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Sample records for fusion peptide rescues

  1. Potent peptidic fusion inhibitors of influenza virus

    Energy Technology Data Exchange (ETDEWEB)

    Kadam, Rameshwar U.; Juraszek, Jarek; Brandenburg, Boerries; Buyck, Christophe; Schepens, Wim B. G.; Kesteleyn, Bart; Stoops, Bart; Vreeken, Rob J.; Vermond, Jan; Goutier, Wouter; Tang, Chan; Vogels, Ronald; Friesen, Robert H. E.; Goudsmit, Jaap; van Dongen, Maria J. P.; Wilson, Ian A.

    2017-09-28

    Influenza therapeutics with new targets and mechanisms of action are urgently needed to combat potential pandemics, emerging viruses, and constantly mutating strains in circulation. We report here on the design and structural characterization of potent peptidic inhibitors of influenza hemagglutinin. The peptide design was based on complementarity-determining region loops of human broadly neutralizing antibodies against the hemagglutinin (FI6v3 and CR9114). The optimized peptides exhibit nanomolar affinity and neutralization against influenza A group 1 viruses, including the 2009 H1N1 pandemic and avian H5N1 strains. The peptide inhibitors bind to the highly conserved stem epitope and block the low pH–induced conformational rearrangements associated with membrane fusion. These peptidic compounds and their advantageous biological properties should accelerate the development of new small molecule– and peptide-based therapeutics against influenza virus.

  2. Monitoring and Information Fusion for Search and Rescue Operations in Large-Scale Disasters

    National Research Council Canada - National Science Library

    Nardi, Daniele

    2002-01-01

    ... for information fusion with application to search-and-rescue and large scale disaster relief. The objective is to develop and to deploy tools to support the monitoring activities in an intervention caused by a large-scale disaster...

  3. Paramyxovirus F1 protein has two fusion peptides: implications for the mechanism of membrane fusion.

    Science.gov (United States)

    Peisajovich, S G; Samuel, O; Shai, Y

    2000-03-10

    Viral fusion proteins contain a highly hydrophobic segment, named the fusion peptide, which is thought to be responsible for the merging of the cellular and viral membranes. Paramyxoviruses are believed to contain a single fusion peptide at the N terminus of the F1 protein. However, here we identified an additional internal segment in the Sendai virus F1 protein (amino acids 214-226) highly homologous to the fusion peptides of HIV-1 and RSV. A synthetic peptide, which includes this region, was found to induce membrane fusion of large unilamellar vesicles, at concentrations where the known N-terminal fusion peptide is not effective. A scrambled peptide as well as several peptides from other regions of the F1 protein, which strongly bind to membranes, are not fusogenic. The functional and structural characterization of this active segment suggest that the F1 protein has an additional internal fusion peptide that could participate in the actual fusion event. The presence of homologous regions in other members of the same family suggests that the concerted action of two fusion peptides, one N-terminal and the other internal, is a general feature of paramyxoviruses. Copyright 2000 Academic Press.

  4. Sifuvirtide, a potent HIV fusion inhibitor peptide

    International Nuclear Information System (INIS)

    Wang, Rui-Rui; Yang, Liu-Meng; Wang, Yun-Hua; Pang, Wei; Tam, Siu-Cheung; Tien, Po; Zheng, Yong-Tang

    2009-01-01

    Enfuvirtide (ENF) is currently the only FDA approved HIV fusion inhibitor in clinical use. Searching for more drugs in this category with higher efficacy and lower toxicity seems to be a logical next step. In line with this objective, a synthetic peptide with 36 amino acid residues, called Sifuvirtide (SFT), was designed based on the crystal structure of gp41. In this study, we show that SFT is a potent anti-HIV agent with relatively low cytotoxicity. SFT was found to inhibit replication of all tested HIV strains. The effective concentrations that inhibited 50% viral replication (EC 50 ), as determined in all tested strains, were either comparable or lower than benchmark values derived from well-known anti-HIV drugs like ENF or AZT, while the cytotoxic concentrations causing 50% cell death (CC 50 ) were relatively high, rendering it an ideal anti-HIV agent. A GST-pull down assay was performed to confirm that SFT is a fusion inhibitor. Furthermore, the activity of SFT on other targets in the HIV life cycle was also investigated, and all assays showed negative results. To further understand the mechanism of action of HIV peptide inhibitors, resistant variants of HIV-1 IIIB were derived by serial virus passage in the presence of increasing doses of SFT or ENF. The results showed that there was cross-resistance between SFT and ENF. In conclusion, SFT is an ideal anti-HIV agent with high potency and low cytotoxicity, but may exhibit a certain extent of cross-resistance with ENF.

  5. Peptide-Mediated Liposome Fusion: The Effect of Anchor Positioning

    Directory of Open Access Journals (Sweden)

    Niek S. A. Crone

    2018-01-01

    Full Text Available A minimal model system for membrane fusion, comprising two complementary peptides dubbed “E” and “K” joined to a cholesterol anchor via a polyethyleneglycol spacer, has previously been developed in our group. This system promotes the fusion of large unilamellar vesicles and facilitates liposome-cell fusion both in vitro and in vivo. Whilst several aspects of the system have previously been investigated to provide an insight as to how fusion is facilitated, anchor positioning has not yet been considered. In this study, the effects of placing the anchor at either the N-terminus or in the center of the peptide are investigated using a combination of circular dichroism spectroscopy, dynamic light scattering, and fluorescence assays. It was discovered that anchoring the “K” peptide in the center of the sequence had no effect on its structure, its ability to interact with membranes, or its ability to promote fusion, whereas anchoring the ‘E’ peptide in the middle of the sequence dramatically decreases fusion efficiency. We postulate that anchoring the ‘E’ peptide in the middle of the sequence disrupts its ability to form homodimers with peptides on the same membrane, leading to aggregation and content leakage.

  6. Multimerized CHR-derived peptides as HIV-1 fusion inhibitors.

    Science.gov (United States)

    Nomura, Wataru; Hashimoto, Chie; Suzuki, Takaharu; Ohashi, Nami; Fujino, Masayuki; Murakami, Tsutomu; Yamamoto, Naoki; Tamamura, Hirokazu

    2013-08-01

    To date, several HIV-1 fusion inhibitors based on the carboxy-terminal leucine/isoleucine heptad repeat (CHR) region of an HIV-1 envelope protein gp41 have been discovered. We have shown that a synthetic peptide mimetic of a trimer form of the CHR-derived peptide C34 has potent inhibitory activity against the HIV-1 fusion mechanism, compared to a monomer C34 peptide. The present study revealed that a dimeric form of C34 is evidently structurally critical for fusion inhibitors, and that the activity of multimerized CHR-derived peptides in fusion inhibition is affected by the properties of the unit peptides C34, SC34EK, and T20. The fluorescence-based study suggested that the N36-interactive sites of the C34 trimer, including hydrophobic residues, are exposed outside the trimer and that trimerization of C34 caused a remarkable increase in fusion inhibitory activity. The present results could be useful in the design of fusion inhibitors against viral infections which proceed via membrane fusion with host cells. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  7. Heterologous production of peptides in plants: fusion proteins and beyond.

    Science.gov (United States)

    Viana, Juliane Flávia Cançado; Dias, Simoni Campos; Franco, Octávio Luiz; Lacorte, Cristiano

    2013-11-01

    Recombinant DNA technology has allowed the ectopic production of proteins and peptides of different organisms leading to biopharmaceutical production in large cultures of bacterial, yeasts and mammalian cells. Otherwise, the expression of recombinant proteins and peptides in plants is an attractive alternative presenting several advantages over the commonly used expression systems including reduced production costs, easy scale-up and reduced risks of pathogen contamination. Different types of proteins and peptides have been expressed in plants, including antibodies, antigens, and proteins and peptides of medical, veterinary and industrial applications. However, apart from providing a proof of concept, the use of plants as platforms for heterologous protein and peptide production still depends on key steps towards optimization including the enhancement of expression levels, manipulation of post-transcriptional modifications and improvements in purification methods. In this review, strategies to increase heterologous protein and peptide stability and accumulation are discussed, focusing on the expression of peptides through the use of gene fusions.

  8. Determination of the minimal fusion peptide of bovine leukemia virus gp30

    International Nuclear Information System (INIS)

    Lorin, Aurelien; Lins, Laurence; Stroobant, Vincent; Brasseur, Robert; Charloteaux, Benoit

    2007-01-01

    In this study, we determined the minimal N-terminal fusion peptide of the gp30 of the bovine leukemia virus on the basis of the tilted peptide theory. We first used molecular modelling to predict that the gp30 minimal fusion peptide corresponds to the 15 first residues. Liposome lipid-mixing and leakage assays confirmed that the 15-residue long peptide induces fusion in vitro and that it is the shortest peptide inducing optimal fusion since longer peptides destabilize liposomes to the same extent but not shorter ones. The 15-residue long peptide can thus be considered as the minimal fusion peptide. The effect of mutations reported in the literature was also investigated. Interestingly, mutations related to glycoproteins unable to induce syncytia in cell-cell fusion assays correspond to peptides predicted as non-tilted. The relationship between obliquity and fusogenicity was also confirmed in vitro for one tilted and one non-tilted mutant peptide

  9. Construction of hybrid peptide synthetases by module and domain fusions.

    Science.gov (United States)

    Mootz, H D; Schwarzer, D; Marahiel, M A

    2000-05-23

    Nonribosomal peptide synthetases are modular enzymes that assemble peptides of diverse structures and important biological activities. Their modular organization provides a great potential for the rational design of novel compounds by recombination of the biosynthetic genes. Here we describe the extension of a dimodular system to trimodular ones based on whole-module fusion. The recombinant hybrid enzymes were purified to monitor product assembly in vitro. We started from the first two modules of tyrocidine synthetase, which catalyze the formation of the dipeptide dPhe-Pro, to construct such hybrid systems. Fusion of the second, proline-specific module with the ninth and tenth modules of the tyrocidine synthetases, specific for ornithine and leucine, respectively, resulted in dimodular hybrid enzymes exhibiting the combined substrate specificities. The thioesterase domain was fused to the terminal module. Upon incubation of these dimodular enzymes with the first tyrocidine module, TycA, incorporating dPhe, the predicted tripeptides dPhe-Pro-Orn and dPhe-Pro-Leu were obtained at rates of 0.15 min(-1) and 2.1 min(-1). The internal thioesterase domain was necessary and sufficient to release the products from the hybrid enzymes and thereby facilitate a catalytic turnover. Our approach of whole-module fusion is based on an improved definition of the fusion sites and overcomes the recently discovered editing function of the intrinsic condensation domains. The stepwise construction of hybrid peptide synthetases from catalytic subunits reinforces the inherent potential for the synthesis of novel, designed peptides.

  10. The dengue virus type 2 envelope protein fusion peptide is essential for membrane fusion

    International Nuclear Information System (INIS)

    Huang, Claire Y.-H.; Butrapet, Siritorn; Moss, Kelly J.; Childers, Thomas; Erb, Steven M.; Calvert, Amanda E.; Silengo, Shawn J.; Kinney, Richard M.; Blair, Carol D.; Roehrig, John T.

    2010-01-01

    The flaviviral envelope (E) protein directs virus-mediated membrane fusion. To investigate membrane fusion as a requirement for virus growth, we introduced 27 unique mutations into the fusion peptide of an infectious cDNA clone of dengue 2 virus and recovered seven stable mutant viruses. The fusion efficiency of the mutants was impaired, demonstrating for the first time the requirement for specific FP AAs in optimal fusion. Mutant viruses exhibited different growth kinetics and/or genetic stabilities in different cell types and adult mosquitoes. Virus particles could be recovered following RNA transfection of cells with four lethal mutants; however, recovered viruses could not re-infect cells. These viruses could enter cells, but internalized virus appeared to be retained in endosomal compartments of infected cells, thus suggesting a fusion blockade. Mutations of the FP also resulted in reduced virus reactivity with flavivirus group-reactive antibodies, confirming earlier reports using virus-like particles.

  11. Computational design of a PDZ domain peptide inhibitor that rescues CFTR activity.

    Directory of Open Access Journals (Sweden)

    Kyle E Roberts

    Full Text Available The cystic fibrosis transmembrane conductance regulator (CFTR is an epithelial chloride channel mutated in patients with cystic fibrosis (CF. The most prevalent CFTR mutation, ΔF508, blocks folding in the endoplasmic reticulum. Recent work has shown that some ΔF508-CFTR channel activity can be recovered by pharmaceutical modulators ("potentiators" and "correctors", but ΔF508-CFTR can still be rapidly degraded via a lysosomal pathway involving the CFTR-associated ligand (CAL, which binds CFTR via a PDZ interaction domain. We present a study that goes from theory, to new structure-based computational design algorithms, to computational predictions, to biochemical testing and ultimately to epithelial-cell validation of novel, effective CAL PDZ inhibitors (called "stabilizers" that rescue ΔF508-CFTR activity. To design the "stabilizers", we extended our structural ensemble-based computational protein redesign algorithm K* to encompass protein-protein and protein-peptide interactions. The computational predictions achieved high accuracy: all of the top-predicted peptide inhibitors bound well to CAL. Furthermore, when compared to state-of-the-art CAL inhibitors, our design methodology achieved higher affinity and increased binding efficiency. The designed inhibitor with the highest affinity for CAL (kCAL01 binds six-fold more tightly than the previous best hexamer (iCAL35, and 170-fold more tightly than the CFTR C-terminus. We show that kCAL01 has physiological activity and can rescue chloride efflux in CF patient-derived airway epithelial cells. Since stabilizers address a different cellular CF defect from potentiators and correctors, our inhibitors provide an additional therapeutic pathway that can be used in conjunction with current methods.

  12. A compensatory mutation provides resistance to disparate HIV fusion inhibitor peptides and enhances membrane fusion.

    Directory of Open Access Journals (Sweden)

    Matthew P Wood

    Full Text Available Fusion inhibitors are a class of antiretroviral drugs used to prevent entry of HIV into host cells. Many of the fusion inhibitors being developed, including the drug enfuvirtide, are peptides designed to competitively inhibit the viral fusion protein gp41. With the emergence of drug resistance, there is an increased need for effective and unique alternatives within this class of antivirals. One such alternative is a class of cyclic, cationic, antimicrobial peptides known as θ-defensins, which are produced by many non-human primates and exhibit broad-spectrum antiviral and antibacterial activity. Currently, the θ-defensin analog RC-101 is being developed as a microbicide due to its specific antiviral activity, lack of toxicity to cells and tissues, and safety in animals. Understanding potential RC-101 resistance, and how resistance to other fusion inhibitors affects RC-101 susceptibility, is critical for future development. In previous studies, we identified a mutant, R5-tropic virus that had evolved partial resistance to RC-101 during in vitro selection. Here, we report that a secondary mutation in gp41 was found to restore replicative fitness, membrane fusion, and the rate of viral entry, which were compromised by an initial mutation providing partial RC-101 resistance. Interestingly, we show that RC-101 is effective against two enfuvirtide-resistant mutants, demonstrating the clinical importance of RC-101 as a unique fusion inhibitor. These findings both expand our understanding of HIV drug-resistance to diverse peptide fusion inhibitors and emphasize the significance of compensatory gp41 mutations.

  13. Protein-induced fusion can be modulated by target membrane lipids through a structural switch at the level of the fusion peptide

    NARCIS (Netherlands)

    Pecheur, EI; Martin, [No Value; Bienvenue, A; Ruysschaert, JM; Hoekstra, D

    2000-01-01

    Regulatory features of protein-induced membrane fusion are largely unclear, particularly at the level of the fusion peptide. Fusion peptides being part of larger protein complexes, such investigations are met with technical limitations. Here, we show that the fusion activity of influenza virus or

  14. A fusion-inhibiting peptide against Rift Valley fever virus inhibits multiple, diverse viruses.

    Directory of Open Access Journals (Sweden)

    Jeffrey W Koehler

    Full Text Available For enveloped viruses, fusion of the viral envelope with a cellular membrane is critical for a productive infection to occur. This fusion process is mediated by at least three classes of fusion proteins (Class I, II, and III based on the protein sequence and structure. For Rift Valley fever virus (RVFV, the glycoprotein Gc (Class II fusion protein mediates this fusion event following entry into the endocytic pathway, allowing the viral genome access to the cell cytoplasm. Here, we show that peptides analogous to the RVFV Gc stem region inhibited RVFV infectivity in cell culture by inhibiting the fusion process. Further, we show that infectivity can be inhibited for diverse, unrelated RNA viruses that have Class I (Ebola virus, Class II (Andes virus, or Class III (vesicular stomatitis virus fusion proteins using this single peptide. Our findings are consistent with an inhibition mechanism similar to that proposed for stem peptide fusion inhibitors of dengue virus in which the RVFV inhibitory peptide first binds to both the virion and cell membranes, allowing it to traffic with the virus into the endocytic pathway. Upon acidification and rearrangement of Gc, the peptide is then able to specifically bind to Gc and prevent fusion of the viral and endocytic membranes, thus inhibiting viral infection. These results could provide novel insights into conserved features among the three classes of viral fusion proteins and offer direction for the future development of broadly active fusion inhibitors.

  15. Spike Protein Fusion Peptide and Feline Coronavirus Virulence

    Science.gov (United States)

    Chang, Hui-Wen; Egberink, Herman F.; Halpin, Rebecca; Spiro, David J.

    2012-01-01

    Coronaviruses are well known for their potential to change their host or tissue tropism, resulting in unpredictable new diseases and changes in pathogenicity; severe acute respiratory syndrome and feline coronaviruses, respectively, are the most recognized examples. Feline coronaviruses occur as 2 pathotypes: nonvirulent feline enteric coronaviruses (FECVs), which replicate in intestinal epithelium cells, and lethal feline infectious peritonitis viruses (FIPVs), which replicate in macrophages. Evidence indicates that FIPV originates from FECV by mutation, but consistent distinguishing differences have not been established. We sequenced the full genome of 11 viruses of each pathotype and then focused on the single most distinctive site by additionally sequencing hundreds of viruses in that region. As a result, we identified 2 alternative amino acid differences in the putative fusion peptide of the spike protein that together distinguish FIPV from FECV in >95% of cases. By these and perhaps other mutations, the virus apparently acquires its macrophage tropism and spreads systemically. PMID:22709821

  16. Information-Fusion Methods Based Simultaneous Localization and Mapping for Robot Adapting to Search and Rescue Postdisaster Environments

    Directory of Open Access Journals (Sweden)

    Hongling Wang

    2018-01-01

    Full Text Available The first application of utilizing unique information-fusion SLAM (IF-SLAM methods is developed for mobile robots performing simultaneous localization and mapping (SLAM adapting to search and rescue (SAR environments in this paper. Several fusion approaches, parallel measurements filtering, exploration trajectories fusing, and combination sensors’ measurements and mobile robots’ trajectories, are proposed. The novel integration particle filter (IPF and optimal improved EKF (IEKF algorithms are derived for information-fusion systems to perform SLAM task in SAR scenarios. The information-fusion architecture consists of multirobots and multisensors (MAM; multiple robots mount on-board laser range finder (LRF sensors, localization sonars, gyro odometry, Kinect-sensor, RGB-D camera, and other proprioceptive sensors. This information-fusion SLAM (IF-SLAM is compared with conventional methods, which indicates that fusion trajectory is more consistent with estimated trajectories and real observation trajectories. The simulations and experiments of SLAM process are conducted in both cluttered indoor environment and outdoor collapsed unstructured scenario, and experimental results validate the effectiveness of the proposed information-fusion methods in improving SLAM performances adapting to SAR scenarios.

  17. Early and late HIV-1 membrane fusion events are impaired by sphinganine lipidated peptides that target the fusion site.

    Science.gov (United States)

    Klug, Yoel A; Ashkenazi, Avraham; Viard, Mathias; Porat, Ziv; Blumenthal, Robert; Shai, Yechiel

    2014-07-15

    Lipid-conjugated peptides have advanced the understanding of membrane protein functions and the roles of lipids in the membrane milieu. These lipopeptides modulate various biological systems such as viral fusion. A single function has been suggested for the lipid, binding to the membrane and thus elevating the local concentration of the peptide at the target site. In the present paper, we challenged this argument by exploring in-depth the antiviral mechanism of lipopeptides, which comprise sphinganine, the lipid backbone of DHSM (dihydrosphingomyelin), and an HIV-1 envelope-derived peptide. Surprisingly, we discovered a partnership between the lipid and the peptide that impaired early membrane fusion events by reducing CD4 receptor lateral diffusion and HIV-1 fusion peptide-mediated lipid mixing. Moreover, only the joint function of sphinganine and its conjugate peptide disrupted HIV-1 fusion protein assembly and folding at the later fusion steps. Via imaging techniques we revealed for the first time the direct localization of these lipopeptides to the virus-cell and cell-cell contact sites. Overall, the findings of the present study may suggest lipid-protein interactions in various biological systems and may help uncover a role for elevated DHSM in HIV-1 and its target cell membranes.

  18. Fusion peptides from oncogenic chimeric proteins as putative specific biomarkers of cancer.

    Science.gov (United States)

    Conlon, Kevin P; Basrur, Venkatesha; Rolland, Delphine; Wolfe, Thomas; Nesvizhskii, Alexey I; MacCoss, Michael J; Lim, Megan S; Elenitoba-Johnson, Kojo S J

    2013-10-01

    Chromosomal translocations encoding chimeric fusion proteins constitute one of the most common mechanisms underlying oncogenic transformation in human cancer. Fusion peptides resulting from such oncogenic chimeric fusions, though unique to specific cancer subtypes, are unexplored as cancer biomarkers. Here we show, using an approach termed fusion peptide multiple reaction monitoring mass spectrometry, the direct identification of different cancer-specific fusion peptides arising from protein chimeras that are generated from the juxtaposition of heterologous genes fused by recurrent chromosomal translocations. Using fusion peptide multiple reaction monitoring mass spectrometry in a clinically relevant scenario, we demonstrate the specific, sensitive, and unambiguous detection of a specific diagnostic fusion peptide in clinical samples of anaplastic large cell lymphoma, but not in a diverse array of benign lymph nodes or other forms of primary malignant lymphomas and cancer-derived cell lines. Our studies highlight the utility of fusion peptides as cancer biomarkers and carry broad implications for the use of protein biomarkers in cancer detection and monitoring.

  19. Inhibition of the Hantavirus Fusion Process by Predicted Domain III and Stem Peptides from Glycoprotein Gc.

    Science.gov (United States)

    Barriga, Gonzalo P; Villalón-Letelier, Fernando; Márquez, Chantal L; Bignon, Eduardo A; Acuña, Rodrigo; Ross, Breyan H; Monasterio, Octavio; Mardones, Gonzalo A; Vidal, Simon E; Tischler, Nicole D

    2016-07-01

    Hantaviruses can cause hantavirus pulmonary syndrome or hemorrhagic fever with renal syndrome in humans. To enter cells, hantaviruses fuse their envelope membrane with host cell membranes. Previously, we have shown that the Gc envelope glycoprotein is the viral fusion protein sharing characteristics with class II fusion proteins. The ectodomain of class II fusion proteins is composed of three domains connected by a stem region to a transmembrane anchor in the viral envelope. These fusion proteins can be inhibited through exogenous fusion protein fragments spanning domain III (DIII) and the stem region. Such fragments are thought to interact with the core of the fusion protein trimer during the transition from its pre-fusion to its post-fusion conformation. Based on our previous homology model structure for Gc from Andes hantavirus (ANDV), here we predicted and generated recombinant DIII and stem peptides to test whether these fragments inhibit hantavirus membrane fusion and cell entry. Recombinant ANDV DIII was soluble, presented disulfide bridges and beta-sheet secondary structure, supporting the in silico model. Using DIII and the C-terminal part of the stem region, the infection of cells by ANDV was blocked up to 60% when fusion of ANDV occurred within the endosomal route, and up to 95% when fusion occurred with the plasma membrane. Furthermore, the fragments impaired ANDV glycoprotein-mediated cell-cell fusion, and cross-inhibited the fusion mediated by the glycoproteins from Puumala virus (PUUV). The Gc fragments interfered in ANDV cell entry by preventing membrane hemifusion and pore formation, retaining Gc in a non-resistant homotrimer stage, as described for DIII and stem peptide inhibitors of class II fusion proteins. Collectively, our results demonstrate that hantavirus Gc shares not only structural, but also mechanistic similarity with class II viral fusion proteins, and will hopefully help in developing novel therapeutic strategies against hantaviruses.

  20. Fusion peptide of influenza hemagglutinin requires a fixed angle boomerang structure for activity.

    Science.gov (United States)

    Lai, Alex L; Park, Heather; White, Judith M; Tamm, Lukas K

    2006-03-03

    The fusion peptide of influenza hemagglutinin is crucial for cell entry of this virus. Previous studies showed that this peptide adopts a boomerang-shaped structure in lipid model membranes at the pH of membrane fusion. To examine the role of the boomerang in fusion, we changed several residues proposed to stabilize the kink in this structure and measured fusion. Among these, mutants E11A and W14A expressed hemagglutinins with hemifusion and no fusion activities, and F9A and N12A had no effect on fusion, respectively. Binding enthalpies and free energies of mutant peptides to model membranes and their ability to perturb lipid bilayer structures correlated well with the fusion activities of the parent full-length molecules. The structure of W14A determined by NMR and site-directed spin labeling features a flexible kink that points out of the membrane, in sharp contrast to the more ordered boomerang of the wild-type, which points into the membrane. A specific fixed angle boomerang structure is thus required to support membrane fusion.

  1. Sera from Children with Autism Induce Autistic Features Which Can Be Rescued with a CNTF Small Peptide Mimetic in Rats

    Science.gov (United States)

    Kazim, Syed Faraz; Cardenas-Aguayo, Maria del Carmen; Arif, Mohammad; Blanchard, Julie; Fayyaz, Fatima; Grundke-Iqbal, Inge; Iqbal, Khalid

    2015-01-01

    Autism is a neurodevelopmental disorder characterized clinically by impairments in social interaction and verbal and non-verbal communication skills as well as restricted interests and repetitive behavior. It has been hypothesized that altered brain environment including an imbalance in neurotrophic support during early development contributes to the pathophysiology of autism. Here we report that sera from children with autism which exhibited abnormal levels of various neurotrophic factors induced cell death and oxidative stress in mouse primary cultured cortical neurons. The effects of sera from autistic children were rescued by pre-treatment with a ciliary neurotrophic factor (CNTF) small peptide mimetic, Peptide 6 (P6), which was previously shown to exert its neuroprotective effect by modulating CNTF/JAK/STAT pathway and LIF signaling and by enhancing brain derived neurotrophic factor (BDNF) expression. Similar neurotoxic effects and neuroinflammation were observed in young Wistar rats injected intracerebroventricularly with autism sera within hours after birth. The autism sera injected rats demonstrated developmental delay and deficits in social communication, interaction, and novelty. Both the neurobiological changes and the behavioral autistic phenotype were ameliorated by P6 treatment. These findings implicate the involvement of neurotrophic imbalance during early brain development in the pathophysiology of autism and a proof of principle of P6 as a potential therapeutic strategy for autism. PMID:25769033

  2. Sera from children with autism induce autistic features which can be rescued with a CNTF small peptide mimetic in rats.

    Science.gov (United States)

    Kazim, Syed Faraz; Cardenas-Aguayo, Maria Del Carmen; Arif, Mohammad; Blanchard, Julie; Fayyaz, Fatima; Grundke-Iqbal, Inge; Iqbal, Khalid

    2015-01-01

    Autism is a neurodevelopmental disorder characterized clinically by impairments in social interaction and verbal and non-verbal communication skills as well as restricted interests and repetitive behavior. It has been hypothesized that altered brain environment including an imbalance in neurotrophic support during early development contributes to the pathophysiology of autism. Here we report that sera from children with autism which exhibited abnormal levels of various neurotrophic factors induced cell death and oxidative stress in mouse primary cultured cortical neurons. The effects of sera from autistic children were rescued by pre-treatment with a ciliary neurotrophic factor (CNTF) small peptide mimetic, Peptide 6 (P6), which was previously shown to exert its neuroprotective effect by modulating CNTF/JAK/STAT pathway and LIF signaling and by enhancing brain derived neurotrophic factor (BDNF) expression. Similar neurotoxic effects and neuroinflammation were observed in young Wistar rats injected intracerebroventricularly with autism sera within hours after birth. The autism sera injected rats demonstrated developmental delay and deficits in social communication, interaction, and novelty. Both the neurobiological changes and the behavioral autistic phenotype were ameliorated by P6 treatment. These findings implicate the involvement of neurotrophic imbalance during early brain development in the pathophysiology of autism and a proof of principle of P6 as a potential therapeutic strategy for autism.

  3. Functional rescue of dystrophin-deficient mdx mice by a chimeric peptide-PMO.

    Science.gov (United States)

    Yin, Haifang; Moulton, Hong M; Betts, Corinne; Merritt, Thomas; Seow, Yiqi; Ashraf, Shirin; Wang, Qingsong; Boutilier, Jordan; Wood, Matthew Ja

    2010-10-01

    Splice modulation using antisense oligonucleotides (AOs) has been shown to yield targeted exon exclusion to restore the open reading frame and generate truncated but partially functional dystrophin protein. This has been successfully demonstrated in dystrophin-deficient mdx mice and in Duchenne muscular dystrophy (DMD) patients. However, DMD is a systemic disease; successful therapeutic exploitation of this approach will therefore depend on effective systemic delivery of AOs to all affected tissues. We have previously shown the potential of a muscle-specific/arginine-rich chimeric peptide-phosphorodiamidate morpholino (PMO) conjugate, but its long-term activity, optimized dosing regimen, capacity for functional correction and safety profile remain to be established. Here, we report the results of this chimeric peptide-PMO conjugate in the mdx mouse using low doses (3 and 6 mg/kg) administered via a 6 biweekly systemic intravenous injection protocol. We show 100% dystrophin-positive fibers and near complete correction of the dystrophin transcript defect in all peripheral muscle groups, with restoration of 50% dystrophin protein over 12 weeks, leading to correction of the DMD pathological phenotype and restoration of muscle function in the absence of detectable toxicity or immune response. Chimeric muscle-specific/cell-penetrating peptides therefore represent highly promising agents for systemic delivery of splice-correcting PMO oligomers for DMD therapy.

  4. Membrane fusion is induced by a distinct peptide sequence of the sea urchin fertilization protein bindin

    NARCIS (Netherlands)

    Ulrich, AS; Glabe, CG; Hoekstra, D

    1998-01-01

    Fertilization in the sea urchin is mediated by the membrane-associated acrosomal protein bindin, which plays a key role in the adhesion and fusion between sperm and egg. We have investigated the structure/function relationship of an 18-amino acid peptide fragment "B18," which represents the minimal

  5. Genetic selection of peptide aptamers that interact and inhibit both Small protein B and alternative ribosome-rescue factor A of Aeromonas veronii C4

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    Peng Liu

    2016-08-01

    Full Text Available Aeromonas veronii is a pathogenic gram-negative bacterium, which infects a variety of animals and results in mass mortality. The stalled-ribosome rescues are reported to ensure viability and virulence under stress conditions, of which primarily include trans-translation and alternative ribosome-rescue factor A (ArfA in A. veronii. For identification of specific peptides that interact and inhibit the stalled-ribosome rescues, peptide aptamer library (pTRG-SN-peptides was constructed using pTRG as vector and Staphylococcus aureus nuclease (SN as scaffold protein, in which 16 random amino acids were introduced to form an exposed surface loop. In the meantime both Small Protein B (SmpB which acts as one of the key components in trans-translation, and alternative ribosome-rescue factor A (ArfA were inserted to pBT to constitute pBT-SmpB and pBT-ArfA, respectively. The peptide aptamer PA-2 was selected from pTRG-SN-peptides by bacterial two-hybrid system (B2H employing pBT-SmpB or pBT-ArfA as baits. The conserved sites G133K134 and D138K139R140 of C-terminal SmpB were identified by interacting with N-terminal SN, and concurrently the residue K62 of ArfA was recognized by interacting with the surface loop of the specific peptide aptamer PA-2. The expression plasmids pN-SN or pN-PA-2, which combined the duplication origin of pRE112 with the neokanamycin promoter expressing SN or PA-2, were created and transformed into A. veronii C4, separately. The engineered A. veronii C4 which endowing SN or PA-2 expression impaired growth capabilities under stress conditions including temperatures, sucrose, glucose, potassium chloride (KCl and antibiotics, and the stress-related genes rpoS and nhaP were down-regulated significantly by Quantitative Real-time PCR (qRT-PCR when treating in 2.0% KCl. Thus,the engineered A. veronii C4 conferring PA-2 expression might be potentially attenuated vaccine, and also the peptide aptamer PA-2 could develop as anti

  6. Effect of a Fusion Peptide by Covalent Conjugation of a Mitochondrial Cell-Penetrating Peptide and a Glutathione Analog Peptide

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    Carmine Pasquale Cerrato

    2017-06-01

    Full Text Available Previously, we designed and synthesized a library of mitochondrial antioxidative cell-penetrating peptides (mtCPPs superior to the parent peptide, SS31, to protect mitochondria from oxidative damage. A library of antioxidative glutathione analogs called glutathione peptides (UPFs, exceptional in hydroxyl radical elimination compared with glutathione, were also designed and synthesized. Here, a follow-up study is described, investigating the effects of the most promising members from both libraries on reactive oxidative species scavenging ability. None of the peptides influenced cell viability at the concentrations used. Fluorescence microscopy studies showed that the fluorescein-mtCPP1-UPF25 (mtgCPP internalized into cells, and spectrofluorometric analysis determined the presence and extent of peptide into different cell compartments. mtgCPP has superior antioxidative activity compared with mtCPP1 and UPF25 against H2O2 insult, preventing ROS formation by 2- and 3-fold, respectively. Moreover, we neither observed effects on mitochondrial membrane potential nor production of ATP. These data indicate that mtgCPP is targeting mitochondria, protecting them from oxidative damage, while also being present in the cytosol. Our hypothesis is based on a synergistic effect resulting from the fused peptide. The mitochondrial peptide segment is targeting mitochondria, whereas the glutathione analog peptide segment is active in the cytosol, resulting in increased scavenging ability.

  7. Genetic Selection of Peptide Aptamers That Interact and Inhibit Both Small Protein B and Alternative Ribosome-Rescue Factor A of Aeromonas veronii C4.

    Science.gov (United States)

    Liu, Peng; Chen, Yong; Wang, Dan; Tang, Yanqiong; Tang, Hongqian; Song, Haichao; Sun, Qun; Zhang, Yueling; Liu, Zhu

    2016-01-01

    Aeromonas veronii is a pathogenic gram-negative bacterium, which infects a variety of animals and results in mass mortality. The stalled-ribosome rescues are reported to ensure viability and virulence under stress conditions, of which primarily include trans-translation and alternative ribosome-rescue factor A (ArfA) in A. veronii. For identification of specific peptides that interact and inhibit the stalled-ribosome rescues, peptide aptamer library (pTRG-SN-peptides) was constructed using pTRG as vector and Staphylococcus aureus nuclease (SN) as scaffold protein, in which 16 random amino acids were introduced to form an exposed surface loop. In the meantime both Small Protein B (SmpB) which acts as one of the key components in trans-translation, and ArfA were inserted to pBT to constitute pBT-SmpB and pBT-ArfA, respectively. The peptide aptamer PA-2 was selected from pTRG-SN-peptides by bacterial two-hybrid system (B2H) employing pBT-SmpB or pBT-ArfA as baits. The conserved sites G133K134 and D138K139R140 of C-terminal SmpB were identified by interacting with N-terminal SN, and concurrently the residue K62 of ArfA was recognized by interacting with the surface loop of the specific peptide aptamer PA-2. The expression plasmids pN-SN or pN-PA-2, which combined the duplication origin of pRE112 with the neokanamycin promoter expressing SN or PA-2, were created and transformed into A. veronii C4, separately. The engineered A. veronii C4 which endowing SN or PA-2 expression impaired growth capabilities under stress conditions including temperatures, sucrose, glucose, potassium chloride (KCl) and antibiotics, and the stress-related genes rpoS and nhaP were down-regulated significantly by Quantitative Real-time PCR (qRT-PCR) when treating in 2.0% KCl. Thus, the engineered A. veronii C4 conferring PA-2 expression might be potentially attenuated vaccine, and also the peptide aptamer PA-2 could develop as anti-microbial drugs targeted to the ribosome rescued factors in A

  8. Peptide and small molecules rescue the functional activity and agonist potency of dysfunctional human melanocortin-4 receptor polymorphisms.

    Science.gov (United States)

    Xiang, Zhimin; Pogozheva, Irina D; Sorenson, Nicholas B; Wilczynski, Andrzej M; Holder, Jerry Ryan; Litherland, Sally A; Millard, William J; Mosberg, Henry I; Haskell-Luevano, Carrie

    2007-07-17

    The melanocortin pathway, specifically the melanocortin-4 receptor and the cognate endogenous agonist and antagonist ligands, have been strongly implicated in the regulation of energy homeostasis and satiety. Genetic studies of morbidly obese human patients and normal weight control patients have resulted in the discovery of over 70 human melanocortin-4 receptor (MC4R) polymorphisms observed as both heterozygous and homozygous forms. A number of laboratories have been studying these hMC4R polymorphisms attempting to understand the molecular mechanism(s) that might explain the obese human phenotype. Herein, we have studied 13 polymorphic hMC4Rs that have been identified to possess statistically significant decreased endogenous agonist potency with synthetic peptides and small molecules attempting to identify ligands that can pharmacologically rescue the hMC4R polymorphic agonist response. The ligands examined in this study include NDP-MSH, MTII, Ac-His-DPhe-Arg-Trp-NH2 (JRH887-9), Ac-Anc-DPhe-Arg-Trp-NH2 (amino-2-naphtylcarboxylic acid, Anc, JRH420-12), Ac-His-(pI)DPhe-Arg-Trp-NH2 (JRH322-18), chimeric AGRP-melanocortin based ligands (Tyr-c[Cys-His-DPhe-Arg-Trp-Asn-Ala-Phe-Cys]-Tyr-NH2, AMW3-130 and Ac-mini-(His-DPhe-Arg-Trp)-hAGRP-NH2, AMW3-106), and the small molecules JB25 and THIQ. The hMC4R polymorphisms included in this study are S58C, N97D, I102S, L106P, S127L, T150I, R165Q, R165W, L250Q, G252S, C271Y, Y287Stop, and I301T. These studies resulted in the NDP-MSH, MTII, AMW3-130, THIQ, and AMW3-106 ligands possessing nanomolar to subnanomolar agonist potency at the hMC4R polymorphisms examined in this study. Thus, these ligands could generically rescue the potency and stimulatory response of the abnormally functioning hMC4Rs studied and may provide tools to further clarify the molecular mechanism(s) involving these receptor modifications.

  9. Measuring the strength of interaction between the Ebola fusion peptide and lipid rafts: implications for membrane fusion and virus infection.

    Directory of Open Access Journals (Sweden)

    Mônica S Freitas

    Full Text Available The Ebola fusion peptide (EBO₁₆ is a hydrophobic domain that belongs to the GP2 membrane fusion protein of the Ebola virus. It adopts a helical structure in the presence of mimetic membranes that is stabilized by the presence of an aromatic-aromatic interaction established by Trp8 and Phe12. In spite of its infectious cycle becoming better understood recently, several steps still remain unclear, a lacuna that makes it difficult to develop strategies to block infection. In order to gain insight into the mechanism of membrane fusion, we probed the structure, function and energetics of EBO₁₆ and its mutant W8A, in the absence or presence of different lipid membranes, including isolated domain-resistant membranes (DRM, a good experimental model for lipid rafts. The depletion of cholesterol from living mammalian cells reduced the ability of EBO₁₆ to induce lipid mixing. On the other hand, EBO₁₆ was structurally sensitive to interaction with lipid rafts (DRMs, but the same was not observed for W8A mutant. In agreement with these data, W8A showed a poor ability to promote membrane aggregation in comparison to EBO₁₆. Single molecule AFM experiments showed a high affinity force pattern for the interaction of EBO₁₆ and DRM, which seems to be a complex energetic event as observed by the calorimetric profile. Our study is the first to show a strong correlation between the initial step of Ebola virus infection and cholesterol, thus providing a rationale for Ebola virus proteins being co-localized with lipid-raft domains. In all, the results show how small fusion peptide sequences have evolved to adopt highly specific and strong interactions with membrane domains. Such features suggest these processes are excellent targets for therapeutic and vaccine approaches to viral diseases.

  10. Measuring the strength of interaction between the Ebola fusion peptide and lipid rafts: implications for membrane fusion and virus infection.

    Science.gov (United States)

    Freitas, Mônica S; Follmer, Cristian; Costa, Lilian T; Vilani, Cecília; Bianconi, M Lucia; Achete, Carlos Alberto; Silva, Jerson L

    2011-01-13

    The Ebola fusion peptide (EBO₁₆) is a hydrophobic domain that belongs to the GP2 membrane fusion protein of the Ebola virus. It adopts a helical structure in the presence of mimetic membranes that is stabilized by the presence of an aromatic-aromatic interaction established by Trp8 and Phe12. In spite of its infectious cycle becoming better understood recently, several steps still remain unclear, a lacuna that makes it difficult to develop strategies to block infection. In order to gain insight into the mechanism of membrane fusion, we probed the structure, function and energetics of EBO₁₆ and its mutant W8A, in the absence or presence of different lipid membranes, including isolated domain-resistant membranes (DRM), a good experimental model for lipid rafts. The depletion of cholesterol from living mammalian cells reduced the ability of EBO₁₆ to induce lipid mixing. On the other hand, EBO₁₆ was structurally sensitive to interaction with lipid rafts (DRMs), but the same was not observed for W8A mutant. In agreement with these data, W8A showed a poor ability to promote membrane aggregation in comparison to EBO₁₆. Single molecule AFM experiments showed a high affinity force pattern for the interaction of EBO₁₆ and DRM, which seems to be a complex energetic event as observed by the calorimetric profile. Our study is the first to show a strong correlation between the initial step of Ebola virus infection and cholesterol, thus providing a rationale for Ebola virus proteins being co-localized with lipid-raft domains. In all, the results show how small fusion peptide sequences have evolved to adopt highly specific and strong interactions with membrane domains. Such features suggest these processes are excellent targets for therapeutic and vaccine approaches to viral diseases.

  11. Universal antibodies against the highly conserved influenza fusion peptide cross-neutralize several subtypes of influenza A virus

    Energy Technology Data Exchange (ETDEWEB)

    Hashem, Anwar M. [Centre for Vaccine Evaluation, Biologics and Genetic Therapies Directorate, HPFB, Health Canada, Ottawa, ON (Canada); Department of Microbiology, Faculty of Medicine, King Abdulaziz University, Jeddah (Saudi Arabia); Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON (Canada); Van Domselaar, Gary [National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB (Canada); Li, Changgui; Wang, Junzhi [National Institute for the Control of Pharmaceutical and Biological Products, Beijing (China); She, Yi-Min; Cyr, Terry D. [Centre for Vaccine Evaluation, Biologics and Genetic Therapies Directorate, HPFB, Health Canada, Ottawa, ON (Canada); Sui, Jianhua [Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Department of Medicine, Harvard Medical School, 44 Binney Street, Boston, MA 02115 (United States); He, Runtao [National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB (Canada); Marasco, Wayne A. [Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Department of Medicine, Harvard Medical School, 44 Binney Street, Boston, MA 02115 (United States); Li, Xuguang, E-mail: Sean.Li@hc-sc.gc.ca [Centre for Vaccine Evaluation, Biologics and Genetic Therapies Directorate, HPFB, Health Canada, Ottawa, ON (Canada); Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON (Canada)

    2010-12-10

    Research highlights: {yields} The fusion peptide is the only universally conserved epitope in all influenza viral hemagglutinins. {yields} Anti-fusion peptide antibodies are universal antibodies that cross-react with all influenza HA subtypes. {yields} The universal antibodies cross-neutralize different influenza A subtypes. {yields} The universal antibodies inhibit the fusion process between the viruses and the target cells. -- Abstract: The fusion peptide of influenza viral hemagglutinin plays a critical role in virus entry by facilitating membrane fusion between the virus and target cells. As the fusion peptide is the only universally conserved epitope in all influenza A and B viruses, it could be an attractive target for vaccine-induced immune responses. We previously reported that antibodies targeting the first 14 amino acids of the N-terminus of the fusion peptide could bind to virtually all influenza virus strains and quantify hemagglutinins in vaccines produced in embryonated eggs. Here we demonstrate that these universal antibodies bind to the viral hemagglutinins in native conformation presented in infected mammalian cell cultures and neutralize multiple subtypes of virus by inhibiting the pH-dependant fusion of viral and cellular membranes. These results suggest that this unique, highly-conserved linear sequence in viral hemagglutinin is exposed sufficiently to be attacked by the antibodies during the course of infection and merits further investigation because of potential importance in the protection against diverse strains of influenza viruses.

  12. Universal antibodies against the highly conserved influenza fusion peptide cross-neutralize several subtypes of influenza A virus

    International Nuclear Information System (INIS)

    Hashem, Anwar M.; Van Domselaar, Gary; Li, Changgui; Wang, Junzhi; She, Yi-Min; Cyr, Terry D.; Sui, Jianhua; He, Runtao; Marasco, Wayne A.; Li, Xuguang

    2010-01-01

    Research highlights: → The fusion peptide is the only universally conserved epitope in all influenza viral hemagglutinins. → Anti-fusion peptide antibodies are universal antibodies that cross-react with all influenza HA subtypes. → The universal antibodies cross-neutralize different influenza A subtypes. → The universal antibodies inhibit the fusion process between the viruses and the target cells. -- Abstract: The fusion peptide of influenza viral hemagglutinin plays a critical role in virus entry by facilitating membrane fusion between the virus and target cells. As the fusion peptide is the only universally conserved epitope in all influenza A and B viruses, it could be an attractive target for vaccine-induced immune responses. We previously reported that antibodies targeting the first 14 amino acids of the N-terminus of the fusion peptide could bind to virtually all influenza virus strains and quantify hemagglutinins in vaccines produced in embryonated eggs. Here we demonstrate that these universal antibodies bind to the viral hemagglutinins in native conformation presented in infected mammalian cell cultures and neutralize multiple subtypes of virus by inhibiting the pH-dependant fusion of viral and cellular membranes. These results suggest that this unique, highly-conserved linear sequence in viral hemagglutinin is exposed sufficiently to be attacked by the antibodies during the course of infection and merits further investigation because of potential importance in the protection against diverse strains of influenza viruses.

  13. A Fusion-Inhibiting Peptide against Rift Valley Fever Virus Inhibits Multiple, Diverse Viruses

    Science.gov (United States)

    2013-09-12

    performance liquid chroma- tography to greater than 95% purity (Bio-synthesis, Inc., Lewisville, TX). Lyophilized peptides were initially resuspended in...lesser extent RVFV-6sc, were found to precipitate Gc (Figure 5); however, in the presence of the non- ionic detergent Triton-X, which will solubilize...Viral membrane fusion. Nat Struct Mol Biol 15: 690–698. 12. Allison SL, Schalich J, Stiasny K, Mandl CW, Kunz C, et al. (1995) Oligomeric rearrangement

  14. Impact of peptide clustering on unbinding forces in the context of fusion mimetics

    International Nuclear Information System (INIS)

    Pähler, Gesa; Lorenz, Bärbel; Janshoff, Andreas

    2013-01-01

    Highlights: ► Coiled-coil peptides as SNARE mimetics for membrane fusion. ► Interaction forces assessed by colloidal probe microscopy. ► Lateral organization of lipopeptides visualized by atomic force microscopy. -- Abstract: Coiled-coil zipping and unzipping is a pivotal process in SNARE-regulated membrane fusion. In this study we examine this process mediated by a minimal model for coiled-coil formation employing force spectroscopy in the context of membrane-coated surfaces and probes. The interaction forces of several hundred pN are surprisingly low considering the proposed amount of molecular bonds in the contact zone. However, by means of high-resolution imaging employing atomic force microscopy and studying the lateral mobility of lipids and peptides as a function of coiled-coil formation, we are able to supply a detailed view on processes occurring on the membrane surfaces during force measurements. The interaction forces determined here are not only dependent on the peptide concentration on the surface, but also on the regional organization of lateral peptide clusters found prior to coiled-coil formation

  15. A general strategy to endow natural fusion-protein-derived peptides with potent antiviral activity.

    Directory of Open Access Journals (Sweden)

    Antonello Pessi

    Full Text Available Fusion between the viral and target cell membranes is an obligatory step for the infectivity of all enveloped virus, and blocking this process is a clinically validated therapeutic strategy.Viral fusion is driven by specialized proteins which, although specific to each virus, act through a common mechanism, the formation of a complex between two heptad repeat (HR regions. The HR regions are initially separated in an intermediate termed "prehairpin", which bridges the viral and cell membranes, and then fold onto each other to form a 6-helical bundle (6HB, driving the two membranes to fuse. HR-derived peptides can inhibit viral infectivity by binding to the prehairpin intermediate and preventing its transition to the 6HB.The antiviral activity of HR-derived peptides differs considerably among enveloped viruses. For weak inhibitors, potency can be increased by peptide engineering strategies, but sequence-specific optimization is time-consuming. In seeking ways to increase potency without changing the native sequence, we previously reported that attachment to the HR peptide of a cholesterol group ("cholesterol-tagging" dramatically increases its antiviral potency, and simultaneously increases its half-life in vivo. We show here that antiviral potency may be increased by combining cholesterol-tagging with dimerization of the HR-derived sequence, using as examples human parainfluenza virus, Nipah virus, and HIV-1. Together, cholesterol-tagging and dimerization may represent strategies to boost HR peptide potency to levels that in some cases may be compatible with in vivo use, possibly contributing to emergency responses to outbreaks of existing or novel viruses.

  16. Structural Study of a New HIV-1 Entry Inhibitor and Interaction with the HIV-1 Fusion Peptide in Dodecylphosphocholine Micelles.

    Science.gov (United States)

    Pérez, Yolanda; Gómara, Maria José; Yuste, Eloísa; Gómez-Gutierrez, Patricia; Pérez, Juan Jesús; Haro, Isabel

    2017-08-25

    Previous studies support the hypothesis that the envelope GB virus C (GBV-C) E1 protein interferes the HIV-1 entry and that a peptide, derived from the region 139-156 of this protein, has been defined as a novel HIV-1 entry inhibitor. In this work, we firstly focus on the characterization of the structural features of this peptide, which are determinant for its anti-HIV-1 activity and secondly, on the study of its interaction with the proposed viral target (i.e., the HIV-1 fusion peptide). We report the structure of the peptide determined by NMR spectroscopy in dodecylphosphocholine (DPC) micelles solved by using restrained molecular dynamics calculations. The acquisition of different NMR experiments in DPC micelles (i.e., peptide-peptide titration, diffusion NMR spectroscopy, and addition of paramagnetic relaxation agents) allows a proposal of an inhibition mechanism. We conclude that a 18-mer peptide from the non-pathogenic E1 GBV-C protein, with a helix-turn-helix structure inhibits HIV-1 by binding to the HIV-1 fusion peptide at the membrane level, thereby interfering with those domains in the HIV-1, which are critical for stabilizing the six-helix bundle formation in a membranous environment. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Coiled-coil formation of the membrane-fusion K/E peptides viewed by electron paramagnetic resonance.

    Directory of Open Access Journals (Sweden)

    Pravin Kumar

    Full Text Available The interaction of the complementary K (Ac-(KIAALKE3-GW-NH2 and E (Ac-(EIAALEK3-GY-NH2 peptides, components of the zipper of an artificial membrane fusion system (Robson Marsden H. et al. Angew Chemie Int Ed. 2009 is investigated by electron paramagnetic resonance (EPR. By frozen solution continuous-wave EPR and double electron-electron resonance (DEER, the distance between spin labels attached to the K- and to the E-peptide is measured. Three constructs of spin-labelled K- and E-peptides are used in five combinations for low temperature investigations. The K/E heterodimers are found to be parallel, in agreement with previous studies. Also, K homodimers in parallel orientation were observed, a finding that was not reported before. Comparison to room-temperature, solution EPR shows that the latter method is less specific to detect this peptide-peptide interaction. Combining frozen solution cw-EPR for short distances (1.8 nm to 2.0 nm and DEER for longer distances thus proves versatile to detect the zipper interaction in membrane fusion. As the methodology can be applied to membrane samples, the approach presented suggests itself for in-situ studies of the complete membrane fusion process, opening up new avenues for the study of membrane fusion.

  18. Expression and Purification of Neurotrophin-Elastin-Like Peptide Fusion Proteins for Neural Regeneration.

    Science.gov (United States)

    Johnson, Tamina; Koria, Piyush

    2016-04-01

    Neural injuries such as spinal cord injuries, traumatic brain injuries, or nerve transection injuries pose a major health problem. Neurotrophins such as nerve growth factor (NGF) or brain-derived neurotrophic factor (BDNF) have been shown to improve the outcome of neural injuries in several pre-clinical models, but their use in clinics is limited by the lack of a robust delivery system that enhances their bioavailability and half-life. We describe two fusion proteins comprising NGF or BDNF fused with elastin-like peptides (ELPs). The aim of this study was to investigate the biological activity of neurotrophin-ELP (N-ELP) fusion proteins via in vitro culture models. NGF and BDNF were cloned in front of an elastin-like polypeptide sequence V40C2. These proteins were expressed in bacteria as inclusion bodies. These fusion proteins underwent solubilization via 8 M urea and purification via inverse transition cycling (ITC). We measured the particle size and the effect of temperature on precipitated particles using dynamic light scattering (DLS). We used western blot analysis to confirm the specificity of NGF-ELP to tropomyosin receptor kinase A (TrkA) antibody and to confirm the specificity of BDNF-ELP to TrkB antibody. PC12 cells were used to perform a neurite outgrowth assay to determine the biological activity of NGF-ELP. Bioactivity of BDNF-ELP was ascertained via transfecting human epithelial kidney (HEK 293-T) cells to express the TrkB receptor. The proteins were successfully purified to high homogeneity by exploiting the phase transition property of ELPs and urea, which solubilize inclusion bodies. Using PC12 neurite outgrowth assay, we further demonstrated that the biological activity of NGF was retained in the fusion. Similarly, BDNF-ELP phosphorylated the TrkB receptor, suggesting the biological activity of BDNF was also retained in the fusion. We further show that owing to the phase transition property of ELPs in the fusion, these proteins self-assembled into

  19. Solid-State Nuclear Magnetic Resonance Investigation of the Structural Topology and Lipid Interactions of a Viral Fusion Protein Chimera Containing the Fusion Peptide and Transmembrane Domain.

    Science.gov (United States)

    Yao, Hongwei; Lee, Myungwoon; Liao, Shu-Yu; Hong, Mei

    2016-12-13

    The fusion peptide (FP) and transmembrane domain (TMD) of viral fusion proteins play important roles during virus-cell membrane fusion, by inducing membrane curvature and transient dehydration. The structure of the water-soluble ectodomain of viral fusion proteins has been extensively studied crystallographically, but the structures of the FP and TMD bound to phospholipid membranes are not well understood. We recently investigated the conformations and lipid interactions of the separate FP and TMD peptides of parainfluenza virus 5 (PIV5) fusion protein F using solid-state nuclear magnetic resonance. These studies provide structural information about the two domains when they are spatially well separated in the fusion process. To investigate how these two domains are structured relative to each other in the postfusion state, when the ectodomain forms a six-helix bundle that is thought to force the FP and TMD together in the membrane, we have now expressed and purified a chimera of the FP and TMD, connected by a Gly-Lys linker, and measured the chemical shifts and interdomain contacts of the protein in several lipid membranes. The FP-TMD chimera exhibits α-helical chemical shifts in all the membranes examined and does not cause strong curvature of lamellar membranes or membranes with negative spontaneous curvature. These properties differ qualitatively from those of the separate peptides, indicating that the FP and TMD interact with each other in the lipid membrane. However, no 13 C- 13 C cross peaks are observed in two-dimensional correlation spectra, suggesting that the two helices are not tightly associated. These results suggest that the ectodomain six-helix bundle does not propagate into the membrane to the two hydrophobic termini. However, the loosely associated FP and TMD helices are found to generate significant negative Gaussian curvature to membranes that possess spontaneous positive curvature, consistent with the notion that the FP-TMD assembly may

  20. Evaluation of cell binding peptide (p15) with silk fibre enhanced hydroxyappatite bone substitute for posterolateral spinal fusion in sheep

    DEFF Research Database (Denmark)

    Axelsen, M.; Jespersen, Stig; Overgaard, Søren

    2015-01-01

    Background: Spinal fusion is indicated in the surgical management of various spinal disorders. To ensure stabile fusion, bone graft materials are essential. Traditionally allo- or autograft has been used, but both are associated with limitations. Synthetic bone graft materials that reassemble today......: In this study, we compared fusion rates between silk fibre enhanced anorganic bovine derived hydroxyapatite matrix (ABM) with and without P15 peptide coating in uninstrumented PLF in a preclinical setting. Study design: Randomised prospective study in sheep. Method/materials: Twelve Tex/got sheep underwent open...

  1. Nematode Peptides with host-directed anti-inflammatory activity rescue Caenorhabditis elegans from a Burkholderia pseudomallei infection

    Directory of Open Access Journals (Sweden)

    Mei-Perng Lim

    2016-09-01

    Full Text Available Burkholderia pseudomallei, the causative agent of melioidosis, is among a growing number of bacterial pathogens that are increasingly antibiotic resistant. Antimicrobial peptides (AMPs have been investigated as an alternative approach to treat microbial infections, as generally, there is a lower likelihood that a pathogen will develop resistance to AMPs. In this study, 36 candidate Caenorhabditis elegans genes that encode secreted peptides of <150 amino acids and previously shown to be overexpressed during infection by B. pseudomallei were identified from the expression profile of infected nematodes. RNA interference (RNAi-based knockdown of 12/34 peptide-encoding genes resulted in enhanced nematode susceptibility to B. pseudomallei without affecting worm fitness. A microdilution test demonstrated that two peptides, NLP-31 and Y43C5A.3, exhibited anti-B. pseudomallei activity in a dose dependent manner on different pathogens. Time kill analysis proposed that these peptides were bacteriostatic against B. pseudomallei at concentrations up to 8× MIC90. The SYTOX green assay demonstrated that NLP-31 and Y43C5A.3 did not disrupt the B. pseudomallei membrane. Instead, gel retardation assays revealed that both peptides were able to bind to DNA and interfere with bacterial viability. In parallel, microscopic examination showed induction of cellular filamentation, a hallmark of DNA synthesis inhibition, of NLP-31 and Y43C5A.3 treated cells. In addition, the peptides also regulated the expression of inflammatory cytokines in B. pseudomallei infected macrophage cells. Collectively, these findings demonstrate the potential of NLP-31 and Y43C5A.3 as anti-B. pseudomallei peptides based on their function as immune modulators.

  2. Characterisation and evaluation of antiviral recombinant peptides based on the heptad repeat regions of NDV and IBV fusion glycoproteins

    International Nuclear Information System (INIS)

    Wang Xiaojia; Li Chuangen; Chi Xiaojing; Wang Ming

    2011-01-01

    Mixed virus infections can cause livestock losses that are more devastating than those caused by single virus infections. Newcastle disease virus (NDV) and infectious bronchitis virus (IBV), serious threats to the poultry industry, can give rise to complex mixed infections that hinder diagnosis and prevention. In this study, we show that newly designed peptides, which are based on the heptad repeat (HR) region of the fusion glycoproteins from NDV and IBV, have more potent antiviral activity than the mother HR peptides. Plaque formation and chicken embryo infectivity assays confirmed these results. The novel peptides completely inhibited single virus infections and mixed infections caused by NDV and IBV. Furthermore, we assessed cell toxicity and possible targets for the peptides, thereby strengthening the notion that HR2 is an attractive site for therapeutic intervention. These results suggest the possibility of designing a relatively broad-spectrum class of antiviral peptides that can reduce the effects of mixed-infections.

