Paramyxovirus fusion: Real-time measurement of parainfluenza virus 5 virus-cell fusion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Connolly, Sarah A.; Lamb, Robert A.

2006-11-25

Although cell-cell fusion assays are useful surrogate methods for studying virus fusion, differences between cell-cell and virus-cell fusion exist. To examine paramyxovirus fusion in real time, we labeled viruses with fluorescent lipid probes and monitored virus-cell fusion by fluorimetry. Two parainfluenza virus 5 (PIV5) isolates (W3A and SER) and PIV5 containing mutations within the fusion protein (F) were studied. Fusion was specific and temperature-dependent. Compared to many low pH-dependent viruses, the kinetics of PIV5 fusion was slow, approaching completion within several minutes. As predicted from cell-cell fusion assays, virus containing an F protein with an extended cytoplasmic tail (rSV5 F551)more » had reduced fusion compared to wild-type virus (W3A). In contrast, virus-cell fusion for SER occurred at near wild-type levels, despite the fact that this isolate exhibits a severely reduced cell-cell fusion phenotype. These results support the notion that virus-cell and cell-cell fusion have significant differences.« less

Benchmarking of data fusion algorithms in support of earth observation based Antarctic wildlife monitoring

NASA Astrophysics Data System (ADS)

Witharana, Chandi; LaRue, Michelle A.; Lynch, Heather J.

2016-03-01

Remote sensing is a rapidly developing tool for mapping the abundance and distribution of Antarctic wildlife. While both panchromatic and multispectral imagery have been used in this context, image fusion techniques have received little attention. We tasked seven widely-used fusion algorithms: Ehlers fusion, hyperspherical color space fusion, high-pass fusion, principal component analysis (PCA) fusion, University of New Brunswick fusion, and wavelet-PCA fusion to resolution enhance a series of single-date QuickBird-2 and Worldview-2 image scenes comprising penguin guano, seals, and vegetation. Fused images were assessed for spectral and spatial fidelity using a variety of quantitative quality indicators and visual inspection methods. Our visual evaluation elected the high-pass fusion algorithm and the University of New Brunswick fusion algorithm as best for manual wildlife detection while the quantitative assessment suggested the Gram-Schmidt fusion algorithm and the University of New Brunswick fusion algorithm as best for automated classification. The hyperspherical color space fusion algorithm exhibited mediocre results in terms of spectral and spatial fidelities. The PCA fusion algorithm showed spatial superiority at the expense of spectral inconsistencies. The Ehlers fusion algorithm and the wavelet-PCA algorithm showed the weakest performances. As remote sensing becomes a more routine method of surveying Antarctic wildlife, these benchmarks will provide guidance for image fusion and pave the way for more standardized products for specific types of wildlife surveys.

Nighttime images fusion based on Laplacian pyramid

NASA Astrophysics Data System (ADS)

Wu, Cong; Zhan, Jinhao; Jin, Jicheng

2018-02-01

This paper expounds method of the average weighted fusion, image pyramid fusion, the wavelet transform and apply these methods on the fusion of multiple exposures nighttime images. Through calculating information entropy and cross entropy of fusion images, we can evaluate the effect of different fusion. Experiments showed that Laplacian pyramid image fusion algorithm is suitable for processing nighttime images fusion, it can reduce the halo while preserving image details.

FusionHub: A unified web platform for annotation and visualization of gene fusion events in human cancer.

PubMed

Panigrahi, Priyabrata; Jere, Abhay; Anamika, Krishanpal

2018-01-01

Gene fusion is a chromosomal rearrangement event which plays a significant role in cancer due to the oncogenic potential of the chimeric protein generated through fusions. At present many databases are available in public domain which provides detailed information about known gene fusion events and their functional role. Existing gene fusion detection tools, based on analysis of transcriptomics data usually report a large number of fusion genes as potential candidates, which could be either known or novel or false positives. Manual annotation of these putative genes is indeed time-consuming. We have developed a web platform FusionHub, which acts as integrated search engine interfacing various fusion gene databases and simplifies large scale annotation of fusion genes in a seamless way. In addition, FusionHub provides three ways of visualizing fusion events: circular view, domain architecture view and network view. Design of potential siRNA molecules through ensemble method is another utility integrated in FusionHub that could aid in siRNA-based targeted therapy. FusionHub is freely available at https://fusionhub.persistent.co.in.

Complementation between avirulent Newcastle disease virus and a fusion protein gene expressed from a retrovirus vector: requirements for membrane fusion.

PubMed Central

Morrison, T; McQuain, C; McGinnes, L

1991-01-01

The cDNA derived from the fusion gene of the virulent AV strain of Newcastle disease virus (NDV) was expressed in chicken embryo cells by using a retrovirus vector. The fusion protein expressed in this system was transported to the cell surface and was efficiently cleaved into the disulfide-linked F1-F2 form found in infectious virions. The cells expressing the fusion gene grew normally and could be passaged many times. Monolayers of these cells would plaque, in the absence of trypsin, avirulent NDV strains (strains which encode a fusion protein which is not cleaved in tissue culture). Fusion protein-expressing cells would not fuse if mixed with uninfected cells or uninfected cells expressing the hemagglutinin-neuraminidase (HN) protein. However, the fusion protein-expressing cells, if infected with avirulent strains of NDV, would fuse with uninfected cells, suggesting that fusion requires both the fusion protein and another viral protein expressed in the same cell. Fusion was also seen after transfection of the HN protein gene into fusion protein-expressing cells. Thus, the expressed fusion protein gene is capable of complementing the virus infection, providing an active cleaved fusion protein required for the spread of infection. However, the fusion protein does not mediate cell fusion unless the cell also expresses the HN protein. Fusion protein-expressing cells would not plaque influenza virus in the absence of trypsin, nor would influenza virus-infected fusion protein-expressing cells fuse with uninfected cells. Thus, the influenza virus HA protein will not substitute for the NDV HN protein in cell-to-cell fusion. Images PMID:1987376

Systematic identification and analysis of frequent gene fusion events in metabolic pathways

DOE Office of Scientific and Technical Information (OSTI.GOV)

Henry, Christopher S.; Lerma-Ortiz, Claudia; Gerdes, Svetlana Y.

Here, gene fusions are the most powerful type of in silico-derived functional associations. However, many fusion compilations were made when <100 genomes were available, and algorithms for identifying fusions need updating to handle the current avalanche of sequenced genomes. The availability of a large fusion dataset would help probe functional associations and enable systematic analysis of where and why fusion events occur. As a result, here we present a systematic analysis of fusions in prokaryotes. We manually generated two training sets: (i) 121 fusions in the model organism Escherichia coli; (ii) 131 fusions found in B vitamin metabolism. These setsmore » were used to develop a fusion prediction algorithm that captured the training set fusions with only 7 % false negatives and 50 % false positives, a substantial improvement over existing approaches. This algorithm was then applied to identify 3.8 million potential fusions across 11,473 genomes. The results of the analysis are available in a searchable database. A functional analysis identified 3,000 reactions associated with frequent fusion events and revealed areas of metabolism where fusions are particularly prevalent. In conclusion, customary definitions of fusions were shown to be ambiguous, and a stricter one was proposed. Exploring the genes participating in fusion events showed that they most commonly encode transporters, regulators, and metabolic enzymes. The major rationales for fusions between metabolic genes appear to be overcoming pathway bottlenecks, avoiding toxicity, controlling competing pathways, and facilitating expression and assembly of protein complexes. Finally, our fusion dataset provides powerful clues to decipher the biological activities of domains of unknown function.« less

Systematic identification and analysis of frequent gene fusion events in metabolic pathways

DOE PAGES

Henry, Christopher S.; Lerma-Ortiz, Claudia; Gerdes, Svetlana Y.; ...

