft tissue modeling. Patient-specific modeling has been the subject of serious research over the last seven years and interest in the area is continually growing and this area is expected to further develop in the near future.

  9. Youth job market specific features

    Directory of Open Access Journals (Sweden)

    Evgeniya Yu. Zhuravleva


    Full Text Available The article considers youth job market peculiarities, its specific features and regulation means, determines theoretical and application tasks of qualitative and quantitative comparison of vocations, which are highly in demand at the job market.


    Directory of Open Access Journals (Sweden)

    Pavel Skopec


    Full Text Available This paper deals with determining the specific emissions from the combustion of two kinds of biomass fuels in a small-scale boiler. The tested fuels were pellets made of wood and pellets made of rape plant straw. In order to evaluate the specific emissions, several combustion experiments were carried out using a commercial 25 kW pellet-fired boiler. The specific emissions of CO, SO2 and NOx were evaluated in relation to a unit of burned fuel, a unit of calorific value and a unit of produced heat. The specific emissions were compared with some data acquired from the reference literature, with relatively different results. The differences depend mainly on the procedure used for determining the values, and references provide no information about this. Although some of our experimental results may fit with one of the reference sources, they do not fit with the other. The reliability of the references is therefore disputable.

  11. Eternity Variables to Simulate Specifications

    NARCIS (Netherlands)

    Hesselink, WH; Boiten, EA; Moller, B


    Simulation of specifications is introduced as a unification and generalization of refinement mappings, history variables, forward simulations, prophecy variables, and backward simulations. Eternity variables are introduced as a more powerful alternative for prophecy variables and backward simulation

  12. CCL22-specific T Cells

    DEFF Research Database (Denmark)

    Martinenaite, Evelina; Munir Ahmad, Shamaila; Hansen, Morten


    Tumor cells and tumor-infiltrating macrophages produce the chemokine CCL22, which attracts regulatory T cells (Tregs) into the tumor microenvironment, decreasing anticancer immunity. Here, we investigated the possibility of targeting CCL22-expressing cells by activating specific T cells. We...... analyzed the CCL22 protein signal sequence, identifying a human leukocyte antigen A2- (HLA-A2-) restricted peptide epitope, which we then used to stimulate peripheral blood mononuclear cells (PMBCs) to expand populations of CCL22-specific T cells in vitro. T cells recognizing an epitope derived from...... the signal-peptide of CCL22 will recognize CCL22-expressing cells even though CCL22 is secreted out of the cell. CCL22-specific T cells recognized and killed CCL22-expressing cancer cells. Furthermore, CCL22-specific T cells lysed acute monocytic leukemia cells in a CCL22 expression-dependent manner. Using...

  13. EEG in Specific Language Impairment

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap


    Full Text Available The value of routine wake electroencephalography in children with specific language impairment was reviewed retrospectively in 111 children examined over a 10-year interval at Montreal Children’s Hospital, Quebec, Çanada.

  14. GFF Specification for SAR Systems

    Energy Technology Data Exchange (ETDEWEB)

    Sweet, Nathan [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Bielek, Timothy P. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Matthews, John D. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Coakley, Henry John [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Pan, Len [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)


    This document provides the basic GFF format definition for a GFF file. This document covers the contents of the main header and the basic GFF file structure. The contents of specific extensions are covered in a separate document.

  15. Site Specific Weed Control Technologies

    DEFF Research Database (Denmark)

    Christensen, Svend; Søgaard, Henning Tangen; Kudsk, Per;


    describe the basic parts of site specific weed control technologies, comprising of weed sensing systems, weed management models and precision weed control implements. A review of state-of-the-art technologies shows that several weed sensing systems and precision implements have been developed over the last...... of knowledge about the economic and environmental potential for increasing the resolution of weed control. The integration of site-specific information on weed distribution, weed species composition and density, and the effect on crop yield, is decisive for successful site-specific weed management.   Keywords......Site-specific weed control technologies are defined as machinery or equipment embedded with technologies that detect weeds growing in a crop and, taking into account predefined factors such as economics, takes action to maximise the chances of successfully controlling them. In the article, we...

  16. A Domain Specific DSP Processor


    Tell, Eric


    This thesis describes the design of a domain specific DSP processor. The thesis is divided into two parts. The first part gives some theoretical background, describes the different steps of the design process (both for DSP processors in general and for this project) and motivates the design decisions made for this processor. The second part is a nearly complete design specification. The intended use of the processor is as a platform for hardware acceleration units. Support for this has howe...

  17. [Specificities of pneumonia in geriatrics]. (United States)

    Pepersack, T


    Pneumonia is a major cause of morbidity and mortality leading to a high rate of hospitalization especially in theelderly. It is often a sign of frailty and is associated with a poor prognosis. However, taking into account the geriatric specificities (risk factors, atypical clinical presentations with "geriatric syndromes", ethical debate) using an interdisciplinary and a comprehensive geriatric approach remains an important responsibility of the general practitionner. This article summarizes these specificities and offers interventions targeted on the characteristics of elderly patients.

  18. CASL, the Common Algebraic Specification Language

    DEFF Research Database (Denmark)

    Mossakowski, Till; Haxthausen, Anne Elisabeth; Sannella, Donald;


    CASL is an expressive specification language that has been designed to supersede many existing algebraic specification languages and provide a standard. CASL consists of several layers, including basic (unstructured) specifications, structured specifications and architectural specifications...

  19. NIF optical specifications - the importance of the RMS gradient specification

    Energy Technology Data Exchange (ETDEWEB)

    Auerbach, J M; Cotton, C T; English, R E; Henesian, M A; Hunt J T; Kelly, J H; Lawson, J K; Sacks, J B; Shoup, M J; Trenholme, W H


    The performance of the National Ignition Facility (NIF), especially in terms of laser focusability, will be determined by several key factors. One of these key factors is the optical specification for the thousands of large aperture optics that will comprise the 192 beamlines. We have previously reported on the importance of the specification of the power spectral density (PSD) on NIF performance. Recently, we have been studying the importance of long spatial wavelength (>33 mm) phase errors on focusability. We have concluded that the preferred metric for determining the impact of these long spatial wavelength phase errors is the rms phase gradient. In this paper, we outline the overall approach to NIF optical specifications, detail the impact of the rms phase gradient on NIF focusability, discuss its trade-off with the PSD in determining the spot size and review measurements of optics similar to those to be manufactured for NIF.

  20. VHDL Specification Methodology from High-level Specification

    Directory of Open Access Journals (Sweden)

    M. Benmohammed


    Full Text Available Design complexity has been increasing exponentially this last decade. In order to cope with such an increase and to keep up designers' productivity, higher level specifications were required. Moreover new synthesis systems, starting with a high level specification, have been developed in order to automate and speed up processor design. This study presents a VHDL specification methodology aimed to extend structured design methodologies to the behavioral level. The goal is to develop VHDL modeling strategies in order to master the design and analysis of large and complex systems. Structured design methodologies are combined with a high-level synthesis system, a VHDL based behavioral synthesis tool, in order to allow hierarchical design and component re-use.

  1. Technical specification for vacuum systems

    Energy Technology Data Exchange (ETDEWEB)

    Khaw, J. (ed.)


    The vacuum systems at the Stanford Linear Accelerator Center (SLAC) are primarily of all-metal construction and operate at pressures from 10/sup -5/ to 10/sup -11/ Torr. The primary gas loads during operation result from thermal desorption and beam-induced desorption from the vacuum chamber walls. These desorption rates can be extremely high in the case of hydrocarbons and other contaminants. These specifications place a major emphasis on eliminating contamination sources. The specifications and procedures have been written to insure the cleanliness and vacuum integrity of all SLAC vacuum systems, and to assist personnel involved with SLAC vacuum systems in choosing and designing components that are compatible with existing systems and meet the quality and reliability of SLAC vacuum standards. The specification includes requirements on design, procurement, fabrication, chemical cleaning, clean room practices, welding and brazing, helium leak testing, residual gas analyzer testing, bakeout, venting, and pumpdown. Also appended are specifications regarding acceptable vendors, isopropyl alcohol, bakeable valve cleaning procedure, mechanical engineering safety inspection, notes on synchrotron radiation, and specifications of numerous individual components. (LEW)

  2. 1997 hybrid electric vehicle specifications

    Energy Technology Data Exchange (ETDEWEB)

    Sluder, S.; Larsen, R.; Duoba, M.


    The US DOE sponsors Advanced Vehicle Technology competitions to help educate the public and advance new vehicle technologies. For several years, DOE has provided financial and technical support for the American Tour de Sol. This event showcases electric and hybrid electric vehicles in a road rally across portions of the northeastern United States. The specifications contained in this technical memorandum apply to vehicles that will be entered in the 1997 American Tour de Sol. However, the specifications were prepared to be general enough for use by other teams and individuals interested in developing hybrid electric vehicles. The purpose of the specifications is to ensure that the vehicles developed do not present a safety hazard to the teams that build and drive them or to the judges, sponsors, or public who attend the competitions. The specifications are by no means the definitive sources of information on constructing hybrid electric vehicles - as electric and hybrid vehicles technologies advance, so will the standards and practices for their construction. In some cases, the new standards and practices will make portions of these specifications obsolete.

  3. Compiler writing system detail design specification. Volume 1: Language specification (United States)

    Arthur, W. J.


    Construction within the Meta language for both language and target machine specification is reported. The elements of the function language as a meaning and syntax are presented, and the structure of the target language is described which represents the target dependent object text representation of applications programs.

  4. Program Construction by Verifying Specification

    Institute of Scientific and Technical Information of China (English)

    林洪; 陈国良


    A program construction method based on Gamma language is proposed.The problem to be solved is specified by first-order predicate logic and a semantic verification program is constructed directly from the specification.Ways for improving efficiency of the program are also studied.The method differs from the one proposed by Manna and Waldinger,where a program is extracted from the proof of the existence of an object meeting the given specification.On the other hand,it also differs from the classical one used for deriving Gamma programs of Banatre and Le metayes,which consists in decomposing the specification into an invariant and a termination conditon.

  5. Specific probiotics or 'fecal transplantation'. (United States)

    Kruis, Wolfgang


    The intestinal ecosystem consists mainly of the enteric flora and to a large extent determines intestinal but also extraintestinal health and disease. General alterations and specific molecular changes of intestinal bacteria cause local as well as systemic immune reactions. Nonantibiotic treatment of the enteric flora has a long tradition and spans a range of different interventions from nutrition to specific probiotics and complete fecal transplantation. When comparing therapy to specific probiotics and fecal transplantation, several aspects need to be considered, like biological consequences, safety and therapeutic evidence. The introduction of probiotics into therapy occurred more than hundred years ago. In contrast, experiences with fecal transplantation are more recent and more limited. Safety issues have not been definitively clarified. Because of the different biological activities of probiotics and fecal transplantation, it can be hypothesized that they may play different roles in the treatment of various diseases. More research is needed before the details, safety and therapeutic effects of bacteriotherapy for IBD become sufficiently clear.

  6. Methylation-Specific PCR Unraveled

    Directory of Open Access Journals (Sweden)

    Sarah Derks


    Full Text Available Methylation‐specific PCR (MSP is a simple, quick and cost‐effective method to analyze the DNA methylation status of virtually any group of CpG sites within a CpG island. The technique comprises two parts: (1 sodium bisulfite conversion of unmethylated cytosine's to uracil under conditions whereby methylated cytosines remains unchanged and (2 detection of the bisulfite induced sequence differences by PCR using specific primer sets for both unmethylated and methylated DNA. This review discusses the critical parameters of MSP and presents an overview of the available MSP variants and the (clinical applications.

  7. Domain specific MT in use

    DEFF Research Database (Denmark)

    Offersgaard, Lene; Povlsen, Claus; Almsten, Lisbeth Kjeldgaard


    The paper focuses on domain specific use of MT with a special focus on SMT in the workflow of a Language Service Provider (LSP). We report on the feedback of post-editors using fluency/adequacy evaluation and the evaluation metric ’Usability’, understood in this context as where users on a three ...

  8. Vibrio chromosome-specific families

    DEFF Research Database (Denmark)

    Lukjancenko, Oksana; Ussery, David


    We have compared chromosome-specific genes in a set of 18 finished Vibrio genomes, and, in addition, also calculated the pan- and core-genomes from a data set of more than 250 draft Vibrio genome sequences. These genomes come from 9 known species and 2 unknown species. Within the finished...


    First California Commission on School Construction Systems, Palo Alto.


  10. [Specificities in children wound healing]. (United States)

    Sanchez, J; Antonicelli, F; Tuton, D; Mazouz Dorval, S; François, C


    Children have specific characteristics of wound healing. The aim of this study was to describe the specific clinical characteristics of wounds healing in children and to present the current knowledge on the specific mechanisms with regard to infant age. The tissue insult or injury in fetus can heal without scar, mainly due to reduced granulation tissue associated to diminished or even no inflammatory phase, modified extracellular matrix such as the concentration of hyaluronic acid in amniotic liquid, expression and arrangement of collagen and tenascin. Thickness of children skin is a serious negative factor in case of trauma, whereas poor co-morbidities and efficient growth tissue mechanisms are beneficial to good evolution, even in cases of extensive damage and loss of tissue. The subsequent tissue mechanical forces, wound healing during childhood, spanning from the age of 2 until the end of puberty, is associated with more hypertrophic scars, both in duration and in intensity. Consequently, unnecessary surgery has to be avoided during this period when possible, and children with abnormal or pathologic wound healing should benefit from complementary treatments (hydration, massage, brace, silicone, hydrotherapy…), which represent efficient factors to minimize tissue scarring. After wound healing, the growth body rate can be responsible for specific complications, such as contractures, alopecia, and scar intussusceptions. Its evolutionary character implies the need of an attentive follow-up until adult age. Psychologic repercussions, as a consequence of pathologic scars, must be prevented and investigated by the surgeon.

  11. Final Empirical Test Case Specification

    DEFF Research Database (Denmark)

    Kalyanova, Olena; Heiselberg, Per

    This document includes the empirical specification on the IEA task of evaluation building energy simulation computer programs for the Double Skin Facades (DSF) constructions. There are two approaches involved into this procedure, one is the comparative approach and another is the empirical one....

  12. Priming the Query Specification Process. (United States)

    Toms, Elaine G.; Freund, Luanne


    Tests the use of questions as a technique in the query specification process. Using a within-subjects design, 48 people interacted with a modified Google interface to solve four information problems in four domains. Half the tasks were entered as typical keyword queries, and half as questions or statements. Results suggest the typical search box…

  13. Adaptive Assessments Using Open Specifications (United States)

    Leon, Hector Barbosa; Garcia-Penalvo, Francisco J.; Rodriguez-Conde, Maria Jose; Morales, Erla M.; de Pablos, Patricia Ordonez


    Evaluation is a key element in formal education processes; it must be constructed in a way that the item questions within help students understand by adapting them to the learning style as well. The focus of the present research work specifically in the convenience to adapt an associated multimedia material in each single question besides the…

  14. Specific yield, High Plains aquifer (United States)

    U.S. Geological Survey, Department of the Interior — This raster data set represents specific-yield ranges in the High Plains aquifer of the United States. The High Plains aquifer underlies 112.6 million acres (176,000...

  15. Epididymis-specific lipocalin promoters

    Institute of Scientific and Technical Information of China (English)

    Kichiya Suzuki; Xiuping Yu; Pierre Chaurand; Yoshihiko Araki; Jean-Jacques Lareyre; Richard M. Caprioli; Marie-Claire Orgebin-Crist; Robert J. Matusik


    Our goal is to decipher which DNA sequences are required for tissue-specific expression of epididymal genes. At least 6 epididymis-specific lipocalin genes are known. These are differently regulated and regionalized in the epididymis.Lipocalin 5 (Lcn5 or mE-RABP) and Lipocalin 8 (Lcn8 or mEP17) are homologous genes belonging to the epididymis-specific lipocalin gene cluster. Both the 5 kb promoter fragment of the Lcn5 gene and the 5.3 kb promoter fragment of the Lcn8 gene can direct transgene expression in the epididymis (Lcn5 to the distal caput and Lcn8 to the initial segment), indicating that these promoter fragments contain important cis-regulatory element(s) for epididymisspecific gene expression. To define further the fragments regulating gene expression, the Lcn5 promoter was examined in transgenic mice and immortalized epididymal cell lines. After serial deletion, the 1.8 kb promoter fragment of the Lcn5 gene was sufficient for tissue-specific and region-specific gene expression in transgenic mice. Transient transfection analysis revealed that a transcription factor forkhead box A2 (Foxa2) interacts with androgen receptor and binds to the 100 bp fragment of the Lcn5 promoter between 1.2 kb and 1.3 kb and that Foxa2 expression inhibitsandrogen-dependent induction of the Lcn5 promoter activity. Immunohistochemistry indicated a restricted expression of Foxa2 in the epididymis where endogenous Lcn5 gene expression is suppressed and that the Foxa2 inhibition of the Lcn5 promoter is consistent with the lack of expression of Lcn5 in the corpus and cauda. Our approach provides a basic strategy for further analysis of the epididymal lipocalin gene regulation and flexible control of epididymal function.

  16. Rapid Estimation of Specific Impulse

    Directory of Open Access Journals (Sweden)

    V. K. Bhat


    Full Text Available Specific impulse (Isp is one of the important criteria for propellant characterisation. In the present paper a semiempirical approach has been suggested to calculate Isp of composite modified doublebase(CMDB propellant formulations by utilizing calorimetric value(Cal-Val of the propellant composition. The Cal-Val of aluminium has been computed on the basis of oxygen balance of the propellant composition. The validity of the new approach has been demonstratedby comparing predicted values witli actual results.

  17. A development calculus for specifications

    Institute of Scientific and Technical Information of China (English)



    A first order inference system, named R-calculus, is defined to develop the specifications.This system intends to eliminate the laws which are not consistent with users' requirements. TheR-calculus consists of the structural rules, an axiom, a cut rule, and the rules for logical connectives.Some examples are given to demonstrate the usage of the R-calculus. Furthermore, the propertiesregarding reachability and completeness of the R-calculus are formally defined and proved.

  18. Lack of specificity of commercially available antisera: better specifications needed. (United States)

    Pradidarcheep, Wisuit; Labruyère, Wil T; Dabhoiwala, Noshir F; Lamers, Wouter H


    The ideal antiserum for immunohistochemical (IHC) applications contains monospecific high-affinity antibodies with little nonspecific adherence to sections. Many commercially available antibodies are "affinity" purified, but it is unknown if they meet "hard" specificity criteria, such as absence of staining in tissues genetically deficient for the antigen or a staining pattern that is identical to that of an antibody raised against a different epitope on the same protein. Reviewers, therefore, often require additional characterization. Although the affinity-purified antibodies used in our study on the distribution of muscarinic receptors produced selective staining patterns on sections, few passed the preabsorption test, and none produced bands of the anticipated size on Western blots. More importantly, none showed a difference in staining pattern on sections or Western blots between wild-type and knockout mice. Because these antibodies were used in most studies published thus far, our findings cast doubts on the validity of the extant body of morphological knowledge of the whole family of muscarinic receptors. We formulate requirements that antibody-specification data sheets should meet and propose that journals for which IHC is a core technique facilitate consumer rating of antibodies. "Certified" antibodies could avoid fruitless and costly validation assays and should become the standard of commercial suppliers.

  19. How specific is specific phobia? Different neural response patterns in two subtypes of specific phobia. (United States)

    Lueken, Ulrike; Kruschwitz, Johann Daniel; Muehlhan, Markus; Siegert, Jens; Hoyer, Jürgen; Wittchen, Hans-Ulrich


    Specific phobia of the animal subtype has been employed as a model disorder exploring the neurocircuitry of anxiety disorders, but evidence is lacking whether the detected neural response pattern accounts for all animal subtypes, nor across other phobia subtypes. The present study aimed at directly comparing two subtypes of specific phobia: snake phobia (SP) representing the animal, and dental phobia (DP) representing the blood-injection-injury subtype. Using functional magnetic resonance imaging (fMRI), brain activation and skin conductance was measured during phobogenic video stimulation in 12 DP, 12 SP, and 17 healthy controls. For SP, the previously described activation of fear circuitry structures encompassing the insula, anterior cingulate cortex and thalamus could be replicated and was furthermore associated with autonomic arousal. In contrast, DP showed circumscribed activation of the prefrontal and orbitofrontal cortex (PFC/OFC) when directly compared to SP, being dissociated from autonomic arousal. Results provide preliminary evidence for the idea that snake and dental phobia are characterized by distinct underlying neural systems during sustained emotional processing with evaluation processes in DP being controlled by orbitofrontal areas, whereas phobogenic reactions in SP are primarily guided by limbic and paralimbic structures. Findings support the current diagnostic classification conventions, separating distinct subtypes in DSM-IV-TR. They highlight that caution might be warranted though for generalizing findings derived from animal phobia to other phobic and anxiety disorders. If replicated, results could contribute to a better understanding of underlying neurobiological mechanisms of specific phobia and their respective classification.

  20. Advances in bacterial specific imaging

    Energy Technology Data Exchange (ETDEWEB)

    Wareham, David; Das, Satya [St Bartholomew' s Hospital, London (United Kingdom). Dept. of Medical Microbiology; London Univ. (United Kingdom). Queen Mary' s School of Medicine and Dentistry. Inst. of Cell and Molecular Science


    Nuclear medicine is a powerful diagnostic technique able to detect inflammatory foci in human disease. A wide range of agents have been evaluated for their ability to distinguish lesions due to microbial infection from those due to sterile inflammation. Advances continue to be made on the use of radiolabelled antibiotics which as well as being highly specific in the diagnosis of infection may be useful in monitoring the treatment and course of disease. Here we provide an update on in-vitro and clinical studies with a number of established and novel radiopharmaceuticals. (author)

  1. Central Solenoid Insert Technical Specification

    Energy Technology Data Exchange (ETDEWEB)

    Martovetsky, Nicolai N [ORNL; Smirnov, Alexandre [ORNL


    The US ITER Project Office (USIPO) is responsible for the ITER central solenoid (CS) contribution to the ITER project. The Central Solenoid Insert (CSI) project will allow ITER validation the appropriate lengths of the conductors to be used in the full-scale CS coils under relevant conditions. The ITER Program plans to build and test a CSI to verify the performance of the CS conductor. The CSI is a one-layer solenoid with an inner diameter of 1.48 m and a height of 4.45 m between electric terminal ends. The coil weight with the terminals is approximately 820 kg without insulation. The major goal of the CSI is to measure the temperature margin of the CS under the ITER direct current (DC) operating conditions, including determining sensitivity to load cycles. Performance of the joints, ramp rate sensitivity, and stability against thermal or electromagnetic disturbances, electrical insulation, losses, and instrumentation are addressed separately and therefore are not major goals in this project. However, losses and joint performance will be tested during the CSI testing campaign. The USIPO will build the CSI that will be tested at the Central Solenoid Model Coil (CSMC) Test Facility at the Japan Atomic Energy Agency (JAEA), Naka, Japan. The industrial vendors (the Suppliers) will report to the USIPO (the Company). All approvals to proceed will be issued by the Company, which in some cases, as specified in this document, will also require the approval of the ITER Organization. Responsibilities and obligations will be covered by respective contracts between the USIPO, called Company interchangeably, and the industrial Prime Contractors, called Suppliers. Different stages of work may be performed by more than one Prime Contractor, as described in this specification. Technical requirements of the contract between the Company and the Prime Contractor will be covered by the Fabrication Specifications developed by the Prime Contractor based on this document and approved by

  2. IntelliCable Interface Specification (United States)


    manager on how to use this. Some will factor the priority into account and always consume the highest priority while others...Battlefield Air Operations power manager uses a 10 pin Glenair Mighty Mouse connector with default keying . Pin 9 is specified as the IntelliCable pin. A BAO...standard Soldier Power Manager uses a 7 pin Glenair Mighty Mouse Connector, using alternative keying distinct from the Land Warrior battery specification, and the Li-145 battery. Pin 3 is defined as the IntelliCable pin.

  3. Specifications of EA-BRACHI

    Energy Technology Data Exchange (ETDEWEB)

    Taguchi, Mitsumasa; Namba, Hideki; Aoki, Yasushi; Watanabe, Ritsuko; Matsumoto, Yuuichi; Watanabe, Hiroshi [Japan Atomic Energy Research Inst., Takasaki, Gunma (Japan). Takasaki Radiation Chemistry Research Establishment


    EA-BRACHI (Experimental Apparatus for Basic study of Radiation Chemistry with Heavy Ions) has been constructed at a vertical port of AVF cyclotron in TIARA (Takasaki Ion Accelerators for Advanced Radiation Application) facility. This apparatus is used for measurement of the spatial distribution of energy deposited around the ion`s path, and the reaction of radicals and other intermediates produced by heavy ion irradiation in solid and liquid samples. This report detailed specifications and performance of this apparatus, including operational procedures and some basic data. (author)

  4. Flight Guidance System Requirements Specification (United States)

    Miller, Steven P.; Tribble, Alan C.; Carlson, Timothy M.; Danielson, Eric J.


    This report describes a requirements specification written in the RSML-e language for the mode logic of a Flight Guidance System of a typical regional jet aircraft. This model was created as one of the first steps in a five-year project sponsored by the NASA Langley Research Center, Rockwell Collins Inc., and the Critical Systems Research Group of the University of Minnesota to develop new methods and tools to improve the safety of avionics designs. This model will be used to demonstrate the application of a variety of methods and techniques, including safety analysis of system and subsystem requirements, verification of key properties using theorem provers and model checkers, identification of potential sources mode confusion in system designs, partitioning of applications based on the criticality of system hazards, and autogeneration of avionics quality code. While this model is representative of the mode logic of a typical regional jet aircraft, it does not describe an actual or planned product. Several aspects of a full Flight Guidance System, such as recovery from failed sensors, have been omitted, and no claims are made regarding the accuracy or completeness of this specification.

  5. Arithmetic Memory Is Modality Specific.

    Directory of Open Access Journals (Sweden)

    Timothy Myers

    Full Text Available In regards to numerical cognition and working memory, it is an open question as to whether numbers are stored into and retrieved from a central abstract representation or from separate notation-specific representations. This study seeks to help answer this by utilizing the numeral modality effect (NME in three experiments to explore how numbers are processed by the human brain. The participants were presented with numbers (1-9 as either Arabic digits or written number words (Arabic digits and dot matrices in Experiment 2 at the first (S1 and second (S2 stimuli. The participant's task was to add the first two stimuli together and verify whether the answer (S3, presented simultaneously with S2, was correct. We hypothesized that if reaction time (RT at S2/S3 depends on the modality of S1 then numbers are retrieved from modality specific memory stores. Indeed, RT depended on the modality of S1 whenever S2 was an Arabic digit which argues against the concept of numbers being stored and retrieved from a central, abstract representation.

  6. [Pharmacological gender-specific medicine]. (United States)

    Ueno, Koichi; Negishi, Etsuko


    In recent years, the concept of Gender-specific Medicine has become more widespread in Japan. We need to understand gender differences in the use patterns of prescription drugs for proper use of medicines. We therefore investigated gender differences in the use of prescription drugs using the data of 9 hospitals in Japan. The data on prescription drugs were extracted from the drug ordering system for a month from March 1 to 31, 2003. We analyzed the data according to sex and age. As a result, we found that the prescription frequency of central nervous system drugs and Kampo medications for females was higher than that for males. There was also the same trend for hormone medicines and vitamins. On the other hand, the prescription frequency of cardiovascular drugs for males was higher than that for females. Moreover, there was the same trend for unclassified metabolic drugs such as arthrifuge. As a result of detailed analysis by age, a correlation between age-specificity of prescription drugs and gender difference of diseases was suggested. Such information has not been investigated in Japan. Since these results are thought to be useful, we will perform a detailed examination and accumulate evidence for their future exploitation in drug therapy.

  7. MATISSE: specifications and expected performances

    CERN Document Server

    Matter, A; Petrov, R G; Berio, P; Robbe-Dubois, S; Lopez, B; Antonelli, P; Allouche, F; Cruzalebes, P; Millour, F; Bazin, G; Bourgès, L


    MATISSE (Multi AperTure mid-Infrared SpectroScopic Experiment) is the next generation spectro-interferometer at the European Southern Observatory VLTI operating in the spectral bands L, M and N, and combining four beams from the unit and auxiliary telescopes. MATISSE is now fully integrated at the Observatoire de la C\\^ote d'Azur in Nice (France), and has entered very recently its testing phase in laboratory. This paper summarizes the equations describing the MATISSE signal and the associated sources of noise. The specifications and the expected performances of the instrument are then evaluated taking into account the current characteristics of the instrument and the VLTI infrastructure, including transmission and contrast degradation budgets. In addition, we present the different MATISSE simulation tools that will be made available to the future users.

  8. Specifications for gas treatment apparatus

    Energy Technology Data Exchange (ETDEWEB)

    Teraoka, Yuden; Yoshigoe, Akitaka [Japan Atomic Energy Research Inst., Kansai Research Establishment, Synchrotron Radiation Research Center, Mikazuki, Hyogo (Japan)


    A surface reaction analysis apparatus was installed as an experimental end-station for the study of surface chemistry at the JAERI soft x-ray beamline in the SPring-8. The surface reaction analysis apparatus is devoted to the study of reaction mechanisms on solid surfaces with incident gas molecules. It is necessary to supply reagent gases to the apparatus. Chlorine and metal organic molecules will be used in the apparatus as well as oxygen molecules. Since the chlorine is corrosive and virulent, the metal organic molecules are flammable, the satiety treatments and the removal of virulence from the exhaust gas are needed. This gas supply and exhaust system is mainly composed of a cylinder cabinet, a gas mixer, a virulence removal cell and an urgent virulence removal apparatus. The former three devices are considered to take a countermeasure against virulent gas leak. The detail specifications concerning the gas supply and exhaust system are described in this report. (author)

  9. Distribution-Specific Agnostic Boosting

    CERN Document Server

    Feldman, Vitaly


    We consider the problem of boosting the accuracy of weak learning algorithms in the agnostic learning framework of Haussler (1992) and Kearns et al. (1992). Known algorithms for this problem (Ben-David et al., 2001; Gavinsky, 2002; Kalai et al., 2008) follow the same strategy as boosting algorithms in the PAC model: the weak learner is executed on the same target function but over different distributions on the domain. We demonstrate boosting algorithms for the agnostic learning framework that only modify the distribution on the labels of the points (or, equivalently, modify the target function). This allows boosting a distribution-specific weak agnostic learner to a strong agnostic learner with respect to the same distribution. When applied to the weak agnostic parity learning algorithm of Goldreich and Levin (1989) our algorithm yields a simple PAC learning algorithm for DNF and an agnostic learning algorithm for decision trees over the uniform distribution using membership queries. These results substantia...

  10. The Specificity of Human Aesthetics

    DEFF Research Database (Denmark)

    Bouchet, Dominique


    Today, humankind is being reintroduced within nature. Humankind is no longer presented as supernatural to nature. There is no longer a clear divide between animal and human. What makes us human is neither culture, nor language nor labor, nor art, but the degree of complexity those products and ca...... creativity. Art is fundamentally about shaping visions and very closely related to this specific human ability to make projects. Especially in times of crisis, when the old sources of meaning hardly can make sense in a new context, imagination must be used in order to survive......., and the craving to make sense of all kinds of relations that characterizes humans. Being able to produce artworks as external representations aimed at “the other,” made of internal representations is thus essential to humanity. Human aesthetics is not so much an issue of beauty but of imagination and social...

  11. Genetic specificity of face recognition. (United States)

    Shakeshaft, Nicholas G; Plomin, Robert


    Specific cognitive abilities in diverse domains are typically found to be highly heritable and substantially correlated with general cognitive ability (g), both phenotypically and genetically. Recent twin studies have found the ability to memorize and recognize faces to be an exception, being similarly heritable but phenotypically substantially uncorrelated both with g and with general object recognition. However, the genetic relationships between face recognition and other abilities (the extent to which they share a common genetic etiology) cannot be determined from phenotypic associations. In this, to our knowledge, first study of the genetic associations between face recognition and other domains, 2,000 18- and 19-year-old United Kingdom twins completed tests assessing their face recognition, object recognition, and general cognitive abilities. Results confirmed the substantial heritability of face recognition (61%), and multivariate genetic analyses found that most of this genetic influence is unique and not shared with other cognitive abilities.

  12. Specific Carbohydrate Diet: Does It Work? (United States)

    ... Specific Carbohydrate Diet (SCD) Go Back The Specific Carbohydrate Diet (SCD) Email Print + Share There is no ... diet that has received attention is the Specific Carbohydrate Diet. This diet limits poorly digestible carbohydrates to ...

  13. FY97 ICCS prototype specification

    Energy Technology Data Exchange (ETDEWEB)

    Woodruff, J.


    The ICCS software team will implement and test two iterations of their software product during FY97. The first of these iterations will concentrate on construction of selected framework components; the subsequent iteration will extend the product and perform measurements of performance based on emulated FEP devices. This document specifies the products to be delivered in that first prototype and projects the direction that the second prototype will take. Detailed specification of the later iteration will be written when the results of the first iteration are complete. The selection of frameworks to be implemented early is made on a basis of risk analysis from the point of view of future development in the ICCS project. The prototype will address risks in integration of object- oriented components, in refining our development process, and in emulation testing for FEP devices. This document is a specification that identifies products and processes to undertake for resolving these risks. The goals of this activity are to exercise our development process at a modest scale and to probe our architecture plan for fundamental limits and failure modes. The product of the iterations will be the framework software which will be useful in future ICCS code. Thus the FY97 products are intended for internal usage by the ICCS team and for demonstration to the FEP software developers of the strategy for integrating supervisory software with FEP computers. This will be the first of several expected iterations of the software development process and the performance measurements that ICCS will demonstrate, intended to support confidence in our ability to meet project RAM goals. The design of the application software is being carried out in a separate WBS 1.5.2 activity. The design activity has as its FY97 product a series of Software Design Documents that will specify the functionality of the controls software of ICCS. During the testing of this year`s prototypes, the application

  14. Tumor specific cytotoxicity of glucosylceramide. (United States)

    Oku, Hirosuke; Wongtangtintharn, Sawitree; Iwasaki, Hironori; Inafuku, Masashi; Shimatani, Masayuki; Toda, Takayoshi


    To develop a new taxon of anti-cancer agent with lower side effect, this study described a tumor selective cytotoxicity of glucosylceramide extracted from malt feed of beer brewing waste. Interpretation of (13)C- and (1)H-NMR spectra identified the chemical structure of major component of glucosylceramide as 1-O-beta-D: -glucopyranosyl-2(2'-hydroxyeicosanoylamino)-4,11-octadecadiene-1,3-diol. Selective cytotoxicity was studied with three pairs of normal and cancer cells: liver, skin and lung. The glucosylceramide selectively lowered the relative viability of cancer cells. Of the pairs, the selectivity was most pronounced with the liver cells, and, for this reason, further experiment was conducted with this pair of normal (CS-HC) and cancer cells (HepG2) to get more insight into the selective toxicity. The glucosylceramide significantly increased the cell population at G(2)/M phase in HepG2 cells, and also increased the numbers of apoptotic (sub-G(0)/G(1)) cells, but to much lesser extent compared with the increase in G(2)/M phase. Treatment of HepG2 cells with this agent selectively disrupted the mitochondrial membrane integrity without activation of caspase pathway to induce apoptosis. These findings suggested that the glucosylceramide specifically suppressed the growth of cancer cells by inhibiting cell renewal capacity rather than induction of apoptosis. The underlying mechanism for the selectivity remains to be answered in the forthcoming study.

  15. RNB-specific linac development

    CERN Document Server

    Ratzinger, U


    The acceleration of secondary, radioactive beams from primary beam driven ion sources provides many challenges when compared to the case of conventional ion beams. The clean separation of the specific ion species, the low beam current, the short life time of the ions as well as the needed energy variability have consequences on the layout of the accelerator. As also experiments with astrophysical relevance are performed, the energy range should go down below 1 MeV/u in some cases. Additionally, to investigate nuclear reactions around the Coulomb barrier, the beam energy should be flexible up to around 8 MeV/u. Short isotope life times below a few milliseconds do not allow for charge breeding. In these cases, low charged ions from 'simple' ion sources have to be accepted by the accelerator. Furthermore, stripping processes along the linac are excluded in case of low beam currents. Multicoincidence experiments profit a lot from cw operation of ion source and accelerators. During the last three decades, room tem...

  16. Advances in bacterial specific imaging

    Directory of Open Access Journals (Sweden)

    David Wareham


    Full Text Available Nuclear medicine is a powerful diagnostic technique able to detect inflammatory foci in human disease. A wide range of agents have been evaluated for their ability to distinguish lesions due to microbial infection from those due to sterile inflammation. Advances continue to be made on the use of radiolabelled antibiotics which as well as being highly specific in the diagnosis of infection may be useful in monitoring the treatment and course of disease. Here we provide an update on in-vitro and clinical studies with a number of established and novel radiopharmaceuticalsA medicina nuclear é uma técnica poderosa de diagnóstico capaz de detectar focos inflamatórios em doenças humanas. Uma ampla gama de agentes tem sido avaliada em sua capacidade de distinguir lesões, devidas a infecções microbianas daquelas causadas por inflamações estéreis. Avanços continuam sendo realizados no uso de antibióticos radiomarcados que, da mesma forma que têm sido usados no diagnóstico altamente específico de infecções, podem ser úteis na monitoração do tratamento e do curso da doença. Neste estudo, nós apresentamos uma atualização sobre estudos in vitro e clínicos, com alguns novos radiofármacos e outros já consagrados.

  17. Are specific emotions narrated differently? (United States)

    Habermas, Tilmann; Meier, Michaela; Mukhtar, Barbara


    Two studies test the assertion that anger, sadness, fear, pride, and happiness are typically narrated in different ways. Everyday events eliciting these 5 emotions were narrated by young women (Study 1) and 5- and 8-year-old girls (Study 2). Negative narratives were expected to engender more effort to process the event, be longer, more grammatically complex, more often have a complication section, and use more specific emotion labels than global evaluations. Narratives of Hogan's (2003) juncture emotions anger and fear were expected to focus more on action and to contain more core narrative sections of orientation, complication, and resolution than narratives of the outcome emotions sadness and happiness. Hypotheses were confirmed for adults except for syntactic complexity, whereas children showed only some of these differences. Hogan's theory that juncture emotions are restricted to the complication section was not confirmed. Finally, in adults, indirect speech was more frequent in anger narratives and internal monologue in fear narratives. It is concluded that different emotions should be studied in how they are narrated, and that narratives should be analyzed according to qualitatively different emotions.

  18. Specifications in early conceptual design work

    DEFF Research Database (Denmark)

    Hansen, Claus Thorp; Andreasen, Mogens Myrup


    specifications, which express attractive product goals, and has to synthesise the product idea. The authors of this paper see a challenge to enhance and improve our understanding of the nature of design specifications as a means to support the synthesis of a product idea. In this empirical study we analyse...... the structure and content of design specifications during early ideation activities, where initial design specifications are formulated and a product idea is synthesised. We have analysed specification documents of 19 teams of novice designers. Our analysis indicates that a productive product design...... specification in early conceptual design consists of few specification statements, which express value, important aspects of product context and articulate key functions. A product design specification, which contains a lot of specification statements about product properties, is not productive to support...

  19. Model Commissioning Plan and Guide Specifications

    Energy Technology Data Exchange (ETDEWEB)



    The objectives of Model Commissioning Plan and Guide Specifications are to ensure that the design team applies commissioning concepts to the design and prepares commissioning specifications and a commission plan for inclusion in the bid construction documents.

  20. Ion specific effects on charged interfaces


    Medda, Luca


    The physico-chemical phenomena occurring at charged interfaces are specifically affected by the type and the concentration of electrolytes. This has implications both in living and in inorganic systems. The discovery of the ‘ion specific effects’ dates back to Hofmeister (1888), who observed the specific effect of salts in promoting egg white proteins precipitation. Nowadays we are aware that ion specific effects are ubiquitous in all fields of science and technology where electrolytes play a...

  1. Genre-Specific Semantic Video Indexing

    NARCIS (Netherlands)

    Wu, J.; Worring, M.


    In many applications, we find large video collections from different genres where the user is often only interested in one or two specific video genres. So, when users are querying the system with a specific semantic concept, they are likely aiming a genre specific instantiation of this concept. Thu

  2. Map Specifications and Exchange of Geographical Information

    DEFF Research Database (Denmark)

    Frederiksen, Poul


    Specifications for Technical Maps 1993 – 99 are described giving an overview of the specification structure including the object description of the latest version: TK99.The technical map specifications are related to the standards for topographical maps - especially the TOP10DK standard. Common o...

  3. Programming Bacteriophages by Swapping Their Specificity Determinants. (United States)

    Goren, Moran G; Yosef, Ido; Qimron, Udi


    Bacteriophages, bacteria's natural enemies, may serve as potent antibacterial agents. Their specificity for certain bacterial sub-species limits their effectiveness, but allows selective targeting of bacteria. Lu and colleagues present a platform for such targeting through alteration of bacteriophages' host specificity by swapping specificity domains in their host-recognition ligand.

  4. 31 CFR 515.318 - Specific license. (United States)


    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Specific license. 515.318 Section 515.318 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF... § 515.318 Specific license. A specific license is any license or authorization issued pursuant to...