  3. Blocking the Interaction between EphB2 and ADDLs by a Small Peptide Rescues Impaired Synaptic Plasticity and Memory Deficits in a Mouse Model of Alzheimer's Disease.

    Science.gov (United States)

    Shi, Xiao-Dong; Sun, Kai; Hu, Rui; Liu, Xiao-Ya; Hu, Qiu-Mei; Sun, Xiao-Yu; Yao, Bin; Sun, Nan; Hao, Jing-Ru; Wei, Pan; Han, Yuan; Gao, Can

    2016-11-23

    Soluble amyloid-β (Aβ) oligomers, also known as Aβ-derived diffusible ligands (ADDLs), are thought to be the key pathogenic factor in Alzheimer's disease (AD), but there is still no effective treatment for preventing or reversing the progression of the disease. Targeting NMDA receptor trafficking and regulation is a new strategy for early treatment of AD. Aβ oligomers have been found to bind to the fibronectin (FN) type III repeat domain of EphB2 to trigger EphB2 degradation, thereby impairing the normal functioning of NMDA receptors and resulting in cognitive deficits. Here, we identified for the first time the interaction sites of the EphB2 FN domain with ADDLs by applying the peptide array method to design and synthesize four candidate peptides (Pep21, Pep25, Pep32, and Pep63) that might be able to block the EphB2-ADDL interaction. Among them, Pep63 was found to be the most effective at inhibiting the binding between EphB2 and ADDLs. We found that Pep63 not only rescued the ADDL-induced depletion of EphB2- and GluN2B-containing NMDA receptors from the neuronal surface in cultured hippocampal neurons, but also improved impaired memory deficits in APPswe/PS1dE9 (APP/PS1) transgenic mice and the phosphorylation and surface expression of GluN2B-containing NMDA receptors in cultures. Together, these results suggest that blocking the EphB2-ADDL interaction by small interfering peptides may be a promising strategy for AD treatment. Alzheimer's disease (AD) is an age-dependent neurodegenerative disorder and amyloid β-derived diffusible ligands (ADDLs) play a key role in triggering the early cognitive deficits that constitute AD. ADDLs may bind EphB2 and alter NMDA receptor trafficking and synaptic plasticity. Here, we identified the interaction sites of the EphB2 FN domain with ADDLs for the first time to develop a small (10 aa) peptide (Pep63) capable of blocking the EphB2-ADDL interaction. We found that Pep63 not only rescued the ADDL-induced depletion of EphB2

  4. Design, Recombinant Fusion Expression and Biological Evaluation of Vasoactive Intestinal Peptide Analogue as Novel Antimicrobial Agent

    Directory of Open Access Journals (Sweden)

    Chunlan Xu

    2017-11-01

    Full Text Available Antimicrobial peptides represent an emerging category of therapeutic agents with remarkable structural and functional diversity. Modified vasoactive intestinal peptide (VIP (VIP analogue 8 with amino acid sequence “FTANYTRLRRQLAVRRYLAAILGRR” without haemolytic activity and cytotoxicity displayed enhanced antimicrobial activities against Staphylococcus aureus (S. aureus ATCC 25923 and Escherichia coli (E. coli ATCC 25922 than parent VIP even in the presence of 180 mM NaCl or 50 mM MgCl2, or in the range of pH 4–10. VIP analogue 8 was expressed as fusion protein thioredoxin (Trx-VIP8 in E. coli BL21(DE at a yield of 45.67 mg/L. The minimum inhibitory concentration (MIC of the recombinant VIP analogue 8 against S. aureus ATCC 25923 and E. coli ATCC 25922 were 2 μM. These findings suggest that VIP analogue 8 is a promising candidate for application as a new and safe antimicrobial agent.

  5. Structural and functional characterization of EIAV gp45 fusion peptide proximal region and asparagine-rich layer

    Energy Technology Data Exchange (ETDEWEB)

    Duan, Liangwei; Du, Jiansen [State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071 (China); Wang, Xuefeng; Zhou, Jianhua; Wang, Xiaojun [State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150001 (China); Liu, Xinqi, E-mail: liu2008@nankai.edu.cn [State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071 (China)

    2016-04-15

    Equine infectious anaemia virus (EIAV) and human immunodeficiency virus (HIV) are members of the lentiviral genus. Similar to HIV gp41, EIAV gp45 is a fusogenic protein that mediates fusion between the viral particle and the host cell membrane. The crystal structure of gp45 reported reveals a different conformation in the here that includes the fusion peptide proximal region (FPPR) and neighboring asparagine-rich layer compared with previous HIV-1 gp41 structures. A complicated hydrogen-bond network containing a cluster of solvent molecules appears to be critical for the stability of the gp45 helical bundle. Interestingly, viral replication was relatively unaffected by site-directed mutagenesis of EIAV, in striking contrast to that of HIV-1. Based on these observations, we speculate that EIAV is more adaptable to emergent mutations, which might be important for the evolution of EIAV as a quasi-species, and could potentially contribute to the success of the EIAV vaccine. - Highlights: • The crystal structure of EIAV gp45 was determined. • The fusion peptide proximal region adopts a novel conformation different to HIV-1. • The asparagine-rich layer includes an extensive hydrogen-bond network. • These regions of EIAV are highly tolerant to mutations. • The results provide insight into the mechanism of gp41/gp45-mediated membrane fusion.

  6. Gene design, fusion technology and TEV cleavage conditions influence the purification of oxidized disulphide-rich venom peptides in Escherichia coli.

    Science.gov (United States)

    Sequeira, Ana Filipa; Turchetto, Jeremy; Saez, Natalie J; Peysson, Fanny; Ramond, Laurie; Duhoo, Yoan; Blémont, Marilyne; Fernandes, Vânia O; Gama, Luís T; Ferreira, Luís M A; Guerreiro, Catarina I P I; Gilles, Nicolas; Darbon, Hervé; Fontes, Carlos M G A; Vincentelli, Renaud

    2017-01-17

    Animal venoms are large, complex libraries of bioactive, disulphide-rich peptides. These peptides, and their novel biological activities, are of increasing pharmacological and therapeutic importance. However, recombinant expression of venom peptides in Escherichia coli remains difficult due to the significant number of cysteine residues requiring effective post-translational processing. There is also an urgent need to develop high-throughput recombinant protocols applicable to the production of reticulated peptides to enable efficient screening of their drug potential. Here, a comprehensive study was developed to investigate how synthetic gene design, choice of fusion tag, compartment of expression, tag removal conditions and protease recognition site affect levels of solubility of oxidized venom peptides produced in E. coli. The data revealed that expression of venom peptides imposes significant pressure on cysteine codon selection. DsbC was the best fusion tag for venom peptide expression, in particular when the fusion was directed to the bacterial periplasm. While the redox activity of DsbC was not essential to maximize expression of recombinant fusion proteins, redox activity did lead to higher levels of correctly folded target peptides. With the exception of proline, the canonical TEV protease recognition site tolerated all other residues at its C-terminus, confirming that no non-native residues, which might affect activity, need to be incorporated at the N-terminus of recombinant peptides for tag removal. This study reveals that E. coli is a convenient heterologous host for the expression of soluble and functional venom peptides. Using the optimal construct design, a large and diverse range of animal venom peptides were produced in the µM scale. These results open up new possibilities for the high-throughput production of recombinant disulphide-rich peptides in E. coli.

  7. Flunarizine Prevents Hepatitis C Virus Membrane Fusion in a Genotype-dependent Manner by Targeting the Potential Fusion Peptide within E1

    Science.gov (United States)

    Perin, Paula M.; Haid, Sibylle; Brown, Richard J. P.; Doerrbecker, Juliane; Schulze, Kai; Zeilinger, Carsten; von Schaewen, Markus; Heller, Brigitte; Vercauteren, Koen; Luxenburger, Eva; Baktash, Yasmine M.; Vondran, Florian W. R.; Speerstra, Sietkse; Awadh, Abdullah; Mukhtarov, Furkat; Schang, Luis M; Kirschning, Andreas; Müller, Rolf; Guzman, Carlos A.; Kaderali, Lars; Randall, Glenn; Meuleman, Philip; Ploss, Alexander; Pietschmann, Thomas

    2015-01-01

    To explore mechanisms of hepatitis C virus (HCV) replication we screened a compound library including licensed drugs. Flunarizine, a diphenylmethylpiperazine used to treat migraine, inhibited HCV cell entry in vitro and in vivo in a genotype-dependent fashion. Analysis of mosaic viruses between susceptible and resistant strains revealed that E1 and E2 glycoproteins confer susceptibility to flunarizine. Time of addition experiments and single particle tracking of HCV demonstrated that flunarizine specifically prevents membrane fusion. Related phenothiazines and pimozide also inhibited HCV infection and preferentially targeted HCV genotype 2 viruses. However, phenothiazines and pimozide exhibited improved genotype coverage including the difficult to treat genotype 3. Flunarizine-resistant HCV carried mutations within the alleged fusion peptide and displayed cross-resistance to these compounds, indicating that these drugs have a common mode of action. Conclusion: These observations reveal novel details about HCV membrane fusion. Moreover, flunarizine and related compounds represent first-in-class HCV fusion inhibitors that merit consideration for repurposing as cost-effective component of HCV combination therapies. PMID:26248546

  8. Expression and purification of chimeric peptide comprising EGFR B-cell epitope and measles virus fusion protein T-cell epitope in Escherichia coli.

    Science.gov (United States)

    Wu, Meizhi; Zhao, Lin; Zhu, Lei; Chen, Zhange; Li, Huangjin

    2013-03-01

    Chimeric peptide MVF-EGFR(237-267), comprising a B-cell epitope from the dimerization interface of human epidermal growth factor receptor (EGFR) and a promiscuous T-cell epitope from measles virus fusion protein (MVF), is a promising candidate antigen peptide for therapeutic vaccine. To establish a high-efficiency preparation process of this small peptide, the coding sequence was cloned into pET-21b and pET-32a respectively, to be expressed alone or in the form of fusion protein with thioredoxin (Trx) and His(6)-tag in Escherichia coli BL21 (DE3). The chimeric peptide failed to be expressed alone, but over-expressed in the fusion form, which presented as soluble protein and took up more than 30% of total proteins of host cells. The fusion protein was seriously degraded during the cell disruption, in which endogenous metalloproteinase played a key role. Degradation of target peptide was inhibited by combined application of EDTA in the cell disruption buffer and a step of Source 30Q anion exchange chromatography (AEC) before metal-chelating chromatography (MCAC) for purifying His(6)-tagged fusion protein. The chimeric peptide was recovered from the purified fusion protein by enterokinase digestion at a yield of 3.0 mg/L bacteria culture with a purity of more than 95%. Immunogenicity analysis showed that the recombinant chimeric peptide was able to arouse more than 1×10(4) titers of specific antibody in BALB/c mice. Present work laid a solid foundation for the development of therapeutic peptide vaccine targeting EGFR dimerization and provided a convenient and low-cost preparation method for small peptides. Copyright © 2012 Elsevier Inc. All rights reserved.

  9. Specific expression of GFPuv-β1,3-N-acetylglucosaminyltransferase 2 fusion protein in fat body of Bombyx mori silkworm larvae using signal peptide

    International Nuclear Information System (INIS)

    Kato, Tatsuya; Park, Enoch Y.

    2007-01-01

    Bombyxin (bx) and prophenoloxidase-activating enzyme (ppae) signal peptides from Bombyx mori, their modified signal peptides, and synthetic signal peptides were investigated for the secretion of GFP uv -β1,3-N-acetylglucosaminyltransferase 2 (GGT2) fusion protein in B. mori Bm5 cells and silkworm larvae using cysteine protease deficient B. mori multiple nucleopolyhedrovirus (BmMNPV-CP - ) and its bacmid. The secretion efficiencies of all signal peptides were 15-30% in Bm5 cells and 24-30% in silkworm larvae, while that of the +16 signal peptide was 0% in Bm5 cells and 1% in silkworm larvae. The fusion protein that contained the +16 signal peptide was expressed specifically in the endoplasmic reticulum (ER) and in the fractions of cell precipitations. Ninety-four percent of total intracellular β1,3-N-acetylglucosaminyltransferase (β3GnT) activity was detected in cell precipitations following the 600, 8000, and 114,000g centrifugations. In the case of the +38 signal peptide, 60% of total intracellular activity was detected in the supernatant from the 114,000g spin, and only 1% was found in the precipitate. Our results suggest that the +16 signal peptide might be situated in the transmembrane region and not cleaved by signal peptidase in silkworm or B. mori cells. Therefore, the fusion protein connected to the +16 signal peptide stayed in the fat body of silkworm larvae with biological function, and was not secreted extracellularly

  10. Intracerebroventricular Infusion of Vasoactive Intestinal Peptide (VIP Rescues the Luteinizing Hormone Surge in Middle-Aged Female Rats

    Directory of Open Access Journals (Sweden)

    Yan eSun

    2012-02-01

    Full Text Available Reproductive aging is characterized by delayed and attenuated luteinizing hormone (LH surges apparent in middle-aged rats. The suprachiasmatic nucleus (SCN contains the circadian clock that is responsible for the timing of diverse neuroendocrine rhythms. Electrophysiological studies suggest vasoactive intestinal peptide (VIP originating from the SCN excites gonadotropin-releasing hormone (GnRH neurons and affects daily patterns of GnRH-LH release. Age-related LH surge dysfunction correlates with reduced VIP mRNA expression in the SCN and fewer GnRH neurons with VIP contacts expressing c-fos, a marker of neuronal activation, on the day of the LH surge. To determine if age-related LH surge dysfunction reflects reduced VIP availability or altered VIP responsiveness under estradiol positive feedback conditions, we assessed the effect of intracerebroventricular (icv VIP infusion on c-fos expression in GnRH neurons and on LH release in ovariohysterectomized, hormone-primed young and middle-aged rats. Icv infusion of VIP between 1300 and 1600 h significantly advanced the time of peak LH release, increased total and peak LH release, and increased the number of GnRH neurons expressing c-fos on the day of the LH surge in middle-aged rats. Surprisingly, icv infusion of VIP in young females significantly reduced the number of GnRH neurons expressing c-fos and delayed and reduced the LH surge. These observations suggest that a critical balance of VIP signaling is required to activate GnRH neurons for an appropriately timed and robust LH surge in young and middle-aged females. Age-related LH surge changes may, in part, result from decreased availability and reduced VIP-mediated neurotransmission under estradiol positive feedback conditions.

  11. Control of silicification by genetically engineered fusion proteins: Silk–silica binding peptides

    Science.gov (United States)

    Zhou, Shun; Huang, Wenwen; Belton, David J.; Simmons, Leo O.; Perry, Carole C.; Wang, Xiaoqin; Kaplan, David L.

    2014-01-01

    In the present study, an artificial spider silk gene, 6mer, derived from the consensus sequence of Nephila clavipes dragline silk gene, was fused with different silica-binding peptides (SiBPs), A1, A3 and R5, to study the impact of the fusion protein sequence chemistry on silica formation and the ability to generate a silk–silica composite in two different bioinspired silicification systems: solution–solution and solution– solid. Condensed silica nanoscale particles (600–800 nm) were formed in the presence of the recombinant silk and chimeras, which were smaller than those formed by 15mer-SiBP chimeras [1], revealing that the molecular weight of the silk domain correlated to the sizes of the condensed silica particles in the solution system. In addition, the chimeras (6mer-A1/A3/R5) produced smaller condensed silica particles than the control (6mer), revealing that the silica particle size formed in the solution system is controlled by the size of protein assemblies in solution. In the solution–solid interface system, silicification reactions were performed on the surface of films fabricated from the recombinant silk proteins and chimeras and then treated to induce β-sheet formation. A higher density of condensed silica formed on the films containing the lowest β-sheet content while the films with the highest β-sheet content precipitated the lowest density of silica, revealing an inverse correlation between the β-sheet secondary structure and the silica content formed on the films. Intriguingly, the 6mer-A3 showed the highest rate of silica condensation but the lowest density of silica deposition on the films, compared with 6mer-A1 and -R5, revealing antagonistic crosstalk between the silk and the SiBP domains in terms of protein assembly. These findings offer a path forward in the tailoring of biopolymer–silica composites for biomaterial related needs. PMID:25462851

  12. Intracellular delivery of cell-penetrating peptide-transcriptional factor fusion protein and its role in selective osteogenesis

    Science.gov (United States)

    Suh, Jin Sook; Lee, Jue Yeon; Choi, Yoon Jung; You, Hyung Keun; Hong, Seong-Doo; Chung, Chong Pyoung; Park, Yoon Jeong

    2014-01-01

    Protein-transduction technology has been attempted to deliver macromolecular materials, including protein, nucleic acids, and polymeric drugs, for either diagnosis or therapeutic purposes. Herein, fusion protein composed of an arginine-rich cell-penetrating peptide, termed low-molecular-weight protamine (LMWP), and a transcriptional coactivator with a PDZ-binding motif (TAZ) protein was prepared and applied in combination with biomaterials to increase bone-forming capacity. TAZ has been recently identified as a specific osteogenic stimulating transcriptional coactivator in human mesenchymal stem cell (hMSC) differentiation, while simultaneously blocking adipogenic differentiation. However, TAZ by itself cannot penetrate the cells, and thus needs a transfection tool for translocalization. The LMWP-TAZ fusion proteins were efficiently translocalized into the cytosol of hMSCs. The hMSCs treated with cell-penetrating LMWP-TAZ exhibited increased expression of osteoblastic genes and protein, producing significantly higher quantities of mineralized matrix compared to free TAZ. In contrast, adipogenic differentiation of the hMSCs was blocked by treatment of LMWP-TAZ fusion protein, as reflected by reduced marker-protein expression, adipocyte fatty acid-binding protein 2, and peroxisome proliferator-activated receptor-γ messenger ribonucleic acid levels. LMWP-TAZ was applied in alginate gel for the purpose of localization and controlled release. The LMWP-TAZ fusion protein-loaded alginate gel matrix significantly increased bone formation in rabbit calvarial defects compared with alginate gel matrix mixed with free TAZ protein. The protein transduction of TAZ fused with cell-penetrating LMWP peptide was able selectively to stimulate osteogenesis in vitro and in vivo. Taken together, this fusion protein-transduction technology for osteogenic protein can thus be applied in combination with biomaterials for tissue regeneration and controlled release for tissue

  13. Structural Insights into the Mechanisms of Action of Short-Peptide HIV-1 Fusion Inhibitors Targeting the Gp41 Pocket

    Directory of Open Access Journals (Sweden)

    Xiujuan Zhang

    2018-02-01

    Full Text Available The deep hydrophobic pocket of HIV-1 gp41 has been considered a drug target, but short-peptides targeting this site usually lack potent antiviral activity. By applying the M-T hook structure, we previously generated highly potent short-peptide fusion inhibitors that specifically targeted the pocket site, such as MT-SC22EK, HP23L, and LP-11. Here, the crystal structures of HP23L and LP-11 bound to the target mimic peptide N36 demonstrated the critical intrahelical and interhelical interactions, especially verifying that the hook-like conformation was finely adopted while the methionine residue was replaced by the oxidation-less prone residue leucine, and that addition of an extra glutamic acid significantly enhanced the binding and inhibitory activities. The structure of HP23L bound to N36 with two mutations (E49K and L57R revealed the critical residues and motifs mediating drug resistance and provided new insights into the mechanism of action of inhibitors. Therefore, the present data help our understanding for the structure-activity relationship (SAR of HIV-1 fusion inhibitors and facilitate the development of novel antiviral drugs.

  14. Antimicrobial Peptides Derived from Fusion Peptides of Influenza A Viruses, a Promising Approach to Designing Potent Antimicrobial Agents.

    Science.gov (United States)

    Wang, Jingyu; Zhong, Wenjing; Lin, Dongguo; Xia, Fan; Wu, Wenjiao; Zhang, Heyuan; Lv, Lin; Liu, Shuwen; He, Jian

    2015-10-01

    The emergence and dissemination of antibiotic-resistant bacterial pathogens have spurred the urgent need to develop novel antimicrobial agents with different mode of action. In this respect, we turned several fusogenic peptides (FPs) derived from the hemagglutinin glycoproteins (HAs) of IAV into potent antibacterials by replacing the negatively or neutrally charged residues of FPs with positively charged lysines. Their antibacterial activities were evaluated by testing the MICs against a panel of bacterial strains including S. aureus, S. mutans, P. aeruginosa, and E. coli. The results showed that peptides HA-FP-1, HA-FP-2-1, and HA-FP-3-1 were effective against both Gram-positive and Gram-negative bacteria with MICs ranging from 1.9 to 16.0 μm, while the toxicities toward mammalian cells were low. In addition, the mode of action and the secondary structure of these peptides were also discussed. These data not only provide several potent peptides displaying promising potential in development as broad antimicrobial agents, but also present a useful strategy in designing new antimicrobial agents. © 2015 John Wiley & Sons A/S.

  15. Space Rescue

    Science.gov (United States)

    Muratore, John F.

    2007-01-01

    Space Rescue has been a topic of speculation for a wide community of people for decades. Astronauts, aerospace engineers, diplomats, medical and rescue professionals, inventors and science fiction writers have all speculated on this problem. Martin Caidin's 1964 novel Marooned dealt with the problems of rescuing a crew stranded in low earth orbit. Legend at the Johnson Space Center says that Caidin's portrayal of a Russian attempt to save the American crew played a pivotal role in convincing the Russians to join the real joint Apollo-Soyuz mission. Space Rescue has been a staple in science fiction television and movies portrayed in programs such as Star Trek, Stargate-SG1 and Space 1999 and movies such as Mission To Mars and Red Planet. As dramatic and as difficult as rescue appears in fictional accounts, in the real world it has even greater drama and greater difficulty. Space rescue is still in its infancy as a discipline and the purpose of this chapter is to describe the issues associated with space rescue and the work done so far in this field. For the purposes of this chapter, the term space rescue will refer to any system which allows for rescue or escape of personnel from situations which endanger human life in a spaceflight operation. This will span the period from crew ingress prior to flight through crew egress postlanding. For the purposes of this chapter, the term primary system will refer to the spacecraft system that a crew is either attempting to escape from or from which an attempt is being made to rescue the crew.

  16. In Vivo Efficacy of Measles Virus Fusion Protein-Derived Peptides Is Modulated by the Properties of Self-Assembly and Membrane Residence

    Science.gov (United States)

    Figueira, T. N.; Palermo, L. M.; Veiga, A. S.; Huey, D.; Alabi, C. A.; Santos, N. C.; Welsch, J. C.; Mathieu, C.; Niewiesk, S.; Moscona, A.

    2016-01-01

    ABSTRACT Measles virus (MV) infection is undergoing resurgence and remains one of the leading causes of death among young children worldwide despite the availability of an effective measles vaccine. MV infects its target cells by coordinated action of the MV hemagglutinin (H) and fusion (F) envelope glycoproteins; upon receptor engagement by H, the prefusion F undergoes a structural transition, extending and inserting into the target cell membrane and then refolding into a postfusion structure that fuses the viral and cell membranes. By interfering with this structural transition of F, peptides derived from the heptad repeat (HR) regions of F can inhibit MV infection at the entry stage. In previous work, we have generated potent MV fusion inhibitors by dimerizing the F-derived peptides and conjugating them to cholesterol. We have shown that prophylactic intranasal administration of our lead fusion inhibitor efficiently protects from MV infection in vivo. We show here that peptides tagged with lipophilic moieties self-assemble into nanoparticles until they reach the target cells, where they are integrated into cell membranes. The self-assembly feature enhances biodistribution and the half-life of the peptides, while integration into the target cell membrane increases fusion inhibitor potency. These factors together modulate in vivo efficacy. The results suggest a new framework for developing effective fusion inhibitory peptides. IMPORTANCE Measles virus (MV) infection causes an acute illness that may be associated with infection of the central nervous system (CNS) and severe neurological disease. No specific treatment is available. We have shown that fusion-inhibitory peptides delivered intranasally provide effective prophylaxis against MV infection. We show here that specific biophysical properties regulate the in vivo efficacy of MV F-derived peptides. PMID:27733647

  17. Fusion

    CERN Document Server

    Mahaffey, James A

    2012-01-01

    As energy problems of the world grow, work toward fusion power continues at a greater pace than ever before. The topic of fusion is one that is often met with the most recognition and interest in the nuclear power arena. Written in clear and jargon-free prose, Fusion explores the big bang of creation to the blackout death of worn-out stars. A brief history of fusion research, beginning with the first tentative theories in the early 20th century, is also discussed, as well as the race for fusion power. This brand-new, full-color resource examines the various programs currently being funded or p

  18. Control of silicification by genetically engineered fusion proteins: silk-silica binding peptides.

    Science.gov (United States)

    Zhou, Shun; Huang, Wenwen; Belton, David J; Simmons, Leo O; Perry, Carole C; Wang, Xiaoqin; Kaplan, David L

    2015-03-01

    In the present study, an artificial spider silk gene, 6mer, derived from the consensus sequence of Nephila clavipes dragline silk gene, was fused with different silica-binding peptides (SiBPs), A1, A3 and R5, to study the impact of the fusion protein sequence chemistry on silica formation and the ability to generate a silk-silica composite in two different bioinspired silicification systems: solution-solution and solution-solid. Condensed silica nanoscale particles (600-800 nm) were formed in the presence of the recombinant silk and chimeras, which were smaller than those formed by 15mer-SiBP chimeras, revealing that the molecular weight of the silk domain correlated to the sizes of the condensed silica particles in the solution system. In addition, the chimeras (6mer-A1/A3/R5) produced smaller condensed silica particles than the control (6mer), revealing that the silica particle size formed in the solution system is controlled by the size of protein assemblies in solution. In the solution-solid interface system, silicification reactions were performed on the surface of films fabricated from the recombinant silk proteins and chimeras and then treated to induce β-sheet formation. A higher density of condensed silica formed on the films containing the lowest β-sheet content while the films with the highest β-sheet content precipitated the lowest density of silica, revealing an inverse correlation between the β-sheet secondary structure and the silica content formed on the films. Intriguingly, the 6mer-A3 showed the highest rate of silica condensation but the lowest density of silica deposition on the films, compared with 6mer-A1 and -R5, revealing antagonistic crosstalk between the silk and the SiBP domains in terms of protein assembly. These findings offer a path forward in the tailoring of biopolymer-silica composites for biomaterial related needs. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  19. Binding of cholesterol and inhibitory peptide derivatives with the fusogenic hydrophobic sequence of F-glycoprotein of HVJ (Sendai virus): possible implication in the fusion reaction

    International Nuclear Information System (INIS)

    Asano, K.; Asano, A.

    1988-01-01

    Specificity of the binding of sterols and related compounds with purified F-protein (fusion protein) of the HVJ (Sendai virus) was studied by binding competition with [ 3 H] cholesterol. Requirement for cholesterol or the A/B ring trans structure and nonrequirement for the 3-hydroxyl group were found in this binding. Binding of 125 I-labeled Z-Phe-Tyr, an inhibitory peptide of viral membrane-cell membrane fusion, was studied by using purified proteins and virions. F-Protein and virions showed a specific binding with the peptide, whereas the result was negative with hemagglutinin and neuraminidase protein. Thermolysin-truncated F-protein (an F-protein derivative deprived of a 2.5-kDa fragment from the N-terminal of the F 1 subunit and without fusogenic activity) exhibited a considerably diminished binding ability both to cholesterol and to inhibitory peptides. Therefore, the N-terminal hydrophobic sequence that was previously assigned as fusogenic seems to be the binding site of these molecules. In support of this, the binding of cholesterol with F-protein was inhibited by Z-Phe-Tyr and other fusion inhibitory peptides, whereas it was not affected with non-fusion-inhibitory Z-Gly-Phe. These results are discussed in relation to the notion that the binding of the N-terminal portion of the F 1 subunit of F-protein with cholesterol in the target cell membranes facilitiates the fusion reaction

  20. Fusing simulation and experiment: The effect of mutations on the structure and activity of the influenza fusion peptide

    Science.gov (United States)

    Lousa, Diana; Pinto, Antónia R. T.; Victor, Bruno L.; Laio, Alessandro; Veiga, Ana S.; Castanho, Miguel A. R. B.; Soares, Cláudio M.

    2016-01-01

    During the infection process, the influenza fusion peptide (FP) inserts into the host membrane, playing a crucial role in the fusion process between the viral and host membranes. In this work we used a combination of simulation and experimental techniques to analyse the molecular details of this process, which are largely unknown. Although the FP structure has been obtained by NMR in detergent micelles, there is no atomic structure information in membranes. To answer this question, we performed bias-exchange metadynamics (BE-META) simulations, which showed that the lowest energy states of the membrane-inserted FP correspond to helical-hairpin conformations similar to that observed in micelles. BE-META simulations of the G1V, W14A, G12A/G13A and G4A/G8A/G16A/G20A mutants revealed that all the mutations affect the peptide’s free energy landscape. A FRET-based analysis showed that all the mutants had a reduced fusogenic activity relative to the WT, in particular the mutants G12A/G13A and G4A/G8A/G16A/G20A. According to our results, one of the major causes of the lower activity of these mutants is their lower membrane affinity, which results in a lower concentration of peptide in the bilayer. These findings contribute to a better understanding of the influenza fusion process and open new routes for future studies. PMID:27302370

  1. Intracellular delivery of cell-penetrating peptide-transcriptional factor fusion protein and its role in selective osteogenesis

    Directory of Open Access Journals (Sweden)

    Suh JS

    2014-03-01

    Full Text Available Jin Sook Suh,1,* Jue Yeon Lee,2,* Yoon Jung Choi,1 Hyung Keun You,3 Seong-Doo Hong,4 Chong Pyoung Chung,2 Yoon Jeong Park1,2 1Dental Regenerative Biotechnology, Dental Research Institute, School of Dentistry, Seoul National University, Seoul, 2Central Research Institute, Nano Intelligent Biomedical Engineering Corporation (NIBEC, Seoul, 3Department of Periodontology, College of Dentistry, Wonkwang University, Iksan, 4Department of Oral Pathology, School of Dentistry, Seoul National University, Seoul, Republic of Korea *These authors contributed equally to this work Abstract: Protein-transduction technology has been attempted to deliver macromolecular materials, including protein, nucleic acids, and polymeric drugs, for either diagnosis or therapeutic purposes. Herein, fusion protein composed of an arginine-rich cell-penetrating peptide, termed low-molecular-weight protamine (LMWP, and a transcriptional coactivator with a PDZ-binding motif (TAZ protein was prepared and applied in combination with biomaterials to increase bone-forming capacity. TAZ has been recently identified as a specific osteogenic stimulating transcriptional coactivator in human mesenchymal stem cell (hMSC differentiation, while simultaneously blocking adipogenic differentiation. However, TAZ by itself cannot penetrate the cells, and thus needs a transfection tool for translocalization. The LMWP-TAZ fusion proteins were efficiently translocalized into the cytosol of hMSCs. The hMSCs treated with cell-penetrating LMWP-TAZ exhibited increased expression of osteoblastic genes and protein, producing significantly higher quantities of mineralized matrix compared to free TAZ. In contrast, adipogenic differentiation of the hMSCs was blocked by treatment of LMWP-TAZ fusion protein, as reflected by reduced marker-protein expression, adipocyte fatty acid-binding protein 2, and peroxisome proliferator-activated receptor-γ messenger ribonucleic acid levels. LMWP-TAZ was applied in

  2. Peptide-Based Membrane Fusion Inhibitors Targeting HCoV-229E Spike Protein HR1 and HR2 Domains

    Directory of Open Access Journals (Sweden)

    Shuai Xia

    2018-02-01

    Full Text Available Human coronavirus 229E (HCoV-229E infection in infants, elderly people, and immunocompromised patients can cause severe disease, thus calling for the development of effective and safe therapeutics to treat it. Here we reported the design, synthesis and characterization of two peptide-based membrane fusion inhibitors targeting HCoV-229E spike protein heptad repeat 1 (HR1 and heptad repeat 2 (HR2 domains, 229E-HR1P and 229E-HR2P, respectively. We found that 229E-HR1P and 229E-HR2P could interact to form a stable six-helix bundle and inhibit HCoV-229E spike protein-mediated cell-cell fusion with IC50 of 5.7 and 0.3 µM, respectively. 229E-HR2P effectively inhibited pseudotyped and live HCoV-229E infection with IC50 of 0.5 and 1.7 µM, respectively. In a mouse model, 229E-HR2P administered intranasally could widely distribute in the upper and lower respiratory tracts and maintain its fusion-inhibitory activity. Therefore, 229E-HR2P is a promising candidate for further development as an antiviral agent for the treatment and prevention of HCoV-229E infection.

  3. Evaluation of the amyloid beta-GFP fusion protein as a model of amyloid beta peptides-mediated aggregation: A study of DNAJB6 chaperone

    Directory of Open Access Journals (Sweden)

    Rasha Mohamed Hussein

    2015-07-01

    Full Text Available Alzheimer’s disease is a progressive neurodegenerative disease characterized by the accumulation and aggregation of extracellular amyloid β (Aβ peptides and intracellular aggregation of hyper-phosphorylated tau protein. Recent evidence indicates that accumulation and aggregation of intracellular amyloid β peptides may also play a role in disease pathogenesis. This would suggest that intracellular Heat Shock Proteins (HSP that maintain cellular protein homeostasis might be candidates for disease amelioration. We recently found that DNAJB6, a member of DNAJ family of heat shock proteins, effectively prevented the aggregation of short aggregation-prone peptides containing large poly glutamines (associated with CAG repeat diseases both in vitro and in cells. Moreover, recent in vitro data showed that DNAJB6 can delay the aggregation of Aβ42 peptides. In this study, we investigated the ability of DNAJB6 to prevent the aggregation of extracellular and intracellular Aβ peptides using transfection of HEK293 cells with Aβ-GFP fusion construct and performing western blotting and immunofluorescence techniques. We found that DNAJB6 indeed suppresses Aβ-GFP aggregation, but not seeded aggregation initiated by extracellular Aβ peptides. Unexpectedly and unlike what we found for peptide-mediated aggregation, DNAJB6 required interaction with HSP70 to prevent the aggregation of the Aβ-GFP fusion protein and its J-domain was crucial for its anti-aggregation effect. In addition, other DNAJ proteins as well as HSPA1a overexpression also suppressed Aβ-GFP aggregation efficiently. Our findings suggest that Aβ aggregation differs from poly Q peptide induced aggregation in terms of chaperone handling and sheds doubt on the usage of Aβ-GFP fusion construct for studying Aβ peptide aggregation in cells.

  4. Effect of specific amino acid substitutions in the putative fusion peptide of structural glycoprotein E2 on Classical Swine Fever Virus replication

    International Nuclear Information System (INIS)

    Fernández-Sainz, I.J.; Largo, E.; Gladue, D.P.; Fletcher, P.; O’Donnell, V.; Holinka, L.G.; Carey, L.B.; Lu, X.; Nieva, J.L.; Borca, M.V.

    2014-01-01

    E2, along with E rns and E1, is an envelope glycoprotein of Classical Swine Fever Virus (CSFV). E2 is involved in several virus functions: cell attachment, host range susceptibility and virulence in natural hosts. Here we evaluate the role of a specific E2 region, 818 CPIGWTGVIEC 828 , containing a putative fusion peptide (FP) sequence. Reverse genetics utilizing a full-length infectious clone of the highly virulent CSFV strain Brescia (BICv) was used to evaluate how individual amino acid substitutions within this region of E2 may affect replication of BICv. A synthetic peptide representing the complete E2 FP amino acid sequence adopted a β-type extended conformation in membrane mimetics, penetrated into model membranes, and perturbed lipid bilayer integrity in vitro. Similar peptides harboring amino acid substitutions adopted comparable conformations but exhibited different membrane activities. Therefore, a preliminary characterization of the putative FP 818 CPIGWTGVIEC 828 indicates a membrane fusion activity and a critical role in virus replication. - Highlights: • A putative fusion peptide (FP) region in CSFV E2 protein was shown to be critical for virus growth. • Synthetic FPs were shown to efficiently penetrate into lipid membranes using an in vitro model. • Individual residues in the FP affecting virus replication were identified by reverse genetics. • The same FP residues are also responsible for mediating membrane fusion

  5. Effect of specific amino acid substitutions in the putative fusion peptide of structural glycoprotein E2 on Classical Swine Fever Virus replication

    Energy Technology Data Exchange (ETDEWEB)

    Fernández-Sainz, I.J. [Plum Island Animal Disease Center, ARS, USDA (United States); Largo, E. [Biophysics Unit (CSIC-UPV/EHU), Department of Biochemistry and Molecular Biology, University of the Basque Country (UPV/EHU), P.O. Box 644, 48080 Bilbao (Spain); Gladue, D.P.; Fletcher, P. [Plum Island Animal Disease Center, ARS, USDA (United States); O’Donnell, V. [Plum Island Animal Disease Center, ARS, USDA (United States); Plum Island Animal Disease Center, DHS, Greenport, NY 11944 (United States); Holinka, L.G. [Plum Island Animal Disease Center, ARS, USDA (United States); Carey, L.B. [Department of Experimental and Health Sciences, Universitat Pompeu Fabra (UPF), E-08003 Barcelona (Spain); Lu, X. [Plum Island Animal Disease Center, DHS, Greenport, NY 11944 (United States); Nieva, J.L. [Biophysics Unit (CSIC-UPV/EHU), Department of Biochemistry and Molecular Biology, University of the Basque Country (UPV/EHU), P.O. Box 644, 48080 Bilbao (Spain); Borca, M.V., E-mail: manuel.borca@ars.usda.gov [Plum Island Animal Disease Center, ARS, USDA (United States)

    2014-05-15

    E2, along with E{sup rns} and E1, is an envelope glycoprotein of Classical Swine Fever Virus (CSFV). E2 is involved in several virus functions: cell attachment, host range susceptibility and virulence in natural hosts. Here we evaluate the role of a specific E2 region, {sup 818}CPIGWTGVIEC{sup 828}, containing a putative fusion peptide (FP) sequence. Reverse genetics utilizing a full-length infectious clone of the highly virulent CSFV strain Brescia (BICv) was used to evaluate how individual amino acid substitutions within this region of E2 may affect replication of BICv. A synthetic peptide representing the complete E2 FP amino acid sequence adopted a β-type extended conformation in membrane mimetics, penetrated into model membranes, and perturbed lipid bilayer integrity in vitro. Similar peptides harboring amino acid substitutions adopted comparable conformations but exhibited different membrane activities. Therefore, a preliminary characterization of the putative FP {sup 818}CPIGWTGVIEC{sup 828} indicates a membrane fusion activity and a critical role in virus replication. - Highlights: • A putative fusion peptide (FP) region in CSFV E2 protein was shown to be critical for virus growth. • Synthetic FPs were shown to efficiently penetrate into lipid membranes using an in vitro model. • Individual residues in the FP affecting virus replication were identified by reverse genetics. • The same FP residues are also responsible for mediating membrane fusion.

  6. Translocation of cell penetrating peptides and calcium-induced membrane fusion share same mechanism

    Czech Academy of Sciences Publication Activity Database

    Magarkar, Aniket; Allolio, Christoph; Jurkiewicz, Piotr; Baxová, Katarína; Šachl, Radek; Horinek, D.; Heinz, V.; Rachel, R.; Ziegler, C.; Jungwirth, Pavel

    2017-01-01

    Roč. 46, Suppl 1 (2017), S386 ISSN 0175-7571. [IUPAB congress /19./ and EBSA congress /11./. 16.07.2017-20.07.2017, Edinburgh] Institutional support: RVO:61388963 ; RVO:61388955 Keywords : membrane interactions * membrane fusion * cell penetration Subject RIV: BO - Biophysics

  7. Targeted recombinant fusion proteins of IFNγ and mimetic IFNγ with PDGFβR bicyclic peptide inhibits liver fibrogenesis in vivo.

    Directory of Open Access Journals (Sweden)

    Ruchi Bansal

    Full Text Available Hepatic stellate cells (HSCs, following transdifferentiation to myofibroblasts plays a key role in liver fibrosis. Therefore, attempts to attenuate this myofibroblastic phenotype would be a promising therapeutic approach. Interferon gamma (IFNγ is a potent anti-fibrotic cytokine, but its pleiotropic receptor expression leading to severe adverse effects has limited its clinical application. Since, activated HSC express high-level of platelet derived growth factor beta receptor (PDGFβR, we investigated the potential of PDGFβR-specific targeting of IFNγ and its signaling peptide that lacks IFNγR binding site (mimetic IFNγ or mimIFNγ in liver fibrosis. We prepared DNA constructs expressing IFNγ, mimIFNγ or BiPPB (PDGFβR-specific bicyclic peptide-IFNγ, BiPPB-mimIFNγ fusion proteins. Both chimeric proteins alongwith IFNγ and mimIFNγ were produced in E.coli. The expressed proteins were purified and analyzed for PDGFβR-specific binding and in vitro effects. Subsequently, these recombinant proteins were investigated for the liver uptake (pSTAT1α signaling pathway, for anti-fibrotic effects and adverse effects (platelet counts in CCl4-induced liver fibrogenesis in mice. The purified HSC-targeted IFNγ and mimIFNγ fusion proteins showed PDGFβR-specific binding and significantly reduced TGFβ-induced collagen-I expression in human HSC (LX2 cells, while mouse IFNγ and mimIFNγ did not show any effect. Conversely, mouse IFNγ and BiPPB-IFNγ induced activation and dose-dependent nitric oxide release in mouse macrophages (express IFNγR while lack PDGFβR, which was not observed with mimIFNγ and BiPPB-mimIFNγ, due to the lack of IFNγR binding sites. In vivo, targeted BiPPB-IFNγ and BiPPB-mimIFNγ significantly activated intrahepatic IFNγ-signaling pathway compared to IFNγ and mimIFNγ suggesting increased liver accumulation. Furthermore, the targeted fusion proteins ameliorated liver fibrogenesis in mice by significantly reducing

  8. Novel β-lactamase-random peptide fusion libraries for phage display selection of cancer cell-targeting agents suitable for enzyme prodrug therapy

    Science.gov (United States)

    Shukla, Girja S.; Krag, David N.

    2010-01-01

    Novel phage-displayed random linear dodecapeptide (X12) and cysteine-constrained decapeptide (CX10C) libraries constructed in fusion to the amino-terminus of P99 β-lactamase molecules were used for identifying β-lactamase-linked cancer cell-specific ligands. The size and quality of both libraries were comparable to the standards of other reported phage display systems. Using the single-round panning method based on phage DNA recovery, we identified severalβ-lactamase fusion peptides that specifically bind to live human breast cancer MDA-MB-361 cells. The β-lactamase fusion to the peptides helped in conducting the enzyme activity-based clone normalization and cell-binding screening in a very time- and cost-efficient manner. The methods were suitable for 96-well readout as well as microscopic imaging. The success of the biopanning was indicated by the presence of ~40% cancer cell-specific clones among recovered phages. One of the binding clones appeared multiple times. The cancer cell-binding fusion peptides also shared several significant motifs. This opens a new way of preparing and selecting phage display libraries. The cancer cell-specific β-lactamase-linked affinity reagents selected from these libraries can be used for any application that requires a reporter for tracking the ligand molecules. Furthermore, these affinity reagents have also a potential for their direct use in the targeted enzyme prodrug therapy of cancer. PMID:19751096

  9. Fusion Peptide Improves Stability and Bioactivity of Single Chain Antibody against Rabies Virus.

    Science.gov (United States)

    Xi, Hualong; Zhang, Kaixin; Yin, Yanchun; Gu, Tiejun; Sun, Qing; Shi, Linqing; Zhang, Renxia; Jiang, Chunlai; Kong, Wei; Wu, Yongge

    2017-04-28

    The combination of rabies immunoglobulin (RIG) with a vaccine is currently effective against rabies infections, but improvements are needed. Genetic engineering antibody technology is an attractive approach for developing novel antibodies to replace RIG. In our previous study, a single-chain variable fragment, scFv57R, against rabies virus glycoprotein was constructed. However, its inherent weak stability and short half-life compared with the parent RIG may limit its diagnostic and therapeutic application. Therefore, an acidic tail of synuclein (ATS) derived from the C-terminal acidic tail of human alpha-synuclein protein was fused to the C-terminus of scFv57R in order to help it resist adverse stress and improve the stability and halflife. The tail showed no apparent effect on the preparation procedure and affinity of the protein, nor did it change the neutralizing potency in vitro. In the ELISA test of molecular stability, the ATS fusion form of the protein, scFv57R-ATS, showed an increase in thermal stability and longer half-life in serum than scFv57R. The protection against fatal rabies virus challenge improved after fusing the tail to the scFv, which may be attributed to the improved stability. Thus, the ATS fusion approach presented here is easily implemented and can be used as a new strategy to improve the stability and half-life of engineered antibody proteins for practical applications.

  10. Structure-Related Roles for the Conservation of the HIV-1 Fusion Peptide Sequence Revealed by Nuclear Magnetic Resonance.

    Science.gov (United States)

    Serrano, Soraya; Huarte, Nerea; Rujas, Edurne; Andreu, David; Nieva, José L; Jiménez, María Angeles

    2017-10-17

    Despite extensive characterization of the human immunodeficiency virus type 1 (HIV-1) hydrophobic fusion peptide (FP), the structure-function relationships underlying its extraordinary degree of conservation remain poorly understood. Specifically, the fact that the tandem repeat of the FLGFLG tripeptide is absolutely conserved suggests that high hydrophobicity may not suffice to unleash FP function. Here, we have compared the nuclear magnetic resonance (NMR) structures adopted in nonpolar media by two FP surrogates, wtFP-tag and scrFP-tag, which had equal hydrophobicity but contained wild-type and scrambled core sequences LFLGFLG and FGLLGFL, respectively. In addition, these peptides were tagged at their C-termini with an epitope sequence that folded independently, thereby allowing Western blot detection without interfering with FP structure. We observed similar α-helical FP conformations for both specimens dissolved in the low-polarity medium 25% (v/v) 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP), but important differences in contact with micelles of the membrane mimetic dodecylphosphocholine (DPC). Thus, whereas wtFP-tag preserved a helix displaying a Gly-rich ridge, the scrambled sequence lost in great part the helical structure upon being solubilized in DPC. Western blot analyses further revealed the capacity of wtFP-tag to assemble trimers in membranes, whereas membrane oligomers were not observed in the case of the scrFP-tag sequence. We conclude that, beyond hydrophobicity, preserving sequence order is an important feature for defining the secondary structures and oligomeric states adopted by the HIV FP in membranes.

  11. Detection of closed influenza virus hemagglutinin fusion peptide structures in membranes by backbone {sup 13}CO-{sup 15}N rotational-echo double-resonance solid-state NMR

    Energy Technology Data Exchange (ETDEWEB)

    Ghosh, Ujjayini; Xie Li; Weliky, David P., E-mail: weliky@chemistry.msu.edu [Michigan State University, Department of Chemistry (United States)

    2013-02-15

    The influenza virus fusion peptide is the N-terminal {approx}20 residues of the HA2 subunit of the hemagglutinin protein and this peptide plays a key role in the fusion of the viral and endosomal membranes during initial infection of a cell. The fusion peptide adopts N-helix/turn/C-helix structure in both detergent and membranes with reports of both open and closed interhelical topologies. In the present study, backbone {sup 13}CO-{sup 15}N REDOR solid-state NMR was applied to the membrane-associated fusion peptide to detect the distribution of interhelical distances. The data clearly showed a large fraction of closed and semi-closed topologies and were best-fitted to a mixture of two structures that do not exchange. One of the earlier open structural models may have incorrect G13 dihedral angles derived from TALOS analysis of experimentally correct {sup 13}C shifts.

  12. Therapeutic Fc-fusion proteins and peptides as successful alternatives to antibodies.

    Science.gov (United States)

    Beck, Alain; Reichert, Janice M

    2011-01-01

    Therapeutic antibodies have captured substantial attention due to the relatively high rate at which these products reach marketing approval, and the subsequent commercial success they frequently achieve. In the 2000s, a total of 20 antibodies (18 full-length IgG and 2 Fab) were approved by the Food and Drug Administration (FDA) or European Medicines Agency (EMA). In the 2010s to date, an additional 3 antibodies (denosumab, belimumab, ipilimumab) have been approved and one antibody-drug conjugate (brentuximab vedotin) is undergoing regulatory review and may be approved in the US by August 30, 2011. However, a less heralded group of antibody-based therapeutics comprising proteins or peptides fused with an Fc is following the success of classical antibodies.

  13. Long-term rescue of dystrophin expression and improvement in muscle pathology and function in dystrophic mdx mice by peptide-conjugated morpholino.

    Science.gov (United States)

    Wu, Bo; Lu, Peijuan; Cloer, Caryn; Shaban, Mona; Grewal, Snimar; Milazi, Stephanie; Shah, Sapana N; Moulton, Hong M; Lu, Qi Long

    2012-08-01

    Exon skipping is capable of correcting frameshift and nonsense mutations in Duchenne muscular dystrophy. Phase 2 clinical trials in the United Kingdom and the Netherlands have reported induction of dystrophin expression in muscle of Duchenne muscular dystrophy patients by systemic administration of both phosphorodiamidate morpholino oligomers (PMO) and 2'-O-methyl phosphorothioate. Peptide-conjugated phosphorodiamidate morpholino offers significantly higher efficiency than phosphorodiamidate morpholino, with the ability to induce near-normal levels of dystrophin, and restores function in both skeletal and cardiac muscle. We examined 1-year systemic efficacy of peptide-conjugated phosphorodiamidate morpholino targeting exon 23 in dystrophic mdx mice. The LD(50) of peptide-conjugated phosphorodiamidate morpholino was determined to be approximately 85 mg/kg. The half-life of dystrophin expression was approximately 2 months in skeletal muscle, but shorter in cardiac muscle. Biweekly injection of 6 mg/kg peptide-conjugated phosphorodiamidate morpholino produced >20% dystrophin expression in all skeletal muscles and ≤5% in cardiac muscle, with improvement in muscle function and pathology and reduction in levels of serum creatine kinase. Monthly injections of 30 mg/kg peptide-conjugated phosphorodiamidate morpholino restored dystrophin to >50% normal levels in skeletal muscle, and 15% in cardiac muscle. This was associated with greatly reduced serum creatine kinase levels, near-normal histology, and functional improvement of skeletal muscle. Our results demonstrate for the first time that regular 1-year administration of peptide-conjugated phosphorodiamidate morpholino can be safely applied to achieve significant therapeutic effects in an animal model. Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  14. Advanced multivariate data analysis to determine the root cause of trisulfide bond formation in a novel antibody–peptide fusion

    Science.gov (United States)

    Goldrick, Stephen; Holmes, William; Bond, Nicholas J.; Lewis, Gareth; Kuiper, Marcel; Turner, Richard

    2017-01-01

    ABSTRACT Product quality heterogeneities, such as a trisulfide bond (TSB) formation, can be influenced by multiple interacting process parameters. Identifying their root cause is a major challenge in biopharmaceutical production. To address this issue, this paper describes the novel application of advanced multivariate data analysis (MVDA) techniques to identify the process parameters influencing TSB formation in a novel recombinant antibody–peptide fusion expressed in mammalian cell culture. The screening dataset was generated with a high‐throughput (HT) micro‐bioreactor system (AmbrTM 15) using a design of experiments (DoE) approach. The complex dataset was firstly analyzed through the development of a multiple linear regression model focusing solely on the DoE inputs and identified the temperature, pH and initial nutrient feed day as important process parameters influencing this quality attribute. To further scrutinize the dataset, a partial least squares model was subsequently built incorporating both on‐line and off‐line process parameters and enabled accurate predictions of the TSB concentration at harvest. Process parameters identified by the models to promote and suppress TSB formation were implemented on five 7 L bioreactors and the resultant TSB concentrations were comparable to the model predictions. This study demonstrates the ability of MVDA to enable predictions of the key performance drivers influencing TSB formation that are valid also upon scale‐up. Biotechnol. Bioeng. 2017;114: 2222–2234. © 2017 The Authors. Biotechnology and Bioengineering Published by Wiley Periodicals, Inc. PMID:28500668

  15. Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance

    International Nuclear Information System (INIS)

    Anastassopoulou, Cleo G.; Ketas, Thomas J.; Sanders, Rogier W.; Johan Klasse, Per; Moore, John P.

    2012-01-01

    A rare pathway of HIV-1 resistance to small molecule CCR5 inhibitors such as Vicriviroc (VCV) involves changes solely in the gp41 fusion peptide (FP). Here, we show that the G516V change is critical to VCV resistance in PBMC and TZM-bl cells, although it must be accompanied by either M518V or F519I to have a substantial impact. Modeling VCV inhibition data from the two cell types indicated that G516V allows both double mutants to use VCV-CCR5 complexes for entry. The model further identified F519I as an independent determinant of preference for the unoccupied, high-VCV affinity form of CCR5. From inhibitor-free reversion cultures, we also identified a substitution in the inner domain of gp120, T244A, which appears to counter the resistance phenotype created by the FP substitutions. Examining the interplay of these changes will enhance our understanding of Env complex interactions that influence both HIV-1 entry and resistance to CCR5 inhibitors.

  16. Soluble expression and purification of the recombinant bioactive peptide precursor BPP-1 in Escherichia coli using a cELP-SUMO dual fusion system.

    Science.gov (United States)

    Rao, Shengqi; Zang, Xiangyu; Yang, Zhenquan; Gao, Lu; Yin, Yongqi; Fang, Weiming

    2016-02-01

    A bioactive peptide precursor (BPP-1, 14.3 kDa/115AA), a newly designed polypeptide that may exert a potential antihypertensive effect in vivo, is composed of many different ACE inhibitory peptides and antioxidant peptides tandemly linked according to the restriction sites of gastrointestinal proteases. In this report, we present a novel method to obtain soluble BPP-1 in Escherichia coli using cationic elastin-like polypeptide and SUMO (cELP-SUMO) tags. The cELP-SUMO-tagged fusion protein was expressed in soluble form at 20 °C for 20 h. After purification based on the inverse transition cycling (ITC) method, the purified cELP-SUMO-CFPP fusion protein was subsequently cleaved by a SUMO protease to release the mature BPP-1. After a subsequent simple salt precipitation process, approximately 167.2 mg of recombinant BPP-1 was obtained from 1 l of bacterial culture with at least 92% purity. The molecular mass (Mr) of the recombinant BPP-1 was confirmed by MALDI-TOF MS to equal 14,347. The purified BPP-1 was subjected to simulated gastrointestinal digestion, and the resulting hydrolysates exhibited notable ACE inhibitory and antioxidant activities in vitro. This report provides the first description of the soluble production of a bioactive peptide multimer with potential ACE inhibitory and antioxidant activities in E. coli using a cELP-SUMO tag. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Advanced multivariate data analysis to determine the root cause of trisulfide bond formation in a novel antibody-peptide fusion.

    Science.gov (United States)

    Goldrick, Stephen; Holmes, William; Bond, Nicholas J; Lewis, Gareth; Kuiper, Marcel; Turner, Richard; Farid, Suzanne S

    2017-10-01

    Product quality heterogeneities, such as a trisulfide bond (TSB) formation, can be influenced by multiple interacting process parameters. Identifying their root cause is a major challenge in biopharmaceutical production. To address this issue, this paper describes the novel application of advanced multivariate data analysis (MVDA) techniques to identify the process parameters influencing TSB formation in a novel recombinant antibody-peptide fusion expressed in mammalian cell culture. The screening dataset was generated with a high-throughput (HT) micro-bioreactor system (Ambr TM 15) using a design of experiments (DoE) approach. The complex dataset was firstly analyzed through the development of a multiple linear regression model focusing solely on the DoE inputs and identified the temperature, pH and initial nutrient feed day as important process parameters influencing this quality attribute. To further scrutinize the dataset, a partial least squares model was subsequently built incorporating both on-line and off-line process parameters and enabled accurate predictions of the TSB concentration at harvest. Process parameters identified by the models to promote and suppress TSB formation were implemented on five 7 L bioreactors and the resultant TSB concentrations were comparable to the model predictions. This study demonstrates the ability of MVDA to enable predictions of the key performance drivers influencing TSB formation that are valid also upon scale-up. Biotechnol. Bioeng. 2017;114: 2222-2234. © 2017 The Authors. Biotechnology and Bioengineering Published by Wiley Periodicals, Inc. © 2017 The Authors. Biotechnology and Bioengineering Published by Wiley Periodicals, Inc.

  18. Expression and Immunogenicity of the Mycobacterial Ag85B/ESAT-6 Antigens Produced in Transgenic Plants by Elastin-Like Peptide Fusion Strategy

    Directory of Open Access Journals (Sweden)

    Doreen Manuela Floss

    2010-01-01

    Full Text Available This study explored a novel system combining plant-based production and the elastin-like peptide (ELP fusion strategy to produce vaccinal antigens against tuberculosis. Transgenic tobacco plants expressing the mycobacterial antigens Ag85B and ESAT-6 fused to ELP (TBAg-ELP were generated. Purified TBAg-ELP was obtained by the highly efficient, cost-effective, inverse transition cycling (ICT method and tested in mice. Furthermore, safety and immunogenicity of the crude tobacco leaf extracts were assessed in piglets. Antibodies recognizing mycobacterial antigens were produced in mice and piglets. A T-cell immune response able to recognize the native mycobacterial antigens was detected in mice. These findings showed that the native Ag85B and ESAT-6 mycobacterial B- and T-cell epitopes were conserved in the plant-expressed TBAg-ELP. This study presents the first results of an efficient plant-expression system, relying on the elastin-like peptide fusion strategy, to produce a safe and immunogenic mycobacterial Ag85B-ESAT-6 fusion protein as a potential vaccine candidate against tuberculosis.

  19. Rescue Manual. Module 6.

    Science.gov (United States)

    Ohio State Univ., Columbus. Instructional Materials Lab.

    This learner manual for rescuers covers the current techniques or practices required in the rescue service. The sixth of 10 modules contains 4 chapters: (1) industrial rescue; (2) rescue from a confined space; (3) extrication from heavy equipment; and (4) rescue operations involving elevators. Key points, an introduction, and conclusion accompany…

  20. A neuroligin-1-derived peptide stimulates phosphorylation of the NMDA receptor NR1 subunit and rescues MK-801-induced decrease in long-term potentiation and memory impairment

    DEFF Research Database (Denmark)

    Korshunova, Irina; Gjørlund, Michelle D; Jacobsen, Sylwia Owczarek

    2015-01-01

    neurolide-1 effects on short- and long-term social and spatial memory in social recognition, Morris water-maze, and Y-maze tests. We found that subcutaneous neurolide-1 administration, restored hippocampal LTP compromised by NMDA receptor inhibitor MK-801. It counteracted MK-801-induced memory deficit...... in the water-maze and Y-maze tests after long-term treatment (24 h and 1-2 h before the test), but not after short-term exposure (1-2 h). Long-term exposure to neurolide-1 also facilitated social recognition memory. In addition, neurolide-1-induced phosphorylation of the NMDA receptor NR1 subunit on a site...... receptor phosphorylation after treatment with NL1 or a mimetic peptide, neurolide-1, was quantified by immunoblotting. Subsequently, we investigated effects of neurolide-1 on long-term potentiation (LTP) induction in hippocampal slices compromised by NMDA receptor inhibitor MK-801. Finally, we investigated...