2016-06-24

Here, gene fusions are the most powerful type of in silico-derived functional associations. However, many fusion compilations were made when <100 genomes were available, and algorithms for identifying fusions need updating to handle the current avalanche of sequenced genomes. The availability of a large fusion dataset would help probe functional associations and enable systematic analysis of where and why fusion events occur. As a result, here we present a systematic analysis of fusions in prokaryotes. We manually generated two training sets: (i) 121 fusions in the model organism Escherichia coli; (ii) 131 fusions found in B vitamin metabolism. These setsmore » were used to develop a fusion prediction algorithm that captured the training set fusions with only 7 % false negatives and 50 % false positives, a substantial improvement over existing approaches. This algorithm was then applied to identify 3.8 million potential fusions across 11,473 genomes. The results of the analysis are available in a searchable database. A functional analysis identified 3,000 reactions associated with frequent fusion events and revealed areas of metabolism where fusions are particularly prevalent. In conclusion, customary definitions of fusions were shown to be ambiguous, and a stricter one was proposed. Exploring the genes participating in fusion events showed that they most commonly encode transporters, regulators, and metabolic enzymes. The major rationales for fusions between metabolic genes appear to be overcoming pathway bottlenecks, avoiding toxicity, controlling competing pathways, and facilitating expression and assembly of protein complexes. Finally, our fusion dataset provides powerful clues to decipher the biological activities of domains of unknown function.« less

Membrane fusion triggers rapid degradation of two gamete-specific, fusion-essential proteins in a membrane block to polygamy in Chlamydomonas.

PubMed

Liu, Yanjie; Misamore, Michael J; Snell, William J

2010-05-01

The plasma membranes of gametes are specialized for fusion, yet, once fusion occurs, in many organisms the new zygote becomes incapable of further membrane fusion reactions. The molecular mechanisms that underlie this loss of fusion capacity (block to polygamy) remain unknown. During fertilization in the green alga Chlamydomonas, the plus gamete-specific membrane protein FUS1 is required for adhesion between the apically localized sites on the plasma membranes of plus and minus gametes that are specialized for fusion, and the minus-specific membrane protein HAP2 is essential for completion of the membrane fusion reaction. HAP2 (GCS1) family members are also required for fertilization in Arabidopsis, and for the membrane fusion reaction in the malaria organism Plasmodium berghei. Here, we tested whether Chlamydomonas gamete fusion triggers alterations in FUS1 and HAP2 and renders the plasma membranes of the cells incapable of subsequent fusion. We find that, even though the fusogenic sites support multi-cell adhesions, triploid zygotes are rare, indicating a fusion-triggered block to the membrane fusion reaction. Consistent with the extinction of fusogenic capacity, both FUS1 and HAP2 are degraded upon fusion. The rapid, fusion-triggered cleavage of HAP2 in zygotes is distinct from degradation occurring during constitutive turnover in gametes. Thus, gamete fusion triggers specific degradation of fusion-essential proteins and renders the zygote incapable of fusion. Our results provide the first molecular explanation for a membrane block to polygamy in any organism.

Kinetic advantage of controlled intermediate nuclear fusion

NASA Astrophysics Data System (ADS)

Guo, Xiaoming

2012-09-01

The dominated process of controlled fusion is to let nuclei gain enough kinetic energy to overcome Coulomb barrier. As a result, a fusion scheme can consider two factors in its design: to increase kinetic energy of nuclei and to alter the Coulomb barrier. Cold Fusion and Hot fusion are all one-factor schemes while Intermediate Fusion is a twofactors scheme. This made CINF kinetically superior. Cold Fusion reduces deuteron-deuteron distance, addressing Coulomb barrier, and Hot Fusion heat up plasma into extreme high temperature, addressing kinetic energy. Without enough kinetic energy made Cold Fusion skeptical. Extreme high temperature made Hot Fusion very difficult to engineer. Because CIFN addresses both factors, CIFN is a more promising technique to be industrialized.

Direct current stimulation of titanium interbody fusion devices in primates.

PubMed

Cook, Stephen D; Patron, Laura P; Christakis, Petros M; Bailey, Kirk J; Banta, Charles; Glazer, Paul A

2004-01-01

The fusion rate for anterior lumbar interbody fusion (ALIF) varies widely with the use of different interbody devices and bone graft options. Adjunctive techniques such as electrical stimulation may improve the rate of bony fusion. To determine if direct current (DC) electrical stimulation of a metallic interbody fusion device enhanced the incidence or extent of anterior bony fusion. ALIF was performed using titanium alloy interbody fusion devices with and without adjunctive DC electrical stimulation in nonhuman primates. ALIF was performed through an anterolateral approach in 35 macaques with autogenous bone graft and either a titanium alloy (Ti-6Al-4V) fusion device or femoral allograft ring. The fusion devices of 19 animals received high (current density 19.6 microA/cm2) or low (current density 5.4 microA/cm2) DC electrical stimulation using an implanted generator for a 12- or 26-week evaluation period. Fusion sites were studied using serial radiographs, computed tomography imaging, nondestructive mechanical testing and qualitative and semiquantitative histology. Fusion was achieved with the titanium fusion device and autogenous bone graft. At 12 weeks, the graft was consolidating and early to moderate bridging callus was observed in and around the device. By 26 weeks, the anterior callus formation was more advanced with increased evidence of bridging trabeculations and early bone remodeling. The callus formation was not as advanced or abundant for the allograft ring group. Histology revealed the spinal fusion device had an 86% incidence of bony fusion at 26 weeks compared with a 50% fusion rate for the allograft rings. DC electrical stimulation of the fusion device had a positive effect on anterior interbody fusion by increasing both the presence and extent of bony fusion in a current density-dependent manner. Adjunctive DC electrical stimulation of the fusion device improved the rate and extent of bony fusion compared with a nonstimulated device. The fusion device was equivalent to or better than the femoral allograft ring in all evaluations. The use of adjunctive direct current electrical stimulation may provide a means of improving anterior interbody fusion.

76 FR 49757 - Fusion Energy Sciences Advisory Committee

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-11

... DEPARTMENT OF ENERGY Fusion Energy Sciences Advisory Committee AGENCY: Office of Science... Services Administration, notice is hereby given that the Fusion Energy Sciences Advisory Committee will be... science, fusion science, and fusion technology related to the Fusion Energy Sciences program. Additionally...

Exploration of the gene fusion landscape of glioblastoma using transcriptome sequencing and copy number data.

PubMed

Shah, Nameeta; Lankerovich, Michael; Lee, Hwahyung; Yoon, Jae-Geun; Schroeder, Brett; Foltz, Greg

2013-11-22

RNA-seq has spurred important gene fusion discoveries in a number of different cancers, including lung, prostate, breast, brain, thyroid and bladder carcinomas. Gene fusion discovery can potentially lead to the development of novel treatments that target the underlying genetic abnormalities. In this study, we provide comprehensive view of gene fusion landscape in 185 glioblastoma multiforme patients from two independent cohorts. Fusions occur in approximately 30-50% of GBM patient samples. In the Ivy Center cohort of 24 patients, 33% of samples harbored fusions that were validated by qPCR and Sanger sequencing. We were able to identify high-confidence gene fusions from RNA-seq data in 53% of the samples in a TCGA cohort of 161 patients. We identified 13 cases (8%) with fusions retaining a tyrosine kinase domain in the TCGA cohort and one case in the Ivy Center cohort. Ours is the first study to describe recurrent fusions involving non-coding genes. Genomic locations 7p11 and 12q14-15 harbor majority of the fusions. Fusions on 7p11 are formed in focally amplified EGFR locus whereas 12q14-15 fusions are formed by complex genomic rearrangements. All the fusions detected in this study can be further visualized and analyzed using our website: http://ivygap.swedish.org/fusions. Our study highlights the prevalence of gene fusions as one of the major genomic abnormalities in GBM. The majority of the fusions are private fusions, and a minority of these recur with low frequency. A small subset of patients with fusions of receptor tyrosine kinases can benefit from existing FDA approved drugs and drugs available in various clinical trials. Due to the low frequency and rarity of clinically relevant fusions, RNA-seq of GBM patient samples will be a vital tool for the identification of patient-specific fusions that can drive personalized therapy.

