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Sample records for fusion inhibitory complex

  1. Isolation of virus-cell fusion inhibitory components from the stem bark of Styrax japonica S. et Z.

    PubMed

    Lee, Dung Gun; Jin, Qinglong; Jin, Hong-Guang; Shin, Ji Eun; Choi, Eun Jin; Woo, Eun-Rhan

    2010-06-01

    Five compounds, styraxjaponoside A (1), matairesinoside (2), egonol glucoside (3), dihydrodehydrodiconiferyl alcohol 9'-O-glucoside (4), and styraxjaponoside B (5) were isolated from the stem bark of Styrax japonica. Among them, compounds 1 and 5 showed significantly high virus-cell fusion inhibitory activity. In addition, compound 5 exhibited almost equivalent virus-cell fusion inhibitory activity to that of dextran sulfate, which is used as a positive control.

  2. Broad spectrum antiviral activity for paramyxoviruses is modulated by biophysical properties of fusion inhibitory peptides

    PubMed Central

    Mathieu, Cyrille; Augusto, Marcelo T.; Niewiesk, Stefan; Horvat, Branka; Palermo, Laura M.; Sanna, Giuseppina; Madeddu, Silvia; Huey, Devra; Castanho, Miguel A. R. B.; Porotto, Matteo; Santos, Nuno C.; Moscona, Anne

    2017-01-01

    Human paramyxoviruses include global causes of lower respiratory disease like the parainfluenza viruses, as well as agents of lethal encephalitis like Nipah virus. Infection is initiated by viral glycoprotein-mediated fusion between viral and host cell membranes. Paramyxovirus viral fusion proteins (F) insert into the target cell membrane, and form a transient intermediate that pulls the viral and cell membranes together as two heptad-repeat regions refold to form a six-helix bundle structure that can be specifically targeted by fusion-inhibitory peptides. Antiviral potency can be improved by sequence modification and lipid conjugation, and by adding linkers between the protein and lipid components. We exploit the uniquely broad spectrum antiviral activity of a parainfluenza F-derived peptide sequence that inhibits both parainfluenza and Nipah viruses, to investigate the influence of peptide orientation and intervening linker length on the peptides’ interaction with transitional states of F, solubility, membrane insertion kinetics, and protease sensitivity. We assessed the impact of these features on biodistribution and antiviral efficacy in vitro and in vivo. The engineering approach based on biophysical parameters resulted in a peptide that is a highly effective inhibitor of both paramyxoviruses and a set of criteria to be used for engineering broad spectrum antivirals for emerging paramyxoviruses. PMID:28344321

  3. Inhibitory Effect of mTOR Activator MHY1485 on Autophagy: Suppression of Lysosomal Fusion

    PubMed Central

    Choi, Yeon Ja; Park, Yun Jung; Park, Ji Young; Jeong, Hyoung Oh; Kim, Dae Hyun; Ha, Young Mi; Kim, Ji Min; Song, Yu Min; Heo, Hyoung-Sam; Yu, Byung Pal; Chun, Pusoon; Moon, Hyung Ryong; Chung, Hae Young

    2012-01-01

    Autophagy is a major degradative process responsible for the disposal of cytoplasmic proteins and dysfunctional organelles via the lysosomal pathway. During the autophagic process, cells form double-membraned vesicles called autophagosomes that sequester disposable materials in the cytoplasm and finally fuse with lysosomes. In the present study, we investigated the inhibition of autophagy by a synthesized compound, MHY1485, in a culture system by using Ac2F rat hepatocytes. Autophagic flux was measured to evaluate the autophagic activity. Autophagosomes were visualized in Ac2F cells transfected with AdGFP-LC3 by live-cell confocal microscopy. In addition, activity of mTOR, a major regulatory protein of autophagy, was assessed by western blot and docking simulation using AutoDock 4.2. In the result, treatment with MHY1485 suppressed the basal autophagic flux, and this inhibitory effect was clearly confirmed in cells under starvation, a strong physiological inducer of autophagy. The levels of p62 and beclin-1 did not show significant change after treatment with MHY1485. Decreased co-localization of autophagosomes and lysosomes in confocal microscopic images revealed the inhibitory effect of MHY1485 on lysosomal fusion during starvation-induced autophagy. These effects of MHY1485 led to the accumulation of LC3II and enlargement of the autophagosomes in a dose- and time- dependent manner. Furthermore, MHY1485 induced mTOR activation and correspondingly showed a higher docking score than PP242, a well-known ATP-competitive mTOR inhibitor, in docking simulation. In conclusion, MHY1485 has an inhibitory effect on the autophagic process by inhibition of fusion between autophagosomes and lysosomes leading to the accumulation of LC3II protein and enlarged autophagosomes. MHY1485 also induces mTOR activity, providing a possibility for another regulatory mechanism of autophagy by the MHY compound. The significance of this study is the finding of a novel inhibitor of autophagy

  4. Inhibitory effect of mTOR activator MHY1485 on autophagy: suppression of lysosomal fusion.

    PubMed

    Choi, Yeon Ja; Park, Yun Jung; Park, Ji Young; Jeong, Hyoung Oh; Kim, Dae Hyun; Ha, Young Mi; Kim, Ji Min; Song, Yu Min; Heo, Hyoung-Sam; Yu, Byung Pal; Chun, Pusoon; Moon, Hyung Ryong; Chung, Hae Young

    2012-01-01

    Autophagy is a major degradative process responsible for the disposal of cytoplasmic proteins and dysfunctional organelles via the lysosomal pathway. During the autophagic process, cells form double-membraned vesicles called autophagosomes that sequester disposable materials in the cytoplasm and finally fuse with lysosomes. In the present study, we investigated the inhibition of autophagy by a synthesized compound, MHY1485, in a culture system by using Ac2F rat hepatocytes. Autophagic flux was measured to evaluate the autophagic activity. Autophagosomes were visualized in Ac2F cells transfected with AdGFP-LC3 by live-cell confocal microscopy. In addition, activity of mTOR, a major regulatory protein of autophagy, was assessed by western blot and docking simulation using AutoDock 4.2. In the result, treatment with MHY1485 suppressed the basal autophagic flux, and this inhibitory effect was clearly confirmed in cells under starvation, a strong physiological inducer of autophagy. The levels of p62 and beclin-1 did not show significant change after treatment with MHY1485. Decreased co-localization of autophagosomes and lysosomes in confocal microscopic images revealed the inhibitory effect of MHY1485 on lysosomal fusion during starvation-induced autophagy. These effects of MHY1485 led to the accumulation of LC3II and enlargement of the autophagosomes in a dose- and time-dependent manner. Furthermore, MHY1485 induced mTOR activation and correspondingly showed a higher docking score than PP242, a well-known ATP-competitive mTOR inhibitor, in docking simulation. In conclusion, MHY1485 has an inhibitory effect on the autophagic process by inhibition of fusion between autophagosomes and lysosomes leading to the accumulation of LC3II protein and enlarged autophagosomes. MHY1485 also induces mTOR activity, providing a possibility for another regulatory mechanism of autophagy by the MHY compound. The significance of this study is the finding of a novel inhibitor of autophagy

  5. Biochemical and Functional Studies of Cortical Vesicle Fusion: The SNARE Complex and Ca2+ Sensitivity

    PubMed Central

    Coorssen, Jens R.; Blank, Paul S.; Tahara, Masahiro; Zimmerberg, Joshua

    1998-01-01

    Cortical vesicles (CV) possess components critical to the mechanism of exocytosis. The homotypic fusion of CV centrifuged or settled into contact has a sigmoidal Ca2+ activity curve comparable to exocytosis (CV–PM fusion). Here we show that Sr2+ and Ba2+ also trigger CV–CV fusion, and agents affecting different steps of exocytotic fusion block Ca2+, Sr2+, and Ba2+-triggered CV–CV fusion. The maximal number of active fusion complexes per vesicle, Max, was quantified by NEM inhibition of fusion, showing that CV–CV fusion satisfies many criteria of a mathematical analysis developed for exocytosis. Both Max and the Ca2+ sensitivity of fusion complex activation were comparable to that determined for CV–PM fusion. Using Ca2+-induced SNARE complex disruption, we have analyzed the relationship between membrane fusion (CV–CV and CV–PM) and the SNARE complex. Fusion and complex disruption have different sensitivities to Ca2+, Sr2+, and Ba2+, the complex remains Ca2+- sensitive on fusion-incompetent CV, and disruption does not correlate with the quantified activation of fusion complexes. Under conditions which disrupt the SNARE complex, CV on the PM remain docked and fusion competent, and isolated CV still dock and fuse, but with a markedly reduced Ca2+ sensitivity. Thus, in this system, neither the formation, presence, nor disruption of the SNARE complex is essential to the Ca2+-triggered fusion of exocytotic membranes. Therefore the SNARE complex alone cannot be the universal minimal fusion machine for intracellular fusion. We suggest that this complex modulates the Ca2+ sensitivity of fusion. PMID:9864359

  6. Complexity versus availability for fusion: The potential advantages of inertial fusion energy

    SciTech Connect

    Perkins, L.J.,

    1996-09-05

    Probably the single largest advantage of the inertial route to fusion energy (IFE) is the perception that its power plant embodiments could achieve acceptable capacity factors. This is a result of its relative simplicity, the decoupling of the driver and reactor chamber, and the potential to employ thick liquid walls. We examine these issues in terms of the complexity, reliability, maintainability and, therefore, availability of both magnetic and inertial fusion power plants and compare these factors with corresponding scheduled and unscheduled outage data from present day fission experience. We stress that, given the simple nature of a fission core, the vast majority of unplanned outages in fission plants are due to failures outside the reactor vessel itself Given we must be prepared for similar outages in the analogous plant external to a fusion power core, this puts severe demands on the reliability required of the fusion core itself. We indicate that such requirements can probably be met for IFE plants. We recommend that this advantage be promoted by performing a quantitative reliability and availability study for a representative IFE power plant and suggest that databases are probably adequate for this task.

  7. The MARVEL domain protein, Singles Bar, is required for progression past the pre-fusion complex stage of myoblast fusion

    PubMed Central

    Estrada, Beatriz; Maeland, Anne D.; Gisselbrecht, Stephen S.; Bloor, James W.; Brown, Nicholas H.; Michelson, Alan M.

    2007-01-01

    Summary Multinucleated myotubes develop by the sequential fusion of individual myoblasts. Using a convergence of genomic and classical genetic approaches, we have discovered a novel gene, singles bar (sing), that is essential for myoblast fusion. sing encodes a small multipass transmembrane protein containing a MARVEL domain, which is found in vertebrate proteins involved in processes such as tight junction formation and vesicle trafficking where—as in myoblast fusion—membrane apposition occurs. sing is expressed in both founder cells and fusion competent myoblasts preceding and during myoblast fusion. Examination of embryos injected with double-stranded sing RNA or embryos homozygous for ethane methyl sulfonate-induced sing alleles revealed an identical phenotype: replacement of multinucleated myofibers by groups of single, myosin-expressing myoblasts at a stage when formation of the mature muscle pattern is complete in wild-type embryos. Unfused sing mutant myoblasts form clusters, suggesting that early recognition and adhesion of these cells is unimpaired. To further investigate this phenotype, we undertook electron microscopic ultrastructural studies of fusing myoblasts in both sing and wild-type embryos. These experiments revealed that more sing mutant myoblasts than wild-type contain pre-fusion complexes, which are characterized by electron-dense vesicles paired on either side of the fusing plasma membranes. In contrast, embryos mutant for another muscle fusion gene, blown fuse (blow), have a normal number of such complexes. Together, these results lead to the hypothesis that sing acts at a step distinct from that of blow, and that sing is required on both founder cell and fusion-competent myoblast membranes to allow progression past the pre-fusion complex stage of myoblast fusion, possibly by mediating fusion of the electron-dense vesicles to the plasma membrane. PMID:17537424

  8. Inhibitory effects of a peptide-fusion protein (Latarcin-PAP1-Thanatin) against chikungunya virus.

    PubMed

    Rothan, Hussin A; Bahrani, Hirbod; Shankar, Esaki M; Rahman, Noorsaadah Abd; Yusof, Rohana

    2014-08-01

    Chikungunya virus (CHIKV) outbreaks have led to a serious economic burden, as the available treatment strategies can only alleviate disease symptoms, and no effective therapeutics or vaccines are currently available for human use. Here, we report the use of a new cost-effective approach involving production of a recombinant antiviral peptide-fusion protein that is scalable for the treatment of CHIKV infection. A peptide-fusion recombinant protein LATA-PAP1-THAN that was generated by joining Latarcin (LATA) peptide with the N-terminus of the PAP1 antiviral protein, and the Thanatin (THAN) peptide to the C-terminus, was produced in Escherichia coli as inclusion bodies. The antiviral LATA-PAP1-THAN protein showed 89.0% reduction of viral plaque formation compared with PAP1 (46.0%), LATA (67.0%) or THAN (79.3%) peptides alone. The LATA-PAP1-THAN protein reduced the viral RNA load that was 0.89-fold compared with the untreated control cells. We also showed that PAP1 resulted in 0.44-fold reduction, and THAN and LATA resulting in 0.78-fold and 0.73-fold reductions, respectively. The LATA-PAP1-THAN protein inhibited CHIKV replication in the Vero cells at an EC50 of 11.2μg/ml, which is approximately half of the EC50 of PAP1 (23.7μg/ml) and protected the CHIKV-infected mice at the dose of 0.75mg/ml. We concluded that production of antiviral peptide-fusion protein in E. coli as inclusion bodies could accentuate antiviral activities, enhance cellular internalisation, and could reduce product toxicity to host cells and is scalable to epidemic response quantities.

  9. Structural Insight into Anaphase Promoting Complex 3 Structure and Docking with a Natural Inhibitory Compound

    PubMed Central

    Rahimi, Hamzeh; Shokrgozar, Mohammad Ali; Madadkar-Sobhani, Armin; Mahdian, Reza; Foroumadi, Alireza; Karimipoor, Morteza

    2017-01-01

    Background: Anaphase promoting complex (APC) is the biggest Cullin-RING E3 ligase and is very important in cell cycle control; many anti-cancer agents target this. APC controls the onset of chromosome separation and mitotic exit through securin and cyclin B degradation, respectively. Its APC3 subunit identifies the APC activators-Cdh1 and Cdc20. Materials and Methods: The structural model of the APC3 subunit of APC was developed by means of computational techniques; the binding of a natural inhibitory compound to APC3 was also investigated. Results: It was found that APC3 structure consists of numerous helices organized in anti-parallel and the overall model is superhelical of tetratrico-peptide repeat (TPR) domains. Furthermore, binding pocket of the natural inhibitory compound as APC3 inhibitor was shown. Conclusion: The findings are beneficial to understand the mechanism of the APC activation and design inhibitory compounds.

  10. GM-CSF-neuroantigen fusion proteins reverse experimental autoimmune encephalomyelitis and mediate tolerogenic activity in adjuvant-primed environments: association with inflammation-dependent, inhibitory antigen presentation2

    PubMed Central

    Islam, S.M. Touhidul; Curtis, Alan D.; Taslim, Najla; Wilkinson, Daniel S.; Mannie, Mark D.

    2014-01-01

    Single-chain fusion proteins comprised of GM-CSF and neuroantigen (NAg) are potent, NAg-specific inhibitors of experimental autoimmune encephalomyelitis (EAE). An important question was whether GMCSF-NAg tolerogenic vaccines retained inhibitory activity within inflammatory environments or were contingent upon steady-state conditions. A GMCSF-MOG fusion protein reversed established paralytic disease in both passive and active models of EAE in C57BL/6 mice. The fusion protein also reversed EAE in CD4-deficient and B cell-deficient mice. Notably, GMCSF-MOG inhibited EAE when co-injected adjacent to the MOG35-55/CFA emulsion. GMCSF-MOG also retained dominant inhibitory activity when directly emulsified with MOG35-55 in the CFA emulsion in both C57BL/6 or B cell-deficient models of EAE. Likewise, when combined with PLP139-151 in CFA, GMCSF-PLP inhibited EAE in SJL mice. When deliberately emulsified in CFA with the NAg, GMCSF-NAg inhibited EAE even though NAg was present at more than a 30-fold molar excess. In vitro studies revealed that the GMCSF domain of GMCSF-MOG stimulated growth and differentiation of inflammatory dendritic cells (DC) and simultaneously targeted the MOG35-55 domain for enhanced presentation by these DC. These inflammatory DC presented MOG35-55 to MOG-specific T cells by an inhibitory mechanism that was mediated in part by IFN-γ signaling and NO production. In conclusion, GMCSF-NAg was tolerogenic in CFA-primed pro-inflammatory environments by a mechanism associated with targeted antigen presentation by inflammatory DC and an inhibitory IFN-γ/ NO pathway. The inhibitory activity of GMCSF-NAg in CFA-primed lymphatics distinguishes GMCSF-NAg fusion proteins as a unique class of inflammation-dependent tolerogens that are mechanistically distinct from naked peptide or protein-based tolerogens. PMID:25049359

  11. Inhibitory effects of NAMI-A-like ruthenium complexes on prion neuropeptide fibril formation.

    PubMed

    Wang, Xuesong; Zhu, Dengsen; Zhao, Cong; He, Lei; Du, Weihong

    2015-05-01

    Prion diseases are a group of infectious and fatal neurodegenerative disorders caused by the conformational conversion of a cellular prion protein (PrP) into its abnormal isoform PrP(Sc). PrP106-126 resembles PrP(Sc) in terms of physicochemical and biological characteristics and is used as a common model for the treatment of prion diseases. Inhibitory effects on fibril formation and neurotoxicity of the prion neuropeptide PrP106-126 have been investigated using metal complexes as potential inhibitors. Nevertheless, the binding mechanism between metal complexes and the peptide remains unclear. The present study is focused on the interaction of PrP106-126 with NAMI-A and NAMI-A-like ruthenium complexes, including KP418, KP1019, and KP1019-2. Results demonstrated that these ruthenium complexes could bind to PrP106-126 in a distinctive binding mode through electrostatic and hydrophobic interactions. NAMI-A-like ruthenium complexes can also effectively inhibit the aggregation and fibril formation of PrP106-126. The complex KP1019 demonstrated the optimal inhibitory ability upon peptide aggregation, and cytotoxicity because of its large aromatic ligand contribution. The studied complexes could also regulate the copper redox chemistry of PrP106-126 and effectually inhibit the formation of reactive oxygen species. Given these findings, ruthenium complexes with relatively low cellular toxicity may be used to develop potential pharmaceutical products against prion diseases.

  12. Gene flow despite complex Robertsonian fusions among rock-wallaby (Petrogale) species

    PubMed Central

    Potter, Sally; Moritz, Craig; Eldridge, Mark D. B.

    2015-01-01

    Complex Robertsonian rearrangements, with shared arms in different fusions, are expected to prevent gene flow between hybrids through missegregation during meiosis. Here, we estimate gene flow between recently diverged and chromosomally diverse rock-wallabies (Petrogale) to test for this form of chromosomal speciation. Contrary to expectations, we observe relatively high admixture among species with complex fusions. Our results reinforce the need to consider alternative roles of chromosome change, together with genic divergence, in driving speciation. PMID:26445985

  13. Inhibitory factors associated with anaphase-promoting complex/cylosome in mitotic checkpoint

    PubMed Central

    Braunstein, Ilana; Miniowitz, Shirly; Moshe, Yakir; Hershko, Avram

    2007-01-01

    The mitotic (or spindle assembly) checkpoint system ensures accurate chromosome segregation by preventing anaphase initiation until all chromosomes are correctly attached to the mitotic spindle. It affects the activity of the anaphase-promoting complex/cyclosome (APC/C), a ubiquitin ligase that targets inhibitors of anaphase initiation for degradation. The mechanisms by which this system regulates APC/C remain obscure. Some models propose that the system promotes sequestration of the APC/C activator Cdc20 by binding to the checkpoint proteins Mad2 and BubR1. A different model suggests that a mitotic checkpoint complex (MCC) composed of BubR1, Bub3, Cdc20, and Mad2 inhibits APC/C in mitotic checkpoint [Sudakin V, Chan GKT, Yen TJ (2001) J Cell Biol 154:925–936]. We examined this problem by using extracts from nocodazole-arrested cells that reproduce some downstream events of the mitotic checkpoint system, such as lag kinetics of the degradation of APC/C substrate. Incubation of extracts with adenosine-5′-(γ-thio)triphosphate (ATP[γS]) stabilized the checkpoint-arrested state, apparently by stable thiophosphorylation of some proteins. By immunoprecipitation of APC/C from stably checkpoint-arrested extracts, followed by elution with increased salt concentration, we isolated inhibitory factors associated with APC/C. A part of the inhibitory material consists of Cdc20 associated with BubR1 and Mad2, and is thus similar to MCC. Contrary to the original MCC hypothesis, we find that MCC disassembles upon exit from the mitotic checkpoint. Thus, the requirement of the mitotic checkpoint system for the binding of Mad2 and BubR1 to Cdc20 may be for the assembly of the inhibitory complex rather than for Cdc20 sequestration. PMID:17360335

  14. Fusion

    NASA Astrophysics Data System (ADS)

    Herman, Robin

    1990-10-01

    The book abounds with fascinating anecdotes about fusion's rocky path: the spurious claim by Argentine dictator Juan Peron in 1951 that his country had built a working fusion reactor, the rush by the United States to drop secrecy and publicize its fusion work as a propaganda offensive after the Russian success with Sputnik; the fortune Penthouse magazine publisher Bob Guccione sank into an unconventional fusion device, the skepticism that met an assertion by two University of Utah chemists in 1989 that they had created "cold fusion" in a bottle. Aimed at a general audience, the book describes the scientific basis of controlled fusion--the fusing of atomic nuclei, under conditions hotter than the sun, to release energy. Using personal recollections of scientists involved, it traces the history of this little-known international race that began during the Cold War in secret laboratories in the United States, Great Britain and the Soviet Union, and evolved into an astonishingly open collaboration between East and West.

  15. Synthesis, structures and urease inhibitory activity of cobalt(III) complexes with Schiff bases.

    PubMed

    Jing, Changling; Wang, Cunfang; Yan, Kai; Zhao, Kedong; Sheng, Guihua; Qu, Dan; Niu, Fang; Zhu, Hailiang; You, Zhonglu

    2016-01-15

    A series of new cobalt(III) complexes were prepared. They are [CoL(1)(py)3]·NO3 (1), [CoL(2)(bipy)(N3)]·CH3OH (2), [CoL(3)(HL(3))(N3)]·NO3 (3), and [CoL(4)(MeOH)(N3)] (4), where L(1), L(2), L(3) and L(4) are the deprotonated form of N'-(2-hydroxy-5-methoxybenzylidene)-3-methylbenzohydrazide, N'-(2-hydroxybenzylidene)-3-hydroxylbenzohydrazide, 2-[(2-dimethylaminoethylimino)methyl]-4-methylphenol, and N,N'-bis(5-methylsalicylidene)-o-phenylenediamine, respectively, py is pyridine, and bipy is 2,2'-bipyridine. The complexes were characterized by infrared and UV-Vis spectra, and single crystal X-ray diffraction. The Co atoms in the complexes are in octahedral coordination. Complexes 1 and 4 show effective urease inhibitory activities, with IC50 values of 4.27 and 0.35 μmol L(-1), respectively. Complex 2 has medium activity against urease, with IC50 value of 68.7 μmol L(-1). While complex 3 has no activity against urease. Molecular docking study of the complexes with Helicobacter pylori urease was performed.

  16. SNARE Complex Zipping as a Driving Force in the Dilation of Proteinaceous Fusion Pores

    PubMed Central

    Jackson, Meyer B.

    2010-01-01

    The assembly of SNARE proteins into a tight complex has been hypothesized to drive membrane fusion. A model of the initial fusion pore as a proteinaceous channel formed by SNARE proteins places their membrane anchors in separate membranes. This leaves the possibility of a final assembly step that brings the membrane anchors together and drives fusion pore expansion. The present study develops a model for expansion in which the final SNARE complex zipping step drives a transition from a proteinaceous fusion pore to a lipidic fusion pore. An estimate of the energy released upon merger of the helical segment of the SNARE motif with the helical membrane anchor indicates that completing the assembly of a few SNARE complexes can overcome the elastic energy that opposes lipid bilayer deformation into a narrow fusion pore. The angle between the long axes of membrane anchor and SNARE motif serves as a useful reaction coordinate for this transition. Energy was calculated as a function of this angle, incorporating contributions from membrane bending, SNARE complex assembly, membrane anchor flexing, and hydrophobic interactions. The rate of this transition was evaluated as a process of diffusion over the barrier imposed by these combined energies, and the rates estimated were consistent with experimental measurements. PMID:20512644

  17. GM-CSF-neuroantigen fusion proteins reverse experimental autoimmune encephalomyelitis and mediate tolerogenic activity in adjuvant-primed environments: association with inflammation-dependent, inhibitory antigen presentation.

    PubMed

    Islam, S M Touhidul; Curtis, Alan D; Taslim, Najla; Wilkinson, Daniel S; Mannie, Mark D

    2014-09-01

    Single-chain fusion proteins comprised of GM-CSF and neuroantigen (NAg) are potent, NAg-specific inhibitors of experimental autoimmune encephalomyelitis (EAE). An important question was whether GMCSF-NAg tolerogenic vaccines retained inhibitory activity within inflammatory environments or were contingent upon steady-state conditions. GM-CSF fused to the myelin oligodendrocyte glycoprotein MOG35-55 peptide (GMCSF-MOG) reversed established paralytic disease in both passive and active models of EAE in C57BL/6 mice. The fusion protein also reversed EAE in CD4-deficient and B cell-deficient mice. Notably, GMCSF-MOG inhibited EAE when coinjected adjacent to the MOG35-55/CFA emulsion. GMCSF-MOG also retained dominant inhibitory activity when directly emulsified with MOG35-55 in the CFA emulsion in both C57BL/6 or B cell-deficient models of EAE. Likewise, when combined with proteolipid protein 139-151 in CFA, GM-CSF fused to proteolipid protein 139-151 peptide inhibited EAE in SJL mice. When deliberately emulsified in CFA with the NAg, GMCSF-NAg inhibited EAE even though NAg was present at >30-fold molar excess. In vitro studies revealed that the GM-CSF domain of GMCSF-MOG stimulated growth and differentiation of inflammatory dendritic cells (DC) and simultaneously targeted the MOG35-55 domain for enhanced presentation by these DC. These inflammatory DC presented MOG35-55 to MOG-specific T cells by an inhibitory mechanism that was mediated in part by IFN-γ signaling and NO production. In conclusion, GMCSF-NAg was tolerogenic in CFA-primed proinflammatory environments by a mechanism associated with targeted Ag presentation by inflammatory DC and an inhibitory IFN-γ/NO pathway. The inhibitory activity of GMCSF-NAg in CFA-primed lymphatics distinguishes GMCSF-NAg fusion proteins as a unique class of inflammation-dependent tolerogens that are mechanistically distinct from naked peptide or protein-based tolerogens.

  18. Inhibitory effect of Disulfiram/copper complex on non-small cell lung cancer cells

    SciTech Connect

    Duan, Lincan; Shen, Hongmei; Zhao, Guangqiang; Yang, Runxiang; Cai, Xinyi; Zhang, Lijuan; Jin, Congguo; Huang, Yunchao

    2014-04-18

    Highlights: • Disulfiram and copper synergistically inhibit lung cancer cell proliferation. • Lung cancer cell colony formation ability is inhibited by Disulfiram/copper. • Disulfiram/copper increases the sensitivity of cisplatin to lung cancer cells. • Lung cancer stem cells are specifically targeted by Disulfiram/copper complex. - Abstract: Non-small cell lung cancer (NSCLC) is the most common cause of cancer-related death in both men and women worldwide. Recently, Disulfiram has been reported to be able to inhibit glioblastoma, prostate, or breast cancer cell proliferation. In this study, the synergistic effect of Disulfiram and copper on NSCLC cell growth was investigated. Inhibition of cancer cell proliferation was detected by 1-(4,5-Dimethylthiazol-2-yl)-3,5-diphenylformazan (MTT) assay and cell cycle analysis. Liquid colony formation and tumor spheroid formation assays were used to evaluate their effect on cancer cell clonogenicity. Real-time PCR was performed to test the mRNA level of cancer stem cell related genes. We found that Disulfiram or copper alone did not potently inhibit NSCLC cell proliferation in vitro. However, the presence of copper significantly enhanced inhibitory effect of Disulfiram on NSCLC cell growth, indicating a synergistic effect between Disulfiram and copper. Cell cycle analysis showed that Disulfiram/copper complex caused NSCLC cell cycle arrest in G2/M phase. Furthermore, Disulfiram/copper significantly increased the sensitivity of cisplatin in NSCLC cells tested by MTT assay. Liquid colony formation assay revealed that copper dramatically increased the inhibitory effect of Disulfiram on NSCLC cell colony forming ability. Disulfiram combined with copper significantly attenuated NSCLC cell spheroid formation and recuded the mRNA expression of lung cancer stem cell related genes. Our data suggest that Disulfiram/copper complex alone or combined with other chemotherapy is a potential therapeutic strategy for NSCLC patients.

  19. Inhibitory Effects of Amorphigenin on the Mitochondrial Complex I of Culex pipiens pallens Coquillett (Diptera: Culicidae)

    PubMed Central

    Ji, Mingshan; Liang, Yaping; Gu, Zumin; Li, Xiuwei

    2015-01-01

    Previous studies in our laboratory found that the extract from seeds of Amorpha fruticosa in the Leguminosae family had lethal effects against mosquito larvae, and an insecticidal compound amorphigenin was isolated. In this study, the inhibitory effects of amorphigenin against the mitochondrial complex I of Culex pipiens pallens (Diptera: Culicidae) were investigated and compared with that of rotenone. The results showed that amorphigenin and rotenone can decrease the mitochondrial complex I activity both in vivo and in vitro as the in vivo IC50 values (the inhibitor concentrations leading to 50% of the enzyme activity lost) were determined to be 2.4329 and 2.5232 μmol/L, respectively, while the in vitro IC50 values were 2.8592 and 3.1375 μmol/L, respectively. Both amorphigenin and rotenone were shown to be reversible and mixed-I type inhibitors of the mitochondrial complex I of Cx. pipiens pallens, indicating that amorphigenin and rotenone inhibited the enzyme activity not only by binding with the free enzyme but also with the enzyme-substrate complex, and the values of KI and KIS for amorphigenin were determined to be 20.58 and 87.55 μM, respectively, while the values for rotenone were 14.04 and 69.23 μM, respectively. PMID:26307964

  20. Identification of a Potent and Broad-Spectrum Hepatitis C Virus Fusion Inhibitory Peptide from the E2 Stem Domain

    PubMed Central

    Chi, Xiaojing; Niu, Yuqiang; Cheng, Min; Liu, Xiuying; Feng, Yetong; Zheng, Fuxiang; Fan, Jingjing; Li, Xiang; Jin, Qi; Zhong, Jin; Li, Yi-Ping; Yang, Wei

    2016-01-01

    Hepatitis C virus (HCV) envelope proteins E1 and E2 play an essential role in virus entry. However, the fusion mechanisms of HCV remain largely unclear, hampering the development of efficient fusion inhibitors. Here, we developed two cell-based membrane fusion models that allow for screening a peptide library covering the full-length E1 and E2 amino acid sequences. A peptide from the E2 stem domain, named E27, was found to possess the ability to block E1E2-mediated cell-cell fusion and inhibit cell entry of HCV pseudoparticles and infection of cell culture-derived HCV at nanomolar concentrations. E27 demonstrated broad-spectrum inhibition of the major genotypes 1 to 6. A time-of-addition experiment revealed that E27 predominantly functions in the late steps during HCV entry, without influencing the expression and localization of HCV co-receptors. Moreover, we demonstrated that E27 interfered with hetero-dimerization of ectopically expressed E1E2 in cells, and mutational analysis suggested that E27 might target a conserved region in E1. Taken together, our findings provide a novel candidate as well as a strategy for developing potent and broad-spectrum HCV fusion inhibitors, which may complement the current direct-acting antiviral medications for chronic hepatitis C, and shed light on the mechanism of HCV membrane fusion. PMID:27121372

  1. Nanoluciferase as a novel quantitative protein fusion tag: Application for overexpression and bioluminescent receptor-binding assays of human leukemia inhibitory factor.

    PubMed

    He, Sheng-Xiang; Song, Ge; Shi, Jia-Ping; Guo, Yu-Qi; Guo, Zhan-Yun

    2014-11-01

    Nanoluciferase (NanoLuc) is a newly developed small luciferase reporter with the brightest bioluminescence reported to date. In the present work, we developed NanoLuc as a novel quantitative protein fusion tag for efficient overexpression in Escherichia coli and ultrasensitive bioluminescent assays using human leukemia inhibitory factor (LIF) as a model protein. LIF is an interleukin 6 family cytokine that elicits pleiotropic effects on a diverse range of cells by activating a heterodimeric LIFR/gp130 receptor. Recombinant preparation of the biologically active LIF protein is quite difficult due to its hydrophobic nature and three disulfide bonds. Using the novel NanoLuc-fusion approach, soluble 6×His-NanoLuc-LIF fusion protein was efficiently overexpressed in E. coli and enzymatically converted to monomeric mature LIF. Both the mature LIF and the NanoLuc-fused LIF had high biological activities in a leukemia M1 cell proliferation inhibition assay and in a STAT3 signaling activation assay. The NanoLuc-fused LIF retained high binding affinities with the overexpressed LIFR (Kd = 1.4 ± 0.4 nM, n = 3), the overexpressed LIFR/gp130 (Kd = 115 ± 8 pM, n = 3), and the endogenously expressed LIFR/gp130 (Kd = 33.1 ± 3.2 pM, n = 3), with a detection limit of less than 10 receptors per cell. Thus, the novel NanoLuc-fusion strategy not only provided an efficient approach for preparation of recombinant LIF protein but also provided a novel ultrasensitive bioluminescent tracer for ligand-receptor interaction studies. The novel NanoLuc-fusion approach could be extended to other proteins for both efficient sample preparation and various bioluminescent quantitative assays in future studies.

  2. Inhibitory effect of Disulfiram/copper complex on non-small cell lung cancer cells.

    PubMed

    Duan, Lincan; Shen, Hongmei; Zhao, Guangqiang; Yang, Runxiang; Cai, Xinyi; Zhang, Lijuan; Jin, Congguo; Huang, Yunchao

    2014-04-18

    Non-small cell lung cancer (NSCLC) is the most common cause of cancer-related death in both men and women worldwide. Recently, Disulfiram has been reported to be able to inhibit glioblastoma, prostate, or breast cancer cell proliferation. In this study, the synergistic effect of Disulfiram and copper on NSCLC cell growth was investigated. Inhibition of cancer cell proliferation was detected by 1-(4,5-Dimethylthiazol-2-yl)-3,5-diphenylformazan (MTT) assay and cell cycle analysis. Liquid colony formation and tumor spheroid formation assays were used to evaluate their effect on cancer cell clonogenicity. Real-time PCR was performed to test the mRNA level of cancer stem cell related genes. We found that Disulfiram or copper alone did not potently inhibit NSCLC cell proliferation in vitro. However, the presence of copper significantly enhanced inhibitory effect of Disulfiram on NSCLC cell growth, indicating a synergistic effect between Disulfiram and copper. Cell cycle analysis showed that Disulfiram/copper complex caused NSCLC cell cycle arrest in G2/M phase. Furthermore, Disulfiram/copper significantly increased the sensitivity of cisplatin in NSCLC cells tested by MTT assay. Liquid colony formation assay revealed that copper dramatically increased the inhibitory effect of Disulfiram on NSCLC cell colony forming ability. Disulfiram combined with copper significantly attenuated NSCLC cell spheroid formation and recuded the mRNA expression of lung cancer stem cell related genes. Our data suggest that Disulfiram/copper complex alone or combined with other chemotherapy is a potential therapeutic strategy for NSCLC patients.

  3. Preparation and crystallization of the stimulatory and inhibitory complexes of GTP cyclohydrolase I and its feedback regulatory protein GFRP.

    PubMed

    Maita, N; Okada, K; Hirotsu, S; Hatakeyama, K; Hakoshima, T

    2001-08-01

    Mammalian GTP cyclohydrolase I is a decameric enzyme in the first and rate-limiting step in the biosynthesis of tetrahydrobiopterin, which is an essential cofactor for enzymes producing neurotransmitters such as catecholamines and for nitric oxide synthases. The enzyme is dually regulated by its feedback regulatory protein GFRP in the presence of its stimulatory effector phenylalanine and its inhibitory effector biopterin. Here, both the stimulatory and inhibitory complexes of rat GTP cyclohydrolase I bound to GFRP were crystallized by vapour diffusion. Diffraction data sets at resolutions of 3.0 and 2.64 A were collected for the stimulatory and inhibitory complexes, respectively. Each complex consists of two GTPCHI pentamer rings and two GFRP pentamer rings, with pseudo-52 point-group symmetry.

  4. Importin beta negatively regulates nuclear membrane fusion and nuclear pore complex assembly.

    PubMed

    Harel, Amnon; Chan, Rene C; Lachish-Zalait, Aurelie; Zimmerman, Ella; Elbaum, Michael; Forbes, Douglass J

    2003-11-01

    Assembly of a eukaryotic nucleus involves three distinct events: membrane recruitment, fusion to form a double nuclear membrane, and nuclear pore complex (NPC) assembly. We report that importin beta negatively regulates two of these events, membrane fusion and NPC assembly. When excess importin beta is added to a full Xenopus nuclear reconstitution reaction, vesicles are recruited to chromatin but their fusion is blocked. The importin beta down-regulation of membrane fusion is Ran-GTP reversible. Indeed, excess RanGTP (RanQ69L) alone stimulates excessive membrane fusion, leading to intranuclear membrane tubules and cytoplasmic annulate lamellae-like structures. We propose that a precise balance of importin beta to Ran is required to create a correct double nuclear membrane and simultaneously to repress undesirable fusion events. Interestingly, truncated importin beta 45-462 allows membrane fusion but produces nuclei lacking any NPCs. This reveals distinct importin beta-regulation of NPC assembly. Excess full-length importin beta and beta 45-462 act similarly when added to prefused nuclear intermediates, i.e., both block NPC assembly. The importin beta NPC block, which maps downstream of GTPgammaS and BAPTA-sensitive steps in NPC assembly, is reversible by cytosol. Remarkably, it is not reversible by 25 microM RanGTP, a concentration that easily reverses fusion inhibition. This report, using a full reconstitution system and natural chromatin substrates, significantly expands the repertoire of importin beta. Its roles now encompass negative regulation of two of the major events of nuclear assembly: membrane fusion and NPC assembly.

  5. Novel BRD4-NUT fusion isoforms increase the pathogenic complexity in NUT midline carcinoma.

    PubMed

    Thompson-Wicking, K; Francis, R W; Stirnweiss, A; Ferrari, E; Welch, M D; Baker, E; Murch, A R; Gout, A M; Carter, K W; Charles, A K; Phillips, M B; Kees, U R; Beesley, A H

    2013-09-26

    Nuclear protein in testis (NUT)-midline carcinoma (NMC) is a rare, aggressive disease typically presenting with a single t(15;19) translocation that results in the generation of a bromodomain-containing protein 4 (BRD4)-NUT fusion. PER-624 is a cell line generated from an NMC patient with an unusually complex karyotype that gave no initial indication of the involvement of the NUT locus. Analysis of PER-624 next-generation transcriptome sequencing (RNA-Seq) using the algorithm FusionFinder identified a novel transcript in which Exon 15 of BRD4 was fused to Exon 2 of NUT, therefore differing from all published NMC fusion transcripts. The three additional exons contained in the PER-624 fusion encode a series of polyproline repeats, with one predicted to form a helix. In the NMC cell line PER-403, we identified the 'standard' NMC fusion and two novel isoforms. Knockdown by small interfering RNA in either cell line resulted in decreased proliferation, increased cell size and expression of cytokeratins consistent with epithelial differentiation. These data demonstrate that the novel BRD4-NUT fusion in PER-624 encodes a functional protein that is central to the oncogenic mechanism in these cells. Genomic PCR indicated that in both PER-624 and PER-403, the translocation fuses an intron of BRD4 to a region upstream of the NUT coding sequence. Thus, the generation of BRD4-NUT fusion transcripts through post-translocation RNA-splicing appears to be a common feature of these carcinomas that has not previously been appreciated, with the mechanism facilitating the expression of alternative isoforms of the fusion. Finally, ectopic expression of wild-type NUT, a protein normally restricted to the testis, could be demonstrated in PER-403, indicating additional pathways for aberrant cell signaling in NMC. This study contributes to our understanding of the genetic diversity of NMC, an important step towards finding therapeutic targets for a disease that is refractory to current

  6. Sec3 promotes the initial binary t-SNARE complex assembly and membrane fusion

    PubMed Central

    Yue, Peng; Zhang, Yubo; Mei, Kunrong; Wang, Shaoxiao; Lesigang, Johannes; Zhu, Yueyao; Dong, Gang; Guo, Wei

    2017-01-01

    The soluble N-ethylmaleimide-sensitive factor-attachment protein receptors (SNAREs) constitute the core machinery for membrane fusion during eukaryotic cell vesicular trafficking. However, how the assembly of the SNARE complex is initiated is unknown. Here we report that Sec3, a component of the exocyst complex that mediates vesicle tethering during exocytosis, directly interacts with the t-SNARE protein Sso2. This interaction promotes the formation of an Sso2-Sec9 ‘binary' t-SNARE complex, the early rate-limiting step in SNARE complex assembly, and stimulates membrane fusion. The crystal structure of the Sec3-Sso2 complex suggests that Sec3 binding induces conformational changes of Sso2 that are crucial for the relief of its auto-inhibition. Interestingly, specific disruption of the Sec3–Sso2 interaction in cells blocks exocytosis without affecting the function of Sec3 in vesicle tethering. Our study reveals an activation mechanism for SNARE complex assembly, and uncovers a role of the exocyst in promoting membrane fusion in addition to vesicle tethering. PMID:28112172

  7. Complex synchronous behavior in interneuronal networks with delayed inhibitory and fast electrical synapses

    NASA Astrophysics Data System (ADS)

    Guo, Daqing; Wang, Qingyun; Perc, Matjaž

    2012-06-01

    Networks of fast-spiking interneurons are crucial for the generation of neural oscillations in the brain. Here we study the synchronous behavior of interneuronal networks that are coupled by delayed inhibitory and fast electrical synapses. We find that both coupling modes play a crucial role by the synchronization of the network. In addition, delayed inhibitory synapses affect the emerging oscillatory patterns. By increasing the inhibitory synaptic delay, we observe a transition from regular to mixed oscillatory patterns at a critical value. We also examine how the unreliability of inhibitory synapses influences the emergence of synchronization and the oscillatory patterns. We find that low levels of reliability tend to destroy synchronization and, moreover, that interneuronal networks with long inhibitory synaptic delays require a minimal level of reliability for the mixed oscillatory pattern to be maintained.

  8. Positively charged amino acids at the SNAP-25 C terminus determine fusion rates, fusion pore properties, and energetics of tight SNARE complex zippering.

    PubMed

    Fang, Qinghua; Zhao, Ying; Herbst, Adam Drew; Kim, Brian N; Lindau, Manfred

    2015-02-18

    SNAP-25 is a Q-SNARE protein mediating exocytosis of neurosecretory vesicles including chromaffin granules. Previous results with a SNAP-25 construct lacking the nine C terminal residues (SNAP-25Δ9) showed changed fusion pore properties (Fang et al., 2008), suggesting a model for fusion pore mechanics that couple C terminal zipping of the SNARE complex to the opening of the fusion pore. The deleted fragment contains the positively charged residues R198 and K201, adjacent to layers 7 and 8 of the SNARE complex. To determine how fusion pore conductance and dynamics depend on these residues, single exocytotic events in bovine chromaffin cells expressing R198Q, R198E, K201Q, or K201E mutants were investigated by carbon fiber amperometry and cell-attached patch capacitance measurements. Coarse grain molecular dynamics simulations revealed spontaneous transitions between a loose and tightly zippered state at the SNARE complex C terminus. The SNAP-25 K201Q mutant showed no changes compared with SNAP-25 wild-type. However, K201E, R198Q, and R198E displayed reduced release frequencies, slower release kinetics, and prolonged fusion pore duration that were correlated with reduced probability to engage in the tightly zippered state. The results show that the positively charged amino acids at the SNAP-25 C terminus promote tight SNARE complex zippering and are required for high release frequency and rapid release in individual fusion events.

  9. A structural model of the anaphase promoting complex co-activator (Cdh1) and in silico design of inhibitory compounds

    PubMed Central

    Rahimi, H.; Negahdari, B.; Shokrgozar, M.A.; Madadkar-Sobhani, A.; Mahdian, R.; Foroumadi, A.; Amin, M. Kafshdouzi; Karimipoor, M.

    2015-01-01

    Anaphase promoting complex (APC) controls cell cycle and chromosome segregation. The APC activation occurs after binding of co-activators, cdh1 and cdc20. Cdh1 plays a role in cancer pathogenesis and is known as a potential drug target. The main aim of this study was prediction of 3D structure of cdh1 and designing the inhibitory compounds based on the structural model. First, 3D structure of cdh1 was predicted by means of homology modelling and molecular dynamics tools, MODELLER and Gromacs package, respectively. Then, inhibitory compounds were designed using virtual screening and molecular docking by means AutoDock package. The overall structure of cdh1 is propeller like and each DW40 repeat contains four anti-parallel beta-sheets. Moreover, binding pocket of the inhibitory compounds was determined. The results might be helpful in finding a suitable cdh1 inhibitor for the treatment of cancer. PMID:26430458

  10. A structural model of the anaphase promoting complex co-activator (Cdh1) and in silico design of inhibitory compounds.

    PubMed

    Rahimi, H; Negahdari, B; Shokrgozar, M A; Madadkar-Sobhani, A; Mahdian, R; Foroumadi, A; Amin, M Kafshdouzi; Karimipoor, M

    2015-01-01

    Anaphase promoting complex (APC) controls cell cycle and chromosome segregation. The APC activation occurs after binding of co-activators, cdh1 and cdc20. Cdh1 plays a role in cancer pathogenesis and is known as a potential drug target. The main aim of this study was prediction of 3D structure of cdh1 and designing the inhibitory compounds based on the structural model. First, 3D structure of cdh1 was predicted by means of homology modelling and molecular dynamics tools, MODELLER and Gromacs package, respectively. Then, inhibitory compounds were designed using virtual screening and molecular docking by means AutoDock package. The overall structure of cdh1 is propeller like and each DW40 repeat contains four anti-parallel beta-sheets. Moreover, binding pocket of the inhibitory compounds was determined. The results might be helpful in finding a suitable cdh1 inhibitor for the treatment of cancer.

  11. Complex epithelial remodeling underlie the fusion event in early fetal development of the human penile urethra.

    PubMed

    Shen, Joel; Overland, Maya; Sinclair, Adriane; Cao, Mei; Yue, Xuan; Cunha, Gerald; Baskin, Laurence

    We recently described a two-step process of urethral plate canalization and urethral fold fusion to form the human penile urethra. Canalization ("opening zipper") opens the solid urethral plate into a groove, and fusion ("closing zipper") closes the urethral groove to form the penile urethra. We hypothesize that failure of canalization and/or fusion during human urethral formation can lead to hypospadias. Herein, we use scanning electron microscopy (SEM) and analysis of transverse serial sections to better characterize development of the human fetal penile urethra as contrasted to the development of the human fetal clitoris. Eighteen 7-13 week human fetal external genitalia specimens were analyzed by SEM, and fifteen additional human fetal specimens were sectioned for histologic analysis. SEM images demonstrate canalization of the urethral/vestibular plate in the developing male and female external genitalia, respectively, followed by proximal to distal fusion of the urethral folds in males only. The fusion process during penile development occurs sequentially in multiple layers and through the interlacing of epidermal "cords". Complex epithelial organization is also noted at the site of active canalization. The demarcation between the epidermis of the shaft and the glans becomes distinct during development, and the epithelial tag at the distal tip of the penile and clitoral glans regresses as development progresses. In summary, SEM analysis of human fetal specimens supports the two-zipper hypothesis of formation of the penile urethra. The opening zipper progresses from proximal to distal along the shaft of the penis and clitoris into the glans in identical fashion in both sexes. The closing zipper mechanism is active only in males and is not a single process but rather a series of layered fusion events, uniquely different from the simple fusion of two epithelial surfaces as occurs in formation of the palate and neural tube.

  12. Improving image classification in a complex wetland ecosystem through image fusion techniques

    NASA Astrophysics Data System (ADS)

    Kumar, Lalit; Sinha, Priyakant; Taylor, Subhashni

    2014-01-01

    The aim of this study was to evaluate the impact of image fusion techniques on vegetation classification accuracies in a complex wetland system. Fusion of panchromatic (PAN) and multispectral (MS) Quickbird satellite imagery was undertaken using four image fusion techniques: Brovey, hue-saturation-value (HSV), principal components (PC), and Gram-Schmidt (GS) spectral sharpening. These four fusion techniques were compared in terms of their mapping accuracy to a normal MS image using maximum-likelihood classification (MLC) and support vector machine (SVM) methods. Gram-Schmidt fusion technique yielded the highest overall accuracy and kappa value with both MLC (67.5% and 0.63, respectively) and SVM methods (73.3% and 0.68, respectively). This compared favorably with the accuracies achieved using the MS image. Overall, improvements of 4.1%, 3.6%, 5.8%, 5.4%, and 7.2% in overall accuracies were obtained in case of SVM over MLC for Brovey, HSV, GS, PC, and MS images, respectively. Visual and statistical analyses of the fused images showed that the Gram-Schmidt spectral sharpening technique preserved spectral quality much better than the principal component, Brovey, and HSV fused images. Other factors, such as the growth stage of species and the presence of extensive background water in many parts of the study area, had an impact on classification accuracies.

  13. Combinatorial SNARE complexes with VAMP7 or VAMP8 define different late endocytic fusion events.

    PubMed

    Pryor, Paul R; Mullock, Barbara M; Bright, Nicholas A; Lindsay, Margaret R; Gray, Sally R; Richardson, Simon C W; Stewart, Abigail; James, David E; Piper, Robert C; Luzio, J Paul

    2004-06-01

    Both heterotypic and homotypic fusion events are required to deliver endocytosed macromolecules to lysosomes and remodel late endocytic organelles. A trans-SNARE complex consisting of Q-SNAREs syntaxin 7, Vti1b and syntaxin 8 and the R-SNARE VAMP8 has been shown by others to be responsible for homotypic fusion of late endosomes. Using antibody inhibition experiments in rat liver cell-free systems, we confirmed this result, but found that the same Q-SNAREs can combine with an alternative R-SNARE, namely VAMP7, for heterotypic fusion between late endosomes and lysosomes. Co-immunoprecipitation demonstrated separate syntaxin 7 complexes with either VAMP7 or VAMP8 in solubilized rat liver membranes. Additionally, overexpression of the N-terminal domain of VAMP7, in cultured fibroblastic cells, inhibited the mixing of a preloaded lysosomal content marker with a marker delivered to late endosomes. These data show that combinatorial interactions of SNAREs determine whether late endosomes undergo homotypic or heterotypic fusion events.

  14. Figure-ground discrimination in the avian brain: The nucleus rotundus and its inhibitory complex

    PubMed Central

    Acerbo, Martin J.; Lazareva, Olga F.; McInnerney, John; Leiker, Emily; Wasserman, Edward A.; Poremba, Amy

    2012-01-01

    In primates, neurons sensitive to figure-ground status are located in striate cortex (area V1) and extrastriate cortex (area V2). Although much is known about the anatomical structure and connectivity of the avian visual pathway, the functional organization of the avian brain remains largely unexplored. To pinpoint the areas associated with figure-ground segregation in the avian brain, we used a radioactively labeled glucose analog to compare differences in glucose uptake after figure-ground, color, and shape discriminations. We also included a control group that received food on a variable-interval schedule, but was not required to learn a visual discrimination. Although the discrimination task depended on group assignment, the stimulus displays were identical for all three experimental groups, ensuring that all animals were exposed to the same visual input. Our analysis concentrated on the primary thalamic nucleus associated with visual processing, the nucleus rotundus (Rt), and two nuclei providing regulatory feedback, the pretectum (PT) and the nucleus subpretectalis/interstitio-pretecto-subpretectalis complex (SP/IPS). We found that figure-ground discrimination was associated with strong and nonlateralized activity of Rt and SP/IPS, whereas color discrimination produced strong and lateralized activation in Rt alone. Shape discrimination was associated with lower activity of Rt than in the control group. Taken together, our results suggest that figure-ground discrimination is associated with Rt and that SP/IPS may be a main source of inhibitory control. Thus, figure-ground segregation in the avian brain may occur earlier than in the primate brain. PMID:22917681

  15. Regression of anterior disc-osteophyte complex following cervical laminectomy and fusion for cervical spondylotic myelopathy

    PubMed Central

    Ashana, Adedayo O.; Cohen, Jeremiah R.; Evans, Brandon; Holly, Langston T.

    2014-01-01

    Study Design Retrospective case control study Objective To investigate whether posterior cervical laminectomy and fusion modifies the natural course of anterior disc-osteophyte complex in patients with multilevel CSM Summary of Background Data Dorsal migration of the spinal cord is the main purported mechanism of spinal cord decompression following cervical laminectomy and fusion but other potential mechanisms have received scant attention in the literature. This study was conducted to investigate whether cervical laminectomy and fusion affects the size of anterior disc osteophyte complex. Methods The medical records and radiographical imaging of 44 patients that underwent cervical laminectomy and fusion for CSM between 2006 and 2013 were analyzed. The size of the anterior disc osteophyte complex was measured pre and postoperatively on MR images taken at an interval of > 3 months apart. A control group consisted of 20 non-operatively treated advanced cervical spondylosis patients. Patients in the control met the same inclusion and exclusion criteria and also had sequential MRI taken at an interval of > 3 months apart. Results The nonoperative and operative groups were statistically similar in the pertinent patient demographics and characteristics including gender, age, time to second MRI, size of anterior disc-osteophyte complex on baseline MRI, mean number of levels affected, and percentage of patients with T2 signal change. As expected the mJOA scores were significantly lower in the operative versus nonoperative cohort (13.6 vs. 16.5, P<0.01). A significant decrease in the size of anterior disc osteophyte was observed in the operative group postoperatively (P<0.01). In comparison, there was no statistically significant change in the size of the anterior disc osteophyte complex in the control group (P > 0.05). The magnitude of the change in disc size between the two groups was statistically significant (P <0.01). Conclusion The findings of this study suggest that

  16. Feature level fusion for enhanced geological mapping of ophiolile complex using ASTER and Landsat TM data

    NASA Astrophysics Data System (ADS)

    Pournamdari, M.; Hashim, M.

    2014-02-01

    Chromite ore deposit occurrence is related to ophiolite complexes as a part of the oceanic crust and provides a good opportunity for lithological mapping using remote sensing data. The main contribution of this paper is a novel approaches to discriminate different rock units associated with ophiolite complex using the Feature Level Fusion technique on ASTER and Landsat TM satellite data at regional scale. In addition this study has applied spectral transform approaches, consisting of Spectral Angle Mapper (SAM) to distinguish the concentration of high-potential areas of chromite and also for determining the boundary between different rock units. Results indicated both approaches show superior outputs compared to other methods and can produce a geological map for ophiolite complex rock units in the arid and the semi-arid region. The novel technique including feature level fusion and Spectral Angle Mapper (SAM) discriminated ophiolitic rock units and produced detailed geological maps of the study area. As a case study, Sikhoran ophiolite complex located in SE, Iran has been selected for image processing techniques. In conclusion, a suitable approach for lithological mapping of ophiolite complexes is demonstrated, this technique contributes meaningfully towards economic geology in terms of identifying new prospects.

  17. Data fusion for QRS complex detection in multi-lead electrocardiogram recordings

    NASA Astrophysics Data System (ADS)

    Ledezma, Carlos A.; Perpiñan, Gilberto; Severeyn, Erika; Altuve, Miguel

    2015-12-01

    Heart diseases are the main cause of death worldwide. The first step in the diagnose of these diseases is the analysis of the electrocardiographic (ECG) signal. In turn, the ECG analysis begins with the detection of the QRS complex, which is the one with the most energy in the cardiac cycle. Numerous methods have been proposed in the bibliography for QRS complex detection, but few authors have analyzed the possibility of taking advantage of the information redundancy present in multiple ECG leads (simultaneously acquired) to produce accurate QRS detection. In our previous work we presented such an approach, proposing various data fusion techniques to combine the detections made by an algorithm on multiple ECG leads. In this paper we present further studies that show the advantages of this multi-lead detection approach, analyzing how many leads are necessary in order to observe an improvement in the detection performance. A well known QRS detection algorithm was used to test the fusion techniques on the St. Petersburg Institute of Cardiological Technics database. Results show improvement in the detection performance with as little as three leads, but the reliability of these results becomes interesting only after using seven or more leads. Results were evaluated using the detection error rate (DER). The multi-lead detection approach allows an improvement from DER = 3:04% to DER = 1:88%. Further works are to be made in order to improve the detection performance by implementing further fusion steps.

  18. Crystal structure of the conserved herpes virus fusion regulator complex gH-gL

    SciTech Connect

    Chowdary, Tirumala K; Cairns, Tina M; Atanasiu, Doina; Cohen, Gary H; Eisenberg, Roselyn J; Heldwein, Ekaterina E

    2010-09-13

    Herpesviruses, which cause many incurable diseases, infect cells by fusing viral and cellular membranes. Whereas most other enveloped viruses use a single viral catalyst called a fusogen, herpesviruses, inexplicably, require two conserved fusion-machinery components, gB and the heterodimer gH-gL, plus other nonconserved components. gB is a class III viral fusogen, but unlike other members of its class, it does not function alone. We determined the crystal structure of the gH ectodomain bound to gL from herpes simplex virus 2. gH-gL is an unusually tight complex with a unique architecture that, unexpectedly, does not resemble any known viral fusogen. Instead, we propose that gH-gL activates gB for fusion, possibly through direct binding. Formation of a gB-gH-gL complex is critical for fusion and is inhibited by a neutralizing antibody, making the gB-gH-gL interface a promising antiviral target.

  19. Crystal Structure of the Conserved Herpes Virus Fusion Regulator Complex gH–gL

    SciTech Connect

    Chowdary, T.; Cairns, T; Atanasiu, D; Cohen, G; Eisenberg, R; Heldwein, E

    2010-01-01

    Herpesviruses, which cause many incurable diseases, infect cells by fusing viral and cellular membranes. Whereas most other enveloped viruses use a single viral catalyst called a fusogen, herpesviruses, inexplicably, require two conserved fusion-machinery components, gB and the heterodimer gH-gL, plus other nonconserved components. gB is a class III viral fusogen, but unlike other members of its class, it does not function alone. We determined the crystal structure of the gH ectodomain bound to gL from herpes simplex virus 2. gH-gL is an unusually tight complex with a unique architecture that, unexpectedly, does not resemble any known viral fusogen. Instead, we propose that gH-gL activates gB for fusion, possibly through direct binding. Formation of a gB-gH-gL complex is critical for fusion and is inhibited by a neutralizing antibody, making the gB-gH-gL interface a promising antiviral target.

  20. Crystal structure of the conserved herpesvirus fusion regulator complex gH—gL

    SciTech Connect

    Chowdary, Tirumala K.; Cairns, Tina M.; Atanasiu, Doina; Cohen, Gary H.; Eisenberg, Roselyn J.; Heldwein, Ekaterina E.

    2015-02-09

    Herpesviruses, which cause many incurable diseases, infect cells by fusing viral and cellular membranes. Whereas most other enveloped viruses use a single viral catalyst called a fusogen, herpesviruses, inexplicably, require two conserved fusion-machinery components, gB and the heterodimer gH–gL, plus other nonconserved components. gB is a class III viral fusogen, but unlike other members of its class, it does not function alone. We determined the crystal structure of the gH ectodomain bound to gL from herpes simplex virus 2. gH–gL is an unusually tight complex with a unique architecture that, unexpectedly, does not resemble any known viral fusogen. Instead, we propose that gH–gL activates gB for fusion, possibly through direct binding. Formation of a gB–gH–gL complex is critical for fusion and is inhibited by a neutralizing antibody, making the gB–gH–gL interface a promising antiviral target.

  1. Structure of the human factor VIII C2 domain in complex with the 3E6 inhibitory antibody

    SciTech Connect

    Wuerth, Michelle E.; Cragerud, Rebecca K.; Spiegel, P. Clint

    2015-11-24

    Blood coagulation factor VIII is a glycoprotein cofactor that is essential for the intrinsic pathway of the blood coagulation cascade. Inhibitory antibodies arise either spontaneously or in response to therapeutic infusion of functional factor VIII into hemophilia A patients, many of which are specific to the factor VIII C2 domain. The immune response is largely parsed into “classical” and “non-classical” inhibitory antibodies, which bind to opposing faces cooperatively. In this study, the 2.61 Å resolution structure of the C2 domain in complex with the antigen-binding fragment of the 3E6 classical inhibitory antibody is reported. The binding interface is largely conserved when aligned with the previously determined structure of the C2 domain in complex with two antibodies simultaneously. Further inspection of the B factors for the C2 domain in various X-ray crystal structures indicates that 3E6 antibody binding decreases the thermal motion behavior of surface loops in the C2 domain on the opposing face, thereby suggesting that cooperative antibody binding is a dynamic effect. Furthermore, understanding the structural nature of the immune response to factor VIII following hemophilia A treatment will help lead to the development of better therapeutic reagents.

  2. Structure of the human factor VIII C2 domain in complex with the 3E6 inhibitory antibody

    DOE PAGES

    Wuerth, Michelle E.; Cragerud, Rebecca K.; Spiegel, P. Clint

    2015-11-24

    Blood coagulation factor VIII is a glycoprotein cofactor that is essential for the intrinsic pathway of the blood coagulation cascade. Inhibitory antibodies arise either spontaneously or in response to therapeutic infusion of functional factor VIII into hemophilia A patients, many of which are specific to the factor VIII C2 domain. The immune response is largely parsed into “classical” and “non-classical” inhibitory antibodies, which bind to opposing faces cooperatively. In this study, the 2.61 Å resolution structure of the C2 domain in complex with the antigen-binding fragment of the 3E6 classical inhibitory antibody is reported. The binding interface is largely conservedmore » when aligned with the previously determined structure of the C2 domain in complex with two antibodies simultaneously. Further inspection of the B factors for the C2 domain in various X-ray crystal structures indicates that 3E6 antibody binding decreases the thermal motion behavior of surface loops in the C2 domain on the opposing face, thereby suggesting that cooperative antibody binding is a dynamic effect. Furthermore, understanding the structural nature of the immune response to factor VIII following hemophilia A treatment will help lead to the development of better therapeutic reagents.« less

  3. Structure of the Human Factor VIII C2 Domain in Complex with the 3E6 Inhibitory Antibody.

    PubMed

    Wuerth, Michelle E; Cragerud, Rebecca K; Spiegel, P Clint

    2015-11-24

    Blood coagulation factor VIII is a glycoprotein cofactor that is essential for the intrinsic pathway of the blood coagulation cascade. Inhibitory antibodies arise either spontaneously or in response to therapeutic infusion of functional factor VIII into hemophilia A patients, many of which are specific to the factor VIII C2 domain. The immune response is largely parsed into "classical" and "non-classical" inhibitory antibodies, which bind to opposing faces cooperatively. In this study, the 2.61 Å resolution structure of the C2 domain in complex with the antigen-binding fragment of the 3E6 classical inhibitory antibody is reported. The binding interface is largely conserved when aligned with the previously determined structure of the C2 domain in complex with two antibodies simultaneously. Further inspection of the B factors for the C2 domain in various X-ray crystal structures indicates that 3E6 antibody binding decreases the thermal motion behavior of surface loops in the C2 domain on the opposing face, thereby suggesting that cooperative antibody binding is a dynamic effect. Understanding the structural nature of the immune response to factor VIII following hemophilia A treatment will help lead to the development of better therapeutic reagents.

  4. Structure of the malaria vaccine candidate antigen CyRPA and its complex with a parasite invasion inhibitory antibody.

    PubMed

    Favuzza, Paola; Guffart, Elena; Tamborrini, Marco; Scherer, Bianca; Dreyer, Anita M; Rufer, Arne C; Erny, Johannes; Hoernschemeyer, Joerg; Thoma, Ralf; Schmid, Georg; Gsell, Bernard; Lamelas, Araceli; Benz, Joerg; Joseph, Catherine; Matile, Hugues; Pluschke, Gerd; Rudolph, Markus G

    2017-02-14

    Invasion of erythrocytes by Plasmodial merozoites is a composite process involving the interplay of several proteins. Among them, the Plasmodium falciparum Cysteine-Rich Protective Antigen (PfCyRPA) is a crucial component of a ternary complex, including Reticulocyte binding-like Homologous protein 5 (PfRH5) and the RH5-interacting protein (PfRipr), essential for erythrocyte invasion. Here we present the crystal structure of PfCyRPA and of its complex with the antigen-binding fragment of a parasite growth inhibitory antibody. While PfCyRPA adopts a 6-bladed β-propeller structure with similarity to the classic sialidase fold, it possesses no sialidase activity, indicating that it fulfills a non-enzymatic function. Characterization of the epitope recognized by protective antibodies will facilitate design of peptidomimetics that focus vaccine responses on protective epitopes. Both in vitro and in vivo anti-PfCyRPA and anti-PfRH5 antibodies showed more potent parasite growth inhibitory activity in combination than on their own, supporting a combined delivery of PfCyRPA and PfRH5 in vaccines.

  5. Structure of the malaria vaccine candidate antigen CyRPA and its complex with a parasite invasion inhibitory antibody

    PubMed Central

    Favuzza, Paola; Guffart, Elena; Tamborrini, Marco; Scherer, Bianca; Dreyer, Anita M; Rufer, Arne C; Erny, Johannes; Hoernschemeyer, Joerg; Thoma, Ralf; Schmid, Georg; Gsell, Bernard; Lamelas, Araceli; Benz, Joerg; Joseph, Catherine; Matile, Hugues; Pluschke, Gerd; Rudolph, Markus G

    2017-01-01

    Invasion of erythrocytes by Plasmodial merozoites is a composite process involving the interplay of several proteins. Among them, the Plasmodium falciparum Cysteine-Rich Protective Antigen (PfCyRPA) is a crucial component of a ternary complex, including Reticulocyte binding-like Homologous protein 5 (PfRH5) and the RH5-interacting protein (PfRipr), essential for erythrocyte invasion. Here, we present the crystal structures of PfCyRPA and its complex with the antigen-binding fragment of a parasite growth inhibitory antibody. PfCyRPA adopts a 6-bladed β-propeller structure with similarity to the classic sialidase fold, but it has no sialidase activity and fulfills a purely non-enzymatic function. Characterization of the epitope recognized by protective antibodies may facilitate design of peptidomimetics to focus vaccine responses on protective epitopes. Both in vitro and in vivo anti-PfCyRPA and anti-PfRH5 antibodies showed more potent parasite growth inhibitory activity in combination than on their own, supporting a combined delivery of PfCyRPA and PfRH5 in vaccines. DOI: http://dx.doi.org/10.7554/eLife.20383.001 PMID:28195038

  6. Oscillations, complex spatiotemporal behavior, and information transport in networks of excitatory and inhibitory neurons

    SciTech Connect

    Destexhe, A. )

    1994-08-01

    Various types of spatiotemporal behavior are described for two-dimensional networks of excitatory and inhibitory neurons with time delayed interactions. It is described how the network behaves as several structural parameters are varied, such as the number of neurons, the connectivity, and the values of synaptic weights. A transition from spatially uniform oscillations to spatiotemporal chaos via intermittentlike behavior is observed. The properties of spatiotemporally chaotic solutions are investigated by evaluating the largest positive Lyapunov exponent and the loss of correlation with distance. Finally, properties of information transport are evaluated during uniform oscillations and spatiotemporal chaos. It is shown that the diffusion coefficient increases significantly in the spatiotemporal phase similar to the increase of transport coefficients at the onset of fluid turbulence. It is proposed that such a property should be seen in other media, such as chemical turbulence or networks of oscillators. The possibility of measuring information transport from appropriate experiments is also discussed.

  7. Dynamic function of the alkyl spacer of acetogenins in their inhibitory action with mitochondrial complex I (NADH-ubiquinone oxidoreductase).

    PubMed

    Abe, Masato; Murai, Masatoshi; Ichimaru, Naoya; Kenmochi, Atsushi; Yoshida, Takehiko; Kubo, Akina; Kimura, Yuka; Moroda, Aki; Makabe, Hidefumi; Nishioka, Takaaki; Miyoshi, Hideto

    2005-11-15

    Studies on the inhibitory mechanism of acetogenins, the most potent inhibitors of mitochondrial complex I (NADH-ubiquinone oxidoreductase), are useful for elucidating the structural and functional features of the terminal electron transfer step of this enzyme. Previous studies of the structure-activity relationship revealed that except for the alkyl spacer linking the two toxophores (i.e., the hydroxylated THF and the gamma-lactone rings), none of the multiple functional groups of these inhibitors is essential for potent inhibition. To elucidate the function of the alkyl spacer, two sets of systematically selected analogues were synthesized. First, the length of the spacer was varied widely. Second, the local flexibility of the spacer was specifically reduced by introducing multiple bond(s) into different regions of the spacer. The optimal length of the spacer for inhibition was approximately 13 carbon atoms. The decrease in the strength of the inhibitory effect caused by elongating the spacer from 13 carbons was much more drastic than that caused by shortening. Local flexibility in a specific region of the spacer was not important for the inhibition. These observations indicate that the active conformation of the spacer is not an extended form, and is not necessarily restricted to a certain rigid shape. Moreover, an analogue in which a spacer covering 10 carbon atoms was hardened into a rodlike shape still maintained a potent inhibitory effect. Our results strongly suggest that the spacer portion is free from steric congestion arising from the putative binding site probably because there is no cavity-like binding site for the spacer portion. The manner of acetogenin binding to the enzyme may not be explained by a simple "key and keyhole" analogy.

  8. Structure of a Major Antigenic Site on the Respiratory Syncytial Virus Fusion Glycoprotein in Complex with Neutralizing Antibody 101F

    SciTech Connect

    McLellan, Jason S.; Chen, Man; Chang, Jung-San; Yang, Yongping; Kim, Albert; Graham, Barney S.; Kwong, Peter D.

    2010-11-19

    Respiratory syncytial virus (RSV) is a major cause of pneumonia and bronchiolitis in infants and elderly people. Currently there is no effective vaccine against RSV, but passive prophylaxis with neutralizing antibodies reduces hospitalizations. To investigate the mechanism of antibody-mediated RSV neutralization, we undertook structure-function studies of monoclonal antibody 101F, which binds a linear epitope in the RSV fusion glycoprotein. Crystal structures of the 101F antigen-binding fragment in complex with peptides from the fusion glycoprotein defined both the extent of the linear epitope and the interactions of residues that are mutated in antibody escape variants. The structure allowed for modeling of 101F in complex with trimers of the fusion glycoprotein, and the resulting models suggested that 101F may contact additional surfaces located outside the linear epitope. This hypothesis was supported by surface plasmon resonance experiments that demonstrated 101F bound the peptide epitope {approx}16,000-fold more weakly than the fusion glycoprotein. The modeling also showed no substantial clashes between 101F and the fusion glycoprotein in either the pre- or postfusion state, and cell-based assays indicated that 101F neutralization was not associated with blocking virus attachment. Collectively, these results provide a structural basis for RSV neutralization by antibodies that target a major antigenic site on the fusion glycoprotein.