  5. 31 CFR 535.318 - Specific license. (United States)


    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Specific license. 535.318 Section 535.318 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF... § 535.318 Specific license. A specific license is any license or authorization issued pursuant to...

  6. 31 CFR 585.308 - Specific license. (United States)


    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Specific license. 585.308 Section 585.308 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF... General Definitions § 585.308 Specific license. The term specific license means any license...

  7. 31 CFR 500.318 - Specific license. (United States)


    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Specific license. 500.318 Section 500.318 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF... § 500.318 Specific license. A specific license is any license or authorization issued pursuant to...

  8. 31 CFR 586.315 - Specific license. (United States)


    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Specific license. 586.315 Section 586...) KOSOVO SANCTIONS REGULATIONS General Definitions § 586.315 Specific license. The term specific license means any license or authorization not set forth in this part but issued pursuant to this part....

  9. 31 CFR 536.313 - Specific license. (United States)


    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Specific license. 536.313 Section 536.313 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF... Definitions § 536.313 Specific license. The term specific license means any license or authorization not...

  10. 31 CFR 595.312 - Specific license. (United States)


    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Specific license. 595.312 Section 595.312 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF... § 595.312 Specific license. The term specific license means any license or authorization not set...

  11. 31 CFR 560.312 - Specific license. (United States)


    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Specific license. 560.312 Section 560.312 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF... § 560.312 Specific license. The term specific license means any license or authorization not set...

  12. 31 CFR 538.311 - Specific license. (United States)


    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Specific license. 538.311 Section 538.311 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF... § 538.311 Specific license. The term specific license means any license or authorization not set...

  13. 50 CFR 648.260 - Specifications. (United States)


    .... Specifications include the specification of OY, the setting of any target TACs, allocation of DAS, and/or... allocation based on target TAC. For purposes of determining the appropriate DAS allocation, any overage of... developing the management measures and specifications, the PDT shall review at least the following data,...

  14. The etiology of specific phobias : A review

    NARCIS (Netherlands)

    Merckelbach, H; de Jong, Peter; Muris, P; vandenHout, MA


    The present article summarizes theory and data about symptomatology, epidemiology, and etiology of specific phobias. Additionally, the cognitive mechanisms involved in specific Phobias are briefly discussed By and large, the general pattern behind the development of specific phobias can be summarize

  15. Normalized Specifications for Identifying Reusable Software




    An approach to retrieving reusable software components by means of module specifications is described. The approach depends on normalizing specifications to reduce the variations in the representation of software concepts. The concept is illustrated in terms of both formal and informal approaches to component specifications.

  16. Checking MSC Specifications for Timing Inconsistency

    Institute of Scientific and Technical Information of China (English)

    LI Xuandong(李宣东); TAN Wenkai(谭文凯); ZHENG Guoliang(郑国梁)


    Message sequence chart (MSC) is a graphical and textual language for the description and specification of the interactions between system components. MSC specifica tions allow convenient expression of multiple scenarios, and offer an intuitive and visual way of describing design requirements. Like any other aspect of the specification and design process, MSCs are amenable to errors, and their analysis is important. In this paper, the verification problem of MSC specification for timing inconsistency is studied, which means that no execu tion scenario described by an MSC specification is timing consistent. An algorithm is developed to check MSC specifications for timing inconsistency.

  17. 75 FR 55809 - Prospective Grant of Exclusive License: The Development of Immunotoxins/Targeted Toxins for the... (United States)


    ... ``Immunoconjugates Having High Binding Affinity'' [HHS Ref. E-139-1999/ 0-US-01], U.S. Patent Application 60/067,175 entitled ``Antibodies, Including Fv Molecules, and Immunoconjugates Having High Binding Affinity for..., thereby improving the therapeutic value of PE while maintaining its ability to trigger cell death....

  18. Using Abduction to Evolve Inconsistent Requirements Specification

    Directory of Open Access Journals (Sweden)

    Bashar Nuseibeh


    Full Text Available Requirements specifications are often inconsistent. Inconsistencies may arise because multiple conflicting requirements are embodied in these specifications, or because the specifications themselves are in a transient stage of evolutionary development. In this paper we argue that such inconsistencies, rather than being undesirable, are actually useful drivers for changing the requirements specifications in which they arise. We present a formal technique to reason about inconsistency handling changes. Our technique is an adaptation of logical abduction - adapted to generate changes that address some specification inconsistencies, while leaving others. We represent our specifications in quasi-classical (QC logic - an adaptation of classical logic that allows continued reasoning in the presence of inconsistency. The paper develops a sound algorithm for automating our abductive reasoning technique and presents illustrative examples drawn from a library system case study.

  19. Towards a theory of product design specifications

    DEFF Research Database (Denmark)

    Hansen, Claus Thorp; Andreasen, Mogens Myrup


    The product design specification is an important element in a product development project because it defines the target to be met. One requirement on the product design specification is to articulate and communicate the aspects, which makes the product attractive seen from the users' viewpoint....... In the design methodology literature we find guidelines and methods to compile a product design specification. The contributions are based on the common underlying assumption that it is meaningful and the only feasible approach to interpret the result of a need analysis into a set of technical specifications......, which express the customers¿ need and perception of value. In this paper we will scrutinize this assumption. We outline the roles and tasks of the product design specification in order to identify the requirements on a theory of product design specifications and we identify existing theory elements...

  20. Peptide binding specificity of the chaperone calreticulin

    DEFF Research Database (Denmark)

    Sandhu, N.; Duus, K.; Jorgensen, C.S.;


    Calreticulin is a molecular chaperone with specificity for polypeptides and N-linked monoglucosylated glycans. In order to determine the specificity of polypeptide binding, the interaction of calreticulin with polypeptides was investigated using synthetic peptides of different length and composit......Calreticulin is a molecular chaperone with specificity for polypeptides and N-linked monoglucosylated glycans. In order to determine the specificity of polypeptide binding, the interaction of calreticulin with polypeptides was investigated using synthetic peptides of different length...... and composition. A large set of available synthetic peptides (n=127) was tested for binding to calreticulin and the results analysed by multivariate data analysis. The parameter that correlated best with binding was hydrophobicity while beta-turn potential disfavoured binding. Only hydrophobic peptides longer...... a peptide-binding specificity for hydrophobic sequences and delineate the fine specificity of calreticulin for hydrophobic amino acid residues....

  1. Embedded systems specification and design languages

    CERN Document Server

    Villar, Eugenio


    This book is the latest contribution to the Chip Design Languages series and it consists of selected papers presented at the Forum on Specifications and Design Languages (FDL'07), in September 2007. The book represents the state-of-the-art in research and practice, and it identifies new research directions. It highlights the role of specification and modelling languages, and presents practical experiences with specification and modelling languages.

  2. Domain-Specific Ontology of Botany

    Institute of Scientific and Technical Information of China (English)

    Fang Gu; Cun-Gen Cao; Yue-Fei Sui; Wen Tian


    Domain-specific ontologies are greatly useful in knowledge acquisition, sharing and analysis. In this paper, botany-specific ontology for acquiring and analyzing botanical knowledge is presented. The ontology is represented in a set of well-defined categories, and each concept is viewed as an instance of certain category. The authors also introduce botany-specific axioms, an integral part of the ontology, for checking and reasoning with the acquired knowledge. Consistency, completeness and redundancy of the axioms are discussed.

  3. Standards and methods for software requirements specification



    This thesis presents the comparison between three selected standards and methods for software requirements specifications. IEEE 830 specification and use cases represent older, while user stories represent newer generation of methods for specification writing. Each method is first explained in theory and then on a practical example. E-študent, a well-known application to the students of the Faculty of computer and information science, serves as our practical example. The application is onl...

  4. Specifications in early conceptual design work

    DEFF Research Database (Denmark)

    Hansen, Claus Thorp; Andreasen, Mogens Myrup


    In early conceptual design the design team is working in an uncertain situation, where the understanding of a need is limited and not much is known about the solution space. In this situation the design team has to both analyse need and explore solution space. Thus, the team has to formulate design...... specification in early conceptual design consists of few specification statements, which express value, important aspects of product context and articulate key functions. A product design specification, which contains a lot of specification statements about product properties, is not productive to support...

  5. 77 FR 27814 - Model Safety Evaluation for Plant-Specific Adoption of Technical Specifications Task Force... (United States)


    ... COMMISSION Model Safety Evaluation for Plant-Specific Adoption of Technical Specifications Task Force... availability. SUMMARY: The U.S. Nuclear Regulatory Commission (NRC) is announcing the availability of the model safety evaluation (SE) for plant-specific adoption of Technical Specifications (TSs) Task Force...

  6. 77 FR 27490 - Plant-Specific Adoption, Revision 4 of the Improved Standard Technical Specifications (United States)


    ... Technical Specifications, NUREG-1430, ``Standard Technical Specifications, Babcock and Wilcox . NUREG-1430, ``Standard Technical Specifications, Babcock and Wilcox Plants'' Revision 4... ML12100A177 ML12100A178 Specifications, Babcock and Wilcox Plants'' NUREG-1431, ``Standard...

  7. User Interface Technology for Formal Specification Development (United States)

    Lowry, Michael; Philpot, Andrew; Pressburger, Thomas; Underwood, Ian; Lum, Henry, Jr. (Technical Monitor)


    Formal specification development and modification are an essential component of the knowledge-based software life cycle. User interface technology is needed to empower end-users to create their own formal specifications. This paper describes the advanced user interface for AMPHION1 a knowledge-based software engineering system that targets scientific subroutine libraries. AMPHION is a generic, domain-independent architecture that is specialized to an application domain through a declarative domain theory. Formal specification development and reuse is made accessible to end-users through an intuitive graphical interface that provides semantic guidance in creating diagrams denoting formal specifications in an application domain. The diagrams also serve to document the specifications. Automatic deductive program synthesis ensures that end-user specifications are correctly implemented. The tables that drive AMPHION's user interface are automatically compiled from a domain theory; portions of the interface can be customized by the end-user. The user interface facilitates formal specification development by hiding syntactic details, such as logical notation. It also turns some of the barriers for end-user specification development associated with strongly typed formal languages into active sources of guidance, without restricting advanced users. The interface is especially suited for specification modification. AMPHION has been applied to the domain of solar system kinematics through the development of a declarative domain theory. Testing over six months with planetary scientists indicates that AMPHION's interactive specification acquisition paradigm enables users to develop, modify, and reuse specifications at least an order of magnitude more rapidly than manual program development.

  8. Understanding the substrate specificity of conventional calpains. (United States)

    Sorimachi, Hiroyuki; Mamitsuka, Hiroshi; Ono, Yasuko


    Calpains are intracellular Ca(2+)-dependent Cys proteases that play important roles in a wide range of biological phenomena via the limited proteolysis of their substrates. Genetic defects in calpain genes cause lethality and/or functional deficits in many organisms, including humans. Despite their biological importance, the mechanisms underlying the action of calpains, particularly of their substrate specificities, remain largely unknown. Studies show that certain sequence preferences influence calpain substrate recognition, and some properties of amino acids have been related successfully to substrate specificity and to the calpains' 3D structure. The full spectrum of this substrate specificity, however, has not been clarified using standard sequence analysis algorithms, e.g., the position-specific scoring-matrix method. More advanced bioinformatics techniques were used recently to identify the substrate specificities of calpains and to develop a predictor for calpain cleavage sites, demonstrating the potential of combining empirical data acquisition and machine learning. This review discusses the calpains' substrate specificities, introducing the benefits of bioinformatics applications. In conclusion, machine learning has led to the development of useful predictors for calpain cleavage sites, although the accuracy of the predictions still needs improvement. Machine learning has also elucidated information about the properties of calpains' substrate specificities, including a preference for sequences over secondary structures and the existence of a substrate specificity difference between two similar conventional calpains, which has never been indicated biochemically.

  9. Determining the specific electric resistance of rock

    Energy Technology Data Exchange (ETDEWEB)

    Persad' ko, V.Ia.


    Data are presented on perfecting the method of laboratory determination of the specific electric resistance of a rock formation. The average error in determining the specific electric resistance of the core at various locations is no more than two percent with low resistance values (2-5 ohms).

  10. PCR specific for Actinobacillus pleuropneumoniae serotype 3

    DEFF Research Database (Denmark)

    Zhou, L.; Jones, S.C.P.; Angen, Øystein


    , but the method has liminations, for example, cross-reactions between serotypes 3, 6, and 8. This study describes the development of a serotype 3-specific PCR, based on the capsule locus, which can be used in a multiplex format with the organism's specific gene apxIV. The PCR test was evaluated on 266 strains...

  11. An Institution for Imperative RSL Specifications

    DEFF Research Database (Denmark)

    Haxthausen, Anne Elisabeth


    -oriented type definitions, declaration of state variables, axiomatic specification of values (including functions), and explicit function definitions. Functions may be imperative. The semantics of an RSLI specification is defined to be the loose semantics of a theory presentation consisting of a signature Σ...

  12. 21 CFR 107.100 - Nutrient specifications. (United States)


    ... 21 Food and Drugs 2 2010-04-01 2010-04-01 false Nutrient specifications. 107.100 Section 107.100... FOR HUMAN CONSUMPTION INFANT FORMULA Nutrient Requirements § 107.100 Nutrient specifications. (a) An infant formula shall contain the following nutrients at a level not less than the minimum level...

  13. Cell-Type-Specific Optogenetics in Monkeys. (United States)

    Namboodiri, Vijay Mohan K; Stuber, Garret D


    The recent advent of technologies enabling cell-type-specific recording and manipulation of neuronal activity spurred tremendous progress in neuroscience. However, they have been largely limited to mice, which lack the richness in behavior of primates. Stauffer et al. now present a generalizable method for achieving cell-type specificity in monkeys.

  14. Specific phobia predicts psychopathology in young women

    NARCIS (Netherlands)

    Trumpf, J.; Margraf, J.; Vriends, N.; Meyer, A.H.; Becker, E.S.


    Although specific phobia is characterized by an early age at onset and by high rates of comorbidity, few studies have examined comorbid relationships prospectively. The present study investigated the association between specific phobia and the risk of a broad range of psychopathology among young wom


    NARCIS (Netherlands)



    Generalization of skills is a major problem in social skills training for schizophrenic patients. Assessment of skills is mostly not based on objective indices of specific skill deficits. The results of this study show that global competence of schizophrenics can be differentiated from specific comp

  16. Some Approaches for Integration of Specification Techniques

    DEFF Research Database (Denmark)

    Haxthausen, Anne Elisabeth


    It is often useful to apply several specification techniques within the same software development project. This raises the question how specification techniques can be integrated. In this presentation we give three different examples of how this can be done. In the first example, we summarise how...

  17. Specific and social phobias in ICD-11

    NARCIS (Netherlands)

    Emmelkamp, P.M.G.


    The purpose of this article is to discuss the current status of research with respect to specific phobias and social phobia as defined in the ICD-10 and DSM-IV, and to provide op- tions for their classification in the ICD-11. Both ICD-10 and DSM-IV identify three main classes of phobias: specific ph

  18. 28 CFR 0.101 - Specific functions. (United States)


    ... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Specific functions. 0.101 Section 0.101 Judicial Administration DEPARTMENT OF JUSTICE ORGANIZATION OF THE DEPARTMENT OF JUSTICE Drug Enforcement Administration § 0.101 Specific functions. The Administrator of the Drug Enforcement Administration shall...

  19. 14 CFR 398.3 - Specific airports. (United States)


    ... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Specific airports. 398.3 Section 398.3... STATEMENTS GUIDELINES FOR INDIVIDUAL DETERMINATIONS OF BASIC ESSENTIAL AIR SERVICE § 398.3 Specific airports. (a) At an eligible place, essential air service may be specified as service to a particular...

  20. 28 CFR 0.131 - Specific functions. (United States)


    ... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Specific functions. 0.131 Section 0.131 Judicial Administration DEPARTMENT OF JUSTICE ORGANIZATION OF THE DEPARTMENT OF JUSTICE Bureau of Alcohol, Tobacco, Firearms, and Explosives § 0.131 Specific functions. The Director of the Bureau of...

  1. Specific vulnerability of substantia nigra compacta neurons

    NARCIS (Netherlands)

    Smidt, M.P.; Giovanni, G.; Di Matteo, V.; Esposito, E.


    The specific loss of substantia nigra compacta (SNc) neurons in Parkinson’s disease (PD) has been the main driving force in initiating research efforts to unravel the apparent SNc-specific vulnerability. Initially, metabolic constraints due to high dopamine turnover have been the main focus in the a

  2. Introduction to the ISO specification language LOTOS

    NARCIS (Netherlands)

    Bolognesi, Tomasso; Brinksma, Ed


    LOTOS is a specification language that has been specifically developed for the formal description of the OSI (Open Systems Interconnection) architecture, although it is applicable to distributed, concurrent systems in general. In LOTOS a system is seen as a set of processes which interact and exchan

  3. 14 CFR 23.1397 - Color specifications. (United States)


    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Color specifications. 23.1397 Section 23.1397 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT... Color specifications. Each position light color must have the applicable International Commission...

  4. 14 CFR 27.1397 - Color specifications. (United States)


    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Color specifications. 27.1397 Section 27... AIRWORTHINESS STANDARDS: NORMAL CATEGORY ROTORCRAFT Equipment Lights § 27.1397 Color specifications. Each position light color must have the applicable International Commission on Illumination...

  5. 14 CFR 25.1397 - Color specifications. (United States)


    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Color specifications. 25.1397 Section 25... AIRWORTHINESS STANDARDS: TRANSPORT CATEGORY AIRPLANES Equipment Lights § 25.1397 Color specifications. Each position light color must have the applicable International Commission on Illumination...

  6. 14 CFR 29.1397 - Color specifications. (United States)


    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Color specifications. 29.1397 Section 29... AIRWORTHINESS STANDARDS: TRANSPORT CATEGORY ROTORCRAFT Equipment Lights § 29.1397 Color specifications. Each position light color must have the applicable International Commission on Illumination...

  7. Tissue Specific Promoters in Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    A. R. Rama


    Full Text Available Colorectal carcinoma is the third most prevalent cancer in the world. In the most advanced stages, the use of chemotherapy induces a poor response and is usually accompanied by other tissue damage. Significant progress based on suicide gene therapy has demonstrated that it may potentiate the classical cytotoxic effects in colorectal cancer. The inconvenience still rests with the targeting and the specificity efficiency. The main target of gene therapy is to achieve an effective vehicle to hand over therapeutic genes safely into specific cells. One possibility is the use of tumor-specific promoters overexpressed in cancers. They could induce a specific expression of therapeutic genes in a given tumor, increasing their localized activity. Several promoters have been assayed into direct suicide genes to cancer cells. This review discusses the current status of specific tumor-promoters and their great potential in colorectal carcinoma treatment.

  8. Task-specific dystonia: pathophysiology and management. (United States)

    Sadnicka, Anna; Kassavetis, Panagiotis; Pareés, Isabel; Meppelink, Anne Marthe; Butler, Katherine; Edwards, Mark


    Task-specific dystonia is a form of isolated focal dystonia with the peculiarity of being displayed only during performance of a specific skilled motor task. This distinctive feature makes task-specific dystonia a particularly mysterious and fascinating neurological condition. In this review, we cover phenomenology and its increasingly broad-spectrum risk factors for the disease, critically review pathophysiological theories and evaluate current therapeutic options. We conclude by highlighting the unique features of task-specific dystonia within the wider concept of dystonia. We emphasise the central contribution of environmental risk factors, and propose a model by which these triggers may impact on the motor control of skilled movement. By viewing task-specific dystonia through this new lens which considers the disorder a modifiable disorder of motor control, we are optimistic that research will yield novel therapeutic avenues for this highly motivated group of patients.

  9. Fundamental Characteristics of Industrial Variant Specification Systems

    DEFF Research Database (Denmark)

    Hansen, Benjamin Loer; Hvam, Lars


    This paper focuses on the operational task of creating customised variants of industrial specifications (e.g. drawings, routings and bill-of-materials). Rooted in a lack of existing literature on the subject the paper describes the nature of variant specification systems. It introduces some funda...... examples. In general the paper discusses an important focus area within mass customization and build-to-order production: the nature of industrial variant specification systems.......This paper focuses on the operational task of creating customised variants of industrial specifications (e.g. drawings, routings and bill-of-materials). Rooted in a lack of existing literature on the subject the paper describes the nature of variant specification systems. It introduces some...

  10. Breckinridge Project, initial effort. Report III, Volume 2. Specifications

    Energy Technology Data Exchange (ETDEWEB)



    Report III, Volume 2 contains those specifications numbered K through Y, as follows: Specifications for Compressors (K); Specifications for Piping (L); Specifications for Structures (M); Specifications for Insulation (N); Specifications for Electrical (P); Specifications for Concrete (Q); Specifications for Civil (S); Specifications for Welding (W); Specifications for Painting (X); and Specifications for Special (Y). The standard specifications of Bechtel Petroleum Incorporated have been amended as necessary to reflect the specific requirements of the Breckinridge Project and the more stringent specifications of Ashland Synthetic Fuels, Inc. These standard specifications are available for the Initial Effort (Phase Zero) work performed by all contractors and subcontractors.

  11. Validating Avionics Conceptual Architectures with Executable Specifications

    Directory of Open Access Journals (Sweden)

    Nils Fischer


    Full Text Available Current avionics systems specifications, developed after conceptual design, have a high degree of uncertainty. Since specifications are not sufficiently validated in the early development process and no executable specification exists at aircraft level, system designers cannot evaluate the impact of their design decisions at aircraft or aircraft application level. At the end of the development process of complex systems, e. g. aircraft, an average of about 65 per cent of all specifications have to be changed because they are incorrect, incomplete or too vaguely described. In this paper, a model-based design methodology together with a virtual test environment is described that makes complex high level system specifications executable and testable during the very early levels of system design. An aircraft communication system and its system context is developed to demonstrate the proposed early validation methodology. Executable specifications for early conceptual system architectures enable system designers to couple functions, architecture elements, resources and performance parameters, often called non-functional parameters. An integrated executable specification at Early Conceptual Architecture Level is developed and used to determine the impact of different system architecture decisions on system behavior and overall performance.

  12. Isothermal Gravitational Segregation: Algorithms and Specifications

    DEFF Research Database (Denmark)

    Halldórsson, Snorri; Stenby, Erling Halfdan


    New algorithms for calculating the isothermal equilibrium state of reservoir fluids under the influence of gravity are presented. Two types of specifications are considered: the specification of pressure and composition at a reference depth; and the specification of the total overall content...... of the reservoir, along with the reservoir geometry. It is shown how both types of calculations can be performed in an efficient and robust manner using volume-based thermodynamics. The new method makes it possible to evaluate the influence of reservoir geometry and gravity segregation on the hydrocarbon reserves...

  13. Mining software specifications methodologies and applications

    CERN Document Server

    Lo, David


    An emerging topic in software engineering and data mining, specification mining tackles software maintenance and reliability issues that cost economies billions of dollars each year. The first unified reference on the subject, Mining Software Specifications: Methodologies and Applications describes recent approaches for mining specifications of software systems. Experts in the field illustrate how to apply state-of-the-art data mining and machine learning techniques to address software engineering concerns. In the first set of chapters, the book introduces a number of studies on mining finite

  14. Autoethnographic Mother-Writing: Advocating Radical Specificity

    Directory of Open Access Journals (Sweden)

    Patty Sotirin


    Full Text Available In considering the similarities between "momoirs"--popular memoirs written by mothers about motherhood experiences--and evocative autoethnographic mother-writing, I argue that differentiating these two forms of intimate observation and personal narrative requires a rethinking of autoethnographic practice. Specifically, I draw on the work of Gilles Deleuze to advocate for a radical specificity in autoethnographic writing. Thinking the autoethnographic narrative in terms of specificities and differences encourages us to think creatively about personal experiences and cultural relations beyond what is shared and communicable.

  15. Cdc42-mediated tubulogenesis controls cell specification

    DEFF Research Database (Denmark)

    Kesavan, Gokul; Sand, Fredrik Wolfhagen; Greiner, Thomas Uwe


    Understanding how cells polarize and coordinate tubulogenesis during organ formation is a central question in biology. Tubulogenesis often coincides with cell-lineage specification during organ development. Hence, an elementary question is whether these two processes are independently controlled......, or whether proper cell specification depends on formation of tubes. To address these fundamental questions, we have studied the functional role of Cdc42 in pancreatic tubulogenesis. We present evidence that Cdc42 is essential for tube formation, specifically for initiating microlumen formation and later...... for maintaining apical cell polarity. Finally, we show that Cdc42 controls cell specification non-cell-autonomously by providing the correct microenvironment for proper control of cell-fate choices of multipotent progenitors. For a video summary of this article, see the PaperFlick file with the Supplemental Data...

  16. Specification Editing and Discovery Assistant Project (United States)

    National Aeronautics and Space Administration — The project will prototype a specification editing and discovery tool (SPEEDY) for C/C++ that will assist software developers with modular formal verification tasks...

  17. Physician Fee Schedule Carrier Specific Files (United States)

    U.S. Department of Health & Human Services — The Centers for Medicare and Medicaid Services (CMS) has condensed all 56 Physician Fee Schedule (PFS) carrier specific pricing files into one zip file. It is...

  18. New visions in specific immunotherapy in children

    DEFF Research Database (Denmark)

    Halken, Susanne; Lau, Susanne; Valovirta, Erkka


    Specific immunotherapy is indicated for confirmed immunoglobulin E-mediated airway diseases using standardized allergen products with documented clinical efficacy and safety. For decades the subcutaneous route of administration (SCIT) has been the gold standard. Recently, the sublingual...

  19. Firm-Specific Foreign Exchange Exposure Identification

    DEFF Research Database (Denmark)

    Aabo, Tom; Brodin, Danielle


    of market index. Aggregate numbers have been shown to be (marginally) sensitive to the methodology employed. However, a corporate manager, an investor, or a stock analyst following a specific firm is not interested in the sensitivity on an aggregated level but on a firm-specific level. If the results......Previous studies have used the stock market approach to find the aggregate number of (firms with) foreign exchange exposures in a given country, region, or industry. Methodologies have differed in many aspects but two of the most basic differences relate to observation frequency and the choice...... for a specific firm are robust across methodologies, the corporate manager, the investor, or the stock analyst will rely on such results to a larger extent that if the results are highly sensitive to e.g. a change in observation frequency. We apply firm-specific sensitivity analysis to Scandinavian non...

  20. Specific detection of proteins using Nanomechanical resonators

    DEFF Research Database (Denmark)

    Fischer, Lee MacKenzie; Wright, V.A.; Guthy, C.;


    of probes onto their surfaces in order to enable the specificity of the detection. Such nanoresonator-based specific detection of proteins is here reported using streptavidin as target system, and immobilized biotin as probe. Nanomechanical resonators resistant to stiction were first realized from silicon...... carbonitride using a novel fabrication method. Vapor-phase deposition of mercaptopropyl trimethoxysilane was performed, and an added mass of 2.22 +/- 0.07 fg/mu m(2) was measured. This linker molecule was used to attach biotin onto the devices, enabling the specific detection of streptavidin. A mass of 3.6 fg....../mu m(2) was attributed to the added streptavidin, corresponding to one molecule per 27 nm(2). The specificity of this recognition was confirmed by exposing the devices to a solution of streptavidin that was already saturated with biotin. An additional negative control was also performed by also...

  1. Frameworks of competence: common or specific?

    NARCIS (Netherlands)

    Grant, Simon


    Please, cite this publication as: Grant, S. (2006). Frameworks of competence: common or specific?. Proceedings of International Workshop in Learning Networks for Lifelong Competence Development, TENCompetence Conference. September 12th, Sofia, Bulgaria: TENCompetence. Retrieved June 30th, 2006, from

  2. TELNET under Single-Connection TCP Specification (United States)


    TTYOUTPUTINTERRUPTSERVICE, COMPOSEHESSAGE, AUAKENPRINTER, TYPENEXT. TYPE. nini -Telnet Implementation February 2, 197B Each list of routines is... nini -Telnet Implementation February 2. 1976 References 1 V. Cerf, Y. Dalai, C. Sunshine, "Specification of Internet

  3. Specific heat and thermal conductivity of nanomaterials (United States)

    Bhatt, Sandhya; Kumar, Raghuvesh; Kumar, Munish


    A model is proposed to study the size and shape effects on specific heat and thermal conductivity of nanomaterials. The formulation developed for specific heat is based on the basic concept of cohesive energy and melting temperature. The specific heat of Ag and Au nanoparticles is reported and the effect of size and shape has been studied. We observed that specific heat increases with the reduction of particle size having maximum shape effect for spherical nanoparticle. To provide a more critical test, we extended our model to study the thermal conductivity and used it for the study of Si, diamond, Cu, Ni, Ar, ZrO2, BaTiO3 and SrTiO3 nanomaterials. A significant reduction is found in the thermal conductivity for nanomaterials by decreasing the size. The model predictions are consistent with the available experimental and simulation results. This demonstrates the suitability of the model proposed in this paper.

  4. Surface cleanliness of fluid systems, specification for (United States)


    This specification establishes surface cleanliness levels, test methods, cleaning and packaging requirements, and protection and inspection procedures for determining surface cleanliness. These surfaces pertain to aerospace parts, components, assemblies, subsystems, and systems in contact with any fluid medium.

  5. Modal Specifications for Probabilistic Timed Systems

    Directory of Open Access Journals (Sweden)

    Tingting Han


    Full Text Available Modal automata are a classic formal model for component-based systems that comes equipped with a rich specification theory supporting abstraction, refinement and compositional reasoning. In recent years, quantitative variants of modal automata were introduced for specifying and reasoning about component-based designs for embedded and mobile systems. These respectively generalize modal specification theories for timed and probabilistic systems. In this paper, we define a modal specification language for combined probabilistic timed systems, called abstract probabilistic timed automata, which generalizes existing formalisms. We introduce appropriate syntactic and semantic refinement notions and discuss consistency of our specification language, also with respect to time-divergence. We identify a subclass of our models for which we define the fundamental operations for abstraction, conjunction and parallel composition, and show several compositionality results.

  6. Cockpit management and Specific Behavioral Objectives (SBOs) (United States)

    Mudge, R. W.


    One of the primary tools used to accomplish the task of effective training is the specific behavioral objective (SBO). An SBO is simply a statement which specifically identifies a small segment of the final behavior sought, and a little more. The key word is specific. The company pinpoints exactly what it is it wants the pilot to do after completing training, and what it should evaluate from the point of view of both the program and the pilot. It tells the junior crewmember exactly, specifically, what he should monitor and support insofar as the management function is concerned. It gives greater meaning to the term second in command. And finally, it tells the supervisory pilot exactly what he should observe, evaluate, and instruct, insofar as the management function is concerned.

  7. Standard specification for silvered flat glass mirror

    CERN Document Server

    American Society for Testing and Materials. Philadelphia


    1.1 This specification covers the requirements for silvered flat glass mirrors of rectangular shape supplied as cut sizes, stock sheets or as lehr ends and to which no further processing (such as edgework or other fabrication) has been done. 1.2 This specification covers the quality requirements of silvered annealed monolithic clear and tinted flat glass mirrors up to 6 mm (¼ in.) thick. The mirrors are intended to be used indoors for mirror glazing, for components of decorative accessories or for similar uses. 1.3 This specification does not address safety glazing materials nor requirements for mirror applications. Consult model building codes and other applicable standards for safety glazing applications. 1.4 Mirrors covered in this specification are not intended for use in environments where high humidity or airborne corrosion promoters, or both, are consistently present (such as swimming pool areas, ocean-going vessels, chemical laboratories and other corrosive environments). 1.5 The dimensional val...

  8. Female-specific DNA sequences in geese. (United States)

    Huang, M C; Lin, W C; Horng, Y M; Rouvier, R; Huang, C W


    1. The OPAE random primers (Operon Technologies, Inc., CA) were used for random amplified polymorphic DNA (RAPD) fingerprinting in Chinese, White Roman and Landaise geese. One of these primers, OPAE-06, produced a 938-bp sex-specific fragment in all females and in no males of Chinese geese only. 2. A novel female-specific DNA sequence in Chinese goose was cloned and sequenced. Two primers, CGSex-F and CGSex-R, were designed in order to amplify a 912-bp sex-specific polymerase chain reaction (PCR) fragment on genomic DNA from female geese. 3. It was shown that a simple and effective PCR-based sexing technique could be used in the three goose breeds studied. 4. Nucleotide sequencing of the sex-specific fragments in White Roman and Landaise geese was performed and sequence differences were observed among these three breeds.

  9. Specifications and programs for computer software validation (United States)

    Browne, J. C.; Kleir, R.; Davis, T.; Henneman, M.; Haller, A.; Lasseter, G. L.


    Three software products developed during the study are reported and include: (1) FORTRAN Automatic Code Evaluation System, (2) the Specification Language System, and (3) the Array Index Validation System.

  10. Thermodynamic stability contributes to immunoglobulin specificity. (United States)

    Dimitrov, Jordan D; Kaveri, Srinivas V; Lacroix-Desmazes, Sébastien


    Antigen-binding specificity of immunoglobulins is important for their function in immune defense. However, immune repertoires contain a considerable fraction of immunoglobulins with promiscuous binding behavior, the physicochemical basis of which is not well understood. Evolution of immunoglobulin specificity occurs through iterative processes of mutation and selection, referred to as affinity maturation. Recent studies reveal that some somatic mutations could compromise the thermodynamic stability of the variable regions of immunoglobulins. By integrating this observation with the wealth of data on the evolution of novel enzyme activities, we propose that antibody specificity is linked to the thermodynamic stability of the antigen-binding regions, which provides a quantitative distinction between highly specific and promiscuous antibodies.

  11. Specification For ST-5 Li Ion Battery (United States)

    Castell, Karen D.; Day, John H. (Technical Monitor)


    This Specification defines the general requirements for rechargeable Space Flight batteries intended for use in the ST-5 program. The battery chemistry chosen for this mission is lithium ion (Li-Ion).

  12. Reflections on the specificity of synaptic connections. (United States)

    White, Edward L


    The principal focus of this treatise is the specificity of synaptic connectivity in the mammalian central nervous system. The occurrence of stereotypical patterns of connection at the macro level (e.g., the general consistency with which axonal pathways impinge on and originate within specific cortical areas and layers) implies that the cerebral cortex is a highly ordered structure. Order is seen also at the more micro level of synaptic connectivity, for instance, in the contrasting synaptic patterns of spiny vs. non-spiny neurons. Quantitative electron microscopic studies of synapses between identified neurons and correlative anatomical/electrophysiological investigations indicate that the high degree of order characterizing many aspects of cortical organization is mirrored by an equally ordered arrangement of synaptic connections between specific types of neurons. The recognition of recurring synaptic patterns has generated increased support for the notion of synaptic specificity as opposed to randomness, and we have begun now to understand the role of specificity in cortical function. At the core of cortical processing lie myriad possibilities for computation provided by the wealth of synaptic connections involving each neuron. Specificity, by limiting possibilities for connection, imposes an order on synaptic interactions even as processes of dynamic selection or synaptic remodeling ensure the constant formation and dissolution of cortical circuits. Collectively, these operations make maximal use of the richness of cortical synaptic connections to produce a highly flexible system, irrespective of the degree of hard-wiring, mutability, randomness or specificity that obtains for cortical wiring at any particular time. A brief, historical account of developments leading to our current understanding of cortical synaptic organization will precede the presentation of evidence for synaptic specificity.

  13. Simple Equational Specifications of Rational Arithmetic

    Directory of Open Access Journals (Sweden)

    Lawrence S. Moss


    Full Text Available We exhibit an initial specification of the rational numbers equipped with addition, subtraction, multiplication, greatest integer function, and absolute value. Our specification uses only the sort of rational numbers. It uses one hidden function; that function is unary. But it does not use an error constant, or extra (hidden sorts, or conditional equations. All of our work is elementary and self-contained.

  14. Military Specification Updates & Deicing Working Group Initiatives (United States)


    Air Force Petroleum Agency I n t e g r i t y - S e r v i c e - E x c e l l e n c e Military Specification Updates & Deicing Working Group...00-2011 4. TITLE AND SUBTITLE Military Specification Updates & Deicing Working Group Initiatives 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c...Corrosion Runway Deicing Fluid Partnership with Battelle Memorial Institute (lead agency), AFRL/ ASC, Army (CRREL), Navy (NAVAIR), Octagon, AMIL

  15. Specification and Construction of Control Flow Semantics


    Smelik, R.; Rensink, A.; Kastenberg, H.; Grundy, J.; Howse, J.


    In this paper we propose a visual language CFSL for specifying control flow semantics of programming languages. We also present a translation from CFSL to graph production systems (GPS) for flow graph construction; that is, any CFSL specification, say for a language L, gives rise to a GPS that constructs from any L-program (represented as an abstract syntax graph) the corresponding flow graph. The specification language is rich enough to capture complex language constructs, including all of J...

  16. Research on High-Specific-Heat Dielectrics. (United States)


    spinels have been the magnetocaloric measurements at T<TN/ 2 . Both spinels display adiabatic-demagnetization cooling and adiabatic-magnetization heating ...resulting in anomolously large specific heats and magnetocaloric effects. Furthermore, distortions of the lattice, which remove the frustration, can...A w - 0 U -$ 0 Lqn C >~ CL ’-4D -~CD L4.H* mo IV. SPECIFIC HEAT , MAGNETOCALORIC , AND DIELECTRIC CONSTANT MEASUREMENTS AT LOW TEMPERATURES This Section

  17. Measuring Specific Heats at High Temperatures (United States)

    Vandersande, Jan W.; Zoltan, Andrew; Wood, Charles


    Flash apparatus for measuring thermal diffusivities at temperatures from 300 to 1,000 degrees C modified; measures specific heats of samples to accuracy of 4 to 5 percent. Specific heat and thermal diffusivity of sample measured. Xenon flash emits pulse of radiation, absorbed by sputtered graphite coating on sample. Sample temperature measured with thermocouple, and temperature rise due to pulse measured by InSb detector.

  18. Specific phobia predicts psychopathology in young women


    Trumpf, Julia; Margraf, Jürgen; Vriends, Noortje; Meyer, Andrea Hans; Becker, Eni S


    Background Although specific phobia is characterized by an early age at onset and by high rates of comorbidity, few studies have examined comorbid relationships prospectively. Objectives The present study investigated the association between specific phobia and the risk of a broad range of psychopathology among young women in the community. Method Data came from the Dresden Predictor Study in which 1,538 German women (18–25 years) completed a diagnostic interview at two time points. Results W...

  19. Language translation, doman specific languages and ANTLR (United States)

    Craymer, Loring; Parr, Terence


    We will discuss the features of ANTLR that make it an attractive tool for rapid developement of domain specific language translators and present some practical examples of its use: extraction of information from the Cassini Command Language specification, the processing of structured binary data, and IVL--an English-like language for generating VRML scene graph, which is used in configuring the server.

  20. Steps in Modular Specifications for Concurrent Modules

    DEFF Research Database (Denmark)

    Da Rocha Pinto, Pedro; Dinsdale-Young, Thomas; Gardner, Philippa


    The specification of a concurrent program module is a difficult problem. The specifications must be strong enough to enable reasoning about the intended clients without reference to the underlying module implementation. We survey a range of verification techniques for specifying concurrent modules......, in particular highlighting four key concepts: auxiliary state, interference abstraction, resource ownership and atomicity. We show how these concepts combine to provide powerful approaches to specifying concurrent modules....

  1. TRIO specification of a steam boiler controller

    Energy Technology Data Exchange (ETDEWEB)

    Gargantini, A. [Politecnico di Milano (Italy). Dipt. di Electronica e Informazione; Morzenti, A. [Politecnico di Milano (Italy). Dipt. di Electronica e Informazione


    We specify a controller for a steam boiler starting from an informal descriptions of its requirements. The specification is formalized in the temporal logic TRIO and its object-oriented extension TRIO+. To obtain a maximum of abstraction and reuse we make the specification parametric with respect to all equipment and hardware features, and we avoid to impose any particular strategy in the management of the available resources and in the control of the critical physical quantities. (orig.)

  2. Patient-Specific Modeling in Tomorrow's Medicine

    CERN Document Server


    This book reviews the frontier of research and clinical applications of Patient Specific Modeling, and provides a state-of-the-art update as well as perspectives on future directions in this exciting field. The book is useful for medical physicists, biomedical engineers and other engineers who are interested in the science and technology aspects of Patient Specific Modeling, as well as for radiologists and other medical specialists who wish to be updated about the state of implementation.



    Smolčić Jurdana, Dora


    Management of ecotourism destinations is very demanding because of the specific and interdisciplinary knowledge that is necessary. Great knowledge, which consists of knowledge from human and natural sciences at the same time, emphasizes the need for permanent education, formal and informal of ecotourism destination managers. In should be generally stated that countries which have a great areas and resources for ecotourism development should create a specific program for education about the...

  4. Structure and specificity of lamprey monoclonal antibodies


    Herrin, Brantley R.; Alder, Matthew N; Roux, Kenneth H.; Sina, Christina; Ehrhardt, Götz R. A.; Boydston, Jeremy A.; Turnbough, Charles L.; Cooper, Max D.