  1. Adding an Artificial Tail—Anchor to a Peptide-Based HIV-1 Fusion Inhibitor for Improvement of Its Potency and Resistance Profile

    Directory of Open Access Journals (Sweden)

    Shan Su

    2017-11-01

    Full Text Available Peptides derived from the C-terminal heptad repeat (CHR of human immunodeficiency virus type 1 (HIV-1 envelope protein transmembrane subunit gp41, such as T20 (enfuvirtide, can bind to the N-terminal heptad repeat (NHR of gp41 and block six-helix bundle (6-HB formation, thus inhibiting HIV-1 fusion with the target cell. However, clinical application of T20 is limited because of its low potency and genetic barrier to resistance. HP23, the shortest CHR peptide, exhibits better anti-HIV-1 activity than T20, but the HIV-1 strains with E49K mutations in gp41 will become resistant to it. Here, we modified HP23 by extending its C-terminal sequence using six amino acid residues (E6 and adding IDL (Ile-Asp-Leu to the C-terminus of E6, which is expected to bind to the shallow pocket in the gp41 NHR N-terminal region. The newly designed peptide, designated HP23-E6-IDL, was about 2- to 16-fold more potent than HP23 against a broad spectrum of HIV-1 strains and more than 12-fold more effective against HIV-1 mutants resistant to HP23. These findings suggest that addition of an anchor–tail to the C-terminus of a CHR peptide will allow binding with the pocket in the gp41 NHR that may increase the peptide’s antiviral efficacy and its genetic barrier to resistance.

  2. Solid-state nuclear magnetic resonance measurements of HIV fusion peptide 13CO to lipid 31P proximities support similar partially inserted membrane locations of the α helical and β sheet peptide structures.

    Science.gov (United States)

    Gabrys, Charles M; Qiang, Wei; Sun, Yan; Xie, Li; Schmick, Scott D; Weliky, David P

    2013-10-03

    Fusion of the human immunodeficiency virus (HIV) membrane and the host cell membrane is an initial step of infection of the host cell. Fusion is catalyzed by gp41, which is an integral membrane protein of HIV. The fusion peptide (FP) is the ∼25 N-terminal residues of gp41 and is a domain of gp41 that plays a key role in fusion catalysis likely through interaction with the host cell membrane. Much of our understanding of the FP domain has been accomplished with studies of "HFP", i.e., a ∼25-residue peptide composed of the FP sequence but lacking the rest of gp41. HFP catalyzes fusion between membrane vesicles and serves as a model system to understand fusion catalysis. HFP binds to membranes and the membrane location of HFP is likely a significant determinant of fusion catalysis perhaps because the consequent membrane perturbation reduces the fusion activation energy. In the present study, many HFPs were synthesized and differed in the residue position that was (13)CO backbone labeled. Samples were then prepared that each contained a singly (13)CO labeled HFP incorporated into membranes that lacked cholesterol. HFP had distinct molecular populations with either α helical or oligomeric β sheet structure. Proximity between the HFP (13)CO nuclei and (31)P nuclei in the membrane headgroups was probed by solid-state NMR (SSNMR) rotational-echo double-resonance (REDOR) measurements. For many samples, there were distinct (13)CO shifts for the α helical and β sheet structures so that the proximities to (31)P nuclei could be determined for each structure. Data from several differently labeled HFPs were then incorporated into a membrane location model for the particular structure. In addition to the (13)CO labeled residue position, the HFPs also differed in sequence and/or chemical structure. "HFPmn" was a linear peptide that contained the 23 N-terminal residues of gp41. "HFPmn_V2E" contained the V2E mutation that for HIV leads to greatly reduced extent of fusion and

  3. Analysis of the thermodynamics of binding of an SH3 domain to proline-rich peptides using a chimeric fusion protein.

    Science.gov (United States)

    Candel, Adela M; van Nuland, Nico A J; Martin-Sierra, Francisco M; Martinez, Jose C; Conejero-Lara, Francisco

    2008-03-14

    A complete understanding of the thermodynamic determinants of binding between SH3 domains and proline-rich peptides is crucial to the development of rational strategies for designing ligands for these important domains. Recently we engineered a single-chain chimeric protein by fusing the alpha-spectrin Src homology region 3 (SH3) domain to the decapeptide APSYSPPPPP (p41). This chimera mimics the structural and energetic features of the interaction between SH3 domains and proline-rich peptides. Here we show that analysing the unfolding thermodynamics of single-point mutants of this chimeric fusion protein constitutes a very useful approach to deciphering the thermodynamics of SH3-ligand interactions. To this end, we investigated the contribution of each proline residue of the ligand sequence to the SH3-peptide interaction by producing six single Pro-Ala mutants of the chimeric protein and analysing their unfolding thermodynamics by differential scanning calorimetry (DSC). Structural analyses of the mutant chimeras by circular dichroism, fluorescence and NMR together with NMR-relaxation measurements indicate conformational flexibility at the binding interface, which is strongly affected by the different Pro-Ala mutations. An analysis of the DSC thermograms on the basis of a three-state unfolding model has allowed us to distinguish and separate the thermodynamic magnitudes of the interaction at the binding interface. The model assumes equilibrium between the "unbound" and "bound" states at the SH3-peptide binding interface. The resulting thermodynamic magnitudes classify the different proline residues according to their importance in the interaction as P2 approximately P7 approximately P10>P9 approximately P6>P8, which agrees well with Lim's model for the interaction between SH3 domains and proline-rich peptides. In addition, the thermodynamic signature of the interaction is the same as that usually found for this type of binding, with a strong enthalpy

  4. A novel strategy to improve antigen presentation for active immunotherapy in cancer. Fusion of the human papillomavirus type 16 E7 antigen to a cell penetrating peptide

    International Nuclear Information System (INIS)

    Granadillo, Milaid; Torrens, Isis; Guerra, Maribel

    2012-01-01

    Facilitating the delivery of exogenous antigens to antigen-presenting cells, ensuing processing and presentation via the major histocompatibility complex class I and induction of an effective immune response are fundamental for an effective therapeutic cancer vaccine. In this regard, we propose the use of cell-penetrating peptides fused to a tumor antigen. To demonstrate this concept we designed a fusion protein comprising a novel cell-penetrating and immunostimulatory peptide corresponding to residues 32 to 51 of the Limulus anti-lipopolysaccharide factor protein (LALF 32-51 ) linked to human papillomavirus 16 E7 antigen (LALF 32-51 -E7). In this work, we demonstrated that the immunization with LALF 32-51 -E7 using the TC-1 mouse model induces a potent and long-lasting anti-tumor response supported on an effective E7-specific CD8 +T -cell response. The finding that therapeutic immunization with LALF 32-51 or E7 alone, or an admixture of LALF32-51 and E7, does not induce significant tumor reduction indicates that covalent linkage between LALF 32-51 and E7 is required for the anti-tumor effect. These results support the use of this novel cell-penetrating peptide as an efficient means for delivering therapeutic targets into cellular compartments with the induction of a cytotoxic CD8 +T lymphocyte immune response. This approach is promissory for the treatment of tumors associated with the human papillomavirus 16, which is responsible for the 50% of cervical cancer cases worldwide and other malignancies. Furthermore, protein-based vaccines can circumvent the major histocompatibility complex specificity limitation associated with peptide vaccines providing a greater extent in their application

  5. The Asia 2 specific signal peptide region and other domains in fusion protein genes characterized Asia 1 and Asia 2 canine distemper viruses

    Science.gov (United States)

    Sultan, Serageldeen; Charoenvisal, Nataya; Lan, Nguyen Thi; Yamaguchi, Ryoji; Maeda, Ken; Kai, Kazushige

    2009-01-01

    Background Although the presence of Asia 2 group of canine distemper virus (CDV) was known by the sequencing and phylogenetic analysis of hemagglutinin (H) gene, the fusion (F) protein gene sequence of Asia 2 group had not been identified. So, the sequence analysis of F gene was carried out to elucidate the genotypic varaitons among Asian isolates. Results The phylogenetic analysis of F and H gene sequences from fourteen CDV isolates obtained from diseased dogs in Japan and Thailand indicated that the F genes had a new initiation codon and extra 27 nucleotides upstream of the usual open reading frame (ORF) and the F proteins had extra 9 amino acids at the N-terminal position only in Asia 2 isolates. On the contrary, the Asia 1 isolates had three extra putative N-glycosylation sites (two sites in the signal peptide region and one site in the F1 region) except for two strains of Th12 and Ac96I (two sites in signal peptide region) adding to four putative N-glycosylation sites that were conserved among all Asian isolates and Onderstepoort strain. In addition to this difference in N-glycosylation sites, the signal peptide region had a great diversity between Asia 1 and Asia 2 isolates. Also, characteristic amino acids were detected for some strains. Conclusion Asia 2 isolates were distinguished from other CDV lineages by the extra 27 nucleotide sequence. The signal peptide region of F gene gives a remarkable differentiation between Asia 1 and Asia 2 isolates. Strains Th12 and Ac96I were differentiated from other Asia 1 strains by the F protein glycosylation sites. PMID:19807927

  6. Virus-cell fusion inhibitory activity of novel analogue peptides based on the HP (2-20) derived from N-terminus of Helicobacter pylori Ribosomal Protein L1.

    Science.gov (United States)

    Woo, Eun-Rhan; Lee, Dong Gun; Chang, Young-Su; Park, Yoonkyung; Hahm, Kyung-Soo

    2002-12-01

    HP (2-20) (AKKVFKRLEKLFSKIQNDK) is the antibacterial sequence derived from N-terminus of Helicobacter pylori Ribosomal Protein L1 (RPL1). It has a broad-spectrum microbicidal activity in vitro that is thought to be related to the membrane-disruptive properties of the peptide. Based on the putative membrane-targeted mode of action, we postulated that HP (2-20) might be possessed virus-cell fusion inhibitory activity. To develop the novel virus-cell fusion inhibitory peptides, several analogues with amino acid substitution were designed to increase or decrease only net hydrophobic region. In particular, substitution of Gln and Asp for hydrophobic amino acid, Trp at position 17 and 19 of HP (2-20) (Anal 3) caused a dramatic increase in virus-cell fusion inhibitory activity without hemolytic effect.

  7. A novel TNFα antagonizing peptide-Fc fusion protein designed based on CDRs of TNFα neutralizing monoclonal antibody

    International Nuclear Information System (INIS)

    Qin Weisong; Feng Jiannan; Zhang Wei; Li Yan; Shen, Beifen

    2004-01-01

    The variable regions of antibody molecules bind antigens with high affinity and specificity. The binding sites are imparted largely to the hypervariable portions (i.e., CDRs) of the variable region. Peptides derived from CDRs can bind antigen with similar specificity acting as mimic of antibody and become drug-designing core, although with markedly lower affinity. In order to increase the affinity and bioactivity, in this study, a novel peptide (PT) designed on CDRs of a TNFα neutralizing monoclonal antibody Z12 was linked with Fc fragment of human IgG1. The interaction mode of PT-linker-Fc (PLF) with TNFα was analyzed with computer-guided molecular modeling method. After expression in Escherichia coli and purification, recombinant PT-linker-Fc could bind directly with the TNFα coated on the ELISA plates. Furthermore, PLF could competitively inhibit the binding of Z12 to TNFα and also inhibit the TNFα-induced cytotoxicity on L929 cells. The TNFα antagonizing activity of PLF was significantly higher than that of the free peptide. This study highlights the potential of human Fc to enhance the potency of peptides designed on the CDRs of antibodies and could be useful in developing new TNFα antagonists

  8. The fusion protein signal-peptide-coding region of canine distemper virus: a useful tool for phylogenetic reconstruction and lineage identification.

    Directory of Open Access Journals (Sweden)

    Nicolás Sarute

    Full Text Available Canine distemper virus (CDV; Paramyxoviridae, Morbillivirus is the etiologic agent of a multisystemic infectious disease affecting all terrestrial carnivore families with high incidence and mortality in domestic dogs. Sequence analysis of the hemagglutinin (H gene has been widely employed to characterize field strains, permitting the identification of nine CDV lineages worldwide. Recently, it has been established that the sequences of the fusion protein signal-peptide (Fsp coding region are extremely variable, suggesting that analysis of its sequence might be useful for strain characterization studies. However, the divergence of Fsp sequences among worldwide strains and its phylogenetic resolution has not yet been evaluated. We constructed datasets containing the Fsp-coding region and H gene sequences of the same strains belonging to eight CDV lineages. Both datasets were used to evaluate their phylogenetic resolution. The phylogenetic analysis revealed that both datasets clustered the same strains into eight different branches, corresponding to CDV lineages. The inter-lineage amino acid divergence was fourfold greater for the Fsp peptide than for the H protein. The likelihood mapping revealed that both datasets display strong phylogenetic signals in the region of well-resolved topologies. These features indicate that Fsp-coding region sequence analysis is suitable for evolutionary studies as it allows for straightforward identification of CDV lineages.

  9. The fusion protein signal-peptide-coding region of canine distemper virus: a useful tool for phylogenetic reconstruction and lineage identification.

    Science.gov (United States)

    Sarute, Nicolás; Calderón, Marina Gallo; Pérez, Ruben; La Torre, José; Hernández, Martín; Francia, Lourdes; Panzera, Yanina

    2013-01-01

    Canine distemper virus (CDV; Paramyxoviridae, Morbillivirus) is the etiologic agent of a multisystemic infectious disease affecting all terrestrial carnivore families with high incidence and mortality in domestic dogs. Sequence analysis of the hemagglutinin (H) gene has been widely employed to characterize field strains, permitting the identification of nine CDV lineages worldwide. Recently, it has been established that the sequences of the fusion protein signal-peptide (Fsp) coding region are extremely variable, suggesting that analysis of its sequence might be useful for strain characterization studies. However, the divergence of Fsp sequences among worldwide strains and its phylogenetic resolution has not yet been evaluated. We constructed datasets containing the Fsp-coding region and H gene sequences of the same strains belonging to eight CDV lineages. Both datasets were used to evaluate their phylogenetic resolution. The phylogenetic analysis revealed that both datasets clustered the same strains into eight different branches, corresponding to CDV lineages. The inter-lineage amino acid divergence was fourfold greater for the Fsp peptide than for the H protein. The likelihood mapping revealed that both datasets display strong phylogenetic signals in the region of well-resolved topologies. These features indicate that Fsp-coding region sequence analysis is suitable for evolutionary studies as it allows for straightforward identification of CDV lineages.

  10. Controlled chondrogenesis from adipose-derived stem cells by recombinant transforming growth factor-β3 fusion protein in peptide scaffolds.

    Science.gov (United States)

    Zheng, Dong; Dan, Yang; Yang, Shu-hua; Liu, Guo-hui; Shao, Zeng-wu; Yang, Cao; Xiao, Bao-jun; Liu, Xiangmei; Wu, Shuilin; Zhang, Tainjin; Chu, Paul K

    2015-01-01

    Adipose-derived stem cells (ADSCs) are promising for cartilage repair due to their easy accessibility and chondrogenic potential. Although chondrogenesis of transforming growth factor-β (TGF-β) mediated mesenchymal stem cells (MSCs) is well established in vitro, clinical tissue engineering requires effective and controlled delivery of TGF-β in vivo. In this work, a self-assembled peptide scaffold was employed to construct cartilages in vivo through the chondrogenesis from ADSCs controlled by recombinant fusion protein LAP-MMP-mTGF-β3 that was transfected by lentiviral vectors. During this course, the addition of matrix metalloproteinases (MMPs) can trigger the release of mTGF-β3 from the recombinant fusion protein of LAP-MMP-mTGF-β3 in the combined scaffolds, thus stimulating the differentiation of ADSCs into chondrogenesis. The specific expression of cartilage genes was analyzed by real-time polymerase chain reaction and Western blot. The expression of chondrocytic markers was obviously upregulated to a higher level compared to the one by commonly used TGF-β3 alone. After 3 weeks of in vitro culturing, the hybrids with differentiated chondrogenesis were then injected subcutaneously into nude mice and retrieved after 4 weeks of culturing in vivo. Histological analysis also confirmed that the recombinant fusion protein was more effective for the formation of cartilage matrix than the cases either with TGF-β3 alone or without LAP-MMP-mTGF-β3 (P<0.05). This study demonstrates that controlled local delivery of the LAP-MMP-mTGF-β3 constructs can accelerate differentiation of ADSCs into the cartilage in vivo, which indicates the great potential of this hybrid in rapid therapy of osteoarthritis. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  11. Effects of dietary supplementation with an expressed fusion peptide bovine lactoferricin-lactoferrampin on performance, immune function and intestinal mucosal morphology in piglets weaned at age 21 d.

    Science.gov (United States)

    Tang, Zhiru; Yin, Yulong; Zhang, Youming; Huang, Ruilin; Sun, Zhihong; Li, Tiejun; Chu, Wuying; Kong, Xiangfeng; Li, Lili; Geng, Meimei; Tu, Qiang

    2009-04-01

    Lactoferrin has antimicrobial activity associated with peptide fragments lactoferricin (LFC) and lactoferrampin (LFA) released on digestion. These two fragments have been expressed in Photorhabdus luminescens as a fusion peptide linked to protein cipB. The construct cipB-LFC-LFA was tested as an alternative to antimicrobial growth promoters in pig production. Sixty piglets with an average live body weight of 5.42 (sem 0.59) kg were challenged with enterotoxigenic Escherichia coli and randomly assigned to four treatment groups fed a maize-soyabean meal diet containing either no addition (C), cipB at 100 mg/kg (C+B), cipB-LFC-LFA at 100 mg/kg (C+L) or colistin sulfate at 100 mg/kg (C+CS) for 3 weeks. Compared with C, dietary supplementation with C+L for 3 weeks increased daily weight gain by 21 %, increased recovery from diarrhoea, enhanced serum glutathione peroxidase (GPx), peroxidase (POD) and total antioxidant content (T-AOC), liver GPx, POD, superoxide dismutase and T-AOC, Fe, total Fe-binding capacity, IgA, IgG and IgM levels (P < 0.05), decreased the concentration of E. coli in the ileum, caecum and colon (P < 0.05), increased the concentration of lactobacilli and bifidobacteria in the ileum, caecum and colon (P < 0.05), and promoted development of the villus-crypt architecture of the small intestine. Growth performance was similar between C+L- and C+CS-supplemented pigs. The present results indicate that LFC-LFA is an effective alternative to the feed antibiotic CS for enhancing growth performance in piglets weaned at age 21 d.

  12. Use of green fluorescent protein fusions to analyse the N- and C-terminal signal peptides of GPI-anchored cell wall proteins in Candida albicans.

    Science.gov (United States)

    Mao, Yuxin; Zhang, Zimei; Wong, Brian

    2003-12-01

    Glycophosphatidylinositol (GPI)-anchored proteins account for 26-35% of the Candida albicans cell wall. To understand the signals that regulate these proteins' cell surface localization, green fluorescent protein (GFP) was fused to the N- and C-termini of the C. albicans cell wall proteins (CWPs) Hwp1p, Als3p and Rbt5p. C. albicans expressing all three fusion proteins were fluorescent at the cell surface. GFP was released from membrane fractions by PI-PLC and from cell walls by beta-glucanase, which implied that GFP was GPI-anchored to the plasma membrane and then covalently attached to cell wall glucans. Twenty and 25 amino acids, respectively, from the N- and C-termini of Hwp1p were sufficient to target GFP to the cell surface. C-terminal substitutions that are permitted by the omega rules (G613D, G613N, G613S, G613A, G615S) did not interfere with GFP localization, whereas some non-permitted substitutions (G613E, G613Q, G613R, G613T and G615Q) caused GFP to accumulate in intracellular ER-like structures and others (G615C, G613N/G615C and G613D/G615C) did not. These results imply that (i) GFP fusions can be used to analyse the N- and C-terminal signal peptides of GPI-anchored CWPs, (ii) the omega amino acid in Hwp1p is G613, and (iii) C can function at the omega+2 position in C. albicans GPI-anchored proteins.

  13. Combat Rescue Helicopter (CRH)

    Science.gov (United States)

    2015-12-01

    Selected Acquisition Report (SAR) RCS: DD-A&T(Q&A)823-479 Combat Rescue Helicopter (CRH) As of FY 2017 President’s Budget Defense Acquisition...Name Combat Rescue Helicopter (CRH) DoD Component Air Force Responsible Office References SAR Baseline (Development Estimate) Defense Acquisition... Helicopter (CRH) system will provide Personnel Recovery (PR) forces with a vertical takeoff and landing aircraft that is quickly deployable and

  14. Line-Tension Controlled Mechanism for Influenza Fusion

    NARCIS (Netherlands)

    Risselada, Herre Jelger; Marelli, Giovanni; Fuhrmans, Marc; Smirnova, Yuliya G.; Grubmueller, Helmut; Marrink, Siewert Jan; Mueller, Marcus

    2012-01-01

    Our molecular simulations reveal that wild-type influenza fusion peptides are able to stabilize a highly fusogenic pre-fusion structure, i.e. a peptide bundle formed by four or more trans-membrane arranged fusion peptides. We rationalize that the lipid rim around such bundle has a non-vanishing rim

  15. Streptavidin-binding peptides and uses thereof

    Science.gov (United States)

    Szostak, Jack W. (Inventor); Wilson, David S. (Inventor); Keefe, Anthony D. (Inventor)

    2006-01-01

    The invention provides peptides with high affinity for streptavidin. These peptides may be expressed as part of fusion proteins to facilitate the detection, quantitation, and purification of proteins of interest.

  16. Rescue US energy innovation

    Science.gov (United States)

    Anadon, Laura Diaz; Gallagher, Kelly Sims; Holdren, John P.

    2017-10-01

    President Trump has proposed severe cuts to US government spending on energy research, development and demonstration, but Congress has the `power of the purse' and can rescue US energy innovation. If serious cuts are enacted, the pace of innovation will slow, harming the economy, energy security and global environmental quality.

  17. Rescue workers and trauma

    DEFF Research Database (Denmark)

    Romano, Eugenia; Elklit, Ask

    2017-01-01

    Introduction: This study investigates which factors had the biggest impact on developing distress in rescue workers who were involved in a firework factory explosion. Method: Four hundred sixty-five rescuers were assessed using items investigating demographic factors, organizational variables, so...

  18. Signal peptide of eosinophil cationic protein is toxic to cells lacking signal peptide peptidase

    International Nuclear Information System (INIS)

    Wu, C.-M.; Chang, Margaret Dah-Tsyr

    2004-01-01

    Eosinophil cationic protein (ECP) is a toxin secreted by activated human eosinophils. The properties of mature ECP have been well studied but those of the signal peptide of ECP (ECPsp) are not clear. In this study, several chimeric proteins containing N-terminal fusion of ECPsp were generated, and introduced into Escherichia coli, Pichia pastoris, and human epidermoid carcinoma cell line A431 to study the function of ECPsp. We found that expression of ECPsp chimeric proteins inhibited the growth of E. coli and P. pastoris but not A431 cells. Primary sequence analysis and in vitro transcription/translation of ECPsp have revealed that it is a potential substrate for human signal peptide peptidase (hSPP), an intramembrane protease located in endoplasmic reticulum. In addition, knockdown of the hSPP mRNA expression in ECPsp-eGFP/A431 cells caused the growth inhibitory effect, whereas complementally expression of hSPP in P. pastoris system rescued the cell growth. Taken together, we have demonstrated that ECPsp is a toxic signal peptide, and expression of hSPP protects the cells from growth inhibition

  19. Microtubule catastrophe and rescue.

    Science.gov (United States)

    Gardner, Melissa K; Zanic, Marija; Howard, Jonathon

    2013-02-01

    Microtubules are long cylindrical polymers composed of tubulin subunits. In cells, microtubules play an essential role in architecture and motility. For example, microtubules give shape to cells, serve as intracellular transport tracks, and act as key elements in important cellular structures such as axonemes and mitotic spindles. To accomplish these varied functions, networks of microtubules in cells are very dynamic, continuously remodeling through stochastic length fluctuations at the ends of individual microtubules. The dynamic behavior at the end of an individual microtubule is termed 'dynamic instability'. This behavior manifests itself by periods of persistent microtubule growth interrupted by occasional switching to rapid shrinkage (called microtubule 'catastrophe'), and then by switching back from shrinkage to growth (called microtubule 'rescue'). In this review, we summarize recent findings which provide new insights into the mechanisms of microtubule catastrophe and rescue, and discuss the impact of these findings in regards to the role of microtubule dynamics inside of cells. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. The rule of rescue.

    Science.gov (United States)

    McKie, John; Richardson, Jeff

    2003-06-01

    Jonsen coined the term "Rule of Rescue"(RR) to describe the imperative people feel to rescue identifiable individuals facing avoidable death. In this paper we attempt to draw a more detailed picture of the RR, identifying its conflict with cost-effectiveness analysis, the preference it entails for identifiable over statistical lives, the shock-horror response it elicits, the preference it entails for lifesaving over non-lifesaving measures, its extension to non-life-threatening conditions, and whether it is motivated by duty or sympathy. We also consider the measurement problems it raises, and argue that quantifying the RR would probably require a two-stage procedure. In the first stage the size of the individual utility gain from a health intervention would be assessed using a technique such as the Standard Gamble or the Time Trade-Off, and in the second the social benefits arising from the RR would be quantified employing the Person Trade-Off. We also consider the normative status of the RR. We argue that it can be defended from a utilitarian point of view, on the ground that rescues increase well-being by reinforcing people's belief that they live in a community that places great value upon life. However, utilitarianism has long been criticised for failing to take sufficient account of fairness, and the case is no different here: fairness requires that we do not discriminate between individuals on morally irrelevant grounds, whereas being "identifiable" does not seem to be a morally relevant ground for discrimination.

  1. Rescuing--a universal phenomenon.

    Science.gov (United States)

    Little, John

    2014-12-01

    Rescuing, where the person is delivered from the immediacy of their conundrum by another, complicates management. The object of this paper is to understand the difficulty in relinquishing the rescuing role. Rescuing is a universal phenomenon in parenting, teaching and therapy that has developed over time through a variety of interwoven social, economic, psychological and clinical variables. © The Royal Australian and New Zealand College of Psychiatrists 2014.

  2. Genetically Controlled Fusion, Exocytosis and Fission of Artificial Vesicles

    DEFF Research Database (Denmark)

    Bönzli, Eva; Hadorn, Maik; De Lucrezia, Davide

    if a special class of viral proteins, termed fusogenic peptides, were added to the external medium. In the present work, we intend to develop genetically controlled fusion, fission and exocytosis of vesicles by the synthesis of peptides within vesicles. First, we enclosed synthesized peptides in vesicles...... to induce in a next step fusion of adjacent vesicles, fission and exocytosis of nested vesicles. Second, we will replace the peptides by an enclosed cell-free expression system to internally synthesize fusion peptides. To control the gene expression, different mechanisms are available, e.g. addition...... fusion, fission and exocytosis....

  3. Sex, Deportation and Rescue

    DEFF Research Database (Denmark)

    Plambech, Sine

    2017-01-01

    recirculating the claim that human trafficking is the “third largest” criminal economy after drugs and weapons. Based on ethnographic fieldwork among Nigerian sex worker migrants conducted in Benin City, Nigeria, in 2011 and 2012, this study brings together four otherwise isolated migration economies......This contribution explores the economies interlinked by the migration of Nigerian women sex workers. The literature and politics of sex work migration and human trafficking economies are commonly relegated to the realm that focuses on profits for criminal networks and pimps, in particular...... – facilitation, remittances, deportation, and rescue – and suggests that we have to examine multiple sites and relink these in order to more fully understand the complexity of sex work migration. Drawing upon literature within transnational feminist analysis, critical human trafficking studies, and migration...

  4. Rescuing Quadratic Inflation

    CERN Document Server

    Ellis, John; Sueiro, Maria

    2014-01-01

    Inflationary models based on a single scalar field $\\phi$ with a quadratic potential $V = \\frac{1}{2} m^2 \\phi^2$ are disfavoured by the recent Planck constraints on the scalar index, $n_s$, and the tensor-to-scalar ratio for cosmological density perturbations, $r_T$. In this paper we study how such a quadratic inflationary model can be rescued by postulating additional fields with quadratic potentials, such as might occur in sneutrino models, which might serve as either curvatons or supplementary inflatons. Introducing a second scalar field reduces but does not remove the pressure on quadratic inflation, but we find a sample of three-field models that are highly compatible with the Planck data on $n_s$ and $r_T$. We exhibit a specific three-sneutrino example that is also compatible with the data on neutrino mass difference and mixing angles.

  5. The problem with rescue medicine.

    Science.gov (United States)

    Jecker, Nancy S

    2013-02-01

    Is there a rational and ethical basis for efforts to rescue individuals in dire straits? When does rescue have ethical support, and when does it reflect an irrational impulse? This paper defines a Rule of Rescue and shows its intuitive appeal. It then proceeds to argue that this rule lacks support from standard principles of justice and from ethical principles more broadly, and should be rejected in many situations. I distinguish between agent-relative and agent-neutral reasons, and argue that the Rule of Rescue qualifies only in a narrow range of cases where agent-relative considerations apply. I conclude that it would be wise to set aside the Rule of Rescue in many cases, especially those involving public policies, where it has only weak normative justification. The broader implications of this analysis are noted.

  6. A single-chain fusion molecule consisting of peptide, major histocompatibility gene complex class I heavy chain and beta2-microglobulin can fold partially correctly, but binds peptide inefficiently

    DEFF Research Database (Denmark)

    Sylvester-Hvid, C; Buus, S

    1999-01-01

    of a recombinant murine MHC-I molecule, which could be produced in large amounts in bacteria. The recombinant MHC-I protein was expressed as a single molecule (PepSc) consisting of the antigenic peptide linked to the MHC-I heavy chain and further linked to human beta2-microglobulin (hbeta2m). The PepSc molecule...... electrophoresis (SDS-PAGE). Serological analysis revealed the presence of some, but not all, MHC-I-specific epitopes. Biochemically, PepSc could bind peptide, however, rather ineffectively. We suggest that a partially correctly refolded MHC-I has been obtained....

  7. Determination of the equilibrium micelle-inserting position of the fusion peptide of gp41 of human immunodeficiency virus type 1 at amino acid resolution by exchange broadening of amide proton resonances

    International Nuclear Information System (INIS)

    Chang, D.-K.; Cheng, S.-F.

    1998-01-01

    The exchange broadening of backbone amide proton resonances of a 23-mer fusion peptide of the transmembrane subunit of HIV-1 envelope glycoprotein gp41, gp41-FP, was investigated at pH 5 and 7 at room temperature in perdeuterated sodium dodecyl sulfate (SDS) micellar solution. Comparison of resonance peaks for these pHs revealed an insignificant change in exchange rate between pH 5 and 7 for amide protons of residues 4 through 14, while the exchange rate increase at neutral pH was more prominent for amide protons of the remaining residues, with peaks from some protons becoming undetectable. The relative insensitivity to pH of the exchange for the amide protons of residues 4 through 14 is attributable to the drastic reduction in [OH-] in the micellar interior, leading to a decreased exchange rate. The A15-G16 segment represents a transition between these two regimes. The data are thus consistent with the notion that the peptide inserts into the hydrophobic core of a membrane-like structure and the A15-G16 dipeptide is located at the micellar-aqueous boundary

  8. Membrane fusion and exocytosis.

    Science.gov (United States)

    Jahn, R; Südhof, T C

    1999-01-01

    Membrane fusion involves the merger of two phospholipid bilayers in an aqueous environment. In artificial lipid bilayers, fusion proceeds by means of defined transition states, including hourglass-shaped intermediates in which the proximal leaflets of the fusing membranes are merged whereas the distal leaflets are separate (fusion stalk), followed by the reversible opening of small aqueous fusion pores. Fusion of biological membranes requires the action of specific fusion proteins. Best understood are the viral fusion proteins that are responsible for merging the viral with the host cell membrane during infection. These proteins undergo spontaneous and dramatic conformational changes upon activation. In the case of the paradigmatic fusion proteins of the influenza virus and of the human immunodeficiency virus, an amphiphilic fusion peptide is inserted into the target membrane. The protein then reorients itself, thus forcing the fusing membranes together and inducing lipid mixing. Fusion of intracellular membranes in eukaryotic cells involves several protein families including SNAREs, Rab proteins, and Sec1/Munc-18 related proteins (SM-proteins). SNAREs form a novel superfamily of small and mostly membrane-anchored proteins that share a common motif of about 60 amino acids (SNARE motif). SNAREs reversibly assemble into tightly packed helical bundles, the core complexes. Assembly is thought to pull the fusing membranes closely together, thus inducing fusion. SM-proteins comprise a family of soluble proteins that bind to certain types of SNAREs and prevent the formation of core complexes. Rab proteins are GTPases that undergo highly regulated GTP-GDP cycles. In their GTP form, they interact with specific proteins, the effector proteins. Recent evidence suggests that Rab proteins function in the initial membrane contact connecting the fusing membranes but are not involved in the fusion reaction itself.

  9. Expression of the cationic antimicrobial peptide lactoferricin fused with the anionic peptide in Escherichia coli.

    Science.gov (United States)

    Kim, Ha-Kun; Chun, Dae-Sik; Kim, Joon-Sik; Yun, Cheol-Ho; Lee, Ju-Hoon; Hong, Soon-Kwang; Kang, Dae-Kyung

    2006-09-01

    Direct expression of lactoferricin, an antimicrobial peptide, is lethal to Escherichia coli. For the efficient production of lactoferricin in E. coli, we developed an expression system in which the gene for the lysine- and arginine-rich cationic lactoferricin was fused to an anionic peptide gene to neutralize the basic property of lactoferricin, and successfully overexpressed the concatemeric fusion gene in E. coli. The lactoferricin gene was linked to a modified magainin intervening sequence gene by a recombinational polymerase chain reaction, thus producing an acidic peptide-lactoferricin fusion gene. The monomeric acidic peptide-lactoferricin fusion gene was multimerized and expressed in E. coli BL21(DE3) upon induction with isopropyl-beta-D-thiogalactopyranoside. The expression levels of the fusion peptide reached the maximum at the tetramer, while further increases in the copy number of the fusion gene substantially reduced the peptide expression level. The fusion peptides were isolated and cleaved to generate the separate lactoferricin and acidic peptide. About 60 mg of pure recombinant lactoferricin was obtained from 1 L of E. coli culture. The purified recombinant lactoferricin was found to have a molecular weight similar to that of chemically synthesized lactoferricin. The recombinant lactoferricin showed antimicrobial activity and disrupted bacterial membrane permeability, as the native lactoferricin peptide does.

  10. 46 CFR 133.135 - Rescue boats.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 4 2010-10-01 2010-10-01 false Rescue boats. 133.135 Section 133.135 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OFFSHORE SUPPLY VESSELS LIFESAVING SYSTEMS Requirements for All OSVs § 133.135 Rescue boats. (a) Each OSV must carry at least one rescue boat. Each rescue...

  11. 46 CFR 199.262 - Rescue boats.

    Science.gov (United States)

    2010-10-01

    ... SYSTEMS FOR CERTAIN INSPECTED VESSELS Additional Requirements for Cargo Vessels § 199.262 Rescue boats. (a) Each cargo vessel must carry at least one rescue boat. Each rescue boat must be approved under approval... 46 Shipping 7 2010-10-01 2010-10-01 false Rescue boats. 199.262 Section 199.262 Shipping COAST...

  12. Fusion energy

    International Nuclear Information System (INIS)

    Gross, R.A.

    1984-01-01

    This textbook covers the physics and technology upon which future fusion power reactors will be based. It reviews the history of fusion, reaction physics, plasma physics, heating, and confinement. Descriptions of commercial plants and design concepts are included. Topics covered include: fusion reactions and fuel resources; reaction rates; ignition, and confinement; basic plasma directory; Tokamak confinement physics; fusion technology; STARFIRE: A commercial Tokamak fusion power plant. MARS: A tandem-mirror fusion power plant; and other fusion reactor concepts

  13. Robust expression and secretion of Xylanase1 in Chlamydomonas reinhardtii by fusion to a selection gene and processing with the FMDV 2A peptide.

    Directory of Open Access Journals (Sweden)

    Beth A Rasala

    Full Text Available Microalgae have recently received attention as a potential low-cost host for the production of recombinant proteins and novel metabolites. However, a major obstacle to the development of algae as an industrial platform has been the poor expression of heterologous genes from the nuclear genome. Here we describe a nuclear expression strategy using the foot-and-mouth-disease-virus 2A self-cleavage peptide to transcriptionally fuse heterologous gene expression to antibiotic resistance in Chlamydomonas reinhardtii. We demonstrate that strains transformed with ble-2A-GFP are zeocin-resistant and accumulate high levels of GFP that is properly 'cleaved' at the FMDV 2A peptide resulting in monomeric, cytosolic GFP that is easily detectable by in-gel fluorescence analysis or fluorescent microscopy. Furthermore, we used our ble2A nuclear expression vector to engineer the heterologous expression of the industrial enzyme, xylanase. We demonstrate that linking xyn1 expression to ble2A expression on the same open reading frame led to a dramatic (~100-fold increase in xylanase activity in cells lysates compared to the unlinked construct. Finally, by inserting an endogenous secretion signal between the ble2A and xyn1 coding regions, we were able to target monomeric xylanase for secretion. The novel microalgae nuclear expression strategy described here enables the selection of transgenic lines that are efficiently expressing the heterologous gene-of-interest and should prove valuable for basic research as well as algal biotechnology.

  14. Joseph Conrad's tormented Rescue (fantasy).

    Science.gov (United States)

    Freedman, William

    2014-02-01

    Joseph Conrad was a notoriously tormented writer for whom the creative act was often a punishment severe enough to drive him into paralyzing depressions that delayed the completion of his novels, sometimes for years. By far the most agonizing of these projects was The Rescue, a novel he began in 1898, abandoned a year later, tried unsuccessfully to continue several times over the next two decades, but was only able to resume in 1918 and to complete, after another tortured two-year struggle, in 1920. An explanation for this incapacity, that is powerfully suggested by the novel's evocative title and perhaps unintentionally ironic subtitle (A Romance of the Shallows) has not yet been explored. Using Freud's 1910 essay on the rescue fantasy, "Contributions to the Psychology of Love: A Special Type of Choice of Object Made by Men," and Emanuel Berman's instructive revision and expansion of the concept in his 2003 American Imago essay, "Ferenczi, Rescue, and Utopia," I argue that a substantial explanation for Conrad's tormented history with The Rescue is ascribable to its quite remarkably faithful treatment of a rescue fantasy with deep and disabling resonance for its author. More specifically, the difficulty was compounded by the novel's dramatization of the soul-crushing conflict between two such fantasies: one in the service of the masculine ideal of unflinching dedication to a heroic purpose, the other promising satisfaction to the equally potent demands of emotional and sexual desire. Features of Conrad's narrative fit so tightly and consistently with the theory as Freud (and Abraham) proposed and as Berman elaborated it that The Rescue offers itself as one of those rare and reinforcing instances wherein the literary text seems to validate the psychoanalytic theory at least as persuasively as the theory "understands" the text.

  15. CERN Fire Brigade rescue simulation

    CERN Multimedia

    Maximilien Brice

    2004-01-01

    The CERN Fire Brigade is made up of experienced firemen from all of the 20 Member States. In these images they are seen at a 'Discovery Monday' held at the Microcosm exhibition. Here visitors learn how the Fire Brigade deal with various situations, including a simulated cave rescue performed by the Hazardous Environments Response Team.

  16. The RESCueH Programme

    DEFF Research Database (Denmark)

    Søgaard Nielsen, Anette; Nielsen, Bent; Andersen, Kjeld

    2016-01-01

    Excessive alcohol consumption is one of the most important lifestyle factors affecting the disease burden in the Western world. The results of treatment in daily practice are modest at best. The aim of the RESCueH programme is to develop and evaluate methods, which are as practice-near as possible...

  17. Self-Rescue Mask Training

    CERN Multimedia

    2013-01-01

    Nine new self-rescue mask instructors have been trained since early 2013, which provides CERN with a total of 26 self-rescue mask instructors to date. This will allow us to meet the increasing training needs caused by the Long Shut Down LS1.   The self-rescue mask instructors have trained 1650 persons in 2012 and about 500 persons since the beginning of the year on how to wear the masks properly. We thank all the instructors and all the persons that made this training possible. Please remember that the self-rescue masks training sessions are scheduled as follows: Basic course: Tuesday and Thursday mornings (2 sessions – 8.30 AM and 10.30 AM), duration:  1.30 hour, in French and English – registration via CERN online training catalogue – Course code 077Y00. Refresher training : Monday mornings (2 sessions – 8.30 AM and 10.30 AM), duration: 1.30 hour , in French and English – registration via CERN online training catalogue &...

  18. 46 CFR 199.202 - Rescue boats.

    Science.gov (United States)

    2010-10-01

    ... SYSTEMS FOR CERTAIN INSPECTED VESSELS Additional Requirements for Passenger Vessels § 199.202 Rescue boats... 46 Shipping 7 2010-10-01 2010-10-01 false Rescue boats. 199.202 Section 199.202 Shipping COAST... least one rescue boat approved under approval series 160.156 that is equipped as specified in table 199...

  19. Rope rescue in National fire-fighting and rescue system

    OpenAIRE

    SOCHACKI MARIAN

    2008-01-01

    Автор описывает организацию, функционирование и место системы спасения с высоты в Государственной спасательно-гасящей системе.The author describes organization, working and place of rope rescue in National Firefighting and Rescue System (KSRG).

  20. Cholera toxin subunit B peptide fusion proteins reveal impaired oral tolerance induction in diabetes-prone but not in diabetes-resistant mice.

    Science.gov (United States)

    Presa, Maximiliano; Ortiz, Angela Zarama; Garabatos, Nahir; Izquierdo, Cristina; Rivas, Elisa I; Teyton, Luc; Mora, Conchi; Serreze, David; Stratmann, Thomas

    2013-11-01

    The cholera toxin B subunit (CTB) has been used as adjuvant to improve oral vaccine delivery in type 1 diabetes. The effect of CTB/peptide formulations on Ag-specific CD4(+) T cells has remained largely unexplored. Here, using tetramer analysis, we investigated how oral delivery of CTB fused to two CD4(+) T-cell epitopes, the BDC-2.5 T-cell 2.5 mi mimotope and glutamic acid decarboxylase (GAD) 286-300, affected diabetogenic CD4(+) T cells in nonobese diabetic (NOD) mice. When administered i.p., CTB-2.5 mi activated 2.5 mi(+) T cells and following intragastric delivery generated Ag-specific Foxp3(+) Treg and Th2 cells. While 2.5 mi(+) and GAD-specific T cells were tolerized in diabetes-resistant NODxB6.Foxp3(EGFP) F1 and nonobese resistant (NOR) mice, this did not occur in NOD mice. This indicated that NOD mice had a recessive genetic resistance to induce oral tolerance to both CTB-fused epitopes. In contrast to NODxB6.Foxp3(EGFP) F1 mice, oral treatment in NOD mice lead to strong 2.5 mi(+) T-cell activation and the sequestration of these cells to the effector-memory pool. Oral treatment of NOD mice with CTB-2.5 mi failed to prevent diabetes. These findings underline the importance of investigating the effect of oral vaccine formulations on diabetogenic T cells as in selected cases they may have counterproductive consequences in human patients. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Facilitating protein solubility by use of peptide extensions

    Science.gov (United States)

    Freimuth, Paul I; Zhang, Yian-Biao; Howitt, Jason

    2013-09-17

    Expression vectors for expression of a protein or polypeptide of interest as a fusion product composed of the protein or polypeptide of interest fused at one terminus to a solubility enhancing peptide extension are provided. Sequences encoding the peptide extensions are provided. The invention further comprises antibodies which bind specifically to one or more of the solubility enhancing peptide extensions.

  2. EMP Fusion

    OpenAIRE

    KUNTAY, Isık

    2010-01-01

    This paper introduces a novel fusion scheme, called EMP Fusion, which has the promise of achieving breakeven and realizing commercial fusion power. The method is based on harnessing the power of an electromagnetic pulse generated by the now well-developed flux compression technology. The electromagnetic pulse acts as a means of both heating up the plasma and confining the plasma, eliminating intermediate steps. The EMP Fusion device is simpler compared to other fusion devices and this reduces...

  3. GIS Support for Flood Rescue

    DEFF Research Database (Denmark)

    Liang, Gengsheng; Mioc, Darka; Anton, François

    2007-01-01

    Under flood events, the ground traffic is blocked in and around the flooded area due to damages to roads and bridges. The traditional transportation network may not always help people to make a right decision for evacuation. In order to provide dynamic road information needed for flood rescue, we...... to retrieve the shortest and safest route in Fredericton road network during flood event. It enables users to make a timely decision for flood rescue. We are using Oracle Spatial to deal with emergency situations that can be applied to other constrained network applications as well....... developed an adaptive web-based transportation network application using Oracle technology. Moreover, the geographic relationships between the road network and flood areas are taken into account. The overlay between the road network and flood polygons is computed on the fly. This application allows users...

  4. [Design and application of portable rescue vehicle].

    Science.gov (United States)

    Guo, Ying; Qi, Huaying; Wang, Shen

    2017-12-01

    The disease of critically ill patients was with rapid changes, and at any time faced the risk of emergency. The current commonly used rescue vehicles were larger and bulky implementation, which were not conducive to the operation, therefore the design of a portable rescue vehicle was needed. This new type of rescue vehicle is multi-layer folding structure, with small footprint, large storage space, so a variety of first aid things can be classified and put, easy to be cleaned and disinfected. In the rescue process, the portable rescue vehicles can be placed in the required position; box of various emergency items can be found at a glance with easy access; the height of the infusion stand can adjust freely according to the user height; the rescue vehicle handle can be easy to pull and adjust accord with human body mechanics principle. The portable rescue vehicle facilitates the operation of medical staff, and is worthy of clinical application.

  5. Peptide dendrimers

    Czech Academy of Sciences Publication Activity Database

    Niederhafner, Petr; Šebestík, Jaroslav; Ježek, Jan

    2005-01-01

    Roč. 11, - (2005), 757-788 ISSN 1075-2617 R&D Projects: GA ČR(CZ) GA203/03/1362 Institutional research plan: CEZ:AV0Z40550506 Keywords : multiple antigen peptides * peptide dendrimers * synthetic vaccine * multipleantigenic peptides Subject RIV: CC - Organic Chemistry Impact factor: 1.803, year: 2005

  6. Rescue Implantation of Expandable Cages for Severe Osteolysis and Cage Dislocation in the Lumbosacral Junction.

    Science.gov (United States)

    Schatlo, Bawarjan; Rohde, Veit; Solomiichuk, Volodymyr; von Eckardstein, Kajetan; Behm, Timo

    2017-11-01

    Osteolysis and implant loosening are commonly encountered problems after spinal instrumentation. In a patient who had previously undergone a posterior lumbar interbody fusion procedure, fusion did not occur, and a secondary cage dislocation led to an impingement of the L5 nerve root with severe radiculopathy. Revision surgery was performed. Intraoperatively, osteolysis was found to be so severe that conventional cages did not fill the void to allow for sufficient anterior column support. We used expandable transforaminal lumbar interbody fusion cages and implanted them bilaterally to replace the dislodged posterior lumbar interbody fusion cages. Clinical follow-up was uneventful. Imaging performed at 1 year showed satisfactory cage position and fusion. We propose the use of cages with the ability of ventral distraction in similar rescue interventions with cage dislocation and bone resorption. This may prevent a second surgery via a ventral approach. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Osteoclast Fusion

    DEFF Research Database (Denmark)

    Marie Julie Møller, Anaïs; Delaissé, Jean-Marie; Søe, Kent

    2017-01-01

    on the nuclearity of fusion partners. While CD47 promotes cell fusions involving mono-nucleated pre-osteoclasts, syncytin-1 promotes fusion of two multi-nucleated osteoclasts, but also reduces the number of fusions between mono-nucleated pre-osteoclasts. Furthermore, CD47 seems to mediate fusion mostly through...... individual fusion events using time-lapse and antagonists of CD47 and syncytin-1. All time-lapse recordings have been studied by two independent observers. A total of 1808 fusion events were analyzed. The present study shows that CD47 and syncytin-1 have different roles in osteoclast fusion depending...... broad contact surfaces between the partners' cell membrane while syncytin-1 mediate fusion through phagocytic-cup like structure. J. Cell. Physiol. 9999: 1-8, 2016. © 2016 Wiley Periodicals, Inc....

  8. Fusion power

    International Nuclear Information System (INIS)

    Hancox, R.

    1981-01-01

    The principles of fusion power, and its advantages and disadvantages, are outlined. Present research programmes and future plans directed towards the development of a fusion power reactor, are summarized. (U.K.)

  9. Fusion rings and fusion ideals

    DEFF Research Database (Denmark)

    Andersen, Troels Bak

    by the so-called fusion ideals. The fusion rings of Wess-Zumino-Witten models have been widely studied and are well understood in terms of precise combinatorial descriptions and explicit generating sets of the fusion ideals. They also appear in another, more general, setting via tilting modules for quantum......This dissertation investigates fusion rings, which are Grothendieck groups of rigid, monoidal, semisimple, abelian categories. Special interest is in rational fusion rings, i.e., fusion rings which admit a finite basis, for as commutative rings they may be presented as quotients of polynomial rings...

  10. The Data Rescue @ Home Project

    Science.gov (United States)

    Stickler, A.; Allan, R.; Valente, M. A.; Tinz, B.; Brönnimann, S.

    2012-04-01

    Climate science as a whole as well as reanalyses as a special case can significantly profit from the recovery, imaging and digitisation of historical observations. The importance of this fact is reflected in large, global data rescue projects and initiatives such as the Atmospheric Circulation Reconstructions over the Earth (ACRE, www.met-acre.org) or the EU FP7 ERA-CLIM project (www.era-clim.eu). From the time before 1957, there are still large amounts of surface data e.g. from former colonies and from overseas territories of European countries )e.g. Portugal, France and Germany) that need to be rescued. Also in case of the very early upper-air observations before the 1930s, even Europe and North America still hold an important quantity of data to be recovered in digital form. Here, we present the web platform "Data Rescue @ Home" (www.data-rescue-at-home.org), which has been developed at ETH Zurich and Oeschger Centre for Climate Change Research, and which has been designed to take advantage of the voluntary assistance of the thousands of people on the web who are interested in climate or old weather data. On the website, these volunteers can enter meteorological data shown on digital images into entry masks that resemble the original. By registering, the users get access to their personal digitisation statistics and help optimising the project. At the moment, 4 digitisation projects are online: One project is dealing with German upper-air data from the Second World War period. In a second project, station data from Tulagi (Solomon Islands) is being digitised. Finally, two collaborative projects have been included: One in cooperation with the Instituto Dom Luiz (Univ. Lisbon, Portugal), where Portuguese station data from Angra (Azores) is digitised, and a further one in cooperation with the German Meteorological Service (DWD), in which precipitation data from former German colonies is being digitised. On our poster, we will report on the status of the projects

  11. Fusion: introduction

    International Nuclear Information System (INIS)

    Decreton, M.

    2006-01-01

    The article gives an overview and introduction to the activities of SCK-CEN's research programme on fusion. The decision to construct the ITER international nuclear fusion experiment in Cadarache is highlighted. A summary of the Belgian contributions to fusion research is given with particular emphasis on studies of radiation effects on diagnostics systems, radiation effects on remote handling sensing systems, fusion waste management and socio-economic studies

  12. Membrane fusion

    DEFF Research Database (Denmark)

    Bendix, Pól Martin

    2015-01-01

    At Stanford University, Boxer lab, I worked on membrane fusion of small unilamellar lipid vesicles to flat membranes tethered to glass surfaces. This geometry closely resembles biological systems in which liposomes fuse to plasma membranes. The fusion mechanism was studied using DNA zippering...... between complementary strands linked to the two apposing membranes closely mimicking the zippering mechanism of SNARE fusion complexes....

  13. Fusion Canada

    International Nuclear Information System (INIS)

    1987-07-01

    This first issue of a quarterly newsletter announces the startup of the Tokamak de Varennes, describes Canada's national fusion program, and outlines the Canadian Fusion Fuels Technology Program. A map gives the location of the eleven principal fusion centres in Canada. (L.L.)

  14. Advances in search and rescue at sea

    Science.gov (United States)

    Breivik, Øyvind; Allen, Arthur Addoms; Maisondieu, Christophe; Olagnon, Michel

    2013-01-01

    A topical collection on "Advances in Search and Rescue at Sea" has appeared in recent issues of Ocean Dynamics following the latest in a series of workshops on "Technologies for Search and Rescue and other Emergency Marine Operations" (2004, 2006, 2008, and 2011), hosted by IFREMER in Brest, France. Here, we give a brief overview of the history of search and rescue at sea before we summarize the main results of the papers that have appeared in the topical collection.

  15. Genetically controlled fusion, exocytosis and fission of artificial vesicles-a roadmap

    DEFF Research Database (Denmark)

    Bönzli, Eva; Hadorn, Maik; de Lucrezia, Davide

    2011-01-01

    were shown to fuse if a special class of viral proteins, termed fusogenic peptides, were added to the external medium (Nomura et al. 2004). In the present work, we intend to develop genetically controlled fusion, fission and exocytosis of vesicles by the synthesis of peptides within vesicles. First, we...... enclosed synthesized peptides in vesicles to induce in a next step fusion of adjacent vesicles, fission and exocytosis of nested vesicles. Second, we will replace the peptides by an enclosed cell-free expression system to internally synthesize fusion peptides. To control the gene expression, different...

  16. Fusion neutronics

    CERN Document Server

    Wu, Yican

    2017-01-01

    This book provides a systematic and comprehensive introduction to fusion neutronics, covering all key topics from the fundamental theories and methodologies, as well as a wide range of fusion system designs and experiments. It is the first-ever book focusing on the subject of fusion neutronics research. Compared with other nuclear devices such as fission reactors and accelerators, fusion systems are normally characterized by their complex geometry and nuclear physics, which entail new challenges for neutronics such as complicated modeling, deep penetration, low simulation efficiency, multi-physics coupling, etc. The book focuses on the neutronics characteristics of fusion systems and introduces a series of theories and methodologies that were developed to address the challenges of fusion neutronics, and which have since been widely applied all over the world. Further, it introduces readers to neutronics design’s unique principles and procedures, experimental methodologies and technologies for fusion systems...

  17. 46 CFR 133.140 - Stowage of rescue boats.

    Science.gov (United States)

    2010-10-01

    ... SYSTEMS Requirements for All OSVs § 133.140 Stowage of rescue boats. (a) Rescue boats must be stowed as follows: (1) Each rescue boat must be ready for launching in not more than 5 minutes. (2) Each rescue boat... 46 Shipping 4 2010-10-01 2010-10-01 false Stowage of rescue boats. 133.140 Section 133.140...

  18. Teaching Holocaust Rescue: A Problematic Pedagogy

    Science.gov (United States)

    Lindquist, David H.

    2008-01-01

    Determining how to teach about rescue during the Holocaust presents many dilemmas to teachers as they plan Holocaust curricula. Rescue is often overemphasized, and faulty perspectives about rescuers and their actions may cause students to develop distorted views about this aspect of Holocaust history. This article explores several factors that…

  19. Fusion Physics

    Energy Technology Data Exchange (ETDEWEB)

    Kikuchi, Mitsuru; Lackner, Karl; Tran, Minh Quang [eds.

    2012-09-15

    Recreating the energy production process of the Sun - nuclear fusion - on Earth in a controlled fashion is one of the greatest challenges of this century. If achieved at affordable costs, energy supply security would be greatly enhanced and environmental degradation from fossil fuels greatly diminished. Fusion Physics describes the last fifty years or so of physics and research in innovative technologies to achieve controlled thermonuclear fusion for energy production. The International Atomic Energy Agency (IAEA) has been involved since its establishment in 1957 in fusion research. It has been the driving force behind the biennial conferences on Plasma Physics and Controlled Thermonuclear Fusion, today known as the Fusion Energy Conference. Hosted by several Member States, this biennial conference provides a global forum for exchange of the latest achievements in fusion research against the backdrop of the requirements for a net energy producing fusion device and, eventually, a fusion power plant. The scientific and technological knowledge compiled during this series of conferences, as well as by the IAEA Nuclear Fusion journal, is immense and will surely continue to grow in the future. It has led to the establishment of the International Thermonuclear Experimental Reactor (ITER), which represents the biggest experiment in energy production ever envisaged by humankind.

  20. Fusion breeder

    International Nuclear Information System (INIS)

    Moir, R.W.

    1982-01-01

    The fusion breeder is a fusion reactor designed with special blankets to maximize the transmutation by 14 MeV neutrons of uranium-238 to plutonium or thorium to uranium-233 for use as a fuel for fission reactors. Breeding fissile fuels has not been a goal of the US fusion energy program. This paper suggests it is time for a policy change to make the fusion breeder a goal of the US fusion program and the US nuclear energy program. The purpose of this paper is to suggest this policy change be made and tell why it should be made, and to outline specific research and development goals so that the fusion breeder will be developed in time to meet fissile fuel needs

  1. Fusion Implementation

    International Nuclear Information System (INIS)

    Schmidt, J.A.

    2002-01-01

    If a fusion DEMO reactor can be brought into operation during the first half of this century, fusion power production can have a significant impact on carbon dioxide production during the latter half of the century. An assessment of fusion implementation scenarios shows that the resource demands and waste production associated with these scenarios are manageable factors. If fusion is implemented during the latter half of this century it will be one element of a portfolio of (hopefully) carbon dioxide limiting sources of electrical power. It is time to assess the regional implications of fusion power implementation. An important attribute of fusion power is the wide range of possible regions of the country, or countries in the world, where power plants can be located. Unlike most renewable energy options, fusion energy will function within a local distribution system and not require costly, and difficult, long distance transmission systems. For example, the East Coast of the United States is a prime candidate for fusion power deployment by virtue of its distance from renewable energy sources. As fossil fuels become less and less available as an energy option, the transmission of energy across bodies of water will become very expensive. On a global scale, fusion power will be particularly attractive for regions separated from sources of renewable energy by oceans

  2. Solid-state nuclear magnetic resonance (NMR) spectroscopy of human immunodeficiency virus gp41 protein that includes the fusion peptide: NMR detection of recombinant Fgp41 in inclusion bodies in whole bacterial cells and structural characterization of purified and membrane-associated Fgp41.