Fusion activity of HIV gp41 fusion domain is related to its secondary structure and depth of membrane insertion in a cholesterol-dependent fashion.

PubMed

Lai, Alex L; Moorthy, Anna Eswara; Li, Yinling; Tamm, Lukas K

2012-04-20

The human immunodeficiency virus (HIV) gp41 fusion domain plays a critical role in membrane fusion during viral entry. A thorough understanding of the relationship between the structure and the activity of the fusion domain in different lipid environments helps to formulate mechanistic models on how it might function in mediating membrane fusion. The secondary structure of the fusion domain in small liposomes composed of different lipid mixtures was investigated by circular dichroism spectroscopy.  The fusion domain formed an α-helix in membranes containing less than 30 mol% cholesterol and  formed β-sheet secondary structure in membranes containing ≥30 mol% cholesterol. EPR spectra of spin-labeled fusion domains also indicated different conformations in membranes with and without cholesterol. Power saturation EPR data were further used to determine the orientation and depth of α-helical fusion domains in lipid bilayers. Fusion and membrane perturbation activities of the gp41 fusion domain were measured by lipid mixing and contents leakage. The fusion domain fused membranes in both its helical form and its β-sheet form. High cholesterol, which induced β-sheets, promoted fusion; however, acidic lipids, which promoted relatively deep membrane insertion as an α-helix, also induced fusion. The results indicate that the structure of the HIV gp41 fusion domain is plastic and depends critically on the lipid environment. Provided that their membrane insertion is deep, α-helical and β-sheet conformations contribute to membrane fusion. Copyright © 2012 Elsevier Ltd. All rights reserved.

Spatial focalization of pheromone/MAPK signaling triggers commitment to cell–cell fusion

PubMed Central

Merlini, Laura

2016-01-01

Cell fusion is universal in eukaryotes for fertilization and development, but what signals this process is unknown. Here, we show in Schizosaccharomyces pombe that fusion does not require a dedicated signal but is triggered by spatial focalization of the same pheromone–GPCR (G-protein-coupled receptor)–MAPK signaling cascade that drives earlier mating events. Autocrine cells expressing the receptor for their own pheromone trigger fusion attempts independently of cell–cell contact by concentrating pheromone release at the fusion focus, a dynamic actin aster underlying the secretion of cell wall hydrolases. Pheromone receptor and MAPK cascade are similarly enriched at the fusion focus, concomitant with fusion commitment in wild-type mating pairs. This focalization promotes cell fusion by immobilizing the fusion focus, thus driving local cell wall dissolution. We propose that fusion commitment is imposed by a local increase in MAPK concentration at the fusion focus, driven by a positive feedback between fusion focus formation and focalization of pheromone release and perception. PMID:27798845

Structural Transition and Antibody Binding of EBOV GP and ZIKV E Proteins from Pre-Fusion to Fusion-Initiation State.

PubMed

Lappala, Anna; Nishima, Wataru; Miner, Jacob; Fenimore, Paul; Fischer, Will; Hraber, Peter; Zhang, Ming; McMahon, Benjamin; Tung, Chang-Shung

2018-05-10

Membrane fusion proteins are responsible for viral entry into host cells—a crucial first step in viral infection. These proteins undergo large conformational changes from pre-fusion to fusion-initiation structures, and, despite differences in viral genomes and disease etiology, many fusion proteins are arranged as trimers. Structural information for both pre-fusion and fusion-initiation states is critical for understanding virus neutralization by the host immune system. In the case of Ebola virus glycoprotein (EBOV GP) and Zika virus envelope protein (ZIKV E), pre-fusion state structures have been identified experimentally, but only partial structures of fusion-initiation states have been described. While the fusion-initiation structure is in an energetically unfavorable state that is difficult to solve experimentally, the existing structural information combined with computational approaches enabled the modeling of fusion-initiation state structures of both proteins. These structural models provide an improved understanding of four different neutralizing antibodies in the prevention of viral host entry.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wurth, Mark A.; Schowalter, Rachel M.; Smith, Everett Clinton

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 cytoplasmicmore » 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.« less

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

PubMed

Gao, Qingsong; Liang, Wen-Wei; Foltz, Steven M; Mutharasu, Gnanavel; Jayasinghe, Reyka G; Cao, Song; Liao, Wen-Wei; Reynolds, Sheila M; Wyczalkowski, Matthew A; Yao, Lijun; Yu, Lihua; Sun, Sam Q; Chen, Ken; Lazar, Alexander J; Fields, Ryan C; Wendl, Michael C; Van Tine, Brian A; Vij, Ravi; Chen, Feng; Nykter, Matti; Shmulevich, Ilya; Ding, Li

2018-04-03

Gene fusions represent an important class of somatic alterations in cancer. We systematically investigated fusions in 9,624 tumors across 33 cancer types using multiple fusion calling tools. We identified a total of 25,664 fusions, with a 63% validation rate. Integration of gene expression, copy number, and fusion annotation data revealed that fusions involving oncogenes tend to exhibit increased expression, whereas fusions involving tumor suppressors have the opposite effect. For fusions involving kinases, we found 1,275 with an intact kinase domain, the proportion of which varied significantly across cancer types. Our study suggests that fusions drive the development of 16.5% of cancer cases and function as the sole driver in more than 1% of them. Finally, we identified druggable fusions involving genes such as TMPRSS2, RET, FGFR3, ALK, and ESR1 in 6.0% of cases, and we predicted immunogenic peptides, suggesting that fusions may provide leads for targeted drug and immune therapy. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

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

PubMed Central

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

2010-01-01

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. PMID:20537366

Myomaker is a membrane activator of myoblast fusion and muscle formation.

PubMed

Millay, Douglas P; O'Rourke, Jason R; Sutherland, Lillian B; Bezprozvannaya, Svetlana; Shelton, John M; Bassel-Duby, Rhonda; Olson, Eric N

2013-07-18

Fusion of myoblasts is essential for the formation of multi-nucleated muscle fibres. However, the identity of muscle-specific proteins that directly govern this fusion process in mammals has remained elusive. Here we identify a muscle-specific membrane protein, named myomaker, that controls myoblast fusion. Myomaker is expressed on the cell surface of myoblasts during fusion and is downregulated thereafter. Overexpression of myomaker in myoblasts markedly enhances fusion, and genetic disruption of myomaker in mice causes perinatal death due to an absence of multi-nucleated muscle fibres. Remarkably, forced expression of myomaker in fibroblasts promotes fusion with myoblasts, demonstrating the direct participation of this protein in the fusion process. Pharmacological perturbation of the actin cytoskeleton abolishes the activity of myomaker, consistent with previous studies implicating actin dynamics in myoblast fusion. These findings reveal a long-sought myogenic fusion protein that controls mammalian myoblast fusion and provide new insights into the molecular underpinnings of muscle formation.

Hemi-fused structure mediates and controls fusion and fission in live cells

PubMed Central

Zhao, Wei-Dong; Hamid, Edaeni; Shin, Wonchul; Wen, Peter J.; Krystofiak, Evan S.; Villarreal, Seth A.; Chiang, Hsueh-Cheng; Kachar, Bechara; Wu, Ling-Gang

2016-01-01

Membrane fusion and fission are vital to eukaryotes’ life1–5. For three decades, it has been proposed that fusion is mediated by fusion between proximal leaflets of two bilayers (hemi-fusion) that produces a hemi-fused structure, followed by fusion between distal leaflets, whereas fission is via hemi-fission, which also produces a hemi-fused structure, followed by full fission1, 4, 6–10. This hypothesis remained unsupported owing to the lack of observation of hemi-fusion/hemi-fission in live cells. A competing fusion hypothesis involving protein-lined pore formation has also been proposed2, 11–15. Using confocal and super-resolution STED microscopy, we observed the hemi-fused Ω-shaped structure for the first time in live cells, neuroendocrine chromaffin cells and pancreatic β-cells. This structure was generated from fusion pore opening or closure (fission) at the plasma membrane. Unexpectedly, its transition to full fusion or fission was determined by competition between fusion and calcium/dynamin-dependent fission mechanisms, and was surprisingly slow (seconds to tens of seconds) in a significant fraction of the events. These results provide key missing evidence over the past three decades proving the hemi-fusion and hemi-fission hypothesis in live cells, and reveal the hemi-fused intermediate as a key structure controlling fusion/fission, as fusion and fission mechanisms compete to determine its transition to fusion or fission. PMID:27309816

Response to FESAC survey, non-fusion connections to Fusion Energy Sciences. Applications of the FES-supported beam and plasma simulation code, Warp

DOE Office of Scientific and Technical Information (OSTI.GOV)

Friedman, A.; Grote, D. P.; Vay, J. L.

