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Sample records for ha-mediated cell-cell fusion

  1. Regulation of cell-cell fusion by nanotopography.

    PubMed

    Padmanabhan, Jagannath; Augelli, Michael J; Cheung, Bettina; Kinser, Emily R; Cleary, Barnett; Kumar, Priyanka; Wang, Renhao; Sawyer, Andrew J; Li, Rui; Schwarz, Udo D; Schroers, Jan; Kyriakides, Themis R

    2016-01-01

    Cell-cell fusion is fundamental to a multitude of biological processes ranging from cell differentiation and embryogenesis to cancer metastasis and biomaterial-tissue interactions. Fusogenic cells are exposed to biochemical and biophysical factors, which could potentially alter cell behavior. While biochemical inducers of fusion such as cytokines and kinases have been identified, little is known about the biophysical regulation of cell-cell fusion. Here, we designed experiments to examine cell-cell fusion using bulk metallic glass (BMG) nanorod arrays with varying biophysical cues, i.e. nanotopography and stiffness. Through independent variation of stiffness and topography, we found that nanotopography constitutes the primary biophysical cue that can override biochemical signals to attenuate fusion. Specifically, nanotopography restricts cytoskeletal remodeling-associated signaling, which leads to reduced fusion. This finding expands our fundamental understanding of the nanoscale biophysical regulation of cell fusion and can be exploited in biomaterials design to induce desirable biomaterial-tissue interactions. PMID:27615159

  2. Rho GTPase activity modulates paramyxovirus fusion protein-mediated cell-cell fusion

    SciTech Connect

    Schowalter, Rachel M.; Wurth, Mark A.; Aguilar, Hector C.; Lee, Benhur; Moncman, Carole L.; McCann, Richard O.; Dutch, Rebecca Ellis . E-mail: rdutc2@uky.edu

    2006-07-05

    The paramyxovirus fusion protein (F) promotes fusion of the viral envelope with the plasma membrane of target cells as well as cell-cell fusion. The plasma membrane is closely associated with the actin cytoskeleton, but the role of actin dynamics in paramyxovirus F-mediated membrane fusion is unclear. We examined cell-cell fusion promoted by two different paramyxovirus F proteins in three cell types in the presence of constitutively active Rho family GTPases, major cellular coordinators of actin dynamics. Reporter gene and syncytia assays demonstrated that expression of either Rac1{sup V12} or Cdc42{sup V12} could increase cell-cell fusion promoted by the Hendra or SV5 glycoproteins, though the effect was dependent on the cell type expressing the viral glycoproteins. In contrast, RhoA{sup L63} decreased cell-cell fusion promoted by Hendra glycoproteins but had little affect on SV5 F-mediated fusion. Also, data suggested that GTPase activation in the viral glycoprotein-containing cell was primarily responsible for changes in fusion. Additionally, we found that activated Cdc42 promoted nuclear rearrangement in syncytia.

  3. Genetic basis of cell-cell fusion mechanisms

    PubMed Central

    Aguilar, Pablo S.; Baylies, Mary K.; Fleissner, Andre; Helming, Laura; Inoue, Naokazu; Podbilewicz, Benjamin; Wang, Hongmei; Wong, Melissa

    2013-01-01

    Cell-cell fusion in sexually reproducing organisms is a mechanism to merge gamete genomes, and in multicellular organisms, it is a strategy to sculpt organs such as muscles, bones, and placenta. Moreover, this mechanism has been implicated in pathological conditions such as infection and cancer. Study of genetic model organisms has uncovered a unifying principle: cell fusion is a genetically programmed process. This process can be divided in three stages: (i) competence: cell induction and differentiation, (ii) commitment: cell determination, migration and adhesion, and (iii) cell fusion: membrane merging and cytoplasmic mixing. Recent work has led to the discovery of fusogens, cell fusion proteins that are necessary and sufficient to fuse cell membranes. Two unrelated families of fusogens have been discovered, one in mouse placenta and one in Caenorhabditis elegans (Syncytins and F proteins, respectively). Current research aims to identify new fusogens and determine the mechanisms by which fusogens merge membranes. PMID:23453622

  4. Genetic basis of cell-cell fusion mechanisms.

    PubMed

    Aguilar, Pablo S; Baylies, Mary K; Fleissner, Andre; Helming, Laura; Inoue, Naokazu; Podbilewicz, Benjamin; Wang, Hongmei; Wong, Melissa

    2013-07-01

    Cell-cell fusion in sexually reproducing organisms is a mechanism to merge gamete genomes and, in multicellular organisms, it is a strategy to sculpt organs, such as muscle, bone, and placenta. Moreover, this mechanism has been implicated in pathological conditions, such as infection and cancer. Studies of genetic model organisms have uncovered a unifying principle: cell fusion is a genetically programmed process. This process can be divided in three stages: competence (cell induction and differentiation); commitment (cell determination, migration, and adhesion); and cell fusion (membrane merging and cytoplasmic mixing). Recent work has led to the discovery of fusogens, which are cell fusion proteins that are necessary and sufficient to fuse cell membranes. Two unrelated families of fusogens have been discovered, one in mouse placenta and one in Caenorhabditis elegans (syncytins and F proteins, respectively). Current research aims to identify new fusogens and determine the mechanisms by which they merge membranes. PMID:23453622

  5. The actin cytoskeleton inhibits pore expansion during PIV5 fusion protein-promoted cell-cell fusion

    SciTech Connect

    Wurth, Mark A.; Schowalter, Rachel M.; Smith, Everett Clinton; Moncman, Carole L.; Ellis Dutch, Rebecca; McCann, Richard O.

    2010-08-15

    Paramyxovirus fusion (F) proteins promote both virus-cell fusion, required for viral entry, and cell-cell fusion, resulting in syncytia formation. We used the F-actin stabilizing drug, jasplakinolide, and the G-actin sequestrant, latrunculin A, to examine the role of actin dynamics in cell-cell fusion mediated by the parainfluenza virus 5 (PIV5) F protein. Jasplakinolide treatment caused a dose-dependent increase in cell-cell fusion as measured by both syncytia and reporter gene assays, and latrunculin A treatment also resulted in fusion stimulation. Treatment with jasplakinolide or latrunculin A partially rescued a fusion pore opening defect caused by deletion of the PIV5 F protein cytoplasmic tail, but these drugs had no effect on fusion inhibited at earlier stages by either temperature arrest or by a PIV5 heptad repeat peptide. These data suggest that the cortical actin cytoskeleton is an important regulator of fusion pore enlargement, an energetically costly stage of viral fusion protein-mediated membrane merger.

  6. Methodologies in the study of cell-cell fusion.

    PubMed

    Cohen, F S; Melikyan, G B

    1998-10-01

    The process of membrane fusion has been profitably studied by fusing cells that express fusion proteins on their surfaces to the membranes of target cells. Primary methods for monitoring the occurrence of fusion between cells are measurement of formation of heterokaryons, measurement of activation of reporter genes, measurement of transfer of lipidic and aqueous fluorescent dyes, and electrophysiological recording of fusion pores. Fluorescence and electrical methods have been well developed for fusion of a nucleated cell expressing viral fusion proteins to red blood cell targets. These techniques are now being extended to the study of fusion between two nucleated cells. Microscopic observation of spread of fluorescent dyes from one cell to another is a sensitive and convenient means of detecting fusion on the level of single events. In such studies, both the membrane and the aqueous continuities that occur as a result of fusion can be measured in the same experiment. By following spread of aqueous dyes of different sizes from one cell to another, the growth of a fusion pore can also be followed. By labeling cells with fluorescent probes, a state of hemifusion can be identified if probes in outer membrane leaflets transfer but probes in inner leaflets or aqueous spaces do not. Electrical measurements-both capacitance and double-whole-cell voltage-clamp techniques-are the most sensitive methods yet developed for detecting the formation of pores and for quantifying their growth. These powerful single-event methodologies should be directly applicable to further advances in expressing nonviral fusion proteins on cell surfaces. PMID:9790869

  7. RAB-5- and DYNAMIN-1-Mediated Endocytosis of EFF-1 Fusogen Controls Cell-Cell Fusion.

    PubMed

    Smurova, Ksenia; Podbilewicz, Benjamin

    2016-02-16

    Cell-cell fusion plays essential roles during fertilization and organogenesis. Previous studies in C. elegans led to the identification of the eukaryotic fusion protein (EFF-1 fusogen), which has structural homology to class II viral fusogens. Transcriptional repression of EFF-1 ensures correct fusion fates, and overexpression of EFF-1 results in embryonic lethality. EFF-1 must be expressed on the surface of both fusing cells; however, little is known regarding how cells regulate EFF-1 surface exposure. Here, we report that EFF-1 is actively removed from the plasma membrane of epidermal cells by dynamin- and RAB-5-dependent endocytosis and accumulates in early endosomes. EFF-1 was transiently localized to apical domains of fusion-competent cells. Effective cell-cell fusion occurred only between pairs of cell membranes in which EFF-1 localized. Downregulation of dynamin or RAB-5 caused EFF-1 mislocalization to all apical membrane domains and excessive fusion. Thus, internalization of EFF-1 is a safety mechanism preventing excessive cell fusion. PMID:26854231

  8. RAB-5- and DYNAMIN-1-Mediated Endocytosis of EFF-1 Fusogen Controls Cell-Cell Fusion

    PubMed Central

    Smurova, Ksenia; Podbilewicz, Benjamin

    2016-01-01

    Summary Cell-cell fusion plays essential roles during fertilization and organogenesis. Previous studies in C. elegans led to the identification of the eukaryotic fusion protein (EFF-1 fusogen), which has structural homology to class II viral fusogens. Transcriptional repression of EFF-1 ensures correct fusion fates, and overexpression of EFF-1 results in embryonic lethality. EFF-1 must be expressed on the surface of both fusing cells; however, little is known regarding how cells regulate EFF-1 surface exposure. Here, we report that EFF-1 is actively removed from the plasma membrane of epidermal cells by dynamin- and RAB-5-dependent endocytosis and accumulates in early endosomes. EFF-1 was transiently localized to apical domains of fusion-competent cells. Effective cell-cell fusion occurred only between pairs of cell membranes in which EFF-1 localized. Downregulation of dynamin or RAB-5 caused EFF-1 mislocalization to all apical membrane domains and excessive fusion. Thus, internalization of EFF-1 is a safety mechanism preventing excessive cell fusion. PMID:26854231

  9. Sialic Acids on Varicella-Zoster Virus Glycoprotein B Are Required for Cell-Cell Fusion*

    PubMed Central

    Suenaga, Tadahiro; Matsumoto, Maki; Arisawa, Fuminori; Kohyama, Masako; Hirayasu, Kouyuki; Mori, Yasuko; Arase, Hisashi

    2015-01-01

    Varicella-zoster virus (VZV) is a member of the human Herpesvirus family that causes varicella (chicken pox) and zoster (shingles). VZV latently infects sensory ganglia and is also responsible for encephalomyelitis. Myelin-associated glycoprotein (MAG), a member of the sialic acid (SA)-binding immunoglobulin-like lectin family, is mainly expressed in neural tissues. VZV glycoprotein B (gB) associates with MAG and mediates membrane fusion during VZV entry into host cells. The SA requirements of MAG when associating with its ligands vary depending on the specific ligand, but it is unclear whether the SAs on gB are involved in the association with MAG. In this study, we found that SAs on gB are essential for the association with MAG as well as for membrane fusion during VZV infection. MAG with a point mutation in the SA-binding site did not bind to gB and did not mediate cell-cell fusion or VZV entry. Cell-cell fusion and VZV entry mediated by the gB-MAG interaction were blocked by sialidase treatment. N-glycosylation or O-glycosylation inhibitors also inhibited the fusion and entry mediated by gB-MAG interaction. Furthermore, gB with mutations in N-glycosylation sites, i.e. asparagine residues 557 and 686, did not associate with MAG, and the cell-cell fusion efficiency was low. Fusion between the viral envelope and cellular membrane is essential for host cell entry by herpesviruses. Therefore, these results suggest that SAs on gB play important roles in MAG-mediated VZV infection. PMID:26105052

  10. Sialic Acids on Varicella-Zoster Virus Glycoprotein B Are Required for Cell-Cell Fusion.

    PubMed

    Suenaga, Tadahiro; Matsumoto, Maki; Arisawa, Fuminori; Kohyama, Masako; Hirayasu, Kouyuki; Mori, Yasuko; Arase, Hisashi

    2015-08-01

    Varicella-zoster virus (VZV) is a member of the human Herpesvirus family that causes varicella (chicken pox) and zoster (shingles). VZV latently infects sensory ganglia and is also responsible for encephalomyelitis. Myelin-associated glycoprotein (MAG), a member of the sialic acid (SA)-binding immunoglobulin-like lectin family, is mainly expressed in neural tissues. VZV glycoprotein B (gB) associates with MAG and mediates membrane fusion during VZV entry into host cells. The SA requirements of MAG when associating with its ligands vary depending on the specific ligand, but it is unclear whether the SAs on gB are involved in the association with MAG. In this study, we found that SAs on gB are essential for the association with MAG as well as for membrane fusion during VZV infection. MAG with a point mutation in the SA-binding site did not bind to gB and did not mediate cell-cell fusion or VZV entry. Cell-cell fusion and VZV entry mediated by the gB-MAG interaction were blocked by sialidase treatment. N-glycosylation or O-glycosylation inhibitors also inhibited the fusion and entry mediated by gB-MAG interaction. Furthermore, gB with mutations in N-glycosylation sites, i.e. asparagine residues 557 and 686, did not associate with MAG, and the cell-cell fusion efficiency was low. Fusion between the viral envelope and cellular membrane is essential for host cell entry by herpesviruses. Therefore, these results suggest that SAs on gB play important roles in MAG-mediated VZV infection. PMID:26105052

  11. Localization of a Region in the Fusion Protein of Avian Metapneumovirus That Modulates Cell-Cell Fusion

    PubMed Central

    Wei, Yongwei; Feng, Kurtis; Yao, Xiangjie; Cai, Hui; Li, Junan; Mirza, Anne M.; Iorio, Ronald M.

    2012-01-01

    The genus Metapneumovirus within the subfamily Pneumovirinae of the family Paramyxoviridae includes two members, human metapneumovirus (hMPV) and avian metapneumovirus (aMPV), causing respiratory tract infections in humans and birds, respectively. Paramyxoviruses enter host cells by fusing the viral envelope with a host cell membrane. Membrane fusion of hMPV appears to be unique, in that fusion of some hMPV strains requires low pH. Here, we show that the fusion (F) proteins of aMPV promote fusion in the absence of the attachment protein and low pH is not required. Furthermore, there are notable differences in cell-cell fusion among aMPV subtypes. Trypsin was required for cell-cell fusion induced by subtype B but not subtypes A and C. The F protein of aMPV subtype A was highly fusogenic, whereas those from subtypes B and C were not. By construction and evaluation of chimeric F proteins composed of domains from the F proteins of subtypes A and B, we localized a region composed of amino acid residues 170 to 338 in the F protein that is responsible for the hyperfusogenic phenotype of the F from subtype A. Further mutagenesis analysis revealed that residues R295, G297, and K323 in this region collectively contributed to the hyperfusogenicity. Taken together, we have identified a region in the aMPV F protein that modulates the extent of membrane fusion. A model for fusion consistent with these data is presented. PMID:22915815

  12. Fragments of Target Cells are Internalized into Retroviral Envelope Protein-Expressing Cells during Cell-Cell Fusion by Endocytosis

    PubMed Central

    Izumida, Mai; Kamiyama, Haruka; Suematsu, Takashi; Honda, Eri; Koizumi, Yosuke; Yasui, Kiyoshi; Hayashi, Hideki; Ariyoshi, Koya; Kubo, Yoshinao

    2016-01-01

    Retroviruses enter into host cells by fusion between viral and host cell membranes. Retroviral envelope glycoprotein (Env) induces the membrane fusion, and also mediates cell-cell fusion. There are two types of cell-cell fusions induced by the Env protein. Fusion-from-within is induced by fusion between viral fusogenic Env protein-expressing cells and susceptible cells, and virions induce fusion-from-without by fusion between adjacent cells. Although entry of ecotropic murine leukemia virus (E-MLV) requires host cell endocytosis, the involvement of endocytosis in cell fusion is unclear. By fluorescent microscopic analysis of the fusion-from-within, we found that fragments of target cells are internalized into Env-expressing cells. Treatment of the Env-expressing cells with an endocytosis inhibitor more significantly inhibited the cell fusion than that of the target cells, indicating that endocytosis in Env-expressing cells is required for the cell fusion. The endocytosis inhibitor also attenuated the fusion-from-without. Electron microscopic analysis suggested that the membrane fusion resulting in fusion-from-within initiates in endocytic membrane dents. This study shows that two types of the viral cell fusion both require endocytosis, and provides the cascade of fusion-from-within. PMID:26834711

  13. Induction of Cell-Cell Fusion by Ebola Virus Glycoprotein: Low pH Is Not a Trigger

    PubMed Central

    Zheng, Yi-Min; Melikyan, Gregory B.; Liu, Shan-Lu; Cohen, Fredric S.

    2016-01-01

    Ebola virus (EBOV) is a highly pathogenic filovirus that causes hemorrhagic fever in humans and animals. Currently, how EBOV fuses its envelope membrane within an endosomal membrane to cause infection is poorly understood. We successfully measure cell-cell fusion mediated by the EBOV fusion protein, GP, assayed by the transfer of both cytoplasmic and membrane dyes. A small molecule fusion inhibitor, a neutralizing antibody, as well as mutations in EBOV GP known to reduce viral infection, all greatly reduce fusion. By monitoring redistribution of small aqueous dyes between cells and by electrical capacitance measurements, we discovered that EBOV GP-mediated fusion pores do not readily enlarge—a marked difference from the behavior of other viral fusion proteins. EBOV GP must be cleaved by late endosome-resident cathepsins B or L in order to become fusion-competent. Cleavage of cell surface-expressed GP appears to occur in endosomes, as evidenced by the fusion block imposed by cathepsin inhibitors, agents that raise endosomal pH, or an inhibitor of anterograde trafficking. Treating effector cells with a recombinant soluble cathepsin B or thermolysin, which cleaves GP into an active form, increases the extent of fusion, suggesting that a fraction of surface-expressed GP is not cleaved. Whereas the rate of fusion is increased by a brief exposure to acidic pH, fusion does occur at neutral pH. Importantly, the extent of fusion is independent of external pH in experiments in which cathepsin activity is blocked and EBOV GP is cleaved by thermolysin. These results imply that low pH promotes fusion through the well-known pH-dependent activity of cathepsins; fusion induced by cleaved EBOV GP is a process that is fundamentally independent of pH. The cell-cell fusion system has revealed some previously unappreciated features of EBOV entry, which could not be readily elucidated in the context of endosomal entry. PMID:26730950

  14. Induction of Cell-Cell Fusion by Ebola Virus Glycoprotein: Low pH Is Not a Trigger.

    PubMed

    Markosyan, Ruben M; Miao, Chunhui; Zheng, Yi-Min; Melikyan, Gregory B; Liu, Shan-Lu; Cohen, Fredric S

    2016-01-01

    Ebola virus (EBOV) is a highly pathogenic filovirus that causes hemorrhagic fever in humans and animals. Currently, how EBOV fuses its envelope membrane within an endosomal membrane to cause infection is poorly understood. We successfully measure cell-cell fusion mediated by the EBOV fusion protein, GP, assayed by the transfer of both cytoplasmic and membrane dyes. A small molecule fusion inhibitor, a neutralizing antibody, as well as mutations in EBOV GP known to reduce viral infection, all greatly reduce fusion. By monitoring redistribution of small aqueous dyes between cells and by electrical capacitance measurements, we discovered that EBOV GP-mediated fusion pores do not readily enlarge-a marked difference from the behavior of other viral fusion proteins. EBOV GP must be cleaved by late endosome-resident cathepsins B or L in order to become fusion-competent. Cleavage of cell surface-expressed GP appears to occur in endosomes, as evidenced by the fusion block imposed by cathepsin inhibitors, agents that raise endosomal pH, or an inhibitor of anterograde trafficking. Treating effector cells with a recombinant soluble cathepsin B or thermolysin, which cleaves GP into an active form, increases the extent of fusion, suggesting that a fraction of surface-expressed GP is not cleaved. Whereas the rate of fusion is increased by a brief exposure to acidic pH, fusion does occur at neutral pH. Importantly, the extent of fusion is independent of external pH in experiments in which cathepsin activity is blocked and EBOV GP is cleaved by thermolysin. These results imply that low pH promotes fusion through the well-known pH-dependent activity of cathepsins; fusion induced by cleaved EBOV GP is a process that is fundamentally independent of pH. The cell-cell fusion system has revealed some previously unappreciated features of EBOV entry, which could not be readily elucidated in the context of endosomal entry. PMID:26730950

  15. Identification of Domains on the Fusion (F) Protein Trimer That Influence the Hemagglutinin-Neuraminidase Specificity of the F Protein in Mediating Cell-Cell Fusion

    PubMed Central

    Tsurudome, Masato; Ito, Morihiro; Nishio, Machiko; Nakahashi, Mito; Kawano, Mitsuo; Komada, Hiroshi; Nosaka, Tetsuya; Ito, Yasuhiko

    2011-01-01

    For most paramyxoviruses, virus type-specific interaction between fusion (F) protein and attachment protein (hemagglutinin-neuraminidase [HN], hemagglutinin [H], or glycoprotein [G]) is a prerequisite for mediating virus-cell fusion and cell-cell fusion. Our previous cell-cell fusion assay using the chimeric F proteins of human parainfluenza virus 2 (HPIV2) and simian virus 41 (SV41) suggested that the middle region of the HPIV2 F protein contains the site(s) that determines its specificity for the HPIV2 HN protein. In the present study, we further investigated the sites of the F protein that could be critical for determining the HN protein specificity. By analyzing the reported structure of the F protein of parainfluenza virus 5 (PIV5), we found that four major domains (M1, M2, M3, and M4) and five minor domains (A to E) in the middle region of the PIV5 F protein were exposed on the trimer surface. We then replaced these domains with the SV41 F counterparts individually or in combination and examined whether the resulting chimeras could mediate cell-cell fusion when coexpressed with the SV41 HN protein. The results showed that a chimera designated M(1+2), which harbored SV41 F-derived domains M1 and M2, mediated cell-cell fusion with the coexpressed SV41 HN protein, suggesting that these domains are involved in determining the HN protein specificity. Intriguingly, another chimera which harbored the SV41 F-derived domain B in addition to domains M1 and M2 showed increased specificity for the SV41 HN protein compared to that of M(1+2), although it was capable of mediating cell-cell fusion by itself. PMID:21270148

  16. Development and characterization of a Rift Valley fever virus cell-cell fusion assay using alphavirus replicon vectors

    SciTech Connect

    Filone, Claire Marie; Heise, Mark; Doms, Robert W. . E-mail: doms@mail.med.upenn.edu; Bertolotti-Ciarlet, Andrea . E-mail: aciarlet@mail.med.upenn.edu

    2006-12-20

    Rift Valley fever virus (RVFV), a member of the Phlebovirus genus in the Bunyaviridae family, is transmitted by mosquitoes and infects both humans and domestic animals, particularly cattle and sheep. Since primary RVFV strains must be handled in BSL-3+ or BSL-4 facilities, a RVFV cell-cell fusion assay will facilitate the investigation of RVFV glycoprotein function under BSL-2 conditions. As for other members of the Bunyaviridae family, RVFV glycoproteins are targeted to the Golgi, where the virus buds, and are not efficiently delivered to the cell surface. However, overexpression of RVFV glycoproteins using an alphavirus replicon vector resulted in the expression of the glycoproteins on the surface of multiple cell types. Brief treatment of RVFV glycoprotein expressing cells with mildly acidic media (pH 6.2 and below) resulted in rapid and efficient syncytia formation, which we quantified by {beta}-galactosidase {alpha}-complementation. Fusion was observed with several cell types, suggesting that the receptor(s) for RVFV is widely expressed or that this acid-dependent virus does not require a specific receptor to mediate cell-cell fusion. Fusion occurred over a broad temperature range, as expected for a virus with both mosquito and mammalian hosts. In contrast to cell fusion mediated by the VSV-G glycoprotein, RVFV glycoprotein-dependent cell fusion could be prevented by treating target cells with trypsin, indicating that one or more proteins (or protein-associated carbohydrate) on the host cell surface are needed to support membrane fusion. The cell-cell fusion assay reported here will make it possible to study the membrane fusion activity of RVFV glycoproteins in a high-throughput format and to screen small molecule inhibitors for the ability to block virus-specific membrane fusion.

  17. 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

  18. Herpes B Virus Utilizes Human Nectin-1 but Not HVEM or PILRα for Cell-Cell Fusion and Virus Entry

    PubMed Central

    Fan, Qing; Amen, Melanie; Harden, Mallory; Severini, Alberto; Griffiths, Anthony

    2012-01-01

    To investigate the requirements of herpesvirus entry and fusion, the four homologous glycoproteins necessary for herpes simplex virus (HSV) fusion were cloned from herpes B virus (BV) (or macacine herpesvirus 1, previously known as cercopithecine herpesvirus 1) and cercopithecine herpesvirus 2 (CeHV-2), both related simian simplexviruses belonging to the alphaherpesvirus subfamily. Western blots and cell-based enzyme-linked immunosorbent assay (ELISA) showed that glycoproteins gB, gD, and gH/gL were expressed in whole-cell lysates and on the cell surface. Cell-cell fusion assays indicated that nectin-1, an HSV-1 gD receptor, mediated fusion of cells expressing glycoproteins from both BV and CeHV-2. However, herpesvirus entry mediator (HVEM), another HSV-1 gD receptor, did not facilitate BV- and CeHV-2-induced cell-cell fusion. Paired immunoglobulin-like type 2 receptor alpha (PILRα), an HSV-1 gB fusion receptor, did not mediate fusion of cells expressing glycoproteins from either simian virus. Productive infection with BV was possible only with nectin-1-expressing cells, indicating that nectin-1 mediated entry while HVEM and PILRα did not function as entry receptors. These results indicate that these alphaherpesviruses have differing preferences for entry receptors. The usage of the HSV-1 gD receptor nectin-1 may explain interspecies transfer of the viruses, and altered receptor usage may result in altered virulence, tropism, or pathogenesis in the new host. A heterotypic cell fusion assay resulting in productive fusion may provide insight into interactions that occur to trigger fusion. These findings may be of therapeutic significance for control of deadly BV infections. PMID:22345445

  19. Human papillomavirus 16 E5 induces bi-nucleated cell formation by cell-cell fusion

    SciTech Connect

    Hu Lulin; Plafker, Kendra; Vorozhko, Valeriya; Zuna, Rosemary E.; Hanigan, Marie H.; Gorbsky, Gary J.; Plafker, Scott M.; Angeletti, Peter C.; Ceresa, Brian P.