    Science.gov (United States)

    Vogel, Erica P; Curtis-Fisk, Jaime; Young, Kaitlin M; Weliky, David P

    2011-11-22

    Human immunodeficiency virus (HIV) infection of a host cell begins with fusion of the HIV and host cell membranes and is mediated by the gp41 protein, a single-pass integral membrane protein of HIV. The 175 N-terminal residues make up the ectodomain that lies outside the virus. This work describes the production and characterization of an ectodomain construct containing the 154 N-terminal gp41 residues, including the fusion peptide (FP) that binds to target cell membranes. The Fgp41 sequence was derived from one of the African clade A strains of HIV-1 that have been less studied than European/North American clade B strains. Fgp41 expression at a level of ~100 mg/L of culture was evidenced by an approach that included amino acid type (13)CO and (15)N labeling of recombinant protein and solid-state NMR (SSNMR) spectroscopy of lyophilized whole cells. The approach did not require any protein solubilization or purification and may be a general approach for detection of recombinant protein. The purified Fgp41 yield was ~5 mg/L of culture. SSNMR spectra of membrane-associated Fgp41 showed high helicity for the residues C-terminal of the FP. This was consistent with a "six-helix bundle" (SHB) structure that is the final gp41 state during membrane fusion. This observation and negligible Fgp41-induced vesicle fusion supported a function for SHB gp41 of membrane stabilization and fusion arrest. SSNMR spectra of residues in the membrane-associated FP provided evidence of a mixture of molecular populations with either helical or β-sheet FP conformation. These and earlier SSNMR data strongly support the existence of these populations in the SHB state of membrane-associated gp41. © 2011 American Chemical Society

  3. Precision Rescue Behavior in North American Ants

    Directory of Open Access Journals (Sweden)

    Katherine Taylor

    2013-07-01

    Full Text Available Altruistic behavior, in which one individual provides aid to another at some cost to itself, is well documented. However, some species engage in a form of altruism, called rescue, that places the altruist in immediate danger. Here we investigate one such example, namely rescuing victims captured by predators. In a field experiment with two North American ant species, Tetramorium sp. E and Prenolepis imparis, individuals were held in artificial snares simulating capture. T. sp. E, but not P. imparis, exhibited digging, pulling, and snare biting, the latter precisely targeted to the object binding the victim. These results are the first to document precision rescue in a North American ant species; moreover, unlike rescue in other ants, T. sp. E rescues conspecifics from different colonies, mirroring their atypical social behavior, namely the lack of aggression between non-nestmate (heterocolonial conspecifics. In a second, observational study designed to demonstrate rescue from an actual predator, T. sp. E victims were dropped into an antlion's pit and the behavior of a single rescuer was observed. Results showed that T. sp. E not only attempted to release the victim, but also risked attacking the predator, suggesting that precision rescue may play an important role in this species' antipredator behavior.

  4. A new approach to road accident rescue.

    Science.gov (United States)

    Morales, Alejandro; González-Aguilera, Diego; López, Alfonso I; Gutiérrez, Miguel A

    2016-01-01

    This article develops and validates a new methodology and tool for rescue assistance in traffic accidents, with the aim of improving its efficiency and safety in the evacuation of people, reducing the number of victims in road accidents. Different tests supported by professionals and experts have been designed under different circumstances and with different categories of damaged vehicles coming from real accidents and simulated trapped victims in order to calibrate and refine the proposed methodology and tool. To validate this new approach, a tool called App_Rescue has been developed. This tool is based on the use of a computer system that allows an efficient access to the technical information of the vehicle and sanitary information of the common passengers. The time spent during rescue using the standard protocol and the proposed method was compared. This rescue assistance system allows us to make vital information accessible in posttrauma care services, improving the effectiveness of interventions by the emergency services, reducing the rescue time and therefore minimizing the consequences involved and the number of victims. This could often mean saving lives. In the different simulated rescue operations, the rescue time has been reduced an average of 14%.

  5. Material Binding Peptides for Nanotechnology

    Directory of Open Access Journals (Sweden)

    Urartu Ozgur Safak Seker

    2011-02-01

    Full Text Available Remarkable progress has been made to date in the discovery of material binding peptides and their utilization in nanotechnology, which has brought new challenges and opportunities. Nowadays phage display is a versatile tool, important for the selection of ligands for proteins and peptides. This combinatorial approach has also been adapted over the past decade to select material-specific peptides. Screening and selection of such phage displayed material binding peptides has attracted great interest, in particular because of their use in nanotechnology. Phage display selected peptides are either synthesized independently or expressed on phage coat protein. Selected phage particles are subsequently utilized in the synthesis of nanoparticles, in the assembly of nanostructures on inorganic surfaces, and oriented protein immobilization as fusion partners of proteins. In this paper, we present an overview on the research conducted on this area. In this review we not only focus on the selection process, but also on molecular binding characterization and utilization of peptides as molecular linkers, molecular assemblers and material synthesizers.

  6. Thermonuclear fusion

    International Nuclear Information System (INIS)

    Weisse, J.

    2000-01-01

    This document takes stock of the two ways of thermonuclear fusion research explored today: magnetic confinement fusion and inertial confinement fusion. The basic physical principles are recalled first: fundamental nuclear reactions, high temperatures, elementary properties of plasmas, ignition criterion, magnetic confinement (charged particle in a uniform magnetic field, confinement and Tokamak principle, heating of magnetized plasmas (ohmic, neutral particles, high frequency waves, other heating means), results obtained so far (scale laws and extrapolation of performances, tritium experiments, ITER project), inertial fusion (hot spot ignition, instabilities, results (Centurion-Halite program, laser experiments). The second part presents the fusion reactor and its associated technologies: principle (tritium production, heat source, neutron protection, tritium generation, materials), magnetic fusion (superconducting magnets, divertor (role, principle, realization), inertial fusion (energy vector, laser adaptation, particle beams, reaction chamber, stresses, chamber concepts (dry and wet walls, liquid walls), targets (fabrication, injection and pointing)). The third chapter concerns the socio-economic aspects of thermonuclear fusion: safety (normal operation and accidents, wastes), costs (costs structure and elementary comparison, ecological impact and external costs). (J.S.)

  7. Fusion devices

    International Nuclear Information System (INIS)

    Fowler, T.K.

    1977-01-01

    Three types of thermonuclear fusion devices currently under development are reviewed for an electric utilities management audience. Overall design features of laser fusion, tokamak, and magnetic mirror type reactors are described and illustrated. Thrusts and trends in current research on these devices that promise to improve performance are briefly reviewed. Twenty photographs and drawings are included

  8. Amphibious Search and Rescue: Shaping the Future

    National Research Council Canada - National Science Library

    Dowling, Michael

    2002-01-01

    The current Amphibious Search and Rescue (ASAR) mission is outdated, lacks integration with the mission/doctrine of the amphibious force and fails to exploit the multi-mission and tactical capabilities of the MH-60S helicopter...

  9. Atomic fusion, Gerrard atomic fusion

    International Nuclear Information System (INIS)

    Gerrard, T.H.

    1980-01-01

    In the approach to atomic fusion described here the heat produced in a fusion reaction, which is induced in a chamber by the interaction of laser beams and U.H.F. electromagnetic beams with atom streams, is transferred to a heat exchanger for electricity generation by a coolant flowing through a jacket surrounding the chamber. (U.K.)

  10. Peaceful fusion

    Energy Technology Data Exchange (ETDEWEB)

    Englert, Matthias [IANUS, TU Darmstadt (Germany)

    2014-07-01

    Like other intense neutron sources fusion reactors have in principle a potential to be used for military purposes. Although the use of fissile material is usually not considered when thinking of fusion reactors (except in fusion-fission hybrid concepts) quantitative estimates about the possible production potential of future commercial fusion reactor concepts show that significant amounts of weapon grade fissile materials could be produced even with very limited amounts of source materials. In this talk detailed burnup calculations with VESTA and MCMATH using an MCNP model of the PPCS-A will be presented. We compare different irradiation positions and the isotopic vectors of the plutonium bred in different blankets of the reactor wall with the liquid lead-lithium alloy replaced by uranium. The technical, regulatory and policy challenges to manage the proliferation risks of fusion power will be addressed as well. Some of these challenges would benefit if addressed at an early stage of the research and development process. Hence, research on fusion reactor safeguards should start as early as possible and accompany the current research on experimental fusion reactors.

  11. Factors influencing mine rescue team behaviors.

    Science.gov (United States)

    Jansky, Jacqueline H; Kowalski-Trakofler, K M; Brnich, M J; Vaught, C

    2016-01-01

    A focus group study of the first moments in an underground mine emergency response was conducted by the National Institute for Occupational Safety and Health (NIOSH), Office for Mine Safety and Health Research. Participants in the study included mine rescue team members, team trainers, mine officials, state mining personnel, and individual mine managers. A subset of the data consists of responses from participants with mine rescue backgrounds. These responses were noticeably different from those given by on-site emergency personnel who were at the mine and involved with decisions made during the first moments of an event. As a result, mine rescue team behavior data were separated in the analysis and are reported in this article. By considering the responses from mine rescue team members and trainers, it was possible to sort the data and identify seven key areas of importance to them. On the basis of the responses from the focus group participants with a mine rescue background, the authors concluded that accurate and complete information and a unity of purpose among all command center personnel are two of the key conditions needed for an effective mine rescue operation.

  12. Ligand-regulated peptides: a general approach for modulating protein-peptide interactions with small molecules.

    Science.gov (United States)

    Binkowski, Brock F; Miller, Russell A; Belshaw, Peter J

    2005-07-01

    We engineered a novel ligand-regulated peptide (LiRP) system where the binding activity of intracellular peptides is controlled by a cell-permeable small molecule. In the absence of ligand, peptides expressed as fusions in an FKBP-peptide-FRB-GST LiRP scaffold protein are free to interact with target proteins. In the presence of the ligand rapamycin, or the nonimmunosuppressive rapamycin derivative AP23102, the scaffold protein undergoes a conformational change that prevents the interaction of the peptide with the target protein. The modular design of the scaffold enables the creation of LiRPs through rational design or selection from combinatorial peptide libraries. Using these methods, we identified LiRPs that interact with three independent targets: retinoblastoma protein, c-Src, and the AMP-activated protein kinase. The LiRP system should provide a general method to temporally and spatially regulate protein function in cells and organisms.

  13. 49 CFR 238.114 - Rescue access windows.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Rescue access windows. 238.114 Section 238.114... § 238.114 Rescue access windows. (a) Number and location. Except as provided in paragraph (a)(1)(ii) of... rescue access windows. At least one rescue access window shall be located in each side of the car...

  14. Cold fusion

    International Nuclear Information System (INIS)

    Suh, Suk Yong; Sung, Ki Woong; Kang, Joo Sang; Lee, Jong Jik

    1995-02-01

    So called 'cold fusion phenomena' are not confirmed yet. Excess heat generation is very delicate one. Neutron generation is most reliable results, however, the records are erratic and the same results could not be repeated. So there is no reason to exclude the malfunction of testing instruments. The same arguments arise in recording 4 He, 3 He, 3 H, which are not rich in quantity basically. An experiment where plenty of 4 He were recorded is attached in appendix. The problem is that we are trying to search cold fusion which is permitted by nature or not. The famous tunneling effect in quantum mechanics will answer it, however, the most fusion rate is known to be negligible. The focus of this project is on the theme that how to increase that negligible fusion rate. 6 figs, 4 tabs, 1512 refs. (Author)

  15. Cold fusion

    Energy Technology Data Exchange (ETDEWEB)

    Suh, Suk Yong; Sung, Ki Woong; Kang, Joo Sang; Lee, Jong Jik [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

    1995-02-01

    So called `cold fusion phenomena` are not confirmed yet. Excess heat generation is very delicate one. Neutron generation is most reliable results, however, the records are erratic and the same results could not be repeated. So there is no reason to exclude the malfunction of testing instruments. The same arguments arise in recording {sup 4}He, {sup 3}He, {sup 3}H, which are not rich in quantity basically. An experiment where plenty of {sup 4}He were recorded is attached in appendix. The problem is that we are trying to search cold fusion which is permitted by nature or not. The famous tunneling effect in quantum mechanics will answer it, however, the most fusion rate is known to be negligible. The focus of this project is on the theme that how to increase that negligible fusion rate. 6 figs, 4 tabs, 1512 refs. (Author).

  16. Laser fusion

    International Nuclear Information System (INIS)

    Ashby, D.E.T.F.

    1976-01-01

    A short survey is given on laser fusion its basic concepts and problems and the present theoretical and experimental methods. The future research program of the USA in this field is outlined. (WBU) [de

  17. Programmable fusion of liposomes mediated by lipidated PNA

    DEFF Research Database (Denmark)

    Rabe, A; Löffler, P M G; Ries, O

    2017-01-01

    We recently reported a DNA-programmed fusion cascade enabling the use of liposomes as nanoreactors for compartmentalized chemical reactions. This communication reports an alternative and robust strategy based on lipidated peptide nucleic acids (LiPs). LiPs enabled fusion of liposomes with remarka...... with remarkable 31% efficiency at 50 °C with low leakage (5%)....

  18. Structural characterization of Mumps virus fusion protein core

    International Nuclear Information System (INIS)

    Liu Yueyong; Xu Yanhui; Lou Zhiyong; Zhu Jieqing; Hu Xuebo; Gao, George F.; Qiu Bingsheng; Rao Zihe; Tien, Po

    2006-01-01

    The fusion proteins of enveloped viruses mediating the fusion between the viral and cellular membranes comprise two discontinuous heptad repeat (HR) domains located at the ectodomain of the enveloped glycoproteins. The crystal structure of the fusion protein core of Mumps virus (MuV) was determined at 2.2 A resolution. The complex is a six-helix bundle in which three HR1 peptides form a central highly hydrophobic coiled-coil and three HR2 peptides pack against the hydrophobic grooves on the surface of central coiled-coil in an oblique antiparallel manner. Fusion core of MuV, like those of simian virus 5 and human respiratory syncytium virus, forms typical 3-4-4-4-3 spacing. The similar charecterization in HR1 regions, as well as the existence of O-X-O motif in extended regions of HR2 helix, suggests a basic rule for the formation of the fusion core of viral fusion proteins

  19. Fusion energy

    International Nuclear Information System (INIS)

    Anon.

    1979-01-01

    The efforts of the Chemical Technology Division in fusion energy include the areas of fuel handling, processing, and containment. Current studies are concerned largely with the development of vacuum pumps for fusion reactors and experiments and with development and evaluation of techniques for recovering tritium from solid or liquid breeding blankets. In addition, a small effort is devoted to support of the ORNL design of a major Tokamak experiment, The Next Step (TNS)

  20. Laser fusion

    International Nuclear Information System (INIS)

    Key, M.H.; Oxford Univ.

    1990-04-01

    The use of lasers to drive implosions for the purpose of inertially confined fusion is an area of intense activity where progress compares favourably with that made in magnetic fusion and there are significant prospects for future development. In this brief review the basic concept is summarised and the current status is outlined both in the area of laser technology and in the most recent results from implosion experiments. Prospects for the future are also considered. (author)

  1. Nuclear fusion

    International Nuclear Information System (INIS)

    Al-zaelic, M.M.

    2013-01-01

    Nuclear fusion can be relied on to solve the global energy crisis if the process of limiting the heat produced by the fusion reaction (Plasma) is successful. Currently scientists are progressively working on this aspect whereas there are two methods to limit the heat produced by fusion reaction, the two methods are auto-restriction using laser beam and magnetic restriction through the use of magnetic fields and research is carried out to improve these two methods. It is expected that at the end of this century the nuclear fusion energy will play a vital role in overcoming the global energy crisis and for these reasons, acquiring energy through the use of nuclear fusion reactors is one of the most urge nt demands of all mankind at this time. The conclusion given is that the source of fuel for energy production is readily available and inexpensive ( hydrogen atoms) and whole process is free of risks and hazards, especially to general health and the environment . Nuclear fusion importance lies in the fact that energy produced by the process is estimated to be about four to five times the energy produced by nuclear fission. (author)

  2. Organizations of food redistribution and rescue.

    Science.gov (United States)

    Mousa, T Y; Freeland-Graves, J H

    2017-11-01

    Food insecurity affects 13.4% of the USA population, despite the fact that 30-40% of all food is deposited in a landfill. Food rescue nutrition is the process of redistribution of surplus food to the impoverished. The aim of this study is to document the extent of involvement of organizations in food rescue nutrition. In this cross-sectional study, a survey about organizations involved in food rescue nutrition was developed, validated, and then tested. Directors of 100 organizations involved in food rescue nutrition from eight Southwestern States in the USA participated in this research. These organizations provided an average of 2 million kg of food to more than 40,000 clients each month. Food assistance programs had an average of eight workers and 3081 volunteers. In addition to food, these organizations provided other services such as clothing, clinical, and childcare. The agencies encountered several challenges, including lack of resources that resulted in reducing food portions and turning away clients. The extent of involvement of community-based programs in food rescue nutrition was strong in eight Southwestern states in the USA. Organizations involved in food redistribution helped alleviate food insecurity in their clients. Sustainability of these charitable networks was dependent on availability of resources and sufficient volunteers. Health professionals should encourage these organizations by providing support through donations of time, money, and/or food. Copyright © 2017 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

  3. Cold fusion

    International Nuclear Information System (INIS)

    Koster, J.

    1989-01-01

    In this contribution the author the phenomenom of so-called cold fusion, inspired by the memorable lecture of Moshe Gai on his own search for this effect. Thus much of what follows was presented by Dr. Gai; the rest is from independent reading. What is referred to as cold fusion is of course the observation of possible products of deuteron-deuteron (d-d) fusion within deuterium-loaded (dentended) electrodes. The debate over the two vanguard cold fusion experiments has raged under far more public attention than usually accorded new scientific phenomena. The clamor commenced with the press conference of M. Fleishmann and S. Pons on March 23, 1989 and the nearly simultaneous wide circulation of a preprint of S. Jones and collaborators. The majority of work attempting to confirm these observations has at the time of this writing yet to appear in published form, but contributions to conferences and electronic mail over computer networks were certainly filled with preliminary results. To keep what follows to a reasonable length the author limit this discussion to the searches for neutron (suggested by ref. 2) or for excessive heat production (suggested by ref. 1), following a synopsis of the hypotheses of cold fusion

  4. Endovascular rescue method for undesirably stretched coil.

    Science.gov (United States)

    Cho, Jae Hoon

    2014-10-01

    Undesirable detachment or stretching of coils within the parent artery during aneurysm embolization can be related with thrombus formation, which can be caused occlusion of parent artery or embolic event(s). To escape from this situation, several rescue methods have been reported. A case with undesirably stretched coil in which another rescue method was used, is presented. When the stretched coil is still located in the coil delivery microcatheter, the stretched coil can be removed safely using a snare and a handmade monorail microcatheter. After a snare is lodged in the handmade monorail microcatheter, the snare is introduced over the coil delivery micorcatheter and located in the distal part of the stretched coil. After then, the handmade monorail microcatheter captures the stretched coil and the snare as one unit. This technique using a handmade monorail microcatheter and a snare can be a good rescue modality for the undesirably stretched coil, still remained within the coil delivery microcatheter.

  5. Fusion events

    International Nuclear Information System (INIS)

    Aboufirassi, M; Angelique, J.C.; Bizard, G.; Bougault, R.; Brou, R.; Buta, A.; Colin, J.; Cussol, D.; Durand, D.; Genoux-Lubain, A.; Horn, D.; Kerambrun, A.; Laville, J.L.; Le Brun, C.; Lecolley, J.F.; Lefebvres, F.; Lopez, O.; Louvel, M.; Meslin, C.; Metivier, V.; Nakagawa, T.; Peter, J.; Popescu, R.; Regimbart, R.; Steckmeyer, J.C.; Tamain, B.; Vient, E.; Wieloch, A.; Yuasa-Nakagawa, K.

    1998-01-01

    The fusion reactions between low energy heavy ions have a very high cross section. First measurements at energies around 30-40 MeV/nucleon indicated no residue of either complete or incomplete fusion, thus demonstrating the disappearance of this process. This is explained as being due to the high amount o energies transferred to the nucleus, what leads to its total dislocation in light fragments and particles. Exclusive analyses have permitted to mark clearly the presence of fusion processes in heavy systems at energies above 30-40 MeV/nucleon. Among the complete events of the Kr + Au reaction at 60 MeV/nucleon the majority correspond to binary collisions. Nevertheless, for the most considerable energy losses, a class of events do occur for which the detected fragments appears to be emitted from a unique source. These events correspond to an incomplete projectile-target fusion followed by a multifragmentation. Such events were singled out also in the reaction Xe + Sn at 50 MeV/nucleon. For the events in which the energy dissipation was maximal it was possible to isolate an isotropic group of events showing all the characteristics of fusion nuclei. The fusion is said to be incomplete as pre-equilibrium Z = 1 and Z = 2 particles are emitted. The cross section is of the order of 25 mb. Similar conclusions were drown for the systems 36 Ar + 27 Al and 64 Zn + nat Ti. A cross section value of ∼ 20 mb was determined at 55 MeV/nucleon in the first case, while the measurement of evaporation light residues in the last system gave an upper limit of 20-30 mb for the cross section at 50 MeV/nucleon

  6. Peptide chemistry toolbox - Transforming natural peptides into peptide therapeutics.

    Science.gov (United States)

    Erak, Miloš; Bellmann-Sickert, Kathrin; Els-Heindl, Sylvia; Beck-Sickinger, Annette G

    2018-06-01

    The development of solid phase peptide synthesis has released tremendous opportunities for using synthetic peptides in medicinal applications. In the last decades, peptide therapeutics became an emerging market in pharmaceutical industry. The need for synthetic strategies in order to improve peptidic properties, such as longer half-life, higher bioavailability, increased potency and efficiency is accordingly rising. In this mini-review, we present a toolbox of modifications in peptide chemistry for overcoming the main drawbacks during the transition from natural peptides to peptide therapeutics. Modifications at the level of the peptide backbone, amino acid side chains and higher orders of structures are described. Furthermore, we are discussing the future of peptide therapeutics development and their impact on the pharmaceutical market. Copyright © 2018 Elsevier Ltd. All rights reserved.

  7. Failure to Rescue, Rescue Surgery and Centralization of Postoperative Complications: A Challenge for General and Acute Care Surgeons.

    Science.gov (United States)

    Zago, Mauro; Bozzo, Samantha; Carrara, Giulia; Mariani, Diego

    2017-01-01

    To explore the current literature on the failure to rescue and rescue surgery concepts, to identify the key items for decreasing the failure to rescue rate and improve outcome, to verify if there is a rationale for centralization of patients suffering postoperative complications. There is a growing awareness about the need to assess and measure the failure to rescue rate, on institutional, regional and national basis. Many factors affect failure to rescue, and all should be individually analyzed and considered. Rescue surgery is one of these factors. Rescue surgery assumes an acute care surgery background. Measurement of failure to rescue rate should become a standard for quality improvement programs. Implementation of all clinical and organizational items involved is the key for better outcomes. Preparedness for rescue surgery is a main pillar in this process. Centralization of management, audit, and communication are important as much as patient centralization. Celsius.

  8. Extracellular secretion of a recombinant therapeutic peptide by Bacillus halodurans utilizing a modified flagellin type III secretion system

    CSIR Research Space (South Africa)

    Berger, E

    2011-08-01

    Full Text Available further 3.5-fold increase in the secretion of recombinant peptide fusions. Conclusions: The type III flagellar secretion system of B. halodurans has been shown to successfully secrete a therapeutic peptide as a heterologous flagellin fusion. Improvements...

  9. Driver Fusions and Their Implications in the Development and Treatment of Human Cancers

    Directory of Open Access Journals (Sweden)

    Qingsong Gao

    2018-04-01

    Full Text Available Summary: Gene fusions represent an important class of somatic alterations in cancer. We systematically investigated fusions in 9,624 tumors across 33 cancer types using multiple fusion calling tools. We identified a total of 25,664 fusions, with a 63% validation rate. Integration of gene expression, copy number, and fusion annotation data revealed that fusions involving oncogenes tend to exhibit increased expression, whereas fusions involving tumor suppressors have the opposite effect. For fusions involving kinases, we found 1,275 with an intact kinase domain, the proportion of which varied significantly across cancer types. Our study suggests that fusions drive the development of 16.5% of cancer cases and function as the sole driver in more than 1% of them. Finally, we identified druggable fusions involving genes such as TMPRSS2, RET, FGFR3, ALK, and ESR1 in 6.0% of cases, and we predicted immunogenic peptides, suggesting that fusions may provide leads for targeted drug and immune therapy. : Gao et al. analyze a 9,624 sample TCGA cohort with 33 cancer types to detect gene fusion events. They provide a landscape of fusion events detected, relate fusions to gene expression, focus on kinase fusion structures, examine mutually exclusive mutation and fusion patterns, and highlight fusion druggability. Keywords: fusion, cancer, RNA, translocation, gene fusions

  10. Nuclear fusion

    International Nuclear Information System (INIS)

    Huber, H.

    1978-01-01

    A comprehensive survey is presented of the present state of knowledge in nuclear fusion research. In the first part, potential thermonuclear reactions, basic energy balances of the plasma (Lawson criterion), and the main criteria to be observed in the selection of appropriate thermonuclear reactions are dealt with. This is followed by a discussion of the problems encountered in plasma physics (plasma confinement and heating, transport processes, plasma impurities, plasma instabilities and plasma diagnostics) and by a consideration of the materials problems involved, such as material of the first wall, fuel inlet and outlet, magnetic field generation, as well as repair work and in-service inspections. Two main methods have been developed to tackle these problems: reactor concepts using the magnetic pinch (stellarator, Tokamak, High-Beta reactors, mirror machines) on the one hand, and the other concept using the inertial confinement (laser fusion reactor). These two approaches and their specific problems as well as past, present and future fusion experiments are treated in detail. The last part of the work is devoted to safety and environmental aspects of the potential thermonuclear aspects of the potential thermonuclear reactor, discussing such problems as fusion-specific hazards, normal operation and potential hazards, reactor incidents, environmental pollution by thermal effluents, radiological pollution, radioactive wastes and their disposal, and siting problems. (orig./GG) [de

  11. Short fusion

    CERN Multimedia

    2002-01-01

    French and UK researchers are perfecting a particle accelerator technique that could aid the quest for fusion energy or make X-rays that are safer and produce higher-resolution images. Led by Dr Victor Malka from the Ecole Nationale Superieure des Techniques Avancees in Paris, the team has developed a better way of accelerating electrons over short distances (1 page).

  12. Magnetic fusion

    International Nuclear Information System (INIS)

    2002-01-01

    This document is a detailed lecture on thermonuclear fusion. The basic physics principles are recalled and the technological choices that have led to tokamaks or stellarators are exposed. Different aspects concerning thermonuclear reactors such as safety, economy and feasibility are discussed. Tore-supra is described in details as well as the ITER project

  13. Cold fusion

    International Nuclear Information System (INIS)

    Seo, Suk Yong; You, Jae Jun

    1996-01-01

    Nearly every technical information is chased in the world. All of them are reviewed and analyzed. Some of them are chosen to study further more to review every related documents. And a probable suggestion about the excitonic process in deuteron absorbed condensed matter is proposed a way to cold fusion. 8 refs. (Author)

  14. Rescuing Dogs in the Frederick Community | Poster

    Science.gov (United States)

    Many Frederick National Lab employees have a favorite cause to which they volunteer a significant amount of time. For Dianna Kelly, IT program manager/scientific program analyst, Office of Scientific Operations, and Courtney Kennedy, associate technical project manager, Business Enterprise Systems, that cause is dog rescue.

  15. Rescuing Downed Aircrews: The Value of Time

    Science.gov (United States)

    2015-01-01

    Make a tax -deductible charitable contribution at www.rand.org/giving/contribute www.rand.org Library of Congress Control Number: 2015955037 ISBN...Predictors of Survival and Evasion ............................................................ 40   Table 5.2. Regression Predictors...a damaged aircraft, and the ability to avoid immediate capture. Combat rescue records and anecdotal evidence show that if the pilot were able to

  16. Emergency Medical Rescue in a Radiation Environment

    International Nuclear Information System (INIS)

    Briesmeister, L.; Ellington, Y.; Hollis, R.; Kunzman, J.; McNaughton, M.; Ramsey, G.; Somers, B.; Turner, A.; Finn, J.

    1999-01-01

    Previous experience with emergency medical rescues in the presence of radiation or contamination indicates that the training provided to emergency responders is not always appropriate. A new course developed at Los Alamos includes specific procedures for emergency response in a variety of radiological conditions

  17. REM sleep rescues learning from interference

    Science.gov (United States)

    McDevitt, Elizabeth A.; Duggan, Katherine A.; Mednick, Sara C.

    2015-01-01

    Classical human memory studies investigating the acquisition of temporally-linked events have found that the memories for two events will interfere with each other and cause forgetting (i.e., interference; Wixted, 2004). Importantly, sleep helps consolidate memories and protect them from subsequent interference (Ellenbogen, Hulbert, Stickgold, Dinges, & Thompson-Schill, 2006). We asked whether sleep can also repair memories that have already been damaged by interference. Using a perceptual learning paradigm, we induced interference either before or after a consolidation period. We varied brain states during consolidation by comparing active wake, quiet wake, and naps with either non-rapid eye movement sleep (NREM), or both NREM and REM sleep. When interference occurred after consolidation, sleep and wake both produced learning. However, interference prior to consolidation impaired memory, with retroactive interference showing more disruption than proactive interference. Sleep rescued learning damaged by interference. Critically, only naps that contained REM sleep were able to rescue learning that was highly disrupted by retroactive interference. Furthermore, the magnitude of rescued learning was correlated with the amount of REM sleep. We demonstrate the first evidence of a process by which the brain can rescue and consolidate memories damaged by interference, and that this process requires REM sleep. We explain these results within a theoretical model that considers how interference during encoding interacts with consolidation processes to predict which memories are retained or lost. PMID:25498222

  18. Fc-fusion Proteins in Therapy: An Updated View.

    Science.gov (United States)

    Jafari, Reza; Zolbanin, Naime M; Rafatpanah, Houshang; Majidi, Jafar; Kazemi, Tohid

    2017-01-01

    Fc-fusion proteins are composed of Fc region of IgG antibody (Hinge-CH2-CH3) and a desired linked protein. Fc region of Fc-fusion proteins can bind to neonatal Fc receptor (FcRn) thereby rescuing it from degradation. The first therapeutic Fc-fusion protein was introduced for the treatment of AIDS. The molecular designing is the first stage in production of Fc-fusion proteins. The amino acid residues in the Fc region and linked protein are very important in the bioactivity and affinity of the fusion proteins. Although, therapeutic monoclonal antibodies are the top selling biologics but the application of therapeutic Fc-fusion proteins in clinic is in progress and among these medications Etanercept is the most effective in therapy. At present, eleven Fc-fusion proteins have been approved by FDA. There are novel Fc-fusion proteins which are in pre-clinical and clinical development. In this article, we review the molecular and biological characteristics of Fc-fusion proteins and then further discuss the features of novel therapeutic Fc-fusion proteins. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  19. The yeast complex I equivalent NADH dehydrogenase rescues pink1 mutants.

    Directory of Open Access Journals (Sweden)

    Sven Vilain

    2012-01-01

    Full Text Available Pink1 is a mitochondrial kinase involved in Parkinson's disease, and loss of Pink1 function affects mitochondrial morphology via a pathway involving Parkin and components of the mitochondrial remodeling machinery. Pink1 loss also affects the enzymatic activity of isolated Complex I of the electron transport chain (ETC; however, the primary defect in pink1 mutants is unclear. We tested the hypothesis that ETC deficiency is upstream of other pink1-associated phenotypes. We expressed Saccaromyces cerevisiae Ndi1p, an enzyme that bypasses ETC Complex I, or sea squirt Ciona intestinalis AOX, an enzyme that bypasses ETC Complex III and IV, in pink1 mutant Drosophila and find that expression of Ndi1p, but not of AOX, rescues pink1-associated defects. Likewise, loss of function of subunits that encode for Complex I-associated proteins displays many of the pink1-associated phenotypes, and these defects are rescued by Ndi1p expression. Conversely, expression of Ndi1p fails to rescue any of the parkin mutant phenotypes. Additionally, unlike pink1 mutants, fly parkin mutants do not show reduced enzymatic activity of Complex I, indicating that Ndi1p acts downstream or parallel to Pink1, but upstream or independent of Parkin. Furthermore, while increasing mitochondrial fission or decreasing mitochondrial fusion rescues mitochondrial morphological defects in pink1 mutants, these manipulations fail to significantly rescue the reduced enzymatic activity of Complex I, indicating that functional defects observed at the level of Complex I enzymatic activity in pink1 mutant mitochondria do not arise from morphological defects. Our data indicate a central role for Complex I dysfunction in pink1-associated defects, and our genetic analyses with heterologous ETC enzymes suggest that Ndi1p-dependent NADH dehydrogenase activity largely acts downstream of, or in parallel to, Pink1 but upstream of Parkin and mitochondrial remodeling.

  20. In vitro embryo rescue and plant regeneration following self ...

    African Journals Online (AJOL)

    In vitro embryo rescue and plant regeneration following self-pollination with irradiated ... AFRICAN JOURNALS ONLINE (AJOL) · Journals · Advanced Search ... shows that pollen irradiation coupled with self-pollination and embryo rescue ...

  1. Expectations of a business rescue plan: international directives for ...

    African Journals Online (AJOL)

    Expectations of a business rescue plan: international directives for Chapter 6 implementation. ... AFRICAN JOURNALS ONLINE (AJOL) · Journals · Advanced Search ... Preliminary analysis of business rescue plans suggested that a significant ...

  2. Neurotrauma and the rule of rescue.

    Science.gov (United States)

    Honeybul, S; Gillett, G R; Ho, K M; Lind, C R P

    2011-12-01

    The rule of rescue describes the powerful human proclivity to rescue identified endangered lives, regardless of cost or risk. Deciding whether or not to perform a decompressive craniectomy as a life-saving or 'rescue' procedure for a young person with a severe traumatic brain injury provides a good example of the ethical tensions that occur in these situations. Unfortunately, there comes a point when the primary brain injury is so severe that if the patient survives they are likely to remain severely disabled and fully dependent. The health resource implications of this outcome are significant. By using a web-based outcome prediction model this study compares the long-term outcome and designation of two groups of patients. One group had a very severe injury as adjudged by the model and the other group a less severe injury. At 18 month follow-up there were significant differences in outcome and healthcare requirements. This raises important ethical issues when considering life-saving but non-restorative surgical intervention. The discussion about realistic outcome cannot be dichotomised into simply life or death so that the outcome for the patient must enter the equation. As in other 'rescue situations', the utility of the procedure cannot be rationalised on a mere cost-benefit analysis. A compromise has to be reached to determine at what point either the likely outcome would be unacceptable to the person on whom the procedure is being performed or the social utility gained from the rule of rescue intervention fails to justify the utilitarian value and justice of equitable resource allocation.

  3. [Medical rescue of China National Earthquake Disaster Emergency Search and Rescue Team in Lushan earthquake].

    Science.gov (United States)

    Liu, Ya-hua; Yang, Hui-ning; Liu, Hui-liang; Wang, Fan; Hu, Li-bin; Zheng, Jing-chen

    2013-05-01

    To summarize and analyze the medical mission of China National Earthquake Disaster Emergency Search and Rescue Team (CNESAR) in Lushan earthquake, to promote the medical rescue effectiveness incorporated with search and rescue. Retrospective analysis of medical work data by CNESAR from April 21th, 2013 to April 27th during Lushan earthquake rescue, including the medical staff dispatch and the wounded case been treated. The reasonable medical corps was composed by 22 members, including 2 administrators, 11 doctors [covering emergency medicine, orthopedics (joints and limbs, spinal), obstetrics and gynecology, gastroenterology, cardiology, ophthalmology, anesthesiology, medical rescue, health epidemic prevention, clinical laboratory of 11 specialties], 1 ultrasound technician, 5 nurses, 1 pharmacist, 1 medical instrument engineer and 1 office worker for propaganda. There were two members having psychological consultants qualifications. The medical work were carried out in seven aspects, including medical care assurance for the CNESAR members, first aid cooperation with search and rescue on site, clinical work in refugees' camp, medical round service for scattered village people, evacuation for the wounded, mental intervention, and the sanitary and anti-epidemic work. The medical work covered 24 small towns, and medical staff established 3 medical clinics at Taiping Town, Shuangshi Town of Lushan County and Baoxing County. Medical rescue, mental intervention for the old and kids, and sanitary and anti-epidemic were performed at the above sites. The medical corps had successful evacuated 2 severe wounded patients and treated the wounded over thousands. Most of the wounded were soft tissue injuries, external injury, respiratory tract infections, diarrhea, and heat stroke. Compared with the rescue action in 2008 Wenchuan earthquake, the aggregation and departure of rescue team in Lushan earthquake, the traffic control order in disaster area, the self-aid and buddy aid

  4. A GALA lipopeptide mediates pH- and membrane charge dependent fusion with stable giant unilamellar vesicles

    DEFF Research Database (Denmark)

    Etzerodt, Thomas P.; Trier, Sofie; Henriksen, Jonas R.

    2012-01-01

    sporadic and there is a strong need to characterize and increase our understanding of the membrane fusion properties of these peptides. Many fusion studies have focused on the ability of free peptides in solution that mediate fusion between liposomes. For drug delivery purposes it is a necessity to attach......,2-diamino propanoic acid (Dap) moiety, yielding the lipopeptide dimyristoyl-Dap-GALA (DMDGALA). We have investigated DMDGALA as a component in large unilamellar vesicles (LUVs) and demonstrate pH-triggered fusion of peptide containing LUVs with stable target giant unilamellar vesicles (GUVs), which were...

  5. Cold fusion, Alchemist's dream

    International Nuclear Information System (INIS)

    Clayton, E.D.

    1989-09-01

    In this report the following topics relating to cold fusion are discussed: muon catalysed cold fusion; piezonuclear fusion; sundry explanations pertaining to cold fusion; cosmic ray muon catalysed cold fusion; vibrational mechanisms in excited states of D 2 molecules; barrier penetration probabilities within the hydrogenated metal lattice/piezonuclear fusion; branching ratios of D 2 fusion at low energies; fusion of deuterons into 4 He; secondary D+T fusion within the hydrogenated metal lattice; 3 He to 4 He ratio within the metal lattice; shock induced fusion; and anomalously high isotopic ratios of 3 He/ 4 He

  6. Magnetic fusion; La fusion magnetique

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2002-07-01

    This document is a detailed lecture on thermonuclear fusion. The basic physics principles are recalled and the technological choices that have led to tokamaks or stellarators are exposed. Different aspects concerning thermonuclear reactors such as safety, economy and feasibility are discussed. Tore-supra is described in details as well as the ITER project.

  7. Splenogonadal Fusion

    Directory of Open Access Journals (Sweden)

    Sung-Lang Chen

    2008-11-01

    Full Text Available Splenogonadal fusion (SGF is a rare congenital non-malignant anomaly characterized by fusion of splenic tissue to the gonad, and can be continuous or discontinuous. Very few cases have been diagnosed preoperatively, and many patients who present with testicular swelling undergo unnecessary orchiectomy under the suspicion of testicular neoplasm. A 16-year-old boy presented with a left scrotal mass and underwent total excision of a 1.6-cm tumor without damaging the testis, epididymis or its accompanying vessels. Pathologic examination revealed SFG (discontinuous type. If clinically suspected before surgery, the diagnosis may be confirmed by Tc-99m sulfur colloid imaging, which shows uptake in both the spleen and accessory splenic tissue within the scrotum. Frozen section should be considered if there remains any doubt regarding the diagnosis during operation.

  8. Laser fusion

    International Nuclear Information System (INIS)

    Eliezer, S.

    1982-02-01

    In this paper, the physics of laser fusion is described on an elementary level. The irradiated matter consists of a dense inner core surrounded by a less dense plasma corona. The laser radiation is mainly absorbed in the outer periphery of the plasma. The absorbed energy is transported inward to the ablation surface where plasma flow is created. Due to this plasma flow, a sequence of inward going shock waves and heat waves are created, resulting in the compression and heating of the core to high density and temperature. The interaction physics between laser and matter leading to thermonuclear burn is summarized by the following sequence of events: Laser absorption → Energy transport → Compression → Nuclear Fusion. This scenario is shown in particular for a Nd:laser with a wavelength of 1 μm. The wavelength scaling of the physical processes is also discussed. In addition to the laser-plasma physics, the Nd high power pulsed laser is described. We give a very brief description of the oscillator, the amplifiers, the spatial filters, the isolators and the diagnostics involved. Last, but not least, the concept of reactors for laser fusion and the necessary laser system are discussed. (author)

  9. Fusion spectroscopy

    International Nuclear Information System (INIS)

    Peacock, N.J.

    1995-09-01

    This article traces developments in the spectroscopy of high temperature laboratory plasma used in controlled fusion research from the early 1960's until the present. These three and a half decades have witnessed many orders of magnitude increase in accessible plasma parameters such as density and temperature as well as particle and energy confinement timescales. Driven by the need to interpret the radiation in terms of the local plasma parameters, the thrust of fusion spectroscopy has been to develop our understanding of (i) the atomic structure of highly ionised atoms, usually of impurities in the hydrogen isotope fuel; (ii) the atomic collision rates and their incorporation into ionization structure and emissivity models that take into account plasma phenomena like plasma-wall interactions, particle transport and radiation patterns; (iii) the diagnostic applications of spectroscopy aided by increasingly sophisticated characterisation of the electron fluid. These topics are discussed in relation to toroidal magnetically confined plasmas, particularly the Tokamak which appears to be the most promising approach to controlled fusion to date. (author)

  10. Combat Search and Rescue in Desert Storm

    Science.gov (United States)

    2006-09-01

    in the United States also sup- ported civil SAR. Almost daily, the veterans of Southeast Asia were called upon to rescue lost hikers and foundering ...Ridge in the Persian Gulf. Under the NRCC, Combined Task Force (CTF) 151 served as the regional SAR controller for Battle Force Zulu in the Persian...was ZULU + 3 [i.e., Greenwich Mean Time plus three hours]. Saudi Arabia local time was ZULU + 3:30. All times in the log extracts that follow are

  11. Emergency Air Rescue System in Romania

    Directory of Open Access Journals (Sweden)

    Tranca Sebastian

    2018-03-01

    Full Text Available The helicopter, as a means of transport, has facilitated a significant decrease in intervention time at the site of request, increasing the chances of survival of the critical patient. Since 2003, SMURD has managed to form a fleet composed of nine helicopters and two airplanes. From an operational and strategic point of view, the SMURD intervention unit, set up seven Aeromedical Operational Bases (A.O.B. equipped with helicopters and materials necessary for their operation. There is a dynamic increase in the number of air rescue missions in Romania, with most missions being carried out by the air rescue bases in Târgu Mureş and Bucharest. Specialty literature has clearly demonstrated the positive impact on the survival of critical patients assisted by airborne crews, so it is necessary for the Romanian air rescue system to grow up. It is necessary to increase the number of air bases, purchase new helicopters and to continue the training programs of both pilots and medical personnel.

  12. Design, synthesis, and actions of a novel chimeric natriuretic peptide: CD-NP.

    Science.gov (United States)

    Lisy, Ondrej; Huntley, Brenda K; McCormick, Daniel J; Kurlansky, Paul A; Burnett, John C

    2008-07-01

    Our aim was to design, synthesize and test in vivo and in vitro a new chimeric peptide that would combine the beneficial properties of 2 distinct natriuretic peptides with a biological profile that goes beyond native peptides. Studies have established the beneficial vascular and antiproliferative properties of C-type natriuretic peptide (CNP). While lacking renal actions, CNP is less hypotensive than the cardiac peptides atrial natriuretic peptide and B-type natriuretic peptide but unloads the heart due to venodilation. Dendroaspis natriuretic peptide is a potent natriuretic and diuretic peptide that is markedly hypotensive and functions via a separate guanylyl cyclase receptor compared with CNP. Here we engineered a novel chimeric peptide CD-NP that represents the fusion of the 22-amino acid peptide CNP together with the 15-amino acid linear C-terminus of Dendroaspis natriuretic peptide. We also determined in vitro in cardiac fibroblasts cyclic guanosine monophosphate-activating and antiproliferative properties of CD-NP. Our studies demonstrate in vivo that CD-NP is natriuretic and diuretic, glomerular filtration rate enhancing, cardiac unloading, and renin inhibiting. CD-NP also demonstrates less hypotensive properties when compared with B-type natriuretic peptide. In addition, CD-NP in vitro activates cyclic guanosine monophosphate and inhibits cardiac fibroblast proliferation. The current findings advance an innovative design strategy in natriuretic peptide drug discovery and development to create therapeutic peptides with favorable properties that may be preferable to those associated with native natriuretic peptides.

  13. Fusion Machines

    International Nuclear Information System (INIS)

    Weynants, R.R.

    2004-01-01

    A concise overview is given of the principles of inertial and magnetic fusion, with an emphasis on the latter in view of the aim of this summer school. The basis of magnetic confinement in mirror and toroidal geometry is discussed and applied to the tokamak concept. A brief discussion of the reactor prospects of this configuration identifies which future developments are crucial and where alternative concepts might help in optimising the reactor design. The text also aims at introducing the main concepts encountered in tokamak research that will be studied and used in the subsequent lectures

  14. A highly scalable peptide-based assay system for proteomics.

    Directory of Open Access Journals (Sweden)

    Igor A Kozlov

    Full Text Available We report a scalable and cost-effective technology for generating and screening high-complexity customizable peptide sets. The peptides are made as peptide-cDNA fusions by in vitro transcription/translation from pools of DNA templates generated by microarray-based synthesis. This approach enables large custom sets of peptides to be designed in silico, manufactured cost-effectively in parallel, and assayed efficiently in a multiplexed fashion. The utility of our peptide-cDNA fusion pools was demonstrated in two activity-based assays designed to discover protease and kinase substrates. In the protease assay, cleaved peptide substrates were separated from uncleaved and identified by digital sequencing of their cognate cDNAs. We screened the 3,011 amino acid HCV proteome for susceptibility to cleavage by the HCV NS3/4A protease and identified all 3 known trans cleavage sites with high specificity. In the kinase assay, peptide substrates phosphorylated by tyrosine kinases were captured and identified by sequencing of their cDNAs. We screened a pool of 3,243 peptides against Abl kinase and showed that phosphorylation events detected were specific and consistent with the known substrate preferences of Abl kinase. Our approach is scalable and adaptable to other protein-based assays.

  15. Fusion Canada issue 10

    International Nuclear Information System (INIS)

    1990-02-01

    A short bulletin from the National Fusion Program. Included in this issue is a report on Fusion Materials Research, ITER physics research, fusion performance record at JET, and design options for reactor building. 4 figs

  16. Characterization of a structural intermediate of flavivirus membrane fusion.

    Directory of Open Access Journals (Sweden)

    Karin Stiasny

    2007-02-01

    Full Text Available Viral membrane fusion proceeds through a sequence of steps that are driven by triggered conformational changes of viral envelope glycoproteins, so-called fusion proteins. Although high-resolution structural snapshots of viral fusion proteins in their prefusion and postfusion conformations are available, it has been difficult to define intermediate structures of the fusion pathway because of their transient nature. Flaviviruses possess a class II viral fusion protein (E mediating fusion at acidic pH that is converted from a dimer to a trimer with a hairpin-like structure during the fusion process. Here we show for tick-borne encephalitis virus that exposure of virions to alkaline instead of acidic pH traps the particles in an intermediate conformation in which the E dimers dissociate and interact with target membranes via the fusion peptide without proceeding to the merger of the membranes. Further treatment to low pH, however, leads to fusion, suggesting that these monomers correspond to an as-yet-elusive intermediate required to convert the prefusion dimer into the postfusion trimer. Thus, the use of nonphysiological conditions allows a dissection of the flavivirus fusion process and the identification of two separate steps, in which membrane insertion of multiple copies of E monomers precedes the formation of hairpin-like trimers. This sequence of events provides important new insights for understanding the dynamic process of viral membrane fusion.

  17. Human peptide transporters

    DEFF Research Database (Denmark)

    Nielsen, Carsten Uhd; Brodin, Birger; Jørgensen, Flemming Steen

    2002-01-01

    Peptide transporters are epithelial solute carriers. Their functional role has been characterised in the small intestine and proximal tubules, where they are involved in absorption of dietary peptides and peptide reabsorption, respectively. Currently, two peptide transporters, PepT1 and PepT2, wh...

  18. Motivations for volunteers in food rescue nutrition.

    Science.gov (United States)

    Mousa, T Y; Freeland-Graves, J H

    2017-08-01

    A variety of organizations redistribute surplus food to low-income populations through food rescue nutrition. Why volunteers participate in these charitable organizations is unclear. The aim of this study is to document the participation and motivations of volunteers who are involved specifically in food rescue nutrition. A cross-sectional study was conducted in two phases. In phase 1, a new instrument, Motivations to Volunteer Scale, was developed and validated in 40 participants (aged ≥18 years). In phase 2, the new scale and a demographics questionnaire were administered to 300 participants who were volunteering in food pantries and churches. The pilot study showed that Motivations to Volunteer Scale exhibited an internal consistency of Cronbach's α of 0.73 (P  0.05). The scale was validated also by comparison to the Volunteer Function Inventory (r = 0.86, P social life, and altruism. The mean motivation score of the 300 volunteers was 9.15 ± 0.17. Greater motivations were observed among participants who were aged >45 years, women, Hispanics, college/university graduates, physically inactive, non-smokers, and had an income ≥ $48,000. The Motivations to Volunteer Scale is a valid tool to assess why individuals volunteer in food rescue nutrition. The extent of motivations of participants was relatively high, and the primary reason for volunteering was altruism. Health professionals should be encouraged to participate in food redistribution. Copyright © 2017 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

  19. Revitalizing Fusion via Fission Fusion

    Science.gov (United States)

    Manheimer, Wallace

    2001-10-01

    Existing tokamaks could generate significant nuclear fuel. TFTR, operating steady state with DT might generate enough fuel for a 300 MW nuclear reactor. The immediate goals of the magnetic fusion program would necessarily shift from a study of advanced plasma regimes in larger sized devices, to mostly known plasmas regimes, but at steady state or high duty cycle operation in DT plasmas. The science and engineering of breeding blankets would be equally important. Follow on projects could possibly produce nuclear fuel in large quantity at low price. Although today there is strong opposition to nuclear power in the United States, in a 21st century world of 10 billion people, all of whom will demand a middle class life style, nuclear energy will be important. Concern over greenhouse gases will also drive the world toward nuclear power. There are studies indicating that the world will need 10 TW of carbon free energy by 2050. It is difficult to see how this can be achieved without the breeding of nuclear fuel. By using the thorium cycle, proliferation risks are minimized. [1], [2]. 1 W. Manheimer, Fusion Technology, 36, 1, 1999, 2.W. Manheimer, Physics and Society, v 29, #3, p5, July, 2000

  20. Drone configuration for seaside rescue missions

    OpenAIRE

    Garro Fernandez, Jose Miguel

    2017-01-01

    The project is based on creating a first aid tool to perform a coastline rescue with an unmanned. The System is formed by a ground segment, where the ground station will be placed and an air segment, where the unmanned vehicle, equipped with all the necessary extra devices to perform the mission will be found. For notices of possible drownings, the ground station will receive notifications that users will publish using a Mobile application. This app will allow users to capture images of the v...

  1. Arginine-rich intracellular delivery peptides noncovalently transport protein into living cells

    International Nuclear Information System (INIS)

    Wang, Y.-H.; Chen, C.-P.; Chan, M.-H.; Chang, M.; Hou, Y.-W.; Chen, H.-H.; Hsu, H.-R.; Liu, Kevin; Lee, H.-J.

    2006-01-01

    Plasma membranes of plant or animal cells are generally impermeable to peptides or proteins. Many basic peptides have previously been investigated and covalently cross-linked with cargoes for cellular internalization. In the current study, we demonstrate that arginine-rich intracellular delivery (AID) peptides are able to deliver fluorescent proteins or β-galactosidase enzyme into animal and plant cells, as well as animal tissue. Cellular internalization and transdermal delivery of protein could be mediated by effective and nontoxic AID peptides in a neither fusion protein nor conjugation fashion. Therefore, noncovalent AID peptides may provide a useful strategy to have active proteins function in living cells and tissues in vivo

  2. Catalysed fusion

    CERN Document Server

    Farley, Francis

    2012-01-01

    A sizzling romance and a romp with subatomic particles at CERN. Love, discovery and adventure in the city where nations meet and beams collide. Life in a large laboratory. As always, the challenges are the same. Who leads? Who follows? Who succeeds? Who gets the credit? Who gets the women or the men? Young Jeremy arrives in CERN and joins the quest for green energy. Coping with baffling jargon and manifold dangers, he is distracted by radioactive rats, lovely ladies and an unscrupulous rival. Full of doubts and hesitations, he falls for a dazzling Danish girl, who leads him astray. His brilliant idea leads to a discovery and a new route to cold fusion. But his personal life is scrambled. Does it bring fame or failure? Tragedy or triumph?

  3. Fusion cuisine

    DEFF Research Database (Denmark)

    Peters, Chris; Broersma, Marcel

    2018-01-01

    JJournalism studies as an academic field is characterized by multidisciplinarity. Focusing on one object of study, journalism and the news, it established itself by integrating and synthesizing approaches from established disciplines – a tendency that lives on today. This constant gaze to the out......JJournalism studies as an academic field is characterized by multidisciplinarity. Focusing on one object of study, journalism and the news, it established itself by integrating and synthesizing approaches from established disciplines – a tendency that lives on today. This constant gaze...... to the outside for conceptual inspiration and methodological tools lends itself to a journalism studies that is a fusion cuisine of media, communication, and related scholarship. However, what happens when this object becomes as fragmented and multifaceted as the ways we study it? This essay addresses...

  4. Inhibition of Nipah virus infection in vivo: targeting an early stage of paramyxovirus fusion activation during viral entry.

    Directory of Open Access Journals (Sweden)

    Matteo Porotto

    2010-10-01

    Full Text Available In the paramyxovirus cell entry process, receptor binding triggers conformational changes in the fusion protein (F leading to viral and cellular membrane fusion. Peptides derived from C-terminal heptad repeat (HRC regions in F have been shown to inhibit fusion by preventing formation of the fusogenic six-helix bundle. We recently showed that the addition of a cholesterol group to HRC peptides active against Nipah virus targets these peptides to the membrane where fusion occurs, dramatically increasing their antiviral effect. In this work, we report that unlike the untagged HRC peptides, which bind to the postulated extended intermediate state bridging the viral and cell membranes, the cholesterol tagged HRC-derived peptides interact with F before the fusion peptide inserts into the target cell membrane, thus capturing an earlier stage in the F-activation process. Furthermore, we show that cholesterol tagging renders these peptides active in vivo: the cholesterol-tagged peptides cross the blood brain barrier, and effectively prevent and treat in an established animal model what would otherwise be fatal Nipah virus encephalitis. The in vivo efficacy of cholesterol-tagged peptides, and in particular their ability to penetrate the CNS, suggests that they are promising candidates for the prevention or therapy of infection by Nipah and other lethal paramyxoviruses.

  5. Clinical and economic analysis of rescue intracytoplasmic sperm injection cycles.

    Science.gov (United States)

    Shalom-paz, Einat; Alshalati, Jana; Shehata, Fady; Jimenez, Luis; Son, Weon-Young; Holzer, Hananel; Tan, Seang Lin; Almog, Benny

    2011-12-01

    To identify clinical and embryological factors that may predict success in rescue intracytoplasmic sperm injection (ICSI) cycles (after total fertilization failure has occurred) and to evaluate the cost effectiveness of rescue ICSI strategy. Additionally, follow-up of 20 rescue ICSI pregnancies is reported. Retrospective analysis of total fertilization failure cycles. University-based tertiary medical center. In total, 92 patients who had undergone conventional in-vitro fertilization (IVF) cycles with total fertilization failure were included. The patients were divided into two subgroups: those who conceived through rescue ICSI and those who did not. The pregnant members of the rescue ICSI subgroup were found to be significantly younger (32.9 ± 4.2 vs. 36.3 ± 4.5, respectively, p = 0.0035,) and to have better-quality embryos than those who did not conceive (cumulative embryo score: 38.3 ± 20.4 vs. 29.3 ± 14.7, p = 0.025). Cost effectiveness analysis showed 25% reduction in the cost per live birth when rescue ICSI is compared to cycle cancellation approach. The pregnancies follow-up did not show adverse perinatal outcome. Rescue ICSI is an option for salvaging IVF cycles complicated by total fertilization failure. Success in rescue ICSI was found to be associated with younger age and higher quality of embryos. Furthermore, the cost effectiveness of rescue ICSI in terms of total fertilization failure was found to be worthwhile.

  6. Towards nuclear fusion reactors

    International Nuclear Information System (INIS)

    1993-11-01

    The results of nuclear fusion researches in JAERI are summarized. In this report, following themes are collected: the concept of fusion reactor (including ITER), fusion reactor safety, plasma confinement, fusion reactor equipment, and so on. Includes glossary. (J.P.N.)

  7. Fusion Canada issue 28

    International Nuclear Information System (INIS)

    1995-06-01

    A short bulletin from the National Fusion Program highlighting in this issue the Canada - US fusion meeting in Montreal, fusion breeder work in Chile, new management at CFFTP, fast electrons in tokamaks: new data from TdeV, a program review of CCFM and Velikhov to address Montreal fusion meeting. 1 fig

  8. Fusion systems engineering

    International Nuclear Information System (INIS)

    Anon.

    1977-01-01

    Summaries of research are included for each of the following topics: (1) fusion reactor systems studies, (2) development of blanket processing technology for fusion reactors, (3) safety studies of fusion concepts, (4) the MACK/MACKLIB system for nuclear response functions, and (5) energy storage and power supply systems for fusion reactors

  9. Peptide inhibitors of botulinum neurotoxin by mRNA display

    International Nuclear Information System (INIS)

    Yiadom, Kwabena P.A.B.; Muhie, Seid; Yang, David C.H.

    2005-01-01

    Botulinum neurotoxins (BoNTs) are extremely toxic. The metalloproteases associated with the toxins cleave proteins essential for neurotransmitter secretion. Inhibitors of the metalloprotease are currently sought to control the toxicity of BoNTs. Toward that goal, we produced a synthetic cDNA for the expression and purification of the metalloprotease of BoNT/A in Escherichia coli as a biotin-ubiquitin fusion protein, and constructed a combinatorial peptide library to screen for BoNT/A light chain inhibitors using mRNA display. A protease assay was developed using immobilized intact SNAP-25 as the substrate. The new peptide inhibitors showed a 10-fold increase in affinity to BoNT/A light chain than the parent peptide. Interestingly, the sequences of the new peptide inhibitors showed abundant hydrophobic residues but few hydrophilic residues. The results suggest that mRNA display may provide a general approach in developing peptide inhibitors of BoNTs

  10. Transcriptomic Profiling and Functional Characterization of Fusion Genes in Recurrent Ovarian Cancer

    Science.gov (United States)

    2017-09-01

    late lesion (Figure 1A). 152 fusions were predicted to produce an in-frame, chimeric protein—48 being acquired in late disease and 55 being...recurrence, fusions of particular interest included an acquired WNT2-CTTNBP2 in case OVCA_04, which retained a Wnt signaling peptide in the N-terminal

  11. HIV-1 gp41 Fusion Intermediate: A Target for HIV Therapeutics

    Directory of Open Access Journals (Sweden)

    Chungen Pan

    2010-02-01

    Full Text Available Human immunodeficiency virus (HIV-1 infection is initiated by the binding of gp120 envelope glyco-protein to its cell receptor (CD4 and a coreceptor (CXCR4 or CCR5, followed by a series of conformational changes in the gp41 transmembrane subunit. These changes include insertion of fusion peptide into the target cell membrane and association of C-heptad repeat (CHR peptide with the N-heptad repeat (NHR trimer, a pre-hairpin fusion intermediate. A stable six-helix bundle core is then formed, bringing the viral envelope and target cell membrane into close proximity for fusion. Peptides derived from the CHR region, such as T20 and C34, inhibit HIV-1 fusion by interacting with the gp41 fusion intermediate. A number of anti-HIV-1 peptides and small molecule compounds targeting the gp41 NHR-trimer have been identified. By combining HIV fusion/entry inhibitors targeting different sites in the gp41 fusion intermediate, a potent synergistic effect takes place, resulting in a potential new therapeutic strategy for the HIV infection/AIDS. Here, we present an overview of the current development of anti-HIV drugs, particularly those targeting the gp41 fusion intermediate.