  9. Novel Findings from CNVs Implicate Inhibitory and Excitatory Signaling Complexes in Schizophrenia

    PubMed Central

    Pocklington, Andrew J.; Rees, Elliott; Walters, James T.R.; Han, Jun; Kavanagh, David H.; Chambert, Kimberly D.; Holmans, Peter; Moran, Jennifer L.; McCarroll, Steven A.; Kirov, George; O’Donovan, Michael C.; Owen, Michael J.

    2015-01-01

    Summary We sought to obtain novel insights into schizophrenia pathogenesis by exploiting the association between the disorder and chromosomal copy number (CNV) burden. We combined data from 5,745 cases and 10,675 controls with other published datasets containing genome-wide CNV data. In this much-enlarged sample of 11,355 cases and 16,416 controls, we show for the first time that case CNVs are enriched for genes involved in GABAergic neurotransmission. Consistent with non-genetic reports of GABAergic deficits in schizophrenia, our findings now show disrupted GABAergic signaling is of direct causal relevance, rather than a secondary effect or due to confounding. Additionally, we independently replicate and greatly extend previous findings of CNV enrichment among genes involved in glutamatergic signaling. Given the strong functional links between the major inhibitory GABAergic and excitatory glutamatergic systems, our findings converge on a broad, coherent set of pathogenic processes, providing firm foundations for studies aimed at dissecting disease mechanisms. PMID:26050040

  10. Advances and challenges in deformable image registration: From image fusion to complex motion modelling.

    PubMed

    Schnabel, Julia A; Heinrich, Mattias P; Papież, Bartłomiej W; Brady, Sir J Michael

    2016-10-01

    Over the past 20 years, the field of medical image registration has significantly advanced from multi-modal image fusion to highly non-linear, deformable image registration for a wide range of medical applications and imaging modalities, involving the compensation and analysis of physiological organ motion or of tissue changes due to growth or disease patterns. While the original focus of image registration has predominantly been on correcting for rigid-body motion of brain image volumes acquired at different scanning sessions, often with different modalities, the advent of dedicated longitudinal and cross-sectional brain studies soon necessitated the development of more sophisticated methods that are able to detect and measure local structural or functional changes, or group differences. Moving outside of the brain, cine imaging and dynamic imaging required the development of deformable image registration to directly measure or compensate for local tissue motion. Since then, deformable image registration has become a general enabling technology. In this work we will present our own contributions to the state-of-the-art in deformable multi-modal fusion and complex motion modelling, and then discuss remaining challenges and provide future perspectives to the field.

  11. Represent and fuse bimodal biometric images at the feature level: complex-matrix-based fusion scheme

    NASA Astrophysics Data System (ADS)

    Xu, Yong; Zhang, David

    2010-03-01

    Multibiometrics can obtain a higher accuracy than the single biometrics by simultaneously using multiple biometric traits of the subject. We note that biometric traits are usually in the form of images. Thus, how to properly fuse the information of multiple biometric images of the subject for authentication is crucial for multibiometrics. We propose a novel image-based linear discriminant analysis (IBLDA) approach to fuse two biometric traits (i.e., bimodal biometric images) of the same subject in the form of matrix at the feature level. IBLDA first integrates two biometric traits of one subject into a complex matrix and then directly extracts low-dimensional features for the integrated biometric traits. IBLDA also enables more information to be exploited than the matching score level fusion and the decision level fusion. Compared to linear discriminant analysis (LDA), IBLDA has the following advantages: First, it can overcome the small sample size problem that conventional LDA usually suffers from. Second, IBLDA solves the eigenequation at a low computational cost. Third, when storing the scatter matrices IBLDA will not bring as heavy a memory burden as conventional LDA. We also clearly show the theoretical foundation of the proposed method. The experiment result shows that the proposed method can obtain a high classification accuracy.

  12. Reversibility of the inhibitory effect of atrazine and lindane on cytosol 5. alpha. -dihydrotestosterone receptor complex formation in rat prostate

    SciTech Connect

    Simic, B.; Kniewald, Z.; Kniewald, J. ); Davies, J.E. )

    1991-01-01

    Once entering the bloodstream, most toxic substances, including pesticides, can reach organs involved in the reproductive system. They can cross the placenta, as well as the brain barrier, posing various risks to the reproductive processes. The organochlorine insecticide lindane and the s-triazine herbicide atrazine produce changes in hormone-dependent reactions in the rat hypothalamus, anterior pituitary, and prostate. Lindane also causes histological and biochemical alterations in the rat testis. In vivo treatment with atrazine produces a markedly inhibitory influence of 5{alpha}-dihydrotestosterone - receptor complex formation in rat prostate cytosol. Therefore, the aim of this study was to investigate whether such changes in the crucial step in the reproductive process are reversible. A parallel investigation using lindane was also undertaken.

  13. Live simian immunodeficiency virus vaccine correlate of protection: immune complex-inhibitory Fc receptor interactions that reduce target cell availability.

    PubMed

    Smith, Anthony J; Wietgrefe, Stephen W; Shang, Liang; Reilly, Cavan S; Southern, Peter J; Perkey, Katherine E; Duan, Lijie; Kohler, Heinz; Müller, Sybille; Robinson, James; Carlis, John V; Li, Qingsheng; Johnson, R Paul; Haase, Ashley T

    2014-09-15

    Principles to guide design of an effective vaccine against HIV are greatly needed, particularly to protect women in the pandemic's epicenter in Africa. We have been seeking these principles by identifying correlates of the robust protection associated with SIVmac239Δnef vaccination in the SIV-rhesus macaque animal model of HIV-1 transmission to women. We identified one correlate of SIVmac239Δnef protection against vaginal challenge as a resident mucosal system for SIV-gp41 trimer Ab production and neonatal FcR-mediated concentration of these Abs on the path of virus entry to inhibit establishment of infected founder populations at the portal of entry. In this study, we identify blocking CD4(+) T cell recruitment to thereby inhibit local expansion of infected founder populations as a second correlate of protection. Virus-specific immune complex interactions with the inhibitory FcγRIIb receptor in the epithelium lining the cervix initiate expression of genes that block recruitment of target cells to fuel local expansion. Immune complex-FcγRIIb receptor interactions at mucosal frontlines to dampen the innate immune response to vaginal challenge could be a potentially general mechanism for the mucosal immune system to sense and modulate the response to a previously encountered pathogen. Designing vaccines to provide protection without eliciting these transmission-promoting innate responses could contribute to developing an effective HIV-1 vaccine.

  14. Live SIV vaccine correlate of protection: immune complex-inhibitory Fc receptor interactions that reduce target cell availability

    PubMed Central

    Smith, Anthony J; Wietgrefe, Stephen W.; Shang, Liang; Reilly, Cavan S.; Southern, Peter J.; Perkey, Katherine E.; Duan, Lijie; Kohler, Heinz; Muller, Sybille; Robinson, James; Carlis, John V.; Li, Qingsheng; Johnson, R. Paul; Haase, Ashley T.

    2014-01-01

    Principles to guide design of an effective vaccine against HIV are greatly needed, particularly to protect women in the pandemic’s epicentre in Africa. We have been seeking these principles by identifying correlates of the robust protection associated with SIVmac239Δnef vaccination in the SIV-rhesus macaque animal model of HIV-1 transmission to women. We have identified one correlate of SIVmac239Δnef protection against vaginal challenge as a resident mucosal system for SIV-gp41 trimer antibody production and neonatal Fc receptor (FcRn)-mediated concentration of these antibodies on the path of virus entry to inhibit establishment of infected founder populations at the portal of entry. Here we identify as a second protection correlate, blocking CD4+ T cell recruitment to inhibit local expansion of infected founder populations. Virus-specific immune complex interactions with the inhibitory FcγRIIb receptor in the epithelium lining the cervix initiate expression of genes that block recruitment of target cells to fuel local expansion. Immune complex-FcγRIIb receptor interactions at mucosal frontlines to dampen the innate immune response to vaginal challenge could be a potentially general mechanism for the mucosal immune system to sense and modulate the response to a previously encountered pathogen. Designing vaccines to provide protection without eliciting these transmission-promoting innate responses could contribute to developing an effective HIV-1 vaccine. PMID:25143442

  15. Human Cytomegalovirus gH/gL Forms a Stable Complex with the Fusion Protein gB in Virions.

    PubMed

    Vanarsdall, Adam L; Howard, Paul W; Wisner, Todd W; Johnson, David C

    2016-04-01

    Human cytomegalovirus (HCMV) is a ubiquitous virus that is a major pathogen in newborns and immunocompromised or immunosuppressed patients. HCMV infects a wide variety of cell types using distinct entry pathways that involve different forms of the gH/gL glycoprotein: gH/gL/gO and gH/gL/UL128-131 as well as the viral fusion glycoprotein, gB. However, the minimal or core fusion machinery (sufficient for cell-cell fusion) is just gH/gL and gB. Here, we demonstrate that HCMV gB and gH/gL form a stable complex early after their synthesis and in the absence of other viral proteins. gH/gL can interact with gB mutants that are unable to mediate cell-cell fusion. gB-gH/gL complexes included as much as 16-50% of the total gH/gL in HCMV virus particles. In contrast, only small amounts of gH/gL/gO and gH/gL/UL128-131 complexes were found associated with gB. All herpesviruses express gB and gH/gL molecules and most models describing herpesvirus entry suggest that gH/gL interacts with gB to mediate membrane fusion, although there is no direct evidence for this. For herpes simplex virus (HSV-1) it has been suggested that after receptor binding gH/gL binds to gB either just before, or coincident with membrane fusion. Therefore, our results have major implications for these models, demonstrating that HCMV gB and gH/gL forms stable gB-gH/gL complexes that are incorporated virions without receptor binding or membrane fusion. Moreover, our data is the best support to date for the proposal that gH/gL interacts with gB.

  16. Human Cytomegalovirus gH/gL Forms a Stable Complex with the Fusion Protein gB in Virions

    PubMed Central

    Vanarsdall, Adam L.; Howard, Paul W.; Wisner, Todd W.; Johnson, David C.

    2016-01-01

    Human cytomegalovirus (HCMV) is a ubiquitous virus that is a major pathogen in newborns and immunocompromised or immunosuppressed patients. HCMV infects a wide variety of cell types using distinct entry pathways that involve different forms of the gH/gL glycoprotein: gH/gL/gO and gH/gL/UL128-131 as well as the viral fusion glycoprotein, gB. However, the minimal or core fusion machinery (sufficient for cell-cell fusion) is just gH/gL and gB. Here, we demonstrate that HCMV gB and gH/gL form a stable complex early after their synthesis and in the absence of other viral proteins. gH/gL can interact with gB mutants that are unable to mediate cell-cell fusion. gB-gH/gL complexes included as much as 16–50% of the total gH/gL in HCMV virus particles. In contrast, only small amounts of gH/gL/gO and gH/gL/UL128-131 complexes were found associated with gB. All herpesviruses express gB and gH/gL molecules and most models describing herpesvirus entry suggest that gH/gL interacts with gB to mediate membrane fusion, although there is no direct evidence for this. For herpes simplex virus (HSV-1) it has been suggested that after receptor binding gH/gL binds to gB either just before, or coincident with membrane fusion. Therefore, our results have major implications for these models, demonstrating that HCMV gB and gH/gL forms stable gB-gH/gL complexes that are incorporated virions without receptor binding or membrane fusion. Moreover, our data is the best support to date for the proposal that gH/gL interacts with gB. PMID:27082872

  17. Catalytic Features of the Botulinum Neurotoxin A Light Chain Revealed by High Resolution Structure of an Inhibitory Peptide Complex

    SciTech Connect

    Silvaggi,N.; Wilson, D.; Tzipori, S.; Allen, K.

    2008-01-01

    The Clostridium botulinum neurotoxin serotype A light chain (BoNT/A-LC) is a Zn(II)-dependent metalloprotease that blocks the release of acetylcholine at the neuromuscular junction by cleaving SNAP-25, one of the SNARE proteins required for exocytosis. Because of the potential for use of the toxin in bioterrorism and the increasingly widespread application of the toxin in the medical field, there is significant interest in the development of small-molecule inhibitors of the metalloprotease. Efforts to design such inhibitors have not benefited from knowledge of how peptides bind to the active site since the enzyme-peptide structures available previously either were not occupied in the vicinity of the catalytic Zn(II) ion or did not represent the product of SNAP-25 substrate cleavage. Herein we report the 1.4 Angstroms-resolution X-ray crystal structure of a complex between the BoNT/A-LC and the inhibitory peptide N-Ac-CRATKML, the first structure of the light chain with an inhibitory peptide bound at the catalytic Zn(II) ion. The peptide is bound with the Cys S? atom coordinating the metal ion. Surprisingly, the cysteine sulfur is oxidized to the sulfenic acid form. Given the unstable nature of this species in solution, is it likely that oxidation occurs on the enzyme. In addition to the peptide-bound structure, we report two structures of the unliganded light chain with and without the Zn(II) cofactor bound at 1.25 and 1.20 Angstroms resolution, respectively. The two structures are nearly identical, confirming that the Zn(II) ion plays a purely catalytic role. Additionally, the structure of the Zn(II)-bound uncomplexed enzyme allows identification of the catalytic water molecule and a second water molecule that occupies the same position as the peptidic oxygen in the tetrahedral intermediate. This observation suggests that the enzyme active site is prearranged to stabilize the tetrahedral intermediate of the protease reaction.

  18. Nonsubsampled rotated complex wavelet transform (NSRCxWT) for medical image fusion related to clinical aspects in neurocysticercosis.

    PubMed

    Chavan, Satishkumar S; Mahajan, Abhishek; Talbar, Sanjay N; Desai, Subhash; Thakur, Meenakshi; D'cruz, Anil

    2017-02-01

    Neurocysticercosis (NCC) is a parasite infection caused by the tapeworm Taenia solium in its larvae stage which affects the central nervous system of the human body (a definite host). It results in the formation of multiple lesions in the brain at different locations during its various stages. During diagnosis of such symptomatic patients, these lesions can be better visualized using a feature based fusion of Computed Tomography (CT) and Magnetic Resonance Imaging (MRI). This paper presents a novel approach to Multimodality Medical Image Fusion (MMIF) used for the analysis of the lesions for the diagnostic purpose and post treatment review of NCC. The MMIF presented here is a technique of combining CT and MRI data of the same patient into a new slice using a Nonsubsampled Rotated Complex Wavelet Transform (NSRCxWT). The forward NSRCxWT is applied on both the source modalities separately to extract the complementary and the edge related features. These features are then combined to form a composite spectral plane using average and maximum value selection fusion rules. The inverse transformation on this composite plane results into a new, visually better, and enriched fused image. The proposed technique is tested on the pilot study data sets of patients infected with NCC. The quality of these fused images is measured using objective and subjective evaluation metrics. Objective evaluation is performed by estimating the fusion parameters like entropy, fusion factor, image quality index, edge quality measure, mean structural similarity index measure, etc. The fused images are also evaluated for their visual quality using subjective analysis with the help of three expert radiologists. The experimental results on 43 image data sets of 17 patients are promising and superior when compared with the state of the art wavelet based fusion algorithms. The proposed algorithm can be a part of computer-aided detection and diagnosis (CADD) system which assists the radiologists in

  19. Design and construction of self-assembling supramolecular protein complexes using artificial and fusion proteins as nanoscale building blocks.

    PubMed

    Kobayashi, Naoya; Arai, Ryoichi

    2017-02-01

    The central goal of nanobiotechnology is to design and construct novel biomaterials of nanometer sizes. In this short review, we describe recent progress of several approaches for designing and creating artificial self-assembling protein complexes and primarily focus on the following biotechnological strategies for using artificial and fusion proteins as nanoscale building blocks: fusion proteins designed for symmetrical self-assembly; three-dimensional domain-swapped oligomers; self-assembling designed coiled-coil peptide modules; metal-directed self-assembling engineered proteins; computationally designed self-assembling de novo proteins; and self-assembling protein nanobuilding blocks (PN-Blocks) using an intermolecularly folded dimeric de novo protein. These state-of-the-art nanobiotechnologies for designing supramolecular protein complexes will facilitate the development of novel functional nanobiomaterials.

  20. Low-dose ionizing radiation induces mitochondrial fusion and increases expression of mitochondrial complexes I and III in hippocampal neurons

    PubMed Central

    Chang, Chuang-Rung; Kao, Mou-Chieh; Chen, Kuan-Wei; Chiu, Shih-Che; Hsu, Ming-Ling; Hsiang, I-Chou; Chen, Yu-Jen; Chen, Linyi

    2015-01-01

    High energy ionizing radiation can cause DNA damage and cell death. During clinical radiation therapy, the radiation dose could range from 15 to 60 Gy depending on targets. While 2 Gy radiation has been shown to cause cancer cell death, studies also suggest a protective potential by low dose radiation. In this study, we examined the effect of 0.2-2 Gy radiation on hippocampal neurons. Low dose 0.2 Gy radiation treatment increased the levels of MTT. Since hippocampal neurons are post-mitotic, this result reveals a possibility that 0.2 Gy irradiation may increase mitochondrial activity to cope with stimuli. Maintaining neural plasticity is an energy-demanding process that requires high efficient mitochondrial function. We thus hypothesized that low dose radiation may regulate mitochondrial dynamics and function to ensure survival of neurons. Our results showed that five days after 0.2 Gy irradiation, no obvious changes on neuronal survival, neuronal synapses, membrane potential of mitochondria, reactive oxygen species levels, and mitochondrial DNA copy numbers. Interestingly, 0.2 Gy irradiation promoted the mitochondria fusion, resulting in part from the increased level of a mitochondrial fusion protein, Mfn2, and inhibition of Drp1 fission protein trafficking to the mitochondria. Accompanying with the increased mitochondrial fusion, the expressions of complexes I and III of the electron transport chain were also increased. These findings suggest that, hippocampal neurons undergo increased mitochondrial fusion to modulate cellular activity as an adaptive mechanism in response to low dose radiation. PMID:26415228

  1. Low-dose ionizing radiation induces mitochondrial fusion and increases expression of mitochondrial complexes I and III in hippocampal neurons.

    PubMed

    Chien, Ling; Chen, Wun-Ke; Liu, Szu-Ting; Chang, Chuang-Rung; Kao, Mou-Chieh; Chen, Kuan-Wei; Chiu, Shih-Che; Hsu, Ming-Ling; Hsiang, I-Chou; Chen, Yu-Jen; Chen, Linyi

    2015-10-13

    High energy ionizing radiation can cause DNA damage and cell death. During clinical radiation therapy, the radiation dose could range from 15 to 60 Gy depending on targets. While 2 Gy radiation has been shown to cause cancer cell death, studies also suggest a protective potential by low dose radiation. In this study, we examined the effect of 0.2-2 Gy radiation on hippocampal neurons. Low dose 0.2 Gy radiation treatment increased the levels of MTT. Since hippocampal neurons are post-mitotic, this result reveals a possibility that 0.2 Gy irradiation may increase mitochondrial activity to cope with stimuli. Maintaining neural plasticity is an energy-demanding process that requires high efficient mitochondrial function. We thus hypothesized that low dose radiation may regulate mitochondrial dynamics and function to ensure survival of neurons. Our results showed that five days after 0.2 Gy irradiation, no obvious changes on neuronal survival, neuronal synapses, membrane potential of mitochondria, reactive oxygen species levels, and mitochondrial DNA copy numbers. Interestingly, 0.2 Gy irradiation promoted the mitochondria fusion, resulting in part from the increased level of a mitochondrial fusion protein, Mfn2, and inhibition of Drp1 fission protein trafficking to the mitochondria. Accompanying with the increased mitochondrial fusion, the expressions of complexes I and III of the electron transport chain were also increased. These findings suggest that, hippocampal neurons undergo increased mitochondrial fusion to modulate cellular activity as an adaptive mechanism in response to low dose radiation.

  2. Crystal Structure of Plasmodium knowlesi Apical Membrane Antigen 1 and Its Complex with an Invasion-Inhibitory Monoclonal Antibody

    PubMed Central

    van der Eijk, Marjolein; Thomas, Alan W.; Singh, Balbir; Kocken, Clemens H. M.

    2015-01-01

    The malaria parasite Plasmodium knowlesi, previously associated only with infection of macaques, is now known to infect humans as well and has become a significant public health problem in Southeast Asia. This species should therefore be targeted in vaccine and therapeutic strategies against human malaria. Apical Membrane Antigen 1 (AMA1), which plays a role in Plasmodium merozoite invasion of the erythrocyte, is currently being pursued in human vaccine trials against P. falciparum. Recent vaccine trials in macaques using the P. knowlesi orthologue PkAMA1 have shown that it protects against infection by this parasite species and thus should be developed for human vaccination as well. Here, we present the crystal structure of Domains 1 and 2 of the PkAMA1 ectodomain, and of its complex with the invasion-inhibitory monoclonal antibody R31C2. The Domain 2 (D2) loop, which is displaced upon binding the Rhoptry Neck Protein 2 (RON2) receptor, makes significant contacts with the antibody. R31C2 inhibits binding of the Rhoptry Neck Protein 2 (RON2) receptor by steric blocking of the hydrophobic groove and by preventing the displacement of the D2 loop which is essential for exposing the complete binding site on AMA1. R31C2 recognizes a non-polymorphic epitope and should thus be cross-strain reactive. PkAMA1 is much less polymorphic than the P. falciparum and P. vivax orthologues. Unlike these two latter species, there are no polymorphic sites close to the RON2-binding site of PkAMA1, suggesting that P. knowlesi has not developed a mechanism of immune escape from the host’s humoral response to AMA1. PMID:25886591

  3. Dual-tree complex wavelet transform and image block residual-based multi-focus image fusion in visual sensor networks.

    PubMed

    Yang, Yong; Tong, Song; Huang, Shuying; Lin, Pan

    2014-11-26

    This paper presents a novel framework for the fusion of multi-focus images explicitly designed for visual sensor network (VSN) environments. Multi-scale based fusion methods can often obtain fused images with good visual effect. However, because of the defects of the fusion rules, it is almost impossible to completely avoid the loss of useful information in the thus obtained fused images. The proposed fusion scheme can be divided into two processes: initial fusion and final fusion. The initial fusion is based on a dual-tree complex wavelet transform (DTCWT). The Sum-Modified-Laplacian (SML)-based visual contrast and SML are employed to fuse the low- and high-frequency coefficients, respectively, and an initial composited image is obtained. In the final fusion process, the image block residuals technique and consistency verification are used to detect the focusing areas and then a decision map is obtained. The map is used to guide how to achieve the final fused image. The performance of the proposed method was extensively tested on a number of multi-focus images, including no-referenced images, referenced images, and images with different noise levels. The experimental results clearly indicate that the proposed method outperformed various state-of-the-art fusion methods, in terms of both subjective and objective evaluations, and is more suitable for VSNs.

  4. Dual-Tree Complex Wavelet Transform and Image Block Residual-Based Multi-Focus Image Fusion in Visual Sensor Networks

    PubMed Central

    Yang, Yong; Tong, Song; Huang, Shuying; Lin, Pan

    2014-01-01

    This paper presents a novel framework for the fusion of multi-focus images explicitly designed for visual sensor network (VSN) environments. Multi-scale based fusion methods can often obtain fused images with good visual effect. However, because of the defects of the fusion rules, it is almost impossible to completely avoid the loss of useful information in the thus obtained fused images. The proposed fusion scheme can be divided into two processes: initial fusion and final fusion. The initial fusion is based on a dual-tree complex wavelet transform (DTCWT). The Sum-Modified-Laplacian (SML)-based visual contrast and SML are employed to fuse the low- and high-frequency coefficients, respectively, and an initial composited image is obtained. In the final fusion process, the image block residuals technique and consistency verification are used to detect the focusing areas and then a decision map is obtained. The map is used to guide how to achieve the final fused image. The performance of the proposed method was extensively tested on a number of multi-focus images, including no-referenced images, referenced images, and images with different noise levels. The experimental results clearly indicate that the proposed method outperformed various state-of-the-art fusion methods, in terms of both subjective and objective evaluations, and is more suitable for VSNs. PMID:25587878

  5. An unusual cytokine:Ig-domain interaction revealed in the crystal structure of leukemia inhibitory factor (LIF) in complex with the LIF receptor

    PubMed Central

    Huyton, Trevor; Zhang, Jian-Guo; Luo, Cindy S.; Lou, Mei-Zhen; Hilton, Douglas J.; Nicola, Nicos A.; Garrett, Thomas P. J.

    2007-01-01

    Leukemia inhibitory factor (LIF) receptor is a cell surface receptor that mediates the actions of LIF and other IL-6 type cytokines through the formation of high-affinity signaling complexes with gp130. Here we present the crystal structure of a complex of mouse LIF receptor with human LIF at 4.0 Å resolution. The structure is, to date, the largest cytokine receptor fragment determined by x-ray crystallography. The binding of LIF to its receptor via the central Ig-like domain is unlike other cytokine receptor complexes that bind ligand predominantly through their cytokine-binding modules. This structure, in combination with previous crystallographic studies, also provides a structural template to understand the formation and orientation of the high-affinity signaling complex between LIF, LIF receptor, and gp130. PMID:17652170

  6. Copper(II) complexes with cyanoguanidine and o-phenanthroline: Theoretical studies, in vitro antimicrobial activity and alkaline phosphatase inhibitory effect

    NASA Astrophysics Data System (ADS)

    Martínez Medina, Juan J.; Islas, María S.; López Tévez, Libertad L.; Ferrer, Evelina G.; Okulik, Nora B.; Williams, Patricia A. M.

    2014-01-01

    Calculations based on density functional methods are carried out for two Cu(II) complexes with cyanoguanidine (cnge) and o-phenanthroline (o-phen): [Cu(o-phen)2(cnge)](NO3)2ṡ2H2O (1) and [Cu(o-phen)(cnge)(H2O)(NO3)2] (2). The calculated geometrical parameters are in agreement with the experimental values. The results of Atoms in Molecules (AIM) topological analysis of the electron density indicate that the Cu-N(phen) bonds in complex (1) have lower electron density, suggesting that those bonds are stronger in complex (2). Moreover, the ionic character of the Cu-N bond in the complex (1) is slightly stronger than that in the complex (2) and this situation would explain the fact that only complex (2) was stable in water solution. For this reason, the antimicrobial and enzymatic assays were performed using complex (2). It is well known that the increased use of antibiotics has resulted in the development of resistant bacterial and fungal strains. In this context, the study of novel antimicrobial agents has an enormous importance and metal complexes represent an interesting alternative for the treatment of infectious diseases. The aim of this work is to prove the modification of some biological properties like antimicrobial activity or alkaline phosphatase inhibitory activity upon copper complexation.

  7. Vaccinia mature virus fusion regulator A26 protein binds to A16 and G9 proteins of the viral entry fusion complex and dissociates from mature virions at low pH.

    PubMed

    Chang, Shu-Jung; Shih, Ao-Chun; Tang, Yin-Liang; Chang, Wen

    2012-04-01

    Vaccinia mature virus enters cells through either endocytosis or plasma membrane fusion, depending on virus strain and cell type. Our previous results showed that vaccinia virus mature virions containing viral A26 protein enter HeLa cells preferentially through endocytosis, whereas mature virions lacking A26 protein enter through plasma membrane fusion, leading us to propose that A26 acts as an acid-sensitive fusion suppressor for mature virus (S. J. Chang, Y. X. Chang, R. Izmailyan R, Y. L. Tang, and W. Chang, J. Virol. 84:8422-8432, 2010). In the present study, we investigated the fusion suppression mechanism of A26 protein. We found that A26 protein was coimmunoprecipitated with multiple components of the viral entry-fusion complex (EFC) in infected HeLa cells. Transient expression of viral EFC components in HeLa cells revealed that vaccinia virus A26 protein interacted directly with A16 and G9 but not with G3, L5 and H2 proteins of the EFC components. Consistently, a glutathione S-transferase (GST)-A26 fusion protein, but not GST, pulled down A16 and G9 proteins individually in vitro. Together, our results supported the idea that A26 protein binds to A16 and G9 protein at neutral pH contributing to suppression of vaccinia virus-triggered membrane fusion from without. Since vaccinia virus extracellular envelope proteins A56/K2 were recently shown to bind to the A16/G9 subcomplex to suppress virus-induced fusion from within, our results also highlight an evolutionary convergence in which vaccinia viral fusion suppressor proteins regulate membrane fusion by targeting the A16 and G9 components of the viral EFC complex. Finally, we provide evidence that acid (pH 4.7) treatment induced A26 protein and A26-A27 protein complexes of 70 kDa and 90 kDa to dissociate from mature virions, suggesting that the structure of A26 protein is acid sensitive.

  8. Fusion of Epstein-Barr virus nuclear antigen-1-derived glycine-alanine repeat to trans-dominant HIV-1 Gag increases inhibitory activities and survival of transduced cells in vivo.

    PubMed

    Hammer, Diana; Wild, Jens; Ludwig, Christine; Asbach, Benedikt; Notka, Frank; Wagner, Ralf

    2008-06-01

    Trans-dominant human immunodeficiency virus type 1 (HIV-1) Gag derivatives have been shown to efficiently inhibit late steps of HIV-1 replication in vitro by interfering with Gag precursor assembly, thus ranking among the interesting candidates for gene therapy approaches. However, efficient antiviral activities of corresponding transgenes are likely to be counteracted in particular by cell-mediated host immune responses toward the transgene-expressing cells. To decrease this potential immunogenicity, a 24-amino acid Gly-Ala (GA) stretch derived from Epstein-Barr virus nuclear antigen-1 (EBNA1) and known to overcome proteasomal degradation was fused to a trans-dominant Gag variant (sgD1). To determine the capacity of this fusion polypeptide to repress viral replication, PM-1 cells were transduced with sgD1 and GAsgD1 transgenes, using retroviral gene transfer. Challenge of stably transfected permissive cell lines with various viral strains indicated that N-terminal GA fusion even enhanced the inhibitory properties of sgD1. Further studies revealed that the GA stretch increased protein stability by blocking proteasomal degradation of Gag proteins. Immunization of BALB/c mice with a DNA vaccine vector expressing sgD1 induced substantial Gag-specific immune responses that were, however, clearly diminished in the presence of GA. Furthermore, recognition of cells expressing the GA-fused transgene by CD8(+) T cells was drastically reduced, both in vitro and in vivo, resulting in prolonged survival of the transduced cells in recipient mice.

  9. Inhibitory effect of lactone fractions and individual components from three species of the Achillea millefolium complex of Bulgarian origin on the human neutrophils respiratory burst activity.

    PubMed

    Choudhary, Muhammad Iqbal; Jalil, Saima; Todorova, M; Trendafilova, A; Mikhova, B; Duddeck, H; Atta-ur-Rahman

    2007-09-01

    Achillea species are widely used in folk medicine for treatment of inflammatory diseases. The inhibitory effect on the human neutrophils respiratory burst activity of total extracts, their fractions and some main constituents of the flower heads from Achillea asplenifolia, A. collina and A. distans belonging to A. millefolium complex of Bulgarian origin, were tested by the modified method of Tan and Berridge. Seven from the investigated fractions showed activity similar or higher than that of indomethacine and might be evaluated as nonsteroidal anti-inflammatory agents.

  10. Enhanced damage localization for complex structures through statistical modeling and sensor fusion

    NASA Astrophysics Data System (ADS)

    Haynes, Colin; Todd, Michael

    2015-03-01

    Ultrasonic guided waves represent a promising technique for detecting and localizing structural damage, but their application to realistic structures has been hampered by the complicated interference patterns produced by scattering from geometric features. This work presents a new damage localization paradigm based on a statistical approach to dealing with uncertainty in the guided wave signals. A bolted frame and a section of a fuselage rib are tested with different simulated damage conditions and used to conduct a detailed comparison between the proposed solution and other sparse-array localization approaches. After establishing the superiority of the statistical approach, two novel innovations to the localization procedure are proposed: an approach to sensor fusion based on the Neyman-Pearson criterion, and a method of constructing simple models of geometrical features. Including the sensor fusion and geometrical models produces a substantial improvement in the system's localization accuracy. The final result is a robust and accurate framework for single-site damage localization that moves structural health monitoring towards practical implementation on a much broader range of structures.

  11. Interaction between the G3 and L5 proteins of the vaccinia virus entry-fusion complex

    SciTech Connect

    Wolfe, Cindy L.; Moss, Bernard

    2011-04-10

    The vaccinia virus entry-fusion complex (EFC) consists of 10 to 12 proteins that are embedded in the viral membrane and individually required for fusion with the cell and entry of the core into the cytoplasm. The architecture of the EFC is unknown except for information regarding two pair-wise interactions: A28 with H2 and A16 with G9. Here we used a technique to destabilize the EFC by repressing the expression of individual components and identified a third pair-wise interaction: G3 with L5. These two proteins remained associated under several different EFC destabilization conditions and in each case were immunopurified together as demonstrated by Western blotting. Further evidence for the specific interaction of G3 and L5 was obtained by mass spectrometry. This interaction also occurred when G3 and L5 were expressed in uninfected cells, indicating that no other viral proteins were required. Thus, the present study extends our knowledge of the protein interactions important for EFC assembly and stability.

  12. Role of angular momentum in the production of complex fragments in fusion and quasifission reactions

    SciTech Connect

    Kalandarov, Sh. A.; Adamian, G. G.; Antonenko, N. V.; Scheid, W.

    2011-05-15

    The influence of angular momentum on the competition between complete fusion followed by the decay of compound nucleus and quasifission channels is treated within the dinuclear system model. The charge distributions of the products in the reactions {sup 28}Si+{sup 96}Zr, {sup 4}He+{sup 130}Te, and {sup 40}Ca+{sup 82}Kr are predicted at bombarding energies above the Coulomb barrier. The results of calculations for the reactions {sup 93}Nb+{sup 9}Be,{sup 12}C,{sup 27}Al; {sup 84}Kr+{sup 27}Al; {sup 86}Kr+{sup 63}Cu; {sup 139}La+{sup 12}C,{sup 27}Al; and {sup 45}Sc+{sup 65}Cu are compared with the available experimental data.

  13. Heterologous expression of mycobacterial Esx complexes in Escherichia coli for structural studies is facilitated by the use of maltose binding protein fusions.

    PubMed

    Arbing, Mark A; Chan, Sum; Harris, Liam; Kuo, Emmeline; Zhou, Tina T; Ahn, Christine J; Nguyen, Lin; He, Qixin; Lu, Jamie; Menchavez, Phuong T; Shin, Annie; Holton, Thomas; Sawaya, Michael R; Cascio, Duilio; Eisenberg, David

    2013-01-01

    The expression of heteroligomeric protein complexes for structural studies often requires a special coexpression strategy. The reason is that the solubility and proper folding of each subunit of the complex requires physical association with other subunits of the complex. The genomes of pathogenic mycobacteria encode many small protein complexes, implicated in bacterial fitness and pathogenicity, whose characterization may be further complicated by insolubility upon expression in Escherichia coli, the most common heterologous protein expression host. As protein fusions have been shown to dramatically affect the solubility of the proteins to which they are fused, we evaluated the ability of maltose binding protein fusions to produce mycobacterial Esx protein complexes. A single plasmid expression strategy using an N-terminal maltose binding protein fusion to the CFP-10 homolog proved effective in producing soluble Esx protein complexes, as determined by a small-scale expression and affinity purification screen, and coupled with intracellular proteolytic cleavage of the maltose binding protein moiety produced protein complexes of sufficient purity for structural studies. In comparison, the expression of complexes with hexahistidine affinity tags alone on the CFP-10 subunits failed to express in amounts sufficient for biochemical characterization. Using this strategy, six mycobacterial Esx complexes were expressed, purified to homogeneity, and subjected to crystallization screening and the crystal structures of the Mycobacterium abscessus EsxEF, M. smegmatis EsxGH, and M. tuberculosis EsxOP complexes were determined. Maltose binding protein fusions are thus an effective method for production of Esx complexes and this strategy may be applicable for production of other protein complexes.

  14. Mechanochemical synthesis and in vitro anti-Helicobacter pylori and uresase inhibitory activities of novel zinc(II)-famotidine complex.

    PubMed

    Amin, Muhammad; Iqbal, Mohammad S; Hughes, Roy W; Khan, Safyan A; Reynolds, Paul A; Enne, Virve I; Sajjad-ur-Rahman; Mirza, Akmal S

    2010-06-01

    The mechanochemical synthesis and characterization of a zinc complex with famotidine is described. The complex was characterized by microanalysis and a number of spectroscopic techniques. The complex was of M:L dihydrate type. Derivatization of famotidine with zinc appears to enhance the activity of the drug by inhibiting the growth of Helicobacter pylori (two reference and 34 clinical isolates). The complex inhibited the growth of H. pylori in an MIC range of 1-8 microg mL(-1). The anti-H. pylori activity of the zinc-famotidine complex against antibiotic-resistant strains was nearly comparable to that of antibiotic-susceptible strains. The complex was found to be far less toxic than the parent drug, as demonstrated by its higher LD(50) value. In the human urease enzyme inhibition assay the complex exhibited significant inhibition. The new complex appears to be more useful in eradicating both the antibiotic-susceptible and antibiotic-resistant strains of H. pylori.

  15. Preserving Posterior Complex Can Prevent Adjacent Segment Disease following Posterior Lumbar Interbody Fusion Surgeries: A Finite Element Analysis

    PubMed Central

    Huang, Yun-Peng; Du, Cheng-Fei; Cheng, Cheng-Kung; Zhong, Zheng-Cheng; Chen, Xuan-Wei; Wu, Gui; Li, Zhe-Cheng; Ye, Jin-Duo; Lin, Jian-Hua; Wang, Li Zhen

    2016-01-01

    Objective To investigate the biomechanical effects of the lumbar posterior complex on the adjacent segments after posterior lumbar interbody fusion (PLIF) surgeries. Methods A finite element model of the L1–S1 segment was modified to simulate PLIF with total laminectomy (PLIF-LAM) and PLIF with hemilaminectomy (PLIF-HEMI) procedures. The models were subjected to a 400N follower load with a 7.5-N.m moment of flexion, extension, torsion, and lateral bending. The range of motion (ROM), intradiscal pressure (IDP), and ligament force were compared. Results In Flexion, the ROM, IDP and ligament force of posterior longitudinal ligament, intertransverse ligament, and capsular ligament remarkably increased at the proximal adjacent segment in the PLIF-LAM model, and slightly increased in the PLIF-HEMI model. There was almost no difference for the ROM, IDP and ligament force at L5-S1 level between the two PLIF models although the ligament forces of ligamenta flava remarkably increased compared with the intact lumbar spine (INT) model. For the other loading conditions, these two models almost showed no difference in ROM, IDP and ligament force on the adjacent discs. Conclusions Preserved posterior complex acts as the posterior tension band during PLIF surgery and results in less ROM, IDP and ligament forces on the proximal adjacent segment in flexion. Preserving the posterior complex during decompression can be effective on preventing adjacent segment degeneration (ASD) following PLIF surgeries. PMID:27870867

  16. A Fluorescence Polarization Assay for Binding to Macrophage Migration Inhibitory Factor and Crystal Structures for Complexes of Two Potent Inhibitors

    PubMed Central

    2016-01-01

    Human macrophage migration inhibitory factor (MIF) is both a keto–enol tautomerase and a cytokine associated with numerous inflammatory diseases and cancer. Consistent with observed correlations between inhibition of the enzymatic and biological activities, discovery of MIF inhibitors has focused on monitoring the tautomerase activity using l-dopachrome methyl ester or 4-hydroxyphenyl pyruvic acid as substrates. The accuracy of these assays is compromised by several issues including substrate instability, spectral interference, and short linear periods for product formation. In this work, we report the syntheses of fluorescently labeled MIF inhibitors and their use in the first fluorescence polarization-based assay to measure the direct binding of inhibitors to the active site. The assay allows the accurate and efficient identification of competitive, noncompetitive, and covalent inhibitors of MIF in a manner that can be scaled for high-throughput screening. The results for 22 compounds show that the most potent MIF inhibitors bind with Kd values of ca. 50 nM; two are from our laboratory, and the other is a compound from the patent literature. X-ray crystal structures for two of the most potent compounds bound to MIF are also reported here. Striking combinations of protein–ligand hydrogen bonding, aryl–aryl, and cation−π interactions are responsible for the high affinities. A new chemical series was then designed using this knowledge to yield two more strong MIF inhibitors/binders. PMID:27299179

  17. Disassembly of the reconstituted synaptic vesicle membrane fusion complex in vitro.

    PubMed Central

    Hayashi, T; Yamasaki, S; Nauenburg, S; Binz, T; Niemann, H

    1995-01-01

    The interaction of the presynaptic membrane proteins SNAP-25 and syntaxin with the synaptic vesicle protein synaptobrevin (VAMP) plays a key role in the regulated exocytosis of neurotransmitters. Clostridial neurotoxins, which proteolyze these polypeptides, are potent inhibitors of neurotransmission. The cytoplasmic domains of the three membrane proteins join into a tight SDS-resistant complex (Hayashi et al., 1994). Here, we show that this reconstituted complex, as well as heterodimers composed of syntaxin and SNAP-25, can be disassembled by the concerted action of the N-ethylmaleimide-sensitive factor, NSF, and the soluble NSF attachment protein, alpha-SNAP. alpha-SNAP binds to predicted alpha-helical coiled-coil regions of syntaxin and SNAP-25, shown previously to be engaged in their direct interaction. Synaptobrevin, although incapable of binding alpha-SNAP individually, induced a third alpha-SNAP binding site when associated with syntaxin and SNAP-25 into heterotrimers. NSF released prebound alpha-SNAP from full-length syntaxin but not from a syntaxin derivative truncated at the N-terminus. Disassembly of complexes containing this syntaxin mutant was impaired, indicating a critical role for the N-terminal domain in the alpha-SNAP/NSF-mediated dissociation process. Complexes containing C-terminally deleted SNAP-25 derivatives, as generated by botulinal toxins type A and E, were dissociated more efficiently. In contrast, the N-terminal fragment generated from synaptobrevin by botulinal toxin type F produced an SDS-sensitive complex that was poorly dissociated. Images PMID:7774590

  18. The inhibitory effects of steroidal and non-steroidal antirheumatic drugs on articular cartilage in osteoarthrosis and its counteraction by a biological GAG-peptide complex (Rumalon).

    PubMed

    Kalbhen, D A

    1982-01-01

    In-vitro studies have confirmed that various corticosteroids and also many nonsteroidal antirheumatic drugs exert inhibitory effects on anabolic processes in connective tissue cells. Depending on dose and at concentrations that in many cases correspond to therapeutic plasma levels, these drugs may lead to a pronounced reduction or complete blockade of synthesis of the proteoglycans and collagen of the cartilage matrix. Our in-vivo animal experiments have shown that single or repeated intraarticular applications of various antiinflammatory antirheumatics into the knee joint of hens or rats can induce progressive joint degeneration within 3-4 months. The degenerative process was monitored by macroscopic, radiological, histological, biochemical, and stereoelectronmicroscopic methods and corresponded very well with the pathology of human osteoarthrosis. Our experimental osteoarthrosis, induced by metabolic lesions or inhibition of chondrocytes, can be influenced therapeutically by intraarticular or intramuscular treatment with the biological GAG-peptide complex (Rumalon) or with its high molecular fraction DAK-16. These compounds significantly reduce or even stop the degenerative progression in the osteoarthrotic knee joints. The chondroprotective and anti-arthritic properties of Rumalon or DAK-16 can be explained by its stimulation of connective tissue anabolism as well as by its inhibitory effect on catabolic enzymes responsible for cartilage breakdown. Our experiments also indicate that catabolic reactions of corticosteroids on articular cartilage can be counteracted or reduced by concomitant administration of the chondroprotective agents. This effect might be desirable and beneficial during treatment of inflammatory phases of osteoarthrosis with intraarticular injections of corticosteroids.

  19. Bioassay-guided preparative separation of angiotensin-converting enzyme inhibitory C-flavone glycosides from Desmodium styracifolium by recycling complexation high-speed counter-current chromatography.

    PubMed

    Zhang, Ying-Qi; Luo, Jian-Guang; Han, Chao; Xu, Jin-Fang; Kong, Ling-Yi

    2015-01-01

    A new strategy of the convergence of high-speed counter-current chromatography (HSCCC) and bioactive assay technique was developed for rapidly screening and separating the angiotensin-converting enzyme (ACE) inhibitors from the aerial parts of Desmodium styracifolium. Bioactivity-guided fractionation of the crude extract was first established to target the bioactive fractions based on HSCCC coupled with in vitro ACE inhibitory assay. Subsequently, the bioactive fractions were further separated by the recycling complexation HSCCC respectively, using 0.10 mol/L copper sulfate in the lower phase of two-phase solvent system composed of n-butanol/water (1:1, v/v). Five C-glycosylflavones, vicenin 2 (1), carlinoside (2), vicenin 1 (3), schaftoside (4) and vicenin 3 (5), were successfully obtained. Their chemical structures were identified using ESI-MS and NMR. All the isolates showed in vitro ACE inhibitory activity with the IC50 values between 33.62 and 58.37 μM. The results demonstrated that the established method was proposed as an excellent strategy to systematically screen and purify active compounds from traditional Chinese medicines.

  20. Modern spectroscopic technique in the characterization of biosensitive macrocyclic Schiff base ligand and its complexes: Inhibitory activity against plantpathogenic fungi

    NASA Astrophysics Data System (ADS)

    Tyagi, Monika; Chandra, Sulekh; Akhtar, Jameel; Chand, Dinesh

    2014-01-01

    Complexes of the type [M(L)Cl2], where M = Co(II), Ni(II) and Cu(II) have been synthesized with a macrocyclic Schiff base ligand (1,4,5,7,10,11,12,15-octaaza,5,11,16,18-tetraphenyl, 3,4,12,13-tetramethyl cyclo-octadecane) derived from Schiff base (obtained by the condensation of 4-aminoantipyrine and dibenzoyl methane) and ethylenediamine. The ligand was characterized on the basis of elemental analysis, IR, 1H NMR, EI Mass and molecular modeling studies while the complexes were characterized by elemental analysis, molar conductance measurements, magnetic susceptibility measurements, IR, electronic and EPR spectral studies. All the complexes are non-electrolyte in nature. The covalency factor (β) and coefficient factor (α) suggest the covalent nature of the complexes. The ligand and its metal complexes have shown antifungal activity with their LD50 values determined by probit analysis against two economically important fungal plant pathogens i.e. Macrophomina phaseolina and Fusarium solani.

  1. Inhibitory motor control based on complex stopping goals relies on the same brain network as simple stopping.

    PubMed

    Wessel, Jan R; Aron, Adam R

    2014-12-01

    Much research has modeled action-stopping using the stop-signal task (SST), in which an impending response has to be stopped when an explicit stop-signal occurs. A limitation of the SST is that real-world action-stopping rarely involves explicit stop-signals. Instead, the stopping-system engages when environmental features match more complex stopping goals. For example, when stepping into the street, one monitors path, velocity, size, and types of objects and only stops if there is a vehicle approaching. Here, we developed a task in which participants compared the visual features of a multidimensional go-stimulus to a complex stopping-template, and stopped their go-response if all features matched the template. We used independent component analysis of EEG data to show that the same motor inhibition brain network that explains action-stopping in the SST also implements motor inhibition in the complex-stopping task. Furthermore, we found that partial feature overlap between go-stimulus and stopping-template led to motor slowing, which also corresponded with greater stopping-network activity. This shows that the same brain system for action-stopping to explicit stop-signals is recruited to slow or stop behavior when stimuli match a complex stopping goal. The results imply a generalizability of the brain's network for simple action-stopping to more ecologically valid scenarios.

  2. Ligand binding to the inhibitory and stimulatory GTP cyclohydrolase I/GTP cyclohydrolase I feedback regulatory protein complexes.

    PubMed

    Yoneyama, T; Hatakeyama, K

    2001-04-01

    GTP cyclohydrolase I feedback regulatory protein (GFRP) mediates feedback inhibition of GTP cyclohydrolase I activity by 6R-L-erythro-5,6,7,8-tetrahydrobiopterin (BH4), which is an essential cofactor for key enzymes producing catecholamines, serotonin, and nitric oxide as well as phenylalanine hydroxylase. GFRP also mediates feed-forward stimulation of GTP cyclohydrolase I activity by phenylalanine at subsaturating GTP levels. These ligands, BH4 and phenylalanine, induce complex formation between one molecule of GTP cyclohydrolase I and two molecules of GFRP. Here, we report the analysis of ligand binding using the gel filtration method of Hummel and Dreyer. BH4 binds to the GTP cyclohydrolase I/GFRP complex with a Kd of 4 microM, and phenylalanine binds to the protein complex with a Kd of 94 microM. The binding of BH4 is enhanced by dGTP. The binding stoichiometrics of BH4 and phenylalanine were estimated to be 10 molecules of each per protein complex, in other words, one molecule per subunit of protein, because GTP cyclohydrolase I is a decamer and GFRP is a pentamer. These findings were corroborated by data from equilibrium dialysis experiments. Regarding ligand binding to free proteins, BH4 binds weakly to GTP cyclohydrolase I but not to GFRP, and phenylalanine binds weakly to GFRP but not to GTP cyclohydrolase I. These results suggest that the overall structure of the protein complex contributes to binding of BH4 and phenylalanine but also that each binding site of BH4 and phenylalanine may be primarily composed of residues of GTP cyclohydrolase I and GFRP, respectively.

  3. ETV6-NTRK3 fusion oncogene initiates breast cancer from committed mammary progenitors via activation of AP1 complex

    PubMed Central

    Li, Zhe; Tognon, Cristina E.; Godinho, Frank J.; Yasaitis, Laura; Hock, Hanno; Herschkowitz, Jason I.; Lannon, Chris L.; Cho, Eunah; Kim, Seong-Jin; Bronson, Roderick T.; Perou, Charles M.; Sorensen, Poul H.; Orkin, Stuart H.

    2007-01-01

    SUMMARY To better understand the cellular origin of breast cancer, we developed a mouse model that recapitulates expression of the ETV6-NTRK3 (EN) fusion oncoprotein, the product of the t(12;15)(p13;q25) translocation characteristic of human secretory breast carcinoma. Activation of EN expression in mammary tissues by Wap-Cre leads to fully penetrant, multifocal malignant breast cancer with short latency. We provide genetic evidence that in nulliparous Wap-Cre;EN females, committed alveolar bipotent or CD61+ luminal progenitors, are targets of tumorigenesis. Furthermore, EN transforms these otherwise transient progenitors through activation of the AP1 complex. Given increasing relevance of chromosomal translocations in epithelial cancers, such mice serve as a paradigm for the study of their genetic pathogenesis and cellular origins, and generation of novel preclinical models. SIGNIFICANCE For the largest class of human tumors, those of epithelial origin, little is known about their initiating genetic hits or cells of origin. Whether tissue stem cells or more committed progenitors are targets for transformation is uncertain. We developed a system in which epithelial tumorigenesis can be assessed from the initial event to frank malignancy. In this breast cancer model based on chromosomal translocation, we show through genetic marking that committed mammary progenitors, rather than mammary stem cells, are direct targets of transformation. We show that activation of the AP1 complex represents a critical downstream event of the ETV6-NTRK3 translocation. Further focus on this transcriptional complex as a target in human breast cancer is warranted. PMID:18068631

  4. Role of organic cation/carnitine transporter 1 in uptake of phenformin and inhibitory effect on complex I respiration in mitochondria.

    PubMed

    Shitara, Yoshihisa; Nakamichi, Noritaka; Norioka, Misaki; Shima, Hiroyo; Kato, Yukio; Horie, Toshiharu

    2013-03-01

    Phenformin causes lactic acidosis in clinical situations due to inhibition of mitochondrial respiratory chain complex I. It is reportedly taken up by hepatocytes and exhibits mitochondrial toxicity in the liver. In this study, uptake of phenformin and [(14)C]tetraethylammonium (TEA) and complex I inhibition by phenformin were examined in isolated liver and heart mitochondria. Uptake of phenformin into isolated rat liver mitochondria was higher than that into heart mitochondria. It was inhibited by several cat ionic compounds, which suggests the involvement of multispecific transport system(s). Similar characteristics were also observed for uptake of TEA; however, uptake of phenformin into mitochondria of organic cation/carnitine transporter 1 (OCTN1) knockout mice was lower than that in wild-type mice, whereas uptake of TEA was comparable between the two strains, suggesting the involvement of distinct transport mechanisms for these two cations in mitochondria. Inhibition by phenformin of oxygen consumption via complex I respiration in isolated rat liver mitochondria was greater than that in heart mitochondria, whereas inhibitory effect of phenformin on complex I respiration was similar in inside-out structured submitochondrial particles prepared from rat livers and hearts. Lactic acidosis provoked by iv infusion of phenformin was weaker in octn1(-/-) mice than that in wild-type mice. These observations suggest that uptake of phenformin into liver mitochondria is at least partly mediated by OCTN1 and functionally relevant to its inhibition potential of complex I respiration. This study was, thus, the first to demonstrate OCTN1-mediated mitochondrial transport and toxicity of biguanide in vivo in rodents.

  5. The tail domain of tomosyn controls membrane fusion through tomosyn displacement by VAMP2

    SciTech Connect

    Yamamoto, Yasunori; Fujikura, Kohei; Sakaue, Mio; Okimura, Kenjiro; Kobayashi, Yuta; Nakamura, Toshihiro; Sakisaka, Toshiaki

    2010-08-13

    Research highlights: {yields} The tail domain of tomosyn has no effect on the tomosyn-SNARE complex formation. {yields} The tail domain binding to the VAMP-like domain allows VAMP2 to displace tomosyn. {yields} Tomosyn displacement by VAMP2 leads to SNARE complex formation. {yields} The SNARE complex formation drives membrane fusion. -- Abstract: Neurotransmitter release is regulated by SNARE complex-mediated synaptic vesicle fusion. Tomosyn sequesters target SNAREs (t-SNAREs) through its C-terminal VAMP-like domain (VLD). Cumulative biochemical results suggest that the tomosyn-SNARE complex is so tight that VAMP2 cannot displace tomosyn. Based on these results, the tomosyn-SNARE complex has been believed to be a dead-end complex to inhibit neurotransmitter release. On the other hand, some studies using siRNA depletion of tomosyn suggest that tomosyn positively regulates exocytosis. Therefore, it is still controversial whether tomosyn is a simple inhibitor for neurotransmitter release. We recently reported that the inhibitory activity of tomosyn is regulated by the tail domain binding to the VLD. In this study, we employed the liposome fusion assay in order to further understand modes of action of tomosyn in detail. The tail domain unexpectedly had no effect on binding of the VLD to t-SNARE-bearing liposomes. Nonetheless, the tail domain decreased the inhibitory activity of the VLD on the SNARE complex-mediated liposome fusion. These results indicate that the tail domain controls membrane fusion through tomosyn displacement by VAMP2. Deletion of the tail domain-binding region in the VLD retained the binding to t-SNAREs and promoted the liposome fusion. Together, we propose here a novel mechanism of tomosyn that controls synaptic vesicle fusion positively by serving as a placeholder for VAMP2.

  6. NSF- and SNARE-mediated membrane fusion is required for nuclear envelope formation and completion of nuclear pore complex assembly in Xenopus laevis egg extracts.

    PubMed

    Baur, Tina; Ramadan, Kristijan; Schlundt, Andreas; Kartenbeck, Jürgen; Meyer, Hemmo H

    2007-08-15

    Despite the progress in understanding nuclear envelope (NE) reformation after mitosis, it has remained unclear what drives the required membrane fusion and how exactly this is coordinated with nuclear pore complex (NPC) assembly. Here, we show that, like other intracellular fusion reactions, NE fusion in Xenopus laevis egg extracts is mediated by SNARE proteins that require activation by NSF. Antibodies against Xenopus NSF, depletion of NSF or the dominant-negative NSF(E329Q) variant specifically inhibited NE formation. Staging experiments further revealed that NSF was required until sealing of the envelope was completed. Moreover, excess exogenous alpha-SNAP that blocks SNARE function prevented membrane fusion and caused accumulation of non-flattened vesicles on the chromatin surface. Under these conditions, the nucleoporins Nup107 and gp210 were fully recruited, whereas assembly of FxFG-repeat-containing nucleoporins was blocked. Together, we define NSF- and SNARE-mediated membrane fusion events as essential steps during NE formation downstream of Nup107 recruitment, and upstream of membrane flattening and completion of NPC assembly.

  7. Symmetric covalent linkage of N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) results in novel derivatives with increased inhibitory activities against calcium/calmodulin complex.

    PubMed

    Yokokura, H; Osawa, M; Inoue, T; Umezawa, I; Naito, Y; Ikura, M; Hidaka, H

    1999-11-01

    A useful calmodulin (CaM) antagonist, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), was invented by Hidaka et al. in 1978 (J. Pharmacol. Exp. Ther. 207, 8-15). Here, we have designed new CaM antagonists on the basis of the three-dimensional structure of Ca2+/CaM complexed with W-7. Eleven new compounds all share a similar architecture, in which two W-7 molecules are linked between their aminohexyl termini by a linker with different functionalities. A wide range of inhibitory activities against Ca2+/CaM-dependent protein kinase I (CaM kinase I) has been observed with these self-crosslinked W-7 analogs, (W-7)2. In vitro competitive CaM kinase I assays using CaM kinase I and nuclear magnetic resonance studies indicated that one (W-7)2 molecule binds to one CaM molecule as expected, with the two chloronaphthalene rings of (W-7)2 being anchored separately to the N- and C-terminal hydrophobic pockets of Ca2+/CaM. The most potent compound, N,N'-bis[6-(5-chloro-1-naphthalenesulfonyl)-amino-1-hexyl]-p-xylen e-diamine ((W-7)2 - 10), inhibits CaM kinase I activity at an IC50 value of 0.23 microM; about 75 times more effectively than W-7. The length and basicity of the linker sequence in (W-7)2 significantly contribute to inhibitory activity. The present study opens an avenue for developing powerful CaM antagonists that could be used at low doses in vivo.

  8. Vaccinia virus entry/fusion complex subunit A28 is a target of neutralizing and protective antibodies

    SciTech Connect

    Nelson, Gretchen E.; Sisler, Jerry R.; Chandran, Dev; Moss, Bernard

    2008-10-25

    The vaccinia virus entry/fusion complex (EFC) is comprised of at least eight transmembrane proteins that are conserved in all poxviruses. However, neither the physical structure of the EFC nor the immunogenicity of the individual components has been determined. We prepared soluble forms of two EFC components, A28 and H2, by replacing the transmembrane domain with a signal peptide and adding a polyhistidine tail. The proteins were expressed by baculoviruses, secreted from insect cells, purified by affinity chromatography and used to raise antibodies in rabbits. The antibodies recognized the viral proteins but only the antibody to recombinant A28 bound intact virions and neutralized infectivity. Analyses with a set of overlapping peptides revealed a neutralizing epitope between residues 73 and 92 of A28. Passive immunization of mice with IgG purified from the anti-A28 serum provided partial protection against a vaccinia virus intranasal challenge, whereas IgG from the anti-H2 serum did not.

  9. Crystal Structure of Snake Venom Acetylcholinesterase in Complex with Inhibitory Antibody Fragment Fab410 Bound at the Peripheral Site

    PubMed Central

    Bourne, Yves; Renault, Ludovic; Marchot, Pascale

    2015-01-01

    The acetylcholinesterase found in the venom of Bungarus fasciatus (BfAChE) is produced as a soluble, non-amphiphilic monomer with a canonical catalytic domain but a distinct C terminus compared with the other vertebrate enzymes. Moreover, the peripheral anionic site of BfAChE, a surface site located at the active site gorge entrance, bears two substitutions altering sensitivity to cationic inhibitors. Antibody Elec410, generated against Electrophorus electricus acetylcholinesterase (EeAChE), inhibits EeAChE and BfAChE by binding to their peripheral sites. However, both complexes retain significant residual catalytic activity, suggesting incomplete gorge occlusion by bound antibody and/or high frequency back door opening. To explore a novel acetylcholinesterase species, ascertain the molecular bases of inhibition by Elec410, and document the determinants and mechanisms for back door opening, we solved a 2.7-Å resolution crystal structure of natural BfAChE in complex with antibody fragment Fab410. Crystalline BfAChE forms the canonical dimer found in all acetylcholinesterase structures. Equally represented open and closed states of a back door channel, associated with alternate positions of a tyrosine phenol ring at the active site base, coexist in each subunit. At the BfAChE molecular surface, Fab410 is seated on the long Ω-loop between two N-glycan chains and partially occludes the gorge entrance, a position that fully reflects the available mutagenesis and biochemical data. Experimentally based flexible molecular docking supports a similar Fab410 binding mode onto the EeAChE antigen. These data document the molecular and dynamic peculiarities of BfAChE with high frequency back door opening, and the mode of action of Elec410 as one of the largest peptidic inhibitors targeting the acetylcholinesterase peripheral site. PMID:25411244

  10. Anticipatory Monitoring and Control of Complex Systems using a Fuzzy based Fusion of Support Vector Regressors

    SciTech Connect

    Miltiadis Alamaniotis; Vivek Agarwal

    2014-10-01

    This paper places itself in the realm of anticipatory systems and envisions monitoring and control methods being capable of making predictions over system critical parameters. Anticipatory systems allow intelligent control of complex systems by predicting their future state. In the current work, an intelligent model aimed at implementing anticipatory monitoring and control in energy industry is presented and tested. More particularly, a set of support vector regressors (SVRs) are trained using both historical and observed data. The trained SVRs are used to predict the future value of the system based on current operational system parameter. The predicted values are then inputted to a fuzzy logic based module where the values are fused to obtain a single value, i.e., final system output prediction. The methodology is tested on real turbine degradation datasets. The outcome of the approach presented in this paper highlights the superiority over single support vector regressors. In addition, it is shown that appropriate selection of fuzzy sets and fuzzy rules plays an important role in improving system performance.

  11. Protection against lethal measles virus infection in mice by immune-stimulating complexes containing the hemagglutinin or fusion protein.

    PubMed Central

    Varsanyi, T M; Morein, B; Löve, A; Norrby, E

    1987-01-01

    The importance of each of the two surface glycoproteins of measles virus in active and passive immunization was examined in mice. Infected-cell lysates were depleted of either the hemagglutinin (H) or fusion (F) glycoprotein by using multiple cycles of immunoaffinity chromatography. The products were used to prepare immune-stimulating complexes (iscoms) containing either F or H glycoprotein. Such complexes are highly immunogenic, possibly as a result of effective presentation of viral proteins to the immune system [B. Morein, B. Sundquist, S. Höglund, K. Dalsgaard, and A. Osterhaus, Nature (London) 308:457-460, 1984]. Groups of 3-week-old BALB/c mice were inoculated with the iscom preparations. All animals developed hemolysis-inhibiting antibodies, whereas only sera of animals immunized with the iscoms containing the H glycoprotein had hemagglutination-inhibiting antibodies. Sera from animals immunized with the H or F preparation only precipitated the homologous glycoprotein in radioimmune precipitation assays. The immunized animals were challenged with a lethal dose of the hamster neurotropic variant of measles virus. Of the 7-week-old animals in the nonimmunized control group, 50% died within 10 days after challenge. No animals in the immunized groups showed symptoms of disease throughout the observation period of 3 months. Passive administration of anti-H monoclonal antibodies gave full protection against the 100% lethal acute infection with the hamster neurotropic variant of measles virus in newborn mice, whereas anti-F monoclonal antibodies failed to protect the animals. This study emphasizes that both H and F glycoproteins need to be considered in the development of measles virus subunit vaccines. Images PMID:2960833

  12. In vitro inhibitory activity of terpenic derivatives against clinical and environmental strains of the Sporothrix schenkii complex.

    PubMed

    Brilhante, Raimunda Sâmia Nogueira; Silva, Natalya Fechine; Marques, Francisca Jakelyne de Farias; Castelo-Branco, Débora de Souza Collares Maia; de Lima, Rita Amanda Chaves; Malaquias, Angela Donato Maia; Caetano, Erica Pacheco; Barbosa, Giovanna Riello; de Camargo, Zoilo Pires; Rodrigues, Anderson Messias; Monteiro, André Jalles; Bandeira, Tereza de Jesus Pinheiro Gomes; Cordeiro, Rossana de Aguiar; Sidrim, José Júlio Costa; Moreira, José Luciano Bezerra; Rocha, Marcos Fábio Gadelha

    2015-02-01

    Sporotrichosis is a subacute or chronic subcutaneous infection, caused by the fungus Sporothrix schenkii complex, occurring in human and animal tissues. Potassium iodide and itraconazole have been used as effective therapy for first-choice treatment, while amphotericin B may be indicated for disseminated infection. However, the adverse effects of potassium iodide and amphotericin B or the long duration of therapy with itraconazole often weigh against their use, leading to the search for alternatives for the treatment of severe infections. Terpinen-4-ol and farnesol are components of essential oils present in many plant species and have been described to have antifungal activity against microorganisms. In this study, 40 strains of Sporothrix spp. were tested for the susceptibility to terpinen-4-ol and farnesol. Changes in cytoplasmic membrane permeability were also investigated. Terpenes inhibited all Sporothrix strains with MIC values ranging from 87.9 to 1,429.8 μg/ml for terpinen-4-ol and from 0.003 to 0.222 μg/ml for farnesol. The MFC values ranged from 177.8 to 5,722.6 μg/ml and from 0.027 to 0.88 μg/ml, respectively, for terpinen-4-ol and farnesol. Farnesol was the most active compound for the Sporothrix strains. Significant loss of 260 and 280 nm-absorbing material did not occur after treatment with concentrations equivalent to the MIC and sub-MIC of the tested terpenes, when compared to corresponding untreated samples. The failure of terpenes to lyse Sporothrix cells suggests that their primary mechanism of action is not by causing irreversible cell membrane damage. Thus, new studies are needed to better understand the mechanisms involved in the antifungal activity.

  13. Structures of native and complexed complement factor D: implications of the atypical His57 conformation and self-inhibitory loop in the regulation of specific serine protease activity.

    PubMed

    Jing, H; Babu, Y S; Moore, D; Kilpatrick, J M; Liu, X Y; Volanakis, J E; Narayana, S V

    1998-10-09

    Factor D is a serine protease essential for the activation of the alternative pathway of complement. The structures of native factor D and a complex formed with isatoic anhydride inhibitor were determined at resolution of 2.3 and 1.5 A, respectively, in an isomorphous monoclinic crystal form containing one molecule per asymmetric unit. The native structure was compared with structures determined previously in a triclinic cell containing two molecules with different active site conformations. The current structure shows greater similarity with molecule B in the triclinic cell, suggesting that this may be the dominant factor D conformation in solution. The major conformational differences with molecule A in the triclinic cell are located in four regions, three of which are close to the active site and include some of the residues shown to be critical for factor D catalytic activity. The conformational flexibility associated with these regions is proposed to provide a structural basis for the previously proposed substrate-induced reversible conformational changes in factor D. The high-resolution structure of the factor D/isatoic anhydride complex reveals the binding mode of the mechanism-based inhibitor. The higher specificity towards factor D over trypsin and thrombin is based on hydrophobic interactions between the inhibitor benzyl ring and the aliphatic side-chain of Arg218 that is salt bridged with Asp189 at the bottom of the primary specificity (S1) pocket. Comparison of factor D structural variants with other serine protease structures revealed the presence of a unique "self-inhibitory loop". This loop (214-218) dictates the resting-state conformation of factor D by (1) preventing His57 from adopting active tautomer conformation, (2) preventing the P1 to P3 residues of the substrate from forming anti-parallel beta-sheets with the non-specific substrate binding loop, and (3) blocking the accessibility of Asp189 to the positive1y charged P1 residue of the

  14. [The inhibitory effect and the mechanism of ethanol absorption by L-carnosine zinc complex in mouse gastrointestinal tract].

    PubMed

    Natsuki, R; Nozaki, M; Fujimura, H

    1998-12-01

    The effect of L-carnosine-zinc complex(Car-Zn) on ethanol absorption was investigated after oral administration(adm) to mice. One hour after oral adm of Car-Zn, and 14C-ethanol was given orally or intraperitoneally(i.p.). After passage of time, the blood was drawn from the tail vein, and 14C-radioactivities determined. The Car-Zn showed a dose-dependent inhibition of the appearance of 14C-radioactivities in blood following oral 14C-ethanol loading, while Zn acetate did not induce any alteration as compared with control. Car-Zn pretreatment did not induce any change in the blood 14C-radioactivity when ethanol was given i.p. The 14C-radioactivity and zinc in gastrointestinal tract after oral adm of Car-Zn and 14C-ethanol showed significantly higher levels than those of control for 7 hr. Distribution of 14C-radioactivities in other organs of Car-Zn treated mice were lower than those of control 3 hr after adm, while it was similar or higher than those of control 7 hr after adm. The excretions of 14C-radioactivity through expiration in Car-Zn group was a lower than that of control. Also, the urinary and fecal excretions of 14C-radioactivity were low values at 5.0% and 0.5% of the administered dose 72 hr after adm, respectively. Also, the 14C-radioactivities remaining in the organs did not detect or were very low values. In vitro study, Car-Zn stimulated the metabolism of ethanol to acetaldehyde and acetic acid in 9,000 g supernatant of small intestine. The major route of excretions of 14C-radioactivity may be excreted into the expired air. The results suggest that Car-Zn shows a long-term adhesive and permeable action on gastrointestinal tract in the mouse; as a result, this may inhibited ethanol absorption.

  15. Relationship between SU subdomains that regulate the receptor-mediated transition from the native (fusion-inhibited) to the fusion-active conformation of the murine leukemia virus glycoprotein.