    2009-02-05

    Human papillomaviruses (HPV) 16 is a DNA virus encoding three oncogenes - E5, E6, and E7. The E6 and E7 proteins have well-established roles as inhibitors of tumor suppression, but the contribution of E5 to malignant transformation is controversial. Using spontaneously immortalized human keratinocytes (HaCaT cells), we demonstrate that expression of HPV16 E5 is necessary and sufficient for the formation of bi-nucleated cells, a common characteristic of precancerous cervical lesions. Expression of E5 from non-carcinogenic HPV6b does not produce bi-nucleate cells. Video microscopy and biochemical analyses reveal that bi-nucleates arise through cell-cell fusion. Although most E5-induced bi-nucleates fail to propagate, co-expression of HPV16 E6/E7 enhances the proliferation of these cells. Expression of HPV16 E6/E7 also increases bi-nucleated cell colony formation. These findings identify a new role for HPV16 E5 and support a model in which complementary roles of the HPV16 oncogenes lead to the induction of carcinogenesis.

  20. Antibodies to CD9, a Tetraspan Transmembrane Protein, Inhibit Canine Distemper Virus-Induced Cell-Cell Fusion but Not Virus-Cell Fusion

    PubMed Central

    Schmid, Erik; Zurbriggen, Andreas; Gassen, Uta; Rima, Bert; ter Meulen, Volker; Schneider-Schaulies, Jürgen

    2000-01-01

    Canine distemper virus (CDV) causes a life-threatening disease in several carnivores including domestic dogs. Recently, we identified a molecule, CD9, a member of the tetraspan transmembrane protein family, which facilitates, and antibodies to which inhibit, the infection of tissue culture cells with CDV (strain Onderstepoort). Here we describe that an anti-CD9 monoclonal antibody (MAb K41) did not interfere with binding of CDV to cells and uptake of virus. In addition, in single-step growth experiments, MAb K41 did not induce differences in the levels of viral mRNA and proteins. However, the virus release of syncytium-forming strains of CDV, the virus-induced cell-cell fusion in lytically infected cultures, and the cell-cell fusion of uninfected with persistently CDV-infected HeLa cells were strongly inhibited by MAb K41. These data indicate that anti-CD9 antibodies selectively block virus-induced cell-cell fusion, whereas virus-cell fusion is not affected. PMID:10906209

  1. Roles of the Putative Integrin-Binding Motif of the Human Metapneumovirus Fusion (F) Protein in Cell-Cell Fusion, Viral Infectivity, and Pathogenesis

    PubMed Central

    Wei, Yongwei; Zhang, Yu; Cai, Hui; Mirza, Anne M.; Iorio, Ronald M.; Peeples, Mark E.; Niewiesk, Stefan

    2014-01-01

    ABSTRACT Human metapneumovirus (hMPV) is a relatively recently identified paramyxovirus that causes acute upper and lower respiratory tract infection. Entry of hMPV is unusual among the paramyxoviruses, in that fusion is accomplished by the fusion (F) protein without the attachment glycoprotein (G protein). It has been suggested that hMPV F protein utilizes integrin αvβ1 as a cellular receptor. Consistent with this, the F proteins of all known hMPV strains possess an integrin-binding motif (329RGD331). The role of this motif in viral entry, infectivity, and pathogenesis is poorly understood. Here, we show that α5β1 and αv integrins are essential for cell-cell fusion and hMPV infection. Mutational analysis found that residues R329 and G330 in the 329RGD331 motif are essential for cell-cell fusion, whereas mutations at D331 did not significantly impact fusion activity. Furthermore, fusion-defective RGD mutations were either lethal to the virus or resulted in recombinant hMPVs that had defects in viral replication in cell culture. In cotton rats, recombinant hMPV with the R329K mutation in the F protein (rhMPV-R329K) and rhMPV-D331A exhibited significant defects in viral replication in nasal turbinates and lungs. Importantly, inoculation of cotton rats with these mutants triggered a high level of neutralizing antibodies and protected against hMPV challenge. Taken together, our data indicate that (i) α5β1 and αv integrins are essential for cell-cell fusion and viral replication, (ii) the first two residues in the RGD motif are essential for fusion activity, and (iii) inhibition of the interaction of the integrin-RGD motif may serve as a new target to rationally attenuate hMPV for the development of live attenuated vaccines. IMPORTANCE Human metapneumovirus (hMPV) is one of the major causative agents of acute respiratory disease in humans. Currently, there is no vaccine or antiviral drug for hMPV. hMPV enters host cells via a unique mechanism, in that viral

  2. Different activities of the reovirus FAST proteins and influenza hemagglutinin in cell-cell fusion assays and in response to membrane curvature agents

    SciTech Connect

    Clancy, Eileen K.; Barry, Chris; Ciechonska, Marta; Duncan, Roy

    2010-02-05

    The reovirus fusion-associated small transmembrane (FAST) proteins evolved to induce cell-cell, rather than virus-cell, membrane fusion. It is unclear whether the FAST protein fusion reaction proceeds in the same manner as the enveloped virus fusion proteins. We now show that fluorescence-based cell-cell and cell-RBC hemifusion assays are unsuited for detecting lipid mixing in the absence of content mixing during FAST protein-mediated membrane fusion. Furthermore, membrane curvature agents that inhibit hemifusion or promote pore formation mediated by influenza hemagglutinin had no effect on p14-induced cell-cell fusion, even under conditions of limiting p14 concentrations. Standard assays used to detect fusion intermediates induced by enveloped virus fusion proteins are therefore not applicable to the FAST proteins. These results suggest the possibility that the nature of the fusion intermediates or the mechanisms used to transit through the various stages of the fusion reaction may differ between these distinct classes of viral fusogens.

  3. Furin cleavage of the SARS coronavirus spike glycoprotein enhances cell-cell fusion but does not affect virion entry

    SciTech Connect

    Follis, Kathryn E.; York, Joanne; Nunberg, Jack H. . E-mail: jack.nunberg@umontana.edu

    2006-07-05

    The fusogenic potential of Class I viral envelope glycoproteins is activated by proteloytic cleavage of the precursor glycoprotein to generate the mature receptor-binding and transmembrane fusion subunits. Although the coronavirus (CoV) S glycoproteins share membership in this class of envelope glycoproteins, cleavage to generate the respective S1 and S2 subunits appears absent in a subset of CoV species, including that responsible for the severe acute respiratory syndrome (SARS). To determine whether proteolytic cleavage of the S glycoprotein might be important for the newly emerged SARS-CoV, we introduced a furin recognition site at single basic residues within the putative S1-S2 junctional region. We show that furin cleavage at the modified R667 position generates discrete S1 and S2 subunits and potentiates membrane fusion activity. This effect on the cell-cell fusion activity by the S glycoprotein is not, however, reflected in the infectivity of pseudotyped lentiviruses bearing the cleaved glycoprotein. The lack of effect of furin cleavage on virion infectivity mirrors that observed in the normally cleaved S glycoprotein of the murine coronavirus and highlights an additional level of complexity in coronavirus entry.

  4. Geometry of the Contact Zone between Fused Membrane-Coated Beads Mimicking Cell-Cell Fusion.

    PubMed

    Savić, Filip; Kliesch, Torben-Tobias; Verbeek, Sarah; Bao, Chunxiao; Thiart, Jan; Kros, Alexander; Geil, Burkhard; Janshoff, Andreas

    2016-05-24

    The fusion of lipid membranes is a key process in biology. It enables cells and organelles to exchange molecules with their surroundings, which otherwise could not cross the membrane barrier. To study such complex processes we use simplified artificial model systems, i.e., an optical fusion assay based on membrane-coated glass spheres. We present a technique to analyze membrane-membrane interactions in a large ensemble of particles. Detailed information on the geometry of the fusion stalk of fully fused membranes is obtained by studying the diffusional lipid dynamics with fluorescence recovery after photobleaching experiments. A small contact zone is a strong obstruction for the particle exchange across the fusion spot. With the aid of computer simulations, fluorescence-recovery-after-photobleaching recovery times of both fused and single-membrane-coated beads allow us to estimate the size of the contact zones between two membrane-coated beads. Minimizing delamination and bending energy leads to minimal angles close to those geometrically allowed. PMID:27224487

  5. Flagellar membrane fusion and protein exchange in trypanosomes; a new form of cell-cell communication?

    PubMed Central

    Imhof, Simon; Fragoso, Cristina; Hemphill, Andrew; von Schubert, Conrad; Li, Dong; Legant, Wesley; Betzig, Eric; Roditi, Isabel

    2016-01-01

    Diverse structures facilitate direct exchange of proteins between cells, including plasmadesmata in plants and tunnelling nanotubes in bacteria and higher eukaryotes.  Here we describe a new mechanism of protein transfer, flagellar membrane fusion, in the unicellular parasite Trypanosoma brucei. When fluorescently tagged trypanosomes were co-cultured, a small proportion of double-positive cells were observed. The formation of double-positive cells was dependent on the presence of extracellular calcium and was enhanced by placing cells in medium supplemented with fresh bovine serum. Time-lapse microscopy revealed that double-positive cells arose by bidirectional protein exchange in the absence of nuclear transfer.  Furthermore, super-resolution microscopy showed that this process occurred in ≤1 minute, the limit of temporal resolution in these experiments. Both cytoplasmic and membrane proteins could be transferred provided they gained access to the flagellum. Intriguingly, a component of the RNAi machinery (Argonaute) was able to move between cells, raising the possibility that small interfering RNAs are transported as cargo. Transmission electron microscopy showed that shared flagella contained two axonemes and two paraflagellar rods bounded by a single membrane. In some cases flagellar fusion was partial and interactions between cells were transient. In other cases fusion occurred along the entire length of the flagellum, was stable for several hours and might be irreversible. Fusion did not appear to be deleterious for cell function: paired cells were motile and could give rise to progeny while fused. The motile flagella of unicellular organisms are related to the sensory cilia of higher eukaryotes, raising the possibility that protein transfer between cells via cilia or flagella occurs more widely in nature. PMID:27239276

  6. Characterization of the plasma membrane localization and orientation of HPV16 E5 for cell-cell fusion

    SciTech Connect

    Hu Lulin; Ceresa, Brian P.

    2009-10-10

    Human papillomavirus (HPV) is a non-enveloped DNA virus with an approx 8000 base pair genome. Infection with certain types of HPV is associated with cervical cancer, although the molecular mechanism by which HPV induces carcinogenesis is poorly understood. Three genes encoded by HPV16 are regarded as oncogenic - E5, E6, and E7. The role of E5 has been controversial. Expression of HPV16 E5 causes cell-cell fusion, an event that can lead to increased chromosomal instability, particularly in the presence of cell cycle checkpoint inhibitors like HPV16 E6 and E7. Using biochemical and cell biological assays to better understand HPV16 E5, we find that HPV16 E5 localizes to the plasma membrane with an intracellular amino terminus and an extracellular carboxyl-terminus. Further, HPV16 E5 must be expressed on both cells for cell fusion to occur. When the extracellular epitope of HPV16 E5 is targeted with an antibody, the number of bi-nucleated cells decreases.

  7. Different host cell proteases activate the SARS-coronavirus spike-protein for cell-cell and virus-cell fusion

    SciTech Connect

    Simmons, Graham; Bertram, Stephanie; Glowacka, Ilona; Steffen, Imke; Chaipan, Chawaree; Agudelo, Juliet; Lu Kai; Rennekamp, Andrew J.; Hofmann, Heike; Bates, Paul; Poehlmann, Stefan

    2011-05-10

    Severe acute respiratory syndrome coronavirus (SARS-CoV) poses a considerable threat to human health. Activation of the viral spike (S)-protein by host cell proteases is essential for viral infectivity. However, the cleavage sites in SARS-S and the protease(s) activating SARS-S are incompletely defined. We found that R667 was dispensable for SARS-S-driven virus-cell fusion and for SARS-S-activation by trypsin and cathepsin L in a virus-virus fusion assay. Mutation T760R, which optimizes the minimal furin consensus motif 758-RXXR-762, and furin overexpression augmented SARS-S activity, but did not result in detectable SARS-S cleavage. Finally, SARS-S-driven cell-cell fusion was independent of cathepsin L, a protease essential for virus-cell fusion. Instead, a so far unknown leupeptin-sensitive host cell protease activated cellular SARS-S for fusion with target cells expressing high levels of ACE2. Thus, different host cell proteases activate SARS-S for virus-cell and cell-cell fusion and SARS-S cleavage at R667 and 758-RXXR-762 can be dispensable for SARS-S activation.

  8. Using a split luciferase assay (SLA) to measure the kinetics of cell-cell fusion mediated by herpes simplex virus glycoproteins.

    PubMed

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

    2015-11-15

    Herpes simplex virus (HSV) entry and cell-cell fusion require the envelope proteins gD, gH/gL and gB. We propose that receptor-activated conformational changes to gD activate gH/gL, which then triggers gB (the fusogen) into an active form. To study this dynamic process, we have adapted a dual split protein assay originally developed to study the kinetics of human immunodeficiency virus (HIV) mediated fusion. This assay uses a chimera of split forms of renilla luciferase (RL) and green fluorescent protein (GFP). Effector cells are co-transfected with the glycoproteins and one of the split reporters. Receptor-bearing target cells are transfected with the second reporter. Co-culture results in fusion and restoration of RL, which can convert a membrane permeable substrate into a luminescent product, thereby enabling one to monitor initiation and extent of fusion in live cells in real time. Restoration of GFP can also be studied by fluorescence microscopy. Two sets of split reporters have been developed: the original one allows one to measure fusion kinetics over hours whereas the more recent version was designed to enhance the sensitivity of RL activity allowing one to monitor both initiation and rates of fusion in minutes. Here, we provide a detailed, step-by-step protocol for the optimization of the assay (which we call the SLA for split luciferase assay) using the HSV system. We also show several examples of the power of this assay to examine both the initiation and kinetics of cell-cell fusion by wild type forms of gD, gB, gH/gL of both serotypes of HSV as well as the effect of mutations and antibodies that alter the kinetics of fusion. The SLA can be applied to other viral systems that carry out membrane fusion. PMID:26022509

  9. Ezrin Is a Component of the HIV-1 Virological Presynapse and Contributes to the Inhibition of Cell-Cell Fusion

    PubMed Central

    Roy, Nathan H.; Lambelé, Marie; Chan, Jany; Symeonides, Menelaos

    2014-01-01

    coresponsible for key features of HIV-1 pathogenesis, including killing of bystander cells and establishment of latently infected T lymphocytes. Here we identify the ERM protein family member ezrin as a cellular factor that contributes to the inhibition of cell-cell fusion and thus to suppressing excessive syncytium formation. Our analyses further suggest that ezrin, which connects integral membrane proteins with actin, functions in concert with CD81, a member of the tetraspanin family of proteins. Additional evidence, documented here and elsewhere, suggests that ezrin and CD81 cooperate to prevent cytoskeleton rearrangements that need to take place during the fusion of cellular membranes. PMID:24760896

  10. Palmitoylation of SARS-CoV S protein is necessary for partitioning into detergent-resistant membranes and cell-cell fusion but not interaction with M protein

    SciTech Connect

    McBride, Corrin E.; Machamer, Carolyn E.

    2010-09-15

    Coronaviruses are enveloped RNA viruses that generally cause mild disease in humans. However, the recently emerged coronavirus that caused severe acute respiratory syndrome (SARS-CoV) is the most pathogenic human coronavirus discovered to date. The SARS-CoV spike (S) protein mediates virus entry by binding cellular receptors and inducing fusion between the viral envelope and the host cell membrane. Coronavirus S proteins are palmitoylated, which may affect function. Here, we created a non-palmitoylated SARS-CoV S protein by mutating all nine cytoplasmic cysteine residues. Palmitoylation of SARS-CoV S was required for partitioning into detergent-resistant membranes and for cell-cell fusion. Surprisingly, however, palmitoylation of S was not required for interaction with SARS-CoV M protein. This contrasts with the requirement for palmitoylation of mouse hepatitis virus S protein for interaction with M protein and may point to important differences in assembly and infectivity of these two coronaviruses.

  11. Low-density Lipoprotein Receptor Deficiency Causes Impaired Osteoclastogenesis and Increased Bone Mass in Mice because of Defect in Osteoclastic Cell-Cell Fusion*

    PubMed Central

    Okayasu, Mari; Nakayachi, Mai; Hayashida, Chiyomi; Ito, Junta; Kaneda, Toshio; Masuhara, Masaaki; Suda, Naoto; Sato, Takuya; Hakeda, Yoshiyuki

    2012-01-01

    Osteoporosis is associated with both atherosclerosis and vascular calcification attributed to hyperlipidemia. However, the cellular and molecular mechanisms explaining the parallel progression of these diseases remain unclear. Here, we used low-density lipoprotein receptor knockout (LDLR−/−) mice to elucidate the role of LDLR in regulating the differentiation of osteoclasts, which are responsible for bone resorption. Culturing wild-type osteoclast precursors in medium containing LDL-depleted serum decreased receptor activator of NF-κB ligand (RANKL)-induced osteoclast formation, and this defect was additively rescued by simultaneous treatment with native and oxidized LDLs. Osteoclast precursors constitutively expressed LDLR in a RANKL-independent manner. Osteoclast formation from LDLR−/− osteoclast precursors was delayed, and the multinucleated cells formed in culture were smaller and contained fewer nuclei than wild-type cells, implying impaired cell-cell fusion. Despite these findings, RANK signaling, including the activation of Erk and Akt, was normal in LDLR−/− preosteoclasts, and RANKL-induced expression of NFATc1 (a master regulator of osteoclastogenesis), cathepsin K, and tartrate-resistant acid phosphatase was equivalent in LDLR-null and wild-type cells. In contrast, the amounts of the osteoclast fusion-related proteins v-ATPase V0 subunit d2 and dendritic cell-specific transmembrane protein in LDLR−/− plasma membranes were reduced when compared with the wild type, suggesting a correlation with impaired cell-cell fusion, which occurs on the plasma membrane. LDLR−/− mice consistently exhibited increased bone mass in vivo. This change was accompanied by decreases in bone resorption parameters, with no changes in bone formation parameters. These findings provide a novel mechanism for osteoclast differentiation and improve the understanding of the correlation between osteoclast formation and lipids. PMID:22500026

  12. An Inducible Cell-Cell Fusion System with Integrated Ability to Measure the Efficiency and Specificity of HIV-1 Entry Inhibitors

    PubMed Central

    Herschhorn, Alon; Finzi, Andres; Jones, David M.; Courter, Joel R.; Sugawara, Akihiro; Smith, Amos B.; Sodroski, Joseph G.

    2011-01-01

    HIV-1 envelope glycoproteins (Envs) mediate virus entry by fusing the viral and target cell membranes, a multi-step process that represents an attractive target for inhibition. Entry inhibitors with broad-range activity against diverse isolates of HIV-1 may be extremely useful as lead compounds for the development of therapies or prophylactic microbicides. To facilitate the identification of such inhibitors, we have constructed a cell-cell fusion system capable of simultaneously monitoring inhibition efficiency and specificity. In this system, effector cells stably express a tetracycline-controlled transactivator (tTA) that enables tightly inducible expression of both HIV-1 Env and the Renilla luciferase (R-Luc) reporter protein. Target cells express the HIV-1 receptors, CD4 and CCR5, and carry the firefly luciferase (F-Luc) reporter gene under the control of a tTA-responsive promoter. Thus, Env-mediated fusion of these two cell types allows the tTA to diffuse to the target cell and activate the expression of the F-Luc protein. The efficiency with which an inhibitor blocks cell-cell fusion is measured by a decrease in the F-Luc activity, while the specificity of the inhibitor is evaluated by its effect on the R-Luc activity. The system exhibited a high dynamic range and high Z'-factor values. The assay was validated with a reference panel of inhibitors that target different steps in HIV-1 entry, yielding inhibitory concentrations comparable to published virus inhibition data. Our system is suitable for large-scale screening of chemical libraries and can also be used for detailed characterization of inhibitory and cytotoxic properties of known entry inhibitors. PMID:22069466

  13. Sulphated polysaccharides from Ulva clathrata and Cladosiphon okamuranus seaweeds both inhibit viral attachment/entry and cell-cell fusion, in NDV infection.

    PubMed

    Aguilar-Briseño, José Alberto; Cruz-Suarez, Lucia Elizabeth; Sassi, Jean-François; Ricque-Marie, Denis; Zapata-Benavides, Pablo; Mendoza-Gamboa, Edgar; Rodríguez-Padilla, Cristina; Trejo-Avila, Laura María

    2015-02-01

    Sulphated polysaccharides (SP) extracted from seaweeds have antiviral properties and are much less cytotoxic than conventional drugs, but little is known about their mode of action. Combination antiviral chemotherapy may offer advantages over single agent therapy, increasing efficiency, potency and delaying the emergence of resistant virus. The paramyxoviridae family includes pathogens causing morbidity and mortality worldwide in humans and animals, such as the Newcastle Disease Virus (NDV) in poultry. This study aims at determining the antiviral activity and mechanism of action in vitro of an ulvan (SP from the green seaweed Ulva clathrata), and of its mixture with a fucoidan (SP from Cladosiphon okamuranus), against La Sota NDV strain. The ulvan antiviral activity was tested using syncytia formation, exhibiting an IC50 of 0.1 μg/mL; ulvan had a better anti cell-cell spread effect than that previously shown for fucoidan, and inhibited cell-cell fusion via a direct effect on the F0 protein, but did not show any virucidal effect. The mixture of ulvan and fucoidan showed a greater anti-spread effect than SPs alone, but ulvan antagonizes the effect of fucoidan on the viral attachment/entry. Both SPs may be promising antivirals against paramyxovirus infection but their mixture has no clear synergistic advantage. PMID:25629385

  14. Sulphated Polysaccharides from Ulva clathrata and Cladosiphon okamuranus Seaweeds both Inhibit Viral Attachment/Entry and Cell-Cell Fusion, in NDV Infection

    PubMed Central

    Aguilar-Briseño, José Alberto; Cruz-Suarez, Lucia Elizabeth; Sassi, Jean-François; Ricque-Marie, Denis; Zapata-Benavides, Pablo; Mendoza-Gamboa, Edgar; Rodríguez-Padilla, Cristina; Trejo-Avila, Laura María

    2015-01-01

    Sulphated polysaccharides (SP) extracted from seaweeds have antiviral properties and are much less cytotoxic than conventional drugs, but little is known about their mode of action. Combination antiviral chemotherapy may offer advantages over single agent therapy, increasing efficiency, potency and delaying the emergence of resistant virus. The paramyxoviridae family includes pathogens causing morbidity and mortality worldwide in humans and animals, such as the Newcastle Disease Virus (NDV) in poultry. This study aims at determining the antiviral activity and mechanism of action in vitro of an ulvan (SP from the green seaweed Ulva clathrata), and of its mixture with a fucoidan (SP from Cladosiphon okamuranus), against La Sota NDV strain. The ulvan antiviral activity was tested using syncytia formation, exhibiting an IC50 of 0.1 μg/mL; ulvan had a better anti cell-cell spread effect than that previously shown for fucoidan, and inhibited cell-cell fusion via a direct effect on the F0 protein, but did not show any virucidal effect. The mixture of ulvan and fucoidan showed a greater anti-spread effect than SPs alone, but ulvan antagonizes the effect of fucoidan on the viral attachment/entry. Both SPs may be promising antivirals against paramyxovirus infection but their mixture has no clear synergistic advantage. PMID:25629385

  15. Clustering and Mobility of HIV-1 Env at Viral Assembly Sites Predict Its Propensity To Induce Cell-Cell Fusion

    PubMed Central

    Roy, Nathan H.; Chan, Jany; Lambelé, Marie

    2013-01-01

    HIV-1 Env mediates virus attachment to and fusion with target cell membranes, and yet, while Env is still situated at the plasma membrane of the producer cell and before its incorporation into newly formed particles, Env already interacts with the viral receptor CD4 on target cells, thus enabling the formation of transient cell contacts that facilitate the transmission of viral particles. During this first encounter with the receptor, Env must not induce membrane fusion, as this would prevent the producer cell and the target cell from separating upon virus transmission, but how Env's fusion activity is controlled remains unclear. To gain a better understanding of the Env regulation that precedes viral transmission, we examined the nanoscale organization of Env at the surface of producer cells. Utilizing superresolution microscopy (stochastic optical reconstruction microscopy [STORM]) and fluorescence recovery after photobleaching (FRAP), we quantitatively assessed the clustering and dynamics of Env upon its arrival at the plasma membrane. We found that Gag assembly induced the aggregation of small Env clusters into larger domains and that these domains were completely immobile. Truncation of the cytoplasmic tail (CT) of Env abrogated Gag's ability to induce Env clustering and restored Env mobility at assembly sites, both of which correlated with increased Env-induced fusion of infected and uninfected cells. Hence, while Env trapping by Gag secures Env incorporation into viral particles, Env clustering and its sequestration at assembly sites likely also leads to the repression of its fusion function, and thus, by preventing the formation of syncytia, Gag helps to secure efficient transfer of viral particles to target cells. PMID:23637402

  16. Integrin αvβ1 Modulation Affects Subtype B Avian Metapneumovirus Fusion Protein-mediated Cell-Cell Fusion and Virus Infection.