  12. Fusion systems engineering

    International Nuclear Information System (INIS)

    Anon.

    1978-01-01

    Research during this report period has covered the following areas: (1) fusion reactor systems studies, (2) development of blanket processing technology for fusion reactors, (3) safety studies of fusion concepts, (4) MACKLIB-IV, a new library of nuclear response functions, (5) energy storage and power supply requirements for commercial fusion reactors, (6) blanket/shield design evaluation for commercial fusion reactors, and (7) cross section measurements, evaluations, and techniques

  13. Fusion fuel and renewables

    International Nuclear Information System (INIS)

    Entler, Slavomir

    2015-01-01

    It is shown that fusion fuel meets all aspects applied when defining renewables. A table of definitions of renewables is presented. The sections of the paper are as follows: An industrial renewable source; Nuclear fusion; Current situation in research; Definitions of renewable sources; Energy concept of nuclear fusion; Fusion fuel; Natural energy flow; Environmental impacts; Fusion fuel assessment; Sustainable power; and Energy mix from renewables. (P.A.)

  14. Perspective of Use of Antiviral Peptides against Influenza Virus

    Directory of Open Access Journals (Sweden)

    Sylvie Skalickova

    2015-10-01

    Full Text Available The threat of a worldwide influenza pandemic has greatly increased over the past decade with the emergence of highly virulent avian influenza strains. The increased frequency of drug-resistant influenza strains against currently available antiviral drugs requires urgent development of new strategies for antiviral therapy, too. The research in the field of therapeutic peptides began to develop extensively in the second half of the 20th century. Since then, the mechanisms of action for several peptides and their antiviral prospect received large attention due to the global threat posed by viruses. Here, we discussed the therapeutic properties of peptides used in influenza treatment. Peptides with antiviral activity against influenza can be divided into three main groups. First, entry blocker peptides such as a Flupep that interact with influenza hemagglutinin, block its binding to host cells and prevent viral fusion. Second, several peptides display virucidal activity, disrupting viral envelopes, e.g., Melittin. Finally, a third set of peptides interacts with the viral polymerase complex and act as viral replication inhibitors such as PB1 derived peptides. Here, we present a review of the current literature describing the antiviral activity, mechanism and future therapeutic potential of these influenza antiviral peptides.

  15. 30 CFR 49.17 - Physical requirements for mine rescue team.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Physical requirements for mine rescue team. 49... EDUCATION AND TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Coal Mines § 49.17 Physical requirements for mine rescue team. (a) Each member of a mine rescue team shall be examined annually by a...

  16. Cold fusion

    International Nuclear Information System (INIS)

    Bush, R.T.

    1991-01-01

    The transmission resonance model (TRM) is combined with some electrochemistry of the cathode surface and found to provide a good fit to new data on excess heat. For the first time, a model for cold fusion not only fits calorimetric data but also predicts optimal trigger points. This suggests that the model is meaningful and that the excess heat phenomenon claimed by Fleischmann and Pons is genuine. A crucial role is suggested for the overpotential and, in particular, for the concentration overpotential, i.e., the hydrogen overvoltage. Self-similar geometry, or scale invariance, i.e., a fractal nature, is revealed by the relative excess power function. Heat bursts are predicted with a scale invariance in time, suggesting a possible link between the TRM and chaos theory. The model describes a near-surface phenomenon with an estimated excess power yield of ∼1 kW/cm 3 Pd, as compared to 50 W/cm 3 of reactor core for a good fission reactor. Transmission resonance-induced nuclear transmutation, a new type of nuclear reaction, is strongly suggested with two types emphasized: transmission resonance-induced neutron transfer reactions yielding essentially the same end result as Teller's hypothesized catalytic neutron transfer and a three-body reaction promoted by standing de Broglie waves. In this paper suggestions for the anomalous production of heat, particles, and radiation are given

  17. Fusion energy

    International Nuclear Information System (INIS)

    1990-09-01

    The main purpose of the International Thermonuclear Experimental Reactor (ITER) is to develop an experimental fusion reactor through the united efforts of many technologically advanced countries. The ITER terms of reference, issued jointly by the European Community, Japan, the USSR, and the United States, call for an integrated international design activity and constitute the basis of current activities. Joint work on ITER is carried out under the auspices of the International Atomic Energy Agency (IAEA), according to the terms of quadripartite agreement reached between the European Community, Japan, the USSR, and the United States. The site for joint technical work sessions is at the MaxPlanck Institute of Plasma Physics. Garching, Federal Republic of Germany. The ITER activities have two phases: a definition phase performed in 1988 and the present design phase (1989--1990). During the definition phase, a set of ITER technical characteristics and supporting research and development (R ampersand D) activities were developed and reported. The present conceptual design phase of ITER lasts until the end of 1990. The objectives of this phase are to develop the design of ITER, perform a safety and environmental analysis, develop site requirements, define future R ampersand D needs, and estimate cost, manpower, and schedule for construction and operation. A final report will be submitted at the end of 1990. This paper summarizes progress in the ITER program during the 1989 design phase

  18. Identification of a human protein-derived HIV-1 fusion inhibitor targeting the gp41 fusion core structure.

    Directory of Open Access Journals (Sweden)

    Lijun Chao

    Full Text Available The HIV-1 envelope glycoprotein (Env gp41 plays a crucial role in the viral fusion process. The peptides derived from the C-terminal heptad repeat (CHR of gp41 are potent HIV fusion inhibitors. However, the activity of these anti-HIV-1 peptides in vivo may be attenuated by their induction of anti-gp41 antibodies. Thus, it is essential to identify antiviral peptides or proteins with low, or no, immunogenicity to humans. Here, we found that the C-terminal fragment (aa 462-521 of the human POB1 (the partner of RalBP1, designated C60, is an HIV-1 fusion inhibitor. It bound to N36, the peptide derived from the N-terminal heptad repeat (NHR of gp41, and to the six-helix bundle (6-HB formed by N36 and C34, a CHR-peptide, but it did not bind to C34. Unlike the CHR-peptides, C60 did not block gp41 6-HB formation. Rather, results suggest that C60 inhibits HIV-1 fusion by binding to the 6-HB, in particular, the residues in the gp41 NHR domain that are exposed on the surface of 6-HB. Since 6-HB plays a crucial role in the late stage of fusion between the viral envelope and endosomal membrane during the endocytic process of HIV-1, C60 may serve as a host restriction factor to suppress HIV-1 entry into CD4+ T lymphocytes. Taken together, it can be concluded from these results that C60 can be used as a lead for the development of anti-HIV-1 therapeutics or microbicides for the treatment and prevention of HIV-1 infection, as well as a molecular probe to study the fusogenic mechanism of HIV-1.

  19. PeptideAtlas

    Data.gov (United States)

    U.S. Department of Health & Human Services — PeptideAtlas is a multi-organism, publicly accessible compendium of peptides identified in a large set of tandem mass spectrometry proteomics experiments. Mass...

  20. Embryo rescue of crosses between diploid and tetraploid grape ...

    African Journals Online (AJOL)

    ajl yemi

    2011-12-19

    Dec 19, 2011 ... embryo rescue from interspecific hybridization between diploid and tetraploid grape species. Wakana et al. (2003) and Motosugi et al. (2003) studied the formation and developments of hybrid seeds from cross between diploid and tetraploid, and then obtained triploid progenies through embryo rescue.

  1. 29 CFR 553.215 - Ambulance and rescue service employees.

    Science.gov (United States)

    2010-07-01

    ... activities, the applicable standard is the one which applies to the activity in which the employee spends the majority of work time during the work period. (b) Ambulance and rescue service employees of public agencies... 29 Labor 3 2010-07-01 2010-07-01 false Ambulance and rescue service employees. 553.215 Section 553...

  2. Emotional Reactions of Rescue Workers Following a Tornado.

    Science.gov (United States)

    McCammon, Susan L.; And Others

    Rescue and medical workers may be at risk for negative emotional experience following intervention efforts in disaster situations. To examine this possibility, 120 rescue and hospital personnel responded to a survey of their emotional reactions and coping behaviors 3 months after a devastating tornado. Twenty-eight subjects had been involved in…

  3. Review and expectations of terror attack emergency rescue

    Directory of Open Access Journals (Sweden)

    De-wen WANG

    2012-03-01

    Full Text Available Ten years of anti-terror struggle since the 9/11 event has indicated adequately that terrorism is a global problem and international danger. Likewise, anti-terror emergency rescue is also an important task which will influence the safety and benefit of every country all over the world. This paper reviews the main progress and result of international anti-terror struggle in the last ten years, and also introduces the new characteristic of the international anti-terror activity. Besides that, this paper also brings forward the further consideration about the anti-terror emergency medical rescue and the researches remaining to be carried out. The latter includes: (1 to further perfect the high-efficient medical rescue command organization; (2 to further perfect the emergency medical rescue prearranged scheme; (3 to further perfect the construction of rescue system and rescue base after various types of terror attack; (4 to further promote the anti-terror consciousness in the public, and pay more attention to the prevention and investigation of the psychological disaster; (5 to further carry out the basic investigation on emergency medical rescue after various terror attack injuries (for example the types and characteristics of new injuries, pathophysiology and prevention and treatment of stress-psychological effect induced by terror attack, new high-efficient medical rescue measure and equipments, and so on.

  4. 78 FR 79010 - Criteria to Certify Coal Mine Rescue Teams

    Science.gov (United States)

    2013-12-27

    ... coal requires more heat to combust; (3) anthracite dust does not propagate an explosion; and (4) there... to Certify Coal Mine Rescue Teams AGENCY: Mine Safety and Health Administration, Labor. ACTION... updated the coal mine rescue team certification criteria. The Mine Improvement and New Emergency Response...

  5. Syncytin is involved in breast cancer-endothelial cell fusions

    DEFF Research Database (Denmark)

    Bjerregaard, Bolette; Holck, S.; Christensen, I.J.

    2006-01-01

    Cancer cells can fuse spontaneously with normal host cells, including endothelial cells, and such fusions may strongly modulate the biological behaviour of tumors. However, the underlying mechanisms are unknown. We now show that human breast cancer cell lines and 63 out of 165 (38%) breast cancer...... specimens express syncytin, an endogenous retroviral envelope protein, previously implicated in fusions between placental trophoblast cells. Additionally, endothelial and cancer cells are shown to express ASCT-2, a receptor for syncytin. Syncytin antisense treatment decreases syncytin expression...... and inhibits fusions between breast cancer cells and endothelial cells. Moreover, a syncytin inhibitory peptide also inhibits fusions between cancer and endothelial cells. These results are the first to show that syncytin is expressed by human cancer cells and is involved in cancer-endothelial cell fusions....

  6. Medical rescue for nuclear or radiologic emergencies

    International Nuclear Information System (INIS)

    Chen Xiaohua; Nie Suifeng

    2011-01-01

    Nuclear or radiologic emergencies are defined as incidents that are caused by radioactive substance or by other sources of radiation and can pose a serious hazard to public health. In case of nuclear or radiologic emergencies, radioactive rays will damage the human body and bring about psychological and mental stress, resulting in a series of social psychological effects. The key to medical rescue for nuclear or radiologic emergencies is to take effective measures which can minimize the body harm resulting from nuclear or radiologic emergencies and maintain social stability. This article reviews the personnel protection, on-the-spot salvage, treatments of various harm, and prevention of public psychological effect following nuclear or radiologic emergencies. (authors)

  7. Rescue from replication stress during mitosis.

    Science.gov (United States)

    Fragkos, Michalis; Naim, Valeria

    2017-04-03

    Genomic instability is a hallmark of cancer and a common feature of human disorders, characterized by growth defects, neurodegeneration, cancer predisposition, and aging. Recent evidence has shown that DNA replication stress is a major driver of genomic instability and tumorigenesis. Cells can undergo mitosis with under-replicated DNA or unresolved DNA structures, and specific pathways are dedicated to resolving these structures during mitosis, suggesting that mitotic rescue from replication stress (MRRS) is a key process influencing genome stability and cellular homeostasis. Deregulation of MRRS following oncogene activation or loss-of-function of caretaker genes may be the cause of chromosomal aberrations that promote cancer initiation and progression. In this review, we discuss the causes and consequences of replication stress, focusing on its persistence in mitosis as well as the mechanisms and factors involved in its resolution, and the potential impact of incomplete replication or aberrant MRRS on tumorigenesis, aging and disease.

  8. Teleautonomous Control on Rescue Robot Prototype

    Directory of Open Access Journals (Sweden)

    Son Kuswadi

    2012-12-01

    Full Text Available Robot application in disaster area can help responder team to save victims. In order to finish task, robot must have flexible movement mechanism so it can pass through uncluttered area. Passive linkage can be used on robot chassis so it can give robot flexibility. On physical experiments, robot is succeeded to move through gravels and 5 cm obstacle. Rescue robot also has specialized control needs. Robot must able to be controlled remotely. It also must have ability to move autonomously. Teleautonomous control method is combination between those methods. It can be concluded from experiments that on teleoperation mode, operator must get used to see environment through robot’s camera. While on autonomous mode, robot is succeeded to avoid obstacle and search target based on sensor reading and controller program. On teleautonomous mode, robot can change control mode by using bluetooth communication for data transfer, so robot control will be more flexible.

  9. Data Rescue Case Studies from the Cryosphere

    Science.gov (United States)

    Fetterer, F. M.

    2017-12-01

    A simple definition of the cryosphere is "where the world is frozen", or where water takes the form of snow and ice. The cryosphere is shrinking as the Earth warms. Data, particularly old data, document this in often eye-opening fashion. A photograph of Alaska's Muir Glacier taken in 1902 next to one taken in 2005 has impact that a line graph of air temperature anomalies from a weather station can't match, even though temperature data are fundamental to climate research and to understanding the glacier retreat captured in the photographs. Whaling logbooks from the late 1800s, maps of sea ice shared internationally in the 1930s, and satellite images of the polar oceans from the 1960s are not as immediately thought-provoking as are glacier photographs, but when preserved and documented they provide a record of sea ice coverage that is more than 100 years long. We developed a data product from these and other sources that is used in meteorological reanalysis and to answer questions about ice in the Arctic prior to 1978, when commonly used satellite-data-derived sea ice records begin. Preserving glacier photographs and making them available online, and publishing a gridded sea ice data product that builds on the preservation work of others are examples of data rescue projects that benefit scientific research and mobilize knowledge. These and other case studies suggest that even absent secure funding and an organizational setting that supports data rescue, important data make the transition from someone's office to archived and online with metadata because scientists are impassioned about the data they collect and want others to be able to use these data. In these cases from the cryosphere, student interns, collaborations with librarians, and cooperation with colleagues in other data centers have made it possible to preserve data at low cost.

  10. Rational site-directed mutations of the LLP-1 and LLP-2 lentivirus lytic peptide domains in the intracytoplasmic tail of human immunodeficiency virus type 1 gp41 indicate common functions in cell-cell fusion but distinct roles in virion envelope incorporation.

    Science.gov (United States)

    Kalia, Vandana; Sarkar, Surojit; Gupta, Phalguni; Montelaro, Ronald C

    2003-03-01

    Two highly conserved cationic amphipathic alpha-helical motifs, designated lentivirus lytic peptides 1 and 2 (LLP-1 and LLP-2), have been characterized in the carboxyl terminus of the transmembrane (TM) envelope glycoprotein (Env) of lentiviruses. Although various properties have been attributed to these domains, their structural and functional significance is not clearly understood. To determine the specific contributions of the Env LLP domains to Env expression, processing, and incorporation and to viral replication and syncytium induction, site-directed LLP mutants of a primary dualtropic infectious human immunodeficiency virus type 1 (HIV-1) isolate (ME46) were examined. Substitutions were made for highly conserved arginine residues in either the LLP-1 or LLP-2 domain (MX1 or MX2, respectively) or in both domains (MX4). The HIV-1 mutants with altered LLP domains demonstrated distinct phenotypes. The LLP-1 mutants (MX1 and MX4) were replication defective and showed an average of 85% decrease in infectivity, which was associated with an evident decrease in gp41 incorporation into virions without a significant decrease in Env expression or processing in transfected 293T cells. In contrast, MX2 virus was replication competent and incorporated a full complement of Env into its virions, indicating a differential role for the LLP-1 domain in Env incorporation. Interestingly, the replication-competent MX2 virus was impaired in its ability to induce syncytia in T-cell lines. This defect in cell-cell fusion did not correlate with apparent defects in the levels of cell surface Env expression, oligomerization, or conformation. The lack of syncytium formation, however, correlated with a decrease of about 90% in MX2 Env fusogenicity compared to that of wild-type Env in quantitative luciferase-based cell-cell fusion assays. The LLP-1 mutant MX1 and MX4 Envs also exhibited an average of 80% decrease in fusogenicity. Altogether, these results demonstrate for the first time that

  11. Peptide-Carrier Conjugation

    DEFF Research Database (Denmark)

    Hansen, Paul Robert

    2015-01-01

    To produce antibodies against synthetic peptides it is necessary to couple them to a protein carrier. This chapter provides a nonspecialist overview of peptide-carrier conjugation. Furthermore, a protocol for coupling cysteine-containing peptides to bovine serum albumin is outlined....

  12. PH dependent adhesive peptides

    Science.gov (United States)

    Tomich, John; Iwamoto, Takeo; Shen, Xinchun; Sun, Xiuzhi Susan

    2010-06-29

    A novel peptide adhesive motif is described that requires no receptor or cross-links to achieve maximal adhesive strength. Several peptides with different degrees of adhesive strength have been designed and synthesized using solid phase chemistries. All peptides contain a common hydrophobic core sequence flanked by positively or negatively charged amino acids sequences.

  13. Peptide Nucleic Acids

    DEFF Research Database (Denmark)

    2003-01-01

    A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

  14. Peptide Nucleic Acids

    DEFF Research Database (Denmark)

    1998-01-01

    A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

  15. Peptide Nucleic Acids (PNA)

    DEFF Research Database (Denmark)

    2002-01-01

    A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

  16. Peptide Nucleic Acid Synthons

    DEFF Research Database (Denmark)

    2004-01-01

    A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

  17. Antimicrobial Peptides in 2014

    Directory of Open Access Journals (Sweden)

    Guangshun Wang

    2015-03-01

    Full Text Available This article highlights new members, novel mechanisms of action, new functions, and interesting applications of antimicrobial peptides reported in 2014. As of December 2014, over 100 new peptides were registered into the Antimicrobial Peptide Database, increasing the total number of entries to 2493. Unique antimicrobial peptides have been identified from marine bacteria, fungi, and plants. Environmental conditions clearly influence peptide activity or function. Human α-defensin HD-6 is only antimicrobial under reduced conditions. The pH-dependent oligomerization of human cathelicidin LL-37 is linked to double-stranded RNA delivery to endosomes, where the acidic pH triggers the dissociation of the peptide aggregate to release its cargo. Proline-rich peptides, previously known to bind to heat shock proteins, are shown to inhibit protein synthesis. A model antimicrobial peptide is demonstrated to have multiple hits on bacteria, including surface protein delocalization. While cell surface modification to decrease cationic peptide binding is a recognized resistance mechanism for pathogenic bacteria, it is also used as a survival strategy for commensal bacteria. The year 2014 also witnessed continued efforts in exploiting potential applications of antimicrobial peptides. We highlight 3D structure-based design of peptide antimicrobials and vaccines, surface coating, delivery systems, and microbial detection devices involving antimicrobial peptides. The 2014 results also support that combination therapy is preferred over monotherapy in treating biofilms.

  18. Posture manipulation for rescue activity via small traction robots

    International Nuclear Information System (INIS)

    Iwano, Yuki; Osuka, Koichi; Amano, Hisanori

    2006-01-01

    We discuss a conceptual design of rescue robots against nuclear-power plant accidents. We claim that the rescue robots in nuclear-power plants should have the following properties. (1) The size is small. (2) The structure is simple. (3) The number of the robots is large. This paper studies the rescue robots to rescue people in an area polluted with radioactive leakage in nuclear power institutions. In particular, we propose a rescue system which consists of a group of small mobile robots. First, small traction robots set the posture of the fainted victims to carry easily, and carry them to the safety space with the mobile robots for the stretcher composition. In this paper, we describe the produced small traction robots. And, we confirm that the robots can manipulate a 40 kg dummy doll's posture. We also examine the optimal number of robots from a perspective of working efficiency in the assumption spot. (author)

  19. Fusion technology: The Iter fusion experiment

    International Nuclear Information System (INIS)

    Dietz, K.J.

    1994-01-01

    Plans for the Iter international fusion experiment, in which the European Union, Japan, Canada, Russia, Sweden, Switzerland, and the USA cooperate, were begun in 1985, and construction work started in early 1994. These activities serve for the preparation of the design and construction documents for a research reactor in which a stable fusion plasma is to be generated. This is to be the basis for the construction of a fusion reactor for electricity generation. Preparatory work was performed in the Tokamak experiments with JET and TFTR. The fusion power of 1.5 GW will be attained, thus enabling Iter to keep a deuterium-tritium plasma burning. (orig.) [de

  20. Viral membrane fusion: is glycoprotein G of rhabdoviruses a representative of a new class of viral fusion proteins?

    Directory of Open Access Journals (Sweden)

    A.T. Da Poian

    2005-06-01

    Full Text Available Enveloped viruses always gain entry into the cytoplasm by fusion of their lipid envelope with a cell membrane. Some enveloped viruses fuse directly with the host cell plasma membrane after virus binding to the cell receptor. Other enveloped viruses enter the cells by the endocytic pathway, and fusion depends on the acidification of the endosomal compartment. In both cases, virus-induced membrane fusion is triggered by conformational changes in viral envelope glycoproteins. Two different classes of viral fusion proteins have been described on the basis of their molecular architecture. Several structural data permitted the elucidation of the mechanisms of membrane fusion mediated by class I and class II fusion proteins. In this article, we review a number of results obtained by our laboratory and by others that suggest that the mechanisms involved in rhabdovirus fusion are different from those used by the two well-studied classes of viral glycoproteins. We focus our discussion on the electrostatic nature of virus binding and interaction with membranes, especially through phosphatidylserine, and on the reversibility of the conformational changes of the rhabdovirus glycoprotein involved in fusion. Taken together, these data suggest the existence of a third class of fusion proteins and support the idea that new insights should emerge from studies of membrane fusion mediated by the G protein of rhabdoviruses. In particular, the elucidation of the three-dimensional structure of the G protein or even of the fusion peptide at different pH's might provide valuable information for understanding the fusion mechanism of this new class of fusion proteins.

  1. Review of fusion synfuels

    International Nuclear Information System (INIS)

    Fillo, J.A.

    1980-01-01

    Thermonuclear fusion offers an inexhaustible source of energy for the production of hydrogen from water. Depending on design, electric generation efficiencies of approx. 40 to 60% and hydrogen production efficiencies by high-temperature electrolysis of approx. 50 to 65% are projected for fusion reactors using high-temperatures blankets. Fusion/coal symbiotic systems appear economically promising for the first generation of commercial fusion synfuels plants. Coal production requirements and the environmental effects of large-scale coal usage would be greatly reduced by a fusion/coal system. In the long term, there could be a gradual transition to an inexhaustible energy system based solely on fusion

  2. Barriers to fusion

    International Nuclear Information System (INIS)

    Berriman, A.C.; Butt, R.D.; Dasgupta, M.; Hinde, D.J.; Morton, C.R.; Newton, J.O.

    1999-01-01

    The fusion barrier is formed by the combination of the repulsive Coulomb and attractive nuclear forces. Recent research at the Australian National University has shown that when heavy nuclei collide, instead of a single fusion barrier, there is a set of fusion barriers. These arise due to intrinsic properties of the interacting nuclei such deformation, rotations and vibrations. Thus the range of barrier energies depends on the properties of both nuclei. The transfer of matter between nuclei, forming a neck, can also affect the fusion process. High precision data have been used to determine fusion barrier distributions for many nuclear reactions, leading to new insights into the fusion process

  3. Lipid raft-like liposomes used for targeted delivery of a chimeric entry-inhibitor peptide with anti-HIV-1 activity.

    Science.gov (United States)

    Gómara, María José; Pérez-Pomeda, Ignacio; Gatell, José María; Sánchez-Merino, Victor; Yuste, Eloisa; Haro, Isabel

    2017-02-01

    The work reports the design and synthesis of a chimeric peptide that is composed of the peptide sequences of two entry inhibitors which target different sites of HIV-1 gp41. The chimeric peptide offers the advantage of targeting two gp41 regions simultaneously: the fusion peptide and the loop both of which are membrane active and participate in the membrane fusion process. We therefore use lipid raft-like liposomes as a tool to specifically direct the chimeric inhibitor peptide to the membrane domains where the HIV-1 envelope protein is located. Moreover, the liposomes that mimic the viral membrane composition protect the chimeric peptide against proteolytic digestion thereby increasing the stability of the peptide. The described liposome preparations are suitable nanosystems for managing hydrophobic entry-inhibitor peptides as putative therapeutics. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. RESCUE: An artificial neural network tool for the NMR spectral assignment of proteins

    International Nuclear Information System (INIS)

    Pons, J.L.; Delsuc, M.A.

    1999-01-01

    The assignment of the 1 H spectrum of a protein or a polypeptide is the prerequisite for advanced NMR studies. We present here an assignment tool based on the artificial neural network technology, which determines the type of the amino acid from the chemical shift values observed in the 1 H spectrum. Two artificial neural networks have been trained and extensively tested against a non-redundant subset of the BMRB chemical shift data bank [Seavey, B.R. et al. (1991) J. Biomol. NMR, 1, 217-236]. The most promising of the two accomplishes the analysis in two steps, grouping related amino acids together. It presents a mean rate of success above 80% on the test set. The second network tested separates down to the single amino acid; it presents a mean rate of success of 63%. This tool has been used to assist the manual assignment of peptides and proteins and can also be used as a block in an automated approach to assignment. The program has been called RESCUE and is made publicly available at the following URL: http://www.infobiosud.univ-montp1.fr/rescue

  5. HIPdb: a database of experimentally validated HIV inhibiting peptides.

    Science.gov (United States)

    Qureshi, Abid; Thakur, Nishant; Kumar, Manoj

    2013-01-01

    Besides antiretroviral drugs, peptides have also demonstrated potential to inhibit the Human immunodeficiency virus (HIV). For example, T20 has been discovered to effectively block the HIV entry and was approved by the FDA as a novel anti-HIV peptide (AHP). We have collated all experimental information on AHPs at a single platform. HIPdb is a manually curated database of experimentally verified HIV inhibiting peptides targeting various steps or proteins involved in the life cycle of HIV e.g. fusion, integration, reverse transcription etc. This database provides experimental information of 981 peptides. These are of varying length obtained from natural as well as synthetic sources and tested on different cell lines. Important fields included are peptide sequence, length, source, target, cell line, inhibition/IC(50), assay and reference. The database provides user friendly browse, search, sort and filter options. It also contains useful services like BLAST and 'Map' for alignment with user provided sequences. In addition, predicted structure and physicochemical properties of the peptides are also included. HIPdb database is freely available at http://crdd.osdd.net/servers/hipdb. Comprehensive information of this database will be helpful in selecting/designing effective anti-HIV peptides. Thus it may prove a useful resource to researchers for peptide based therapeutics development.

  6. Monoclonal antibodies against a synthetic peptide from human immunodeficiency virus type 1 Nef protein

    DEFF Research Database (Denmark)

    Steinaa, L; Wulff, A M; Saermark, T

    1994-01-01

    Monoclonal antibodies against a synthetic peptide (aa 138-152) from HIV-1 Nef protein were produced and characterized. Three hybridoma lines producing monoclonal antibodies (MAbs) against the synthetic peptide were generated by fusion between P3-X63 Ag8.653 myeloma cells and BALB/c splenocytes from...... mice immunized with the synthetic peptide coupled to keyhole limpet hemocyanin (KLH). The hybridomas were screened and selected by ELISA with the peptide coupled to bovine serum albumin (BSA) immobilized to the polystyrene surface and specificity for the peptide was confirmed by competitive ELISA...... with the peptide free in solution. The reactions of the MAbs with a 5-aa motif (WCYKL) included in the sequence were examined with synthetic peptides and two of the MAbs reacted with the motif. The recognitions of recombinant full-length Nef protein were also tested. One MAb reacted with the protein in both ELISA...

  7. Design and expression of a short peptide as an HIV detection probe

    Energy Technology Data Exchange (ETDEWEB)

    Lines, Jamie A.; Yu, Zhiqiang; Dedkova, Larisa M.; Chen, Shengxi, E-mail: shengxi.chen.1@asu.edu

    2014-01-03

    Highlights: •We designed a short fusion peptide (FP-50) for in vivo expression. •This peptide is a very promising component for detection of gp120 protein. •The detectable level is about 20–200 times lower than previously published methods. •It is a novel probe to detect HIV-1 gp120 during early stages of HIV infection. -- Abstract: To explore a low-cost novel probe for HIV detection, we designed and prepared a 50-amino acid-length short fusion peptide (FP-50) via Escherichia coli in vivo expression. It was employed as a novel probe to detect HIV-1 gp120 protein. The detectable level of gp120 protein using the FP-50 peptide was approximately 20–200 times lower than previously published methods that used a pair of monoclonal antibodies. Thus, this short peptide is a very promising component for detection of gp120 protein during early stages of HIV infection.

  8. Fusion reactor design studies

    International Nuclear Information System (INIS)

    Emmert, G.A.; Kulcinski, G.L.; Santarius, J.F.

    1990-01-01

    This report discusses the following topics on the ARIES tokamak: systems; plasma power balance; impurity control and fusion ash removal; fusion product ripple loss; energy conversion; reactor fueling; first wall design; shield design; reactor safety; and fuel cost and resources

  9. Laser fusion: an overview

    International Nuclear Information System (INIS)

    Boyer, K.

    1975-01-01

    The laser fusion concept is described along with developments in neodymium and carbon dioxide lasers. Fuel design and fabrication are reviewed. Some spin-offs of the laser fusion program are discussed. (U.S.)

  10. Fusion Canada issue 23

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1994-01-01

    A short bulletin from the National Fusion Program highlighting in this issue TdeV tokamak updates, fusion research in Korea, CCFM program review, TdeV divertor plasma, and CFFTP program review. 4 figs.

  11. Fusion Canada issue 27

    International Nuclear Information System (INIS)

    1995-03-01

    A short bulletin from the National Fusion Program highlighting in this issue ITER reactor siting, a major upgrade for TdeV tokamak, Ceramic Breeders: new tritium mapping technique and Joint Fusion Symposium. 2 figs

  12. Fusion Canada issue 20

    International Nuclear Information System (INIS)

    1993-03-01

    Fusion Canada's publication of the National Fusion Program. Included in this issue is the CFFTP Industrial Impact Study, CCFM/TdeV Update:helium pumping, research funds, and deuterium in beryllium - high temperature behaviour. 3 figs

  13. Fusion Canada issue 23

    International Nuclear Information System (INIS)

    1994-01-01

    A short bulletin from the National Fusion Program highlighting in this issue TdeV tokamak updates, fusion research in Korea, CCFM program review, TdeV divertor plasma, and CFFTP program review. 4 figs

  14. Canada's Fusion Program

    International Nuclear Information System (INIS)

    Jackson, D. P.

    1990-01-01

    Canada's fusion strategy is based on developing specialized technologies in well-defined areas and supplying these technologies to international fusion projects. Two areas are specially emphasized in Canada: engineered fusion system technologies, and specific magnetic confinement and materials studies. The Canadian Fusion Fuels Technology Project focuses on the first of these areas. It tritium and fusion reactor fuel systems, remote maintenance and related safety studies. In the second area, the Centre Canadian de fusion magnetique operates the Tokamak de Varennes, the main magnetic fusion device in Canada. Both projects are partnerships linking the Government of Canada, represented by Atomic Energy of Canada Limited, and provincial governments, electrical utilities, universities and industry. Canada's program has extensive international links, through which it collaborates with the major world fusion programs, including participation in the International Thermonuclear Experimental Reactor project

  15. Fusion systems engineering

    International Nuclear Information System (INIS)

    Anon.

    1977-01-01

    Information is given on each of the following topics: (1) fusion reactor systems studies, (2) development of blanket processing technology for fusion reactors, (3) safety studies of CTR concepts, and (4) cross section measurements and techniques

  16. Fusion Canada issue 6

    International Nuclear Information System (INIS)

    1989-02-01

    A short bulletin from the National Fusion Program. Included in this issue is a funding report for CFFTP, a technical update for Tokamak de Varennes and a network for university research by the National Fusion Program. 4 figs

  17. [Plant signaling peptides. Cysteine-rich peptides].

    Science.gov (United States)

    Ostrowski, Maciej; Kowalczyk, Stanisław

    2015-01-01

    Recent bioinformatic and genetic analyses of several model plant genomes have revealed the existence of a highly abundant group of signaling peptides that are defined as cysteine-rich peptides (CRPs). CRPs are usually in size between 50 and 90 amino acid residues, they are positively charged, and they contain 4-16 cysteine residues that are important for the correct conformational folding. Despite the structural differences among CRP classes, members from each class have striking similarities in their molecular properties and function. The present review presents the recent progress in research on signaling peptides from several families including: EPF/EPFL, SP11/SCR, PrsS, RALF, LURE, and some other peptides belonging to CRP group. There is convincing evidence indicating multiple roles for these CRPs as signaling molecules during the plant life cycle, ranging from stomata development and patterning, self-incompatibility, pollen tube growth and guidance, reproductive processes, and nodule formation.

  18. Physical capacity of rescue personnel in the mining industry

    Directory of Open Access Journals (Sweden)

    Hunt Andrew P

    2008-10-01

    Full Text Available Abstract Background The mining industry has one of the highest occupational rates of serious injury and fatality. Mine staff involved with rescue operations are often required to respond to physically challenging situations. This paper describes the physical attributes of mining rescue personnel. Methods 91 rescue personnel (34 ± 8.6 yrs, 1.79 ± 0.07 m, 90 ± 15.0 kg participating in the Queensland Mines Rescue Challenge completed a series of health-related and rescue-related fitness tasks. Health-related tasks comprised measurements of aerobic capacity (VO2max, abdominal endurance, abdominal strength, flexibility, lower back strength, leg strength, elbow flexion strength, shoulder strength, lower back endurance, and leg endurance. Rescue-related tasks comprised an incremental carry (IC, coal shovel (CS, and a hose drag (HD, completed in this order. Results Cardiovascular (VO2max and muscular endurance was average or below average compared with the general population. Isometric strength did not decline with age. The rescue-related tasks were all extremely demanding with heart rate responses averaging greater than 88% of age predicted maximal heart rates. Heart rate recovery responses were more discriminating than heart rates recorded during the tasks, indicating the hose drag as the most physically demanding of the tasks. Conclusion Relying on actual rescues or mining related work to provide adequate training is generally insufficient to maintain, let alone increase, physical fitness. It is therefore recommended that standards of required physical fitness be developed and mines rescue personnel undergo regularly training (and assessment in order to maintain these standards.

  19. Development of stretcher component robots for rescue against nuclear disaster

    International Nuclear Information System (INIS)

    Iwano, Yuki; Osuka, Koichi; Amano, Hisanori

    2006-01-01

    This paper studies the rescue robots to rescue people in an area polluted with radioactive leakage in nuclear power institutions. In particular, we propose the rescue system which consists of a group of small mobile robots. First, small traction robots set the posture of the fainted victims to carry easily, and carry them to the safety space with the mobile robots for the stretcher composition. In this paper, we confirm that the stretcher component robots could transport and convey a 40 [kg] dummy doll. And, we also show an application usage of stretcher robot. (author)

  20. Emergency rescue in accidents with HDR afterloading units

    International Nuclear Information System (INIS)

    Kaulich, T.W.; Nuesslin, F.; Becker, G.; Lamprecht, U.; Bamberg, M.

    1999-01-01

    Problem: HDR brachyradiotherapy has minimized the exposure to radiation of the personnel working in this field. Nonetheless there are periodically reported troubles with afterloading units concerning the retraction of sources that require immediate action for the limitation of possible damage. Legal Principles according to the German Regulation Concerning Protection against Radiation (Strahlenschutzverordnung=StrlSchV): If in afterloading brachyradiotherapy the radiation source remains extended through malfunction we deal with an emergency according to the StrlSchV. The rescue personnel should be chosen in accordance with Paragraph 50 StrlSchV. Organization of the Rescue of the Patient: The quickest possible rescue of a patient in an emergency demands an unequivocal definition of responsibilities. Our recommendations in this instance: The physicist is responsible for the organization of the emergency rescue. The radiation oncologist in charge informs himself about the necessary emergency measures before starting the treatment and carries out the emergency rescue. If the physicist diagnoses a failure in the retraction of the source he tries to remove the failure. If he doesn't succeed in retracting the source the radiation oncologist carries out the rescue of the patient. The organizational structure of the clinic allowing, the emergency physician should invariably be the physician who placed the applicator. In the emergency rescue the radiation oncologist should be protected by a lead barrier and use manipulators. Dose Assessment in Personnel and Patient: The radiation exposure of the rescue personnel is calculated from the photon-equivalence dose H x with the help of the dose-rate constant of 192 Ir. According to the same procedure there can be evaluated the local radiation exposure of the patient concerned. Conclusions: Generally speaking, all considerations regarding the topic of emergency rescue should always start out from a worst-case scenario. Of all the

  1. Medical rescue of naval combat: challenges and future.

    Science.gov (United States)

    Jin, Hai; Hou, Li-Jun; Fu, Xiao-Bing

    2015-01-01

    There has been no large-scale naval combat in the last 30 years. With the rapid development of battleships, weapons manufacturing and electronic technology, naval combat will present some new characteristics. Additionally, naval combat is facing unprecedented challenges. In this paper, we discuss the topic of medical rescue at sea: what challenges we face and what we could do. The contents discussed in this paper contain battlefield self-aid buddy care, clinical skills, organized health services, medical training and future medical research programs. We also discuss the characteristics of modern naval combat, medical rescue challenges, medical treatment highlights and future developments of medical rescue at sea.

  2. Fusion Canada issue 18

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1992-08-01

    A short bulletin from the National Fusion Program. Included in this issue is a report on the ITER agreement signed with the EDA, the robotic maintenance for NET, the CFFTP Fusion Pilot Study, the new IEA joint programs on environment, safety and economic aspects of fusion power, and a review by the CCFM advisory committee. 3 figs.

  3. User's perspective on fusion

    International Nuclear Information System (INIS)

    Ashworth, C.P.

    1976-01-01

    The need in fusion, from the electric utilities viewpoint, is for fusion to be a real option, not huge, complicated nuclear plants costing $10 billion each and requiring restructuring the energy industry to provide and use them. A course for future fusion reactor work in order to be a real option is discussed. The advantages of alternate concepts to the tokamak are presented

  4. Fusion Canada issue 17

    International Nuclear Information System (INIS)

    1992-05-01

    A short bulletin from the National Fusion Program. Included in this issue is a report on increased funding for the Canadian Fusion Program, news of the compact Toroid fuelling gun, an update on Tokamak de Varennes, the Canada - U.S. fusion meeting, measurements of plasma flow velocity, and replaceable Tokamak divertors. 4 figs

  5. Fusion Canada issue 18

    International Nuclear Information System (INIS)

    1992-08-01

    A short bulletin from the National Fusion Program. Included in this issue is a report on the ITER agreement signed with the EDA, the robotic maintenance for NET, the CFFTP Fusion Pilot Study, the new IEA joint programs on environment, safety and economic aspects of fusion power, and a review by the CCFM advisory committee. 3 figs

  6. CO2-laser fusion

    International Nuclear Information System (INIS)

    Stark, E.E. Jr.

    1978-01-01

    The basic concept of laser fusion is described, with a set of requirements on the laser system. Systems and applications concepts are presented and discussed. The CO 2 laser's characteristics and advantages for laser fusion are described. Finally, technological issues in the development of CO 2 laser systems for fusion applications are discussed

  7. Fusion Canada issue 9

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1989-11-01

    A short bulletin from the National Fusion Program. Included in this issue is a report on availability of Canadian Tritium, an ITER update, a CCFM update on Tokamak and the new team organization, an international report on Fusion in Canada and a Laser Fusion Project at the University of Toronto. 3 figs.

  8. Heavy ion fusion

    International Nuclear Information System (INIS)

    Bangerter, R.O.

    1986-01-01

    This report on the International Symposium on Heavy Ion Fusion held May 27-29, 1986 summarizes the problems and achievements in the areas of targets, accelerators, focussing, reactor studies, and system studies. The symposium participants recognize that there are large uncertainties in Heavy Ion Fusion but many of them are also optimistic that HIF may ultimately be the best approach to fusion

  9. Fusion Canada issue 17

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1992-05-01

    A short bulletin from the National Fusion Program. Included in this issue is a report on increased funding for the Canadian Fusion Program, news of the compact Toroid fuelling gun, an update on Tokamak de Varennes, the Canada - U.S. fusion meeting, measurements of plasma flow velocity, and replaceable Tokamak divertors. 4 figs.

  10. Fusion Canada issue 25

    International Nuclear Information System (INIS)

    1994-08-01

    A short bulletin from the National Fusion Program highlighting in this issue an economic impact study of the Canadian site for ITER, Harvey Skarsgard: fusion pioneer retires, NFP: Phillips and Holtslander exchange roles, Europe's fusion funding proposals and an update of CCFM/TdeV. 1 fig

  11. Fusion reactors - types - problems

    International Nuclear Information System (INIS)

    Schmitter, K.H.

    1979-07-01

    A short account is given of the principles of fusion reactions and of the expected advantages of fusion reactors. Descriptions are presented of various Tokamak experimental devices being developed in a number of countries and of some mirror machines. The technical obstacles to be overcome before a fusion reactor could be self-supporting are discussed. (U.K.)

  12. Cold fusion research

    International Nuclear Information System (INIS)

    1989-11-01

    I am pleased to forward to you the Final Report of the Cold Fusion Panel. This report reviews the current status of cold fusion and includes major chapters on Calorimetry and Excess Heat, Fusion Products and Materials Characterization. In addition, the report makes a number of conclusions and recommendations, as requested by the Secretary of Energy

  13. Fusion Canada issue 9

    International Nuclear Information System (INIS)

    1989-11-01

    A short bulletin from the National Fusion Program. Included in this issue is a report on availability of Canadian Tritium, an ITER update, a CCFM update on Tokamak and the new team organization, an international report on Fusion in Canada and a Laser Fusion Project at the University of Toronto. 3 figs

  14. Computer Security: DNS to the rescue!

    CERN Multimedia

    Stefan Lueders, Computer Security Team

    2016-01-01

    Why you should be grateful to the Domain Name System at CERN.   Incidents involving so-called “drive-by” infections and “ransomware” are on the rise. Whilst an up-to-date and fully patched operating system is essential; whilst running anti-virus software with current virus signature files is a must; whilst “stop --- think --- don’t click” surely helps, we can still go one step further in better protecting your computers: DNS to the rescue. The DNS, short for Domain Name System, translates the web address you want to visit (like “http://cern.ch”) to a machine-readable format (the IP address, here: “188.184.9.234”). For years, we have automatically monitored the DNS translation requests made by your favourite web browser (actually by your operating system, but that doesn’t matter here), and we have automatically informed you if your computer tried to access a website known to hos...

  15. Biochemistry and biophysics of HIV-1 gp41 - membrane interactions and implications for HIV-1 envelope protein mediated viral-cell fusion and fusion inhibitor design.

    Science.gov (United States)

    Cai, Lifeng; Gochin, Miriam; Liu, Keliang

    2011-12-01

    Human immunodeficiency virus type 1 (HIV-1), the pathogen of acquired immunodeficiency syndrome (AIDS), causes ~2 millions death every year and still defies an effective vaccine. HIV-1 infects host cells through envelope protein - mediated virus-cell fusion. The transmembrane subunit of envelope protein, gp41, is the molecular machinery which facilitates fusion. Its ectodomain contains several distinguishing functional domains, fusion peptide (FP), Nterminal heptad repeat (NHR), C-terminal heptad repeat (CHR) and membrane proximal extracellular region (MPER). During the fusion process, FP inserts into the host cell membrane, and an extended gp41 prehairpin conformation bridges the viral and cell membranes through MPER and FP respectively. Subsequent conformational change of the unstable prehairpin results in a coiled-coil 6-helix bundle (6HB) structure formed between NHR and CHR. The energetics of 6HB formation drives membrane apposition and fusion. Drugs targeting gp41 functional domains to prevent 6HB formation inhibit HIV-1 infection. T20 (enfuvirtide, Fuzeon) was approved by the US FDA in 2003 as the first fusion inhibitor. It is a 36-residue peptide from the gp41 CHR, and it inhibits 6HB formation by targeting NHR and lipids. Development of new fusion inhibitors, especially small molecule drugs, is encouraged to overcome the shortcomings of T20 as a peptide drug. Hydrophobic characteristics and membrane association are critical for gp41 function and mechanism of action. Research in gp41-membrane interactions, using peptides corresponding to specific functional domains, or constructs including several interactive domains, are reviewed here to get a better understanding of gp41 mediated virus-cell fusion that can inform or guide the design of new HIV-1 fusion inhibitors.

  16. Peptide inhibition of human cytomegalovirus infection

    Directory of Open Access Journals (Sweden)

    Morris Cindy A

    2011-02-01

    Full Text Available Abstract Background Human cytomegalovirus (HCMV is the most prevalent congenital viral infection in the United States and Europe causing significant morbidity and mortality to both mother and child. HCMV is also an opportunistic pathogen in immunocompromised individuals, including human immunodeficiency virus (HIV- infected patients with AIDS, and solid organ and allogeneic stem cell transplantation recipients. Current treatments for HCMV-associated diseases are insufficient due to the emergence of drug-induced resistance and cytotoxicity, necessitating novel approaches to limit HCMV infection. The aim of this study was to develop therapeutic peptides targeting glycoprotein B (gB, a major glycoprotein of HCMV that is highly conserved across the Herpesviridae family, that specifically inhibit fusion of the viral envelope with the host cell membrane preventing HCMV entry and infection. Results Using the Wimley-White Interfacial Hydrophobicity Scale (WWIHS, several regions within gB were identified that display a high potential to interact with lipid bilayers of cell membranes and hydrophobic surfaces within proteins. The ability of synthetic peptides analogous to WWIHS-positive sequences of HCMV gB to inhibit viral infectivity was evaluated. Human foreskin fibroblasts (HFF were infected with the Towne-GFP strain of HCMV (0.5 MOI, preincubated with peptides at a range of concentrations (78 nm to 100 μM, and GFP-positive cells were visualized 48 hours post-infection by fluorescence microscopy and analyzed quantitatively by flow cytometry. Peptides that inhibited HCMV infection demonstrated different inhibitory concentration curves indicating that each peptide possesses distinct biophysical properties. Peptide 174-200 showed 80% inhibition of viral infection at a concentration of 100 μM, and 51% and 62% inhibition at concentrations of 5 μM and 2.5 μM, respectively. Peptide 233-263 inhibited infection by 97% and 92% at concentrations of 100

  17. Modulation of NF-KB in rescued irradiated cells

    International Nuclear Information System (INIS)

    Lam, R.K.K.; Fung, Y.K.; Han, W.; Li, L.; Chiu, S.K.; Cheng, S.H.; Yu, K.N.

    2015-01-01

    Studies by different groups on the rescue effect, where unirradiated bystander cells mitigated the damages in the irradiated cells, since its discovery by the authors' group in 2011 were first reviewed. The properties of the rescue effect were then examined using a novel experimental set-up to physically separate the rescue signals from the bystander signals. The authors' results showed that the rescue effect was mediated through activation of the nuclear factor-KB (NF-KB) response pathway in the irradiated cells, and that the NF-KB activation inhibitor BAy -1 1-7082 did not affect the activation of this response pathway in the irradiated cells induced by direct irradiation. (authors)

  18. Expectations of a business rescue plan: international directives for ...

    African Journals Online (AJOL)

    Kirstam

    2014-09-01

    Sep 1, 2014 ... 10Key words: business rescue, South African Companies Act, business ... countries such as Germany, Australia, the United Kingdom (UK) and ...... operating statistics and detailed cash flow projections is needed for sound risk.

  19. Achievements in emergency medical rescue service, North-West ...

    African Journals Online (AJOL)

    2006-08-28

    Aug 28, 2006 ... In North-West province this process of provincialisation took place in ... Emergency Medical Rescue Service, Department of Health, North-West. Victor R .... recovery after CPR treatment should be started as soon as possible ...

  20. Guidance of Autonomous Amphibious Vehicles for Flood Rescue Support

    Directory of Open Access Journals (Sweden)

    Shankarachary Ragi

    2013-01-01

    Full Text Available We develop a path-planning algorithm to guide autonomous amphibious vehicles (AAVs for flood rescue support missions. Specifically, we develop an algorithm to control multiple AAVs to reach/rescue multiple victims (also called targets in a flood scenario in 2D, where the flood water flows across the scene and the targets move (drifted by the flood water along the flood stream. A target is said to be rescued if an AAV lies within a circular region of a certain radius around the target. The goal is to control the AAVs such that each target gets rescued while optimizing a certain performance objective. The algorithm design is based on the theory of partially observable Markov decision process (POMDP. In practice, POMDP problems are hard to solve exactly, so we use an approximation method called nominal belief-state optimization (NBO. We compare the performance of the NBO approach with a greedy approach.

  1. The Cognitive Dissonance between Child Rescue and Child Protection

    NARCIS (Netherlands)

    K.E. Cheney (Kristen)

    2015-01-01

    textabstract‘Saving orphans’ has become an industry that irrevocably harms children and undermines the development of child welfare systems. We must replace the drive to rescue with the desire to protect.

  2. That Others May Live: USAF Air Rescue in Korea

    National Research Council Canada - National Science Library

    Marion, Forrest L

    2004-01-01

    When the Korean War began in June 1950, the United States Air Force's Air Rescue Service was a fledgling organization possessing a variety of aircraft types, most having seen service during World War II...

  3. Water Supply Systems For Aircraft Fire And Rescue Protection

    Science.gov (United States)

    1995-01-01

    This Advisory Circular (AC) provides guidance for the selection : of a water source and standards for the design of a distribution system to : support aircraft rescue and fire fighting (ARFF) service operations on : airports.

  4. Viral membrane fusion

    International Nuclear Information System (INIS)

    Harrison, Stephen C.

    2015-01-01

    Membrane fusion is an essential step when enveloped viruses enter cells. Lipid bilayer fusion requires catalysis to overcome a high kinetic barrier; viral fusion proteins are the agents that fulfill this catalytic function. Despite a variety of molecular architectures, these proteins facilitate fusion by essentially the same generic mechanism. Stimulated by a signal associated with arrival at the cell to be infected (e.g., receptor or co-receptor binding, proton binding in an endosome), they undergo a series of conformational changes. A hydrophobic segment (a “fusion loop” or “fusion peptide”) engages the target-cell membrane and collapse of the bridging intermediate thus formed draws the two membranes (virus and cell) together. We know of three structural classes for viral fusion proteins. Structures for both pre- and postfusion conformations of illustrate the beginning and end points of a process that can be probed by single-virion measurements of fusion kinetics. - Highlights: • Viral fusion proteins overcome the high energy barrier to lipid bilayer merger. • Different molecular structures but the same catalytic mechanism. • Review describes properties of three known fusion-protein structural classes. • Single-virion fusion experiments elucidate mechanism

  5. Viral membrane fusion

    Energy Technology Data Exchange (ETDEWEB)

    Harrison, Stephen C., E-mail: harrison@crystal.harvard.edu

    2015-05-15

    Membrane fusion is an essential step when enveloped viruses enter cells. Lipid bilayer fusion requires catalysis to overcome a high kinetic barrier; viral fusion proteins are the agents that fulfill this catalytic function. Despite a variety of molecular architectures, these proteins facilitate fusion by essentially the same generic mechanism. Stimulated by a signal associated with arrival at the cell to be infected (e.g., receptor or co-receptor binding, proton binding in an endosome), they undergo a series of conformational changes. A hydrophobic segment (a “fusion loop” or “fusion peptide”) engages the target-cell membrane and collapse of the bridging intermediate thus formed draws the two membranes (virus and cell) together. We know of three structural classes for viral fusion proteins. Structures for both pre- and postfusion conformations of illustrate the beginning and end points of a process that can be probed by single-virion measurements of fusion kinetics. - Highlights: • Viral fusion proteins overcome the high energy barrier to lipid bilayer merger. • Different molecular structures but the same catalytic mechanism. • Review describes properties of three known fusion-protein structural classes. • Single-virion fusion experiments elucidate mechanism.

  6. Fusion technology 1992

    International Nuclear Information System (INIS)

    Ferro, C.; Gasparatto, M.; Knoepfel, H.

    1993-01-01

    The aim of the biennial series of symposia on the title subject, organized by the European Fusion Laboratories, is the exchange of information on the design, construction and operation of fusion experiments and on the technology being developed for the next step devices and fusion reactors. The coverage of the volume includes the technological aspects of fusion reactors in relation to new developments, this forming a guideline for the definition of future work. These proceedings comprise three volumes and contain both the invited lectures and contributed papers presented at the symposium which was attended by 569 participants from around the globe. The 343 papers, including 12 invited papers, characterize the increasing interest of industry in the fusion programme, giving a broad and current overview on the progress and trends fusion technology is experiencing now, as well as indicating the future for fusion devices

  7. Peptides in melanoma therapy.

    Science.gov (United States)

    Mocellin, Simone

    2012-01-01

    Peptides derived from tumor associated antigens can be utilized to elicit a therapeutically effective immune response against melanoma in experimental models. However, patient vaccination with peptides - although it is often followed by the induction of melanoma- specific T lymphocytes - is rarely associated with tumor response of clinical relevance. In this review I summarize the principles of peptide design as well as the results so far obtained in the clinical setting while treating cutaneous melanoma by means of this active immunotherapy strategy. I also discuss some immunological and methodological issues that might be helpful for the successful development of peptide-based vaccines.

  8. Antimicrobial Peptides in Reptiles

    Science.gov (United States)

    van Hoek, Monique L.

    2014-01-01

    Reptiles are among the oldest known amniotes and are highly diverse in their morphology and ecological niches. These animals have an evolutionarily ancient innate-immune system that is of great interest to scientists trying to identify new and useful antimicrobial peptides. Significant work in the last decade in the fields of biochemistry, proteomics and genomics has begun to reveal the complexity of reptilian antimicrobial peptides. Here, the current knowledge about antimicrobial peptides in reptiles is reviewed, with specific examples in each of the four orders: Testudines (turtles and tortosises), Sphenodontia (tuataras), Squamata (snakes and lizards), and Crocodilia (crocodilans). Examples are presented of the major classes of antimicrobial peptides expressed by reptiles including defensins, cathelicidins, liver-expressed peptides (hepcidin and LEAP-2), lysozyme, crotamine, and others. Some of these peptides have been identified and tested for their antibacterial or antiviral activity; others are only predicted as possible genes from genomic sequencing. Bioinformatic analysis of the reptile genomes is presented, revealing many predicted candidate antimicrobial peptides genes across this diverse class. The study of how these ancient creatures use antimicrobial peptides within their innate immune systems may reveal new understandings of our mammalian innate immune system and may also provide new and powerful antimicrobial peptides as scaffolds for potential therapeutic development. PMID:24918867

  9. Rescue of failed filtering blebs with ab interno trephination.

    Science.gov (United States)

    Shihadeh, Wisam A; Ritch, Robert; Liebmann, Jeffrey M

    2006-06-01

    We evaluated the effectiveness of ab interno automated trephination as a technique for rescuing failed mature filtering blebs. A retrospective chart review of 40 failed blebs of 38 patients who had a posttrephination follow-up period of at least 3 months was done. With success defined as intraocular pressure (IOP) control with other modalities of management. Complications were few. We believe that ab interno trephination is an excellent option for rescuing selected failed filtering blebs.

  10. Rescue Effects: Irradiated Cells Helped by Unirradiated Bystander Cells

    Science.gov (United States)

    Lam, R. K. K.; Fung, Y. K.; Han, W.; Yu, K. N.

    2015-01-01

    The rescue effect describes the phenomenon where irradiated cells or organisms derive benefits from the feedback signals sent from the bystander unirradiated cells or organisms. An example of the benefit is the mitigation of radiation-induced DNA damages in the irradiated cells. The rescue effect can compromise the efficacy of radioimmunotherapy (RIT) (and actually all radiotherapy). In this paper, the discovery and subsequent confirmation studies on the rescue effect were reviewed. The mechanisms and the chemical messengers responsible for the rescue effect studied to date were summarized. The rescue effect between irradiated and bystander unirradiated zebrafish embryos in vivo sharing the same medium was also described. In the discussion section, the mechanism proposed for the rescue effect involving activation of the nuclear factor κB (NF-κB) pathway was scrutinized. This mechanism could explain the promotion of cellular survival and correct repair of DNA damage, dependence on cyclic adenosine monophosphate (cAMP) and modulation of intracellular reactive oxygen species (ROS) level in irradiated cells. Exploitation of the NF-κB pathway to improve the effectiveness of RIT was proposed. Finally, the possibility of using zebrafish embryos as the model to study the efficacy of RIT in treating solid tumors was also discussed. PMID:25625514

  11. A versatile sensor network for urban search and rescue operations

    Science.gov (United States)

    Känsälä, Klaus; Korkalainen, Marko; Mäyrä, Aki

    2011-11-01

    The presentation is based in the research work carried out in EU funded project SGL for USaR (Second Generation Locator for Urban Search and Rescue Operations). The aim of this project is to develop wireless standalone communication system with embedded sensor network which can be globally used in rescue operations after accidents or terrorist attacks. The system should be able to operate without external support for several days: it should have autonomy with power supply and communication. The devices must be lightweight so that rescue team can easily carry them and finally they must be easy to install and use. The range of the wireless communication must cover an area of several square kilometers. The embedded sensor system must be able to detect sings of life but also detect hazards threatening the rescue operators thus preventing more accidents. It should also support positioning and digital mapping as well as the management of the search and rescue operation. This sensor network for urban search and rescue operations has been tested on a field conditions and it has proven to be robust and reliable and provides an energy efficient way of communication and positioning on harsh conditions.

  12. Rescuing the ischemic penumbra: Our experience

    Directory of Open Access Journals (Sweden)

    Milosavljević Tamara

    2013-12-01

    Full Text Available Objectives: Over one million strokes per year are occurring in Europe. Brain stroke is one of the most important death and disability causes in Europe and USA. The main role of perfusion is to determine the border of insult core and ischemic penumbra. Penumbra can be saved with thrombolytic therapy but core have irreversible injuries and represent death of brain cells. Aim: to determine the role of CT brain perfusion in cases of acute brain stroke and following thrombolytic therapy. Methods: We examined 64 patients with acute brain stroke who received thrombolytic therapy after that. All patients were examining on 16 MDCT with 50 ml of iodine contrast agent following the standard procedure for CT perfusion. Patients were 34 male and 30 female with middle age of 64 years. MRI was made after thrombolytic therapy and compare with perfusion results before therapy. Results: Using an artery and a vein as reference three parameters were measured - blood flow (CBF, blood volume (CBV and mean transit time (MTT, for each patient. Hemorrhagic was find in 9 (14.01% patients after thrombolytic therapy. 4 (6.25% other patients develop new stroke of same but mostly other side of brain. 8 (12.50% more patients finished lethally. From other 42 patients with thrombolytic therapy we can positively say that in 31 (48.44% patients penumbra was rescued. For other 11 (17.19% stroke was same size like firstly involved core and penumbra but not bigger. Conclusion: CT perfusion plays major role by showing a curable parts of tissue in brain strokes.