    PubMed

    Lavillette, Dimitri; Ruggieri, Alessia; Boson, Bertrand; Maurice, Marielle; Cosset, François-Loïc

    2002-10-01

    Envelope glycoproteins (Env) of retroviruses are trimers of SU (surface) and TM (transmembrane) heterodimers and are expressed on virions in fusion-competent forms that are likely to be metastable. Activation of the viral receptor-binding domain (RBD) via its interaction with a cell surface receptor is thought to initiate a cascade of events that lead to refolding of the Env glycoprotein into its stable fusion-active conformation. While the fusion-active conformation of the TM subunit has been described in detail for several retroviruses, little is known about the fusion-competent structure of the retroviral glycoproteins or the molecular events that mediate the transition between the two conformations. By characterizing Env chimeras between the ecotropic and amphotropic murine leukemia virus (MLV) SUs as well as a set of point mutants, we show that alterations of the conformation of the SU glycoprotein strongly elevate Env fusogenicity by disrupting the stability of the Env complex. Compensatory mutations that restored both Env stability and fusion control were also identified, allowing definition of interactions within the Env complex that maintain the stability of the native Env complex. We show that, in the receptor-unbound form, structural interactions between the N terminus of the viral RBD (NTR domain), the proline-rich region (PRR), and the distal part of the C-terminal domain of the SU subunit maintain a conformation of the glycoprotein that is fusion inhibitory. Additionally, we identified mutations that disrupt this fusion-inhibitory conformation and allow fusion activation in the absence of viral receptors, provided that receptor-activated RBD fragments are added in trans during infection. Other mutations were identified that allow fusion activation in the absence of receptors for both the viral glycoprotein and the trans-acting RBD. Finally, we found mutations of the SU that bypass in cis the requirement for the NTR domain in fusion activation. All

  16. Relationship between SU Subdomains That Regulate the Receptor-Mediated Transition from the Native (Fusion-Inhibited) to the Fusion-Active Conformation of the Murine Leukemia Virus Glycoprotein

    PubMed Central

    Lavillette, Dimitri; Ruggieri, Alessia; Boson, Bertrand; Maurice, Marielle; Cosset, François-Loïc

    2002-01-01

    Envelope glycoproteins (Env) of retroviruses are trimers of SU (surface) and TM (transmembrane) heterodimers and are expressed on virions in fusion-competent forms that are likely to be metastable. Activation of the viral receptor-binding domain (RBD) via its interaction with a cell surface receptor is thought to initiate a cascade of events that lead to refolding of the Env glycoprotein into its stable fusion-active conformation. While the fusion-active conformation of the TM subunit has been described in detail for several retroviruses, little is known about the fusion-competent structure of the retroviral glycoproteins or the molecular events that mediate the transition between the two conformations. By characterizing Env chimeras between the ecotropic and amphotropic murine leukemia virus (MLV) SUs as well as a set of point mutants, we show that alterations of the conformation of the SU glycoprotein strongly elevate Env fusogenicity by disrupting the stability of the Env complex. Compensatory mutations that restored both Env stability and fusion control were also identified, allowing definition of interactions within the Env complex that maintain the stability of the native Env complex. We show that, in the receptor-unbound form, structural interactions between the N terminus of the viral RBD (NTR domain), the proline-rich region (PRR), and the distal part of the C-terminal domain of the SU subunit maintain a conformation of the glycoprotein that is fusion inhibitory. Additionally, we identified mutations that disrupt this fusion-inhibitory conformation and allow fusion activation in the absence of viral receptors, provided that receptor-activated RBD fragments are added in trans during infection. Other mutations were identified that allow fusion activation in the absence of receptors for both the viral glycoprotein and the trans-acting RBD. Finally, we found mutations of the SU that bypass in cis the requirement for the NTR domain in fusion activation. All

  17. Inhibitory effect of beta-diketones and their metal complexes on TNF-alpha induced expression of ICAM-1 on human endothelial cells.

    PubMed

    Caruso, Francesco; Pettinari, Claudio; Marchetti, Fabio; Rossi, Miriam; Opazo, Cristian; Kumar, Sarvesh; Balwani, Sakshi; Ghosh, Balaram

    2009-09-01

    Recent reports show that the natural beta-diketone curcumin displays important biological properties regarding the intercellular adhesion molecule-1 (ICAM-1), which plays a critical role in the immune responses and inflammation. In this study the ICAM-1 inhibitory activity of beta-diketone compounds, which are curcumin models lacking aromatic peripheral hydroxyl and methoxy groups, along with some metal derivatives is investigated. Beta-diketones are systematically more active than metal complexes and the best obtained inhibition is 75% for both groups. The best inhibitors are 4-benzoyl-3-methyl-1-phenyl-pyrazol-5-one (HQ(Ph)) among the ligands, and sodium benzoylacetonato among metal derivatives. These results appear in line with the reported antitumor activity of related species. Since 4-acyl-5-pyrazolones posses four tautomeric forms, those corresponding to HQ(Ph) were investigated using density functional theory. Docking of all HQ(Ph) tautomers on ICAM-1 protein was performed suggesting one keto-enol form favored to act in biological environment.

  18. Proteolytic Cleavage of the Fusion Protein but Not Membrane Fusion Is Required for Measles Virus-Induced Immunosuppression In Vitro

    PubMed Central

    Weidmann, Armin; Maisner, Andrea; Garten, Wolfgang; Seufert, Marion; ter Meulen, Volker; Schneider-Schaulies, Sibylle

    2000-01-01

    Immunosuppression induced by measles virus (MV) is associated with unresponsiveness of peripheral blood lymphocytes (PBL) to mitogenic stimulation ex vivo and in vitro. In mixed lymphocyte cultures and in an experimental animal model, the expression of the MV glycoproteins on the surface of UV-inactivated MV particles, MV-infected cells, or cells transfected to coexpress the MV fusion (F) and the hemagglutinin (H) proteins was found to be necessary and sufficient for this phenomenon. We now show that MV fusion-inhibitory peptides do not interfere with the induction of immunosuppression in vitro, indicating that MV F-H-mediated fusion is essentially not involved in this process. Proteolytic cleavage of MV F0 protein by cellular proteases, such as furin, into the F1-F2 subunits is, however, an absolute requirement, since (i) the inhibitory activity of MV-infected BJAB cells was significantly impaired in the presence of a furin-inhibitory peptide and (ii) cells expressing or viruses containing uncleaved F0 proteins revealed a strongly reduced inhibitory activity which was improved following trypsin treatment. The low inhibitory activity of effector structures containing mainly F0 proteins was not due to an impaired F0-H interaction, since both surface expression and cocapping efficiencies were similar to those found with the authentic MV F and H proteins. These results indicate that the fusogenic activity of the MV F-H complexes can be uncoupled from their immunosuppressive activity and that the immunosuppressive domains of these proteins are exposed only after proteolytic activation of the MV F0 protein. PMID:10644371

  19. Magnetic fusion reactor economics

    SciTech Connect

    Krakowski, R.A.

    1995-12-01

    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 {yields} 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. Magnetic-confinement fusion

    NASA Astrophysics Data System (ADS)

    Ongena, J.; Koch, R.; Wolf, R.; Zohm, H.

    2016-05-01

    Our modern society requires environmentally friendly solutions for energy production. Energy can be released not only from the fission of heavy nuclei but also from the fusion of light nuclei. Nuclear fusion is an important option for a clean and safe solution for our long-term energy needs. The extremely high temperatures required for the fusion reaction are routinely realized in several magnetic-fusion machines. Since the early 1990s, up to 16 MW of fusion power has been released in pulses of a few seconds, corresponding to a power multiplication close to break-even. Our understanding of the very complex behaviour of a magnetized plasma at temperatures between 150 and 200 million °C surrounded by cold walls has also advanced substantially. This steady progress has resulted in the construction of ITER, a fusion device with a planned fusion power output of 500 MW in pulses of 400 s. ITER should provide answers to remaining important questions on the integration of physics and technology, through a full-size demonstration of a tenfold power multiplication, and on nuclear safety aspects. Here we review the basic physics underlying magnetic fusion: past achievements, present efforts and the prospects for future production of electrical energy. We also discuss questions related to the safety, waste management and decommissioning of a future fusion power plant.

  1. Kinetically coupled folding of a single HIV-1 glycoprotein 41 complex in viral membrane fusion and inhibition.

    PubMed

    Jiao, Junyi; Rebane, Aleksander A; Ma, Lu; Gao, Ying; Zhang, Yongli

    2015-06-02

    HIV-1 glycoprotein 41 (gp41) mediates viral entry into host cells by coupling its folding energy to membrane fusion. Gp41 folding is blocked by fusion inhibitors, including the commercial drug T20, to treat HIV/AIDS. However, gp41 folding intermediates, energy, and kinetics are poorly understood. Here, we identified the folding intermediates of a single gp41 trimer-of-hairpins and measured their associated energy and kinetics using high-resolution optical tweezers. We found that folding of gp41 hairpins was energetically independent but kinetically coupled: Each hairpin contributed a folding energy of ∼-23 kBT, but folding of one hairpin successively accelerated the folding rate of the next one by ∼20-fold. Membrane-mimicking micelles slowed down gp41 folding and reduced the stability of the six-helix bundle. However, the stability was restored by cooperative folding of the membrane-proximal external region. Surprisingly, T20 strongly inhibited gp41 folding by actively displacing the C-terminal hairpin strand in a force-dependent manner. The inhibition was abolished by a T20-resistant gp41 mutation. The energetics and kinetics of gp41 folding established by us provides a basis to understand viral membrane fusion, infection, and therapeutic intervention.

  2. Characterization of fusion genes and the significantly expressed fusion isoforms in breast cancer by hybrid sequencing.

    PubMed

    Weirather, Jason L; Afshar, Pegah Tootoonchi; Clark, Tyson A; Tseng, Elizabeth; Powers, Linda S; Underwood, Jason G; Zabner, Joseph; Korlach, Jonas; Wong, Wing Hung; Au, Kin Fai

    2015-10-15

    We developed an innovative hybrid sequencing approach, IDP-fusion, to detect fusion genes, determine fusion sites and identify and quantify fusion isoforms. IDP-fusion is the first method to study gene fusion events by integrating Third Generation Sequencing long reads and Second Generation Sequencing short reads. We applied IDP-fusion to PacBio data and Illumina data from the MCF-7 breast cancer cells. Compared with the existing tools, IDP-fusion detects fusion genes at higher precision and a very low false positive rate. The results show that IDP-fusion will be useful for unraveling the complexity of multiple fusion splices and fusion isoforms within tumorigenesis-relevant fusion genes.

  3. The separation of platinum, palladium and gold from silicate rocks by the anion exchange separation of chloro complexes after a sodium peroxide fusion: an investigation of low recoveries.

    PubMed

    Enzweiler, J; Potts, P J

    1995-10-01

    A series of experiments was undertaken to measure the recovery efficiency of platinum, palladium and gold from silicate rocks using a sodium peroxide fusion followed by anion exchange separation of the analytes as chloro complexes. Results obtained by graphite furnace atomic absorption spectrometric analysis of standard solutions prepared in dilute HCl or HCl-acidified sodium peroxide solution showed that recoveries were near quantitative. However, when standard solutions were added to an alkaline sodium peroxide solution, which was then acidified, low results were obtained for platinum and gold (46% and 76% respectively). Low and variable results were also obtained when standard solutions were added to a peridotite sample that had been dissolved by the state procedure, and in the analysis of the South African Bureau of Standards certified reference material, SARM 7. Various experiments were undertaken to investigate these low recoveries, but the reason proposed here is the formation of hydroxychloro compounds in alkaline solution which are not, on acidification with HCl, converted quantitatively to the chloro complex necessary for quantitative anion exchange separation. It is concluded that a sodium peroxide fusion followed by an anion-exchange separation does not appear to form the basis of a successful technique for the determination of platinum, palladium and gold in silicate rocks.

  4. Antibody raised against soluble CD4-rgp120 complex recognizes the CD4 moiety and blocks membrane fusion without inhibiting CD4-gp120 binding

    PubMed Central

    1990-01-01

    We studied the humoral response of mice immunized with soluble CD4- rgp120 complex, testing polyclonal and monoclonal antibodies (mAbs) with the aim of identifying molecular changes that take place after the first interaction between human immunodeficiency virus and the cell surface. The antisera had a paradoxically high syncytia-blocking titer associated with anti-CD4 specificity, while their capacity to inhibit CD4-gp120 binding was relatively modest. One of the mAbs produced from these responders blocks syncytia formation but does not inhibit CD4 interaction with gp120. Apparently, this mAb interacts with the CD4 moiety of CD4-gp120 complex and prevents a post-binding event necessary for membrane fusion and viral infection. PMID:2212945

  5. Spinal Fusion

    MedlinePlus

    ... concept of fusion is similar to that of welding in industry. Spinal fusion surgery, however, does not ... bone taken from the patient has a long history of use and results in predictable healing. Autograft ...

  6. Synthesis, crystal structures, molecular docking, in vitro monoamine oxidase-B inhibitory activity of transition metal complexes with 2-{4-[bis (4-fluorophenyl)methyl]piperazin-1-yl} acetic acid

    NASA Astrophysics Data System (ADS)

    Yang, Dan-dan; Wang, Riu; Zhu, Jin-long; Cao, Qi-yue; Qin, Jie; Zhu, Hai-liang; Qian, Shao-song

    2017-01-01

    Three novel complexes, [Cu(L)2(H2O)](1), [Zn(L)2(H2O)2]·CH3OH·1.5H2O(2), and [Ni(L)2(H2O)1.8]·CH3OH·1.2H2O (3) (HL = 2-{4-[bis(4-fluorophenyl)methyl]pipera-zin-1-yl} acetic acid), were synthesized and structurally determined by single-crystal X-ray diffraction. Molecular docking study preliminarily revealed that complex 1 had potential Monoamine oxidase B inhibitory activity. All acquired compounds were tested against rat brain MAO-B in vitro. In accordance with the result of calculation, it showed complex 1 (IC50 = 1.85 ± 0.31 μM) have good inhibitory activity against MAO-B at the same micromolar concentrations with positive control Iproniazid Phosphate (IP, IC50 = 7.59 ± 1.17 μM). These results indicated that complex 1 was a potent MAO-B inhibitor.

  7. Radioscapholunate Fusions

    PubMed Central

    McGuire, Duncan Thomas; Bain, Gregory Ian

    2012-01-01

    Radiocarpal fusions are performed for a variety of indications, most commonly for debilitating painful arthritis. The goal of a wrist fusion is to fuse the painful, diseased joints and to preserve motion through the healthy joints. Depending on the extent of the disease process, radiocarpal fusions may take the form of radiolunate, radioscapholunate, or total wrist fusions. Surgical techniques and instrumentation have advanced over the last few decades, and consequently the functional outcomes have improved and complications decreased. Techniques for partial carpal fusions have improved and now include distal scaphoid and triquetrum excision, which improves range of motion and fusion rates. In this article we discuss the various surgical techniques and fixation methods available and review the corresponding evidence in the literature. The authors' preferred surgical technique of radioscapholunate fusion with distal scaphoid and triquetrum excision is outlined. New implants and new concepts are also discussed. PMID:24179717

  8. NUP98 fusion oncoproteins interact with the APC/C(Cdc20) as a pseudosubstrate and prevent mitotic checkpoint complex binding.

    PubMed

    Salsi, Valentina; Fantini, Sebastian; Zappavigna, Vincenzo

    2016-09-01

    NUP98 is a recurrent partner gene in translocations causing acute myeloid leukemias and myelodisplastic syndrome. The expression of NUP98 fusion oncoproteins has been shown to induce mitotic spindle defects and chromosome missegregation, which correlate with the capability of NUP98 fusions to cause mitotic checkpoint attenuation. We show that NUP98 oncoproteins physically interact with the APC/C(Cdc20) in the absence of the NUP98 partner protein RAE1, and prevent the binding of the mitotic checkpoint complex to the APC/C(Cdc20). NUP98 oncoproteins require the GLEBS-like domain present in their NUP98 moiety to bind the APC/C(Cdc20). We found that NUP98 wild-type is a substrate of APC/C(Cdc20) prior to mitotic entry, and that its binding to APC/C(Cdc20) is controlled via phosphorylation of a PEST sequence located within its C-terminal portion. We identify S606, within the PEST sequence, as a key target site, whose phosphorylation modulates the capability of NUP98 to interact with APC/C(Cdc20). We finally provide evidence for an involvement of the peptidyl-prolyl isomerase PIN1 in modulating the possible conformational changes within NUP98 that lead to its dissociation from the APC/C(Cdc20) during mitosis. Our results provide novel insight into the mechanisms underlying the aberrant capability of NUP98 oncoproteins to interact with APC/C(Cdc20) and to interfere with its function.

  9. Role of nucleotides in stabilization of the phospholamban/cardiac Ca²⁺ pump inhibitory complex examined with use of metal fluorides.

    PubMed

    Chen, Zhenhui

    2015-11-01

    Phospholamban (PLB) inhibits the activity of the cardiac calcium pump SERCA2a. We previously showed that PLB with engineered Cys residues only cross-linked with the Ca(2+) -free E2 intermediate of SERCA2a. Formation of E2•PLB prevents Ca(2+) binding at the high-affinity Ca(2+) binding sites, blocking the enzyme kinetic cycle. Here we further studied the synergistic action of PLB and ATP on E2 in terms of prevention of formation of the phosphorylated E2P-like states stabilized by metal fluorides. SERCA2a was co-expressed in insect cell microsomes with PLB mutants of normal or super-inhibitory strength, with cross-linkable mutations at either the cytosolic side (N30C) or the luminal side (V49C) of PLB. For normal-strength PLB mutants, in the absence of nucleotide, metal fluorides totally inhibited both SERCA2a enzyme activity and cross-linking of PLB to SERCA2a at both sites, suggesting that PLB dissociates from SERCA2a in the E2P-like states. However, under the same conditions, super-inhibitory PLB mutants prevented total enzyme inhibition by metal fluorides. Further, the cross-linking of super-inhibitory PLB to SERCA2a was only partially inhibited by metal fluorides, but was drastically restored upon sequential addition of ATP. These results revealed the equilibrium between E2•PLB, E2•ATP, or E2•ATP•PLB states and E2P-like states, suggesting that the synergistic binding of ATP and PLB to SERCA is very strong, sufficient to prevent formation of E2 phosphoenzymes, even when stabilized by metal fluorides.

  10. Transcriptional Repression and RNA Silencing Act Synergistically To Demonstrate the Function of the Eleventh Component of the Vaccinia Virus Entry-Fusion Complex

    PubMed Central

    Wolfe, Cindy L.; Ojeda, Suany

    2012-01-01

    Poxviruses have an elaborate system for infecting cells comprising several proteins for attachment and a larger number dedicated to membrane fusion and entry. Thus far, 11 proteins have been identified as components of the vaccinia virus (VACV) entry-fusion complex (EFC), and 10 of these proteins have been shown to be required for entry. J5, the remaining functionally uncharacterized component of the complex, is conserved in all poxviruses, has a predicted C-terminal transmembrane domain, and is an N-terminally truncated paralog of two other EFC proteins. To determine the role of J5, we constructed a mutant that inducibly regulates J5 transcription. Although the virus yield was reduced only about 80% without inducer, the inability to isolate a J5 deletion mutant suggested an essential function. To enhance stringency, we employed RNA silencing alone and together with transcriptional repression of the inducible mutant. The yield of infectious virus was reduced 4- to 5-fold by repression, 2-fold by silencing, and 60-fold by the combination of the two. Virus particles made under the latter conditions appeared to contain a full complement of proteins excluding J5 but had very low infectivity. Further studies indicated that after binding to cells, J5-deficient virions had a defect in core entry and an inability to induce syncytium formation. In addition, we confirmed that J5 is associated with the EFC by affinity purification. These data indicate that J5 is a functional component of the EFC and highlights the advantage of combining transcriptional repression and RNA silencing for stringent reduction of gene expression. PMID:22013036

  11. Inheritance of skeletal deformities in gilthead seabream (Sparus aurata) - lack of operculum, lordosis, vertebral fusion and LSK complex.

    PubMed

    Negrín-Báez, D; Navarro, A; Lee-Montero, I; Soula, M; Afonso, J M; Zamorano, M J

    2015-01-01

    Morphological abnormalities in farmed gilthead seabream (Sparus aurata) are a major problem as it entails significant economic losses. In this study, 3 large scale experiments under different conditions of spawning, offspring handling and breeders phenotype were performed to analyze the inheritance of 4 types of deformities in this species: lack of operculum, lordosis, vertebral fusion, which are 3 of the most important skeletal deformities, and LSK, which is a consecutive repetition of lordosis/scoliosis/kyphosis. In Exp. [1] (mass spawning and fingerling sorting), 900 fish were analyzed at 509 d post-hatching: 846 fish that had been on-grown in a farm and 54 LSK-deformed fish that had been reared separately after being selected during the fingerling sorting process. A total of 89 families were represented. A statistically significant association between 5 of these families (from 6 breeders) and LSK-deformed fish was found. In Exp. [2] (mass spawning and no fingerling sorting), 810 fish were analyzed at 2 ages: 179 and 689 d post-hatching. Significant relationships between 2 of the breeders and 2 of the families with the lack of operculum prevalence of their descendants were found at 689 d but not at 179 d. Heritabilities: 0.09 ± 0.09 at 179 d and 0.17 ± 0.08 at 689 d. Column deformities prevalence was low and no association with family was observed. Family relationships were determined by microsatellites multiplex PCR in both experiments. In Exp. [3] (designed mating), sires suffering from lordosis or lack of operculum or vertebral fusion deformities were mated with non-deformed dams and a mass-spawning mating was considered as a control. After analyzing 11,503 offspring at 159 d post-hatching, a significant relationship between each deformity prevalence and the mating of breeders suffering from the same deformity was observed. In addition, a significant prevalence of lack of operculum in offspring from lordotic matings was observed. Heritabilities ranged from

  12. Fusion breeder

    SciTech Connect

    Moir, R.W.

    1982-04-20

    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.

  13. Fusion breeder

    SciTech Connect

    Moir, R.W.

    1982-02-22

    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.

  14. Inhibitory control of hippocampal inhibitory neurons

    PubMed Central

    Chamberland, Simon; Topolnik, Lisa

    2012-01-01

    Information processing within neuronal networks is determined by a dynamic partnership between principal neurons and local circuit inhibitory interneurons. The population of GABAergic interneurons is extremely heterogeneous and comprises, in many brain regions, cells with divergent morphological and physiological properties, distinct molecular expression profiles, and highly specialized functions. GABAergic interneurons have been studied extensively during the past two decades, especially in the hippocampus, which is a relatively simple cortical structure. Different types of hippocampal inhibitory interneurons control spike initiation [e.g., axo-axonic and basket cells (BCs)] and synaptic integration (e.g., bistratified and oriens–lacunosum moleculare interneurons) within pyramidal neurons and synchronize local network activity, providing a means for functional segregation of neuronal ensembles and proper routing of hippocampal information. Thus, it is thought that, at least in the hippocampus, GABAergic inhibitory interneurons represent critical regulating elements at all stages of information processing, from synaptic integration and spike generation to large-scale network activity. However, this raises an important question: if inhibitory interneurons are fundamental for network computations, what are the mechanisms that control the activity of the interneurons themselves? Given the essential role of synaptic inhibition in the regulation of neuronal activity, it would be logical to expect that specific inhibitory mechanisms have evolved to control the operation of interneurons. Here, we review the mechanisms of synaptic inhibition of interneurons and discuss their role in the operation of hippocampal inhibitory circuits. PMID:23162426

  15. Studies on DNA binding behaviour of biologically active transition metal complexes of new tetradentate N2O2 donor Schiff bases: Inhibitory activity against bacteria

    NASA Astrophysics Data System (ADS)

    Sobha, S.; Mahalakshmi, R.; Raman, N.

    A series of Cu(II), Ni(II) and Zn(II) complexes of the type ML have been synthesized with Schiff bases derived from o-acetoacetotoluidide, 2-hydroxybenzaldehyde and o-phenylenediamine/1,4-diaminobutane. The complexes are insoluble in common organic solvents but soluble in DMF and DMSO. The measured molar conductance values in DMSO indicate that the complexes are non-electrolytic in nature. All the six metal complexes have been fully characterized with the help of elemental analyses, molecular weights, molar conductance values, magnetic moments and spectroscopic data. The analytical data helped to elucidate the structure of the metal complexes. The Schiff bases are found to act as tetradentate ligands using N2O2 donor set of atoms leading to a square-planar geometry for the complexes around all the metal ions. The binding properties of metal complexes with DNA were investigated by absorption spectra, viscosity measurements and cyclic voltammetry. Detailed analysis reveals that the metal complexes intercalate into the DNA base stack as intercalators. All the metal complexes cleave the pUC19 DNA in presence of H2O2. The Schiff bases and their complexes have been screened for their antibacterial activity against five bacterial strains (Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Staphylococcus epidermidis, Klebsiella pneumoniae) by disk diffusion method. All the metal complexes have potent biocidal activity than the free ligands.

  16. Studies on DNA binding behaviour of biologically active transition metal complexes of new tetradentate N2O2 donor Schiff bases: inhibitory activity against bacteria.

    PubMed

    Sobha, S; Mahalakshmi, R; Raman, N

    2012-06-15

    A series of Cu(II), Ni(II) and Zn(II) complexes of the type ML have been synthesized with Schiff bases derived from o-acetoacetotoluidide, 2-hydroxybenzaldehyde and o-phenylenediamine/1,4-diaminobutane. The complexes are insoluble in common organic solvents but soluble in DMF and DMSO. The measured molar conductance values in DMSO indicate that the complexes are non-electrolytic in nature. All the six metal complexes have been fully characterized with the help of elemental analyses, molecular weights, molar conductance values, magnetic moments and spectroscopic data. The analytical data helped to elucidate the structure of the metal complexes. The Schiff bases are found to act as tetradentate ligands using N(2)O(2) donor set of atoms leading to a square-planar geometry for the complexes around all the metal ions. The binding properties of metal complexes with DNA were investigated by absorption spectra, viscosity measurements and cyclic voltammetry. Detailed analysis reveals that the metal complexes intercalate into the DNA base stack as intercalators. All the metal complexes cleave the pUC19 DNA in presence of H(2)O(2.) The Schiff bases and their complexes have been screened for their antibacterial activity against five bacterial strains (Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Staphylococcus epidermidis, Klebsiella pneumoniae) by disk diffusion method. All the metal complexes have potent biocidal activity than the free ligands.

  17. Image fusion

    NASA Technical Reports Server (NTRS)

    Pavel, M.

    1993-01-01

    The topics covered include the following: a system overview of the basic components of a system designed to improve the ability of a pilot to fly through low-visibility conditions such as fog; the role of visual sciences; fusion issues; sensor characterization; sources of information; image processing; and image fusion.

  18. Synthesis, spectroscopic studies and inhibitory activity against bactria and fungi of acyclic and macrocyclic transition metal complexes containing a triamine coumarine Schiff base ligand

    NASA Astrophysics Data System (ADS)

    Abou-Hussein, A. A.; Linert, Wolfgang

    2015-04-01

    Two series of new mono and binuclear complexes with a Schiff base ligand derived from the condensation of 3-acetylcoumarine and diethylenetriamine, in the molar ratio 2:1 have been prepared. The ligand was characterized by elemental analysis, IR, UV-visible, 1H-NMR and mass spectra. The reaction of the Schiff base ligand with cobalt(II), nickel(II), copper(II), zinc(II) and oxovanadium(IV) lead to mono or binuclear species of cyclic or macrocyclic complexes, depending on the mole ratio of metal to ligand and as well as on the method of preparation. The Schiff base ligand behaves as a cyclic bidentate, tetradendate or pentaentadentae ligand. The formation of macrocyclic complexes depends significantly on the dimension of the internal cavity, the rigidity of the macrocycles, the nature of its donor atoms and on the complexing properties of the anion involved in the coordination. Electronic spectra and magnetic moments of the complexes indicate that the geometries of the metal centers are either square pyramidal or octahedral for acyclic or macro-cyclic complexes. The structures are consistent with the IR, UV-visible, ESR, 1H-NMR, mass spectra as well as conductivity and magnetic moment measurements. The Schiff base ligand and its metal complexes were tested against two pathogenic bacteria as Gram-positive and Gram-negative bacteria as well as one kind of fungi. Most of the complexes exhibit mild antibacterial and antifungal activities against these organisms.

  19. Membrane fusion in muscle development and repair

    PubMed Central

    Demonbreun, Alexis R.; Biersmith, Bridget H.

    2015-01-01

    Mature skeletal muscle forms from the fusion of skeletal muscle precursor cells, myoblasts. Myoblasts fuse to other myoblasts to generate multinucleate myotubes during myogenesis, and myoblasts also fuse to other myotubes during muscle growth and repair. Proteins within myoblasts and myotubes regulate complex processes such as elongation, migration, cell adherence, cytoskeletal reorganization, membrane coalescence, and ultimately fusion. Recent studies have identified cell surface proteins, intracellular proteins, and extracellular signaling molecules required for the proper fusion of muscle. Many proteins that actively participate in myoblast fusion also coordinate membrane repair. Here we will review mammalian membrane fusion with specific attention to proteins that mediate myoblast fusion and muscle repair. PMID:26537430

  20. The Path to Magnetic Fusion Energy

    SciTech Connect

    Prager, Stewart

    2011-05-04

    When the possibility of fusion as an energy source for electricity generation was realized in the 1950s, understanding of the plasma state was primitive. The fusion goal has been paced by, and has stimulated, the development of plasma physics. Our understanding of complex, nonlinear processes in plasmas is now mature. We can routinely produce and manipulate 100 million degree plasmas with remarkable finesse, and we can identify a path to commercial fusion power. The international experiment, ITER, will create a burning (self-sustained) plasma and produce 500 MW of thermal fusion power. This talk will summarize the progress in fusion research to date, and the remaining steps to fusion power.

  1. The Diversity of Cortical Inhibitory Synapses

    PubMed Central

    Kubota, Yoshiyuki; Karube, Fuyuki; Nomura, Masaki; Kawaguchi, Yasuo

    2016-01-01

    The most typical and well known inhibitory action in the cortical microcircuit is a strong inhibition on the target neuron by axo-somatic synapses. However, it has become clear that synaptic inhibition in the cortex is much more diverse and complicated. Firstly, at least ten or more inhibitory non-pyramidal cell subtypes engage in diverse inhibitory functions to produce the elaborate activity characteristic of the different cortical states. Each distinct non-pyramidal cell subtype has its own independent inhibitory function. Secondly, the inhibitory synapses innervate different neuronal domains, such as axons, spines, dendrites and soma, and their inhibitory postsynaptic potential (IPSP) size is not uniform. Thus, cortical inhibition is highly complex, with a wide variety of anatomical and physiological modes. Moreover, the functional significance of the various inhibitory synapse innervation styles and their unique structural dynamic behaviors differ from those of excitatory synapses. In this review, we summarize our current understanding of the inhibitory mechanisms of the cortical microcircuit. PMID:27199670

  2. Tandem recombineering by SLIC cloning and Cre-LoxP fusion to generate multigene expression constructs for protein complex research.

    PubMed

    Haffke, Matthias; Viola, Cristina; Nie, Yan; Berger, Imre

    2013-01-01

    A robust protocol to generate recombinant DNA containing multigene expression cassettes by using sequence and ligation independent cloning (SLIC) followed by multiplasmid Cre-LoxP recombination in tandem for multiprotein complex research is described. The protocol includes polymerase chain reaction (PCR) amplification of the desired genes, seamless insertion into the target vector via SLIC, and Cre-LoxP recombination of specific donor and acceptor plasmid molecules, optionally in a robotic setup. This procedure, called tandem recombineering, has been implemented for multiprotein expression in E. coli and mammalian cells, and also for insect cells using a recombinant baculovirus.

  3. Ubiquitin fusion constructs allow the expression and purification of multi-KOW domain complexes of the Saccharomyces cerevisiae transcription elongation factor Spt4/5.

    PubMed

    Blythe, Amanda; Gunasekara, Sanjika; Walshe, James; Mackay, Joel P; Hartzog, Grant A; Vrielink, Alice

    2014-08-01

    Spt4/5 is a hetero-dimeric transcription elongation factor that can both inhibit and promote transcription elongation by RNA polymerase II (RNAPII). However, Spt4/5's mechanism of action remains elusive. Spt5 is an essential protein and the only universally-conserved RNAP-associated transcription elongation factor. The protein contains multiple Kyrpides, Ouzounis and Woese (KOW) domains. These domains, in other proteins, are thought to bind RNA although there is little direct evidence in the literature to support such a function in Spt5. This could be due, at least in part, to difficulties in expressing and purifying recombinant Spt5. When expressed in Escherichia coli (E. coli), Spt5 is innately insoluble. Here we report a new approach for the successful expression and purification of milligram quantities of three different multi-KOW domain complexes of Saccharomyces cerevisiae Spt4/5 for use in future functional studies. Using the E. coli strain Rosetta2 (DE3) we have developed strategies for co-expression of Spt4 and multi-KOW domain Spt5 complexes from the bi-cistronic pET-Duet vector. In a second strategy, Spt4/5 was expressed via co-transformation of Spt4 in the vector pET-M11 with Spt5 ubiquitin fusion constructs in the vector pHUE. We characterized the multi-KOW domain Spt4/5 complexes by Western blot, limited proteolysis, circular dichroism, SDS-PAGE and size exclusion chromatography-multiangle light scattering and found that the proteins are folded with a Spt4:Spt5 hetero-dimeric stoichiometry of 1:1. These expression constructs encompass a larger region of Spt5 than has previously been reported, and will provide the opportunity to elucidate the biological function of the multi-KOW containing Spt5.

  4. Leukemia Inhibitory Factor (LIF)

    PubMed Central

    Nicola, Nicos A; Babon, Jeffrey J

    2015-01-01

    Leukemia inhibitory factor (LIF) is the most pleiotropic member of the interleukin-6 family of cytokines. It utilises a receptor that consists of the LIF receptor β and gp130 and this receptor complex is also used by ciliary neurotrophic growth factor (CNTF), oncostatin M, cardiotrophin1 (CT1) and cardiotrophin-like cytokine (CLC). Despite common signal transduction mechanisms (JAK/STAT, MAPK and PI3K) LIF can have paradoxically opposite effects in different cell types including stimulating or inhibiting each of cell proliferation, differentiation and survival. While LIF can act on a wide range of cell types, LIF knockout mice have revealed that many of these actions are not apparent during ordinary development and that they may be the result of induced LIF expression during tissue damage or injury. Nevertheless LIF does appear to have non-redundant actions in maternal receptivity to blastocyst implantation, placental formation and in the development of the nervous system. LIF has also found practical use in the maintenance of self-renewal and totipotency of embryonic stem cells and induced pluripotent stem cells. PMID:26187859

  5. Fusion Power.

    ERIC Educational Resources Information Center

    Dingee, David A.

    1979-01-01

    Discusses the extraordinary potential, the technical difficulties, and the financial problems that are associated with research and development of fusion power plants as a major source of energy. (GA)

  6. Doubly end-on azido bridged mixed-valence cobalt trinuclear complex: Spectral study, VTM, inhibitory effect and antimycobacterial activity on human carcinoma and tuberculosis cells

    NASA Astrophysics Data System (ADS)

    Datta, Amitabha; Das, Kuheli; Sen, Chandana; Karan, Nirmal Kumar; Huang, Jui-Hsien; Lin, Chia-Her; Garribba, Eugenio; Sinha, Chittaranjan; Askun, Tulin; Celikboyun, Pinar; Mane, Sandeep B.

    2015-09-01

    Doubly end-on azido-bridged mixed-valence trinuclear cobalt complex, [Co3(L)2(N3)6(CH3OH)2] (1) is afforded by employing a potential monoanionic tetradentate-N2O2 Schiff base precursor (2-[{[2-(dimethylamino)ethyl]imino}methyl]-6-methoxyphenol; HL). Single crystal X-ray structure reveals that in 1, the adjacent CoII and CoIII ions are linked by double end-on azido bridges and thus the full molecule is generated by the site symmetry of a crystallographic twofold rotation axis. Complex 1 is subjected on different spectral analysis such as IR, UV-vis, emission and EPR spectroscopy. On variable temperature magnetic study, we observe that during cooling, the χMT values decrease smoothly until 15 K and then reaches to the value 1.56 cm3 K mol-1 at 2 K. Complex 1 inhibits the cell growth on human lung carcinoma (A549 cells), human colorectal (COLO 205 and HT-29 cells), and human heptacellular (PLC5 cells) carcinoma cells. Complex 1 exhibits anti-mycobacterial activity and considerable efficacy on Mycobacterium tuberculosis H37Rv ATCC 27294 and H37Ra ATCC 25177 strains.

  7. Membrane fusion during poxvirus entry.

    PubMed

    Moss, Bernard

    2016-12-01

    Poxviruses comprise a large family of enveloped DNA viruses that infect vertebrates and invertebrates. Poxviruses, unlike most DNA viruses, replicate in the cytoplasm and encode enzymes and other proteins that enable entry, gene expression, genome replication, virion assembly and resistance to host defenses. Entry of vaccinia virus, the prototype member of the family, can occur at the plasma membrane or following endocytosis. Whereas many viruses encode one or two proteins for attachment and membrane fusion, vaccinia virus encodes four proteins for attachment and eleven more for membrane fusion and core entry. The entry-fusion proteins are conserved in all poxviruses and form a complex, known as the Entry Fusion Complex (EFC), which is embedded in the membrane of the mature virion. An additional membrane that encloses the mature virion and is discarded prior to entry is present on an extracellular form of the virus. The EFC is held together by multiple interactions that depend on nine of the eleven proteins. The entry process can be divided into attachment, hemifusion and core entry. All eleven EFC proteins are required for core entry and at least eight for hemifusion. To mediate fusion the virus particle is activated by low pH, which removes one or more fusion repressors that interact with EFC components. Additional EFC-interacting fusion repressors insert into cell membranes and prevent secondary infection. The absence of detailed structural information, except for two attachment proteins and one EFC protein, is delaying efforts to determine the fusion mechanism.

  8. Glioma-associated Oncogene 2 Is Essential for Trophoblastic Fusion by Forming a Transcriptional Complex with Glial Cell Missing-a*

    PubMed Central

    Tang, Chao; Tang, Lanfang; Wu, Xiaokai; Xiong, Wenyi; Ruan, Hongfeng; Hussain, Musaddique; Wu, Junsong; Zou, Chaochun; Wu, Ximei

    2016-01-01

    Cell-cell fusion of human villous trophoblasts, referred to as a process of syncytialization, acts as a prerequisite for the proper development and functional maintenance of the human placenta. Given the fact that the main components of the Hedgehog signaling pathway are expressed predominantly in the syncytial layer of human placental villi, in this study, we investigated the potential roles and underlying mechanisms of Hedgehog signaling in trophoblastic fusion. Activation of Hedgehog signaling by a variety of approaches robustly induced cell fusion and the expression of syncytial markers, whereas suppression of Hedgehog signaling significantly attenuated cell fusion and the expression of syncytial markers in both human primary cytotrophoblasts and trophoblast-like BeWo cells. Moreover, among glioma-associated oncogene (GLI) family transcriptional factors in Hedgehog signaling, knockdown of GLI2 but not GLI1 and GLI3 significantly attenuated Hedgehog-induced cell fusion, whereas overexpression of the GLI2 activator alone was sufficient to induce cell fusion. Finally, GLI2 not only stabilized glial cell missing-a, a pivotal transcriptional factor for trophoblastic syncytialization, but also formed a transcriptional heterodimer with glial cell missing-a to transactivate syncytin-1, a trophoblastic fusogen, and promote trophoblastic syncytialization. Taken together, this study uncovered a so far uncharacterized role of Hedgehog/GLI2 signaling in trophoblastic fusion, implicating that Hedgehog signaling, through GLI2, could be required for human placental development and pregnancy maintenance. PMID:26769961

  9. Glioma-associated Oncogene 2 Is Essential for Trophoblastic Fusion by Forming a Transcriptional Complex with Glial Cell Missing-a.

    PubMed

    Tang, Chao; Tang, Lanfang; Wu, Xiaokai; Xiong, Wenyi; Ruan, Hongfeng; Hussain, Musaddique; Wu, Junsong; Zou, Chaochun; Wu, Ximei

    2016-03-11

    Cell-cell fusion of human villous trophoblasts, referred to as a process of syncytialization, acts as a prerequisite for the proper development and functional maintenance of the human placenta. Given the fact that the main components of the Hedgehog signaling pathway are expressed predominantly in the syncytial layer of human placental villi, in this study, we investigated the potential roles and underlying mechanisms of Hedgehog signaling in trophoblastic fusion. Activation of Hedgehog signaling by a variety of approaches robustly induced cell fusion and the expression of syncytial markers, whereas suppression of Hedgehog signaling significantly attenuated cell fusion and the expression of syncytial markers in both human primary cytotrophoblasts and trophoblast-like BeWo cells. Moreover, among glioma-associated oncogene (GLI) family transcriptional factors in Hedgehog signaling, knockdown of GLI2 but not GLI1 and GLI3 significantly attenuated Hedgehog-induced cell fusion, whereas overexpression of the GLI2 activator alone was sufficient to induce cell fusion. Finally, GLI2 not only stabilized glial cell missing-a, a pivotal transcriptional factor for trophoblastic syncytialization, but also formed a transcriptional heterodimer with glial cell missing-a to transactivate syncytin-1, a trophoblastic fusogen, and promote trophoblastic syncytialization. Taken together, this study uncovered a so far uncharacterized role of Hedgehog/GLI2 signaling in trophoblastic fusion, implicating that Hedgehog signaling, through GLI2, could be required for human placental development and pregnancy maintenance.

  10. Monofunctional platinum(II) complexes with potent tumor cell growth inhibitory activity: the effect of a hydrogen-bond donor/acceptor N-heterocyclic ligand.

    PubMed

    Margiotta, Nicola; Savino, Salvatore; Gandin, Valentina; Marzano, Christine; Natile, Giovanni

    2014-06-01

    In this paper we investigate the possibility of further increase the role of the N-donor aromatic base in antitumor Hollis-type compounds by conferring the possibility to act as a hydrogen-bond donor/acceptor. Therefore, we synthesized the Pt(II) complex cis-[PtCl(NH3 )2 (naph)]NO3 (1) containing the 1,8-naphthyridine (naph) ligand. The naphthyridine ligand is generally monodentate, and the second nitrogen atom can act as H-bond donor/acceptor depending upon its protonation state. The possibility of forming such an H-bond could be crucial in the interaction of the drug with DNA or proteins. Apart from the synthesis of the compound, in this study we evaluated its in vitro antitumor activity in a wide panel of tumor cell lines, also including cells selected for their sensitivity/resistance to oxaliplatin, which was compared with that of previously reported complex 2 ([PtI(2,9-dimethyl-1,10-phenanthroline)(1-methyl-cytosine)]I) and oxaliplatin and cisplatin as reference compounds. The cytotoxicity data were correlated with the cellular uptake and the DNA platination levels. Finally, the reactivity of 1 towards guanosine 5'-monophosphate (5'-GMP) and glutathione was investigated to provide insights into its mechanism of action.

  11. Laser fusion

    SciTech Connect

    Smit, W.A.; Boskma, P.

    1980-12-01

    Unrestricted laser fusion offers nations an opportunity to circumvent arms control agreements and develop thermonuclear weapons. Early laser weapons research sought a clean radiation-free bomb to replace the fission bomb, but this was deceptive because a fission bomb was needed to trigger the fusion reaction and additional radioactivity was induced by generating fast neutrons. As laser-implosion experiments focused on weapons physics, simulating weapons effects, and applications for new weapons, the military interest shifted from developing a laser-ignited hydrogen bomb to more sophisticated weapons and civilian applications for power generation. Civilian and military research now overlap, making it possible for several countries to continue weapons activities and permitting proliferation of nuclear weapons. These countries are reluctant to include inertial confinement fusion research in the Non-Proliferation Treaty. 16 references. (DCK)

  12. Structure of the fusion core and inhibition of fusion by a heptad repeat peptide derived from the S protein of Middle East respiratory syndrome coronavirus.

    PubMed

    Gao, Jing; Lu, Guangwen; Qi, Jianxun; Li, Yan; Wu, Ying; Deng, Yao; Geng, Heyuan; Li, Hongbin; Wang, Qihui; Xiao, Haixia; Tan, Wenjie; Yan, Jinghua; Gao, George F

    2013-12-01

    Middle East respiratory syndrome coronavirus (MERS-CoV) recently emerged as a severe worldwide public health concern. The virus is highly pathogenic, manifesting in infected patients with an approximately 50% fatality rate. It is known that the surface spike (S) proteins of coronaviruses mediate receptor recognition and membrane fusion, thereby playing an indispensable role in initiating infection. In this process, heptad repeats 1 and 2 (HR1 and HR2) of the S protein assemble into a complex called the fusion core, which represents a key membrane fusion architecture. To date, however, the MERS-CoV fusion core remains uncharacterized. In this study, we performed a series of biochemical and biophysical analyses characterizing the HR1/HR2 complexes of this novel virus. The HR sequences were variably truncated and then connected with a flexible amino acid linker. In each case, the recombinant protein automatically assembled into a trimer in solution, displaying a typical α-helical structure. One of these trimers was successfully crystallized, and its structure was solved at a resolution of 1.9 Å. A canonical 6-helix bundle, like those reported for other coronaviruses, was revealed, with three HR1 helices forming the central coiled-coil core and three HR2 chains surrounding the core in the HR1 side grooves. This demonstrates that MERS-CoV utilizes a mechanism similar to those of other class I enveloped viruses for membrane fusion. With this notion, we further identified an HR2-based peptide that could potently inhibit MERS-CoV fusion and entry by using a pseudotyped-virus system. These results lay the groundwork for future inhibitory peptidic drug design.

  13. β-cyclodextrin complex containing Lippia grata leaf essential oil reduces orofacial nociception in mice - evidence of possible involvement of descending inhibitory pain modulation pathway.

    PubMed

    Siqueira-Lima, Pollyana S; Araújo, Adriano A S; Lucchese, Angélica M; Quintans, Jullyana S S; Menezes, Paula P; Alves, Péricles B; de Lucca Júnior, Waldecy; Santos, Marcio R V; Bonjardim, Leonardo R; Quintans-Júnior, Lucindo J

    2014-02-01

    The treatment of orofacial pain remains a major challenge for modern medicine. Thus, we prepared and physicochemically characterized a new β-cyclodextrin complex containing Lippia grata leaf essential oil (β-CD/EO) to investigate their possible antinociceptive activity in animal models of orofacial pain. The results of Differential scanning calorimeter (DSC) and Thermogravimetry/derivative thermogravimetry (TG/DTG) showed that the products prepared by Slurry complexation (SC) method were able to incorporate greater amounts of EO. In the X-ray diffractogram, it was shown that complex between EO and β-CD was formed. Male Swiss mice were pre-treated with β-CD/EO (6, 12 or 24 mg/kg, per os, gavage, p.o.), morphine (5 mg/kg, i.p.) or vehicle (distilled water, p.o.) 1 hr before treatment with formalin (20 μL, 2%), capsaicin (20 μL, 2.5 μg) or glutamate (40 μL, 25 μM) into the right upper lip. Our results demonstrated that p.o. treatment with β-CD/EO was significantly (p < 0.05 or p < 0.001) capable of reducing the nociceptive face-rubbing behaviour in both phases of the formalin test. β-CD/EO-treated mice were also significantly (p < 0.05 or p < 0.001) protected against nociception induced by capsaicin and glutamate. For the action in the central nervous system (CNS), ninety minutes after the treatment, the mice were perfused, the brains collected, crioprotected, cut in a criostate and submitted to an immunofluorescence protocol for Fos protein. The immunofluorescence protocol demonstrated that the β-CD/EO significantly activated (p < 0.05; p < 0.01 or p < 0.001) the motor cortex, the Locus ceruleus, the nucleus raphe magnus and the periaqueductal gray of the CNS. These effects apparently did not alter, in tested doses, the motor coordination of mice in the rota-rod test. Our results proposed that β-CD/EO might present an important draft of drug to the study of new compounds for the treatment of orofacial pain.

  14. Synthesis, structural characterization and in vitro inhibitory studies against human breast cancer of the bis-(2,6-di-tert-butylphenol)tin(IV) dichloride and its complexes.

    PubMed

    Shpakovsky, D B; Banti, C N; Beaulieu-Houle, G; Kourkoumelis, N; Manoli, M; Manos, M J; Tasiopoulos, A J; Hadjikakou, S K; Milaeva, E R; Charalabopoulos, K; Bakas, T; Butler, I S; Hadjiliadis, N

    2012-12-28

    Four new organotin(IV) complexes of bis-(2,6-di-tert-butylphenol)tin(IV) dichloride [(tert-Bu-)(2)(HO-Ph)](2)SnCl(2) (1) with the heterocyclic thioamides 2-mercapto-pyrimidine (PMTH), 2-mercapto-4-methyl-pyrimidine (MPMTH), 2-mercapto-pyridine (PYTH) and 2-mercapto-benzothiazole (MBZTH), of formulae {[(tert-Bu-)(2)(HO-Ph)](2)Sn(PMT)(2)} (2), {[(tert-Bu-)(2)(HO-Ph)](2)Sn(MPMT)(2)} (3), {[(tert-Bu-)(2)(HO-Ph)](2)SnCl(PYT)} (4) and {[(tert-Bu-)(2)(HO-Ph)](2)SnCl(MBZT)} (5), have been synthesized and characterized by elemental analysis, (1)H-, (13)C-, (119)Sn-NMR, EPR, FT-IR, Raman and Mössbauer spectroscopic techniques. The crystal and molecular structures of compounds 1–5 have been determined by X-ray diffraction. The geometries around the metal center adopted in complexes 1–5 varied between tetrahedral in 1, trigonal bipyramidal in 3, 4, 5 and distorted octahedral in 2. Two carbon atoms from aryl groups and two chlorine atoms form a distorted tetrahedron in the case of 1. Two carbon, two sulfur and two nitrogen atoms from thione ligands form a distorted octahedral geometry around tin(IV) with trans-C(2), cis-N(2), cis-S(2)-configurations in 2. However, in the case of 4 and 5 complexes two carbon, one sulfur, one nitrogen and one chloride atom form a distorted trigonal bipyramidal arrangement. Finally, in the case of 3 the trigonal bipyramidal geometry is achieved by two carbon, two sulfur and one nitrogen atom in a unique coordination mode of thioamides toward the tin(IV) cation. Compounds 1–5 were tested for their in vitro cytotoxicity against the human breast adenocarcinoma (MCF-7) cell line. Compound 3 exhibits strong cytotoxic activity against MCF-7 cells (IC(50) = 0.58 ± 0.1 μM).

  15. Maltose binding protein-fusion enhances the bioactivity of truncated forms of pig myostatin propeptide produced in E. coli

    PubMed Central

    Lee, Sang Beum; Park, Sung Kwon

    2017-01-01

    Myostatin (MSTN) is a potent negative regulator of skeletal muscle growth. MSTN propeptide (MSTNpro) inhibits MSTN binding to its receptor through complex formation with MSTN, implying that MSTNpro can be a useful agent to improve skeletal muscle growth in meat-producing animals. Four different truncated forms of pig MSTNpro containing N-terminal maltose binding protein (MBP) as a fusion partner were expressed in E. coli, and purified by the combination of affinity chromatography and gel filtration. The MSTN-inhibitory capacities of these proteins were examined in an in vitro gene reporter assay. A MBP-fused, truncated MSTNpro containing residues 42–175 (MBP-Pro42-175) exhibited the same MSTN-inhibitory potency as the full sequence MSTNpro. Truncated MSTNpro proteins containing either residues 42–115 (MBP-Pro42-115) or 42–98 (MBP-Pro42-98) also exhibited MSTN-inhibitory capacity even though the potencies were significantly lower than that of full sequence MSTNpro. In pull-down assays, MBP-Pro42-175, MBP-Pro42-115, and MBP-Pro42-98 demonstrated their binding to MSTN. MBP was removed from the truncated MSTNpro proteins by incubation with factor Xa to examine the potential role of MBP on MSTN-inhibitory capacity of those proteins. Removal of MBP from MBP-Pro42-175 and MBP-Pro42-98 resulted in 20-fold decrease in MSTN-inhibitory capacity of Pro42-175 and abolition of MSTN-inhibitory capacity of Pro42-98, indicating that MBP as fusion partner enhanced the MSTN-inhibitory capacity of those truncated MSTNpro proteins. In summary, this study shows that MBP is a very useful fusion partner in enhancing MSTN-inhibitory potency of truncated forms of MSTNpro proteins, and MBP-fused pig MSTNpro consisting of amino acid residues 42–175 is sufficient to maintain the full MSTN-inhibitory capacity. PMID:28369115

  16. Inhibitory effect of 1,2,4,5-tetramethoxybenzene on mast cell-mediated allergic inflammation through suppression of IκB kinase complex

    SciTech Connect

    Je, In-Gyu; Choi, Hyun Gyu; Kim, Hui-Hun; Lee, Soyoung; Choi, Jin Kyeong; Kim, Sung-Wan; Kim, Duk-Sil; Kwon, Taeg Kyu; Shin, Tae-Yong; Park, Pil-Hoon; Khang, Dongwoo; Kim, Sang-Hyun

    2015-09-01

    As the importance of allergic disorders such as atopic dermatitis and allergic asthma, research on potential drug candidates becomes more necessary. Mast cells play an important role as initiators of allergic responses through the release of histamine; therefore, they should be the target of pharmaceutical development for the management of allergic inflammation. In our previous study, anti-allergic effect of extracts of Amomum xanthioides was demonstrated. To further investigate improved candidates, 1,2,4,5-tetramethoxybenzene (TMB) was isolated from methanol extracts of A. xanthioides. TMB dose-dependently attenuated the degranulation of mast cells without cytotoxicity by inhibiting calcium influx. TMB decreased the expression of pro-inflammatory cytokines such as tumor necrosis factor-α and interleukin (IL)-4 at both the transcriptional and translational levels. Increased expression of these cytokines was caused by translocation of nuclear factor-κB into the nucleus, and it was hindered by suppressing activation of IκB kinase complex. To confirm the effect of TMB in vivo, the ovalbumin (OVA)-induced active systemic anaphylaxis (ASA) and IgE-mediated passive cutaneous anaphylaxis (PCA) models were used. In the ASA model, hypothermia was decreased by oral administration of TMB, which attenuated serum histamine, OVA-specific IgE, and IL-4 levels. Increased pigmentation of Evans blue was reduced by TMB in a dose-dependent manner in the PCA model. Our results suggest that TMB is a possible therapeutic candidate for allergic inflammatory diseases that acts through the inhibition of mast cell degranulation and expression of pro-inflammatory cytokines. - Highlights: • TMB reduced the degranulation of mast cells. • TMB inhibited the production of pro-inflammatory cytokines. • TMB suppressed both active and passive anaphylaxis. • Anti-allergic inflammatory effects of TMB might be due to the blocking IKK complex. • TMB might be a candidate for the treatment of

  17. Sequence-Divergent Chordopoxvirus Homologs of the O3 Protein Maintain Functional Interactions with Components of the Vaccinia Virus Entry-Fusion Complex

    PubMed Central

    Satheshkumar, P. S.

    2012-01-01

    Composed of 35 amino acids, O3 is the smallest characterized protein encoded by vaccinia virus (VACV) and is an integral component of the entry-fusion complex (EFC). O3 is conserved with 100% identity in all orthopoxviruses except for monkeypox viruses, whose O3 homologs have 2 to 3 amino acid substitutions. Since O3 is part of the EFC, high conservation could suggest an immutable requirement for interaction with multiple proteins. Chordopoxviruses of other genera also encode small proteins with a characteristic predicted N-terminal α-helical hydrophobic domain followed by basic amino acids and proline in the same relative genome location as that of VACV O3. However, the statistical significance of their similarity to VACV O3 is low due to the large contribution of the transmembrane domain, their small size, and their sequence diversity. Nevertheless, trans-complementation experiments demonstrated the ability of a representative O3-like protein from each chordopoxvirus genus to rescue the infectivity of a VACV mutant that was unable to express endogenous O3. Moreover, recombinant viruses expressing O3 homologs in place of O3 replicated and formed plaques as well or nearly as well as wild-type VACV. The O3 homologs expressed by the recombinant VACVs were incorporated into the membranes of mature virions and, with one exception, remained stably associated with the detergent-extracted and affinity-purified EFC. The ability of the sequence-divergent O3 homologs to coordinate function with VACV entry proteins suggests the conservation of structural motifs. Analysis of chimeras formed by swapping domains of O3 with those of other proteins indicated that the N-terminal transmembrane segment was responsible for EFC interactions and for the complementation of infectivity. PMID:22114343

  18. Inhibitory function of adapter-related protein complex 2 alpha 1 subunit in the process of nuclear translocation of human immunodeficiency virus type 1 genome

    SciTech Connect

    Kitagawa, Yukiko; Kameoka, Masanori Shoji-Kawata, Sanae; Iwabu, Yukie; Mizuta, Hiroyuki; Tokunaga, Kenzo; Fujino, Masato; Natori, Yukikazu; Yura, Yoshiaki; Ikuta, Kazuyoshi

    2008-03-30

    The transfection of human cells with siRNA against adapter-related protein complex 2 alpha 1 subunit (AP2{alpha}) was revealed to significantly up-regulate the replication of human immunodeficiency virus type 1 (HIV-1). This effect was confirmed by cell infection with vesicular stomatitis virus G protein-pseudotyped HIV-1 as well as CXCR4-tropic and CCR5-tropic HIV-1. Viral adsorption, viral entry and reverse transcription processes were not affected by cell transfection with siRNA against AP2{alpha}. In contrast, viral nuclear translocation as well as the integration process was significantly up-regulated in cells transfected with siRNA against AP2{alpha}. Confocal fluorescence microscopy revealed that a subpopulation of AP2{alpha} was not only localized in the cytoplasm but was also partly co-localized with lamin B, importin {beta} and Nup153, implying that AP2{alpha} negatively regulates HIV-1 replication in the process of nuclear translocation of viral DNA in the cytoplasm or the perinuclear region. We propose that AP2{alpha} may be a novel target for disrupting HIV-1 replication in the early stage of the viral life cycle.

  19. Synergistic inhibitory effect of nicotine plus oral contraceptive on mitochondrial complex-IV is mediated by estrogen receptor-β in female rats.

    PubMed

    Raval, Ami P; Dave, Kunjan R; Saul, Isabel; Gonzalez, Gabriel J; Diaz, Francisca

    2012-04-01

    Chronic nicotine and oral contraceptive (NOC) exposure caused significant loss of hippocampal membrane-bound estrogen receptor-beta (ER-β) in female rats compared with exposure to nicotine alone. Mitochondrial ER-β regulates estrogen-mediated mitochondrial structure and function; therefore, investigating the impact of NOC on mitochondrial ER-β and its function could help delineate the harmful synergism between nicotine and OC. In this study, we tested the hypothesis that NOC-induced loss of mitochondrial ER-β alters the oxidative phosphorylation system protein levels and mitochondrial respiratory function. This hypothesis was tested in hippocampal mitochondria isolated from female rats exposed to saline, nicotine, OC or NOC for 16 days. NOC decreased the mitochondrial ER-β protein levels and reduced oxygen consumption and complex IV (CIV) activity by 34% and 26% compared with saline- or nicotine-administered groups, respectively. We also observed significantly low protein levels of all mitochondrial-encoded CIV subunits after NOC as compared with the nicotine or saline groups. Similarly, the silencing of ER-β reduced the phosphorylation of cyclic-AMP response element binding protein, and also reduced levels of CIV mitochondrial-encoded subunits after estrogen stimulation. Overall, these results suggest that mitochondrial ER-β loss is responsible for mitochondrial malfunction after NOC.

  20. Spinal fusion

    MedlinePlus

    Liu G, Wong HK. Laminectomy and fusion. In: Shen FH, Samartzis D, Fessler RG, eds. Textbook of the Cervical Spine . Philadelphia, PA: Elsevier Saunders; 2015:chap 34. Wood GW. Arthrodesis of the spine. In: Canale ST, Beaty JH, eds. Campbell's Operative ...

  1. An inhibitory corticostriatal pathway

    PubMed Central

    Rock, Crystal; Zurita, Hector; Wilson, Charles; Apicella, Alfonso junior

    2016-01-01

    Anatomical and physiological studies have led to the assumption that the dorsal striatum receives exclusively excitatory afferents from the cortex. Here we test the hypothesis that the dorsal striatum receives also GABAergic projections from the cortex. We addressed this fundamental question by taking advantage of optogenetics and directly examining the functional effects of cortical GABAergic inputs to spiny projection neurons (SPNs) of the mouse auditory and motor cortex. We found that the cortex, via corticostriatal somatostatin neurons (CS-SOM), has a direct inhibitory influence on the output of the striatum SPNs. Our results describe a corticostriatal long-range inhibitory circuit (CS-SOM inhibitory projections → striatal SPNs) underlying the control of spike timing/generation in SPNs and attributes a specific function to a genetically defined type of cortical interneuron in corticostriatal communication. DOI: http://dx.doi.org/10.7554/eLife.15890.001 PMID:27159237

  2. Organotypic three-dimensional culture model of mesenchymal and epithelial cells to examine tissue fusion events.

    EPA Science Inventory

    Tissue fusion during early mammalian development requires coordination of multiple cell types, the extracellular matrix, and complex signaling pathways. Fusion events during processes including heart development, neural tube closure, and palatal fusion are dependent on signaling ...

  3. Cold fusion, Alchemist's dream

    SciTech Connect

    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{sub 2} molecules; barrier penetration probabilities within the hydrogenated metal lattice/piezonuclear fusion; branching ratios of D{sub 2} fusion at low energies; fusion of deuterons into {sup 4}He; secondary D+T fusion within the hydrogenated metal lattice; {sup 3}He to {sup 4}He ratio within the metal lattice; shock induced fusion; and anomalously high isotopic ratios of {sup 3}He/{sup 4}He.

  4. A lycopene β-cyclase/lycopene ε-cyclase/light-harvesting complex-fusion protein from the green alga Ostreococcus lucimarinus can be modified to produce α-carotene and β-carotene at different ratios.

    PubMed

    Blatt, Andreas; Bauch, Matthias E; Pörschke, Yvonne; Lohr, Martin

    2015-05-01

    Biosynthesis of asymmetric carotenoids such as α-carotene and lutein in plants and green algae involves the two enzymes lycopene β-cyclase (LCYB) and lycopene ε-cyclase (LCYE). The two cyclases are closely related and probably resulted from an ancient gene duplication. While in most plants investigated so far the two cyclases are encoded by separate genes, prasinophyte algae of the order Mamiellales contain a single gene encoding a fusion protein comprised of LCYB, LCYE and a C-terminal light-harvesting complex (LHC) domain. Here we show that the lycopene cyclase fusion protein from Ostreococcus lucimarinus catalyzed the simultaneous formation of α-carotene and β-carotene when heterologously expressed in Escherichia coli. The stoichiometry of the two products in E. coli could be altered by gradual truncation of the C-terminus, suggesting that the LHC domain may be involved in modulating the relative activities of the two cyclase domains in the algae. Partial deletions of the linker region between the cyclase domains or replacement of one or both cyclase domains with the corresponding cyclases from the green alga Chlamydomonas reinhardtii resulted in pronounced shifts of the α-carotene-to-β-carotene ratio, indicating that both the relative activities of the cyclase domains and the overall structure of the fusion protein have a strong impact on the product stoichiometry. The possibility to tune the product ratio of the lycopene cyclase fusion protein from Mamiellales renders it useful for the biotechnological production of the asymmetric carotenoids α-carotene or lutein in bacteria or fungi.

  5. Complexity.

    PubMed

    Gómez-Hernández, J Jaime

    2006-01-01

    It is difficult to define complexity in modeling. Complexity is often associated with uncertainty since modeling uncertainty is an intrinsically difficult task. However, modeling uncertainty does not require, necessarily, complex models, in the sense of a model requiring an unmanageable number of degrees of freedom to characterize the aquifer. The relationship between complexity, uncertainty, heterogeneity, and stochastic modeling is not simple. Aquifer models should be able to quantify the uncertainty of their predictions, which can be done using stochastic models that produce heterogeneous realizations of aquifer parameters. This is the type of complexity addressed in this article.

  6. The Fusion Energy Option

    NASA Astrophysics Data System (ADS)

    Dean, Stephen O.

    2004-06-01

    Presentations from a Fusion Power Associates symposium, The Fusion Energy Option, are summarized. The topics include perspectives on fossil fuel reserves, fusion as a source for hydrogen production, status and plans for the development of inertial fusion, planning for the construction of the International Thermonuclear Experimental Reactor, status and promise of alternate approaches to fusion and the need for R&D now on fusion technologies.

  7. Carbon Nanotubes Mediate Fusion of Lipid Vesicles.

    PubMed

    Bhaskara, Ramachandra M; Linker, Stephanie M; Vögele, Martin; Köfinger, Jürgen; Hummer, Gerhard

    2017-02-28

    The fusion of lipid membranes is opposed by high energetic barriers. In living organisms, complex protein machineries carry out this biologically essential process. Here we show that membrane-spanning carbon nanotubes (CNTs) can trigger spontaneous fusion of small lipid vesicles. In coarse-grained molecular dynamics simulations, we find that a CNT bridging between two vesicles locally perturbs their lipid structure. Their outer leaflets merge as the CNT pulls lipids out of the membranes, creating an hourglass-shaped fusion intermediate with still intact inner leaflets. As the CNT moves away from the symmetry axis connecting the vesicle centers, the inner leaflets merge, forming a pore that completes fusion. The distinct mechanism of CNT-mediated membrane fusion may be transferable, providing guidance in the development of fusion agents, e.g., for the targeted delivery of drugs or nucleic acids.

  8. Revitalizing Fusion via Fission Fusion

    NASA Astrophysics Data System (ADS)

    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

  9. Fusion energy

    NASA Astrophysics Data System (ADS)

    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 Max Planck 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 to 1990). During the definition phase, a set of ITER technical characteristics and supporting research and development (R and 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 and 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.

  10. Fusion energy

    SciTech Connect

    Not Available

    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 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 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.

  11. Inhibition of HIV-1 by fusion inhibitors.

    PubMed

    Eggink, Dirk; Berkhout, Ben; Sanders, Rogier W

    2010-01-01

    The envelope glycoprotein complex (Env) is responsible for entry of the human immunodeficiency virus type 1 (HIV-1) into cells by mediating attachment to target cells and subsequent membrane fusion. Env consists of three gp120 subunits that mediate receptor and co-receptor attachment and three gp41 subunits responsible for membrane fusion. Several steps of the entry process can serve as drug targets. Receptor antagonists prevent attachment of gp120 to the receptor or co-receptor and conformational changes within gp41 required for membrane fusion can be inhibited by fusion inhibitors. Enfuvirtide (T20, Fuzeon) is a peptide based on the gp41 sequence and is the only approved fusion inhibitor. It prevents membrane fusion by competitively binding to gp41 and blocking the formation of the post-fusion structure. New generations of T20-like peptides have been developed with improved potency and stability. Besides T20 and derivatives, other fusion inhibitors have been developed that target different domains of gp41. Here we discuss the development of fusion inhibitors, their mode of action and their potential for incorporation in future drug regimens.

  12. Receptor signaling lymphocyte-activation molecule family 1 (Slamf1) regulates membrane fusion and NADPH oxidase 2 (NOX2) activity by recruiting a Beclin-1/Vps34/ultraviolet radiation resistance-associated gene (UVRAG) complex.

    PubMed

    Ma, Chunyan; Wang, Ninghai; Detre, Cynthia; Wang, Guoxing; O'Keeffe, Michael; Terhorst, Cox

    2012-05-25

    Phagocytosis is a pivotal process by which macrophages eliminate microorganisms upon recognition by pathogen sensors. Surprisingly, the self-ligand cell surface receptor Slamf1 functions not only as a co-stimulatory molecule but also as a microbial sensor of several Gram-negative bacteria. Upon entering the phagosome of macrophages Slamf1 induces production of phosphatidylinositol 3-phosphate, which positively regulates the activity of the NOX2 enzyme and phagolysosomal maturation. Here, we report that in Escherichia coli-containing phagosomes of mouse macrophages, Slamf1 interacts with the class III PI3K Vps34 in a complex with Beclin-1 and UVRAG. Upon phagocytosis of bacteria the NOX2 activity was reduced in macrophages isolated from Beclin-1(+/-) mice compared with wild-type mice. This Slamf1/Beclin-1/Vps34/UVRAG protein complex is formed in intracellular membrane compartments as it is found without inducing phagocytosis in macrophages, human chronic lymphocytic leukemia cells, and transfectant HEK293 cells. Elimination of its cytoplasmic tail abolished the interaction of Slamf1 with the complex, but deletion or mutation of the two ITAM motifs did not. Both the BD and CCD domains of Beclin-1 were required for efficient binding to Slamf1. Because Slamf1 did not interact with Atg14L or Rubicon, which can also form a complex with Vps34 and Beclin-1, we conclude that Slamf1 recruits a subset of Vps34-associated proteins, which is involved in membrane fusion and NOX2 regulation.

  13. Inhibitory effects of antimicrobial agents against Fusarium species.

    PubMed

    Kawakami, Hideaki; Inuzuka, Hiroko; Hori, Nobuhide; Takahashi, Nobumichi; Ishida, Kyoko; Mochizuki, Kiyofumi; Ohkusu, Kiyofumi; Muraosa, Yasunori; Watanabe, Akira; Kamei, Katsuhiko

    2015-08-01

    We investigated the inhibitory effects of antibacterial, biocidal, and antifungal agents against Fusarium spp. Seven Fusarium spp: four F. falciforme (Fusarium solani species complex), one Fusarium spp, one Fusarium spp. (Fusarium incarnatum-equiseti species complex), and one F. napiforme (Gibberella fujikuroi species complex), isolated from eyes with fungal keratitis were used in this study. Their susceptibility to antibacterial agents: flomoxef, imipenem, gatifloxacin, levofloxacin, moxifloxacin, gentamicin, tobramycin, and Tobracin® (contained 3,000 μg/ml of tobramycin and 25 μg/ml of benzalkonium chloride (BAK), a biocidal agent: BAK, and antifungal agents: amphotericin B, pimaricin (natamycin), fluconazole, itraconazole, miconazole, voriconazole, and micafungin, was determined by broth microdilution tests. The half-maximal inhibitory concentration (IC50), 100% inhibitory concentration (IC100), and minimum inhibitory concentration (MIC) against the Fusarium isolates were determined. BAK had the highest activity against the Fusarium spp. except for the antifungal agents. Three fluoroquinolones and two aminoglycosides had inhibitory effects against the Fusarium spp. at relatively high concentrations. Tobracin® had a higher inhibitory effect against Fusarium spp. than tobramycin alone. Amphotericin B had the highest inhibitory effect against the Fusarium spp, although it had different degrees of activity against each isolate. Our findings showed that fluoroquinolones, aminoglycosides, and BAK had some degree of inhibitory effect against the seven Fusarium isolates, although these agents had considerably lower effect than amphotericin B. However, the inhibitory effects of amphotericin B against the Fusarium spp. varied for the different isolates. Further studies for more effective medications against Fusarium, such as different combinations of antibacterial, biocidal, and antifungal agents are needed.

  14. Resolving Extreme Rainfall from Space: A New Class of Algorithms for Precipitation Retrieval and Data Fusion/Assimilation with Emphasis on Extremes over Complex Terrain and Coastal Areas

    NASA Astrophysics Data System (ADS)

    Foufoula-Georgiou, E.; Ebtehaj, A.

    2015-12-01

    The increasing availability of precipitation observations from the Global Precipitation Measuring (GPM) Mission, has fueled renewed interest in developing frameworks for accurate estimation of precipitation extremes especially over ungauged mountainous terrains and coastal regions to improve hydro-geological hazard prediction and control. Our recent research has shown that treating precipitation retrieval and data fusion/assimilation as inverse problems and using a regularized variational approach with the regularization term(s) selected to impose desired smoothness in the solution, leads to improved representation of extremes. Here we present some new theoretical and computational developments which extend the ideas to a model-agnostic framework of retrieval via a regularized search within properly constructed data bases. We test the framework in several tropical storms over the Ganges-Brahmaputra delta region and over the Himalayas and compare the results with the standard retrieval algorithms currently used for operational purposes.