    Adaptive immunity in jawless vertebrates (lamprey and hagfish) is mediated by lymphocytes that undergo combinatorial assembly of leucine-rich repeat (LRR) gene segments to create a diverse repertoire of variable lymphocyte receptor (VLR) genes. Immunization with particulate antigens induces VLR-B-bearing lymphocytes to secrete antigen-specific VLR-B antibodies. Here, we describe the production of recombinant VLR-B antibodies specific for BclA, a major coat protein of Bacillus anthracis spores...

  5. Simple Benchmark Specifications for Space Radiation Protection (United States)

    Singleterry, Robert C. Jr.; Aghara, Sukesh K.


    This report defines space radiation benchmark specifications. This specification starts with simple, monoenergetic, mono-directional particles on slabs and progresses to human models in spacecraft. This report specifies the models and sources needed to what the team performing the benchmark needs to produce in a report. Also included are brief descriptions of how OLTARIS, the NASA Langley website for space radiation analysis, performs its analysis.

  6. Tissue-specific and substrate-specific mitochondrial bioenergetics in feline cardiac and skeletal muscles

    DEFF Research Database (Denmark)

    Christiansen, Liselotte Bruun; Dela, Flemming; Koch, Jørgen;


    No studies have investigated the mitochondrial function in permeabilized muscle fiber from cats. The aim of this study was to investigate tissue-specific and substrate-specific characteristics of mitochondrial oxidative phosphorylation (OXPHOS) capacity in feline permeabilized oxidative muscle...

  7. Germ cell specification and regeneration in planarians. (United States)

    Newmark, P A; Wang, Y; Chong, T


    In metazoans, two apparently distinct mechanisms specify germ cell fate: Determinate specification (observed in animals including Drosophila, Caenorhabditis elegans, zebra fish, and Xenopus) uses cytoplasmic factors localized to specific regions of the egg, whereas epigenetic specification (observed in many basal metazoans, urodeles, and mammals) involves inductive interactions between cells. Much of our understanding of germ cell specification has emerged from studies of model organisms displaying determinate specification. In contrast, our understanding of epigenetic/inductive specification is less advanced and would benefit from studies of additional organisms. Freshwater planarians--widely known for their remarkable powers of regeneration--are well suited for studying the mechanisms by which germ cells can be induced. Classic experiments showed that planarians can regenerate germ cells from body fragments entirely lacking reproductive structures, suggesting that planarian germ cells could be specified by inductive signals. Furthermore, the availability of the genome sequence of the planarian Schmidtea mediterranea, coupled with the animal's susceptibility to systemic RNA interference (RNAi), facilitates functional genomic analyses of germ cell development and regeneration. Here, we describe recent progress in studies of planarian germ cells and frame some of the critical unresolved questions for future work.

  8. Age-specific reference ranges of serum prostate-specific antigen in Iranian men

    Directory of Open Access Journals (Sweden)

    Gholamreza Pourmand


    Conclusion: Findings of the present study showed that PSA levels are correlated with age. It was also revealed that the PSA age-specific reference range obtained in this study is different from other races and is specific to Iranian men. Therefore, age-specific reference ranges of PSA obtained in the present study can increase PSA test sensitivity and specificity by reducing unnecessary diagnostic procedures and early detection of prostate cancer in Iranian men.

  9. The Role of Non-specific and Specific Immune Systems in Poultry against Newcastle Disease

    Directory of Open Access Journals (Sweden)

    Dyah Ayu Hewajuli


    Full Text Available Newcastle disease (ND is caused by avian paramyxovirus-1 which belong to Avulavirus genus and Paramyxoviridae family. The birds have abnormalities in humoral (bursa fabricius and cellular (thymus and spleen lymphoid organs. Lesions decrease the immune system. Immune system consists of non-specific and specific immune systems. The main components of non-specific immunity are physical and chemical barrier (feather and skin or mucosa, phagocytic cells (macrophages and natural killer, protein complement and the mediator of inflammation and cytokines. Interferons (IFNs belong to a group of cytokines that play a major role in the nonspecific or innate (natural immunity. The virulent ND virus encodes protein of V gene can be suppressed IFN type I. This leads to non-specific immune system fail to respond to the virulent strains resulting in severe pathogenicity. The defense mechanism of the host is replaced by specific immunity (adaptive immunity when natural immunity fails to overcome the infection. The specific immune system consists of humoral mediated immunity (HMI and cell-mediated immunity (CMI. The cells of immune system that react specifically with the antigen are B lymphocytes producing the antibodies, T lymphocytes that regulate the synthesis of antibodies and T cells as effector or the direct cytotoxic cells. Both non-specific and specific immunities are complementary against the invasion of ND virus in the birds. The objective of this article is to discuss the role of non specific and specific immune system in ND.

  10. Face recognition: a model specific ability

    Directory of Open Access Journals (Sweden)

    Jeremy B Wilmer


    Full Text Available In our everyday lives, we view it as a matter of course that different people are good at different things. It can be surprising, in this context, to learn that most of what is known about cognitive ability variation across individuals concerns the broadest of all cognitive abilities, often labeled g. In contrast, our knowledge of specific abilities, those that correlate little with g, is severely constrained. Here, we draw upon our experience investigating an exceptionally specific ability, face recognition, to make the case that many specific abilities could easily have been missed. In making this case, we derive key insights from earlier false starts in the measurement of face recognition’s variation across individuals, and we highlight the convergence of factors that enabled the recent discovery that this variation is specific. We propose that the case of face recognition ability illustrates a set of tools and perspectives that could accelerate fruitful work on specific cognitive abilities. By revealing relatively independent dimensions of human ability, such work would enhance our capacity to understand the uniqueness of individual minds.

  11. Formal specification level concepts, methods, and algorithms

    CERN Document Server

    Soeken, Mathias


    This book introduces a new level of abstraction that closes the gap between the textual specification of embedded systems and the executable model at the Electronic System Level (ESL). Readers will be enabled to operate at this new, Formal Specification Level (FSL), using models which not only allow significant verification tasks in this early stage of the design flow, but also can be extracted semi-automatically from the textual specification in an interactive manner.  The authors explain how to use these verification tasks to check conceptual properties, e.g. whether requirements are in conflict, as well as dynamic behavior, in terms of execution traces. • Serves as a single-source reference to a new level of abstraction for embedded systems, known as the Formal Specification Level (FSL); • Provides a variety of use cases which can be adapted to readers’ specific design flows; • Includes a comprehensive illustration of Natural Language Processing (NLP) techniques, along with examples of how to i...

  12. Chromosome-specific DNA Repeat Probes

    Energy Technology Data Exchange (ETDEWEB)

    Baumgartner, Adolf; Weier, Jingly Fung; Weier, Heinz-Ulrich G.


    In research as well as in clinical applications, fluorescence in situ hybridization (FISH) has gained increasing popularity as a highly sensitive technique to study cytogenetic changes. Today, hundreds of commercially available DNA probes serve the basic needs of the biomedical research community. Widespread applications, however, are often limited by the lack of appropriately labeled, specific nucleic acid probes. We describe two approaches for an expeditious preparation of chromosome-specific DNAs and the subsequent probe labeling with reporter molecules of choice. The described techniques allow the preparation of highly specific DNA repeat probes suitable for enumeration of chromosomes in interphase cell nuclei or tissue sections. In addition, there is no need for chromosome enrichment by flow cytometry and sorting or molecular cloning. Our PCR-based method uses either bacterial artificial chromosomes or human genomic DNA as templates with {alpha}-satellite-specific primers. Here we demonstrate the production of fluorochrome-labeled DNA repeat probes specific for human chromosomes 17 and 18 in just a few days without the need for highly specialized equipment and without the limitation to only a few fluorochrome labels.

  13. Reduced goal specificity is associated with reduced memory specificity in depressed adults. (United States)

    Belcher, Jessica; Kangas, Maria


    Models of autobiographical memory suggest a close association between memories, future imagination and setting specific personal goals. However this association has yet to be tested with depressed individuals. The aim of this study was to examine whether the specificity of remembering past and imagining future personal events is associated with the specificity of approach and avoidance goals in depressed individuals. Two samples comprising adults who met criteria for major depressive disorder (MDD; N=30) and adults who had no prior history or current depression (N=30) completed autobiographical memory and future event tests, and a personal goal task. In the depressed sample, the specificity with which participants remembered the past was significantly associated with the specificity with which they generated future goals. The depressed sample also elicited fewer specific approach and avoidance goals compared to the non-depressed sample. These findings suggest that an overgeneral memory deficit extends to impairments in goal specificity.

  14. Functional specificity of rat vibrissal primary afferents. (United States)

    Lucianna, Facundo A; Farfán, Fernando D; Pizá, Gabriel A; Albarracín, Ana L; Felice, Carmelo J


    In this study, we propose to analyze the peripheral vibrissal system specificity through its neuronal responses. Receiver operating characteristics (ROC) curve analyses were used, which required the implementation of a binary classifier (artificial neural network) trained to identify the applied stimulus. The training phase consisted of the observation of a predetermined amount of vibrissal sweeps on two surfaces of different texture and similar roughness. Our results suggest that the specificity of the peripheral vibrissal system easily permits the discrimination between perceived stimuli, quantified through neuronal responses, and that it can be evaluated through an ROC curve analysis. We found that such specificity makes a linear binary classifier capable of detecting differences between stimuli with five sweeps at most.

  15. [Specific features of written medical English language]. (United States)

    Zorica, Antić


    Medical language is a special language used by experts in mutual communication. One of the characteristics of medical discourse community is writing research papers in English. When writing a research paper, it is necessary to apply appropriate rules based on the IMRAD structure. This structure has its own clearly defined style which is clear, precise, exact and objective. This style of writing reflects the characteristics of medical language. The most frequent problems that doctors encounter in this context predominantly refer to linguistic elements of English. Namely, a very common dilemma is related to the use of English tenses in specific parts of the IMRAD structure. Another problem is the use of specific expressions for introducing a research, presenting results and methods used, developing discussion and stating conclusions. This work aims to point out the specific style and structure of medical research papers in English with an outline of the linguistic elements used in this context.

  16. Testing Library Specifications by Verifying Conformance Tests

    DEFF Research Database (Denmark)

    Kiniry, Joseph Roland; Zimmerman, Daniel; Hyland, Ralph


    the Formal CTD Process (FCTD), to address this problem. Although FCTD is primarily targeted toward those who write Java libraries (or specifications for existing Java libraries) using the Java Modeling Language (JML), its techniques are broadly applicable. The key to FCTD is its novel usage of library......Formal specifications of standard libraries are necessary when statically verifying software that uses those libraries. Library specifications must be both correct, accurately reflecting library behavior, and useful, describing library behavior in sufficient detail to allow static verification...... of client programs. Specication and verification researchers regularly face the question of whether the library specications we use are correct and useful, and we have collectively provided no good answers. Over the past few years we have created and refined a software engineering process, which we call...

  17. Analysis on judo specific and unspecific test

    Directory of Open Access Journals (Sweden)

    Luis Santos Rodríguez


    Full Text Available In specialized literature it is not easy to find test which give us information about judokas developing their specific kinetic habits. Although judo is included in sociomotor sports (Parlebas, 2001, judokas physical fitness is normally evaluated through test which come from other type of sports, mainly from phychomotor sports. At the same time, batteries as the battery Eurofit (Conseil de L´Europe, 1989, are use to evaluate perceptive-motors aspects. In this article, we describe some of the tests found in specific western bibliography. Once finished this analysis, we mention the need of creating test which value the reality of competition confrontation more specifically, and which can be reliable, objective and reproductive (López and cols. 2004 being easy and useful to the trainer as well.

  18. Spent nuclear fuel project product specification

    Energy Technology Data Exchange (ETDEWEB)

    Pajunen, A.L.


    Product specifications are limits and controls established for each significant parameter that potentially affects safety and/or quality of the Spent Nuclear Fuel (SNF) packaged for transport to dry storage. The product specifications in this document cover the spent fuel packaged in MultiCanister Overpacks (MCOs) to be transported throughout the SNF Project. The SNF includes N Reactor fuel and single-pass reactor fuel. The FRS removes the SNF from the storage canisters, cleans it, and places it into baskets. The MCO loading system places the baskets into MCO/Cask assembly packages. These packages are then transferred to the Cold Vacuum Drying (CVD) Facility. After drying at the CVD Facility, the MCO cask packages are transferred to the Canister Storage Building (CSB), where the MCOs are removed from the casks, staged, inspected, sealed (by welding), and stored until a suitable permanent disposal option is implemented. The key criteria necessary to achieve these goals are documented in this specification.

  19. Polysaccharides in colon-specific drug delivery. (United States)

    Sinha, V R; Kumria, R


    Natural polysaccharides are now extensively used for the development of solid dosage forms for delivery of drug to the colon. The rationale for the development of a polysaccharide based delivery system for colon is the presence of large amounts of polysaccharidases in the human colon as the colon is inhabited by a large number and variety of bacteria which secrete many enzymes e.g. beta-D-glucosidase, beta-D-galactosidase, amylase, pectinase, xylanase, beta-D-xylosidase, dextranase, etc. Various major approaches utilizing polysaccharides for colon-specific delivery are fermentable coating of the drug core, embedding of the drug in biodegradable matrix, formulation of drug-saccharide conjugate (prodrugs). A large number of polysaccharides have already been studied for their potential as colon-specific drug carrier systems, such as chitosan, pectin, chondroitin sulphate, cyclodextrin, dextrans, guar gum, inulin, amylose and locust bean gum. Recent efforts and approaches exploiting these polysaccharides in colon-specific drug delivery are discussed.

  20. Computational network design from functional specifications

    KAUST Repository

    Peng, Chi Han


    Connectivity and layout of underlying networks largely determine agent behavior and usage in many environments. For example, transportation networks determine the flow of traffic in a neighborhood, whereas building floorplans determine the flow of people in a workspace. Designing such networks from scratch is challenging as even local network changes can have large global effects. We investigate how to computationally create networks starting from only high-level functional specifications. Such specifications can be in the form of network density, travel time versus network length, traffic type, destination location, etc. We propose an integer programming-based approach that guarantees that the resultant networks are valid by fulfilling all the specified hard constraints and that they score favorably in terms of the objective function. We evaluate our algorithm in two different design settings, street layout and floorplans to demonstrate that diverse networks can emerge purely from high-level functional specifications.


    Institute of Scientific and Technical Information of China (English)

    Liu Linquan


    With respect m dialectal-accented speech recognition, dialect-specific lexicon adaptation is an indispensable component to improve the performance. In this paper, a phone-based confusion matrix is adopted to obtain dialect-specific pronunciation variants. A weighting method, improved context-dependent weighting (ICDW) is proposed to characterize the pronunciation probability precisely by taking both the surface form left-context-dependency and the base form left-context-dependency into account. To make a much robust lexicon, a pruning criterion, syllable-dependent pruning (SDP), is also proposed which achieves the most effective result. In summary, the dialect-specific dialect adaptation reduces a 2.9% absolute and a 3.6% absolute in syllable error rate (SER) respectively on read speech and spontaneous speech from Shanghai-accented speakers.

  2. Disease specific productivity of american cancer hospitals.

    Directory of Open Access Journals (Sweden)

    Jeffery A Goldstein

    Full Text Available Research-oriented cancer hospitals in the United States treat and study patients with a range of diseases. Measures of disease specific research productivity, and comparison to overall productivity, are currently lacking.Different institutions are specialized in research of particular diseases.To report disease specific productivity of American cancer hospitals, and propose a summary measure.We conducted a retrospective observational survey of the 50 highest ranked cancer hospitals in the 2013 US News and World Report rankings. We performed an automated search of PubMed and for published reports and registrations of clinical trials (respectively addressing specific cancers between 2008 and 2013. We calculated the summed impact factor for the publications. We generated a summary measure of productivity based on the number of Phase II clinical trials registered and the impact factor of Phase II clinical trials published for each institution and disease pair. We generated rankings based on this summary measure.We identified 6076 registered trials and 6516 published trials with a combined impact factor of 44280.4, involving 32 different diseases over the 50 institutions. Using a summary measure based on registered and published clinical trails, we ranked institutions in specific diseases. As expected, different institutions were highly ranked in disease-specific productivity for different diseases. 43 institutions appeared in the top 10 ranks for at least 1 disease (vs 10 in the overall list, while 6 different institutions were ranked number 1 in at least 1 disease (vs 1 in the overall list.Research productivity varies considerably among the sample. Overall cancer productivity conceals great variation between diseases. Disease specific rankings identify sites of high academic productivity, which may be of interest to physicians, patients and researchers.

  3. Specificity in Legume-Rhizobia Symbioses. (United States)

    Andrews, Mitchell; Andrews, Morag E


    Most species in the Leguminosae (legume family) can fix atmospheric nitrogen (N₂) via symbiotic bacteria (rhizobia) in root nodules. Here, the literature on legume-rhizobia symbioses in field soils was reviewed and genotypically characterised rhizobia related to the taxonomy of the legumes from which they were isolated. The Leguminosae was divided into three sub-families, the Caesalpinioideae, Mimosoideae and Papilionoideae. Bradyrhizobium spp. were the exclusive rhizobial symbionts of species in the Caesalpinioideae, but data are limited. Generally, a range of rhizobia genera nodulated legume species across the two Mimosoideae tribes Ingeae and Mimoseae, but Mimosa spp. show specificity towards Burkholderia in central and southern Brazil, Rhizobium/Ensifer in central Mexico and Cupriavidus in southern Uruguay. These specific symbioses are likely to be at least in part related to the relative occurrence of the potential symbionts in soils of the different regions. Generally, Papilionoideae species were promiscuous in relation to rhizobial symbionts, but specificity for rhizobial genus appears to hold at the tribe level for the Fabeae (Rhizobium), the genus level for Cytisus (Bradyrhizobium), Lupinus (Bradyrhizobium) and the New Zealand native Sophora spp. (Mesorhizobium) and species level for Cicer arietinum (Mesorhizobium), Listia bainesii (Methylobacterium) and Listia angolensis (Microvirga). Specificity for rhizobial species/symbiovar appears to hold for Galega officinalis (Neorhizobium galegeae sv. officinalis), Galega orientalis (Neorhizobium galegeae sv. orientalis), Hedysarum coronarium (Rhizobium sullae), Medicago laciniata (Ensifer meliloti sv. medicaginis), Medicago rigiduloides (Ensifer meliloti sv. rigiduloides) and Trifolium ambiguum (Rhizobium leguminosarum sv. trifolii). Lateral gene transfer of specific symbiosis genes within rhizobial genera is an important mechanism allowing legumes to form symbioses with rhizobia adapted to particular soils

  4. Clojure for domain-specific languages

    CERN Document Server

    Kelker, Ryan D


    An example-oriented approach to develop custom domain-specific languages.If you've already developed a few Clojure applications and wish to expand your knowledge on Clojure or domain-specific languages in general, then this book is for you. If you're an absolute Clojure beginner, then you may only find the detailed examples of the core Clojure components of value. If you've developed DSLs in other languages, this Lisp and Java-based book might surprise you with the power of Clojure.

  5. Non-specific ileojejunitis in Arequipa, Peru. (United States)

    Perea, V D; Fernan-Zegarra, L; Cruz, V M; Ballon, R; Picoaga, J L


    Non-specific ileojejunitis, characterised by mild to moderate structural changes in the intestinal mucosa and often associated with asymptomatic malabsorption, is known to occur in the tropics and in countries with hot climates. This acquired condition is probably related to environmental factors, and some consider it to be a subclinical form of tropical sprue. Changes in the intestinal mucosa typical of non-specific ileojejunitis were found in 10 indigenous Indians as well as 5 people of Latin stock living in the Southern Peruvian sierra, where tropical sprue has not as yet been demonstrated and which has a temperate climate.

  6. Automated effect-specific mammographic pattern measures. (United States)

    Raundahl, Jakob; Loog, Marco; Pettersen, Paola; Tanko, Laszlo B; Nielsen, Mads


    We investigate the possibility to develop methodologies for assessing effect specific structural changes of the breast tissue using a general statistical machine learning framework. We present an approach of obtaining objective mammographic pattern measures quantifying a specific biological effect, such as hormone replacement therapy (HRT). We compare results using this approach to using standard density measures. We show that the proposed method can quantify both age related effects and effects caused by HRT. Age effects are significantly detected by our method where standard methodologies fail. The separation of HRT subpopulations using our approach is comparable to the best methodology, which is interactive.

  7. Specific learning processes and indigenous teacher training

    Directory of Open Access Journals (Sweden)

    Adir Casaro Nascimento


    Full Text Available Indigenous teacher formation and the issue of specific learning processes, as a right of the indigenous peoples derived from the 1988 Constitution, aim at the re-signification of pedagogical practices in specific socio-cultural contexts and at the visibility of indigenous education. Taking indigenous children as a reference, or rather, the agents that produce knowledge within the context of their particularities and territorialities, the essay points to the necessity of constructing new theoretical bases and a pedagogy that gives visibility to other local epistemic logics produced by “power coloniality”. They are different from the dominant Western logic in the process of training indigenous educators.

  8. Specifications from a biotechnology industry perspective. (United States)

    Garnick, R L


    The emergence of new analytical technology and the production of pharmaceuticals for a global market in a cost-effective manner necessitate the establishment of worldwide specifications that are appropriate for the product and the manufacturing process. This requires a thorough knowledge of the protein and control of the systems that produce it as well as an understanding of the accuracy and precision of the assays used for testing. Harmonization of specifications among the worldwide regulatory authorities is critical for the future development of new pharmaceuticals. A continuing dialogue between industry and regulators to achieve this goal needs to be encouraged and supported.

  9. Shape configuration and category-specificity

    DEFF Research Database (Denmark)

    Gerlach, Christian; Law, I; Paulson, Olaf B.


    in difficult object decision tasks, which is also found in the present experiments with outlines, is reversed when the stimuli are fragmented. This interaction between category (natural versus artefacts) and stimulus type (outlines versus fragmented forms) is in accordance with predictions derived from...... a recent account of category-specificity and lends support to the notion that category-specific impairments can occur for both natural objects and artefacts following damage to pre-semantic stages in visual object recognition. The implications of the present findings are discussed in relation to theories...

  10. Engineered waste-package-system design specification

    Energy Technology Data Exchange (ETDEWEB)


    This report documents the waste package performance requirements and geologic and waste form data bases used in developing the conceptual designs for waste packages for salt, tuff, and basalt geologies. The data base reflects the latest geotechnical information on the geologic media of interest. The parameters or characteristics specified primarily cover spent fuel, defense high-level waste, and commercial high-level waste forms. The specification documents the direction taken during the conceptual design activity. A separate design specification will be developed prior to the start of the preliminary design activity.

  11. [Development of domain specific search engines]. (United States)

    Takai, T; Tokunaga, M; Maeda, K; Kaminuma, T


    As cyber space exploding in a pace that nobody has ever imagined, it becomes very important to search cyber space efficiently and effectively. One solution to this problem is search engines. Already a lot of commercial search engines have been put on the market. However these search engines respond with such cumbersome results that domain specific experts can not tolerate. Using a dedicate hardware and a commercial software called OpenText, we have tried to develop several domain specific search engines. These engines are for our institute's Web contents, drugs, chemical safety, endocrine disruptors, and emergent response for chemical hazard. These engines have been on our Web site for testing.

  12. Automated effect-specific mammographic pattern measures

    DEFF Research Database (Denmark)

    Raundahl, Jakob; Loog, Marco; Pettersen, Paola;


    We investigate the possibility to develop methodologies for assessing effect specific structural changes of the breast tissue using a general statistical machine learning framework. We present an approach of obtaining objective mammographic pattern measures quantifying a specific biological effect......, such as hormone replacement therapy (HRT). We compare results using this approach to using standard density measures. We show that the proposed method can quantify both age related effects and effects caused by HRT. Age effects are significantly detected by our method where standard methodologies fail...

  13. A Class-Specific Optimizing Compiler

    Directory of Open Access Journals (Sweden)

    Michael D. Sharp


    Full Text Available Class-specific optimizations are compiler optimizations specified by the class implementor to the compiler. They allow the compiler to take advantage of the semantics of the particular class so as to produce better code. Optimizations of interest include the strength reduction of class:: array address calculations, elimination of large temporaries, and the placement of asynchronous send/recv calls so as to achieve computation/communication overlap. We will outline our progress towards the implementation of a C++ compiler capable of incorporating class-specific optimizations.

  14. Shape configuration and category-specificity

    DEFF Research Database (Denmark)

    Gerlach, Christian; Law, Ian; Paulson, Olaf B


    and fragmented drawings. We also examined whether fragmentation had different impact on the recognition of natural objects and artefacts and found that recognition of artefacts was more affected by fragmentation than recognition of natural objects. Thus, the usual finding of an advantage for artefacts...... a recent account of category-specificity and lends support to the notion that category-specific impairments can occur for both natural objects and artefacts following damage to pre-semantic stages in visual object recognition. The implications of the present findings are discussed in relation to theories...

  15. Biofilm-specific antibiotic tolerance and resistance. (United States)

    Olsen, I


    Biofilms are heterogeneous structures composed of bacterial cells surrounded by a matrix and attached to solid surfaces. The bacteria here are 100 to 1,000 times more tolerant to antimicrobials than corresponding planktonic cells. Biofilms can be difficult to eradicate when they cause biofilm-related diseases, e.g., implant infections, cystic fibrosis, urinary tract infections, and periodontal diseases. A number of phenotypic features of the biofilm can be involved in biofilm-specific tolerance and resistance. Little is known about the molecular mechanisms involved. The current review deals with both phenotypic and molecular mechanisms of biofilm-specific antibiotic tolerance and resistance.

  16. Domain-Specific Languages for Enterprise Systems

    DEFF Research Database (Denmark)

    Andersen, Jesper; Bahr, Patrick; Henglein, Fritz;


    The process-oriented event-driven transaction systems (POETS) architecture introduced by Henglein et al. is a novel software architecture for enterprise resource planning (ERP) systems. POETS employs a pragmatic separation between (i) transactional data, that is, what has happened; (ii) reports......, that is, what can be derived from the transactional data; and (iii) contracts, that is, which transactions are expected in the future. Moreover, POETS applies domain-specific languages (DSLs) for specifying reports and contracts, in order to enable succinct declarative specifications as well as rapid...

  17. From UML Specification into FPGA Implementation

    Directory of Open Access Journals (Sweden)

    Grzegorz Bazydlo


    Full Text Available In the paper a method of using the Unified Modeling Language for specification of digital systems, especially logic controllers, is presented. The proposed method is based mainly on the UML state machine diagrams and uses Hierarchical Concurrent Finite State Machines (HCFSMs as a temporary model. The paper shows a way to transform the UML diagrams, expressed in XML language, to the form that is acceptable by reconfigurable FPGAs (Field Programmable Gate Arrays. The UML specification is used to generate an effective program in Hardware Description Languages (HDLs, especially Verilog.

  18. CASL- The Common Algebraic Specification Language- Summary

    DEFF Research Database (Denmark)

    Haxthausen, Anne


    This Summary is the basis for the Design Proposal [LD97b] for CASL, the Common Algebraic Specification Language, prepared by the Language Design Task Group of CoFI, the Common Framework Initiative. It gives the abstract syntax, and informally describes its intended semantics. It is accompanied...... for approval to the sponsoring IFIP Working Group on Foundations of System Specification, WG 1.3. It received tentative approval, together with a referees' report recommending the reconsideration of some elements of the design [IFI97]; a response has already been made [LD97a]. The present version...

  19. Age-Specific Correlates of Child Growth

    NARCIS (Netherlands)

    M. Rieger (Matthias); S.K. Trommlerová (Sofia Karina)


    textabstractGrowth faltering describes a widespread phenomenon that height- and weight-for-age of children in developing countries collapse rapidly in the first two years of life. We study age-specific correlates of child nutrition using Demographic and Health Surveys from 56 developing countries to

  20. 48 CFR 836.202 - Specifications. (United States)


    ... specifications. (b) During the design stage, contract architect-engineers must not use “brand name or equal” or... OF CONTRACTING CONSTRUCTION AND ARCHITECT-ENGINEER CONTRACTS Special Aspects of Contracting for... contracting officer must inform prospective architect-engineers of this requirement during the...

  1. 30 CFR 22.7 - Specific requirements. (United States)


    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Specific requirements. 22.7 Section 22.7 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR TESTING, EVALUATION, AND... on a wood floor from a height of 3 feet. Parts that are strapped to the user may be subjected to...

  2. Designing Nonwovens to Meet Pore Size Specifications

    Directory of Open Access Journals (Sweden)

    Glen E. Simmonds


    Full Text Available New nonwovens applications in areas such as filtration require a media designed to particular pore size specifications in the 3 to 20 micron range. The purpose of this work was to develop a basis by which to design and construct a fabric with given pore size specifications. While doing so we have provided a validation for two different mathematical models. We have also found that bicomponent spunbonded islands-in-the-sea nonwoven fabrics can be designed very precisely to achieve target pore diameters and porosity. Mathematical models can be used to develop fabric specifications in the standard manufacturing terms of basis weight and fiber diameter. Measured mean flow pore diameters for the test fabrics showed excellent correlation to targeted mean flow pore diameters for both models. The experimental fit to the Bryner model is the better of the two, but requires specification of fabric thickness in addition to basis weight and fiber diameter to achieve actual mean pore diameters that closely match target values. Experimental validation of the influence of fabric thickness on the mean flow pore diameter at constant basis weight and fiber diameter remains open for further investigation. In addition, achieving complete separation of the island and sea polymers along with unbundling of the island fibers remain areas for improvement.

  3. Ontology Assisted Formal Specification Extraction from Text

    Directory of Open Access Journals (Sweden)

    Andreea Mihis


    Full Text Available In the field of knowledge processing, the ontologies are the most important mean. They make possible for the computer to understand better the natural language and to make judgments. In this paper, a method which use ontologies in the semi-automatic extraction of formal specifications from a natural language text is proposed.

  4. 32 CFR 292.4 - Specific policy. (United States)


    ... existing computer program or printout for retrieval of the requested information. (c) The prior application... INFORMATION ACT PROGRAM DEFENSE INTELLIGENCE AGENCY (DIA) FREEDOM OF INFORMATION ACT § 292.4 Specific policy... value as evidence. (2) Administrative tools by which records are created, stored, and retrieved, if...

  5. Teaching Case: Enterprise Architecture Specification Case Study (United States)

    Steenkamp, Annette Lerine; Alawdah, Amal; Almasri, Osama; Gai, Keke; Khattab, Nidal; Swaby, Carval; Abaas, Ramy


    A graduate course in enterprise architecture had a team project component in which a real-world business case, provided by an industry sponsor, formed the basis of the project charter and the architecture statement of work. The paper aims to share the team project experience on developing the architecture specifications based on the business case…

  6. A specification language for organisational performance indicators

    NARCIS (Netherlands)

    Popova, Viara; Treur, Jan


    A specification language for performance indicators and their relations and requirements is presented and illustrated for a case study in logistics. The language can be used in different forms, varying from informal, semiformal, graphical to formal. A software environment has been developed that s

  7. Language specific bootstraps for UG categories

    NARCIS (Netherlands)

    van Kampen, N.J.


    This paper argues that the universal categories N/V are not applied to content words before the grammatical markings for reference D(eterminers) and predication I(nflection) have been acquired (van Kampen, 1997, contra Pinker, 1984). Child grammar starts as proto-grammar with language-specific opera

  8. An Introduction to Product Specifications in China

    Institute of Scientific and Technical Information of China (English)

    Yin Li; Wang Zheng


    @@ Preface The government and enterprises in China started to pay attention to product specifications beginning with the launch of reform and, especially after the state promulgated the following two laws in 1993:the Product Quality Law (Article 15) and the Law on Protection of Consumer Rights and Interests (Articles 8, 13, 18, 22, 23, etc.).

  9. 50 CFR 648.200 - Specifications. (United States)


    ..., DEPARTMENT OF COMMERCE FISHERIES OF THE NORTHEASTERN UNITED STATES Management Measures for the Atlantic... (PRT) to develop and recommend the following specifications for a period of 3 years for consideration... herring fishery; (v) Total world export potential by herring producer countries; (vi) Total world...

  10. The Domain Specificity of Academic Emotional Experiences (United States)

    Goetz, Thomas; Frenzel, Anne C.; Pekrun, Reinhard; Hall, Nathan C.


    The authors analyzed the domain specificity of emotions and focused on experiences of enjoyment, anxiety, and boredom in the domains of mathematics, Latin, German, and English. On the basis of assumptions in R. Pekrun's (2000; in press) control-value theory and findings of pilot studies, the authors hypothesized the existence of a largely…

  11. Sedentary behavior and residual-specific mortality (United States)

    Loprinzi, Paul D.; Edwards, Meghan K.; Sng, Eveleen; Addoh, Ovuokerie


    Background: The purpose of this study was to examine the association of accelerometer-assessed sedentary behavior and residual-specific mortality. Methods: Data from the 2003-2006 National Health and Nutrition Examination Survey (NHANES) were used (N = 5536), with follow-up through 2011. Sedentary behavior was objectively measured over 7 days via accelerometry. Results: When expressing sedentary behavior as a 60 min/day increase, the hazard ratio across the models ranged from 1.07-1.40 (P < 0.05). There was evidence of an interaction effect between sedentary behavior and total physical activity on residual-specific mortality (Hazard ratiointeraction [HR] = 0.9989; 95% CI: 0.9982-0.9997; P = 0.008). Conclusion: Sedentary behavior was independently associated with residual-specific mortality. However, there was evidence to suggest that residual-specific mortality risk was a function of sedentary behavior and total physical activity. These findings highlight the need for future work to not only examine the association between sedentary behavior and health independent of total physical activity, but evaluate whether there is a joint effect of these two parameters on health.

  12. Autobiographical memory specificity in dissociative identity disorder

    NARCIS (Netherlands)

    Huntjens, Rafaële J. C.; Wessel, Ineke; Hermans, Dirk; van Minnen, Agnes


    A lack of adequate access to autobiographical knowledge has been related to psychopathology. More specifically, patients suffering from depression or a history of trauma have been found to be characterized by overgeneral memory, in other words, they show a relative difficulty in retrieving a specifi

  13. Familial Aggregation in Specific Language Impairment. (United States)

    Tallal, Paula; Hirsch, Linda S.; Realpe-Bonilla, Teresa; Miller, Steve; Brzustowicz, Linda M.; Bartlett, Christopher; Flax, Judy F.


    A case-control family study design examined the current language-related abilities of all biological, primary relatives of probands (N=22) with specific language impairment (SLI) and of matched controls. Impairment rates for family members of SLI probands was significantly higher than for controls. Also, impairment rates estimated from a family…

  14. 31 CFR 539.311 - Specific license. (United States)


    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Specific license. 539.311 Section 539.311 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY WEAPONS OF MASS DESTRUCTION TRADE CONTROL...

  15. Measuring Language-Specific Phonetic Settings (United States)

    Mennen, Ineke; Scobbie, James M.; de Leeuw, Esther; Schaeffler, Sonja; Schaeffler, Felix


    While it is well known that languages have different phonemes and phonologies, there is growing interest in the idea that languages may also differ in their "phonetic setting". The term "phonetic setting" refers to a tendency to make the vocal apparatus employ a language-specific habitual configuration. For example, languages may differ in their…

  16. 14 CFR 91.1015 - Management specifications. (United States)


    ... operations and, if different, the address that will serve as the primary point of contact for correspondence... Operations Program Management § 91.1015 Management specifications. (a) Each person conducting operations... authorizations, limitations, and certain procedures under which these operations are to be conducted, (3)...

  17. Public Address Systems. Specifications - Installation - Operation. (United States)

    Palmer, Fred M.

    Provisions for public address in new construction of campus buildings (specifications, installations, and operation of public address systems), are discussed in non-technical terms. Consideration is given to microphones, amplifiers, loudspeakers and the placement and operation of various different combinations. (FS)

  18. Prostate-specific antigen (PSA) blood test (United States)

    Prostate-specific antigen; Prostate cancer screening test; PSA ... special steps are needed to prepare for this test. ... Reasons for a PSA test: This test may be done to screen for prostate cancer. It is also used to follow people after prostate cancer ...

  19. Task-specificity of balance training. (United States)

    Giboin, Louis-Solal; Gruber, Markus; Kramer, Andreas


    Despite much research on balance training, it is still unclear whether balance training leads to highly task-specific adaptations or rather non-specific adaptations. Hence, in this study we examined whether balance training increased performance only in the balance task that was trained or also in non-trained tasks. Forty healthy participants (28 m 12 f, 25 ± 4 years, 177 ± 10 cm, 73 ± 14 kg) were assigned to one of two training groups (TGs) or a control group. Both TGs completed six sessions over 2 weeks, only the training device differed. Before and after the training, performance in the trained task as well as in additional untrained tasks was recorded. ANOVAs showed that each TG outperformed the other groups only in the task they had trained (e.g., task trained by TG1: +225% in TG1, only +41% and +30% in TG2 and control, group*time interaction, pbalance training resulted in highly task-specific effects, no transfer even to very similar tasks was observed. Therefore, we recommend identifying and training exactly those tasks that need improvement, and test the efficacy of training programs using specific tests instead of general tests with limited functional relevance.

  20. Specific Ion Effects in Cholesterol Monolayers

    Directory of Open Access Journals (Sweden)

    Teresa Del Castillo-Santaella


    Full Text Available The interaction of ions with interfaces and, in particular, the high specificity of these interactions to the particular ions considered, are central questions in the field of surface forces. Here we study the effect of different salts (NaI, NaCl, CaCl2 and MgCl2 on monolayers made of cholesterol molecules, both experimentally (surface area vs. lateral pressure isotherms measured by a Langmuir Film Balance and theoretically (molecular dynamics (MD all-atomic simulations. We found that surface isotherms depend, both quantitatively and qualitatively, on the nature of the ions by altering the shape and features of the isotherm. In line with the experiments, MD simulations show clear evidences of specific ionic effects and also provide molecular level details on ion specific interactions with cholesterol. More importantly, MD simulations show that the interaction of a particular ion with the surface depends strongly on its counterion, a feature ignored so far in most theories of specific ionic effects in surface forces.

  1. Isotope specific arbitrary material flow meter

    Energy Technology Data Exchange (ETDEWEB)

    Barty, Christopher P. J.; Post, John C.; Jones, Edwin


    A laser-based mono-energetic gamma-ray source is used to provide non-destructive and non-intrusive, quantitative determination of the absolute amount of a specific isotope contained within pipe as part of a moving fluid or quasi-fluid material stream.

  2. Specific Electrostatic Molecular Recognition in Water

    DEFF Research Database (Denmark)

    Li, Ming; Hoeck, Casper; Schoffelen, Sanne;


    -bead binding assay and by 2D NMR spectroscopy. Molecular dynamics (MD) studies revealed a putative mode of interaction for this unusual electrostatic binding event. High binding specificity occurred through a combination of topological matching and electrostatic and hydrogen-bond complementarities. From MD...

  3. Specific Impulses Losses in Solid Propellant Rockets (United States)


    to use the collision function form proposed by Golovin to simplify this production term: 4C><=) <P- .: Accordingly: m hence, by integration: Now, we...November 21, 1940 in Paris, Seine. VFirst Thesis. "Contribution to the Study of Specific i Impulse Loss in Solid Propellant Rockets." Second Thesis

  4. Autobiographical Memory Specificity in Dissociative Identity Disorder

    NARCIS (Netherlands)

    Huntjens, R.J.C.; Wessel, I.; Hermans, D.; Minnen, Agnes van


    A lack of adequate access to autobiographical knowledge has been related to psychopathology. More specifically, patients suffering from depression or a history of trauma have been found to be characterized by overgeneral memory, in other words, they show a relative difficulty in retrieving a specifi

  5. PD-L1-specific T cells

    DEFF Research Database (Denmark)

    Ahmad, Shamaila Munir; Borch, Troels Holz; Hansen, Morten


    for targeting the tumor microenvironment and for boosting the clinical effects of additional anticancer immunotherapy. This review summarizes present information about PD-L1 as a T cell antigen, depicts the initial findings about the function of PD-L1-specific T cells in the adjustment of immune responses...

  6. Primary Auditory Cortex Regulates Threat Memory Specificity (United States)

    Wigestrand, Mattis B.; Schiff, Hillary C.; Fyhn, Marianne; LeDoux, Joseph E.; Sears, Robert M.


    Distinguishing threatening from nonthreatening stimuli is essential for survival and stimulus generalization is a hallmark of anxiety disorders. While auditory threat learning produces long-lasting plasticity in primary auditory cortex (Au1), it is not clear whether such Au1 plasticity regulates memory specificity or generalization. We used…

  7. Specification and Configuration of Customized Complex Products

    NARCIS (Netherlands)

    Afsarmanesh, H.; Shafahi, M.


    This paper addresses the design of an information system for specification of complex configured products, such as the solar power plants or large intelligent buildings, which by nature are designed, constructed, installed, operated, and maintained through virtual consortium of enterprises. In other

  8. Spent nuclear fuel project product specification

    Energy Technology Data Exchange (ETDEWEB)



    This document establishes the limits and controls for the significant parameters that could potentially affect the safety and/or quality of the Spent Nuclear Fuel (SNF) packaged for processing, transport, and storage. The product specifications in this document cover the SNF packaged in Multi-Canister Overpacks to be transported throughout the SNF Project.