  13. Rescuing loading induced bone formation at senescence.

    Directory of Open Access Journals (Sweden)

    Sundar Srinivasan

    2010-09-01

    Full Text Available The increasing incidence of osteoporosis worldwide requires anabolic treatments that are safe, effective, and, critically, inexpensive given the prevailing overburdened health care systems. While vigorous skeletal loading is anabolic and holds promise, deficits in mechanotransduction accrued with age markedly diminish the efficacy of readily complied, exercise-based strategies to combat osteoporosis in the elderly. Our approach to explore and counteract these age-related deficits was guided by cellular signaling patterns across hierarchical scales and by the insight that cell responses initiated during transient, rare events hold potential to exert high-fidelity control over temporally and spatially distant tissue adaptation. Here, we present an agent-based model of real-time Ca(2+/NFAT signaling amongst bone cells that fully described periosteal bone formation induced by a wide variety of loading stimuli in young and aged animals. The model predicted age-related pathway alterations underlying the diminished bone formation at senescence, and hence identified critical deficits that were promising targets for therapy. Based upon model predictions, we implemented an in vivo intervention and show for the first time that supplementing mechanical stimuli with low-dose Cyclosporin A can completely rescue loading induced bone formation in the senescent skeleton. These pre-clinical data provide the rationale to consider this approved pharmaceutical alongside mild physical exercise as an inexpensive, yet potent therapy to augment bone mass in the elderly. Our analyses suggested that real-time cellular signaling strongly influences downstream bone adaptation to mechanical stimuli, and quantification of these otherwise inaccessible, transient events in silico yielded a novel intervention with clinical potential.

  14. 46 CFR 199.175 - Survival craft and rescue boat equipment.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Survival craft and rescue boat equipment. 199.175....175 Survival craft and rescue boat equipment. (a) All lifeboat and rescue boat equipment— (1) Must be... craft or rescue boat; or (iii) Overload the launching appliance. (b) Each lifeboat, rigid liferaft, and...

  15. 30 CFR 49.7 - Physical requirements for mine rescue team.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Physical requirements for mine rescue team. 49... EDUCATION AND TRAINING MINE RESCUE TEAMS § 49.7 Physical requirements for mine rescue team. (a) Each member of a mine rescue team shall be examined annually by a physician who shall certify that each person is...

  16. Insulin C-peptide test

    Science.gov (United States)

    C-peptide ... the test depends on the reason for the C-peptide measurement. Ask your health care provider if ... C-peptide is measured to tell the difference between insulin the body produces and insulin someone injects ...

  17. Economics of fusion research

    International Nuclear Information System (INIS)

    1977-01-01

    This report provides the results of a study of methods of economic analysis applied to the evaluation of fusion research. The study recognizes that a hierarchy of economic analyses of research programs exists: standard benefit-cost analysis, expected value of R and D information, and expected utility analysis. It is shown that standard benefit-cost analysis, as commonly applied to research programs, is inadequate for the evaluation of a high technology research effort such as fusion research. A methodology for performing an expected value analysis is developed and demonstrated and an overview of an approach to perform an expected utility analysis of fusion research is presented. In addition, a potential benefit of fusion research, not previously identified, is discussed and rough estimates of its magnitude are presented. This benefit deals with the effect of a fusion research program on optimal fossil fuel consumption patterns. The results of this study indicate that it is both appropriate and possible to perform an expected value analysis of fusion research in order to assess the economics of a fusion research program. The results indicate further that the major area of benefits of fusion research is likely due to the impact of a fusion research program on optimal fossil fuel consumption patterns and it is recommended that this benefit be included in future assessments of fusion research economics

  18. Economics of fusion research

    Energy Technology Data Exchange (ETDEWEB)

    None, None

    1977-10-15

    This report provides the results of a study of methods of economic analysis applied to the evaluation of fusion research. The study recognizes that a hierarchy of economic analyses of research programs exists: standard benefit-cost analysis, expected value of R and D information, and expected utility analysis. It is shown that standard benefit-cost analysis, as commonly applied to research programs, is inadequate for the evaluation of a high technology research effort such as fusion research. A methodology for performing an expected value analysis is developed and demonstrated and an overview of an approach to perform an expected utility analysis of fusion research is presented. In addition, a potential benefit of fusion research, not previously identified, is discussed and rough estimates of its magnitude are presented. This benefit deals with the effect of a fusion research program on optimal fossil fuel consumption patterns. The results of this study indicate that it is both appropriate and possible to perform an expected value analysis of fusion research in order to assess the economics of a fusion research program. The results indicate further that the major area of benefits of fusion research is likely due to the impact of a fusion research program on optimal fossil fuel consumption patterns and it is recommended that this benefit be included in future assessments of fusion research economics.

  19. Peptide Vaccines for Leishmaniasis

    Directory of Open Access Journals (Sweden)

    Rory C. F. De Brito

    2018-05-01

    Full Text Available Due to an increase in the incidence of leishmaniases worldwide, the development of new strategies such as prophylactic vaccines to prevent infection and decrease the disease have become a high priority. Classic vaccines against leishmaniases were based on live or attenuated parasites or their subunits. Nevertheless, the use of whole parasite or their subunits for vaccine production has numerous disadvantages. Therefore, the use of Leishmania peptides to design more specific vaccines against leishmaniases seems promising. Moreover, peptides have several benefits in comparison with other kinds of antigens, for instance, good stability, absence of potentially damaging materials, antigen low complexity, and low-cost to scale up. By contrast, peptides are poor immunogenic alone, and they need to be delivered correctly. In this context, several approaches described in this review are useful to solve these drawbacks. Approaches, such as, peptides in combination with potent adjuvants, cellular vaccinations, adenovirus, polyepitopes, or DNA vaccines have been used to develop peptide-based vaccines. Recent advancements in peptide vaccine design, chimeric, or polypeptide vaccines and nanovaccines based on particles attached or formulated with antigenic components or peptides have been increasingly employed to drive a specific immune response. In this review, we briefly summarize the old, current, and future stands on peptide-based vaccines, describing the disadvantages and benefits associated with them. We also propose possible approaches to overcome the related weaknesses of synthetic vaccines and suggest future guidelines for their development.

  20. Peptide Vaccines for Leishmaniasis.

    Science.gov (United States)

    De Brito, Rory C F; Cardoso, Jamille M De O; Reis, Levi E S; Vieira, Joao F; Mathias, Fernando A S; Roatt, Bruno M; Aguiar-Soares, Rodrigo Dian D O; Ruiz, Jeronimo C; Resende, Daniela de M; Reis, Alexandre B

    2018-01-01

    Due to an increase in the incidence of leishmaniases worldwide, the development of new strategies such as prophylactic vaccines to prevent infection and decrease the disease have become a high priority. Classic vaccines against leishmaniases were based on live or attenuated parasites or their subunits. Nevertheless, the use of whole parasite or their subunits for vaccine production has numerous disadvantages. Therefore, the use of Leishmania peptides to design more specific vaccines against leishmaniases seems promising. Moreover, peptides have several benefits in comparison with other kinds of antigens, for instance, good stability, absence of potentially damaging materials, antigen low complexity, and low-cost to scale up. By contrast, peptides are poor immunogenic alone, and they need to be delivered correctly. In this context, several approaches described in this review are useful to solve these drawbacks. Approaches, such as, peptides in combination with potent adjuvants, cellular vaccinations, adenovirus, polyepitopes, or DNA vaccines have been used to develop peptide-based vaccines. Recent advancements in peptide vaccine design, chimeric, or polypeptide vaccines and nanovaccines based on particles attached or formulated with antigenic components or peptides have been increasingly employed to drive a specific immune response. In this review, we briefly summarize the old, current, and future stands on peptide-based vaccines, describing the disadvantages and benefits associated with them. We also propose possible approaches to overcome the related weaknesses of synthetic vaccines and suggest future guidelines for their development.

  1. Peptide Nucleic Acids

    DEFF Research Database (Denmark)

    2004-01-01

    A novel class of compounds known as peptide nucleic acids, bind complementary DNA and RNA strands, and generally do so more strongly than the corresponding DNA or RNA strands while exhibiting increased sequence specificity and solubility. The peptide nucleic acids comprise ligands selected from...

  2. Fusion of protegrin-1 and plectasin to MAP30 shows significant inhibition activity against dengue virus replication.

    Directory of Open Access Journals (Sweden)

    Hussin A Rothan

    Full Text Available Dengue virus (DENV broadly disseminates in tropical and sub-tropical countries and there are no vaccine or anti-dengue drugs available. DENV outbreaks cause serious economic burden due to infection complications that requires special medical care and hospitalization. This study presents a new strategy for inexpensive production of anti-DENV peptide-fusion protein to prevent and/or treat DENV infection. Antiviral cationic peptides protegrin-1 (PG1 and plectasin (PLSN were fused with MAP30 protein to produce recombinant antiviral peptide-fusion protein (PG1-MAP30-PLSN as inclusion bodies in E. coli. High yield production of PG1-MAP30-PLSN protein was achieved by solubilization of inclusion bodies in alkaline buffer followed by the application of appropriate refolding techniques. Antiviral PG1-MAP30-PLSN protein considerably inhibited DENV protease (NS2B-NS3pro with half-maximal inhibitory concentration (IC50 0.5±0.1 μM. The real-time proliferation assay (RTCA and the end-point proliferation assay (MTT assay showed that the maximal-nontoxic dose of the peptide-fusion protein against Vero cells is approximately 0.67±0.2 μM. The cell-based assays showed considerable inhibition of the peptide-fusion protein against binding and proliferating stages of DENV2 into the target cells. The peptide-fusion protein protected DENV2-challeged mice with 100% of survival at the dose of 50 mg/kg. In conclusion, producing recombinant antiviral peptide-fusion protein by combining short antiviral peptide with a central protein owning similar activity could be useful to minimize the overall cost of short peptide production and take advantage of its synergistic antiviral activities.

  3. Recycling fusion materials

    International Nuclear Information System (INIS)

    Ooms, L.

    2005-01-01

    The inherent safety and environmental advantages of fusion power in comparison with other energy sources play an important role in the public acceptance. No waste burden for future generations is therefore one of the main arguments to decide for fusion power. The waste issue has thus been studied in several documents and the final conclusion of which it is stated that there is no permanent disposal waste needed if recycling is applied. But recycling of fusion reactor materials is far to be obvious regarding mostly the very high specific activity of the materials to be handled, the types of materials and the presence of tritium. The main objective of research performed by SCK-CEN is to study the possible ways of recycling fusion materials and analyse the challenges of the materials management from fusion reactors, based on current practices used in fission reactors and the requirements for the manufacture of fusion equipment

  4. The controlled thermonuclear fusion

    International Nuclear Information System (INIS)

    Barre, Bertrand

    2014-01-01

    After some generalities on particle physics, and on fusion and fission reactions, the author outlines that the fission reaction is easier to obtain than the fusion reaction, evokes the fusion which takes place in stars, and outlines the difficulty to manage and control this reaction: one of its application is the H bomb. The challenge is therefore to find a way to control this reaction and make it a steady and continuous source of energy. The author then presents the most promising way: the magnetic confinement fusion. He evokes its main issues, the already performed experiments (tokamak), and gives a larger presentation of the ITER project. Then, he evokes another way, the inertial confinement fusion, and the two main experimental installations (National Ignition Facility in Livermore, and the Laser Megajoule in Bordeaux). Finally, he gives a list of benefits and drawbacks of an industrial nuclear fusion

  5. Laser fusion overview

    International Nuclear Information System (INIS)

    Nuckolls, J.

    1976-01-01

    Because of recent breakthroughs in the target area, and in the glass laser area, the scientific feasibility of laser fusion--and of inertial fusion--may be demonstrated in the early 1980's. Then the development in that time period of a suitable laser (or storage ring or other driving source) would make possible an operational inertial fusion reactor in this century. These are roughly the same time scales as projected by the Tokamak magnetic confinement approach. It thus appears that the 15-20 year earlier start by magnetic confinement fusion may be overcome. Because inertial confinement has been demonstrated, and inertial fusion reactors may operate on smaller scales than Tokamaks, laser fusion may have important technical and economic advantages

  6. Synthetic fuels and fusion

    Energy Technology Data Exchange (ETDEWEB)

    Fillo, J A; Powell, J; Steinberg, M [Brookhaven National Lab., Upton, NY (USA)

    1981-03-01

    The decreasing availability of fossil fuels emphasizes the need to develop systems which will produce synthetic fuel to substitute for and supplement the natural supply. An important first step in the synthesis of liquid and gaseous fuels is the production of hydrogen. Thermonuclear fusion offers an inexhaustible source of energy for the production of hydrogen from water. Depending on design, electric generation efficiencies of approx. equal to 40-60% and hydrogen production efficiencies by high temperature electrolysis of approx. equal to 50-70% are projected for fusion reactors using high temperature blankets. Fusion/coal symbiotic systems appear economically promising for the first generation of commercial fusion synfuels plants. Coal production requirements and the environmental effects of large-scale coal usage would be greatly reduced by a fusion/coal system. In the long-term, there could be a gradual transition to an inexhaustible energy system based solely on fusion.

  7. Magnetic-fusion program

    International Nuclear Information System (INIS)

    1980-08-01

    In February 1980, the Director of Energy Research requested that the Energy Research Advisory Board (ERAB) review the Department of Energy (DOE) Magnetic Fusion Program. Of particular concern to the DOE was the judicious choice of the next major steps toward demonstration of economic power production from fusion. Of equal concern was the overall soundness of the DOE Magnetic Fusion Program: its pace, scope, and funding profiles. Their finding and recommendations are included

  8. Magnetic fusion technology

    CERN Document Server

    Dolan, Thomas J

    2014-01-01

    Magnetic Fusion Technology describes the technologies that are required for successful development of nuclear fusion power plants using strong magnetic fields. These technologies include: ? magnet systems, ? plasma heating systems, ? control systems, ? energy conversion systems, ? advanced materials development, ? vacuum systems, ? cryogenic systems, ? plasma diagnostics, ? safety systems, and ? power plant design studies. Magnetic Fusion Technology will be useful to students and to specialists working in energy research.

  9. Status of fusion maintenance

    International Nuclear Information System (INIS)

    Fuller, G.M.

    1984-01-01

    Effective maintenance will be an essential ingredient in determining fusion system productivity. This level of productivity will result only after close attention is paid to the entire system as an entity and appropriate integration of the elements is made. The status of fusion maintenance is reviewed in the context of the entire system. While there are many challenging developmental tasks ahead in fusion maintenance, the required technologies are available in several high-technology industries, including nuclear fission

  10. Fusion facility siting considerations

    International Nuclear Information System (INIS)

    Bussell, G.T.

    1985-01-01

    Inherent in the fusion program's transition from hydrogen devices to commercial power machines is a general increase in the size and scope of succeeding projects. This growth will lead to increased emphasis on safety, environmental impact, and the external effects of fusion in general, and of each new device in particular. A critically important consideration in this regard is site selection. The purpose of this paper is to examine major siting issues that may affect the economics, safety, and environmental impact of fusion

  11. Fusion research principles

    CERN Document Server

    Dolan, Thomas James

    2013-01-01

    Fusion Research, Volume I: Principles provides a general description of the methods and problems of fusion research. The book contains three main parts: Principles, Experiments, and Technology. The Principles part describes the conditions necessary for a fusion reaction, as well as the fundamentals of plasma confinement, heating, and diagnostics. The Experiments part details about forty plasma confinement schemes and experiments. The last part explores various engineering problems associated with reactor design, vacuum and magnet systems, materials, plasma purity, fueling, blankets, neutronics

  12. Nuclear fusion power

    International Nuclear Information System (INIS)

    Dinghee, D.A.

    1983-01-01

    In this chapter, fusion is compared with other inexhaustible energy sources. Research is currently being conducted both within and outside the USA. The current confinement principles of thermonuclear reactions are reveiwed with the discussion of economics mainly focusing on the magnetic confinement concepts. Environmental, health and safety factors are of great concern to the public and measures are being taken to address them. The magnetic fusion program logic and the inertial fusion program logic are compared

  13. Inertial confinement fusion (ICF)

    International Nuclear Information System (INIS)

    Nuckolls, J.

    1977-01-01

    The principal goal of the inertial confinement fusion program is the development of a practical fusion power plant in this century. Rapid progress has been made in the four major areas of ICF--targets, drivers, fusion experiments, and reactors. High gain targets have been designed. Laser, electron beam, and heavy ion accelerator drivers appear to be feasible. Record-breaking thermonuclear conditions have been experimentally achieved. Detailed diagnostics of laser implosions have confirmed predictions of the LASNEX computer program. Experimental facilities are being planned and constructed capable of igniting high gain fusion microexplosions in the mid 1980's. A low cost long lifetime reactor design has been developed

  14. Inertial fusion energy

    International Nuclear Information System (INIS)

    Decroisette, M.; Andre, M.; Bayer, C.; Juraszek, D.; Le Garrec, B.; Deutsch, C.; Migus, A.

    2005-01-01

    We first recall the scientific basis of inertial fusion and then describe a generic fusion reactor with the different components: the driver, the fusion chamber, the material treatment unit, the target factory and the turbines. We analyse the options proposed at the present time for the driver and for target irradiation scheme giving the state of art for each approach. We conclude by the presentation of LMJ (laser Megajoule) and NIF (national ignition facility) projects. These facilities aim to demonstrate the feasibility of laboratory DT ignition, first step toward Inertial Fusion Energy. (authors)

  15. Laser fusion program overview

    International Nuclear Information System (INIS)

    Emmett, J.L.

    1977-01-01

    This program is structured to proceed through a series of well defined fusion milestones to proof of the scientific feasibility, of laser fusion with the Shiva Nova system. Concurrently, those key technical areas, such as advanced lasers, which are required to progress beyond proof of feasibility, are being studied. We have identified and quantified the opportunities and key technical issues in military applications, such as weapons effects simulations, and in civilian applications, such as central-station electric power production. We summarize the current status and future plans for the laser fusion program at LLL, emphasizing the civilian applications of laser fusion

  16. Frontiers in fusion research

    CERN Document Server

    Kikuchi, Mitsuru

    2011-01-01

    Frontiers in Fusion Research provides a systematic overview of the latest physical principles of fusion and plasma confinement. It is primarily devoted to the principle of magnetic plasma confinement, that has been systematized through 50 years of fusion research. Frontiers in Fusion Research begins with an introduction to the study of plasma, discussing the astronomical birth of hydrogen energy and the beginnings of human attempts to harness the Sun's energy for use on Earth. It moves on to chapters that cover a variety of topics such as: * charged particle motion, * plasma kinetic theory, *

  17. Fusion of Nonionic Vesicles

    DEFF Research Database (Denmark)

    Bulut, Sanja; Oskolkova, M. Z.; Schweins, R.

    2010-01-01

    We present an experimental study of vesicle fusion using light and neutron scattering to monitor fusion events. Vesicles are reproducibly formed with an extrusion procedure using an single amphiphile triethylene glycol mono-n-decyl ether in water. They show long-term stability for temperatures ar...... a barrier to fusion changing from 15 k(B)T at T = 26 degrees C to 10k(H) T at T = 35 degrees C. These results are compatible with the theoretical predictions using the stalk model of vesicle fusion....

  18. Fusion reactor safety

    International Nuclear Information System (INIS)

    1987-12-01

    Nuclear fusion could soon become a viable energy source. Work in plasma physics, fusion technology and fusion safety is progressing rapidly in a number of Member States and international collaboration continues on work aiming at the demonstration of fusion power generation. Safety of fusion reactors and technological and radiological aspects of waste management are important aspects in the development and design of fusion machines. In order to provide an international forum to review and discuss the status and the progress made since 1983 in programmes related to operational safety aspects of fusion reactors, their waste management and decommissioning concepts, the IAEA had organized the Technical Committee on ''Fusion Reactor Safety'' in Culham, 3-7 November 1986. All presentations of this meeting were divided into four sessions: 1. Statements on National-International Fusion Safety Programmes (5 papers); 2. Operation and System Safety (15 papers); 3. Waste Management and Decommissioning (5 papers); 4. Environmental Impacts (6 papers). A separate abstract was prepared for each of these 31 papers. Refs, figs, tabs

  19. Magnetic fusion reactor economics

    International Nuclear Information System (INIS)

    Krakowski, R.A.

    1995-01-01

    An almost primordial trend in the conversion and use of energy is an increased complexity and cost of conversion systems designed to utilize cheaper and more-abundant fuels; this trend is exemplified by the progression fossil fission → fusion. The present projections of the latter indicate that capital costs of the fusion ''burner'' far exceed any commensurate savings associated with the cheapest and most-abundant of fuels. These projections suggest competitive fusion power only if internal costs associate with the use of fossil or fission fuels emerge to make them either uneconomic, unacceptable, or both with respect to expensive fusion systems. This ''implementation-by-default'' plan for fusion is re-examined by identifying in general terms fusion power-plant embodiments that might compete favorably under conditions where internal costs (both economic and environmental) of fossil and/or fission are not as great as is needed to justify the contemporary vision for fusion power. Competitive fusion power in this context will require a significant broadening of an overly focused program to explore the physics and simbiotic technologies leading to more compact, simplified, and efficient plasma-confinement configurations that reside at the heart of an attractive fusion power plant

  20. The Multifaceted Role of SNARE Proteins in Membrane Fusion.

    Science.gov (United States)

    Han, Jing; Pluhackova, Kristyna; Böckmann, Rainer A

    2017-01-01

    Membrane fusion is a key process in all living organisms that contributes to a variety of biological processes including viral infection, cell fertilization, as well as intracellular transport, and neurotransmitter release. In particular, the various membrane-enclosed compartments in eukaryotic cells need to exchange their contents and communicate across membranes. Efficient and controllable fusion of biological membranes is known to be driven by cooperative action of SNARE proteins, which constitute the central components of the eukaryotic fusion machinery responsible for fusion of synaptic vesicles with the plasma membrane. During exocytosis, vesicle-associated v-SNARE (synaptobrevin) and target cell-associated t-SNAREs (syntaxin and SNAP-25) assemble into a core trans-SNARE complex. This complex plays a versatile role at various stages of exocytosis ranging from the priming to fusion pore formation and expansion, finally resulting in the release or exchange of the vesicle content. This review summarizes current knowledge on the intricate molecular mechanisms underlying exocytosis triggered and catalyzed by SNARE proteins. Particular attention is given to the function of the peptidic SNARE membrane anchors and the role of SNARE-lipid interactions in fusion. Moreover, the regulatory mechanisms by synaptic auxiliary proteins in SNARE-driven membrane fusion are briefly outlined.

  1. Burnout syndrome in nurses of prehospital rescue team

    Directory of Open Access Journals (Sweden)

    Rosemeire Pereira Bezerra

    2009-09-01

    Full Text Available Objective: To verify the presence and evaluate the levels of burnout syndrome in nurses of the prehospital rescue team. Methods: A cross-sectional study with a sample of 17 nurses from the prehospital rescue team, by application of the Maslach burnout Inventory and a questionnaire prepared by the authors. Rresults: In the group studied, 76% of the nurses of the prehospital rescue team were female. Ages varied from 30 to 49 years old. As to time already in the profession, 59% reported having worked from five to ten years in prehospital rescue. As to Maslach burnout Inventory subscale means, in the group analyzed of 17 prehospital rescue team nurses, low/moderate level (31.53 of reduced professional accomplishment, low/moderate level (18.41 of emotional exhaustion, and low/moderate level (8.88 of depersonalization were observed. As to dimensions of burnout levels, it was noted that 76.47% of the nurses displayed a low/moderate level of emotional exhaustion, depersonalization, and reduced professional accomplishment. Cconclusions: It was demonstrated that this sample showed no evidence of burnout syndrome, since its presence is proven only when there are high scores of emotional exhaustion, depersonalization, and reduced professional accomplishment.

  2. Development of a Mine Rescue Drilling System (MRDS)

    Energy Technology Data Exchange (ETDEWEB)

    Raymond, David W. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Gaither, Katherine N. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Polsky, Yarom [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Knudsen, Steven D. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Broome, Scott Thomas [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Su, Jiann-Cherng [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Blankenship, Douglas A. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Costin, Laurence S. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2014-06-01

    Sandia National Laboratories (Sandia) has a long history in developing compact, mobile, very high-speed drilling systems and this technology could be applied to increasing the rate at which boreholes are drilled during a mine accident response. The present study reviews current technical approaches, primarily based on technology developed under other programs, analyzes mine rescue specific requirements to develop a conceptual mine rescue drilling approach, and finally, proposes development of a phased mine rescue drilling system (MRDS) that accomplishes (1) development of rapid drilling MRDS equipment; (2) structuring improved web communication through the Mine Safety & Health Administration (MSHA) web site; (3) development of an improved protocol for employment of existing drilling technology in emergencies; (4) deployment of advanced technologies to complement mine rescue drilling operations during emergency events; and (5) preliminary discussion of potential future technology development of specialized MRDS equipment. This phased approach allows for rapid fielding of a basic system for improved rescue drilling, with the ability to improve the system over time at a reasonable cost.

  3. Strategies to improve sleep during extended search and rescue operations.

    Science.gov (United States)

    Jenkins, Jennifer Lee; Fredericksen, Kim; Stone, Roger; Tang, Nelson

    2007-01-01

    This study investigated strategies to improve sleeping conditions during search and rescue operations during disaster response. Forty members of the Montgomery County (Maryland) Urban Search and Rescue Team were surveyed for individual sleep habits and sleeping aids used during extended deployments. Team members were also asked to suggest methods to improve sleep on future deployments. The average amount of sleep during field operations was 5.4 hours with a range of 4-8 hours. Eight percent surveyed would prefer another schedule besides the 12-hour work day, all of whom proposed three 8-hour shifts. Fifteen percent of participants were interested in a pharmacological sleeping aid. Fifty percent of search and rescue members interviewed would consider using nonpharmacological sleeping aids. Furthermore, 40% of participants stated they had successfully devised self-employed methods of sleep aids for previous deployments, such as ear plugs, massage, mental imagery, personal routines, music and headphones, reading, and blindfolds. This study suggests that availability of both pharmacological and nonpharmacological sleeping aids to search and rescue workers via the team cache could impact the quantity of sleep. Further investigation into methods of optimizing sleep during field missions could theoretically show enhanced performance through various aspects of missions including mitigation of errors, improved productivity, and improved overall physiological and emotional well-being of search and rescue personnel.

  4. Incomplete fusion studies

    International Nuclear Information System (INIS)

    Singh, B.P.

    2011-01-01

    In order to study the incomplete fusion reaction dynamics at energies ≅ 4-7 MeV/nucleon, several experiments have been carried out using accelerator facilities available in India. The measurements presented here cover a wide range of projectile-target combinations and enhance significantly our knowledge about incomplete fusion reaction dynamics. Here, the three sets of measurements have been presented; (i) excitation functions, (ii) forward recoil range distributions and (iii) the spin distributions. The first evidence of these reactions has been obtained from the measurement and analysis of excitation functions for xn/αxn/2αxn-channels. The measured excitation functions have been analyzed within the framework of compound nucleus model. The results obtained indicate the occurrence of fusion incompleteness at low beam energies. However, in order to determine the relative contribution of complete and incomplete fusion reaction processes, the recoil range distributions of the heavy residues have also been measured and analyzed within the framework of breakup fusion model which confirmed the fusion incompleteness in several heavy ion reactions involving α-emitting reaction channels. Further, in order to study the role of l-values in these reactions the spin distributions of the residues populated in case of complete and incomplete channels have been measured and are found to be distinctly different. The analysis of the data on spin distribution measurements indicate that the mean values of driving input angular momenta associated with direct-α-emitting (incomplete fusion) channels are higher than that observed for fusion-evaporation xn or α-emitting (complete fusion) channels, and is found to increase with direct α-multiplicity in the forward cone. One of the important conclusions drawn in the present work is that, there is significant incomplete fusion contribution even at energies slightly above the barrier. Further, the projectile structure has been found to

  5. An unmanned search and rescue mission

    Science.gov (United States)

    Novaro Mascarello, Laura; Quagliotti, Fulvia; Bertini, Mario

    2016-04-01

    The Remotely Piloted Aircraft Systems (RPAS) are becoming more and more powerful and innovative and they have an increased interest in civil applications, in particular, after natural hazard phenomena. The RPAS is useful in search and rescue missions in high mountain where scenarios are unfriendly and the use of helicopters is often not profitable. First, the unmanned configuration is safer because there is no hazards for human life that is not on board. Moreover, it is cheaper due to the use of electric propulsion instead of internal combustion engine and to its small dimensions and weights. Finally, the use of the RPAS is faster while the helicopter is often not available because is involved in other missions or it cannot be used if the search mission is in impervious scenario, such as forests with thick vegetation. For instance, the RPAS can be used after an avalanche when victims have little time to be saved before the death by hypothermia. In most conditions, the body maintains a healthy temperature. However, if it is exposed to cold temperatures, especially with a high cooling factor from wind and high humidity, for extended periods, the control mechanisms of the body may not be able to maintain a normal body temperature. When you lose more heat than the body can generate, it takes over hypothermia, defined as a body temperature below 35° C. Wet clothing, fall into cold water or not adequately cover themselves during the cold season, are all factors that can increase the chances of hypothermia. Signs and symptoms (tremor, slurred speech, breathing abnormally slow, cold and pale skin, loss of coordination, fatigue, lethargy or apathy, confusion or memory loss) usually develop slowly. People with hypothermia typically experience a gradual loss of mental acuity and physical capacity, and realize that you have need of emergency medical care. For these reasons, the use of an RPAS could be crucial for the survival of disappeared people in high mountain. In

  6. Mirror fusion--fission hybrids

    International Nuclear Information System (INIS)

    Lee, J.D.

    1978-01-01

    The fusion-fission concept and the mirror fusion-fission hybrid program are outlined. Magnetic mirror fusion drivers and blankets for hybrid reactors are discussed. Results of system analyses are presented and a reference design is described

  7. Circulatory CNP Rescues Craniofacial Hypoplasia in Achondroplasia.

    Science.gov (United States)

    Yamanaka, S; Nakao, Kazumasa; Koyama, N; Isobe, Y; Ueda, Y; Kanai, Y; Kondo, E; Fujii, T; Miura, M; Yasoda, A; Nakao, Kazuwa; Bessho, K

    2017-12-01

    Achondroplasia is the most common genetic form of human dwarfism, characterized by midfacial hypoplasia resulting in occlusal abnormality and foramen magnum stenosis, leading to serious neurologic complications and hydrocephalus. Currently, surgery is the only way to manage jaw deformity, neurologic complications, and hydrocephalus in patients with achondroplasia. We previously showed that C-type natriuretic peptide (CNP) is a potent stimulator of endochondral bone growth of long bones and vertebrae and is also a potent stimulator in the craniofacial region, which is crucial for midfacial skeletogenesis. In this study, we analyzed craniofacial morphology in a mouse model of achondroplasia, in which fibroblast growth factor receptor 3 (FGFR3) is specifically activated in cartilage ( Fgfr3 ach mice), and investigated the mechanisms of jaw deformities caused by this mutation. Furthermore, we analyzed the effect of CNP on the maxillofacial area in these animals. Fgfr3 ach mice exhibited midfacial hypoplasia, especially in the sagittal direction, caused by impaired endochondral ossification in craniofacial cartilage and by premature closure of the spheno-occipital synchondrosis, an important growth center in craniomaxillofacial skeletogenesis. We crossed Fgfr3 ach mice with transgenic mice in which CNP is expressed in the liver under the control of the human serum amyloid-P component promoter, resulting in elevated levels of circulatory CNP ( Fgfr3 ach /SAP-Nppc-Tg mice). In the progeny, midfacial hypoplasia in the sagittal direction observed in Fgfr3 ach mice was improved significantly by restoring the thickness of synchondrosis and promoting proliferation of chondrocytes in the craniofacial cartilage. In addition, the foramen magnum stenosis observed in Fgfr3 ach mice was significantly ameliorated in Fgfr3 ach /SAP-Nppc-Tg mice due to enhanced endochondral bone growth of the anterior intraoccipital synchondrosis. These results clearly demonstrate the therapeutic

  8. Cell fusion and nuclear fusion in plants.

    Science.gov (United States)

    Maruyama, Daisuke; Ohtsu, Mina; Higashiyama, Tetsuya

    2016-12-01

    Eukaryotic cells are surrounded by a plasma membrane and have a large nucleus containing the genomic DNA, which is enclosed by a nuclear envelope consisting of the outer and inner nuclear membranes. Although these membranes maintain the identity of cells, they sometimes fuse to each other, such as to produce a zygote during sexual reproduction or to give rise to other characteristically polyploid tissues. Recent studies have demonstrated that the mechanisms of plasma membrane or nuclear membrane fusion in plants are shared to some extent with those of yeasts and animals, despite the unique features of plant cells including thick cell walls and intercellular connections. Here, we summarize the key factors in the fusion of these membranes during plant reproduction, and also focus on "non-gametic cell fusion," which was thought to be rare in plant tissue, in which each cell is separated by a cell wall. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Genetic Information, the Principle of Rescue, and Special Obligations.

    Science.gov (United States)

    Liao, S Matthew; Mackenzie, Jordan

    2018-05-01

    In "Genetic Privacy, Disease Prevention, and the Principle of Rescue," Madison Kilbride argues that patients have a duty to warn biological family members about clinically actionable adverse genetic findings. The duty does not stem from the special obligations that we may have to family members, she argues, but rather follows from the principle of rescue, which she understands as the idea that one ought to prevent, reduce, or mitigate the risk of harm to another person when the expected harm is serious and the cost or risk to oneself is sufficiently moderate. We doubt, however, whether the principle of rescue can ground a duty to warn in the cases Kilbride envisages, and we suggest that Kilbride may have underappreciated the role that special obligations could play in generating a duty to warn family members. © 2018 The Hastings Center.

  10. Design and implementation of fishery rescue data mart system

    Science.gov (United States)

    Pan, Jun; Huang, Haiguang; Liu, Yousong

    A novel data mart based system for fishery rescue field was designed and implemented. The system runs ETL process to deal with original data from various databases and data warehouses, and then reorganized the data into the fishery rescue data mart. Next, online analytical processing (OLAP) are carried out and statistical reports are generated automatically. Particularly, quick configuration schemes are designed to configure query dimensions and OLAP data sets. The configuration file will be transformed into statistic interfaces automatically through a wizard-style process. The system provides various forms of reporting files, including crystal reports, flash graphical reports, and two-dimensional data grids. In addition, a wizard style interface was designed to guide users customizing inquiry processes, making it possible for nontechnical staffs to access customized reports. Characterized by quick configuration, safeness and flexibility, the system has been successfully applied in city fishery rescue department.

  11. Rescue US: Birth, Django, and the Violence of Racial Redemption

    Directory of Open Access Journals (Sweden)

    Joseph Winters

    2018-01-01

    Full Text Available In this article, I show how the relationship between race, violence, and redemption is articulated and visualized through film. By juxtaposing DW Griffith’s The Birth of a Nation and Quentin Tarantino’s Django Unchained, I contend that the latter inverts the logic of the former. While Birth sacrifices black bodies and explains away anti-black violence for the sake of restoring white sovereignty (or rescuing the nation from threatening forms of blackness, Django adopts a rescue narrative in order to show the excessive violence that structured slavery and the emergence of the nation-state. As an immanent break within the rescue narrative, Tarantino’s film works to “rescue” images and sounds of anguish from forgetful versions of history.

  12. Diversity-oriented peptide stapling

    DEFF Research Database (Denmark)

    Tran, Thu Phuong; Larsen, Christian Ørnbøl; Røndbjerg, Tobias

    2017-01-01

    as a powerful method for peptide stapling. However, to date CuAAC stapling has not provided a simple method for obtaining peptides that are easily diversified further. In the present study, we report a new diversity-oriented peptide stapling (DOPS) methodology based on CuAAC chemistry. Stapling of peptides...

  13. The fusion reactor

    International Nuclear Information System (INIS)

    Brennan, M.H.

    1974-01-01

    Basic principles of the fusion reactor are outlined. Plasma heating and confinement schemes are described. These confinement systems include the linear Z pinch, magnetic mirrors and Tokamaks. A fusion reactor is described and a discussion is given of its environmental impact and its fuel situation. (R.L.)

  14. Fusion Canada issue 8

    International Nuclear Information System (INIS)

    1989-08-01

    A short bulletin from the National Fusion Program. Included in this issue are Canada-ITER contributions, NET Fuel Processing Loop, Bilateral Meeting for Canada-Europe, report from Tokamak de Varennes and a report from the University of Toronto on materials research for Fusion Reactors. 3 figs

  15. Fusion Canada issue 15

    International Nuclear Information System (INIS)

    1991-10-01

    A short bulletin from the National Fusion Program. Included in this issue is a report on the 1996 IAEA Fusion Conference site, operations at the Tokamak de Varennes including divertor pumping of impurities and pumping of carbon monoxide and methane, a discussion of the CFFTP and it's role. 1 fig

  16. Energy by nuclear fusion

    International Nuclear Information System (INIS)

    Buende, R.; Daenner, W.; Herold, H.; Raeder, J.

    1976-12-01

    This report reviews the state of knowledge in a number of fields of fusion research up to autumn 1976. Section 1 gives a very brief presentation of the elementary fusion reactions, the energies delivered by them and the most basic energy balances leading to Lawson-type diagrams. Section 2 outlines the reserves and cost of lithium and deuterium, gives estimates of the total energy available from DT fusion and comments on production technology, availlability and handling of the fuels. In section 3 a survey is given of the different concepts of magnetic confinement (stellarators, tokamaks, toroidal pinches, mirror machines, two-component plasmas), of confinement by walls, gas blankets and imploding liners and, finally, of the concepts of interial confinement (laser fusion, beam fusion). The reactors designed or outlined on the basis of the tokamak, high-β, mirror, and laser fusion concepts are presented in section 4, which is followed in section 5 by a discussion of the key problems of fusion power plants. The present-day knowledge of the cost structure of fusion power plants and the sensitivity of this structure with respect to the physical and technical assumptions made is analysed in section 6. Section 7 and 8 treat the aspects of safety and environment. The problems discussed include the hazard potentials of different designs (radiological, toxicological, and with respect to stored energies), release of radioactivity, possible kinds of malfunctioning, and the environmental impact of waste heat, radiation and radioactive waste (orig.) [de

  17. Fusion helps diversification

    NARCIS (Netherlands)

    Liang, S.; Ren, Z.; de Rijke, M.

    2014-01-01

    A popular strategy for search result diversification is to first retrieve a set of documents utilizing a standard retrieval method and then rerank the results. We adopt a different perspective on the problem, based on data fusion. Starting from the hypothesis that data fusion can improve performance

  18. Fusion Canada issue 22

    International Nuclear Information System (INIS)

    1993-10-01

    A short bulletin from the National Fusion Program highlighting in this issue a bi-lateral meeting between Canada and Japan, water and hydrogen detritiation, in-situ tokamak surface analysis, an update of CCFM/TdeV and tritium accounting Industry guidance in Fusion, fast probe for plasma-surface interaction. 4 figs

  19. International fusion research council

    International Nuclear Information System (INIS)

    Belozerov, A.N.

    1977-01-01

    A brief history of the International Fusion Research Council (IFRC) is given and the minutes of the 1976 meeting in Garching are summarized. At the Garching meeting, the IFRC evaluated the quality of papers presented at recent IAEA conferences on plasma physics and controlled thermonuclear research, and made recommendations on the organization and timing of future meetings on nuclear fusion

  20. Fusion Canada issue 15

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1991-10-01

    A short bulletin from the National Fusion Program. Included in this issue is a report on the 1996 IAEA Fusion Conference site, operations at the Tokamak de Varennes including divertor pumping of impurities and pumping of carbon monoxide and methane, a discussion of the CFFTP and it`s role. 1 fig.

  1. Magnetic Fusion Program Plan

    International Nuclear Information System (INIS)

    1985-02-01

    This Plan reflects the present conditions of the energy situation and is consistent with national priorities for the support of basic and applied research. It is realistic in taking advantage of the technical position that the United States has already established in fusion research to make cost-effective progress toward the development of fusion power as a future energy option

  2. Fusion Canada issue 8

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1989-08-01

    A short bulletin from the National Fusion Program. Included in this issue are Canada-ITER contributions, NET Fuel Processing Loop, Bilateral Meeting for Canada-Europe, report from Tokamak de Varennes and a report from the University of Toronto on materials research for Fusion Reactors. 3 figs.

  3. Sensor Data Fusion

    DEFF Research Database (Denmark)

    Plascencia, Alfredo; Stepán, Petr

    2006-01-01

    The main contribution of this paper is to present a sensor fusion approach to scene environment mapping as part of a Sensor Data Fusion (SDF) architecture. This approach involves combined sonar array with stereo vision readings.  Sonar readings are interpreted using probability density functions...

  4. Coatings for laser fusion

    International Nuclear Information System (INIS)

    Lowdermilk, W.H.

    1981-01-01

    Optical coatings are used in lasers systems for fusion research to control beam propagation and reduce surface reflection losses. The performance of coatings is important in the design, reliability, energy output, and cost of the laser systems. Significant developments in coating technology are required for future lasers for fusion research and eventual power reactors

  5. Fusion reactor materials

    International Nuclear Information System (INIS)

    Sethi, V.K.; Scholz, R.; Nolfi, F.V. Jr.; Turner, A.P.L.

    1980-01-01

    Data are given for each of the following areas: (1) effects of irradiation on fusion reactor materials, (2) hydrogen permeation and materials behavior in alloys, (3) carbon coatings for fusion applications, (4) surface damage of TiB 2 coatings under energetic D + and 4 He + irradiations, and (5) neutron dosimetry

  6. The IGNITEX fusion project

    International Nuclear Information System (INIS)

    Carrera, R.

    1987-01-01

    The author discusses the recently proposed fusion ignition experiment, IGNITEX. He emphasizes the basic ideas of this concept rather than the specific details of the physics and engineering aspects of the experiment. This concept is a good example of the importance of maintaining an adequate balance between the basic scientific progress in fusion physics and the new technologies that are becoming available in order to make fusion work. The objective of the IGNITEX project is to produce and control ignited plasmas for scientific study in the simplest and least expensive way possible. Being able to study this not-yet-produced regime of plasma operation is essential to fusion research. Two years after the fission nuclear reaction was discovered, a non-self-sustained fission reaction was produced in a laboratory, and in one more year a self-sustained reaction was achieved at the University of Chicago. However, after almost forty years of fusion research, a self-sustained fusion reaction has yet not been produced in a laboratory experiment. This fact indicates the greater difficulty of the fusion experiment. Because of the difficulty involved in the production of a self-sustained fusion reaction, it is necessary to propose such an experiment with maximum ignition margins, maximum simplicity, and minimum financial risk

  7. Controlled thermonuclear fusion

    CERN Document Server

    Bobin, Jean Louis

    2014-01-01

    The book is a presentation of the basic principles and main achievements in the field of nuclear fusion. It encompasses both magnetic and inertial confinements plus a few exotic mechanisms for nuclear fusion. The state-of-the-art regarding thermonuclear reactions, hot plasmas, tokamaks, laser-driven compression and future reactors is given.

  8. Fusion Power Deployment

    International Nuclear Information System (INIS)

    Schmidt, J.A.; Ogden, J.M.

    2002-01-01

    Fusion power plants could be part of a future portfolio of non-carbon dioxide producing energy supplies such as wind, solar, biomass, advanced fission power, and fossil energy with carbon dioxide sequestration. In this paper, we discuss key issues that could impact fusion energy deployment during the last half of this century. These include geographic issues such as resource availability, scale issues, energy storage requirements, and waste issues. The resource needs and waste production associated with fusion deployment in the U.S. should not pose serious problems. One important feature of fusion power is the fact that a fusion power plant should be locatable within most local or regional electrical distribution systems. For this reason, fusion power plants should not increase the burden of long distance power transmission to our distribution system. In contrast to fusion power, regional factors could play an important role in the deployment of renewable resources such as wind, solar and biomass or fossil energy with CO2 sequestration. We examine the role of these regional factors and their implications for fusion power deployment

  9. Fusion Canada issue 4

    International Nuclear Information System (INIS)

    1988-05-01

    A short bulletin from the National Fusion Program. Included in this issue is a technical update on Tokamak de Varennes, a report on the Beatrix II Breeding Materials Test Program, the Tritium glovebox system for UPM, Saudi Arabia, a broad update of the Canadian Fusion Fuels Technology Project is also included. 1 fig

  10. Fusion Canada issue 12

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1990-10-01

    A short bulletin from the National Fusion Program. Included in this issue is a report on Darlington`s Tritium Removal Facility, work at universities on Deuterium Diffusivity in Beryllium, Fusion Studies, confinement research and the operation of divertors at Tokamak de Varennes. 5 figs.

  11. Fusion Canada issue 22

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1993-10-01

    A short bulletin from the National Fusion Program highlighting in this issue a bi-lateral meeting between Canada and Japan, water and hydrogen detritiation, in-situ tokamak surface analysis, an update of CCFM/TdeV and tritium accounting Industry guidance in Fusion, fast probe for plasma-surface interaction. 4 figs.

  12. Fusion Canada issue 4

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1988-05-01

    A short bulletin from the National Fusion Program. Included in this issue is a technical update on Tokamak de Varennes, a report on the Beatrix II Breeding Materials Test Program, the Tritium glovebox system for UPM, Saudi Arabia, a broad update of the Canadian Fusion Fuels Technology Project is also included. 1 fig.

  13. Fusion Canada issue 19

    International Nuclear Information System (INIS)

    1992-12-01

    A short bulletin from the National Fusion Program. Included in this issue is a report on the IAEA Plasma Biasing Meeting, the new IEA program -Nuclear Technology of Fusion reactors, TFTR tritium purification system, an update by CCFM on machine additions and modifications, and news of a new compact Toroid injector at the University of Saskatchewan. 1 fig

  14. Fusion Canada issue 14

    International Nuclear Information System (INIS)

    1991-05-01

    A short bulletin from the National Fusion Program. Included in this issue is a report on a fusion cooperation agreement between Japan and Canada, an update at Tokamak de Varennes on plasma biasing experiments and boronization tests and a collaboration between Canada and the U.S. on a compact toroid fuelling gun. 4 figs

  15. Fusion Canada issue 12

    International Nuclear Information System (INIS)

    1990-10-01

    A short bulletin from the National Fusion Program. Included in this issue is a report on Darlington's Tritium Removal Facility, work at universities on Deuterium Diffusivity in Beryllium, Fusion Studies, confinement research and the operation of divertors at Tokamak de Varennes. 5 figs

  16. Controlled Nuclear Fusion.

    Science.gov (United States)

    Glasstone, Samuel

    This publication is one of a series of information booklets for the general public published by The United States Atomic Energy Commission. Among the topics discussed are: Importance of Fusion Energy; Conditions for Nuclear Fusion; Thermonuclear Reactions in Plasmas; Plasma Confinement by Magnetic Fields; Experiments With Plasmas; High-Temperature…

  17. Flash flood swift water rescues, Texas, 2005–2014

    Directory of Open Access Journals (Sweden)

    Vaidehi Shah

    2017-01-01

    Full Text Available Although rainfall patterns are complex and difficult to predict, climate models suggest precipitation in Texas will occur less frequently and with greater intensity in the future. In combination with rapid population growth and development, extreme rainfall events are likely to lead to flash floods and necessitate swift water rescues. Swift water rescues are used to retrieve person(s from swift water flowing at a rate of 1 knot or greater. Data were obtained from the Texas Fire Marshal’s Office and analyzed to describe spatial and temporal characteristics of rescues. Between 2005 and 2014, 3256 swift water rescues were reported from 136 of 254 (54% counties. Over half (54.6%, n = 1777 occurred in counties known as Flash Flood Alley, which includes Texas’ largest and fastest growing cities. Less than 1.0% (n = 18 were reported from 49 counties designated as completely rural, or with an urban population less than 2500. Increases in swift water rescues were seen between March and September and during major weather events such as tropical storms. Because county-level data was utilized and demographic data was missing in all but 2% (n = 47 of the incidents, our ability to identify populations at risk or target interventions in the future using this data is limited. Despite the frequency of flash flood events and swift water rescues in Texas, knowledge gaps persist that should be addressed through the conduct of interdisciplinary research by epidemiologists and climatologists and by disseminating evidence-based health education and safety programs, particularly in rapidly growing counties that make up Texas’ Flash Flood Alley.

  18. Industry's role in inertial fusion

    International Nuclear Information System (INIS)

    Glass, A.J.

    1983-01-01

    This paper is an address to the Tenth Symposium on Fusion Engineering. The speaker first addressed the subject of industry's role in inertial fusion three years earlier in 1980, outlining programs that included participation in the Shiva construction project, and the industrial participants' program set up in the laser fusion program to bring industrial scientists and engineers into the laboratory to work on laser fusion. The speaker is now the president of KMS Fusion, Inc., the primary industrial participant in the inertial fusion program. The outlook for fusion energy and the attitude of the federal government toward the fusion program is discussed

  19. Towards fusion power

    International Nuclear Information System (INIS)

    Venkataraman, G.

    1975-01-01

    An attempt has been made to present general but broad review of the recent developments in the field of plasma physics and its application to fusion power. The first chapter describes the fusion reactions and fusion power systems. The second chapter deals in detail with production and behaviour of plasma, screening, oscillations, instability, energy losses, temperature effects, etc. Magnetic confinements, including pinch systems, toroidal systems such as Tokamac and stellarator, minor machine, etc. are discussed in detail in chapter III. Laser produced plasma, laser implosion and problems associated with it and future prospects are explained in chapter IV. Chapter V is devoted entirely to the various aspects of hybrid systems. The last chapter throws light on problems of fusion technology, such as plasma heating, vacuum requirements, radiation damage, choice of materials, blanket problems, hazards of fusion reactions, etc. (K.B.)

  20. Fusion fuel blanket technology

    International Nuclear Information System (INIS)

    Hastings, I.J.; Gierszewski, P.

    1987-05-01

    The fusion blanket surrounds the burning hydrogen core of a fusion reactor. It is in this blanket that most of the energy released by the nuclear fusion of deuterium-tritium is converted into useful product, and where tritium fuel is produced to enable further operation of the reactor. As fusion research turns from present short-pulse physics experiments to long-burn engineering tests in the 1990's, energy removal and tritium production capabilities become important. This technology will involve new materials, conditions and processes with applications both to fusion and beyond. In this paper, we introduce features of proposed blanket designs and update and status of international research. In focusing on the Canadian blanket technology program, we discuss the aqueous lithium salt blanket concept, and the in-reactor tritium recovery test program

  1. Decomposition of incomplete fusion

    International Nuclear Information System (INIS)

    Sobotka, L.B.; Sarantities, D.G.; Stracener, D.W.; Majka, Z.; Abenante, V.; Semkow, T.M.; Hensley, D.C.; Beene, J.R.; Halbert, M.L.

    1989-01-01

    The velocity distribution of fusion-like products formed in the reaction 701 MeV 28 Si+ 100 Mo is decomposed into 26 incomplete fusion channels. The momentum deficit of the residue per nonevaporative mass unit is approximately equal to the beam momentum per nucleon. The yields of the incomplete fusion channels correlate with the Q-value for projectile fragmentation rather than that for incomplete fusion. The backward angle multiplicities of light particles and heavy ions increase with momentum transfer, however, the heavy ion multiplicities also depend on the extent of the fragmentation of the incomplete fusion channel. These data indicate that at fixed linear momentum transfer, increased fragmentation of the unfused component is related to a reduced transferred angular momentum. 22 refs., 6 figs., 1 tab

  2. Nuclear fusion: The issues

    International Nuclear Information System (INIS)

    Griffin, R.D.

    1993-01-01

    The taming of fusion energy, has proved one of the most elusive quests of modern science. For four decades, the United States has doggedly pursued energy's holy grail, pumping more than $9 billion into research and reactor prototypes. This year, the federal government is slated to spend $339 million on fusion, more than the combined amount the government will spend for research on oil, natural gas, solar power, wind power, geothermal energy, biofuels and conservation. This article summarizes the technical, political in terms of international cooperation, economic, planning, etc. issues surrounding the continued development of fusion as a possible power source for the next century. Brief descriptions of how fusion works and of the design of a tokamak fusion machine are included

  3. Fusion safety data base

    International Nuclear Information System (INIS)

    Laats, E.T.; Hardy, H.A.

    1983-01-01

    The purpose of this Fusion Safety Data Base Program is to provide a repository of data for the design and development of safe commercial fusion reactors. The program is sponsored by the United States Department of Energy (DOE), Office of Fusion Energy. The function of the program is to collect, examine, permanently store, and make available the safety data to the entire US magnetic-fusion energy community. The sources of data will include domestic and foreign fusion reactor safety-related research programs. Any participant in the DOE Program may use the Data Base Program from his terminal through user friendly dialog and can view the contents in the form of text, tables, graphs, or system diagrams

  4. Compact fusion reactors

    CERN Multimedia

    CERN. Geneva

    2015-01-01

    Fusion research is currently to a large extent focused on tokamak (ITER) and inertial confinement (NIF) research. In addition to these large international or national efforts there are private companies performing fusion research using much smaller devices than ITER or NIF. The attempt to achieve fusion energy production through relatively small and compact devices compared to tokamaks decreases the costs and building time of the reactors and this has allowed some private companies to enter the field, like EMC2, General Fusion, Helion Energy, Lawrenceville Plasma Physics and Lockheed Martin. Some of these companies are trying to demonstrate net energy production within the next few years. If they are successful their next step is to attempt to commercialize their technology. In this presentation an overview of compact fusion reactor concepts is given.

  5. Some fusion perspectives

    International Nuclear Information System (INIS)

    McNally, J.R. Jr.

    1977-01-01

    Some of the concepts of nuclear fusion reactions, advanced fusion fuels, environmental impacts, etc., are explored using the following general outline: I. Principles of Fusion (Nuclear Fuels and Reactions, Lawson Condition, n tau vs T, Nuclear Burn Characteristics); II. Magnetic Mirror Possibilities (the Ion Layer and Electron Layer, Exponential Build-up at MeV energies, Lorentz trapping at GeV energies); III. Pellet Fuel Fusion Prospects (Advanced Pellet Fuel Fusion Prospects, Burn Characteristics and Applications, Excitation-heating Prospects for Runaway Ion Temperatures). Inasmuch as the outline is very skeletal, a significant research and development effort may be in order to evaluate these prospects in more detail and hopefully ''harness the H-bomb'' for peaceful applications, the author concludes. 28 references

  6. PNA Peptide chimerae

    DEFF Research Database (Denmark)

    Koch, T.; Næsby, M.; Wittung, P.

    1995-01-01

    Radioactive labelling of PNA has been performed try linking a peptide segment to the PNA which is substrate for protein kinase A. The enzymatic phosphorylation proceeds in almost quantitative yields....

  7. Strategies to rescue the consequences of inducible arginase-1 deficiency in mice.

    Directory of Open Access Journals (Sweden)

    Laurel L Ballantyne

    Full Text Available Arginase-1 catalyzes the conversion of arginine to ornithine and urea, which is the final step of the urea cycle used to remove excess ammonia from the body. Arginase-1 deficiency leads to hyperargininemia in mice and man with severe lethal consequences in the former and progressive neurological impairment to varying degrees in the latter. In a tamoxifen-induced arginase-1 deficient mouse model, mice succumb to the enzyme deficiency within 2 weeks after inducing the knockout and retain <2 % enzyme in the liver. Standard clinical care regimens for arginase-1 deficiency (low-protein diet, the nitrogen-scavenging drug sodium phenylbutyrate, ornithine supplementation either failed to extend lifespan (ornithine or only minimally prolonged lifespan (maximum 8 days with low-protein diet and drug. A conditional, tamoxifen-inducible arginase-1 transgenic mouse strain expressing the enzyme from the Rosa26 locus modestly extended lifespan of neonatal mice, but not that of 4-week old mice, when crossed to the inducible arginase-1 knockout mouse strain. Delivery of an arginase-1/enhanced green fluorescent fusion construct by adeno-associated viral delivery (rh10 serotype with a strong cytomegalovirus-chicken β-actin hybrid promoter rescued about 30% of male mice with lifespan prolongation to at least 6 months, extensive hepatic expression and restoration of significant enzyme activity in liver. In contrast, a vector of the AAV8 serotype driven by the thyroxine-binding globulin promoter led to weaker liver expression and did not rescue arginase-1 deficient mice to any great extent. Since the induced arginase-1 deficient mouse model displays a much more severe phenotype when compared to human arginase-1 deficiency, these studies reveal that it may be feasible with gene therapy strategies to correct the various manifestations of the disorder and they provide optimism for future clinical studies.

  8. Tumor penetrating peptides

    Directory of Open Access Journals (Sweden)

    Tambet eTeesalu

    2013-08-01

    Full Text Available Tumor-homing peptides can be used to deliver drugs into tumors. Phage library screening in live mice has recently identified homing peptides that specifically recognize the endothelium of tumor vessels, extravasate, and penetrate deep into the extravascular tumor tissue. The prototypic peptide of this class, iRGD (CRGDKGPDC, contains the integrin-binding RGD motif. RGD mediates tumor homing through binding to αv integrins, which are selectively expressed on various cells in tumors, including tumor endothelial cells. The tumor-penetrating properties of iRGD are mediated by a second sequence motif, R/KXXR/K. This C-end Rule (or CendR motif is active only when the second basic residue is exposed at the C-terminus of the peptide. Proteolytic processing of iRGD in tumors activates the cryptic CendR motif, which then binds to neuropilin-1 activating an endocytic bulk transport pathway through tumor tissue. Phage screening has also yielded tumor-penetrating peptides that function like iRGD in activating the CendR pathway, but bind to a different primary receptor. Moreover, novel tumor-homing peptides can be constructed from tumor-homing motifs, CendR elements and protease cleavage sites. Pathologies other than tumors can be targeted with tissue-penetrating peptides, and the primary receptor can also be a vascular zip code of a normal tissue. The CendR technology provides a solution to a major problem in tumor therapy, poor penetration of drugs into tumors. The tumor-penetrating peptides are capable of taking a payload deep into tumor tissue in mice, and they also penetrate into human tumors ex vivo. Targeting with these peptides specifically increases the accumulation in tumors of a variety of drugs and contrast agents, such as doxorubicin, antibodies and nanoparticle-based compounds. Remarkably the drug to be targeted does not have to be coupled to the peptide; the bulk transport system activated by the peptide sweeps along any compound that is

  9. Investigations of image fusion

    Science.gov (United States)

    Zhang, Zhong

    1999-12-01

    The objective of image fusion is to combine information from multiple images of the same scene. The result of image fusion is a single image which is more suitable for the purpose of human visual perception or further image processing tasks. In this thesis, a region-based fusion algorithm using the wavelet transform is proposed. The identification of important features in each image, such as edges and regions of interest, are used to guide the fusion process. The idea of multiscale grouping is also introduced and a generic image fusion framework based on multiscale decomposition is studied. The framework includes all of the existing multiscale-decomposition- based fusion approaches we found in the literature which did not assume a statistical model for the source images. Comparisons indicate that our framework includes some new approaches which outperform the existing approaches for the cases we consider. Registration must precede our fusion algorithms. So we proposed a hybrid scheme which uses both feature-based and intensity-based methods. The idea of robust estimation of optical flow from time- varying images is employed with a coarse-to-fine multi- resolution approach and feature-based registration to overcome some of the limitations of the intensity-based schemes. Experiments show that this approach is robust and efficient. Assessing image fusion performance in a real application is a complicated issue. In this dissertation, a mixture probability density function model is used in conjunction with the Expectation- Maximization algorithm to model histograms of edge intensity. Some new techniques are proposed for estimating the quality of a noisy image of a natural scene. Such quality measures can be used to guide the fusion. Finally, we study fusion of images obtained from several copies of a new type of camera developed for video surveillance. Our techniques increase the capability and reliability of the surveillance system and provide an easy way to obtain 3-D

  10. Immunogenicity of peptides of measles virus origin and influence of adjuvants.

    Science.gov (United States)

    Halassy, Beata; Mateljak, Sanja; Bouche, Fabienne B; Pütz, Mike M; Muller, Claude P; Frkanec, Ruza; Habjanec, Lidija; Tomasić, Jelka

    2006-01-12

    Epitope-based peptide antigens have been under development for protection against measles virus. The immunogenicity of five peptides composed of the same B cell epitope (BCE) (H236-250 of the measles virus hemagglutinin), and different T cell epitopes of measles virus fusion protein (F421-435, F256-270, F288-302) and nucleoprotein (NP335-345) was studied in mice (subcutaneous immunisation). The adjuvant effects of peptidoglycan monomer (PGM), Montanide ISA 720 and 206 were also investigated. Results showed basic differences in peptide immunogenicity that were consistent with already described structural differences. PGM elevated peptide-specific IgG when applied together with four of five tested peptides. A strong synergistic effect was observed after co-immunisation of mice with a mixture containing all five chimeric peptides in small and equal amounts. Results revealed for the first time that immunisation with several peptides having the common BCE generated significantly higher levels of both anti-peptide and anti-BCE IgG in comparison to those obtained after immunisation with a single peptide in much higher quantity. Further improvement of immune response was obtained after incorporation of such a peptide mixture into oil-based adjuvants.