  15. Measles virus transmembrane fusion protein synthesized de novo or presented in immunostimulating complexes is endogenously processed for HLA class I- and class II-restricted cytotoxic T cell recognition

    PubMed Central

    1992-01-01

    The routes used by antigen-presenting cells (APC) to convert the transmembrane fusion glycoprotein (F) of measles virus (MV) to HLA class I and class II presentable peptides have been examined, using cloned cytotoxic T lymphocytes in functional assays. Presentation by Epstein-Barr virus-transformed B lymphoblastoid cell lines was achieved using live virus, ultraviolet light-inactivated virus, and purified MV- F delivered either as such or incorporated in immunostimulating complexes (MV-F-ISCOM). Only live virus and MV-F-ISCOM allow presentation by class I molecules, while all antigen preparations permit class II-restricted presentation. We observe presentation of MV- F from live virus and as MV-F-ISCOM by class II molecules in a fashion that is not perturbed by chloroquine. Our studies visualize novel presentation pathways of type I transmembrane proteins. PMID:1613454

  16. Mechanics of membrane fusion/pore formation.

    PubMed

    Fuhrmans, Marc; Marelli, Giovanni; Smirnova, Yuliya G; Müller, Marcus

    2015-01-01

    Lipid bilayers play a fundamental role in many biological processes, and a considerable effort has been invested in understanding their behavior and the mechanism of topological changes like fusion and pore formation. Due to the time- and length-scale on which these processes occur, computational methods have proven to be an especially useful tool in their study. With their help, a number of interesting findings about the shape of fusion intermediates could be obtained, and novel hypotheses about the mechanism of topological changes and the involvement of peptides therein were suggested. In this work, we try to present a summary of these developments together with some hitherto unpublished results, featuring, among others, the shape of stalks and fusion pores, possible modes of action of the influenza HA fusion peptide and the SNARE protein complex, the mechanism of supported lipid bilayer formation by vesicle spreading, and the free energy and transition pathway of the fusion process.

  17. Review of fusion synfuels

    SciTech Connect

    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.

  18. Laser powder-bed fusion additive manufacturing: Physics of complex melt flow and formation mechanisms of pores, spatter, and denudation zones

    DOE PAGES

    Khairallah, Saad A.; Anderson, Andrew T.; Rubenchik, Alexander; ...

    2016-02-23

    Our study demonstrates the significant effect of the recoil pressure and Marangoni convection in laser powder bed fusion (L-PBF) of 316L stainless steel. A three-dimensional high fidelity powder-scale model reveals how the strong dynamical melt flow generates pore defects, material spattering (sparking), and denudation zones. The melt track is divided into three sections: a topological depression, a transition and a tail region, each being the location of specific physical effects. The inclusion of laser ray-tracing energy deposition in the powder-scale model improves over traditional volumetric energy deposition. It enables partial particle melting, which impacts pore defects in the denudation zone.more » Different pore formation mechanisms are observed at the edge of a scan track, at the melt pool bottom (during collapse of the pool depression), and at the end of the melt track (during laser power ramp down). Finally, we discuss remedies to these undesirable pores are discussed. The results are validated against the experiments and the sensitivity to laser absorptivity.« less

  19. Spatially addressable chemoselective C-terminal ligation of an intein fusion protein from a complex mixture to a hydrazine-terminated surface.

    PubMed

    Yang, Peng; Marinakos, Stella M; Chilkoti, Ashutosh

    2011-02-15

    Protein immobilization on surfaces is useful in many areas of research, including biological characterization, antibody purification, and clinical diagnostics. A critical limitation in the development of protein microarrays and heterogeneous protein-based assays is the enormous amount of work and associated costs in the purification of proteins prior to their immobilization onto a surface. Methods to address this problem would simplify the development of interfacial diagnostics that use a protein as the recognition element. Herein, we describe an approach for the facile, site-specific immobilization of proteins on a surface without any preprocessing or sample purification steps that ligates an intein fusion protein at its C-terminus by reaction with a hydrazine group presented by a surface. Furthermore, we demonstrate that this methodology can directly immobilize a protein directly from cell lysate onto a protein-resistant surface. This methodology is also compatible with soft lithography and inkjet printing so that one or more proteins can be patterned on a surface without the need for purification.

  20. Laser powder-bed fusion additive manufacturing: Physics of complex melt flow and formation mechanisms of pores, spatter, and denudation zones

    SciTech Connect

    Khairallah, Saad A.; Anderson, Andrew T.; Rubenchik, Alexander; King, Wayne E.

    2016-02-23

    Our study demonstrates the significant effect of the recoil pressure and Marangoni convection in laser powder bed fusion (L-PBF) of 316L stainless steel. A three-dimensional high fidelity powder-scale model reveals how the strong dynamical melt flow generates pore defects, material spattering (sparking), and denudation zones. The melt track is divided into three sections: a topological depression, a transition and a tail region, each being the location of specific physical effects. The inclusion of laser ray-tracing energy deposition in the powder-scale model improves over traditional volumetric energy deposition. It enables partial particle melting, which impacts pore defects in the denudation zone. Different pore formation mechanisms are observed at the edge of a scan track, at the melt pool bottom (during collapse of the pool depression), and at the end of the melt track (during laser power ramp down). Finally, we discuss remedies to these undesirable pores are discussed. The results are validated against the experiments and the sensitivity to laser absorptivity.

  1. ROM-1 potentiates photoreceptor specific membrane fusion processes.

    PubMed

    Boesze-Battaglia, Kathleen; Stefano, Frank P; Fitzgerald, Catherine; Muller-Weeks, Susan

    2007-01-01

    Photoreceptor outer segment (OS) renewal requires a series of tightly regulated membrane fusion events which are mediated by a fusion complex containing protein and lipid components. The best characterized of these components, is a unique photoreceptor specific tetraspanin, peripherin/rds (P/rds, a.k.a., peripherin-2, Rds and Prph). In these studies we investigated the role of peripherin's non-glycosylated homolog, ROM-1, in OS fusion using a COS cell heterologous expression system and a well characterized cell free fusion assay system. Membranes isolated from COS-7 cells transfected with either FLAG-tagged P/rds or HA-tagged ROM-1 or both proteins were assayed for their ability to merge with fluorescently labeled OS plasma membrane (PM). Such membrane merger is one measure of membrane fusogenicity. The highest percent fusion was observed when the proteins were co-expressed. Furthermore detailed analysis of the fusion kinetics between fluorescently labeled PM and proteo-liposomes containing either, pure P/rds, pure ROM-1 or the ROM-1-P/rds complex clearly demonstrated that optimal fusion requires an ROM-1/P/rds complex. Proteo-liposomes composed of ROM-1 alone were not fusogenic. Peptide competition studies suggest that optimization of fusion may be due to the formation of a fusion competent peripherin/rds C-terminus in the presence of ROM-1. These studies provide further support for the hypothesis that a P/rds dependent membrane fusion complex is involved in photoreceptor renewal processes.

  2. Viral membrane fusion.

    PubMed

    Harrison, Stephen C

    2015-05-01

    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.

  3. Viral membrane fusion

    PubMed Central

    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. PMID:25866377

  4. Multivalent Rab interactions determine tether-mediated membrane fusion

    PubMed Central

    Lürick, Anna; Gao, Jieqiong; Kuhlee, Anne; Yavavli, Erdal; Langemeyer, Lars; Perz, Angela; Raunser, Stefan; Ungermann, Christian

    2017-01-01

    Membrane fusion at endomembranes requires cross-talk between Rab GTPases and tethers to drive SNARE-mediated lipid bilayer mixing. Several tethers have multiple Rab-binding sites with largely untested function. Here we dissected the lysosomal HOPS complex as a tethering complex with just two binding sites for the Rab7-like Ypt7 protein to determine their relevance for fusion. Using tethering and fusion assays combined with HOPS mutants, we show that HOPS-dependent fusion requires both Rab-binding sites, with Vps39 being the stronger Ypt7 interactor than Vps41. The intrinsic amphipathic lipid packaging sensor (ALPS) motif within HOPS Vps41, a target of the vacuolar kinase Yck3, is dispensable for tethering and fusion but can affect tethering if phosphorylated. In combination, our data demonstrate that a multivalent tethering complex uses its two Rab bindings to determine the place of SNARE assembly and thus fusion at endomembranes. PMID:27852901

  5. Cold fusion research

    SciTech Connect

    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.

  6. Magneto-Inertial Fusion

    SciTech Connect

    Wurden, G. A.; Hsu, S. C.; Intrator, T. P.; Grabowski, T. C.; Degnan, J. H.; Domonkos, M.; Turchi, P. J.; Campbell, E. M.; Sinars, D. B.; Herrmann, M. C.; Betti, R.; Bauer, B. S.; Lindemuth, I. R.; Siemon, R. E.; Miller, R. L.; Laberge, M.; Delage, M.

    2015-11-17

    In this community white paper, we describe an approach to achieving fusion which employs a hybrid of elements from the traditional magnetic and inertial fusion concepts, called magneto-inertial fusion (MIF). The status of MIF research in North America at multiple institutions is summarized including recent progress, research opportunities, and future plans.

  7. Inhibitory mechanisms of glabridin on tyrosinase

    NASA Astrophysics Data System (ADS)

    Chen, Jianmin; Yu, Xiaojing; Huang, Yufeng

    2016-11-01

    Tyrosinase is an oxidase that is the rate-limiting enzyme for controlling the production of melanin in the human body. Overproduction of melanin could lead to a variety of skin disorders. Glabridin, an isoflavan, isolated from the root of Glycyrrhiza glabra Linn, has exhibited several pharmacological activities, including excellent inhibitory effects on tyrosinase. In this paper, the inhibitory kinetics of glabridin on tyrosinase and their binding mechanisms were determined using spectroscopic, zebrafish model and molecular docking techniques. The results indicate that glabridin reversibly inhibits tyrosinase in a noncompetitive manner through a multiphase kinetic process with the IC50 of 0.43 μmol/L. It has been shown that glabridin had a strong ability to quench the intrinsic fluorescence of tyrosinase mainly through a static quenching procedure, suggesting a stable glabridin-tyrosinase complex may be generated. The results of molecular docking suggest that glabridin did not directly bind to the active site of tyrosinase. Moreover, according to the results of zebrafish model system, glabridin shows no effects on melanin synthesis in zebrafish but presents toxicity to zebrafish embryo. The possible inhibitory mechanisms, which will help to design and search for tyrosinase inhibitors especially for glabridin analogues, were proposed.

  8. Magnetized target fusion and fusion propulsion

    NASA Astrophysics Data System (ADS)

    Kirkpatrick, Ronald C.

    2002-01-01

    Magnetized target fusion (MTF) is a thermonuclear fusion concept that is intermediate between the two mainline approaches, magnetic confinement and inertial confinement fusion (MCF and ICF). MTF incorporates some aspects of each and offers advantages over each of the mainline approaches. First, it provides a means of reducing the driver power requirements, thereby admitting a wider range of drivers than ICF. Second, the magnetic field is only used for insulation, not confinement, and the plasma is wall confined, so that plasma instabilities are traded in for hydrodynamic instabilities. However, the degree of compression required to reach fusion condition is lower than for ICF, so that hydrodynamic instabilities are much less threatening. The standoff driver innovation proposes to dynamically form the target plasma and a gaseous shell that compresses and confines the target plasma. Therefore, fusion target fabrication is traded in for a multiplicity of plasma guns, which must work in synchrony. The standoff driver embodiment of MTF leads to a fusion propulsion system concept that is potentially compact and lightweight. We will discuss the underlying physics of MTF and some of the details of the fusion propulsion concept using the standoff driver approach. We discuss here the optimization of an MTF target design for space propulsion. .

  9. Mixed ligand complexes of Cu(II)/Zn(II) ions containing (m-)/(p-) carboxylato phenyl azo pentane 2,4-dione and 2,2‧-bipyridine/1,10 phenanthroline: Synthesis, characterization, DNA binding, nuclease and topoisomerase I inhibitory activity

    NASA Astrophysics Data System (ADS)

    Hasan, Md. Amin; Kumari, Niraj; Singh, Kanhaiya; Singh, Kiran; Mishra, Lallan

    2016-01-01

    Metal complexes of type [Cu(L1H)2(bpy)] (1), [Zn(L1H)2(bpy)] (2), [Cu(L2H)2(bpy)] (3) and [Cu(L2H)2(Phen)] (4) (L1H2 = 3-[N‧-(1-acetyl-2-oxo-propylidene)-hydrazino]-benzoic acid, L2H2 = 4-[N‧-(1-acetyl-2-oxo-propylidene)-hydrazino]-benzoic acid, bpy = 2,2‧-bipyridine, Phen = 1,10 phenanthroline) are synthesized and characterized using spectroscopic techniques (FT-IR, 1H NMR, 13C NMR, electronic absorption and emission) and elemental analysis data. The assembly of the complexes involving intramolecular H-bonding is displayed using corresponding crystal structure. Binding of the complexes separately with Calf Thymus DNA is monitored using UV-vis spectral titrations. The displacement of ethidium bromide (EB) bound to DNA by the complexes, in phosphate buffer solution (pH ∼ 7.2) is monitored using fluorescence spectral titrations. Nuclease activity of the complexes follow the order 4 > 3 > 1 > 2. The gel electrophoretic mobility assay measurement in presence of minor groove binder 4‧,6-diamidino-2-phenylindole (DAPI), suggests that complexes preferably bind with the minor groove of DNA. Topoisomerase I inhibitory activity of the complexes 3 and 4 inhibit topoisomerase I activity with IC50 values of 112 and 87 μM respectively.

  10. Viral membrane fusion

    SciTech Connect

    Harrison, Stephen C.

    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.

  11. Fusion research: the past is prologue

    SciTech Connect

    Post, R F

    1998-10-14

    At this juncture fusion research can be viewed as being at a turning point, a time to review its past and to imagine its future. Today, almost 50 years since the first serious attempts to address the daunting problem of achieving controlled fusion, we have both an opportunity and a challenge. Some predictions place fusion research today at a point midway between its first inception and its eventual maturation - in the middle of the 21st century - when fusion would become a major source of energy. Our opportunity therefore is to assess what we have learned from 50 years of hard work and use that knowledge as a starting point for new and better approaches to solving the fusion problem. Our challenge is to prove the "50 more years" prophesy wrong, by finding ways to shorten the time when fusion power becomes a reality. The thesis will be advanced that in the magnetic confinement approach to fusion open-ended magnetic confinement geometries offer much in responding to the challenge. A major advantage of open systems is that, owing to their theoretically and experimentally demonstrated ability to suppress plasma instabilities of both the MHD and the high-frequency wave-particle variety, the confinement becomes predictable from "classical," i.e., Fokker-Planck-type analysis. In a time of straitened budgetary circumstances for magnetic fusion research now being faced in the United States, the theoretical tractability of mirror-based systems is a substantial asset. In pursuing this avenue it is also necessary to keep an open mind as to the forms that mirror-based fusion power plants might take. For example, one can look to the high-energy physics community for a possible model: This community has shown the feasibility of constructing large and complex particle accelerators using superconducting magnets, vacuum chambers and complicated particle-handling technology, housed in underground tunnels that are 20 or more kilometers long. In the paper examples of mirror

  12. Drunken Membranes: Short-Chain Alcohols Alter Fusion of Liposomes to Planar Lipid Bilayers.

    PubMed

    Paxman, Jason; Hunt, Brady; Hallan, David; Zarbock, Samuel R; Woodbury, Dixon J

    2017-01-10

    Although the effects of ethanol on protein receptors and lipid membranes have been studied extensively, ethanol's effect on vesicles fusing to lipid bilayers is not known. To determine the effect of alcohols on fusion rates, we utilized the nystatin/ergosterol fusion assay to measure fusion of liposomes to a planar lipid bilayer (BLM). The addition of ethanol excited fusion when applied on the cis (vesicle) side, and inhibited fusion on the trans side. Other short-chain alcohols followed a similar pattern. In general, the inhibitory effect of alcohols (trans) occurs at lower doses than the excitatory (cis) effect, with a decrease of 29% in fusion rates at the legal driving limit of 0.08% (w/v) ethanol (IC50 = 0.2% v/v, 34 mM). Similar inhibitory effects were observed with methanol, propanol, and butanol, with ethanol being the most potent. Significant variability was observed with different alcohols when applied to the cis side. Ethanol and propanol enhanced fusion, butanol also enhanced fusion but was less potent, and low doses of methanol mildly inhibited fusion. The inhibition by trans addition of alcohols implies that they alter the planar membrane structure and thereby increase the activation energy required for fusion, likely through an increase in membrane fluidity. The cis data are likely a combination of the above effect and a proportionally greater lowering of the vesicle lysis tension and hydration repulsive pressure that combine to enhance fusion. Alternate hypotheses are also discussed. The inhibitory effect of ethanol on liposome-membrane fusion is large enough to provide a possible biophysical explanation of compromised neuronal behavior.

  13. Multimeric complexes of the PML-retinoic acid receptor alpha fusion protein in acute promyelocytic leukemia cells and interference with retinoid and peroxisome-proliferator signaling pathways.

    PubMed Central

    Jansen, J H; Mahfoudi, A; Rambaud, S; Lavau, C; Wahli, W; Dejean, A

    1995-01-01

    The t(15;17) chromosomal translocation, specific for acute promyelocytic leukemia (APL), fuses the PML gene to the retinoic acid receptor alpha (RAR alpha) gene, resulting in expression of a PML-RAR alpha hybrid protein. In this report, we analyzed the nature of PML-RAR alpha-containing complexes in nuclear protein extracts of t(15;17)-positive cells. We show that endogenous PML-RAR alpha can bind to DNA as a homodimer, in contrast to RAR alpha that requires the retinoid X receptor (RXR) dimerization partner. In addition, these cells contain oligomeric complexes of PML-RAR alpha and endogenous RXR. Treatment with retinoic acid results in a decrease of PML-RAR alpha protein levels and, as a consequence, of DNA binding by the different complexes. Using responsive elements from various hormone signaling pathways, we show that PML-RAR alpha homodimers have altered DNA-binding characteristics when compared to RAR alpha-RXR alpha heterodimers. In transfected Drosophila SL-3 cells that are devoid of endogenous retinoid receptors PML-RAR alpha inhibits transactivation by RAR alpha-RXR alpha heterodimers in a dominant fashion. In addition, we show that both normal retinoid receptors and the PML-RAR alpha hybrid bind and activate the peroxisome proliferator-activated receptor responsive element from the Acyl-CoA oxidase gene, indicating that retinoids and peroxisome proliferator receptors may share common target genes. These properties of PML-RAR alpha may contribute to the transformed phenotype of APL cells. Images Fig. 1 Fig. 2 Fig. 3 PMID:7638205

  14. Collagen-derived matricryptins promote inhibitory nerve terminal formation in the developing neocortex

    PubMed Central

    Su, Jianmin; Chen, Jiang; Lippold, Kumiko; Monavarfeshani, Aboozar; Carrillo, Gabriela Lizana; Jenkins, Rachel

    2016-01-01

    Inhibitory synapses comprise only ∼20% of the total synapses in the mammalian brain but play essential roles in controlling neuronal activity. In fact, perturbing inhibitory synapses is associated with complex brain disorders, such as schizophrenia and epilepsy. Although many types of inhibitory synapses exist, these disorders have been strongly linked to defects in inhibitory synapses formed by Parvalbumin-expressing interneurons. Here, we discovered a novel role for an unconventional collagen—collagen XIX—in the formation of Parvalbumin+ inhibitory synapses. Loss of this collagen results not only in decreased inhibitory synapse number, but also in the acquisition of schizophrenia-related behaviors. Mechanistically, these studies reveal that a proteolytically released fragment of this collagen, termed a matricryptin, promotes the assembly of inhibitory nerve terminals through integrin receptors. Collectively, these studies not only identify roles for collagen-derived matricryptins in cortical circuit formation, but they also reveal a novel paracrine mechanism that regulates the assembly of these synapses. PMID:26975851

  15. Statistical label fusion with hierarchical performance models

    NASA Astrophysics Data System (ADS)

    Asman, Andrew J.; Dagley, Alexander S.; Landman, Bennett A.

    2014-03-01

    Label fusion is a critical step in many image segmentation frameworks (e.g., multi-atlas segmentation) as it provides a mechanism for generalizing a collection of labeled examples into a single estimate of the underlying segmentation. In the multi-label case, typical label fusion algorithms treat all labels equally - fully neglecting the known, yet complex, anatomical relationships exhibited in the data. To address this problem, we propose a generalized statistical fusion framework using hierarchical models of rater performance. Building on the seminal work in statistical fusion, we reformulate the traditional rater performance model from a multi-tiered hierarchical perspective. This new approach provides a natural framework for leveraging known anatomical relationships and accurately modeling the types of errors that raters (or atlases) make within a hierarchically consistent formulation. Herein, we describe several contributions. First, we derive a theoretical advancement to the statistical fusion framework that enables the simultaneous estimation of multiple (hierarchical) performance models within the statistical fusion context. Second, we demonstrate that the proposed hierarchical formulation is highly amenable to the state-of-the-art advancements that have been made to the statistical fusion framework. Lastly, in an empirical whole-brain segmentation task we demonstrate substantial qualitative and significant quantitative improvement in overall segmentation accuracy.

  16. Materials research for fusion

    NASA Astrophysics Data System (ADS)

    Knaster, J.; Moeslang, A.; Muroga, T.

    2016-05-01

    Fusion materials research started in the early 1970s following the observation of the degradation of irradiated materials used in the first commercial fission reactors. The technological challenges of fusion energy are intimately linked with the availability of suitable materials capable of reliably withstanding the extremely severe operational conditions of fusion reactors. Although fission and fusion materials exhibit common features, fusion materials research is broader. The harder mono-energetic spectrum associated with the deuterium-tritium fusion neutrons (14.1 MeV compared to <2 MeV on average for fission neutrons) releases significant amounts of hydrogen and helium as transmutation products that might lead to a (at present undetermined) degradation of structural materials after a few years of operation. Overcoming the historical lack of a fusion-relevant neutron source for materials testing is an essential pending step in fusion roadmaps. Structural materials development, together with research on functional materials capable of sustaining unprecedented power densities during plasma operation in a fusion reactor, have been the subject of decades of worldwide research efforts underpinning the present maturity of the fusion materials research programme.

  17. INTRODUCTION: Status report on fusion research

    NASA Astrophysics Data System (ADS)

    Burkart, Werner

    2005-10-01

    A major milestone on the path to fusion energy was reached in June 2005 on the occasion of the signing of the joint declaration of all parties to the ITER negotiations, agreeing on future arrangements and on the construction site at Cadarache in France. The International Atomic Energy Agency has been promoting fusion activities since the late 1950s; it took over the auspices of the ITER Conceptual Design Activities in 1988, and of the ITER Engineering and Design Activities in 1992. The Agency continues its support to Member States through the organization of consultancies, workshops and technical meetings, the most prominent being the series of International Fusion Energy Conferences (formerly called the International Conference on Plasma Physics and Controlled Nuclear Fusion Research). The meetings serve as a platform for experts from all Member States to have open discussions on their latest accomplishments as well as on their problems and eventual solutions. The papers presented at the meetings and conferences are routinely published, many being sent to the journal it Nuclear Fusion, co-published monthly by Institute of Physics Publishing, Bristol, UK. The journal's reputation is reflected in the fact that it is a world-renowned publication, and the International Fusion Research Council has used it for the publication of a Status Report on Controlled Thermonuclear Fusion in 1978 and 1990. This present report marks the conclusion of the preparatory phases of ITER activities. It provides background information on the progress of fusion research within the last 15 years. The International Fusion Research Council (IFRC), which initiated the report, was fully aware of the complexities of including all scientific results in just one paper, and so decided to provide an overview and extensive references for the interested reader who need not necessarily be a fusion specialist. Professor Predhiman K. Kaw, Chairman, prepared the report on behalf of the IFRC, reflecting

  18. Fusion probability in heavy nuclei

    NASA Astrophysics Data System (ADS)

    Banerjee, Tathagata; Nath, S.; Pal, Santanu

    2015-03-01

    Background: Fusion between two massive nuclei is a very complex process and is characterized by three stages: (a) capture inside the potential barrier, (b) formation of an equilibrated compound nucleus (CN), and (c) statistical decay of the CN leading to a cold evaporation residue (ER) or fission. The second stage is the least understood of the three and is the most crucial in predicting yield of superheavy elements (SHE) formed in complete fusion reactions. Purpose: A systematic study of average fusion probability, , is undertaken to obtain a better understanding of its dependence on various reaction parameters. The study may also help to clearly demarcate onset of non-CN fission (NCNF), which causes fusion probability, PCN, to deviate from unity. Method: ER excitation functions for 52 reactions leading to CN in the mass region 170-220, which are available in the literature, have been compared with statistical model (SM) calculations. Capture cross sections have been obtained from a coupled-channels code. In the SM, shell corrections in both the level density and the fission barrier have been included. for these reactions has been extracted by comparing experimental and theoretical ER excitation functions in the energy range ˜5 %-35% above the potential barrier, where known effects of nuclear structure are insignificant. Results: has been shown to vary with entrance channel mass asymmetry, η (or charge product, ZpZt ), as well as with fissility of the CN, χCN. No parameter has been found to be adequate as a single scaling variable to determine . Approximate boundaries have been obtained from where starts deviating from unity. Conclusions: This study quite clearly reveals the limits of applicability of the SM in interpreting experimental observables from fusion reactions involving two massive nuclei. Deviation of from unity marks the beginning of the domain of dynamical models of fusion. Availability of precise ER cross

  19. Hepatitis C virus NS5A replication complex inhibitors. Part 6: Discovery of a novel and highly potent biarylimidazole chemotype with inhibitory activity toward genotypes 1a and 1b replicons.

    PubMed

    Belema, Makonen; Nguyen, Van N; Romine, Jeffrey L; St Laurent, Denis R; Lopez, Omar D; Goodrich, Jason T; Nower, Peter T; O'Boyle, Donald R; Lemm, Julie A; Fridell, Robert A; Gao, Min; Fang, Hua; Krause, Rudolph G; Wang, Ying-Kai; Oliver, A Jayne; Good, Andrew C; Knipe, Jay O; Meanwell, Nicholas A; Snyder, Lawrence B

    2014-03-13

    A medicinal chemistry campaign that was conducted to address a potential genotoxic liability associated with an aniline-derived scaffold in a series of HCV NS5A inhibitors with dual GT-1a/-1b inhibitory activity is described. Anilides 3b and 3c were used as vehicles to explore structural modifications that retained antiviral potency while removing the potential for metabolism-based unmasking of the embedded aniline. This effort resulted in the discovery of a highly potent biarylimidazole chemotype that established a potency benchmark in replicon assays, particularly toward HCV GT-1a, a strain with significant clinical importance. Securing potent GT-1a activity in a chemotype class lacking overt structural liabilities was a critical milestone in the effort to realize the full clinical potential of targeting the HCV NS5A protein.

  20. Optimal percentage of inhibitory synapses in multi-task learning.

    PubMed

    Capano, Vittorio; Herrmann, Hans J; de Arcangelis, Lucilla

    2015-04-22

    Performing more tasks in parallel is a typical feature of complex brains. These are characterized by the coexistence of excitatory and inhibitory synapses, whose percentage in mammals is measured to have a typical value of 20-30%. Here we investigate parallel learning of more Boolean rules in neuronal networks. We find that multi-task learning results from the alternation of learning and forgetting of the individual rules. Interestingly, a fraction of 30% inhibitory synapses optimizes the overall performance, carving a complex backbone supporting information transmission with a minimal shortest path length. We show that 30% inhibitory synapses is the percentage maximizing the learning performance since it guarantees, at the same time, the network excitability necessary to express the response and the variability required to confine the employment of resources.

  1. Magnetic mirror fusion: status and prospects

    SciTech Connect

    Post, R.F.

    1980-02-11

    Two improved mirror systems, the tandem mirror (TM) and the field-reversed mirror (FRM) are being intensively studied. The twin practical aims of these studies: to improve the economic prospects for mirror fusion power plants and to reduce the size and/or complexity of such plants relative to earlier approaches to magnetic fusion. While at the present time the program emphasis is still strongly oriented toward answering scientific questions, the emphasis is shifting as the data accumulates and as larger facilities - ones with a heavy technological and engineering orientation - are being prepared. The experimental and theoretical progress that led to the new look in mirror fusion research is briefly reviewed, the new TM and the FRM ideas are outlined, and the projected future course of mirror fusion research is discussed.

  2. Surgical techniques for lumbo-sacral fusion.

    PubMed

    Tropiano, P; Giorgi, H; Faure, A; Blondel, B

    2017-02-01

    Lumbo-sacral (L5-S1) fusion is a widely performed procedure that has become the reference standard treatment for refractory low back pain. L5-S1 is a complex transition zone between the mobile lordotic distal lumbar spine and the fixed sacral region. The goal is to immobilise the lumbo-sacral junction in order to relieve pain originating from this site. Apart from achieving inter-vertebral fusion, the main challenge lies in the preoperative determination of the fixed L5-S1 position that will be optimal for the patient. Many lumbo-sacral fusion techniques are available. Stabilisation can be achieved using various methods. An anterior, posterior, or combined approach may be used. Recently developed minimally invasive techniques are gaining in popularity based on their good clinical outcomes and high fusion rates. The objective of this conference is to resolve the main issues faced by spinal surgeons in their everyday practice.

  3. Muon Catalyzed Fusion

    NASA Technical Reports Server (NTRS)

    Armour, Edward A.G.

    2007-01-01

    Muon catalyzed fusion is a process in which a negatively charged muon combines with two nuclei of isotopes of hydrogen, e.g, a proton and a deuteron or a deuteron and a triton, to form a muonic molecular ion in which the binding is so tight that nuclear fusion occurs. The muon is normally released after fusion has taken place and so can catalyze further fusions. As the muon has a mean lifetime of 2.2 microseconds, this is the maximum period over which a muon can participate in this process. This article gives an outline of the history of muon catalyzed fusion from 1947, when it was first realised that such a process might occur, to the present day. It includes a description of the contribution that Drachrnan has made to the theory of muon catalyzed fusion and the influence this has had on the author's research.

  4. Inhibitory Control Predicts Grammatical Ability

    PubMed Central

    Ibbotson, Paul; Kearvell-White, Jennifer

    2015-01-01

    We present evidence that individual variation in grammatical ability can be predicted by individual variation in inhibitory control. We tested 81 5-year-olds using two classic tests from linguistics and psychology (Past Tense and the Stroop). Inhibitory control was a better predicator of grammatical ability than either vocabulary or age. Our explanation is that giving the correct response in both tests requires using a common cognitive capacity to inhibit unwanted competition. The implications are that understanding the developmental trajectory of language acquisition can benefit from integrating the developmental trajectory of non-linguistic faculties, such as executive control. PMID:26659926

  5. Heptad repeat 2-based peptides inhibit avian sarcoma and leukosis virus subgroup a infection and identify a fusion intermediate.

    PubMed

    Netter, Robert C; Amberg, Sean M; Balliet, John W; Biscone, Mark J; Vermeulen, Arwen; Earp, Laurie J; White, Judith M; Bates, Paul

    2004-12-01

    Fusion proteins of enveloped viruses categorized as class I are typified by two distinct heptad repeat domains within the transmembrane subunit. These repeats are important structural elements that assemble into the six-helix bundles characteristic of the fusion-activated envelope trimer. Peptides derived from these domains can be potent and specific inhibitors of membrane fusion and virus infection. To facilitate our understanding of retroviral entry, peptides corresponding to the two heptad repeat domains of the avian sarcoma and leukosis virus subgroup A (ASLV-A) TM subunit of the envelope protein were characterized. Two peptides corresponding to the C-terminal heptad repeat (HR2), offset from one another by three residues, were effective inhibitors of infection, while two overlapping peptides derived from the N-terminal heptad repeat (HR1) were not. Analysis of envelope mutants containing substitutions within the HR1 domain revealed that a single amino acid change, L62A, significantly reduced sensitivity to peptide inhibition. Virus bound to cells at 4 degrees C became sensitive to peptide within the first 5 min of elevating the temperature to 37 degrees C and lost sensitivity to peptide after 15 to 30 min, consistent with a transient intermediate in which the peptide binding site is exposed. In cell-cell fusion experiments, peptide inhibitor sensitivity occurred prior to a fusion-enhancing low-pH pulse. Soluble receptor for ASLV-A induces a lipophilic character in the envelope which can be measured by stable liposome binding, and this activation was found to be unaffected by inhibitory HR2 peptide. Finally, receptor-triggered conformational changes in the TM subunit were also found to be unaffected by inhibitory peptide. These changes are marked by a dramatic shift in mobility on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, from a subunit of 37 kDa to a complex of about 80 kDa. Biotinylated HR2 peptide bound specifically to the 80-kDa complex

  6. Cell fusion and nuclear fusion in plants.

    PubMed

    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.

  7. Inhibitory Control in Childhood Stuttering

    ERIC Educational Resources Information Center

    Eggers, Kurt; De Nil, Luc F.; Van den Bergh, Bea R. H.

    2013-01-01

    Purpose: The purpose of this study was to investigate whether previously reported parental questionnaire-based differences in inhibitory control (IC; Eggers, De Nil, & Van den Bergh, 2010) would be supported by direct measurement of IC using a computer task. Method: Participants were 30 children who stutter (CWS; mean age = 7;05 years) and 30…

  8. Controlled Nuclear Fusion.

    ERIC Educational Resources Information Center

    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…

  9. Antiproton catalyzed fusion

    SciTech Connect

    Morgan, D.L. Jr.; Perkins, L.J.; Haney, S.W.

    1995-05-15

    Because of the potential application to power production, it is important to investigate a wide range of possible means to achieve nuclear fusion, even those that may appear initially to be infeasible. In antiproton catalyzed fusion, the negative antiproton shields the repulsion between the positively charged nuclei of hydrogen isotopes, thus allowing a much higher level of penetration through the repulsive Coulomb barrier, and thereby greatly enhancing the fusion cross section. Because of their more compact wave function, the more massive antiprotons offer considerably more shielding than do negative muons. The effects of the shielding on fusion cross sections are most predominate, at low energies. If the antiproton could exist in the ground state with a nucleus for a sufficient time without annihilating, the fusion cross sections are so enhanced that at room temperature energies, values up to about 1,000 barns (that for d+t) would be possible. Unfortunately, the cross section for antiproton annihilation with the incoming nucleus is even higher. A model that provides an upper bound for the fusion to annihilation cross section for all relevant energies indicates that each antiproton will catalyze no more than about one fusion. Because the energy required to make one antiproton greatly exceeds the fusion energy that is released, this level of catalysis is far from adequate for power production.

  10. Fusion Science Education Outreach

    NASA Astrophysics Data System (ADS)

    Danielson, C. A.; DIII-D Education Group

    1996-11-01

    This presentation will focus on education outreach activities at General Atomics that have been expanded to include the general population on science education with a focus on fusion energy. Outreach materials are distributed upon request both nationally and internationally. These materials include a notebook containing copies of DIII--D tour panels, fusion poster, new fusion energy video, new fusion energy brochure, and the electromagnetic spectrum curriculum. The 1996 Fusion Forum (held in the House Caucus Room) included a student/ teacher lunch with Energy Secretary Hazel O'Leary and a private visit to the Forum exhibits. The continuing partnership with Kearny High School includes lectures, job shadowing, internship, equipment donations and an award-winning electric car-racing program. Development of distribution by CD of the existing interactive fusion energy kiosk and a virtual reality tour of the DIII--D facility are underway. The DIII--D fusion education WWW site includes e-mail addresses to ``Ask the Wizard,'' and/or receive GA's outreach materials. Steve Rodecker, a local science teacher, aided by DIII--D fusion staff, won his second Tapestry Award; he also was named the ``1995 National Science Teacher of the Year'' and will be present to share his experiences with the DIII--D educational outreach program.

  11. Two Horizons of Fusion

    ERIC Educational Resources Information Center

    Lo, Mun Ling; Chik, Pakey Pui Man

    2016-01-01

    In this paper, we aim to differentiate the internal and external horizons of "fusion." "Fusion" in the internal horizon relates to the structure and meaning of the object of learning as experienced by the learner. It clarifies the interrelationships among an object's critical features and aspects. It also illuminates the…

  12. Fusion Power Deployment

    SciTech Connect

    J.A. Schmidt; J.M. Ogden

    2002-02-06

    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.

  13. InFusion: Advancing Discovery of Fusion Genes and Chimeric Transcripts from Deep RNA-Sequencing Data

    PubMed Central

    Okonechnikov, Konstantin; Imai-Matsushima, Aki; Seitz, Alexander; Meyer, Thomas F.; Garcia-Alcalde, Fernando

    2016-01-01

    Analysis of fusion transcripts has become increasingly important due to their link with cancer development. Since high-throughput sequencing approaches survey fusion events exhaustively, several computational methods for the detection of gene fusions from RNA-seq data have been developed. This kind of analysis, however, is complicated by native trans-splicing events, the splicing-induced complexity of the transcriptome and biases and artefacts introduced in experiments and data analysis. There are a number of tools available for the detection of fusions from RNA-seq data; however, certain differences in specificity and sensitivity between commonly used approaches have been found. The ability to detect gene fusions of different types, including isoform fusions and fusions involving non-coding regions, has not been thoroughly studied yet. Here, we propose a novel computational toolkit called InFusion for fusion gene detection from RNA-seq data. InFusion introduces several unique features, such as discovery of fusions involving intergenic regions, and detection of anti-sense transcription in chimeric RNAs based on strand-specificity. Our approach demonstrates superior detection accuracy on simulated data and several public RNA-seq datasets. This improved performance was also evident when evaluating data from RNA deep-sequencing of two well-established prostate cancer cell lines. InFusion identified 26 novel fusion events that were validated in vitro, including alternatively spliced gene fusion isoforms and chimeric transcripts that include intergenic regions. The toolkit is freely available to download from http:/bitbucket.org/kokonech/infusion. PMID:27907167

  14. Information Fusion of Conflicting Input Data

    PubMed Central

    Mönks, Uwe; Dörksen, Helene; Lohweg, Volker; Hübner, Michael

    2016-01-01

    Sensors, and also actuators or external sources such as databases, serve as data sources in order to realise condition monitoring of industrial applications or the acquisition of characteristic parameters like production speed or reject rate. Modern facilities create such a large amount of complex data that a machine operator is unable to comprehend and process the information contained in the data. Thus, information fusion mechanisms gain increasing importance. Besides the management of large amounts of data, further challenges towards the fusion algorithms arise from epistemic uncertainties (incomplete knowledge) in the input signals as well as conflicts between them. These aspects must be considered during information processing to obtain reliable results, which are in accordance with the real world. The analysis of the scientific state of the art shows that current solutions fulfil said requirements at most only partly. This article proposes the multilayered information fusion system MACRO (multilayer attribute-based conflict-reducing observation) employing the μBalTLCS (fuzzified balanced two-layer conflict solving) fusion algorithm to reduce the impact of conflicts on the fusion result. The performance of the contribution is shown by its evaluation in the scope of a machine condition monitoring application under laboratory conditions. Here, the MACRO system yields the best results compared to state-of-the-art fusion mechanisms. The utilised data is published and freely accessible. PMID:27801874

  15. Trends in fusion reactor safety research

    SciTech Connect

    Herring, J.S.; Holland, D.F.; Piet, S.J.

    1991-01-01

    Fusion has the potential to be an attractive energy source. From the safety and environmental perspective, fusion must avoid concerns about catastrophic accidents and unsolvable waste disposal. In addition, fusion must achieve an acceptable level of risk from operational accidents that result in public exposure and economic loss. Finally, fusion reactors must control routine radioactive effluent, particularly tritium. Major progress in achieving this potential rests on development of low-activation materials or alternative fuels. The safety and performance of various material choices and fuels for commercial fusion reactors can be investigated relatively inexpensively through reactor design studies. These studies bring together experts in a wide range of backgrounds and force the group to either agree on a reactor design or identify areas for further study. Fusion reactors will be complex with distributed radioactive inventories. The next generation of experiments will be critical in demonstrating that acceptable levels of safe operation can be achieved. These machines will use materials which are available today and for which a large database exists (e.g. for 316 stainless steel). Researchers have developed a good understanding of the risks associated with operation of these devices. Specifically, consequences from coolant system failures, loss of vacuum events, tritium releases, and liquid metal reactions have been studied. Recent studies go beyond next step designs and investigate commercial reactor concerns including tritium release and liquid metal reactions. 18 refs.

  16. Information Fusion of Conflicting Input Data.

    PubMed

    Mönks, Uwe; Dörksen, Helene; Lohweg, Volker; Hübner, Michael

    2016-10-29

    Sensors, and also actuators or external sources such as databases, serve as data sources in order to realise condition monitoring of industrial applications or the acquisition of characteristic parameters like production speed or reject rate. Modern facilities create such a large amount of complex data that a machine operator is unable to comprehend and process the information contained in the data. Thus, information fusion mechanisms gain increasing importance. Besides the management of large amounts of data, further challenges towards the fusion algorithms arise from epistemic uncertainties (incomplete knowledge) in the input signals as well as conflicts between them. These aspects must be considered during information processing to obtain reliable results, which are in accordance with the real world. The analysis of the scientific state of the art shows that current solutions fulfil said requirements at most only partly. This article proposes the multilayered information fusion system MACRO (multilayer attribute-based conflict-reducing observation) employing the μBalTLCS (fuzzified balanced two-layer conflict solving) fusion algorithm to reduce the impact of conflicts on the fusion result. The performance of the contribution is shown by its evaluation in the scope of a machine condition monitoring application under laboratory conditions. Here, the MACRO system yields the best results compared to state-of-the-art fusion mechanisms. The utilised data is published and freely accessible.

  17. Engineered staphylococcal protein A's IgG-binding domain with cathepsin L inhibitory activity

    SciTech Connect

    Bratkovic, Tomaz . E-mail: tomaz.bratkovic@ffa.uni-lj.si; Berlec, Ales; Popovic, Tatjana; Lunder, Mojca; Kreft, Samo; Urleb, Uros; Strukelj, Borut

    2006-10-13

    Inhibitory peptide of papain-like cysteine proteases, affinity selected from a random disulfide constrained phage-displayed peptide library, was grafted to staphylococcal protein A's B domain. Scaffold protein was additionally modified in order to allow solvent exposed display of peptide loop. Correct folding of fusion proteins was confirmed by CD-spectroscopy and by the ability to bind the Fc-region of rabbit IgG, a characteristic of parent domain. The recombinant constructs inhibited cathepsin L with inhibitory constants in the low-micromolar range.

  18. Structural characterization of Mumps virus fusion protein core

    SciTech Connect

    Liu Yueyong; Xu Yanhui; Lou Zhiyong; Zhu Jieqing; Hu Xuebo; Gao, George F.; Qiu Bingsheng . E-mail: Qiubs@sun.im.ac.cn; Rao Zihe . E-mail: raozh@xtal.tsinghua.edu.cn; Tien, Po . E-mail: tienpo@sun.im.ac.cn

    2006-09-29

    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. Mutual control of membrane fission and fusion proteins.

    PubMed

    Peters, Christopher; Baars, Tonie L; Bühler, Susanne; Mayer, Andreas

    2004-11-24

    Membrane fusion and fission are antagonistic reactions controlled by different proteins. Dynamins promote membrane fission by GTP-driven changes of conformation and polymerization state, while SNAREs fuse membranes by forming complexes between t- and v-SNAREs from apposed vesicles. Here, we describe a role of the dynamin-like GTPase Vps1p in fusion of yeast vacuoles. Vps1p forms polymers that couple several t-SNAREs together. At the onset of fusion, the SNARE-activating ATPase Sec18p/NSF and the t-SNARE depolymerize Vps1p and release it from the membrane. This activity is independent of the SNARE coactivator Sec17p/alpha-SNAP and of the v-SNARE. Vps1p release liberates the t-SNAREs for initiating fusion and at the same time disrupts fission activity. We propose that reciprocal control between fusion and fission components exists, which may prevent futile cycles of fission and fusion.

  20. Mixed-mode synchronization between two inhibitory neurons with post-inhibitory rebound

    NASA Astrophysics Data System (ADS)

    Nagornov, Roman; Osipov, Grigory; Komarov, Maxim; Pikovsky, Arkady; Shilnikov, Andrey

    2016-07-01

    We study an array of activity rhythms generated by a half-center oscillator (HCO), represented by a pair of reciprocally coupled neurons with post-inhibitory rebounds (PIR). Such coupling-induced bursting possesses two time scales, one for fast spiking and another for slow quiescent periods, is shown to exhibit an array of synchronization properties. We discuss several HCO configurations constituted by two endogenous bursters, by tonic-spiking and quiescent neurons, as well as mixed-mode configurations composed of neurons of different type. We demonstrate that burst synchronization can be accompanied by complex, often chaotic, interactions of fast spikes within synchronized bursts.

  1. Fusion Studies in Japan

    NASA Astrophysics Data System (ADS)

    Ogawa, Yuichi

    2016-05-01

    A new strategic energy plan decided by the Japanese Cabinet in 2014 strongly supports the steady promotion of nuclear fusion development activities, including the ITER project and the Broader Approach activities from the long-term viewpoint. Atomic Energy Commission (AEC) in Japan formulated the Third Phase Basic Program so as to promote an experimental fusion reactor project. In 2005 AEC has reviewed this Program, and discussed on selection and concentration among many projects of fusion reactor development. In addition to the promotion of ITER project, advanced tokamak research by JT-60SA, helical plasma experiment by LHD, FIREX project in laser fusion research and fusion engineering by IFMIF were highly prioritized. Although the basic concept is quite different between tokamak, helical and laser fusion researches, there exist a lot of common features such as plasma physics on 3-D magnetic geometry, high power heat load on plasma facing component and so on. Therefore, a synergetic scenario on fusion reactor development among various plasma confinement concepts would be important.

  2. Adrenoceptors and colocolonic inhibitory reflex.

    PubMed

    Hughes, S F; Scott, S M; Pilot, M A; Williams, N S

    1999-12-01

    The colocolonic inhibitory reflex is characterized by inhibition of proximal colonic motility induced by distal colonic distension. The aim of this study was to investigate the underlying neural mechanisms of this reflex, in vivo, using an isolated loop of canine colon. In five beagle dogs, motility was recorded from an exteriorized colonic loop via a serosal strain gauge connected to a digital data logger and chart recorder. Inflation of a balloon in the distal colon resulted in inhibition of motility in the isolated loop. Inhibition of motor activity persisted following injection of propranolol (100 microg/kg intravenously), a beta-adrenoceptor antagonist, but was abolished following administration of the alpha2-adrenoceptor antagonist yohimbine (200 microg/kg intravenously). This study confirms that the colocolonic inhibitory reflex is mediated via the extrinsic nerves to the colon. As the reflex was abolished by alpha2-, but not beta-adrenoceptor blockade, this indicates that the reflex pathway involves alpha2-adrenoceptors.

  3. Particle beam fusion

    SciTech Connect

    1980-12-31

    Today, in keeping with Sandia Laboratories` designation by the Department of Energy as the lead laboratory for the pulsed power approach to fusion, its efforts include major research activities and the construction of new facilities at its Albuquerque site. Additionally, in its capacity as lead laboratory, Sandia coordinates DOE-supported pulsed power fusion work at other government operated laboratories, with industrial contractors, and universities. The beginning of Sandia`s involvement in developing fusion power was an outgrowth of its contributions to the nation`s nuclear weapon program. The Laboratories` work in the early 1960`s emphasized the use of pulsed radiation environments to test the resistance of US nuclear weapons to enemy nuclear bursts. A careful study of options for fusion power indicated that Sandia`s expertise in the pulsed power field could provide a powerful match to ignite fusion fuel. Although creating test environments is an achieved goal of Sandia`s overall program, this work and other military tasks protected by appropriate security regulations will continue, making full use of the same pulsed power technology and accelerators as the fusion-for-energy program. Major goals of Sandia`s fusion program including the following: (1) complete a particle accelerator to deliver sufficient beam energy for igniting fusion targets; (2) obtain net energy gain, this goal would provide fusion energy output in excess of energy stored in the accelerator; (3) develop a technology base for the repetitive ignition of pellets in a power reactor. After accomplishing these goals, the technology will be introduced to the nation`s commercial sector.

  4. Cortical neurodynamics of inhibitory control.

    PubMed

    Hwang, Kai; Ghuman, Avniel S; Manoach, Dara S; Jones, Stephanie R; Luna, Beatriz

    2014-07-16

    The ability to inhibit prepotent responses is critical for successful goal-directed behaviors. To investigate the neural basis of inhibitory control, we conducted a magnetoencephalography study where human participants performed the antisaccade task. Results indicated that neural oscillations in the prefrontal cortex (PFC) showed significant task modulations in preparation to suppress saccades. Before successfully inhibiting a saccade, beta-band power (18-38 Hz) in the lateral PFC and alpha-band power (10-18 Hz) in the frontal eye field (FEF) increased. Trial-by-trial prestimulus FEF alpha-band power predicted successful saccadic inhibition. Further, inhibitory control enhanced cross-frequency amplitude coupling between PFC beta-band (18-38 Hz) activity and FEF alpha-band activity, and the coupling appeared to be initiated by the PFC. Our results suggest a generalized mechanism for top-down inhibitory control: prefrontal beta-band activity initiates alpha-band activity for functional inhibition of the effector and/or sensory system.

  5. Cortical Neurodynamics of Inhibitory Control

    PubMed Central

    Ghuman, Avniel S.; Manoach, Dara S.; Jones, Stephanie R.; Luna, Beatriz

    2014-01-01

    The ability to inhibit prepotent responses is critical for successful goal-directed behaviors. To investigate the neural basis of inhibitory control, we conducted a magnetoencephalography study where human participants performed the antisaccade task. Results indicated that neural oscillations in the prefrontal cortex (PFC) showed significant task modulations in preparation to suppress saccades. Before successfully inhibiting a saccade, beta-band power (18–38 Hz) in the lateral PFC and alpha-band power (10–18 Hz) in the frontal eye field (FEF) increased. Trial-by-trial prestimulus FEF alpha-band power predicted successful saccadic inhibition. Further, inhibitory control enhanced cross-frequency amplitude coupling between PFC beta-band (18–38 Hz) activity and FEF alpha-band activity, and the coupling appeared to be initiated by the PFC. Our results suggest a generalized mechanism for top-down inhibitory control: prefrontal beta-band activity initiates alpha-band activity for functional inhibition of the effector and/or sensory system. PMID:25031398

  6. Spherical torus fusion reactor

    DOEpatents

    Martin Peng, Y.K.M.

    1985-10-03

    The object of this invention is to provide a compact torus fusion reactor with dramatic simplification of plasma confinement design. Another object of this invention is to provide a compact torus fusion reactor with low magnetic field and small aspect ratio stable plasma confinement. In accordance with the principles of this invention there is provided a compact toroidal-type plasma confinement fusion reactor in which only the indispensable components inboard of a tokamak type of plasma confinement region, mainly a current conducting medium which carries electrical current for producing a toroidal magnet confinement field about the toroidal plasma region, are retained.

  7. Fusion for Space Propulsion

    NASA Technical Reports Server (NTRS)

    Thio, Y. C. Francis; Schafer, Charles (Technical Monitor)

    2001-01-01

    There is little doubt that humans will attempt to explore and develop the solar system in this century. A large amount of energy will be required for accomplishing this. The need for fusion propulsion is discussed. For a propulsion system, there are three important thermodynamical attributes: (1) The absolute amount of energy available, (2) the propellant exhaust velocity, and (3) the jet power per unit mass of the propulsion system (specific power). For human exploration and development of the solar system, propellant exhaust velocity in excess of 100 km/s and specific power in excess of 10 kW/kg are required. Chemical combustion can produce exhaust velocity up to about 5 km/s. Nuclear fission processes typically result in producing energy in the form of heat that needs to be manipulated at temperatures limited by materials to about 2,800 K. Using the energy to heat a hydrogen propellant increases the exhaust velocity by only a factor of about two. Alternatively the energy can be converted into electricity which is then used to accelerate particles to high exhaust velocity. The necessary power conversion and conditioning equipment, however, increases the mass of the propulsion system for the same jet power by more than two orders of magnitude over chemical system, thus greatly limits the thrust-to-weight ratio attainable. The principal advantage of the fission process is that its development is relatively mature and is available right now. If fusion can be developed, fusion appears to have the best of all worlds in terms of propulsion - it can provide the absolute amount, the propellant exhaust velocity, and the high specific jet power. An intermediate step towards pure fusion propulsion is a bimodal system in which a fission reactor is used to provide some of the energy to drive a fusion propulsion unit. The technical issues related to fusion for space propulsion are discussed. The technical priorities for developing and applying fusion for propulsion are

  8. Laser-Driven Fusion.

    ERIC Educational Resources Information Center

    Gibson, A. F.

    1980-01-01

    Discusses the present status and future prospects of laser-driven fusion. Current research (which is classified under three main headings: laser-matter interaction processes, compression, and laser development) is also presented. (HM)

  9. Viral membrane fusion

    PubMed Central

    Harrison, Stephen C

    2008-01-01

    Infection by viruses having lipid-bilayer envelopes proceeds through fusion of the viral membrane with a membrane of the target cell. Viral ‘fusion proteins’ facilitate this process. They vary greatly in structure, but all seem to have a common mechanism of action, in which a ligand-triggered, large-scale conformational change in the fusion protein is coupled to apposition and merger of the two bilayers. We describe three examples—the influenza virus hemagglutinin, the flavivirus E protein and the vesicular stomatitis virus G protein—in some detail, to illustrate the ways in which different structures have evolved to implement this common mechanism. Fusion inhibitors can be effective antiviral agents. PMID:18596815

  10. Fusion-breeder program

    SciTech Connect

    Moir, R.W.

    1982-11-19

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

  11. Gene Fusion: A Genome Wide Survey

    NASA Technical Reports Server (NTRS)

    Liang, Ping; Riley, Monica

    2001-01-01

    As a well known fact, organisms form larger and complex multimodular (composite or chimeric) and mostly multi-functional proteins through gene fusion of two or more individual genes which have independent evolution histories and functions. We call each of these components a module. The existence of multimodular proteins may improves the efficiency in gene regulation and in cellular functions, and thus may give the host organism advantages in adaptation to environments. Analysis of all gene fusions in present-day organisms should allow us to examine the patterns of gene fusion in context with cellular functions, to trace back the evolution processes from the ancient smaller and uni-functional proteins to the present-day larger and complex multi-functional proteins, and to estimate the minimal number of ancestor proteins that existed in the last common ancestor for all life on earth. Although many multimodular proteins have been experimentally known, identification of gene fusion events systematically at genome scale had not been possible until recently when large number of completed genome sequences have been becoming available. In addition, technical difficulties for such analysis also exist due to the complexity of this biological and evolutionary process. We report from this study a new strategy to computationally identify multimodular proteins using completed genome sequences and the results surveyed from 22 organisms with the data from over 40 organisms to be presented during the meeting. Additional information is contained in the original extended abstract.

  12. Glossary of fusion energy

    NASA Astrophysics Data System (ADS)

    Whitson, M. O.

    1985-02-01

    The Glossary of Fusion Energy is an attempt to present a concise, yet comprehensive collection of terms that may be beneficial to scientists and laymen who are directly or tangentially concerned with this burgeoning energy enterprise. Included are definitions of terms in theoretical plasma physics, controlled thermonuclear fusion, and some related physics concepts. Also, short descriptions of some of the major thermonuclear experiments currently under way in the world today are included.

  13. Cold nuclear fusion

    SciTech Connect

    Tsyganov, E. N.

    2012-02-15

    Recent accelerator experiments on fusion of various elements have clearly demonstrated that the effective cross-sections of these reactions depend on what material the target particle is placed in. In these experiments, there was a significant increase in the probability of interaction when target nuclei are imbedded in a conducting crystal or are a part of it. These experiments open a new perspective on the problem of so-called cold nuclear fusion.

  14. Fusion ignition research experiment

    SciTech Connect

    Dale Meade

    2000-07-18

    Understanding the properties of high gain (alpha-dominated) fusion plasmas in an advanced toroidal configuration is the largest remaining open issue that must be addressed to provide the scientific foundation for an attractive magnetic fusion reactor. The critical parts of this science can be obtained in a compact high field tokamak which is also likely to provide the fastest and least expensive path to understanding alpha-dominated plasmas in advanced toroidal systems.

  15. Magnetized Target Fusion

    NASA Technical Reports Server (NTRS)

    Griffin, Steven T.

    2002-01-01

    Magnetized target fusion (MTF) is under consideration as a means of building a low mass, high specific impulse, and high thrust propulsion system for interplanetary travel. This unique combination is the result of the generation of a high temperature plasma by the nuclear fusion process. This plasma can then be deflected by magnetic fields to provide thrust. Fusion is initiated by a small traction of the energy generated in the magnetic coils due to the plasma's compression of the magnetic field. The power gain from a fusion reaction is such that inefficiencies due to thermal neutrons and coil losses can be overcome. Since the fusion reaction products are directly used for propulsion and the power to initiate the reaction is directly obtained from the thrust generation, no massive power supply for energy conversion is required. The result should be a low engine mass, high specific impulse and high thrust system. The key is to successfully initiate fusion as a proof-of-principle for this application. Currently MSFC is implementing MTF proof-of-principle experiments. This involves many technical details and ancillary investigations. Of these, selected pertinent issues include the properties, orientation and timing of the plasma guns and the convergence and interface development of the "pusher" plasma. Computer simulations of the target plasma's behavior under compression and the convergence and mixing of the gun plasma are under investigation. This work is to focus on the gun characterization and development as it relates to plasma initiation and repeatability.

  16. ITER Fusion Energy

    ScienceCinema

    Dr. Norbert Holtkamp

    2016-07-12

    ITER (in Latin “the way”) is designed to demonstrate the scientific and technological feasibility of fusion energy. Fusion is the process by which two light atomic nuclei combine to form a heavier over one and thus release energy. In the fusion process two isotopes of hydrogen – deuterium and tritium – fuse together to form a helium atom and a neutron. Thus fusion could provide large scale energy production without greenhouse effects; essentially limitless fuel would be available all over the world. The principal goals of ITER are to generate 500 megawatts of fusion power for periods of 300 to 500 seconds with a fusion power multiplication factor, Q, of at least 10. Q ? 10 (input power 50 MW / output power 500 MW). The ITER Organization was officially established in Cadarache, France, on 24 October 2007. The seven members engaged in the project – China, the European Union, India, Japan, Korea, Russia and the United States – represent more than half the world’s population. The costs for ITER are shared by the seven members. The cost for the construction will be approximately 5.5 billion Euros, a similar amount is foreseen for the twenty-year phase of operation and the subsequent decommissioning.

  17. Monetary rewards modulate inhibitory control

    PubMed Central

    Herrera, Paula M.; Speranza, Mario; Hampshire, Adam; Bekinschtein, Tristán A.

    2014-01-01

    The ability to override a dominant response, often referred to as behavioral inhibition, is considered a key element of executive cognition. Poor behavioral inhibition is a defining characteristic of several neurological and psychiatric populations. Recently, there has been increasing interest in the motivational dimension of behavioral inhibition, with some experiments incorporating emotional contingencies in classical inhibitory paradigms such as the Go/NoGo and Stop Signal Tasks (SSTs). Several studies have reported a positive modulatory effect of reward on performance in pathological conditions such as substance abuse, pathological gambling, and Attention Deficit Hyperactive Disorder (ADHD). However, experiments that directly investigate the modulatory effects of reward magnitudes on the performance of inhibitory tasks are scarce and little is known about the finer grained relationship between motivation and inhibitory control. Here we probed the effect of reward magnitude and context on behavioral inhibition with three modified versions of the widely used SST. The pilot study compared inhibition performance during six blocks alternating neutral feedback, low, medium, and high monetary rewards. Study One compared increasing vs. decreasing rewards, with low, high rewards, and neutral feedback; whilst Study Two compared low and high reward magnitudes alone also in an increasing and decreasing reward design. The reward magnitude effect was not demonstrated in the pilot study, probably due to a learning effect induced by practice in this lengthy task. The reward effect per se was weak but the context (order of reward) was clearly suggested in Study One, and was particularly strongly confirmed in study two. In addition, these findings revealed a “kick start effect” over global performance measures. Specifically, there was a long lasting improvement in performance throughout the task when participants received the highest reward magnitudes at the beginning of the

  18. Membrane fusion mediated by coiled coils: a hypothesis.

    PubMed Central

    Bentz, J

    2000-01-01

    A molecular model of the low-pH-induced membrane fusion by influenza hemagglutinin (HA) is proposed based upon the hypothesis that the conformational change to the extended coiled coil creates a high-energy hydrophobic membrane defect in the viral envelope or HA expressing cell. It is known that 1) an aggregate of at least eight HAs is required at the fusion site, yet only two or three of these HAs need to undergo the "essential" conformational change for the first fusion pore to form (Bentz, J. 2000. Biophys. J. 78:000-000); 2) the formation of the first fusion pore signifies a stage of restricted lipid flow into the nascent fusion site; and 3) some HAs can partially insert their fusion peptides into their own viral envelopes at low pH. This suggests that the committed step for HA-mediated fusion begins with a tightly packed aggregate of HAs whose fusion peptides are inserted into their own viral envelope, which causes restricted lateral lipid flow within the HA aggregate. The transition of two or three HAs in the center of the aggregate to the extended coiled coil extracts the fusion peptide and creates a hydrophobic defect in the outer monolayer of the virion, which is stabilized by the closely packed HAs. These HAs are inhibited from diffusing away from the site to admit lateral lipid flow, in part because that would initially increase the surface area of hydrophobic exposure. The other obvious pathway to heal this hydrophobic defect, or some descendent, is recruitment of lipids from the outer monolayer of the apposed target membrane, i.e., fusion. Other viral fusion proteins and the SNARE fusion protein complex appear to fit within this hypothesis. PMID:10653801

  19. Review of the Inertial Fusion Energy Program

    SciTech Connect

    none,

    2004-03-29

    Igniting fusion fuel in the laboratory remains an alluring goal for two reasons: the desire to study matter under the extreme conditions needed for fusion burn, and the potential of harnessing the energy released as an attractive energy source for mankind. The inertial confinement approach to fusion involves rapidly compressing a tiny spherical capsule of fuel, initially a few millimeters in radius, to densities and temperatures higher than those in the core of the sun. The ignited plasma is confined solely by its own inertia long enough for a significant fraction of the fuel to burn before the plasma expands, cools down and the fusion reactions are quenched. The potential of this confinement approach as an attractive energy source is being studied in the Inertial Fusion Energy (IFE) program, which is the subject of this report. A complex set of interrelated requirements for IFE has motivated the study of novel potential solutions. Three types of “drivers” for fuel compression are presently studied: high-averagepower lasers (HAPL), heavy-ion (HI) accelerators, and Z-Pinches. The three main approaches to IFE are based on these drivers, along with the specific type of target (which contains the fuel capsule) and chamber that appear most promising for a particular driver.

  20. Selective control of inhibitory synapse development by Slitrk3-PTPδ trans-synaptic interaction

    PubMed Central

    Takahashi, Hideto; Katayama, Kei-ichi; Sohya, Kazuhiro; Miyamoto, Hiroyuki; Prasad, Tuhina; Matsumoto, Yoshifumi; Ota, Maya; Yasuda, Hiroki; Tsumoto, Tadaharu; Aruga, Jun; Craig, Ann Marie

    2012-01-01

    Balanced development of excitatory and inhibitory synapses is required for normal brain function, and their imbalance may underlie pathogenesis of neuropsychiatric disorders. Compared with many identified trans-synaptic adhesion complexes that organize excitatory synapses, little is known about organizers specific for inhibitory synapses. Here we report Slit and NTRK-like family member 3 (Slitrk3) as a postsynaptic adhesion molecule that selectively regulates inhibitory synapse development via trans-interaction with axonal tyrosine phosphatase receptor PTPδ. Slitrk3 expressed in fibroblasts triggers only inhibitory presynaptic differentiation in contacting axons of cocultured rat hippocampal neurons. Recombinant Slitrk3 preferentially localizes to inhibitory postsynaptic sites. Slitrk3-deficient mice exhibit decreases in inhibitory but not excitatory synapse number and function in hippocampal CA1 neurons and exhibit increased seizure susceptibility and spontaneous epileptiform activity. Slitrk3 requires trans-interaction with axonal PTPδ to induce inhibitory presynaptic differentiation. These results identify Slitrk3-PTPδ as an inhibitory-specific trans-synaptic organizing complex required for normal functional GABAergic synapse development. PMID:22286174

  1. Materials issues in fusion reactors

    NASA Astrophysics Data System (ADS)

    Suri, A. K.; Krishnamurthy, N.; Batra, I. S.

    2010-02-01

    The world scientific community is presently engaged in one of the toughest technological tasks of the current century, namely, exploitation of nuclear fusion in a controlled manner for the benefit of mankind. Scientific feasibility of controlled fusion of the light elements in plasma under magnetic confinement has already been proven. International efforts in a coordinated and co-operative manner are presently being made to build ITER - the International Thermonuclear Experimental Reactor - to test, in this first step, the concept of 'Tokamak' for net fusion energy production. To exploit this new developing option of making energy available through the route of fusion, India too embarked on a robust fusion programme under which we now have a working tokamak - the Aditya and a steady state tokamak (SST-1), which is on the verge of functioning. The programme envisages further development in terms of making SST-2 followed by a DEMO and finally the fusion power reactor. Further, with the participation of India in the ITER program in 2005, and recent allocation of half - a - port in ITER for placing our Lead - Lithium Ceramic Breeder (LLCB) based Test Blanket Module (TBM), meant basically for breeding tritium and extracting high grade heat, the need to understand and address issues related to materials for these complex systems has become all the more necessary. Also, it is obvious that with increasing power from the SST stages to DEMO and further to PROTOTYPE, the increasing demands on performance of materials would necessitate discovery and development of new materials. Because of the 14.1 MeV neutrons that are generated in the D+T reaction exploited in a tokamak, the materials, especially those employed for the construction of the first wall, the diverter and the blanket segments, suffer crippling damage due to the high He/dpa ratios that result due to the high energy of the neutrons. To meet this challenge, the materials that need to be developed for the tokamaks

  2. Fusion for Space Propulsion

    NASA Technical Reports Server (NTRS)

    Thio, Y. C. Francis; Schafer, Charles (Technical Monitor)

    2001-01-01

    There is little doubt that humans will attempt to explore and develop the solar system in this century. A large amount of energy will be required for accomplishing this. The need for fusion propulsion is discussed. For a propulsion system, there are three important thermodynamical attributes: (1) The absolute amount of energy available, (2) the propellant exhaust velocity, and (3) the jet power per unit mass of the propulsion system (specific power). For human exploration and development of the solar system, propellant exhaust velocity in excess of 100 km/s and specific power in excess of 10 kW/kg are required. Chemical combustion can produce exhaust velocity up to about 5 km/s. Nuclear fission processes typically result in producing energy in the form of heat that needs to be manipulated at temperatures limited by materials to about 2,800 K. Using the energy to heat a hydrogen propellant increases the exhaust velocity by only a factor of about two. Alternatively the energy can be converted into electricity which is then used to accelerate particles to high exhaust velocity. The necessary power conversion and conditioning equipment, however, increases the mass of the propulsion system for the same jet power by more than two orders of magnitude over chemical system, thus greatly limits the thrust-to-weight ratio attainable. The principal advantage of the fission process is that its development is relatively mature and is available right now. If fusion can be developed, fusion appears to have the best of all worlds in terms of propulsion - it can provide the absolute amount, the propellant exhaust velocity, and the high specific jet power. An intermediate step towards pure fusion propulsion is a bimodal system in which a fission reactor is used to provide some of the energy to drive a fusion propulsion unit. The technical issues related to fusion for space propulsion are discussed. The technical priorities for developing and applying fusion for propulsion are

  3. Myoblast fusion in Drosophila

    SciTech Connect

    Haralalka, Shruti; Abmayr, Susan M.

    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.

  4. Fusion, magnetic confinement

    SciTech Connect

    Berk, H.L.

    1992-08-06

    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 {sup 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.

  5. Dissociable yet tied inhibitory processes: the structure of inhibitory control.

    PubMed

    Michael, George A; Mizzi, Raphaël; Couffe, Cyril; Gálvez-García, Germán

    2014-09-01

    Cognitive and neural models have proposed the existence of a single inhibitory process that regulates behavior and depends on the right frontal operculum (rFO). The aim of this study was to make a contribution to the ongoing debate as to whether inhibition is a single process or is composed of multiple, independent processes. Here, within a single paradigm, we assessed the links between two inhibitory phenomena-namely, resistance to involuntary visual capture by abrupt onsets and resolving of spatial stimulus-response conflict. We did so by conducting three experiments, two involving healthy volunteers (Exps. 1 and 3), and one with the help of a well-documented patient, R.J., with selectively weakened inhibition following a lesion of the rFO. The results suggest that resistance to capture and stimulus-response conflict are independent, because (a) additive effects were found (Exps. 1 and 3), (b) capture did not correlate with compatibility effects (Exp. 1), (c) dual tasking affected the two phenomena differently (Exp. 3), and (d) a dissociation was found between the two in patient R.J. (Exp. 2). However, the results also show that these two phenomena may share some processing components, given that (a) both were affected in patient R.J., but to different degrees (Exp. 2), and (b) increasing the difficulty of dual tasking produced an increasingly negative correlation between capture and compatibility (Exp. 3), which suggests that when resources are withdrawn from the control of the former, they are used to control the latter.