    PubMed

    Yun, Bing-Ling; Guan, Xiao-Lu; Liu, Yong-Zhen; Zhang, Yao; Wang, Yong-Qiang; Qi, Xiao-Le; Cui, Hong-Yu; Liu, Chang-Jun; Zhang, Yan-Ping; Gao, Hong-Lei; Gao, Li; Li, Kai; Gao, Yu-Long; Wang, Xiao-Mei

    2016-07-01

    Avian metapneumovirus (aMPV) fusion (F) protein mediates virus-cell membrane fusion to initiate viral infection, which requires F protein binding to its receptor(s) on the host cell surface. However, the receptor(s) for aMPV F protein is still not identified. All known subtype B aMPV (aMPV/B) F proteins contain a conserved Arg-Asp-Asp (RDD) motif, suggesting that the aMPV/B F protein may mediate membrane fusion via the binding of RDD to integrin. When blocked with integrin-specific peptides, aMPV/B F protein fusogenicity and viral replication were significantly reduced. Specifically we identified integrin αv and/or β1-mediated F protein fusogenicity and viral replication using antibody blocking, small interfering RNAs (siRNAs) knockdown, and overexpression. Additionally, overexpression of integrin αv and β1 in aMPV/B non-permissive cells conferred aMPV/B F protein binding and aMPV/B infection. When RDD was altered to RAE (Arg-Ala-Glu), aMPV/B F protein binding and fusogenic activity were profoundly impaired. These results suggest that integrin αvβ1 is a functional receptor for aMPV/B F protein-mediated membrane fusion and virus infection, which will provide new insights on the fusogenic mechanism and pathogenesis of aMPV. PMID:27226547

  17. 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.

  18. Regulation of the human endogenous retroviral Syncytin-1 and cell-cell fusion by the nuclear hormone receptors PPARγ/RXRα in placentogenesis.

    PubMed

    Ruebner, Matthias; Langbein, Manuela; Strissel, Pamela L; Henke, Christine; Schmidt, Doreen; Goecke, Tamme W; Faschingbauer, Florian; Schild, Ralf L; Beckmann, Matthias W; Strick, Reiner

    2012-07-01

    Cytotrophoblast (CT) cell fusion into a syncytiotrophoblast is obligatory for placentation and mediated by the human endogenous retrovirus (HERV)-W envelope gene Syncytin-1. Abnormal placentation is associated with preeclampsia (PE), HELLP and intrauterine growth restriction (IUGR). In placentogenesis, the MAP-kinase p38α regulates PPARγ/RXRα signaling and target genes, like leptin, resistin, ABCG2, and hCG. The aim of this study was to analyze PPARγ/RXRα signaling and target gene regulation using primary CT cultures, the trophoblastic cell line BeWo and placental tissues from patients with normal and abnormal placentation. CT from four different human control placentae and BeWo cells demonstrated that Syncytin-1, other signaling members and CT cell fusions were regulated with PPARγ/RXRα activators troglitazone and 9-cis retinoic acid, via protein kinase A and p38α inhibition. Significant discordant regulations between CTs and BeWo were found. Two PPARγ/RXRα-response-elements from upstream regulatory elements and the 5'LTR of HERV-W were confirmed with DNA-protein binding assays using nuclear extracts and recombinant PPARγ/RXRα proteins. These promoter elements were validated with luciferase assays in the presence of PPARγ/RXRα modulators. Furthermore, troglitazone or 9-cis retinoic acid treatment of siRNA-PPARγ and siRNA-RXRα transfected BeWo cells proved the requirement of these proteins for Syncytin-1 regulation. Thirty primary abnormal placentae from PE, HELLP and IUGR patients compared to 10 controls showed significant deregulation of leptin RNA and protein, p38α, phospho-p38α, PPARγ, ABCG2, INSL4 and Syncytin-1. Our study characterized PPARγ/RXRα signaling in human CT and cell fusions identifying Syncytin-1 as a new target gene. Based on these results, a disturbed PPARγ/RXRα pathway could contribute to pathological human pregnancies. PMID:22573555

  19. Reconstitution of Fusion Proteins in Supported Lipid Bilayers for the Study of Cell Surface Receptor-Ligand Interactions in Cell-Cell Contact.

    PubMed

    Ghosh Moulick, R; Afanasenkau, D; Choi, S-E; Albers, J; Lange, W; Maybeck, V; Utesch, T; Offenhäusser, A

    2016-04-12

    Bioactive molecules such as adhesion ligands, growth factors, or enzymes play an important role in modulating cell behavior such as cell adhesion, spreading, and differentiation. Deciphering the mechanism of ligand-mediated cell adhesion and associated signaling is of great interest not only for fundamental biophysical investigations but also for applications in medicine and biotechnology. In the presented work, we developed a new biomimetic platform that enables culturing primary neurons and testing cell surface-receptor ligand interactions in cell-cell contacts as, e.g., in neuronal synapses. This platform consists of a supported lipid bilayer modified with incorporated neuronal adhesion proteins conjugated with the Fc-domain of IgG (ephrin A5 Fc-chimera). We extensively characterized properties of these protein containing bilayers using fluorescence recovery after photobleaching (FRAP), quartz crystal microbalance with dissipation (QCM-D), and immunostaining. We conclude that the Fc-domain is the part responsible for the incorporation of the protein into the bilayer. The biomimetic platform prepared by this new approach was able to promote neuronal cell adhesion and maintain growth as well as facilitate neuronal maturation as shown by electrophysiological measurements. We believe that our approach can be extended to insert other proteins to create a general culture platform for neurons and other cell types. PMID:26986674

  20. INITIAL SIZE AND DYNAMICS OF VIRAL FUSION PORES ARE A FUNCTION OF THE FUSION PROTEIN MEDIATING MEMBRANE FUSION

    PubMed Central

    Plonsky, I.; Kingsley, D. H.; Rashtian, A.; Blank, P.S.; Zimmerberg, J.

    2013-01-01

    To investigate the role of the fusogenic protein in the initial size and dynamics of the pore that widens to finalize membrane fusion, two different fusion proteins expressed in the same cell line were investigated: the major glycoprotein of baculovirus Autographa californica (GP64) and the hemaggluttinin of influenza X31 (HA). The host Sf9 cells expressing these viral proteins, irrespective of protein species, fused to human red blood cells (RBC) upon acidification of the medium. High time resolution electrophysiological study of fusion pore conductance revealed fundamental differences in a) the initial pore conductance (pores created by HA were smaller than those created by GP64), b) the ability of pores to flicker (only HA-mediated pores flickered), and c) the time required for pore formation (HA-mediated pores took much longer to form following acidification). Thus 1) HA and GP64 have divergent electrophysiological phenotypes even when they fuse identical membranes, and 2) fusion proteins play a crucial role in determining initial fusion pore characteristics. The structure of the initial fusion pore detected by electrical conductance measurements is sensitive to the nature of the fusion protein. PMID:18208404

  1. The Pathway of Membrane Fusion Catalyzed by Influenza Hemagglutinin: Restriction of Lipids, Hemifusion, and Lipidic Fusion Pore Formation

    PubMed Central

    Chernomordik, Leonid V.; Frolov, Vadim A.; Leikina, Eugenia; Bronk, Peter; Zimmerberg, Joshua

    1998-01-01

    The mechanism of bilayer unification in biological fusion is unclear. We reversibly arrested hemagglutinin (HA)-mediated cell–cell fusion right before fusion pore opening. A low-pH conformation of HA was required to form this intermediate and to ensure fusion beyond it. We present evidence indicating that outer monolayers of the fusing membranes were merged and continuous in this intermediate, but HA restricted lipid mixing. Depending on the surface density of HA and the membrane lipid composition, this restricted hemifusion intermediate either transformed into a fusion pore or expanded into an unrestricted hemifusion, without pores but with unrestricted lipid mixing. Our results suggest that restriction of lipid flux by a ring of activated HA is necessary for successful fusion, during which a lipidic fusion pore develops in a local and transient hemifusion diaphragm. PMID:9508770

  2. Toll-like Receptor 2 (TLR2), Transforming Growth Factor-β, Hyaluronan (HA), and Receptor for HA-mediated Motility (RHAMM) Are Required for Surfactant Protein A-stimulated Macrophage Chemotaxis*

    PubMed Central

    Foley, Joseph P.; Lam, David; Jiang, Hongmei; Liao, Jie; Cheong, Naeun; McDevitt, Theresa M.; Zaman, Aisha; Wright, Jo Rae; Savani, Rashmin C.

    2012-01-01

    The innate immune system protects the host from bacterial and viral invasion. Surfactant protein A (SPA), a lung-specific collectin, stimulates macrophage chemotaxis. However, the mechanisms regulating this function are unknown. Hyaluronan (HA) and its receptors RHAMM (receptor for HA- mediated motility, CD168) and CD44 also regulate cell migration and inflammation. We therefore examined the role of HA, RHAMM, and CD44 in SPA-stimulated macrophage chemotaxis. Using antibody blockade and murine macrophages, SPA-stimulated macrophage chemotaxis was dependent on TLR2 but not the other SPA receptors examined. Anti-TLR2 blocked SPA-induced production of TGFβ. In turn, TGFβ1-stimulated chemotaxis was inhibited by HA-binding peptide and anti-RHAMM antibody but not anti-TLR2 antibody. Macrophages from TLR2−/− mice failed to migrate in response to SPA but responded normally to TGFβ1 and HA, effects that were blocked by anti-RHAMM antibody. Macrophages from WT and CD44−/− mice had similar responses to SPA, whereas those from RHAMM−/− mice had decreased chemotaxis to SPA, TGFβ1, and HA. In primary macrophages, SPA-stimulated TGFβ production was dependent on TLR2, JNK, and ERK but not p38. Pam3Cys, a specific TLR2 agonist, stimulated phosphorylation of JNK, ERK, and p38, but only JNK and ERK inhibition blocked Pam3Cys-stimulated chemotaxis. We have uncovered a novel pathway for SPA-stimulated macrophage chemotaxis where SPA stimulation via TLR2 drives JNK- and ERK-dependent TGFβ production. TGFβ1, in turn, stimulates macrophage chemotaxis in a RHAMM and HA-dependent manner. These findings are highly relevant to the regulation of innate immune responses by SPA with key roles for specific components of the extracellular matrix. PMID:22948158

  3. New Small Molecule Entry Inhibitors Targeting Hemagglutinin-Mediated Influenza A Virus Fusion

    PubMed Central

    Antanasijevic, Aleksandar; Wang, Minxiu; Li, Bing; Mills, Debra M.; Ames, Jessica A.; Nash, Peter J.; Williams, John D.; Peet, Norton P.; Moir, Donald T.; Prichard, Mark N.; Keith, Kathy A.; Barnard, Dale L.; Caffrey, Michael; Rong, Lijun; Bowlin, Terry L.

    2014-01-01

    Influenza viruses are a major public health threat worldwide, and options for antiviral therapy are limited by the emergence of drug-resistant virus strains. The influenza virus glycoprotein hemagglutinin (HA) plays critical roles in the early stage of virus infection, including receptor binding and membrane fusion, making it a potential target for the development of anti-influenza drugs. Using pseudotype virus-based high-throughput screens, we have identified several new small molecules capable of inhibiting influenza virus entry. We prioritized two novel inhibitors, MBX2329 and MBX2546, with aminoalkyl phenol ether and sulfonamide scaffolds, respectively, that specifically inhibit HA-mediated viral entry. The two compounds (i) are potent (50% inhibitory concentration [IC50] of 0.3 to 5.9 μM); (ii) are selective (50% cytotoxicity concentration [CC50] of >100 μM), with selectivity index (SI) values of >20 to 200 for different influenza virus strains; (iii) inhibit a wide spectrum of influenza A viruses, which includes the 2009 pandemic influenza virus A/H1N1/2009, highly pathogenic avian influenza (HPAI) virus A/H5N1, and oseltamivir-resistant A/H1N1 strains; (iv) exhibit large volumes of synergy with oseltamivir (36 and 331 μM2 % at 95% confidence); and (v) have chemically tractable structures. Mechanism-of-action studies suggest that both MBX2329 and MBX2546 bind to HA in a nonoverlapping manner. Additional results from HA-mediated hemolysis of chicken red blood cells (cRBCs), competition assays with monoclonal antibody (MAb) C179, and mutational analysis suggest that the compounds bind in the stem region of the HA trimer and inhibit HA-mediated fusion. Therefore, MBX2329 and MBX2546 represent new starting points for chemical optimization and have the potential to provide valuable future therapeutic options and research tools to study the HA-mediated entry process. PMID:24198411

  4. Spinal fusion

    MedlinePlus

    ... Anterior spinal fusion; Spine surgery - spinal fusion; Low back pain - fusion; Herniated disk - fusion ... If you had chronic back pain before surgery, you will likely still have some pain afterward. Spinal fusion is unlikely to take away all your pain ...

  5. 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

  6. Role of sequence and structure of the Hendra fusion protein fusion peptide in membrane fusion.

    PubMed

    Smith, Everett Clinton; Gregory, Sonia M; Tamm, Lukas K; Creamer, Trevor P; Dutch, Rebecca Ellis

    2012-08-24

    Viral fusion proteins are intriguing molecular machines that undergo drastic conformational changes to facilitate virus-cell membrane fusion. During fusion a hydrophobic region of the protein, termed the fusion peptide (FP), is inserted into the target host cell membrane, with subsequent conformational changes culminating in membrane merger. Class I fusion proteins contain FPs between 20 and 30 amino acids in length that are highly conserved within viral families but not between. To examine the sequence dependence of the Hendra virus (HeV) fusion (F) protein FP, the first eight amino acids were mutated first as double, then single, alanine mutants. Mutation of highly conserved glycine residues resulted in inefficient F protein expression and processing, whereas substitution of valine residues resulted in hypofusogenic F proteins despite wild-type surface expression levels. Synthetic peptides corresponding to a portion of the HeV F FP were shown to adopt an α-helical secondary structure in dodecylphosphocholine micelles and small unilamellar vesicles using circular dichroism spectroscopy. Interestingly, peptides containing point mutations that promote lower levels of cell-cell fusion within the context of the whole F protein were less α-helical and induced less membrane disorder in model membranes. These data represent the first extensive structure-function relationship of any paramyxovirus FP and demonstrate that the HeV F FP and potentially other paramyxovirus FPs likely require an α-helical structure for efficient membrane disordering and fusion. PMID:22761418

  7. Distinct functional determinants of influenza hemagglutinin-mediated membrane fusion

    PubMed Central

    Ivanovic, Tijana; Harrison, Stephen C

    2015-01-01

    Membrane fusion is the critical step for infectious cell penetration by enveloped viruses. We have previously used single-virion measurements of fusion kinetics to study the molecular mechanism of influenza-virus envelope fusion. Published data on fusion inhibition by antibodies to the 'stem' of influenza virus hemagglutinin (HA) now allow us to incorporate into simulations the provision that some HAs are inactive. We find that more than half of the HAs are unproductive even for virions with no bound antibodies, but that the overall mechanism is extremely robust. Determining the fraction of competent HAs allows us to determine their rates of target-membrane engagement. Comparison of simulations with data from H3N2 and H1N1 viruses reveals three independent functional variables of HA-mediated membrane fusion closely linked to neutralization susceptibility. Evidence for compensatory changes in the evolved mechanism sets the stage for studies aiming to define the molecular constraints on HA evolvability. DOI: http://dx.doi.org/10.7554/eLife.11009.001 PMID:26613408

  8. The Dark Side of Cell Fusion

    PubMed Central

    Bastida-Ruiz, Daniel; Van Hoesen, Kylie; Cohen, Marie

    2016-01-01

    Cell fusion is a physiological cellular process essential for fertilization, viral entry, muscle differentiation and placental development, among others. In this review, we will highlight the different cancer cell-cell fusions and the advantages obtained by these fusions. We will specially focus on the acquisition of metastatic features by cancer cells after fusion with bone marrow-derived cells. The mechanism by which cancer cells fuse with other cells has been poorly studied thus far, but the presence in several cancer cells of syncytin, a trophoblastic fusogen, leads us to a cancer cell fusion mechanism similar to the one used by the trophoblasts. The mechanism by which cancer cells perform the cell fusion could be an interesting target for cancer therapy. PMID:27136533

  9. Myoblast fusion: lessons from flies and mice

    PubMed Central

    Abmayr, Susan M.; Pavlath, Grace K.

    2012-01-01

    The fusion of myoblasts into multinucleate syncytia plays a fundamental role in muscle function, as it supports the formation of extended sarcomeric arrays, or myofibrils, within a large volume of cytoplasm. Principles learned from the study of myoblast fusion not only enhance our understanding of myogenesis, but also contribute to our perspectives on membrane fusion and cell-cell fusion in a wide array of model organisms and experimental systems. Recent studies have advanced our views of the cell biological processes and crucial proteins that drive myoblast fusion. Here, we provide an overview of myoblast fusion in three model systems that have contributed much to our understanding of these events: the Drosophila embryo; developing and regenerating mouse muscle; and cultured rodent muscle cells. PMID:22274696

  10. Cell fusion in Neurospora crassa.

    PubMed

    Herzog, Stephanie; Schumann, Marcel R; Fleißner, André

    2015-12-01

    In recent years, the filamentous fungus Neurospora crassa has advanced as a model organism for studying eukaryotic cell-cell communication and fusion. Cell merger in this fungus employs an unusual mode of communication, in which the fusion partners appear to switch between signal sending and receiving. Many molecular factors mediating this intriguing mechanism and the subsequent membrane merger have been identified. It has become apparent that conserved factors, such as MAP kinases, NADPH oxidases and the STRIPAK complex, together with fungal specific proteins are wired into an intricate signaling network. Here, we will present an overview of recent findings on the molecular mechanism mediating fusion in N. crassa and will discuss the current working model. PMID:26340439

  11. 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.

  12. Fusion Implementation

    SciTech Connect

    J.A. Schmidt

    2002-02-20

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

  13. 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.

  14. A sensitive HIV-1 envelope induced fusion assay identifies fusion enhancement of thrombin

    SciTech Connect

    Cheng, De-Chun; Zhong, Guo-Cai; Su, Ju-Xiang; Liu, Yan-Hong; Li, Yan; Wang, Jia-Ye; Hattori, Toshio; Ling, Hong; Zhang, Feng-Min

    2010-01-22

    To evaluate the interaction between HIV-1 envelope glycoprotein (Env) and target cell receptors, various cell-cell-fusion assays have been developed. In the present study, we established a novel fusion system. In this system, the expression of the sensitive reporter gene, firefly luciferase (FL) gene, in the target cells was used to evaluate cell fusion event. Simultaneously, constitutively expressed Renilla luciferase (RL) gene was used to monitor effector cell number and viability. FL gave a wider dynamic range than other known reporters and the introduction of RL made the assay accurate and reproducible. This system is especially beneficial for investigation of potential entry-influencing agents, for its power of ruling out the false inhibition or enhancement caused by the artificial cell-number variation. As a case study, we applied this fusion system to observe the effect of a serine protease, thrombin, on HIV Env-mediated cell-cell fusion and have found the fusion enhancement activity of thrombin over two R5-tropic HIV strains.

  15. The role of fusion activity of influenza A viruses in their biological properties.

    PubMed

    Jakubcová, L; Hollý, J; Varečková, E

    2016-06-01

    Influenza A viruses (IAVs) cause acute respiratory infections of humans, which are repeated yearly. Human IAV infections are associated with significant morbidity and mortality and therefore they represent a serious health problem. All human IAV strains are originally derived from avian IAVs, which, after their adaptation to humans, can spread in the human population and cause pandemics with more or less severe course of the disease. Presently, however, the potential of avian IAV to infect humans and to cause the disease cannot be predicted. Many studies are therefore focused on factors influencing the virulence and pathogenicity of IAV viruses in a given host. The virus-host interaction starts by virus attachment via the envelope glycoprotein hemagglutinin (HA) to the receptors on the cell surface. In addition to receptor binding, HA mediates also the fusion of viral and endosomal membranes, which follows the virus endocytosis. The fusion potential of HA trimer, primed by proteolytic cleavage, is activated by low pH in endosomes, resulting in HA refolding into the fusion-active form. The HA conformation change is predetermined by its 3-D structure, is pH-dependent, irreversible and strain-specific. The process of fusion activation of IAV hemagglutinin is crucial for virus entry into the cell and for the ability of the virus to replicate in the host. Here we discuss the known data about the characteristics of fusion activation of HA in relation to IAV virulence and pathogenicity. PMID:27265461

  16. 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)

  17. Review: An overview of molecular events occurring in human trophoblast fusion.

    PubMed

    Gerbaud, P; Pidoux, G

    2015-04-01

    During human placentation, mononuclear cytotrophoblasts fuse to form a multinucleated syncytia ensuring hormonal production and nutrient exchanges between the maternal and fetal circulation. Syncytia formation is essential for the maintenance of pregnancy and for fetal growth. The trophoblast cell fusion process first requires the acquisition of cell fusion properties, then cells set up plasma membrane protein macrocomplexes and fusogen machinery that trigger cell-cell fusion. Numerous proteins have been shown to be directly involved in the initiation of trophoblast cell fusion. These proteins must expressed at the right time and in the right place to trigger cell-cell fusion. In this review, we describe the role of certain fusogenic protein macrocomplexes that form the scaffold for the fusogen machinery underlying human trophoblastic-lipid mixing and merging of cell contents that lead to cell fusion in physiological conditions. PMID:25564303

  18. Regulation of promyogenic signal transduction by cell-cell contact and adhesion

    PubMed Central

    Krauss, Robert S.

    2010-01-01

    Skeletal myoblast differentiation involves acquisition of the muscle-specific transcriptional program and morphological changes, including fusion into multinucleated myofibers. Differentiation is regulated by extracellular signaling cues, including cell-cell contact and adhesion. Cadherin and Ig adhesion receptors have been implicated in distinct but overlapping stages of myogenesis. N-cadherin signals through the Ig receptor Cdo to activate p38 MAP kinase, while the Ig receptor neogenin signals to activate FAK; both processes promote muscle-specific gene expression and myoblast fusion. M-cadherin activates Rac1 to enhance fusion. Specific Ig receptors (Kirre, Sns) are essential for myoblast fusion in Drosophila, also signaling through Rac, and vertebrate orthologs of Kirre and Sns have partially conserved function. Mice lacking specific cytoplasmic signaling factors activated by multiple receptors (e.g., Rac1) have strong muscle phenotypes in vivo. In contrast, mice lacking individual adhesion receptors that lie upstream of these factors have modest phenotypes. Redundancy among receptors may account for this. Many of the mammalian Ig receptors and cadherins associate with each other, and multivalent interactions within these complexes may require removal of multiple components to reveal dramatic defects in vivo. Nevertheless, it is possible that the murine adhesion receptors rate-limiting in vivo have not yet been identified or fully assessed. PMID:20471976

  19. Regulation of promyogenic signal transduction by cell-cell contact and adhesion

    SciTech Connect

    Krauss, Robert S.

    2010-11-01

    Skeletal myoblast differentiation involves acquisition of the muscle-specific transcriptional program and morphological changes, including fusion into multinucleated myofibers. Differentiation is regulated by extracellular signaling cues, including cell-cell contact and adhesion. Cadherin and Ig adhesion receptors have been implicated in distinct but overlapping stages of myogenesis. N-cadherin signals through the Ig receptor Cdo to activate p38 MAP kinase, while the Ig receptor neogenin signals to activate FAK; both processes promote muscle-specific gene expression and myoblast fusion. M-cadherin activates Rac1 to enhance fusion. Specific Ig receptors (Kirre and Sns) are essential for myoblast fusion in Drosophila, also signaling through Rac, and vertebrate orthologs of Kirre and Sns have partially conserved function. Mice lacking specific cytoplasmic signaling factors activated by multiple receptors (e.g., Rac1) have strong muscle phenotypes in vivo. In contrast, mice lacking individual adhesion receptors that lie upstream of these factors have modest phenotypes. Redundancy among receptors may account for this. Many of the mammalian Ig receptors and cadherins associate with each other, and multivalent interactions within these complexes may require removal of multiple components to reveal dramatic defects in vivo. Nevertheless, it is possible that the murine adhesion receptors rate-limiting in vivo have not yet been identified or fully assessed.

  20. Cell-cell interactions on solid matrices.

    PubMed

    Louis, Nancy A; Daniels, Dionne; Colgan, Sean P

    2006-01-01

    Models to study molecular, biochemical, and functional responses in vitro generally incorporate an individual cell type or group of cells organized in a random fashion. Normal physiological responses in vivo require that individual cell types be oriented in an organized fashion with three-dimensional architecture and appropriately positioned cellular interfaces. Much recent progress has been made in the development and implementation of models to study cell-cell contact using substrate grown cells. Here, we summarize the use of membrane permeable supports to study functional responses in appropriately positioned cell types. These models incorporate two or more different cells cultured in physiologically positioned locales on solid substrates. Models incorporating nonadherent cells (e.g., leukocytes) in co-culture with such models also are discussed. Such models have been used extensively to discovery both cell-bound as well as soluble mediators of physiological and pathophysiological processes. PMID:16799188

  1. 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)

  2. Crystal Structure of the Pre-fusion Nipah Virus Fusion Glycoprotein Reveals a Novel Hexamer-of-Trimers Assembly

    PubMed Central

    Dutta, Somnath; Yan, Lianying; Feng, YanRu; Wang, Lin-Fa; Skiniotis, Georgios; Lee, Benhur; Zhou, Z. Hong; Broder, Christopher C.; Aguilar, Hector C.; Nikolov, Dimitar B.