  11. Peptide aldehyde inhibitors of bacterial peptide deformylases.

    Science.gov (United States)

    Durand, D J; Gordon Green, B; O'Connell, J F; Grant, S K

    1999-07-15

    Bacterial peptide deformylases (PDF, EC 3.5.1.27) are metalloenzymes that cleave the N-formyl groups from N-blocked methionine polypeptides. Peptide aldehydes containing a methional or norleucinal inhibited recombinant peptide deformylase from gram-negative Escherichia coli and gram-positive Bacillus subtilis. The most potent inhibitor was calpeptin, N-CBZ-Leu-norleucinal, which was a competitive inhibitor of the zinc-containing metalloenzymes, E. coli and B. subtilis PDF with Ki values of 26.0 and 55.6 microM, respectively. Cobalt-substituted E. coli and B. subtilis deformylases were also inhibited by these aldehydes with Ki values for calpeptin of 9.5 and 12.4 microM, respectively. Distinct spectral changes were observed upon binding of calpeptin to the Co(II)-deformylases, consistent with the noncovalent binding of the inhibitor rather than the formation of a covalent complex. In contrast, the chelator 1,10-phenanthroline caused the time-dependent inhibition of B. subtilis Co(II)-PDF activity with the loss of the active site metal. The fact that calpeptin was nearly equipotent against deformylases from both gram-negative and gram-positive bacterial sources lends further support to the idea that a single deformylase inhibitor might have broad-spectrum antibacterial activity. Copyright 1999 Academic Press.

  12. tmRNA-mediated trans-translation as the major ribosome rescue system in a bacterial cell

    Directory of Open Access Journals (Sweden)

    Hyouta eHimeno

    2014-04-01

    Full Text Available tmRNA (transfer messenger RNA; also known as 10Sa RNA or SsrA RNA is a small RNA molecule that is conserved among bacteria. It has structural and functional similarities to tRNA: it has an upper half of the tRNA-like structure, its 5’ end is processed by RNase P, it has typical tRNA-specific base modifications, it is aminoacylated with alanine, it binds to EF-Tu after aminoacylation and it enters the ribosome with EF-Tu and GTP. However, tmRNA lacks an anticodon, and instead it has a coding sequence for a short peptide called tag-peptide. An elaborate interplay of actions of tmRNA as both tRNA and mRNA with the help of a tmRNA-binding protein, SmpB, facilitates trans-translation, which produces a single polypeptide from two mRNA molecules. Initially alanyl-tmRNA in complex with EF-Tu and SmpB enters the vacant A-site of the stalled ribosome like aminoacyl-tRNA but without a codon-anticodon interaction, and subsequently truncated mRNA is replaced with the tag-encoding region of tmRNA. During these processes, not only tmRNA but also SmpB structurally and functionally mimics both tRNA and mRNA. Thus trans-translation rescues the stalled ribosome, thereby allowing recycling of the ribosome. Since the tag-peptide serves as a target of AAA+ proteases, the trans-translation products are preferentially degraded so that they do not accumulate in the cell. Although alternative rescue systems have recently been revealed, trans-translation is the only system that universally exists in bacteria. Furthermore, it is unique in that it employs a small RNA and that it prevents accumulation of nonfunctional proteins from truncated mRNA in the cell. It might play the major role in rescuing the stalled translation in the bacterial cell.

  13. A Peptide-Fc Opsonin with Pan-Amyloid Reactivity

    Directory of Open Access Journals (Sweden)

    James S. Foster

    2017-09-01

    Full Text Available There is a continuing need for therapeutic interventions for patients with the protein misfolding disorders that result in systemic amyloidosis. Recently, specific antibodies have been employed to treat AL amyloidosis by opsonizing tissue amyloid deposits thereby inducing cell-mediated dissolution and organ improvement. To develop a pan-amyloid therapeutic agent, we have produced an Fc-fusion product incorporating a peptide, p5, which binds many if not all forms of amyloid. This protein, designated Fcp5, expressed in mammalian cells, forms the desired bivalent dimer structure and retains pan-amyloid reactivity similar to the p5 peptide as measured by immunosorbent assays, immunohistochemistry, surface plasmon resonance, and pulldown assays using radioiodinated Fcp5. Additionally, Fcp5 was capable of opsonizing amyloid fibrils in vitro using a pH-sensitive fluorescence assay of phagocytosis. In mice,125 I-labeled Fcp5 exhibited an extended serum circulation time, relative to the p5 peptide. It specifically bound AA amyloid deposits in diseased mice, as evidenced by biodistribution and microautoradiographic methods, which coincided with an increase in active, Iba-1-positive macrophages in the liver at 48 h postinjection of Fcp5. In healthy mice, no specific tissue accumulation was observed. The data indicate that polybasic, pan-amyloid-targeting peptides, in the context of an Fc fusion, can yield amyloid reactive, opsonizing reagents that may serve as next-generation immunotherapeutics.

  14. US fusion community discussion on fusion strategies

    International Nuclear Information System (INIS)

    Marton, W.A.

    1998-01-01

    On April 26 - May 1, 1998, a US Fusion Community Forum for Major Next-Step Experiments was held at Madison, Wisconsin, USA. Both the Single Integrated Step strategy and the Multiple Machine strategy have substantial support from the about 180 scientists and engineers who participated

  15. Rescuing Israeli travellers: effects of substance abuse, mental health, geographic region of rescue, gender and age of rescuees.

    Science.gov (United States)

    Bonny-Noach, Hagit; Sagiv-Alayoff, Moran

    2017-09-01

    Research conducted on young Israeli travellers has pointed to high substance usage rates. For some drug-using backpackers, actual extraction and rescue from their trip abroad is necessary. This study represents a first attempt to explore the influence of geographic region in which rescue occurs, cause for rescue and gender and age differences among Israeli rescuees. Sub-analysis of all logs of individual rescuees during a 5-year period from 2011 to 2016 ( N  = 86) included 66 men and 20 women, with an average age of 27.83 (SD = 7.86). The findings demonstrate that Israelis are most frequently rescued from South and Southeast Asia (57%) followed by Europe (22%), South America (17%), North America (2.3%) and Africa (1.2%). India was the country with the highest rate of rescue incidents ( N  = 36) followed by Thailand ( N  = 8) and the Netherlands ( N  = 5). The most common cause for rescue was substance abuse (87%). However, significant regional differences were found based on the variable of age ( F  = 3.21, df = 3,50, P  young travellers should be taken into consideration when thinking about induced acute psychosis caused by substance use. Policymakers need to consider prevention and harm reduction interventions relevant to this risk group. © International Society of Travel Medicine, 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

  16. Materials for fusion reactors

    International Nuclear Information System (INIS)

    Ehrlich, K.; Kaletta, D.

    1978-03-01

    The following report describes five papers which were given during the IMF seminar series summer 1977. The purpose of this series was to discuss especially the irradiation behaviour of materials intended for the first wall of future fusion reactors. The first paper deals with the basic understanding of plasma physics relating to the fusion reactor and presents the current state of art of fusion technology. The next two talks discuss the metals intended for the first wall and structural components of a fusion reactor. Since 14 MeV neutrons play an important part in the process of irradiation damage their role is discussed in detail. The question which machines are presently available to simulate irradiation damage under conditions similar to the ones found in a fusion reactor are investigated in the fourth talk which also presents the limitations of the different methods of simulation. In this context also discussed is the importance future intensive neutron sources and materials test reactors will have for this problem area. The closing paper has as a theme the review of the present status of research of metallic and non-metallic materials in view of the quite different requirements for different fusion systems; a closing topic is the world supply on rare materials required for fusion reactors. (orig) [de

  17. Fusion research in Hungary

    International Nuclear Information System (INIS)

    Zoletnik, S.

    2004-01-01

    Hungarian fusion research started in the 1970s, when the idea of installing a small tokamak experiment emerged. In return to computer equipment a soviet tokamak was indeed sent to Hungary and started to operate as MT-1 at the Central Research Institute for Physics (KFKI) in 1979. Major research topics included diagnostic development, edge plasma studies and investigation of disruptions. Following a major upgrade in 1992 (new vacuum vessel, active position control and PC network based data acquisition system) the MT-1M tokamak was used for the study of transport processes with trace impurity injection, micropellet ablation studies, X-ray tomography and laser blow-off diagnostic development. Although funding ceased in the middle of the 90's the group was held alive by collaborations with EU fusion labs: FZ -Juelich, IPP-Garching and CRPP-EPFL Lausanne. In 1998 the machine was dismantled due to reorganization of the Hungarian Academy of Sciences. New horizons opened to fusion research from 1999, when Hungary joined EURATOM and a fusion Association was formed. Since then fusion physics studies are done in collaboration with major EU fusion laboratories, Hungarian researchers also play an active role in JET diagnostics upgrade and ITER design. Major topics are pellet ablation studies, plasma turbulence diagnosis using Beam Emission Spectroscopy and other techniques, tomography and plasma diagnostics using various neutral beams. In fusion relevant technology R and D Hungary has less records. Before joining EURATOM some materials irradiation studies were done at the Budapest Research Reactor at KFKI-AEKI. The present day fusion technology programme focuses still on irradiation studies, nuclear material database and electromagnetic testing techniques. Increasing the fusion technology research activities is a difficult task, as the competition in Hungarian industry is very strong and the interest of organizations in long-term investments into R and D is rather weak and

  18. Soluble N-Ethylmaleimide-Sensitive Factor Attachment Protein Receptor-Derived Peptides for Regulation of Mast Cell Degranulation.

    Science.gov (United States)

    Yang, Yoosoo; Kong, Byoungjae; Jung, Younghoon; Park, Joon-Bum; Oh, Jung-Mi; Hwang, Jaesung; Cho, Jae Youl; Kweon, Dae-Hyuk

    2018-01-01

    Vesicle-associated V-soluble N -ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins and target membrane-associated T-SNAREs (syntaxin 4 and SNAP-23) assemble into a core trans -SNARE complex that mediates membrane fusion during mast cell degranulation. This complex plays pivotal roles at various stages of exocytosis from the initial priming step to fusion pore opening and expansion, finally resulting in the release of the vesicle contents. In this study, peptides with the sequences of various SNARE motifs were investigated for their potential inhibitory effects against SNARE complex formation and mast cell degranulation. The peptides with the sequences of the N-terminal regions of vesicle-associated membrane protein 2 (VAMP2) and VAMP8 were found to reduce mast cell degranulation by inhibiting SNARE complex formation. The fusion of protein transduction domains to the N-terminal of each peptide enabled the internalization of the fusion peptides into the cells equally as efficiently as cell permeabilization by streptolysin-O without any loss of their inhibitory activities. Distinct subsets of mast cell granules could be selectively regulated by the N-terminal-mimicking peptides derived from VAMP2 and VAMP8, and they effectively decreased the symptoms of atopic dermatitis in mouse models. These results suggest that the cell membrane fusion machinery may represent a therapeutic target for atopic dermatitis.

  19. Autonomous underwater vehicle for research and rescue operations

    CSIR Research Space (South Africa)

    Holtzhausen S

    2008-11-01

    Full Text Available Autonomous under water vehicles are ideal platforms for search and rescue operations. They can also be used for inspection of underwater terrains. These vehicles need to be autonomous and robust to cope with unpredictable current and high pressures...

  20. EMERGENCY VICTIM CARE AND RESCUE, TEXTBOOK FOR SQUADMEN.

    Science.gov (United States)

    Ohio State Dept. of Education, Columbus. Trade and Industrial Education Service.

    DESIGNED FOR TRAINING EMERGENCY SQUAD PERSONNEL IN RESCUE PROCEDURES AND VICTIM CARE BEYOND BASIC FIRST AID, THIS TEXTBOOK WAS DEVELOPED BY A COMMITTEE OF SQUADMEN, DOCTORS, NURSES, FIREMEN, AND STATE TRADE AND INDUSTRIAL PERSONNEL TO BE USED IN ADULT TRAINING CLASSES OF FULL-TIME OR VOLUNTEER SQUADMEN. THE INSTRUCTIONAL MATERIAL INCLUDES 26…

  1. Mine rescue robots requirements: Outcomes from an industry workshop

    CSIR Research Space (South Africa)

    Green, J

    2013-10-01

    Full Text Available and internationally. The paper identifies three definite robot deployments in South Africa as a) box hole deployment (vertical tunnels), b) flying drone reconnaissance and c) proto (rescue) team assistance. These represent applications where there is a market need...

  2. Review of the rescue, rehabilitation and restoration of oiled seabirds ...

    African Journals Online (AJOL)

    Review of the rescue, rehabilitation and restoration of oiled seabirds in South Africa, especially African penguins Spheniscus demersus and Cape gannets Morus capensis , 1983–2005. ... In addition, oiling has a long-term negative impact on the breeding productivity and cost of reproduction in de-oiled birds. The primary ...

  3. Embryo rescue of crosses between diploid and tetraploid grape ...

    African Journals Online (AJOL)

    ajl yemi

    2011-12-19

    Dec 19, 2011 ... Five cross combinations Jumeigui×Xinghua No.1, 87-1×Kyoho, Kyoho×Muscat Hamburg, Jumeigui×. Hongqitezao and Red globle×Kyoho were used as the testing materials. Factors that affect embryo rescue from crossed seeds between diploid and tetraploid grape were studied applying L25(55).

  4. Embryo rescue of crosses between diploid and tetraploid grape ...

    African Journals Online (AJOL)

    Five cross combinations Jumeigui×Xinghua No.1, 87-1×Kyoho, Kyoho×Muscat Hamburg, Jumeigui× Hongqitezao and Red globle×Kyoho were used as the testing materials. Factors that affect embryo rescue from crossed seeds between diploid and tetraploid grape were studied applying L25(55) orthogonal experiment ...

  5. In vitro embryo rescue and plant regeneration following self ...

    African Journals Online (AJOL)

    EJIRO

    2015-07-08

    Jul 8, 2015 ... 2Department of Biological Sciences, College of Natural Sciences, Makerere ... Key words: Cassava, doubled haploids, embryo rescue, plant regeneration, pollen germination, pollen ... breeding as inbred lines are readily tested and used within a ... dominance, allowing the separation of homozygotes from.

  6. Intelligent Robot-assisted Humanitarian Search and Rescue System

    Directory of Open Access Journals (Sweden)

    Henry Y. K. Lau

    2009-11-01

    Full Text Available The unprecedented scale and number of natural and man-made disasters in the past decade has urged international emergency search and rescue communities to seek for novel technology to enhance operation efficiency. Tele-operated search and rescue robots that can navigate deep into rubble to search for victims and to transfer critical field data back to the control console has gained much interest among emergency response institutions. In response to this need, a low-cost autonomous mini robot equipped with thermal sensor, accelerometer, sonar, pin-hole camera, microphone, ultra-bright LED and wireless communication module is developed to study the control of a group of decentralized mini search and rescue robots. The robot can navigate autonomously between voids to look for living body heat and can send back audio and video information to allow the operator to determine if the found object is a living human. This paper introduces the design and control of a low-cost robotic search and rescue system based on an immuno control framework developed for controlling decentralized systems. Design and development of the physical prototype and the immunity-based control system are described in this paper.

  7. RoboCup Rescue Robot and Simulation Leagues

    NARCIS (Netherlands)

    Akin, H.L.; Ito, N.; Jacoff, A.; Kleiner, A.; Pellenz, J.; Visser, A.

    2013-01-01

    The RoboCup Rescue Robot and Simulation competitions have been held since 2000. The experience gained during these competitions has increased the maturity level of the field, which allowed deploying robots after real disasters (for example, Fukushima Daiichi nuclear disaster). This article provides

  8. The role of "rescue saccades" in tracking objects through occlusions.

    Science.gov (United States)

    Zelinsky, Gregory J; Todor, Andrei

    2010-12-29

    We hypothesize that our ability to track objects through occlusions is mediated by timely assistance from gaze in the form of "rescue saccades"-eye movements to tracked objects that are in danger of being lost due to impending occlusion. Observers tracked 2-4 target sharks (out of 9) for 20 s as they swam through a rendered 3D underwater scene. Targets were either allowed to enter into occlusions (occlusion trials) or not (no occlusion trials). Tracking accuracy with 2-3 targets was ≥ 92% regardless of target occlusion but dropped to 74% on occlusion trials with four targets (no occlusion trials remained accurate; 83%). This pattern was mirrored in the frequency of rescue saccades. Rescue saccades accompanied approximatlely 50% of the Track 2-3 target occlusions, but only 34% of the Track 4 occlusions. Their frequency also decreased with increasing distance between a target and the nearest other object, suggesting that it is the potential for target confusion that summons a rescue saccade, not occlusion itself. These findings provide evidence for a tracking system that monitors for events that might cause track loss (e.g., occlusions) and requests help from the oculomotor system to resolve these momentary crises. As the number of crises increase with the number of targets, some requests for help go unsatisfied, resulting in degraded tracking.

  9. Intelligent Robot-Assisted Humanitarian Search and Rescue System

    Directory of Open Access Journals (Sweden)

    Albert W. Y. Ko

    2009-06-01

    Full Text Available The unprecedented scale and number of natural and man-made disasters in the past decade has urged international emergency search and rescue communities to seek for novel technology to enhance operation efficiency. Tele-operated search and rescue robots that can navigate deep into rubble to search for victims and to transfer critical field data back to the control console has gained much interest among emergency response institutions. In response to this need, a low-cost autonomous mini robot equipped with thermal sensor, accelerometer, sonar, pin-hole camera, microphone, ultra-bright LED and wireless communication module is developed to study the control of a group of decentralized mini search and rescue robots. The robot can navigate autonomously between voids to look for living body heat and can send back audio and video information to allow the operator to determine if the found object is a living human. This paper introduces the design and control of a low-cost robotic search and rescue system based on an immuno control framework developed for controlling decentralized systems. Design and development of the physical prototype and the immunity-based control system are described in this paper.

  10. Protecting front-line survey and rescue teams during emergencies

    International Nuclear Information System (INIS)

    Tresise, H.

    1980-01-01

    Means of protecting front-line survey and rescue teams during emergencies are described. The team composition, their apparatus, the selection of the incident control point, the use of guidelines and breathing apparatus and control point trolley and equipment are discussed. (H.K.)

  11. Polyclonal and monoclonal antibodies specific for the six-helix bundle of the human respiratory syncytial virus fusion glycoprotein as probes of the protein post-fusion conformation

    International Nuclear Information System (INIS)

    Palomo, Concepción; Mas, Vicente; Vázquez, Mónica; Cano, Olga; Luque, Daniel; Terrón, María C.; Calder, Lesley J.; Melero, José A.

    2014-01-01

    Human respiratory syncytial virus (hRSV) has two major surface glycoproteins (G and F) anchored in the lipid envelope. Membrane fusion promoted by hRSV F occurs via refolding from a pre-fusion form to a highly stable post-fusion state involving large conformational changes of the F trimer. One of these changes results in assembly of two heptad repeat sequences (HRA and HRB) into a six-helix bundle (6HB) motif. To assist in distinguishing pre- and post-fusion conformations of hRSV F , we have prepared polyclonal (α-6HB) and monoclonal (R145) rabbit antibodies specific for the 6HB. Among other applications, these antibodies were used to explore the requirements of 6HB formation by isolated protein segments or peptides and by truncated mutants of the F protein. Site-directed mutagenesis and electron microscopy located the R145 epitope in the post-fusion hRSV F at a site distantly located from previously mapped epitopes, extending the repertoire of antibodies that can decorate the F molecule. - Highlights: • Antibodies specific for post-fusion respiratory syncytial virus fusion protein are described. • Polyclonal antibodies were obtained in rabbit inoculated with chimeric heptad repeats. • Antibody binding required assembly of a six-helix bundle in the post-fusion protein. • A monoclonal antibody with similar structural requirements is also described. • Binding of this antibody to the post-fusion protein was visualized by electron microscopy

  12. Polyclonal and monoclonal antibodies specific for the six-helix bundle of the human respiratory syncytial virus fusion glycoprotein as probes of the protein post-fusion conformation

    Energy Technology Data Exchange (ETDEWEB)

    Palomo, Concepción; Mas, Vicente; Vázquez, Mónica; Cano, Olga [Unidad de Biología Viral, Centro Nacional de Microbiología, Madrid (Spain); CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Majadahonda, 28220 Madrid (Spain); Luque, Daniel; Terrón, María C. [Unidad de Microscopía Electrónica y Confocal, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, 28220 Madrid (Spain); Calder, Lesley J. [National Institute for Medical Research, MRC, Mill Hill, London NW7 1AA (United Kingdom); Melero, José A., E-mail: jmelero@isciii.es [Unidad de Biología Viral, Centro Nacional de Microbiología, Madrid (Spain); CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Majadahonda, 28220 Madrid (Spain)

    2014-07-15

    Human respiratory syncytial virus (hRSV) has two major surface glycoproteins (G and F) anchored in the lipid envelope. Membrane fusion promoted by hRSV{sub F} occurs via refolding from a pre-fusion form to a highly stable post-fusion state involving large conformational changes of the F trimer. One of these changes results in assembly of two heptad repeat sequences (HRA and HRB) into a six-helix bundle (6HB) motif. To assist in distinguishing pre- and post-fusion conformations of hRSV{sub F}, we have prepared polyclonal (α-6HB) and monoclonal (R145) rabbit antibodies specific for the 6HB. Among other applications, these antibodies were used to explore the requirements of 6HB formation by isolated protein segments or peptides and by truncated mutants of the F protein. Site-directed mutagenesis and electron microscopy located the R145 epitope in the post-fusion hRSV{sub F} at a site distantly located from previously mapped epitopes, extending the repertoire of antibodies that can decorate the F molecule. - Highlights: • Antibodies specific for post-fusion respiratory syncytial virus fusion protein are described. • Polyclonal antibodies were obtained in rabbit inoculated with chimeric heptad repeats. • Antibody binding required assembly of a six-helix bundle in the post-fusion protein. • A monoclonal antibody with similar structural requirements is also described. • Binding of this antibody to the post-fusion protein was visualized by electron microscopy.

  13. Mirror fusion reactors

    International Nuclear Information System (INIS)

    Anon.

    1978-01-01

    Conceptual design studies were made of fusion reactors based on the three current mirror-confinement concepts: the standard mirror, the tandem mirror, and the field-reversed mirror. Recent studies of the standard mirror have emphasized its potential as a fusion-fission hybrid reactor, designed to produce fuel for fission reactors. We have designed a large commercial hybrid and a small pilot-plant hybrid based on standard mirror confinement. Tandem mirror designs include a commercial 1000-MWe fusion power plant and a nearer term tandem mirror hybrid. Field-reversed mirror designs include a multicell commercial reactor producing 75 MWe and a single-cell pilot plant

  14. Mirror fusion reactors

    International Nuclear Information System (INIS)

    Carlson, G.A.; Moir, R.W.

    1978-01-01

    We have carried out conceptual design studies of fusion reactors based on the three current mirror confinement concepts: the standard mirror, the tandem mirror, and the field-reversed mirror. Recent studies of the standard mirror have emphasized its potential as a fusion-fission hybrid reactor, designed to produce fission fuel for fission reactors. We have designed a large commercial hybrid based on standard mirror confinement, and also a small pilot plant hybrid. Tandem mirror designs include a commercial 1000 MWe fusion power plant and a nearer term tandem mirror hybrid. Field-reversed mirror designs include a multicell commercial reactor producing 75 MWe and a single cell pilot plant

  15. Fusion Reactor Materials

    International Nuclear Information System (INIS)

    Decreton, M.

    2002-01-01

    The objective of SCK-CEN's programme on fusion reactor materials is to contribute to the knowledge on the radiation-induced behaviour of fusion reactor materials and components as well as to help the international community in building the scientific and technical basis needed for the construction of the future reactor. Ongoing projects include: the study of the mechanical and chemical (corrosion) behaviour of structural materials under neutron irradiation and water coolant environment; the investigation of the characteristics of irradiated first wall material such as beryllium; investigations on the management of materials resulting from the dismantling of fusion reactors including waste disposal. Progress and achievements in these areas in 2001 are discussed

  16. Remote sensing image fusion

    CERN Document Server

    Alparone, Luciano; Baronti, Stefano; Garzelli, Andrea

    2015-01-01

    A synthesis of more than ten years of experience, Remote Sensing Image Fusion covers methods specifically designed for remote sensing imagery. The authors supply a comprehensive classification system and rigorous mathematical description of advanced and state-of-the-art methods for pansharpening of multispectral images, fusion of hyperspectral and panchromatic images, and fusion of data from heterogeneous sensors such as optical and synthetic aperture radar (SAR) images and integration of thermal and visible/near-infrared images. They also explore new trends of signal/image processing, such as

  17. Beam dancer fusion device

    International Nuclear Information System (INIS)

    Maier, H.B.

    1984-01-01

    To accomplish fusion of two or more fusion fuel elements numerous minute spots of energy or laser light are directed to a micro target area, there to be moved or danced about by a precision mechanical controlling apparatus at the source of the laser light or electromagnetic energy beams, so that merging and coinciding patterns of light or energy beams can occur around the area of the fuel atoms or ions. The projecting of these merging patterns may be considered as target searching techniques to locate responsive clusters of fuel elements and to compress such elements into a condition in which fusion may occur. Computerized programming may be used

  18. Fusion Reactor Materials

    International Nuclear Information System (INIS)

    Decreton, M.

    2001-01-01

    The objective of SCK-CEN's programme on fusion reactor materials is to contribute to the knowledge on the behaviour of fusion reactor materials and components during and after irradiation. Ongoing projects include: the study of the mechanical behaviour of structural materials under neutron irradiation; the investigation of the characteristics of irradiated first wall material such as beryllium; the detection of abrupt electrical degradation of insulating ceramics under high temperature and neutron irradiation; and the study of dismantling and waste disposal strategy for fusion reactors. Progress and achievements in these areas in 2000 are discussed

  19. Japanese fusion research

    International Nuclear Information System (INIS)

    Uchida, T.

    1987-01-01

    The Japan experience during thirty years in nuclear fusion research is reported, after attending the 1st Geneva Conference in 1955, Osaka University, immedeately began linear pinch study using capacitor bank discharge. Subsequently to his trial several groups were organized to ward fusion R and D at universities in Tokyo, Nagoya, Kyoto, Sendai and son on. Based upon the recommendation of Japan Science Council, Institut of Plasma Physics (IPP) was established at Nagoya University in 1961 When the 1st International Conference on Plasma Physics and Controlled Nuclear Fusion Research was held in Saltzburg. The gloomy Bohm barrier had stood in front of many of experiments at that time. (author) [pt

  20. Inertial thermonuclear fusion by laser

    International Nuclear Information System (INIS)

    Watteau, J.P.

    1993-12-01

    The principles of deuterium tritium (DT) magnetic or inertial thermonuclear fusion are given. Even if results would be better with heavy ions beams, most of the results on fusion are obtained with laser beams. Technical and theoretical aspects of the laser fusion are presented with an extrapolation to the future fusion reactor. (A.B.). 34 refs., 17 figs

  1. Inertial fusion commercial power plants

    International Nuclear Information System (INIS)

    Logan, B.G.

    1994-01-01

    This presentation discusses the motivation for inertial fusion energy, a brief synopsis of five recently-completed inertial fusion power plant designs, some general conclusions drawn from these studies, and an example of an IFE hydrogen synfuel plant to suggest that future fusion studies consider broadening fusion use to low-emission fuels production as well as electricity

  2. Why and how of fusion

    International Nuclear Information System (INIS)

    Miley, G.H.

    1977-01-01

    The potential advantages of fusion power are listed. The approaches to plasma containment are mentioned and the status of the fusion program is described. The ERDA and EPRI programs are discussed. The Fusion Energy Foundation's activities are mentioned. Fusion research at the U. of Ill. is described briefly

  3. Fusion in the energy system

    DEFF Research Database (Denmark)

    Fusion energy is the fundamental energy source of the Universe, as the energy of the Sun and the stars are produced by fusion of e.g. hydrogen to helium. Fusion energy research is a strongly international endeavor aiming at realizing fusion energy production in power plants on Earth. Reaching...... of integration into the future electricity system and socio-economic studies of fusion energy will be presented, referring to the programme of Socio-Economic Research on Fusion (SERF) under the European Fusion Energy Agreement (EFDA)....

  4. Peptide Integrated Optics.

    Science.gov (United States)

    Handelman, Amir; Lapshina, Nadezda; Apter, Boris; Rosenman, Gil

    2018-02-01

    Bio-nanophotonics is a wide field in which advanced optical materials, biomedicine, fundamental optics, and nanotechnology are combined and result in the development of biomedical optical chips. Silk fibers or synthetic bioabsorbable polymers are the main light-guiding components. In this work, an advanced concept of integrated bio-optics is proposed, which is based on bioinspired peptide optical materials exhibiting wide optical transparency, nonlinear and electrooptical properties, and effective passive and active waveguiding. Developed new technology combining bottom-up controlled deposition of peptide planar wafers of a large area and top-down focus ion beam lithography provides direct fabrication of peptide optical integrated circuits. Finding a deep modification of peptide optical properties by reconformation of biological secondary structure from native phase to β-sheet architecture is followed by the appearance of visible fluorescence and unexpected transition from a native passive optical waveguiding to an active one. Original biocompatibility, switchable regimes of waveguiding, and multifunctional nonlinear optical properties make these new peptide planar optical materials attractive for application in emerging technology of lab-on-biochips, combining biomedical photonic and electronic circuits toward medical diagnosis, light-activated therapy, and health monitoring. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Antimicrobial Peptides from Plants

    Directory of Open Access Journals (Sweden)

    James P. Tam

    2015-11-01

    Full Text Available Plant antimicrobial peptides (AMPs have evolved differently from AMPs from other life forms. They are generally rich in cysteine residues which form multiple disulfides. In turn, the disulfides cross-braced plant AMPs as cystine-rich peptides to confer them with extraordinary high chemical, thermal and proteolytic stability. The cystine-rich or commonly known as cysteine-rich peptides (CRPs of plant AMPs are classified into families based on their sequence similarity, cysteine motifs that determine their distinctive disulfide bond patterns and tertiary structure fold. Cystine-rich plant AMP families include thionins, defensins, hevein-like peptides, knottin-type peptides (linear and cyclic, lipid transfer proteins, α-hairpinin and snakins family. In addition, there are AMPs which are rich in other amino acids. The ability of plant AMPs to organize into specific families with conserved structural folds that enable sequence variation of non-Cys residues encased in the same scaffold within a particular family to play multiple functions. Furthermore, the ability of plant AMPs to tolerate hypervariable sequences using a conserved scaffold provides diversity to recognize different targets by varying the sequence of the non-cysteine residues. These properties bode well for developing plant AMPs as potential therapeutics and for protection of crops through transgenic methods. This review provides an overview of the major families of plant AMPs, including their structures, functions, and putative mechanisms.

  6. Munc18b Increases Insulin Granule Fusion, Restoring Deficient Insulin Secretion in Type-2 Diabetes Human and Goto-Kakizaki Rat Islets with Improvement in Glucose Homeostasis

    Directory of Open Access Journals (Sweden)

    Tairan Qin

    2017-02-01

    Infusion of Ad-Munc18b into GK rat pancreas led to sustained improvement in glucose homeostasis. However, Munc18b overexpression in normal islets increased only newcomer SG fusion. Therefore, Munc18b could potentially be deployed in human T2D to rescue the deficient GSIS.

  7. Novel anti-HIV peptides containing multiple copies of artificially designed heptad repeat motifs

    International Nuclear Information System (INIS)

    Shi Weiguo; Qi Zhi; Pan Chungen; Xue Na; Debnath, Asim K.; Qie Jiankun; Jiang Shibo; Liu Keliang

    2008-01-01

    The peptidic anti-HIV drug T20 (Fuzeon) and its analog C34 share a common heptad repeat (HR) sequence, but they have different functional domains, i.e., pocket- and lipid-binding domains (PBD and LBD, respectively). We hypothesize that novel anti-HIV peptides may be designed by using artificial sequences containing multiple copies of HR motifs plus zero, one or two functional domains. Surprisingly, we found that the peptides containing only the non-natural HR sequences could significantly inhibit HIV-1 infection, while addition of PBD and/or LBD to the peptides resulted in significant improvement of anti-HIV-1 activity. These results suggest that these artificial HR sequences, which may serve as structural domains, could be used as templates for the design of novel antiviral peptides against HIV and other viruses with class I fusion proteins

  8. Fusion-power demonstration

    International Nuclear Information System (INIS)

    Henning, C.D.; Logan, B.G.; Carlson, G.A.; Neef, W.S.; Moir, R.W.; Campbell, R.B.; Botwin, R.; Clarkson, I.R.; Carpenter, T.J.

    1983-01-01

    As a satellite to the MARS (Mirror Advanced Reactor Study) a smaller, near-term device has been scoped, called the FPD (Fusion Power Demonstration). Envisioned as the next logical step toward a power reactor, it would advance the mirror fusion program beyond MFTF-B and provide an intermediate step toward commercial fusion power. Breakeven net electric power capability would be the goal such that no net utility power would be required to sustain the operation. A phased implementation is envisioned, with a deuterium checkout first to verify the plasma systems before significant neutron activation has occurred. Major tritium-related facilities would be installed with the second phase to produce sufficient fusion power to supply the recirculating power to maintain the neutral beams, ECRH, magnets and other auxiliary equipment

  9. International aspects of fusion

    International Nuclear Information System (INIS)

    Stacey, W.M. Jr.

    1979-12-01

    International collaborative efforts in magnetic confinement fusion in which the USA is involved are reviewed. These efforts are carried under the auspices of international agencies and through bilateral agreements

  10. Magnetic fusion energy

    International Nuclear Information System (INIS)

    Anon.

    1978-01-01

    The efforts of the Chemical Technology Division in the area of fusion energy include fuel handling, processing, and containment. These studies are closely coordinated with the ORNL Fusion Energy Division. Current experimental studies are concerned with the development of vacuum pumps for fusion reactors, the evaluation and development of techniques for recovering tritium (fuel) from either solid or liquid lithium containing blankets, and the use of deep beds of sorbents as roughing pumps and/or transfer operations. In addition, a small effort is devoted to the support of the ORNL design of The Next Step (TNS) in tokamak reactor development. The more applied studies--vacuum pump development and TNS design--are funded by the DOE/Magnetic Fusion Energy, and the more fundamental studies--blanket recovery and sorption in deep beds--are funded by the DOE/Basic Energy Sciences

  11. Fusion technology programme

    International Nuclear Information System (INIS)

    Finken, D.

    1984-04-01

    KfK participates to the Fusion Technology Programme of the European Community. Most of the work in progress addresses the Next European Torus (NET) and the long term technology aspects as defined in the 82/86 programme. A minor part serves to preparation of future contributions and to design studies on fusion concepts in a wider perspective. The Fusion Technology Programme of Euratom covers mainly aspects of nuclear engineering. Plasma engineering, heating, refueling and vacuum technology are at present part of the Physics Programme. In view of NET, integration of the different areas of work will be mandatory. KfK is therefore prepared to address technical aspects beyond the actual scope of the physics experiments. The technology tasks are reported project wise under title and code of the Euratom programme. Most of the projects described here are shared with other European fusion laboratories as indicated in the table annexed to this report. (orig./GG)

  12. Fusion-breeder program

    International Nuclear Information System (INIS)

    Moir, R.W.

    1982-01-01

    The various approaches to a combined fusion-fission reactor for the purpose of breeding 239 Pu and 233 U are described. Design aspects and cost estimates for fuel production and electricity generation are discussed

  13. Cold nuclear fusion device

    International Nuclear Information System (INIS)

    Ogino, Shinji.

    1991-01-01

    Selection of cathode material is a key to the attainment of cold nuclear fusion. However, there are only few reports on the cathode material at present and an effective development has been demanded. The device comprises an anode and a cathode and an electrolytic bath having metal salts dissolved therein and containing heavy water in a glass container. The anode is made of gold or platinum and the cathode is made of metals of V, Sr, Y, Nb, Hf or Ta, and a voltage of 3-25V is applied by way of a DC power source between them. The metal comprising V, Sr, Y, Nb, Hf or Ta absorbs deuterium formed by electrolysis of heavy water effectively to cause nuclear fusion reaction at substantially the same frequency and energy efficiency as palladium and titanium. Accordingly, a cold nuclear fusion device having high nuclear fusion generation frequency can be obtained. (N.H.)

  14. Cell fusions in mammals

    DEFF Research Database (Denmark)

    Larsson, Lars-Inge; Bjerregaard, Bolette; Talts, Jan Fredrik

    2008-01-01

    Cell fusions are important to fertilization, placentation, development of skeletal muscle and bone, calcium homeostasis and the immune defense system. Additionally, cell fusions participate in tissue repair and may be important to cancer development and progression. A large number of factors appear...... to regulate cell fusions, including receptors and ligands, membrane domain organizing proteins, proteases, signaling molecules and fusogenic proteins forming alpha-helical bundles that bring membranes close together. The syncytin family of proteins represent true fusogens and the founding member, syncytin-1......, has been documented to be involved in fusions between placental trophoblasts, between cancer cells and between cancer cells and host ells. We review the literature with emphasis on the syncytin family and propose that syncytins may represent universal fusogens in primates and rodents, which work...

  15. Fusion Canada issue 11

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1990-06-01

    A short bulletin from the National Fusion Program. Included in this issue is a report on operation at Tokamak de Varennes, CRITIC irradiations at AECL, Tritium systems at TFTR, physics contribution at ITER. 4 figs.

  16. Fusion technology (FT)

    International Nuclear Information System (INIS)

    1978-01-01

    The annual report of tha fusion technology (FT) working group discusses the projects carried out by the participating institutes in the fields of 1) fuel injection and plasma heating, 2) magnetic field technology, and 3) systems investigations. (HK) [de

  17. Fusion technology development

    International Nuclear Information System (INIS)

    1979-08-01

    This report includes information on the following chapters: (1) conceptual design studies, (2) magnetics, (3) plasma heating, fueling, and exhaust, (4) materials for fusion reactors, (5) alternate applications, and (6) environment and safety

  18. Fusion reactor materials

    International Nuclear Information System (INIS)

    Rowcliffe, A.F.; Burn, G.L.; Knee', S.S.; Dowker, C.L.

    1994-02-01

    This is the fifteenth in a series of semiannual technical progress reports on fusion reactor materials. This report combines research and development activities which were previously reported separately in the following progress reports: Alloy Development for Irradiation Performance; Damage Analysis and Fundamental Studies; Special purpose Materials. These activities are concerned principally with the effects of the neutronic and chemical environment on the properties and performance of reactor materials; together they form one element of the overall materials programs being conducted in support of the Magnetic Fusion Energy Program of the U.S. Department of Energy. The Fusion Reactor Materials Program is a national effort involving several national laboratories, universities, and industries. The purpose of this series of reports is to provide a working technical record for the use of the program participants, and to provide a means of communicating the efforts of materials scientists to the rest of the fusion community, both nationally and worldwide

  19. Fusion cost normalization

    International Nuclear Information System (INIS)

    Schulte, S.C.; Willke, T.L.

    1978-01-01

    The categorization and accounting methods described in this paper provide a common format that can be used to assess the economic character of magnetically confined fusion reactor design concepts. The format was developed with assistance from the fusion economics community, thus ensuring that the methods meet with the approval of potential users. The format will aid designers in the preparation of design concept cost estimates and also provide policy makers with a tool to assist in appraising which design concepts may be economically promising. Adherence to the format when evaluating prospective fusion reactor design concepts will result in the identification of the more promising concepts, thus enabling the fusion power alternatives with better economic potential to be quickly and efficiently developed

  20. Complimentary Advanced Fusion Exploration

    National Research Council Canada - National Science Library

    Alford, Mark G; Jones, Eric C; Bubalo, Adnan; Neumann, Melissa; Greer, Michael J

    2005-01-01

    .... The focus areas were in the following regimes: multi-tensor homographic computer vision image fusion, out-of-sequence measurement and track data handling, Nash bargaining approaches to sensor management, pursuit-evasion game theoretic modeling...

  1. Fusion plasma physics

    CERN Document Server

    Stacey, Weston M

    2012-01-01

    This revised and enlarged second edition of the popular textbook and reference contains comprehensive treatments of both the established foundations of magnetic fusion plasma physics and of the newly developing areas of active research. It concludes with a look ahead to fusion power reactors of the future. The well-established topics of fusion plasma physics -- basic plasma phenomena, Coulomb scattering, drifts of charged particles in magnetic and electric fields, plasma confinement by magnetic fields, kinetic and fluid collective plasma theories, plasma equilibria and flux surface geometry, plasma waves and instabilities, classical and neoclassical transport, plasma-materials interactions, radiation, etc. -- are fully developed from first principles through to the computational models employed in modern plasma physics. The new and emerging topics of fusion plasma physics research -- fluctuation-driven plasma transport and gyrokinetic/gyrofluid computational methodology, the physics of the divertor, neutral ...

  2. Fusion power demonstration

    International Nuclear Information System (INIS)

    Henning, C.D.; Logan, B.G.

    1983-01-01

    As a satellite to the MARS (Mirror Advanced Reactor Study) a smaller, near-term device has been scoped, called the FPD (Fusion Power Demonstration). Envisioned as the next logical step toward a power reactor, it would advance the mirror fusion program beyond MFTF-B and provide an intermediate step toward commercial fusion power. Breakeven net electric power capability would be the goal such that no net utility power would be required to sustain the operation. A phased implementation is envisioned, with a deuterium checkout first to verify the plasma systems before significant neutron activation has occurred. Major tritium-related facilities would be installed with the second phase to produce sufficient fusion power to supply the recirculating power to maintain the neutral beams, ECRH, magnets and other auxiliary equipment

  3. Optical Fiber Fusion Splicing

    CERN Document Server

    Yablon, Andrew D

    2005-01-01

    This book is an up-to-date treatment of optical fiber fusion splicing incorporating all the recent innovations in the field. It provides a toolbox of general strategies and specific techniques that the reader can apply when optimizing fusion splices between novel fibers. It specifically addresses considerations important for fusion splicing of contemporary specialty fibers including dispersion compensating fiber, erbium-doped gain fiber, polarization maintaining fiber, and microstructured fiber. Finally, it discusses the future of optical fiber fusion splicing including silica and non-silica based optical fibers as well as the trend toward increasing automation. Whilst serving as a self-contained reference work, abundant citations from the technical literature will enable readers to readily locate primary sources.

  4. Controlled thermonuclear fusion

    International Nuclear Information System (INIS)

    Sakanaka, P.H.

    1984-01-01

    A simplified review on the status of the controlled thermonuclear fusion research aiming to present the motivation, objective, necessary conditions and adopted methods to reach the objective. (M.C.K.) [pt

  5. Fusion safety program plan

    International Nuclear Information System (INIS)

    Crocker, J.G.; Holland, D.F.; Herring, J.S.

    1980-09-01

    The program plan consists of research that has been divided into 13 different areas. These areas focus on the radioactive inventories that are expected in fusion reactors, the energy sources potentially available to release a portion of these inventories, and analysis and design techniques to assess and ensure that the safety risks associated with operation of magnetic fusion facilities are acceptably low. The document presents both long-term program requirements that must be fulfilled as part of the commercialization of fusion power and a five-year plan for each of the 13 different program areas. Also presented is a general discussion of magnetic fusion reactor safety, a method for establishing priorities in the program, and specific priority ratings for each task in the five-year plan

  6. Fusion Revisits CERN

    CERN Multimedia

    2001-01-01

    It's going to be a hot summer at CERN. At least in the Main Building, where from 13 July to 20 August an exhibition is being hosted on nuclear fusion, the energy of the Stars. Nuclear fusion is the engine driving the stars but also a potential source of energy for mankind. The exhibition shows the different nuclear fusion techniques and research carried out on the subject in Europe. Inaugurated at CERN in 1993, following collaboration between Lausanne's CRPP-EPFL and CERN, with input from Alessandro Pascolini of Italy's INFN, this exhibition has travelled round Europe before being revamped and returning to CERN. 'Fusion, Energy of the Stars', from 13 July onwards, Main Building

  7. Fusion Simulation Program

    International Nuclear Information System (INIS)

    Greenwald, Martin

    2011-01-01

    Many others in the fusion energy and advanced scientific computing communities participated in the development of this plan. The core planning team is grateful for their important contributions. This summary is meant as a quick overview the Fusion Simulation Program's (FSP's) purpose and intentions. There are several additional documents referenced within this one and all are supplemental or flow down from this Program Plan. The overall science goal of the DOE Office of Fusion Energy Sciences (FES) Fusion Simulation Program (FSP) is to develop predictive simulation capability for magnetically confined fusion plasmas at an unprecedented level of integration and fidelity. This will directly support and enable effective U.S. participation in International Thermonuclear Experimental Reactor (ITER) research and the overall mission of delivering practical fusion energy. The FSP will address a rich set of scientific issues together with experimental programs, producing validated integrated physics results. This is very well aligned with the mission of the ITER Organization to coordinate with its members the integrated modeling and control of fusion plasmas, including benchmarking and validation activities. (1). Initial FSP research will focus on two critical Integrated Science Application (ISA) areas: ISA1, the plasma edge; and ISA2, whole device modeling (WDM) including disruption avoidance. The first of these problems involves the narrow plasma boundary layer and its complex interactions with the plasma core and the surrounding material wall. The second requires development of a computationally tractable, but comprehensive model that describes all equilibrium and dynamic processes at a sufficient level of detail to provide useful prediction of the temporal evolution of fusion plasma experiments. The initial driver for the whole device model will be prediction and avoidance of discharge-terminating disruptions, especially at high performance, which are a critical

  8. The fusion dilemma

    International Nuclear Information System (INIS)

    Carruthers, R.

    1981-01-01

    The present position in fusion research is reviewed and discussed with relation to the requirements of an economic reactor. Meeting these requirements calls for a mission-oriented project of interdisciplinary character whose timely evolution from one with a research orientation, is a challenging management problem. The cost-effectiveness of future expenditure on fusion research is dependent upon acknowledging this challenge and realistically facing the difficult tasks which it presents. (U.K.)

  9. Possible fusion reactor

    International Nuclear Information System (INIS)

    Yoshikawa, S.

    1976-05-01

    A scheme to improve performance characteristics of a tokamak-type fusion reactor is proposed. Basically, the tokamak-type plasma could be moved around so that the plasma could be heated by compression, brought to the region where the blanket surrounds the plasma, and moved so as to keep wall loading below the acceptable limit. This idea should be able to help to economize a fusion reactor

  10. Fusion power plant economics

    International Nuclear Information System (INIS)

    Miller, R.L.

    1996-01-01

    The rationale, methodology, and updated comparative results of cost projections for magnetic-fusion-energy central-station electric power plants are considered. Changing market and regulatory conditions, particularly in the U.S., prompt fundamental reconsideration of what constitutes a competitive future energy-source technology and has implications for the direction and emphasis of appropriate near-term research and development programs, for fusion and other advanced generation systems. 36 refs., 2 figs., 2 tabs

  11. Sonoluminescence and bubble fusion

    OpenAIRE

    Arakeri, Vijay H

    2003-01-01

    Sonoluminescence (SL), the phenomenon of light emission from nonlinear motion of a gas bubble, involves an extreme degree of energy focusing. The conditions within the bubble during the last stages of the nearly catastrophic implosion are thought to parallel the efforts aimed at developing inertial confinement fusion. A limited review on the topic of SL and its possible connection to bubble nuclear fusion is presented here. The emphasis is on looking for a link between the various forms o...

  12. Fusion reactor materials

    International Nuclear Information System (INIS)

    Anon.

    1977-01-01

    The following topics are briefly discussed: (1) surface blistering studies on fusion reactor materials, (2) TFTR design support activities, (3) analysis of samples bombarded in-situ in PLT, (4) chemical sputtering effects, (5) modeling of surface behavior, (6) ion migration in glow discharge tube cathodes, (7) alloy development for irradiation performance, (8) dosimetry and damage analysis, and (9) development of tritium migration in fusion devices and reactors

  13. Bringing together fusion research

    International Nuclear Information System (INIS)

    Leiser, M.

    1982-01-01

    The increasing involvement of the IAEA in fusion, together with the growing efforts devoted to this area, are described. The author puts forward the idea that one of the most important aspects of this involvement is in providing a world-wide forum for scientists. The functions of the IFRC (International Fusion Research Council) as an advisory group are outlined, and the role played by IFRC in the definition and objectives of INTOR (International Tokamak Reactor) are briefly described

  14. Fusion Canada issue 13

    International Nuclear Information System (INIS)

    1991-01-01

    A short bulletin from the National Fusion Program. Included in this issue is a report on Canada's plans to participate in the Engineering Design Activities (EDA), bilateral meetings with Canada and the U.S., committee meeting with Canada-Europe, an update at Tokamak de Varennes on Plasma Biasing experiments and boronized graphite tests, fusion materials research at the University of Toronto using a dual beam accelerator and a review of the CFFTP and the CCFM. 2 figs

  15. Conference on Norwegian fusion research

    International Nuclear Information System (INIS)

    The question of instituting a systematic research programme in Norway on aspects of thermonuclear and plasma physics has been raised. The conference here reported was intended to provide basic information on the status of fusion research internationally and to discuss a possible Norwegian programme. The main contributions covered the present status of fusion research, international cooperation, fusion research in small countries and minor laboratories, fusion research in Denmark and Sweden, and a proposed fusion experiment in Bergen. (JIW)

  16. Acylation of Therapeutic Peptides

    DEFF Research Database (Denmark)

    Trier, Sofie; Henriksen, Jonas Rosager; Jensen, Simon Bjerregaard

    ) , which promotes intestinal growth and is used to treat bowel disorders such as inflammatory bowel diseases and short bowel syndrome, and the 32 amino acid salmon calcitonin (sCT), which lowers blood calcium and is employed in the treatment of post-menopausal osteoporosis and hypercalcemia. The two...... peptides are similar in size and structure, but oppositely charged at physiological pH. Both peptides were acylated with linear acyl chains of systematically increasing length, where sCT was furthermore acylated at two different positions on the peptide backbone. For GLP-2, we found that increasing acyl...... remained optimal overall. The results indicate that rational acylation of GLP-2 can increase its in vitro intestinal absorption, alone or in combination with permeation enhancers, and are consistent with the initial project hypothesis. For sCT, an unpredicted effect of acylation largely superseded...

  17. Status of fusion technology

    International Nuclear Information System (INIS)

    Mohan, Ashok

    1978-01-01

    The current status of fusion technology is surveyed. Limited reserves of fossil fuel and dangers of proliferation from nuclear reactors have brought into focus the need to develop an optional energy source. Fusion is being looked upon as an optional energy source which is free from environmental hazards unlike fossil fuels and nuclear reactors. Investments in R and D of fusion energy have increased rapidly in USA, Japan, USSR and European countries. Out of the various fusion fuels known, a mixture of D and T is widely chosen. The main problem in fusion technology is the confinement of plasma for a time sufficient to start the fusion reaction. This can be done magnetically or inertially. The three approaches to magnetic confinement are : (1) tokamak, (2) mirror and (3) pinch. Inertial confinement makes use of lasers or electron beams or ion beams. Both the methods of confinement i.e. magnetic and inertial have problems which are identified and their nature is discussed. (M.G.B.)

  18. Energy from inertial fusion

    International Nuclear Information System (INIS)

    1995-03-01

    This book contains 22 articles on inertial fusion energy (IFE) research and development written in the framework of an international collaboration of authors under the guidance of an advisory group on inertial fusion energy set up in 1991 to advise the IAEA. It describes the actual scientific, engineering and technological developments in the field of inertial confinement fusion (ICF). It also identifies ways in which international co-operation in ICF could be stimulated. The book is intended for a large audience and provides an introduction to inertial fusion energy and an overview of the various technologies needed for IFE power plants to be developed. It contains chapters on (i) the fundamentals of IFE; (ii) inertial confinement target physics; (iii) IFE power plant design principles (requirements for power plant drivers, solid state laser drivers, gas laser drivers, heavy ion drivers, and light ion drivers, target fabrication and positioning, reaction chamber systems, power generation and conditioning and radiation control, materials management and target materials recovery), (iv) special design issues (radiation damage in structural materials, induced radioactivity, laser driver- reaction chamber interfaces, ion beam driver-reaction chamber interfaces), (v) inertial fusion energy development strategy, (vi) safety and environmental impact, (vii) economics and other figures of merit; (viii) other uses of inertial fusion (both those involving and not involving implosions); and (ix) international activities. Refs, figs and tabs

  19. Perspectives of fusion power

    International Nuclear Information System (INIS)

    Jensen, V.O.

    1984-01-01

    New and practically inexhaustible sources of energy must be developed for the period when oil, coal and uranium will become scarce and expensive. Nuclear fusion holds great promise as one of these practically inexhaustible energy sources. Based on the deuteriumtritium reaction with tritium obtained from naturally occuring lithium, which is also widely available in Europe, the accessible energy resources in the world are 3.10 12 to 3.10 16 toe; based on the deuterium-deuterium reaction, the deuterium content of the oceans corresponds to 10 20 toe. It is presently envisaged that in order to establish fusion as a large-scale energy source, three major thresholds must be reached: - Scientific feasibility, - Technical feasibility, i.e. the proof that the basic technical problems of the fusion reactor can be solved. - Commercial feasibility, i.e. proof that fusion power reactors can be built on an industrial scale, can be operated reliably and produce usable energy at prices competitive with other energy sources. From the above it is clear that the route to commercial fusion will be long and costly and involve the solution of extremely difficult technical problems. In view of the many steps which have to be taken, it appears unlikely that commercial fusion power will be in general use within the next 50 years and by that time world-wide expenditure on research, development and demonstration may well have exceeded 100 Bio ECU. (author)

  20. 46 CFR 133.160 - Rescue boat embarkation, launching and recovery arrangements.

    Science.gov (United States)

    2010-10-01

    ...) OFFSHORE SUPPLY VESSELS LIFESAVING SYSTEMS Requirements for All OSVs § 133.160 Rescue boat embarkation, launching and recovery arrangements. (a) Each davit for a rescue boat must be approved under approval series... 46 Shipping 4 2010-10-01 2010-10-01 false Rescue boat embarkation, launching and recovery...

  1. 46 CFR 199.160 - Rescue boat embarkation, launching and recovery arrangements.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Rescue boat embarkation, launching and recovery...) LIFESAVING APPLIANCES AND ARRANGEMENTS LIFESAVING SYSTEMS FOR CERTAIN INSPECTED VESSELS Requirements for All Vessels § 199.160 Rescue boat embarkation, launching and recovery arrangements. (a) Each rescue boat must...

  2. 46 CFR 111.75-16 - Lighting of survival craft and rescue boats.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 4 2010-10-01 2010-10-01 false Lighting of survival craft and rescue boats. 111.75-16... craft and rescue boats. (a) During preparation, launching, and recovery, each survival craft and rescue... of circuits must be such that the lighting for adjacent launching stations for survival craft or...

  3. Irisin is a pro-myogenic factor that induces skeletal muscle hypertrophy and rescues denervation-induced atrophy.

    Science.gov (United States)

    Reza, Musarrat Maisha; Subramaniyam, Nathiya; Sim, Chu Ming; Ge, Xiaojia; Sathiakumar, Durgalakshmi; McFarlane, Craig; Sharma, Mridula; Kambadur, Ravi

    2017-10-24

    Exercise induces expression of the myokine irisin, which is known to promote browning of white adipose tissue and has been shown to mediate beneficial effects following exercise. Here we show that irisin induces expression of a number of pro-myogenic and exercise response genes in myotubes. Irisin increases myogenic differentiation and myoblast fusion via activation of IL6 signaling. Injection of irisin in mice induces significant hypertrophy and enhances grip strength of uninjured muscle. Following skeletal muscle injury, irisin injection improves regeneration and induces hypertrophy. The effects of irisin on hypertrophy are due to activation of satellite cells and enhanced protein synthesis. In addition, irisin injection rescues loss of skeletal muscle mass following denervation by enhancing satellite cell activation and reducing protein degradation. These data suggest that irisin functions as a pro-myogenic factor in mice.

  4. Controlled thermonuclear fusion: research on magnetic fusion

    International Nuclear Information System (INIS)

    Paris, P.J.