  9. Spent Nuclear Fuel (SNF) Project Product Specification

    Energy Technology Data Exchange (ETDEWEB)



    This document establishes the limits and controls for the significant parameters that could potentially affect the safety and/or quality of the Spent Nuclear Fuel (SNF) packaged for processing, transport, and storage. The product specifications in this document cover the SNF packaged in Multi-Canister Overpacks to be transported throughout the SNF Project.

  10. Volatiles in inter-specific bacterial interactions

    NARCIS (Netherlands)

    Tyc, O.; Zweers, H.; De Boer, W.; Garbeva, P.V.


    The importance of volatile organic compounds for functioning of microbes is receiving increased research attention. However, to date very little is known on how inter-specific bacterial interactions effect volatiles production as most studies have been focused on volatiles produced by monocultures o

  11. Prospects for site specific weed management

    DEFF Research Database (Denmark)

    Christensen, Svend; Rasmussen, Jesper; Pedersen, Søren Marcus;


    Research on Site Specific Weed Management (SSWM) started in the late 80's. Since that moment, considerable research has been conducted on different aspects of SSWM, from fundamental studies on the spatial ecology of weeds to the applied development and testing of new technologies for weed detection...


    Institute of Scientific and Technical Information of China (English)

    MaZhong; YuRuirong; HuaZichun; ZhuDexu


    Urokinsae (UK),one of the principal activators of plasminogen, has been widely used in the clinical therapy of thrombosis. However ,it lacks fibrin specificity ,and can lead to extensive systemic activation of plasminogen when injected into veins in large doses. On the other hand,

  13. Preliminary Anthropometric Specification for Land Vehicles (United States)


    worked for QinetiQ and BAE Systems in the UK. He has provided Human Factors expertise to numerous procurement programs and currently leads the...specification be updated when sufficient data becomes available for the female Army population. 4. It is recommended that the intergenerational change in

  14. Analyzing Languages for Specific Purposes Discourse (United States)

    Bowles, Hugo


    In the last 20 years, technological advancement and increased multidisciplinarity has expanded the range of data regarded as within the scope of languages for specific purposes (LSP) research and the means by which they can be analyzed. As a result, the analytical work of LSP researchers has developed from a narrow focus on specialist terminology…

  15. Canine specific ELISA for coagulation factor VII

    DEFF Research Database (Denmark)

    Knudsen, Tom; Kjelgaard-Hansen, Mads; Tranholm, Mikael;


    available to date. In this study, a canine specific ELISA for measurement of FVII:Ag in plasma was developed and validated. The FVII:Ag ELISA correctly diagnosed homozygous and heterozygous hereditary FVII deficiency. Together with activity based assays, such as FVII:C, the FVII:Ag ELISA should be valuable...

  16. The Formal Specifications for Protocols of Decoders

    Institute of Scientific and Technical Information of China (English)

    YUAN Meng-ting; WU Guo-qing; SHU Feng-di


    This paper presents a formal approach, FSPD (Formal Specifications for Protocols of Decoders), to specify decoder communication protocols. Based on axiomatic, FSPD is a precise language with which programmers could use only one suitable driver to handle various types of decoders. FSPD is helpful for programmers to get high adaptability and reusability of decoder-driver software.

  17. Methodes for identification of specific language impairment

    Directory of Open Access Journals (Sweden)

    Toktam Maleki Shahmahmood


    Full Text Available Background and Aim: Specific language impiarment (SLI is one of the most prevalent developmental language disorders its diagnosis is a problematic issue among researchers and clinicians because of the heterogeneity of language profiles in the affected population and overlapping with other developmental language disorders. The aim of this study was to review the suggested diagnostic criteria for this disorder, controversies about these criteria and identify the most accurate diagnostic methods.Methods: Published article from 1980 to 2012 in bibliographic and publisher databases including Pubmed, Google scholar, Cochran library, Web of Science, ProQuest, Springer, Oxford, Science direct, Ovid, Iran Medex and Magiran about the diagnostic methods for discriminating preschoool children with specific language impiarment from normal developing children were reviewd in this article. These keywords were used for research: “specific language impairment”, “SLI”, “diagnosis or identification”, “standardized tests”, and “tests for language development”.Conclusion: The results of this study show inspite of agreement of researchers and clinicians about exclusionary criteria as one basic part of the diagnosis of specific language impiarment , there is no consensus about the other part, inclusionary criteria. Different studies used different inclusionary criteria which can be divided to categories of clincal judgment, discrepancy-based criteria, standardized testing, clinical markers and markers from spontaneous speech samples. Advantages, disadvantages, and clinical applicability of each diagnostic method are discussed in this article.

  18. 12 CFR 347.119 - Specific consent. (United States)


    ... processing procedure. (d) Specific consent. Direct or indirect investments in or activities of foreign... control such organization as a result of a foreign investment; or (ii) A bank would be establishing a... foreign country. (1) Applicable law or practice in the foreign country where the foreign organization...

  19. Chromosome-specific families in Vibrio genomes

    Directory of Open Access Journals (Sweden)

    Oksana eLukjancenko


    Full Text Available We have compared chromosome-specific genes in a set of 18 finished Vibrio genomes, and, in addition, also calculated the pan- and core-genomes from a data set of more than 250 draft Vibrio genome sequences. These genomes come from 9 known species and 2 unknown species. Within the finished chromosomes, we find a core set of 1269 encoded protein families for chromosome 1, and a core of 252 encoded protein families for chromosome 2. Many of these core proteins are also found in the draft genomes (although which chromosome they are located on is unknown. Of the chromosome specific core protein families, 1169 and 153 are uniquely found in chromosomes 1 and 2, respectively. Gene ontology (GO terms for each of the protein families were determined, and the different sets for each chromosome were compared. A total of 363 different `Molecular Function` GO categories were found for chromosome 1 specific protein families, and these include several broad activities: pyridoxine 5' phosphate synthetase, glucosylceramidase, heme transport, DNA ligase, amino acid binding, and ribosomal components; in contrast, chromosome 2 specific protein families have only 66 Molecular Function GO terms and include many membrane-associated activities, such as ion channels, transmembrane transporters, and electron transport chain proteins. Thus, it appears that whilst there are many 'housekeeping systems' encoded in chromosome 1, there are far fewer core functions found in chromosome 2. However, the presence of many membrane-associated encoded proteins in chromosome 2 is surprising.

  20. Shape configuration and category-specificity

    DEFF Research Database (Denmark)

    Gerlach, Christian; Law, Ian; Paulson, Olaf B.


    We examined the neural correlates of visual shape configuration, the binding of local shape characteristics into wholistic object descriptions, by comparing the regional cerebral blood flow associated with recognition of outline drawings and fragmented drawings. We found no areas that responded m...... of perceptual organization, visual object recognition and category-specificity....

  1. Specification of the somatic musculature in Drosophila. (United States)

    Dobi, Krista C; Schulman, Victoria K; Baylies, Mary K


    The somatic muscle system formed during Drosophila embryogenesis is required for larvae to hatch, feed, and crawl. This system is replaced in the pupa by a new adult muscle set, responsible for activities such as feeding, walking, and flight. Both the larval and adult muscle systems are comprised of distinct muscle fibers to serve these specific motor functions. In this way, the Drosophila musculature is a valuable model for patterning within a single tissue: while all muscle cells share properties such as the contractile apparatus, properties such as size, position, and number of nuclei are unique for a particular muscle. In the embryo, diversification of muscle fibers relies first on signaling cascades that pattern the mesoderm. Subsequently, the combinatorial expression of specific transcription factors leads muscle fibers to adopt particular sizes, shapes, and orientations. Adult muscle precursors (AMPs), set aside during embryonic development, proliferate during the larval phases and seed the formation of the abdominal, leg, and flight muscles in the adult fly. Adult muscle fibers may either be formed de novo from the fusion of the AMPs, or are created by the binding of AMPs to an existing larval muscle. While less is known about adult muscle specification compared to the larva, expression of specific transcription factors is also important for its diversification. Increasingly, the mechanisms required for the diversification of fly muscle have found parallels in vertebrate systems and mark Drosophila as a robust model system to examine questions about how diverse cell types are generated within an organism.

  2. Statistical analysis of protein kinase specificity determinants

    DEFF Research Database (Denmark)

    Kreegipuu, Andres; Blom, Nikolaj; Brunak, Søren;


    The site and sequence specificity of protein kinase, as well as the role of the secondary structure and surface accessibility of the phosphorylation sites on substrate proteins, was statistically analyzed. The experimental data were collected from the literature and are available on the World Wide...

  3. Designing specificity of protein-substrate interactions

    NARCIS (Netherlands)

    Coluzza, I.; Frenkel, D.


    One of the key properties of biological molecules is that they can bind strongly to certain substrates yet interact only weakly with the very large number of other molecules that they encounter. Using a simple lattice model, we test several methods to design molecule-substrate binding specificity. W

  4. Brayton Isotope Power System (BIPS) facility specification

    Energy Technology Data Exchange (ETDEWEB)


    General requirements for the Brayton Isotope Power System (BIPS)/Ground Demonstration System (GDS) assembly and test facility are defined. The facility will include provisions for a complete test laboratory for GDS checkout, performance, and endurance testing, and a contamination-controlled area for assembly, fabrication, storage, and storage preparation of GDS components. Specifications, schedules, and drawings are included.

  5. TAL effectors specificity stems from negative discrimination.

    Directory of Open Access Journals (Sweden)

    Basile I M Wicky

    Full Text Available Transcription Activator-Like (TAL effectors are DNA-binding proteins secreted by phytopathogenic bacteria that interfere with native cellular functions by binding to plant DNA promoters. The key element of their architecture is a domain of tandem-repeats with almost identical sequences. Most of the polymorphism is located at two consecutive amino acids termed Repeat Variable Diresidue (RVD. The discovery of a direct link between the RVD composition and the targeted nucleotide allowed the design of TAL-derived DNA-binding tools with programmable specificities that revolutionized the field of genome engineering. Despite structural data, the molecular origins of this specificity as well as the recognition mechanism have remained unclear. Molecular simulations of the recent crystal structures suggest that most of the protein-DNA binding energy originates from non-specific interactions between the DNA backbone and non-variable residues, while RVDs contributions are negligible. Based on dynamical and energetic considerations we postulate that, while the first RVD residue promotes helix breaks--allowing folding of TAL as a DNA-wrapping super-helix--the second provides specificity through a negative discrimination of matches. Furthermore, we propose a simple pharmacophore-like model for the rationalization of RVD-DNA interactions and the interpretation of experimental findings concerning shared affinities and binding efficiencies. The explanatory paradigm presented herein provides a better comprehension of this elegant architecture and we hope will allow for improved designs of TAL-derived biotechnological tools.

  6. Development of industrial variant specification systems

    DEFF Research Database (Denmark)

    Hansen, Benjamin Loer

    With globalisation and increased competition industrial companies must be prepared to satisfy individual customer needs and still stay competitive with regards to lead times, quality, and prices. These factors require companies to be better prepared to handle specification activities during order...

  7. Development of the Specific Adaptation Mobility Cane. (United States)

    Arrington, S.


    A travel cane was adapted for use by a 10-year-old boy with cortical blindness, severe mental retardation and cerebral palsy affecting his left arm and leg. The Specific Adaptation Mobility Cane utilizes the affected arm to hold the cane while leaving the other hand free for trailing walls, opening doors, carrying objects, and holding handrails.…

  8. An Undergraduate Laboratory Activity Demonstrating Bacteriophage Specificity

    Directory of Open Access Journals (Sweden)

    Mary E. Allen


    Full Text Available Bacteriophage are among the most diverse and numerous microbes inhabiting our planet. Yet many laboratory activities fail to engage students in meaningful exploration of their diversity, unique characteristics, and abundance. In this curriculum activity students use a standard plaque assay to enumerate bacteriophage particles from a natural sample and use the scientific method to address questions about host specificity and diversity. A raw primary sewage sample is enriched for bacteriophage using hosts in the family Enterobacteriaceae. Students hypothesize about host specificity and use quantitative data (serial dilution and plaque assay to test their hypotheses. Combined class data also help them answer questions about phage diversity. The exercise was field tested with a class of 47 students using pre- and posttests. For all learning outcomes posttest scores were higher than pretest scores at or below p = 0.01. Average individualized learning gain (G was also calculated for each learning outcome. Students’ use of scientific language in reference to bacteriophage and host interaction significantly improved (p = 0.002; G = 0.50. Improved means of expression helped students construct better hypotheses on phage host specificity (G = 0.31, p = 0.01 and to explain the plaque assay method (G = 0.33, p = 0.002. At the end of the exercise students also demonstrated improved knowledge and understanding of phage specificity as related to phage therapy in humans (p < 0.001; G = 51.

  9. Ultrahigh Specific Impulse Nuclear Thermal Propulsion

    Energy Technology Data Exchange (ETDEWEB)

    Anne Charmeau; Brandon Cunningham; Samim Anghaie


    Research on nuclear thermal propulsion systems (NTP) have been in forefront of the space nuclear power and propulsion due to their design simplicity and their promise for providing very high thrust at reasonably high specific impulse. During NERVA-ROVER program in late 1950's till early 1970's, the United States developed and ground tested about 18 NTP systems without ever deploying them into space. The NERVA-ROVER program included development and testing of NTP systems with very high thrust (~250,000 lbf) and relatively high specific impulse (~850 s). High thrust to weight ratio in NTP systems is an indicator of high acceleration that could be achieved with these systems. The specific impulse in the lowest mass propellant, hydrogen, is a function of square root of absolute temperature in the NTP thrust chamber. Therefor optimizing design performance of NTP systems would require achieving the highest possible hydrogen temperature at reasonably high thrust to weight ratio. High hydrogen exit temperature produces high specific impulse that is a diret measure of propellant usage efficiency.

  10. Generating focused topic-specific sentiment lexicons

    NARCIS (Netherlands)

    Jijkoun, V.; de Rijke, M.; Weerkamp, W.


    We present a method for automatically generating focused and accurate topic-specific subjectivity lexicons from a general purpose polarity lexicon that allow users to pin-point subjective on-topic information in a set of relevant documents. We motivate the need for such lexicons in the field of medi

  11. Molecular and cellular limits to somatosensory specificity

    Directory of Open Access Journals (Sweden)

    Viana Félix


    Full Text Available Abstract Animals detect environmental changes through sensory neural mechanisms that enable them to differentiate the quality, intensity and temporal characteristics of stimuli. The 'doctrine of specific nervous energies' postulates that the different sensory modalities experienced by humans result of the activation of specific nervous pathways. Identification of functional classes of sensory receptors provided scientific support to the concept that somatosensory modalities (touch, pain, temperature, kinesthesis are subserved by separate populations of sensory receptor neurons specialized in detecting innocuous and injurious stimuli of different quality (mechanical forces, temperature, chemical compounds. The identification of receptor proteins activated by different physicochemical stimuli, in particular ion channels of the Transient Receptor Potential (TRP superfamily, has put forward the concept that specificity of peripheral sensory receptor neurons is determined by their expression of a particular "molecular sensor" that confers to each functional type its selectivity to respond with a discharge of nerve impulses to stimuli of a given quality. Nonetheless, recent experimental data suggest that the various molecular sensors proposed as specific transducer molecules for stimuli of different quality are not as neatly associated with the distinct functional types of sensory receptors as originally proposed. First, many ion channel molecules initially associated to the transduction of only one particular form of energy are also activated by stimuli of different quality, implying a limited degree of specificity in their transducing capacities. Second, molecular sensors associated with a stimulus quality and hence to a sensory receptor type and ultimately to a sensory modality may be concomitantly expressed in sensory receptor neurons functionally defined as specific for another stimulus quality. Finally, activation of voltage gated channels

  12. Are videogame training gains specific or general? (United States)

    Oei, Adam C; Patterson, Michael D


    Many recent studies using healthy adults document enhancements in perception and cognition from playing commercial action videogames (AVGs). Playing action games (e.g., Call of Duty, Medal of Honor) is associated with improved bottom-up lower-level information processing skills like visual-perceptual and attentional processes. One proposal states a general improvement in the ability to interpret and gather statistical information to predict future actions which then leads to better performance across different perceptual/attentional tasks. Another proposal claims all the tasks are separately trained in the AVGs because the AVGs and laboratory tasks contain similar demands. We review studies of action and non-AVGs to show support for the latter proposal. To explain transfer in AVGs, we argue that the perceptual and attention tasks share common demands with the trained videogames (e.g., multiple object tracking (MOT), rapid attentional switches, and peripheral vision). In non-AVGs, several studies also demonstrate specific, limited transfer. One instance of specific transfer is the specific enhancement to mental rotation after training in games with a spatial emphasis (e.g., Tetris). In contrast, the evidence for transfer is equivocal where the game and task do not share common demands (e.g., executive functioning). Thus, the "common demands" hypothesis of transfer not only characterizes transfer effects in AVGs, but also non-action games. Furthermore, such a theory provides specific predictions, which can help in the selection of games to train human cognition as well as in the design of videogames purposed for human cognitive and perceptual enhancement. Finally this hypothesis is consistent with the cognitive training literature where most post-training gains are for tasks similar to the training rather than general, non-specific improvements.

  13. Phenylthiourea specifically reduces zebrafish eye size. (United States)

    Li, Zeran; Ptak, Devon; Zhang, Liyun; Walls, Elwood K; Zhong, Wenxuan; Leung, Yuk Fai


    Phenylthiourea (PTU) is commonly used for inhibiting melanization of zebrafish embryos. In this study, the standard treatment with 0.2 mM PTU was demonstrated to specifically reduce eye size in larval fish starting at three days post-fertilization. This effect is likely the result of a reduction in retinal and lens size of PTU-treated eyes and is not related to melanization inhibition. This is because the eye size of tyr, a genetic mutant of tyrosinase whose activity is inhibited in PTU treatment, was not reduced. As PTU contains a thiocarbamide group which is presented in many goitrogens, suppressing thyroid hormone production is a possible mechanism by which PTU treatment may reduce eye size. Despite the fact that thyroxine level was found to be reduced in PTU-treated larvae, thyroid hormone supplements did not rescue the eye size reduction. Instead, treating embryos with six goitrogens, including inhibitors of thyroid peroxidase (TPO) and sodium-iodide symporter (NIS), suggested an alternative possibility. Specifically, three TPO inhibitors, including those that do not possess thiocarbamide, specifically reduced eye size; whereas none of the NIS inhibitors could elicit this effect. These observations indicate that TPO inhibition rather than a general suppression of thyroid hormone synthesis is likely the underlying cause of PTU-induced eye size reduction. Furthermore, the tissue-specific effect of PTU treatment might be mediated by an eye-specific TPO expression. Compared with treatment with other tyrosinase inhibitors or bleaching to remove melanization, PTU treatment remains the most effective approach. Thus, one should use caution when interpreting results that are obtained from PTU-treated embryos.

  14. Hand Specific Representations in Language Comprehension

    Directory of Open Access Journals (Sweden)

    Claire eMoody-Triantis


    Full Text Available Theories of embodied cognition argue that language comprehension involves sensory-motor re-enactments of the actions described. However, the degree of specificity of these re-enactments as well as the relationship between action and language remains a matter of debate. Here we investigate these issues by examining how hand-specific information (left or right hand is recruited in language comprehension and action execution. An fMRI study tested right-handed participants in two separate tasks that were designed to be as similar as possible to increase sensitivity of the comparison across task: an action execution go/no-go task where participants performed right or left hand actions, and a language task where participants read sentences describing the same left or right handed actions as in the execution task. We found that language-induced activity did not match the hand-specific patterns of activity found for action execution in primary somatosensory and motor cortex, but it overlapped with pre-motor and parietal regions associated with action planning. Within these pre-motor regions, both right hand actions and sentences elicited stronger activity than left hand actions and sentences - a dominant hand effect -. Importantly, both dorsal and ventral sections of the left pre-central gyrus were recruited by both tasks, suggesting different action features being recruited. These results suggest that (a language comprehension elicits motor representations that are hand-specific and akin to multimodal action plans, rather than full action re-enactments; and (b language comprehension and action execution share schematic hand-specific representations that are richer for the dominant hand, and thus linked to previous motor experience.

  15. Mapping UML Component Specifications to JEE Implementations

    Directory of Open Access Journals (Sweden)

    Jyhjong Lin


    Full Text Available Component-based Software Engineering (CbSE has become a well-accepted approach for developing complex software systems due to its significant advantages on composition and reuse. In practice, however, its use still requires the conjunction of a component specification method that describes how system requirements are satisfied in terms of software components. Such a component specification is then implemented in a variety of software component models (e.g., COM+, CORBA, EJB. To achieve this, a sound mapping from the specification to a designated component model is critical. In addition, for rapid advances on Internet technologies, software systems have gradually been architected as processing in distributed environments. Since a distributed environment involves often synchronous/asynchronous messages communicating among various processes, this paper focuses therefore on the mapping issue from a component specification to a component model that particularly takes into consideration of the communicating of synchronous/asynchronous messages. To illustrate, an on-line e-Learning curriculum order system is modeled for demonstrating the mapping idea. In completing the component specification, we adopt the well-known UML Components method, while in the component model we use the Enterprise Java Beans (EJB standard in that EJB is the core component model of the JEE (J2EE platform which supports well distributed operations/services. With such a practical mapping, software systems can be developed in a more effective way by specifying requirements in UML Components and implementing software components in EJB with the communicating of synchronous/asynchronous messages among various processes.

  16. Are videogame training gains specific or general?

    Directory of Open Access Journals (Sweden)

    Adam C. Oei


    Full Text Available Many recent studies using healthy adults document enhancements in perception and cognition from playing commercial action videogames. Playing action games (e.g., Call of Duty, Medal of Honor is associated with improved bottom-up lower-level information processing skills like visual-perceptual and attentional processes. One proposal states a general improvement in the ability to interpret and gather statistical information to predict future actions which then leads to better performance across different perceptual/attentional tasks. Another proposal claims all the tasks are separately trained in the action videogames because the action videogames and laboratory tasks contain similar demands. We review studies of action and non-action videogames to show support for the latter proposal. To explain transfer in action videogames, we argue that the perceptual and attention tasks share common demands with the trained videogames (e.g., multiple object tracking, rapid attentional switches, and peripheral vision. In non-action videogames, several studies also demonstrate specific, limited transfer. One instance of specific transfer is the specific enhancement to mental rotation after training in games with a spatial emphasis (e.g, Tetris. In contrast, the evidence for transfer is equivocal where the game and task do not share common demands (e.g., executive functioning. Thus, the common demands hypothesis of transfer not only characterizes transfer effects in action videogames, but also non-action games. Furthermore, such a theory provides specific predictions, which can help in the selection of games to train human cognition as well as in the design of videogames purposed for human cognitive and perceptual enhancement. Finally this hypothesis is consistent with the cognitive training literature where most post-training gains are for tasks similar to the training rather than general, non-specific improvements.

  17. Phenylthiourea specifically reduces zebrafish eye size.

    Directory of Open Access Journals (Sweden)

    Zeran Li

    Full Text Available Phenylthiourea (PTU is commonly used for inhibiting melanization of zebrafish embryos. In this study, the standard treatment with 0.2 mM PTU was demonstrated to specifically reduce eye size in larval fish starting at three days post-fertilization. This effect is likely the result of a reduction in retinal and lens size of PTU-treated eyes and is not related to melanization inhibition. This is because the eye size of tyr, a genetic mutant of tyrosinase whose activity is inhibited in PTU treatment, was not reduced. As PTU contains a thiocarbamide group which is presented in many goitrogens, suppressing thyroid hormone production is a possible mechanism by which PTU treatment may reduce eye size. Despite the fact that thyroxine level was found to be reduced in PTU-treated larvae, thyroid hormone supplements did not rescue the eye size reduction. Instead, treating embryos with six goitrogens, including inhibitors of thyroid peroxidase (TPO and sodium-iodide symporter (NIS, suggested an alternative possibility. Specifically, three TPO inhibitors, including those that do not possess thiocarbamide, specifically reduced eye size; whereas none of the NIS inhibitors could elicit this effect. These observations indicate that TPO inhibition rather than a general suppression of thyroid hormone synthesis is likely the underlying cause of PTU-induced eye size reduction. Furthermore, the tissue-specific effect of PTU treatment might be mediated by an eye-specific TPO expression. Compared with treatment with other tyrosinase inhibitors or bleaching to remove melanization, PTU treatment remains the most effective approach. Thus, one should use caution when interpreting results that are obtained from PTU-treated embryos.

  18. Nanoparticles for Site Specific Genome Editing (United States)

    McNeer, Nicole Ali

    Triplex-forming peptide nucleic acids (PNAs) can be used to coordinate the recombination of short 50-60 by "donor DNA" fragments into genomic DNA, resulting in site-specific correction of genetic mutations or the introduction of advantageous genetic modifications. Site-specific gene editing in hematopoietic stem and progenitor cells (HSPCs) could result in treatment or cure of inherited disorders of the blood such as beta-thalassemia. Gene editing in HSPCs and differentiated T cells could help combat HIV/AIDs by modifying receptors, such as CCR5, necessary for R5-tropic HIV entry. However, translation of genome modification technologies to clinical practice is limited by challenges in intracellular delivery, especially in difficult-to-transfect hematolymphoid cells. In vivo gene editing could also provide novel treatment for systemic monogenic disorders such as cystic fibrosis, an autosomal recessive disorder caused by mutations in the cystic fibrosis transmembrane receptor. Here, we have engineered biodegradable nanoparticles to deliver oligonucleotides for site-specific genome editing of disease-relevant genes in human cells, with high efficiency, low toxicity, and editing of clinically relevant cell types. We designed nanoparticles to edit the human beta-globin and CCR5 genes in hematopoietic cells. We show that poly(lactic-co-glycolic acid) (PLGA) nanoparticles can delivery PNA and donor DNA for site-specific gene modification in human hematopoietic cells in vitro and in vivo in NOD-scid IL2rgammanull mice. Nanoparticles delivered by tail vein localized to hematopoietic compartments in the spleen and bone marrow of humanized mice, resulting in modification of the beta-globin and CCR5 genes. Modification frequencies ranged from 0.005 to 20% of cells depending on the organ and cell type, without detectable toxicity. This project developed highly versatile methods for delivery of therapeutics to hematolymphoid cells and hematopoietic stem cells, and will help to

  19. Synthesizing Distributed Protocol Specifications from a UML State Machine Modeled Service Specification

    Institute of Scientific and Technical Information of China (English)

    Jehad Al Dallal; Kassem A.Saleh


    The object-oriented paradigm is widely applied in designing and implementing communication systems.Unified Modeling Language (UML) is a standard language used to model the design of object-oriented systems.A protocol state machine is a UML adopted diagram that is widely used in designing communication protocols.It has two key attractive advantages over traditional finite state machines:modeling concurrency and modeling nested hierarchical states.In a distributed communication system,each entity of the system has its own protocol that defines when and how the entity exchanges messages with other communicating entities in the system.The order of the exchanged messages must conform to the overall service specifications of the system.In object-oriented systems,both the service and the protocol specifications are modeled in UML protocol state machines.Protocol specification synthesis methods have to be applied to automatically derive the protocol specification from the service specification.Otherwise,a time-consuming process of design,analysis,and error detection and correction has to be applied iteratively until the design of the protocol becomes error-free and consistent with the service specification.Several synthesis methods are proposed in the literature for models other than UML protocol state machines,and therefore,because of the unique features of the protocol state machines,these methods are inapplicable to services modeled in UML protocol state machines.In this paper,we propose a synthesis method that automatically synthesizes the protocol specification of distributed protocol entities from the service specification,given that both types of specifications are modeled in UML protocol state machines.Our method is based on the latest UML version (UML2.3),and it is proven to synthesize protocol specifications that are syntactically and semantically correct.As an example application,the synthesis method is used to derive the protocol specification of the H.323

  20. Antigen-specific memory B cell development. (United States)

    McHeyzer-Williams, Louise J; McHeyzer-Williams, Michael G


    Helper T (Th) cell-regulated B cell immunity progresses in an ordered cascade of cellular development that culminates in the production of antigen-specific memory B cells. The recognition of peptide MHC class II complexes on activated antigen-presenting cells is critical for effective Th cell selection, clonal expansion, and effector Th cell function development (Phase I). Cognate effector Th cell-B cell interactions then promote the development of either short-lived plasma cells (PCs) or germinal centers (GCs) (Phase II). These GCs expand, diversify, and select high-affinity variants of antigen-specific B cells for entry into the long-lived memory B cell compartment (Phase III). Upon antigen rechallenge, memory B cells rapidly expand and differentiate into PCs under the cognate control of memory Th cells (Phase IV). We review the cellular and molecular regulators of this dynamic process with emphasis on the multiple memory B cell fates that develop in vivo.

  1. Specification of Learning Content Using Feature Diagrams (United States)

    Damaševičius, Robertas

    The main idea of a learning object (LO) is to break educational content down into small chunks that can be reused in various learning environments. When reused, such small chunks of educational content are combined in various ways leading to a great variability of the learning content. We propose using feature diagrams (FDs) for the specification of learning content at different layers of abstraction starting from the organization of teaching material in a lecture down to the specification and demonstration of particular software/hardware components. FDs can be used by (1) designers, teachers, and learners for graphical representation of domain knowledge in LOs; (2) programmers to specify and express variability-commonality relationships of LOs at a higher abstraction level to allow the development and implementation of generative LOs; and (3) researchers as a vehicle for analysis and better understanding of the e-Learning domain itself.

  2. Mode-Specific SN2 Reaction Dynamics. (United States)

    Wang, Yan; Song, Hongwei; Szabó, István; Czakó, Gábor; Guo, Hua; Yang, Minghui


    Despite its importance in chemistry, the microscopic dynamics of bimolecular nucleophilic substitution (SN2) reactions is still not completely elucidated. In this publication, the dynamics of a prototypical SN2 reaction (F(-) + CH3Cl → CH3F + Cl(-)) is investigated using a high-dimensional quantum mechanical model on an accurate potential energy surface (PES) and further analyzed by quasi-classical trajectories on the same PES. While the indirect mechanism dominates at low collision energies, the direct mechanism makes a significant contribution. The reactivity is found to depend on the specific reactant vibrational mode excitation. The mode specificity, which is more prevalent in the direct reaction, is rationalized by a transition-state-based model.

  3. Development of High Specific Strength Envelope Materials (United States)

    Komatsu, Keiji; Sano, Masa-Aki; Kakuta, Yoshiaki

    Progress in materials technology has produced a much more durable synthetic fabric envelope for the non-rigid airship. Flexible materials are required to form airship envelopes, ballonets, load curtains, gas bags and covering rigid structures. Polybenzoxazole fiber (Zylon) and polyalirate fiber (Vectran) show high specific tensile strength, so that we developed membrane using these high specific tensile strength fibers as a load carrier. The main material developed is a Zylon or Vectran load carrier sealed internally with a polyurethane bonded inner gas retention film (EVOH). The external surface provides weather protecting with, for instance, a titanium oxide integrated polyurethane or Tedlar film. The mechanical test results show that tensile strength 1,000 N/cm is attained with weight less than 230g/m2. In addition to the mechanical properties, temperature dependence of the joint strength and solar absorptivity and emissivity of the surface are measured. 

  4. Cell-Specific Aptamers as Emerging Therapeutics

    Directory of Open Access Journals (Sweden)

    Cindy Meyer


    Full Text Available Aptamers are short nucleic acids that bind to defined targets with high affinity and specificity. The first aptamers have been selected about two decades ago by an in vitro process named SELEX (systematic evolution of ligands by exponential enrichment. Since then, numerous aptamers with specificities for a variety of targets from small molecules to proteins or even whole cells have been selected. Their applications range from biosensing and diagnostics to therapy and target-oriented drug delivery. More recently, selections using complex targets such as live cells have become feasible. This paper summarizes progress in cell-SELEX techniques and highlights recent developments, particularly in the field of medically relevant aptamers with a focus on therapeutic and drug-delivery applications.


    Directory of Open Access Journals (Sweden)

    Cristian BUSU


    Full Text Available The universal postal service is part of the general interest economic services in which the state intervention is needed. From the economic and financial point of view, it is absolutely necessary to find the best formula by which a financial aid does not represent the premises of a state aid. The specific features of this market are determined by the minimum conditions imposed on what the frequency and speed delivery are concerned, in conditions of maximal rates. This paper focuses on an analysis on the EU’s postal services’ markets, from the competition point of view, with a special emphasis on the specific features of the players on this market, as well as on the benefits for their clients. The second part of the study focuses on actual situations from two EU’s different states and on competition aspects that these states have confronted with.

  6. Risk based technique for improving technical specifications

    Energy Technology Data Exchange (ETDEWEB)

    Kim, I. S.; Jae, M. S.; Kim, B. S.; Hwang, S. W.; Kang, K. M.; Park, S. S.; Yu, Y. S. [Hanyang Univ., Seoul (Korea, Republic of)


    The objective of this study is to develop the systematic guidance for reviewing the documents associated with the changes of technical specifications. The work done in this fiscal year is the following : surveys in TS requirements, TS improvements and TS regulations in foreign countries as well as Korea, surveys on the state-of-the-art of RITSs and their use in Korea, development of a decision-making framework for both the licensee and the regulation agency, description of risk measures, assessment methodology on STI/AOT, and adverse effects caused by periodic maintenance, which are explained in appendix. The results of this study might contribute to enhancing the quality of the current technical specifications and contribute to preparing the risk informed regulation program using the decision-making framework developed in this study.

  7. Using ontology for domain specific information retrieval (United States)

    Shashirekha, H. L.; Murali, S.; Nagabhushan, P.


    This paper presents a system for retrieving information from a domain specific document collection made up of data rich unnatural language text documents. Instead of conventional keyword based retrieval, our system makes use of domain ontology to retrieve the information from a collection of documents. The system addresses the problem of representing unnatural language text documents and constructing a classifier model that helps in the efficient retrieval of relevant information. Query to this system may be either the key phrases in terms of concepts or a domain specific unnatural language text document. The classifier used in this system can also be used to assign multiple labels to the previously unseen text document belonging to the same domain. An empirical evaluation of the system is conducted on the domain of text documents describing the classified matrimonial advertisements to determine its performance.

  8. The specific targeting of immune regulation

    DEFF Research Database (Denmark)

    Andersen, Mads Hald


    Indoleamine 2,3-dioxygenase (IDO) is an immunoregulatory enzyme that is implicated in suppressing T-cell immunity in many settings including cancer. In recent years, we have described spontaneous CD8(+) as well as CD4(+) T-cell reactivity against IDO in the tumor microenvironment of different...... cancer patients as well as in the peripheral blood of both cancer patients and to a lesser extent in healthy donors. We have demonstrated that IDO-reactive CD8(+) T cells were peptide-specific, cytotoxic effector cells, which are able to recognize and kill IDO-expressing cells including tumor cells....... The current review summarizes current knowledge of IDO as a T-cell antigen, reports the initial results that are suggesting a general function of IDO-specific T cells in immunoregulation, and discusses future opportunities....

  9. Biologic activity of digoxin-specific antisera. (United States)

    Watson, J F; Butler, V P


    Digoxin-specific antibodies are capable of removing essentially all intracellular digoxin from rat renal cortical slices or from human erythrocytes. In removing digoxin from erythrocytes, these antibodies are capable of reversing an effect of the drug on cellular potassium transport. This study provides direct evidence that antibodies are capable of removing, and thereby reversing the biological effect of, physiologically active low molecular weight substances after they have been taken up by mammalian cells. This biologic property of digoxin-specific antibodies suggests that autidigoxin sera may prove useful in the reversal of digoxin toxicity. Rapid and essentially quantitative removal of digoxin from red cells by antibody is not accompanied by an immediate restoration of patassium influx to normal levels. Identification of the mechanism of this phenomenon may provide useful information concerning the mode of action not only of digoxin, but also of the cation transport system of human erythrocytes.

  10. Accessing Specific Peptide Recognition by Combinatorial Chemistry

    DEFF Research Database (Denmark)

    Li, Ming

    Molecular recognition is at the basis of all processes for life, and plays a central role in many biological processes, such as protein folding, the structural organization of cells and organelles, signal transduction, and the immune response. Hence, my PhD project is entitled “Accessing Specific...... Peptide Recognition by Combinatorial Chemistry”. Molecular recognition is a specific interaction between two or more molecules through noncovalent bonding, such as hydrogen bonding, metal coordination, van der Waals forces, π−π, hydrophobic, or electrostatic interactions. The association involves kinetic....... Combinatorial chemistry was invented in 1980s based on observation of functional aspects of the adaptive immune system. It was employed for drug development and optimization in conjunction with high-throughput synthesis and screening. (chapter 2) Combinatorial chemistry is able to rapidly produce many thousands...

  11. Detergent-Specific Membrane Protein Crystallization Screens (United States)

    Wiener, Michael


    A suite of reagents has been developed for three-dimensional crystallization of integral membranes present in solution as protein-detergent complexes (PDCs). The compositions of these reagents have been determined in part by proximity to the phase boundaries (lower consolute boundaries) of the detergents present in the PDCs. The acquisition of some of the requisite phase-boundary data and the preliminary design of several of the detergent- specific screens was supported by a NASA contract. At the time of expiration of the contract, a partial set of preliminary screens had been developed. This work has since been extended under non-NASA sponsorship, leading to near completion of a set of 20 to 30 different and unique detergent- specific 96-condition screens.

  12. Production of high specific activity silicon-32

    Energy Technology Data Exchange (ETDEWEB)

    Phillips, D.R. [Los Alamos National Lab., NM (United States); Brzezinski, M.A. [Univ. of California, Santa Barbara, CA (United States). Marine Biotechnology Center


    This is the final report of a three-year, Laboratory Directed Research and Development Project (LDRD) at Los Alamos National Laboratory (LANL). There were two primary objectives for the work performed under this project. The first was to take advantage of capabilities and facilities at Los Alamos to produce the radionuclide {sup 32}Si in unusually high specific activity. The second was to combine the radioanalytical expertise at Los Alamos with the expertise at the University of California to develop methods for the application of {sup 32}Si in biological oceanographic research related to global climate modeling. The first objective was met by developing targetry for proton spallation production of {sup 32}Si in KCl targets and chemistry for its recovery in very high specific activity. The second objective was met by developing a validated field-useable, radioanalytical technique, based upon gas-flow proportional counting, to measure the dynamics of silicon uptake by naturally occurring diatoms.

  13. Selecting reusable components using algebraic specifications (United States)

    Eichmann, David A.


    A significant hurdle confronts the software reuser attempting to select candidate components from a software repository - discriminating between those components without resorting to inspection of the implementation(s). We outline a mixed classification/axiomatic approach to this problem based upon our lattice-based faceted classification technique and Guttag and Horning's algebraic specification techniques. This approach selects candidates by natural language-derived classification, by their interfaces, using signatures, and by their behavior, using axioms. We briefly outline our problem domain and related work. Lattice-based faceted classifications are described; the reader is referred to surveys of the extensive literature for algebraic specification techniques. Behavioral support for reuse queries is presented, followed by the conclusions.

  14. Cause-specific mortality after stroke

    DEFF Research Database (Denmark)

    Mogensen, Ulla Brasch; Olsen, Tom Skyhøj; Andersen, Klaus Kaae


    We investigated cause-specific mortality in relation to age, sex, stroke severity, and cardiovascular risk factor profile in the Copenhagen Stroke Study cohort with 10 years of follow-up. In a Copenhagen community, all patients admitted to the hospital with stroke during 1992-1993 (n = 988) were...... registered on admission. Evaluation included stroke severity, computed tomography scan, and a cardiovascular risk profile. Cause of death within 10 years according to death certificate information was classified as stroke, heart/arterial disease, or nonvascular disease. Competing-risks analyses were...... performed by cause-specific Cox regression after multiple imputation of missing data, assuming that values were missing at random. Death was due to stroke in 310 patients (31%), to heart/arterial disease in 209 patients (21%), and to nonvascular diseases in 289 patients (29%); 180 patients were still alive...

  15. Towards Dynamic Contrast Specific Ultrasound Tomography (United States)

    Demi, Libertario; van Sloun, Ruud J. G.; Wijkstra, Hessel; Mischi, Massimo


    We report on the first study demonstrating the ability of a recently-developed, contrast-enhanced, ultrasound imaging method, referred to as cumulative phase delay imaging (CPDI), to image and quantify ultrasound contrast agent (UCA) kinetics. Unlike standard ultrasound tomography, which exploits changes in speed of sound and attenuation, CPDI is based on a marker specific to UCAs, thus enabling dynamic contrast-specific ultrasound tomography (DCS-UST). For breast imaging, DCS-UST will lead to a more practical, faster, and less operator-dependent imaging procedure compared to standard echo-contrast, while preserving accurate imaging of contrast kinetics. Moreover, a linear relation between CPD values and ultrasound second-harmonic intensity was measured (coefficient of determination = 0.87). DCS-UST can find clinical applications as a diagnostic method for breast cancer localization, adding important features to multi-parametric ultrasound tomography of the breast.