2015-05-29

The Fusion Energy Sciences Advisory Committee’s subcommittee on non-fusion applications (FESAC NFA) is conducting a survey to obtain information from the fusion community about non-fusion work that has resulted from their DOE-funded fusion research. The subcommittee has requested that members of the community describe recent developments connected to the activities of the DOE Office of Fusion Energy Sciences. Two questions in particular were posed by the subcommittee. This document contains the authors’ responses to those questions.

In vitro assay using engineered yeast vacuoles for neuronal SNARE-mediated membrane fusion

PubMed Central

Ko, Young-Joon; Lee, Miriam; Kang, KyeongJin; Song, Woo Keun; Jun, Youngsoo

2014-01-01

Intracellular membrane fusion requires not only SNARE proteins but also other regulatory proteins such as the Rab and Sec1/Munc18 (SM) family proteins. Although neuronal SNARE proteins alone can drive the fusion between synthetic liposomes, it remains unclear whether they are also sufficient to induce the fusion of biological membranes. Here, through the use of engineered yeast vacuoles bearing neuronal SNARE proteins, we show that neuronal SNAREs can induce membrane fusion between yeast vacuoles and that this fusion does not require the function of the Rab protein Ypt7p or the SM family protein Vps33p, both of which are essential for normal yeast vacuole fusion. Although excess vacuolar SNARE proteins were also shown to mediate Rab-bypass fusion, this fusion required homotypic fusion and vacuole protein sorting complex, which bears Vps33p and was accompanied by extensive membrane lysis. We also show that this neuronal SNARE-driven vacuole fusion can be stimulated by the neuronal SM protein Munc18 and blocked by botulinum neurotoxin serotype E, a well-known inhibitor of synaptic vesicle fusion. Taken together, our results suggest that neuronal SNARE proteins are sufficient to induce biological membrane fusion, and that this new assay can be used as a simple and complementary method for investigating synaptic vesicle fusion mechanisms. PMID:24821814

State-of-the-Art Fusion-Finder Algorithms Sensitivity and Specificity

PubMed Central

Carrara, Matteo; Beccuti, Marco; Lazzarato, Fulvio; Cavallo, Federica; Cordero, Francesca; Donatelli, Susanna; Calogero, Raffaele A.

2013-01-01

Background. Gene fusions arising from chromosomal translocations have been implicated in cancer. RNA-seq has the potential to discover such rearrangements generating functional proteins (chimera/fusion). Recently, many methods for chimeras detection have been published. However, specificity and sensitivity of those tools were not extensively investigated in a comparative way. Results. We tested eight fusion-detection tools (FusionHunter, FusionMap, FusionFinder, MapSplice, deFuse, Bellerophontes, ChimeraScan, and TopHat-fusion) to detect fusion events using synthetic and real datasets encompassing chimeras. The comparison analysis run only on synthetic data could generate misleading results since we found no counterpart on real dataset. Furthermore, most tools report a very high number of false positive chimeras. In particular, the most sensitive tool, ChimeraScan, reports a large number of false positives that we were able to significantly reduce by devising and applying two filters to remove fusions not supported by fusion junction-spanning reads or encompassing large intronic regions. Conclusions. The discordant results obtained using synthetic and real datasets suggest that synthetic datasets encompassing fusion events may not fully catch the complexity of RNA-seq experiment. Moreover, fusion detection tools are still limited in sensitivity or specificity; thus, there is space for further improvement in the fusion-finder algorithms. PMID:23555082

Novel kinase fusion transcripts found in endometrial cancer

PubMed Central

Tamura, Ryo; Yoshihara, Kosuke; Yamawaki, Kaoru; Suda, Kazuaki; Ishiguro, Tatsuya; Adachi, Sosuke; Okuda, Shujiro; Inoue, Ituro; Verhaak, Roel G. W.; Enomoto, Takayuki

2015-01-01

Recent advances in RNA-sequencing technology have enabled the discovery of gene fusion transcripts in the transcriptome of cancer cells. However, it remains difficult to differentiate the therapeutically targetable fusions from passenger events. We have analyzed RNA-sequencing data and DNA copy number data from 25 endometrial cancer cell lines to identify potential therapeutically targetable fusion transcripts, and have identified 124 high-confidence fusion transcripts, of which 69% are associated with gene amplifications. As targetable fusion candidates, we focused on three in-frame kinase fusion transcripts that retain a kinase domain (CPQ-PRKDC, CAPZA2-MET, and VGLL4-PRKG1). We detected only CPQ-PRKDC fusion transcript in three of 122 primary endometrial cancer tissues. Cell proliferation of the fusion-positive cell line was inhibited by knocking down the expression of wild-type PRKDC but not by blocking the CPQ-PRKDC fusion transcript expression. Quantitative real-time RT-PCR demonstrated that the expression of the CPQ-PRKDC fusion transcript was significantly lower than that of wild-type PRKDC, corresponding to a low transcript allele fraction of this fusion, based on RNA-sequencing read counts. In endometrial cancers, the CPQ-PRKDC fusion transcript may be a passenger aberration related to gene amplification. Our findings suggest that transcript allele fraction is a useful predictor to find bona-fide therapeutic-targetable fusion transcripts. PMID:26689674

Novel kinase fusion transcripts found in endometrial cancer.

PubMed

Tamura, Ryo; Yoshihara, Kosuke; Yamawaki, Kaoru; Suda, Kazuaki; Ishiguro, Tatsuya; Adachi, Sosuke; Okuda, Shujiro; Inoue, Ituro; Verhaak, Roel G W; Enomoto, Takayuki

2015-12-22

Recent advances in RNA-sequencing technology have enabled the discovery of gene fusion transcripts in the transcriptome of cancer cells. However, it remains difficult to differentiate the therapeutically targetable fusions from passenger events. We have analyzed RNA-sequencing data and DNA copy number data from 25 endometrial cancer cell lines to identify potential therapeutically targetable fusion transcripts, and have identified 124 high-confidence fusion transcripts, of which 69% are associated with gene amplifications. As targetable fusion candidates, we focused on three in-frame kinase fusion transcripts that retain a kinase domain (CPQ-PRKDC, CAPZA2-MET, and VGLL4-PRKG1). We detected only CPQ-PRKDC fusion transcript in three of 122 primary endometrial cancer tissues. Cell proliferation of the fusion-positive cell line was inhibited by knocking down the expression of wild-type PRKDC but not by blocking the CPQ-PRKDC fusion transcript expression. Quantitative real-time RT-PCR demonstrated that the expression of the CPQ-PRKDC fusion transcript was significantly lower than that of wild-type PRKDC, corresponding to a low transcript allele fraction of this fusion, based on RNA-sequencing read counts. In endometrial cancers, the CPQ-PRKDC fusion transcript may be a passenger aberration related to gene amplification. Our findings suggest that transcript allele fraction is a useful predictor to find bona-fide therapeutic-targetable fusion transcripts.

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

PubMed

Xu, Kai; Chan, Yee-Peng; Bradel-Tretheway, Birgit; Akyol-Ataman, Zeynep; Zhu, Yongqun; 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

2015-12-01

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.

The biomechanics of a multilevel lumbar spine hybrid using nucleus replacement in conjunction with fusion.