    2015-01-01

    Nipah virus (NiV) is a paramyxovirus that infects host cells through the coordinated efforts of two envelope glycoproteins. The G glycoprotein attaches to cell receptors, triggering the fusion (F) glycoprotein to execute membrane fusion. Here we report the first crystal structure of the pre-fusion form of the NiV-F glycoprotein ectodomain. Interestingly this structure also revealed a hexamer-of-trimers encircling a central axis. Electron tomography of Nipah virus-like particles supported the hexameric pre-fusion model, and biochemical analyses supported the hexamer-of-trimers F assembly in solution. Importantly, structure-assisted site-directed mutagenesis of the interfaces between F trimers highlighted the functional relevance of the hexameric assembly. Shown here, in both cell-cell fusion and virus-cell fusion systems, our results suggested that this hexamer-of-trimers assembly was important during fusion pore formation. We propose that this assembly would stabilize the pre-fusion F conformation prior to cell attachment and facilitate the coordinated transition to a post-fusion conformation of all six F trimers upon triggering of a single trimer. Together, our data reveal a novel and functional pre-fusion architecture of a paramyxoviral fusion glycoprotein. PMID:26646856

  3. Changes in Parthenogenetic Imprinting Patterns during Reprogramming by Cell Fusion

    PubMed Central

    Jang, Hyun Sik; Hong, Yean Ju; Choi, Hyun Woo; Song, Hyuk; Byun, Sung June; Uhm, Sang Jun; Seo, Han Geuk; Do, Jeong Tae

    2016-01-01

    Differentiated somatic cells can be reprogrammed into the pluripotent state by cell-cell fusion. In the pluripotent state, reprogrammed cells may then self-renew and differentiate into all three germ layers. Fusion-induced reprogramming also epigenetically modifies the somatic cell genome through DNA demethylation, X chromosome reactivation, and histone modification. In this study, we investigated whether fusion with embryonic stem cells (ESCs) also reprograms genomic imprinting patterns in somatic cells. In particular, we examined imprinting changes in parthenogenetic neural stem cells fused with biparental ESCs, as well as in biparental neural stem cells fused with parthenogenetic ESCs. The resulting hybrid cells expressed the pluripotency markers Oct4 and Nanog. In addition, methylation of several imprinted genes except Peg3 was comparable between hybrid cells and ESCs. This finding indicates that reprogramming by cell fusion does not necessarily reverse the status of all imprinted genes to the state of pluripotent fusion partner. PMID:27232503

  4. 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.

  5. Repulsive cues combined with physical barriers and cell-cell adhesion determine progenitor cell positioning during organogenesis.

    PubMed

    Paksa, Azadeh; Bandemer, Jan; Hoeckendorf, Burkhard; Razin, Nitzan; Tarbashevich, Katsiaryna; Minina, Sofia; Meyen, Dana; Biundo, Antonio; Leidel, Sebastian A; Peyrieras, Nadine; Gov, Nir S; Keller, Philipp J; Raz, Erez

    2016-01-01

    The precise positioning of organ progenitor cells constitutes an essential, yet poorly understood step during organogenesis. Using primordial germ cells that participate in gonad formation, we present the developmental mechanisms maintaining a motile progenitor cell population at the site where the organ develops. Employing high-resolution live-cell microscopy, we find that repulsive cues coupled with physical barriers confine the cells to the correct bilateral positions. This analysis revealed that cell polarity changes on interaction with the physical barrier and that the establishment of compact clusters involves increased cell-cell interaction time. Using particle-based simulations, we demonstrate the role of reflecting barriers, from which cells turn away on contact, and the importance of proper cell-cell adhesion level for maintaining the tight cell clusters and their correct positioning at the target region. The combination of these developmental and cellular mechanisms prevents organ fusion, controls organ positioning and is thus critical for its proper function. PMID:27088892

  6. Quantitative methods for analyzing cell-cell adhesion in development.

    PubMed

    Kashef, Jubin; Franz, Clemens M

    2015-05-01

    During development cell-cell adhesion is not only crucial to maintain tissue morphogenesis and homeostasis, it also activates signalling pathways important for the regulation of different cellular processes including cell survival, gene expression, collective cell migration and differentiation. Importantly, gene mutations of adhesion receptors can cause developmental disorders and different diseases. Quantitative methods to measure cell adhesion are therefore necessary to understand how cells regulate cell-cell adhesion during development and how aberrations in cell-cell adhesion contribute to disease. Different in vitro adhesion assays have been developed in the past, but not all of them are suitable to study developmentally-related cell-cell adhesion processes, which usually requires working with low numbers of primary cells. In this review, we provide an overview of different in vitro techniques to study cell-cell adhesion during development, including a semi-quantitative cell flipping assay, and quantitative single-cell methods based on atomic force microscopy (AFM)-based single-cell force spectroscopy (SCFS) or dual micropipette aspiration (DPA). Furthermore, we review applications of Förster resonance energy transfer (FRET)-based molecular tension sensors to visualize intracellular mechanical forces acting on cell adhesion sites. Finally, we describe a recently introduced method to quantitate cell-generated forces directly in living tissues based on the deformation of oil microdroplets functionalized with adhesion receptor ligands. Together, these techniques provide a comprehensive toolbox to characterize different cell-cell adhesion phenomena during development. PMID:25448695

  7. A generic screening platform for inhibitors of virus induced cell fusion using cellular electrical impedance

    PubMed Central

    Watterson, Daniel; Robinson, Jodie; Chappell, Keith J.; Butler, Mark S.; Edwards, David J.; Fry, Scott R.; Bermingham, Imogen M.; Cooper, Matthew A.; Young, Paul R.

    2016-01-01

    Fusion of the viral envelope with host cell membranes is an essential step in the life cycle of all enveloped viruses. Despite such a clear target for antiviral drug development, few anti-fusion drugs have progressed to market. One significant hurdle is the absence of a generic, high-throughput, reproducible fusion assay. Here we report that real time, label-free measurement of cellular electrical impedance can quantify cell-cell fusion mediated by either individually expressed recombinant viral fusion proteins, or native virus infection. We validated this approach for all three classes of viral fusion and demonstrated utility in quantifying fusion inhibition using antibodies and small molecule inhibitors specific for dengue virus and respiratory syncytial virus. PMID:26976324

  8. A generic screening platform for inhibitors of virus induced cell fusion using cellular electrical impedance.

    PubMed

    Watterson, Daniel; Robinson, Jodie; Chappell, Keith J; Butler, Mark S; Edwards, David J; Fry, Scott R; Bermingham, Imogen M; Cooper, Matthew A; Young, Paul R

    2016-01-01

    Fusion of the viral envelope with host cell membranes is an essential step in the life cycle of all enveloped viruses. Despite such a clear target for antiviral drug development, few anti-fusion drugs have progressed to market. One significant hurdle is the absence of a generic, high-throughput, reproducible fusion assay. Here we report that real time, label-free measurement of cellular electrical impedance can quantify cell-cell fusion mediated by either individually expressed recombinant viral fusion proteins, or native virus infection. We validated this approach for all three classes of viral fusion and demonstrated utility in quantifying fusion inhibition using antibodies and small molecule inhibitors specific for dengue virus and respiratory syncytial virus. PMID:26976324

  9. MFR, a Putative Receptor Mediating the Fusion of Macrophages

    PubMed Central

    Saginario, Charles; Sterling, Hyacinth; Beckers, Cornelius; Kobayashi, Ruji; Solimena, Michele; Ullu, Elisabetta; Vignery, Agnès

    1998-01-01

    We had previously identified a macrophage surface protein whose expression is highly induced, transient, and specific, as it is restricted to actively fusing macrophages in vitro and in vivo. This protein is recognized by monoclonal antibodies that block macrophage fusion. We have now purified this protein and cloned its corresponding cDNA. This protein belongs to the superfamily of immunoglobulins and is similar to immune antigen receptors such as the T-cell receptor, B-cell receptor, and viral receptors such as CD4. We have therefore named this protein macrophage fusion receptor (MFR). We show that the extracellular domain of MFR prevents fusion of macrophages in vitro and therefore propose that MFR belongs to the fusion machinery of macrophages. MFR is identical to SHPS-1 and BIT and is a homologue of P84, SIRPα, and MyD-1, all of which have been recently cloned and implicated in cell signaling and cell-cell interaction events. PMID:9774638

  10. Engineering multicellular systems by cell-cell communication

    PubMed Central

    Pai, Anand; Tanouchi, Yu; Collins, Cynthia; You, Lingchong

    2009-01-01

    Synthetic biology encompasses the design of new biological parts and systems as well as the modulation of existing biological networks to generate novel functions. In recent years, increasing emphasis has been placed on the engineering of population-level behaviors using cell-cell communication. From the engineering perspective, cell-cell communication serves as a versatile regulatory module that enables coordination among cells in and between populations and facilitates the generation of reliable dynamics. In addition to exploring biological “design principles” via the construction of increasingly complex dynamics, communication-based synthetic systems can be used as well-defined model systems to study ecological and social interactions such as competition, cooperation and predation. Here we discuss the dynamic properties of cell-cell communication modules, how they can be engineered for synthetic circuit design, and applications of these systems. PMID:19733047

  11. The cytoplasmic domain of the gamete membrane fusion protein HAP2 targets the protein to the fusion site in Chlamydomonas and regulates the fusion reaction

    PubMed Central

    Liu, Yanjie; Pei, Jimin; Grishin, Nick; Snell, William J.

    2015-01-01

    Cell-cell fusion between gametes is a defining step during development of eukaryotes, yet we know little about the cellular and molecular mechanisms of the gamete membrane fusion reaction. HAP2 is the sole gamete-specific protein in any system that is broadly conserved and shown by gene disruption to be essential for gamete fusion. The wide evolutionary distribution of HAP2 (also known as GCS1) indicates it was present in the last eukaryotic common ancestor and, therefore, dissecting its molecular properties should provide new insights into fundamental features of fertilization. HAP2 acts at a step after membrane adhesion, presumably directly in the merger of the lipid bilayers. Here, we use the unicellular alga Chlamydomonas to characterize contributions of key regions of HAP2 to protein location and function. We report that mutation of three strongly conserved residues in the ectodomain has no effect on targeting or fusion, although short deletions that include those residues block surface expression and fusion. Furthermore, HAP2 lacking a 237-residue segment of the cytoplasmic region is expressed at the cell surface, but fails to localize at the apical membrane patch specialized for fusion and fails to rescue fusion. Finally, we provide evidence that the ancient HAP2 contained a juxta-membrane, multi-cysteine motif in its cytoplasmic region, and that mutation of a cysteine dyad in this motif preserves protein localization, but substantially impairs HAP2 fusion activity. Thus, the ectodomain of HAP2 is essential for its surface expression, and the cytoplasmic region targets HAP2 to the site of fusion and regulates the fusion reaction. PMID:25655701

  12. Integration of AI-2 Based Cell-Cell Signaling with Metabolic Cues in Escherichia coli

    PubMed Central

    Mitra, Arindam; Herren, Christopher D.; Patel, Isha R.; Coleman, Adam; Mukhopadhyay, Suman

    2016-01-01

    The quorum sensing molecule Autoinducer-2 (AI-2) is generated as a byproduct of activated methyl cycle by the action of LuxS in Escherichia coli. AI-2 is synthesized, released and later internalized in a cell-density dependent manner. Here, by mutational analysis of the genes, uvrY and csrA, we describe a regulatory circuit of accumulation and uptake of AI-2. We constructed a single-copy chromosomal luxS-lacZ fusion in a luxS + merodiploid strain and evaluated its relative expression in uvrY and csrA mutants. At the entry of stationary phase, the expression of the fusion and AI-2 accumulation was positively regulated by uvrY and negatively regulated by csrA respectively. A deletion of csrA altered message stability of the luxS transcript and CsrA protein exhibited weak binding to 5’ luxS regulatory region. DNA protein interaction and chromatin immunoprecipitation analysis confirmed direct interaction of UvrY with the luxS promoter. Additionally, reduced expression of the fusion in hfq deletion mutant suggested involvement of small RNA interactions in luxS regulation. In contrast, the expression of lsrA operon involved in AI-2 uptake, is negatively regulated by uvrY and positively by csrA in a cell-density dependent manner. The dual role of csrA in AI-2 synthesis and uptake suggested a regulatory crosstalk of cell signaling with carbon regulation in Escherichia coli. We found that the cAMP-CRP mediated catabolite repression of luxS expression was uvrY dependent. This study suggests that luxS expression is complex and regulated at the level of transcription and translation. The multifactorial regulation supports the notion that cell-cell communication requires interaction and integration of multiple metabolic signals. PMID:27362507

  13. 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.

  14. 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.

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

    SciTech Connect

    Lorin, Aurelien; Lins, Laurence; Stroobant, Vincent; Brasseur, Robert . E-mail: brasseur.r@fsagx.ac.be; Charloteaux, Benoit

    2007-04-13

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

  16. A soluble form of Epstein-Barr virus gH/gL inhibits EBV-induced membrane fusion and does not function in fusion

    SciTech Connect

    Rowe, Cynthia L.; Connolly, Sarah A.; Chen, Jia; Jardetzky, Theodore S.; Longnecker, Richard

    2013-02-05

    We investigated whether soluble EBV gH/gL (sgH/gL) functions in fusion and made a series of truncations of gH/gL domains based on the gH/gL crystal structure. We found sgH/gL failed to mediate cell-cell fusion both when co-expressed with the other entry glycoproteins and when added exogenously to fusion assays. Interestingly, sgH/gL inhibited cell-cell fusion in a dose dependent manner when co-expressed. sgH/gL from HSV was unable to inhibit EBV fusion, suggesting the inhibition was specific to EBV gH/gL. sgH/gL stably binds gp42, but not gB nor gH/gL. The domain mutants, DI/gL, DI-II/gL and DI-II-III/gL were unable to bind gp42. Instead, DI-II/gL, DI-II-III/gL and sgH/gL but not DI/gL decreased the expression of gp42, resulting in decreased overall fusion. Overall, our results suggest that domain IV may be required for proper folding and the transmembrane domain and cytoplasmic tail of EBV gH/gL are required for the most efficient fusion.

  17. A Potent Anti-influenza Compound Blocks Fusion through Stabilization of the Prefusion Conformation of the Hemagglutinin Protein

    PubMed Central

    2015-01-01

    An ultrahigh-throughput screen was performed to identify novel small molecule inhibitors of influenza virus replication. The screen employed a recombinant influenza A/WSN/33 virus expressing Renilla luciferase and yielded a hit rate of 0.5%, of which the vast majority showed little cytotoxicity at the inhibitory concentration. One of the top hits from this screen, designated S20, inhibits HA-mediated membrane fusion. S20 shows potent antiviral activity (IC50 = 80 nM) and low toxicity (CC50 = 40 μM), yielding a selectivity index of 500 and functionality against all of the group 1 influenza A viruses tested in this study, including the pandemic H1N1 and avian H5N1 viruses. Mechanism of action studies proved a direct S20–HA interaction and showed that S20 inhibits fusion by stabilizing the prefusion conformation of HA. In silico docking studies were performed, and the predicted binding site in HA2 corresponds with the area where resistance mutations occurred and correlates with the known role of this region in fusion. This high-throughput screen has yielded many promising new lead compounds, including S20, which will potentially shed light on the molecular mechanisms of viral infection and serve as research tools or be developed for clinical use as antivirals. PMID:25984567

  18. Cell-Cell Communication in Yeast Using Auxin Biosynthesis and Auxin Responsive CRISPR Transcription Factors.

    PubMed

    Khakhar, Arjun; Bolten, Nicholas J; Nemhauser, Jennifer; Klavins, Eric

    2016-04-15

    An engineering framework for synthetic multicellular systems requires a programmable means of cell-cell communication. Such a communication system would enable complex behaviors, such as pattern formation, division of labor in synthetic microbial communities, and improved modularity in synthetic circuits. However, it remains challenging to build synthetic cellular communication systems in eukaryotes due to a lack of molecular modules that are orthogonal to the host machinery, easy to reconfigure, and scalable. Here, we present a novel cell-to-cell communication system in Saccharomyces cerevisiae (yeast) based on CRISPR transcription factors and the plant hormone auxin that exhibits several of these features. Specifically, we engineered a sender strain of yeast that converts indole-3-acetamide (IAM) into auxin via the enzyme iaaH from Agrobacterium tumefaciens. To sense auxin and regulate transcription in a receiver strain, we engineered a reconfigurable library of auxin-degradable CRISPR transcription factors (ADCTFs). Auxin-induced degradation is achieved through fusion of an auxin-sensitive degron (from IAA corepressors) to the CRISPR TF and coexpression with an auxin F-box protein. Mirroring the tunability of auxin perception in plants, our family of ADCTFs exhibits a broad range of auxin sensitivities. We characterized the kinetics and steady-state behavior of the sender and receiver independently as well as in cocultures where both cell types were exposed to IAM. In the presence of IAM, auxin is produced by the sender cell and triggers deactivation of reporter expression in the receiver cell. The result is an orthogonal, rewireable, tunable, and, arguably, scalable cell-cell communication system for yeast and other eukaryotic cells. PMID:26102245

  19. The Conserved Glycine-Rich Segment Linking the N-Terminal Fusion Peptide to the Coiled Coil of Human T-Cell Leukemia Virus Type 1 Transmembrane Glycoprotein gp21 Is a Determinant of Membrane Fusion Function

    PubMed Central

    Wilson, Kirilee A.; Bär, Séverine; Maerz, Anne L.; Alizon, Marc; Poumbourios, Pantelis

    2005-01-01

    Retroviral transmembrane proteins (TMs) contain an N-terminal fusion peptide that initiates virus-cell membrane fusion. The fusion peptide is linked to the coiled-coil core through a conserved sequence that is often rich in glycines. We investigated the functional role of the glycine-rich segment, Met-326 to Ser-337, of the human T-cell leukemia virus type 1 (HTLV-1) TM, gp21, by alanine and proline scanning mutagenesis. Alanine substitution for the hydrophobic residue Ile-334 caused an ∼90% reduction in cell-cell fusion activity without detectable effects on the lipid-mixing and pore formation phases of fusion. Alanine substitutions at other positions had smaller effects (Gly-329, Val-330, and Gly-332) or no effect on fusion function. Proline substitution for glycine residues inhibited cell-cell fusion function with position-dependent effects on the three phases of fusion. Retroviral glycoprotein fusion function thus appears to require flexibility within the glycine-rich segment and hydrophobic contacts mediated by this segment. PMID:15767455

  20. The conserved glycine-rich segment linking the N-terminal fusion peptide to the coiled coil of human T-cell leukemia virus type 1 transmembrane glycoprotein gp21 is a determinant of membrane fusion function.

    PubMed

    Wilson, Kirilee A; Bär, Séverine; Maerz, Anne L; Alizon, Marc; Poumbourios, Pantelis

    2005-04-01

    Retroviral transmembrane proteins (TMs) contain an N-terminal fusion peptide that initiates virus-cell membrane fusion. The fusion peptide is linked to the coiled-coil core through a conserved sequence that is often rich in glycines. We investigated the functional role of the glycine-rich segment, Met-326 to Ser-337, of the human T-cell leukemia virus type 1 (HTLV-1) TM, gp21, by alanine and proline scanning mutagenesis. Alanine substitution for the hydrophobic residue Ile-334 caused an approximately 90% reduction in cell-cell fusion activity without detectable effects on the lipid-mixing and pore formation phases of fusion. Alanine substitutions at other positions had smaller effects (Gly-329, Val-330, and Gly-332) or no effect on fusion function. Proline substitution for glycine residues inhibited cell-cell fusion function with position-dependent effects on the three phases of fusion. Retroviral glycoprotein fusion function thus appears to require flexibility within the glycine-rich segment and hydrophobic contacts mediated by this segment. PMID:15767455

  1. 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

  2. Slow liner fusion

    SciTech Connect

    Shaffer, M.J.

    1997-08-01

    {open_quotes}Slow{close_quotes} liner fusion ({approximately}10 ms compression time) implosions are nondestructive and make repetitive ({approximately} 1 Hz) pulsed liner fusion reactors possible. This paper summarizes a General Atomics physics-based fusion reactor study that showed slow liner feasibility, even with conservative open-line axial magnetic field confinement and Bohm radial transport.

  3. Magneto-Inertial Fusion

    DOE PAGESBeta

    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.; et al

    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.

  4. 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.

  5. Cluster-impact fusion

    SciTech Connect

    Echenique, P.M.; Manson, J.R.; Ritchie, R.H. )

    1990-03-19

    We present a model for the cluster-impact-fusion experiments of Buehler, Friedlander, and Friedman, Calculated fusion rates as a function of bombarding energy for constant cluster size agree well with experiment. The dependence of the fusion rate on cluster size at fixed bombarding energy is explained qualitatively. The role of correlated, coherent collisions in enhanced energy loss by clusters is emphasized.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-07-01

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

  8. Calponin 3 regulates actin cytoskeleton rearrangement in trophoblastic cell fusion.

    PubMed

    Shibukawa, Yukinao; Yamazaki, Natsuko; Kumasawa, Keiichi; Daimon, Etsuko; Tajiri, Michiko; Okada, Yuka; Ikawa, Masahito; Wada, Yoshinao

    2010-11-15

    Cell-cell fusion is an intriguing differentiation process, essential for placental development and maturation. A proteomic approach identified a cytoplasmic protein, calponin 3 (CNN3), related to the fusion of BeWo choriocarcinoma cells. CNN3 was expressed in cytotrophoblasts in human placenta. CNN3 gene knockdown promoted actin cytoskeletal rearrangement and syncytium formation in BeWo cells, suggesting CNN3 to be a negative regulator of trophoblast fusion. Indeed, CNN3 depletion promoted BeWo cell fusion. CNN3 at the cytoplasmic face of cytoskeleton was dislocated from F-actin with forskolin treatment and diffused into the cytoplasm in a phosphorylation-dependent manner. Phosphorylation sites were located at Ser293/296 in the C-terminal region, and deletion of this region or site-specific disruption of Ser293/296 suppressed syncytium formation. These CNN3 mutants were colocalized with F-actin and remained there after forskolin treatment, suggesting that dissociation of CNN3 from F-actin is modulated by the phosphorylation status of the C-terminal region unique to CNN3 in the CNN family proteins. The mutant missing these phosphorylation sites displayed a dominant negative effect on cell fusion, while replacement of Ser293/296 with aspartic acid enhanced syncytium formation. These results indicated that CNN3 regulates actin cytoskeleton rearrangement which is required for the plasma membranes of trophoblasts to become fusion competent. PMID:20861310

  9. A role for a TIMP-3-sensitive, Zn(2+)-dependent metalloprotease in mammalian gamete membrane fusion.

    PubMed

    Correa, L M; Cho, C; Myles, D G; Primakoff, P

    2000-09-01

    During fertilization, sperm and egg plasma membranes adhere and then fuse by a mechanism that is not well understood. Zinc metalloproteases are necessary for some intercellular fusion events, for instance, cell-cell fusion in yeast. In this study we tested the effects of class-specific and family-specific protease inhibitors on mouse gamete fusion. Capacitated, acrosome-reacted sperm and zona-free eggs were used in assays designed to define the effects of inhibitors on sperm-egg plasma membrane binding or fusion. Inhibitors of the aspartic, cysteine, and serine protease classes had no effect on sperm-egg binding or fusion. Both a synthetic metalloprotease substrate (succinyl-Ala-Ala-Phe-amidomethylcoumarin) and the zinc chelator 1,10-phenanthroline inhibited sperm-egg fusion but did not decrease sperm-egg binding. The fusion-inhibition effect of phenanthroline was reversible and activity of the inhibitable zinc metalloprotease was shown to be required during a short time window, the first 15 min after insemination. Tissue inhibitor of metalloprotease-3 and Ro 31-9790, specific inhibitors of zinc metalloproteases in the matrixin and adamalysin families, also inhibited sperm-egg fusion but not sperm-egg binding. These data indicate a role in gamete fusion for one or more zinc metalloproteases of the matrixin and/or adamalysin families that act after plasma membrane binding and before sperm-egg membrane fusion. PMID:10964469

  10. Microtubule-dependent balanced cell contraction and luminal-matrix modification accelerate epithelial tube fusion.

    PubMed

    Kato, Kagayaki; Dong, Bo; Wada, Housei; Tanaka-Matakatsu, Miho; Yagi, Yoshimasa; Hayashi, Shigeo

    2016-01-01

    Connection of tubules into larger networks is the key process for the development of circulatory systems. In Drosophila development, tip cells of the tracheal system lead the migration of each branch and connect tubules by adhering to each other and simultaneously changing into a torus-shape. We show that as adhesion sites form between fusion cells, myosin and microtubules form polarized bundles that connect the new adhesion site to the cells' microtubule-organizing centres, and that E-cadherin and retrograde recycling endosomes are preferentially deposited at the new adhesion site. We demonstrate that microtubules help balancing tip cell contraction, which is driven by myosin, and is required for adhesion and tube fusion. We also show that retrograde recycling and directed secretion of a specific matrix protein into the fusion-cell interface promote fusion. We propose that microtubule bundles connecting these cell-cell interfaces coordinate cell contractility and apical secretion to facilitate tube fusion. PMID:27067650

  11. 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.

  12. The fusion breeder

    NASA Astrophysics Data System (ADS)

    Moir, Ralph W.

    1982-10-01

    The fusion breeder is a fusion reactor designed with special blankets to maximize the transmutation by 14 MeV neutrons of uranium-238 to plutonium or thorium to uranium-233 for use as a fuel for fission reactors. Breeding fissile fuels has not been a goal of the U.S. fusion energy program. This paper suggests it is time for a policy change to make the fusion breeder a goal of the U.S. fusion program and the U.S. nuclear energy program. There is wide agreement that many approaches will work and will produce fuel for five equal-sized LWRs, and some approach as many as 20 LWRs at electricity costs within 20% of those at today's price of uranium (30/lb of U3O8). The blankets designed to suppress fissioning, called symbiotes, fusion fuel factories, or just fusion breeders, will have safety characteristics more like pure fusion reactors and will support as many as 15 equal power LWRs. The blankets designed to maximize fast fission of fertile material will have safety characteristics more like fission reactors and will support 5 LWRs. This author strongly recommends development of the fission suppressed blanket type, a point of view not agreed upon by everyone. There is, however, wide agreement that, to meet the market price for uranium which would result in LWR electricity within 20% of today's cost with either blanket type, fusion components can cost severalfold more than would be allowed for pure fusion to meet the goal of making electricity alone at 20% over today's fission costs. Also widely agreed is that the critical-path-item for the fusion breeder is fusion development itself; however, development of fusion breeder specific items (blankets, fuel cycle) should be started now in order to have the fusion breeder by the time the rise in uranium prices forces other more costly choices.