  16. Stamen specification and anther development in rice

    Institute of Scientific and Technical Information of China (English)

    ZHANG DaBing; WILSON Zoe A


    Male reproductive development is a complex biological process which includes the formation of the stamen with differentiated anther tissues, in which microspores/pollens are generated, then anther dehiscence and subsequently pollination. Stamen specification and anther development involve a number of extraordinary events such as meristem transition, cell division and differentiation, cell to cell communication, etc., which need the cooperative interaction of sporophytic and gametophytic genes. The advent of various tools for rice functional gene identification, such as complete genome sequence, genome-wide microarrays, collections of mutants, has greatly facilitated our understanding of mechanisms of rice stamen specification and anther development. Male sterile lines are critical for hybrid rice breeding, therefore understanding these processes will not only contribute greatly to the basic knowledge of crop developmental biology, but also to the development of new varieties for hybrid rice breeding in the future.

  17. 77 FR 15399 - Model Safety Evaluation for Plant-Specific Adoption of Technical Specifications Task Force... (United States)


    ... COMMISSION Model Safety Evaluation for Plant-Specific Adoption of Technical Specifications Task Force... Regulatory Commission (NRC) is announcing the availability of the model safety evaluation (SE) for plant..., Revision 1, is available in ADAMS under Accession No. ML111650552; the model application is available...

  18. 77 FR 58421 - Model Safety Evaluation for Plant-Specific Adoption of Technical Specifications Task Force... (United States)


    ... COMMISSION Model Safety Evaluation for Plant-Specific Adoption of Technical Specifications Task Force...-415- 4737, or by email to . TSTF-522, Revision 0, includes a model application and is available in ADAMS under Accession No. ML100890316. The model safety evaluation (SE) of...

  19. Measuring Offence-Specific Forgiveness in Marriage: The Marital Offence-Specific Forgiveness Scale (MOFS) (United States)

    Paleari, F. Giorgia; Regalia, Camillo; Fincham, Frank D.


    Three studies involving 328 married couples were conducted to validate the Marital Offence-Specific Forgiveness Scale, a new measure assessing offence-specific forgiveness for marital transgressions. The studies examined the dimensionality; internal consistency; and discriminant, concurrent, and predictive validity of the new measure. The final…

  20. Do Specific Types of Networking Predict Specific Mobility Outcomes? A Two-Year Prospective Study (United States)

    Wolff, Hans-Georg; Moser, Klaus


    Previous research has established a general relation between networking and career outcomes, as postulated by theories on protean careers and career self management. We suggest that specific facets of networking behavior differentially affect specific career mobility outcomes over time. In a 2-year prospective study, we examined the impact of six…

  1. Group specific component in serum and otosclerosis

    DEFF Research Database (Denmark)

    Kjeldsen, A D; Vase, P; Thymann, M;


    An earlier Swedish study suggested a positive association between otosclerosis and the group-specific component GC*1F marker. We investigated the distribution of GC subtypes in 101 Danish patients with otosclerosis who all had surgery performed in the county of Funen. Compared to 1674 Danish cont...... controls we found no evidence of any association between markers from the GC serum protein system and otosclerosis....

  2. ADA Integrated Environment I. System Specification. (United States)


    returned. UNCLASSIFIED SECt AITY CLASSIFICATION O r THiS PAGE ("On’ Dese ,9nA.,d)l ,_ REPORT DOCUMENTATION PAGE BEFO scOL’No RM 1. RqEPl~ORT, NUM1191N 2...the Director, Defense Advanced Research Projects Agency. 2.2 Non-Government Documents [N-li IBM 370/VM Specifications [N-2] Perkin/Elmer 8/32

  3. Geotextile Tube Structures Guidelines for Contract Specifications (United States)


    specifications for the construction of sediment-filled geotextile tube struc- tures. This technical note represents the state of practice within the U.S...coastal, estua- rine, and riverine projects. Several Districts have already constructed such projects. Based on experience with existing projects, some... Nonwoven fabrics: Diaphragm Bursting Strength Tester Method ASTM D 3884 (1992) Abrasion Resistance of Textile Fabrics (Rotary Platform, Double-Head

  4. Test sequence construction from SFC specification


    Provost, Julien; Roussel, Jean-Marc; Faure, Jean-Marc


    International audience; This paper focuses on conformance test of electronic programmable devices whose specification is given in Sequential Function Chart (SFC). More precisely, a method is proposed to obtain automatically, from this specication, one minimum length test sequence which permits the exhaustive test of the behavior of the device. This method takes advantage of previous results on construction of the state machine representation of a SFC and on test of Mealy machines; conversely,...

  5. Learning LM Specificity for Ganglion Cells (United States)

    Ahumada, Albert J.


    Unsupervised learning models have been proposed based on experience (Ahumada and Mulligan, 1990;Wachtler, Doi, Lee and Sejnowski, 2007) that allow the cortex to develop units with LM specific color opponent receptive fields like the blob cells reported by Hubel and Wiesel on the basis of visual experience. These models used ganglion cells with LM indiscriminate wiring as inputs to the learning mechanism, which was presumed to occur at the cortical level.

  6. Specification of security enablers for data management


    Vukolic, Marko


    This deliverable introduces the processing functions for data management in the SUPERCLOUD. In particular, it contains security and dependability component specfications, descriptions of distributed protocols, specifications of cryptographic mechanisms, and descriptions of the data-resilience tools. SUPERCLOUD data management components described in this deliverable are organized in three parts. The first part describes novel components pertaining to state-machine replication, which will be u...

  7. Performance specifications for proton medical facility

    Energy Technology Data Exchange (ETDEWEB)

    Chu, W.T.; Staples, J.W.; Ludewigt, B.A.; Renner, T.R.; Singh, R.P.; Nyman, M.A.; Collier, J.M.; Daftari, I.K.; Petti, P.L.; Alonso, J.R. [Lawrence Berkeley Lab., CA (United States); Kubo, H.; Verhey, L.J. [University of California Davis Medical Center, Sacramento, CA (United States). Cancer Center]|[California Univ., San Francisco, CA (United States). School of Medicine; Castro, J.R. [Lawrence Berkeley Lab., CA (United States)]|[University of California Davis Medical Center, Sacramento, CA (United States). Cancer Center]|[California Univ., San Francisco, CA (United States). School of Medicine


    Performance specifications of technical components of a modern proton radiotherapy facility are presented. The technical items specified include: the accelerator; the beam transport system including rotating gantry; the treatment beamline systems including beam scattering, beam scanning, and dosimetric instrumentation; and an integrated treatment and accelerator control system. Also included are treatment ancillary facilities such as diagnostic tools, patient positioning and alignment devices, and treatment planning systems. The facility specified will accommodate beam scanning enabling the three-dimensional conformal therapy deliver .

  8. HAL/S-FC compiler system specifications (United States)


    This document specifies the informational interfaces within the HAL/S-FC compiler, and between the compiler and the external environment. This Compiler System Specification is for the HAL/S-FC compiler and its associated run time facilities which implement the full HAL/S language. The HAL/S-FC compiler is designed to operate stand-alone on any compatible IBM 360/370 computer and within the Software Development Laboratory (SDL) at NASA/JSC, Houston, Texas.

  9. Tri-Service Construction Guide Specifications (United States)


    items unique to civil works projects, such as relief wells, tunnel grouting, and hydraulic turbines, the CWGSs are used. We found the CWGS to be less...Systems CONTRACT FORMS, AND 02170 Cofferdams CONDITIONS OF THE CONTRACT 02200 Earthwork 02300 Tunneling 00010 Prebid Information 02350 Piles and...DIVISION 3 - CONCRETE Numbers, and Broadscope Section Explanations. 03100 Concrete Formwork SPECIFICATIONS 03200 Concrete Reinforcement 03250 Concrete

  10. Domain-specific control of selective attention. (United States)

    Lin, Szu-Hung; Yeh, Yei-Yu


    Previous research has shown that loading information on working memory affects selective attention. However, whether the load effect on selective attention is domain-general or domain-specific remains unresolved. The domain-general effect refers to the findings that load in one content (e.g. phonological) domain in working memory influences processing in another content (e.g., visuospatial) domain. Attentional control supervises selection regardless of information domain. The domain-specific effect refers to the constraint of influence only when maintenance and processing operate in the same domain. Selective attention operates in a specific content domain. This study is designed to resolve this controversy. Across three experiments, we manipulated the type of representation maintained in working memory and the type of representation upon which the participants must exert control to resolve conflict and select a target into the focus of attention. In Experiments 1a and 1b, participants maintained digits and nonverbalized objects, respectively, in working memory while selecting a target in a letter array. In Experiment 2, we presented auditory digits with a letter flanker task to exclude the involvement of resource competition within the same input modality. In Experiments 3a and 3b, we replaced the letter flanker task with an object flanker task while manipulating the memory load on object and digit representation, respectively. The results consistently showed that memory load modulated distractibility only when the stimuli of the two tasks were represented in the same domain. The magnitude of distractor interference was larger under high load than under low load, reflecting a lower efficacy of information prioritization. When the stimuli of the two tasks were represented in different domains, memory load did not modulate distractibility. Control of processing priority in selective attention demands domain-specific resources.

  11. Treatment of specific phobia in older adults


    Pachana, Nancy A; Rana M Woodward; Gerard JA Byrne


    Nancy A Pachana1, Rana M Woodward1, Gerard JA Byrne21School of Psychology, University of Queensland, Brisbane, Australia 2School of Medicine, University of Queensland, Brisbane, AustraliaAbstract: Phobias are common in later life, yet treatment research in this population remains scant. The efficacy of exposure therapy, in combination with other Cognitive-Behavioral Therapy (CBT) components, in the treatment of specific phobia with a middle and older aged sample was examined. Sixteen adults a...

  12. A Dynamic Algebraic Specification for Social Networks

    CERN Document Server

    Ksystra, Katerina; Triantafyllou, Nikolaos; Stefaneas, Petros


    With the help of the Internet, social networks have grown rapidly. This has increased security requirements. We present a formalization of social networks as composite behavioral objects, defined using the Observational Transition System (OTS) approach. Our definition is then translated to the OTS/CafeOBJ algebraic specification methodology. This translation allows the formal verification of safety properties for social networks via the Proof Score method. Finally, using this methodology we formally verify some security properties.

  13. Volatiles in Inter-Specific Bacterial Interactions. (United States)

    Tyc, Olaf; Zweers, Hans; de Boer, Wietse; Garbeva, Paolina


    The importance of volatile organic compounds for functioning of microbes is receiving increased research attention. However, to date very little is known on how inter-specific bacterial interactions effect volatiles production as most studies have been focused on volatiles produced by monocultures of well-described bacterial genera. In this study we aimed to understand how inter-specific bacterial interactions affect the composition, production and activity of volatiles. Four phylogenetically different bacterial species namely: Chryseobacterium, Dyella, Janthinobacterium, and Tsukamurella were selected. Earlier results had shown that pairwise combinations of these bacteria induced antimicrobial activity in agar media whereas this was not the case for monocultures. In the current study, we examined if these observations were also reflected by the production of antimicrobial volatiles. Thus, the identity and antimicrobial activity of volatiles produced by the bacteria were determined in monoculture as well in pairwise combinations. Antimicrobial activity of the volatiles was assessed against fungal, oomycetal, and bacterial model organisms. Our results revealed that inter-specific bacterial interactions affected volatiles blend composition. Fungi and oomycetes showed high sensitivity to bacterial volatiles whereas the effect of volatiles on bacteria varied between no effects, growth inhibition to growth promotion depending on the volatile blend composition. In total 35 volatile compounds were detected most of which were sulfur-containing compounds. Two commonly produced sulfur-containing volatile compounds (dimethyl disulfide and dimethyl trisulfide) were tested for their effect on three target bacteria. Here, we display the importance of inter-specific interactions on bacterial volatiles production and their antimicrobial activities.

  14. Transforming specifications of observable behaviour into programs


    Gilbert, D.; Hogger, C; Zlatuska, J


    A methodology for deriving programs from specifications of observable behaviour is described. The class of processes to which this methodology is applicable includes those whose state changes are fully definable by labelled transition systems, for example communicating processes without internal state changes. A logic program representation of such labelled transition systems is proposed, interpreters based on path searching techniques are defined, and the use of partial eva...

  15. Fatigue behavior of ADI: Some specific features

    Energy Technology Data Exchange (ETDEWEB)

    Svejcar, J.; Vechet, S.; Pokluda, J. [Technical Univ. of Brno (Czech Republic). Faculty of Mechanical Engineering


    The paper summarizes the results of fatigue tests on austempered ductile iron. Attention is mainly focused on the effect of graphite on crack propagation and on some irregularities exhibited by ADI and other ductile irons, e.g., some specific features of fatigue fracture (especially the occurrence of fatigue striations on intergranular facets), decrease of fatigue limit with increasing UTS, and anomalous dependence of loading cycle amplitude on mean cycle stress.

  16. Domain Specific Languages for Interactive Web Services

    DEFF Research Database (Denmark)

    Brabrand, Claus

    This dissertation shows how domain specific languages may be applied to the domain of interactive Web services to obtain flexible, safe, and efficient solutions. We show how each of four key aspects of interactive Web services involving sessions, dynamic creation of HTML/XML documents, form field......, , that supports virtually all aspects of the development of interactive Web services and provides flexible, safe, and efficient solutions....

  17. Postoperative pain: specific-procedure approach


    Martínez-Vísbal Alfonso Luis; Rodríguez-Betancourt Nancy Tatiana


    Pain is an unpleasant sensorial and emotional experience associated to real or potentialtissue response, in special if the trigger factor is known, as it occurs in a surgicalprocedure. In spite of the advance in analgesic techniques and medication, moderateto severe postoperative pain is presented in 70% of the operated patients. Multimodalanalgesia has been proposed due to it involves preventive analgesia and advanceanalgesia. Equally an specific analgesic management for each surgical proced...

  18. Salt bridges: geometrically specific, designable interactions. (United States)

    Donald, Jason E; Kulp, Daniel W; DeGrado, William F


    Salt bridges occur frequently in proteins, providing conformational specificity and contributing to molecular recognition and catalysis. We present a comprehensive analysis of these interactions in protein structures by surveying a large database of protein structures. Salt bridges between Asp or Glu and His, Arg, or Lys display extremely well-defined geometric preferences. Several previously observed preferences are confirmed, and others that were previously unrecognized are discovered. Salt bridges are explored for their preferences for different separations in sequence and in space, geometric preferences within proteins and at protein-protein interfaces, co-operativity in networked salt bridges, inclusion within metal-binding sites, preference for acidic electrons, apparent conformational side chain entropy reduction on formation, and degree of burial. Salt bridges occur far more frequently between residues at close than distant sequence separations, but, at close distances, there remain strong preferences for salt bridges at specific separations. Specific types of complex salt bridges, involving three or more members, are also discovered. As we observe a strong relationship between the propensity to form a salt bridge and the placement of salt-bridging residues in protein sequences, we discuss the role that salt bridges might play in kinetically influencing protein folding and thermodynamically stabilizing the native conformation. We also develop a quantitative method to select appropriate crystal structure resolution and B-factor cutoffs. Detailed knowledge of these geometric and sequence dependences should aid de novo design and prediction algorithms.

  19. Site-Specific PEGylation of Therapeutic Proteins

    Directory of Open Access Journals (Sweden)

    Jonathan K. Dozier


    Full Text Available The use of proteins as therapeutics has a long history and is becoming ever more common in modern medicine. While the number of protein-based drugs is growing every year, significant problems still remain with their use. Among these problems are rapid degradation and excretion from patients, thus requiring frequent dosing, which in turn increases the chances for an immunological response as well as increasing the cost of therapy. One of the main strategies to alleviate these problems is to link a polyethylene glycol (PEG group to the protein of interest. This process, called PEGylation, has grown dramatically in recent years resulting in several approved drugs. Installing a single PEG chain at a defined site in a protein is challenging. Recently, there is has been considerable research into various methods for the site-specific PEGylation of proteins. This review seeks to summarize that work and provide background and context for how site-specific PEGylation is performed. After introducing the topic of site-specific PEGylation, recent developments using chemical methods are described. That is followed by a more extensive discussion of bioorthogonal reactions and enzymatic labeling.

  20. Treatment of specific phobia in older adults

    Directory of Open Access Journals (Sweden)

    Nancy A Pachana


    Full Text Available Nancy A Pachana1, Rana M Woodward1, Gerard JA Byrne21School of Psychology, University of Queensland, Brisbane, Australia 2School of Medicine, University of Queensland, Brisbane, AustraliaAbstract: Phobias are common in later life, yet treatment research in this population remains scant. The efficacy of exposure therapy, in combination with other Cognitive-Behavioral Therapy (CBT components, in the treatment of specific phobia with a middle and older aged sample was examined. Sixteen adults aged 45–68 with DSM-IV diagnosis of a specific phobia received a manualized intervention over ten weeks, and were compared with a control group. Results indicated significant time effects in the treatment group for the primary outcome variables of phobic severity and avoidance as well as secondary outcome variables including depression and anxiety. Symptom presence and severity also significantly declined in the treatment group. No significant changes in state anxiety were noted across the treatment period. Such results provide support for the efficacy of exposure combined with CBT treatment for specific phobia in middle to older aged adults.Keywords: anxiety, phobia, older adults, cognitive behavioral therapy

  1. The effects of non-specific and specific concepts on tactical creativity in team ball sports. (United States)

    Memmert, Daniel; Roth, Klaus


    The main aim of this study was to examine the efficacy of various training approaches in team ball sports for the development of tactical creativity. Altogether, 135 children aged about 7 years took part in a 15-month field-based study. They participated either in non-specific treatment groups, a specific handball, soccer or field hockey group, or a control group. General and game-oriented tactical creativity were chosen as outcome measures. Our analysis of treatment-related effects showed that the non-specific groups displayed improvements in general creativity, whereas the specific groups showed improvements in the game-oriented creativity in which they were trained. Furthermore, clear transfer-related effects were observed. The analysis of group-related effects indicated no differences between the approaches. Only the soccer-specific group performed better in nearly all creative values. In conclusion, a non-specific concept appears to be a promising alternative to traditional specific treatments. This is further substantiated by several pedagogical, psychological, and medical arguments.

  2. Analysis of Geometrical Specification Model Based on the New GeometricalProduct Specification Language

    Institute of Scientific and Technical Information of China (English)

    马利民; 王金星; 蒋向前; 李柱; 徐振高


    Geometrical Product Specification and verification (GPS) is an ISO standard system coveting standards of size, dimension,geometrical tolerance and surface texture of geometrical product. ISO/TC213 on the GPS has been working towards coordination of the previous standards in tolerance and related metrology in order to publish the next generation of the GPS language. This paper introduces the geometrical product specification model for design, manufacturing and verification based on the improved GPS and its new concepts,i.e., surface models, geometrical features and operations. An application example for the geometrical product specification model is then given.

  3. Formal specification is an experimental science

    Energy Technology Data Exchange (ETDEWEB)

    Bjorner, D. [Technical Univ., Lyngby (Denmark)


    Traditionally, abstract models of large, complex systems have been given in free-form mathematics, combining - often in ad-hoc, not formally supported ways - notions from the disciplines of partial differential equations, functional analysis, mathematical statistics, etc. Such models have been very useful for assimilation of information, analysis (investigation), and prediction (simulation). These models have, however, usually not been helpful in deriving computer representations of the modelled systems - for the purposes of computerized monitoring and control, Computing science, concerned with how to construct objects that can exist within the computer, offers ways of complementing, and in some cases, replacing or combining traditional mathematical models. Formal, model-, as well as property-oriented, specifications in the styles of denotational (respectively, algebraic semantics) represent major approaches to such modelling. In this expository, discursive paper we illustrate what we mean by model-oriented specifications of large, complex technological computing systems. The three modelling examples covers the introvert programming methodological subject of SDEs: software development environments, the distributed computing system subject of wfs`s: (transaction) work flow systems, and the extrovert subject of robots: robotics! the thesis is, just as for mathematical modelling, that we can derive much understanding, etc., from experimentally creating such formally specified models - on paper - and that we gain little in additionally building ad-hoc prototypes. Our models are expressed in a model-oriented style using the VDM specification language Meta-IV In this paper the models only reflect the {open_quotes}data modelling{close_quotes} aspects. We observe that such data models are more easily captured in the model-oriented siyle than in the algebraic semantics property-oriented style which originally was built of the abstraction of operations. 101 refs., 4 figs.

  4. Specific unresponsiveness to skin allografts in burns. (United States)

    Clark, G T; Moon, D J; Cunningham, P R; Johnson, T D; Thomas, J M; Thomas, F T


    We have examined the potential to provide long-term or even permanent wound coverage in a mouse model of a 30% total body surface area burn using skin allografts. Treatment of the recipient mouse with rabbit anti-mouse thymocyte serum (ATS) followed by donor bone marrow infusion induces a state of specific unresponsiveness to the skin allograft without the need for chronic immunosuppression. Specifically, a B6AF1 mouse receives a burn on Day -2 relative to grafting, ATS on Day -1, and Day +2, a skin allograft from a C3H/He mouse on Day 0, and infusion of C3H/He donor bone marrow on Day +6. We studied three groups of burned mice: Group I, allograft control (n = 5); Group II, allograft plus ATS (n = 12); and Group III, allograft plus ATS and bone marrow infusion (n = 15). Mean graft survival was compared using a one-way analysis of variance and a Student-Newman-Keuls post hoc test. There was no statistical difference in animal mortality among any of the three groups, and there was no evidence of infectious morbidity. Mean skin allograft survival was as follows: Group I, 9 days; Group II, 29 days; and Group III, 66 days (P less than 0.05 vs Group I and II). Nine animals in Group III had intact hair bearing grafts at 90 days when the study was terminated. This study suggests the potential use of induced specific unresponsiveness to skin allografts for wound coverage in thermal injury without use of chronic immunosuppression. In our animal study this was accomplished without increased mortality or apparent infectious morbidity.

  5. Cancer immunology: the search for specificity. (United States)

    Old, L J


    The major focus of cancer immunology has shifted away from arguments about the validity of the immunosurveillance theory of cancer to the more basic question of tumor-specific antigens. Despite vast effort aimed at demonstrations of such antigens, their existence in the generality of cancer remains unproved. Serological analysis of 3 tumor types, mouse leukemia and sarcoma and human malignant melanoma, has received the most attention, and a rudimentary classification of the surface antigens expressed by these tumors has begun to emerge. The prime candidates for antigens that can be considered tumor specific are the few instances of Class 1 antigens that have now been serologically defined on mouse and human tumors. These antigens show an absolute restriction to individual tumors and are not demonstrable on any other normal or malignant cell type. Biochemical and genetic characterizations of Class 1 antigens represent an essential next step in an evaluation of the significance of these antigens. The surprising features of the thymus leukemia (TL) antigens of the mouse provide insight into the genetic origin of another key class of tumor antigens, i.e., those with characteristic properties of both differentiation and tumor-specific antigens. In normal mice, TL antigens are restricted to cells in the thymus, and strains differ with regard to expression versus nonexpression of TL antigens. Genetic information for TL is universal in mice, however, as leukemias that develop in mice normally lacking TL are found to express TL. What is clear from the past two decades of research in cancer immunology is that a far more detailed knowledge of surface antigens of tumor cells will be necessary before we can begin to assess the possibility of immunological control of cancer.

  6. Protein diversity confers specificity in plasmid segregation. (United States)

    Fothergill, Timothy J G; Barillà, Daniela; Hayes, Finbarr


    The ParG segregation protein (8.6 kDa) of multidrug resistance plasmid TP228 is a homodimeric DNA-binding factor. The ParG dimer consists of intertwined C-terminal domains that adopt a ribbon-helix-helix architecture and a pair of flexible, unstructured N-terminal tails. A variety of plasmids possess partition loci with similar organizations to that of TP228, but instead of ParG homologs, these plasmids specify a diversity of unrelated, but similarly sized, partition proteins. These include the proteobacterial pTAR, pVT745, and pB171 plasmids. The ParG analogs of these plasmids were characterized in parallel with the ParG homolog encoded by the pseudomonal plasmid pVS1. Like ParG, the four proteins are dimeric. No heterodimerization was detectable in vivo among the proteins nor with the prototypical ParG protein, suggesting that monomer-monomer interactions are specific among the five proteins. Nevertheless, as with ParG, the ParG analogs all possess significant amounts of unordered amino acid residues, potentially highlighting a common structural link among the proteins. Furthermore, the ParG analogs bind specifically to the DNA regions located upstream of their homologous parF-like genes. These nucleoprotein interactions are largely restricted to cognate protein-DNA pairs. The results reveal that the partition complexes of these and related plasmids have recruited disparate DNA-binding factors that provide a layer of specificity to the macromolecular interactions that mediate plasmid segregation.

  7. Modality-specificity of selective attention networks

    Directory of Open Access Journals (Sweden)

    Hannah Jamieson Stewart


    Full Text Available Objective: To establish the modality specificity and generality of selective attention networks. Method: Forty-eight young adults completed a battery of four auditory and visual selective attention tests based upon the Attention Network framework: the visual and auditory Attention Network Tests (vANT, aANT, the Test of Everyday Attention (TEA, and the Test of Attention in Listening (TAiL. These provided independent measures for auditory and visual alerting, orienting, and conflict resolution networks. The measures were subjected to an exploratory factor analysis to assess underlying attention constructs. Results: The analysis yielded a four-component solution. The first component comprised of a range of measures from the TEA and was labeled ‘general attention’. The third component was labeled ‘auditory attention’, as it only contained measures from the TAiL using pitch as the attended stimulus feature. The second and fourth components were labeled as ‘spatial orienting’ and ‘spatial conflict’, respectively – they were comprised of orienting and conflict resolution measures from the vANT, aANT and TAiL attend-location task – all tasks based upon spatial judgments (e.g., the direction of a target arrow or sound location. Conclusions: These results do not support our a-priori hypothesis that attention networks are either modality specific or supramodal. Auditory attention separated into selectively attending to spatial and non-spatial features, with the auditory spatial attention loading onto the same factor as visual spatial attention, suggesting spatial attention is supramodal. However, since our study did not include a non-spatial measure of visual attention, further research will be required to ascertain whether non-spatial attention is modality-specific.

  8. Gender-specific information search behavior

    Directory of Open Access Journals (Sweden)

    Parinaz Maghferat


    Full Text Available This paper presents an empirical gender study in the context of information science. It discusses an exploratory investigation, which provides empirical data about differences of information seeking activities by female and male students. The research focus was on whether there are gender-specific differences when people perform searches with the aid of general search engines and specialized Deep Web information services. It has been observed how the participants behaved in getting information and how the gender groups differ from each other. Which search system (search engine or professional information supplier has been preferred by the gender groups at first? How did the gender groups search (applied operators, modifications of query formulations, targeted search? How far were the users satisfied with their results? For data collection paper-questionnaires have been used and the answers have been statistically analyzed with the help of SPSS. The questionnaire consisted of four different search tasks each with seven sub-questions. The research and the obtained result data indicate at least in the choice of search sources, the satisfaction with this source and the results obtained a gender-specific difference. Men tried to use professional information services as well as search engines for search, regardless of the difficulty of the search task and its formulation. In contrast, women behaved cautiously in choosing search sources. They decided either on sources, which they knew skillfully or where their use was assigned. Women were generally more satisfied with the obtained results as men. These data can represent an initial approach for further analysis of gender-specific Web search behavior.

  9. How specific halide adsorption varies hydrophobic interactions. (United States)

    Stock, Philipp; Müller, Melanie; Utzig, Thomas; Valtiner, Markus


    Hydrophobic interactions (HI) are driven by the water structure around hydrophobes in aqueous electrolytes. How water structures at hydrophobic interfaces and how this influences the HI was subject to numerous studies. However, the effect of specific ion adsorption on HI and hydrophobic interfaces remains largely unexplored or controversial. Here, the authors utilized atomic force microscopy force spectroscopy at well-defined nanoscopic hydrophobic interfaces to experimentally address how specific ion adsorption of halide ions as well as NH4 (+), Cs(+), and Na(+) cations alters interaction forces across hydrophobic interfaces. Our data demonstrate that iodide adsorption at hydrophobic interfaces profoundly varies the hydrophobic interaction potential. A long-range and strong hydration repulsion at distances D > 3 nm, is followed by an instability which could be explained by a subsequent rapid ejection of adsorbed iodides from approaching hydrophobic interfaces. In addition, the authors find only a weakly pronounced influence of bromide, and as expected no influence of chloride. Also, all tested cations do not have any significant influence on HI. Complementary, x-ray photoelectron spectroscopy and quartz-crystal-microbalance with dissipation monitoring showed a clear adsorption of large halide ions (Br(-)/I(-)) onto hydrophobic self-assembled monolayers (SAMs). Interestingly, iodide can even lead to a full disintegration of SAMs due to specific and strong interactions of iodide with gold. Our data suggest that hydrophobic surfaces are not intrinsically charged negatively by hydroxide adsorption, as it was generally believed. Hydrophobic surfaces rather interact strongly with negatively charged large halide ions, leading to a surface charging and significant variation of interaction forces.

  10. Ultrastructural changes in non-specific duodenitis

    Institute of Scientific and Technical Information of China (English)

    Cheng-Xin Wang; Li-Jiang Liu; Jing Guan; Xiao-Ling Zhao


    AIM: To investigate the ultrastructural and morphological changes of non-specific duodenitis (NSD) in an attempt to grade them according to the extent of the lesions.METHODS: Biopsies were taken from the mucosa of duodenal bulb of 44 patients selected from the patients undergoing upper gastrointestinal endoscopy for epigastric discomforts. From each patient, two pinch biopsies on the same area were obtained from duodenal bulb. One was for scanning electron microscopy and the other was stained with hematoxylin-eosin, Warthin-Starry silver and both were then examined under light microscope. A total of 12 specimens (three from each degree of the normal and Ⅰ-Ⅲ of NSD diagnosed and graded by histology) selected from the 44patients were dehydrated, critical point dried, coated with gold palladium and examined under a JEOL JSM-30 scanning electron microscope (SEM) at 20 kV.RESULTS: According to the ultrastructural morphologic changes, non-specific duodenitis was divided into normal (as control group), mild, moderate and severe degrees according to results of SEM. The normal villi of duodenal bulb were less than 0.2 mm. There were inflammation cells,occasionally red blood cells and macrophages on the mucosal epithelial surface. Erosion and desquamation of epithelium could be seen. Three cases (25%, 3/12) had gastric metaplasia and Helicobacter pylori(H pylori) infection could be found in 5 cases (41.67%, 5/12) in duodenal bulb mucosa. The most distinctive feature was the ulcer-like defect on the surface of epithelial cells.CONCLUSION: Non-specific duodenitis is a separate entity disease caused by different factors. SEM is of value as an aid in the diagnosis of mucosal diseases of duodenum.

  11. On emotion specificity in decision making

    Directory of Open Access Journals (Sweden)

    Marcel Zeelenberg


    Full Text Available We present a motivational account of the impact of emotion on decision making, termed the feeling-is-for-doing approach. We first describe the psychology of emotion and argue for a need to be specific when studying emotion's impact on decision making. Next we describe what our approach entails and how it relates emotion, via motivation to behavior. Then we offer two illustrations of our own research that provide support for two important elements in our reasoning. We end with specifying four criteria that we consider to be important when studying how feeling guides our everyday doing.

  12. Cue-Specific Reactivity in Experienced Gamblers



    To examine whether gambling cue reactivity is cue-specific, 47 scratch-off lottery players and 47 horse race gamblers were presented with video clips of their preferred and non-preferred modes of gambling, and two control stimuli including an exciting car race and a mental stressor task while heart rates, excitement, and urge to gamble were being measured. Heart rates for both groups of gamblers were highest to the mental stressor and did not differ in response to the other three cues. Excite...

  13. Cardiac specific expression of Xenopus Popeye-1. (United States)

    Hitz, Marc P; Pandur, Petra; Brand, Thomas; Kühl, Michael


    Popeye genes code for putative transmembrane proteins that are predominantly expressed in heart and skeletal muscle. Here we report on the isolation and expression of a previously unknown Xenopus member of this family, Xenopus Popeye-1 (Xpop-1). Xpop-1 is 60-65% identical to other vertebrate Pop-1 genes at the protein level. Whole-mount in situ hybridization studies revealed a highly specific expression of Xpop-1 whose transcripts are restricted to the embryonic heart and become enriched in the forming ventricle. Interestingly, unlike other known vertebrate Popeye genes, Xpop-1 is exclusively expressed in cardiac tissue and absent from skeletal muscle.

  14. HAL/S-360 compiler system specification (United States)

    Johnson, A. E.; Newbold, P. N.; Schulenberg, C. W.; Avakian, A. E.; Varga, S.; Helmers, P. H.; Helmers, C. T., Jr.; Hotz, R. L.


    A three phase language compiler is described which produces IBM 360/370 compatible object modules and a set of simulation tables to aid in run time verification. A link edit step augments the standard OS linkage editor. A comprehensive run time system and library provide the HAL/S operating environment, error handling, a pseudo real time executive, and an extensive set of mathematical, conversion, I/O, and diagnostic routines. The specifications of the information flow and content for this system are also considered.


    Directory of Open Access Journals (Sweden)

    Maria B. Ponyavina


    Full Text Available The article presents methodological and methodical bases of research relevant specifics of Internet marketing conducted by Russian companies in the Interenet. The paper is focused on the research of the leading Russian online publications, their practices and characteristics. This work dwells on the comparison of competitiveness with adjacent categories. It is established that the development of information technologies, among which one of the key places has taken the Internet, the emergence and rapid growth of e-Commerce became the basis for the emergence of a new trend in the modern concept of relationship marketing - Internet marketing.

  16. Orientation specific deposition of mesoporous particles

    Directory of Open Access Journals (Sweden)

    Tomas Kjellman


    Full Text Available We present a protocol for a facile orientation specific deposition of plate-like mesoporous SBA-15 silica particles onto a surface (mesopores oriented normal to surface. A drop of an aqueous dispersion of particles is placed on the surface and water vaporizes under controlled relative humidity. Three requirements are essential for uniform coverage: particle dispersion should not contain aggregates, a weak attraction between particles and surface is needed, and evaporation rate should be low. Aggregates are removed by stirring/sonication. Weak attraction is realized by introducing cationic groups to the surface. Insight into the mechanisms of the so-called coffee stain effect is also provided.

  17. From Design Specification to SystemC

    Directory of Open Access Journals (Sweden)

    Rachid Boudour


    Full Text Available In this paper, we present a framework for transforming the design model into SystemC code. Such a framework uses as input UML state machine and object diagrams, which are more and more used as design models in embedded systems. To do this, we have firstly used Poseidon tool for editing the design model and generating the XMI representation, and secondly integrated a transformation module leading to SystemC code. The mapping to SystemC code offers not only a system-level executable specification, but also a means to facilitating the system partitioning in hardware and software parts.

  18. Subject-specific modeling of intracranial aneurysms (United States)

    Cebral, Juan R.; Hernandez, Monica; Frangi, Alejandro; Putman, Christopher; Pergolizzi, Richard; Burgess, James


    Characterization of the blood flow patterns in cerebral aneurysms is important to explore possible correlations between the hemodynamics conditions and the morphology, location, type and risk of rupture of intracranial aneurysms. For this purpose, realistic patient-specific models are constructed from computed tomography angiography and 3D rotational angiography image data. Visualizations of the distribution of hemodynamics forces on the aneurysm walls as well as the intra-aneurysmal flow patterns are presented for a number of cerebral aneurysms of different sizes, types and locations. The numerical models indicate that there are different classes of intra-aneurysmal flow patterns, that may carry different risks of rupture.

  19. EMI Execution Service Specification 1.0

    CERN Document Server

    Schuller, B. (JUELICH); Smirnova, O (Lund University); Konstantinov, A. (Oslo University); Skou Andersen, M. (University of Copenhagen); Riedel, M. (JUELICH); Memon, A.S. (JUELICH); Memon, M.S. (JUELICH); Zangrando, L. (INFN); Sgaravatto, M. (INFN); Frizziero, E. (INFN)


    This document provides the interface specification, including related data models such as state model, activity description, resource and activity information, of an execution service, matching the needs of the EMI production middleware stack composed of ARC, gLite and UNICORE components. This service therefore is referred to as the EMI Execution Service (or “ES” for short). This document is a continuation of the work previously known as the GENEVA, then AGU (“ARC, gLite UNICORE”), then PGI execution service.

  20. EMI Execution Service (EMI-ES) Specification

    CERN Document Server

    Schuller, B


    This document provides the interface specification, including related data models such as state model, activity description, resource and activity information, of an execution service, matching the needs of the EMI production middleware stack composed of ARC, gLite and UNICORE components. This service therefore is referred to as the EMI Execution Service (or “ES” for short). This document is a continuation of the work previously know as the GENEVA, then AGU (“ARC, gLite UNICORE”), then PGI execution service. As a starting point, the v0.42 of the “PGI Execution Service Specification” (doc15839) was used.

  1. A Specification Test of Stochastic Diffusion Models

    Institute of Scientific and Technical Information of China (English)

    Shu-lin ZHANG; Zheng-hong WEI; Qiu-xiang BI


    In this paper,we propose a hypothesis testing approach to checking model mis-specification in continuous-time stochastic diffusion model.The key idea behind the development of our test statistic is rooted in the generalized information equality in the context of martingale estimating equations.We propose a bootstrap resampling method to implement numerically the proposed diagnostic procedure.Through intensive simulation studies,we show that our approach is well performed in the aspects of type Ⅰ error control,power improvement as well as computational efficiency.

  2. Subspecies specific RAPD markers in rice

    Institute of Scientific and Technical Information of China (English)


    The cultivated rice (Oryza sativa L.) is known to contain two major subspecies, indica (O. sativa L. ssp. indica) and japonica (O. sativa L. ssp. japonica). The indica and japonica differentiation resulted in significance of hybrid sterility and hybrid breakdown, which are barriers of gene flow between the two major subgene pools within O. sativa. Traditional classification of indica and japonica germplasm based on isozymes. Here, we report the identification of several random amplified polymorphic DNA (RAPD) markers that have alleles specific in indica or japonica varieties and thus provide a quick and accurate tool to distinguish japonica lines from indica ones.

  3. Age-Specific Correlates of Child Growth. (United States)

    Rieger, Matthias; Trommlerová, Sofia Karina


    Growth faltering describes a widespread phenomenon that height- and weight-for-age of children in developing countries collapse rapidly in the first two years of life. We study age-specific correlates of child nutrition using Demographic and Health Surveys from 56 developing countries to shed light on the potential drivers of growth faltering. Applying nonparametric techniques and exploiting within-mother variation, we find that maternal and household factors predict best the observed shifts and bends in child nutrition age curves. The documented interaction between age and maternal characteristics further underlines the need not only to provide nutritional support during the first years of life but also to improve maternal conditions.

  4. A Framework for the Specificity of Addictions

    Directory of Open Access Journals (Sweden)

    Myriam Forster


    Full Text Available Research over the last two decades suggests that a wide range of substance and behavioral addictions may serve similar functions. Yet, co-occurrence of addictions has only been reported among a minority of addicts. “Addiction specificity” pertains to a phenomenon in which one pattern of addictive behaviors may be acquired whereas another is not. This paper presents the PACE model as a framework which might help explain addiction specificity. Pragmatics, attraction, communication, and expectation (PACE variables are described, which may help give some direction to future research needs in this arena.

  5. An introduction to programming with specifications

    CERN Document Server


    A feature of modern advanced computing is the functional approach to programming. In this book, the authors present an introduction to the mathematics which underline functional programming, emphasizing the understanding of definition and specification--a prerequisite of good programming and problem solving with a computer. The book is self-contained, requiring a low level of mathematical sophistication and may be used as an introduction to the mathematics of programming.Provides an introduction to the functional approach to programming**Emphasizes the problem to be solved, not the pro

  6. Species-specific challenges in dog cloning. (United States)

    Kim, G A; Oh, H J; Park, J E; Kim, M J; Park, E J; Jo, Y K; Jang, G; Kim, M K; Kim, H J; Lee, B C


    Somatic cell nuclear transfer (SCNT) is now an established procedure used in cloning of several species. SCNT in dogs involves multiple steps including the removal of the nuclear material, injection of a donor cell, fusion, activation of the reconstructed oocytes and finally transfer to a synchronized female recipient. There are therefore many factors that contribute to cloning efficiency. By performing a retrospective analysis of 2005-2012 published papers regarding dog cloning, we define the optimum procedure and summarize the specific feature for dog cloning.

  7. Specific and non-specific symptoms of colorectal cancer and contact to general practice

    DEFF Research Database (Denmark)

    Rasmussen, Sanne; Larsen, Pia Veldt; Søndergaard, Jens;


    , were randomly selected in the general population and invited to participate in an internet-based survey. Items regarding experience of specific and non-specific alarm symptoms of colorectal cancer within the preceding 4 weeks and contact to GP were included. RESULTS: A total of 49706 subjects completed......BACKGROUND: To improve survival rates for colorectal cancer, referral guidelines have been implemented. First step in the diagnostic process is for the individual to recognize the symptoms and contact his/her general practitioner (GP) for evaluation. OBJECTIVES: To determine (i) the prevalence...... of specific and non-specific symptom experiences indicative of colorectal cancer, (ii) the proportion of subsequent contacts to GPs, (iii) to explore the possible differences in symptom experience and contact to GPs between age and sex. METHODS: A nationwide study of 100000 adults, aged 20 years and older...