PubMed

Dahl, Michael C; Ellingson, Arin M; Mehta, Hitesh P; Huelman, Justin H; Nuckley, David J

2013-02-01

Degenerative disc disease is commonly a multilevel pathology with varying deterioration severity. The use of fusion on multiple levels can significantly affect functionality and has been linked to persistent adjacent disc degeneration. A hybrid approach of fusion and nucleus replacement (NR) has been suggested as a solution for mildly degenerated yet painful levels adjacent to fusion. To compare the biomechanical metrics of different hybrid implant constructs, hypothesizing that an NR+fusion hybrid would be similar to a single-level fusion and perform more naturally compared with a two-level fusion. A cadaveric in vitro repeated-measures study was performed to evaluate a multilevel lumbar NR+fusion hybrid. Eight cadaveric spines (L3-S1) were tested in a Spine Kinetic Simulator (Instron, Norwood, MA, USA). Pure moments of 8 Nm were applied in flexion/extension, lateral bending, and axial rotation as well as compression loading. Specimens were tested intact; fused (using transforaminal lumbar interbody fusion instrumentation with posterior rods) at L5-S1; with a nuclectomy at L4-L5 including fusion at L5-S1; with NR at L4-L5 including fusion at L5-S1; and finally with a two-level fusion spanning L4-S1. Repeated-measures analysis of variance and corrected t tests were used to statistically compare outcomes. The NR+fusion hybrid and single-level fusion exhibited no statistical differences for range of motion (ROM), stiffness, neutral zone, and intradiscal pressure in all loading directions. Compared with two-level fusion, the hybrid affords the construct 41.9% more ROM on average. Two-level fusion stiffness was statistically higher than all other constructs and resulted in significantly lower ROM in flexion, extension, and lateral bending. The hybrid construct produced approximately half of the L3-L4 adjacent-level pressures as the two-level fusion case while generating similar pressures to the single-level fusion case. These data portend more natural functional outcomes and fewer adjacent disc complications for a multilevel NR+fusion hybrid compared with the classical two-level fusion. Copyright © 2013 Elsevier Inc. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guo Xiaoming

The dominated process of controlled fusion is to let nuclei gain enough kinetic energy to overcome Coulomb barrier. As a result, a fusion scheme can consider two factors in its design: to increase kinetic energy of nuclei and to alter the Coulomb barrier. Cold Fusion and Hot fusion are all one-factor schemes while Intermediate Fusion is a twofactors scheme. This made CINF kinetically superior. Cold Fusion reduces deuteron-deuteron distance, addressing Coulomb barrier, and Hot Fusion heat up plasma into extreme high temperature, addressing kinetic energy. Without enough kinetic energy made Cold Fusion skeptical. Extreme high temperature made Hot Fusion verymore » difficult to engineer. Because CIFN addresses both factors, CIFN is a more promising technique to be industrialized.« less

Shallow boomerang-shaped influenza hemagglutinin G13A mutant structure promotes leaky membrane fusion.

PubMed

Lai, Alex L; Tamm, Lukas K

2010-11-26

Our previous studies showed that an angled boomerang-shaped structure of the influenza hemagglutinin (HA) fusion domain is critical for virus entry into host cells by membrane fusion. Because the acute angle of ∼105° of the wild-type fusion domain promotes efficient non-leaky membrane fusion, we asked whether different angles would still support fusion and thus facilitate virus entry. Here, we show that the G13A fusion domain mutant produces a new leaky fusion phenotype. The mutant fusion domain structure was solved by NMR spectroscopy in a lipid environment at fusion pH. The mutant adopted a boomerang structure similar to that of wild type but with a shallower kink angle of ∼150°. G13A perturbed the structure of model membranes to a lesser degree than wild type but to a greater degree than non-fusogenic fusion domain mutants. The strength of G13A binding to lipid bilayers was also intermediate between that of wild type and non-fusogenic mutants. These membrane interactions provide a clear link between structure and function of influenza fusion domains: an acute angle is required to promote clean non-leaky fusion suitable for virus entry presumably by interaction of the fusion domain with the transmembrane domain deep in the lipid bilayer. A shallower angle perturbs the bilayer of the target membrane so that it becomes leaky and unable to form a clean fusion pore. Mutants with no fixed boomerang angle interacted with bilayers weakly and did not promote any fusion or membrane perturbation.

Shallow Boomerang-shaped Influenza Hemagglutinin G13A Mutant Structure Promotes Leaky Membrane Fusion*

PubMed Central

Lai, Alex L.; Tamm, Lukas K.

2010-01-01

Our previous studies showed that an angled boomerang-shaped structure of the influenza hemagglutinin (HA) fusion domain is critical for virus entry into host cells by membrane fusion. Because the acute angle of ∼105° of the wild-type fusion domain promotes efficient non-leaky membrane fusion, we asked whether different angles would still support fusion and thus facilitate virus entry. Here, we show that the G13A fusion domain mutant produces a new leaky fusion phenotype. The mutant fusion domain structure was solved by NMR spectroscopy in a lipid environment at fusion pH. The mutant adopted a boomerang structure similar to that of wild type but with a shallower kink angle of ∼150°. G13A perturbed the structure of model membranes to a lesser degree than wild type but to a greater degree than non-fusogenic fusion domain mutants. The strength of G13A binding to lipid bilayers was also intermediate between that of wild type and non-fusogenic mutants. These membrane interactions provide a clear link between structure and function of influenza fusion domains: an acute angle is required to promote clean non-leaky fusion suitable for virus entry presumably by interaction of the fusion domain with the transmembrane domain deep in the lipid bilayer. A shallower angle perturbs the bilayer of the target membrane so that it becomes leaky and unable to form a clean fusion pore. Mutants with no fixed boomerang angle interacted with bilayers weakly and did not promote any fusion or membrane perturbation. PMID:20826788

An emergency response team for membrane repair

NASA Technical Reports Server (NTRS)

McNeil, Paul L.; Kirchhausen, Tom

2005-01-01

On demand, rapid Ca(2+)-triggered homotypic and exocytic membrane-fusion events are required to repair a torn plasma membrane, and we propose that this emergency-based fusion differs fundamentally from other rapid, triggered fusion reactions. Emergency fusion might use a specialized protein and organelle emergency response team that can simultaneously promote impromptu homotypic fusion events between organelles and exocytic fusion events along the vertices between these fusion products and the plasma membrane.

Commercial objectives, technology transfer, and systems analysis for fusion power development

NASA Astrophysics Data System (ADS)

Dean, Stephen O.

1988-09-01

Fusion is an inexhaustible source of energy that has the potential for economic commercial applications with excellent safety and environmental characteristics. The primary focus for the fusion energy development program is the generation of central station electricity. Fusion has the potential, however, for many other applications. The fact that a large fraction of the energy released in a DT fusion reaction is carried by high energy neutrons suggests potentially unique applications. In addition, fusion R and D will lead to new products and new markets. Each fusion application must meet certain standards of economic and safety and environmental attractiveness. For this reason, economics on the one hand, and safety and environment and licensing on the other, are the two primary criteria for setting long range commercial fusion objectives. A major function of systems analysis is to evaluate the potential of fusion against these objectives and to help guide the fusion R and D program toward practical applications. The transfer of fusion technology and skills from the national labs and universities to industry is the key to achieving the long range objective of commercial fusion applications.

A pharmacological study of Arabidopsis cell fusion between the persistent synergid and endosperm.

PubMed

Motomura, Kazuki; Kawashima, Tomokazu; Berger, Frédéric; Kinoshita, Tetsu; Higashiyama, Tetsuya; Maruyama, Daisuke

2018-01-29

Cell fusion is a pivotal process in fertilization and multinucleate cell formation. A plant cell is ubiquitously surrounded by a hard cell wall, and very few cell fusions have been observed except for gamete fusions. We recently reported that the fertilized central cell (the endosperm) absorbs the persistent synergid, a highly differentiated cell necessary for pollen tube attraction. The synergid-endosperm fusion (SE fusion) appears to eliminate the persistent synergid from fertilized ovule in Arabidopsis thaliana Here, we analyzed the effects of various inhibitors on SE fusion in an in vitro culture system. Different from other cell fusions, neither disruption of actin polymerization nor protein secretion impaired SE fusion. However, transcriptional and translational inhibitors decreased the SE fusion success rate and also inhibited endosperm division. Failures of SE fusion and endosperm nuclear proliferation were also induced by roscovitine, an inhibitor of cyclin-dependent kinases (CDK). These data indicate unique aspects of SE fusion such as independence of filamentous actin support and the importance of CDK-mediated mitotic control. © 2018. Published by The Company of Biologists Ltd.