  13. 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.

  14. 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.

  15. Macrophages and Cell-Cell Spread of HIV-1

    PubMed Central

    Waki, Kayoko; Freed, Eric O.

    2010-01-01

    Macrophages have been postulated to play an important role in the pathogenesis of HIV-1 infection. Their ability to cross the blood-brain barrier and their resistance to virus-induced cytopathic effects allows them to serve as reservoirs for long-term infection. Thus, exploring the mechanisms of virus transmission from macrophages to target cells such as other macrophages or T lymphocytes is central to our understanding of HIV-1 pathogenesis and progression to AIDS, and is vital to the development of vaccines and novel antiretroviral therapies. This review provides an overview of the current understanding of cell-cell transmission in macrophages. PMID:21552427

  16. Polybasic KKR Motif in the Cytoplasmic Tail of Nipah Virus Fusion Protein Modulates Membrane Fusion by Inside-Out Signaling▿

    PubMed Central

    Aguilar, Hector C.; Matreyek, Kenneth A.; Choi, Daniel Y.; Filone, Claire Marie; Young, Sophia; Lee, Benhur

    2007-01-01

    The cytoplasmic tails of the envelope proteins from multiple viruses are known to contain determinants that affect their fusogenic capacities. Here we report that specific residues in the cytoplasmic tail of the Nipah virus fusion protein (NiV-F) modulate its fusogenic activity. Truncation of the cytoplasmic tail of NiV-F greatly inhibited cell-cell fusion. Deletion and alanine scan analysis identified a tribasic KKR motif in the membrane-adjacent region as important for modulating cell-cell fusion. The K1A mutation increased fusion 5.5-fold, while the K2A and R3A mutations decreased fusion 3- to 5-fold. These results were corroborated in a reverse-pseudotyped viral entry assay, where receptor-pseudotyped reporter virus was used to infect cells expressing wild-type or mutant NiV envelope glycoproteins. Differential monoclonal antibody binding data indicated that hyper- or hypofusogenic mutations in the KKR motif affected the ectodomain conformation of NiV-F, which in turn resulted in faster or slower six-helix bundle formation, respectively. However, we also present evidence that the hypofusogenic phenotypes of the K2A and R3A mutants were effected via distinct mechanisms. Interestingly, the K2A mutant was also markedly excluded from lipid rafts, where ∼20% of wild-type F and the other mutants can be found. Finally, we found a strong negative correlation between the relative fusogenic capacities of these cytoplasmic-tail mutants and the avidities of NiV-F and NiV-G interactions (P = 0.007, r2 = 0.82). In toto, our data suggest that inside-out signaling by specific residues in the cytoplasmic tail of NiV-F can modulate its fusogenicity by multiple distinct mechanisms. PMID:17301148

  17. 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.

  18. Phosphatidylserine directly and positively regulates fusion of myoblasts into myotubes.

    PubMed

    Jeong, Jaemin; Conboy, Irina M

    2011-10-14

    Cell membrane consists of various lipids such as phosphatidylserine (PS), phosphatidylcholine (PC), and phosphatidylethanolamine (PE). Among them, PS is a molecular marker of apoptosis, because it is located to the inner leaflet of plasma membrane generally but it is moved to the outer leaflet during programmed cell death. The process of apoptosis has been implicated in the fusion of muscle progenitor cells, myoblasts, into myotubes. However, it remained unclear whether PS regulates muscle cell differentiation directly. In this paper, localization of PS to the outer leaflet of plasma membrane in proliferating primary myoblasts and during fusion of these myoblasts into myotubes is validated using Annexin V. Moreover, we show the presence of PS clusters at the cell-cell contact points, suggesting the importance of membrane ruffling and PS exposure for the myogenic cell fusion. Confirming this conclusion, experimentally constructed PS, but not PC liposomes dramatically enhance the formation of myotubes from myoblasts, thus demonstrating a direct positive effect of PS on the muscle cell fusion. In contrast, myoblasts exposed to PC liposomes produce long myotubes with low numbers of myonuclei. Moreover, pharmacological masking of PS on the myoblast surface inhibits fusion of these cells into myotubes in a dose-dependent manner. PMID:21910971

  19. Proteomics of cell-cell interactions in health and disease.

    PubMed

    Lindoso, Rafael S; Sandim, Vanessa; Collino, Federica; Carvalho, Adriana B; Dias, Juliana; da Costa, Milene R; Zingali, Russolina B; Vieyra, Adalberto

    2016-01-01

    The mechanisms of cell-cell communications are now under intense study by proteomic approaches. Proteomics has unraveled changes in protein profiling as the result of cell interactions mediated by ligand/receptor, hormones, soluble factors, and the content of extracellular vesicles. Besides being a brief overview of the main and profitable methodologies now available (evaluating theory behind the methods, their usefulness, and pitfalls), this review focuses on-from a proteome perspective-some signaling pathways and post-translational modifications (PTMs), which are essential for understanding ischemic lesions and their recovery in two vital organs in mammals, the heart, and the kidney. Knowledge of misdirection of the proteome during tissue recovery, such as represented by the convergence between fibrosis and cancer, emerges as an important tool in prognosis. Proteomics of cell-cell interaction is also especially useful for understanding how stem cells interact in injured tissues, anticipating clues for rational therapeutic interventions. In the effervescent field of induced pluripotency and cell reprogramming, proteomic studies have shown what proteins from specialized cells contribute to the recovery of infarcted tissues. Overall, we conclude that proteomics is at the forefront in helping us to understand the mechanisms that underpin prevalent pathological processes. PMID:26552723

  20. 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.

  1. 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…

  2. 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…

  3. Decomposition of incomplete fusion

    SciTech Connect

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

    1989-01-01

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

  4. Identification and characterization of LFD1, a novel protein involved in membrane merger during cell fusion in Neurospora crassa.

    PubMed

    Palma-Guerrero, Javier; Leeder, Abigail C; Welch, Juliet; Glass, N Louise

    2014-04-01

    Despite its essential role in development, molecular mechanisms of membrane merger during cell-cell fusion in most eukaryotic organisms remain elusive. In the filamentous fungus Neurospora crassa, cell fusion occurs during asexual spore germination, where genetically identical germlings show chemotropic interactions and cell-cell fusion. Fusion of germlings and hyphae is required for the formation of the interconnected mycelial network characteristic of filamentous fungi. Previously, a multipass membrane protein, PRM1, was characterized and acts at the step of bilayer fusion in N. crassa. Here we describe the identification and characterization of lfd-1, encoding a single pass transmembrane protein, which is also involved in membrane merger. lfd-1 was identified by a targeted analysis of a transcriptional profile of a transcription factor mutant (Δpp-1) defective in germling fusion. The Δlfd-1 mutant shows a similar, but less severe, membrane merger defect as a ΔPrm1 mutant. By genetic analyses, we show that LFD1 and PRM1 act independently, but share a redundant function. The cell fusion frequency of both Δlfd-1 and ΔPrm1 mutants was sensitive to extracellular calcium concentration and was associated with an increase in cell lysis, which was suppressed by a calcium-dependent mechanism involving a homologue to synaptotagmin. PMID:24673848

  5. Manipulation of cellular spheroid composition and the effects on vascular tissue fusion.

    PubMed

    Olsen, T R; Mattix, B; Casco, M; Herbst, A; Williams, C; Tarasidis, A; Simionescu, D; Visconti, R P; Alexis, F

    2015-02-01

    Cellular spheroids were investigated as tissue-engineered building blocks that can be fused to form functional tissue constructs. While spheroids can be assembled using passive contacts for the fusion of complex tissues, physical forces can be used to promote active contacts to improve tissue homogeneity and accelerate tissue fusion. Understanding the mechanisms affecting the fusion of spheroids is critical to fabricating tissues. Here, manipulation of the spheroid composition was used to accelerate the fusion process mediated by magnetic forces. The Janus structure of magnetic cellular spheroids spatially controls iron oxide magnetic nanoparticles (MNPs) to form two distinct domains: cells and extracellular MNPs. Studies were performed to evaluate the influence of extracellular matrix (ECM) content and cell number on the fusion of Janus magnetic cellular spheroids (JMCSs). Results showed that the integration of iron oxide MNPs into spheroids increased the production of collagen over time when compared to spheroids without MNPs. The results also showed that ring tissues composed of JMCSs with high ECM concentrations and high cell numbers fused together, but exhibited less contraction when compared to their lower concentration counterparts. Results from spheroid fusion in capillary tubes showed that low ECM concentrations and high cell numbers experienced more fusion and cellular intermixing over time when compared to their higher counterparts. These findings indicate that cell-cell and cell-matrix interactions play an important role in regulating fusion, and this understanding sets the rationale of spheroid composition to fabricate larger and more complex tissue-engineered constructs. PMID:25463485

  6. Cell-Cell Interactions during pollen tube guidance

    SciTech Connect

    Daphne Preuss

    2009-03-31

    The long-term goal of this research is to identify the signaling molecules that mediate plant cell-cell interactions during pollination. The immediate goals of this project are to perform genetic and molecular analysis of pollen tube guidance. Specifically, we proposed to: 1. Characterize the pistil components that direct pollen tube navigation using the Arabidopsis thaliana in vitro pollen tube guidance system 2. Identify pistil signals that direct pollen tube guidance by a) using microarrays to profile gene expression in developing pistils, and b) employing proteomics and metabolomics to isolate pollen tube guidance signals. 3. Explore the genetic basis of natural variation in guidance signals, comparing the in vitro interactions between pollen and pistils from A. thaliana and its close relatives.

  7. Rapid Prototyping of Heterotypic Cell-Cell Contacts

    PubMed Central

    Scott, Carl; Ho, Chia-Chi; Co, Carlos C.

    2014-01-01

    Disparities in cellular behaviour between cultures of a single cell type and heterogeneous co-cultures require constructing spatially-defined arrays of multiple cell types. Such arrays are critical for investigating cellular properties as they exist in vivo. Current methods rely upon covalent surface modification or external physical micromanipulation to control cellular organization on a limited range of substrates. Here, we report a direct approach for creating co-cultures of different cell types by microcontact printing a photosensitive cell resist. The cell-resistant polymer converts to cell adhesive 0 with light exposure, thus the initial copolymer pattern dictates the position of both cell types. This strategy enables straightforward preparation of tailored heterotypic cell-cell contacts on materials ranging from polymers to metallic substrates. PMID:24466428

  8. A Continuum Approach to Modelling Cell-Cell Adhesion

    PubMed Central

    Armstrong, Nicola J.; Painter, Kevin J.; Sherratt, Jonathan A.

    2007-01-01

    Cells adhere to each other through the binding of cell adhesion molecules at the cell surface. This process, known as cell-cell adhesion, is fundamental in many areas of biology, including early embryo development, tissue homeostasis and tumour growth. In this paper we develop a new continuous mathematical model of this phenomenon by considering the movement of cells in response to the adhesive forces generated through binding. We demonstrate that our model predicts the aggregation behaviour of a disassociated adhesive cell population. Further, when the model is extended to represent the interactions between multiple populations, we demonstrate that it is capable of replicating the different types of cell sorting behaviour observed experimentally. The resulting pattern formation is a direct consequence of the relative strengths of self-population and cross-population adhesive bonds in the model. While cell sorting behaviour has been captured previously with discrete approaches, it has not, until now, been observed with a fully continuous model. PMID:16860344

  9. Hepatitis C virus cell-cell transmission and resistance to direct-acting antiviral agents.

    PubMed

    Xiao, Fei; Fofana, Isabel; Heydmann, Laura; Barth, Heidi; Soulier, Eric; Habersetzer, François; Doffoël, Michel; Bukh, Jens; Patel, Arvind H; Zeisel, Mirjam B; Baumert, Thomas F

    2014-05-01

    Hepatitis C virus (HCV) is transmitted between hepatocytes via classical cell entry but also uses direct cell-cell transfer to infect neighboring hepatocytes. Viral cell-cell transmission has been shown to play an important role in viral persistence allowing evasion from neutralizing antibodies. In contrast, the role of HCV cell-cell transmission for antiviral resistance is unknown. Aiming to address this question we investigated the phenotype of HCV strains exhibiting resistance to direct-acting antivirals (DAAs) in state-of-the-art model systems for cell-cell transmission and spread. Using HCV genotype 2 as a model virus, we show that cell-cell transmission is the main route of viral spread of DAA-resistant HCV. Cell-cell transmission of DAA-resistant viruses results in viral persistence and thus hampers viral eradication. We also show that blocking cell-cell transmission using host-targeting entry inhibitors (HTEIs) was highly effective in inhibiting viral dissemination of resistant genotype 2 viruses. Combining HTEIs with DAAs prevented antiviral resistance and led to rapid elimination of the virus in cell culture model. In conclusion, our work provides evidence that cell-cell transmission plays an important role in dissemination and maintenance of resistant variants in cell culture models. Blocking virus cell-cell transmission prevents emergence of drug resistance in persistent viral infection including resistance to HCV DAAs. PMID:24830295

  10. Hepatitis C Virus Cell-Cell Transmission and Resistance to Direct-Acting Antiviral Agents

    PubMed Central

    Heydmann, Laura; Barth, Heidi; Soulier, Eric; Habersetzer, François; Doffoël, Michel; Bukh, Jens; Patel, Arvind H.; Zeisel, Mirjam B.; Baumert, Thomas F.

    2014-01-01

    Hepatitis C virus (HCV) is transmitted between hepatocytes via classical cell entry but also uses direct cell-cell transfer to infect neighboring hepatocytes. Viral cell-cell transmission has been shown to play an important role in viral persistence allowing evasion from neutralizing antibodies. In contrast, the role of HCV cell-cell transmission for antiviral resistance is unknown. Aiming to address this question we investigated the phenotype of HCV strains exhibiting resistance to direct-acting antivirals (DAAs) in state-of-the-art model systems for cell-cell transmission and spread. Using HCV genotype 2 as a model virus, we show that cell-cell transmission is the main route of viral spread of DAA-resistant HCV. Cell-cell transmission of DAA-resistant viruses results in viral persistence and thus hampers viral eradication. We also show that blocking cell-cell transmission using host-targeting entry inhibitors (HTEIs) was highly effective in inhibiting viral dissemination of resistant genotype 2 viruses. Combining HTEIs with DAAs prevented antiviral resistance and led to rapid elimination of the virus in cell culture model. In conclusion, our work provides evidence that cell-cell transmission plays an important role in dissemination and maintenance of resistant variants in cell culture models. Blocking virus cell-cell transmission prevents emergence of drug resistance in persistent viral infection including resistance to HCV DAAs. PMID:24830295

  11. 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.

  12. The Plasma Membrane Proteins Prm1 and Fig1 Ascertain Fidelity of Membrane Fusion during Yeast Mating

    PubMed Central

    Engel, Alex; Walter, Peter

    2007-01-01

    As for most cell–cell fusion events, the molecular details of membrane fusion during yeast mating are poorly understood. The multipass membrane protein Prm1 is the only known component that acts at the step of bilayer fusion. In its absence, mutant mating pairs lyse or arrest in the mating reaction with tightly apposed plasma membranes. We show that deletion of FIG 1, which controls pheromone-induced Ca2+ influx, yields similar cell fusion defects. Although extracellular Ca2+ is not required for efficient cell fusion of wild-type cells, cell fusion in prm1 mutant mating pairs is dramatically reduced when Ca2+ is removed. This enhanced fusion defect is due to lysis. Time-lapse microscopy reveals that fusion and lysis events initiate with identical kinetics, suggesting that both outcomes result from engagement of the fusion machinery. The yeast synaptotagmin orthologue and Ca2+ binding protein Tcb3 has a role in reducing lysis of prm1 mutants, which opens the possibility that the observed role of Ca2+ is to engage a wound repair mechanism. Thus, our results suggest that Prm1 and Fig1 have a role in enhancing membrane fusion and maintaining its fidelity. Their absence results in frequent mating pair lysis, which is counteracted by Ca2+-dependent membrane repair. PMID:17151357

  13. 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.

  14. 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

  15. Progress toward fusion energy

    SciTech Connect

    Thomassen, K.I.

    1981-03-11

    This paper summarizes the basis for the present optimism in the magnetic fusion program, and describes some of the remaining tasks leading to a demonstration power reactor and the primary technologies necessary for that endeavor.

  16. Label fusion strategy selection.

    PubMed

    Robitaille, Nicolas; Duchesne, Simon

    2012-01-01

    Label fusion is used in medical image segmentation to combine several different labels of the same entity into a single discrete label, potentially more accurate, with respect to the exact, sought segmentation, than the best input element. Using simulated data, we compared three existing label fusion techniques-STAPLE, Voting, and Shape-Based Averaging (SBA)-and observed that none could be considered superior depending on the dissimilarity between the input elements. We thus developed an empirical, hybrid technique called SVS, which selects the most appropriate technique to apply based on this dissimilarity. We evaluated the label fusion strategies on two- and three-dimensional simulated data and showed that SVS is superior to any of the three existing methods examined. On real data, we used SVS to perform fusions of 10 segmentations of the hippocampus and amygdala in 78 subjects from the ICBM dataset. SVS selected SBA in almost all cases, which was the most appropriate method overall. PMID:22518113

  17. HIV-1 Fusion Assay

    PubMed Central

    Cavrois, Marielle; Neidleman, Jason; Greene, Warner C.

    2016-01-01

    The HIV-1 fusion assay measures all steps in the HIV-1 life cycle up to and including viral fusion. It relies on the incorporation of a β-lactamase Vpr (BlaM-Vpr) protein chimera into the virion and the subsequent transfer of this chimera into the target cell by fusion (Figure 1). The transfer is monitored by the enzymatic cleavage of CCF2, a fluorescent dye substrate of β-lactamase, loaded into the target cells. Cleavage of the β-lactam ring in CCF2 by β-lactamase changes the fluorescence emission spectrum of the dye from green (520 nm) to blue (447 nm). This change reflects virion fusion and can be detected by flow cytometry (Figure 2).

  18. Fusion power demonstration

    SciTech Connect

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

    1983-09-01

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

  19. 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)

  20. 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.

  1. Glossary of fusion energy

    SciTech Connect

    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.

  2. Advances in fusion technology

    NASA Astrophysics Data System (ADS)

    Baker, Charles C.

    2000-12-01

    The US fusion technology program is an essential element in the development of the knowledge base for an attractive fusion power source. The technology program incorporates both near and long term R&D, contributes to material and engineering sciences as well as technology development, ranges from hardware production to theory and modeling, contributes significantly to spin-off applications, and performs global systems assessments and focused design studies.

  3. 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.

  4. ITER Fusion Energy

    ScienceCinema

    Dr. Norbert Holtkamp

    2010-01-08

    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.

  5. Protrusive Activity Guides Changes in Cell-Cell Tension during Epithelial Cell Scattering

    PubMed Central

    Maruthamuthu, Venkat; Gardel, Margaret L.

    2014-01-01

    Knowing how epithelial cells regulate cell-matrix and cell-cell adhesions is essential to understand key events in morphogenesis as well as pathological events such as metastasis. During epithelial cell scattering, epithelial cell islands rupture their cell-cell contacts and migrate away as single cells on the extracellular matrix (ECM) within hours of growth factor stimulation, even as adhesion molecules such as E-cadherin are present at the cell-cell contact. How the stability of cell-cell contacts is modulated to effect such morphological transitions is still unclear. Here, we report that in the absence of ECM, E-cadherin adhesions continue to sustain substantial cell-generated forces upon hepatocyte growth factor (HGF) stimulation, consistent with undiminished adhesion strength. In the presence of focal adhesions, constraints that preclude the spreading and movement of cells at free island edges also prevent HGF-mediated contact rupture. To explore the role of cell motion and cell-cell contact rupture, we examine the biophysical changes that occur during the scattering of cell pairs. We show that the direction of cell movement with respect to the cell-cell contact is correlated with changes in the average intercellular force as well as the initial direction of cell-cell contact rupture. Our results suggest an important role for protrusive activity resulting in cell displacement and force redistribution in guiding cell-cell contact rupture during scattering. PMID:25099795

  6. Surface density of the Hendra G protein modulates Hendra F protein-promoted membrane fusion: Role for Hendra G protein trafficking and degradation

    SciTech Connect

    Whitman, Shannon D.; Dutch, Rebecca Ellis . E-mail: rdutc2@uky.edu

    2007-07-05

    Hendra virus, like most paramyxoviruses, requires both a fusion (F) and attachment (G) protein for promotion of cell-cell fusion. Recent studies determined that Hendra F is proteolytically processed by the cellular protease cathepsin L after endocytosis. This unique cathepsin L processing results in a small percentage of Hendra F on the cell surface. To determine how the surface densities of the two Hendra glycoproteins affect fusion promotion, we performed experiments that varied the levels of glycoproteins expressed in transfected cells. Using two different fusion assays, we found a marked increase in fusion when expression of the Hendra G protein was increased, with a 1:1 molar ratio of Hendra F:G on the cell surface resulting in optimal membrane fusion. Our results also showed that Hendra G protein levels are modulated by both more rapid protein turnover and slower protein trafficking than is seen for Hendra F.

  7. Phosphatidylserine directly and positively regulates fusion of myoblasts into myotubes

    SciTech Connect

    Jeong, Jaemin; Conboy, Irina M.

    2011-10-14

    Highlights: {yields} PS broadly and persistently trans-locates to the outer leaflet of plasma membrane during myoblast fusion into myotubes. {yields} Robust myotubes are formed when PS liposomes are added exogenously. {yields} PS increases the width of de novo myotubes and the numbers of myonuclei, but not the myotube length. {yields} Annexin V or PS antibody inhibits myotube formation by masking exposed PS. -- Abstract: Cell membrane consists of various lipids such as phosphatidylserine (PS), phosphatidylcholine (PC), and phosphatidylethanolamine (PE). Among them, PS is a molecular marker of apoptosis, because it is located to the inner leaflet of plasma membrane generally but it is moved to the outer leaflet during programmed cell death. The process of apoptosis has been implicated in the fusion of muscle progenitor cells, myoblasts, into myotubes. However, it remained unclear whether PS regulates muscle cell differentiation directly. In this paper, localization of PS to the outer leaflet of plasma membrane in proliferating primary myoblasts and during fusion of these myoblasts into myotubes is validated using Annexin V. Moreover, we show the presence of PS clusters at the cell-cell contact points, suggesting the importance of membrane ruffling and PS exposure for the myogenic cell fusion. Confirming this conclusion, experimentally constructed PS, but not PC liposomes dramatically enhance the formation of myotubes from myoblasts, thus demonstrating a direct positive effect of PS on the muscle cell fusion. In contrast, myoblasts exposed to PC liposomes produce long myotubes with low numbers of myonuclei. Moreover, pharmacological masking of PS on the myoblast surface inhibits fusion of these cells into myotubes in a dose-dependent manner.

  8. N-Glycans on the Nipah Virus Attachment Glycoprotein Modulate Fusion and Viral Entry as They Protect against Antibody Neutralization

    PubMed Central

    Biering, Scott B.; Huang, Andrew; Vu, Andy T.; Robinson, Lindsey R.; Bradel-Tretheway, Birgit; Choi, Eric

    2012-01-01

    Nipah virus (NiV) is the deadliest known paramyxovirus. Membrane fusion is essential for NiV entry into host cells and for the virus' pathological induction of cell-cell fusion (syncytia). The mechanism by which the attachment glycoprotein (G), upon binding to the cell receptors ephrinB2 or ephrinB3, triggers the fusion glycoprotein (F) to execute membrane fusion is largely unknown. N-glycans on paramyxovirus glycoproteins are generally required for proper protein conformational integrity, transport, and sometimes biological functions. We made conservative mutations (Asn to Gln) at the seven potential N-glycosylation sites in the NiV G ectodomain (G1 to G7) individually or in combination. Six of the seven N-glycosylation sites were found to be glycosylated. Moreover, pseudotyped virions carrying these N-glycan mutants had increased antibody neutralization sensitivities. Interestingly, our results revealed hyperfusogenic and hypofusogenic phenotypes for mutants that bound ephrinB2 at wild-type levels, and the mutant's cell-cell fusion phenotypes generally correlated to viral entry levels. In addition, when removing multiple N-glycans simultaneously, we observed synergistic or dominant-negative membrane fusion phenotypes. Interestingly, our data indicated that 4- to 6-fold increases in fusogenicity resulted from multiple mechanisms, including but not restricted to the increase of F triggering. Altogether, our results suggest that NiV-G N-glycans play a role in shielding virions against antibody neutralization, while modulating cell-cell fusion and viral entry via multiple mechanisms. PMID:22915812

  9. Optofluidic realization and retaining of cell-cell contact using an abrupt tapered optical fibre

    NASA Astrophysics Data System (ADS)

    Xin, Hongbao; Zhang, Yao; Lei, Hongxiang; Li, Yayi; Zhang, Huixian; Li, Baojun

    2013-06-01

    Studies reveal that there exists much interaction and communication between bacterial cells, with parts of these social behaviors depending on cell-cell contacts. The cell-cell contact has proved to be crucial for determining various biochemical processes. However, for cell culture with relatively low cell concentration, it is difficult to precisely control and retain the contact of a small group of cells. Particularly, the retaining of cell-cell contact is difficult when flows occur in the medium. Here, we report an optofluidic method for realization and retaining of Escherichia coli cell-cell contact in a microfluidic channel using an abrupt tapered optical fibre. The contact process is based on launching a 980-nm wavelength laser into the fibre, E. coli cells were trapped onto the fibre tip one after another, retaining cell-cell contact and forming a highly organized cell chain. The formed chains further show the ability as bio-optical waveguides.