  8. Compartment-Specific Phosphorylation of Squid Neurofilaments. (United States)

    Grant, Philip; Pant, Harish C


    Studies of the giant axon and synapse of third-order neurons in the squid stellate ganglion have provided a vast literature on neuronal physiology and axon transport. Large neuronal size also lends itself to comparative biochemical studies of cell body versus axon. These have focused on the regulation of synthesis, assembly, posttranslational modification and function of neuronal cytoskeletal proteins (microtubules (MTs) and neurofilaments (NFs)), the predominant proteins in axoplasm. These contribute to axonal organization, stability, transport, and impulse transmission responsible for rapid contractions of mantle muscles underlying jet propulsion. Studies of vertebrate NFs have established an extensive literature on NF structure, organization, and function; studies of squid NFs, however, have made it possible to compare compartment-specific regulation of NF synthesis, assembly, and function in soma versus axoplasm. Since NFs contain over 100 eligible sites for phosphorylation by protein kinases, the compartment-specific patterns of phosphorylation have been a primary focus of biochemical studies. We have learned that NF phosphorylation is tightly compartmentalized; extensive phosphorylation occurs only in the axonal compartment in squid and in vertebrate neurons. This extensive phosphorylation plays a key role in organizing NFs, in association with microtubules (MTs), into a stable, dynamic functional lattice that supports axon growth, diameter, impulse transmission, and synaptic activity. To understand how cytoskeletal phosphorylation is topographically regulated, the kinases and phosphatases, bound to NFs isolated from cell bodies and axoplasm, have also been studied.

  9. Patient-specific simulation of tidal breathing (United States)

    Walters, M.; Wells, A. K.; Jones, I. P.; Hamill, I. S.; Veeckmans, B.; Vos, W.; Lefevre, C.; Fetitia, C.


    Patient-specific simulation of air flows in lungs is now straightforward using segmented airways trees from CT scans as the basis for Computational Fluid Dynamics (CFD) simulations. These models generally use static geometries, which do not account for the motion of the lungs and its influence on important clinical indicators, such as airway resistance. This paper is concerned with the simulation of tidal breathing, including the dynamic motion of the lungs, and the required analysis workflow. Geometries are based on CT scans obtained at the extremes of the breathing cycle, Total Lung Capacity (TLC) and Functional Residual Capacity (FRC). It describes how topologically consistent geometries are obtained at TLC and FRC, using a `skeleton' of the network of airway branches. From this a 3D computational mesh which morphs between TLC and FRC is generated. CFD results for a number of patient-specific cases, healthy and asthmatic, are presented. Finally their potential use in evaluation of the progress of the disease is discussed, focusing on an important clinical indicator, the airway resistance.

  10. Nausea in specific phobia of vomiting. (United States)

    Höller, Yvonne; van Overveld, Mark; Jutglar, Heili; Trinka, Eugen


    Specific phobia of vomiting (SPOV) is a clinical condition with early onset, chronic course and substantial psychosocial impairment due to a rigorous avoidance behavior. A primary symptom which drives patients to consult a medical practitioner is nausea. In this study our aim was to further analyze this symptom of SPOV and examined its role in the development and manifestation of the phobia. We conducted an internet survey in the german SPOV-internet-forum. We calculated a nausea score and grouped participants in a high-and low-nausea group to examine the relationship between nausea and characteristics of the fear of vomiting. In this sample (N = 131), nausea was fairly common in most participants with fear of vomiting. Participants in the high-nausea group had significantly higher ratings of subjective fear and significantly longer duration of fear of vomiting. Additionally, the high-nausea group contained more participants with a body mass index below 19 than the low-nausea group. The present findings suggest that nausea is a core symptom in SPOV which is closely related to intensity of the fear, duration of the fear, and body weight. Future research should investigate if nausea-specific design of treatment could improve therapy outcome.

  11. Treatment of specific phobia in adults. (United States)

    Choy, Yujuan; Fyer, Abby J; Lipsitz, Josh D


    This is a comprehensive review of treatment studies in specific phobia. Acute and long-term efficacy studies of in vivo exposure, virtual reality, cognitive therapy and other treatments from 1960 to 2005 were retrieved from computer search engines. Although specific phobia is a chronic illness and animal extinction studies suggest that relapse is a common phenomenon, little is known about long-term outcome. Treatment gains are generally maintained for one year, but longer follow-up studies are needed to better understand and prevent relapse. Acutely, the treatments are not equally effective among the phobia subtypes. Most phobias respond robustly to in vivo exposure, but it is associated with high dropout rates and low treatment acceptance. Response to systematic desensitization is more moderate. A few studies suggest that virtual reality may be effective in flying and height phobia, but this needs to be substantiated by more controlled trials. Cognitive therapy is most helpful in claustrophobia, and blood-injury phobia is uniquely responsive to applied tension. The limited data on medication have not been promising with the exception of adjunctive D-clycoserine. Despite the acute benefits of in vivo exposure, greater attention should be paid to improve treatment acceptance and retention, and additional controlled studies of more acceptable treatments are needed.

  12. Pairing and specific heat in hot nuclei

    CERN Document Server

    Gambacurta, Danilo; Sandulescu, Nicu


    The thermodynamics of pairing phase-transition in nuclei is studied in the canonical ensemble and treating the pairing correlations in a finite-temperature variation after projection BCS approach (FT-VAP). Due to the restoration of particle number conservation, the pairing gap and the specific heat calculated in the FT-VAP approach vary smoothly with the temperature, indicating a gradual transition from the superfluid to the normal phase, as expected in finite systems. We have checked that the predictions of the FT-VAP approach are very accurate when compared to the results obtained by an exact diagonalization of the pairing Hamiltonian. The influence of pairing correlations on specific heat is analysed for the isotopes $^{161,162}$Dy and $^{171,172}$Yb. It is shown that the FT-VAP approach, applied with a level density provided by mean field calculations and supplemented, at high energies, by the level density of the back-shifted Fermi gas model, can approximate reasonably well the main properties of specifi...

  13. Arginine specific aminopeptidase from Lactobacillus brevis

    Directory of Open Access Journals (Sweden)

    Arya Nandan


    Full Text Available The proteolytic system of lactic acid bacteria contribute to the development of flavor during the ripening of cheese through the generation of short peptides and free amino acids, which directly or indirectly act as flavor precursors. Newly isolated lactic acid bacteria (LAB as well as those procured from culture collection centers were screened for the production of various substrate specific aminopeptidases. Among all the strains screened, L. brevis (NRRL B-1836 was found to produce quantifiable amount of intracellular arginine specific aminopeptidase (EC The productivity of arginine aminopeptidase in 5 L fermentor was 36 IU/L/h. The Luedeking and Piret model was tested for intracellular production of aminopeptidase and the data seemed to fit well, as the correlation coefficient was 0.9964 for MRS. The αAP and βAP was 0.4865 and 0.0046, respectively in MRS medium indicating that the yield was predominantly depended on growth. The culture produced lactic acid and also tolerated pH 2.0-3.0 and 0.3-0.5% bile salts, the most important probiotic features.

  14. Forum on Specifications and Design Languages 2012

    CERN Document Server


    This book brings together a selection of the best papers from the fifteenth edition of the Forum on specification and Design Languages Conference (FDL), which was held in September 2012 at Vienna University of Technology, Vienna, Austria.  FDL is a well-established international forum devoted to dissemination of research results, practical experiences and new ideas in the application of specification, design and verification languages to the design, modeling and verification of integrated circuits, complex hardware/software embedded systems, and mixed-technology systems.  ·         Covers Assertion Based Design, Verification & Debug; ·         Includes language-based modeling and design techniques for embedded systems; ·         Covers design, modeling and verification of mixed physical domain and mixed signal systems that include significant analog parts in electrical and non-electrical domains; ·         Includes formal and semi-formal system level design methods fo...

  15. Subset specification of central serotonergic neurons

    Directory of Open Access Journals (Sweden)

    Marten P Smidt


    Full Text Available The last decade the serotonin (5-hydroxytryptamine; 5-HT system has received enormous attention due to its role in regulation of behavior, exemplified by the discovery that increased 5-HT tone in the central nervous system is able to alleviate affective disorders. Here, we review the developmental processes, with a special emphasis on subset specification, leading to the formation of the 5-HT system in the brain. Molecular classification of 5-HT neuronal groups leads to the definition of two independent rostral groups positioned in rhombomere 1 and 2/3 and a caudal group in rhombomere 5-8. In addition, more disperse refinement of these subsets is present as shown by the selective expression of the 5-HT1A autoreceptor, indicating functional diversity between 5-HT subsets. The functional significance of the molecular coding differences is not well known and the molecular basis of described specific connectivity patterns remain to be elucidated. Recent developments in genetic lineage tracing models will provide these data and form a major step-up towards the full understanding of the importance of developmental programming and function of 5-HT neuronal subsets.

  16. Evolution and Development of Effective Feedstock Specifications

    Energy Technology Data Exchange (ETDEWEB)

    Garold Gresham; Rachel Emerson; Amber Hoover; Amber Miller; William Bauer; Kevin Kenney


    The U.S. Department of Energy promotes the production of a range of liquid fuels and fuel blend stocks from lignocellulosic biomass feedstocks by funding fundamental and applied research that advances the state of technology in biomass collection, conversion, and sustainability. As part of its involvement in this program, the Idaho National Laboratory (INL) investigates the feedstock logistics economics and sustainability of these fuels. The 2012 feedstock logistics milestone demonstrated that for high-yield areas that minimize the transportation distances of a low-density, unstable biomass, we could achieve a delivered cost of $35/ton. Based on current conventional equipment and processes, the 2012 logistics design is able to deliver the volume of biomass needed to fulfill the 2012 Renewable Fuel Standard’s targets for ethanol. However, the Renewable Fuel Standard’s volume targets are continuing to increase and are expected to peak in 2022 at 36 billion gallons. Meeting these volume targets and achieving a national-scale biofuels industry will require expansion of production capacity beyond the 2012 Conventional Feedstock Supply Design Case to access diverse available feedstocks, regardless of their inherent ability to meet preliminary biorefinery quality feedstock specifications. Implementation of quality specifications (specs), as outlined in the 2017 Design Case – “Feedstock Supply System Design and Economics for Conversion of Lignocellulosic Biomass to Hydrocarbon Fuels” (in progress), requires insertion of deliberate, active quality controls into the feedstock supply chain, whereas the 2012 Conventional Design only utilizes passive quality controls.

  17. From "magic bullets" to specific cancer immunotherapy. (United States)

    Riether, Carsten; Schürch, Christian; Ochsenbein, Adrian F


    The immune system is able to specifically target antigen-expressing cancer cells. The promise of immunotherapy was to eliminate cancer cells without harming normal tissue and, therefore, with no or very few side effects. Immunotherapy approaches have, for several decades, been tested against several tumours, most often against malignant melanoma. However, although detectable immune responses have regularly been induced, the clinical outcome has often been disappointing. The development of molecular methods and an improved understanding of tumour immunosurveillance led to novel immunotherapy approaches in the last few years. First randomised phase III trials proved that immunotherapy can prolong survival of patients with metastatic melanoma or prostate cancer. The development in the field is very rapid and various molecules (mainly monoclonal antibodies) that activate the immune system are currently being tested in clinical trials and will possibly change our treatment of cancer. The ultimate goal of any cancer therapy and also immunotherapy is to cure cancer. However, this depends on the elimination of the disease originating cancer stem cells. Unfortunately, cancer stem cells seem resistant to most available treatment options. Recent developments in immunotherapy may allow targeting these cancer stem cells specifically in the future. In this review, we summarise the current state of immunotherapy in clinical routine and the expected developments in the near future.

  18. Nausea in Specific Phobia of Vomiting

    Directory of Open Access Journals (Sweden)

    Eugen Trinka


    Full Text Available Specific phobia of vomiting (SPOV is a clinical condition with early onset, chronic course and substantial psychosocial impairment due to a rigorous avoidance behavior. A primary symptom which drives patients to consult a medical practitioner is nausea. In this study our aim was to further analyze this symptom of SPOV and examined its role in the development and manifestation of the phobia. We conducted an internet survey in the german SPOV-internet-forum. We calculated a nausea score and grouped participants in a high- and low-nausea group to examine the relationship between nausea and characteristics of the fear of vomiting. In this sample (N = 131, nausea was fairly common in most participants with fear of vomiting. Participants in the high-nausea group had significantly higher ratings of subjective fear and significantly longer duration of fear of vomiting. Additionally, the high-nausea group contained more participants with a body mass index below 19 than the low-nausea group. The present findings suggest that nausea is a core symptom in SPOV which is closely related to intensity of the fear, duration of the fear, and body weight. Future research should investigate if nausea-specific design of treatment could improve therapy outcome.

  19. Optimizing the specificity of nucleic acid hybridization. (United States)

    Zhang, David Yu; Chen, Sherry Xi; Yin, Peng


    The specific hybridization of complementary sequences is an essential property of nucleic acids, enabling diverse biological and biotechnological reactions and functions. However, the specificity of nucleic acid hybridization is compromised for long strands, except near the melting temperature. Here, we analytically derived the thermodynamic properties of a hybridization probe that would enable near-optimal single-base discrimination and perform robustly across diverse temperature, salt and concentration conditions. We rationally designed 'toehold exchange' probes that approximate these properties, and comprehensively tested them against five different DNA targets and 55 spurious analogues with energetically representative single-base changes (replacements, deletions and insertions). These probes produced discrimination factors between 3 and 100+ (median, 26). Without retuning, our probes function robustly from 10 °C to 37 °C, from 1 mM Mg(2+) to 47 mM Mg(2+), and with nucleic acid concentrations from 1 nM to 5 µM. Experiments with RNA also showed effective single-base change discrimination.

  20. Specific identification of Bacillus anthracis strains (United States)

    Krishnamurthy, Thaiya; Deshpande, Samir; Hewel, Johannes; Liu, Hongbin; Wick, Charles H.; Yates, John R., III


    Accurate identification of human pathogens is the initial vital step in treating the civilian terrorism victims and military personnel afflicted in biological threat situations. We have applied a powerful multi-dimensional protein identification technology (MudPIT) along with newly generated software termed Profiler to identify the sequences of specific proteins observed for few strains of Bacillus anthracis, a human pathogen. Software termed Profiler was created to initially screen the MudPIT data of B. anthracis strains and establish the observed proteins specific for its strains. A database was also generated using Profiler containing marker proteins of B. anthracis and its strains, which in turn could be used for detecting the organism and its corresponding strains in samples. Analysis of the unknowns by our methodology, combining MudPIT and Profiler, led to the accurate identification of the anthracis strains present in samples. Thus, a new approach for the identification of B. anthracis strains in unknown samples, based on the molecular mass and sequences of marker proteins, has been ascertained.

  1. CLP application to nanomaterials: a specific aspect

    Directory of Open Access Journals (Sweden)

    Maria Alessandrelli


    Full Text Available This paper aims at describing some relevant aspects related to the classification, labelling and packaging of nanomaterials. Concerns have been raised about potential adverse effects to humans or the environment as result of impacts of nanomaterials. The new Regulation (EC no. 1272/2008 on classification, labelling and packaging of substances and mixtures (CLP does not contain any specific definition or provision related to nanomaterials nevertheless they are covered by the definition of substance set in the Regulation. It is recognized that different particle sizes or forms of the same substance can have different classification. Thus, if substances are placed on the market both at nanoscale and as bulk, a separate classification and labelling may be required if the available data on the intrinsic properties indicate a difference in hazard class between the two forms. CLP Regulation requires the manufacturer or importer to ensure that the information used to classify relates to the forms or physical states in which the substance is placed on the market and in which it can reasonably be expected to be used. Moreover, CLP demands testing relating to physical hazards to be performed if such information is missing or not adequate to conclude on classification. Further developments of the CLP guidance documents and implementation tools are needed in order to cover nanomaterials more specifically.

  2. Autoantibodies in SLE: Specificities, Isotypes and Receptors

    Directory of Open Access Journals (Sweden)

    Barbara Dema


    Full Text Available Systemic Lupus Erythematosus (SLE is characterized by a wide spectrum of auto-antibodies which recognize several cellular components. The production of these self-reactive antibodies fluctuates during the course of the disease and the involvement of different antibody-secreting cell populations are considered highly relevant for the disease pathogenesis. These cells are developed and stimulated through different ways leading to the secretion of a variety of isotypes, affinities and idiotypes. Each of them has a particular mechanism of action binding to a specific antigen and recognized by distinct receptors. The effector responses triggered lead to a chronic tissue inflammation. DsDNA autoantibodies are the most studied as well as the first in being characterized for its pathogenic role in Lupus nephritis. However, others are of growing interest since they have been associated with other organ-specific damage, such as anti-NMDAR antibodies in neuropsychiatric clinical manifestations or anti-β2GP1 antibodies in vascular symptomatology. In this review, we describe the different auto-antibodies reported to be involved in SLE. How autoantibody isotypes and affinity-binding to their antigen might result in different pathogenic responses is also discussed.

  3. Allergen specific immunotherapy in nasobronchial allergy.

    Directory of Open Access Journals (Sweden)

    Joshi S


    Full Text Available BACKGROUND: More than one antigen has been used for immunotherapy of allergic disorders. So far less than five antigens have been employed with variable results. AIM: To evaluate effect of multiple antigens up to six in the immunotherapy of nasobronchial allergy. SETTING AND DESIGN: Based on clinical history, symptoms present for at least 3 years with set criteria of immunomodulation for asthma and rhinitis: documented IgE mediated asthma and rhinitis, failure in allergen avoidance and moderate to severe clinical manifestations. MATERIAL AND METHODS: Five hundred cases of various allergic disorders attending allergy clinic of Bombay hospital were screened. Allergen specific immunotherapy was initiated in 131 subjects (56 -rhinitis and 75 asthma with prior consent. Patients suffering from allergic disorders secondary to diseases or drug therapy were excluded. Multiple allergen immunotherapy was given at specific intervals up to a period of one year. Allergen extracts were prepared as per standard technique. For statistical analysis "students′t test" was used. RESULTS AND CONCLUSIONS: Significant improvement in PEFR, reduction in skin sensitivity to allergens used in immunotherapy formulation and symptomatic relief without any untoward reaction show that multiple allergen immunotherapy is as effective as monoallergen immunotherapy in nasobronchial allergy.

  4. Peptide arrays for screening cancer specific peptides. (United States)

    Ahmed, Sahar; Mathews, Anu Stella; Byeon, Nara; Lavasanifar, Afsaneh; Kaur, Kamaljit


    In this paper, we describe a novel method to screen peptides for specific recognition by cancer cells. Seventy peptides were synthesized on a cellulose membrane in an array format, and a direct method to study the peptide-whole cell interaction was developed. The relative binding affinity of the cells for different peptides with respect to a lead 12-mer p160 peptide, identified by phage display, was evaluated using the CyQUANT fluorescence of the bound cells. Screening allowed identification of at least five new peptides that displayed higher affinity (up to 3-fold) for MDA-MB-435 and MCF-7 human cancer cells compared to the p160 peptide. These peptides showed very little binding to the control (noncancerous) human umbilical vein endothelial cells (HUVECs). Three of these peptides were synthesized separately and labeled with fluorescein isothiocyanate (FITC) to study their uptake and interaction with the cancer and control cells using confocal laser scanning microscopy and flow cytometry. The results confirmed the high and specific affinity of an 11-mer peptide 11 (RGDPAYQGRFL) and a 10-mer peptide 18 (WXEAAYQRFL) for the cancer cells versus HUVECs. Peptide 11 binds different receptors on target cancer cells as its sequence contains multiple recognition motifs, whereas peptide 18 binds mainly to the putative p160 receptor. The peptide array-whole cell binding assay reported here is a complementary method to phage display for further screening and optimization of cancer targeting peptides for cancer therapy and diagnosis.

  5. Toward patient-specific articular contact mechanics. (United States)

    Ateshian, Gerard A; Henak, Corinne R; Weiss, Jeffrey A


    The mechanics of contacting cartilage layers is fundamentally important to understanding the development, homeostasis and pathology of diarthrodial joints. Because of the highly nonlinear nature of both the materials and the contact problem itself, numerical methods such as the finite element method are typically incorporated to obtain solutions. Over the course of five decades, we have moved from an initial qualitative understanding of articular cartilage material behavior to the ability to perform complex, three-dimensional contact analysis, including multiphasic material representations. This history includes the development of analytical and computational contact analysis methods that now provide the ability to perform highly nonlinear analyses. Numerical implementations of contact analysis based on the finite element method are rapidly advancing and will soon enable patient-specific analysis of joint contact mechanics using models based on medical image data. In addition to contact stress on the articular surfaces, these techniques can predict variations in strain and strain through the cartilage layers, providing the basis to predict damage and failure. This opens up exciting areas for future research and application to patient-specific diagnosis and treatment planning applied to a variety of pathologies that affect joint function and cartilage homeostasis.

  6. Changing the specificity of a bacterial chemoreceptor. (United States)

    Derr, Paige; Boder, Eric; Goulian, Mark


    The methyl-accepting chemotaxis proteins are a family of receptors in bacteria that mediate chemotaxis to diverse signals. To explore the plasticity of these proteins, we have developed a simple method for selecting cells that swim to target attractants. The procedure is based on establishing a diffusive gradient in semi-soft agar plates and does not require that the attractant be metabolized or degraded. We have applied this method to select for variants of the Escherichia coli aspartate receptor, Tar, that have a new or improved response to different amino acids. We found that Tar can be readily mutated to respond to new chemical signals. However, the overall change in specificity depended on the target compound. A Tar variant that could detect cysteic acid still showed a strong sensitivity to aspartate, indicating that the new receptor had a broadened specificity relative to wild-type Tar. Tar variants that responded to phenylalanine or N-methyl aspartate, or that had an increased sensitivity to glutamate showed a strong decrease in their response to aspartate. In at least some of the cases, the maximal level of sensitivity that was obtained could not be attributed solely to substitutions within the binding pocket. The new tar alleles and the techniques described here provide a new approach for exploring the relationship between ligand binding and signal transduction by chemoreceptors and for engineering new receptors for applications in biotechnology.

  7. Chemical and radiochemical specifications - PWR power plants; Specifications chimiques et radiochimiques - Centrales REP

    Energy Technology Data Exchange (ETDEWEB)

    Stutzmann, A. [Electricite de France (EDF), 93 - Saint-Denis (France)


    Published by EDF this document gives the chemical specifications of the PWR (Pressurized Water Reactor) nuclear power plants. Among the chemical parameters, some have to be respected for the safety. These parameters are listed in the STE (Technical Specifications of Exploitation). The values to respect, the analysis frequencies and the time states of possible drops are noticed in this document with the motion STE under the concerned parameter. (A.L.B.)

  8. Tissue-specific overexpression of lipoprotein lipase causes tissue-specific insulin resistance


    Kim, Jason K.; Fillmore, Jonathan J.; Chen, Yan; Yu, Chunli; Moore, Irene K.; Pypaert, Marc; Lutz, E. Peer; Kako, Yuko; Velez-Carrasco, Wanda; Goldberg, Ira J.; Breslow, Jan L.; Shulman, Gerald I.


    Insulin resistance in skeletal muscle and liver may play a primary role in the development of type 2 diabetes mellitus, and the mechanism by which insulin resistance occurs may be related to alterations in fat metabolism. Transgenic mice with muscle- and liver-specific overexpression of lipoprotein lipase were studied during a 2-h hyperinsulinemic–euglycemic clamp to determine the effect of tissue-specific increase in fat on insulin action and signaling. Muscle–lipoprotein lipase mice had a 3...

  9. Cell type-specific properties and environment shape tissue specificity of cancer genes. (United States)

    Schaefer, Martin H; Serrano, Luis


    One of the biggest mysteries in cancer research remains why mutations in certain genes cause cancer only at specific sites in the human body. The poor correlation between the expression level of a cancer gene and the tissues in which it causes malignant transformations raises the question of which factors determine the tissue-specific effects of a mutation. Here, we explore why some cancer genes are associated only with few different cancer types (i.e., are specific), while others are found mutated in a large number of different types of cancer (i.e., are general). We do so by contrasting cellular functions of specific-cancer genes with those of general ones to identify properties that determine where in the body a gene mutation is causing malignant transformations. We identified different groups of cancer genes that did not behave as expected (i.e., DNA repair genes being tissue specific, immune response genes showing a bimodal specificity function or strong association of generally expressed genes to particular cancers). Analysis of these three groups demonstrates the importance of environmental impact for understanding why certain cancer genes are only involved in the development of some cancer types but are rarely found mutated in other types of cancer.

  10. Standard technical specifications: Combustion engineering plants. Volume 1, Revision 1: Specifications

    Energy Technology Data Exchange (ETDEWEB)



    This report documents the results of the combined effort of the NRC and the industry to produce improved Standard Technical Specifications (STS), Revision 1 for Combustion Engineering Plants. The changes reflected in Revision 1 resulted from the experience gained from license amendment applications to convert to these improved STS or to adopt partial improvements to existing technical specifications. This NUREG is the result of extensive public technical meetings and discussions between the Nuclear Regulatory Commission (NRC) staff and various nuclear power plant licensees, Nuclear Steam Supply System (NSSS) Owners Groups, NSSS vendors, and the Nuclear Energy Institute (NEI). The improved STS were developed based on the criteria in the Final Commission Policy Statement on Technical Specifications Improvements for Nuclear Power Reactors, dated July 22, 1993. The improved STS will be used as the basis for individual nuclear power plant licensees to develop improved plant-specific technical specifications. This report contains three volumes. Volume 1 contains the Specifications for all chapters and sections of the improved STS. Volume 2 contains the Bases for Chapters 2.0 and 3.0, and Sections 3.1--3.3 of the improved STS. Volume 3 contains the Bases for Sections 3.4--3.9 of the improved STS.

  11. Specific genomic cues regulate Cajal body assembly. (United States)

    Sawyer, Iain A; Hager, Gordon L; Dundr, Miroslav


    The assembly of specialized sub-nuclear microenvironments known as nuclear bodies (NBs) is important for promoting efficient nuclear function. In particular, the Cajal body (CB), a prominent NB that facilitates spliceosomal snRNP biogenesis, assembles in response to genomic cues. Here, we detail the factors that regulate CB assembly and structural maintenance. These include the importance of transcription at nucleating gene loci, the grouping of these genes on human chromosomes 1, 6 and 17, as well as cell cycle and biochemical regulation of CB protein function. We also speculate on the correlation between CB formation and RNA splicing levels in neurons and cancer. The timing and location of these specific molecular events is critical to CB assembly and its contribution to genome function. However, further work is required to explore the emerging biophysical characteristics of CB assembly and the impact upon subsequent genome reorganization.

  12. 1-Meter Digital Elevation Model specification (United States)

    Arundel, Samantha T.; Archuleta, Christy-Ann M.; Phillips, Lori A.; Roche, Brittany L.; Constance, Eric W.


    In January 2015, the U.S. Geological Survey National Geospatial Technical Operations Center began producing the 1-Meter Digital Elevation Model data product. This new product was developed to provide high resolution bare-earth digital elevation models from light detection and ranging (lidar) elevation data and other elevation data collected over the conterminous United States (lower 48 States), Hawaii, and potentially Alaska and the U.S. territories. The 1-Meter Digital Elevation Model consists of hydroflattened, topographic bare-earth raster digital elevation models, with a 1-meter x 1-meter cell size, and is available in 10,000-meter x 10,000-meter square blocks with a 6-meter overlap. This report details the specifications required for the production of the 1-Meter Digital Elevation Model.

  13. Orientation specificity of learning vernier discriminations. (United States)

    Spang, K; Grimsen, C; Herzog, M H; Fahle, M


    Orientation selective neurons in the primary visual cortex typically respond to a range of orientations that covers 20 degrees or more, while in psychophysical experiments, orientation bandwidth is often clearly narrower. Here, we measure the orientation specificity of perceptual learning for vernier discriminations. More than 70 observers, in separate groups, practiced a vernier discrimination task with a constant stimulus orientation. After a 1h session of training, the vernier was rotated by 2 degrees, 4 degrees, 10 degrees, 20 degrees, 45 degrees or 90 degrees. Improvement through training in the first session transferred to the second session (tested on the next day) up to 10 degrees of stimulus rotation. We found no transfer for rotations of 20 degrees, 45 degrees and 90 degrees. Hence, the orientation half-bandwidth of perceptual learning is around 15 degrees, leading to a bandwidth of 30 degrees and corresponding to that of single neurons in early visual cortices, while being narrower than that in higher cortical areas.

  14. Communication Language Specifications For Digital Ecosystems

    CERN Document Server

    Bassil, Youssef


    Service-based IT infrastructures are today's trend and the future for every enterprise willing to support dynamic and agile business to contend with the ever changing e-demands and requirements. A digital ecosystem is an emerging business IT model for developing agile e-enterprises made out of self-adaptable, self-manageable, self-organizing, and sustainable service components. This paper defines the specifications of a communication language for exchanging data between connecting entities in digital ecosystems. It is called ECL short for Ecosystem Communication Language and is based on XML to format its request and response messages. An ECU short for Ecosystem Communication Unit is also presented which interprets, validates, parses ECL messages and routes them to their destination entities. ECL is open and provides transparent, portable, and interoperable communication between the different heterogeneous distributed components to send requests, and receive responses from each other, regardless of their incom...

  15. Education and Cause-specific Mortality

    DEFF Research Database (Denmark)

    Nordahl, Helene; Lange, Theis; Osler, Merete;


    BACKGROUND: Differential exposures to behavioral risk factors have been shown to play an important mediating role on the education-mortality relation. However, little is known about the extent to which educational attainment interacts with health behavior, possibly through differential...... vulnerability. METHODS: In a cohort study of 76,294 participants 30 to 70 years of age, we estimated educational differences in cause-specific mortality from 1980 through 2009 and the mediating role of behavioral risk factors (smoking, alcohol intake, physical activity, and body mass index). With the use...... of marginal structural models and three-way effect decomposition, we simultaneously regarded the behavioral risk factors as intermediates and clarified the role of their interaction with educational exposure. RESULTS: Rate differences in mortality comparing participants with low to high education were 1...

  16. Signal Peptidase Enzymology and Substrate Specificity Profiling. (United States)

    Dalbey, R E; Pei, D; Ekici, Ö D


    Signal peptidases are membrane proteases that play crucial roles in the protein transport pathway of bacteria. They cleave off the signal peptide from precursor proteins that are membrane inserted by the SecYEG or Tat translocons. Signal peptide cleavage releases the translocated protein from the inner membrane allowing the protein to be exported to the periplasm, outer membrane, or secreted into the medium. Signal peptidases are very important proteins to study. They are unique serine proteases with a Ser-Lys dyad, catalyze cleavage at the membrane surface, and are promising potential antibacterial drug targets. This chapter will focus on the isolation of signal peptidases and the preprotein substrates, as well as describe a peptide library approach for characterizing the substrate specificity.

  17. Specific Mindfulness Skills Differentially Predict Creative Performance. (United States)

    Baas, Matthijs; Nevicka, Barbara; Ten Velden, Femke S


    Past work has linked mindfulness to improved emotion regulation, interpersonal skills, and basic cognitive abilities, but is unclear about the relation between mindfulness and creativity. Studies examining effects of mindfulness on factors pertinent to creativity suggest a uniform and positive relation, whereas work on specific mindfulness skills suggests that mindfulness skills may differentially predict creativity. To test whether the relation between mindfulness and creativity is positive and uniform (the uniform hypothesis) or differentially depends on particular components of mindfulness (the differential hypothesis), we conducted four studies in which mindfulness skills were measured, extensively trained, or manipulated with a short, incidental meditation session. Results supported a differential relation between mindfulness and creativity: Only the ability to observe and attend to various stimuli consistently and positively predicted creativity. Results regarding other mindfulness skills were less consistent. Implications for theory and practice are discussed.

  18. Chiral specific electron vortex beam spectroscopy

    CERN Document Server

    Yuan, J; Babiker, M


    Electron vortex beams carry well-defined orbital angular momentum (OAM) about the propagation axis. Such beams are thus characterised by chirality features which make them potentially useful as probes of magnetic and other chiral materials. An analysis of the inelastic processes in which electron vortex beams interact with atoms and which involve OAM exchange is outlined, leading to the multipolar selection rules governing this chiral specific electron vortex beam spectroscopy. Our results show clearly that the selection rules are dependent on the dynamical state and location of the atoms involved. In the most favorable scenario, this form of electron spectroscopy can induce magnetic sublevel transitions which are commonly probed using circularly polarized photon beams.

  19. Specific anion effects in Artemia salina. (United States)

    Lo Nostro, Pierandrea; Ninham, Barry W; Carretti, Emiliano; Dei, Luigi; Baglioni, Piero


    The specific anion effect on the vitality of Artemia salina was investigated by measuring the Lethal Time LT50 of the crustaceans in the presence of different sodium salts solutions at room temperature and at the same ionic strength as natural seawater. Fluoride, thiocyanate and perchlorate are the most toxic agents, while chloride, bromide and sulfate are well tolerated. The rates of oxygen consumption of brine shrimps were recorded in mixed NaCl+NaF or NaCl+NaSCN solutions as a function of time. The results are discussed in terms of the Hofmeister series, and suggest that, besides the biochemical processes that involve F(-), SCN(-) and ClO4(-), the different physico-chemical properties of the strong kosmotropic and chaotropic anions may contribute in determining their strong toxicity for A. salina.

  20. Interobserver variability in prostate cancer specific survival. (United States)

    Clark, J Y; Lillis, P K; O'Rourke, T J; Jones, C; Higgins, B A; Thompson, I M


    We evaluated the reliability of disease-specific survival (DSS) as an outcome measure in patients with carcinoma of the prostate (CaP). The records of 50 patients had a diagnosis of CaP and had expired were selected from the hospital tumor registry. Records were reviewed by six individuals and each individual was asked to specify cause of death as due to CaP or some other cause. DSS curves were generated based on the determinations of each reviewer. Although the DSS curves were generally parallel, a high degree of variability was seen at various intervals, leading us to conclude that DSS is dependent upon the individual reviewer. Published by Elsevier Science Inc.

  1. Specific Features of Internal Audit in Banks

    Directory of Open Access Journals (Sweden)

    Ivo Mijoč


    Full Text Available The aim of the paper is to investigate internal audit in Croatian banks and to point to its more efficient implementation. The paper provides an explanation of key terms related to internal audit in banks, defining audit, types of audit as well as its objectives and roles. In addition to specific properties of the banking system, implementation of internal audit in banks is explained as well. The year 2005 is significant due to the adoption of the Bank Act which is primarily based on provisions of BIS (Banking Information System. The Act has brought about significant changes in the concept of internal audit in banks. The general message of this paper is that internal audit, being a relatively young profession, is marked by accelerated growth, and Croatian banks should adapt their business accordingly.

  2. Animal models of antimuscle specific kinase myasthenia (United States)

    Richman, David P.; Nishi, Kayoko; Ferns, Michael J.; Schnier, Joachim; Pytel, Peter; Maselli, Ricardo A.; Agius, Mark A.


    Antimuscle specific kinase (anti-MuSK) myasthenia (AMM) differs from antiacetylcholine receptor myasthenia gravis in exhibiting more focal muscle involvement (neck, shoulder, facial, and bulbar muscles) with wasting of the involved, primarily axial, muscles. AMM is not associated with thymic hyperplasia and responds poorly to anticholinesterase treatment. Animal models of AMM have been induced in rabbits, mice, and rats by immunization with purified xenogeneic MuSK ectodomain, and by passive transfer of large quantities of purified serum IgG from AMM patients into mice. The models have confirmed the pathogenic role of the MuSK antibodies in AMM and have demonstrated the involvement of both the presynaptic and postsynaptic components of the neuromuscular junction. The observations in this human disease and its animal models demonstrate the role of MuSK not only in the formation of this synapse but also in its maintenance. PMID:23252909

  3. Visual object recognition and category-specificity

    DEFF Research Database (Denmark)

    Gerlach, Christian

    This thesis is based on seven published papers. The majority of the papers address two topics in visual object recognition: (i) category-effects at pre-semantic stages, and (ii) the integration of visual elements into elaborate shape descriptions corresponding to whole objects or large object parts...... is a description that can be matched with structural representations of whole objects or object parts stored in visual long-term memory. The process of finding a match between the configured description and stored object representations is thought of as a race among stored object representations that compete...... in visual long-term memory. In the thesis it is described how this simple model can account for a wide range of findings on category-specificity in both patients with brain damage and normal subjects. Finally, two hypotheses regarding the neural substrates of the model's components - and how activation...

  4. Sandia Data Archive (SDA) file specifications

    Energy Technology Data Exchange (ETDEWEB)

    Dolan, Daniel H. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Ao, Tommy [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)


    The Sandia Data Archive (SDA) format is a specific implementation of the HDF5 (Hierarchal Data Format version 5) standard. The format was developed for storing data in a universally accessible manner. SDA files may contain one or more data records, each associated with a distinct text label. Primitive records provide basic data storage, while compound records support more elaborate grouping. External records allow text/binary files to be carried inside an archive and later recovered. This report documents version 1.0 of the SDA standard. The information provided here is sufficient for reading from and writing to an archive. Although the format was original designed for use in MATLAB, broader use is encouraged.

  5. Business System Planning Project System Requirements Specification

    Energy Technology Data Exchange (ETDEWEB)

    NELSON, R.E.


    The purpose of the Business Systems Planning Project System Requirements Specification (SRS) is to provide the outline and contents of the requirements for the CH2M HILL Hanford Group, Inc. (CHG) integrated business and technical information systems. The SRS will translate proposed objectives into the statement of the functions that are to be performed and data and information flows that they require. The requirements gathering methodology will use (1) facilitated group requirement sessions; (2) individual interviews; (3) surveys; and (4) document reviews. The requirements will be verified and validated through coordination of the technical requirement team and CHG Managers. The SRS document used the content and format specified in Lockheed Martin Services, Inc. Organization Standard Software Practices in conjunction with the Institute of Electrical and Electronics Engineers Standard 8340-1984 for Systems Requirements Documents.

  6. RD53A Integrated Circuit Specifications

    CERN Document Server

    Garcia-Sciveres, Mauricio


    Specifications for the RD53 collaboration’s first engineering wafer run of an integrated circuit (IC) for hybrid pixel detector readout, called RD53A. RD53A is intended to demonstrate in a large format IC the suitability of the technology (including radiation tolerance), the stable low threshold operation, and the high hit and trigger rate capabilities, required for HL-LHC upgrades of ATLAS and CMS. The wafer scale production will permit the experiments to prototype bump bonding assembly with realistic sensors in this new technology and to measure the performance of hybrid assemblies. RD53A is not intended to be a final production IC for use in an experiment, and will contain design variations for testing purposes, making the pixel matrix non-uniform.

  7. Structural similarity and category-specificity

    DEFF Research Database (Denmark)

    Gerlach, Christian; Law, Ian; Paulson, Olaf B


    It has been suggested that category-specific recognition disorders for natural objects may reflect that natural objects are more structurally (visually) similar than artefacts and therefore more difficult to recognize following brain damage. On this account one might expect a positive relationship...... between blood flow and structural similarity in areas involved in visual object recognition. Contrary to this expectation we report a negative relationship in that identification of articles of clothing cause more extensive activation than identification of vegetables/fruit and animals even though items...... from the categories of animals and vegetables/fruit are rated as more structurally similar than items from the category of articles of clothing. Given that this pattern cannot be explained in terms of a tradeoff between activation and accuracy, we interpret these findings within a model where...

  8. Cyclic nucleotide specific phosphodiesterases of Leishmania major

    Directory of Open Access Journals (Sweden)

    Linder Markus


    Full Text Available Abstract Background Leishmania represent a complex of important human pathogens that belong to the systematic order of the kinetoplastida. They are transmitted between their human and mammalian hosts by different bloodsucking sandfly vectors. In their hosts, the Leishmania undergo several differentiation steps, and their coordination and optimization crucially depend on numerous interactions between the parasites and the physiological environment presented by the fly and human hosts. Little is still known about the signalling networks involved in these functions. In an attempt to better understand the role of cyclic nucleotide signalling in Leishmania differentiation and host-parasite interaction, we here present an initial study on the cyclic nucleotide-specific phosphodiesterases of Leishmania major. Results This paper presents the identification of three class I cyclic-nucleotide-specific phosphodiesterases (PDEs from L. major, PDEs whose catalytic domains exhibit considerable sequence conservation with, among other, all eleven human PDE families. In contrast to other protozoa such as Dictyostelium, or fungi such as Saccharomyces cerevisiae, Candida ssp or Neurospora, no genes for class II PDEs were found in the Leishmania genomes. LmjPDEA contains a class I catalytic domain at the C-terminus of the polypeptide, with no other discernible functional domains elsewhere. LmjPDEB1 and LmjPDEB2 are coded for by closely related, tandemly linked genes on chromosome 15. Both PDEs contain two GAF domains in their N-terminal region, and their almost identical catalytic domains are located at the C-terminus of the polypeptide. LmjPDEA, LmjPDEB1 and LmjPDEB2 were further characterized by functional complementation in a PDE-deficient S. cerevisiae strain. All three enzymes conferred complementation, demonstrating that all three can hydrolyze cAMP. Recombinant LmjPDEB1 and LmjPDEB2 were shown to be cAMP-specific, with Km values in the low micromolar range

  9. Improving Datapath Testability by Modifying Controller Specification

    Directory of Open Access Journals (Sweden)

    M. L. Flottes


    Full Text Available A digital circuit includes two main parts: a controller and a datapath. After connection of these two parts, both are subject to a sharp fall in testability due to the lack of controllability and observability at the interface. In this paper, we propose a method for specifying the control part in order to restore the testability of the datapath to a level close to the initial one, in other words its testability before connection. This testability driven specification affects the next state logic as well as the decoder part of the controller but does not make use of any scan-based element. Based on the finite automata theory and on results of a testability analysis performed on the datapath, the proposed method entails very little area penalty.