    1988-12-01

    Recent progress in thermonuclear fusion research indicates that the scientists' schedule for the demonstration of the scientific feasibility will be kept and that break-even will be attained in the course of the next decade. To see the implementation of ignition, however, the generation of future experiments must be awaited. These projects are currently under study. With technological research going on in parallel, they should at the same time contribute to the design of a reactor. Fusion reactors will be quite different from the fission nuclear reactors we know, and the waste of the plants will also be of a different nature. It is still too early to define the precise design of a fusion reactor. On the basis of a toric machine concept like that of the tokamak, we can, however, envisage that the problems with which we are confronted will be solved one after the other. As we have just seen, these will be the objectives of the future experimental installations where ignition will be possible and where the flux of fast neutrons will be so strong that they will allow the study of low-activation materials which will be used in the structure of the reactor. But this is also a task in which from now onwards numerous laboratories in Europe and in the world participate. The works are in fact punctiform, and often the mutual incidences can only be determined by an approach simulated by numerical codes. (author) 19 figs., 6 tabs., 8 refs

  5. Phase I vaccination trial of SYT-SSX junction peptide in patients with disseminated synovial sarcoma

    Directory of Open Access Journals (Sweden)

    Asanuma Hiroko

    2005-01-01

    Full Text Available Abstract Background Synovial sarcoma is a high-grade malignant tumor of soft tissue, characterized by the specific chromosomal translocation t(X;18, and its resultant SYT-SSX fusion gene. Despite intensive multimodality therapy, the majority of metastatic or relapsed diseases still remain incurable, thus suggesting a need for new therapeutic options. We previously demonstrated the antigenicity of SYT-SSX gene-derived peptides by in vitro analyses. The present study was designed to evaluate in vivo immunological property of a SYT-SSX junction peptide in selected patients with synovial sarcoma. Methods A 9-mer peptide (SYT-SSX B: GYDQIMPKK spanning the SYT-SSX fusion region was synthesized. Eligible patients were those (i who have histologically and genetically confirmed, unresectable synovial sarcoma (SYT-SSX1 or SYT-SSX2 positive, (ii HLA-A*2402 positive, (iii between 20 and 70 years old, (iv ECOG performance status between 0 and 3, and (v who gave informed consent. Vaccinations with SYT-SSX B peptide (0.1 mg or 1.0 mg were given subcutaneously six times at 14-day intervals. These patients were evaluated for DTH skin test, adverse events, tumor size, tetramer staining, and peptide-specific CTL induction. Results A total of 16 vaccinations were carried out in six patients. The results were (i no serious adverse effects or DTH reactions, (ii suppression of tumor progression in one patient, (iii increases in the frequency of peptide-specific CTLs in three patients and a decrease in one patient, and (iv successful induction of peptide-specific CTLs from four patients. Conclusions Our findings indicate the safety of the SYT-SSX junction peptide in the use of vaccination and also give support to the property of the peptide to evoke in vivo immunological responses. Modification of both the peptide itself and the related protocol is required to further improve the therapeutic efficacy.

  6. A phage display selected 7-mer peptide inhibitor of the Tannerella forsythia metalloprotease-like enzyme Karilysin can be truncated to Ser-Trp-Phe-Pro.

    Science.gov (United States)

    Skottrup, Peter Durand; Sørensen, Grete; Ksiazek, Miroslaw; Potempa, Jan; Riise, Erik

    2012-01-01

    Tannerella forsythia is a gram-negative bacteria, which is strongly associated with the development of periodontal disease. Karilysin is a newly identified metalloprotease-like enzyme, that is secreted from T. forsythia. Karilysin modulates the host immune response and is therefore considered a likely drug target. In this study peptides were selected towards the catalytic domain from Karilysin (Kly18) by phage display. The peptides were linear with low micromolar binding affinities. The two best binders (peptide14 and peptide15), shared the consensus sequence XWFPXXXGGG. A peptide15 fusion with Maltose Binding protein (MBP) was produced with peptide15 fused to the N-terminus of MBP. The peptide15-MBP was expressed in E. coli and the purified fusion-protein was used to verify Kly18 specific binding. Chemically synthesised peptide15 (SWFPLRSGGG) could inhibit the enzymatic activity of both Kly18 and intact Karilysin (Kly48). Furthermore, peptide15 could slow down the autoprocessing of intact Kly48 to Kly18. The WFP motif was important for inhibition and a truncation study further demonstrated that the N-terminal serine was also essential for Kly18 inhibition. The SWFP peptide had a Ki value in the low micromolar range, which was similar to the intact peptide15. In conclusion SWFP is the first reported inhibitor of Karilysin and can be used as a valuable tool in structure-function studies of Karilysin.

  7. A phage display selected 7-mer peptide inhibitor of the Tannerella forsythia metalloprotease-like enzyme Karilysin can be truncated to Ser-Trp-Phe-Pro.

    Directory of Open Access Journals (Sweden)

    Peter Durand Skottrup

    Full Text Available Tannerella forsythia is a gram-negative bacteria, which is strongly associated with the development of periodontal disease. Karilysin is a newly identified metalloprotease-like enzyme, that is secreted from T. forsythia. Karilysin modulates the host immune response and is therefore considered a likely drug target. In this study peptides were selected towards the catalytic domain from Karilysin (Kly18 by phage display. The peptides were linear with low micromolar binding affinities. The two best binders (peptide14 and peptide15, shared the consensus sequence XWFPXXXGGG. A peptide15 fusion with Maltose Binding protein (MBP was produced with peptide15 fused to the N-terminus of MBP. The peptide15-MBP was expressed in E. coli and the purified fusion-protein was used to verify Kly18 specific binding. Chemically synthesised peptide15 (SWFPLRSGGG could inhibit the enzymatic activity of both Kly18 and intact Karilysin (Kly48. Furthermore, peptide15 could slow down the autoprocessing of intact Kly48 to Kly18. The WFP motif was important for inhibition and a truncation study further demonstrated that the N-terminal serine was also essential for Kly18 inhibition. The SWFP peptide had a Ki value in the low micromolar range, which was similar to the intact peptide15. In conclusion SWFP is the first reported inhibitor of Karilysin and can be used as a valuable tool in structure-function studies of Karilysin.

  8. Therapeutic HIV Peptide Vaccine

    DEFF Research Database (Denmark)

    Fomsgaard, Anders

    2015-01-01

    Therapeutic vaccines aim to control chronic HIV infection and eliminate the need for lifelong antiretroviral therapy (ART). Therapeutic HIV vaccine is being pursued as part of a functional cure for HIV/AIDS. We have outlined a basic protocol for inducing new T cell immunity during chronic HIV-1...... infection directed to subdominant conserved HIV-1 epitopes restricted to frequent HLA supertypes. The rationale for selecting HIV peptides and adjuvants are provided. Peptide subunit vaccines are regarded as safe due to the simplicity, quality, purity, and low toxicity. The caveat is reduced immunogenicity...

  9. Descriptors for antimicrobial peptides

    DEFF Research Database (Denmark)

    Jenssen, Håvard

    2011-01-01

    of these are currently being used in quantitative structure--activity relationship (QSAR) studies for AMP optimization. Additionally, some key commercial computational tools are discussed, and both successful and less successful studies are referenced, illustrating some of the challenges facing AMP scientists. Through...... examples of different peptide QSAR studies, this review highlights some of the missing links and illuminates some of the questions that would be interesting to challenge in a more systematic fashion. Expert opinion: Computer-aided peptide QSAR using molecular descriptors may provide the necessary edge...

  10. Genetic and biochemical analysis of peptide transport in Escherichia coli

    International Nuclear Information System (INIS)

    Andrews, J.C.

    1986-01-01

    E. coli peptide transport mutants have been isolated based on their resistance to toxic tripeptides. These genetic defects were found to map in two distinct chromosomal locations. The transport systems which require expression of the trp-linked opp genes and the oppE gene(s) for activity were shown to have different substrate preferences. Growth of E. coli in medium containing leucine results in increased entry of exogenously supplied tripeptides into the bacterial cell. This leucine-mediated elevation of peptide transport required expression of the trp-linked opp operon and was accompanied by increased sensitivity to toxic tripeptides, by an enhanced capacity to utilize nutritional peptides, and by an increase in both the velocity and apparent steady-state level of L-(U- 14 C)alanyl-L-alanyl-L-alanine accumulation for E. coli grown in leucine-containing medium relative to these parameters of peptide transport measured with bacteria grown in media lacking leucine. Direct measurement of opp operon expression by pulse-labeling experiments demonstrated that growth of E. coli in the presence of leucine resulted in increased synthesis of the oppA-encoded periplasmic binding protein. The transcriptional regulation of the trp-linked opp operon of E. coli was investigated using λ placMu51-generated lac operon fusions. Synthesis of β-galactosidase by strains harboring oppA-lac, oppB-lac, and oppD-lac fusions occurred at a basal level when the fusion-containing strains were grown in minimal medium

  11. Non-fusion and fusion expression of beta-galactosidase from Lactobacillus bulgaricus in Lactococcus lactis.

    Science.gov (United States)

    Wang, Chuan; Zhang, Chao-Wu; Liu, Heng-Chuan; Yu, Qian; Pei, Xiao-Fang

    2008-10-01

    To construct four recombinant Lactococcus lactis strains exhibiting high beta-galactosidase activity in fusion or non-fusion ways, and to study the influence factors for their protein expression and secretion. The gene fragments encoding beta-galactosidase from two strains of Lactobacillus bulgaricus, wch9901 isolated from yogurt and 1.1480 purchased from the Chinese Academy of Sciences, were amplified and inserted into lactococcal expression vector pMG36e. For fusion expression, the open reading frame of the beta-galactosidase gene was amplified, while for non-fusion expression, the open reading frame of the beta-galactosidase gene was amplified with its native Shine-Dalgarno sequence upstream. The start codon of the beta-galactosidase gene partially overlapped with the stop codon of vector origin open reading frame. Then, the recombinant plasmids were transformed into Escherichia coli DH5 alpha and Lactococcus lactis subsp. lactis MG1363 and confirmed by determining beta-galactosidase activities. The non-fusion expression plasmids showed a significantly higher beta-galactosidase activity in transformed strains than the fusion expression plasmids. The highest enzyme activity was observed in Lactococcus lactis transformed with the non-fusion expression plasmids which were inserted into the beta-galactosidase gene from Lactobacillus bulgaricus wch9901. The beta-galactosidase activity was 2.75 times as high as that of the native counterpart. In addition, beta-galactosidase expressed by recombinant plasmids in Lactococcus lactis could be secreted into the culture medium. The highest secretion rate (27.1%) was observed when the culture medium contained 20 g/L of lactose. Different properties of the native bacteria may have some effects on the protein expression of recombinant plasmids. Non-fusion expression shows a higher enzyme activity in host bacteria. There may be a host-related weak secretion signal peptide gene within the structure gene of Lb. bulgaricus beta

  12. Chemical rescue of cleft palate and midline defects in conditional GSK-3beta mice.

    Science.gov (United States)

    Liu, Karen J; Arron, Joseph R; Stankunas, Kryn; Crabtree, Gerald R; Longaker, Michael T

    2007-03-01

    Glycogen synthase kinase-3beta (GSK-3beta) has integral roles in a variety of biological processes, including development, diabetes, and the progression of Alzheimer's disease. As such, a thorough understanding of GSK-3beta function will have a broad impact on human biology and therapeutics. Because GSK-3beta interacts with many different pathways, its specific developmental roles remain unclear. We have discovered a genetic requirement for GSK-3beta in midline development. Homozygous null mice display cleft palate, incomplete fusion of the ribs at the midline and bifid sternum as well as delayed sternal ossification. Using a chemically regulated allele of GSK-3beta (ref. 6), we have defined requirements for GSK-3beta activity during discrete temporal windows in palatogenesis and skeletogenesis. The rapamycin-dependent allele of GSK-3beta produces GSK-3beta fused to a tag, FRB* (FKBP/rapamycin binding), resulting in a rapidly destabilized chimaeric protein. In the absence of drug, GSK-3beta(FRB)*(/FRB)* mutants appear phenotypically identical to GSK-3beta-/- mutants. In the presence of drug, GSK-3betaFRB* is rapidly stabilized, restoring protein levels and activity. Using this system, mutant phenotypes were rescued by restoring endogenous GSK-3beta activity during two distinct periods in gestation. This technology provides a powerful tool for defining windows of protein function during development.

  13. CDKL5 protein substitution therapy rescues neurological phenotypes of a mouse model of CDKL5 disorder.

    Science.gov (United States)

    Trazzi, Stefania; De Franceschi, Marianna; Fuchs, Claudia; Bastianini, Stefano; Viggiano, Rocchina; Lupori, Leonardo; Mazziotti, Raffaele; Medici, Giorgio; Lo Martire, Viviana; Ren, Elisa; Rimondini, Roberto; Zoccoli, Giovanna; Bartesaghi, Renata; Pizzorusso, Tommaso; Ciani, Elisabetta

    2018-05-01

    Cyclin-dependent kinase like-5 (CDKL5) disorder is a rare neurodevelopmental disease caused by mutations in the CDKL5 gene. The consequent misexpression of the CDKL5 protein in the nervous system leads to a severe phenotype characterized by intellectual disability, motor impairment, visual deficits and early-onset epilepsy. No therapy is available for CDKL5 disorder. It has been reported that a protein transduction domain (TAT) is able to deliver macromolecules into cells and even into the brain when fused to a given protein. We demonstrate that TAT-CDKL5 fusion protein is efficiently internalized by target cells and retains CDKL5 activity. Intracerebroventricular infusion of TAT-CDKL5 restored hippocampal development, hippocampus-dependent memory and breathing pattern in Cdkl5-null mice. Notably, systemically administered TAT-CDKL5 protein passed the blood-brain-barrier, reached the CNS, and rescued various neuroanatomical and behavioral defects, including breathing pattern and visual responses. Our results suggest that CDKL5 protein therapy may be an effective clinical tool for the treatment of CDKL5 disorder.

  14. Fusion of Selected Cells and Vesicles Mediated by Optically Trapped Plasmonic Nanoparticles

    DEFF Research Database (Denmark)

    Bahadori, Azra

    . In this work, we introduce a novel and extremely flexible physical method which can trigger membrane fusion in a highly selective manner not only between synthetic GUVs of different compositions, but also between live cells which remain viable after fusion. Optical tweezers’ laser (1064 nm) is used to position....... The concept of cellular delivery is also known as targeted drug delivery and is quite a hot research topic internationally. Therefore, there have been efforts to develop various chemical molecules, proteins/peptides and physical approaches to trigger membrane fusion between synthetic giant unilamellar...... and merging of the two membranes results in merging the two membranes thereby completes the fusion. Complete fusion is associated with lipid mixing and lumen mixing which are both imaged by a high resolution confocal microscope. The confocal imaging enables quantification of the associated lipid mixing...

  15. Advanced fusion reactor

    International Nuclear Information System (INIS)

    Tomita, Yukihiro

    2003-01-01

    The main subjects on fusion research are now on D-T fueled fusion, mainly due to its high fusion reaction rate. However, many issues are still remained on the wall loading by the 14 MeV neutrons. In the case of D-D fueled fusion, the neutron wall loading is still remained, though the technology related to tritium breeding is not needed. The p- 6 Li and p- 11 B fueled fusions are not estimated to be the next generation candidate until the innovated plasma confinement technologies come in useful to achieve the high performance plasma parameters. The fusion reactor of D- 3 He fuels has merits on the smaller neutron wall loading and tritium handling. However, there are difficulties on achieving the high temperature plasma more than 100 keV. Furthermore the high beta plasma is needed to decrease synchrotron radiation loss. In addition, the efficiency of the direct energy conversion from protons coming out from fusion reaction is one of the key parameters in keeping overall power balance. Therefore, open magnetic filed lines should surround the plasma column. In this paper, we outlined the design of the commercial base reactor (ARTEMIS) of 1 GW electric output power configured by D- 3 He fueled FRC (Field Reversed Configuration). The ARTEMIS needs 64 kg of 3 He per a year. On the other hand, 1 million tons of 3 He is estimated to be in the moon. The 3 He of about 10 23 kg are to exist in gaseous planets such as Jupiter and Saturn. (Y. Tanaka)

  16. Ion beam inertial fusion

    International Nuclear Information System (INIS)

    Bangerter, R.O.

    1995-01-01

    About twenty years ago, A. W. Maschke of Brookhaven National Laboratory and R. L. Martin of Argonne National Laboratory recognized that the accelerators that have been developed for high energy and nuclear physics are, in many ways, ideally suited to the requirements of inertial fusion power production. These accelerators are reliable, they have a long operating life, and they can be efficient. Maschke and Martin noted that they can focus ion beams to small focal spots over distances of many meters and that they can readily operate at the high pulse repetition rates needed for commercial power production. Fusion, however, does impose some important new constraints that are not important for high energy or nuclear physics applications. The most challenging new constraint from a scientific standpoint is the requirement that the accelerator deliver more than 10 14 W of beam power to a small quantity (less than 100 mg) of matter. The most challenging constraint from an engineering standpoint is accelerator cost. Maschke showed theoretically that accelerators could produce adequate work. Heavy-ion fusion is widely recognized to be a promising approach to inertial fusion power production. It provides an excellent opportunity to apply methods and technology developed for basic science to an important societal need. The pulsed-power community has developed a complementary, parallel approach to ion beam fusion known as light-ion fusion. The talk will discuss both heavy-ion and light-ion fusion. It will explain target physics requirements and show how they lead to constraints on the usual accelerator parameters such as kinetic energy, current, and emittance. The talk will discuss experiments that are presently underway, specifically experiments on high-current ion sources and injectors, pulsed-power machines recirculating induction accelerators, and transverse beam combining. The talk will give a brief description of a proposed new accelerator called Elise

  17. Fusion Canada issue 29

    International Nuclear Information System (INIS)

    1995-10-01

    A short bulletin from the National Fusion Program highlighting in this issue Canada-Europe Accords: 5 year R and D collaboration for the International Thermonuclear Experimental Reactor (ITER) AECL is designated to arrange and implement the Memorandum of Understanding (MOU) and the ITER Engineering Design Activities (EDA) while EUROTAM is responsible for operating Europe's Fusion R and D programs plus MOU and EDA. The MOU includes tokamaks, plasma physics, fusion technology, fusion fuels and other approaches to fusion energy (as alternatives to tokamaks). STOR-M Tokamak was restarted at the University of Saskatchewan following upgrades to the plasma chamber to accommodate the Compact Toroid (CT) injector. The CT injector has a flexible attachment thus allowing for injection angle adjustments. Real-time video images of a single plasma discharge on TdeV showing that as the plasma density increases, in a linear ramp divertor, the plasma contact with the horizontal plate decreases while contact increases with the oblique plate. Damage-resistant diffractive optical elements (DOE) have been developed for Inertial Confinement Fusion (ICF) research by Gentac Inc. and the National Optics Institute, laser beam homogeniser and laser harmonic separator DOE can also be made using the same technology. Studies using TdeV indicate that a divertor will be able to pump helium from the tokamak with a detached-plasma divertor but helium extraction performance must first be improved, presently the deuterium:helium retention radio-indicates that in order to pump enough helium through a fusion reactor, too much deuterium-tritium fuel would be pumped out. 2 fig

  18. Advanced fusion reactor

    Energy Technology Data Exchange (ETDEWEB)

    Tomita, Yukihiro [National Inst. for Fusion Science, Toki, Gifu (Japan)

    2003-04-01

    The main subjects on fusion research are now on D-T fueled fusion, mainly due to its high fusion reaction rate. However, many issues are still remained on the wall loading by the 14 MeV neutrons. In the case of D-D fueled fusion, the neutron wall loading is still remained, though the technology related to tritium breeding is not needed. The p-{sup 6}Li and p-{sup 11}B fueled fusions are not estimated to be the next generation candidate until the innovated plasma confinement technologies come in useful to achieve the high performance plasma parameters. The fusion reactor of D-{sup 3}He fuels has merits on the smaller neutron wall loading and tritium handling. However, there are difficulties on achieving the high temperature plasma more than 100 keV. Furthermore the high beta plasma is needed to decrease synchrotron radiation loss. In addition, the efficiency of the direct energy conversion from protons coming out from fusion reaction is one of the key parameters in keeping overall power balance. Therefore, open magnetic filed lines should surround the plasma column. In this paper, we outlined the design of the commercial base reactor (ARTEMIS) of 1 GW electric output power configured by D-{sup 3}He fueled FRC (Field Reversed Configuration). The ARTEMIS needs 64 kg of {sup 3}He per a year. On the other hand, 1 million tons of {sup 3}He is estimated to be in the moon. The {sup 3}He of about 10{sup 23} kg are to exist in gaseous planets such as Jupiter and Saturn. (Y. Tanaka)

  19. Reliable Rescue Routing Optimization for Urban Emergency Logistics under Travel Time Uncertainty

    Directory of Open Access Journals (Sweden)

    Qiuping Li

    2018-02-01

    Full Text Available The reliability of rescue routes is critical for urban emergency logistics during disasters. However, studies on reliable rescue routing under stochastic networks are still rare. This paper proposes a multiobjective rescue routing model for urban emergency logistics under travel time reliability. A hybrid metaheuristic integrating ant colony optimization (ACO and tabu search (TS was designed to solve the model. An experiment optimizing rescue routing plans under a real urban storm event, was carried out to validate the proposed model. The experimental results showed how our approach can improve rescue efficiency with high travel time reliability.

  20. Antimicrobial Peptides: An Introduction.

    Science.gov (United States)

    Haney, Evan F; Mansour, Sarah C; Hancock, Robert E W

    2017-01-01

    The "golden era" of antibiotic discovery has long passed, but the need for new antibiotics has never been greater due to the emerging threat of antibiotic resistance. This urgency to develop new antibiotics has motivated researchers to find new methods to combat pathogenic microorganisms resulting in a surge of research focused around antimicrobial peptides (AMPs; also termed host defense peptides) and their potential as therapeutics. During the past few decades, more than 2000 AMPs have been identified from a diverse range of organisms (animals, fungi, plants, and bacteria). While these AMPs share a number of common features and a limited number of structural motifs; their sequences, activities, and targets differ considerably. In addition to their antimicrobial effects, AMPs can also exhibit immunomodulatory, anti-biofilm, and anticancer activities. These diverse functions have spurred tremendous interest in research aimed at understanding the activity of AMPs, and various protocols have been described to assess different aspects of AMP function including screening and evaluating the activities of natural and synthetic AMPs, measuring interactions with membranes, optimizing peptide function, and scaling up peptide production. Here, we provide a general overview of AMPs and introduce some of the methodologies that have been used to advance AMP research.

  1. Evolutionary rescue: linking theory for conservation and medicine.

    Science.gov (United States)

    Alexander, Helen K; Martin, Guillaume; Martin, Oliver Y; Bonhoeffer, Sebastian

    2014-12-01

    Evolutionary responses that rescue populations from extinction when drastic environmental changes occur can be friend or foe. The field of conservation biology is concerned with the survival of species in deteriorating global habitats. In medicine, in contrast, infected patients are treated with chemotherapeutic interventions, but drug resistance can compromise eradication of pathogens. These contrasting biological systems and goals have created two quite separate research communities, despite addressing the same central question of whether populations will decline to extinction or be rescued through evolution. We argue that closer integration of the two fields, especially of theoretical understanding, would yield new insights and accelerate progress on these applied problems. Here, we overview and link mathematical modelling approaches in these fields, suggest specific areas with potential for fruitful exchange, and discuss common ideas and issues for empirical testing and prediction.

  2. The conserved glycine residues in the transmembrane domain of the Semliki Forest virus fusion protein are not required for assembly and fusion

    International Nuclear Information System (INIS)

    Liao Maofu; Kielian, Margaret

    2005-01-01

    The alphavirus Semliki Forest virus (SFV) infects cells via a low pH-triggered fusion reaction mediated by the viral E1 protein. Both the E1 fusion peptide and transmembrane (TM) domain are essential for membrane fusion, but the functional requirements for the TM domain are poorly understood. Here we explored the role of the five TM domain glycine residues, including the highly conserved glycine pair at E1 residues 415/416. SFV mutants with alanine substitutions for individual or all five glycine residues (5G/A) showed growth kinetics and fusion pH dependence similar to those of wild-type SFV. Mutants with increasing substitution of glycine residues showed an increasingly more stringent requirement for cholesterol during fusion. The 5G/A mutant showed decreased fusion kinetics and extent in fluorescent lipid mixing assays. TM domain glycine residues thus are not required for efficient SFV fusion or assembly but can cause subtle effects on the properties of membrane fusion

  3. A change of attitude: from rescue to prevention

    International Nuclear Information System (INIS)

    Covalschi, Valentina I.

    2003-01-01

    The qualitative and quantitative leap recorded by economical companies after the Romanian Revolution occurred in 1989, has positively influenced the functioning of the workplaces and working environment by increasing the employees' occupational safety, well being, health and results of their activities. In fact it has determined a new approach of safety culture. This has resulted in a change of attitude: from rescue to prevention. The paper is addressing the steps in which this change has been occurred. (author)

  4. A change of attitude: From rescue to prevention

    International Nuclear Information System (INIS)

    Covalschi, Valentina

    2002-01-01

    The qualitative and quantitative leap recorded by economical companies after the Romanian Revolution occurred in 1989, has positively influenced the functioning of the workplaces and working environment by increasing the employees' occupational safety, well being, health and results of their activities. In fact it has determined a new approach of safety culture. This has resulted in a change of attitude: from rescue to prevention. (author)

  5. Reforming The Governance Of Corporate Rescue: The Enterprise Act 2002

    OpenAIRE

    John Armour; Rizwaan Jameel Mokal

    2004-01-01

    English corporate insolvency law has been reshaped by the Enterprise Act 2002. The Act was intended to ‘to facilitate company rescue and to produce better returns for creditors as a whole’. Administrative receivership, which placed control of insolvency proceedings in the hands of banks, is for most purposes being abolished. It is being replaced by a ‘streamlined’ administration procedure. Whilst it will still be possible for banks to control the appointment process, the administrator once in...

  6. A competency framework for the business rescue practitioner profession

    Directory of Open Access Journals (Sweden)

    Marius Pretorius

    2014-08-01

    Research purpose: Competencies required by business rescue practitioners (BRPs to navigate a distressed venture were investigated. What BRPs actually ‘do’ during a rescue guided the development of a competency framework to inform future qualification guidelines for BRP education and accreditation. Motivation for the study: To investigate the research question: ‘What are the competencies that underlie the activities of a business rescue practitioner?’. Research design, approach and method: A modified ‘interview to the double’ (ITTD process was used to elicit instructions that a BRP would give to an imaginary ‘double’. These instructions were analysed and rated for importance, transferability, knowledge requirement and skills requirement; in conclusion, these instructions were ranked and subjected to a content analysis. Main findings: Based on the main activities that were derived from the practices and praxis, one assignment and four supra (higher-level competencies were consequent to the analysis. A BRP able to successfully navigate a distressed venture towards normal operations should demonstrate a high level of competency in sense-making, decision making and integration, achieved through collaboration as the central competency. Practical implications: Firstly, the study addresses educators’ need for a framework of competencies to guide education. Secondly, it paves the way for the Regulator to develop a qualifications framework for accreditation. Contribution: The findings gave structure to the competencies underlying the activities of a BRP to navigate a rescue. Pre-business and financial acumen appears limited without these competencies containing insight, experience, intuition, heuristics, tacit knowledge, perceptive induction and more.

  7. Mechanisms by which heme oxygenase rescue renal dysfunction in obesity

    Directory of Open Access Journals (Sweden)

    Joseph Fomusi Ndisang

    2014-01-01

    Collectively, these data suggest that hemin ameliorates nephropathy by potentiating the expression of proteins of repair/regeneration, abating oxidative/inflammatory mediators, reducing renal histo-pathological lesions, while enhancing nephrin, podocin, podocalyxin, CD2AP and creatinine clearance, with corresponding reduction of albuminuria/proteinuria suggesting improved renal function in hemin-treated ZFs. Importantly, the concomitant potentiation regeneration proteins and podocyte cytoskeletal proteins are novel mechanisms by which hemin rescue nephropathy in obesity.

  8. Rescue apparatus for a high working oil derrick

    Energy Technology Data Exchange (ETDEWEB)

    Prokopov, O.P.; Yagudin, S.Z.

    1980-05-18

    In order to improve reliability of the rescue apparatus a device for lowering a basket is made in the form of a collapsible forked support installed in the vertical plane inclined away from the tower. Its lower ends are attached by hinges to the base of the derrick. The upper end is connected to the derrick by means of a fastener. The apparatus has brakes with shock straps for receiving forked support.

  9. Medical rescue of naval combat: challenges and future

    OpenAIRE

    Jin, Hai; Hou, Li-Jun; Fu, Xiao-Bing

    2015-01-01

    There has been no large-scale naval combat in the last 30?years. With the rapid development of battleships, weapons manufacturing and electronic technology, naval combat will present some new characteristics. Additionally, naval combat is facing unprecedented challenges. In this paper, we discuss the topic of medical rescue at sea: what challenges we face and what we could do. The contents discussed in this paper contain battlefield self-aid buddy care, clinical skills, organized health servi...

  10. Simulation Optimization of Search and Rescue in Disaster Relief Based on Distributed Auction Mechanism

    Directory of Open Access Journals (Sweden)

    Jian Tang

    2017-11-01

    Full Text Available In this paper, we optimize the search and rescue (SAR in disaster relief through agent-based simulation. We simulate rescue teams’ search behaviors with the improved Truncated Lévy walks. Then we propose a cooperative rescue plan based on a distributed auction mechanism, and illustrate it with the case of landslide disaster relief. The simulation is conducted in three scenarios, including “fatal”, “serious” and “normal”. Compared with the non-cooperative rescue plan, the proposed rescue plan in this paper would increase victims’ relative survival probability by 7–15%, increase the ratio of survivors getting rescued by 5.3–12.9%, and decrease the average elapsed time for one site getting rescued by 16.6–21.6%. The robustness analysis shows that search radius can affect the rescue efficiency significantly, while the scope of cooperation cannot. The sensitivity analysis shows that the two parameters, the time limit for completing rescue operations in one buried site and the maximum turning angle for next step, both have a great influence on rescue efficiency, and there exists optimal value for both of them in view of rescue efficiency.

  11. Myoblast fusion in Drosophila

    Energy Technology Data Exchange (ETDEWEB)

    Haralalka, Shruti [Stowers Institute for Medical Research, Kansas City, MO 64110 (United States); Abmayr, Susan M., E-mail: sma@stowers.org [Stowers Institute for Medical Research, Kansas City, MO 64110 (United States); Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, MO 66160 (United States)

    2010-11-01

    The body wall musculature of a Drosophila larva is composed of an intricate pattern of 30 segmentally repeated muscle fibers in each abdominal hemisegment. Each muscle fiber has unique spatial and behavioral characteristics that include its location, orientation, epidermal attachment, size and pattern of innervation. Many, if not all, of these properties are dictated by founder cells, which determine the muscle pattern and seed the fusion process. Myofibers are then derived from fusion between a specific founder cell and several fusion competent myoblasts (FCMs) fusing with as few as 3-5 FCMs in the small muscles on the most ventral side of the embryo and as many as 30 FCMs in the larger muscles on the dorsal side of the embryo. The focus of the present review is the formation of the larval muscles in the developing embryo, summarizing the major issues and players in this process. We have attempted to emphasize experimentally-validated details of the mechanism of myoblast fusion and distinguish these from the theoretically possible details that have not yet been confirmed experimentally. We also direct the interested reader to other recent reviews that discuss myoblast fusion in Drosophila, each with their own perspective on the process . With apologies, we use gene nomenclature as specified by Flybase (http://flybase.org) but provide Table 1 with alternative names and references.

  12. Fusion, magnetic confinement

    International Nuclear Information System (INIS)

    Berk, H.L.

    1992-01-01

    An overview is presented of the principles of magnetic confinement of plasmas for the purpose of achieving controlled fusion conditions. Sec. 1 discusses the different nuclear fusion reactions which can be exploited in prospective fusion reactors and explains why special technologies need to be developed for the supply of tritium or 3 He, the probable fuels. In Sec. 2 the Lawson condition, a criterion that is a measure of the quality of confinement relative to achieving fusion conditions, is explained. In Sec. 3 fluid equations are used to describe plasma confinement. Specific confinement configurations are considered. In Sec. 4 the orbits of particle sin magneti and electric fields are discussed. In Sec. 5 stability considerations are discussed. It is noted that confinement systems usually need to satisfy stability constraints imposed by ideal magnetohydrodynamic (MHD) theory. The paper culminates with a summary of experimental progress in magnetic confinement. Present experiments in tokamaks have reached the point that the conditions necessary to achieve fusion are being satisfied

  13. Fusion technology programme

    International Nuclear Information System (INIS)

    Finken, D.

    1986-05-01

    In 1982, KfK joined the fusion programme of EURATOM as a further association introducing its experience in nuclear technology. KfK closely cooperates with IPP Garching, the two institutions forming a research unit aiming at planning and realization of future development steps of fusion. KfK has combined its forces in the Nuclear Fusion Project (PKF) with participation of several KfK departments to the project tasks. Previous work of KfK in magnetic fusion has addressed mainly superconducting magnets, plasma heating by cluster ions and studies on structural materials. At present, emphasis of our work has concentrated increasingly on the nuclear part, i.e. the first wall and blanket structures and the elements of the tritium extraction and purification system. Associated to this component development are studies of remote maintenance and safety. Most of the actual work addresses NET, the next step to a demonstration of fusion feasibility. NET is supposed to follow JET, the operating plasma physics experiment of Euratom, on the 1990's. Detailed progress of the work in the past half year is described in this report. (orig./GG)

  14. Challenges of nuclear fusion

    International Nuclear Information System (INIS)

    Kunkel, W.B.

    1987-01-01

    After 30 years of research and development in many countries, the magnetic confinement fusion experiments finally seem to be getting close to the original first goal: the point of ''scientific break-even''. Plans are being made for a generation of experiments and tests with actual controlled thermonuclear fusion conditions. Therefore engineers and material scientists are hard at work to develop the required technology. In this paper the principal elements of a generic fusion reactor are described briefly to introduce the reader to the nature of the problems at hand. The main portion of the presentation summarises the recent advances made in this field and discusses the major issues that still need to be addressed in regard to materials and technology for fusion power. Specific examples are the problems of the first wall and other components that come into direct contact with the plasma, where both lifetime and plasma contamination are matters of concern. Equally challenging are the demands on structural materials and on the magnetic-field coils, particularly in connection with the neutron-radiation environment of fusion reactors. Finally, the role of ceramics must be considered, both for insulators and for fuel breeding purposes. It is evident that we still have a formidable task before us, but at this point none of the problems seem to be insoluble. (author)

  15. The need for fusion

    International Nuclear Information System (INIS)

    Llewellyn Smith, Chris

    2005-01-01

    World energy use is predicted to double in the next 40 years. Currently 80% is provided by burning fossil fuels, but this is not sustainable indefinitely because (i) it is driving climate change, and (ii) fossil fuels will eventually be exhausted (starting with oil). The resulting potential energy crisis requires increased investment in energy research and development (which is currently very small on the scale of the $3 trillion p.a. energy market, and falling). The wide portfolio of energy work that should be supported must include fusion, which is one of the very few options that are capable in principle of supplying a large fraction of need. The case for fusion has been strengthened by recent advances in plasma physics and fusion technology that are reflected in the forthcoming European Fusion Power Plant Conceptual Study, which addresses safety and cost issues. The big questions are - How can we deliver fusion power as fast as possible? How long is it likely to take? I argue for a fast track programme, and describe a fast-track model developed at Culham, which is intended to stimulate debate on the way ahead and the resources that are needed

  16. Myoblast fusion in Drosophila

    International Nuclear Information System (INIS)

    Haralalka, Shruti; Abmayr, Susan M.

    2010-01-01

    The body wall musculature of a Drosophila larva is composed of an intricate pattern of 30 segmentally repeated muscle fibers in each abdominal hemisegment. Each muscle fiber has unique spatial and behavioral characteristics that include its location, orientation, epidermal attachment, size and pattern of innervation. Many, if not all, of these properties are dictated by founder cells, which determine the muscle pattern and seed the fusion process. Myofibers are then derived from fusion between a specific founder cell and several fusion competent myoblasts (FCMs) fusing with as few as 3-5 FCMs in the small muscles on the most ventral side of the embryo and as many as 30 FCMs in the larger muscles on the dorsal side of the embryo. The focus of the present review is the formation of the larval muscles in the developing embryo, summarizing the major issues and players in this process. We have attempted to emphasize experimentally-validated details of the mechanism of myoblast fusion and distinguish these from the theoretically possible details that have not yet been confirmed experimentally. We also direct the interested reader to other recent reviews that discuss myoblast fusion in Drosophila, each with their own perspective on the process . With apologies, we use gene nomenclature as specified by Flybase (http://flybase.org) but provide Table 1 with alternative names and references.

  17. Material for fusion reactor

    International Nuclear Information System (INIS)

    Abhishek, Anuj; Ranjan, Prem

    2011-01-01

    To make nuclear fusion power a reality, the scientists are working restlessly to find the materials which can confine the power generated by the fusion of two atomic nuclei. A little success in this field has been achieved, though there are still miles to go. Fusion reaction is a special kind of reaction which must occur at very high density and temperature to develop extremely large amount of energy, which is very hard to control and confine within using the present techniques. As a whole it requires the physical condition that rarely exists on the earth to carry out in an efficient manner. As per the growing demand and present scenario of the world energy, scientists are working round the clock to make effective fusion reactions to real. In this paper the work presently going on is considered in this regard. The progress of the Joint European Torus 2010, ITER 2005, HiPER and minor works have been studied to make the paper more object oriented. A detailed study of the technological and material requirement has been discussed in the paper and a possible suggestion is provided to make a contribution in the field of building first ever nuclear fusion reactor

  18. Coatings for fusion reactor environments

    International Nuclear Information System (INIS)

    Mattox, D.M.

    1979-01-01

    The internal surfaces of a tokamak fusion reactor control the impurity injection and gas recycling into the fusion plasma. Coating of internal surfaces may provide a desirable and possibly necessary design flexibility for achieving the temperatures, ion densities and containment times necessary for net energy production from fusion reactions to take place. In this paper the reactor environments seen by various componentare reviewed along with possible materials responses. Characteristics of coating-substrate systems, important to fusion applications, are delineated and the present status of coating development for fusion applications is reviewed. Coating development for fusion applications is just beginning and poses a unique and important challenge for materials development

  19. Fusion: Energy for the future

    International Nuclear Information System (INIS)

    1991-05-01

    Fusion, which occurs in the sun and the stars, is a process of transforming matter into energy. If we can harness the fusion process on Earth, it opens the way to assuring that future generations will not want for heat and electric power. The purpose of this booklet is to introduce the concept of fusion energy as a viable, environmentally sustainable energy source for the twenty-first century. The booklet presents the basic principles of fusion, the global research and development effort in fusion, and Canada's programs for fusion research and development

  20. Evolutionary rescue of a parasite population by mutation rate evolution.

    Science.gov (United States)

    Greenspoon, Philip B; Mideo, Nicole

    2017-10-01

    The risk of antibiotic resistance evolution in parasites is a major problem for public health. Identifying factors which promote antibiotic resistance evolution is thus a priority in evolutionary medicine. The rate at which new mutations enter the parasite population is one important predictor; however, mutation rate is not necessarily a fixed quantity, as is often assumed, but can itself evolve. Here we explore the possible impacts of mutation rate evolution on the fate of a disease circulating in a host population, which is being treated with drugs, the use of which varies over time. Using an evolutionary rescue framework, we find that mutation rate evolution provides a dramatic increase in the probability that a parasite population survives treatment in only a limited region, while providing little or no advantage in other regions. Both epidemiological features, such as the virulence of infection, and population genetic parameters, such as recombination rate, play important roles in determining the probability of evolutionary rescue and whether mutation rate evolution enhances the probability of evolutionary rescue or not. While efforts to curtail mutation rate evolution in parasites may be worthwhile under some circumstances, our results suggest that this need not always be the case. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Vulture rescue and rehabilitation in South Africa: An urban perspective

    Directory of Open Access Journals (Sweden)

    V. Naidoo

    2011-04-01

    Full Text Available SouthAfrica is home to 9 vulture species, of which 7 are endangered. While the cause of the population declines remains largely speculative, a vast amount of effort has been dedicated towards the protection of populations by ensuring sustainable and safe food sources for the various colonies. Limited focus was placed in the past on efforts related to the rescue and/or rehabilitation (R&R of injured birds and the release of these birds back into the wild. This paper provides an overview of the causes, the impact and success of 3 organisations involved in R&R efforts of vultures in the Magaliesberg mountain range and surrounding areas over a period of 10 years. Study material included 162 Cape griffon (CGV and 38 African white-backed (AWBV vultures. Datasets include the number, sex and age of birds received, the reason the vultures were brought in for R&R, surgical interventions performed and outcomes of rescue efforts. The CGV dominated the rehabilitation attempts. Results further show that a large number of apparently healthy birds were presented for veterinary treatment. The R&R data clearly indicate that the major cause of injuries was birds colliding with overhead pylons, as a high number of soft tissue and skeletal injuries were observed. The study also shows that successful releases of rescued birds are possible. It is concluded that urbanisation has had a major negative impact on vultures around the Magaliesberg mountain range.

  2. Rescue Medicine for Epilepsy: New Options for Education Settings.

    Science.gov (United States)

    Galemore, Cynthia A

    2016-11-01

    The American Academy of Pediatrics (AAP) recently published a clinical report recommending expanded options for seizure rescue medications in the school setting. School nurses rely on prescribing professionals for medical orders to manage children with epilepsy in the school setting. The report suggests additional medications beyond rectal diazepam gel along with discussing the purpose of the medications, the variations in prescribing practices for seizure rescue medications, inconsistencies in legislation based on jurisdictions, and the need for school medical orders for students with epilepsy. There are many issues faced by school personnel when caring for students with a diagnosis of epilepsy, chief among them the presence of licensed health professions for the school to be able to respond quickly and appropriately in the event of a seizure. School nurses can assist health care providers in determining the rescue medication most easily delivered and monitored in the variety of activities that are part of the school experience, including transportation to and from school, field trips, and before- and after-school activities, all beyond the regular classroom setting.

  3. High-throughput expression of animal venom toxins in Escherichia coli to generate a large library of oxidized disulphide-reticulated peptides for drug discovery.

    Science.gov (United States)

    Turchetto, Jeremy; Sequeira, Ana Filipa; Ramond, Laurie; Peysson, Fanny; Brás, Joana L A; Saez, Natalie J; Duhoo, Yoan; Blémont, Marilyne; Guerreiro, Catarina I P D; Quinton, Loic; De Pauw, Edwin; Gilles, Nicolas; Darbon, Hervé; Fontes, Carlos M G A; Vincentelli, Renaud

    2017-01-17

    Animal venoms are complex molecular cocktails containing a wide range of biologically active disulphide-reticulated peptides that target, with high selectivity and efficacy, a variety of membrane receptors. Disulphide-reticulated peptides have evolved to display improved specificity, low immunogenicity and to show much higher resistance to degradation than linear peptides. These properties make venom peptides attractive candidates for drug development. However, recombinant expression of reticulated peptides containing disulphide bonds is challenging, especially when associated with the production of large libraries of bioactive molecules for drug screening. To date, as an alternative to artificial synthetic chemical libraries, no comprehensive recombinant libraries of natural venom peptides are accessible for high-throughput screening to identify novel therapeutics. In the accompanying paper an efficient system for the expression and purification of oxidized disulphide-reticulated venom peptides in Escherichia coli is described. Here we report the development of a high-throughput automated platform, that could be adapted to the production of other families, to generate the largest ever library of recombinant venom peptides. The peptides were produced in the periplasm of E. coli using redox-active DsbC as a fusion tag, thus allowing the efficient formation of correctly folded disulphide bridges. TEV protease was used to remove fusion tags and recover the animal venom peptides in the native state. Globally, within nine months, out of a total of 4992 synthetic genes encoding a representative diversity of venom peptides, a library containing 2736 recombinant disulphide-reticulated peptides was generated. The data revealed that the animal venom peptides produced in the bacterial host were natively folded and, thus, are putatively biologically active. Overall this study reveals that high-throughput expression of animal venom peptides in E. coli can generate large

  4. Modulation of taste responsiveness by the satiation hormone peptide YY

    Science.gov (United States)

    La Sala, Michael S.; Hurtado, Maria D.; Brown, Alicia R.; Bohórquez, Diego V.; Liddle, Rodger A.; Herzog, Herbert; Zolotukhin, Sergei; Dotson, Cedrick D.

    2013-01-01

    It has been hypothesized that the peripheral taste system may be modulated in the context of an animal's metabolic state. One purported mechanism for this phenomenon is that circulating gastrointestinal peptides modulate the functioning of the peripheral gustatory system. Recent evidence suggests endocrine signaling in the oral cavity can influence food intake (FI) and satiety. We hypothesized that these hormones may be affecting FI by influencing taste perception. We used immunohistochemistry along with genetic knockout models and the specific reconstitution of peptide YY (PYY) in saliva using gene therapy protocols to identify a role for PYY signaling in taste. We show that PYY is expressed in subsets of taste cells in murine taste buds. We also show, using brief-access testing with PYY knockouts, that PYY signaling modulates responsiveness to bitter-tasting stimuli, as well as to lipid emulsions. We show that salivary PYY augmentation, via viral vector therapy, rescues behavioral responsiveness to a lipid emulsion but not to bitter stimuli and that this response is likely mediated via activation of Y2 receptors localized apically in taste cells. Our findings suggest distinct functions for PYY produced locally in taste cells vs. that circulating systemically.—La Sala, M. S., Hurtado, M. D., Brown, A. R., Bohórquez, D. V., Liddle, R. A., Herzog, H., Zolotukhin, S., Dotson, C. D. Modulation of taste responsiveness by the satiation hormone peptide YY. PMID:24043261

  5. Vacuum engineering for fusion research and fusion reactors

    International Nuclear Information System (INIS)

    Pittenger, L.C.

    1976-01-01

    The following topics are described: (1) surface pumping by cryogenic condensation, (2) operation of large condensing cryopumps, (3) pumping for large fusion experiments, and (4) vacuum technology for fusion reactors

  6. [Distiller Yeasts Producing Antibacterial Peptides].

    Science.gov (United States)

    Klyachko, E V; Morozkina, E V; Zaitchik, B Ts; Benevolensky, S V

    2015-01-01

    A new method of controlling lactic acid bacteria contamination was developed with the use of recombinant Saccharomyces cerevisiae strains producing antibacterial peptides. Genes encoding the antibacterial peptides pediocin and plantaricin with codons preferable for S. cerevisiae were synthesized, and a system was constructed for their secretory expression. Recombinant S. cerevisiae strains producing antibacterial peptides effectively inhibit the growth of Lactobacillus sakei, Pediacoccus pentasaceus, Pediacoccus acidilactici, etc. The application of distiller yeasts producing antibacterial peptides enhances the ethanol yield in cases of bacterial contamination. Recombinant yeasts producing the antibacterial peptides pediocin and plantaricin can successfully substitute the available industrial yeast strains upon ethanol production.

  7. Identification and Characterization of a Small Inhibitory Peptide That Can Target DNA-PKcs Autophosphorylation and Increase Tumor Radiosensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Sun Xiaonan [Department of Radiation Oncology, Sir Run Run Shaw Hospital, Sir Run Run Shaw Institute of Clinical Medicine of Zhejiang University, Hangzhou (China); Yang Chunying [Department of Radiation Oncology, Methodist Hospital Research Institute, Weill Cornell Medical College, Houston, TX (United States); Liu Hai; Wang Qi [Department of Radiation Oncology, Sir Run Run Shaw Hospital, Sir Run Run Shaw Institute of Clinical Medicine of Zhejiang University, Hangzhou (China); Wu Shixiu [Department of Radiation Oncology, The First Affiliated Hospital of Wenzhou Medical College, Wenzhou (China); Li Xia; Xie Tian [Research Center of Biomedicine and Health, Hangzhou Normal University, Hangzhou (China); Brinkman, Kathryn L.; Teh, Bin S.; Butler, E. Brian [Department of Radiation Oncology, Methodist Hospital Research Institute, Weill Cornell Medical College, Houston, TX (United States); Xu Bo, E-mail: bxu@tmhs.org [Department of Radiation Oncology, Methodist Hospital Research Institute, Weill Cornell Medical College, Houston, TX (United States); Zheng, Shu, E-mail: zhengshu@zju.edu.cn [Cancer Institute, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou (China)

    2012-12-01

    Purpose: The DNA protein kinase catalytic subunit (DNA-PKcs) is one of the critical elements involved in the DNA damage repair process. Inhibition of DNA-PKcs results in hypersensitivity to ionizing radiation (IR); therefore, this approach has been explored to develop molecular targeted radiosensitizers. Here, we aimed to develop small inhibitory peptides that could specifically target DNA-PKcs autophosphorylation, a critical step for the enzymatic activation of the kinase in response to IR. Methods and Materials: We generated several small fusion peptides consisting of 2 functional domains, 1 an internalization domain and the other a DNA-PKcs autophosphorylation inhibitory domain. We characterized the internalization, toxicity, and radiosensitization activities of the fusion peptides. Furthermore, we studied the mechanisms of the inhibitory peptides on DNA-PKcs autophosphorylation and DNA repair. Results: We found that among several peptides, the biotin-labeled peptide 3 (BTW3) peptide, which targets DNA-PKcs threonine 2647 autophosphorylation, can abrogate IR-induced DNA-PKcs activation and cause prolonged {gamma}-H2AX focus formation. We demonstrated that BTW3 exposure led to hypersensitivity to IR in DNA-PKcs-proficient cells but not in DNA-PKcs-deficient cells. Conclusions: The small inhibitory peptide BTW3 can specifically target DNA-PKcs autophosphorylation and enhance radiosensitivity; therefore, it can be further developed as a novel class of radiosensitizer.

  8. Identification and Characterization of a Small Inhibitory Peptide That Can Target DNA-PKcs Autophosphorylation and Increase Tumor Radiosensitivity

    International Nuclear Information System (INIS)

    Sun Xiaonan; Yang Chunying; Liu Hai; Wang Qi; Wu Shixiu; Li Xia; Xie Tian; Brinkman, Kathryn L.; Teh, Bin S.; Butler, E. Brian; Xu Bo; Zheng, Shu

    2012-01-01

    Purpose: The DNA protein kinase catalytic subunit (DNA-PKcs) is one of the critical elements involved in the DNA damage repair process. Inhibition of DNA-PKcs results in hypersensitivity to ionizing radiation (IR); therefore, this approach has been explored to develop molecular targeted radiosensitizers. Here, we aimed to develop small inhibitory peptides that could specifically target DNA-PKcs autophosphorylation, a critical step for the enzymatic activation of the kinase in response to IR. Methods and Materials: We generated several small fusion peptides consisting of 2 functional domains, 1 an internalization domain and the other a DNA-PKcs autophosphorylation inhibitory domain. We characterized the internalization, toxicity, and radiosensitization activities of the fusion peptides. Furthermore, we studied the mechanisms of the inhibitory peptides on DNA-PKcs autophosphorylation and DNA repair. Results: We found that among several peptides, the biotin-labeled peptide 3 (BTW3) peptide, which targets DNA-PKcs threonine 2647 autophosphorylation, can abrogate IR-induced DNA-PKcs activation and cause prolonged γ-H2AX focus formation. We demonstrated that BTW3 exposure led to hypersensitivity to IR in DNA-PKcs-proficient cells but not in DNA-PKcs-deficient cells. Conclusions: The small inhibitory peptide BTW3 can specifically target DNA-PKcs autophosphorylation and enhance radiosensitivity; therefore, it can be further developed as a novel class of radiosensitizer.

  9. Controlled thermonuclear fusion

    International Nuclear Information System (INIS)

    Trocheris, M.

    1975-01-01

    An outline is given of the present position of research into controlled fusion. After a brief reminder of the nuclear reactions of fusion and the principle of their use as a source of energy, the results obtained by the method of magnetic confinement are summarized. Among the many solutions that have been imagined and tried out to achieve a magnetic containing vessel capable of holding the thermonuclear plasma, the devices of the Tokamak type have a good lead and that is why they are described in greater detail. An idea is then given of the problems that arise when one intends conceiving the thermonuclear reactor based on the principle of the Tokamaks. The last section deals with fusion by lasers which is a new and most attractive alternative, at least from the viewpoint of basis physics. The report concludes with an indication of the stages to be passed through to reach production of energy on an industrial scale [fr

  10. Peaceful Uses of Fusion

    Science.gov (United States)

    Teller, E.

    1958-07-03

    Applications of thermonuclear energy for peaceful and constructive purposes are surveyed. Developments and problems in the release and control of fusion energy are reviewed. It is pointed out that the future of thermonuclear power reactors will depend upon the construction of a machine that produces more electric energy than it consumes. The fuel for thermonuclear reactors is cheap and practically inexhaustible. Thermonuclear reactors produce less dangerous radioactive materials than fission reactors and, when once brought under control, are not as likely to be subject to dangerous excursions. The interaction of the hot plasma with magnetic fields opens the way for the direct production of electricity. It is possible that explosive fusion energy released underground may be harnessed for the production of electricity before the same feat is accomplished in controlled fusion processes. Applications of underground detonations of fission devices in mining and for the enhancement of oil flow in large low-specific-yield formations are also suggested.

  11. Ceramics for fusion applications

    International Nuclear Information System (INIS)

    Clinard, F.W. Jr.

    1987-01-01

    Ceramics are required for a variety of uses in both near-term fusion devices and in commercial powerplants. These materials must retain adequate structural and electrical properties under conditions of neutron, particle and ionizing irradiation; thermal and applied stresses; and physical and chemical sputtering. Ceramics such as Al 2 O 3 , MgAl 2 O 4 , BeO, Si 3 N 4 and SiC are currently under study for fusion applications, and results to date show widely-varying responses to the fusion environment. Materials can be identified today that will meet initial operating requirements, but improvements in physical properties are needed to achieve satisfactory lifetimes for critical applications. (author)

  12. Inverse fusion PCR cloning.

    Directory of Open Access Journals (Sweden)

    Markus Spiliotis

    Full Text Available Inverse fusion PCR cloning (IFPC is an easy, PCR based three-step cloning method that allows the seamless and directional insertion of PCR products into virtually all plasmids, this with a free choice of the insertion site. The PCR-derived inserts contain a vector-complementary 5'-end that allows a fusion with the vector by an overlap extension PCR, and the resulting amplified insert-vector fusions are then circularized by ligation prior transformation. A minimal amount of starting material is needed and experimental steps are reduced. Untreated circular plasmid, or alternatively bacteria containing the plasmid, can be used as templates for the insertion, and clean-up of the insert fragment is not urgently required. The whole cloning procedure can be performed within a minimal hands-on time and results in the generation of hundreds to ten-thousands of positive colonies, with a minimal background.

  13. Laser for fusion energy

    International Nuclear Information System (INIS)

    Holzrichter, J.F.

    1995-01-01

    Solid state lasers have proven to be very versatile tools for the study and demonstration of inertial confinement fusion principles. When lasers were first contemplated to be used for the compression of fusion fuel in the late 1950s, the laser output energy levels were nominally one joule and the power levels were 10 3 watts (pulse duration's of 10 -3 sec). During the last 25 years, lasers optimized for fusion research have been increased in power to typically 100,000 joules with power levels approaching 10 14 watts. As a result of experiments with such lasers at many locations, DT target performance has been shown to be consistent with high gain target output. However, the demonstration of ignition and gain requires laser energies of several megajoules. Laser technology improvements demonstrated over the past decade appear to make possible the construction of such multimegajoule lasers at affordable costs. (author)

  14. Ceramics for fusion applications

    International Nuclear Information System (INIS)

    Clinard, F.W. Jr.

    1986-01-01

    Ceramics are required for a variety of uses in both near-term fusion devices and in commercial powerplants. These materials must retain adequate structural and electrical properties under conditions of neutron, particle, and ionizing irradiation; thermal and applied stresses; and physical and chemical sputtering. Ceramics such as Al 2 O 3 , MgAl 2 O 4 , BeO, Si 3 N 4 and SiC are currently under study for fusion applications, and results to date show widely-varying response to the fusion environment. Materials can be identified today which will meet initial operating requirements, but improvements in physical properties are needed to achieve satisfactory lifetimes for critical applications

  15. Fusion Reactor Materials

    Energy Technology Data Exchange (ETDEWEB)

    Decreton, M

    2002-04-01

    The objective of SCK-CEN's programme on fusion reactor materials is to contribute to the knowledge on the radiation-induced behaviour of fusion reactor materials and components as well as to help the international community in building the scientific and technical basis needed for the construction of the future reactor. Ongoing projects include: the study of the mechanical and chemical (corrosion) behaviour of structural materials under neutron irradiation and water coolant environment; the investigation of the characteristics of irradiated first wall material such as beryllium; investigations on the management of materials resulting from the dismantling of fusion reactors including waste disposal. Progress and achievements in these areas in 2001 are discussed.

  16. Fusion reactor wastes

    International Nuclear Information System (INIS)

    Young, J.R.

    1976-01-01

    The fusion reactor currently is being developed as a clean source of electricity with an essentially infinite source of fuel. These reactors are visualized as using a fusion reaction to generate large quantities of high temperature energy which can be used as process heat or for the generation of electricity. The energy would be created primarily as the kinetic energy of neutrons or other reaction products. Neutron energy could be converted to high-temperature heat by moderation and capture of the neutrons. The energy of other reaction products could be converted to high-temperature heat by capture, or directly to electricity by direct conversion electrostatic equipment. An analysis to determine the wastes released as a result of operation of fusion power plants is presented

  17. Heavy ion inertial fusion

    International Nuclear Information System (INIS)

    Keefe, D.; Sessler, A.M.

    1980-01-01

    Inertial fusion has not yet been as well explored as magnetic fusion but can offer certain advantages as an alternative source of electric energy for the future. Present experiments use high-power beams from lasers and light-ion diodes to compress the deuterium-tritium (D-T) pellets but these will probably be unsuitable for a power plant. A more promising method is to use intense heavy-ion beams from accelerator systems similar to those used for nuclear and high-energy physics; the present paper addresses itself to this alternative. As will be demonstrated the very high beam power needed poses new design questions, from the ion-source through the accelerating system, the beam transport system, to the final focus. These problems will require extensive study, both theoretically and experimentally, over the next several years before an optimum design for an inertial fusion driver can be arrived at. (Auth.)

  18. On impact fusion

    International Nuclear Information System (INIS)

    Winterberg, F.

    1997-01-01

    Impact fusion is a promising, but much less developed road towards inertial confinement fusion. It offers an excellent solution to the so-called stand-off problem for thermonuclear microexplosions but is confronted with the challenge to accelerate macroscopic particles to the needed high velocities of 10 2 -10 3 km/s. To reach these velocities, two ways have been studied in the past. The electric acceleration of a beam of microparticles, with the particles as small as large clusters, and the magnetic acceleration of gram-size ferromagnetic or superconducting projectiles. For the generation of an intense burst of soft X-rays used for the indirect drive, impact fusion may offer new promising possibilities

  19. Fusion research at ORNL

    International Nuclear Information System (INIS)

    1982-03-01

    The ORNL Fusion Program includes the experimental and theoretical study of two different classes of magnetic confinement schemes - systems with helical magnetic fields, such as the tokamak and stellarator, and the ELMO Bumpy Torus (EBT) class of toroidally linked mirror systems; the development of technologies, including superconducting magnets, neutral atomic beam and radio frequency (rf) heating systems, fueling systems, materials, and diagnostics; the development of databases for atomic physics and radiation effects; the assessment of the environmental impact of magnetic fusion; and the design of advanced demonstration fusion devices. The program involves wide collaboration, both within ORNL and with other institutions. The elements of this program are shown. This document illustrates the program's scope; and aims by reviewing recent progress

  20. Canadian fusion program

    International Nuclear Information System (INIS)

    Brown, T.S.

    1982-06-01

    The National Research Council of Canada is establishing a coordinated national program of fusion research and development that is planned to grow to a total annual operating level of about $20 million in 1985. The long-term objective of the program is to put Canadian industry in a position to manufacture sub-systems and components of fusion power reactors. In the near term the program is designed to establish a minimum base of scientific and technical expertise sufficient to make recognized contributions and thereby gain access to the international effort. The Canadian program must be narrowly focussed on a few specializations where Canada has special indigenous skills or technologies. The programs being funded are the Tokamak de Varennes, the Fusion Fuels Technology Project centered on tritium management, and high-power gas laser technology and associated diagnostic instrumentation