  10. Robotic adherent cell injection for characterizing cell-cell communication.

    PubMed

    Liu, Jun; Siragam, Vinayakumar; Gong, Zheng; Chen, Jun; Fridman, Michael D; Leung, Clement; Lu, Zhe; Ru, Changhai; Xie, Shaorong; Luo, Jun; Hamilton, Robert M; Sun, Yu

    2015-01-01

    Compared to robotic injection of suspended cells (e.g., embryos and oocytes), fewer attempts were made to automate the injection of adherent cells (e.g., cancer cells and cardiomyocytes) due to their smaller size, highly irregular morphology, small thickness (a few micrometers thick), and large variations in thickness across cells. This paper presents a robotic system for automated microinjection of adherent cells. The system is embedded with several new capabilities: automatically locating micropipette tips; robustly detecting the contact of micropipette tip with cell culturing surface and directly with cell membrane; and precisely compensating for accumulative positioning errors. These new capabilities make it practical to perform adherent cell microinjection truly via computer mouse clicking in front of a computer monitor, on hundreds and thousands of cells per experiment (versus a few to tens of cells as state of the art). System operation speed, success rate, and cell viability rate were quantitatively evaluated based on robotic microinjection of over 4000 cells. This paper also reports the use of the new robotic system to perform cell-cell communication studies using large sample sizes. The gap junction function in a cardiac muscle cell line (HL-1 cells), for the first time, was quantified with the system. PMID:25073160

  11. Heterochrony as Diachronically Modified Cell-Cell Interactions

    PubMed Central

    Torday, John S.

    2016-01-01

    Heterochrony is an enabling concept in evolution theory that metaphorically captures the mechanism of biologic change due to mechanisms of growth and development. The spatio-temporal patterns of morphogenesis are determined by cell-to-cell signaling mediated by specific soluble growth factors and their cognate receptors on nearby cells of different germline origins. Subsequently, down-stream production of second messengers generates patterns of form and function. Environmental upheavals such as Romer’s hypothesized drying up of bodies of water globally caused the vertebrate water-land transition. That transition caused physiologic stress, modifying cell-cell signaling to generate terrestrial adaptations of the skeleton, lung, skin, kidney and brain. These tissue-specific remodeling events occurred as a result of the duplication of the Parathyroid Hormone-related Protein Receptor (PTHrPR) gene, expressed in mesodermal fibroblasts in close proximity to ubiquitously expressed endodermal PTHrP, amplifying this signaling pathway. Examples of how and why PTHrPR amplification affected the ontogeny, phylogeny, physiology and pathophysiology of the lung are used to substantiate and further our understanding through insights to the heterochronic mechanisms of evolution, such as the fish swim bladder evolving into the vertebrate lung, interrelated by such functional homologies as surfactant and mechanotransduction. Instead of the conventional description of this phenomenon, lung evolution can now be understood as adaptive changes in the cellular-molecular signaling mechanisms underlying its ontogeny and phylogeny. PMID:26784244

  12. Heterochrony as Diachronically Modified Cell-Cell Interactions.

    PubMed

    Torday, John S

    2016-01-01

    Heterochrony is an enabling concept in evolution theory that metaphorically captures the mechanism of biologic change due to mechanisms of growth and development. The spatio-temporal patterns of morphogenesis are determined by cell-to-cell signaling mediated by specific soluble growth factors and their cognate receptors on nearby cells of different germline origins. Subsequently, down-stream production of second messengers generates patterns of form and function. Environmental upheavals such as Romer's hypothesized drying up of bodies of water globally caused the vertebrate water-land transition. That transition caused physiologic stress, modifying cell-cell signaling to generate terrestrial adaptations of the skeleton, lung, skin, kidney and brain. These tissue-specific remodeling events occurred as a result of the duplication of the Parathyroid Hormone-related Protein Receptor (PTHrPR) gene, expressed in mesodermal fibroblasts in close proximity to ubiquitously expressed endodermal PTHrP, amplifying this signaling pathway. Examples of how and why PTHrPR amplification affected the ontogeny, phylogeny, physiology and pathophysiology of the lung are used to substantiate and further our understanding through insights to the heterochronic mechanisms of evolution, such as the fish swim bladder evolving into the vertebrate lung, interrelated by such functional homologies as surfactant and mechanotransduction. Instead of the conventional description of this phenomenon, lung evolution can now be understood as adaptive changes in the cellular-molecular signaling mechanisms underlying its ontogeny and phylogeny. PMID:26784244

  13. Precision of multicellular gradient sensing with cell-cell communication

    NASA Astrophysics Data System (ADS)

    Mugler, Andrew; Levchenko, Andre; Nemenman, Ilya

    Gradient sensing underlies diverse biological processes. In principle, bigger ``detectors'' (cells or groups of cells) make better sensors, since then concentrations measured at the front and back of a detector are more different, and the gradient can be determined with higher precision. Indeed, experiments have shown that populations of cells detect gradients more precisely than single cells. However, this argument neglects the fact that information must be communicated between different parts of the detector, and the communication process introduces its own noise. Here we derive the fundamental limits to the precision of gradient sensing with cell-cell communication and temporal integration. We find that communication imposes its own sensory length scale, beyond which the precision cannot increase no matter how large the cell population grows. We also find that temporal integration couples the internal communication with the external signal diffusion, imposing an additional limit on the precision. We discuss how these limits can be improved by a strategy with two communicated molecular species, which we term ``regional excitation--global inhibition''. We compare our findings to experiments with communicating epithelial cells, and infer a sensor length scale of about 4 cells.

  14. The Evolutionary Origin of Epithelial Cell-Cell Adhesion Mechanisms

    PubMed Central

    Miller, Phillip W.; Clarke, Donald N.; Weis, William I.; Lowe, Christopher J.; Nelson, W. James

    2014-01-01

    SUMMARY A simple epithelium forms a barrier between the outside and the inside of an organism, and is the first organized multicellular tissue found in evolution. We examine the relationship between the evolution of epithelia and specialized cell-cell adhesion proteins comprising the classical cadherin/β-catenin/α-catenin complex (CCC). A review of the divergent functional properties of the CCC in metazoans and non-metazoans, and an updated phylogenetic coverage of the CCC using recent genomic data reveal: 1) The core CCC likely originated before the last common ancestor of unikonts and their closest bikont sister taxa. 2) Formation of the CCC may have constrained sequence evolution of the classical cadherin cytoplasmic domain and β-catenin in metazoa. 3) The α-catenin binding domain in β-catenin appears to be the favored mutation site for disrupting β-catenin function in the CCC. 4) The ancestral function of the α/β-catenin heterodimer appears to be an actin-binding module. In some metazoan groups, more complex functions of α-catenin were gained by sequence divergence in the non-actin binding (N-, M-) domains. 5) Allosteric regulation of α-catenin, rather than loss of function mutations, may have evolved for more complex regulation of the actin cytoskeleton. PMID:24210433

  15. Microvesicles as cell-cell messengers in cardiovascular diseases.

    PubMed

    Loyer, Xavier; Vion, Anne-Clémence; Tedgui, Alain; Boulanger, Chantal M

    2014-01-17

    Cell-cell communication has proven to be even more complex than previously thought since the discovery that extracellular vesicles serve as containers of biological information on various pathophysiological settings. Extracellular vesicles are classified into exosomes, microvesicles/microparticles, or apoptotic bodies, originating from different subcellular compartments. The cellular machinery controlling their formation and composition, as well as the mechanisms regulating their extracellular release, remain unfortunately much unknown. Extracellular vesicles have been found in plasma, urine, saliva, and inflammatory tissues. Their biomarker potential has raised significant interest in the cardiovascular field because the vesicle composition and microRNA content are specific signatures of cellular activation and injury. More than simply cell dust, extracellular vesicles are capable of transferring biological information to neighboring cells and play an active role in inflammatory diseases, including atherosclerosis and angiogenesis. The molecular interactions regulating these effects involve specific receptor activation, proteolytic enzymes, reactive oxygen species, or delivery of genetic information to target cells. Unraveling their mechanisms of action will likely open new therapeutic avenues. PMID:24436430

  16. 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

  17. Novel Inhibitors of Influenza Virus Fusion: Structure-Activity Relationship and Interaction with the Viral Hemagglutinin▿

    PubMed Central

    Vanderlinden, Evelien; Göktaş, Fusun; Cesur, Zafer; Froeyen, Matheus; Reed, Mark L.; Russell, Charles J.; Cesur, Nesrin; Naesens, Lieve

    2010-01-01

    A new class of N-(1-thia-4-azaspiro[4.5]decan-4-yl)carboxamide inhibitors of influenza virus hemagglutinin (HA)-mediated membrane fusion that has a narrow and defined structure-activity relationship was identified. In Madin-Darby canine kidney (MDCK) cells infected with different strains of human influenza virus A/H3N2, the lead compound, 4c, displayed a 50% effective concentration of 3 to 23 μM and an antiviral selectivity index of 10. No activity was observed for A/H1N1, A/H5N1, A/H7N2, and B viruses. The activity of 4c was reduced considerably when added 30 min or later postinfection, indicating that 4c inhibits an early step in virus replication. 4c and its congeners inhibited influenza A/H3N2 virus-induced erythrocyte hemolysis at low pH. 4c-resistant virus mutants, selected in MDCK cells, contained either a single D112N change in the HA2 subunit of the viral HA or a combination of three substitutions, i.e., R220S (in HA1) and E57K (in HA2) and an A-T substitution at position 43 or 96 of HA2. The mutants showed efficiency for receptor binding and replication similar to that of wild-type virus yet displayed an increased pH of erythrocyte hemolysis. In polykaryon assays with cells expressing single-mutant HA proteins, the E57K, A96T, and D112N mutations resulted in 4c resistance, and the HA proteins containing R220S, A96T, and D112N mutations displayed an increased fusion pH. Molecular modeling identified a binding cavity for 4c involving arginine-54 and glutamic acid-57 in the HA2 subunit. Our studies with the new fusion inhibitor 4c confirm the importance of this HA region in the development of influenza virus fusion inhibitors. PMID:20181685

  18. Lateral Lumbar Interbody Fusion

    PubMed Central

    Hughes, Alexander; Girardi, Federico; Sama, Andrew; Lebl, Darren; Cammisa, Frank

    2015-01-01

    The lateral lumbar interbody fusion (LLIF) is a relatively new technique that allows the surgeon to access the intervertebral space from a direct lateral approach either anterior to or through the psoas muscle. This approach provides an alternative to anterior lumbar interbody fusion with instrumentation, posterior lumbar interbody fusion, and transforaminal lumbar interbody fusion for anterior column support. LLIF is minimally invasive, safe, better structural support from the apophyseal ring, potential for coronal plane deformity correction, and indirect decompression, which have has made this technique popular. LLIF is currently being utilized for a variety of pathologies including but not limited to adult de novo lumbar scoliosis, central and foraminal stenosis, spondylolisthesis, and adjacent segment degeneration. Although early clinical outcomes have been good, the potential for significant neurological and vascular vertebral endplate complications exists. Nevertheless, LLIF is a promising technique with the potential to more effectively treat complex adult de novo scoliosis and achieve predictable fusion while avoiding the complications of traditional anterior surgery and posterior interbody techniques. PMID:26713134

  19. Lateral Lumbar Interbody Fusion.

    PubMed

    Pawar, Abhijit; Hughes, Alexander; Girardi, Federico; Sama, Andrew; Lebl, Darren; Cammisa, Frank

    2015-12-01

    The lateral lumbar interbody fusion (LLIF) is a relatively new technique that allows the surgeon to access the intervertebral space from a direct lateral approach either anterior to or through the psoas muscle. This approach provides an alternative to anterior lumbar interbody fusion with instrumentation, posterior lumbar interbody fusion, and transforaminal lumbar interbody fusion for anterior column support. LLIF is minimally invasive, safe, better structural support from the apophyseal ring, potential for coronal plane deformity correction, and indirect decompression, which have has made this technique popular. LLIF is currently being utilized for a variety of pathologies including but not limited to adult de novo lumbar scoliosis, central and foraminal stenosis, spondylolisthesis, and adjacent segment degeneration. Although early clinical outcomes have been good, the potential for significant neurological and vascular vertebral endplate complications exists. Nevertheless, LLIF is a promising technique with the potential to more effectively treat complex adult de novo scoliosis and achieve predictable fusion while avoiding the complications of traditional anterior surgery and posterior interbody techniques. PMID:26713134

  20. 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.

  1. 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.

  2. 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.

  3. Colliding Beam Fusion Reactors

    NASA Astrophysics Data System (ADS)

    Rostoker, Norman; Qerushi, Artan; Binderbauer, Michl

    2003-06-01

    The recirculating power for virtually all types of fusion reactors has previously been calculated [1] with the Fokker-Planck equation. The reactors involve non-Maxwellian plasmas. The calculations are generic in that they do not relate to specific confinement devices. In all cases except for a Tokamak with D-T fuel the recirculating power was found to exceed the fusion power by a large factor. In this paper we criticize the generality claimed for this calculation. The ratio of circulating power to fusion power is calculated for the Colliding Beam Reactor with fuels D-T, D-He3 and p-B11. The results are respectively, 0.070, 0.141 and 0.493.

  4. 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.

  5. Simulation of Fusion Plasmas

    ScienceCinema

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

    2010-01-08

    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.

  6. 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.

  7. 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.

  8. 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.

  9. Full Conversion of the Hemagglutinin-Neuraminidase Specificity of the Parainfluenza Virus 5 Fusion Protein by Replacement of 21 Amino Acids in Its Head Region with Those of the Simian Virus 41 Fusion Protein

    PubMed Central

    Nakahashi, Mito; Matsushima, Yoshiaki; Ito, Morihiro; Nishio, Machiko; Kawano, Mitsuo; Komada, Hiroshi; Nosaka, Tetsuya

    2013-01-01

    For most parainfluenza viruses, a virus type-specific interaction between the hemagglutinin-neuraminidase (HN) and fusion (F) proteins is a prerequisite for mediating virus-cell fusion and cell-cell fusion. The molecular basis of this functional interaction is still obscure partly because it is unknown which region of the F protein is responsible for the physical interaction with the HN protein. Our previous cell-cell fusion assay using the chimeric F proteins of parainfluenza virus 5 (PIV5) and simian virus 41 (SV41) indicated that replacement of two domains in the head region of the PIV5 F protein with the SV41 F counterparts bestowed on the PIV5 F protein the ability to induce cell-cell fusion on coexpression with the SV41 HN protein while retaining its ability to induce fusion with the PIV5 HN protein. In the study presented here, we furthered the chimeric analysis of the F proteins of PIV5 and SV41, finding that the PIV5 F protein could be converted to an SV41 HN-specific chimeric F protein by replacing five domains in the head region with the SV41 F counterparts. The five SV41 F-protein-derived domains of this chimera were then divided into 16 segments; 9 out of 16 proved to be not involved in determining its specificity for the SV41 HN protein. Finally, mutational analyses of a chimeric F protein, which harbored seven SV41 F-protein-derived segments, revealed that replacement of at most 21 amino acids of the PIV5 F protein with the SV41 F-protein counterparts was enough to convert its HN protein specificity. PMID:23698295

  10. DD fusion in crystals

    SciTech Connect

    Tsyganov, E. N.

    2010-12-15

    The article discusses the mechanism of DD {sup {yields} 4}He fusion and so-called nonradiative thermalization of the reaction in crystals. The dynamics of this process is considered. The assumption that the decay time of the compound nucleus depends on its excitation energy makes experiments in crystals compatible with the acceleration data.We consider the processes in the crystals that increase the intensity ofDD fusion in comparison to the amorphous media, and the yield of the reaction is estimated.

  11. 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

  12. 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.

  13. 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.

  14. Seeing and believing: recent advances in imaging cell-cell interactions

    PubMed Central

    Yap, Alpha S.; Michael, Magdalene; Parton, Robert G.

    2015-01-01

    Advances in cell and developmental biology have often been closely linked to advances in our ability to visualize structure and function at many length and time scales. In this review, we discuss how new imaging technologies and new reagents have provided novel insights into the biology of cadherin-based cell-cell junctions. We focus on three developments: the application of super-resolution optical technologies to characterize the nanoscale organization of cadherins at cell-cell contacts, new approaches to interrogate the mechanical forces that act upon junctions, and advances in electron microscopy which have the potential to transform our understanding of cell-cell junctions. PMID:26543555

  15. 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.

  16. Fusion technology status and requirements

    SciTech Connect

    Thomassen, K.I.

    1982-01-26

    This paper summarizes the status of fusion technology and discusses the requirements to be met in order to build a demonstration fusion plant. Strategies and programmatic considerations in pursuing engineering feasibility are also outlined.

  17. Trypsin- and low pH-mediated fusogenicity of avian metapneumovirus fusion proteins is determined by residues at positions 100, 101 and 294

    PubMed Central

    Yun, Bingling; Guan, Xiaolu; Liu, Yongzhen; Gao, Yanni; Wang, Yongqiang; Qi, Xiaole; Cui, Hongyu; Liu, Changjun; Zhang, Yanping; Gao, Li; Li, Kai; Gao, Honglei; Gao, Yulong; Wang, Xiaomei

    2015-01-01

    Avian metapneumovirus (aMPV) and human metapneumovirus (hMPV) are members of the genus Metapneumovirus in the subfamily Pneumovirinae. Metapneumovirus fusion (F) protein mediates the fusion of host cells with the virus membrane for infection. Trypsin- and/or low pH-induced membrane fusion is a strain-dependent phenomenon for hMPV. Here, we demonstrated that three subtypes of aMPV (aMPV/A, aMPV/B, and aMPV/C) F proteins promoted cell-cell fusion in the absence of trypsin. Indeed, in the presence of trypsin, only aMPV/C F protein fusogenicity was enhanced. Mutagenesis of the amino acids at position 100 and/or 101, located at a putative cleavage region in aMPV F proteins, revealed that the trypsin-mediated fusogenicity of aMPV F proteins is regulated by the residues at positions 100 and 101. Moreover, we demonstrated that aMPV/A and aMPV/B F proteins mediated cell-cell fusion independent of low pH, whereas the aMPV/C F protein did not. Mutagenesis of the residue at position 294 in the aMPV/A, aMPV/B, and aMPV/C F proteins showed that 294G played a critical role in F protein-mediated fusion under low pH conditions. These findings on aMPV F protein-induced cell-cell fusion provide new insights into the molecular mechanisms underlying membrane fusion and pathogenesis of aMPV. PMID:26498473

  18. Trypsin- and low pH-mediated fusogenicity of avian metapneumovirus fusion proteins is determined by residues at positions 100, 101 and 294.

    PubMed

    Yun, Bingling; Guan, Xiaolu; Liu, Yongzhen; Gao, Yanni; Wang, Yongqiang; Qi, Xiaole; Cui, Hongyu; Liu, Changjun; Zhang, Yanping; Gao, Li; Li, Kai; Gao, Honglei; Gao, Yulong; Wang, Xiaomei

    2015-01-01

    Avian metapneumovirus (aMPV) and human metapneumovirus (hMPV) are members of the genus Metapneumovirus in the subfamily Pneumovirinae. Metapneumovirus fusion (F) protein mediates the fusion of host cells with the virus membrane for infection. Trypsin- and/or low pH-induced membrane fusion is a strain-dependent phenomenon for hMPV. Here, we demonstrated that three subtypes of aMPV (aMPV/A, aMPV/B, and aMPV/C) F proteins promoted cell-cell fusion in the absence of trypsin. Indeed, in the presence of trypsin, only aMPV/C F protein fusogenicity was enhanced. Mutagenesis of the amino acids at position 100 and/or 101, located at a putative cleavage region in aMPV F proteins, revealed that the trypsin-mediated fusogenicity of aMPV F proteins is regulated by the residues at positions 100 and 101. Moreover, we demonstrated that aMPV/A and aMPV/B F proteins mediated cell-cell fusion independent of low pH, whereas the aMPV/C F protein did not. Mutagenesis of the residue at position 294 in the aMPV/A, aMPV/B, and aMPV/C F proteins showed that 294G played a critical role in F protein-mediated fusion under low pH conditions. These findings on aMPV F protein-induced cell-cell fusion provide new insights into the molecular mechanisms underlying membrane fusion and pathogenesis of aMPV. PMID:26498473

  19. 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.

  20. Status of inertial fusion

    NASA Astrophysics Data System (ADS)

    Keefe, D.

    1987-04-01

    The technology advancement to high-power beams has also given birth to new technologies. That class of Free Electron Lasers that employs RF linacs, synchrotrons, and storage rings - although the use of the tools of High Energy Physics (HEP) - was developed well behind the kinetic energy frontier. The induction linac, however, is something of an exception; it was born directly from the needs of the magnetic fusion program, and was not motivated by a high-energy physics application. The heavy-ion approach to inertial fusion starts with picking from the rich menu of accelerator technologies those that have, ab initio, the essential ingredients needed for a power plant driver: multigap acceleration - which leads to reliability/lifetime; electrical efficiency; repetition rate; and beams that can be reliably focused over a suitably long distance. The report describes the programs underway in Heavy Ion Fusion Accelerator Research as well as listing expected advances in driver, target, and beam quality areas in the inertial fusion power program.

  1. Separating Fusion from Rivalry

    PubMed Central

    Dechent, Peter; Forster, Clemens; von Steinbüchel, Nicole; Wüstenberg, Torsten; Strasburger, Hans

    2014-01-01

    Visual fusion is the process in which differing but compatible binocular information is transformed into a unified percept. Even though this is at the basis of binocular vision, the underlying neural processes are, as yet, poorly understood. In our study we therefore aimed to investigate neural correlates of visual fusion. To this end, we presented binocularly compatible, fusible (BF), and incompatible, rivaling (BR) stimuli, as well as an intermediate stimulus type containing both binocularly fusible and monocular, incompatible elements (BFR). Comparing BFR stimuli with BF and BR stimuli, respectively, we were able to disentangle brain responses associated with either visual fusion or rivalry. By means of functional magnetic resonance imaging, we measured brain responses to these stimulus classes in the visual cortex, and investigated them in detail at various retinal eccentricities. Compared with BF stimuli, the response to BFR stimuli was elevated in visual cortical areas V1 and V2, but not in V3 and V4 – implying that the response to monocular stimulus features decreased from V1 to V4. Compared to BR stimuli, the response to BFR stimuli decreased with increasing eccentricity, specifically within V3 and V4. Taken together, it seems that although the processing of exclusively monocular information decreases from V1 to V4, the processing of binocularly fused information increases from earlier to later visual areas. Our findings suggest the presence of an inhibitory neural mechanism which, depending on the presence of fusion, acts differently on the processing of monocular information. PMID:25054904

  2. 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.

  3. 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.

  4. Multilevel fusion exploitation

    NASA Astrophysics Data System (ADS)

    Lindberg, Perry C.; Dasarathy, Belur V.; McCullough, Claire L.

    1996-06-01

    This paper describes a project that was sponsored by the U.S. Army Space and Strategic Defense Command (USASSDC) to develop, test, and demonstrate sensor fusion algorithms for target recognition. The purpose of the project was to exploit the use of sensor fusion at all levels (signal, feature, and decision levels) and all combinations to improve target recognition capability against tactical ballistic missile (TBM) targets. These algorithms were trained with simulated radar signatures to accurately recognize selected TBM targets. The simulated signatures represent measurements made by two radars (S-band and X- band) with the targets at a variety of aspect and roll angles. Two tests were conducted: one with simulated signatures collected at angles different from those in the training database and one using actual test data. The test results demonstrate a high degree of recognition accuracy. This paper describes the training and testing techniques used; shows the fusion strategy employed; and illustrates the advantages of exploiting multi-level fusion.

  5. 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.

  6. 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.

  7. Cell-based analysis of Chikungunya virus E1 protein in membrane fusion

    PubMed Central

    2012-01-01

    Background Chikungunya fever is a pandemic disease caused by the mosquito-borne Chikungunya virus (CHIKV). E1 glycoprotein mediation of viral membrane fusion during CHIKV infection is a crucial step in the release of viral genome into the host cytoplasm for replication. How the E1 structure determines membrane fusion and whether other CHIKV structural proteins participate in E1 fusion activity remain largely unexplored. Methods A bicistronic baculovirus expression system to produce recombinant baculoviruses for cell-based assay was used. Sf21 insect cells infected by recombinant baculoviruses bearing wild type or single-amino-acid substitution of CHIKV E1 and EGFP (enhanced green fluorescence protein) were employed to investigate the roles of four E1 amino acid residues (G91, V178, A226, and H230) in membrane fusion activity. Results Western blot analysis revealed that the E1 expression level and surface features in wild type and mutant substituted cells were similar. However, cell fusion assay found that those cells infected by CHIKV E1-H230A mutant baculovirus showed little fusion activity, and those bearing CHIKV E1-G91D mutant completely lost the ability to induce cell-cell fusion. Cells infected by recombinant baculoviruses of CHIKV E1-A226V and E1-V178A mutants exhibited the same membrane fusion capability as wild type. Although the E1 expression level of cells bearing monomeric-E1-based constructs (expressing E1 only) was greater than that of cells bearing 26S-based constructs (expressing all structural proteins), the sizes of syncytial cells induced by infection of baculoviruses containing 26S-based constructs were larger than those from infections having monomeric-E1 constructs, suggesting that other viral structure proteins participate or regulate E1 fusion activity. Furthermore, membrane fusion in cells infected by baculovirus bearing the A226V mutation constructs exhibited increased cholesterol-dependences and lower pH thresholds. Cells bearing the V178

  8. Microfluidic device for high-yield pairing and fusion of stem cells with somatic cells

    NASA Astrophysics Data System (ADS)

    Gel, Murat; Hirano, Kunio; Oana, Hidehiro; Kotera, Hidetoshi; Tada, Takashi; Washizu, Masao

    2011-12-01

    Electro cell fusion has significant potential as a biotechnology tool with applications ranging from antibody production to cellular reprogramming. However due to low fusion efficiency of the conventional electro fusion methodology the true potential of the technique has not been reached. In this paper, we report a new method which takes cell fusion efficiency two orders magnitude higher than the conventional electro fusion method. The new method, based on one-toone pairing, fusion and selection of fused cells was developed using a microfabricated device. The device was composed of two microfluidic channels, a micro slit array and a petri dish integrated with electrodes. The electrodes positioned in each channel were used to generate electric field lines concentrating in the micro slits. Cells were introduced into channels and brought in to contact through the micro slit array using dielectrophoresis. The cells in contact were fused by applying a DC pulse to electrodes. As the electric field lines were concentrated at the micro slits the membrane potential was induced only at the vicinity of the micro slits, namely only at the cell-cell contact point. This mechanism assured the minimum damage to cells in the fusion as well as the ability to control the strength and location of induced membrane potential. We introduced mouse embryonic stem cells and mouse embryonic fibroblasts to the microfluidic channels and demonstrated high-yield fusion (> 80%). Post-fusion study showed the method can generate viable hybrids of stem cells and embryonic fibroblasts. Multinucleated hybrid cells adhering on the chip surface were routinely obtained by using this method and on-chip culturing.