  10. Specific Property of Ultrafine Particle Classification

    Institute of Scientific and Technical Information of China (English)

    LI Guo-hua; HUANG Zhi-chu; ZHANG You-lin


    In the process of ultrafine particle classification,the separation curve,which reflects the characteristics of separating process,is frequently influenced by the characteristics of separation flow field and operating parameters,etc.This paper introduces the concept of system deviation and deduces the calculating method of the separation curves.Meanwhile,it analyses the influences of classification flow field's specific properties and some operating parameters on the separation curves.The results show that,in the process of ultrafine particle classification,the local vortex in the separation field improves the separation efficiency to a certain degree,but the accuracy will decrease;the coacervation action of particles will seriously influence the classification accuracy.

  11. Domain-specific knowledge as playful interaction

    DEFF Research Database (Denmark)

    Valente, Andrea; Marchetti, Emanuela


    Starting from reflections on designing games for learning, aimed at providing a tangible grounding to abstract knowledge, we designed Prime Slaughter, a game to support learning of factorisation and prime numbers, targeted to primary and early secondary school children. This new study draws upon ...... on activity theory, aimed at facilitating the transposition of abstract knowledge into playful interactions, so to develop new learning games of this kind, also keeping into account children’s individual needs regarding play....... the design process of Prime Slaughter, to move further in developing a general approach in developing games, aimed at effectively conveying knowledge from a specific domain. Hence this paper will discuss the past design process, as a concrete case, and then formulate a theoretical framework, based...


    Directory of Open Access Journals (Sweden)

    Viorel TATU


    Full Text Available The English common law has its roots in the times of William the Conqueror who invaded England in 1066. He is known to be the one who has laid the foundations of the English legal system. At that time, the system comprised of a series of oral rules and it was of high importance to have a unitary, national legal system. This article examines the specific legal institutions: personal property, real property, settlement and trust in order to provide the reader an overview of some of the key aspects to understand its mechanism. The research methods used facilitate the reader’s perception of the common law and its role in the society.

  13. Climate-Specific Passive Building Standards

    Energy Technology Data Exchange (ETDEWEB)

    Wright, Graham S. [Passive House Inst., Westford, MA (United States); Klingenberg, Katrin [Passive House Inst., Westford, MA (United States)


    Passive design principles (super insulation, airtight envelopes, elimination of thermal bridges, etc.) - pioneered in North America in the 70s and 80s and refined in Europe in the 90s have proven to be universally effective to significantly reduce heating and cooling loads. However, a single, rigid performance metric developed in Germany has led to limited uptake of passive building principles in many regions of the United States. It has also, in many cases, promoted some design decisions that had negative effects on economic feasibility and thermal comfort. This study's main objective is to validate (in a theoretical sense) verifiable, climate-specific passive standards and space conditioning criteria that retain ambitious, environmentally-necessary energy reduction targets and are economically feasible, such standards provide designers an ambitious but achievable performance target on the path to zero.

  14. Peptidoglycan hydrolase fusions maintain their parental specificities. (United States)

    Donovan, David M; Dong, Shengli; Garrett, Wes; Rousseau, Geneviève M; Moineau, Sylvain; Pritchard, David G


    The increased incidence of bacterial antibiotic resistance has led to a renewed search for novel antimicrobials. Avoiding the use of broad-range antimicrobials through the use of specific peptidoglycan hydrolases (endolysins) might reduce the incidence of antibiotic-resistant pathogens worldwide. Staphylococcus aureus and Streptococcus agalactiae are human pathogens and also cause mastitis in dairy cattle. The ultimate goal of this work is to create transgenic cattle that are resistant to mastitis through the expression of an antimicrobial protein(s) in their milk. Toward this end, two novel antimicrobials were produced. The (i) full-length and (ii) 182-amino-acid, C-terminally truncated S. agalactiae bacteriophage B30 endolysins were fused to the mature lysostaphin protein of Staphylococcus simulans. Both fusions display lytic specificity for streptococcal pathogens and S. aureus. The full lytic ability of the truncated B30 protein also suggests that the SH3b domain at the C terminus is dispensable. The fusions are active in a milk-like environment. They are also active against some lactic acid bacteria used to make cheese and yogurt, but their lytic activity is destroyed by pasteurization (63 degrees C for 30 min). Immunohistochemical studies indicated that the fusion proteins can be expressed in cultured mammalian cells with no obvious deleterious effects on the cells, making it a strong candidate for use in future transgenic mice and cattle. Since the fusion peptidoglycan hydrolase also kills multiple human pathogens, it also may prove useful as a highly selective, multipathogen-targeting antimicrobial agent that could potentially reduce the use of broad-range antibiotics in fighting clinical infections.

  15. CRISPR interference directs strand specific spacer acquisition.

    Directory of Open Access Journals (Sweden)

    Daan C Swarts

    Full Text Available BACKGROUND: CRISPR/Cas is a widespread adaptive immune system in prokaryotes. This system integrates short stretches of DNA derived from invading nucleic acids into genomic CRISPR loci, which function as memory of previously encountered invaders. In Escherichia coli, transcripts of these loci are cleaved into small RNAs and utilized by the Cascade complex to bind invader DNA, which is then likely degraded by Cas3 during CRISPR interference. RESULTS: We describe how a CRISPR-activated E. coli K12 is cured from a high copy number plasmid under non-selective conditions in a CRISPR-mediated way. Cured clones integrated at least one up to five anti-plasmid spacers in genomic CRISPR loci. New spacers are integrated directly downstream of the leader sequence. The spacers are non-randomly selected to target protospacers with an AAG protospacer adjacent motif, which is located directly upstream of the protospacer. A co-occurrence of PAM deviations and CRISPR repeat mutations was observed, indicating that one nucleotide from the PAM is incorporated as the last nucleotide of the repeat during integration of a new spacer. When multiple spacers were integrated in a single clone, all spacer targeted the same strand of the plasmid, implying that CRISPR interference caused by the first integrated spacer directs subsequent spacer acquisition events in a strand specific manner. CONCLUSIONS: The E. coli Type I-E CRISPR/Cas system provides resistance against bacteriophage infection, but also enables removal of residing plasmids. We established that there is a positive feedback loop between active spacers in a cluster--in our case the first acquired spacer--and spacers acquired thereafter, possibly through the use of specific DNA degradation products of the CRISPR interference machinery by the CRISPR adaptation machinery. This loop enables a rapid expansion of the spacer repertoire against an actively present DNA element that is already targeted, amplifying the


    Energy Technology Data Exchange (ETDEWEB)

    Raymond, Kenneth N.; Smith, William L.; Weitl, Frederick L.; Durbin, Patricia W.; Jones, E.Sarah; Abu-Dari, Kamal; Sofen, Stephen R.; Cooper, Stephen R.


    This paper summarizes the current status of a continuing project directed toward the synthesis and characterization of chelating agents which are specific for actinide ions - especially Pu(IV) - using a biomimetic approach that relies on the observation that Pu(IV) and Fe(III) has marked similarities that include their biological transport and distribution in mammals. Since the naturally-occurring Fe(III) sequestering agents produced by microbes commonly contain hydroxamate and catecholate functional groups, these groups should complex the actinides very strongly and macrocyclic ligands incorporating these moieties are being prepared. We have reported the isolation and structure analysis of an isostructural series of tetrakis(catecholato) complexes with the general stoichiometry Na{sub 4}[M(C{sub 6}H{sub 4}O{sub 2}){sub 4}] • 21 H{sub 2}O (M = Th, U, Ce, Hf). These complexes are structural archetypes for the cavity that must be formed if an actinide-specific sequestering agent is to conform ideally to the coordination requirements of the central metal ion. The [M(cat){sub 4}]{sup 4-} complexes have the D{sub 2d} symmetry of the trigonal-faced dodecahedron.. The complexes Th [R'C(0)N(O)R]{sub 4} have been prepared where R = isopropyl and R' = t-butyl or neopentyl. The neopentyl derivative is also relatively close to an idealized D{sub 2d} dodecahedron, while the sterically more hindered t-butyl compound is distorted toward a cubic geometry. The synthesis of a series of 2, 3-dihydroxy-benzoyl amide derivatives of linear and cyclic tetraaza- and diazaalkanes is reported. Sulfonation of these compounds improves the metal complexation and in vivo removal of plutonium from test animals. These results substantially exceed the capabilities of compounds presently used for the therapeutic treatment of actinide contamination.

  17. 40 CFR 75.14 - Specific provisions for monitoring opacity. (United States)


    ... performance specifications in Performance Specification 1 in appendix B to part 60 of this chapter. Any continuous opacity monitoring system previously certified to meet Performance Specification 1 shall be...

  18. Influence of specific and non-specific solvent effects on frontal MO of DMABI system (United States)

    Kampars, V.; Pastors, P.; Ornicane, G.


    Derivatives of 2-(4'-dimethylaminobenzylidene)-1,3-indandione (DMABI) are classical push-pull chromophores containing carbonyl groups like numerous other non-linear chromophores for electro-optical devices. The energy of the intramolecular charge transfer exciton of DMABI is determined by the difference of HOMO-LUMO energies and can be varied in width range by chemical modifications of the DMABI structure or by the nonspecific and specific solvent effects if the chromophore is incorporated into condensed environment. The condensed medium in a thin film (polymer or molecular glass) exhibits a solid state solvation effect similar to the effect of the organic solvents in a solution. The value of the medium effect depends on specific and non-specific interactions between the chromophore and medium. The main purpose of this work is to evaluate the specific effects. The chromophores often contain few centres for specific interaction, and thus we have synthesised and investigated UV-Vis spectra of three derivatives of DMABI and also three derivatives of 4-aza-DMABI in solutions with strong H-bond donor properties. The experimentally obtained results show that the strong H-bond with carbonyl group lowers the intramolecular charge-transfer energy by 900 cm-1, the strong H-bond with carbonyl group and heterocyclic nitrogen in 4-aza-DMABI by 1500 cm-1 and the protonation of heterocyclic nitrogen in 4-aza-DMABI by 3250 cm-1 respectivelly.

  19. The specificity triad: notions of disease and therapeutic specificity in biomedical reasoning. (United States)

    Mulinari, Shai


    Biomedicine is typically defined as the branch of medicine that is based on the principles of biology and biochemistry. A central tenet for biomedicine is the notion of disease and therapeutic specificity, i.e. the idea of tailored treatments for discrete disorders underpinned by specific pathologies. The present paper is concerned with how notions of disease and therapeutic specificity guide biomedical reasoning. To that end, the author proposes a model - the specificity triad - that draws on late philosopher and physician Ludwik Fleck's concept of "style of thought" to offer a frame for investigating the intricate process through which links between disorders, mechanisms, and therapeutics are established by biomedicine. Next by applying the specificity triad model to scrutinize research efforts in two discrete areas of medicine-psychiatry and regenerative medicine-this paper seeks to stimulate pertinent discussions in and about biomedicine. These include discussions on the ambiguous epistemic status of psychiatry within contemporary biomedicine, as well as the relationship between developmental biology - historically relatively disjointed from biomedical enterprise - and the burgeoning field of regenerative medicine.

  20. Face recognition deficits in autism spectrum disorders are both domain specific and process specific. (United States)

    Weigelt, Sarah; Koldewyn, Kami; Kanwisher, Nancy


    Although many studies have reported face identity recognition deficits in autism spectrum disorders (ASD), two fundamental question remains: 1) Is this deficit "process specific" for face memory in particular, or does it extend to perceptual discrimination of faces as well? And 2) Is the deficit "domain specific" for faces, or is it found more generally for other social or even nonsocial stimuli? The answers to these questions are important both for understanding the nature of autism and its developmental etiology, and for understanding the functional architecture of face processing in the typical brain. Here we show that children with ASD are impaired (compared to age and IQ-matched typical children) in face memory, but not face perception, demonstrating process specificity. Further, we find no deficit for either memory or perception of places or cars, indicating domain specificity. Importantly, we further showed deficits in both the perception and memory of bodies, suggesting that the relevant domain of deficit may be social rather than specifically facial. These results provide a more precise characterization of the cognitive phenotype of autism and further indicate a functional dissociation between face memory and face perception.


    Energy Technology Data Exchange (ETDEWEB)

    Harbour, J; Vickie Williams, V


    One of the goals of the Saltstone variability study is to identify (and quantify the impact of) the operational and compositional variables that control or influence the important processing and performance properties of Saltstone grout mixtures. The heat capacity of the Saltstone waste form is one of the important properties of Saltstone mixes that was last measured at SRNL in 1997. It is therefore important to develop a core competency for rapid and accurate analysis of the specific heat capacity of the Saltstone mixes in order to quantify the impact of compositional and operational variations on this property as part of the variability study. The heat capacity, coupled with the heat of hydration data obtained from isothermal calorimetry for a given Saltstone mix, can be used to predict the maximum temperature increase in the cells within the vaults of the Saltstone Disposal Facility (SDF). The temperature increase controls the processing rate and the pour schedule. The maximum temperature is also important to the performance properties of the Saltstone. For example, in mass pours of concrete or grout of which Saltstone is an example, the maximum temperature increase and the maximum temperature difference (between the surface and the hottest location) are controlled to ensure durability of the product and prevent or limit the cracking caused by the thermal gradients produced during curing. This report details the development and implementation of a method for the measurement of the heat capacities of Saltstone mixes as well as the heat capacities of the cementitious materials of the premix and the simulated salt solutions used to batch the mixes. The developed method utilizes the TAM Air isothermal calorimeter and takes advantage of the sophisticated heat flow measurement capabilities of the instrument. Standards and reference materials were identified and used to validate the procedure and ensure accuracy of testing. Heat capacities of Saltstone mixes were

  2. Are Specific Early-Life Adversities Associated With Specific Symptoms of Psychosis? (United States)

    Wickham, Sophie; Bentall, Richard


    Abstract Epidemiological studies have suggested that there may be associations between specific adversities and specific psychotic symptoms. There is also evidence that beliefs about justice may play a role in paranoid symptoms. In this study, we determined whether these associations could be replicated in a patient sample and whether beliefs about a just world played a specific role in the relationship between adversity and paranoia. We examined associations between childhood trauma, belief in justice, and paranoia and hallucinatory experiences in 144 individuals: 72 individuals with a diagnosis of schizophrenia spectrum disorders and 72 comparison controls. There was a dose-response relationship between cumulative trauma and psychosis. When controlling for comorbidity between symptoms, childhood sexual abuse predicted hallucinatory experiences, and experiences of childhood emotional neglect predicted paranoia. The relationship between neglect and paranoia was mediated by a perception of personal injustice. The findings replicate in a patient sample previous observations from epidemiological research. PMID:27065105

  3. Lipopolysaccharide Specific Immunochromatography Based Lateral Flow Assay for Serogroup Specific Diagnosis of Leptospirosis in India.

    Directory of Open Access Journals (Sweden)

    Shanmugam Vanithamani

    Full Text Available Leptospirosis is a re-emerging infectious disease that is under-recognized due to low-sensitivity and cumbersome serological tests. MAT is the gold standard test and it is the only serogroup specific test used till date. Rapid reliable alternative serogroup specific tests are needed for surveillance studies to identify locally circulating serogroups in the study area.In the present investigation the serological specificity of leptospiral lipopolysaccharides (LPS was evaluated by enzyme linked immunosorbent assay (ELISA, dot blot assay and rapid immunochromatography based lateral flow assay (ICG-LFA. Sera samples from 120 MAT positive cases, 174 cases with febrile illness other than leptospirosis, and 121 seronegative healthy controls were evaluated for the diagnostic sensitivity and specificity of the developed assays. LPS was extracted from five locally predominant circulating serogroups including: Australis (27.5%, Autumnalis (11.7%, Ballum (25.8%, Grippotyphosa (12.5%, Pomona (10% and were used as antigens in the diagnostics to detect IgM antibodies in patients' sera. The sensitivity observed by IgM ELISA and dot blot assay using various leptospiral LPS was >90% for homologous sera. Except for Ballum LPS, no other LPS showed cross-reactivity to heterologous sera. An attempt was made to develop LPS based ICG-LFA for rapid and sensitive serogroup specific diagnostics of leptospirosis. The developed ICG-LFA showed sensitivity in the range between 93 and 100% for homologous sera. The Wilcoxon analysis showed LPS based ICG-LFA did not differ significantly from the gold standard MAT (P>0.05.The application of single array of LPS for serogroup specific diagnosis is first of its kind. The developed assay could potentially be evaluated and employed for as MAT alternative.

  4. Data mining of enzymes using specific peptides

    Directory of Open Access Journals (Sweden)

    Lavi Yair


    Full Text Available Abstract Background Predicting the function of a protein from its sequence is a long-standing challenge of bioinformatic research, typically addressed using either sequence-similarity or sequence-motifs. We employ the novel motif method that consists of Specific Peptides (SPs that are unique to specific branches of the Enzyme Commission (EC functional classification. We devise the Data Mining of Enzymes (DME methodology that allows for searching SPs on arbitrary proteins, determining from its sequence whether a protein is an enzyme and what the enzyme's EC classification is. Results We extract novel SP sets from Swiss-Prot enzyme data. Using a training set of July 2006, and test sets of July 2008, we find that the predictive power of SPs, both for true-positives (enzymes and true-negatives (non-enzymes, depends on the coverage length of all SP matches (the number of amino-acids matched on the protein sequence. DME is quite different from BLAST. Comparing the two on an enzyme test set of July 2008, we find that DME has lower recall. On the other hand, DME can provide predictions for proteins regarded by BLAST as having low homologies with known enzymes, thus supplying complementary information. We test our method on a set of proteins belonging to 10 bacteria, dated July 2008, establishing the usefulness of the coverage-length cutoff to determine true-negatives. Moreover, sifting through our predictions we find that some of them have been substantiated by Swiss-Prot annotations by July 2009. Finally we extract, for production purposes, a novel SP set trained on all Swiss-Prot enzymes as of July 2009. This new set increases considerably the recall of DME. The new SP set is being applied to three metagenomes: Sargasso Sea with over 1,000,000 proteins, producing predictions of over 220,000 enzymes, and two human gut metagenomes. The outcome of these analyses can be characterized by the enzymatic profile of the metagenomes, describing the relative

  5. Mechanisms of allergen-specific immunotherapy

    Directory of Open Access Journals (Sweden)

    Fujita Hiroyuki


    Full Text Available Abstract Allergen-specific immunotherapy (allergen-SIT is a potentially curative treatment approach in allergic diseases. It has been used for almost 100 years as a desensitizing therapy. The induction of peripheral T cell tolerance and promotion of the formation of regulatory T-cells are key mechanisms in allergen-SIT. Both FOXP3+CD4+CD25+ regulatory T (Treg cells and inducible IL-10- and TGF-β-producing type 1 Treg (Tr1 cells may prevent the development of allergic diseases and play a role in successful allergen-SIT and healthy immune response via several mechanisms. The mechanisms of suppression of different pro-inflammatory cells, such as eosinophils, mast cells and basophils and the development of allergen tolerance also directly or indirectly involves Treg cells. Furthermore, the formation of non-inflammatory antibodies particularly IgG4 is induced by IL-10. Knowledge of these molecular basis is crucial in the understanding the regulation of immune responses and their possible therapeutic targets in allergic diseases.

  6. Motif-specific sampling of phosphoproteomes. (United States)

    Ruse, Cristian I; McClatchy, Daniel B; Lu, Bingwen; Cociorva, Daniel; Motoyama, Akira; Park, Sung Kyu; Yates, John R


    Phosphoproteomics, the targeted study of a subfraction of the proteome which is modified by phosphorylation, has become an indispensable tool to study cell signaling dynamics. We described a methodology that linked phosphoproteome and proteome analysis based on Ba2+ binding properties of amino acids. This technology selected motif-specific phosphopeptides independent of the system under analysis. MudPIT (Multidimensional Identification Technology) identified 1037 precipitated phosphopeptides from as little as 250 microg of proteins. To extend coverage of the phosphoproteome, we sampled the nuclear extract of HeLa cells with three values of Ba2+ ions molarity. The presence of more than 70% of identified phosphoproteins was further substantiated by their nonmodified peptides. Upon isoproterenol stimulation of HEK cells, we identified an increasing number of phosphoproteins from MAPK cascades and AKAP signaling hubs. We quantified changes in both protein and phosphorylation levels of 197 phosphoproteins including a critical kinase, MAPK1. Integration of differential phosphorylation of MAPK1 with knowledge bases constructed modules that correlated well with its role as node in cross-talk of canonical pathways.

  7. Notch pathway is dispensable for adipocyte specification. (United States)

    Nichols, Amy M; Pan, Yonghua; Herreman, An; Hadland, Brandon K; De Strooper, Bart; Kopan, Raphael; Huppert, Stacey S


    In the past decade we have witnessed an epidemic of obesity in developed countries. Therefore, understanding the mechanisms involved in regulation of body weight is becoming an increasingly important goal shared by the public and the scientific community. The key to fat deposition is the adipocyte, a specialized cell that plays a critical role in energy balance and appetite regulation. Much of our knowledge of adipogenesis comes from studies using preadipocytic cell lines that have provided important information regarding molecular control of adipocyte differentiation. However, they fall short of revealing how naive cells acquire competence for adipogenesis. Studies in preadipocytes indicate that the Notch pathway plays a role in regulating adipogenesis (Garces et al.: J Biol Chem 272:29729-29734, 1997). Given the known biological functions of Notch in mediating cell fate decisions (Artavanis-Tsakonas et al.: Science 284:770-776, 1999), we wished to test the hypothesis that the Notch pathway is required for this cellular program by examining adipogenesis in several genetic loss-of-function models that encompass the entire pathway. We conclude that the "canonical" Notch signaling pathway is dispensable for adipocyte specification and differentiation from either mesenchymal or epithelial progenitors.

  8. [Intoxications specific to the Aquitaine region]. (United States)

    Bédry, R; Gromb, S


    Some intoxications are more specifically linked to the Aquitaine region than to other regions of France, due to environmental circumstances (fauna, flora, climate) or traditional activities (gastronomy). Three types of intoxications are particular in this area. Pine processionary caterpillar envenomations (Thaumetopoea pityocampa), a Southern Europe pinewood parasite, are frequently encountered in the Landes' forest. They are responsible of ocular and/or skin lesions with urticaria or contact dermatitis, seldom associated with immediate IgE hypersensitivity. According to the south Atlantic coastal region geology and the marine streams, venomous marine animals are mainly located in Charente-Maritime for jellyfish, in Gironde and in Landes for weeverfish and in Atlantic Pyrenees for sea anemone. Usually not dangerous, first-aid workers treat most cases of these envenomations. Some endemic mushrooms (Tricholoma auratum) which grow on the dunes of the Atlantic coastal region, are usually considered as very good comestibles, but were recently responsible for serious intoxications: T.auratum was responsible of several cases of rhabdomyolysis, without neurological involvement, nor renal or hepatic lesion. Three deaths were notified. Animal studies confirmed the responsibility of the mushrooms.

  9. Technical specification for IR rig manufacture

    Energy Technology Data Exchange (ETDEWEB)

    Han Hyon Soo; Cho, W. K.; Kim, S. D.; Park, U. J.; Hong, S. B.; Yoo, K. M


    IR Rig is one of the equipments are required in HANARO core for a radioisotope target. The various conditions like high radiation, high heat, rapid flow and vibration may cause swelling, Brittleness and acceleration of corrosion in HANARO core. These specific problems can be prevented and the safety of such equipment are prerequisite as well as durableness and surveillance. Therefore, the selection of material has to be made on the basis of small cross-section area, low energy emission by the gamma ray due to the absorption of neutron and short half life. The body is consist of aluminum and Inconel-750 was used for the internal spring(coil) which is known to be durable. The whole production process including the purchase of accessory, mechanical processing, welding and assembly was carried out according to the standard procedure to meet the requirement. A design, manufacture, utilization of reactor core and the other relevant uses were fit to class ''T'' to certify the whole process as general. And design, fabrication, analytical test, materials and accessory were carried out based on the ASME, ASTM, ANSI, AWS, JIS and KS standard.

  10. Cue-specific reactivity in experienced gamblers. (United States)

    Wulfert, Edelgard; Maxson, Julie; Jardin, Bianca


    To examine whether gambling cue reactivity is cue-specific, 47 scratch-off lottery players and 47 horse race gamblers were presented with video clips of their preferred and nonpreferred modes of gambling, and two control stimuli including an exciting car race and a mental stressor task while heart rates, excitement, and urge to gamble were being measured. Heart rates for both groups of gamblers were highest to the mental stressor and did not differ in response to the other three cues. Excitement for both groups was highest in response to the action cues (horse race and car chase). Urge to gamble was significantly higher for each group to their preferred mode of gambling. A post hoc exploratory analysis comparing social gamblers (n = 54) and probable pathological gamblers (n = 40) revealed a similar pattern of responses. However, pathological gamblers reported overall significantly higher urges to gamble than social gamblers. As urges have been shown to play a pivotal role in addictive behaviors and relapse, the current findings may have implications for the development of gambling problems and relapse after successful treatment.

  11. Specificity, transfer, and the development of expertise

    Directory of Open Access Journals (Sweden)

    David T. Brookes


    Full Text Available In this paper we present the results of two experiments designed to understand how physics students’ learning of the concept of refraction is influenced by the cognitive phenomenon of “specificity.” In both experiments participants learned why light bends as it travels from one optical medium to another with an analogy made to a car driving from paved road into mud and vice versa. They then learned how to qualitatively draw the direction of refracted light rays with an example of a glass prism. One group learned with a rectangular prism example while a second group learned with a triangular prism example. In a transfer test, the participants revealed how, even when they seemed able to implement the refraction concept, their responses were biased by the example they had seen. Participants frequently violated the refraction principle they had just learned (reversing the bend direction in order to make sure their response matched the surface features of their learning example. This tended to happen when their test question looked superficially similar to their learning example. We discuss the implications of these results for physics instruction.

  12. Specific industrial medicine in lignite mining

    Energy Technology Data Exchange (ETDEWEB)

    Zerlett, G.; Toussaint, R.; Hilfert, R.; Koehne, G.


    Lignite is almost exclusively mined open-cast in West Germany. Mining is carried out at present in deep open-cast mines (with depths up to 400 m) using modern mining conveyer techniques with large-scale equipment (rotary bucket excavators and thickeners) conveyer belt and railway links as well as earth-moving equipment (accessory equipment). Specific occupational diseases are not known in lignite mining. Occupational diseases in the sense of degenerative processes of the lumbar spine and avulsion fractures of spinous processes of the lower cervical spine in drivers of earth-moving equipment as a result of whole-body vibration stress have been observed. In the context of occupational disease and industrial accident prevention, close collaboration and a division of labor between industrial physicians and safety engineers of ergonomics specialists have proved to be very efficient. Industrial medical preventive examinations based on statutory regulations and the lignite mining ordinance have a long tradition and are given a great deal of space. First aid at work is organized in a largely decentralized manner owing to the extensiveness of the mining area. The industrial medical care of the employees takes place on site in the various sections (open-cast mining, workshops, brickett factories, processing units etc.). The entire medical technical diagnostics is carried out centrally in an industrial medical center.

  13. Compound specific isotope analysis of organophosphorus pesticides. (United States)

    Wu, Langping; Yao, Jun; Trebse, Polonca; Zhang, Ning; Richnow, Hans H


    Compound-specific isotope analysis (CSIA) has been established as a tool to study the environmental fate of a wide range of contaminants. In this study, CSIA was developed to analyse the stable carbon isotope signatures of the widely used organophosphorus pesticides: dichlorvos, omethoate and dimethoate. The linearity of the GC-C-IRMS system was tested for target pesticides and led to an acceptable isotope composition within the uncertainty of the instrument. In order to assess the accuracy of the developed method, the effect of the evaporation procedure on measured carbon isotope composition (δ(13)C) values was studied and showed that concentration by evaporation of solvents had no significant isotope effect. The CSIA was then applied to investigate isotope fractionation of the hydrolysis and photolysis of selected pesticides. The carbon isotope fractionation of tested pesticides was quantified by the Rayleigh model, which revealed a bulk enrichment factor (ε) of -0.2±0.1‰ for hydrolysis of dichlorvos, -1.0±0.1‰ and -3.7±1.1‰ for hydrolysis and photolysis of dimethoate respectively. This study is a first step towards the application of CSIA to trace the transport and degradation of organophosphorus pesticides in the environment.

  14. Intestinal absorption of specific structured triacylglycerols

    DEFF Research Database (Denmark)

    Mu, Huiling; Høy, Carl-Erik


    To clarify the intestinal absorption pathway of medium-chain fatty acids from MMM-type structured triaclyglycerols containing both medium- and long-chain fatty acids, we studied the lymphatic transport of 1,3-dioctanoyl-2-linoleoyl-sn- glycerol (8:0/18:2/8:0), 1,3-didecanoyl-2-linoleoyl...... and activated into CoA, and reacylated into triacylglycerols in the enterocyte, The hydrolysis of MLM-type STAG is predominantly partial hydrolysis, whereas part of the STAG can also be hydrolyzed to free glycerol and free fatty acids. - Mu, H., and CE. Hoy. Intestinal absorption of specific structured......-sn-glycerol (10:0/18:2/10:0), and 1,3-didodecanoyl-2-linoleoyl-sn-glycerol (12:0/18:2/12:0) in a rat model. Safflower oil was used in the absorption study in order to compare the absorption of medium- chain fatty acids and long-chain fatty acids, The triacylglycerol species of lymph Lipids were separated...

  15. Specification of the ESS Accelerator Cryoplant (United States)

    Wang, Xilong; Arnold, Philipp; Fydrych, Jaroslaw; Hees, Wolfgang; Jurns, John M.; Piso, Daniel; Weisend, John

    The European Spallation Source (ESS) is a neutron-scattering facility being built with extensive international collaboration at Lund, Sweden. The ESS accelerator will deliver protons with 5 MW of power to the target at 2.0 GeV, with a nominal current of 62.5 mA. The superconducting part of the accelerator is about 300 meters long and contains 43 cryomodules. The ESS accelerator cryoplant will provide the cooling for the cryomodules and the cryogenic distribution systeminterconnecting cryoplant and cryomodules. The cryoplant will cover three cryogenic circuits: bath cooling for the cavities at 2 K, the thermal shields at around 40-50 K and 4.5 K forced helium cooling for the power couplers. This paper describes project stages,the cryogenic architecture andthe design basis including cooling capacity, operation modes and interfaces. The important design choices comprising no liquid nitrogen pre-cooling,one integrated cold box, waste heat recovery and process control system strategy as well as the principles of evaluation are presented. All the topics above are implemented and addressed in the technical specification, which has been finished and issued in June 2014. That is a very important step in the development of the ESS cryogenics system.

  16. A Three Doublet Lepton-Specific Model

    CERN Document Server

    Merchand, Marco


    In the lepton-specific version of two Higgs doublet models, a discrete symmetry is used to couple one Higgs, $\\Phi_2$, to quarks and the other, $\\Phi_1$, to leptons. The symmetry eliminates tree level flavor changing neutral currents (FCNC). Motivated by strong constraints on such currents in the quark sector from meson-antimeson mixing, and by hints of $h \\to \\mu\\tau$ in the lepton sector, we study a simple three Higgs doublet model in which one doublet couples to quarks and the other two to leptons. Unlike most other studies of three Higgs doublet models, we impose no flavor symmetry and just use a $Z_2$ symmetry to constrain the Yukawa couplings. We present the model and discuss the various mixing angles. Constraining the parameters to be consistent with observations of the Higgs boson at the LHC, we study the properties of the charged Higgs boson(s) in the model, focusing on the case in which the charged Higgs is above the top threshold. It is found that one can have the branching fraction of the charged ...

  17. Age specific dioxin TEQ reference range

    Energy Technology Data Exchange (ETDEWEB)

    Patterson, D.G. Jr.; Patterson, D.; Wong, L.Y.; Lee, R.; Turner, W.; Caudill, S.; Needham, L.; Henderson, A. [CDC/ATSDR, Atlanta (Georgia); Canady, R. [U.S FDA, Rockville (United States)


    Worldwide public concern of the toxicity of polychlorinated dibenzo-p-dioxins (PCDDs) and Dibenzofurans (PCDFs) has catalyzed extensive research in many toxicologically related areas. However, to date there have been no large-scale studies that have statistically been able to describe the overall dioxin reference levels of the U.S. population. Nor has there been significant information on background levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD), which has been called the most toxic of the dioxin compounds and contributes the most to the dioxin toxicity equivalent (TEQ). Attempts at determining a reference level have been made, however, the levels of PCDDs, PCDFs and PCBs in the environment have been declining in past 2 decades. Therefore estimates from years past may not be a valid measure of today's background dioxin levels. In addition, PCDDs and PCDFs are lipophilic compounds that tend to accumulate in the lipid stores of the body and are resistant to metabolism in the body. Thus it is plausible to hypothesize that older persons will have higher dioxin levels than younger persons. The purpose of this research is to (1) to determine the relationship between overall blood dioxin TEQs and TCDD with respect to age and (2) present a current estimate of age-specific reference ranges for dioxin TEQ and TCDD for a sample of U.S. studies.

  18. Specific "scientific" data structures, and their processing

    Directory of Open Access Journals (Sweden)

    Jerzy Karczmarczuk


    Full Text Available Programming physicists use, as all programmers, arrays, lists, tuples, records, etc., and this requires some change in their thought patterns while converting their formulae into some code, since the "data structures" operated upon, while elaborating some theory and its consequences, are rather: power series and Padé approximants, differential forms and other instances of differential algebras, functionals (for the variational calculus, trajectories (solutions of differential equations, Young diagrams and Feynman graphs, etc. Such data is often used in a [semi-]numerical setting, not necessarily "symbolic", appropriate for the computer algebra packages. Modules adapted to such data may be "just libraries", but often they become specific, embedded sub-languages, typically mapped into object-oriented frameworks, with overloaded mathematical operations. Here we present a functional approach to this philosophy. We show how the usage of Haskell datatypes and - fundamental for our tutorial - the application of lazy evaluation makes it possible to operate upon such data (in particular: the "infinite" sequences in a natural and comfortable manner.

  19. Specific remodeling of splenic architecture by cytomegalovirus.

    Directory of Open Access Journals (Sweden)

    Chris A Benedict


    Full Text Available Efficient immune defenses are facilitated by the organized microarchitecture of lymphoid organs, and this organization is regulated by the compartmentalized expression of lymphoid tissue chemokines. Mouse cytomegalovirus (MCMV infection induces significant remodeling of splenic microarchitecture, including loss of marginal zone macrophage populations and dissolution of T and B cell compartmentalization. MCMV preferentially infected the splenic stroma, targeting endothelial cells (EC as revealed using MCMV-expressing green fluorescent protein. MCMV infection caused a specific, but transient transcriptional suppression of secondary lymphoid chemokine (CCL21. The loss of CCL21 was associated with the failure of T lymphocytes to locate within the T cell zone, although trafficking to the spleen was unaltered. Expression of CCL21 in lymphotoxin (LT-alpha-deficient mice is dramatically reduced, however MCMV infection further reduced CCL21 levels, suggesting that viral modulation of CCL21 was independent of LTalpha signaling. Activation of LTbeta-receptor signaling with an agonistic antibody partially restored CCL21 mRNA expression and redirected transferred T cells to the splenic T cell zone in MCMV-infected mice. These results indicate that virus-induced alterations in lymphoid tissues can occur through an LT-independent modulation of chemokine transcription, and targeting of the LT cytokine system can counteract lymphoid tissue remodeling by MCMV.

  20. Sequence-specific recognition of DNA nanostructures. (United States)

    Rusling, David A; Fox, Keith R


    DNA is the most exploited biopolymer for the programmed self-assembly of objects and devices that exhibit nanoscale-sized features. One of the most useful properties of DNA nanostructures is their ability to be functionalized with additional non-nucleic acid components. The introduction of such a component is often achieved by attaching it to an oligonucleotide that is part of the nanostructure, or hybridizing it to single-stranded overhangs that extend beyond or above the nanostructure surface. However, restrictions in nanostructure design and/or the self-assembly process can limit the suitability of these procedures. An alternative strategy is to couple the component to a DNA recognition agent that is capable of binding to duplex sequences within the nanostructure. This offers the advantage that it requires little, if any, alteration to the nanostructure and can be achieved after structure assembly. In addition, since the molecular recognition of DNA can be controlled by varying pH and ionic conditions, such systems offer tunable properties that are distinct from simple Watson-Crick hybridization. Here, we describe methodology that has been used to exploit and characterize the sequence-specific recognition of DNA nanostructures, with the aim of generating functional assemblies for bionanotechnology and synthetic biology applications.

  1. Specific remodeling of splenic architecture by cytomegalovirus. (United States)

    Benedict, Chris A; De Trez, Carl; Schneider, Kirsten; Ha, Sukwon; Patterson, Ginelle; Ware, Carl F


    Efficient immune defenses are facilitated by the organized microarchitecture of lymphoid organs, and this organization is regulated by the compartmentalized expression of lymphoid tissue chemokines. Mouse cytomegalovirus (MCMV) infection induces significant remodeling of splenic microarchitecture, including loss of marginal zone macrophage populations and dissolution of T and B cell compartmentalization. MCMV preferentially infected the splenic stroma, targeting endothelial cells (EC) as revealed using MCMV-expressing green fluorescent protein. MCMV infection caused a specific, but transient transcriptional suppression of secondary lymphoid chemokine (CCL21). The loss of CCL21 was associated with the failure of T lymphocytes to locate within the T cell zone, although trafficking to the spleen was unaltered. Expression of CCL21 in lymphotoxin (LT)-alpha-deficient mice is dramatically reduced, however MCMV infection further reduced CCL21 levels, suggesting that viral modulation of CCL21 was independent of LTalpha signaling. Activation of LTbeta-receptor signaling with an agonistic antibody partially restored CCL21 mRNA expression and redirected transferred T cells to the splenic T cell zone in MCMV-infected mice. These results indicate that virus-induced alterations in lymphoid tissues can occur through an LT-independent modulation of chemokine transcription, and targeting of the LT cytokine system can counteract lymphoid tissue remodeling by MCMV.

  2. RESRAD. Site-Specific Residual Radioactivity

    Energy Technology Data Exchange (ETDEWEB)

    Yu, C. [Argonne National Laboratory, IL (United States)


    RESRAD is designed to derive site-specific guidelines for allowable residual concentrations of radionuclides in soil. A guideline is defined as a radionuclide concentration or a level of radiation or radioactivity that is acceptable if a site is to be used without radiological restrictions. Guidelines are expressed as (1) concentrations of residual radionuclides in soil, (2) concentrations of airborne radon decay products, (3) levels of external gamma radiation, (4) levels of radioactivity from surface contamination, and (5) concentrations of residual radionuclides in air and water. Soil is defined as unconsolidated earth material, including rubble and debris that may be present. The controlling principles of all guidelines are (1) the annual radiation dose received by a member of the critical population group from the residual radioactive material - predicted by a realistic but reasonably conservative analysis and averaged over a 50 year period - should not exceed 100 mrem/yr, and (2) doses should be kept as low as reasonably achievable. All significant exposure pathways for the critical population group are considered in deriving soil guidelines. These pathways include direct exposure to external radiation from the contaminated soil material; internal radiation from inhalation of airborne radionuclides; and internal radiation from ingestion of plant foods grown in the contaminated soil, meat and milk from livestock fed with contaminated fodder and water, drinking water from a contaminated well, and fish from a contaminated pond.

  3. [Advances in lineage-specific genes]. (United States)

    Huanping, Zhang; Tongming, Yin


    Lineage-specific genes (LSGs) are defined as genes found in one particular taxonomic group but have no significant sequence similarity with genes from other lineages, which compose about 10%?20% of the total genes in the genome of a focal organism. LSGs were first uncovered in the yeast genome in 1996. The development of the whole genome sequencing leads to the emergence of studies on LSGs as a hot topic in comparative genomics. LSGs have been extensively studied on microbial species, lower marine organisms, plant (such as Arabidopsis thaliana, Oryza sativa, Populus), insects, primate, etc; the biological functions of LSGs are important to clarify the evolution and adaptability of a species. In this review, we summarize the progress of LSGs studies, including LSGs identification, gene characterization, origin and evolution of LSGs, biological function, and expression analysis of LSGs. In addition, we discuss the existing problems and future directions for studies in this area. Our purpose is to provide some unique insights into the researches of LSGs.

  4. Talker-specific auditory imagery during reading (United States)

    Nygaard, Lynne C.; Duke, Jessica; Kawar, Kathleen; Queen, Jennifer S.