  6. Nuclear Fusion Award 2009 speech Nuclear Fusion Award 2009 speech

    NASA Astrophysics Data System (ADS)

    Sabbagh, Steven Anthony

    2011-01-01

    of Dr Todd Evans, another significant mentor of mine, as winner of this prestigious award? Then, it happened. The paper covers several key topics related to high beta tokamak physics. For me, the greatest satisfaction in receiving this award is because it was the first Nuclear Fusion Award to recognize research on the National Spherical Torus Experiment (NSTX) located at the Princeton Plasma Physics Laboratory. The achievement of record stability parameters in a mega-Ampere class spherical torus (ST) device reported in the paper represents a multi-year effort, contributed to by the entire research team. Research to maintain such plasmas for an indefinite period continues today. Understanding RWM stabilization physics is crucial for this goal, and leveraging the high beta ST operating space uniquely tests theory for application to future STs and to tokamaks in general, including advanced operational scenarios of ITER. For instance, the RWM was found to have significant amplitude in components with the toroidal mode number greater than unity. This has important implications for general active RWM control. Evidence that the RWM passive stabilization physics and marginal stability criterion are indeed more complex than originally thought was shown in this paper. Present work shows the greater complexity has a direct impact on how we should extrapolate RWM stabilization to future devices. The paper also reported the qualitative observation of neoclassical toroidal viscosity (NTV), followed by a companion paper by our group in 2006 reporting the quantitative observation of this effect and comparison to theory. The physics of this interesting and important phenomenon was introduced to me by Professor J. Callen (who has given an overview talk at this conference including this subject) and Professor Kerchung Shaing of the University of Wisconsin, to whom I am quite indebted. The paper also reported the first measurement of resonant field amplification at high beta in the NSTX

  7. Liposome reconstitution of a minimal protein-mediated membrane fusion machine

    PubMed Central

    Top, Deniz; de Antueno, Roberto; Salsman, Jayme; Corcoran, Jennifer; Mader, Jamie; Hoskin, David; Touhami, Ahmed; Jericho, Manfred H; Duncan, Roy

    2005-01-01

    Biological membrane fusion is dependent on protein catalysts to mediate localized restructuring of lipid bilayers. A central theme in current models of protein-mediated membrane fusion involves the sequential refolding of complex homomeric or heteromeric protein fusion machines. The structural features of a new family of fusion-associated small transmembrane (FAST) proteins appear incompatible with existing models of membrane fusion protein function. While the FAST proteins function to induce efficient cell–cell fusion when expressed in transfected cells, it was unclear whether they function on their own to mediate membrane fusion or are dependent on cellular protein cofactors. Using proteoliposomes containing the purified p14 FAST protein of reptilian reovirus, we now show via liposome–cell and liposome–liposome fusion assays that p14 is both necessary and sufficient for membrane fusion. Stoichiometric and kinetic analyses suggest that the relative efficiency of p14-mediated membrane fusion rivals that of the more complex cellular and viral fusion proteins, making the FAST proteins the simplest known membrane fusion machines. PMID:16079913

  8. An Approach to Automated Fusion System Design and Adaptation

    PubMed Central

    Fritze, Alexander; Mönks, Uwe; Holst, Christoph-Alexander; Lohweg, Volker

    2017-01-01

    Industrial applications are in transition towards modular and flexible architectures that are capable of self-configuration and -optimisation. This is due to the demand of mass customisation and the increasing complexity of industrial systems. The conversion to modular systems is related to challenges in all disciplines. Consequently, diverse tasks such as information processing, extensive networking, or system monitoring using sensor and information fusion systems need to be reconsidered. The focus of this contribution is on distributed sensor and information fusion systems for system monitoring, which must reflect the increasing flexibility of fusion systems. This contribution thus proposes an approach, which relies on a network of self-descriptive intelligent sensor nodes, for the automatic design and update of sensor and information fusion systems. This article encompasses the fusion system configuration and adaptation as well as communication aspects. Manual interaction with the flexibly changing system is reduced to a minimum. PMID:28300762

  9. Peaceful Uses of Fusion

    DOE R&D Accomplishments Database

    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.

  10. Spherical torus fusion reactor

    DOEpatents

    Peng, Yueng-Kay M.

    1989-01-01

    A fusion reactor is provided having a near spherical-shaped plasma with a modest central opening through which straight segments of toroidal field coils extend that carry electrical current for generating a toroidal magnet plasma confinement fields. By retaining only the indispensable components inboard of the plasma torus, principally the cooled toroidal field conductors and in some cases a vacuum containment vessel wall, the fusion reactor features an exceptionally small aspect ratio (typically about 1.5), a naturally elongated plasma cross section without extensive field shaping, requires low strength magnetic containment fields, small size and high beta. These features combine to produce a spherical torus plasma in a unique physics regime which permits compact fusion at low field and modest cost.

  11. Spherical torus fusion reactor

    DOEpatents

    Peng, Yueng-Kay M.

    1989-04-04

    A fusion reactor is provided having a near spherical-shaped plasma with a modest central opening through which straight segments of toroidal field coils extend that carry electrical current for generating a toroidal magnet plasma confinement fields. By retaining only the indispensable components inboard of the plasma torus, principally the cooled toroidal field conductors and in some cases a vacuum containment vessel wall, the fusion reactor features an exceptionally small aspect ratio (typically about 1.5), a naturally elongated plasma cross section without extensive field shaping, requires low strength magnetic containment fields, small size and high beta. These features combine to produce a spherical torus plasma in a unique physics regime which permits compact fusion at low field and modest cost.

  12. Ceramics for fusion applications

    SciTech Connect

    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/sub 2/O/sub 3/, MgAl/sub 2/O/sub 4/, BeO, Si/sub 3/N/sub 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.

  13. Fusion research at ORNL

    SciTech Connect

    Not Available

    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.

  14. Simulation of Fusion Plasmas

    ScienceCinema

    Holland, Chris [UC San Diego, San Diego, California, United States

    2016-07-12

    The upcoming ITER experiment (www.iter.org) represents the next major milestone in realizing the promise of using nuclear fusion as a commercial energy source, by moving into the “burning plasma” regime where the dominant heat source is the internal fusion reactions. As part of its support for the ITER mission, the US fusion community is actively developing validated predictive models of the behavior of magnetically confined plasmas. In this talk, I will describe how the plasma community is using the latest high performance computing facilities to develop and refine our models of the nonlinear, multiscale plasma dynamics, and how recent advances in experimental diagnostics are allowing us to directly test and validate these models at an unprecedented level.

  15. Intense fusion neutron sources

    NASA Astrophysics Data System (ADS)

    Kuteev, B. V.; Goncharov, P. R.; Sergeev, V. Yu.; Khripunov, V. I.

    2010-04-01

    The review describes physical principles underlying efficient production of free neutrons, up-to-date possibilities and prospects of creating fission and fusion neutron sources with intensities of 1015-1021 neutrons/s, and schemes of production and application of neutrons in fusion-fission hybrid systems. The physical processes and parameters of high-temperature plasmas are considered at which optimal conditions for producing the largest number of fusion neutrons in systems with magnetic and inertial plasma confinement are achieved. The proposed plasma methods for neutron production are compared with other methods based on fusion reactions in nonplasma media, fission reactions, spallation, and muon catalysis. At present, intense neutron fluxes are mainly used in nanotechnology, biotechnology, material science, and military and fundamental research. In the near future (10-20 years), it will be possible to apply high-power neutron sources in fusion-fission hybrid systems for producing hydrogen, electric power, and technological heat, as well as for manufacturing synthetic nuclear fuel and closing the nuclear fuel cycle. Neutron sources with intensities approaching 1020 neutrons/s may radically change the structure of power industry and considerably influence the fundamental and applied science and innovation technologies. Along with utilizing the energy produced in fusion reactions, the achievement of such high neutron intensities may stimulate wide application of subcritical fast nuclear reactors controlled by neutron sources. Superpower neutron sources will allow one to solve many problems of neutron diagnostics, monitor nano-and biological objects, and carry out radiation testing and modification of volumetric properties of materials at the industrial level. Such sources will considerably (up to 100 times) improve the accuracy of neutron physics experiments and will provide a better understanding of the structure of matter, including that of the neutron itself.

  16. Atomic data for fusion

    SciTech Connect

    Hunter, H.T.; Kirkpatrick, M.I.; Alvarez, I.; Cisneros, C.; Phaneuf, R.A.; Barnett, C.F.

    1990-07-01

    This report provides a handbook of recommended cross-section and rate-coefficient data for inelastic collisions between hydrogen, helium and lithium atoms, molecules and ions, and encompasses more than 400 different reactions of primary interest in fusion research. Published experimental and theoretical data have been collected and evaluated, and the recommended data are presented in tabular, graphical and parametrized form. Processes include excitation and spectral line emission, charge exchange, ionization, stripping, dissociation and particle interchange reactions. The range of collision energies is appropriate to applications in fusion-energy research.

  17. Fusion welding process

    DOEpatents

    Thomas, Kenneth C.; Jones, Eric D.; McBride, Marvin A.

    1983-01-01

    A process for the fusion welding of nickel alloy steel members wherein a ferrite containing pellet is inserted into a cavity in one member and melted by a welding torch. The resulting weld nugget, a fusion of the nickel containing alloy from the members to be welded and the pellet, has a composition which is sufficiently low in nickel content such that ferrite phases occur within the weld nugget, resulting in improved weld properties. The steel alloys encompassed also include alloys containing carbon and manganese, considered nickel equivalents.

  18. Fusion for Space Propulsion

    NASA Technical Reports Server (NTRS)

    Thio, Y. C. Francis; Schmidt, George R.; Santarius, John F.; Turchi, Peter J.; Siemon, Richard E.; Rodgers, Stephen L. (Technical Monitor)

    2002-01-01

    The need for fusion propulsion for interplanetary flights is discussed. For a propulsion system, there are three important system attributes: (1) The absolute amount of energy available, (2) the propellant exhaust velocity, and (3) the jet power per unit mass of the propulsion system (specific power). For efficient and affordable human exploration of the solar system, propellant exhaust velocity in excess of 100 km/s and specific power in excess of 10 kW/kg are required. Chemical combustion obviously cannot meet the requirement in propellant exhaust velocity. Nuclear fission processes typically result in producing energy in the form of heat that needs to be manipulated at temperatures limited by materials to about 2,800 K. Using the fission energy to heat a low atomic weight propellant produces propellant velocity of the order of 10 kinds. Alternatively the fission energy can be converted into electricity that is used to accelerate particles to high exhaust velocity. However, the necessary power conversion and conditioning equipment greatly increases the mass of the propulsion system. Fundamental considerations in waste heat rejection and power conditioning in a fission electric propulsion system place a limit on its jet specific power to the order of about 0.2 kW/kg. If fusion can be developed for propulsion, it appears to have the best of all worlds - it can provide the largest absolute amount of energy, the propellant exhaust velocity (> 100 km/s), and the high specific jet power (> 10 kW/kg). An intermediate step towards fusion propulsion might be a bimodal system in which a fission reactor is used to provide some of the energy to drive a fusion propulsion unit. There are similarities as well as differences between applying fusion to propulsion and to terrestrial electrical power generation. The similarities are the underlying plasma and fusion physics, the enabling component technologies, the computational and the diagnostics capabilities. These physics and

  19. Measles Virus Fusion Protein: Structure, Function and Inhibition

    PubMed Central

    Plattet, Philippe; Alves, Lisa; Herren, Michael; Aguilar, Hector C.

    2016-01-01

    Measles virus (MeV), a highly contagious member of the Paramyxoviridae family, causes measles in humans. The Paramyxoviridae family of negative single-stranded enveloped viruses includes several important human and animal pathogens, with MeV causing approximately 120,000 deaths annually. MeV and canine distemper virus (CDV)-mediated diseases can be prevented by vaccination. However, sub-optimal vaccine delivery continues to foster MeV outbreaks. Post-exposure prophylaxis with antivirals has been proposed as a novel strategy to complement vaccination programs by filling herd immunity gaps. Recent research has shown that membrane fusion induced by the morbillivirus glycoproteins is the first critical step for viral entry and infection, and determines cell pathology and disease outcome. Our molecular understanding of morbillivirus-associated membrane fusion has greatly progressed towards the feasibility to control this process by treating the fusion glycoprotein with inhibitory molecules. Current approaches to develop anti-membrane fusion drugs and our knowledge on drug resistance mechanisms strongly suggest that combined therapies will be a prerequisite. Thus, discovery of additional anti-fusion and/or anti-attachment protein small-molecule compounds may eventually translate into realistic therapeutic options. PMID:27110811

  20. Multisensor data fusion algorithm development

    SciTech Connect

    Yocky, D.A.; Chadwick, M.D.; Goudy, S.P.; Johnson, D.K.

    1995-12-01

    This report presents a two-year LDRD research effort into multisensor data fusion. We approached the problem by addressing the available types of data, preprocessing that data, and developing fusion algorithms using that data. The report reflects these three distinct areas. First, the possible data sets for fusion are identified. Second, automated registration techniques for imagery data are analyzed. Third, two fusion techniques are presented. The first fusion algorithm is based on the two-dimensional discrete wavelet transform. Using test images, the wavelet algorithm is compared against intensity modulation and intensity-hue-saturation image fusion algorithms that are available in commercial software. The wavelet approach outperforms the other two fusion techniques by preserving spectral/spatial information more precisely. The wavelet fusion algorithm was also applied to Landsat Thematic Mapper and SPOT panchromatic imagery data. The second algorithm is based on a linear-regression technique. We analyzed the technique using the same Landsat and SPOT data.

  1. Workmanship standards for fusion welding

    NASA Technical Reports Server (NTRS)

    Phillips, M. D.

    1967-01-01

    Workmanship standards manual defines practices, that adhere to rigid codes and specifications, for fusion welding of component piping, assemblies, and systems. With written and pictorial presentations, it is part of the operating procedure for fusion welding.

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

    PubMed

    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.

  3. The Multifaceted Role of SNARE Proteins in Membrane Fusion

    PubMed Central

    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. PMID:28163686

  4. Fusion Engineering Device design description

    SciTech Connect

    Flanagan, C.A.; Steiner, D.; Smith, G.E.

    1981-12-01

    The US Magnetic Fusion Engineering Act of 1980 calls for the operation of a Fusion Engineering Device (FED) by 1990. It is the intent of the Act that the FED, in combination with other testing facilities, will establish the engineering feasibility of magnetic fusion energy. During 1981, the Fusion Engineering Design Center (FEDC), under the guidance of a Technical Management Board (TMB), developed a baseline design for the FED. This design is summarized herein.

  5. Fusion engineering device design description

    SciTech Connect

    Flanagan, C.A.; Steiner, D.; Smith, G.E.

    1981-12-01

    The US Magnetic Fusion Engineering Act of 1980 calls for the operation of a Fusion Engineering Device (FED) by 1990. It is the intent of the Act that the FED, in combination with other testing facilities, will establish the engineering feasibility of magnetic fusion energy. During 1981, the Fusion Engineering Design Center (FEDC), under the guidance of a Technical Management Board (TMB), developed a baseline design for the FED. This design is summarized herein.

  6. Neuregulin-1 Regulates Cortical Inhibitory Neuron Dendrite and Synapse Growth through DISC1

    PubMed Central

    Kwan, Vickie

    2016-01-01

    Cortical inhibitory neurons play crucial roles in regulating excitatory synaptic networks and cognitive function and aberrant development of these cells have been linked to neurodevelopmental disorders. The secreted neurotrophic factor Neuregulin-1 (NRG1) and its receptor ErbB4 are established regulators of inhibitory neuron connectivity, but the developmental signalling mechanisms regulating this process remain poorly understood. Here, we provide evidence that NRG1-ErbB4 signalling functions through the multifunctional scaffold protein, Disrupted in Schizophrenia 1 (DISC1), to regulate the development of cortical inhibitory interneuron dendrite and synaptic growth. We found that NRG1 increases inhibitory neuron dendrite complexity and glutamatergic synapse formation onto inhibitory neurons and that this effect is blocked by expression of a dominant negative DISC1 mutant, or DISC1 knockdown. We also discovered that NRG1 treatment increases DISC1 expression and its localization to glutamatergic synapses being made onto cortical inhibitory neurons. Mechanistically, we determined that DISC1 binds ErbB4 within cortical inhibitory neurons. Collectively, these data suggest that a NRG1-ErbB4-DISC1 signalling pathway regulates the development of cortical inhibitory neuron dendrite and synaptic growth. Given that NRG1, ErbB4, and DISC1 are schizophrenia-linked genes, these findings shed light on how independent risk factors may signal in a common developmental pathway that contributes to neural connectivity defects and disease pathogenesis. PMID:27847649

  7. Mars manned fusion spaceship

    SciTech Connect

    Hedrick, J.; Buchholtz, B.; Ward, P.; Freuh, J.; Jensen, E.

    1991-01-01

    Fusion Propulsion has an enormous potential for space exploration in the near future. In the twenty-first century, a usable and efficient fusion rocket will be developed and in use. Because of the great distance between other planets and Earth, efficient use of time, fuel, and payload is essential. A nuclear spaceship would provide greater fuel efficiency, less travel time, and a larger payload. Extended missions would give more time for research, experiments, and data acquisition. With the extended mission time, a need for an artificial environment exists. The topics of magnetic fusion propulsion, living modules, artificial gravity, mass distribution, space connection, and orbital transfer to Mars are discussed. The propulsion system is a magnetic fusion reactor based on a tandem mirror design. This allows a faster, shorter trip time and a large thrust to weight ratio. The fuel proposed is a mixture of deuterium and helium. Helium can be obtained from lunar mining. There will be minimal external radiation from the reactor resulting in a safe, efficient propulsion system.

  8. Mars manned fusion spaceship

    NASA Technical Reports Server (NTRS)

    Hedrick, James; Buchholtz, Brent; Ward, Paul; Freuh, Jim; Jensen, Eric

    1991-01-01

    Fusion Propulsion has an enormous potential for space exploration in the near future. In the twenty-first century, a usable and efficient fusion rocket will be developed and in use. Because of the great distance between other planets and Earth, efficient use of time, fuel, and payload is essential. A nuclear spaceship would provide greater fuel efficiency, less travel time, and a larger payload. Extended missions would give more time for research, experiments, and data acquisition. With the extended mission time, a need for an artificial environment exists. The topics of magnetic fusion propulsion, living modules, artificial gravity, mass distribution, space connection, and orbital transfer to Mars are discussed. The propulsion system is a magnetic fusion reactor based on a tandem mirror design. This allows a faster, shorter trip time and a large thrust to weight ratio. The fuel proposed is a mixture of deuterium and helium-3. Helium-3 can be obtained from lunar mining. There will be minimal external radiation from the reactor resulting in a safe, efficient propulsion system.

  9. Auditory Fusion in Children.

    ERIC Educational Resources Information Center

    Davis, Sylvia M.; McCroskey, Robert L.

    1980-01-01

    Focuses on auditory fusion (defined in terms of a listerner's ability to distinguish paired acoustic events from single acoustic events) in 3- to 12-year-old children. The subjects listened to 270 pairs of tones controlled for frequency, intensity, and duration. (CM)

  10. A fusion of minds

    NASA Astrophysics Data System (ADS)

    Corfield, Richard

    2013-02-01

    Mystery still surrounds the visit of the astronomer Sir Bernard Lovell to the Soviet Union in 1963. But his collaboration - and that of other British scientists - eased geopolitical tensions at the height of the Cold War and paved the way for today's global ITER fusion project, as Richard Corfield explains.

  11. Synergetic Multisensor Fusion

    DTIC Science & Technology

    1990-11-30

    technology have led to increased interest in using DEMs for navigation and other applications. In particular, DEMs are attractive for use in aircraft...Multisensor Fusion for Computer Vision [67]. 30 6. POSI!IONAL zSTIM&TION TECEnIQUzs FOR AN OUTDOOR MOBLE ROBOT The autonomous navigation of mobile robots is

  12. Fusion reactor materials

    SciTech Connect

    none,

    1989-01-01

    This paper discuses the following topics on fusion reactor materials: irradiation, facilities, test matrices, and experimental methods; dosimetry, damage parameters, and activation calculations; materials engineering and design requirements; fundamental mechanical behavior; radiation effects; development of structural alloys; solid breeding materials; and ceramics.

  13. LASSA: Emotion Detection via Information Fusion

    PubMed Central

    Yu, Ning; Kübler, Sandra; Herring, Joshua; Hsu, Yu-Yin; Israel, Ross; Smiley, Charese

    2012-01-01

    Due to the complexity of emotions in suicide notes and the subtle nature of sentiments, this study proposes a fusion approach to tackle the challenge of sentiment classification in suicide notes: leveraging WordNet-based lexicons, manually created rules, character-based n-grams, and other linguistic features. Although our results are not satisfying, some valuable lessons are learned and promising future directions are identified. PMID:22879762

  14. Human-Centered Fusion Framework

    SciTech Connect

    Posse, Christian; White, Amanda M.; Beagley, Nathaniel

    2007-05-16

    In recent years the benefits of fusing signatures extracted from large amounts of distributed and/or heterogeneous data sources have been largely documented in various problems ranging from biological protein function prediction to cyberspace monitoring. In spite of significant progress in information fusion research, there is still no formal theoretical framework for defining various types of information fusion systems, defining and analyzing relations among such types, and designing information fusion systems using a formal method approach. Consequently, fusion systems are often poorly understood, are less than optimal, and/or do not suit user needs. To start addressing these issues, we outline a formal humancentered fusion framework for reasoning about fusion strategies. Our approach relies on a new taxonomy for fusion strategies, an alternative definition of information fusion in terms of parameterized paths in signature related spaces, an algorithmic formalization of fusion strategies and a library of numeric and dynamic visual tools measuring the impact as well as the impact behavior of fusion strategies. Using a real case of intelligence analysis we demonstrate that the proposed framework enables end users to rapidly 1) develop and implement alternative fusion strategies, 2) understand the impact of each strategy, 3) compare the various strategies, and 4) perform the above steps without having to know the mathematical foundations of the framework. We also demonstrate that the human impact on a fusion system is critical in the sense that small changes in strategies do not necessarily correspond to small changes in results.

  15. Graphite for fusion energy applications

    SciTech Connect

    Eatherly, W.P.; Clausing, R.E.; Strehlow, R.A.; Kennedy, C.R.; Mioduszewski, P.K.

    1987-03-01

    Graphite is in widespread and beneficial use in present fusion energy devices. This report reflects the view of graphite materials scientists on using graphite in fusion devices. Graphite properties are discussed with emphasis on application to fusion reactors. This report is intended to be introductory and descriptive and is not intended to serve as a definitive information source. (JDH)

  16. Physiological Awareness Is Negatively Related to Inhibitory Functioning in Tourette Syndrome.

    PubMed

    Eddy, Clare M; Rickards, Hugh E; Cavanna, Andrea E

    2014-03-01

    In Tourette syndrome (TS), tics are characteristically preceded by subjective bodily experiences referred to as premonitory sensations. Premonitory sensory phenomena play a key role in behavior therapy for tics, the success of which has also been suggested to be related to inhibitory functioning. We investigated whether TS was associated with altered internal physiological awareness and how this may interact with the neuropsychological characteristics of TS. We compared the awareness of bodily sensations and inhibitory functioning in 18 adult patients with uncomplicated TS and 18 healthy controls. We also explored relationships between these factors, tic severity, and premonitory sensations. Patients with TS exhibited significantly higher scores on the Private Body Consciousness (PBC) scale and inhibitory deficits on traditional and emotional Stroop tests. PBC scores were not correlated with premonitory sensations or tic severity. However, inhibitory functioning was negatively related to PBC scores and premonitory sensations. Relationships between inhibitory performance and tic severity were complex. In conclusion, patients with TS exhibit increased PBC in addition to inhibitory deficits. Aspects of inhibitory functioning are related to PBC, premonitory sensations, and tic severity. Complex interplay between neuropsychological and neurophysiological mechanisms could therefore determine tic severity and the success of behavioral treatments.

  17. Identification of candidate angiogenic inhibitors processed by matrix metalloproteinase 2 (MMP-2) in cell-based proteomic screens: disruption of vascular endothelial growth factor (VEGF)/heparin affin regulatory peptide (pleiotrophin) and VEGF/Connective tissue growth factor angiogenic inhibitory complexes by MMP-2 proteolysis.

    PubMed

    Dean, Richard A; Butler, Georgina S; Hamma-Kourbali, Yamina; Delbé, Jean; Brigstock, David R; Courty, José; Overall, Christopher M

    2007-12-01

    Matrix metalloproteinases (MMPs) exert both pro- and antiangiogenic functions by the release of cytokines or proteolytically generated angiogenic inhibitors from extracellular matrix and basement membrane remodeling. In the Mmp2-/- mouse neovascularization is greatly reduced, but the mechanistic aspects of this remain unclear. Using isotope-coded affinity tag labeling of proteins analyzed by multidimensional liquid chromatography and tandem mass spectrometry we explored proteome differences between Mmp2-/- cells and those rescued by MMP-2 transfection. Proteome signatures that are hallmarks of proteolysis revealed cleavage of many known MMP-2 substrates in the cellular context. Proteomic evidence of MMP-2 processing of novel substrates was found. Insulin-like growth factor binding protein 6, follistatin-like 1, and cystatin C protein cleavage by MMP-2 was biochemically confirmed, and the cleavage sites in heparin affin regulatory peptide (HARP; pleiotrophin) and connective tissue growth factor (CTGF) were sequenced by matrix-assisted laser desorption ionization-time of flight mass spectrometry. MMP-2 processing of HARP and CTGF released vascular endothelial growth factor (VEGF) from angiogenic inhibitory complexes. The cleaved HARP N-terminal domain increased HARP-induced cell proliferation, whereas the HARP C-terminal domain was antagonistic and decreased cell proliferation and migration. Hence the unmasking of cytokines, such as VEGF, by metalloproteinase processing of their binding proteins is a new mechanism in the control of cytokine activation and angiogenesis.

  18. Defining inhibitory neurone function in respiratory circuits: opportunities with optogenetics?

    PubMed

    Abdala, Ana Paula; Paton, Julian F R; Smith, Jeffrey C

    2015-07-15

    Pharmacological and mathematical modelling studies support the view that synaptic inhibition in mammalian brainstem respiratory circuits is essential for generating normal and stable breathing movements. GABAergic and glycinergic neurones are known components of these circuits but their precise functional roles have not been established, especially within key microcircuits of the respiratory pre-Bötzinger (pre-BötC) and Bötzinger (BötC) complexes involved in phasic control of respiratory pump and airway muscles. Here, we review briefly current concepts of relevant complexities of inhibitory synapses and the importance of synaptic inhibition in the operation of these microcircuits. We highlight results and limitations of classical pharmacological studies that have suggested critical functions of synaptic inhibition. We then explore the potential opportunities for optogenetic strategies that represent a promising new approach for interrogating function of inhibitory circuits, including a hypothetical wish list for optogenetic approaches to allow expedient application of this technology. We conclude that recent technical advances in optogenetics should provide a means to understand the role of functionally select and regionally confined subsets of inhibitory neurones in key respiratory circuits such as those in the pre-BötC and BötC.

  19. The role of the C terminus of the SNARE protein SNAP-25 in fusion pore opening and a model for fusion pore mechanics

    PubMed Central

    Fang, Qinghua; Berberian, Khajak; Gong, Liang-Wei; Hafez, Ismail; Sørensen, Jakob B.; Lindau, Manfred

    2008-01-01

    Formation of a fusion pore between a vesicle and its target membrane is thought to involve the so-called SNARE protein complex. However, there is no mechanistic model explaining how the fusion pore is opened by conformational changes in the SNARE complex. It has been suggested that C-terminal zipping triggers fusion pore opening. A SNAP-25 mutant named SNAP-25Δ9 (lacking the last nine C-terminal residues) should lead to a less-tight C-terminal zipping. Single exocytotic events in chromaffin cells expressing this mutant were characterized by carbon fiber amperometry and cell-attached patch capacitance measurements. Cells expressing SNAP-25Δ9 displayed smaller amperometric “foot-current” currents, reduced fusion pore conductances, and lower fusion pore expansion rates. We propose that SNARE/lipid complexes form proteolipid fusion pores. Fusion pores involving the SNAP-25Δ9 mutant will be less tightly zipped and may lead to a longer fusion pore structure, consistent with the observed decrease of fusion pore conductance. PMID:18829435

  20. Molecular inhibitory mechanism of tricin on tyrosinase

    NASA Astrophysics Data System (ADS)

    Mu, Yan; Li, Lin; Hu, Song-Qing

    2013-04-01

    Tricin was evaluated as a type of tyrosinase inhibitor with good efficacy compared to arbutin. Tricin functioned as a non-competitive inhibitor of tyrosinase, with an equilibrium constant of 2.30 mmol/L. The molecular mechanisms underlying the inhibition of tyrosinase by tricin were investigated by means of circular dichroism spectra, fluorescence quenching and molecular docking. These assays demonstrated that the interactions between tricin and tyrosinase did not change the secondary structure. The interaction of tricin with residues in the hydrophobic pocket of tyrosinase was revealed by fluorescence quenching; the complex was stabilized by hydrophobic associations and hydrogen bonding (with residues Asn80 and Arg267). Docking results implied that the possible inhibitory mechanisms may be attributed to the stereospecific blockade effects of tricin on substrates or products and flexible conformation alterations in the tyrosinase active center caused by weak interactions between tyrosinase and tricin. The application of this type of flavonoid as a tyrosinase inhibitor will lead to significant advances in the field of depigmentation.

  1. Accelerators for heavy ion fusion

    SciTech Connect

    Bangerter, R.O.

    1985-10-01

    Large fusion devices will almost certainly produce net energy. However, a successful commercial fusion energy system must also satisfy important engineering and economic constraints. Inertial confinement fusion power plants driven by multi-stage, heavy-ion accelerators appear capable of meeting these constraints. The reasons behind this promising outlook for heavy-ion fusion are given in this report. This report is based on the transcript of a talk presented at the Symposium on Lasers and Particle Beams for Fusion and Strategic Defense at the University of Rochester on April 17-19, 1985.

  2. Surgical fusion in childhood spondylolisthesis.

    PubMed

    Stanton, R P; Meehan, P; Lovell, W W

    1985-01-01

    Twenty cases of surgical fusion for spondylolisthesis were reviewed at the Scottish Rite Hospital (Atlanta, GA, U.S.A.) to determine whether a procedure other than a simple posterolateral fusion is necessary for most patients. The patients were treated postoperatively with pantaloon spica cast immobilization. The fusion rate was high (90%), and patient satisfaction was high. One patient developed neurologic loss postoperatively. Two patients' slips progressed greater than 10% before solid fusion occurred. Thus, bilateral posterolateral fusion, followed by pantaloon spica cast immobilization, is effective for patients with symptomatic spondylolisthesis or asymptomatic children with grade 3 or greater slips. Reduction was not performed in this series.

  3. The spheromak as a compact fusion reactor

    SciTech Connect

    Hagenson, R.L.; Krakowski, R.A.

    1987-03-01

    After summarizing the economic and utility-based rationale for compact, higher-power-density fusion reactors, the gun-sustained spheromak concept is explored as one of a number of poloidal-field-dominated confinement configurations that might improve the prospects for economically attractive and operationally simplified fusion power plants. Using a comprehensive physics/engineering/costing model for the spheromak, guided by realistic engineering constraints and physics extrapolation, a range of cost-optimized reactor design points is presented, and the sensitivity of cost to key physics, engineering, and operational variables is reported. The results presented herein provide the basis for conceptual engineering designs of key fusion-power-core (FPC) subsystems and more detailed plasma modeling of this promising, high mass-power-density concept, which stresses single-piece FPC maintenance, steady-state current drive through electrostatic magnetic helicity injection, a simplified co-axial electrode-divertor, and efficient resistive-coal equilibrium-field coils. The optimal FPC size and the cost estimates project a system that competes aggressively with the best offered by alternative energy sources while simplifying considerably the complexity that has generally been associated with most approaches to magnetic fusion energy.

  4. Simultaneous Segmentation and Statistical Label Fusion.

    PubMed

    Asman, Andrew J; Landmana, Bennett A

    2012-02-23

    Labeling or segmentation of structures of interest in medical imaging plays an essential role in both clinical and scientific understanding. Two of the common techniques to obtain these labels are through either fully automated segmentation or through multi-atlas based segmentation and label fusion. Fully automated techniques often result in highly accurate segmentations but lack the robustness to be viable in many cases. On the other hand, label fusion techniques are often extremely robust, but lack the accuracy of automated algorithms for specific classes of problems. Herein, we propose to perform simultaneous automated segmentation and statistical label fusion through the reformulation of a generative model to include a linkage structure that explicitly estimates the complex global relationships between labels and intensities. These relationships are inferred from the atlas labels and intensities and applied to the target using a non-parametric approach. The novelty of this approach lies in the combination of previously exclusive techniques and attempts to combine the accuracy benefits of automated segmentation with the robustness of a multi-atlas based approach. The accuracy benefits of this simultaneous approach are assessed using a multi-label multi- atlas whole-brain segmentation experiment and the segmentation of the highly variable thyroid on computed tomography images. The results demonstrate that this technique has major benefits for certain types of problems and has the potential to provide a paradigm shift in which the lines between statistical label fusion and automated segmentation are dramatically blurred.

  5. Developmental broadening of inhibitory sensory maps.

    PubMed

    Quast, Kathleen B; Ung, Kevin; Froudarakis, Emmanouil; Huang, Longwen; Herman, Isabella; Addison, Angela P; Ortiz-Guzman, Joshua; Cordiner, Keith; Saggau, Peter; Tolias, Andreas S; Arenkiel, Benjamin R

    2017-02-01

    Sensory maps are created by networks of neuronal responses that vary with their anatomical position, such that representations of the external world are systematically and topographically organized in the brain. Current understanding from studying excitatory maps is that maps are sculpted and refined throughout development and/or through sensory experience. Investigating the mouse olfactory bulb, where ongoing neurogenesis continually supplies new inhibitory granule cells into existing circuitry, we isolated the development of sensory maps formed by inhibitory networks. Using in vivo calcium imaging of odor responses, we compared functional responses of both maturing and established granule cells. We found that, in contrast to the refinement observed for excitatory maps, inhibitory sensory maps became broader with maturation. However, like excitatory maps, inhibitory sensory maps are sensitive to experience. These data describe the development of an inhibitory sensory map as a network, highlighting the differences from previously described excitatory maps.

  6. An invasive podosome-like structure promotes fusion pore formation during myoblast fusion

    PubMed Central

    Sens, Kristin L.; Zhang, Shiliang; Jin, Peng; Duan, Rui; Zhang, Guofeng; Luo, Fengbao; Parachini, Lauren

    2010-01-01

    Recent studies in Drosophila have implicated actin cytoskeletal remodeling in myoblast fusion, but the cellular mechanisms underlying this process remain poorly understood. Here we show that actin polymerization occurs in an asymmetric and cell type–specific manner between a muscle founder cell and a fusion-competent myoblast (FCM). In the FCM, a dense F-actin–enriched focus forms at the site of fusion, whereas a thin sheath of F-actin is induced along the apposing founder cell membrane. The FCM-specific actin focus invades the apposing founder cell with multiple finger-like protrusions, leading to the formation of a single-channel macro fusion pore between the two muscle cells. Two actin nucleation–promoting factors of the Arp2/3 complex, WASP and Scar, are required for the formation of the F-actin foci, whereas WASP but not Scar promotes efficient foci invasion. Our studies uncover a novel invasive podosome-like structure (PLS) in a developing tissue and reveal a previously unrecognized function of PLSs in facilitating cell membrane juxtaposition and fusion. PMID:21098115

  7. The path to fusion power.

    PubMed

    Llewellyn Smith, Chris; Ward, David

    2007-04-15

    Fusion is potentially an environmentally responsible and intrinsically safe source of essentially limitless power. It should be possible to build viable fusion power stations, and it looks as if the cost of fusion power will be reasonable. But time is needed to further develop the technology and to test in power station conditions the materials that would be used in their construction. Assuming no major adverse surprises, an orderly fusion development programme could lead to a prototype fusion power station putting electricity into the grid within 30 years, with commercial fusion power following some 10 or more years later. In the second half of the century, fusion could therefore be an important part of the portfolio of measures that are needed to cope with rising demand for energy in an environmentally responsible manner. In this paper, we describe the basics of fusion, its potential attractions, the status of fusion R&D, the remaining challenges and how they will be tackled at the International Tokamak Experimental Reactor and the proposed International Fusion Materials Irradiation Facility, and the timetable for the subsequent commercialization of fusion power.

  8. The Need for Fusion Propulsion

    NASA Technical Reports Server (NTRS)

    Cassibry, Jason

    2005-01-01

    Fusion propulsion is inevitable if the human race remains dedicated to exploration of the solar system. There are fundamental reasons why fusion surpasses more traditional approaches to routine crewed missions to Mars, crewed missions to the outer planets, and deep space high speed robotic missions, assuming that reduced trip times, increased payloads, and higher available power are desired. A recent series of informal discussions were held among members from government, academia, and industry concerning fusion propulsion. We compiled a sufficient set of arguments for utilizing fusion in space. If the U.S. is to lead the effort and produce a working system in a reasonable amount of time, NASA must take the initiative, relying on, but not waiting for, DOE guidance. In this talk those arguments for fusion propulsion are presented, along with fusion enabled mission examples, fusion technology trade space, and a proposed outline for future efforts.

  9. Capturing a fusion intermediate of influenza hemagglutinin with a cholesterol-conjugated peptide, a new antiviral strategy for influenza virus.

    PubMed

    Lee, Kelly K; Pessi, Antonello; Gui, Long; Santoprete, Alessia; Talekar, Aparna; Moscona, Anne; Porotto, Matteo

    2011-12-09

    We previously described fusion-inhibitory peptides that are targeted to the cell membrane by cholesterol conjugation and potently inhibit enveloped viruses that fuse at the cell surface, including HIV, parainfluenza, and henipaviruses. However, for viruses that fuse inside of intracellular compartments, fusion-inhibitory peptides have exhibited very low antiviral activity. We propose that for these viruses, too, membrane targeting via cholesterol conjugation may yield potent compounds. Here we compare the activity of fusion-inhibitory peptides derived from the influenza hemagglutinin (HA) and show that although the unconjugated peptides are inactive, the cholesterol-conjugated compounds are effective inhibitors of infectivity and membrane fusion. We hypothesize that the cholesterol moiety, by localizing the peptides to the target cell membrane, allows the peptides to follow the virus to the intracellular site of fusion. The cholesterol-conjugated peptides trap HA in a transient intermediate state after fusion is triggered but before completion of the refolding steps that drive the merging of the viral and cellular membranes. These results provide proof of concept for an antiviral strategy that is applicable to intracellularly fusing viruses, including known and emerging viral pathogens.

  10. Capturing a Fusion Intermediate of Influenza Hemagglutinin with a Cholesterol-conjugated Peptide, a New Antiviral Strategy for Influenza Virus*

    PubMed Central

    Lee, Kelly K.; Pessi, Antonello; Gui, Long; Santoprete, Alessia; Talekar, Aparna; Moscona, Anne; Porotto, Matteo

    2011-01-01

    We previously described fusion-inhibitory peptides that are targeted to the cell membrane by cholesterol conjugation and potently inhibit enveloped viruses that fuse at the cell surface, including HIV, parainfluenza, and henipaviruses. However, for viruses that fuse inside of intracellular compartments, fusion-inhibitory peptides have exhibited very low antiviral activity. We propose that for these viruses, too, membrane targeting via cholesterol conjugation may yield potent compounds. Here we compare the activity of fusion-inhibitory peptides derived from the influenza hemagglutinin (HA) and show that although the unconjugated peptides are inactive, the cholesterol-conjugated compounds are effective inhibitors of infectivity and membrane fusion. We hypothesize that the cholesterol moiety, by localizing the peptides to the target cell membrane, allows the peptides to follow the virus to the intracellular site of fusion. The cholesterol-conjugated peptides trap HA in a transient intermediate state after fusion is triggered but before completion of the refolding steps that drive the merging of the viral and cellular membranes. These results provide proof of concept for an antiviral strategy that is applicable to intracellularly fusing viruses, including known and emerging viral pathogens. PMID:21994935

  11. Fusion Data Grid Service

    NASA Astrophysics Data System (ADS)

    Shasharina, Svetlana; Wang, Nanbor

    2004-11-01

    Simulations and experiments in the fusion and plasma physics community generate large datasets at remote sites. Visualization and analysis of these datasets are difficult because of the incompatibility among the various data formats adopted by simulation, experiments, and analysis tools, and the large sizes of analyzed data. Grids and Web Services technologies are capable of providing solutions for such heterogeneous settings, but need to be customized to the field-specific needs and merged with distributed technologies currently used by the community. This paper describes how we are addressing these issues in the Fusion Grid Service under development. We also present performance results of relevant data transfer mechanisms including binary SOAP, DIME, GridFTP and MDSplus and CORBA. We will describe the status of data converters (between HDF5 and MDSplus data types), developed in collaboration with MIT (J. Stillerman). Finally, we will analyze bottlenecks of MDSplus data transfer mechanism (work performed in collaboration with General Atomics (D. Schissel and M. Qian).

  12. Experiments in cold fusion

    SciTech Connect

    Palmer, E.P.

    1986-03-28

    The work of Steve Jones and others in muon-catalyzed cold fusion of deuterium and hydrogen suggests the possibility of such fusion catalyzed by ions, or combinations of atoms, or more-or-less free electrons in solid and liquid materials. A hint that this might occur naturally comes from the heat generated in volcanic action in subduction zones on the earth. It is questionable whether the potential energy of material raised to the height of a midocean ridge and falling to the depth of an ocean trench can produce the geothermal effects seen in the volcanoes of subduction zones. If the ridge, the trench, the plates, and the asthenosphere are merely visible effects of deeper density-gradient driven circulations, it is still uncertain that observed energy-concentration effects fit the models.

  13. Fusion pumped laser

    DOEpatents

    Pappas, D.S.

    1987-07-31

    The apparatus of this invention may comprise a system for generating laser radiation from a high-energy neutron source. The neutron source is a tokamak fusion reactor generating a long pulse of high-energy neutrons and having a temperature and magnetic field effective to generate a neutron flux of at least 10/sup 15/ neutrons/cm/sup 2//center dot/s. Conversion means are provided adjacent the fusion reactor at a location operable for converting the high-energy neutrons to an energy source with an intensity and energy effective to excite a preselected lasing medium. A lasing medium is spaced about and responsive to the energy source to generate a population inversion effective to support laser oscillations for generating output radiation. 2 figs., 2 tabs.

  14. Unconventional approaches to fusion

    SciTech Connect

    Brunelli, B.; Leotta, G.G.

    1982-01-01

    This volume is dedicated to unconventional approaches to fusionthose thermonuclear reactors that, in comparison with Tokamak and other main lines, have received little attention in the worldwide scientific community. Many of the approaches considered are still in the embryonic stages. The authors-an international group of active nuclear scientists and engineers-focus on the parameters achieved in the use of these reactors and on the meaning of the most recent physical studies and their implications for the future. They also compare these approaches with conventional ones, the Tokamak in particular, stressing the non-plasma-physics requirements of fusion reactors. Unconventional compact toroids, linear systems, and multipoles are considered, as are the ''almost conventional'' fusion machines: stellarators, mirrors, reversed-field pinches, and EBT.

  15. Maximum Likelihood Fusion Model

    DTIC Science & Technology

    2014-08-09

    data fusion, hypothesis testing,maximum likelihood estimation, mobile robot navigation REPORT DOCUMENTATION PAGE 11. SPONSOR/MONITOR’S REPORT...61 vi 9 Bibliography 62 vii 10 LIST OF FIGURES 1.1 Illustration of mobile robotic agents. Land rovers such as (left) Pioneer robots ...simultaneous localization and mapping 1 15 Figure 1.1: Illustration of mobile robotic agents. Land rovers such as (left) Pioneer robots , (center) Segways

  16. Fusion development and technology

    SciTech Connect

    Montgomery, D.B.

    1992-01-01

    This report discusses the following: superconducting magnet technology; high field superconductors; advanced magnetic system and divertor development; poloidal field coils; gyrotron development; commercial reactor studies--aries; ITER physics: alpha physics and alcator R D for ITER; lower hybrid current drive and heating in the ITER device; ITER superconducting PF scenario and magnet analysis; ITER systems studies; and safety, environmental and economic factors in fusion development.

  17. (Fusion energy research)

    SciTech Connect

    Phillips, C.A.

    1988-01-01

    This report discusses the following topics: principal parameters achieved in experimental devices (FY88); tokamak fusion test reactor; Princeton beta Experiment-Modification; S-1 Spheromak; current drive experiment; x-ray laser studies; spacecraft glow experiment; plasma deposition and etching of thin films; theoretical plasma; tokamak modeling; compact ignition tokamak; international thermonuclear experimental reactor; Engineering Department; Project Planning and Safety Office; quality assurance and reliability; and technology transfer.

  18. Modular Aneutronic Fusion Engine

    SciTech Connect

    Gary Pajer, Yosef Razin, Michael Paluszek, A.H. Glasser and Samuel Cohen

    2012-05-11

    NASA's JUNO mission will arrive at Jupiter in July 2016, after nearly five years in space. Since operational costs tend to rise with mission time, minimizing such times becomes a top priority. We present the conceptual design for a 10MW aneutronic fusion engine with high exhaust velocities that would reduce transit time for a Jupiter mission to eighteen months and enable more challenging exploration missions in the solar system and beyond. __________________________________________________

  19. Cold fusion studies

    NASA Astrophysics Data System (ADS)

    Hembree, D. M.; Burchfield, L. A.; Fuller, E. L., Jr.; Perey, F. G.; Mamantov, G.

    1990-06-01

    A series of experiments designed to detect the by-products expected from deuterium fusion occurring in the palladium and titanium cathodes of heavy water, D2O, electrolysis cells is reported. The primary purpose of this account is to outline the integrated experimental design developed to test the cold fusion hypothesis and to report preliminary results that support continuing the investigation. Apparent positive indicators of deuterium fusion were observed, but could not be repeated or proved to originate from the electrochemical cells. In one instance, two large increases in the neutron count rate, the largest of which exceeded the background by 27 standard deviations, were observed. In a separate experiment, one of the calorimetry cells appeared to be producing approximately 18 percent more power that the input value, but thermistor failure prevented an accurate recording of the event as a function of time. In general, the tritium levels in most cells followed the slow enrichment expected from the electrolysis of D2O containing a small amount of tritium. However, after 576 hours of electrolysis, one cell developed a tritium concentration approximately seven times greater than expected level.

  20. Stabilized Spheromak Fusion Reactors

    SciTech Connect

    Fowler, T

    2007-04-03

    The U.S. fusion energy program is focused on research with the potential for studying plasmas at thermonuclear temperatures, currently epitomized by the tokamak-based International Thermonuclear Experimental Reactor (ITER) but also continuing exploratory work on other plasma confinement concepts. Among the latter is the spheromak pursued on the SSPX facility at LLNL. Experiments in SSPX using electrostatic current drive by coaxial guns have now demonstrated stable spheromaks with good heat confinement, if the plasma is maintained near a Taylor state, but the anticipated high current amplification by gun injection has not yet been achieved. In future experiments and reactors, creating and maintaining a stable spheromak configuration at high magnetic field strength may require auxiliary current drive using neutral beams or RF power. Here we show that neutral beam current drive soon to be explored on SSPX could yield a compact spheromak reactor with current drive efficiency comparable to that of steady state tokamaks. Thus, while more will be learned about electrostatic current drive in coming months, results already achieved in SSPX could point to a productive parallel development path pursuing auxiliary current drive, consistent with plans to install neutral beams on SSPX in the near future. Among possible outcomes, spheromak research could also yield pulsed fusion reactors at lower capital cost than any fusion concept yet proposed.

  1. COG lobe B sub-complex engages v-SNARE GS15 and functions via regulated interaction with lobe A sub-complex

    PubMed Central

    Willett, Rose; Blackburn, Jessica Bailey; Climer, Leslie; Pokrovskaya, Irina; Kudlyk, Tetyana; Wang, Wei; Lupashin, Vladimir

    2016-01-01

    The conserved oligomeric Golgi (COG) complex is a peripheral membrane protein complex which orchestrates tethering of intra-Golgi vesicles. We found that COG1-4 (lobe A) and 5–8 (lobe B) protein assemblies are present as independent sub-complexes on cell membranes. Super-resolution microscopy demonstrates that COG sub-complexes are spatially separated on the Golgi with lobe A preferential localization on Golgi stacks and the presence of lobe B on vesicle-like structures, where it physically interacts with v-SNARE GS15. The localization and specific interaction of the COG sub-complexes with the components of vesicle tethering/fusion machinery suggests their different roles in the vesicle tethering cycle. We propose and test a novel model that employs association/disassociation of COG sub-complexes as a mechanism that directs vesicle tethering at Golgi membranes. We demonstrate that defective COG assembly or restriction of tethering complex disassembly by a covalent COG1-COG8 linkage is inhibitory to COG complex activity, supporting the model. PMID:27385402

  2. COG lobe B sub-complex engages v-SNARE GS15 and functions via regulated interaction with lobe A sub-complex.

    PubMed

    Willett, Rose; Blackburn, Jessica Bailey; Climer, Leslie; Pokrovskaya, Irina; Kudlyk, Tetyana; Wang, Wei; Lupashin, Vladimir

    2016-07-07

    The conserved oligomeric Golgi (COG) complex is a peripheral membrane protein complex which orchestrates tethering of intra-Golgi vesicles. We found that COG1-4 (lobe A) and 5-8 (lobe B) protein assemblies are present as independent sub-complexes on cell membranes. Super-resolution microscopy demonstrates that COG sub-complexes are spatially separated on the Golgi with lobe A preferential localization on Golgi stacks and the presence of lobe B on vesicle-like structures, where it physically interacts with v-SNARE GS15. The localization and specific interaction of the COG sub-complexes with the components of vesicle tethering/fusion machinery suggests their different roles in the vesicle tethering cycle. We propose and test a novel model that employs association/disassociation of COG sub-complexes as a mechanism that directs vesicle tethering at Golgi membranes. We demonstrate that defective COG assembly or restriction of tethering complex disassembly by a covalent COG1-COG8 linkage is inhibitory to COG complex activity, supporting the model.

  3. Trainable fusion rules. II. Small sample-size effects.

    PubMed

    Raudys, Sarunas

    2006-12-01

    Profound theoretical analysis is performed of small-sample properties of trainable fusion rules to determine in which situations neural network ensembles can improve or degrade classification results. We consider small sample effects, specific only to multiple classifiers system design in the two-category case of two important fusion rules: (1) linear weighted average (weighted voting), realized either by the standard Fisher classifier or by the single-layer perceptron, and (2) the non-linear Behavior-Knowledge-Space method. The small sample effects include: (i) training bias, i.e. learning sample size influence on generalization error of the base experts or of the fusion rule, (ii) optimistic biased outputs of the experts (self-boasting effect) and (iii) sample size impact on determining optimal complexity of the fusion rule. Correction terms developed to reduce the self-boasting effect are studied. It is shown that small learning sets increase classification error of the expert classifiers and damage correlation structure between their outputs. If the sizes of learning sets used to develop the expert classifiers are too small, non-trainable fusion rules can outperform more sophisticated trainable ones. A practical technique to fight sample size problems is a noise injection technique. The noise injection reduces the fusion rule's complexity and diminishes the expert's boasting bias.

  4. Dust in fusion plasmas: theory and modeling

    SciTech Connect

    Smirnov, R. D.; Pigarov, A. Yu.; Krasheninnikov, S. I.; Mendis, D. A.; Rosenberg, M.; Rudakov, D.; Tanaka, Y.; Rognlien, T. D.; Soboleva, T. K.; Shukla, P. K.; Bray, B. D.; West, W. P.; Roquemore, A. L.; Skinner, C. H.

    2008-09-07

    Dust may have a large impact on ITER-scale plasma experiments including both safety and performance issues. However, the physics of dust in fusion plasmas is very complex and multifaceted. Here, we discuss different aspects of dust dynamics including dust-plasma, and dust-surface interactions. We consider the models of dust charging, heating, evaporation/sublimation, dust collision with material walls, etc., which are suitable for the conditions of fusion plasmas. The physical models of all these processes have been incorporated into the DUST Transport (DUSTT) code. Numerical simulations demonstrate that dust particles are very mobile and accelerate to large velocities due to the ion drag force (cruise speed >100 m/s). Deep penetration of dust particles toward the plasma core is predicted. It is shown that DUSTT is capable of reproducing many features of recent dust-related experiments, but much more work is still needed.

  5. From nucleons to nuclei to fusion reactions

    NASA Astrophysics Data System (ADS)

    Quaglioni, S.; Navrátil, P.; Roth, R.; Horiuchi, W.

    2012-12-01

    Nuclei are prototypes of many-body open quantum systems. Complex aggregates of protons and neutrons that interact through forces arising from quantum chromo-dynamics, nuclei exhibit both bound and unbound states, which can be strongly coupled. In this respect, one of the major challenges for computational nuclear physics, is to provide a unified description of structural and reaction properties of nuclei that is based on the fundamental underlying physics: the constituent nucleons and the realistic interactions among them. This requires a combination of innovative theoretical approaches and high-performance computing. In this contribution, we present one of such promising techniques, the ab initio no-core shell model/resonating-group method, and discuss applications to light nuclei scattering and fusion reactions that power stars and Earth-base fusion facilities.

  6. Health-Enabled Smart Sensor Fusion Technology

    NASA Technical Reports Server (NTRS)

    Wang, Ray

    2012-01-01

    A process was designed to fuse data from multiple sensors in order to make a more accurate estimation of the environment and overall health in an intelligent rocket test facility (IRTF), to provide reliable, high-confidence measurements for a variety of propulsion test articles. The object of the technology is to provide sensor fusion based on a distributed architecture. Specifically, the fusion technology is intended to succeed in providing health condition monitoring capability at the intelligent transceiver, such as RF signal strength, battery reading, computing resource monitoring, and sensor data reading. The technology also provides analytic and diagnostic intelligence at the intelligent transceiver, enhancing the IEEE 1451.x-based standard for sensor data management and distributions, as well as providing appropriate communications protocols to enable complex interactions to support timely and high-quality flow of information among the system elements.

  7. From Nucleons To Nuclei To Fusion Reactions

    SciTech Connect

    Quaglioni, S; Navratil, P; Roth, R; Horiuchi, W

    2012-02-15

    Nuclei are prototypes of many-body open quantum systems. Complex aggregates of protons and neutrons that interact through forces arising from quantum chromo-dynamics, nuclei exhibit both bound and unbound states, which can be strongly coupled. In this respect, one of the major challenges for computational nuclear physics, is to provide a unified description of structural and reaction properties of nuclei that is based on the fundamental underlying physics: the constituent nucleons and the realistic interactions among them. This requires a combination of innovative theoretical approaches and high-performance computing. In this contribution, we present one of such promising techniques, the ab initio no-core shell model/resonating-group method, and discuss applications to light nuclei scattering and fusion reactions that power stars and Earth-base fusion facilities.

  8. IM30 triggers membrane fusion in cyanobacteria and chloroplasts.

    PubMed

    Hennig, Raoul; Heidrich, Jennifer; Saur, Michael; Schmüser, Lars; Roeters, Steven J; Hellmann, Nadja; Woutersen, Sander; Bonn, Mischa; Weidner, Tobias; Markl, Jürgen; Schneider, Dirk

    2015-05-08

    The thylakoid membrane of chloroplasts and cyanobacteria is a unique internal membrane system harbouring the complexes of the photosynthetic electron transfer chain. Despite their apparent importance, little is known about the biogenesis and maintenance of thylakoid membranes. Although membrane fusion events are essential for the formation of thylakoid membranes, proteins involved in membrane fusion have yet to be identified in photosynthetic cells or organelles. Here we show that IM30, a conserved chloroplast and cyanobacterial protein of approximately 30 kDa binds as an oligomeric ring in a well-defined geometry specifically to membranes containing anionic lipids. Triggered by Mg(2+), membrane binding causes destabilization and eventually results in membrane fusion. We propose that IM30 establishes contacts between internal membrane sites and promotes fusion to enable regulated exchange of proteins and/or lipids in cyanobacteria and chloroplasts.

  9. TRPM7 facilitates cholinergic vesicle fusion with the plasma membrane.

    PubMed

    Brauchi, Sebastian; Krapivinsky, Grigory; Krapivinsky, Luba; Clapham, David E

    2008-06-17

    TRPM7, of the transient receptor potential (TRP) family, is both an ion channel and a kinase. Previously, we showed that TRPM7 is located in the membranes of acetylcholine (ACh)-secreting synaptic vesicles of sympathetic neurons, forms a molecular complex with proteins of the vesicular fusion machinery, and is critical for stimulated neurotransmitter release. Here, we targeted pHluorin to small synaptic-like vesicles (SSLV) in PC12 cells and demonstrate that it can serve as a single-vesicle plasma membrane fusion reporter. In PC12 cells, as in sympathetic neurons, TRPM7 is located in ACh-secreting SSLVs. TRPM7 knockdown by siRNA, or abolishing channel activity by expression of a dominant negative TRPM7 pore mutant, decreased the frequency of spontaneous and voltage-stimulated SSLV fusion events without affecting large dense core vesicle secretion. We conclude that the conductance of TRPM7 across the vesicle membrane is important in SSLV fusion.

  10. Role of the synaptobrevin C terminus in fusion pore formation

    PubMed Central

    Ngatchou, Annita N.; Kisler, Kassandra; Fang, Qinghua; Walter, Alexander M.; Zhao, Ying; Bruns, Dieter; Sørensen, Jakob B.; Lindau, Manfred

    2010-01-01

    Neurotransmitter release is mediated by the SNARE proteins synaptobrevin II (sybII, also known as VAMP2), syntaxin, and SNAP-25, generating a force transfer to the membranes and inducing fusion pore formation. However, the molecular mechanism by which this force leads to opening of a fusion pore remains elusive. Here we show that the ability of sybII to support exocytosis is inhibited by addition of one or two residues to the sybII C terminus depending on their energy of transfer from water to the membrane interface, following a Boltzmann distribution. These results suggest that following stimulation, the SNARE complex pulls the C terminus of sybII deeper into the vesicle membrane. We propose that this movement disrupts the vesicular membrane continuity leading to fusion pore formation. In contrast to current models, the experiments suggest that fusion pore formation begins with molecular rearrangements at the intravesicular membrane leaflet and not between the apposed cytoplasmic leaflets. PMID:20937897

  11. [Image fusion in medical radiology].

    PubMed

    Burger, C

    1996-07-20

    Image fusion supports the correlation between images of two or more studies of the same organ. First, the effect of differing geometries during image acquisitions, such as a head tilt, is compensated for. As a consequence, congruent images can easily be obtained. Instead of merely putting them side by side in a static manner and burdening the radiologist with the whole correlation task, image fusion supports him with interactive visualization techniques. This is especially worthwhile for small lesions as they can be more precisely located. Image fusion is feasible today. Easy and robust techniques are readily available, and furthermore DICOM, a rapidly evolving data exchange standard, diminishes the once severe compatibility problems for image data originating from systems of different manufacturers. However, the current solutions for image fusion are not yet established enough for a high throughput of fusion studies. Thus, for the time being image fusion is most appropriately confined to clinical research studies.

  12. Inhibitory Receptors of the Immune System: Functions and Therapeutic Implications

    PubMed Central

    Zhang, Jian; Xiao, Xiang; Liu, Wentao; Demirci, Gulcin; Li, Xian C

    2009-01-01

    The immune system has a remarkable ability to respond to seemingly endless antigens. In essence, a productive immune response takes place along a well defined but treacherous line, that is to effectively eradicate pathogens, and at the same time avoid causing damage to self organs. This type of response is fine-tuned, at least in part, by a complex array of pathways that either promote or inhibit the activation of innate and adaptive immune cells. Much effort has been focused on pathways that can support immune activation. In this article, we review specifically pathways that can inhibit immune responses and maintain immune homeostasis, highlighting our recent understanding on the role of inhibitory receptors that selectively engage the self MHC class I molecules and the B7 superfamily members, we also discuss the inhibitory Fc receptors and inhibitory cytokines and how such pathways, either individually or collectively, regulate innate and adaptive immune responses. Finally, we summarize new emerging approaches on how such negative pathways can be therapeutically modulated in various disease settings. PMID:20003816

  13. Inhibitory Circuits in Cortical Layer 5

    PubMed Central

    Naka, Alexander; Adesnik, Hillel

    2016-01-01

    Inhibitory neurons play a fundamental role in cortical computation and behavior. Recent technological advances, such as two photon imaging, targeted in vivo recording, and molecular profiling, have improved our understanding of the function and diversity of cortical interneurons, but for technical reasons most work has been directed towards inhibitory neurons in the superficial cortical layers. Here we review current knowledge specifically on layer 5 (L5) inhibitory microcircuits, which play a critical role in controlling cortical output. We focus on recent work from the well-studied rodent barrel cortex, but also draw on evidence from studies in primary visual cortex and other cortical areas. The diversity of both deep inhibitory neurons and their pyramidal cell targets make this a challenging but essential area of study in cortical computation and sensory processing. PMID:27199675

  14. HLA and NK cell inhibitory receptor genes in resolving hepatitis C virus infection.

    PubMed

    Khakoo, Salim I; Thio, Chloe L; Martin, Maureen P; Brooks, Collin R; Gao, Xiaojiang; Astemborski, Jacquie; Cheng, Jie; Goedert, James J; Vlahov, David; Hilgartner, Margaret; Cox, Steven; Little, Ann-Margeret; Alexander, Graeme J; Cramp, Matthew E; O'Brien, Stephen J; Rosenberg, William M C; Thomas, David L; Carrington, Mary

    2004-08-06

    Natural killer (NK) cells provide a central defense against viral infection by using inhibitory and activation receptors for major histocompatibility complex class I molecules as a means of controlling their activity. We show that genes encoding the inhibitory NK cell receptor KIR2DL3 and its human leukocyte antigen C group 1 (HLA-C1) ligand directly influence resolution of hepatitis C virus (HCV) infection. This effect was observed in Caucasians and African Americans with expected low infectious doses of HCV but not in those with high-dose exposure, in whom the innate immune response is likely overwhelmed. The data strongly suggest that inhibitory NK cell interactions are important in determining antiviral immunity and that diminished inhibitory responses confer protection against HCV.

  15. Whisker Deprivation Drives Two Phases of Inhibitory Synapse Weakening in Layer 4 of Rat Somatosensory Cortex.

    PubMed

    Gainey, Melanie A; Wolfe, Renna; Pourzia, Olivia; Feldman, Daniel E

    2016-01-01

    Inhibitory synapse development in sensory neocortex is experience-dependent, with sustained sensory deprivation yielding fewer and weaker inhibitory synapses. Whether this represents arrest of synapse maturation, or a more complex set of processes, is unclear. To test this, we measured the dynamics of inhibitory synapse development in layer 4 of rat somatosensory cortex (S1) during continuous whisker deprivation from postnatal day 7, and in age-matched controls. In deprived columns, spontaneous miniature inhibitory postsynaptic currents (mIPSCs) and evoked IPSCs developed normally until P15, when IPSC amplitude transiently decreased, recovering by P16 despite ongoing deprivation. IPSCs remained normal until P22, when a second, sustained phase of weakening began. Delaying deprivation onset by 5 days prevented the P15 weakening. Both early and late phase weakening involved measurable reduction in IPSC amplitude relative to prior time points. Thus, deprivation appears to drive two distinct phases of active IPSC weakening, rather than simple arrest of synapse maturation.

  16. High Level Information Fusion (HLIF) with nested fusion loops

    NASA Astrophysics Data System (ADS)

    Woodley, Robert; Gosnell, Michael; Fischer, Amber

    2013-05-01

    Situation modeling and threat prediction require higher levels of data fusion in order to provide actionable information. Beyond the sensor data and sources the analyst has access to, the use of out-sourced and re-sourced data is becoming common. Through the years, some common frameworks have emerged for dealing with information fusion—perhaps the most ubiquitous being the JDL Data Fusion Group and their initial 4-level data fusion model. Since these initial developments, numerous models of information fusion have emerged, hoping to better capture the human-centric process of data analyses within a machine-centric framework. 21st Century Systems, Inc. has developed Fusion with Uncertainty Reasoning using Nested Assessment Characterizer Elements (FURNACE) to address challenges of high level information fusion and handle bias, ambiguity, and uncertainty (BAU) for Situation Modeling, Threat Modeling, and Threat Prediction. It combines JDL fusion levels with nested fusion loops and state-of-the-art data reasoning. Initial research has shown that FURNACE is able to reduce BAU and improve the fusion process by allowing high level information fusion (HLIF) to affect lower levels without the double counting of information or other biasing issues. The initial FURNACE project was focused on the underlying algorithms to produce a fusion system able to handle BAU and repurposed data in a cohesive manner. FURNACE supports analyst's efforts to develop situation models, threat models, and threat predictions to increase situational awareness of the battlespace. FURNACE will not only revolutionize the military intelligence realm, but also benefit the larger homeland defense, law enforcement, and business intelligence markets.

  17. Network-centric data fusion

    NASA Astrophysics Data System (ADS)

    Nicholson, David; Lloyd, C. M.; Collins, Peter R. C.

    2002-08-01

    The performance of three distributed sensor fusion network architectures is investigated: a fully-connected and a partially-connected measurement fusion system and a partially-connected track fusion system. The investigation employs an advanced military scenario generator, FLAMES, which was customised for exercising a range of distributed data fusion experiments. Specifically, it includes a representative model of the delays in a communication system (such as JTIDS or Link 16). Here the delays were used to modify communication bandwidth and to evaluate how this affected the performance of the fusion architectures/algorithms. Under certain specific scenario conditions, it was found that decentralised measurement fusion system was severely affected by reduced bandwidth. This is because each node loads its communication buffer with every measurement and consequently some measurements are never transmitted. The decentralised track fusion system exhibits improved performance because it lumps measurements into tracks and thereby it makes much more effective use of the bandwidth. Moreover, it was found that the performance of the partially connected decentralised track fusion system was very close to the optimal performance achieved by the fully-connected decentralised measurement fusion system.

  18. OCULUS Sea Track Fusion Service

    NASA Astrophysics Data System (ADS)

    Panagiotou, Stylianos C.; Rizogiannis, Constantinos; Katsoulis, Stavros; Lampropoulos, Vassilis; Kanellopoulos, Sotirios; Thomopoulos, Stelios C. A.

    2015-06-01

    Oculus Sea is a complete solution regarding maritime surveillance and communications at Local as well as Central Command and Control level. It includes a robust and independent track fusion service whose main functions include: 1) Interaction with the User to suggest the fusion of two or more tracks, confirm Track ID and Vessel Metadata creation for the fused track, and suggest de-association of two tracks 2) Fusion of same vessel tracks arriving simultaneously from multiple radar sensors featuring track Association, track Fusion of associated tracks to produce a more accurate track, and Multiple tracking filters and fusion algorithms 3) Unique Track ID Generator for each fused track 4) Track Dissemination Service. Oculus Sea Track Fusion Service adopts a system architecture where each sensor is associated with a Kalman estimator/tracker that obtains an estimate of the state vector and its respective error covariance matrix. Finally, at the fusion center, association and track state estimation fusion are carried out. The expected benefits of this system include multi-sensor information fusion, enhanced spatial resolution, and improved target detection.

  19. Economic potential of inertial fusion

    SciTech Connect

    Nuckolls, J.H.

    1984-04-01

    Beyond the achievement of scientific feasibility, the key question for fusion energy is: does it have the economic potential to be significantly cheaper than fission and coal energy. If fusion has this high economic potential then there are compelling commercial and geopolitical incentives to accelerate the pace of the fusion program in the near term, and to install a global fusion energy system in the long term. Without this high economic potential, fusion's success depends on the failure of all alternatives, and there is no real incentive to accelerate the program. If my conjectures on the economic potential of inertial fusion are approximately correct, then inertial fusion energy's ultimate costs may be only half to two-thirds those of advanced fission and coal energy systems. Relative cost escalation is not assumed and could increase this advantage. Both magnetic and inertial approaches to fusion potentially have a two-fold economic advantage which derives from two fundamental properties: negligible fuel costs and high quality energy which makes possible more efficient generation of electricity. The wining approach to fusion may excel in three areas: electrical generating efficiency, minimum material costs, and adaptability to manufacture in automated factories. The winning approach must also rate highly in environmental potential, safety, availability factor, lifetime, small 0 and M costs, and no possibility of utility-disabling accidents.

  20. Cold nuclear fusion

    NASA Astrophysics Data System (ADS)

    Tsyganov, E. N.; Bavizhev, M. D.; Buryakov, M. G.; Dabagov, S. B.; Golovatyuk, V. M.; Lobastov, S. P.

    2015-07-01

    If target deuterium atoms were implanted in a metal crystal in accelerator experiments, a sharp increase in the probability of DD-fusion reaction was clearly observed when compared with the reaction's theoretical value. The electronic screening potential, which for a collision of free deuterium atoms is about 27 eV, reached 300-700 eV in the case of the DD-fusion in metallic crystals. These data leads to the conclusion that a ban must exist for deuterium atoms to be in the ground state 1s in a niche filled with free conduction electrons. At the same time, the state 2p whose energy level is only 10 eV above that of state 1s is allowed in these conditions. With anisotropy of 2p, 3p or above orbitals, their spatial positions are strictly determined in the lattice coordinate system. When filling out the same potential niches with two deuterium atoms in the states 2p, 3p or higher, the nuclei of these atoms can be permanently positioned without creating much Coulomb repulsion at a very short distance from each other. In this case, the transparency of the potential barrier increases dramatically compared to the ground state 1s for these atoms. The probability of the deuterium nuclei penetrating the Coulomb barrier by zero quantum vibration of the DD-system also increases dramatically. The so-called cold nuclear DD-fusion for a number of years was registered in many experiments, however, was still rejected by mainstream science for allegedly having no consistent scientific explanation. Finally, it received the validation. Below, we outline the concept of this explanation and give the necessary calculations. This paper also considers the further destiny of the formed intermediate state of 4He∗.

  1. Physics of Fusion Welding

    NASA Technical Reports Server (NTRS)

    Nunes, A. C., Jr.

    1986-01-01

    Applicabilities and limitations of three techniques analyzed. NASA technical memorandum discusses physics of electron-beam, gas/ tungsten-arc, and laser-beam welding. From comparison of capabilities and limitations of each technique with regard to various welding conditions and materials, possible to develop criteria for selecting best welding technique in specific application. All three techniques classified as fusion welding; small volume of workpiece melted by intense heat source. Heat source moved along seam, leaving in wake solid metal that joins seam edges together.

  2. Cold Fusion Verification.

    DTIC Science & Technology

    1991-03-01

    published work, talking with others in the field, and attending conferences, that CNF probably is chimera and will go the way of N-rays and polywater ...way of N-rays and polywater . To date, no one, including Pons and Fleischmann, has been able to construct a so-called CNF electrochemical cell that...Cold Nuclear Fusion (CNF), as originally reported in 1989. The conclusion is that CNF probably is chimera and will go the way of N-rays and polywater

  3. Fusion reactor pumped laser

    DOEpatents

    Jassby, Daniel L.

    1988-01-01

    A nuclear pumped laser capable of producing long pulses of very high power laser radiation is provided. A toroidal fusion reactor provides energetic neutrons which are slowed down by a moderator. The moderated neutrons are converted to energetic particles capable of pumping a lasing medium. The lasing medium is housed in an annular cell surrounding the reactor. The cell includes an annular reflecting mirror at the bottom and an annular output window at the top. A neutron reflector is disposed around the cell to reflect escaping neutrons back into the cell. The laser radiation from the annular window is focused onto a beam compactor which generates a single coherent output laser beam.