Discovering and understanding oncogenic gene fusions through data intensive computational approaches

PubMed Central

Latysheva, Natasha S.; Babu, M. Madan

2016-01-01

Abstract Although gene fusions have been recognized as important drivers of cancer for decades, our understanding of the prevalence and function of gene fusions has been revolutionized by the rise of next-generation sequencing, advances in bioinformatics theory and an increasing capacity for large-scale computational biology. The computational work on gene fusions has been vastly diverse, and the present state of the literature is fragmented. It will be fruitful to merge three camps of gene fusion bioinformatics that appear to rarely cross over: (i) data-intensive computational work characterizing the molecular biology of gene fusions; (ii) development research on fusion detection tools, candidate fusion prioritization algorithms and dedicated fusion databases and (iii) clinical research that seeks to either therapeutically target fusion transcripts and proteins or leverages advances in detection tools to perform large-scale surveys of gene fusion landscapes in specific cancer types. In this review, we unify these different—yet highly complementary and symbiotic—approaches with the view that increased synergy will catalyze advancements in gene fusion identification, characterization and significance evaluation. PMID:27105842

Commercial objectives, technology transfer, and systems analysis for fusion power development

NASA Technical Reports Server (NTRS)

Dean, Stephen O.

1988-01-01

Fusion is an inexhaustible source of energy that has the potential for economic commercial applications with excellent safety and environmental characteristics. The primary focus for the fusion energy development program is the generation of central station electricity. Fusion has the potential, however, for many other applications. The fact that a large fraction of the energy released in a DT fusion reaction is carried by high energy neutrons suggests potentially unique applications. In addition, fusion R and D will lead to new products and new markets. Each fusion application must meet certain standards of economic and safety and environmental attractiveness. For this reason, economics on the one hand, and safety and environment and licensing on the other, are the two primary criteria for setting long range commercial fusion objectives. A major function of systems analysis is to evaluate the potential of fusion against these objectives and to help guide the fusion R and D program toward practical applications. The transfer of fusion technology and skills from the national labs and universities to industry is the key to achieving the long range objective of commercial fusion applications.

Characterization of the functional requirements of West Nile virus membrane fusion.

PubMed

Moesker, Bastiaan; Rodenhuis-Zybert, Izabela A; Meijerhof, Tjarko; Wilschut, Jan; Smit, Jolanda M

2010-02-01

Flaviviruses infect their host cells by a membrane fusion reaction. In this study, we performed a functional analysis of the membrane fusion properties of West Nile virus (WNV) with liposomal target membranes. Membrane fusion was monitored continuously using a lipid mixing assay involving the fluorophore, pyrene. Fusion of WNV with liposomes occurred on the timescale of seconds and was strictly dependent on mildly acidic pH. Optimal fusion kinetics were observed at pH 6.3, the threshold for fusion being pH 6.9. Preincubation of the virus alone at pH 6.3 resulted in a rapid loss of fusion capacity. WNV fusion activity is strongly promoted by the presence of cholesterol in the target membrane. Furthermore, we provide direct evidence that cleavage of prM to M is a requirement for fusion activity of WNV.

A New Approach to Image Fusion Based on Cokriging

NASA Technical Reports Server (NTRS)

Memarsadeghi, Nargess; LeMoigne, Jacqueline; Mount, David M.; Morisette, Jeffrey T.

2005-01-01

We consider the image fusion problem involving remotely sensed data. We introduce cokriging as a method to perform fusion. We investigate the advantages of fusing Hyperion with ALI. The evaluation is performed by comparing the classification of the fused data with that of input images and by calculating well-chosen quantitative fusion quality metrics. We consider the Invasive Species Forecasting System (ISFS) project as our fusion application. The fusion of ALI with Hyperion data is studies using PCA and wavelet-based fusion. We then propose utilizing a geostatistical based interpolation method called cokriging as a new approach for image fusion.

Myomaker: A membrane activator of myoblast fusion and muscle formation

PubMed Central

Millay, Douglas P.; O’Rourke, Jason R.; Sutherland, Lillian B.; Bezprozvannaya, Svetlana; Shelton, John M.; Bassel-Duby, Rhonda; Olson, Eric N.

2013-01-01

Summary Fusion of myoblasts is essential for the formation of multi-nucleated muscle fibers. However, the identity of myogenic proteins that directly govern this fusion process has remained elusive. Here, we discovered a muscle-specific membrane protein, named Myomaker, that controls myoblast fusion. Myomaker is expressed on the cell surface of myoblasts during fusion and is down-regulated thereafter. Over-expression of Myomaker in myoblasts dramatically enhances fusion and genetic disruption of Myomaker in mice causes perinatal death due to an absence of multi-nucleated muscle fibers. Remarkably, forced expression of Myomaker in fibroblasts promotes fusion with myoblasts, demonstrating the direct participation of this protein in the fusion process. Pharmacologic perturbation of the actin cytoskeleton abolishes the activity of Myomaker, consistent with prior studies implicating actin dynamics in myoblast fusion. These findings reveal a long-sought myogenic fusion protein both necessary and sufficient for mammalian myoblast fusion and provide new insights into the molecular underpinnings of muscle formation. PMID:23868259

Sensor fusion II: Human and machine strategies; Proceedings of the Meeting, Philadelphia, PA, Nov. 6-9, 1989

NASA Technical Reports Server (NTRS)

Schenker, Paul S. (Editor)

1990-01-01

Various papers on human and machine strategies in sensor fusion are presented. The general topics addressed include: active vision, measurement and analysis of visual motion, decision models for sensor fusion, implementation of sensor fusion algorithms, applying sensor fusion to image analysis, perceptual modules and their fusion, perceptual organization and object recognition, planning and the integration of high-level knowledge with perception, using prior knowledge and context in sensor fusion.

Ontological Issues in Higher Levels of Information Fusion: User Refinement of the Fusion Process

DTIC Science & Technology

2003-01-01

fusion question, the thing that is separates the Greek We explore the higher-level purpose offusion systems by philosophical questions and modem day...the The Greeks focused on both data fusion and the Fusion02 conference there are common fusion questions philosophical questions of an ontology - the...data World of Visible Things Belief (pistis) fusion - user refinement. The rest of the paper is as Appearances follows: Section 2 details the Greek

Lumbar lordosis restoration following single-level instrumented fusion comparing 4 commonly used techniques.

PubMed

Dimar, John R; Glassman, Steven D; Vemuri, Venu M; Esterberg, Justin L; Howard, Jennifer M; Carreon, Leah Y

2011-11-09

A major sequelae of lumbar fusion is acceleration of adjacent-level degeneration due to decreased lumbar lordosis. We evaluated the effectiveness of 4 common fusion techniques in restoring lordosis: instrumented posterolateral fusion, translumbar interbody fusion, anteroposterior fusion with posterior instrumentation, and anterior interbody fusion with lordotic threaded (LT) cages (Medtronic Sofamor Danek, Memphis, Tennessee). Radiographs were measured preoperatively, immediately postoperatively, and a minimum of 6 months postoperatively. Parameters measured included anterior and posterior disk space height, lumbar lordosis from L3 to S1, and surgical level lordosis.No significant difference in demographics existed among the 4 groups. All preoperative parameters were similar among the 4 groups. Lumbar lordosis at final follow-up showed no difference between the anteroposterior fusion with posterior instrumentation, translumbar interbody fusion, and LT cage groups, although the posterolateral fusion group showed a significant loss of lordosis (-10°) (P<.001). Immediately postoperatively and at follow-up, the LT cage group had a significantly greater amount of lordosis and showed maintenance of anterior and posterior disk space height postoperatively compared with the other groups. Instrumented posterolateral fusion produces a greater loss of lordosis compared with anteroposterior fusion with posterior instrumentation, translumbar interbody fusion, and LT cages. Maintenance of lordosis and anterior and posterior disk space height is significantly better with anterior interbody fusion with LT cages. Copyright 2011, SLACK Incorporated.