    The present experiment was designed to determine if auditory imagery during reading includes talker-specific characteristics such as speaking rate. Following Kosslyn and Matt (1977), participants were familiarized with two talkers during a brief prerecorded conversation. One talker spoke at a fast speaking rate and one spoke at a slow speaking rate. During familiarization, participants were taught to identify each talker by name. At test, participants were asked to read two passages and told that either the slow or fast talker wrote each passage. In one condition, participants were asked to read each passage aloud, and in a second condition, they were asked to read each passage silently. Participants pressed a key when they had completed reading the passage, and reading times were collected. Reading times were significantly slower when participants thought they were reading a passage written by the slow talker than when reading a passage written by the fast talker. However, the effects of speaking rate were only present in the reading-aloud condition. Additional experiments were conducted to investigate the role of attention to talker's voice during familiarization. These results suggest that readers may engage in auditory imagery while reading that preserves perceptual details of an author's voice.

  5. Ubiquitination of specific mitochondrial matrix proteins. (United States)

    Lehmann, Gilad; Ziv, Tamar; Braten, Ori; Admon, Arie; Udasin, Ronald G; Ciechanover, Aaron


    Several protein quality control systems in bacteria and/or mitochondrial matrix from lower eukaryotes are absent in higher eukaryotes. These are transfer-messenger RNA (tmRNA), The N-end rule ATP-dependent protease ClpAP, and two more ATP-dependent proteases, HslUV and ClpXP (in yeast). The lost proteases resemble the 26S proteasome and the role of tmRNA and the N-end rule in eukaryotic cytosol is performed by the ubiquitin proteasome system (UPS). Therefore, we hypothesized that the UPS might have substituted these systems - at least partially - in the mitochondrial matrix of higher eukaryotes. Using three independent experimental approaches, we demonstrated the presence of ubiquitinated proteins in the matrix of isolated yeast mitochondria. First, we show that isolated mitochondria contain ubiquitin (Ub) conjugates, which remained intact after trypsin digestion. Second, we demonstrate that the mitochondrial soluble fraction contains Ub-conjugates, several of which were identified by mass spectrometry and are localized to the matrix. Third, using immunoaffinity enrichment by specific antibodies recognizing digested ubiquitinated peptides, we identified a group of Ub-modified matrix proteins. The modification was further substantiated by separation on SDS-PAGE and immunoblots. Last, we attempted to identify the ubiquitin ligase(s) involved, and identified Dma1p as a trypsin-resistant protein in our mitochondrial preparations. Taken together, these data suggest a yet undefined role for the UPS in regulation of the mitochondrial matrix proteins.

  6. A CNN-Specific Integrated Processor

    Directory of Open Access Journals (Sweden)

    Suleyman Malki


    Full Text Available Integrated Processors (IP are algorithm-specific cores that either by programming or by configuration can be re-used within many microelectronic systems. This paper looks at Cellular Neural Networks (CNN to become realized as IP. First current digital implementations are reviewed, and the memoryprocessor bandwidth issues are analyzed. Then a generic view is taken on the structure of the network, and a new intra-communication protocol based on rotating wheels is proposed. It is shown that this provides for guaranteed high-performance with a minimal network interface. The resulting node is small and supports multi-level CNN designs, giving the system a 30-fold increase in capacity compared to classical designs. As it facilitates multiple operations on a single image, and single operations on multiple images, with minimal access to the external image memory, balancing the internal and external data transfer requirements optimizes the system operation. In conventional digital CNN designs, the treatment of boundary nodes requires additional logic to handle the CNN value propagation scheme. In the new architecture, only a slight modification of the existing cells is necessary to model the boundary effect. A typical prototype for visual pattern recognition will house 4096 CNN cells with a 2% overhead for making it an IP.

  7. A CNN-Specific Integrated Processor (United States)

    Malki, Suleyman; Spaanenburg, Lambert


    Integrated Processors (IP) are algorithm-specific cores that either by programming or by configuration can be re-used within many microelectronic systems. This paper looks at Cellular Neural Networks (CNN) to become realized as IP. First current digital implementations are reviewed, and the memoryprocessor bandwidth issues are analyzed. Then a generic view is taken on the structure of the network, and a new intra-communication protocol based on rotating wheels is proposed. It is shown that this provides for guaranteed high-performance with a minimal network interface. The resulting node is small and supports multi-level CNN designs, giving the system a 30-fold increase in capacity compared to classical designs. As it facilitates multiple operations on a single image, and single operations on multiple images, with minimal access to the external image memory, balancing the internal and external data transfer requirements optimizes the system operation. In conventional digital CNN designs, the treatment of boundary nodes requires additional logic to handle the CNN value propagation scheme. In the new architecture, only a slight modification of the existing cells is necessary to model the boundary effect. A typical prototype for visual pattern recognition will house 4096 CNN cells with a 2% overhead for making it an IP.

  8. 78 FR 13100 - Models for Plant-Specific Adoption of Technical Specifications Task Force Traveler TSTF-535... (United States)


    ... (STS): NUREG-1433, ``Standard Technical Specifications General Electric Plants BWR/4,'' and NUREG- 1434... the STS, NUREG-1433, ``Standard Technical Specifications General Electric Plants BWR/4,'' and...

  9. Comparison of sensory specific satiety and sensory specific desires to eat in children and adults. (United States)

    Olsen, Annemarie; Ritz, Christian; Hartvig, Ditte L; Møller, Per


    The aim of this experiment is to compare sensory specific satiety (SSS) and sensory specific desire to eat (SSD), which can be described as general wanting for certain taste categories and go beyond specific foods, in children and adults and their impact on subsequent food choices. Eighty-seven children (10.3 ± 0.6 years) and 49 adults (31.0 ± 2.0 years) participated in the study. Sweet pear banana yoghurt was used as the food eaten to satiation, and test foods representing sweet, salty, sour, bitter, "fatty", and "spicy" flavors were also evaluated (foods not eaten). At baseline and post meal participants evaluated hunger, satiation, liking, and wanting for test foods and yoghurt, and desires on a 150 mm visual analogue score (VAS) scale. The yoghurt was eaten until a state of "comfortable satiation" was reached. Results showed that SSS and SSD were expressed differently in children and adults. In children, SSS was primarily product specific and bound to the yoghurt, whereas in adults SSS was transferred to the uneaten foods sharing sensory characteristics with the yoghurt (namely sweet, sour and "fatty"), which all decreased in their liking post meal. Similar differences were found for SSD. We conclude that children and adults differ in their expression of SSS and SSD, and this might have implications for planning meal compositions.

  10. Specific and non-specific interactions of ParB with DNA: implications for chromosome segregation. (United States)

    Taylor, James A; Pastrana, Cesar L; Butterer, Annika; Pernstich, Christian; Gwynn, Emma J; Sobott, Frank; Moreno-Herrero, Fernando; Dillingham, Mark S


    The segregation of many bacterial chromosomes is dependent on the interactions of ParB proteins with centromere-like DNA sequences called parS that are located close to the origin of replication. In this work, we have investigated the binding of Bacillus subtilis ParB to DNA in vitro using a variety of biochemical and biophysical techniques. We observe tight and specific binding of a ParB homodimer to the parS sequence. Binding of ParB to non-specific DNA is more complex and displays apparent positive co-operativity that is associated with the formation of larger, poorly defined, nucleoprotein complexes. Experiments with magnetic tweezers demonstrate that non-specific binding leads to DNA condensation that is reversible by protein unbinding or force. The condensed DNA structure is not well ordered and we infer that it is formed by many looping interactions between neighbouring DNA segments. Consistent with this view, ParB is also able to stabilize writhe in single supercoiled DNA molecules and to bridge segments from two different DNA molecules in trans. The experiments provide no evidence for the promotion of non-specific DNA binding and/or condensation events by the presence of parS sequences. The implications of these observations for chromosome segregation are discussed.

  11. Recent advances in the development of specific antidotes for target-specific oral anticoagulants. (United States)

    Mo, Yoonsun; Yam, Felix K


    Warfarin, a vitamin K antagonist, has been the only orally available anticoagulant for > 60 years. During the past decade, the U.S. Food and Drug Administration has approved several target-specific oral anticoagulants (TSOACs) for the prophylaxis and treatment of arterial and venous thromboembolism and stroke prevention in patients with nonvalvular atrial fibrillation. These new agents have several advantages over warfarin including more predictable pharmacokinetics and pharmacodynamics, fewer food and drug interactions, and lack of need for routine coagulation monitoring. However, unlike warfarin, currently no antidotes are available to reverse the anticoagulant effect of TSOACs. Specific antidotes for TSOACs may not be needed in most situations due to their short half-life, yet the absence of antidotes for these agents is a concern, especially in emergent situations such as life-threatening major bleeding or nonelective major surgery. Several specific antidotes for TSOACs including idarucizumab, andexanet alfa, and aripazine have been developed and have shown promise in early clinical trials evaluating their efficacy and safety. In this narrative review, the progress made in developing specific antidotes for TSOACs is summarized based on the latest available preclinical and clinical data.

  12. MLL rearrangements in pediatric acute lymphoblastic and myeloblastic leukemias: MLL specific and lineage specific signatures

    Directory of Open Access Journals (Sweden)

    te Kronnie Geertruy


    Full Text Available Abstract Background The presence of MLL rearrangements in acute leukemia results in a complex number of biological modifications that still remain largely unexplained. Armstrong et al. proposed MLL rearrangement positive ALL as a distinct subgroup, separated from acute lymphoblastic (ALL and myeloblastic leukemia (AML, with a specific gene expression profile. Here we show that MLL, from both ALL and AML origin, share a signature identified by a small set of genes suggesting a common genetic disregulation that could be at the basis of mixed lineage leukemia in both phenotypes. Methods Using Affymetrix® HG-U133 Plus 2.0 platform, gene expression data from 140 (training set + 78 (test set ALL and AML patients with (24+13 and without (116+65 MLL rearrangements have been investigated performing class comparison (SAM and class prediction (PAM analyses. Results We identified a MLL translocation-specific (379 probes signature and a phenotype-specific (622 probes signature which have been tested using unsupervised methods. A final subset of 14 genes grants the characterization of acute leukemia patients with and without MLL rearrangements. Conclusion Our study demonstrated that a small subset of genes identifies MLL-specific rearrangements and clearly separates acute leukemia samples according to lineage origin. The subset included well-known genes and newly discovered markers that identified ALL and AML subgroups, with and without MLL rearrangements.

  13. Evaluation of nutrient specifications for broiler breeders. (United States)

    Wilson, H R; Harms, R H


    Two experiments were conducted to determine if previously suggested nutrient requirements of broiler breeders (23 g protein, 850 mg sulfur amino acids, 4.5 g calcium, and 750 mg phosphorus/bird/day) are in excess and could be reduced during the laying period. In Experiment 1, Cobb color-sex broiler breeders were fed daily nutrient allowances that were 100.0, 96.3, 92.5, 89.4, and 86.6% of the suggested requirements. In Experiment 2, Cobb feather-sex breeders were fed daily allowances that were 92.5, 89.4, 86.6, 83.4, and 80.9% of the suggested requirements. Birds on all diets were fed the same energy level; however, energy varied with season to maintain body weight. Egg production, fertility, hatchability, egg weight, and shell quality were not significantly affected by the reductions in nutrient intake in either experiment. The diet with the lowest nutrient level (80.9% of the suggested requirement) was adequate, indicating a considerable margin of safety for the stated requirements. Body weight was quite variable but tended to decrease with nutrient restriction. Weights of broilers hatched from treated breeders were not significantly affected at 49 days of age by the breeder dietary treatments. These results indicate that broiler breeder diets formulated to meet presently suggested requirements have a large margin of safety and a reduction of specifications by approximately 10% is suggested. The revised daily intakes recommended are: 20.6 g protein, 754 mg sulfur amino acids, 400 mg methionine, 938 mg lysine, 1379 mg arginine, 256 mg tryptophan, 4.07 g calcium, 683 mg total phosphorus, and 170 mg sodium.

  14. When is category specific in Alzheimer's disease? (United States)

    Laws, Keith R; Gale, Tim M; Leeson, Verity C; Crawford, John R


    Mixed findings have emerged concerning whether category-specific disorders occur in Alzheimer's disease. Factors that may contribute to these inconsistencies include: ceiling effects/skewed distributions for control data in some studies; differences in the severity of cognitive deficit in patients; and differences in the type of analysis (in particular, if and how controls are used to analyse single case data). We examined picture naming in Alzheimer's patients and matched elderly healthy normal controls in three experiments. These experiments used stimuli that did and did not produce ceiling effects/skewed data in controls. In Experiment 1, we examined for category effects in individual DAT patients using commonly used analyses for single cases (chi2 and z-scores). The different techniques produced quite different outcomes. In Experiment 2a, we used the same techniques on a different group of patients with similar outcomes. Finally, in Experiment 2b, we examined the same patients but (a) used stimuli that did not produce ceiling effects/skewed distributions in healthy controls, and (b) used statistical methods that did not treat the control sample as a population. We found that ceiling effects in controls may markedly inflate the incidence of dissociations in which living things are differentially impaired and seriously underestimate dissociations in the opposite direction. In addition, methods that treat the control sample as a population led to inflation in the overall number of dissociations detected. These findings have implications for the reliability of category effects previously reported both in Alzheimer patients and in other pathologies. In particular, they suggest that the greater proportion of living than nonliving deficits reported in the literature may be an artifact of the methods used.

  15. Query Specific Rank Fusion for Image Retrieval. (United States)

    Zhang, Shaoting; Yang, Ming; Cour, Timothee; Yu, Kai; Metaxas, Dimitris N


    Recently two lines of image retrieval algorithms demonstrate excellent scalability: 1) local features indexed by a vocabulary tree, and 2) holistic features indexed by compact hashing codes. Although both of them are able to search visually similar images effectively, their retrieval precision may vary dramatically among queries. Therefore, combining these two types of methods is expected to further enhance the retrieval precision. However, the feature characteristics and the algorithmic procedures of these methods are dramatically different, which is very challenging for the feature-level fusion. This motivates us to investigate how to fuse the ordered retrieval sets, i.e., the ranks of images, given by multiple retrieval methods, to boost the retrieval precision without sacrificing their scalability. In this paper, we model retrieval ranks as graphs of candidate images and propose a graph-based query specific fusion approach, where multiple graphs are merged and reranked by conducting a link analysis on a fused graph. The retrieval quality of an individual method is measured on-the-fly by assessing the consistency of the top candidates' nearest neighborhoods. Hence, it is capable of adaptively integrating the strengths of the retrieval methods using local or holistic features for different query images. This proposed method does not need any supervision, has few parameters, and is easy to implement. Extensive and thorough experiments have been conducted on four public datasets, i.e., the UKbench, Corel-5K, Holidays and the large-scale San Francisco Landmarks datasets. Our proposed method has achieved very competitive performance, including state-of-the-art results on several data sets, e.g., the N-S score 3.83 for UKbench.

  16. Site-Specific, Climate-Friendly Farming (United States)

    Brown, D. J.; Brooks, E. S.; Eitel, J.; Huggins, D. R.; Painter, K.; Rupp, R.; Smith, J. L.; Stockle, C.; Vierling, L. A.


    Of the four most important atmospheric greenhouse gasses (GHG) enriched through human activities, only nitrous oxide (N2O) emissions are due primarily to agriculture. However, reductions in the application of synthetic N fertilizers could have significant negative consequences for a growing world population given the crucial role that these fertilizers have played in cereal yield increases since WWII. Increasing N use efficiency (NUE) through precision management of agricultural N in space and time will therefore play a central role in the reduction of agricultural N2O emissions. Precision N management requires a greater understanding of the spatio-temporal variability of factors supporting N management decisions such as crop yield, water and N availability, utilization and losses. We present an overview of a large, collaborative, multi-disciplinary project designed to improve our basic understanding of nitrogen (N), carbon (C) and water (H2O) spatio-temporal dynamics for wheat-based cropping systems on complex landscapes, and develop management tools to optimize water- and nitrogen-use efficiency for these systems and landscapes. Major components of this project include: (a) cropping systems experiments addressing nitrogen application rate and seeding density for different landscape positions; (b) GHG flux experiments and monitoring; (c) soil microbial genetics and stable isotope analyses to elucidate biochemical pathways for N2O production; (d) proximal soil sensing for construction of detailed soil maps; (e) LiDAR and optical remote sensing for crop growth monitoring; (f) hydrologic experiments, monitoring, and modeling; (g) refining the CropSyst simulation model to estimate biophysical processes and GHG emissions under a variety of management and climatic scenarios; and (h) linking farm-scale enterprise budgets to simulation modeling in order to provide growers with economically viable site-specific climate-friendly farming guidance.

  17. Molecules for Fluorescence Detection of Specific Chemicals (United States)

    Fedor, Steve


    A family of fluorescent dye molecules has been developed for use in on-off fluorescence detection of specific chemicals. By themselves, these molecules do not fluoresce. However, when exposed to certain chemical analytes in liquid or vapor forms, they do fluoresce (see figure). These compounds are amenable to fixation on or in a variety of substrates for use in fluorescence-based detection devices: they can be chemically modified to anchor them to porous or non-porous solid supports or can be incorporated into polymer films. Potential applications for these compounds include detection of chemical warfare agents, sensing of acidity or alkalinity, and fluorescent tagging of proteins in pharmaceutical research and development. These molecules could also be exploited for use as two-photon materials for photodynamic therapy in the treatment of certain cancers and other diseases. A molecule in this family consists of a fluorescent core (such as an anthracene or pyrene) attached to two end groups that, when the dye is excited by absorption of light, transfer an electron to the core, thereby quenching the fluorescence. The end groups can be engineered so that they react chemically with certain analytes. Upon reaction, electrons on the end groups are no longer available for transfer to the core and, consequently, the fluorescence from the core is no longer quenched. The chemoselectivity of these molecules can be changed by changing the end groups. For example, aniline end groups afford a capability for sensing acids or acid halides (including those contained in chemical warfare agents). Pyridine or bipyridyl end groups would enable sensing of metal ions. Other chemicals that can be selectively detected through suitable choice of end groups include glucose and proteins. Moreover, the fluorescent cores can be changed to alter light-absorption and -emission characteristics: anthracene cores fluoresce at wavelengths around 500 nm, whereas perylene cores absorb and emit at

  18. Idiopathic non-specific interstitial pneumonia. (United States)

    Belloli, Elizabeth A; Beckford, Rosemarie; Hadley, Ryan; Flaherty, Kevin R


    Non-specific interstitial pneumonia (NSIP) is an interstitial lung disease that may be idiopathic or secondary to connective tissue disease, toxins or numerous other causes. Idiopathic NSIP is a rare diagnosis and requires exclusion of these other possible causes. Patients typically present in mid-adulthood with dyspnoea, cough and often constitutional symptoms including fever and fatigue. The disease has a female predominance, and more than 50% of patients have never smoked. Physical exam features mild hypoxaemia and inspiratory rales. Pulmonary function tests demonstrate restriction and a low diffusing capacity for carbon monoxide. High-resolution computed tomography abnormalities include predominantly lower lobe subpleural reticular changes, traction bronchiectasis and ground-glass opacities; honeycombing is rarely seen. An evaluation of the underlying pathology is necessary for a firm diagnosis. Histologically, alveolar and interstitial mononuclear cell inflammation and fibrosis are seen in a temporally uniform pattern with preserved underlying alveolar architecture. NSIP must be differentiated from other parenchymal lung diseases including idiopathic pulmonary fibrosis and hypersensitivity pneumonitis. A thorough exposure history and assessment for underlying connective tissue diseases are highly important, as positive findings in these categories would likely denote a case of secondary NSIP. A multi-disciplinary discussion that includes pulmonologist(s), radiologist(s) and pathologist(s) assists in reaching a consensus diagnosis and improves diagnostic accuracy. Treatment of idiopathic NSIP, although not well proven, is generally instituted in the form of immunosuppression. Prognosis is favourable compared with idiopathic pulmonary fibrosis, although the diagnosis still carries an attributable mortality. Herein we will summarize the clinical characteristics and management of idiopathic NSIP.

  19. [Specificities of heart failure in the elderly]. (United States)

    Hanon, Olivier


    Heart failure (HF) is frequent in the elderly population and is associated with high mortality, prolonged and frequent hospitalisations. In old patients with multiple comorbid diseases, clinical symptoms of HF are less typical and the prognosis is poorer. Comprehensive geriatric assessment, using simple tests to evaluate cognitive function, falls, depression, malnutrition, dependency, comorbidities, context of life and social conditions, is needed in order to screen concomitant diseases and loss of autonomy. Because of lack of specific studies on octogenarians, most recommendations for HF treatment in this population have been extrapolated from data based on younger populations. Epidemiological studies show that recommended HF therapies as angiotensin converting enzyme inhibitors and beta-blockers are underused in elderly patients with HF. Reasons for this under prescription are various and include the absence of well-defined therapeutic strategy especially in case of preserved ejection fraction, the existence of comorbidities and the fear of adverse events. Special precautions for the use of HF drugs must be followed because of the comorbidities and age-related changes in drug pharmacokinetics or pharmacodynamics. Increase of drug dose must be closely monitored for adverse reactions. Overall, the therapeutic strategy must not be based on the subject's age, but rather on the individual analysis taking into account the severity of the heart disease, the geriatric assessment, the life expectancy and the quality of life. Clinical and laboratory monitoring should be intensified, especially in case of acute episode (infection, dehydration, introduction of a new treatment, fall…). Therefore, monitoring of heart failure in the elderly, involves multidisciplinary collaboration between cardiologists, geriatricians, general practitioners, pharmacists and paramedical team.

  20. 7 CFR 51.3417 - Optional test for specific gravity. (United States)


    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Optional test for specific gravity. 51.3417 Section 51... specific gravity. Tests to determine specific gravity shall be made in accordance with the procedures set.... The specific gravity for any lot of potatoes shall be the average of at least 3 corrected readings...

  1. 10 CFR 39.13 - Specific licenses for well logging. (United States)


    ... 10 Energy 1 2010-01-01 2010-01-01 false Specific licenses for well logging. 39.13 Section 39.13 Energy NUCLEAR REGULATORY COMMISSION LICENSES AND RADIATION SAFETY REQUIREMENTS FOR WELL LOGGING Specific Licensing Requirements § 39.13 Specific licenses for well logging. The Commission will approve an application for a specific license for the...

  2. Specification Language NUJSL Based on JSP and Its Supporting System

    Institute of Scientific and Technical Information of China (English)

    徐永森; 何飚


    is paper presents the specification languange NUJSL and its supporting system.NUJSL is a modular specification language based on Jackson Program Design Method(JSP).With the module construction,it is convenient to use NUJSL to write larger specifications.The supporting system supports the incremental development of software specification in NUJSL,and implements the transformation both from specification to software procedural description in Jackson Schematic Logic(pseudo code)and from procedural description to PASCAL program.

  3. Associating Specific Materials with Topological Insulation Behavior (United States)

    Zhang, Xiuwen


    The first-principles (a) total-energy/stability calculations combined with (b) electronic structure calculations of band inversion, spin-polarization and topological invariants (Z2) has led to the design and prediction of specific materials that are topological insulators in this study. We classify bulk materials into four types of band-inversion behaviors (TI-1, TI-2, BI-3, BI-4), based on the number of band inversions and their distributions on various time reversal invariant k points. Depending on the inversion type in bulk, the corresponding surface states have different protections e.g., protected by time reversal symmetry (in TI-1 materials), spatial symmetry (in TI-2), or not protected (in BI-3, BI-4). Subject 1 Discovery of new TI by screening materials for a Z2 metric: Such high-throughput search in the framework of Inverse Design methodology predicts a few previously undocumented materials that are TI-1 in their ground state crystal structure. We also predict dozens of materials that are TI-1 however in structures that are not ground states (e.g. perovskite structure of II-Bi-O3). Subject 2 Design Principle to increase the gap of TI-1 materials: In HgTe-like cubic topological materials, the insulating gap is zero since the spin-orbit splitting is positive and so a 4-fold half-filled p-like band is near the Fermi level. By design of hybridization of d-orbitals into the p-like bands, one can create negative spin-orbit splitting and so a finite insulating gap. Subject 3 Unconventional spin textures of TI surface states: Despite the fact that one of our predicted TI-1 KBaBi has inversion symmetry in the bulk-a fact that that would preclude bulk spin polarization-we find a Dresselhaus-like spin texture with non-helical spin texture. This originates from the local spin polarization, anchored on the atomic sites with inversion asymmetric point groups, that is compensated due to global inversion symmetry in bulk. In collaboration with: Jun-Wei Luo, Qihang Liu

  4. Specific cutaneous manifestations of internal malignancy. (United States)

    Kaplan, R P


    shows maculopapular and erosive lesions distributed in a seborrheic pattern. Neuroblastoma derived from cells of the neural crest demonstrates clinically widespread bluish papulonodules. Kaposi's sarcoma, a multifocal vascular malignancy, has a wide spectrum of clinical expression. Those patients who are immunocompromised secondary to concomitant disease or immunosuppressive therapy are more susceptible to a disseminated fulminant course accompanied by opportunistic infection. In conclusion, although specific signs of internal malignancy are less common than nonspecific ones, they are just as important; if the clinician managing the cancer patient is familiar with these clues to internal disease, proper patient management will ensue.(ABSTRACT TRUNCATED AT 400 WORDS)


    Directory of Open Access Journals (Sweden)

    Din Alina Valentina


    Directives as well as at the national level; essential characteristics of the activity to prevent and fight against money laundering in Romania, which is mainly the responsibility of the National Department for Money Laundering Prevention and Control - ONPCSB, as well as the financial analysis of the activity to prevent and combat money laundering in Romania within 1999-2011, identifying the specific typologies of money laundering; the connection between money laundering and terrorism financing.

  6. How Does Attention Relate to the Ability-Specific and Position-Specific Components of Reasoning Measured by APM? (United States)

    Ren, Xuezhu; Goldhammer, Frank; Moosbrugger, Helfried; Schweizer, Karl


    The aim of the present study was to clarify the nature of the ability-specific and position-specific components of Raven's Advanced Progressive Matrices (APM) by relating them to a number of types of attention. The ability-specific component represents the constant part of cognitive performance whereas the position-specific component reflects the…

  7. Biomimetic catalysts responsive to specific chemical signals

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Yan [Iowa State Univ., Ames, IA (United States)


    Part 1. Design of Biomimetic Catalysts Based on Amphiphilic Systems The overall objective of our research is to create biomimetic catalysts from amphiphilic molecules. More specifically, we aim to create supramolecular systems that can be used to control the microenvironment around a catalytic center in a biomimetic fashion and apply the learning to construct supramolecular catalysts with novel functions found in enzymatic catalysts. We have prepared synthetic molecules (i.e., foldamers) that could fold into helical structures with nanometer-sized internal hydrophilic cavities. Cavities of this size are typically observed only in the tertiary and quaternary structures of proteins but were formed in our foldamer prepared in just a few steps from the monomer. Similar to many proteins, our foldamers displayed cooperativity in the folding/unfolding equilibrium and followed a two-state conformational transition. In addition, their conformational change could be triggered by solvent polarity, pH, or presence of metal ions and certain organic molecules. We studied their environmentally dependent conformational changes in solutions, surfactant micelles, and lipid bilayer membranes. Unlike conventional rigid supramolecular host, a foldamer undergoes conformational change during guest binding. Our study in the molecular recognition of an oligocholate host yielded some extremely exciting results. Cooperativity between host conformation and host–guest interactions was found to “magnify” weak binding interactions. In other words, since binding affinity is determined by the overall change of free energy during the binding, guest-induced conformational change of the host, whether near or far from the binding site, affects the binding. This study has strong implications in catalysis because enzymes have been hypothesized to harvest similar intramolecular forces to strengthen their binding with the transition state of an enzyme-catalyzed reaction. The supramolecular and

  8. High Specificity of Quantitative Methylation-Specific PCR Analysis for MGMT Promoter Hypermethylation Detection in Gliomas

    Directory of Open Access Journals (Sweden)

    Paola Parrella


    Full Text Available Normal brain tissue from 28 individuals and 50 glioma samples were analyzed by real-time Quantitative Methylation-Specific PCR (QMSP. Data from this analysis were compared with results obtained on the same samples by MSP. QMSP analysis demonstrated a statistically significant difference in both methylation level (P=.000009 Mann Whitney Test and frequencies (P=.0000007, Z-test in tumour samples as compared with normal brain tissues. Although QMSP and MSP showed similar sensitivity, the specificity of QMSP analysis was significantly higher (93%; CI95%: 84%–100% as compared with MSP (64%; 95%CI: 46%–82%. Our results suggest that QMSP analysis may represent a powerful tool to identify glioma patients that will benefit from alkylating agents chemotherapy.

  9. Specific expression of bioluminescence reporter gene in cardiomyocyte regulated by tissue specific promoter

    Energy Technology Data Exchange (ETDEWEB)

    Nguyen, Vu Hong; Tae, Seong Ho; Le, Nguyen Uyen Chi; Min, Jung Joon [Chonnam National University Medical School, Gwangju (Korea, Republic of)


    As the human heart is not capable of regenerating the great numbers of cardiac cells that are lost after myocardial infarction, impaired cardiac function is the inevitable result of ischemic disease. Recently, human embryonic stem cells (hESCs) have gained popularity as a potentially ideal cell candidate for tissue regeneration. In particular, hESCs are capable of cardiac lineage-specific differentiation and confer improvement of cardiac function following transplantation into animal models. Although such data are encouraging, the specific strategy for in vivo and non-invasive detection of differentiated cardiac lineage is still limited. Therefore, in the present study, we established the gene construction in which the optical reporter gene Firefly luciferase was controlled by Myosin Heavy Chain promoter for specific expressing in heart cells. The vector consisting of - MHC promoter and a firefly luciferase coding sequence flanked by full-length bovine growth hormone (BGH) 3'-polyadenylation sequence based on pcDNA3.1- vector backbone. To test the specific transcription of this promoter in g of MHC-Fluc or CMV-Flue (for control) plasmid DNA in myocardial tissue, 20 phosphate-buffered saline was directly injected into mouse myocardium through a midline sternotomy and liver. After 1 week of injection, MHC-Fluc expression was detected from heart region which was observed under cooled CCD camera of in vivo imaging system but not from liver. In control group injected with CMV-Flue, the bioluminescence was detected from all these organs. The expression of Flue under control of Myosin Heavy Chain promoter may become a suitable optical reporter gene for stem cell-derived cardiac lineage differentiation study.

  10. Time-trends in method-specific suicide rates compared with the availability of specific compounds

    DEFF Research Database (Denmark)

    Nordentoft, Merete; Qin, Ping; Helweg-Larsen, Karin;


    Restriction of means for suicide is an important part of suicide preventive strategies in different countries. All suicides in Denmark between 1970 and 2000 were examined with regard to method used for suicide. Overall suicide mortality and method-specific suicide mortality was compared...... in the number of suicides by self-poisoning with these compounds. Restricted access occurred concomittantly with a 55% decrease in suicide rate....

  11. European refining in front of the new specifications; Le raffinage europeen face aux nouvelles specifications

    Energy Technology Data Exchange (ETDEWEB)



    In the framework of the 3. European fuels conference of March 2002, the World Refining Association (WRA) presented a complete overview of the present day situation of the European refining activity, in front of the evolution of fuel specifications. The impact of the new coming standards about sulfur, the consequences for the refineries, the available technologic solutions, the impact of hydrogen fluxes management, and the possibilities of sites optimization were reviewed. (J.S.)

  12. Attention deficits predict phenotypic outcomes in syndrome-specific and domain-specific ways

    Directory of Open Access Journals (Sweden)

    Kim eCornish


    Full Text Available Attentional difficulties, both at home and in the classroom, are reported across a number of neurodevelopmental disorders. However, exactly how attention influences early socio-cognitive learning remains unclear. We addressed this question both concurrently and longitudinally in a cross-syndrome design, with respect to the communicative domain of vocabulary and to the cognitive domain of early literacy, and then extended the analysis to social behavior. Participants were young children (aged 4 to 9 years at Time 1 with either Williams syndrome (WS, N=26 or Down syndrome (DS, N=26 and typically developing controls (N=103. Children with WS displayed significantly greater attentional deficits (as indexed by teacher report of behavior typical of attention deficit hyperactivity disorder, ADHD than children with DS, but both groups had greater attentional problems than the controls. Despite their attention differences, children with DS and those with WS were equivalent in their cognitive abilities of reading single words, both at Time 1 and 12 months later, at Time 2, although they differed in their early communicative abilities in terms of vocabulary. Greater ADHD-like behaviors predicted poorer subsequent literacy for children with DS, but not for children with WS, pointing to syndrome-specific attentional constraints on specific aspects of early development. Overall, our findings highlight the need to investigate more precisely whether and, if so, how, syndrome-specific profiles of behavioral difficulties constrain learning and socio-cognitive outcomes across different domains.

  13. Broad specificity profiling of TALENs results in engineered nucleases with improved DNA-cleavage specificity. (United States)

    Guilinger, John P; Pattanayak, Vikram; Reyon, Deepak; Tsai, Shengdar Q; Sander, Jeffry D; Joung, J Keith; Liu, David R


    Although transcription activator-like effector nucleases (TALENs) can be designed to cleave chosen DNA sequences, TALENs have activity against related off-target sequences. To better understand TALEN specificity, we profiled 30 unique TALENs with different target sites, array length and domain sequences for their abilities to cleave any of 10(12) potential off-target DNA sequences using in vitro selection and high-throughput sequencing. Computational analysis of the selection results predicted 76 off-target substrates in the human genome, 16 of which were accessible and modified by TALENs in human cells. The results suggest that (i) TALE repeats bind DNA relatively independently; (ii) longer TALENs are more tolerant of mismatches yet are more specific in a genomic context; and (iii) excessive DNA-binding energy can lead to reduced TALEN specificity in cells. Based on these findings, we engineered a TALEN variant that exhibits equal on-target cleavage activity but tenfold lower average off-target activity in human cells.

  14. Detection and specifity of class specific antibodies to whole bacteria cells using a solid phase radioimmunoassay

    Energy Technology Data Exchange (ETDEWEB)

    Czerkinsky, C.; Rees, A.S.; Bergimeier, L.A.; Challacombe, S.J. (Guy' s Hospital Medical and Dental Schools, London (UK))


    A solid phase radioimmunoassay has been developed which can be used for the detection of isotype specific antibodies to whole bacteria and other particulate antigens, and is applicable to a variety of species. Bacteria are bound to the solid phase by the use either of antibodies, or of methyl glyoxal. Both methods result in a sensitive and reproducible assay, and bacteria do not appear to desorb from the solid phase. The specificity of antibodies to whole bacteria was examined by absorption of antisera with various species of bacteria and retesting, or by determining the binding of antisera to various bacteria bound to the solid phase. Both methods revealed specificity for the bacteria examined. Inhibition studies showed that antibodies to Streptococcus mutans whole cells could be inhibited by purified cell surface antigens glucosyltransferase and antigen I/II, but only minimally by lipoteichoic acid, c polysaccharide or dextran. In murine antisera antibodies of the IgG, IgM, and IgA classes could be detected at amounts of less than 1 ng/ml.

  15. Preparation of Polyclonal Antibodies Against Testis-specific Protease 50 and Characterization of Antibody Specificity

    Institute of Scientific and Technical Information of China (English)


    Testis-specific protease 50 (TSP50) is a testis-specific oncogene, which is abnormally activated in most tested patients with breast cancer. This property makes it an attractive molecular marker and a promising target for the diagnosis and therapy of breast cancer. In order to obtain the protective and specific polyclonal antibodies for further research, TSP50 cDNA was amplified by RT-PCR from normal human testicular tissue, and inserted into eukaryotic expression vector pcDNA3.1. Rabbit anti-TSP50 polyclonal antibodies were prepared by means of intramuscular injection of pcDNA3.1-TSP50 into the rabbits. Titers of the anti-sera were measured by ELISA and Western blotting with the E. coli cell lysate containing the induced GST-TSP50 fusion protein as an antigen. In addition, we examined the expression of TSP50 in both breast cancer cell line MCF-7 and breast cancer tissue by immunofluorescent and immunohistochemistry analysis.

  16. Biomimetic catalysts responsive to specific chemical signals

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Yan [Iowa State Univ., Ames, IA (United States)


    Part 1. Design of Biomimetic Catalysts Based on Amphiphilic Systems The overall objective of our research is to create biomimetic catalysts from amphiphilic molecules. More specifically, we aim to create supramolecular systems that can be used to control the microenvironment around a catalytic center in a biomimetic fashion and apply the learning to construct supramolecular catalysts with novel functions found in enzymatic catalysts. We have prepared synthetic molecules (i.e., foldamers) that could fold into helical structures with nanometer-sized internal hydrophilic cavities. Cavities of this size are typically observed only in the tertiary and quaternary structures of proteins but were formed in our foldamer prepared in just a few steps from the monomer. Similar to many proteins, our foldamers displayed cooperativity in the folding/unfolding equilibrium and followed a two-state conformational transition. In addition, their conformational change could be triggered by solvent polarity, pH, or presence of metal ions and certain organic molecules. We studied their environmentally dependent conformational changes in solutions, surfactant micelles, and lipid bilayer membranes. Unlike conventional rigid supramolecular host, a foldamer undergoes conformational change during guest binding. Our study in the molecular recognition of an oligocholate host yielded some extremely exciting results. Cooperativity between host conformation and host–guest interactions was found to “magnify” weak binding interactions. In other words, since binding affinity is determined by the overall change of free energy during the binding, guest-induced conformational change of the host, whether near or far from the binding site, affects the binding. This study has strong implications in catalysis because enzymes have been hypothesized to harvest similar intramolecular forces to strengthen their binding with the transition state of an enzyme-catalyzed reaction. The supramolecular and

  17. The Hierarchical Specification and Mechanical Verification of the SIFT Design (United States)


    The formal specification and proof methodology employed to demonstrate that the SIFT computer system meets its requirements are described. The hierarchy of design specifications is shown, from very abstract descriptions of system function down to the implementation. The most abstract design specifications are simple and easy to understand, almost all details of the realization were abstracted out, and are used to ensure that the system functions reliably and as intended. A succession of lower level specifications refines these specifications into more detailed, and more complex, views of the system design, culminating in the Pascal implementation. The section describes the rigorous mechanical proof that the abstract specifications are satisfied by the actual implementation.

  18. Complexity of Decision Problems for Mixed and Modal Specifications

    DEFF Research Database (Denmark)

    Antonik, Adam; Huth, Michael; Nyman, Ulrik Mathias;


    We consider decision problems for modal and mixed transition systems used as specifications: the common implementation problem (whether a set of specifications has a common implementation), the consistency problem (whether a single specification has an implementation), and the thorough refinement...... problem (whether all implementations of one specification are also implementations of another one). Common implementation and thorough refinement are shown to be PSPACE-hard for modal, and so also for mixed, specifications. Consistency is PSPACE-hard for mixed, while trivial for modal specifications. We...... also supply upper bounds suggesting strong links between these problems....

  19. Statistical and Economic Techniques for Site-specific Nematode Management. (United States)

    Liu, Zheng; Griffin, Terry; Kirkpatrick, Terrence L


    Recent advances in precision agriculture technologies and spatial statistics allow realistic, site-specific estimation of nematode damage to field crops and provide a platform for the site-specific delivery of nematicides within individual fields. This paper reviews the spatial statistical techniques that model correlations among neighboring observations and develop a spatial economic analysis to determine the potential of site-specific nematicide application. The spatial econometric methodology applied in the context of site-specific crop yield response contributes to closing the gap between data analysis and realistic site-specific nematicide recommendations and helps to provide a practical method of site-specifically controlling nematodes.

  20. An integrated in silico approach to design specific inhibitors targeting human poly(a-specific ribonuclease.

    Directory of Open Access Journals (Sweden)

    Dimitrios Vlachakis

    Full Text Available Poly(A-specific ribonuclease (PARN is an exoribonuclease/deadenylase that degrades 3'-end poly(A tails in almost all eukaryotic organisms. Much of the biochemical and structural information on PARN comes from the human enzyme. However, the existence of PARN all along the eukaryotic evolutionary ladder requires further and thorough investigation. Although the complete structure of the full-length human PARN, as well as several aspects of the catalytic mechanism still remain elusive, many previous studies indicate that PARN can be used as potent and promising anti-cancer target. In the present study, we attempt to complement the existing structural information on PARN with in-depth bioinformatics analyses, in order to get a hologram of the molecular evolution of PARNs active site. In an effort to draw an outline, which allows specific drug design targeting PARN, an unequivocally specific platform was designed for the development of selective modulators focusing on the unique structural and catalytic features of the enzyme. Extensive phylogenetic analysis based on all the publicly available genomes indicated a broad distribution for PARN across eukaryotic species and revealed structurally important amino acids which could be assigned as potentially strong contributors to the regulation of the catalytic mechanism of PARN. Based on the above, we propose a comprehensive in silico model for the PARN's catalytic mechanism and moreover, we developed a 3D pharmacophore model, which was subsequently used for the introduction of DNP-poly(A amphipathic substrate analog as a potential inhibitor of PARN. Indeed, biochemical analysis revealed that DNP-poly(A inhibits PARN competitively. Our approach provides an efficient integrated platform for the rational design of pharmacophore models as well as novel modulators of PARN with therapeutic potential.