  4. Munc18a Scaffolds SNARE Assembly to Promote Membrane Fusion

    PubMed Central

    Rodkey, Travis L.; Liu, Song; Barry, Meagan

    2008-01-01

    Munc18a is an SM protein required for SNARE-mediated fusion. The molecular details of how Munc18a acts to enhance neurosecretion have remained elusive. Here, we use in vitro fusion assays to characterize how specific interactions between Munc18a and the neuronal SNAREs enhance the rate and extent of fusion. We show that Munc18a interacts directly and functionally with the preassembled t-SNARE complex. Analysis of Munc18a point mutations indicates that Munc18a interacts with helix C of the Syntaxin1a NRD in the t-SNARE complex. Replacement of the t-SNARE SNAP25b with yeast Sec9c had little effect, suggesting that Munc18a has minimal contact with SNAP25b within the t-SNARE complex. A chimeric Syntaxin built of the Syntaxin1a NRD and the H3 domain of yeast Sso1p and paired with Sec9c eliminated stimulation of fusion, suggesting that Munc18a/Syntaxin1a H3 domain contacts are important. Additionally, a Syntaxin1A mutant lacking a flexible linker region that allows NRD movement abolished stimulation of fusion. These experiments suggest that Munc18a binds to the Syntaxin1a NRD and H3 domain within the assembled t-SNARE complex, positioning them for productive VAMP2 binding. In this capacity, Munc18a serves as a platform for trans-SNARE complex assembly that facilitates efficient SNARE-mediated membrane fusion. PMID:18829865

  5. Report of the Fusion Energy Sciences Advisory Committee. Panel on Integrated Simulation and Optimization of Magnetic Fusion Systems

    SciTech Connect

    Dahlburg, Jill; Corones, James; Batchelor, Donald; Bramley, Randall; Greenwald, Martin; Jardin, Stephen; Krasheninnikov, Sergei; Laub, Alan; Leboeuf, Jean-Noel; Lindl, John; Lokke, William; Rosenbluth, Marshall; Ross, David; Schnack, Dalton

    2002-11-01

    Fusion is potentially an inexhaustible energy source whose exploitation requires a basic understanding of high-temperature plasmas. The development of a science-based predictive capability for fusion-relevant plasmas is a challenge central to fusion energy science, in which numerical modeling has played a vital role for more than four decades. A combination of the very wide range in temporal and spatial scales, extreme anisotropy, the importance of geometric detail, and the requirement of causality which makes it impossible to parallelize over time, makes this problem one of the most challenging in computational physics. Sophisticated computational models are under development for many individual features of magnetically confined plasmas and increases in the scope and reliability of feasible simulations have been enabled by increased scientific understanding and improvements in computer technology. However, full predictive modeling of fusion plasmas will require qualitative improvements and innovations to enable cross coupling of a wider variety of physical processes and to allow solution over a larger range of space and time scales. The exponential growth of computer speed, coupled with the high cost of large-scale experimental facilities, makes an integrated fusion simulation initiative a timely and cost-effective opportunity. Worldwide progress in laboratory fusion experiments provides the basis for a recent FESAC recommendation to proceed with a burning plasma experiment (see FESAC Review of Burning Plasma Physics Report, September 2001). Such an experiment, at the frontier of the physics of complex systems, would be a huge step in establishing the potential of magnetic fusion energy to contribute to the world’s energy security. An integrated simulation capability would dramatically enhance the utilization of such a facility and lead to optimization of toroidal fusion plasmas in general. This science-based predictive capability, which was cited in the FESAC

  6. Identification and Characterization of a Small Inhibitory Peptide That Can Target DNA-PKcs Autophosphorylation and Increase Tumor Radiosensitivity

    SciTech Connect

    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

    2012-12-01

    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.

  7. Inertial confinement fusion

    SciTech Connect

    Powers, L.; Condouris, R.; Kotowski, M.; Murphy, P.W.

    1992-01-01

    This issue of the ICF Quarterly contains seven articles that describe recent progress in Lawrence Livermore National Laboratory's ICF program. The Department of Energy recently initiated an effort to design a 1--2 MJ glass laser, the proposed National Ignition Facility (NIF). These articles span various aspects of a program which is aimed at moving forward toward such a facility by continuing to use the Nova laser to gain understanding of NIF-relevant target physics, by developing concepts for an NIF laser driver, and by envisioning a variety of applications for larger ICF facilities. This report discusses research on the following topics: Stimulated Rotational Raman Scattering in Nitrogen; A Maxwell Equation Solver in LASNEX for the Simulation of Moderately Intense Ultrashort Pulse Experiments; Measurements of Radial Heat-Wave Propagation in Laser-Produced Plasmas; Laser-Seeded Modulation Growth on Directly Driven Foils; Stimulated Raman Scattering in Large-Aperture, High-Fluence Frequency-Conversion Crystals; Fission Product Hazard Reduction Using Inertial Fusion Energy; Use of Inertial Confinement Fusion for Nuclear Weapons Effects Simulations.

  8. Statistics in fusion experiments

    NASA Astrophysics Data System (ADS)

    McNeill, D. H.

    1997-11-01

    Since the reasons for the variability in data from plasma experiments are often unknown or uncontrollable, statistical methods must be applied. Reliable interpretation and public accountability require full data sets. Two examples of data misrepresentation at PPPL are analyzed: Te >100 eV on S-1 spheromak.(M. Yamada, Nucl. Fusion 25, 1327 (1985); reports to DoE; etc.) The reported high values (statistical artifacts of Thomson scattering measurements) were selected from a mass of data with an average of 40 eV or less. ``Correlated'' spectroscopic data were meaningless. (2) Extrapolation to Q >=0.5 for DT in TFTR.(D. Meade et al., IAEA Baltimore (1990), V. 1, p. 9; H. P. Furth, Statements to U. S. Congress (1989).) The DD yield used there was the highest through 1990 (>= 50% above average) and the DT to DD power ratio used was about twice any published value. Average DD yields and published yield ratios scale to Q<0.15 for DT, in accord with the observed performance over the last 3 1/2 years. Press reports of outlier data from TFTR have obscured the fact that the DT behavior follows from trivial scaling of the DD data. Good practice in future fusion research would have confidence intervals and other descriptive statistics accompanying reported numerical values (cf. JAMA).

  9. Two coiled-coil domains of Chlamydia trachomatis IncA affect membrane fusion events during infection.

    PubMed

    Ronzone, Erik; Paumet, Fabienne

    2013-01-01

    Chlamydia trachomatis replicates in a parasitophorous membrane-bound compartment called an inclusion. The inclusions corrupt host vesicle trafficking networks to avoid the degradative endolysosomal pathway but promote fusion with each other in order to sustain higher bacterial loads in a process known as homotypic fusion. The Chlamydia protein IncA (Inclusion protein A) appears to play central roles in both these processes as it participates to homotypic fusion and inhibits endocytic SNARE-mediated membrane fusion. How IncA selectively inhibits or activates membrane fusion remains poorly understood. In this study, we analyzed the spatial and molecular determinants of IncA's fusogenic and inhibitory functions. Using a cell-free membrane fusion assay, we found that inhibition of SNARE-mediated fusion requires IncA to be on the same membrane as the endocytic SNARE proteins. IncA displays two coiled-coil domains showing high homology with SNARE proteins. Domain swap and deletion experiments revealed that although both these domains are capable of independently inhibiting SNARE-mediated fusion, these two coiled-coil domains cooperate in mediating IncA multimerization and homotypic membrane interaction. Our results support the hypothesis that Chlamydia employs SNARE-like virulence factors that positively and negatively affect membrane fusion and promote infection.

  10. Overexpression of PKM2 promotes mitochondrial fusion through attenuated p53 stability

    PubMed Central

    Wu, Haili; Yang, Peng; Hu, Wanglai; Wang, Yingying; Lu, Yangxu; Zhang, Lichao; Fan, Yongsheng; Xiao, Hong; Li, Zhuoyu

    2016-01-01

    M2-type pyruvate kinase (PKM2) contributes to the Warburg effect. However, it remains unknown as to whether PKM2 has an inhibitory effect on mitochondrial function. We report in this work that PKM2 overexpression inhibits the expression of Drp1 and results in the mitochondrial fusion. The ATP production was found to be decreased, the mtDNA copy number elevated and the expression level of electron transport chain (ETC) complex I, III, V depressed in PKM2 overexpressed cells. PKM2 overexpression showed a decreased p53 protein level and a shorter p53 half-life. In contrast, PKM2 knockdown resulted in increased p53 expression and prolonged half-life of p53. PKM2 could directly bind with both p53 and MDM2 and promote MDM2-mediated p53 ubiquitination. The dimeric PKM2 significantly suppressed p53 expression compared with the other PKM2 mutants. The reverse relationship between PKM2 and Drp1 was further confirmed in a large number of clinical samples. Taken together, the present results highlight a new mechanism that link PKM2 to mitochondrial function, based on p53-Drp1 axis down regulation, revealing a novel therapeutic target in patients with abnormal mitochondria. PMID:27801666

  11. Helium Find Thaws the Cold Fusion Trail.

    ERIC Educational Resources Information Center

    Pennisi, E.

    1991-01-01

    Reported is a study of cold fusion in which trace amounts of helium, possible evidence of an actual fusion reaction, were found. Research methodology is detailed. The controversy over the validity of experimental results with cold fusion are reviewed. (CW)

  12. Fusion Power measurement at ITER

    SciTech Connect

    Bertalot, L.; Barnsley, R.; Krasilnikov, V.; Stott, P.; Suarez, A.; Vayakis, G.; Walsh, M.

    2015-07-01

    Nuclear fusion research aims to provide energy for the future in a sustainable way and the ITER project scope is to demonstrate the feasibility of nuclear fusion energy. ITER is a nuclear experimental reactor based on a large scale fusion plasma (tokamak type) device generating Deuterium - Tritium (DT) fusion reactions with emission of 14 MeV neutrons producing up to 700 MW fusion power. The measurement of fusion power, i.e. total neutron emissivity, will play an important role for achieving ITER goals, in particular the fusion gain factor Q related to the reactor performance. Particular attention is given also to the development of the neutron calibration strategy whose main scope is to achieve the required accuracy of 10% for the measurement of fusion power. Neutron Flux Monitors located in diagnostic ports and inside the vacuum vessel will measure ITER total neutron emissivity, expected to range from 1014 n/s in Deuterium - Deuterium (DD) plasmas up to almost 10{sup 21} n/s in DT plasmas. The neutron detection systems as well all other ITER diagnostics have to withstand high nuclear radiation and electromagnetic fields as well ultrahigh vacuum and thermal loads. (authors)

  13. Multi-sensor fusion development

    NASA Astrophysics Data System (ADS)

    Bish, Sheldon; Rohrer, Matthew; Scheffel, Peter; Bennett, Kelly

    2016-05-01

    The U.S. Army Research Laboratory (ARL) and McQ Inc. are developing a generic sensor fusion architecture that involves several diverse processes working in combination to create a dynamic task-oriented, real-time informational capability. Processes include sensor data collection, persistent and observational data storage, and multimodal and multisensor fusion that includes the flexibility to modify the fusion program rules for each mission. Such a fusion engine lends itself to a diverse set of sensing applications and architectures while using open-source software technologies. In this paper, we describe a fusion engine architecture that combines multimodal and multi-sensor fusion within an Open Standard for Unattended Sensors (OSUS) framework. The modular, plug-and-play architecture of OSUS allows future fusion plugin methodologies to have seamless integration into the fusion architecture at the conceptual and implementation level. Although beyond the scope of this paper, this architecture allows for data and information manipulation and filtering for an array of applications.

  14. Cellulose binding domain fusion proteins

    SciTech Connect

    Shoseyov, Oded; Shpiegl, Itai; Goldstein, Marc A.; Doi, Roy H.

    1998-01-01

    A cellulose binding domain (CBD) having a high affinity for crystalline cellulose and chitin is disclosed, along with methods for the molecular cloning and recombinant production thereof. Fusion products comprising the CBD and a second protein are likewise described. A wide range of applications are contemplated for both the CBD and the fusion products, including drug delivery, affinity separations, and diagnostic techniques.

  15. Cold fusion; Myth versus reality

    SciTech Connect

    Rabinowitz, M. )

    1990-01-01

    Experiments indicate that several different nuclear reactions are taking place. Some of the experiments point to D-D fusion with a cominant tritium channel as one of the reactions. The article notes a similarity between Prometheus and the discoveries of cold fusion.

  16. Fusion Policy Advisory Committee (FPAC)

    SciTech Connect

    Not Available

    1990-09-01

    This document is the final report of the Fusion Policy Advisory Committee. The report conveys the Committee's views on the matters specified by the Secretary in his charge and subsequent letters to the Committee, and also satisfies the provisions of Section 7 of the Magnetic Fusion Energy Engineering Act of 1980, Public Law 96-386, which require a triennial review of the conduct of the national Magnetic Fusion Energy program. Three sub-Committee's were established to address the large number of topics associated with fusion research and development. One considered magnetic fusion energy, a second considered inertial fusion energy, and the third considered issues common to both. For many reasons, the promise of nuclear fusion as a safe, environmentally benign, and affordable source of energy is bright. At the present state of knowledge, however, it is uncertain that this promise will become reality. Only a vigorous, well planned and well executed program of research and development will yield the needed information. The Committee recommends that the US commit to a plan that will resolve this critically important issue. It also outlines the first steps in a development process that will lead to a fusion Demonstration Power Plant by 2025. The recommended program is aggressive, but we believe the goal is reasonable and attainable. International collaboration at a significant level is an important element in the plan.

  17. Cold Fusion, A Journalistic Investigation

    NASA Astrophysics Data System (ADS)

    Krivit, Steven B.

    2005-03-01

    Author of the recent book, The Rebirth of Cold Fusion, and founder of New Energy Times, Steven B. Krivit presents a summary of cold fusion's, past, present and possible future. This talk will briefly review five highlights of the recent New Energy Times investigation into cold fusion research:1. Analysis of early studies that supposedly disproved cold fusion.2. Key early corroborations that supported the claims of Fleischmann and Pons.3. The evolving understanding of cold fusion reaction paths and by-products.4. A look at volumetric power density.5. Brief comparison of the progress in hot fusion research as compared to cold fusion research.New Energy Times, founded in 2000, is an independent communications company which currently specializes in reporting on cold fusion researchootnotetextReferences and copies of the presentation are available at www.newenergytimes.com/reports/aps2005.htmhttp://www.newenergytimes.com/reports/aps2005.htm. It has no affiliations with any organization, entity or party which invests in these technologies, nor any individual researcher or research facility.

  18. Cellulose binding domain fusion proteins

    DOEpatents

    Shoseyov, O.; Yosef, K.; Shpiegl, I.; Goldstein, M.A.; Doi, R.H.

    1998-02-17

    A cellulose binding domain (CBD) having a high affinity for crystalline cellulose and chitin is disclosed, along with methods for the molecular cloning and recombinant production. Fusion products comprising the CBD and a second protein are likewise described. A wide range of applications are contemplated for both the CBD and the fusion products, including drug delivery, affinity separations, and diagnostic techniques. 16 figs.

  19. Using gaming engines and editors to construct simulations of fusion algorithms for situation management

    NASA Astrophysics Data System (ADS)

    Lewis, Lundy M.; DiStasio, Nolan; Wright, Christopher

    2010-04-01

    In this paper we discuss issues in testing various cognitive fusion algorithms for situation management. We provide a proof-of-principle discussion and demo showing how gaming technologies and platforms could be used to devise and test various fusion algorithms, including input, processing, and output, and we look at how the proof-of-principle could lead to more advanced test beds and methods for high-level fusion in support of situation management. We develop four simple fusion scenarios and one more complex scenario in which a simple rule-based system is scripted to govern the behavior of battlespace entities.

  20. Is there hope for fusion

    SciTech Connect

    Fowler, T.K. . Dept. of Nuclear Engineering)

    1990-04-12

    From the outset in the 1950's, fusion research has been motivated by environmental concerns as well as long-term fuel supply issues. Compared to fossil fuels both fusion and fission would produce essentially zero emissions to the atmosphere. Compared to fission, fusion reactors should offer high demonstrability of public protection from accidents and a substantial amelioration of the radioactive waste problem. Fusion still requires lengthy development, the earliest commercial deployment being likely to occur around 2025--2050. However, steady scientific progress is being made and there is a wide consensus that it is time to plan large-scale engineering development. A major international effort, called the International Thermonuclear Experimental Reactor (ITER), is being carried out under IAEA auspices to design the world's first fusion engineering test reactor, which could be constructed in the 1990's. 4 figs., 3 tabs.

  1. Adjoint affine fusion and tadpoles

    NASA Astrophysics Data System (ADS)

    Urichuk, Andrew; Walton, Mark A.

    2016-06-01

    We study affine fusion with the adjoint representation. For simple Lie algebras, elementary and universal formulas determine the decomposition of a tensor product of an integrable highest-weight representation with the adjoint representation. Using the (refined) affine depth rule, we prove that equally striking results apply to adjoint affine fusion. For diagonal fusion, a coefficient equals the number of nonzero Dynkin labels of the relevant affine highest weight, minus 1. A nice lattice-polytope interpretation follows and allows the straightforward calculation of the genus-1 1-point adjoint Verlinde dimension, the adjoint affine fusion tadpole. Explicit formulas, (piecewise) polynomial in the level, are written for the adjoint tadpoles of all classical Lie algebras. We show that off-diagonal adjoint affine fusion is obtained from the corresponding tensor product by simply dropping non-dominant representations.

  2. Dendritic-tumor fusion cells in cancer immunotherapy.

    PubMed

    Takakura, Kazuki; Kajihara, Mikio; Ito, Zensho; Ohkusa, Toshifumi; Gong, Jianlin; Koido, Shigeo

    2015-03-01

    A promising area of clinical investigation is the use of cancer immunotherapy to treat cancer patients. Dendritic cells (DCs) operate as professional antigen-presenting cells (APCs) and play a critical role in the induction of antitumor immune responses. Thus, DC-based cancer immunotherapy represents a powerful strategy. One DC-based cancer immunotherapy strategy that has been investigated is the administration of fusion cells generated with DCs and whole tumor cells (DC-tumor fusion cells). The DC-tumor fusion cells can process a broad array of tumor-associated antigens (TAAs), including unidentified molecules, and present them through major histocompatibility complex (MHC) class I and II pathways in the context of co-stimulatory signals. Improving the therapeutic efficacy of DC-tumor fusion cell-based cancer immunotherapy requires increased immunogenicity of DCs and whole tumor cells. We discuss the potential ability of DC-tumor fusion cells to activate antigen-specific T cells and strategies to improve the immunogenicity of DC-tumor fusion cells as anticancer vaccines.

  3. Information integration for data fusion

    SciTech Connect

    Bray, O.H.

    1997-01-01

    Data fusion has been identified by the Department of Defense as a critical technology for the U.S. defense industry. Data fusion requires combining expertise in two areas - sensors and information integration. Although data fusion is a rapidly growing area, there is little synergy and use of common, reusable, and/or tailorable objects and models, especially across different disciplines. The Laboratory-Directed Research and Development project had two purposes: to see if a natural language-based information modeling methodology could be used for data fusion problems, and if so, to determine whether this methodology would help identify commonalities across areas and achieve greater synergy. The project confirmed both of the initial hypotheses: that the natural language-based information modeling methodology could be used effectively in data fusion areas and that commonalities could be found that would allow synergy across various data fusion areas. The project found five common objects that are the basis for all of the data fusion areas examined: targets, behaviors, environments, signatures, and sensors. Many of the objects and the specific facts related to these objects were common across several areas and could easily be reused. In some cases, even the terminology remained the same. In other cases, different areas had their own terminology, but the concepts were the same. This commonality is important with the growing use of multisensor data fusion. Data fusion is much more difficult if each type of sensor uses its own objects and models rather than building on a common set. This report introduces data fusion, discusses how the synergy generated by this LDRD would have benefited an earlier successful project and contains a summary information model from that project, describes a preliminary management information model, and explains how information integration can facilitate cross-treaty synergy for various arms control treaties.

  4. Evolution of an Intelligent Information Fusion System

    NASA Technical Reports Server (NTRS)

    Campbell, William J.; Cromp, Robert F.

    1990-01-01

    Consideration is given to the hardware and software needed to manage the enormous amount and complexity of data that the next generation of space-borne sensors will provide. An anthology is presented illustrating the evolution of artificial intelligence, science data processing, and management from the 1960s to the near future. Problems and limitations of technologies, data structures, data standards, and conceptual thinking are addressed. The development of an end-to-end Intelligent Information Fusion System that embodies knowledge of the user's domain-specific goals is proposed.

  5. Dynamic clustering and dispersion of lipid rafts contribute to fusion competence of myogenic cells

    SciTech Connect

    Mukai, Atsushi; Kurisaki, Tomohiro; Sato, Satoshi B.; Kobayashi, Toshihide; Kondoh, Gen; Hashimoto, Naohiro

    2009-10-15

    Recent research indicates that the leading edge of lamellipodia of myogenic cells (myoblasts and myotubes) contains presumptive fusion sites, yet the mechanisms that render the plasma membrane fusion-competent remain largely unknown. Here we show that dynamic clustering and dispersion of lipid rafts contribute to both cell adhesion and plasma membrane union during myogenic cell fusion. Adhesion-complex proteins including M-cadherin, {beta}-catenin, and p120-catenin accumulated at the leading edge of lamellipodia, which contains the presumptive fusion sites of the plasma membrane, in a lipid raft-dependent fashion prior to cell contact. In addition, disruption of lipid rafts by cholesterol depletion directly prevented the membrane union of myogenic cell fusion. Time-lapse recording showed that lipid rafts were laterally dispersed from the center of the lamellipodia prior to membrane fusion. Adhesion proteins that had accumulated at lipid rafts were also removed from the presumptive fusion sites when lipid rafts were laterally dispersed. The resultant lipid raft- and adhesion complex-free area at the leading edge fused with the opposing plasma membrane. These results demonstrate a key role for dynamic clustering/dispersion of lipid rafts in establishing fusion-competent sites of the myogenic cell membrane, providing a novel mechanistic insight into the regulation of myogenic cell fusion.

  6. The inhibitory spillover effect: Controlling the bladder makes better liars *

    PubMed Central

    Fenn, Elise; Blandón-Gitlin, Iris; Coons, Jennifer; Pineda, Catherine; Echon, Reinalyn

    2015-01-01

    The Inhibitory-Spillover-Effect (ISE) on a deception task was investigated. The ISE occurs when performance in one self-control task facilitates performance in another (simultaneously conducted) self-control task. Deceiving requires increased access to inhibitory control. We hypothesized that inducing liars to control urination urgency (physical inhibition) would facilitate control during deceptive interviews (cognitive inhibition). Participants drank small (low-control) or large (high-control) amounts of water. Next, they lied or told the truth to an interviewer. Third-party observers assessed the presence of behavioral cues and made true/lie judgments. In the high-control, but not the low-control condition, liars displayed significantly fewer behavioral cues to deception, more behavioral cues signaling truth, and provided longer and more complex accounts than truth-tellers. Accuracy detecting liars in the high-control condition was significantly impaired; observers revealed bias toward perceiving liars as truth-tellers. The ISE can operate in complex behaviors. Acts of deception can be facilitated by covert manipulations of self-control. PMID:26366466

  7. Spatial and functional restriction of regulatory molecules during mammalian myoblast fusion

    SciTech Connect

    Pavlath, Grace K.

    2010-11-01

    Myoblast fusion is a highly regulated process that is key for forming skeletal muscle during development and regeneration in mammals. Much remains to be understood about the molecular regulation of myoblast fusion. Some molecules that influence mammalian muscle fusion display specific cellular localization during myogenesis. Such molecules can be localized to the contact region between two fusing cells either in both cells or only in one of the cells. How distinct localization of molecules contributes to fusion is not clear. Further complexity exists as other molecules are functionally restricted to myoblasts at later stages of myogenesis to regulate their fusion with multinucleated myotubes. This review examines these three categories of molecules and discusses how spatial and functional restriction may contribute to the formation of a multinucleated cell. Understanding how and why molecules become restricted in location or function is likely to provide further insights into the mechanisms regulating mammalian muscle fusion.

  8. Embedding the results of focussed Bayesian fusion into a global context

    NASA Astrophysics Data System (ADS)

    Sander, Jennifer; Heizmann, Michael

    2014-05-01

    Bayesian statistics offers a well-founded and powerful fusion methodology also for the fusion of heterogeneous information sources. However, except in special cases, the needed posterior distribution is not analytically derivable. As consequence, Bayesian fusion may cause unacceptably high computational and storage costs in practice. Local Bayesian fusion approaches aim at reducing the complexity of the Bayesian fusion methodology significantly. This is done by concentrating the actual Bayesian fusion on the potentially most task relevant parts of the domain of the Properties of Interest. Our research on these approaches is motivated by an analogy to criminal investigations where criminalists pursue clues also only locally. This publication follows previous publications on a special local Bayesian fusion technique called focussed Bayesian fusion. Here, the actual calculation of the posterior distribution gets completely restricted to a suitably chosen local context. By this, the global posterior distribution is not completely determined. Strategies for using the results of a focussed Bayesian analysis appropriately are needed. In this publication, we primarily contrast different ways of embedding the results of focussed Bayesian fusion explicitly into a global context. To obtain a unique global posterior distribution, we analyze the application of the Maximum Entropy Principle that has been shown to be successfully applicable in metrology and in different other areas. To address the special need for making further decisions subsequently to the actual fusion task, we further analyze criteria for decision making under partial information.

  9. Fusion heating technology

    SciTech Connect

    Cole, A.J.

    1982-06-01

    John Lawson established the criterion that in order to produce more energy from fusion than is necessary to heat the plasma and replenish the radiation losses, a minimum value for both the product of plasma density and confinement time t, and the temperature must be achieved. There are two types of plasma heating: neutral beam and electromagnetic wave heating. A neutral beam system is shown. Main development work on negative ion beamlines has focused on the difficult problem of the production of high current sources. The development of a 30 keV-1 ampere multisecond source module is close to being accomplished. In electromagnetic heating, the launcher, which provides the means of coupling the power to the plasma, is most important. The status of heating development is reviewed. Electron cyclotron resonance heating (ECRH), lower hybrid heating (HHH), and ion cyclotron resonance heating (ICRH) are reviewed.

  10. Fusion Power Demonstration III

    SciTech Connect

    Lee, J.D.

    1985-07-01

    This is the third in the series of reports covering the Fusion Power Demonstration (FPD) design study. This volume considers the FPD-III configuration that incorporates an octopole end plug. As compared with the quadrupole end-plugged designs of FPD-I and FPD-II, this octopole configuration reduces the number of end cell magnets and shortens the minimum ignition length of the central cell. The end-cell plasma length is also reduced, which in turn reduces the size and cost of the end cell magnets and shielding. As a contiuation in the series of documents covering the FPD, this report does not stand alone as a design description of FPD-III. Design details of FPD-III subsystems that do not differ significantly from those of the FPD-II configuration are not duplicated in this report.

  11. Fusion pumped light source

    DOEpatents

    Pappas, Daniel S.

    1989-01-01

    Apparatus is provided for generating energy in the form of light radiation. A fusion reactor is provided for generating a long, or continuous, pulse of high-energy neutrons. The neutron flux is coupled directly with the lasing medium. The lasing medium includes a first component selected from Group O of the periodic table of the elements and having a high inelastic scattering cross section. Gamma radiation from the inelastic scattering reactions interacts with the first component to excite the first component, which decays by photon emission at a first output wavelength. The first output wavelength may be shifted to a second output wavelength using a second liquid component responsive to the first output wavelength. The light outputs may be converted to a coherent laser output by incorporating conventional optics adjacent the laser medium.

  12. Fusion pumped laser

    DOEpatents

    Pappas, Daniel S.

    1989-01-01

    Apparatus is provided for generating energy in the form of laser radiation. A tokamak fusion reactor is provided for generating a long, or continuous, pulse of high-energy neutrons. The tokamak design provides a temperature and a magnetic field which is effective to generate a neutron flux of at least 10.sup.15 neutrons/cm.sup.2.s. A conversion medium receives neutrons from the tokamak and converts the high-energy neutrons to an energy source with an intensity and an energy effective to excite a preselected lasing medium. The energy source typically comprises fission fragments, alpha particles, and radiation from a fission event. A lasing medium is provided which is responsive to the energy source to generate a population inversion which is effective to support laser oscillations for generating output radiation.

  13. Multiple shell fusion targets

    DOEpatents

    Lindl, J.D.; Bangerter, R.O.

    1975-10-31

    Multiple shell fusion targets for use with electron beam and ion beam implosion systems are described. The multiple shell targets are of the low-power type and use a separate relatively low Z, low density ablator at large radius for the outer shell, which reduces the focusing and power requirements of the implosion system while maintaining reasonable aspect ratios. The targets use a high Z, high density pusher shell placed at a much smaller radius in order to obtain an aspect ratio small enough to protect against fluid instability. Velocity multiplication between these shells further lowers the power requirements. Careful tuning of the power profile and intershell density results in a low entropy implosion which allows breakeven at low powers. For example, with ion beams as a power source, breakeven at 10-20 Terrawatts with 10 MeV alpha particles for imploding a multiple shell target can be accomplished.

  14. Fusion reactor pumped laser

    DOEpatents

    Jassby, D.L.

    1987-09-04

    A nuclear pumped laser capable of producing long pulses of very high power laser radiation is provided. A toroidal fusion reactor provides energetic neutrons which are slowed down by a moderator. The moderated neutrons are converted to energetic particles capable of pumping a lasing medium. The lasing medium is housed in an annular cell surrounding the reactor. The cell includes an annular reflecting mirror at the bottom and an annular output window at the top. A neutron reflector is disposed around the cell to reflect escaping neutrons back into the cell. The laser radiation from the annular window is focused onto a beam compactor which generates a single coherent output laser beam. 10 figs.

  15. Microwave superheaters for fusion

    SciTech Connect

    Campbell, R.B.; Hoffman, M.A.; Logan, B.G.

    1987-10-16

    The microwave superheater uses the synchrotron radiation from a thermonuclear plasma to heat gas seeded with an alkali metal to temperatures far above the temperature of material walls. It can improve the efficiency of the Compact Fusion Advanced Rankine (CFAR) cycle described elsewhere in these proceedings. For a proof-of-principle experiment using helium, calculations show that a gas superheat ..delta..T of 2000/sup 0/K is possible when the wall temperature is maintained at 1000/sup 0/K. The concept can be scaled to reactor grade systems. Because of the need for synchrotron radiation, the microwave superheater is best suited for use with plasmas burning an advanced fuel such as D-/sup 3/He. 5 refs.

  16. Neural networks with excitatory and inhibitory components: Direct and inverse problems by a mean-field approach

    NASA Astrophysics Data System (ADS)

    di Volo, Matteo; Burioni, Raffaella; Casartelli, Mario; Livi, Roberto; Vezzani, Alessandro

    2016-01-01

    We study the dynamics of networks with inhibitory and excitatory leak-integrate-and-fire neurons with short-term synaptic plasticity in the presence of depressive and facilitating mechanisms. The dynamics is analyzed by a heterogeneous mean-field approximation, which allows us to keep track of the effects of structural disorder in the network. We describe the complex behavior of different classes of excitatory and inhibitory components, which give rise to a rich dynamical phase diagram as a function of the fraction of inhibitory neurons. Using the same mean-field approach, we study and solve a global inverse problem: reconstructing the degree probability distributions of the inhibitory and excitatory components and the fraction of inhibitory neurons from the knowledge of the average synaptic activity field. This approach unveils new perspectives on the numerical study of neural network dynamics and the possibility of using these models as a test bed for the analysis of experimental data.

  17. Novel thiourea-based sirtuin inhibitory warheads.

    PubMed

    Zang, Wenwen; Hao, Yujun; Wang, Zhenghe; Zheng, Weiping

    2015-08-15

    N(ε)-Thiocarbamoyl-lysine was recently demonstrated by our laboratory to be a potent catalytic mechanism-based SIRT1/2/3 inhibitory warhead, in the current study, among the prepared analogs of N(ε)-thiocarbamoyl-lysine with its terminal NH2 mono-substituted with alkyl and aryl groups, we found that N(ε)-methyl-thiocarbamoyl-lysine and N(ε)-carboxyethyl-thiocarbamoyl-lysine, respectively, also behaved as strong inhibitory warheads against SIRT1/2/3 and SIRT5, typical deacetylases and deacylase in the human sirtuin family, respectively. Moreover, N(ε)-methyl-thiocarbamoyl-lysine was found in the study to be a ∼ 2.5-18.4-fold stronger SIRT1/2/3 inhibitory warhead than its lead warhead N(ε)-thiocarbamoyl-lysine.

  18. Prospects for bubble fusion

    SciTech Connect

    Nigmatulin, R.I.; Lahey, R.T. Jr.

    1995-09-01

    In this paper a new method for the realization of fusion energy is presented. This method is based on the superhigh compression of a gas bubble (deuterium or deuterium/thritium) in heavy water or another liquid. The superhigh compression of a gas bubble in a liquid is achieved through forced non-linear, non-periodic resonance oscillations using moderate amplitudes of forcing pressure. The key feature of this new method is a coordination of the forced liquid pressure change with the change of bubble volume. The corresponding regime of the bubble oscillation has been called {open_quotes}basketball dribbling (BD) regime{close_quotes}. The analytical solution describing this process for spherically symmetric bubble oscillations, neglecting dissipation and compressibility of the liquid, has been obtained. This solution shown no limitation on the supercompression of the bubble and the corresponding maximum temperature. The various dissipation mechanisms, including viscous, conductive and radiation heat losses have been considered. It is shown that in spite of these losses it is possible to achieve very high gas bubble temperatures. This because the time duration of the gas bubble supercompression becomes very short when increasing the intensity of compression, thus limiting the energy losses. Significantly, the calculated maximum gas temperatures have shown that nuclear fusion may be possible. First estimations of the affect of liquid compressibility have been made to determine possible limitations on gas bubble compression. The next step will be to investigate the role of interfacial instability and breaking down of the bubble, shock wave phenomena around and in the bubble and mutual diffusion of the gas and the liquid.

  19. Soldier systems sensor fusion

    NASA Astrophysics Data System (ADS)

    Brubaker, Kathryne M.

    1998-08-01

    This paper addresses sensor fusion and its applications in emerging Soldier Systems integration and the unique challenges associated with the human platform. Technology that,provides the highest operational payoff in a lightweight warrior system must not only have enhanced capabilities, but have low power components resulting in order of magnitude reductions coupled with significant cost reductions. These reductions in power and cost will be achieved through partnership with industry and leveraging of commercial state of the art advancements in microelectronics and power sources. As new generation of full solution fire control systems (to include temperature, wind and range sensors) and target acquisition systems will accompany a new generation of individual combat weapons and upgrade existing weapon systems. Advanced lightweight thermal, IR, laser and video senors will be used for surveillance, target acquisition, imaging and combat identification applications. Multifunctional sensors will provide embedded training features in combat configurations allowing the soldier to 'train as he fights' without the traditional cost and weight penalties associated with separate systems. Personal status monitors (detecting pulse, respiration rate, muscle fatigue, core temperature, etc.) will provide commanders and highest echelons instantaneous medical data. Seamless integration of GPS and dead reckoning (compass and pedometer) and/or inertial sensors will aid navigation and increase position accuracy. Improved sensors and processing capability will provide earlier detection of battlefield hazards such as mines, enemy lasers and NBC (nuclear, biological, chemical) agents. Via the digitized network the situational awareness database will automatically be updated with weapon, medical, position and battlefield hazard data. Soldier Systems Sensor Fusion will ultimately establish each individual soldier as an individual sensor on the battlefield.

  20. LiWall Fusion - The New Concept of Magnetic Fusion

    SciTech Connect

    L.E. Zakharov

    2011-01-12

    Utilization of the outstanding abilities of a liquid lithium layer in pumping hydrogen isotopes leads to a new approach to magnetic fusion, called the LiWall Fusion. It relies on innovative plasma regimes with low edge density and high temperature. The approach combines fueling the plasma by neutral injection beams with the best possible elimination of outside neutral gas sources, which cools down the plasma edge. Prevention of cooling the plasma edge suppresses the dominant, temperature gradient related turbulence in the core. Such an approach is much more suitable for controlled fusion than the present practice, relying on high heating power for compensating essentially unlimited turbulent energy losses.

  1. Single molecule studies of the neuronal SNARE fusion machinery

    PubMed Central

    Brunger, Axel T.; Weninger, Keith; Bowen, Mark; Chu, Steven

    2010-01-01

    SNAREs are essential components of the machinery for Ca2+-triggered fusion of synaptic vesicles with the plasma membrane, resulting in neurotransmitter release into the synaptic cleft. While much is known about their biophysical and structural properties and their interactions with accessory proteins such as the Ca2+ sensor synaptotagmin, their precise role in membrane fusion remains an enigma. Ensemble studies of liposomes with reconstituted SNAREs have demonstrated that SNAREs and accessory proteins can trigger lipid mixing/fusion, but the inability to study individual fusion events has precluded molecular insights into the fusion process. Thus, this field is ripe for studies with single molecule methodology. In this review we discuss first applications of single-molecule approaches to observe reconstituted SNAREs, their complexes, associated proteins, and their effect on biological membranes. Some of the findings are provocative, such the possibility of parallel and anti-parallel SNARE complexes, or vesicle docking with only syntaxin and synaptobrevin, but have been confirmed by other experiments. PMID:19489736

  2. Analytical performance evaluation for autonomous sensor fusion

    NASA Astrophysics Data System (ADS)

    Chang, K. C.

    2008-04-01

    A distributed data fusion system consists of a network of sensors, each capable of local processing and fusion of sensor data. There has been a great deal of work in developing distributed fusion algorithms applicable to a network centric architecture. Currently there are at least a few approaches including naive fusion, cross-correlation fusion, information graph fusion, maximum a posteriori (MAP) fusion, channel filter fusion, and covariance intersection fusion. However, in general, in a distributed system such as the ad hoc sensor networks, the communication architecture is not fixed. Each node has knowledge of only its local connectivity but not the global network topology. In those cases, the distributed fusion algorithm based on information graph type of approach may not scale due to its requirements to carry long pedigree information for decorrelation. In this paper, we focus on scalable fusion algorithms and conduct analytical performance evaluation to compare their performance. The goal is to understand the performance of those algorithms under different operating conditions. Specifically, we evaluate the performance of channel filter fusion, Chernoff fusion, Shannon Fusion, and Battachayya fusion algorithms. We also compare their results to NaÃve fusion and "optimal" centralized fusion algorithms under a specific communication pattern.

  3. Fusion Simulation Project Workshop Report

    NASA Astrophysics Data System (ADS)

    Kritz, Arnold; Keyes, David

    2009-03-01

    The mission of the Fusion Simulation Project is to develop a predictive capability for the integrated modeling of magnetically confined plasmas. This FSP report adds to the previous activities that defined an approach to integrated modeling in magnetic fusion. These previous activities included a Fusion Energy Sciences Advisory Committee panel that was charged to study integrated simulation in 2002. The report of that panel [Journal of Fusion Energy 20, 135 (2001)] recommended the prompt initiation of a Fusion Simulation Project. In 2003, the Office of Fusion Energy Sciences formed a steering committee that developed a project vision, roadmap, and governance concepts [Journal of Fusion Energy 23, 1 (2004)]. The current FSP planning effort involved 46 physicists, applied mathematicians and computer scientists, from 21 institutions, formed into four panels and a coordinating committee. These panels were constituted to consider: Status of Physics Components, Required Computational and Applied Mathematics Tools, Integration and Management of Code Components, and Project Structure and Management. The ideas, reported here, are the products of these panels, working together over several months and culminating in a 3-day workshop in May 2007.

  4. Discriminating in vitro cell fusion from cell aggregation by flow cytometry combined with fluorescence resonance energy transfer.

    PubMed

    Huerta, Leonor; López-Balderas, Nayali; Larralde, Carlos; Lamoyi, Edmundo

    2006-12-01

    Expression of fusion proteins in the plasma membrane enables cells to bind and fuse with surrounding cells to form syncytia. Cell fusion can have important functional outcomes for the interacting cells, as syncytia formation does in AIDS pathogenesis. Studies on cell fusion would be facilitated by a quantitative method able to discriminate between cellular aggregates and bona fide fused cells in a cell population. Flow cytometry with fluorescence resonance energy transfer is applied here for analyzing fusion of HIV-1 envelope-expressing cells with CD4+ Jurkat cells. Fusion partners were labeled with the vital lipophilic fluorescent probes DiO (green) and DiI (red) and FRET is manifested by an enhancement of the DiI red fluorescence intensity in double fluorescent cells, thus allowing discrimination between fused and aggregated cells. The inhibitory effect of anti-CD4 monoclonal antibodies and the inhibitory peptide T-20 upon cell fusion were readily quantified by this technique. This method allows the distinction of fused and aggregated cells even when they are at low frequencies.

  5. Inhibitory Activities of Alkyl Syringates and Related Compounds on Aflatoxin Production

    PubMed Central

    Furukawa, Tomohiro; Iimura, Kurin; Kimura, Taichi; Yamamoto, Toshiyoshi; Sakuda, Shohei

    2016-01-01

    Inhibitors of aflatoxin production of aflatoxigenic fungi are useful for preventing aflatoxin contamination in crops. As methyl syringate weakly inhibits aflatoxin production, aflatoxin production inhibitory activities of additional alkyl syringates with alkyl chains from ethyl to octyl were examined. Inhibitory activity toward aflatoxin production of Aspergillus flavus became stronger as the length of the alkyl chains on the esters became longer. Pentyl, hexyl, heptyl, and octyl syringates showed strong activity at 0.05 mM. Heptyl and octyl parabens, and octyl gallate also inhibited aflatoxin production as strongly as octyl syringate. Alkyl parabens and alkyl gallates inhibit the complex II activity of the mitochondrial respiration chain; thus, whether alkyl syringates inhibit complex II activity was examined. Inhibitory activities of alkyl syringates toward complex II also became stronger as the length of the alkyl chains increased. The complex II inhibitory activity of octyl syringate was comparable to that of octyl paraben and octyl gallate. These results suggest that alkyl syringates, alkyl parabens, and alkyl gallates, including commonly used food additives, are useful for aflatoxin control. PMID:27338472

  6. Control of mechanically activated polymersome fusion: Factors affecting fusion

    DOE PAGES

    Henderson, Ian M.; Paxton, Walter F.

    2014-12-15

    Previously we have studied the mechanically-activated fusion of extruded (200 nm) polymer vesicles into giant polymersomes using agitation in the presence of salt. In this study we have investigated several factors contributing to this phenomenon, including the effects of (i) polymer vesicle concentration, (ii) agitation speed and duration, and iii) variation of the salt and its concentration. It was found that increasing the concentration of the polymer dramatically increases the production of giant vesicles through the increased collisions of polymersomes. Our investigations also found that increasing the frequency of agitation increased the efficiency of fusion, though ultimately limited the sizemore » of vesicle which could be produced due to the high shear involved. Finally it was determined that salt-mediation of the fusion process was not limited to NaCl, but is instead a general effect facilitated by the presence of solvated ionic compounds, albeit with different salts initiating fusion at different concentration.« less

  7. Control of mechanically activated polymersome fusion: Factors affecting fusion

    SciTech Connect

    Henderson, Ian M.; Paxton, Walter F.

    2014-12-15

    Previously we have studied the mechanically-activated fusion of extruded (200 nm) polymer vesicles into giant polymersomes using agitation in the presence of salt. In this study we have investigated several factors contributing to this phenomenon, including the effects of (i) polymer vesicle concentration, (ii) agitation speed and duration, and iii) variation of the salt and its concentration. It was found that increasing the concentration of the polymer dramatically increases the production of giant vesicles through the increased collisions of polymersomes. Our investigations also found that increasing the frequency of agitation increased the efficiency of fusion, though ultimately limited the size of vesicle which could be produced due to the high shear involved. Finally it was determined that salt-mediation of the fusion process was not limited to NaCl, but is instead a general effect facilitated by the presence of solvated ionic compounds, albeit with different salts initiating fusion at different concentration.

  8. Sec17 can trigger fusion of trans-SNARE paired membranes without Sec18.

    PubMed

    Zick, Michael; Orr, Amy; Schwartz, Matthew L; Merz, Alexey J; Wickner, William T

    2015-05-05

    Sec17 [soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein; α-SNAP] and Sec18 (NSF) perform ATP-dependent disassembly of cis-SNARE complexes, liberating SNAREs for subsequent assembly of trans-complexes for fusion. A mutant of Sec17, with limited ability to stimulate Sec18, still strongly enhanced fusion when ample Sec18 was supplied, suggesting that Sec17 has additional functions. We used fusion reactions where the four SNAREs were initially separate, thus requiring no disassembly by Sec18. With proteoliposomes bearing asymmetrically disposed SNAREs, tethering and trans-SNARE pairing allowed slow fusion. Addition of Sec17 did not affect the levels of trans-SNARE complex but triggered sudden fusion of trans-SNARE paired proteoliposomes. Sec18 did not substitute for Sec17 in triggering fusion, but ADP- or ATPγS-bound Sec18 enhanced this Sec17 function. The extent of the Sec17 effect varied with the lipid headgroup and fatty acyl composition of the proteoliposomes. Two mutants further distinguished the two Sec17 functions: Sec17(L291A,L292A) did not stimulate Sec18 to disassemble cis-SNARE complex but triggered the fusion of trans-SNARE paired membranes. Sec17(F21S,M22S), with diminished apolar character to its hydrophobic loop, fully supported Sec18-mediated SNARE complex disassembly but had lost the capacity to stimulate the fusion of trans-SNARE paired membranes. To model the interactions of SNARE-bound Sec17 with membranes, we show that Sec17, but not Sec17(F21S,M22S), interacted synergistically with the soluble SNARE domains to enable their stable association with liposomes. We propose a model in which Sec17 binds to trans-SNARE complexes, oligomerizes, and inserts apolar loops into the apposed membranes, locally disturbing the lipid bilayer and thereby lowering the energy barrier for fusion.

  9. Sec17 can trigger fusion of trans-SNARE paired membranes without Sec18

    PubMed Central

    Zick, Michael; Orr, Amy; Schwartz, Matthew L.; Merz, Alexey J.; Wickner, William T.

    2015-01-01

    Sec17 [soluble N-ethylmaleimide–sensitive factor (NSF) attachment protein; α-SNAP] and Sec18 (NSF) perform ATP-dependent disassembly of cis-SNARE complexes, liberating SNAREs for subsequent assembly of trans-complexes for fusion. A mutant of Sec17, with limited ability to stimulate Sec18, still strongly enhanced fusion when ample Sec18 was supplied, suggesting that Sec17 has additional functions. We used fusion reactions where the four SNAREs were initially separate, thus requiring no disassembly by Sec18. With proteoliposomes bearing asymmetrically disposed SNAREs, tethering and trans-SNARE pairing allowed slow fusion. Addition of Sec17 did not affect the levels of trans-SNARE complex but triggered sudden fusion of trans-SNARE paired proteoliposomes. Sec18 did not substitute for Sec17 in triggering fusion, but ADP- or ATPγS-bound Sec18 enhanced this Sec17 function. The extent of the Sec17 effect varied with the lipid headgroup and fatty acyl composition of the proteoliposomes. Two mutants further distinguished the two Sec17 functions: Sec17L291A,L292A did not stimulate Sec18 to disassemble cis-SNARE complex but triggered the fusion of trans-SNARE paired membranes. Sec17F21S,M22S, with diminished apolar character to its hydrophobic loop, fully supported Sec18-mediated SNARE complex disassembly but had lost the capacity to stimulate the fusion of trans-SNARE paired membranes. To model the interactions of SNARE-bound Sec17 with membranes, we show that Sec17, but not Sec17F21S,M22S, interacted synergistically with the soluble SNARE domains to enable their stable association with liposomes. We propose a model in which Sec17 binds to trans-SNARE complexes, oligomerizes, and inserts apolar loops into the apposed membranes, locally disturbing the lipid bilayer and thereby lowering the energy barrier for fusion. PMID:25902545

  10. Advanced fusion concepts: project summaries

    SciTech Connect

    1980-12-01

    This report contains descriptions of the activities of all the projects supported by the Advanced Fusion Concepts Branch of the Office of Fusion Energy, US Department of Energy. These descriptions are project summaries of each of the individual projects, and contain the following: title, principle investigators, funding levels, purpose, approach, progress, plans, milestones, graduate students, graduates, other professional staff, and recent publications. Information is given for each of the following programs: (1) reverse-field pinch, (2) compact toroid, (3) alternate fuel/multipoles, (4) stellarator/torsatron, (5) linear magnetic fusion, (6) liners, and (7) Tormac. (MOW)

  11. Effect of aniseikonia on fusion.

    PubMed

    Sharma, P; Prakash, P

    1991-01-01

    Physiological aniseikonia is the basis of stereopsis but beyond certain limits it becomes an obstacle to fusion. It is not well established as to how much aniseikonia can be tolerated by the fusional mechanism. Different tests under different testing conditions have given a wide range of variation. On the synoptophore we had observed tolerance upto 35% aniseikonia in some cases. Under more physiological conditions on a polaroid dissociation stereoprojector we observed lesser baseline fusional vergences but tolerance in about 70% of the cases upto 30% aniseikonia while 25% could tolerate even 35% aniseikonia. However we realise that these indicate the maximal potential and not the symptom free tolerable limits.

  12. The path to fusion power†

    PubMed Central

    Smith, Chris Llewellyn; Cowley, Steve

    2010-01-01

    The promise, status and challenges of developing fusion power are outlined. The key physics and engineering principles are described and recent progress quantified. As the successful demonstration of 16 MW of fusion in 1997 in the Joint European Torus showed, fusion works. The central issue is therefore to make it work reliably and economically on the scale of a power station. We argue that to meet this challenge in 30 years we must follow the aggressive programme known as the ‘Fast Track to Fusion’. This programme is described in some detail. PMID:20123748

  13. Measles virus attachment proteins with impaired ability to bind CD46 interact more efficiently with the homologous fusion protein

    SciTech Connect

    Corey, Elizabeth A.; Iorio, Ronald M.

    2009-01-05

    Fusion promotion by measles virus (MV) depends on an interaction between the hemagglutinin (H) and fusion (F) glycoproteins. Amino acid substitutions in MV H that drastically reduce hemagglutinating activity result in an increase in the amount of H (primarily the 74 kDa isoform) detectable in a complex with F at the cell surface. This is in direct contrast to the loss of the ability to detect a complex between the fusion protein of Newcastle disease virus and most attachment proteins that lack receptor binding activity. These opposing results provide support for the existence of different mechanisms for the regulation of fusion by these two paramyxoviruses.

  14. Generalized Chernoff Fusion Approximation for Practical Distributed Data Fusion

    DTIC Science & Technology

    2009-07-01

    Generalized Chernoff Fusion Approximation for Practical Distributed Data Fusion William J. Farrell III R&D Department Adaptive Methods , Inc...independence or modify legacy systems with pedigree tagging techniques . Leveraging the well- known Covariance Intersection algorithm, its generalization...Adaptive Methods , Inc.,Centreville, VA , , 8. PERFORMING ORGANIZATION REPORT NUMBER 9. SPONSORING/MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR

  15. Inhibitory neurosteroids and the GABAA receptor.

    PubMed

    Seljeset, Sandra; Laverty, Duncan; Smart, Trevor G

    2015-01-01

    γ-Aminobutyric acid type A receptors (GABAARs) are vital proteins that are engaged in regulating neural circuit activity in the central nervous system. Their effectiveness in this task is dependent on the extent of receptor modulation by naturally occurring ligands that are released in the brain. One of the foremost examples of such ligands is the neurosteroids that can either potentiate GABAAR function or cause direct inhibition. To fully understand the underlying mechanisms by which neurosteroids modulate GABAARs, it is necessary to identify their binding sites on the receptors. For potentiating neurosteroids, recent work has made substantive progress in identifying a binding site located in the transmembrane domains of GABAAR α subunits. However, for the inhibitory neurosteroids, several possibilities exist including an ion channel site as well as potential sites in the transmembrane domain. This review systematically analyzes the evidence behind possible binding sites for the inhibitory neurosteroids. We consider the chemical structure-function properties of such inhibitory neurosteroids, their physiological effects on synaptic inhibition, and whether a binding site exists in the GABA ion channel or in other areas of the transmembrane domain. Finally, we discuss how structural homology modeling and Cys-loop receptor homologues may help to locate the inhibitory neurosteroid-binding site on GABAARs.

  16. Inhibitory ability of children with developmental dyscalculia.

    PubMed

    Zhang, Huaiying; Wu, Hanrong

    2011-02-01

    Inhibitory ability of children with developmental dyscalculia (DD) was investigated to explore the cognitive mechanism underlying DD. According to the definition of developmental dyscalculia, 19 children with DD-only and 10 children with DD&RD (DD combined with reading disability) were selected step by step, children in two control groups were matched with children in case groups by gender and age, and the match ratio was 1:1. Psychological testing software named DMDX was used to measure inhibitory ability of the subjects. The differences of reaction time in number Stroop tasks and differences of accuracy in incongruent condition of color-word Stroop tasks and object inhibition tasks between DD-only children and their controls reached significant levels (P<0.05), and the differences of reaction time in number Stroop tasks between dyscalculic and normal children did not disappear after controlling the non-executive components. The difference of accuracy in color-word incongruent tasks between children with DD&RD and normal children reached significant levels (P<0.05). Children with DD-only confronted with general inhibitory deficits, while children with DD&RD confronted with word inhibitory deficits only.

  17. Neuraminidase inhibitory terpenes from endophytic Cochliobolus sp.

    PubMed

    Zhang, Gao-Fei; Guo, Zhi-Kai; Wang, Wei; Cui, Jiang-Tao; Tan, Ren-Xiang; Ge, Hui-Ming

    2011-08-01

    The chemical study of endophytic fungus of Cochliobolus led to the isolation of 10 terpenes (1-10), including one new compound named isocochlioquinone B (1). Their structures were elucidated on the basis of spectroscopic methods, including 2D NMR techniques. Compounds 5-7 showed significant neuraminidase inhibitory activity with IC(50) values of 0.79-1.75 μM.

  18. Bilingualism Influences Inhibitory Control in Auditory Comprehension

    ERIC Educational Resources Information Center

    Blumenfeld, Henrike K.; Marian, Viorica

    2011-01-01

    Bilinguals have been shown to outperform monolinguals at suppressing task-irrelevant information. The present study aimed to identify how processing linguistic ambiguity during auditory comprehension may be associated with inhibitory control. Monolinguals and bilinguals listened to words in their native language (English) and identified them among…

  19. Mitochondrial fusion and fission in cell life and death.

    PubMed

    Westermann, Benedikt

    2010-12-01

    Mitochondria are dynamic organelles that constantly fuse and divide. These processes (collectively termed mitochondrial dynamics) are important for mitochondrial inheritance and for the maintenance of mitochondrial functions. The core components of the evolutionarily conserved fusion and fission machineries have now been identified, and mechanistic studies have revealed the first secrets of the complex processes that govern fusion and fission of a double membrane-bound organelle. Mitochondrial dynamics was recently recognized as an important constituent of cellular quality control. Defects have detrimental consequences on bioenergetic supply and contribute to the pathogenesis of neurodegenerative diseases. These findings open exciting new directions to explore mitochondrial biology.

  20. Demazure Modules, Chari-Venkatesh Modules and Fusion Products

    NASA Astrophysics Data System (ADS)

    Ravinder, Bhimarthi

    2014-12-01

    Let g be a finite-dimensional complex simple Lie algebra with highest root θ. Given two non-negative integers m, n, we prove that the fusion product of m copies of the level one Demazure module D(1,θ) with n copies of the adjoint representation ev_0 V(θ) is independent of the parameters and we give explicit defining relations. As a consequence, for g simply laced, we show that the fusion product of a special family of Chari-Venkatesh modules is again a Chari-Venkatesh module. We also get a description of the truncated Weyl module associated to a multiple of θ.

  1. Synthetic antigens reveal dynamics of BCR endocytosis during inhibitory signaling.

    PubMed

    Courtney, Adam H; Bennett, Nitasha R; Zwick, Daniel B; Hudon, Jonathan; Kiessling, Laura L

    2014-01-17

    B cells detect foreign antigens through their B cell antigen receptor (BCR). The BCR, when engaged by antigen, initiates a signaling cascade. Concurrent with signaling is endocytosis of the BCR complex, which acts to downregulate signaling and facilitate uptake of antigen for processing and display on the cell surface. The relationship between signaling and BCR endocytosis is poorly defined. Here, we explore the interplay between BCR endocytosis and antigens that either promote or inhibit B cell activation. Specifically, synthetic antigens were generated that engage the BCR alone or both the BCR and the inhibitory co-receptor CD22. The lectin CD22, a member of the Siglec family, binds sialic acid-containing glycoconjugates found on host tissues, inhibiting BCR signaling to prevent erroneous B cell activation. At low concentrations, antigens that can cocluster the BCR and CD22 promote rapid BCR endocytosis; whereas, slower endocytosis occurs with antigens that bind only the BCR. At higher antigen concentrations, rapid BCR endocytosis occurs upon treatment with either stimulatory or inhibitory antigens. Endocytosis of the BCR, in response to synthetic antigens, results in its entry into early endocytic compartments. Although the CD22-binding antigens fail to activate key regulators of antigen presentation (e.g., Syk), they also promote BCR endocytosis, indicating that inhibitory antigens can be internalized. Together, our observations support a functional role for BCR endocytosis in downregulating BCR signaling. The reduction of cell surface BCR levels in the absence of B cell activation should raise the threshold for BCR subsequent activation. The ability of the activating synthetic antigens to trigger both signaling and entry of the BCR into early endosomes suggests strategies for targeted antigen delivery.

  2. Osmotic control of bilayer fusion.

    PubMed Central

    Fisher, L R; Parker, N S

    1984-01-01

    We have used photography and capacitance measurement to monitor the steps in the interaction and eventual fusion of optically black lipid bilayers (BLMs), hydrostatically bulged to approximately hemispherical shape and pushed together mechanically. A necessary first step is drainage of aqueous solution from between the bilayers to allow close contact of the bilayers. The drainage can be controlled by varying the osmotic difference across the bilayers. If the differences are such as to remove water from between the bilayers, fusion occurs after a time that depends on the net osmotic difference and the area of contact. If there is an osmotic flow of water into the space between the bilayers, fusion never occurs. In the fusion process, a single central bilayer forms from the original apposed pair of bilayers. The central bilayer may later burst to allow mixing of the two volumes originally bounded by the separate bilayer; the topological equivalent of exocytosis. Images FIGURE 2 PMID:6541065

  3. Overview of fusion reactor safety

    SciTech Connect

    Cohen, S.; Crocker, J.G.

    1981-01-01

    Use of deuterium-tritium burning fusion reactors requires examination of several major safety and environmental issues: (1) tritium inventory control, (2) neutron activation of structural materials, fluid streams and reactor hall environment, (3) release of radioactivity from energy sources including lithium spill reactions, superconducting magnet stored energy release, and plasma disruptions, (4) high magnetic and electromagnetic fields associated with fusion reactor superconducting magnets and radio frequency heating devices, and (5) handling and disposal of radioactive waste. Early recognition of potential safety problems with fusion reactors provides the opportunity for improvement in design and materials to eliminate or greatly reduce these problems. With an early start in this endeavor, fusion should be among the lower risk technologies for generation of commercial electrical power.

  4. Pulsed Power Driven Fusion Energy

    SciTech Connect

    SLUTZ,STEPHEN A.

    1999-11-22

    Pulsed power is a robust and inexpensive technology for obtaining high powers. Considerable progress has been made on developing light ion beams as a means of transporting this power to inertial fusion capsules. However, further progress is hampered by the lack of an adequate ion source. Alternatively, z-pinches can efficiently convert pulsed power into thermal radiation, which can be used to drive an inertial fusion capsule. However, a z-pinch driven fusion explosion will destroy a portion of the transmission line that delivers the electrical power to the z-pinch. They investigate several options for providing standoff for z-pinch driven fusion. Recyclable Transmission Lines (RTLs) appear to be the most promising approach.

  5. Excitatory synaptic activity is associated with a rapid structural plasticity of inhibitory synapses on hippocampal CA1 pyramidal cells.

    PubMed

    Lushnikova, Irina; Skibo, Galina; Muller, Dominique; Nikonenko, Irina

    2011-04-01

    Synaptic activity, such as long-term potentiation (LTP), has been shown to induce morphological plasticity of excitatory synapses on dendritic spines through the spine head and postsynaptic density (PSD) enlargement and reorganization. Much less, however, is known about activity-induced morphological modifications of inhibitory synapses. Using an in vitro model of rat organotypic hippocampal slice cultures and electron microscopy, we studied activity-related morphological changes of somatic inhibitory inputs triggered by a brief oxygen-glucose deprivation (OGD) episode, a condition associated with a synaptic enhancement referred to as anoxic LTP and a structural remodeling of excitatory synapses. Three-dimensional reconstruction of inhibitory axo-somatic synapses at different times before and after brief OGD revealed important morphological changes. The PSD area significantly and markedly increased at synapses with large and complex PSDs, but not at synapses with simple, macular PSDs. Activity-related changes of PSD size and presynaptic bouton volume developed in a strongly correlated manner. Analyses of single and serial sections further showed that the density of inhibitory synaptic contacts on the cell soma did not change within 1 h after OGD. In contrast, the proportion of the cell surface covered with inhibitory PSDs, as well as the complexity of these PSDs significantly increased, with less macular PSDs and more complex, segmented shapes. Together, these data reveal a rapid activity-related restructuring of somatic inhibitory synapses characterized by an enlargement and increased complexity of inhibitory PSDs, providing a new mechanism for a quick adjustment of the excitatory-inhibitory balance. This article is part of a Special Issue entitled 'Synaptic Plasticity & Interneurons'.

  6. World progress toward fusion energy

    NASA Astrophysics Data System (ADS)

    Clarke, J. F.

    1989-09-01

    This paper will describe the progress in fusion science and technology from a world perspective. The paper will cover the current technical status, including the understanding of fusion's economic, environmental, and safety characteristics. Fusion experiments are approaching the energy breakeven condition. An energy gain (Q) of 30 percent has been achieved in magnetic confinement experiments. In addition, temperatures required for an ignited plasma (Ti = 32 KeV) and energy confinements (about 75 percent of that required for ignition) have been achieved in separate experiments. Two major facilities have started the experimental campaign to extend these results and achieve or exceed Q = 1 plasma conditions by 1990. Inertial confinement fusion experiments are also approaching thermonuclear conditions and have achieved a compression factor 100-200 times liquid D-T. Because of this progress, the emphasis in fusion research is turning toward questions of engineering feasibility. Leaders of the major fusion R and D programs in the European Community (EC), Japan, the United States, and the U.S.S.R. have agreed on the major steps that are needed to reach the point at which a practical fusion system can be designed. The United States is preparing for an experiment to address the last unexplored scientific issue, the physics of an ignited plasma, during the late 1990's. The EC, Japan, U.S.S.R., and the United States have joined together under the auspices of the International Atomic Energy Agency (IAEA) to jointly design and prepare the validating R&D for an international facility, the International Thermonuclear Experimental Reactor (ITER), to address all the remaining scientific issues and to explore the engineering technology of fusion around the turn of the century.

  7. Magnetic fusion 1985: what next

    SciTech Connect

    Fowler, T.K.

    1985-03-01

    Recent budget reductions for magnetic fusion have led to a re-examination of program schedules and objectives. Faced with delays and postponement of major facilities as previously planned, some have called for a near-term focus on science, others have stressed technology. This talk will suggest a different focus as the keynote for this conference, namely, the applications of fusion. There is no doubt that plasma science is by now mature and fusion technology is at the forefront. This has and will continue to benefit many fields of endeavor, both in actual new discoveries and techniques and in attracting and training scientists and engineers who move on to make significant contributions in science, defense and industry. Nonetheless, however superb the science or how challenging the technology, these are means, not ends. To maintain its support, the magnetic fusion program must also offer the promise of power reactors that could be competitive in the future. At this conference, several new reactor designs will be described that claim to be smaller and economically competitive with fission reactors while retaining the environmental and safety characteristics that are the hallmark of fusion. The American Nuclear Society is an appropriate forum in which to examine these new designs critically, and to stimulate better ideas and improvements. As a preview, this talk will include brief discussions of new tokamak, tandem mirror and reversed field pinch reactor designs to be presented in later sessions. Finally, as a preview of the session on fusion breeders, the talk will explore once again the economic implications of a new nuclear age, beginning with improved fission reactors fueled by fusion breeders, then ultimately evolving to reactors based solely on fusion.

  8. Horizontal model fusion paradigm

    NASA Astrophysics Data System (ADS)

    Julier, Simon J.; Durrant-Whyte, Hugh F.

    1996-05-01

    In navigation and tracking problems, the identification of an appropriate model of vehicular or target motion is vital to most practical data fusion algorithms. The true system dynamics are rarely known, and approximations are usually employed. Since systems can exhibit strikingly different behaviors, multiple models may be needed to describe each of these behaviors. Current methods either use model switching (a single process model is chosen from the set using a decision rule) or consider the models as a set of competing hypothesis, only one of which is 'correct'. However, these methods fail to exploit the fact that all models are of the same system and that all of them are, to some degree, 'correct'. In this paper we present a new paradigm for fusing information from a set of multiple process models. The predictions from each process model are regarded as observations which are corrupted by correlated noise. By employing the standard Kalman filter equations we combine data from multiple sensors and multiple process models optimally. There are a number of significant practical advantages to this technique. First, the performance of the system always equals or betters that of the best estimator in the set of models being used. Second, the same decision theoretic machinery can be used to select the process models as well as the sensor suites.

  9. Cold fusion verification

    NASA Astrophysics Data System (ADS)

    North, M. H.; Mastny, G. F.; Wesley, E. J.

    1991-03-01

    The objective of this work to verify and reproduce experimental observations of Cold Nuclear Fusion (CNF), as originally reported in 1989. The method was to start with the original report and add such additional information as became available to build a set of operational electrolytic CNF cells. Verification was to be achieved by first observing cells for neutron production, and for those cells that demonstrated a nuclear effect, careful calorimetric measurements were planned. The authors concluded, after laboratory experience, reading published work, talking with others in the field, and attending conferences, that CNF probably is chimera and will go the way of N-rays and polywater. The neutron detector used for these tests was a completely packaged unit built into a metal suitcase that afforded electrostatic shielding for the detectors and self-contained electronics. It was battery-powered, although it was on charge for most of the long tests. The sensor element consists of He detectors arranged in three independent layers in a solid moderating block. The count from each of the three layers as well as the sum of all the detectors were brought out and recorded separately. The neutron measurements were made with both the neutron detector and the sample tested in a cave made of thick moderating material that surrounded the two units on the sides and bottom.

  10. Fusion and infection of influenza and Sendai viruses as modulated by dextran sulfate: a comparative study.

    PubMed

    Ramalho-Santos, J; de Lima, M C

    2001-06-01

    We have directly compared the effect of two types of dextran sulfate with distinct molecular weights (500 kDa and 5 kDa) on the fusion activity and infectivity of both Sendai and influenza viruses, two lipid-enveloped viruses that differ in their routes of entry into target cells. To correlate membrane merging and infectivity MDCK cells were used as targets for the viruses in both approaches. In either case pronounced inhibition of virus-cell interactions by dextran sulfate was only observed at low pH, even though Sendai virus fuses maximally at pH 7.4. Although membrane merging could not be fully abolished, the inhibitory effect was always greater when the higher molecular weight dextran sulfate was used. The presence of this residual fusion activity, that could not be reduced even with high concentrations of agent, suggests that a limited number of binding sites for dextran sulfate may exist on the viral envelopes. The compounds also inhibited fusion of bound virions, and all results could be reproduced using erythrocyte ghosts as target membranes in the fusion assay, instead of MDCK cells. In agreement with these observations only the infectivity of influenza virus (which requires a low pH-dependent step to enter target cells) was affected by dextran sulfate, again the higher molecular weight compound showing a more pronounced inhibitory effect.

  11. Visualization and Sequencing of Membrane Remodeling Leading to Influenza Virus Fusion

    PubMed Central

    Gui, Long; Ebner, Jamie L.; Mileant, Alexander; Williams, James A.

    2016-01-01

    ABSTRACT Protein-mediated membrane fusion is an essential step in many fundamental biological events, including enveloped virus infection. The nature of protein and membrane intermediates and the sequence of membrane remodeling during these essential processes remain poorly understood. Here we used cryo-electron tomography (cryo-ET) to image the interplay between influenza virus and vesicles with a range of lipid compositions. By following the population kinetics of membrane fusion intermediates imaged by cryo-ET, we found that membrane remodeling commenced with the hemagglutinin fusion protein spikes grappling onto the target membrane, followed by localized target membrane dimpling as local clusters of hemagglutinin started to undergo conformational refolding. The local dimples then transitioned to extended, tightly apposed contact zones where the two proximal membrane leaflets were in most cases indistinguishable from each other, suggesting significant dehydration and possible intermingling of the lipid head groups. Increasing the content of fusion-enhancing cholesterol or bis-monoacylglycerophosphate in the target membrane led to an increase in extended contact zone formation. Interestingly, hemifused intermediates were found to be extremely rare in the influenza virus fusion system studied here, most likely reflecting the instability of this state and its rapid conversion to postfusion complexes, which increased in population over time. By tracking the populations of fusion complexes over time, the architecture and sequence of membrane reorganization leading to efficient enveloped virus fusion were thus resolved. IMPORTANCE Enveloped viruses employ specialized surface proteins to mediate fusion of cellular and viral membranes that results in the formation of pores through which the viral genetic material is delivered to the cell. For influenza virus, the trimeric hemagglutinin (HA) glycoprotein spike mediates host cell attachment and membrane fusion. While

  12. Prospects for Tokamak Fusion Reactors

    SciTech Connect

    Sheffield, J.; Galambos, J.

    1995-04-01

    This paper first reviews briefly the status and plans for research in magnetic fusion energy and discusses the prospects for the tokamak magnetic configuration to be the basis for a fusion power plant. Good progress has been made in achieving fusion reactor-level, deuterium-tritium (D-T) plasmas with the production of significant fusion power in the Joint European Torus (up to 2 MW) and the Tokamak Fusion Test Reactor (up to 10 MW) tokamaks. Advances on the technologies of heating, fueling, diagnostics, and materials supported these achievements. The successes have led to the initiation of the design phases of two tokamaks, the International Thermonuclear Experimental Reactor (ITER) and the US Toroidal Physics Experiment (TPX). ITER will demonstrate the controlled ignition and extended bum of D-T plasmas with steady state as an ultimate goal. ITER will further demonstrate technologies essential to a power plant in an integrated system and perform integrated testing of the high heat flux and nuclear components required to use fusion energy for practical purposes. TPX will complement ITER by testing advanced modes of steady-state plasma operation that, coupled with the developments in ITER, will lead to an optimized demonstration power plant.

  13. Tritium accountancy in fusion systems

    SciTech Connect

    Klein, J.E.; Clark, E.A.; Harvel, C.D.; Farmer, D.A.; Tovo, L.L.; Poore, A.S.; Moore, M.L.