  9. Enhanced image capture through fusion

    NASA Technical Reports Server (NTRS)

    Burt, Peter J.; Hanna, Keith; Kolczynski, Raymond J.

    1993-01-01

    Image fusion may be used to combine images from different sensors, such as IR and visible cameras, to obtain a single composite with extended information content. Fusion may also be used to combine multiple images from a given sensor to form a composite image in which information of interest is enhanced. We present a general method for performing image fusion and show that this method is effective for diverse fusion applications. We suggest that fusion may provide a powerful tool for enhanced image capture with broad utility in image processing and computer vision.

  10. Research on fusion neutron sources

    NASA Astrophysics Data System (ADS)

    Gryaznevich, M. P.

    2012-06-01

    The use of fusion devices as powerful neutron sources has been discussed for decades. Whereas the successful route to a commercial fusion power reactor demands steady state stable operation combined with the high efficiency required to make electricity production economic, the alternative approach to advancing the use of fusion is free of many of complications connected with the requirements for economic power generation and uses the already achieved knowledge of Fusion physics and developed Fusion technologies. "Fusion for Neutrons" (F4N), has now been re-visited, inspired by recent progress achieved on comparably compact fusion devices, based on the Spherical Tokamak (ST) concept. Freed from the requirement to produce much more electricity than used to drive it, a fusion neutron source could be efficiently used for many commercial applications, and also to support the goal of producing energy by nuclear power. The possibility to use a small or medium size ST as a powerful or intense steady-state fusion neutron source (FNS) is discussed in this paper in comparison with the use of traditional high aspect ratio tokamaks. An overview of various conceptual designs of compact fusion neutron sources based on the ST concept is given and they are compared with a recently proposed Super Compact Fusion Neutron Source (SCFNS), with major radius as low as 0.5 metres but still able to produce several MW of neutrons in a steady-state regime.

  11. Acquired spondylolysis after spinal fusion.

    PubMed

    Brunet, J A; Wiley, J J

    1984-11-01

    Spondylolysis occurring after a spinal fusion is considered to result from operative damage to the pars interarticularis on both sides. Fourteen cases are reported, and compared with the 23 cases which have previously been published. The defects are usually recognised within five years of fusion, and usually occur immediately above the fusion mass. Other contributory causes may be: fatigue fracture from concentration of stress; damage and altered function of the posterior ligament complex; and degenerative disc disease immediately above or below the fusion. Fusion technique is critical, since virtually all cases occurred after posterior interlaminar fusions. This complication is easily overlooked in patients with recurrent back pain after an originally successful posterior spinal fusion. PMID:6501368

  12. 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.

  13. 50 years of fusion research

    NASA Astrophysics Data System (ADS)

    Meade, Dale

    2010-01-01

    Fusion energy research began in the early 1950s as scientists worked to harness the awesome power of the atom for peaceful purposes. There was early optimism for a quick solution for fusion energy as there had been for fission. However, this was soon tempered by reality as the difficulty of producing and confining fusion fuel at temperatures of 100 million °C in the laboratory was appreciated. Fusion research has followed two main paths—inertial confinement fusion and magnetic confinement fusion. Over the past 50 years, there has been remarkable progress with both approaches, and now each has a solid technical foundation that has led to the construction of major facilities that are aimed at demonstrating fusion energy producing plasmas.

  14. Adaptive sensor fusion

    NASA Astrophysics Data System (ADS)

    Kadar, Ivan

    1995-07-01

    A perceptual reasoning system adaptively extracting, associating, and fusing information from multiple sources, at various levels of abstraction, is considered as the building block for the next generation of surveillance systems. A system architecture is presented which makes use of both centralized and distributed predetection fusion combined with intelligent monitor and control coupling both on-platform and off-board track and decision level fusion results. The goal of this system is to create a `gestalt fused sensor system' whose information product is greater than the sum of the information products from the individual sensors and has performance superior to either individual or a sub-group of combined sensors. The application of this architectural concept to the law enforcement arena (e.g. drug interdiction) utilizing multiple spatially and temporally diverse surveillance platforms and/or information sources, is used to illustrate the benefits of the adaptive perceptual reasoning system concept.

  15. 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.

  16. Synaptic vesicle fusion

    PubMed Central

    Rizo, Josep; Rosenmund, Christian

    2008-01-01

    The core of the neurotransmitter release machinery is formed by SNARE complexes, which bring the vesicle and plasma membranes together and are key for fusion, and by Munc18-1, which controls SNARE-complex formation and may also have a direct role in fusion. In addition, SNARE complex assembly is likely orchestrated by Munc13s and RIMs, active-zone proteins that function in vesicle priming and diverse forms of presynaptic plasticity. Synaptotagmin-1 mediates triggering of release by Ca2+, probably through interactions with SNAREs and both membranes, as well as through a tight interplay with complexins. Elucidation of the release mechanism will require a full understanding of the network of interactions among all these proteins and the membranes. PMID:18618940

  17. Spectral Label Fusion

    PubMed Central

    Wachinger, Christian; Golland, Polina

    2012-01-01

    We present a new segmentation approach that combines the strengths of label fusion and spectral clustering. The result is an atlas-based segmentation method guided by contour and texture cues in the test image. This offers advantages for datasets with high variability, making the segmentation less prone to registration errors. We achieve the integration by letting the weights of the graph Laplacian depend on image data, as well as atlas-based label priors. The extracted contours are converted to regions, arranged in a hierarchy depending on the strength of the separating boundary. Finally, we construct the segmentation by a region-wise, instead of voxel-wise, voting, increasing the robustness. Our experiments on cardiac MRI show a clear improvement over majority voting and intensity-weighted label fusion. PMID:23286157

  18. Inertial Confinement fusion targets

    NASA Technical Reports Server (NTRS)

    Hendricks, C. D.

    1982-01-01

    Inertial confinement fusion (ICF) targets are made as simple flat discs, as hollow shells or as complicated multilayer structures. Many techniques were devised for producing the targets. Glass and metal shells are made by using drop and bubble techniques. Solid hydrogen shells are also produced by adapting old methods to the solution of modern problems. Some of these techniques, problems, and solutions are discussed. In addition, the applications of many of the techniques to fabrication of ICF targets is presented.

  19. (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.

  20. Fc-fusion mimetics.

    PubMed

    Khalili, H; Khaw, P T; Brocchini, S

    2016-06-24

    The Fc-fusion mimetic RpR 2[combining low line] was prepared by disulfide bridging conjugation using PEG in the place of the Fc. RpR 2[combining low line] displayed higher affinity for VEGF than aflibercept. This is caused primarily by a slower dissociation rate, which can prolong a drug at its site of action. RpRs have considerable potential for development as stable, organ specific therapeutics. PMID:27127811

  1. 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.

  2. 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. __________________________________________________

  3. 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.

  4. 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.

  5. Modeling keratinocyte wound healing dynamics: Cell-cell adhesion promotes sustained collective migration.

    PubMed

    Nardini, John T; Chapnick, Douglas A; Liu, Xuedong; Bortz, David M

    2016-07-01

    The in vitro migration of keratinocyte cell sheets displays behavioral and biochemical similarities to the in vivo wound healing response of keratinocytes in animal model systems. In both cases, ligand-dependent Epidermal Growth Factor Receptor (EGFR) activation is sufficient to elicit collective cell migration into the wound. Previous mathematical modeling studies of in vitro wound healing assays assume that physical connections between cells have a hindering effect on cell migration, but biological literature suggests a more complicated story. By combining mathematical modeling and experimental observations of collectively migrating sheets of keratinocytes, we investigate the role of cell-cell adhesion during in vitro keratinocyte wound healing assays. We develop and compare two nonlinear diffusion models of the wound healing process in which cell-cell adhesion either hinders or promotes migration. Both models can accurately fit the leading edge propagation of cell sheets during wound healing when using a time-dependent rate of cell-cell adhesion strength. The model that assumes a positive role of cell-cell adhesion on migration, however, is robust to changes in the leading edge definition and yields a qualitatively accurate density profile. Using RNAi for the critical adherens junction protein, α-catenin, we demonstrate that cell sheets with wild type cell-cell adhesion expression maintain migration into the wound longer than cell sheets with decreased cell-cell adhesion expression, which fails to exhibit collective migration. Our modeling and experimental data thus suggest that cell-cell adhesion promotes sustained migration as cells pull neighboring cells into the wound during wound healing. PMID:27105673

  6. Morphological changes and spatial regulation of diacylglycerol kinase-zeta, syntrophins, and Rac1 during myoblast fusion.

    PubMed

    Abramovici, Hanan; Gee, Stephen H

    2007-07-01

    The fusion of mononuclear myoblasts into multinucleated myofibers is essential for the formation and growth of skeletal muscle. Myoblast fusion follows a well-defined sequence of cellular events, from initial recognition and adhesion, to alignment, and finally plasma membrane fusion. These processes depend upon coordinated remodeling of the actin cytoskeleton. Our recent studies suggest diacylglycerol kinase-zeta (DGK-zeta), an enzyme that metabolizes diacylglycerol to yield phosphatidic acid, plays an important role in actin reorganization. Here, we investigated whether DGK-zeta has a role in the fusion of cultured C2C12 myoblasts. We show that DGK-zeta and syntrophins, scaffold proteins of the dystrophin glycoprotein complex that bind directly to DGK-zeta, are spatially regulated during fusion. Both proteins accumulated with the GTPase Rac1 at sites where fine filopodia mediate the initial contact between myoblasts. In addition, DGK-zeta codistributed with the Ca(2+)-dependent cell adhesion molecule N-cadherin at nascent, but not previously established cell contacts. We provide evidence that C2 cells are pulled together at cell-cell junctions by N-cadherin-containing filopodia reminiscent of epithelial adhesion zippers, which guide the advance of lamellipodia from apposing cells. At later times, vesicles with properties of macropinosomes formed close to cell-cell junctions. Reconstruction of confocal optical sections showed these form dome-like protrusions from the dorsal surface of contacting cells. Collectively, these results suggest DGK-zeta and syntrophins play a role at multiple stages of the fusion process. Moreover, our findings provide a potential link between changes in the lipid content of the membrane bilayer and reorganization of the actin cytoskeleton during myoblast fusion. PMID:17410543

  7. Dynamic interplay between adhesion surfaces in carcinomas: Cell-cell and cell-matrix crosstalk

    PubMed Central

    Smith, Yvonne E; Vellanki, Sri HariKrishna; Hopkins, Ann M

    2016-01-01

    Cell-cell and cell-matrix signaling and communication between adhesion sites involve mechanisms which are required for cellular functions during normal development and homeostasis; however these cellular functions and mechanisms are often deregulated in cancer. Aberrant signaling at cell-cell and cell-matrix adhesion sites often involves downstream mediators including Rho GTPases and tyrosine kinases. This review discusses these molecules as putative mediators of cellular crosstalk between cell-cell and cell-matrix adhesion sites, in addition to their attractiveness as therapeutic targets in cancer. Interestingly, inter-junctional crosstalk mechanisms are frequently typified by the way in which bacterial and viral pathogens opportunistically infect or intoxicate mammalian cells. This review therefore also discusses the concept of learning from pathogen-host interaction studies to better understand coordinated communication between cell-cell and cell-matrix adhesion sites, in addition to highlighting the potential therapeutic usefulness of exploiting pathogens or their products to tap into inter-junctional crosstalk. Taken together, we feel that increased knowledge around mechanisms of cell-cell and cell-matrix adhesion site crosstalk and consequently a greater understanding of their therapeutic targeting offers a unique opportunity to contribute to the emerging molecular revolution in cancer biology. PMID:26981196

  8. Focal Adhesion Kinase regulates cell-cell contact formation in epithelial cells via modulation of Rho

    SciTech Connect

    Playford, Martin P.; Vadali, Kavita; Cai Xinming; Burridge, Keith; Schaller, Michael D.

    2008-10-15

    Focal Adhesion Kinase (FAK) is a non-receptor tyrosine kinase that plays a key role in cellular processes such as cell adhesion, migration, proliferation and survival. Recent studies have also implicated FAK in the regulation of cell-cell adhesion. Here, evidence is presented showing that siRNA-mediated suppression of FAK levels in NBT-II cells and expression of dominant negative mutants of FAK caused loss of epithelial cell morphology and inhibited the formation of cell-cell adhesions. Rac and Rho have been implicated in the regulation of cell-cell adhesions and can be regulated by FAK signaling. Expression of active Rac or Rho in NBT-II cells disrupted formation of cell-cell contacts, thus promoting a phenotype similar to FAK-depleted cells. The loss of intercellular contacts in FAK-depleted cells is prevented upon expression of a dominant negative Rho mutant, but not a dominant negative Rac mutant. Inhibition of FAK decreased tyrosine phosphorylation of p190RhoGAP and elevated the level of GTP-bound Rho. This suggests that FAK regulates cell-cell contact formation by regulation of Rho.

  9. Dynamic interplay between adhesion surfaces in carcinomas: Cell-cell and cell-matrix crosstalk.

    PubMed

    Smith, Yvonne E; Vellanki, Sri HariKrishna; Hopkins, Ann M

    2016-02-26

    Cell-cell and cell-matrix signaling and communication between adhesion sites involve mechanisms which are required for cellular functions during normal development and homeostasis; however these cellular functions and mechanisms are often deregulated in cancer. Aberrant signaling at cell-cell and cell-matrix adhesion sites often involves downstream mediators including Rho GTPases and tyrosine kinases. This review discusses these molecules as putative mediators of cellular crosstalk between cell-cell and cell-matrix adhesion sites, in addition to their attractiveness as therapeutic targets in cancer. Interestingly, inter-junctional crosstalk mechanisms are frequently typified by the way in which bacterial and viral pathogens opportunistically infect or intoxicate mammalian cells. This review therefore also discusses the concept of learning from pathogen-host interaction studies to better understand coordinated communication between cell-cell and cell-matrix adhesion sites, in addition to highlighting the potential therapeutic usefulness of exploiting pathogens or their products to tap into inter-junctional crosstalk. Taken together, we feel that increased knowledge around mechanisms of cell-cell and cell-matrix adhesion site crosstalk and consequently a greater understanding of their therapeutic targeting offers a unique opportunity to contribute to the emerging molecular revolution in cancer biology. PMID:26981196

  10. Sensor fusion for synthetic vision

    NASA Technical Reports Server (NTRS)

    Pavel, M.; Larimer, J.; Ahumada, A.

    1991-01-01

    Display methodologies are explored for fusing images gathered by millimeter wave sensors with images rendered from an on-board terrain data base to facilitate visually guided flight and ground operations in low visibility conditions. An approach to fusion based on multiresolution image representation and processing is described which facilitates fusion of images differing in resolution within and between images. To investigate possible fusion methods, a workstation-based simulation environment is being developed.

  11. EDITORIAL: The Nuclear Fusion Award The Nuclear Fusion Award

    NASA Astrophysics Data System (ADS)

    Kikuchi, M.

    2011-01-01

    The Nuclear Fusion Award ceremony for 2009 and 2010 award winners was held during the 23rd IAEA Fusion Energy Conference in Daejeon. This time, both 2009 and 2010 award winners were celebrated by the IAEA and the participants of the 23rd IAEA Fusion Energy Conference. The Nuclear Fusion Award is a paper prize to acknowledge the best distinguished paper among the published papers in a particular volume of the Nuclear Fusion journal. Among the top-cited and highly-recommended papers chosen by the Editorial Board, excluding overview and review papers, and by analyzing self-citation and non-self-citation with an emphasis on non-self-citation, the Editorial Board confidentially selects ten distinguished papers as nominees for the Nuclear Fusion Award. Certificates are given to the leading authors of the Nuclear Fusion Award nominees. The final winner is selected among the ten nominees by the Nuclear Fusion Editorial Board voting confidentially. 2009 Nuclear Fusion Award nominees For the 2009 award, the papers published in the 2006 volume were assessed and the following papers were nominated, most of which are magnetic confinement experiments, theory and modeling, while one addresses inertial confinement. Sabbagh S.A. et al 2006 Resistive wall stabilized operation in rotating high beta NSTX plasmas Nucl. Fusion 46 635-44 La Haye R.J. et al 2006 Cross-machine benchmarking for ITER of neoclassical tearing mode stabilization by electron cyclotron current drive Nucl. Fusion 46 451-61 Honrubia J.J. et al 2006 Three-dimensional fast electron transport for ignition-scale inertial fusion capsules Nucl. Fusion 46 L25-8 Ido T. et al 2006 Observation of the interaction between the geodesic acoustic mode and ambient fluctuation in the JFT-2M tokamak Nucl. Fusion 46 512-20 Plyusnin V.V. et al 2006 Study of runaway electron generation during major disruptions in JET Nucl. Fusion 46 277-84 Pitts R.A. et al 2006 Far SOL ELM ion energies in JET Nucl. Fusion 46 82-98 Berk H.L. et al 2006

  12. 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.

  13. Membrane organization and cell fusion during mating in fission yeast requires multipass membrane protein Prm1.

    PubMed

    Curto, M-Ángeles; Sharifmoghadam, Mohammad Reza; Calpena, Eduardo; De León, Nagore; Hoya, Marta; Doncel, Cristina; Leatherwood, Janet; Valdivieso, M-Henar

    2014-04-01

    The involvement of Schizosaccharomyces pombe prm1(+) in cell fusion during mating and its relationship with other genes required for this process have been addressed. S. pombe prm1Δ mutant exhibits an almost complete blockade in cell fusion and an abnormal distribution of the plasma membrane and cell wall in the area of cell-cell interaction. The distribution of cellular envelopes is similar to that described for mutants devoid of the Fig1-related claudin-like Dni proteins; however, prm1(+) and the dni(+) genes act in different subpathways. Time-lapse analyses show that in the wild-type S. pombe strain, the distribution of phosphatidylserine in the cytoplasmic leaflet of the plasma membrane undergoes some modification before an opening is observed in the cross wall at the cell-cell contact region. In the prm1Δ mutant, this membrane modification does not take place, and the cross wall between the mating partners is not extensively degraded; plasma membrane forms invaginations and fingers that sometimes collapse/retract and that are sometimes strengthened by the synthesis of cell-wall material. Neither prm1Δ nor prm1Δ dniΔ zygotes lyse after cell-cell contact in medium containing and lacking calcium. Response to drugs that inhibit lipid synthesis or interfere with lipids is different in wild-type, prm1Δ, and dni1Δ strains, suggesting that membrane structure/organization/dynamics is different in all these strains and that Prm1p and the Dni proteins exert some functions required to guarantee correct membrane organization that are critical for cell fusion. PMID:24514900

  14. Generic magnetic fusion rocket model

    SciTech Connect

    Santarius, J.F.; Logan, B.G.

    1993-06-01

    A generic magnetic fusion rocket model is developed and used to explore the limits of fusion propulsion systems. Two fusion fuels are examined, D-T and D-(He-3), and the D-(He-3) fuel cycle is found to give a higher specific power in almost all parameter regimes. The key findings are that (1) magnetic fusion should ultimately be able to deliver specific powers of about 10 kW/kg and (2) specific powers of 15 kW/kg could be achieved with only modest extrapolations of present technology. 9 refs.

  15. 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.

  16. 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.

  17. COLLABORATIVE: FUSION SIMULATION PROGRAM

    SciTech Connect

    Chang, Choong Seock

    2012-06-05

    New York University, Courant Institute of Mathematical Sciences, participated in the “Fusion Simulation Program (FSP) Planning Activities” [http://www.pppl.gov/fsp], with C.S. Chang as the institutional PI. FSP’s mission was to enable scientific discovery of important new plasma phenomena with associated understanding that emerges only upon integration. This requires developing a predictive integrated simulation capability for magnetically-confined fusion plasmas that are properly validated against experiments in regimes relevant for producing practical fusion energy. Specific institutional goal of the New York University was to participate in the planning of the edge integrated simulation, with emphasis on the usage of large scale HPCs, in connection with the SciDAC CPES project which the PI was leading. New York University successfully completed its mission by participating in the various planning activities, including the edge physics integration, the edge science drivers, and the mathematical verification. The activity resulted in the combined report that can be found in http://www.pppl.gov/fsp/Overview.html. Participation and presentations as part of this project are listed in a separation file.

  18. 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∗.

  19. Development of indole compounds as small molecule fusion inhibitors targeting HIV-1 glycoprotein-41

    PubMed Central

    Zhou, Guangyan; Wu, Dong; Snyder, Beth; Ptak, Roger G.; Kaur, Harmeet; Gochin, Miriam

    2011-01-01

    Non-peptide inhibition of fusion remains an important goal in anti-HIV research, due to its potential for low cost prophylaxis or prevention of cell–cell transmission of the virus. We report here on a series of indole compounds that have been identified as fusion inhibitors of gp41 through a structure-based drug design approach. Experimental binding affinities of the compounds for the hydrophobic pocket were strongly correlated to fusion inhibitory data (R2 = 0.91), and corresponding inhibition of viral replication confirmed the hydrophobic pocket as a valid target for low molecular weight fusion inhibitors. The most active compound bound to the hydrophobic pocket and inhibited cell-cell fusion and viral replication at sub-µM levels. A common binding mode for the inhibitors in this series was established by carrying out docking studies using structures of gp41 in the Protein Data Bank. The molecules were flexible enough to conform to the contours of the pocket, and the most active compound was able to adopt a structure mimicking the hydrophobic contacts of the D-peptide PIE7. The results enhance our understanding of indole compounds as inhibitors of gp41. PMID:21928824

  20. An effective conjugation strategy for designing short peptide-based HIV-1 fusion inhibitors.

    PubMed

    Liang, Guodong; Wang, Huixin; Chong, Huihui; Cheng, Siqi; Jiang, Xifeng; He, Yuxian; Wang, Chao; Liu, Keliang

    2016-08-16

    Lengthy peptides corresponding to the C-terminal heptad repeat (C-peptides) of human immunodeficiency virus type 1 (HIV-1) gp41 are potent inhibitors against virus-cell fusion. Designing short C-peptide-based HIV-1 fusion inhibitors could potentially redress the physicochemical and technical liabilities of a long-peptide therapeutic. However, designing such inhibitors with high potency has been challenging. We generated a conjugated architecture by incorporating small-molecule inhibitors of gp41 into the N-terminus of a panel of truncated C-peptides. Among these small molecule-capped short peptides, the 26-residue peptide Indole-T26 inhibited HIV-1 Env-mediated cell-cell fusion and viral replication at low nanomolar levels, reaching the potency of the only clinically used 36-residue peptide T20 (enfuvirtide). Collectively, our work opens up a new avenue for developing short peptide-based HIV-1 fusion inhibitors, and may have broad applicability to the development of modulators of other class I fusion proteins. PMID:27454320

  1. 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.

  2. 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.

  3. Effects of substrate stiffness and cell-cell contact on mesenchymal stem cell differentiation.

    PubMed

    Mao, Angelo S; Shin, Jae-Won; Mooney, David J

    2016-08-01

    The mechanical properties of the microenvironment and direct contact-mediated cell-cell interactions are two variables known to be important in the determination of stem cell differentiation fate, but little is known about the interplay of these cues. Here, we use a micropatterning approach on polyacrylamide gels of tunable stiffnesses to study how homotypic cell-cell contacts and mechanical stiffness affect different stages of osteogenesis of mesenchymal stem cells (MSCs). Nuclear localization of transcription factors associated with osteogenesis depended on substrate stiffness and was independent of the degree of cell-cell contact. However, expression of alkaline phosphatase, an early protein marker for osteogenesis, increased only in cells with both direct contact with neighboring cells and adhesion to stiffer substrates. Finally, mature osteogenesis, as assessed by calcium deposition, was low in micropatterned cells, even on stiff substrates and in multicellular clusters. These results indicate that substrate stiffness and the presence of neighboring cells regulate osteogenesis in MSCs. PMID:27203745

  4. Cell-cell communication via extracellular membrane vesicles and its role in the immune response.

    PubMed

    Hwang, Inkyu

    2013-08-01

    The host immune response involves a variety of cell types, including specialized immune and non-immune cells. The delicate coordination among these cells via close communication is central for the proper operation of immune system. Cell-cell communication is mediated by a complex network that includes soluble factors such as cytokines, chemokines, and metabolites exported from cells, as well as membrane-bound receptors and their ligands. Cell-cell communication is also mediated by membrane vesicles (e.g., exosomes, ectosomes), which are either shed by distant cells or exchanged by cells that are making direct contact. Intercellular communication via extracellular membrane vesicles has drawn much attention recently, as they have been shown to carry various biomolecules that modulate the activities of recipient cells. In this review, I will discuss current views on cell-cell communication via extra-cellular membrane vesicles, especially shedded membrane vesicles, and their effects on the control of the immune system. PMID:23807045

  5. Topographical control of cell-cell interaction in C6 glioma by nanodot arrays

    NASA Astrophysics Data System (ADS)

    Lee, Chia-Hui; Cheng, Ya-Wen; Huang, G. Steven

    2014-05-01

    Nanotopography modulates the physiological behavior of cells and cell-cell interactions, but the manner of communication remains unclear. Cell networking (syncytium) of astroglia provides the optimal microenvironment for communication of the nervous system. C6 glioma cells were seeded on nanodot arrays with dot diameters ranging from 10 to 200 nm. Cell viability, morphology, cytoskeleton, and adhesion showed optimal cell growth on 50-nm nanodots if sufficient incubation was allowed. In particular, the astrocytic syncytium level maximized at 50 nm. The gap junction protein Cx43 showed size-dependent and time-dependent transport from the nucleus to the cell membrane. The transport efficiency was greatly enhanced by incubation on 50-nm nanodots. In summary, nanotopography is capable of modulating cell behavior and influencing the cell-cell interactions of astrocytes. By fine-tuning the nanoenvironment, it may be possible to regulate cell-cell communications and optimize the biocompatibility of neural implants.