Technologies for Army Knowledge Fusion

DTIC Science & Technology

2004-09-01

interpret it in context and understand the implications (Alberts et al., 2002). Note that the knowledge / information fusion issue arises immediately here...Army Knowledge Fusion Richard Scherl Department of Computer Science Monmouth University Dana L. Ulery Computational and Information Sciences...civilian and military sources. Knowledge fusion, also called information fusion and multisensor data fusion, names the body of techniques needed to

Osteoclasts and giant cells: macrophage–macrophage fusion mechanism

PubMed Central

Vignery, Agnès

2000-01-01

Membrane fusion is a ubiquitous event that occurs in a wide range of biological processes. While intracellular membrane fusion mediating organelle trafficking is well understood, much less is known about cell–cell fusion mediating sperm cell–oocyte, myoblast–myoblast and macrophage–macrophage fusion. In the case of mononuclear phagocytes, their fusion is not only associated with the differentiation of osteoclasts, cells which play a key role in the pathogenesis of osteoporosis, but also of giant cells that are present in chronic inflammatory reactions and in tumours. Despite the biological and pathophysiological importance of intercellular fusion events, the actual molecular mechanism of macrophage fusion is still unclear. One of the main research themes in my laboratory has been to investigate the molecular mechanism of mononuclear phagocyte fusion. Our hypothesis has been that macrophage–macrophage fusion, similar to virus–cell fusion, is mediated by specific cell surface proteins. But, in contrast with myoblasts and sperm cells, macrophage fusion is a rare event that occurs in specific instances. To test our hypothesis, we established an in vitro cell–cell fusion assay as a model system which uses alveolar macrophages. Upon multinucleation, these macrophages acquire the osteoclast phenotype. This indicates that multinucleation of macrophages leads to a specific and novel functional phenotype in macrophages. To identify the components of the fusion machinery, we generated four monoclonal antibodies (mAbs) which block the fusion of alveolar macrophages and purified the unique antigen recognized by these mAbs. This led us to the cloning of MFR (Macrophage Fusion Receptor). MFR was cloned simultaneously as P84/SHPS-1/SIRPα/BIT by other laboratories. We subsequently showed that the recombinant extracellular domain of MFR blocks fusion. Most recently, we identified a lower molecular weight form of MFR that is missing two extracellular immunoglobulin (Ig) C domains. Shortly after we cloned MFR, CD47 was reported to be a ligand for P84/SIRPα. We have since generated preliminary results which suggest that CD47 interacts with MFR during adhesion/fusion and is a member of the fusion machinery. We also identified CD44 as a plasma membrane protein which, like MFR, is highly expressed at the onset of fusion. The recombinant soluble extracellular domain of CD44 blocks fusion by interacting with a cell-surface binding site. We now propose a model in which both forms of MFR, CD44, and CD47 mediate macrophage adhesion/fusion and therefore the differentiation of osteoclasts and giant cells. PMID:11168677

RNA-seq of 272 gliomas revealed a novel, recurrent PTPRZ1-MET fusion transcript in secondary glioblastomas.

PubMed

Bao, Zhao-Shi; Chen, Hui-Min; Yang, Ming-Yu; Zhang, Chuan-Bao; Yu, Kai; Ye, Wan-Lu; Hu, Bo-Qiang; Yan, Wei; Zhang, Wei; Akers, Johnny; Ramakrishnan, Valya; Li, Jie; Carter, Bob; Liu, Yan-Wei; Hu, Hui-Min; Wang, Zheng; Li, Ming-Yang; Yao, Kun; Qiu, Xiao-Guang; Kang, Chun-Sheng; You, Yong-Ping; Fan, Xiao-Long; Song, Wei Sonya; Li, Rui-Qiang; Su, Xiao-Dong; Chen, Clark C; Jiang, Tao

2014-11-01

Studies of gene rearrangements and the consequent oncogenic fusion proteins have laid the foundation for targeted cancer therapy. To identify oncogenic fusions associated with glioma progression, we catalogued fusion transcripts by RNA-seq of 272 gliomas. Fusion transcripts were more frequently found in high-grade gliomas, in the classical subtype of gliomas, and in gliomas treated with radiation/temozolomide. Sixty-seven in-frame fusion transcripts were identified, including three recurrent fusion transcripts: FGFR3-TACC3, RNF213-SLC26A11, and PTPRZ1-MET (ZM). Interestingly, the ZM fusion was found only in grade III astrocytomas (1/13; 7.7%) or secondary GBMs (sGBMs, 3/20; 15.0%). In an independent cohort of sGBMs, the ZM fusion was found in three of 20 (15%) specimens. Genomic analysis revealed that the fusion arose from translocation events involving introns 3 or 8 of PTPRZ and intron 1 of MET. ZM fusion transcripts were found in GBMs irrespective of isocitrate dehydrogenase 1 (IDH1) mutation status. sGBMs harboring ZM fusion showed higher expression of genes required for PIK3CA signaling and lowered expression of genes that suppressed RB1 or TP53 function. Expression of the ZM fusion was mutually exclusive with EGFR overexpression in sGBMs. Exogenous expression of the ZM fusion in the U87MG glioblastoma line enhanced cell migration and invasion. Clinically, patients afflicted with ZM fusion harboring glioblastomas survived poorly relative to those afflicted with non-ZM-harboring sGBMs (P < 0.001). Our study profiles the shifting RNA landscape of gliomas during progression and reveled ZM as a novel, recurrent fusion transcript in sGBMs. © 2014 Bao et al.; Published by Cold Spring Harbor Laboratory Press.

RNA-seq of 272 gliomas revealed a novel, recurrent PTPRZ1-MET fusion transcript in secondary glioblastomas

PubMed Central

Bao, Zhao-Shi; Yang, Ming-Yu; Zhang, Chuan-Bao; Yu, Kai; Ye, Wan-Lu; Hu, Bo-Qiang; Yan, Wei; Zhang, Wei; Akers, Johnny; Ramakrishnan, Valya; Li, Jie; Carter, Bob; Liu, Yan-Wei; Hu, Hui-Min; Wang, Zheng; Li, Ming-Yang; Yao, Kun; Qiu, Xiao-Guang; Kang, Chun-Sheng; You, Yong-Ping; Fan, Xiao-Long; Song, Wei Sonya; Li, Rui-Qiang

2014-01-01

Studies of gene rearrangements and the consequent oncogenic fusion proteins have laid the foundation for targeted cancer therapy. To identify oncogenic fusions associated with glioma progression, we catalogued fusion transcripts by RNA-seq of 272 gliomas. Fusion transcripts were more frequently found in high-grade gliomas, in the classical subtype of gliomas, and in gliomas treated with radiation/temozolomide. Sixty-seven in-frame fusion transcripts were identified, including three recurrent fusion transcripts: FGFR3-TACC3, RNF213-SLC26A11, and PTPRZ1-MET (ZM). Interestingly, the ZM fusion was found only in grade III astrocytomas (1/13; 7.7%) or secondary GBMs (sGBMs, 3/20; 15.0%). In an independent cohort of sGBMs, the ZM fusion was found in three of 20 (15%) specimens. Genomic analysis revealed that the fusion arose from translocation events involving introns 3 or 8 of PTPRZ and intron 1 of MET. ZM fusion transcripts were found in GBMs irrespective of isocitrate dehydrogenase 1 (IDH1) mutation status. sGBMs harboring ZM fusion showed higher expression of genes required for PIK3CA signaling and lowered expression of genes that suppressed RB1 or TP53 function. Expression of the ZM fusion was mutually exclusive with EGFR overexpression in sGBMs. Exogenous expression of the ZM fusion in the U87MG glioblastoma line enhanced cell migration and invasion. Clinically, patients afflicted with ZM fusion harboring glioblastomas survived poorly relative to those afflicted with non-ZM-harboring sGBMs (P < 0.001). Our study profiles the shifting RNA landscape of gliomas during progression and reveled ZM as a novel, recurrent fusion transcript in sGBMs. PMID:25135958