    2015-03-15

    The US Department of Energy (DOE) has clearly defined requirements for nuclear material control and accountability (MCA) of tritium whereas the International Atomic Energy Agency (IAEA) does not since tritium is not a fissile material. MCA requirements are expected for tritium fusion machines and will be dictated by the host country or regulatory body where the machine is operated. Material Balance Areas (MBA) are defined to aid in the tracking and reporting of nuclear material movements and inventories. Material sub-accounts (MSA) are established along with key measurement points (KMP) to further subdivide a MBA to localize and minimize uncertainties in the inventory difference (ID) calculations for tritium accountancy. Fusion systems try to minimize tritium inventory which may require continuous movement of material through the MSA. The ability of making meaningful measurements of these material transfers is described in terms of establishing the MSA structure to perform and reconcile ID calculations. For fusion machines, changes to the traditional ID equation will be discussed which includes breeding, burn-up, and retention of tritium in the fusion device. The concept of 'net' tritium quantities consumed or lost in fusion devices is described in terms of inventory taking strategies and how it is used to track the accumulation of tritium in components or fusion machines. (authors)

  14. TRITIUM ACCOUNTANCY IN FUSION SYSTEMS

    SciTech Connect

    Klein, J. E.; Farmer, D. A.; Moore, M. L.; Tovo, L. L.; Poore, A. S.; Clark, E. A.; Harvel, C. D.

    2014-03-06

    The US Department of Energy (DOE) has clearly defined requirements for nuclear material control and accountability (MC&A) of tritium whereas the International Atomic Energy Agency (IAEA) does not since tritium is not a fissile material. MC&A requirements are expected for tritium fusion machines and will be dictated by the host country or regulatory body where the machine is operated. Material Balance Areas (MBAs) are defined to aid in the tracking and reporting of nuclear material movements and inventories. Material subaccounts (MSAs) are established along with key measurement points (KMPs) to further subdivide a MBA to localize and minimize uncertainties in the inventory difference (ID) calculations for tritium accountancy. Fusion systems try to minimize tritium inventory which may require continuous movement of material through the MSAs. The ability of making meaningful measurements of these material transfers is described in terms of establishing the MSA structure to perform and reconcile ID calculations. For fusion machines, changes to the traditional ID equation will be discussed which includes breading, burn-up, and retention of tritium in the fusion device. The concept of “net” tritium quantities consumed or lost in fusion devices is described in terms of inventory taking strategies and how it is used to track the accumulation of tritium in components or fusion machines.

  15. Modeling of Heat and Mass Transfer in Fusion Welding

    SciTech Connect

    Zhang, Wei

    2011-01-01

    In fusion welding, parts are joined together by melting and subsequent solidification. Although this principle is simple, complex transport phenomena take place during fusion welding, and they determine the final weld quality and performance. The heat and mass transfer in the weld pool directly affect the size and shape of the pool, the solidification microstructure, the formation of weld defects such as porosity and humping, and the temperature distribution in the fusion zone and heat-affected zone (HAZ). Furthermore, the temperature evolution affects the kinetics and extent of various solid-state phase transformations, which in turn determine the final weld microstructure and mechanical properties. The formation of residual stresses and distortion originates from the thermal expansion and contraction during welding heating and cooling, respectively.

  16. Comparison of fusion imageries with spectral fidelity using SPOT5

    NASA Astrophysics Data System (ADS)

    Chen, Weitao; Zhang, Lin; Zhang, Zhi; Wang, Yanxin

    2009-10-01

    Gram-Schmidt and Ehlers fusion, which are well known for spectral fidelity, are described. Selecting a sandrock mine using SPOT5 as study area, spectral fidelity and high spatial information gain are used to assess the two fusion methods, which are compared with multiplication and Andorr fusion. In the whole, the Gram-Schmidt method is the best, preserving highly the original spectral information, and can provide spectrum control foundation for interpreting mine targets in the complex geology environment. Ehlers method is the second. Then Andorr method is the third, and it has the highest spatial information gain, but high frequency information is enlarged excessively, effecting on the identification of mine exploitation state. The multiplication method is the worst, because it loses the high and low frequency information, which is the most important for mine targets recognition.

  17. Nuclear fusion and genome encounter during yeast zygote formation.

    PubMed

    Tartakoff, Alan Michael; Jaiswal, Purnima

    2009-06-01

    When haploid cells of Saccharomyces cerevisiae are crossed, parental nuclei congress and fuse with each other. To investigate underlying mechanisms, we have developed assays that evaluate the impact of drugs and mutations. Nuclear congression is inhibited by drugs that perturb the actin and tubulin cytoskeletons. Nuclear envelope (NE) fusion consists of at least five steps in which preliminary modifications are followed by controlled flux of first outer and then inner membrane proteins, all before visible dilation of the waist of the nucleus or coalescence of the parental spindle pole bodies. Flux of nuclear pore complexes occurs after dilation. Karyogamy requires both the Sec18p/NSF ATPase and ER/NE luminal homeostasis. After fusion, chromosome tethering keeps tagged parental genomes separate from each other. The process of NE fusion and evidence of genome independence in yeast provide a prototype for understanding related events in higher eukaryotes.

  18. How and why intralumenal membrane fragments form during vacuolar lysosome fusion

    PubMed Central

    Mattie, Sevan; McNally, Erin K.; Karim, Mahmoud A.; Vali, Hojatollah; Brett, Christopher L.

    2017-01-01

    Lysosomal membrane fusion mediates the last step of the autophagy and endocytosis pathways and supports organelle remodeling and biogenesis. Because fusogenic proteins and lipids concentrate in a ring at the vertex between apposing organelle membranes, the encircled area of membrane can be severed and internalized within the lumen as a fragment upon lipid bilayer fusion. How or why this intralumenal fragment forms during fusion, however, is not entirely clear. To better understand this process, we studied fragment formation during homotypic vacuolar lysosome membrane fusion in Saccharomyces cerevisiae. Using cell-free fusion assays and light microscopy, we find that GTPase activation and trans-SNARE complex zippering have opposing effects on fragment formation and verify that this affects the morphology of the fusion product and regulates transporter protein degradation. We show that fragment formwation is limited by stalk expansion, a key intermediate of the lipid bilayer fusion reaction. Using electron microscopy, we present images of hemifusion diaphragms that form as stalks expand and propose a model describing how the fusion machinery regulates fragment formation during lysosome fusion to control morphology and protein lifetimes. PMID:27881666

  19. Inhibitory connections in the honeybee antennal lobe are spatially patchy.

    PubMed

    Girardin, Cyrille C; Kreissl, Sabine; Galizia, C Giovanni

    2013-01-01

    The olfactory system is a classical model for studying sensory processing. The first olfactory brain center [the olfactory bulb of vertebrates and the antennal lobe (AL) of insects] contains spherical neuropiles called glomeruli. Each glomerulus receives the information from one olfactory receptor type. Interglomerular computation is accomplished by lateral connectivity via interneurons. However, the spatial and functional organization of these lateral connections is not completely understood. Here we studied the spatial logic in the AL of the honeybee. We combined topical application of neurotransmitters, olfactory stimulations, and in vivo calcium imaging to visualize the arrangement of lateral connections. Suppression of activity in a single glomerulus with γ-aminobutyric acid (GABA) while presenting an odor reveals the existence of inhibitory interactions. Stimulating a glomerulus with acetylcholine (ACh) activates inhibitory interglomerular connections that can reduce odor-evoked responses. We show that this lateral network is patchy, in that individual glomeruli inhibit other glomeruli with graded strength, but in a spatially discontinuous manner. These results suggest that processing of olfactory information requires combinatorial activity patterns with complex topologies across the AL.

  20. Genetically Enhanced Lysozyme Evades a Pathogen Derived Inhibitory Protein

    PubMed Central

    Dostal, Sarah M.; Fang, Yongliang; Guerrette, Jonathan C.; Scanlon, Thomas C.; Griswold, Karl E.

    2015-01-01

    The accelerating spread of drug-resistant bacteria is creating demand for novel antibiotics. Bactericidal enzymes, such as human lysozyme (hLYZ), are interesting drug candidates due to their inherent catalytic nature and lack of susceptibility to the resistance mechanisms typically directed towards chemotherapeutics. However, natural antibacterial enzymes have their own limitations. For example, hLYZ is susceptible to pathogen derived inhibitory proteins, such as Escherichia coli Ivy. Here, we describe proof of concept studies demonstrating that hLYZ can be effectively redesigned to evade this potent lysozyme inhibitor. Large combinatorial libraries of hLYZ were analyzed using an innovative screening platform based on microbial co-culture in hydrogel microdroplets. Isolated hLYZ variants were orders of magnitude less susceptible to E. coli Ivy yet retained high catalytic proficiency and inherent antibacterial activity. Interestingly, the engineered escape variants showed a disadvantageous increase in susceptibility to the related Ivy ortholog from Pseudomonas aeruginosa as well as an unrelated E. coli inhibitory protein, MliC. Thus, while we have achieved our original objective with respect to escaping E. coli Ivy, engineering hLYZ for broad-spectrum evasion of proteinaceous inhibitors will require consideration of the complex and varied determinants that underlie molecular recognition by these emerging virulence factors. PMID:25607237

  1. Inhibitory mechanism of red globe amaranth on tyrosinase.

    PubMed

    Mu, Yan; Li, Lin; Zhou, Yong; Wei, Hai-Liu; Hu, Song-Qing

    2013-01-01

    Tyrosinase inhibitors from natural plants are currently attracting great interest. In this study, vanillic acid (VA) from red globe amaranth flower was identified as an effective tyrosinase inhibitor. The 50% inhibitory concentration values of VA were 0.53 and 0.63 mg/ml for the monophenolase and diphenolase activities of tyrosinase, respectively. VA did not function as a simple copper chelator, and it did not induce detectable changes in the enzyme conformation. An investigation into the interaction between VA and tyrosinase by docking method revealed that VA was bound to residues at the entrance to the dicopper center. This suggests that VA could strongly inhibit tyrosinase activity by hampering the binding of substrates to tyrosinase. Because of the stability of the complex, VA hindered binding of monophenol substrates better than that of diphenol substrates, which resulted in different inhibitory efficacies. A study of the mechanism of tyrosinase inhibition provided new evidence to elucidate the molecular mechanism of depigmentation by red globe amaranth plant.

  2. A burning plasma program strategy to advance fusion energy. Report of the Fusion Energy Sciences Advisory Committee, Burning Plasma Strategy Panel

    SciTech Connect

    None, None

    2002-09-01

    Fusion energy shows great promise to contribute to securing the energy future of humanity. The risk of conflicts arising from energy shortages and supply cutoffs, as well as the risk of severe environmental impacts from existing methods of energy production, are strong reasons to pursue fusion energy now. The world effort to develop fusion energy is at the threshold of a new stage in its research: the investigation of burning plasmas. This investigation, at the frontier of the physics of complex systems, would be a huge step in establishing the potential of magnetic fusion energy to contribute to the world’s energy security. The defining feature of a burning plasma is that it is self-heated: the 100 million degree temperature of the plasma is maintained mainly by the heat generated by the fusion reactions themselves, as occurs in burning stars. The fusion-generated alpha particles produce new physical phenomena that are strongly coupled together as a nonlinear complex system. Understanding all elements of this system poses a major challenge to fundamental plasma physics. The technology needed to produce and control a burning plasma presents challenges in engineering science similarly essential to the development of fusion energy.

  3. Multimerized HIV-gp41-derived peptides as fusion inhibitors and vaccines.

    PubMed

    Nomura, Wataru; Mizuguchi, Takaaki; Tamamura, Hirokazu

    2016-11-04

    To date, several antigens based on the amino-terminal leucine/isoleucine heptad repeat (NHR) region of an HIV-1 envelope protein gp41 and fusion inhibitors based on the carboxy-terminal leucine/isoleucine heptad repeat (CHR) region of gp41 have been reported. We have developed a synthetic antigen targeting the membrane-fusion mechanism of HIV-1. This uses a template designed with C3-symmetric linkers and mimics the trimeric form of the NHR-derived peptide N36. The antiserum obtained by immunization of the N36 trimeric antigen binds preferentially to the N36 trimer and blocks HIV-1 infection effectively, compared with the antiserum obtained by immunization of the N36 monomer. Using another template designed with different C3-symmetric linkers, we have also developed a synthetic peptide mimicking the trimeric form of the CHR-derived peptide C34, with ∼100 times the inhibitory activity against the HIV-1 fusion mechanism than that of the monomer C34 peptide. A dimeric derivative of C34 has potent inhibitory activity at almost the same levels as this C34 trimer mimic, suggesting that presence of a dimeric form of C34 is structurally critical for fusion inhibitors. As examples of rising mid-size drugs, this review describes an effective strategy for the design of HIV vaccines and fusion inhibitors based on a relationship with the native structure of proteins involved in HIV fusion mechanisms. © 2015 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 622-628, 2016.

  4. Successful anterior fusion following posterior cervical fusion for revision of anterior cervical discectomy and fusion pseudarthrosis.

    PubMed

    Elder, Benjamin D; Sankey, Eric W; Theodros, Debebe; Bydon, Mohamad; Goodwin, C Rory; Lo, Sheng-Fu; Kosztowski, Thomas A; Belzberg, Allen J; Wolinsky, Jean-Paul; Sciubba, Daniel M; Gokaslan, Ziya L; Bydon, Ali; Witham, Timothy F

    2016-02-01

    Pseudarthrosis occurs after approximately 2-20% of anterior cervical discectomy and fusion (ACDF) procedures; it is unclear if posterior or anterior revision should be pursued. In this study, we retrospectively evaluate the outcomes in 22 patients with pseudarthrosis following ACDF and revision via posterior cervical fusion (PCF). Baseline demographics, preoperative symptoms, operative data, time to fusion failure, symptoms of pseudarthrosis, and revision method were assessed. Fusion outcome and clinical outcome were determined at last follow-up (LFU). Thirteen females (59%) and 9 (41%) males experienced pseudarthrosis at a median of 11 (range: 3-151)months after ACDF. Median age at index surgery was 51 (range: 33-67)years. All patients with pseudarthrosis presented with progressive neck pain, with median visual analog scale (VAS) score of 8 (range: 0-10), and/or myeloradiculopathy. Patients with pseudarthrosis <12 months compared to >12 months after index surgery were older (p=0.013), had more frequent preoperative neurological deficits (p=0.064), and lower baseline VAS scores (p=0.006). Fusion was successful after PCF in all patients, with median time to fusion of 10 (range: 2-14)months. Eighteen patients fused both anteriorly and posteriorly, two patients fused anteriorly only, and two patients fused posteriorly only. Median VAS neck score at LFU significantly improved from the time of pseudarthrosis (p=0.012). While uncommon, pseudarthrosis may occur after ACDF. All patients achieved successful fusion after subsequent posterior cervical fusion, with 91% fusing a previous anterior pseudarthrosis after posterior stabilization. Neck pain significantly improved by LFU in the majority of patients in this study.

  5. Protein functional links in Trypanosoma brucei, identified by gene fusion analysis

    PubMed Central

    2011-01-01

    Background Domain or gene fusion analysis is a bioinformatics method for detecting gene fusions in one organism by comparing its genome to that of other organisms. The occurrence of gene fusions suggests that the two original genes that participated in the fusion are functionally linked, i.e. their gene products interact either as part of a multi-subunit protein complex, or in a metabolic pathway. Gene fusion analysis has been used to identify protein functional links in prokaryotes as well as in eukaryotic model organisms, such as yeast and Drosophila. Results In this study we have extended this approach to include a number of recently sequenced protists, four of which are pathogenic, to identify fusion linked proteins in Trypanosoma brucei, the causative agent of African sleeping sickness. We have also examined the evolution of the gene fusion events identified, to determine whether they can be attributed to fusion or fission, by looking at the conservation of the fused genes and of the individual component genes across the major eukaryotic and prokaryotic lineages. We find relatively limited occurrence of gene fusions/fissions within the protist lineages examined. Our results point to two trypanosome-specific gene fissions, which have recently been experimentally confirmed, one fusion involving proteins involved in the same metabolic pathway, as well as two novel putative functional links between fusion-linked protein pairs. Conclusions This is the first study of protein functional links in T. brucei identified by gene fusion analysis. We have used strict thresholds and only discuss results which are highly likely to be genuine and which either have already been or can be experimentally verified. We discuss the possible impact of the identification of these novel putative protein-protein interactions, to the development of new trypanosome therapeutic drugs. PMID:21729286

  6. Regulation of HSV glycoprotein induced cascade of events governing cell-cell fusion.

    PubMed

    Atanasiu, Doina; Saw, Wan Ting; Eisenberg, Roselyn J; Cohen, Gary H

    2016-09-14

    Receptor dependent HSV-induced fusion requires glycoproteins gD, gH/gL, and gB. Our current model posits that during fusion receptor-activated conformational changes in gD activate gH/gL, which subsequently triggers transformation of the pre-fusion form of gB into a fusogenic state. To examine the role of each glycoprotein in receptor dependent cell-cell fusion we took advantage of our discovery that fusion by wild type HSV-2 glycoproteins occurs twice as fast as that achieved by HSV-1 glycoproteins. By sequentially swapping each glycoprotein between the two serotypes, we established that fusion speed was governed by gH/gL, with gH being the main contributor. While the mutant forms of gB fuse at distinct rates that are dictated by their molecular structure, these restrictions can be overcome by gH2/gL2, thereby enhancing their activity. We also found that deregulated forms of gD1 and gH2/gL2 can alter the fusogenic potential of gB, promoting cell fusion in the absence of a cellular receptor and that deregulated forms of gB can drive the fusion machinery to even higher levels. Low pH enhanced fusion by affecting the structure of both gB and gH/gL mutants. Together, our data highlight the complexity of the fusion machinery, the impact of the activation state of each glycoprotein on the fusion process and the critical role of gH/gL in regulating HSV induced fusion.

  7. STAC: a comprehensive sensor fusion model for scene characterization

    NASA Astrophysics Data System (ADS)

    Kira, Zsolt; Wagner, Alan R.; Kennedy, Chris; Zutty, Jason; Tuell, Grady

    2015-05-01

    We are interested in data fusion strategies for Intelligence, Surveillance, and Reconnaissance (ISR) missions. Advances in theory, algorithms, and computational power have made it possible to extract rich semantic information from a wide variety of sensors, but these advances have raised new challenges in fusing the data. For example, in developing fusion algorithms for moving target identification (MTI) applications, what is the best way to combine image data having different temporal frequencies, and how should we introduce contextual information acquired from monitoring cell phones or from human intelligence? In addressing these questions we have found that existing data fusion models do not readily facilitate comparison of fusion algorithms performing such complex information extraction, so we developed a new model that does. Here, we present the Spatial, Temporal, Algorithm, and Cognition (STAC) model. STAC allows for describing the progression of multi-sensor raw data through increasing levels of abstraction, and provides a way to easily compare fusion strategies. It provides for unambiguous description of how multi-sensor data are combined, the computational algorithms being used, and how scene understanding is ultimately achieved. In this paper, we describe and illustrate the STAC model, and compare it to other existing models.

  8. Mechanism for Active Membrane Fusion Triggering by Morbillivirus Attachment Protein

    PubMed Central

    Ader, Nadine; Brindley, Melinda; Avila, Mislay; Örvell, Claes; Horvat, Branka; Hiltensperger, Georg; Schneider-Schaulies, Jürgen; Vandevelde, Marc; Zurbriggen, Andreas; Plemper, Richard K.

    2013-01-01

    The paramyxovirus entry machinery consists of two glycoproteins that tightly cooperate to achieve membrane fusion for cell entry: the tetrameric attachment protein (HN, H, or G, depending on the paramyxovirus genus) and the trimeric fusion protein (F). Here, we explore whether receptor-induced conformational changes within morbillivirus H proteins promote membrane fusion by a mechanism requiring the active destabilization of prefusion F or by the dissociation of prefusion F from intracellularly preformed glycoprotein complexes. To properly probe F conformations, we identified anti-F monoclonal antibodies (MAbs) that recognize conformation-dependent epitopes. Through heat treatment as a surrogate for H-mediated F triggering, we demonstrate with these MAbs that the morbillivirus F trimer contains a sufficiently high inherent activation energy barrier to maintain the metastable prefusion state even in the absence of H. This notion was further validated by exploring the conformational states of destabilized F mutants and stabilized soluble F variants combined with the use of a membrane fusion inhibitor (3g). Taken together, our findings reveal that the morbillivirus H protein must lower the activation energy barrier of metastable prefusion F for fusion triggering. PMID:23077316

  9. Novel Hydrophobin Fusion Tags for Plant-Produced Fusion Proteins

    PubMed Central

    Ritala, Anneli; Linder, Markus; Joensuu, Jussi

    2016-01-01

    Hydrophobin fusion technology has been applied in the expression of several recombinant proteins in plants. Until now, the technology has relied exclusively on the Trichoderma reesei hydrophobin HFBI. We screened eight novel hydrophobin tags, T. reesei HFBII, HFBIII, HFBIV, HFBV, HFBVI and Fusarium verticillioides derived HYD3, HYD4 and HYD5, for production of fusion proteins in plants and purification by two-phase separation. To study the properties of the hydrophobins, we used N-terminal and C-terminal GFP as a fusion partner. Transient expression of the hydrophobin fusions in Nicotiana benthamiana revealed large variability in accumulation levels, which was also reflected in formation of protein bodies. In two-phase separations, only HFBII and HFBIV were able to concentrate GFP into the surfactant phase from a plant extract. The separation efficiency of both tags was comparable to HFBI. When the accumulation was tested side by side, HFBII-GFP gave a better yield than HFBI-GFP, while the yield of HFBIV-GFP remained lower. Thus we present here two alternatives for HFBI as functional fusion tags for plant-based protein production and first step purification. PMID:27706254

  10. Using the structure of inhibitory networks to unravel mechanisms of spatiotemporal patterning

    PubMed Central

    Assisi, Collins; Stopfer, Mark; Bazhenov, Maxim

    2011-01-01

    Summary Neuronal networks exhibit a rich dynamical repertoire, a consequence of both the intrinsic properties of neurons and the structure of the network. It has been hypothesized that inhibitory interneurons corral principal neurons into transiently synchronous ensembles that encode sensory information and sub–serve behavior. How does the structure of the inhibitory network facilitate such spatiotemporal patterning? We established a relationship between an important structural property of a network, its colorings, and the dynamics it constrains. Using a model of the insect antennal lobe we show that our description allows the explicit identification of the groups of inhibitory interneurons that switch, during odor stimulation, between activity and quiescence in a coordinated manner determined by features of the network structure. This description optimally matches the perspective of the downstream neurons looking for synchrony in ensembles of pre–synaptic cells and allows a low–dimensional description of seemingly complex high–dimensional network activity. PMID:21262473

  11. GAD67-mediated GABA synthesis and signaling regulate inhibitory synaptic innervation in the visual cortex.

    PubMed

    Chattopadhyaya, Bidisha; Di Cristo, Graziella; Wu, Cai Zhi; Knott, Graham; Kuhlman, Sandra; Fu, Yu; Palmiter, Richard D; Huang, Z Josh

    2007-06-21

    The development of GABAergic inhibitory circuits is shaped by neural activity, but the underlying mechanisms are unclear. Here, we demonstrate a novel function of GABA in regulating GABAergic innervation in the adolescent brain, when GABA is mainly known as an inhibitory transmitter. Conditional knockdown of the rate-limiting synthetic enzyme GAD67 in basket interneurons in adolescent visual cortex resulted in cell autonomous deficits in axon branching, perisomatic synapse formation around pyramidal neurons, and complexity of the innervation fields; the same manipulation had little influence on the subsequent maintenance of perisomatic synapses. These effects of GABA deficiency were rescued by suppressing GABA reuptake and by GABA receptor agonists. Germline knockdown of GAD67 but not GAD65 showed similar deficits, suggesting a specific role of GAD67 in the maturation of perisomatic innervation. Since intracellular GABA levels are modulated by neuronal activity, our results implicate GAD67-mediated GABA synthesis in activity-dependent regulation of inhibitory innervation patterns.

  12. Folded monomers and hexamers of the ectodomain of the HIV gp41 membrane fusion protein: potential roles in fusion and synergy between the fusion peptide, hairpin, and membrane-proximal external region.

    PubMed

    Banerjee, Koyeli; Weliky, David P

    2014-11-25

    HIV is an enveloped virus and fusion between the HIV and host cell membranes is catalyzed by the ectodomain of the HIV gp41 membrane protein. Both the N-terminal fusion peptide (FP) and C-terminal membrane-proximal external region (MPER) are critical for fusion and are postulated to bind to the host cell and HIV membranes, respectively. Prior to fusion, the gp41 on the virion is a trimer in noncovalent complex with larger gp120 subunits. The gp120 bind host cell receptors and move away or dissociate from gp41 which subsequently catalyzes fusion. In the present work, large gp41 ectodomain constructs were produced and biophysically and structurally characterized. One significant finding is observation of synergy between the FP, hairpin, and MPER in vesicle fusion. The ectodomain-induced fusion can be very efficient with only ∼15 gp41 per vesicle, which is comparable to the number of gp41 on a virion. Conditions are found with predominant monomer or hexamer but not trimer and these may be oligomeric states during fusion. Monomer gp41 ectodomain is hyperthermostable and has helical hairpin structure. A new HIV fusion model is presented where (1) hemifusion is catalyzed by folding of gp41 ectodomain monomers into hairpins and (2) subsequent fusion steps are catalyzed by assembly into a hexamer with FPs in an antiparallel β sheet. There is also significant interest in the gp41 MPER because it is the epitope of several broadly neutralizing antibodies. Two of these antibodies bind our gp41 ectodomain constructs and support investigation of the gp41 ectodomain as an immunogen in HIV vaccine development.

  13. Fusion Plasma Theory project summaries

    SciTech Connect

    Not Available

    1993-10-01

    This Project Summary book is a published compilation consisting of short descriptions of each project supported by the Fusion Plasma Theory and Computing Group of the Advanced Physics and Technology Division of the Department of Energy, Office of Fusion Energy. The summaries contained in this volume were written by the individual contractors with minimal editing by the Office of Fusion Energy. Previous summaries were published in February of 1982 and December of 1987. The Plasma Theory program is responsible for the development of concepts and models that describe and predict the behavior of a magnetically confined plasma. Emphasis is given to the modelling and understanding of the processes controlling transport of energy and particles in a toroidal plasma and supporting the design of the International Thermonuclear Experimental Reactor (ITER). A tokamak transport initiative was begun in 1989 to improve understanding of how energy and particles are lost from the plasma by mechanisms that transport them across field lines. The Plasma Theory program has actively-participated in this initiative. Recently, increased attention has been given to issues of importance to the proposed Tokamak Physics Experiment (TPX). Particular attention has been paid to containment and thermalization of fast alpha particles produced in a burning fusion plasma as well as control of sawteeth, current drive, impurity control, and design of improved auxiliary heating. In addition, general models of plasma behavior are developed from physics features common to different confinement geometries. This work uses both analytical and numerical techniques. The Fusion Theory program supports research projects at US government laboratories, universities and industrial contractors. Its support of theoretical work at universities contributes to the office of Fusion Energy mission of training scientific manpower for the US Fusion Energy Program.

  14. Interactions between Autophagy and Inhibitory Cytokines

    PubMed Central

    Wu, Tian-tian; Li, Wei-Min; Yao, Yong-Ming

    2016-01-01

    Autophagy is a degradative pathway that plays an essential role in maintaining cellular homeostasis. Most early studies of autophagy focused on its involvement in age-associated degeneration and nutrient deprivation. However, the immunological functions of autophagy have become more widely studied in recent years. Autophagy has been shown to be an intrinsic cellular defense mechanism in the innate and adaptive immune responses. Cytokines belong to a broad and loose category of proteins and are crucial for innate and adaptive immunity. Inhibitory cytokines have evolved to permit tolerance to self while also contributing to the eradication of invading pathogens. Interactions between inhibitory cytokines and autophagy have recently been reported, revealing a novel mechanism by which autophagy controls the immune response. In this review, we discuss interactions between autophagy and the regulatory cytokines IL-10, transforming growth factor-β, and IL-27. We also mention possible interactions between two newly discovered cytokines, IL-35 and IL-37, and autophagy. PMID:27313501

  15. Two networks of electrically coupled inhibitory neurons in neocortex

    NASA Astrophysics Data System (ADS)

    Gibson, Jay R.; Beierlein, Michael; Connors, Barry W.

    1999-11-01

    Inhibitory interneurons are critical to sensory transformations, plasticity and synchronous activity in the neocortex. There are many types of inhibitory neurons, but their synaptic organization is poorly understood. Here we describe two functionally distinct inhibitory networks comprising either fast-spiking (FS) or low-threshold spiking (LTS) neurons. Paired-cell recordings showed that inhibitory neurons of the same type were strongly interconnected by electrical synapses, but electrical synapses between different inhibitory cell types were rare. The electrical synapses were strong enough to synchronize spikes in coupled interneurons. Inhibitory chemical synapses were also common between FS cells, and between FS and LTS cells, but LTS cells rarely inhibited one another. Thalamocortical synapses, which convey sensory information to the cortex, specifically and strongly excited only the FS cell network. The electrical and chemical synaptic connections of different types of inhibitory neurons are specific, and may allow each inhibitory network to function independently.

  16. Circadian Plasticity of Mammalian Inhibitory Interneurons

    PubMed Central

    2017-01-01

    Inhibitory interneurons participate in all neuronal circuits in the mammalian brain, including the circadian clock system, and are indispensable for their effective function. Although the clock neurons have different molecular and electrical properties, their main function is the generation of circadian oscillations. Here we review the circadian plasticity of GABAergic interneurons in several areas of the mammalian brain, suprachiasmatic nucleus, neocortex, hippocampus, olfactory bulb, cerebellum, striatum, and in the retina. PMID:28367335

  17. Inhibitory Gating of Input Comparison in the CA1 Microcircuit.

    PubMed

    Milstein, Aaron D; Bloss, Erik B; Apostolides, Pierre F; Vaidya, Sachin P; Dilly, Geoffrey A; Zemelman, Boris V; Magee, Jeffrey C

    2015-09-23

    Spatial and temporal features of synaptic inputs engage integration mechanisms on multiple scales, including presynaptic release sites, postsynaptic dendrites, and networks of inhibitory interneurons. Here we investigate how these mechanisms cooperate to filter synaptic input in hippocampal area CA1. Dendritic recordings from CA1 pyramidal neurons reveal that proximal inputs from CA3 as well as distal inputs from entorhinal cortex layer III (ECIII) sum sublinearly or linearly at low firing rates due to feedforward inhibition, but sum supralinearly at high firing rates due to synaptic facilitation, producing a high-pass filter. However, during ECIII and CA3 input comparison, supralinear dendritic integration is dynamically balanced by feedforward and feedback inhibition, resulting in suppression of dendritic complex spiking. We find that a particular subpopulation of CA1 interneurons expressing neuropeptide Y (NPY) contributes prominently to this dynamic filter by integrating both ECIII and CA3 input pathways and potently inhibiting CA1 pyramidal neuron dendrites.

  18. Time-coded neurotransmitter release at excitatory and inhibitory synapses

    PubMed Central

    Rodrigues, Serafim; Desroches, Mathieu; Krupa, Martin; Cortes, Jesus M.; Sejnowski, Terrence J.; Ali, Afia B.

    2016-01-01

    Communication between neurons at chemical synapses is regulated by hundreds of different proteins that control the release of neurotransmitter that is packaged in vesicles, transported to an active zone, and released when an input spike occurs. Neurotransmitter can also be released asynchronously, that is, after a delay following the spike, or spontaneously in the absence of a stimulus. The mechanisms underlying asynchronous and spontaneous neurotransmitter release remain elusive. Here, we describe a model of the exocytotic cycle of vesicles at excitatory and inhibitory synapses that accounts for all modes of vesicle release as well as short-term synaptic plasticity (STSP). For asynchronous release, the model predicts a delayed inertial protein unbinding associated with the SNARE complex assembly immediately after vesicle priming. Experiments are proposed to test the model’s molecular predictions for differential exocytosis. The simplicity of the model will also facilitate large-scale simulations of neural circuits. PMID:26858411

  19. Ultrastructural Analysis of Myoblast Fusion in Drosophila

    PubMed Central

    Zhang, Shiliang; Chen, Elizabeth H.

    2015-01-01

    Summary Myoblast fusion in Drosophila has become a powerful genetic system with which to unravel the mechanisms underlying cell fusion. The identification of important components of myoblast fusion by genetic analysis has led to a molecular pathway toward our understanding of this cellular process. In addition to the application of immunohistochemistry and live imaging techniques to visualize myoblast fusion at the light microscopic level, ultrastructural analysis using electron microscopy remains an indispensable tool to reveal fusion intermediates and specific membrane events at sites of fusion. In this chapter, we describe conventional chemical fixation and high-pressure freezing/freeze substitution methods for visualizing fusion intermediates during Drosophila myoblast fusion. Furthermore, we describe an immunoelectron microscopic method for localizing specific proteins relative to the fusion apparatus. PMID:18979250

  20. Kinetic advantage of controlled intermediate nuclear fusion

    SciTech Connect

    Guo Xiaoming

    2012-09-26

    The dominated process of controlled fusion is to let nuclei gain enough kinetic energy to overcome Coulomb barrier. As a result, a fusion scheme can consider two factors in its design: to increase kinetic energy of nuclei and to alter the Coulomb barrier. Cold Fusion and Hot fusion are all one-factor schemes while Intermediate Fusion is a twofactors scheme. This made CINF kinetically superior. Cold Fusion reduces deuteron-deuteron distance, addressing Coulomb barrier, and Hot Fusion heat up plasma into extreme high temperature, addressing kinetic energy. Without enough kinetic energy made Cold Fusion skeptical. Extreme high temperature made Hot Fusion very difficult to engineer. Because CIFN addresses both factors, CIFN is a more promising technique to be industrialized.

  1. Modulation of non steroidal anti-inflammatory drug induced membrane fusion by copper coordination of these drugs: anchoring effect.

    PubMed

    Majumdar, Anupa; Chakraborty, Sreeja; Sarkar, Munna

    2014-12-04

    Membrane fusion, an integral event in several biological processes, is characterized by several intermediate steps guided by specific energy barriers. Hence, it requires the aid of fusogens to complete the process. Common fusogens, such as proteins/peptides, have the ability to overcome theses barriers by their conformational reorganization, an advantage not shared by small drug molecules. Hence, drug induced fusion at physiologically relevant drug concentrations is rare and occurs only in the case of the oxicam group of non steroidal anti-inflammatory drugs (NSAIDs). To use drugs to induce and control membrane fusion in various biochemical processes requires the understanding of how different parameters modulate fusion. Also, fusion efficacy needs to be enhanced. Here we have synthesized and used Cu(II) complexes of fusogenic oxicam NSAIDs, Meloxicam and Piroxicam, to induce fusion in model membranes monitored by using DSC, TEM, steady-state, and time-resolved spectroscopy. The ability of the complexes to anchor apposing model membranes to initiate/facilitate fusion has been demonstrated. This results in better fusion efficacy compared to the bare drugs. These complexes can take the fusion to its final step. Unlike other designed membrane anchors, the role of molecular recognition and strength of interaction between molecular partners is obliterated for these preformed Cu(II)-NSAIDs.

  2. Development of Inhibitory Timescales in Auditory Cortex

    PubMed Central

    Reyes, Alex D.

    2011-01-01

    The time course of inhibition plays an important role in cortical sensitivity, tuning, and temporal response properties. We investigated the development of L2/3 inhibitory circuitry between fast-spiking (FS) interneurons and pyramidal cells (PCs) in auditory thalamocortical slices from mice between postnatal day 10 (P10) and P29. We found that the maturation of the intrinsic and synaptic properties of both FS cells and their connected PCs influence the timescales of inhibition. FS cell firing rates increased with age owing to decreased membrane time constants, shorter afterhyperpolarizations, and narrower action potentials. Between FS–PC pairs, excitatory postsynaptic potentials (EPSPs) and inhibitory postsynaptic potentials (IPSPs) changed with age. The latencies, rise, and peak times of the IPSPs, as well as the decay constants of both EPSPs and IPSPs decreased between P10 and P29. In addition, decreases in short-term depression at excitatory PC–FS synapses resulted in more sustained synaptic responses during repetitive stimulation. Finally, we show that during early development, the temporal properties that influence the recruitment of inhibition lag those of excitation. Taken together, our results suggest that the changes in the timescales of inhibitory recruitment coincide with the development of the tuning and temporal response properties of auditory cortical networks. PMID:21068186

  3. Proactive inhibitory control: A general biasing account.

    PubMed

    Elchlepp, Heike; Lavric, Aureliu; Chambers, Christopher D; Verbruggen, Frederick

    2016-05-01

    Flexible behavior requires a control system that can inhibit actions in response to changes in the environment. Recent studies suggest that people proactively adjust response parameters in anticipation of a stop signal. In three experiments, we tested the hypothesis that proactive inhibitory control involves adjusting both attentional and response settings, and we explored the relationship with other forms of proactive and anticipatory control. Subjects responded to the color of a stimulus. On some trials, an extra signal occurred. The response to this signal depended on the task context subjects were in: in the 'ignore' context, they ignored it; in the 'stop' context, they had to withhold their response; and in the 'double-response' context, they had to execute a secondary response. An analysis of event-related brain potentials for no-signal trials in the stop context revealed that proactive inhibitory control works by biasing the settings of lower-level systems that are involved in stimulus detection, action selection, and action execution. Furthermore, subjects made similar adjustments in the double-response and stop-signal contexts, indicating an overlap between various forms of proactive action control. The results of Experiment 1 also suggest an overlap between proactive inhibitory control and preparatory control in task-switching studies: both require reconfiguration of task-set parameters to bias or alter subordinate processes. We conclude that much of the top-down control in response inhibition tasks takes place before the inhibition signal is presented.

  4. Proactive inhibitory control varies with task context.

    PubMed

    Wardak, Claire; Ramanoël, Stephen; Guipponi, Olivier; Boulinguez, Philippe; Ben Hamed, Suliann

    2012-12-01

    The goal of executive control is to adjust our behaviour to the environment. It involves not only the continuous planning and adaptation of actions but also the inhibition of inappropriate movements. Recently, a proactive form of inhibitory control has been shown, demonstrating that actions can be withheld, in an uncertain environment, thanks to the proactive locking of the mechanism by which motor commands are triggered (e.g. while waiting at traffic lights in a dense pedestrian zone, one will refrain in anticipation of a brisk acceleration when the green light comes on). However, little is known about this executive function and it remains unclear whether the overall amount of inhibitory control can be modulated as a function of the context. Here, we show that the level of this control varies parametrically as a function of the exogenous and endogenous factors setting the task context. We also show that the level of implemented proactive inhibitory control is dynamically readjusted to match the implicit temporal structure of the environment. These observations are discussed in relation to possible underlying functional substrates and related neurological and psychiatric pathologies.

  5. Proactive inhibitory control: A general biasing account☆

    PubMed Central

    Elchlepp, Heike; Lavric, Aureliu; Chambers, Christopher D.; Verbruggen, Frederick

    2016-01-01

    Flexible behavior requires a control system that can inhibit actions in response to changes in the environment. Recent studies suggest that people proactively adjust response parameters in anticipation of a stop signal. In three experiments, we tested the hypothesis that proactive inhibitory control involves adjusting both attentional and response settings, and we explored the relationship with other forms of proactive and anticipatory control. Subjects responded to the color of a stimulus. On some trials, an extra signal occurred. The response to this signal depended on the task context subjects were in: in the ‘ignore’ context, they ignored it; in the ‘stop’ context, they had to withhold their response; and in the ‘double-response’ context, they had to execute a secondary response. An analysis of event-related brain potentials for no-signal trials in the stop context revealed that proactive inhibitory control works by biasing the settings of lower-level systems that are involved in stimulus detection, action selection, and action execution. Furthermore, subjects made similar adjustments in the double-response and stop-signal contexts, indicating an overlap between various forms of proactive action control. The results of Experiment 1 also suggest an overlap between proactive inhibitory control and preparatory control in task-switching studies: both require reconfiguration of task-set parameters to bias or alter subordinate processes. We conclude that much of the top-down control in response inhibition tasks takes place before the inhibition signal is presented. PMID:26859519

  6. Context specificity of inhibitory control in dogs

    PubMed Central

    MacLean, Evan L.; Hare, Brian A.

    2014-01-01

    Across three experiments, we explored whether a dog's capacity for inhibitory control is stable or variable across decision-making contexts. In the social task, dogs were first exposed to the reputations of a stingy experimenter that never shared food and a generous experimenter who always shared food. In subsequent test trials, dogs were required to avoid approaching the stingy experimenter when this individual offered (but withheld) a higher-value reward than the generous experimenter did. In the A-not-B task, dogs were required to inhibit searching for food in a previously rewarded location after witnessing the food being moved from this location to a novel hiding place. In the cylinder task, dogs were required to resist approaching visible food directly (because it was behind a transparent barrier), in favor of a detour reaching response. Overall, dogs exhibited inhibitory control in all three tasks. However, individual scores were not correlated between tasks, suggesting that context has a large effect on dogs' behavior. This result mirrors studies of humans, which have highlighted intra-individual variation in inhibitory control as a function of the decision-making context. Lastly, we observed a correlation between a subject's age and performance on the cylinder task, corroborating previous observations of age-related decline in dogs' executive function. PMID:23584618

  7. Accelerators for Fusion Materials Testing

    NASA Astrophysics Data System (ADS)

    Knaster, Juan; Okumura, Yoshikazu

    Fusion materials research is a worldwide endeavor as old as the parallel one working toward the long term stable confinement of ignited plasma. In a fusion reactor, the preservation of the required minimum thermomechanical properties of the in-vessel components exposed to the severe irradiation and heat flux conditions is an indispensable factor for safe operation; it is also an essential goal for the economic viability of fusion. Energy from fusion power will be extracted from the 14 MeV neutron freed as a product of the deuterium-tritium fusion reactions; thus, this kinetic energy must be absorbed and efficiently evacuated and electricity eventually generated by the conventional methods of a thermal power plant. Worldwide technological efforts to understand the degradation of materials exposed to 14 MeV neutron fluxes >1018 m-2s-1, as expected in future fusion power plants, have been intense over the last four decades. Existing neutron sources can reach suitable dpa (“displacement-per-atom”, the figure of merit to assess materials degradation from being exposed to neutron irradiation), but the differences in the neutron spectrum of fission reactors and spallation sources do not allow one to unravel the physics and to anticipate the degradation of materials exposed to fusion neutrons. Fusion irradiation conditions can be achieved through Li (d, xn) nuclear reactions with suitable deuteron beam current and energy, and an adequate flowing lithium screen. This idea triggered in the late 1970s at Los Alamos National Laboratory (LANL) a campaign working toward the feasibility of continuous wave (CW) high current linacs framed by the Fusion Materials Irradiation Test (FMIT) project. These efforts continued with the Low Energy Demonstrating Accelerator (LEDA) (a validating prototype of the canceled Accelerator Production of Tritium (APT) project), which was proposed in 2002 to the fusion community as a 6.7MeV, 100mA CW beam injector for a Li (d, xn) source to bridge

  8. Accelerators for Fusion Materials Testing

    NASA Astrophysics Data System (ADS)

    Knaster, Juan; Okumura, Yoshikazu

    Fusion materials research is a worldwide endeavor as old as the parallel one working toward the long term stable confinement of ignited plasma. In a fusion reactor, the preservation of the required minimum thermomechanical properties of the in-vessel components exposed to the severe irradiation and heat flux conditions is an indispensable factor for safe operation; it is also an essential goal for the economic viability of fusion. Energy from fusion power will be extracted from the 14 MeV neutron freed as a product of the deuterium-tritium fusion reactions; thus, this kinetic energy must be absorbed and efficiently evacuated and electricity eventually generated by the conventional methods of a thermal power plant. Worldwide technological efforts to understand the degradation of materials exposed to 14 MeV neutron fluxes > 1018 m-2s-1, as expected in future fusion power plants, have been intense over the last four decades. Existing neutron sources can reach suitable dpa ("displacement-per-atom", the figure of merit to assess materials degradation from being exposed to neutron irradiation), but the differences in the neutron spectrum of fission reactors and spallation sources do not allow one to unravel the physics and to anticipate the degradation of materials exposed to fusion neutrons. Fusion irradiation conditions can be achieved through Li (d, xn) nuclear reactions with suitable deuteron beam current and energy, and an adequate flowing lithium screen. This idea triggered in the late 1970s at Los Alamos National Laboratory (LANL) a campaign working toward the feasibility of continuous wave (CW) high current linacs framed by the Fusion Materials Irradiation Test (FMIT) project. These efforts continued with the Low Energy Demonstrating Accelerator (LEDA) (a validating prototype of the canceled Accelerator Production of Tritium (APT) project), which was proposed in 2002 to the fusion community as a 6.7MeV, 100mA CW beam injector for a Li (d, xn) source to bridge

  9. Fusion reactions at low energy

    SciTech Connect

    Beckerman, M.

    1985-01-01

    Fusion measurement methods at low energies are briefly described, and experimental and theoretical fusion cross sections for /sup 58/Ni + /sup 58/Ni, /sup 58/Ni + /sup 64/Ni and /sup 64/Ni + /sup 64/Ni reactions are discussed. It is shown that quantal tunneling calculations do not describe the near- and sub-barrier behavior of the fusion data. Instead, the WKB predictions fall progressively further blow the experimental results as the energy is lowered. At far subbarrier energies the measured cross sections exceed the WKB predictions by more than three orders of magnitude. The unexpectedly strong dependence of the fusion probability upon the nuclear valence structure is illustrated and discussed. The relationship of channel coupling and quantal tunneling is discussed. In conclusion, it was established that atomic nuclei fuse far more readily at low energies that would be expected from quantal tunneling considerations alone. It was found that the behavior of the cross sections for fusion depends strongly upon the valence structure of the collision partners. This structural dependence extends from light 1p-shell systems to systems involving nearly 200 nucleons. These new phenomena may be viewed as characterizing the tunneling of a quantal system with many degrees of freedom. The failure of standard tunneling models may be understood as resulting from the ability of the dinuclear system to tunnel into the classically forbidden region by means of couplings to intrinsic degrees of freedom. 38 refs. (WHK)

  10. A Model for Membrane Fusion

    NASA Astrophysics Data System (ADS)

    Ngatchou, Annita

    2010-01-01

    Pheochromocytoma is a tumor of the adrenal gland which originates from chromaffin cells and is characterized by the secretion of excessive amounts of neurotransmitter which lead to high blood pressure and palpitations. Pheochromocytoma contain membrane bound granules that store neurotransmitter. The release of these stored molecules into the extracellular space occurs by fusion of the granule membrane with the cell plasma membrane, a process called exocytosis. The molecular mechanism of this membrane fusion is not well understood. It is proposed that the so called SNARE proteins [1] are the pillar of vesicle fusion as their cleavage by clostridial toxin notably, Botulinum neurotoxin and Tetanus toxin abrogate the secretion of neurotransmitter [2]. Here, I describe how physical principles are applied to a biological cell to explore the role of the vesicle SNARE protein synaptobrevin-2 in easing granule fusion. The data presented here suggest a paradigm according to which the movement of the C-terminal of synaptobrevin-2 disrupts the lipid bilayer to form a fusion pore through which molecules can exit.

  11. Effects of electrical coupling among layer 4 inhibitory interneurons on contrast-invariant orientation tuning.

    PubMed

    Fortier, Pierre A

    2011-01-01

    Simulations of orientation selectivity in visual cortex have shown that layer 4 complex cells lacking orientation tuning are ideal for providing global inhibition that scales with contrast in order to produce simple cells with contrast-invariant orientation tuning (Lauritzen and Miller in J Neurosci 23:10201-10213, 2003). Inhibitory cortical cells have been shown to be electrically coupled by gap junctions (Fukuda and Kosaka in J Neurosci 120:5-20, 2003). Such coupling promotes, among other effects, spike synchronization and coordination of postsynaptic IPSPs (Beierlein et al. in Nat Neurosci 3:904-910, 2000; Galarreta and Hestrin in Nat Rev Neurosci 2:425-433, 2001). Consequently, it was expected (Miller in Cereb Cortex 13:73-82, 2003) that electrical coupling would promote nonspecific functional responses consistent with the complex inhibitory cells seen in layer 4 which provide broad inhibition in response to stimuli of all orientations (Miller et al. in Curr Opin Neurobiol 11:488-497, 2001). This was tested using a mechanistic modeling approach. The orientation selectivity model of Lauritzen and Miller (J Neurosci 23:10201-10213, 2003) was reproduced with and without electrical coupling between complex inhibitory neurons. Although extensive coupling promotes uniform firing in complex cells, there were no detectable improvements in contrast-invariant orientation selectivity unless there were coincident changes in complex cell firing rates to offset the untuned excitatory component that grows with contrast. Thus, changes in firing rates alone (with or without coupling) could improve contrast-invariant orientation tuning of simple cells but not synchronization of complex inhibitory neurons alone.

  12. Inhibitory Control and Emotion Regulation in Preschool Children

    ERIC Educational Resources Information Center

    Carlson, Stephanie M.; Wang, Tiffany S.

    2007-01-01

    This research investigated the relation between individual differences in inhibitory control and emotion regulation. Preschool children (N=53) ages 4-6 (M=5; 0) were assessed on brief batteries of inhibitory control of prepotent responses and emotion regulation. Individual differences in inhibitory control were significantly correlated with…

  13. Nuclear Fusion prize laudation Nuclear Fusion prize laudation

    NASA Astrophysics Data System (ADS)

    Burkart, W.

    2011-01-01

    Clean energy in abundance will be of critical importance to the pursuit of world peace and development. As part of the IAEA's activities to facilitate the dissemination of fusion related science and technology, the journal Nuclear Fusion is intended to contribute to the realization of such energy from fusion. In 2010, we celebrated the 50th anniversary of the IAEA journal. The excellence of research published in the journal is attested to by its high citation index. The IAEA recognizes excellence by means of an annual prize awarded to the authors of papers judged to have made the greatest impact. On the occasion of the 2010 IAEA Fusion Energy Conference in Daejeon, Republic of Korea at the welcome dinner hosted by the city of Daejeon, we celebrated the achievements of the 2009 and 2010 Nuclear Fusion prize winners. Steve Sabbagh, from the Department of Applied Physics and Applied Mathematics, Columbia University, New York is the winner of the 2009 award for his paper: 'Resistive wall stabilized operation in rotating high beta NSTX plasmas' [1]. This is a landmark paper which reports record parameters of beta in a large spherical torus plasma and presents a thorough investigation of the physics of resistive wall mode (RWM) instability. The paper makes a significant contribution to the critical topic of RWM stabilization. John Rice, from the Plasma Science and Fusion Center, MIT, Cambridge is the winner of the 2010 award for his paper: 'Inter-machine comparison of intrinsic toroidal rotation in tokamaks' [2]. The 2010 award is for a seminal paper that analyzes results across a range of machines in order to develop a universal scaling that can be used to predict intrinsic rotation. This paper has already triggered a wealth of experimental and theoretical work. I congratulate both authors and their colleagues on these exceptional papers. W. Burkart Deputy Director General Department of Nuclear Sciences and Applications International Atomic Energy Agency, Vienna

  14. Inhibitory Gating of Basolateral Amygdala Inputs to the Prefrontal Cortex

    PubMed Central

    McGarry, Laura M.

    2016-01-01

    Interactions between the prefrontal cortex (PFC) and basolateral amygdala (BLA) regulate emotional behaviors. However, a circuit-level understanding of functional connections between these brain regions remains incomplete. The BLA sends prominent glutamatergic projections to the PFC, but the overall influence of these inputs is predominantly inhibitory. Here we combine targeted recordings and optogenetics to examine the synaptic underpinnings of this inhibition in the mouse infralimbic PFC. We find that BLA inputs preferentially target layer 2 corticoamygdala over neighboring corticostriatal neurons. However, these inputs make even stronger connections onto neighboring parvalbumin and somatostatin expressing interneurons. Inhibitory connections from these two populations of interneurons are also much stronger onto corticoamygdala neurons. Consequently, BLA inputs are able to drive robust feedforward inhibition via two parallel interneuron pathways. Moreover, the contributions of these interneurons shift during repetitive activity, due to differences in short-term synaptic dynamics. Thus, parvalbumin interneurons are activated at the start of stimulus trains, whereas somatostatin interneuron activation builds during these trains. Together, these results reveal how the BLA impacts the PFC through a complex interplay of direct excitation and feedforward inhibition. They also highlight the roles of targeted connections onto multiple projection neurons and interneurons in this cortical circuit. Our findings provide a mechanistic understanding for how the BLA can influence the PFC circuit, with important implications for how this circuit participates in the regulation of emotion. SIGNIFICANCE STATEMENT The prefrontal cortex (PFC) and basolateral amygdala (BLA) interact to control emotional behaviors. Here we show that BLA inputs elicit direct excitation and feedforward inhibition of layer 2 projection neurons in infralimbic PFC. BLA inputs are much stronger at

  15. Complex fragment emission from hot compound nuclei

    SciTech Connect

    Moretto, L.G.

    1986-03-01

    The experimental evidence for compound nucleus emission of complex fragments at low energies is used to interpret the emission of the same fragments at higher energies. The resulting experimental picture is that of highly excited compound nuclei formed in incomplete fusion processes which decay statistically. In particular, complex fragments appear to be produced mostly through compound nucleus decay. In the appendix a geometric-kinematic theory for incomplete fusion and the associated momentum transfer is outlined. 10 refs., 19 figs.

  16. Ceramic pebble bed development for fusion blankets

    SciTech Connect

    Gierszewski, P.; Kawamura, H.; Donne, M.D.

    1994-12-31

    Research on lithium ceramic breeders has been intensive since the late 1970`s. The bulk material properties of several candidate lithium ceramics are generally available, although there is still much work to be done on properties under irradiation and on overall behavior in blanket modules. Based on these results, lithium ceramic breeders have been selected in many fusion design studies. These lithium ceramics are incorporated into blankets typically as monolithic pellets of packed pebble beds. There is substantial industrial experience with pebble beds made from other ceramics, notably in chemical processes as catalyst supports and grinding media, and in advanced fission reactor fuels. In fusion blankets, the pebble bed form offers several attractive features, including simpler assembly into complex geometry, uniform pore network, and low sensitivity to cracking or irradiation damage. Ceramic breeder pebbles have been a focus for several research groups. In general, the database is similar to that of monolithic pellets for the materials studied: basic production and material property data are available, but the irradiation and engineering database remains sparse.

  17. Molecular Process Producing Oncogene Fusion in Lung Cancer Cells by Illegitimate Repair of DNA Double-Strand Breaks

    PubMed Central

    Seki, Yoshitaka; Mizukami, Tatsuji; Kohno, Takashi

    2015-01-01

    Constitutive activation of oncogenes by fusion to partner genes, caused by chromosome translocation and inversion, is a critical genetic event driving lung carcinogenesis. Fusions of the tyrosine kinase genes ALK (anaplastic lymphoma kinase), ROS1 (c-ros oncogene 1), or RET (rearranged during transfection) occur in 1%–5% of lung adenocarcinomas (LADCs) and their products constitute therapeutic targets for kinase inhibitory drugs. Interestingly, ALK, RET, and ROS1 fusions occur preferentially in LADCs of never- and light-smokers, suggesting that the molecular mechanisms that cause these rearrangements are smoking-independent. In this study, using previously reported next generation LADC genome sequencing data of the breakpoint junction structures of chromosome rearrangements that cause oncogenic fusions in human cancer cells, we employed the structures of breakpoint junctions of ALK, RET, and ROS1 fusions in 41 LADC cases as “traces” to deduce the molecular processes of chromosome rearrangements caused by DNA double-strand breaks (DSBs) and illegitimate joining. We found that gene fusion was produced by illegitimate repair of DSBs at unspecified sites in genomic regions of a few kb through DNA synthesis-dependent or -independent end-joining pathways, according to DSB type. This information will assist in the understanding of how oncogene fusions are generated and which etiological factors trigger them. PMID:26437441

  18. (Meeting on fusion reactor materials)

    SciTech Connect

    Jones, R.H. ); Klueh, R.L.; Rowcliffe, A.F.; Wiffen, F.W. ); Loomis, B.A. )

    1990-11-01

    During his visit to the KfK, Karlsruhe, F. W. Wiffen attended the IEA 12th Working Group Meeting on Fusion Reactor Materials. Plans were made for a low-activation materials workshop at Culham, UK, for April 1991, a data base workshop in Europe for June 1991, and a molecular dynamics workshop in the United States in 1991. At the 11th IEA Executive Committee on Fusion Materials, discussions centered on the recent FPAC and Colombo panel review in the United States and EC, respectively. The Committee also reviewed recent progress toward a neutron source in the United States (CWDD) and in Japan (ESNIT). A meeting with D. R. Harries (consultant to J. Darvas) yielded a useful overview of the EC technology program for fusion. Of particular interest to the US program is a strong effort on a conventional ferritic/martensitic steel for fist wall/blanket operation beyond NET/ITER.

  19. Fusion power for space propulsion.

    NASA Technical Reports Server (NTRS)

    Roth, R.; Rayle, W.; Reinmann, J.

    1972-01-01

    Principles of operation, interplanetary orbit-to-orbit mission capabilities, technical problems, and environmental safeguards are examined for thermonuclear fusion propulsion systems. Two systems examined include (1) a fusion-electric concept in which kinetic energy of charged particles from the plasma is converted into electric power (for accelerating the propellant in an electrostatic thrustor) by the van de Graaf generator principle and (2) the direct fusion rocket in which energetic plasma lost from the reactor has a suitable amount of added propellant to obtain the optimum exhaust velocity. The deuterium-tritium and the deuterium/helium-3 reactions are considered as suitable candidates, and attention is given to problems of cryogenic refrigeration systems, magnet shielding, and high-energy particle extraction and guidance.

  20. Superconducting magnets for fusion applications

    SciTech Connect

    Henning, C.D.

    1987-07-02

    Fusion magnet technology has made spectacular advances in the past decade; to wit, the Mirror Fusion Test Facility and the Large Coil Project. However, further advances are still required for advanced economical fusion reactors. Higher fields to 14 T and radiation-hardened superconductors and insulators will be necessary. Coupled with high rates of nuclear heating and pulsed losses, the next-generation magnets will need still higher current density, better stability and quench protection. Cable-in-conduit conductors coupled with polyimide insulations and better steels seem to be the appropriate path. Neutron fluences up to 10/sup 19/ neutrons/cm/sup 2/ in niobium tin are achievable. In the future, other amorphous superconductors could raise these limits further to extend reactor life or decrease the neutron shielding and corresponding reactor size.

  1. Tissue fusion over nonadhering surfaces

    PubMed Central

    Nier, Vincent; Deforet, Maxime; Duclos, Guillaume; Yevick, Hannah G.; Cochet-Escartin, Olivier; Marcq, Philippe; Silberzan, Pascal

    2015-01-01

    Tissue fusion eliminates physical voids in a tissue to form a continuous structure and is central to many processes in development and repair. Fusion events in vivo, particularly in embryonic development, often involve the purse-string contraction of a pluricellular actomyosin cable at the free edge. However, in vitro, adhesion of the cells to their substrate favors a closure mechanism mediated by lamellipodial protrusions, which has prevented a systematic study of the purse-string mechanism. Here, we show that monolayers can cover well-controlled mesoscopic nonadherent areas much larger than a cell size by purse-string closure and that active epithelial fluctuations are required for this process. We have formulated a simple stochastic model that includes purse-string contractility, tissue fluctuations, and effective friction to qualitatively and quantitatively account for the dynamics of closure. Our data suggest that, in vivo, tissue fusion adapts to the local environment by coordinating lamellipodial protrusions and purse-string contractions. PMID:26199417

  2. Laser fusion experiments at LLL

    SciTech Connect

    Ahlstrom, H.G.

    1980-06-16

    These notes present the experimental basis and status for laser fusion as developed at LLL. Two other chapters, one authored by K.A. Brueckner and the other by C. Max, present the theoretical implosion physics and laser plasma interaction physics. The notes consist of six sections. The first is an introductory section which provides some of the history of inertial fusion and a simple explanation of the concepts involved. The second section presents an extensive discussion of diagnostic instrumentation used in the LLL Laser Fusion Program. The third section is a presentation of laser facilities and capabilities at LLL. The purpose here is to define capability, not to derive how it was obtained. The fourth and fifth sections present the experimental data on laser-plasma interaction and implosion physics. The last chapter is a short projection of the future.

  3. Development of a 3D co-culture model using human stem cells for studying embryonic palatal fusion.

    EPA Science Inventory

    Morphogenetic tissue fusion is a critical and complex event in embryonic development and failure of this event leads to birth defects, such as cleft palate. Palatal fusion requires adhesion and subsequent dissolution of the medial epithelial layer of the mesenchymal palatal shelv...

  4. Anti-colorectal cancer effect of interleukin-2 and interferon-β fusion gene driven by carcinoembryonic antigen promoter

    PubMed Central

    Wang, Yan; Wang, Mengchun; Li, Yan

    2016-01-01

    This study was designed to investigate the antitumor effects of combined interleukin-2/interferon-β-based gene therapy in colorectal cancer. Transfection of the fusion gene expression plasmid induced significant apoptosis of Lovo cells. Additionally, the fusion gene exhibited strong inhibitory activity against tumor growth and apoptosis when being injected into the nude mice implanted with human colon cancer cells. Furthermore, the tail-vein injection showed a more notable effect than direct injection into tumor. These results suggest that the combined interleukin-2/interferon-β-based gene therapy with the carcinoembryonic antigen promoter might be an effective antitumor strategy. PMID:27313471

  5. Fusion Breeder Program interim report

    SciTech Connect

    Moir, R.; Lee, J.D.; Neef, W.

    1982-06-11

    This interim report for the FY82 Fusion Breeder Program covers work performed during the scoping phase of the study, December, 1981-February 1982. The goals for the FY82 study are the identification and development of a reference blanket concept using the fission suppression concept and the definition of a development plan to further the fusion breeder application. The context of the study is the tandem mirror reactor, but emphasis is placed upon blanket engineering. A tokamak driver and blanket concept will be selected and studied in more detail during FY83.

  6. Percutaneous Hindfoot and Midfoot Fusion.

    PubMed

    Bauer, Thomas

    2016-09-01

    Hindfoot and midfoot fusions can be performed with percutaneous techniques. Preliminary results of these procedures are encouraging because they provide similar results than those obtained with open techniques with less morbidity and quick recovery. The best indications are probably fusions for mild-to-moderate reducible hindfoot and midfoot deformities in fragile patients with general or local bad conditions. The main limit is linked to the surgeon's experience in percutaneous foot surgery because a learning curve with the specific tools is necessary before doing these procedures.

  7. Method for vacuum fusion bonding

    DOEpatents

    Ackler, Harold D.; Swierkowski, Stefan P.; Tarte, Lisa A.; Hicks, Randall K.

    2001-01-01

    An improved vacuum fusion bonding structure and process for aligned bonding of large area glass plates, patterned with microchannels and access holes and slots, for elevated glass fusion temperatures. Vacuum pumpout of all components is through the bottom platform which yields an untouched, defect free top surface which greatly improves optical access through this smooth surface. Also, a completely non-adherent interlayer, such as graphite, with alignment and location features is located between the main steel platform and the glass plate pair, which makes large improvements in quality, yield, and ease of use, and enables aligned bonding of very large glass structures.

  8. Z-Pinch Fusion Propulsion

    NASA Technical Reports Server (NTRS)

    Miernik, Janie

    2011-01-01

    Fusion-based nuclear propulsion has the potential to enable fast interplanetary transportation. Shorter trips are better for humans in the harmful radiation environment of deep space. Nuclear propulsion and power plants can enable high Ispand payload mass fractions because they require less fuel mass. Fusion energy research has characterized the Z-Pinch dense plasma focus method. (1) Lightning is form of pinched plasma electrical discharge phenomena. (2) Wire array Z-Pinch experiments are commonly studied and nuclear power plant configurations have been proposed. (3) Used in the field of Nuclear Weapons Effects (NWE) testing in the defense industry, nuclear weapon x-rays are simulated through Z-Pinch phenomena.

  9. The first fusion reactor: ITER

    NASA Astrophysics Data System (ADS)

    Campbell, D. J.

    2016-11-01

    Established by the signature of the ITER Agreement in November 2006 and currently under construction at St Paul-lez-Durance in southern France, the ITER project [1,2] involves the European Union (including Switzerland), China, India, Japan, the Russian Federation, South Korea and the United States. ITER (`the way' in Latin) is a critical step in the development of fusion energy. Its role is to provide an integrated demonstration of the physics and technology required for a fusion power plant based on magnetic confinement.

  10. Fusion bonding and alignment fixture

    DOEpatents

    Ackler, Harold D.; Swierkowski, Stefan P.; Tarte, Lisa A.; Hicks, Randall K.

    2000-01-01

    An improved vacuum fusion bonding structure and process for aligned bonding of large area glass plates, patterned with microchannels and access holes and slots, for elevated glass fusion temperatures. Vacuum pumpout of all the components is through the bottom platform which yields an untouched, defect free top surface which greatly improves optical access through this smooth surface. Also, a completely non-adherent interlayer, such as graphite, with alignment and location features is located between the main steel platform and the glass plate pair, which makes large improvements in quality, yield, and ease of use, and enables aligned bonding of very large glass structures.

  11. Plasma physics goes beyond fusion

    NASA Astrophysics Data System (ADS)

    Franklin, Raoul

    2008-11-01

    I was interested to read the fusion supplement published with the October issue of Physics World. However, in asserting that fusion created the need to recognize plasma physics as a separate branch of the subject, Stephen Cowley, the new director of the United Kingdom Atomic Energy Authority, was not quite correct. In fact, the word "plasma" was appropriated from the Greek by the chemical physicist (and later Nobel laureate) Irving Langmuir in 1928. It was used to describe the positive column of a gas discharge, which was then the subject of research into better lighting sources and advertising displays, as well as the underlying science.

  12. Identification of novel fusion genes with 28S ribosomal DNA in hematologic malignancies.

    PubMed

    Kobayashi, Satoru; Taki, Tomohiko; Nagoshi, Hisao; Chinen, Yoshiaki; Yokokawa, Yuichi; Kanegane, Hirokazu; Matsumoto, Yosuke; Kuroda, Junya; Horiike, Shigeo; Nishida, Kazuhiro; Taniwaki, Masafumi

    2014-04-01

    Fusion genes are frequently observed in hematologic malignancies and soft tissue sarcomas, and are usually associated with chromosome abnormalities. Many of these fusion genes create in-frame fusion transcripts that result in the production of fusion proteins, and some of which aid tumorigenesis. These fusion proteins are often associated with disease phenotype and clinical outcome, and act as markers for minimal residual disease and indicators of therapeutic targets. Here, we identified the 28S ribosomal DNA (RN28S1) gene as a novel fusion partner of the B-cell leukemia/lymphoma 11B gene (BCL11B), the immunoglobulin κ variable 3-20 gene (IGKV3-20) and the component of oligomeric Golgi complex 1 gene (COG1) in hematologic malignancies. The RN28S1-BCL11B fusion transcript was identified in a case with mixed-lineage (T/myeloid) acute leukemia having t(6;14)(q25;q32) by cDNA bubble PCR using BCL11B primers; however, the gene fused to BCL11B on 14q32 was not on 6q25. IGKV3-20-RN28S1 and COG1-RN28S1 fusion transcripts were identified in the Burkitt lymphoma cell line HBL-5, and the multiple myeloma cell line KMS-18. RN28S1 would not translate, and the breakpoints in partner genes of RN28S1 were within the coding exons, suggesting that disruption of fusion partners by fusion to RN28S1 is the possible mechanism of tumorigenesis. Although further analysis is needed to elucidate the mechanism(s) through which these RN28S1-related fusions play roles in tumorigenesis, our findings provide important insights into the role of rDNA function in human genomic architecture and tumorigenesis.

  13. Equivalence of measurement space solution data fusion and complete fusion

    NASA Astrophysics Data System (ADS)

    Ceccherini, Simone

    2016-10-01

    Many observation systems are operating on space-borne and airborne platforms, as well as from ground-based stations, providing measurements of vertical profiles of atmospheric parameters. When independent measurements of the same profile are available data fusion methods can be used to combine them and exploit all the available information for a more comprehensive and accurate description of the atmospheric state. Several data fusion methods can be used. Among the others, both the measurement space solution data fusion method and the complete fusion method have the remarkable properties of using all the acquired information and of providing results that are independent from a priori information used in the individual retrievals. For this reason, though the two methods use two completely different procedures, it is reasonable to expect that they give the same results and in this paper the rigorous proof of the equivalence of the two methods is given. Therefore, the choice between them is only driven by the advantages of the different implementations.

  14. A Plan for the Development of Fusion Energy. Final Report to Fusion Energy Sciences Advisory Committee, Fusion Development Path Panel

    SciTech Connect

    None, None

    2003-03-05

    This report presents a plan for the deployment of a fusion demonstration power plant within 35 years, leading to commercial application of fusion energy by mid-century. The plan is derived from the necessary features of a demonstration fusion power plant and from the time scale defined by President Bush. It identifies critical milestones, key decision points, needed major facilities and required budgets.

  15. Structural adaptations for ram ventilation: gill fusions in scombrids and billfishes.

    PubMed

    Wegner, Nicholas C; Sepulveda, Chugey A; Aalbers, Scott A; Graham, Jeffrey B

    2013-01-01

    For ram-gill ventilators such as tunas and mackerels (family Scombridae) and billfishes (families Istiophoridae, Xiphiidae), fusions binding the gill lamellae and filaments prevent gill deformation by a fast and continuous ventilatory stream. This study examines the gills from 28 scombrid and seven billfish species in order to determine how factors such as body size, swimming speed, and the degree of dependence upon ram ventilation influence the site of occurrence and type of fusions. In the family Scombridae there is a progressive increase in the reliance on ram ventilation that correlates with the elaboration of gill fusions. This ranges from mackerels (tribe Scombrini), which only utilize ram ventilation at fast cruising speeds and lack gill fusions, to tunas (tribe Thunnini) of the genus Thunnus, which are obligate ram ventilators and have two distinct fusion types (one binding the gill lamellae and a second connecting the gill filaments). The billfishes appear to have independently evolved gill fusions that rival those of tunas in terms of structural complexity. Examination of a wide range of body sizes for some scombrids and billfishes shows that gill fusions begin to develop at lengths as small as 2.0 cm fork length. In addition to securing the spatial configuration of the gill sieve, gill fusions also appear to increase branchial resistance to slow the high-speed current produced by ram ventilation to distribute flow evenly and optimally to the respiratory exchange surfaces.

  16. Data fusion in cyber security: first order entity extraction from common cyber data

    NASA Astrophysics Data System (ADS)

    Giacobe, Nicklaus A.

    2012-06-01

    The Joint Directors of Labs Data Fusion Process Model (JDL Model) provides a framework for how to handle sensor data to develop higher levels of inference in a complex environment. Beginning from a call to leverage data fusion techniques in intrusion detection, there have been a number of advances in the use of data fusion algorithms in this subdomain of cyber security. While it is tempting to jump directly to situation-level or threat-level refinement (levels 2 and 3) for more exciting inferences, a proper fusion process starts with lower levels of fusion in order to provide a basis for the higher fusion levels. The process begins with first order entity extraction, or the identification of important entities represented in the sensor data stream. Current cyber security operational tools and their associated data are explored for potential exploitation, identifying the first order entities that exist in the data and the properties of these entities that are described by the data. Cyber events that are represented in the data stream are added to the first order entities as their properties. This work explores typical cyber security data and the inferences that can be made at the lower fusion levels (0 and 1) with simple metrics. Depending on the types of events that are expected by the analyst, these relatively simple metrics can provide insight on their own, or could be used in fusion algorithms as a basis for higher levels of inference.