  6. Effects of cell-cell contact and oxygen tension on chondrogenic differentiation of stem cells.

    PubMed

    Cao, Bin; Li, Zhenhua; Peng, Rong; Ding, Jiandong

    2015-09-01

    While cell condensation has been thought to enhance chondrogenesis, no direct evidence so far confirms that cell-cell contact itself increases chondrogenic differentiation of stem cells, since the change of cell-cell contact is usually coupled with those of other cell geometry cues and soluble factors in cell culture. The present study semi-quantitatively examined the effect of cell-cell contact in a decoupled way. We fabricated two-dimensional micropatterns with cell-adhesive peptide arginine-glycine-aspartate (RGD) microdomains on a nonfouling poly(ethylene glycol) (PEG) hydrogel. Mesenchymal stem cells (MSCs) were well localized on the microdomains for a long time. Based on our micropattern design, single MSCs or cell clusters with given cell numbers (1, 2, 3, 6 and 15) and a similar spreading area per cell were achieved on the same substrate, thus the interference of soluble factor difference from cell autocrine and that of cell spreading area were ruled out. After 9-day chondrogenic induction, collagen II was stained to characterize the chondrogenic induction results; the mRNA expression levels of SOX9, collagen II, aggrecan, HIF-1α and collagen I were also detected. The statistics confirmed unambiguously that the extent of the chondrogenic differentiation increased with cell-cell contact, and even a linear relation between differentiation extent and contact extent was established within the examined range. The cell-cell contact effect worked under both hypoxia (5% O2) and normoxia (21% O2) conditions, and the hypoxia condition promoted the chondrogenic induction of MSCs on adhesive microdomains more efficiently than the normoxia condition under the same cell-cell contact extents. PMID:26113183

  7. A Social Medium: ASM's 5th Cell-Cell Communication in Bacteria Meeting in Review

    PubMed Central

    Federle, Michael J.

    2015-01-01

    The 5th American Society for Microbiology Conference on Cell-Cell Communication in Bacteria (CCCB-5), which convened from 18 to 21 October 2014 in San Antonio, TX, highlighted recent advances in our understanding of microbial intercellular signaling. While the CCCB meetings arose from interests in pheromone signaling and quorum sensing, it was evident at CCCB-5 that the cell-cell communication field is continuing to mature, expanding into new areas and integrating cutting-edge technologies. In this minireview, we recap some of the research discussed at CCCB-5 and the questions that have arisen from it. PMID:25917904

  8. 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)

  9. 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).

  10. 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.

  11. Fusion processor simulation (FPSim)

    NASA Astrophysics Data System (ADS)

    Barnell, Mark D.; Wynne, Douglas G.; Rahn, Brian J.

    1998-07-01

    The Fusion Processor Simulation (FPSim) is being developed by Rome Laboratory to support the Discrimination Interceptor Technology (DITP) and Advanced Sensor Technology (ASTP) Programs of the Ballistic Missile Defense Organization. The purpose of the FPSim is to serve as a test bed and evaluation tool for establishing the feasibility of achieving threat engagement timelines. The FPSim supports the integration, evaluation, and demonstration of different strategies, system concepts, and Acquisition Tracking & Pointing (ATP) subsystems and components. The environment comprises a simulation capability within which users can integrate and test their application software models, algorithms and databases. The FPSim must evolve as algorithm developments mature to support independent evaluation of contractor designs and the integration of a number of fusion processor subsystem technologies. To accomplish this, the simulation contains validated modules, databases, and simulations. It possesses standardized engagement scenarios, architectures and subsystem interfaces, and provides a hardware and software framework which is flexible to support growth, reconfigurration, and simulation component modification and insertion. Key user interaction features include: (1) Visualization of platform status through displays of the surveillance scene as seen by imaging sensors. (2) User-selectable data analysis and graphics display during the simulation execution as well as during post-simulation analysis. (3) Automated, graphical tools to permit the user to reconfigure the FPSim, i.e., 'Plug and Play' various model/software modules. The FPSim is capable of hosting and executing user's software algorithms of image processing, signal processing, subsystems, and functions for evaluation purposes.

  12. The status of cold fusion

    NASA Astrophysics Data System (ADS)

    Storms, E.

    This report attempts to update the status of the phenomenon of cold fusion. The new field is continuing to grow as a variety of nuclear reactions are discovered to occur in a variety of chemical environments at modest temperatures. However, it must be cautioned that most scientists consider cold fusion as something akin to UFO's, ESP, and numerology.

  13. 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.

  14. Cellulose binding domain fusion proteins

    DOEpatents

    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. 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.

  16. The quest for fusion power

    NASA Astrophysics Data System (ADS)

    Cowley, Steven C.

    2016-05-01

    Fusion power is one of a very few sustainable options to replace fossil fuels as the world's primary energy source. Although the conditions for fusion have been reached, much remains to be done to turn scientific success into commercial electrical power.

  17. Feature-level sensor fusion

    NASA Astrophysics Data System (ADS)

    Peli, Tamar; Young, Mon; Knox, Robert; Ellis, Kenneth K.; Bennett, Frederick

    1999-03-01

    This paper describes two practical fusion techniques for automatic target cueing that combine features derived from each sensor data ta the object-level. In the hybrid fusion method each of the input sensor data is prescreened before the fusion stage. The cued fusion method assumes that one of the sensors is designated as a primary sensor, and thus ATC is only applied to its input data. If one of the sensors exhibits a higher Pd and/or a lower false alarm rate, it can be selected as the primary sensor. However, if the ground coverage can be segmented to regions in which one of the sensors is known to exhibit better performance, then the cued fusion can be applied locally/adaptively by switching the choice of a primary sensor. Otherwise, the cued fusion is applied both ways and the outputs of each cued mode are combined. Both fusion approaches use a back-end discrimination stage that is applied to a combined feature vector to reduce false alarms. The two fusion processes were applied to spectral and radar sensor data nd were shown to provide substantial false alarm reduction. The approaches are easily extendable to more than two sensors.

  18. 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.

  19. Magnetic fusion energy and computers

    SciTech Connect

    Killeen, J.

    1982-01-01

    The application of computers to magnetic fusion energy research is essential. In the last several years the use of computers in the numerical modeling of fusion systems has increased substantially. There are several categories of computer models used to study the physics of magnetically confined plasmas. A comparable number of types of models for engineering studies are also in use. To meet the needs of the fusion program, the National Magnetic Fusion Energy Computer Center has been established at the Lawrence Livermore National Laboratory. A large central computing facility is linked to smaller computer centers at each of the major MFE laboratories by a communication network. In addition to providing cost effective computing services, the NMFECC environment stimulates collaboration and the sharing of computer codes among the various fusion research groups.

  20. 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.

  1. DNA Triplex-Based Complexes Display Anti-HIV-1-Cell Fusion Activity.

    PubMed

    Xu, Liang; Zhang, Tao; Xu, Xiaoyu; Chong, Huihui; Lai, Wenqing; Jiang, Xifeng; Wang, Chao; He, Yuxian; Liu, Keliang

    2015-08-01

    DNA triplexes with hydrophobic modifications were designed and evaluated for their activity as inhibitors of the cell fusion of human immunodeficiency virus type 1 (HIV-1). Triplex inhibitors displayed low micromolar activities in the cell-cell fusion assay and nanomolar activities in the anti-HIV-1 pseudovirus test. Helix structure and the presence of sufficient numbers of hydrophobic regions were essential for the antifusion activity. Results from native polyacrylamide gel electrophoresis and a fluorescent resonance energy transfer-based inhibitory assay indicated that these triplexes may interact with the primary pocket at the glycoprotein 41 (gp41) N-heptad repeat, thereby inhibiting formation of the HIV-1 gp41 6-helical bundle. Triplex-based complexes may represent a novel category of HIV-1 inhibitors in anti-HIV-1 drug discovery. PMID:26192705

  2. Alteration of the pH dependence of coronavirus-induced cell fusion: effect of mutations in the spike glycoprotein.

    PubMed Central

    Gallagher, T M; Escarmis, C; Buchmeier, M J

    1991-01-01

    Infection of susceptible murine cells with the coronavirus mouse hepatitis virus type 4 (MHV4) results in extensive cell-cell fusion at pHs from 5.5 to 8.5. The endosomotropic weak bases chloroquine and ammonium chloride do not prevent MHV4 infection. In marked contrast, we have selected variants from a neural cell line persistently infected with MHV4 which are entirely dependent on acid pH to fuse host cells and are strongly inhibited by endosomotropic weak bases. Wild-type and variant viruses were compared at the level of the fusion-active surface (S) glycoprotein gene. Cloning and sequencing of each 4,131-base open reading frame predicted a total of eight amino acid differences which fell into three distinct clusters. Each S glycoprotein, when expressed from cDNA, was synthesized in equivalent amounts, and similar proportions were transported to the cell surface. Wild-type S induced cell-cell fusion at neutral pH, whereas variant S required prolonged exposure to acidic pH to induce fusion. Expression of hybrid S genes prepared by exchange of restriction fragments between wild-type and variant cDNAs revealed that elimination of neutral pH fusion was solely dependent on amino acid alterations at positions 1067 (Q to H), 1094 (Q to H), and 1114 (L to R). These changes lie within a predicted heptad repeat region of the transmembrane cleavage fragment of S (S2). These findings demonstrate that the pH dependence of coronavirus fusion is highly variable and that this variability can be determined by as few as three amino acid residues. Images PMID:1848311

  3. Genetic Evidence That Captured Retroviral Envelope syncytins Contribute to Myoblast Fusion and Muscle Sexual Dimorphism in Mice.

    PubMed

    Redelsperger, François; Raddi, Najat; Bacquin, Agathe; Vernochet, Cécile; Mariot, Virginie; Gache, Vincent; Blanchard-Gutton, Nicolas; Charrin, Stéphanie; Tiret, Laurent; Dumonceaux, Julie; Dupressoir, Anne; Heidmann, Thierry

    2016-09-01

    Syncytins are envelope genes from endogenous retroviruses, "captured" for a role in placentation. They mediate cell-cell fusion, resulting in the formation of a syncytium (the syncytiotrophoblast) at the fetomaternal interface. These genes have been found in all placental mammals in which they have been searched for. Cell-cell fusion is also pivotal for muscle fiber formation and repair, where the myotubes are formed from the fusion of mononucleated myoblasts into large multinucleated structures. Here we show, taking advantage of mice knocked out for syncytins, that these captured genes contribute to myoblast fusion, with a >20% reduction in muscle mass, mean muscle fiber area and number of nuclei per fiber in knocked out mice for one of the two murine syncytin genes. Remarkably, this reduction is only observed in males, which subsequently show muscle quantitative traits more similar to those of females. In addition, we show that syncytins also contribute to muscle repair after cardiotoxin-induced injury, with again a male-specific effect on the rate and extent of regeneration. Finally, ex vivo experiments carried out on murine myoblasts demonstrate the direct involvement of syncytins in fusion, with a >40% reduction in fusion index upon addition of siRNA against both syncytins. Importantly, similar effects are observed with primary myoblasts from sheep, dog and human, with a 20-40% reduction upon addition of siRNA against the corresponding syncytins. Altogether, these results show a direct contribution of the fusogenic syncytins to myogenesis, with a demonstrated male-dependence of the effect in mice, suggesting that these captured genes could be responsible for the muscle sexual dimorphism observed in placental mammals. PMID:27589388

  4. Modulation of junction tension by tumor suppressors and proto-oncogenes regulates cell-cell contacts.

    PubMed

    Bosveld, Floris; Guirao, Boris; Wang, Zhimin; Rivière, Mathieu; Bonnet, Isabelle; Graner, François; Bellaïche, Yohanns

    2016-02-15

    Tumor suppressors and proto-oncogenes play crucial roles in tissue proliferation. Furthermore, de-regulation of their functions is deleterious to tissue architecture and can result in the sorting of somatic rounded clones minimizing their contact with surrounding wild-type (wt) cells. Defects in the shape of somatic clones correlate with defects in proliferation, cell affinity, cell-cell adhesion, oriented cell division and cortical contractility. Combining genetics, live-imaging, laser ablation and computer simulations, we aim to analyze whether distinct or similar mechanisms can account for the common role of tumor suppressors and proto-oncogenes in cell-cell contact regulation. In Drosophila epithelia, the tumor suppressors Fat (Ft) and Dachsous (Ds) regulate cell proliferation, tissue morphogenesis, planar cell polarity and junction tension. By analyzing the evolution over time of ft mutant cells and clones, we show that ft clones reduce their cell-cell contacts with the surrounding wt tissue in the absence of concomitant cell divisions and over-proliferation. This contact reduction depends on opposed changes of junction tensions in the clone bulk and its boundary with neighboring wt tissue. More generally, either clone bulk or boundary junction tension is modulated by the activation of Yorkie, Myc and Ras, yielding similar contact reductions with wt cells. Together, our data highlight mechanical roles for proto-oncogene and tumor suppressor pathways in cell-cell interactions. PMID:26811379

  5. Cell-cell contact promotes Ebola virus GP-mediated infection.

    PubMed

    Miao, Chunhui; Li, Minghua; Zheng, Yi-Min; Cohen, Fredric S; Liu, Shan-Lu

    2016-01-15

    Ebola virus (EBOV) is a highly pathogenic filovirus that causes hemorrhagic fever in humans and animals. Here we provide evidence that cell-cell contact promotes infection mediated by the glycoprotein (GP) of EBOV. Interestingly, expression of EBOV GP alone, even in the absence of retroviral Gag-Pol, is sufficient to transfer a retroviral vector encoding Tet-off from cell to cell. Cell-to-cell infection mediated by EBOV GP is blocked by inhibitors of actin polymerization, but appears to be less sensitive to KZ52 neutralization. Treatment of co-cultured cells with cathepsin B/L inhibitors, or an entry inhibitor 3.47 that targets the receptor NPC1 for virus binding, also blocks cell-to-cell infection. Cell-cell contact also enhances spread of rVSV bearing GP in monocytes and macrophages, the primary targets of natural EBOV infection. Altogether, our study reveals that cell-cell contact promotes EBOV GP-mediated infection, and provides new insight into understanding EBOV spread and viral pathogenesis. PMID:26655238

  6. Working Together for the Common Good: Cell-Cell Communication in Bacteria

    PubMed Central

    Schuster, Martin; Rumbaugh, Kendra P.

    2012-01-01

    The 4th ASM Conference on Cell-Cell Communication in Bacteria was held in Miami, FL, from 6 to 9 November 2011. This review highlights three key themes that emerged from the many exciting talks and poster presentations in the area of quorum sensing: sociomicrobiology, signal transduction mechanisms, and interspecies communication. PMID:22389476

  7. Working together for the common good: cell-cell communication in bacteria.

    PubMed

    Stevens, Ann M; Schuster, Martin; Rumbaugh, Kendra P

    2012-05-01

    The 4th ASM Conference on Cell-Cell Communication in Bacteria was held in Miami, FL, from 6 to 9 November 2011. This review highlights three key themes that emerged from the many exciting talks and poster presentations in the area of quorum sensing: sociomicrobiology, signal transduction mechanisms, and interspecies communication. PMID:22389476

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. Genetic analysis of heptad-repeat regions in the G2 fusion subunit of the Junin arenavirus envelope glycoprotein

    SciTech Connect

    York, Joanne . E-mail: joanne.york@umontana.edu; Agnihothram, Sudhakar S. . E-mail: sudhakar.agnihothram@umontana.edu; Romanowski, Victor . E-mail: victor@biol.unlp.edu.ar; Nunberg, Jack H. . E-mail: jack.nunberg@umontana.edu

    2005-12-20

    The G2 fusion subunit of the Junin virus envelope glycoprotein GP-C contains two hydrophobic heptad-repeat regions that are postulated to form a six-helix bundle structure required for the membrane fusion activity of Class I viral fusion proteins. We have investigated the role of these heptad-repeat regions and, specifically, the importance of the putative interhelical a and d position sidechains by using alanine-scanning mutagenesis. All the mutant glycoproteins were expressed and transported to the cell surface. Proteolytic maturation at the subtilisin kexin isozyme-1/site-1-protease (SKI-1/S1P) cleavage site was observed in all but two of the mutants. Among the adequately cleaved mutant glycoproteins, four positions in the N-terminal region (I333, L336, L347 and L350) and two positions in the C-terminal region (R392 and W395) were shown to be important determinants of cell-cell fusion. Taken together, our results indicate that {alpha}-helical coiled-coil structures are likely critical in promoting arenavirus membrane fusion. These findings support the inclusion of the arenavirus GP-C among the Class I viral fusion proteins and suggest pharmacologic and immunologic strategies for targeting arenavirus infection and hemorrhagic fever.

  19. Sphingomyelin Synthase 2, but Not Sphingomyelin Synthase 1, Is Involved in HIV-1 Envelope-mediated Membrane Fusion*

    PubMed Central

    Hayashi, Yasuhiro; Nemoto-Sasaki, Yoko; Tanikawa, Takashi; Oka, Saori; Tsuchiya, Kiyoto; Zama, Kouta; Mitsutake, Susumu; Sugiura, Takayuki; Yamashita, Atsushi

    2014-01-01

    Membrane fusion between the viral envelope and plasma membranes of target cells has previously been correlated with HIV-1 infection. Lipids in the plasma membrane, including sphingomyelin, may be crucially involved in HIV-1 infection; however, the role of lipid-metabolic enzymes in membrane fusion remains unclear. In this study, we examined the roles of sphingomyelin synthase (SMS) in HIV-1 Env-mediated membrane fusion using a cell-cell fusion assay with HIV-1 mimetics and their target cells. We employed reconstituted cells as target cells that stably express Sms1 or Sms2 in Sms-deficient cells. Fusion susceptibility was ∼5-fold higher in Sms2-expressing cells (not in Sms1-expressing cells) than in Sms-deficient cells. The enhancement of fusion susceptibility observed in Sms2-expressing cells was reversed and reduced by Sms2 knockdown. We also found that catalytically nonactive Sms2 promoted membrane fusion susceptibility. Moreover, SMS2 co-localized and was constitutively associated with the HIV receptor·co-receptor complex in the plasma membrane. In addition, HIV-1 Env treatment resulted in a transient increase in nonreceptor tyrosine kinase (Pyk2) phosphorylation in Sms2-expressing and catalytically nonactive Sms2-expressing cells. We observed that F-actin polymerization in the region of membrane fusion was more prominent in Sms2-expressing cells than Sms-deficient cells. Taken together, our research provides insight into a novel function of SMS2 which is the regulation of HIV-1 Env-mediated membrane fusion via actin rearrangement. PMID:25231990

  20. Future of Inertial Fusion Energy

    SciTech Connect

    Nuckolls, J H; Wood, L L

    2002-09-04

    In the past 50 years, fusion R&D programs have made enormous technical progress. Projected billion-dollar scale research facilities are designed to approach net energy production. In this century, scientific and engineering progress must continue until the economics of fusion power plants improves sufficiently to win large scale private funding in competition with fission and non-nuclear energy systems. This economic advantage must be sustained: trillion dollar investments will be required to build enough fusion power plants to generate ten percent of the world's energy. For Inertial Fusion Energy, multi-billion dollar driver costs must be reduced by up to an order of magnitude, to a small fraction of the total cost of the power plant. Major cost reductions could be achieved via substantial improvements in target performance-both higher gain and reduced ignition energy. Large target performance improvements may be feasible through a combination of design innovations, e.g., ''fast ignition,'' propagation down density gradients, and compression of fusion fuel with a combination of driver and chemical energy. The assumptions that limit projected performance of fusion targets should be carefully examined. The National Ignition Facility will enable development and testing of revolutionary targets designed to make possible economically competitive fusion power plants.

  1. Simulation Science for Fusion Plasmas

    NASA Astrophysics Data System (ADS)

    Skoric, M. M.; Sudo, S.

    2008-07-01

    The world fusion effort has recently entered a new age with the construction of ITER in Cadarache, France, which will be the first magnetic confinement fusion plasma experiment dominated by the self-heating of fusion reactions. In order to operate and control burning plasmas and future demo fusion reactors, an advanced ability for comprehensive computer simulations that are fully verified and validated against experimental data will be necessary. The ultimate goal is to develop the capability to predict reliably the behavior of plasmas in toroidal magnetic confinement devices on all relevant time and space scales. In addition to developing a sophisticated integrated simulation codes, directed advanced research in fusion physics, applied mathematics and computer science is envisaged. In this talk we review the basic strategy and main research efforts at the Department of Simulation Science of the National Institute for Fusion Science (NIFS)- which is the Inter University Institute and the coordinating Center of Excellence for academic fusion research in Japan. We overview a simulation research at NIFS, in particular relation to experiments in the Large Helical Device (LHD), the world's largest superconducting heliotron device, as a National Users' facility (see Motojima et al. 2003). Our main goal is understanding and systemizing the rich hierarchy of physical mechanisms in fusion plasmas, supported by exploring a basic science of complexity of plasma as a highly nonlinear, non-equilibrium, open system. The aim is to establish a simulation science as a new interdisciplinary field by fostering collaborative research in utilizing the large-scale supercomputer simulators. A concept of the hierarchy-renormalized simulation modelling will be invoked en route toward the LHD numerical test reactor. Finally, a perspective role is given on the ITER Broad Approach program at Rokkasho Center, as an integrated part of ITER and Development of Fusion Energy Agreement.

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

    DOE PAGESBeta

    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

  3. 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.

  4. 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

  5. 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)

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

    PubMed Central

    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

    2015-01-01

    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. PMID:26040699

  7. Systematic analysis of advanced fusion fuel in inertial fusion energy

    NASA Astrophysics Data System (ADS)

    Velarde, G.; Eliezer, S.; Henis, Z.; Piera, M.; Martinez-Val, J. M.

    1997-04-01

    Aneutronic fusion reactions can be considered as the cleanest way to exploit nuclear energy. However, these reactions present in general two main drawbacks.—very high temperatures are needed to reach relevant values of their cross sections—Moderate (and even low) energy yield per reaction. This value is still lower if measured in relation to the Z number of the reacting particles. It is already known that bremsstrahlung overruns the plasma reheating by fusion born charged-particles in most of the advanced fuels. This is for instance the case for proton-boron-11 fusion in a stoichiometric plasma and is also so in lithium isotopes fusion reactions. In this paper, the use of deuterium-tritium seeding is suggested to allow to reach higher burnup fractions of advanced fuels, starting at a lower ignition temperature. Of course, neutron production increases as DT contents does. Nevertheless, the ratio of neutron production to energy generation is much lower in DT-advanced fuel mixtures than in pure DT plasmas. One of the main findings of this work is that some natural resources (as D and Li-7) can be burned-up in a catalytic regime for tritium. In this case, neither external tritium breeding nor tritium storage are needed, because the tritium inventory after the fusion burst is the same as before it. The fusion reactor can thus operate on a pure recycling of a small tritium inventory.

  8. Enabling Technology in Support of Fusion Science

    NASA Astrophysics Data System (ADS)

    Baker, Charles C.

    1999-03-01

    This paper summarizes remarks made at Fusion Power Associates annual meeting, July 17, 2000 in San Diego. It describes the U.S. Department of Energy Office of Fusion Enegy Sciences programs in plasma and fusion technology in support of the U. S. fusion energy sciences program.

  9. High-throughput detection and quantification of mitochondrial fusion through imaging flow cytometry.

    PubMed

    Nascimento, Aldo; Lannigan, Joanne; Kashatus, David

    2016-08-01

    Mitochondria are highly dynamic organelles whose fusion and fission play an increasingly important role in a number of both normal and pathological cellular functions. Despite the increased interest in mitochondrial dynamics, robust, and quantitative methods to analyze mitochondrial fusion and fission activity in intact cells have not been developed. The current state-of-the art method to measure mitochondrial fusion activity is the polyethylene glycol (PEG) fusion assay in which cells expressing distinct mitochondrially-targeted fluorescent proteins (FPs) are fused together and mitochondrial fusion activity is determined by the rate at which color mixing occurs. Although this assay is useful, cell-cell fusion events are rare, and finding the number of fused cells required to generate statistically rigorous data is both tedious and time-consuming. Furthermore, the data-collection methods available for fluorescence microscopy lead to inherent selection biases that are difficult to control for. To that end, we have developed an unbiased and high-throughput method to detect, image, and analyze fused cells using the Amnis ImagestreamX™ MKII. With IDEAS™ software, we developed algorithms for identifying the fused cells (two nuclei within a single cell), distinguishing them from cell aggregates. Additionally, using the fluorescence localization of the mitochondrially-targeted fluorescent proteins (YFP and DsRed), we applied a modified co-localization algorithm to identify those cells that had a high co-localization score indicating mitochondrial fusion activity. These algorithms were tested using negative controls (FPs associated with fusion deficient mitochondria) and positive controls (cells expressing both FPs in the same mitochondria). Once validated these algorithms could be applied to test samples to evaluate the degree of mitochondrial fusion in cells with various genetic mutations. Ultimately, this new method is the first robust, high-throughput way to

  10. Class II virus membrane fusion proteins

    SciTech Connect

    Kielian, Margaret . E-mail: kielian@aecom.yu.edu

    2006-01-05

    Enveloped animal viruses fuse their membrane with a host cell membrane, thus delivering the virus genetic material into the cytoplasm and initiating infection. This critical membrane fusion reaction is mediated by a virus transmembrane protein known as the fusion protein, which inserts its hydrophobic fusion peptide into the cell membrane and refolds to drive the fusion reaction. This review describes recent advances in our understanding of the structure and function of the class II fusion proteins of the alphaviruses and flaviviruses. Inhibition of the fusion protein refolding reaction confirms its importance in fusion and suggests new antiviral strategies for these medically important viruses.