  17. Mechanisms of influenza viral membrane fusion.

    PubMed

    Blijleven, Jelle S; Boonstra, Sander; Onck, Patrick R; van der Giessen, Erik; van Oijen, Antoine M

    2016-12-01

    Influenza viral particles are enveloped by a lipid bilayer. A major step in infection is fusion of the viral and host cellular membranes, a process with large kinetic barriers. Influenza membrane fusion is catalyzed by hemagglutinin (HA), a class I viral fusion protein activated by low pH. The exact nature of the HA conformational changes that deliver the energy required for fusion remains poorly understood. This review summarizes our current knowledge of HA structure and dynamics, describes recent single-particle experiments and modeling studies, and discusses their role in understanding how multiple HAs mediate fusion. These approaches provide a mechanistic picture in which HAs independently and stochastically insert into the target membrane, forming a cluster of HAs that is collectively able to overcome the barrier to membrane fusion. The new experimental and modeling approaches described in this review hold promise for a more complete understanding of other viral fusion systems and the protein systems responsible for cellular fusion.

  18. Collescipoli - An unusual fusion crust glass. [chondrite

    NASA Technical Reports Server (NTRS)

    Nozette, S.

    1979-01-01

    An electron microprobe study was conducted on glass fragments taken from the fusion crust and an internal glass-lined vein in the H-5 chondrite Collescipoli. Microprobe analyses of the glasses revealed an unusual fusion crust composition, and analyses of glass from inside the meteorite showed compositions expected for a melt of an H-group chondrite. Studies of fusion crusts by previous workers, e.g., Krinov and Ramdohr, showed that fusion crusts contain large amounts of magnetite and other oxidized minerals. The Collescipoli fusion crusts do contain these minerals, but they also contain relatively large amounts of reduced metal, sulphide, and a sodium-rich glass. This study seems to indicate that Collescipoli preserved an early type of fusion crust. Oxidation was incomplete in the fusion crust melt that drained into a crack. From this study it is concluded that fusion crust formation does not invariably result in complete oxidation of metal and sulphide phases.

  19. Cold fusion catalyzed by muons and electrons

    SciTech Connect

    Kulsrud, R.M.

    1990-10-01

    Two alternative methods have been suggested to produce fusion power at low temperature. The first, muon catalyzed fusion or MCF, uses muons to spontaneously catalyze fusion through the muon mesomolecule formation. Unfortunately, this method fails to generate enough fusion energy to supply the muons, by a factor of about ten. The physics of MCF is discussed, and a possible approach to increasing the number of MCF fusions generated by each muon is mentioned. The second method, which has become known as Cold Fusion,'' involves catalysis by electrons in electrolytic cells. The physics of this process, if it exists, is more mysterious than MCF. However, it now appears to be an artifact, the claims for its reality resting largely on experimental errors occurring in rather delicate experiments. However, a very low level of such fusion claimed by Jones may be real. Experiments in cold fusion will also be discussed.

  20. Advanced Concepts: Aneutronic Fusion Power and Propulsion

    NASA Technical Reports Server (NTRS)

    Chapman, John J.

    2012-01-01

    Aneutronic Fusion for In-Space thrust, power. Clean energy & potential nuclear gains. Fusion plant concepts, potential to use advanced fuels. Methods to harness ionic momentum for high Isp thrust plus direct power conversion into electricity will be presented.

  1. Decommissioning of the Tokamak Fusion Test Reactor

    SciTech Connect

    E. Perry; J. Chrzanowski; C. Gentile; R. Parsells; K. Rule; R. Strykowsky; M. Viola

    2003-10-28

    The Tokamak Fusion Test Reactor (TFTR) at the Princeton Plasma Physics Laboratory was operated from 1982 until 1997. The last several years included operations with mixtures of deuterium and tritium. In September 2002, the three year Decontamination and Decommissioning (D&D) Project for TFTR was successfully completed. The need to deal with tritium contamination as well as activated materials led to the adaptation of many techniques from the maintenance work during TFTR operations to the D&D effort. In addition, techniques from the decommissioning of fission reactors were adapted to the D&D of TFTR and several new technologies, most notably the development of a diamond wire cutting process for complex metal structures, were developed. These techniques, along with a project management system that closely linked the field crews to the engineering staff who developed the techniques and procedures via a Work Control Center, resulted in a project that was completed safely, on time, and well below budget.

  2. Linear optimal control of tokamak fusion devices

    SciTech Connect

    Kessel, C.E.; Firestone, M.A.; Conn, R.W.

    1989-05-01

    The control of plasma position, shape and current in a tokamak fusion reactor is examined using linear optimal control. These advanced tokamaks are characterized by non up-down symmetric coils and structure, thick structure surrounding the plasma, eddy currents, shaped plasmas, superconducting coils, vertically unstable plasmas, and hybrid function coils providing ohmic heating, vertical field, radial field, and shaping field. Models of the electromagnetic environment in a tokamak are derived and used to construct control gains that are tested in nonlinear simulations with initial perturbations. The issues of applying linear optimal control to advanced tokamaks are addressed, including complex equilibrium control, choice of cost functional weights, the coil voltage limit, discrete control, and order reduction. Results indicate that the linear optimal control is a feasible technique for controlling advanced tokamaks where the more common classical control will be severely strained or will not work. 28 refs., 13 figs.

  3. Numerical Studies of Impurities in Fusion Plasmas

    DOE R&D Accomplishments Database

    Hulse, R. A.

    1982-09-01

    The coupled partial differential equations used to describe the behavior of impurity ions in magnetically confined controlled fusion plasmas require numerical solution for cases of practical interest. Computer codes developed for impurity modeling at the Princeton Plasma Physics Laboratory are used as examples of the types of codes employed for this purpose. These codes solve for the impurity ionization state densities and associated radiation rates using atomic physics appropriate for these low-density, high-temperature plasmas. The simpler codes solve local equations in zero spatial dimensions while more complex cases require codes which explicitly include transport of the impurity ions simultaneously with the atomic processes of ionization and recombination. Typical applications are discussed and computational results are presented for selected cases of interest.

  4. Decisive factor in increase of loading at adjacent segments after lumbar fusion: operative technique, pedicle screws, or fusion itself: biomechanical analysis using finite element

    NASA Astrophysics Data System (ADS)

    Park, Joon-Hee; Kim, Ho-Joong; Kang, Kyoung-Tak; Kim, Ka-Yeon; Chun, Heoung-Jae; Moon, Seong-Hwan; Lee, Hwan-Mo

    2009-12-01

    The aim of this study is to investigate the change in biomechanical milieu following removal of pedicle screws or removal of spinous process with posterior ligament complex in instrumented single level lumbar arthrodesis. We developed and validated a finite element model (FEM) of the intact lumbar spine (L2-4). Four scenarios of L3-4 lumbar fusion were simulated: posterolateral fusion (PLF) at L3-4 using pedicle screw system with preservation of PLC (Pp WiP), L3-4 lumbar posterolateral fusion state after removal of pedicle screw system with preservation of PLC (Pp WoP), L3-4 using pedicle screw system without preservation PLC (Sp WiP), L3-4 lumbar posterolateral fusion state after removal of pedicle screw system without preservation of PLC (Sp WoP). For these models, we investigated the range of motion and maximal Von mises stress of disc in all segments under various moments. All fusion models demonstrated increase in range of motion at adjacent segments compared to the intact model.For the four fusion models, the WiP model s P had the largest increase in range of motion at each adjacent segment. This study demonstrated that removal of pedicle screw system and preservation of PLC after complete lumbar spinal fusion could reduce the stress of adjacent segments synergistically and might have beneficial effects in preventing ASD.

  5. Decisive factor in increase of loading at adjacent segments after lumbar fusion: operative technique, pedicle screws, or fusion itself: biomechanical analysis using finite element

    NASA Astrophysics Data System (ADS)

    Park, Joon-Hee; Kim, Ho-Joong; Kang, Kyoung-Tak; Kim, Ka-yeon; Chun, Heoung-Jae; Moon, Seong-Hwan; Lee, Hwan-Mo

    2010-03-01

    The aim of this study is to investigate the change in biomechanical milieu following removal of pedicle screws or removal of spinous process with posterior ligament complex in instrumented single level lumbar arthrodesis. We developed and validated a finite element model (FEM) of the intact lumbar spine (L2-4). Four scenarios of L3-4 lumbar fusion were simulated: posterolateral fusion (PLF) at L3-4 using pedicle screw system with preservation of PLC (Pp WiP), L3-4 lumbar posterolateral fusion state after removal of pedicle screw system with preservation of PLC (Pp WoP), L3-4 using pedicle screw system without preservation PLC (Sp WiP), L3-4 lumbar posterolateral fusion state after removal of pedicle screw system without preservation of PLC (Sp WoP). For these models, we investigated the range of motion and maximal Von mises stress of disc in all segments under various moments. All fusion models demonstrated increase in range of motion at adjacent segments compared to the intact model.For the four fusion models, the WiP model s P had the largest increase in range of motion at each adjacent segment. This study demonstrated that removal of pedicle screw system and preservation of PLC after complete lumbar spinal fusion could reduce the stress of adjacent segments synergistically and might have beneficial effects in preventing ASD.

  6. Migration Inhibitory Factor and Macrophage Bactericidal Function

    PubMed Central

    Simon, Harvey B.; Sheagren, John N.

    1972-01-01

    A homogeneous population of immunologically active lymphocytes was obtained from peritoneal exudates of guinea pigs with delayed hypersensitivity to bovine gamma globulin (BGG). The lymphocytes were cultured with and without BGG for 24 hr, and cell-free supernatant fluids were then assayed simultaneously for their ability to influence two in vitro parameters of macrophage function: migration from capillary tubes and bactericidal capacity. In four consecutive experiments, supernatants from antigenically stimulated lymphocytes exhibited substantial migration-inhibitory-factor activity without enhancing the ability of macrophages to kill Listeria monocytogenes. Lymphocyte lysates were inactive in both assays. Possible mechanisms of lymphocyte-macrophage interactions are discussed. PMID:4120244

  7. Z-Pinch Fusion for Energy Applications

    SciTech Connect

    SPIELMAN,RICK B.

    2000-01-01

    Z pinches, the oldest fusion concept, have recently been revisited in light of significant advances in the fields of plasma physics and pulsed power engineering. The possibility exists for z-pinch fusion to play a role in commercial energy applications. We report on work to develop z-pinch fusion concepts, the result of an extensive literature search, and the output for a congressionally-mandated workshop on fusion energy held in Snowmass, Co July 11-23,1999.

  8. Exo-endo cellulase fusion protein

    SciTech Connect

    Bower, Benjamin S; Larenas, Edmund A; Mitchinson, Colin

    2012-01-17

    The present invention relates to a heterologous exo-endo cellulase fusion construct, which encodes a fusion protein having cellulolytic activity comprising a catalytic domain derived from a fungal exo-cellobiohydrolase and a catalytic domain derived from an endoglucanase. The invention also relates to vectors and fungal host cells comprising the heterologous exo-endo cellulase fusion construct as well as methods for producing a cellulase fusion protein and enzymatic cellulase compositions.

  9. A review of data fusion techniques.

    PubMed

    Castanedo, Federico

    2013-01-01

    The integration of data and knowledge from several sources is known as data fusion. This paper summarizes the state of the data fusion field and describes the most relevant studies. We first enumerate and explain different classification schemes for data fusion. Then, the most common algorithms are reviewed. These methods and algorithms are presented using three different categories: (i) data association, (ii) state estimation, and (iii) decision fusion.

  10. A Review of Data Fusion Techniques

    PubMed Central

    2013-01-01

    The integration of data and knowledge from several sources is known as data fusion. This paper summarizes the state of the data fusion field and describes the most relevant studies. We first enumerate and explain different classification schemes for data fusion. Then, the most common algorithms are reviewed. These methods and algorithms are presented using three different categories: (i) data association, (ii) state estimation, and (iii) decision fusion. PMID:24288502

  11. Proton Collimators for Fusion Reactors

    NASA Technical Reports Server (NTRS)

    Miley, George H.; Momota, Hiromu

    2003-01-01

    Proton collimators have been proposed for incorporation into inertial-electrostatic-confinement (IEC) fusion reactors. Such reactors have been envisioned as thrusters and sources of electric power for spacecraft and as sources of energetic protons in commercial ion-beam applications.

  12. Magnetic Inertial Confinement Fusion (MICF)

    NASA Astrophysics Data System (ADS)

    Miao, Feng; Zheng, Xianjun; Deng, Baiquan; Liu, Wei; Ou, Wei; Huang, Yi

    2016-11-01

    Based on the similarity in models of the early Sun and the 3-D common focal region of the micro-pinch in X-pinch experiments, a novel hybrid fusion configuration by continuous focusing of multiple Z-pinched plasma beams on spatially symmetric plasma is proposed. By replacing gravity with Lorentz force with subsequent centripetal spherical pinch, the beam-target fusion reactivity is enhanced in a quasi-spherical converging region, thus achieving MICF. An assessment, presented here, suggests that a practical fusion power source could be achieved using deuterium alone. Plasma instabilities can be suppressed by fast rotation resulting from an asymmetric tangential torsion in the spherical focal region of this configuration. Mathematical equivalence with the Sun allows the development of appropriate equations for the focal region of MICF, which are solved numerically to provide density, temperature and pressure distributions that produce net fusion energy output. An analysis of MICF physics and a preliminary experimental demonstration of a single beam are also carried out. supported by National Natural Science Foundation of China (Nos. 11374217 and 11176020)

  13. Advanced algorithms for distributed fusion

    NASA Astrophysics Data System (ADS)

    Gelfand, A.; Smith, C.; Colony, M.; Bowman, C.; Pei, R.; Huynh, T.; Brown, C.

    2008-03-01

    The US Military has been undergoing a radical transition from a traditional "platform-centric" force to one capable of performing in a "Network-Centric" environment. This transformation will place all of the data needed to efficiently meet tactical and strategic goals at the warfighter's fingertips. With access to this information, the challenge of fusing data from across the batttlespace into an operational picture for real-time Situational Awareness emerges. In such an environment, centralized fusion approaches will have limited application due to the constraints of real-time communications networks and computational resources. To overcome these limitations, we are developing a formalized architecture for fusion and track adjudication that allows the distribution of fusion processes over a dynamically created and managed information network. This network will support the incorporation and utilization of low level tracking information within the Army Distributed Common Ground System (DCGS-A) or Future Combat System (FCS). The framework is based on Bowman's Dual Node Network (DNN) architecture that utilizes a distributed network of interlaced fusion and track adjudication nodes to build and maintain a globally consistent picture across all assets.

  14. Prospects for fusion neutron NPLs

    SciTech Connect

    Petra, M.; Miley, G.H.; Batyrbekov, E.; Jassby, D.L.; McArthur, D.

    1996-05-01

    To date, nuclear pumped lasers (NPLs) have been driven by neutrons from pulsed research fission reactors. However, future applications using either a Magnetic Confinement Fusion (MCF) neutron source or an Inertial Confinement Fusion (ICF) source appear attractive. One unique combination proposed earlier would use a neutron feedback NPL driver in an ICF power plant. 14-MeV D-T neutrons (and 2.5-MeV D-D neutrons) provide a unique opportunity for a neutron recoil pumped NPL. Alternatively, these neutrons can be thermalized to provide thermal-neutron induced reactions for pumping. Initial experience with a fusion-pumped NPL can possibly be obtained using the D-T burn experiments in progress/planning at the Tokamak Fusion Test Reactor (TFTR) and Joint European Torus (JET) tokamak devices or at the planned National Ignition Facility (NIF) high-gain ICF target experimental facility. With neutron fluxes presently available, peak thermalized fluxes at a test laser in the shield region could exceed 10{sup 14} n/cm{sup 2}/sec. Several low-threshold NPLs might be utilized in such an experiment, including the He-Ne-H{sub 2} NPL and the Ar-Xe NPL. Experimental set-ups for both the tokamak and the NIF will be described. {copyright} {ital 1996 American Institute of Physics.}

  15. Seismic data fusion anomaly detection

    NASA Astrophysics Data System (ADS)

    Harrity, Kyle; Blasch, Erik; Alford, Mark; Ezekiel, Soundararajan; Ferris, David

    2014-06-01

    Detecting anomalies in non-stationary signals has valuable applications in many fields including medicine and meteorology. These include uses such as identifying possible heart conditions from an Electrocardiography (ECG) signals or predicting earthquakes via seismographic data. Over the many choices of anomaly detection algorithms, it is important to compare possible methods. In this paper, we examine and compare two approaches to anomaly detection and see how data fusion methods may improve performance. The first approach involves using an artificial neural network (ANN) to detect anomalies in a wavelet de-noised signal. The other method uses a perspective neural network (PNN) to analyze an arbitrary number of "perspectives" or transformations of the observed signal for anomalies. Possible perspectives may include wavelet de-noising, Fourier transform, peak-filtering, etc.. In order to evaluate these techniques via signal fusion metrics, we must apply signal preprocessing techniques such as de-noising methods to the original signal and then use a neural network to find anomalies in the generated signal. From this secondary result it is possible to use data fusion techniques that can be evaluated via existing data fusion metrics for single and multiple perspectives. The result will show which anomaly detection method, according to the metrics, is better suited overall for anomaly detection applications. The method used in this study could be applied to compare other signal processing algorithms.

  16. Inertial confinement fusion (ICF) review

    SciTech Connect

    Hammer, D.; Dyson, F.; Fortson, N.; Novick, B.; Panofsky, W.; Rosenbluth, M.; Treiman, S.; York, H.

    1996-03-01

    During its 1996 winter study JASON reviewed the DOE Inertial Confinement Fusion (ICF) program. This included the National Ignition Facility (NIF) and proposed studies. The result of the review was to comment on the role of the ICF program in support of the DOE Science Based Stockpile Stewardship program.

  17. Tritium breeding in fusion reactors

    SciTech Connect

    Abdou, M.A.

    1982-10-01

    Key technological problems that influence tritium breeding in fusion blankets are reviewed. The breeding potential of candidate materials is evaluated and compared to the tritium breeding requirements. The sensitivity of tritium breeding to design and nuclear data parameters is reviewed. A framework for an integrated approach to improve tritium breeding prediction is discussed with emphasis on nuclear data requirements.

  18. Spectral Line Shapes as a Diagnostic Tool in Magnetic Fusion

    SciTech Connect

    Stamm, R; Capes, H; Demura, A; Godbert-Mouret, L; Koubiti, M; Marandet, Y; Mattioli, M; Rosato, J; Rosmej, F; Fournier, K B

    2006-07-22

    Spectral line shapes and intensities are used for obtaining information on the various regions of magnetic fusion devices. Emission from low principal quantum numbers of hydrogen isotopes is analyzed for understanding the complex recycling mechanism. Lines emitted from high principal quantum numbers of hydrogen and helium are dominated by Stark effect, allowing an electronic density diagnostic in the divertor. Intensities of lines emitted by impurities are fitted for a better knowledge of ion transport in the confined plasma.

  19. Characterisation of the role of Vrp1 in cell fusion during the development of visceral muscle of Drosophila melanogaster

    PubMed Central

    2010-01-01

    Background In Drosophila muscle cell fusion takes place both during the formation of the somatic mesoderm and the visceral mesoderm, giving rise to the skeletal muscles and the gut musculature respectively. The core process of myoblast fusion is believed to be similar for both organs. The actin cytoskeleton regulator Verprolin acts by binding to WASP, which in turn binds to the Arp2/3 complex and thus activates actin polymerization. While Verprolin has been shown to be important for somatic muscle cell fusion, the function of this protein in visceral muscle fusion has not been determined. Results Verprolin is specifically expressed in the fusion competent myoblasts of the visceral mesoderm, suggesting a role in visceral mesoderm fusion. We here describe a novel Verprolin mutant allele which displays subtle visceral mesoderm fusion defects in the form of mislocalization of the immunoglobulin superfamily molecule Duf/Kirre, which is required on the myoblast cell surface to facilitate attachment between cells that are about to fuse, indicating a function for Verprolin in visceral mesoderm fusion. We further show that Verprolin mutant cells are capable of both migrating and fusing and that the WASP-binding domain of Verprolin is required for rescue of the Verprolin mutant phenotype. Conclusions Verprolin is expressed in the visceral mesoderm and plays a role in visceral muscle fusion as shown by mislocalization of Duf/Kirre in the Verprolin mutant, however it is not absolutely required for myoblast fusion in either the visceral or the somatic mesoderm. PMID:20701765

  20. Inhibition of HIV-1 Env-Mediated Cell-Cell Fusion by Lectins, Peptide T-20, and Neutralizing Antibodies

    PubMed Central

    Yee, Michael; Konopka, Krystyna; Balzarini, Jan; Düzgüneş, Nejat

    2011-01-01

    Background: Broadly cross-reactive, neutralizing human monoclonal antibodies, including 2F5, 2G12, 4E10 and IgG1 b12, can inhibit HIV-1 infection in vitro at very low concentrations. We examined the ability of these antibodies to inhibit cell-cell fusion between Clone69TRevEnv cells induced to express the viral envelope proteins, gp120/gp41 (Env), and highly CD4-positive SupT1 cells. The cells were loaded with green and red-orange cytoplasmic fluorophores, and fusion was monitored by fluorescence microscopy. Results: Cell-cell fusion was inhibited completely by the carbohydrate binding proteins (CBPs), Hippeastrum hybrid (Amaryllis) agglutinin (HHA), and Galanthus nivalis (Snowdrop) agglutinin (GNA), and by the peptide, T-20, at relatively low concentrations. Anti-gp120 and anti-gp41 antibodies, at concentrations much higher than those required for neutralization, were not particularly effective in inhibiting fusion. Monoclonal antibodies b12, m14 IgG and 2G12 had moderate inhibitory activity; the IC50 of 2G12 was about 80 µg/ml. Antibodies 4E10 and 2F5 had no inhibitory activity at the concentrations tested. Conclusions: These observations raise concerns about the ability of neutralizing antibodies to inhibit the spread of viral genetic material from infected cells to uninfected cells via cell-cell fusion. The interaction of gp120/gp41 with cell membrane CD4 may be different in cell-cell and virus-cell membrane fusion reactions, and may explain the differential effects of antibodies in these two systems. The fluorescence assay described here may be useful in high throughput screening of potential HIV fusion inhibitors. PMID:21660189

  1. Nuclear data requirements for fusion reactor nucleonics

    SciTech Connect

    Bhat, M.R.; Abdou, M.A.

    1980-01-01

    Nuclear data requirements for fusion reactor nucleonics are reviewed and the present status of data are assessed. The discussion is divided into broad categories dealing with data for Fusion Materials Irradiation Test Facility (FMIT), D-T Fusion Reactors, Alternate Fuel Cycles and the Evaluated Data Files that are available or would be available in the near future.

  2. Proceedings of the Office of Fusion Energy/DOE workshop on ceramic matrix composites for structural applications in fusion reactors

    SciTech Connect

    Jones, R.H. ); Lucas, G.E. )

    1990-11-01

    A workshop to assess the potential application of ceramic matrix composites (CMCs) for structural applications in fusion reactors was held on May 21--22, 1990, at University of California, Santa Barbara. Participants included individuals familiar with materials and design requirements in fusion reactors, ceramic composite processing and properties and radiation effects. The primary focus was to list the feasibility issues that might limit the application of these materials in fusion reactors. Clear advantages for the use of CMCs are high-temperature operation, which would allow a high-efficiency Rankine cycle, and low activation. Limitations to their use are material costs, fabrication complexity and costs, lack of familiarity with these materials in design, and the lack of data on radiation stability at relevant temperatures and fluences. Fusion-relevant feasibility issues identified at this workshop include: hermetic and vacuum properties related to effects of matrix porosity and matrix microcracking; chemical compatibility with coolant, tritium, and breeder and multiplier materials, radiation effects on compatibility; radiation stability and integrity; and ability to join CMCs in the shop and at the reactor site, radiation stability and integrity of joints. A summary of ongoing CMC radiation programs is also given. It was suggested that a true feasibility assessment of CMCs for fusion structural applications could not be completed without evaluation of a material tailored'' to fusion conditions or at least to radiation stability. It was suggested that a follow-up workshop be held to design a tailored composite after the results of CMC radiation studies are available and the critical feasibility issues are addressed.

  3. Atomic, Molecular and Plasma-Surface Interaction Data for Fusion Energy Research

    SciTech Connect

    Clark, R. E. H.; Humbert, D.

    2009-05-02

    Research on fusion energy requires a large amount of data in order to predict the behaviour of complex plasma devices. As plasma systems are updated and new machines are designed, data are required for a variety of different materials over a wide range of plasma conditions. The Atomic and Molecular Data Unit of the International Atomic Energy Agency works to coordinate multinational efforts to establish databases for this fusion research effort.

  4. MAD for visual tracker fusion

    NASA Astrophysics Data System (ADS)

    Becker, Stefan; Krah, Sebastian B.; Hübner, Wolfgang; Arens, Michael

    2016-10-01

    Existing tracking methods vary strongly in their approach and therefore have different strengths and weaknesses. For example, a single tracking algorithm may be good at handling variations in illumination, but does not cope well with deformation. Hence, their failures can occur on entirely different time intervals on the same sequence. One possible solution for overcoming limitations of a single tracker and for benefitting from individual strengths, is to run a set of tracking algorithms in parallel and fuse their outputs. But in general, tracking algorithms are not designed to receive feedback from a higher level fusion strategy or require a high degree of integration between individual levels. Towards this end, we introduce a fusion strategy serving the purpose of online single object tracking, for which no knowledge about individual tracker characteristics is needed. The key idea is to combine several independent and heterogeneous tracking approaches and to robustly identify an outlier subset based on the "Median Absolute Deviations" (MAD) measure. The MAD fusion strategy is very generic and only requires frame-based object bounding boxes as input. Thus, it can work with arbitrary tracking algorithms. Furthermore, the MAD fusion strategy can also be applied for combining several instances of the same tracker to form a more robust ensemble for tracking an object. The evaluation is done on public available datasets. With a set of heterogeneous, commonly used trackers we show that the proposed MAD fusion strategy improves the tracking results in comparison to a classical combination of parallel trackers and that the tracker ensemble helps to deal with the initialization uncertainty of a single tracker.

  5. Fusion safety regulations in the United States: Progress and trends

    SciTech Connect

    DeLooper, J.

    1994-07-01

    This paper explores the issue of regulations as they apply to current and future fusion experimental machines. It addresses fusion regulatory issues, current regulations used for fusion, the Tokamak Fusion Test Reactor experience with regulations, and future regulations to achieve fusion`s safety and environmental potential.

  6. Rational Decision-Making in Inhibitory Control

    PubMed Central

    Shenoy, Pradeep; Yu, Angela J.

    2011-01-01

    An important aspect of cognitive flexibility is inhibitory control, the ability to dynamically modify or cancel planned actions in response to changes in the sensory environment or task demands. We formulate a probabilistic, rational decision-making framework for inhibitory control in the stop signal paradigm. Our model posits that subjects maintain a Bayes-optimal, continually updated representation of sensory inputs, and repeatedly assess the relative value of stopping and going on a fine temporal scale, in order to make an optimal decision on when and whether to go on each trial. We further posit that they implement this continual evaluation with respect to a global objective function capturing the various reward and penalties associated with different behavioral outcomes, such as speed and accuracy, or the relative costs of stop errors and go errors. We demonstrate that our rational decision-making model naturally gives rise to basic behavioral characteristics consistently observed for this paradigm, as well as more subtle effects due to contextual factors such as reward contingencies or motivational factors. Furthermore, we show that the classical race model can be seen as a computationally simpler, perhaps neurally plausible, approximation to optimal decision-making. This conceptual link allows us to predict how the parameters of the race model, such as the stopping latency, should change with task parameters and individual experiences/ability. PMID:21647306

  7. When is an inhibitory synapse effective?

    PubMed

    Qian, N; Sejnowski, T J

    1990-10-01

    Interactions between excitatory and inhibitory synaptic inputs on dendrites determine the level of activity in neurons. Models based on the cable equation predict that silent shunting inhibition can strongly veto the effect of an excitatory input. The cable model assumes that ionic concentrations do not change during the electrical activity, which may not be a valid assumption, especially for small structures such as dendritic spines. We present here an analysis and computer simulations to show that for large Cl- conductance changes, the more general Nernst-Planck electrodiffusion model predicts that shunting inhibition on spines should be much less effective than that predicted by the cable model. This is a consequence of the large changes in the intracellular ionic concentration of Cl- that can occur in small structures, which would alter the reversal potential and reduce the driving force for Cl-. Shunting inhibition should therefore not be effective on spines, but it could be significantly more effective on the dendritic shaft at the base of the spine. In contrast to shunting inhibition, hyperpolarizing synaptic inhibition mediated by K+ currents can be very effective in reducing the excitatory synaptic potentials on the same spine if the excitatory conductance change is less than 10 nS. We predict that if the inhibitory synapses found on cortical spines are to be effective, then they should be mediated by K+ through GABAB receptors.

  8. When is an Inhibitory Synapse Effective?

    NASA Astrophysics Data System (ADS)

    Qian, Ning; Sejnowski, Terrence J.

    1990-10-01

    Interactions between excitatory and inhibitory synaptic inputs on dendrites determine the level of activity in neurons. Models based on the cable equation predict that silent shunting inhibition can strongly veto the effect of an excitatory input. The cable model assumes that ionic concentrations do not change during the electrical activity, which may not be a valid assumption, especially for small structures such as dendritic spines. We present here an analysis and computer simulations to show that for large Cl^- conductance changes, the more general Nernst-Planck electrodiffusion model predicts that shunting inhibition on spines should be much less effective than that predicted by the cable model. This is a consequence of the large changes in the intracellular ionic concentration of Cl^- that can occur in small structures, which would alter the reversal potential and reduce the driving force for Cl^-. Shunting inhibition should therefore not be effective on spines, but it could be significantly more effective on the dendritic shaft at the base of the spine. In contrast to shunting inhibition, hyperpolarizing synaptic inhibition mediated by K^+ currents can be very effective in reducing the excitatory synaptic potentials on the same spine if the excitatory conductance change is less than 10 nS. We predict that if the inhibitory synapses found on cortical spines are to be effective, then they should be mediated by K^+ through GABA_B receptors.

  9. Maximizing exposure therapy: an inhibitory learning approach.

    PubMed

    Craske, Michelle G; Treanor, Michael; Conway, Christopher C; Zbozinek, Tomislav; Vervliet, Bram

    2014-07-01

    Exposure therapy is an effective approach for treating anxiety disorders, although a substantial number of individuals fail to benefit or experience a return of fear after treatment. Research suggests that anxious individuals show deficits in the mechanisms believed to underlie exposure therapy, such as inhibitory learning. Targeting these processes may help improve the efficacy of exposure-based procedures. Although evidence supports an inhibitory learning model of extinction, there has been little discussion of how to implement this model in clinical practice. The primary aim of this paper is to provide examples to clinicians for how to apply this model to optimize exposure therapy with anxious clients, in ways that distinguish it from a 'fear habituation' approach and 'belief disconfirmation' approach within standard cognitive-behavior therapy. Exposure optimization strategies include (1) expectancy violation, (2) deepened extinction, (3) occasional reinforced extinction, (4) removal of safety signals, (5) variability, (6) retrieval cues, (7) multiple contexts, and (8) affect labeling. Case studies illustrate methods of applying these techniques with a variety of anxiety disorders, including obsessive-compulsive disorder, posttraumatic stress disorder, social phobia, specific phobia, and panic disorder.

  10. Maximizing Exposure Therapy: An Inhibitory Learning Approach

    PubMed Central

    Craske, Michelle G.; Treanor, Michael; Conway, Chris; Zbozinek, Tomislav; Vervliet, Bram

    2014-01-01

    Exposure therapy is an effective approach for treating anxiety disorders, although a substantial number of individuals fail to benefit or experience a return of fear after treatment. Research suggests that anxious individuals show deficits in the mechanisms believed to underlie exposure therapy, such as inhibitory learning. Targeting these processes may help improve the efficacy of exposure-based procedures. Although evidence supports an inhibitory learning model of extinction, there has been little discussion of how to implement this model in clinical practice. The primary aim of this paper is to provide examples to clinicians for how to apply this model to optimize exposure therapy with anxious clients, in ways that distinguish it from a ‘fear habituation’ approach and ‘belief disconfirmation’ approach within standard cognitive-behavior therapy. Exposure optimization strategies include 1) expectancy violation, 2) deepened extinction, 3) occasional reinforced extinction, 4) removal of safety signals, 5) variability, 6) retrieval cues, 7) multiple contexts, and 8) affect labeling. Case studies illustrate methods of applying these techniques with a variety of anxiety disorders, including obsessive-compulsive disorder, posttraumatic stress disorder, social phobia, specific phobia, and panic disorder. PMID:24864005

  11. Social inhibitory control in five lemur species.

    PubMed

    Reddy, Rachna B; MacLean, Evan L; Sandel, Aaron A; Hare, Brian

    2015-07-01

    We tested five lemur species-ring-tailed lemurs, ruffed lemurs, mongoose lemurs, black lemurs, and Coquerel's sifakas-(N = 52) in an experiment that evaluated skills for inhibitory control in a social context. First, two human experimenters presented identical food rewards; the "generous" experimenter allowed the subject to eat from her hand, whereas the "competitive" experimenter always withheld the reward. Lemurs quickly learned to approach the generous experimenter and avoid the competitive one. In the inhibition test phase, we endowed the competitive experimenter with a more valuable food reward but the competitive experimenter continued to withhold food from the subject. Thus, lemurs were required to inhibit approaching the more desirable reward in favor of the lesser but obtainable reward presented by the generous experimenter. In test trials, lemurs' tendency to approach the competitive experimenter increased from the reputation phase, demonstrating sensitivity to the experimental manipulation. However, subjects approached the larger reward less frequently in test trials compared with pretest food-preference trials, evidencing some capacity for inhibitory control in this context. Despite differences in sociality and ecology, the five lemur species did not differ in this ability. Although the study did not uncover species differences, this experimental task may provide a useful measure of social inhibition in broader comparative studies.

  12. Predicting Monoamine Oxidase Inhibitory Activity through Ligand-Based Models

    PubMed Central

    Vilar, Santiago; Ferino, Giulio; Quezada, Elias; Santana, Lourdes; Friedman, Carol

    2013-01-01

    The evolution of bio- and cheminformatics associated with the development of specialized software and increasing computer power has produced a great interest in theoretical in silico methods applied in drug rational design. These techniques apply the concept that “similar molecules have similar biological properties” that has been exploited in Medicinal Chemistry for years to design new molecules with desirable pharmacological profiles. Ligand-based methods are not dependent on receptor structural data and take into account two and three-dimensional molecular properties to assess similarity of new compounds in regards to the set of molecules with the biological property under study. Depending on the complexity of the calculation, there are different types of ligand-based methods, such as QSAR (Quantitative Structure-Activity Relationship) with 2D and 3D descriptors, CoMFA (Comparative Molecular Field Analysis) or pharmacophoric approaches. This work provides a description of a series of ligand-based models applied in the prediction of the inhibitory activity of monoamine oxidase (MAO) enzymes. The controlled regulation of the enzymes’ function through the use of MAO inhibitors is used as a treatment in many psychiatric and neurological disorders, such as depression, anxiety, Alzheimer’s and Parkinson’s disease. For this reason, multiple scaffolds, such as substituted coumarins, indolylmethylamine or pyridazine derivatives were synthesized and assayed toward MAO-A and MAO-B inhibition. Our intention is to focus on the description of ligand-based models to provide new insights in the relationship between the MAO inhibitory activity and the molecular structure of the different inhibitors, and further study enzyme selectivity and possible mechanisms of action. PMID:23231398

  13. Magnetized Target Fusion: Prospects for Low-Cost Fusion Energy

    NASA Technical Reports Server (NTRS)

    Siemon, Richard E.; Turchi, Peter J.; Barnes, Daniel C.; Degnan, James; Parks, Paul; Ryutov, Dmitri D.; Thio, Y. C. Francis; Schafer, Charles (Technical Monitor)

    2001-01-01

    Magnetized Target Fusion (MTF) has attracted renewed interest in recent years because it has the potential to resolve one of the major problems with conventional fusion energy research - the high cost of facilities to do experiments and in general develop practical fusion energy. The requirement for costly facilities can be traced to fundamental constraints. The Lawson condition implies large system size in the case of conventional magnetic confinement, or large heating power in the case of conventional inertial confinement. The MTF approach is to use much higher fuel density than with conventional magnetic confinement (corresponding to megabar pressures), which results in a much-reduced system size to achieve Lawson conditions. Intrinsically the system must be pulsed because the pressures exceed the strength of any known material. To facilitate heating the fuel (or "target") to thermonuclear conditions with a high-power high-intensity source of energy, magnetic fields are used to insulate the high-pressure fuel from material surroundings (thus "magnetized target"). Because of magnetic insulation, the required heating power intensity is reduced by many orders of magnitude compared to conventional inertial fusion, even with relatively poor energy confinement in the magnetic field, such as that characterized by Bohm diffusion. In this paper we show semi-quantitatively why MTF-should allow fusion energy production without costly facilities within the same generally accepted physical constraints used for conventional magnetic and inertial fusion. We also briefly discuss potential applications of this technology ranging from nuclear rockets for space propulsion to a practical commercial energy system. Finally, we report on the exploratory research underway, and the interesting physics issues that arise in the MTF regime of parameters. Experiments at Los Alamos are focused on formation of a suitable plasma target for compression, utilizing the knowledge base for compact

  14. Assembly and disassembly of the Golgi complex: two processes arranged in a cis-trans direction

    PubMed Central

    1992-01-01

    We have studied the disassembly and assembly of two morphologically and functionally distinct parts of the Golgi complex, the cis/middle and trans cisterna/trans network compartments. For this purpose we have followed the redistribution of three cis/middle- (GMPc-1, GMPc-2, MG 160) and two trans- (GMPt-1 and GMPt-2) Golgi membrane proteins during and after treatment of normal rat kidney (NRK) cells with brefeldin A (BFA). BFA induced complete disassembly of the cis/middle- and trans- Golgi complex and translocation of GMPc and GMPt to the ER. Cells treated for short times (3 min) with BFA showed extensive disorganization of both cis/middle- and trans-Golgi complexes. However, complete disorganization of the trans part required much longer incubations with the drug. Upon removal of BFA the Golgi complex was reassembled by a process consisting of three steps: (a) exist of cis/middle proteins from the ER and their accumulation into vesicular structures scattered throughout the cytoplasm; (b) gradual relocation and accumulation of the trans proteins in the vesicles containing the cis/middle proteins; and (c) assembly of the cisternae, and reconstruction of the Golgi complex within an area located in the vicinity of the centrosome from which the ER was excluded. Reconstruction of the cis/middle-Golgi complex occurred under temperature conditions inhibitory of the reorganization of the trans- Golgi complex, and was dependent on microtubules. Reconstruction of the trans-Golgi complex, disrupted with nocodazole after selective fusion of the cis/middle-Golgi complex with the ER, occurred after the release of cis/middle-Golgi proteins from the ER and the assembly of the cis/middle cisternae. PMID:1730750

  15. Fusion - An energy source for synthetic fuels

    NASA Astrophysics Data System (ADS)

    Fillo, J. A.; Powell, J.; Steinberg, M.

    1980-05-01

    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 40 to 60% and hydrogen production efficiencies by high temperature electrolysis of 50 to 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. In the long term, there could be a gradual transition to an inexhaustible energy system based solely on fusion.

  16. Mechanisms of myoblast fusion during muscle development

    PubMed Central

    Kim, Ji Hoon; Jin, Peng; Duan, Rui; Chen, Elizabeth H.

    2015-01-01

    The development and regeneration of skeletal muscles require the fusion of mononulceated muscle cells to form multinucleated, contractile muscle fibers. Studies using a simple genetic model, Drosophila melanogaster, have discovered many evolutionarily conserved fusion-promoting factors in vivo. Recent work in zebrafish and mouse also identified several vertebrate-specific factors required for myoblast fusion. Here, we integrate progress in multiple in vivo systems and highlight conceptual advance in understanding how muscle cell membranes are brought together for fusion. We focus on the molecular machinery at the fusogenic synapse and present a three-step model to describe the molecular and cellular events leading to fusion pore formation. PMID:25989064

  17. Fruit classification based on weighted score-level feature fusion

    NASA Astrophysics Data System (ADS)

    Kuang, Hulin; Hang Chan, Leanne Lai; Liu, Cairong; Yan, Hong

    2016-01-01

    We describe an object classification method based on weighted score-level feature fusion using learned weights. Our method is able to recognize 20 object classes in a customized fruit dataset. Although the fusion of multiple features is commonly used to distinguish variable object classes, the optimal combination of features is not well defined. Moreover, in these methods, most parameters used for feature extraction are not optimized and the contribution of each feature to an individual class is not considered when determining the weight of the feature. Our algorithm relies on optimizing a single feature during feature selection and learning the weight of each feature for an individual class from the training data using a linear support vector machine before the features are linearly combined with the weights at the score level. The optimal single feature is selected using cross-validation. The optimal combination of features is explored and tested experimentally using a customized fruit dataset with 20 object classes and a variety of complex backgrounds. The experiment results show that the proposed feature fusion method outperforms four state-of-the-art fruit classification algorithms and improves the classification accuracy when compared with some state-of-the-art feature fusion methods.

  18. A new hyperspectral image compression paradigm based on fusion

    NASA Astrophysics Data System (ADS)

    Guerra, Raúl; Melián, José; López, Sebastián.; Sarmiento, Roberto

    2016-10-01

    The on-board compression of remote sensed hyperspectral images is an important task nowadays. One of the main difficulties is that the compression of these images must be performed in the satellite which carries the hyperspectral sensor. Hence, this process must be performed by space qualified hardware, having area, power and speed limitations. Moreover, it is important to achieve high compression ratios without compromising the quality of the decompress image. In this manuscript we proposed a new methodology for compressing hyperspectral images based on hyperspectral image fusion concepts. The proposed compression process has two independent steps. The first one is to spatially degrade the remote sensed hyperspectral image to obtain a low resolution hyperspectral image. The second step is to spectrally degrade the remote sensed hyperspectral image to obtain a high resolution multispectral image. These two degraded images are then send to the earth surface, where they must be fused using a fusion algorithm for hyperspectral and multispectral image, in order to recover the remote sensed hyperspectral image. The main advantage of the proposed methodology for compressing remote sensed hyperspectral images is that the compression process, which must be performed on-board, becomes very simple, being the fusion process used to reconstruct image the more complex one. An extra advantage is that the compression ratio can be fixed in advanced. Many simulations have been performed using different fusion algorithms and different methodologies for degrading the hyperspectral image. The results obtained in the simulations performed corroborate the benefits of the proposed methodology.

  19. Component Framework for Coupled Integrated Fusion Plasma Simulation

    SciTech Connect

    Elwasif, Wael R; Bernholdt, David E; Berry, Lee A; Batchelor, Donald B

    2007-01-01

    Fusion Successful simulation of the complex physics that affect magnetically confined fusion plasma remains an important target milestone towards the development of viable fusion energy. Major advances in the underlying physics formulations, mathematical modeling, and computational tools and techniques are needed to enable a complete fusion simulation on the emerging class of large scale capability parallel computers that are coming on-line in the next few years. Several pilot projects are currently being undertaken to explore different (partial) code integration and coupling problems, and possible solutions that may guide the larger integration endeavor. In this paper, we present the design and implementation details of one such project, a component based approach to couple existing codes to model the interaction between high power radio frequency (RF) electromagnetic waves, and magnetohydrodynamics (MHD) aspects of the burning plasma. The framework and component design utilize a light coupling approach based on high level view of constituent codes that facilitates rapid incorporation of new components into the integrated simulation framework. The work illustrates the viability of the light coupling approach to better understand physics and stand-alone computer code dependencies and interactions, as a precursor to a more tightly coupled integrated simulation environment.

  20. Decisions-to-Data using Level 5 information fusion

    NASA Astrophysics Data System (ADS)

    Blasch, Erik

    2014-06-01

    Over the last decade, there has been interest in presenting information fusion solutions to the user and ways to incorporate visualization, interaction, and command and control. In this paper, we explore Decisions-to-Data (D2D) in information fusion design: (1) sensing: from data to information (D2I) processing, (2) reporting: from human computer interaction (HCI) visualizations to user refinement (H2U), and (3) disseminating: from collected to resourced (C2R) information management. D2I supports net-centric intelligent situation awareness that includes processing of information from non-sensor resources for mission effectiveness. H2U reflects that completely automated systems are not realizable requiring Level 5 user refinement for efficient decision making. Finally, C2R moves from immediate data collection to fusion of information over an enterprise (e.g., data mining, database queries and storage, and source analysis for pedigree). By using D2I, H2U, and C2R concepts, they serve as informative themes for future complex information fusion interoperability standards, integration of man and machines, and efficient networking for distribution user situation understanding.

  1. Functional characterization of syncytin-A, a newly murine endogenous virus envelope protein. Implication for its fusion mechanism.

    PubMed

    Peng, Xiaoxue; Pan, Ji'an; Gong, Rui; Liu, Yang; Kang, Shuli; Feng, Huixing; Qiu, Gang; Guo, Deyin; Tien, Po; Xiao, Gengfu

    2007-01-05

    Trophoblast fusion in placenta is an important event for preservation of a healthy pregnancy. This process takes place throughout the pregnancy and is crucial for the formation of syncytiotrophoblast layer. Syncytin-1 and syncytin-2 are strong candidate regulators of fusion from retroviral origin. Syncytin-A and syncytin-B are other candidates from retroviral origin in Muridae. The active role of syncytin in driving fusion of trophoblast has been identified, but its fusion mechanism is still unclear. As an intact retroviral envelope protein, syncytin-A shares similar structure profiling with other viral envelope fusion proteins, especially in the regions of N- and C-terminal heptad repeats (NHR and CHR, respectively). In this paper, we showed that SynA 1 + 2 of syncytin-A (residues 445-536, including predicted NHR, CHR, and a natural linker) could form trimer and exhibited significant alpha-helix structure and high thermo-stability. Limited proteolysis result identified a stable protease-resistant core of SynA 1 + 2, which was in good agreement with computational modeling data. NHR and CHR could interact with each other in vitro, too. Different from the previous studies, the disulfide-bonded linker was apparently vital to the stability of fusion core structure. By biological assays, NHR was shown to be inhibitive to cell-cell fusion, with IC(50) value about 5.4 microm, but CHR seemed to have no inhibitory activity even at 50 microm. From both biochemical and functional data, we first gave an explanation how syncytin-A mediated cell fusion. The insight into the mechanism of syncytin-A-mediated cell-cell fusion may provide a crucial clue to placental cytotrophoblast morphogenesis.

  2. [Inhibitory action of divalent copper compounds on cumene hydroperoxide oxidative demethylation of N,N-dimethylaniline by cytochrome P-450].

    PubMed

    Kurchenko, V P; Usanov, S A; Metelitsa, D I

    1980-07-01

    The inhibitory action of divalent copper compounds on hydroperoxide-dependent oxidative demethylation of N,N-demethylaniline involving rabbit liver microsomes and highly purified cytochrome P-450 has been studied. CuCl2 is a non-competitive inhibitor, whereas copper tyrosine and lysine complexes are characterized by a mixed type inhibition. The inhibitory action of copper complexes is based on a decrease of cumene hydroperoxide concentration. The reaction results in formation of RO and RO2 radicals destroying cytochrome P-450 CuCl2 (0,001 M) also destroys cytochrome P-450 in the absence of cumene hydroperoxide; the destruction process is characterized by two phases with different rate constants. The nature of the inhibitory action of CuCl2 on N,N-demethylaniline oxidation by hydroperoxides is discussed.

  3. 2014 Nuclear Fusion Prize Acceptance Speech 2014 Nuclear Fusion Prize Acceptance Speech

    NASA Astrophysics Data System (ADS)

    Snyder, P. B.

    2015-01-01

    and numerical techniques which enable efficient quantitative study of peeling-ballooning modes. More broadly, I would like to thank the full DIII-D, C-Mod and JET teams, the LLNL and General Atomics Theory groups, and the York Plasma Institute. In addition, I would like to thank the US DOE Office of Fusion Energy Sciences, EURATOM, and the UK EPSRC for supporting this research. On a more personal note, I would like to thank my mentors over the years, including Nat Fisch, Greg Hammett, Ron Waltz, Vincent Chan, and Tony Taylor, and numerous colleagues who provided insight related to this work, including Lang Lao, Alan Turnbull, Ming Chu, Bob Miller, Rip Perkins, John Greene, Keith Burrell, John Ferron, Mickey Wade, Wayne Solomon, George McKee, Zheng Yan, Andrea Garofalo, Raffi Nazikian, Jack Connor, Jim Hastie, Chris Hegna, Samuli Saarelma, Guido Huijsmans, Alberto Loarte, Yutaka Kamada, Naoyuki Oyama, Hajime Urano, Nobuyuki Aiba, Andrew Kirk, David Dickinson, Lorne Horton, Costanza Maggi, Wolfgang Suttrop, P.A. Schneider, Rajesh Maingi, Amanda Hubbard, Ahmed Diallo, John Walk, and Matthew Leyland. Recently, the model developed in this paper has been used to discover a new regime of operation, the Super H-Mode, and to shed light on mechanisms for suppressing Edge Localized Modes. I hope that the model will continue to be useful, both as a tool for predicting and optimizing pedestal and fusion performance, and as a platform on which the fusion community continues to build our understanding of the complex physics of the edge barrier region, which plays such an important role in overall confinement and stability.

  4. Henipavirus membrane fusion and viral entry.

    PubMed

    Aguilar, Hector C; Iorio, Ronald M

    2012-01-01

    Nipah (NiV) and Hendra (HeV) viruses cause cell-cell fusion (syncytia) in brain, lung, heart, and kidney tissues, leading to encephalitis, pneumonia, and often death. Membrane fusion is essential to both viral entry and virus-induced cell-cell fusion, a hallmark of henipavirus infections. Elucidiation of the mechanism(s) of membrane fusion is critical to understanding henipavirus pathobiology and has the potential to identify novel strategies for the development of antiviral therapeutic agents. Henipavirus membrane fusion requires the coordinated actions of the viral attachment (G) and fusion (F) glycoproteins. Current henipavirus fusion models posit that attachment of NiV or HeV G to its cell surface receptors releases F from its metastable pre-fusion conformation to mediate membrane fusion. The identification of ephrinB2 and ephrinB3 as henipavirus receptors has paved the way for recent advances in our understanding of henipavirus membrane fusion. These advances highlight mechanistic similarities and differences between membrane fusion for the henipavirus and other genera within the Paramyxoviridae family. Here, we review these mechanisms and the current gaps in our knowledge in the field.

  5. High cholesterol obviates a prolonged hemifusion intermediate in fast SNARE-mediated membrane fusion.

    PubMed

    Kreutzberger, Alex J B; Kiessling, Volker; Tamm, Lukas K

    2015-07-21

    Cholesterol is essential for exocytosis in secretory cells, but the exact molecular mechanism by which it facilitates exocytosis is largely unknown. Distinguishing contributions from the lateral organization and dynamics of membrane proteins to vesicle docking and fusion and the promotion of fusion pores by negative intrinsic spontaneous curvature and other mechanical effects of cholesterol have been elusive. To shed more light on this process, we examined the effect of cholesterol on SNARE-mediated membrane fusion in a single-vesicle assay that is capable of resolving docking and elementary steps of fusion with millisecond time resolution. The effect of cholesterol on fusion pore formation between synaptobrevin-2 (VAMP-2)-containing proteoliposomes and acceptor t-SNARE complex-containing planar supported bilayers was examined using both membrane and content fluorescent markers. This approach revealed that increasing cholesterol in either the t-SNARE or the v-SNARE membrane favors a mechanism of direct fusion pore opening, whereas low cholesterol favors a mechanism leading to a long-lived (>5 s) hemifusion state. The amount of cholesterol in the target membrane had no significant effect on docking of synaptobrevin vesicles. Comparative studies with α-tocopherol (vitamin E) show that the negative intrinsic spontaneous curvature of cholesterol and its presumed promotion of a very short-lived (<50 ms) lipid stalk intermediate is the main factor that favors rapid fusion pore opening at high cholesterol. This study also shows that this single-vesicle fusion assay can distinguish between hemifusion and full fusion with only a single lipid dye, thereby freeing up a fluorescence channel for the simultaneous measurement of another parameter in fast time-resolved fusion assays.

  6. Mechanisms of mutations inhibiting fusion and infection by Semliki Forest virus

    PubMed Central

    1996-01-01

    Semliki Forest virus (SFV) infects cells by an acid-dependent membrane fusion reaction catalyzed by the virus spike protein, a complex containing E1 and E2 transmembrane subunits. E1 carries the putative virus fusion peptide, and mutations in this domain of the spike protein were previously shown to shift the pH threshold of cell-cell fusion (G91A), or block cell-cell fusion (G91D). We have used an SFV infectious clone to characterize virus particles containing these mutations. In keeping with the previous spike protein results, G91A virus showed limited secondary infection and an acid-shifted fusion threshold, while G91D virus was noninfectious and inactive in both cell- cell and virus-liposome fusion assays. During the low pH- induced SFV fusion reaction, the E1 subunit exposes new epitopes for monoclonal antibody (mAb) binding and forms an SDS-resistant homotrimer, the virus associates hydrophobically with the target membrane, and fusion of the virus and target membranes occurs. After low pH treatment, G91A spike proteins were shown to bind conformation-specific mAbs, associate with target liposome membranes, and form the E1 homotrimer. However, both G91A membrane association and homotrimer formation had an acid-shifted pH threshold and reduced efficiency compared to wt virus. In contrast, studies of the fusion-defective G91D mutant showed that the virus efficiently reacted with low pH as assayed by mAb binding and liposome association, but was essentially inactive in homotrimer formation. These results suggest that the G91D mutant is noninfectious due to a block in a late step in membrane fusion, separate from the initial reaction to low pH and interaction with the target membrane, and involving the lack of efficient formation of the E1 homotrimer. PMID:8769412

  7. Purdue Contribution of Fusion Simulation Program

    SciTech Connect

    Jeffrey Brooks

    2011-09-30

    The overall science goal of the 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 research related to the International Thermonuclear Experimental Reactor (ITER) 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 areas: 1) the plasma edge and 2) whole device modeling 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 (WDM) will be prediction and avoidance of discharge-terminating disruptions, especially at high performance, which are a critical impediment to successful operation of machines like ITER. If disruptions prove unable to be avoided, their associated dynamics and effects will be addressed in the next phase of the FSP. The FSP plan targets the needed modeling capabilities by developing Integrated Science Applications (ISAs) specific to their needs. The Pedestal-Boundary model will include boundary magnetic topology, cross-field transport of multi-species plasmas, parallel plasma transport, neutral transport, atomic physics and interactions with the plasma wall

  8. Fusion technologies for Laser Inertial Fusion Energy (LIFE)

    NASA Astrophysics Data System (ADS)

    Kramer, K. J.; Latkowski, J. F.; Abbott, R. P.; Anklam, T. P.; Dunne, A. M.; El-Dasher, B. S.; Flowers, D. L.; Fluss, M. J.; Lafuente, A.; Loosmore, G. A.; Morris, K. R.; Moses, E.; Reyes, S.

    2013-11-01

    The Laser Inertial Fusion-based Energy (LIFE) engine design builds upon on going progress at the National Ignition Facility (NIF) and offers a near-term pathway to commercial fusion. Fusion technologies that are critical to success are reflected in the design of the first wall, blanket and tritium separation subsystems. The present work describes the LIFE engine-related components and technologies. LIFE utilizes a thermally robust indirect-drive target and a chamber fill gas. Coolant selection and a large chamber solid-angle coverage provide ample tritium breeding margin and high blanket gain. Target material selection eliminates the need for aggressive chamber clearing, while enabling recycling. Demonstrated tritium separation and storage technologies limit the site tritium inventory to attractive levels. These key technologies, along with the maintenance and advanced materials qualification program have been integrated into the LIFE delivery plan. This describes the development of components and subsystems, through prototyping and integration into a First Of A Kind power plant. This work performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344.

  9. Acoustically Driven Magnetized Target Fusion At General Fusion: An Overview

    NASA Astrophysics Data System (ADS)

    O'Shea, Peter; Laberge, M.; Donaldson, M.; Delage, M.; the Fusion Team, General

    2016-10-01

    Magnetized Target Fusion (MTF) involves compressing an initial magnetically confined plasma of about 1e23 m-3, 100eV, 7 Tesla, 20 cm radius, >100 μsec life with a 1000x volume compression in 100 microseconds. If near adiabatic compression is achieved, the final plasma of 1e26 m-3, 10keV, 700 Tesla, 2 cm radius, confined for 10 μsec would produce interesting fusion energy gain. General Fusion (GF) is developing an acoustic compression system using pneumatic pistons focusing a shock wave on the CT plasma in the center of a 3 m diameter sphere filled with liquid lead-lithium. Low cost driver, straightforward heat extraction, good tritium breeding ratio and excellent neutron protection could lead to a practical power plant. GF (65 employees) has an active plasma R&D program including both full scale and reduced scale plasma experiments and simulation of both. Although acoustic driven compression of full scale plasmas is the end goal, present compression studies use reduced scale plasmas and chemically accelerated Aluminum liners. We will review results from our plasma target development, motivate and review the results of dynamic compression field tests and briefly describe the work to date on the acoustic driver front.

  10. Photoinduced Fusion of Lipid Bilayer Membranes.

    PubMed

    Suzuki, Yui; Nagai, Ken H; Zinchenko, Anatoly; Hamada, Tsutomu

    2017-03-14

    We have developed a novel system for photocontrol of the fusion of lipid vesicles through the use of a photosensitive surfactant containing an azobenzene moiety (AzoTAB). Real-time microscopic observations clarified a change in both the surface area and internal volume of vesicles during fusion. We also determined the optimal cholesterol concentrations and temperature for inducing fusion. The mechanism of fusion can be attributed to a change in membrane tension, which is caused by the solubilization of lipids through the isomerization of AzoTAB. We used a micropipet technique to estimate membrane tension and discuss the mechanism of fusion in terms of membrane elastic energy. The obtained results regarding this novel photoinduced fusion could lead to a better understanding of the mechanism of membrane fusion in living cells and may also see wider applications, such as in drug delivery and biomimetic material design.

  11. Object recognition approach based on feature fusion

    NASA Astrophysics Data System (ADS)

    Wang, Runsheng

    2001-09-01

    Multi-sensor information fusion plays an important pole in object recognition and many other application fields. Fusion performance is tightly depended on the fusion level selected and the approach used. Feature level fusion is a potential and difficult fusion level though there might be mainly three fusion levels. Two schemes are developed for key issues of feature level fusion in this paper. In feature selecting, a normal method developed is to analyze the mutual relationship among the features that can be used, and to be applied to order features. In object recognition, a multi-level recognition scheme is developed, whose procedure can be controlled and updated by analyzing the decision result obtained in order to achieve a final reliable result. The new approach is applied to recognize work-piece objects with twelve classes in optical images and open-country objects with four classes based on infrared image sequence and MMW radar. Experimental results are satisfied.

  12. Asymmetry between excitatory and inhibitory learning.

    PubMed

    Harris, Justin A; Patterson, Angela E; Andrew, Benjamin J; Kwok, Dorothy W S; Loy, Ignacio

    2016-10-01

    Five experiments investigated how learning about the added feature in a feature-positive discrimination or feature-negative discrimination is related to the change in reinforcement rate that the feature signals. Rats were trained in a magazine-approach paradigm with 2 concurrent discriminations between A versus AX and B versus BY. In 2 experiments (1 and 3), X and Y signaled an increase of 0.3 in the probability of reinforcement, from 0.1 to 0.4 (A vs. AX), or from 0.6 to 0.9 (B vs. BY). After extended training, each session included probe test trials in which X and Y were presented alone (Experiment 1) or in compound with another excitatory conditional stimulus (CS), C (Experiment 3). There was no difference in response rate between the 2 types of test trial (X vs. Y; XC vs. YC), consistent with the fact that X and Y signaled the same absolute change in reinforcement. In Experiments 2 and 4, X and Y signaled a decrease of 0.3 in the probability of reinforcement, from 0.4 to 0.1 (A vs. AX) or from 0.9 to 0.6 (B vs. BY). Test trials in which X or Y was presented with C showed that X had greater inhibitory strength than Y, consistent with the fact that X signaled a larger relative change in reinforcement. This was confirmed in Experiment 5, in which X and Y had the same inhibitory strength on test after training in which they signaled the same relative change in reinforcement but different absolute changes (0.3 to 0.1 for A vs. AX; 0.9 to 0.3 for B vs. BY). The results show that excitatory conditioning is linearly related to the increase in reinforcement rate, whereas inhibitory learning is not linearly related to the decrease in reinforcement rate. Implications of this for theories of associative learning are discussed. (PsycINFO Database Record

  13. Distinct genetic programs guide Drosophila circular and longitudinal visceral myoblast fusion

    PubMed Central

    2014-01-01

    Background The visceral musculature of Drosophila larvae comprises circular visceral muscles tightly interwoven with longitudinal visceral muscles. During myogenesis, the circular muscles arise by one-to-one fusion of a circular visceral founder cell (FC) with a visceral fusion-competent myoblast (FCM) from the trunk visceral mesoderm, and longitudinal muscles arise from FCs of the caudal visceral mesoderm. Longitudinal FCs migrate anteriorly under guidance of fibroblast growth factors during embryogenesis; it is proposed that they fuse with FCMs from the trunk visceral mesoderm to give rise to syncytia containing up to six nuclei. Results Using fluorescence in situ hybridization and immunochemical analyses, we investigated whether these fusion events during migration use the same molecular repertoire and cellular components as fusion-restricted myogenic adhesive structure (FuRMAS), the adhesive signaling center that mediates myoblast fusion in the somatic mesoderm. Longitudinal muscles were formed by the fusion of one FC with Sns-positive FCMs, and defects in FCM specification led to defects in longitudinal muscle formation. At the fusion sites, Duf/Kirre and the adaptor protein Rols7 accumulated in longitudinal FCs, and Blow and F-actin accumulated in FCMs. The accumulation of these four proteins at the fusion sites argues for FuRMAS-like adhesion and signaling centers. Longitudinal fusion was disturbed in rols and blow single, and scar wip double mutants. Mutants of wasp or its interaction partner wip had no defects in longitudinal fusion. Conclusions Our results indicated that all embryonic fusion events depend on the same cell-adhesion molecules, but that the need for Rols7 and regulators of F-actin distinctly differs. Rols7 was required for longitudinal visceral and somatic myoblast fusion but not for circular visceral fusion. Importantly, longitudinal fusion depended on Kette and SCAR/Wave but was independent of WASp-dependent Arp2/3 activation. Thus, the

  14. Whisker Deprivation Drives Two Phases of Inhibitory Synapse Weakening in Layer 4 of Rat Somatosensory Cortex

    PubMed Central

    Pourzia, Olivia; Feldman, Daniel E.

    2016-01-01

    Inhibitory synapse development in sensory neocortex is experience-dependent, with sustained sensory deprivation yielding fewer and weaker inhibitory synapses. Whether this represents arrest of synapse maturation, or a more complex set of processes, is unclear. To test this, we measured the dynamics of inhibitory synapse development in layer 4 of rat somatosensory cortex (S1) during continuous whisker deprivation from postnatal day 7, and in age-matched controls. In deprived columns, spontaneous miniature inhibitory postsynaptic currents (mIPSCs) and evoked IPSCs developed normally until P15, when IPSC amplitude transiently decreased, recovering by P16 despite ongoing deprivation. IPSCs remained normal until P22, when a second, sustained phase of weakening began. Delaying deprivation onset by 5 days prevented the P15 weakening. Both early and late phase weakening involved measurable reduction in IPSC amplitude relative to prior time points. Thus, deprivation appears to drive two distinct phases of active IPSC weakening, rather than simple arrest of synapse maturation. PMID:26840956

  15. Nootropic dipeptide noopept enhances inhibitory synaptic transmission in the hippocampus.

    PubMed

    Povarov, I S; Kondratenko, R V; Derevyagin, V I; Ostrovskaya, R U; Skrebitskii, V G

    2015-01-01

    Application of nootropic agent Noopept on hippocampal slices from Wistar rats enhanced the inhibitory component of total current induced by stimulation of Shaffer collaterals in CA1 pyramidal neurons, but did not affect the excitatory component. A direct correlation between the increase in the amplitude of inhibitory current and agent concentration was found. The substance did not affect the release of inhibitory transmitters from terminals in the pyramidal neurons, which indicated changes in GABAergic interneurons.

  16. Measuring time of flight of fusion products in an inertial electrostatic confinement fusion device for spatial profiling of fusion reactions

    SciTech Connect

    Donovan, D. C.; Boris, D. R.; Kulcinski, G. L.; Santarius, J. F.; Piefer, G. R.

    2013-03-15

    A new diagnostic has been developed that uses the time of flight (TOF) of the products from a nuclear fusion reaction to determine the location where the fusion reaction occurred. The TOF diagnostic uses charged particle detectors on opposing sides of the inertial electrostatic confinement (IEC) device that are coupled to high resolution timing electronics to measure the spatial profile of fusion reactions occurring between the two charged particle detectors. This diagnostic was constructed and tested by the University of Wisconsin-Madison Inertial Electrostatic Confinement Fusion Group in the IEC device, HOMER, which accelerates deuterium ions to fusion relevant energies in a high voltage ({approx}100 kV), spherically symmetric, electrostatic potential well [J. F. Santarius, G. L. Kulcinski, R. P. Ashley, D. R. Boris, B. B. Cipiti, S. K. Murali, G. R. Piefer, R. F. Radel, T. E. Radel, and A. L. Wehmeyer, Fusion Sci. Technol. 47, 1238 (2005)]. The TOF diagnostic detects the products of D(d,p)T reactions and determines where along a chord through the device the fusion event occurred. The diagnostic is also capable of using charged particle spectroscopy to determine the Doppler shift imparted to the fusion products by the center of mass energy of the fusion reactants. The TOF diagnostic is thus able to collect spatial profiles of the fusion reaction density along a chord through the device, coupled with the center of mass energy of the reactions occurring at each location. This provides levels of diagnostic detail never before achieved on an IEC device.

  17. Fusion evaporation and fusion-fission with aligned /sup 23/Na ions at energies near and below the fusion barrier

    SciTech Connect

    Butsch, R.; Jaensch, H.; Kraemer, D.; Moebius, K.; Ott, W.; Steffens, E.; Tungate, G.; Weller, a.A.; Becker, K.; Blatt, K.; and others

    1987-10-01

    Using aligned /sup 23/Na beams, fusion cross sections sigma/sup fus/ and second-rank tensor analyzing powers for fusion T/sub 20//sup fus/ have been measured at energies near and below the fusion barrier for /sup 23/Na+ /sup 48/Ti and for /sup 23/Na+ /sup 206/Pb. At sub-barrier energies, large, nearly maximal, values of T/sub 20//sup fus/ occur, especially for fusion with the heavy target /sup 206/Pb. This reflects the strong influence of the spectroscopic deformation of the projectile on the fusion process at energies below the barrier. However, within a quantum-mechanical coupled-channels calculation this degree of freedom is not enough to describe both the fusion cross section and the second-rank tensor analyzing power for fusion in the energy regime below the fusion barrier. It is shown that the coupling of the fusion channel to inelastic excitations of the projectile and the target can describe the magnitude and energy dependence of T/sub 20//sup fus/ for both heavy ion systems, but fails to reproduce the ''sub-barrier enhancement'' of the fusion cross section for both systems.

  18. Studies on the fusion peptide of a paramyxovirus fusion glycoprotein: roles of conserved residues in cell fusion.

    PubMed Central

    Horvath, C M; Lamb, R A

    1992-01-01

    The role of residues in the conserved hydrophobic N-terminal fusion peptide of the paramyxovirus fusion (F) protein in causing cell-cell fusion was examined. Mutations were introduced into the cDNA encoding the simian virus 5 (SV5) F protein, the altered F proteins were expressed by using an eukaryotic vector, and their ability to mediate syncytium formation was determined. The mutant F proteins contained both single- and multiple-amino-acid substitutions, and they exhibited a variety of intracellular transport properties and fusion phenotypes. The data indicate that many substitutions in the conserved amino acids of the simian virus 5 F fusion peptide can be tolerated without loss of biological activity. Mutant F proteins which were not transported to the cell surface did not cause cell-cell fusion, but all of the mutants which were transported to the cell surface were fusion competent, exhibiting fusion properties similar to or better than those of the wild-type F protein. Mutant F proteins containing glycine-to-alanine substitutions had altered intracellular transport characteristics, yet they exhibited a great increase in fusion activity. The potential structural implications of this substitution and the possible importance of these glycine residues in maintaining appropriate levels of fusion activity are discussed. Images PMID:1548771

  19. [Activation and inhibitory mechanisms of blood platelets].

    PubMed

    Suzuki-Inoue, Katsue

    2014-07-01

    Exposure of platelets to subendothelial matrices initiates physiological hemostasis and pathological thrombosis. Under high shear stress, von Willebrand factor bridges newly exposed collagen to glycoprotein (GP) Ib on platelets. This initial tethering facilitates association between the collagen receptor GPVI and collagen, which generates tyrosine kinase-dependent activation signals, followed by release of secondary mediators and integrin activation. Activated integrin can bind to their ligands including fibrinogen. The released secondary mediators, ADP and thromboxane A2, activate integrin of flowing platelets, which enables formation of platelet thrombi by binding of activated flowing platelets and adhered platelets to collagen via binding between activated aIIbbeta3 integrin and fibrinogen. Platelets also have inhibitory mechanisms, which help to prevent unwanted platelet activation in vivo.

  20. Anion channelrhodopsins for inhibitory cardiac optogenetics

    PubMed Central

    Govorunova, Elena G.; Cunha, Shane R.; Sineshchekov, Oleg A.; Spudich, John L.

    2016-01-01

    Optical control of the heart muscle is a promising strategy for cardiology because it is more specific than traditional electrical stimulation, and allows a higher temporal resolution than pharmacological interventions. Anion channelrhodopsins (ACRs) from cryptophyte algae expressed in cultured neonatal rat ventricular cardiomyocytes produced inhibitory currents at less than one-thousandth of the light intensity required by previously available optogenetic tools, such as the proton pump archaerhodopsin-3 (Arch). Because of their greater photocurrents, ACRs permitted complete inhibition of cardiomyocyte electrical activity under conditions in which Arch was inefficient. Most importantly, ACR expression allowed precisely controlled shortening of the action potential duration by switching on the light during its repolarization phase, which was not possible with previously used optogenetic tools. Optical shortening of cardiac action potentials may benefit pathophysiology research and the development of optogenetic treatments for cardiac disorders such as the long QT syndrome. PMID:27628215