The Fusion Gain Analysis of the Inductively Driven Liner Compression Based Fusion

NASA Astrophysics Data System (ADS)

Shimazu, Akihisa; Slough, John

2016-10-01

An analytical analysis of the fusion gain expected in the inductively driven liner compression (IDLC) based fusion is conducted to identify the fusion gain scaling at various operating conditions. The fusion based on the IDLC is a magneto-inertial fusion concept, where a Field-Reversed Configuration (FRC) plasmoid is compressed via the inductively-driven metal liner to drive the FRC to fusion conditions. In the past, an approximate scaling law for the expected fusion gain for the IDLC based fusion was obtained under the key assumptions of (1) D-T fuel at 5-40 keV, (2) adiabatic scaling laws for the FRC dynamics, (3) FRC energy dominated by the pressure balance with the edge magnetic field at the peak compression, and (4) the liner dwell time being liner final diameter divided by the peak liner velocity. In this study, various assumptions made in the previous derivation is relaxed to study the change in the fusion gain scaling from the previous result of G ml1 / 2 El11 / 8 , where ml is the liner mass and El is the peak liner kinetic energy. The implication from the modified fusion gain scaling on the performance of the IDLC fusion reactor system is also explored.

Local electrostatic interactions determine the diameter of fusion pores

PubMed Central

Guček, Alenka; Jorgačevski, Jernej; Górska, Urszula; Rituper, Boštjan; Kreft, Marko; Zorec, Robert

2015-01-01

In regulated exocytosis vesicular and plasma membranes merge to form a fusion pore in response to stimulation. The nonselective cation HCN channels are involved in the regulation of unitary exocytotic events by at least 2 mechanisms. They can affect SNARE-dependent exocytotic activity indirectly, via the modulation of free intracellular calcium; and/or directly, by altering local cation concentration, which affects fusion pore geometry likely via electrostatic interactions. By monitoring membrane capacitance, we investigated how extracellular cation concentration affects fusion pore diameter in pituitary cells and astrocytes. At low extracellular divalent cation levels predominantly transient fusion events with widely open fusion pores were detected. However, fusion events with predominately narrow fusion pores were present at elevated levels of extracellular trivalent cations. These results show that electrostatic interactions likely help determine the stability of discrete fusion pore states by affecting fusion pore membrane composition. PMID:25835258

Capmatinib, Ceritinib, Regorafenib, or Entrectinib in Treating Patients With BRAF/NRAS Wild-Type Stage III-IV Melanoma

ClinicalTrials.gov

2017-12-20

ALK Fusion Protein Expression; BRAF wt Allele; Invasive Skin Melanoma; MET Fusion Gene Positive; NRAS wt Allele; NTRK1 Fusion Positive; NTRK2 Fusion Positive; NTRK3 Fusion Positive; RET Fusion Positive; ROS1 Fusion Positive; Stage III Cutaneous Melanoma AJCC v7; Stage IIIA Cutaneous Melanoma AJCC v7; Stage IIIB Cutaneous Melanoma AJCC v7; Stage IIIC Cutaneous Melanoma AJCC v7; Stage IV Cutaneous Melanoma AJCC v6 and v7

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Wei, E-mail: wang_wei_310@163.com; Lu, Yonghao, E-mail: lu_yonghao@mater.ustb.edu.cn; Ding, Xianfei, E-mail: xfding@ustb.edu.cn

Microstructures and microhardness at fusion boundary of a weld joint were investigated in a 316 stainless steel/Inconel 182 dissimilar weldment. The results showed that there were two alternately distributed typical fusion boundaries, a narrow random boundary (possessed 15% in length) with a clear sharp interface and an epitaxial fusion one with (100){sub BM}//(100){sub WM} at the joint interface. The composition transition, microstructure and hardness across the fusion boundary strongly depended on the type of the fusion boundary. For the random boundary, there was a clear sharp interface and the composition transition with a width of 100 μm took place symmetricallymore » across the grain boundary. For the epitaxial fusion one, however, there were Type-I and Type-II grain boundaries perpendicular and parallel to the epitaxial fusion boundary, respectively. The composition transition took place in the Inconel 182 weld side. Σ3 boundaries in the HAZ of 316SS side and Σ5 grain boundaries in weld metal were usually observed, despite the type of fusion boundary, however the former was much more in epitaxial fusion boundary. Microhardness was continuously decreased across the random fusion boundary from the side of Inconel 182 to 316SS, but a hardening phenomenon appeared in the epitaxial fusion boundary zone because of its fine cellular microstructure. - Highlights: • Two typical fusion boundaries alternately distributed in the fusion interface • The microstructure, composition and hardness across fusion boundary depended on its type. • Different regions in welded joint have different special CSL value boundaries. • Hardening phenomenon only appeared in the epitaxial fusion boundary.« less

Osteoclast fusion is initiated by a small subset of RANKL-stimulated monocyte progenitors, which can fuse to RANKL-unstimulated progenitors.

PubMed

Levaot, Noam; Ottolenghi, Aner; Mann, Mati; Guterman-Ram, Gali; Kam, Zvi; Geiger, Benjamin

2015-10-01

Osteoclasts are multinucleated, bone-resorbing cells formed via fusion of monocyte progenitors, a process triggered by prolonged stimulation with RANKL, the osteoclast master regulator cytokine. Monocyte fusion into osteoclasts has been shown to play a key role in bone remodeling and homeostasis; therefore, aberrant fusion may be involved in a variety of bone diseases. Indeed, research in the last decade has led to the discovery of genes regulating osteoclast fusion; yet the basic cellular regulatory mechanism underlying the fusion process is poorly understood. Here, we applied a novel approach for tracking the fusion processes, using live-cell imaging of RANKL-stimulated and non-stimulated progenitor monocytes differentially expressing dsRED or GFP, respectively. We show that osteoclast fusion is initiated by a small (~2.4%) subset of precursors, termed "fusion founders", capable of fusing either with other founders or with non-stimulated progenitors (fusion followers), which alone, are unable to initiate fusion. Careful examination indicates that the fusion between a founder and a follower cell consists of two distinct phases: an initial pairing of the two cells, typically lasting 5-35 min, during which the cells nevertheless maintain their initial morphology; and the fusion event itself. Interestingly, during the initial pre-fusion phase, a transfer of the fluorescent reporter proteins from nucleus to nucleus was noticed, suggesting crosstalk between the founder and follower progenitors via the cytoplasm that might directly affect the fusion process, as well as overall transcriptional regulation in the developing heterokaryon. Copyright © 2015 Elsevier Inc. All rights reserved.

Line-Tension Controlled Mechanism for Influenza Fusion

PubMed Central

Risselada, Herre Jelger; Smirnova, Yuliya G.; Grubmüller, Helmut; Marrink, Siewert Jan; Müller, Marcus

2012-01-01

Our molecular simulations reveal that wild-type influenza fusion peptides are able to stabilize a highly fusogenic pre-fusion structure, i.e. a peptide bundle formed by four or more trans-membrane arranged fusion peptides. We rationalize that the lipid rim around such bundle has a non-vanishing rim energy (line-tension), which is essential to (i) stabilize the initial contact point between the fusing bilayers, i.e. the stalk, and (ii) drive its subsequent evolution. Such line-tension controlled fusion event does not proceed along the hypothesized standard stalk-hemifusion pathway. In modeled influenza fusion, single point mutations in the influenza fusion peptide either completely inhibit fusion (mutants G1V and W14A) or, intriguingly, specifically arrest fusion at a hemifusion state (mutant G1S). Our simulations demonstrate that, within a line-tension controlled fusion mechanism, these known point mutations either completely inhibit fusion by impairing the peptide’s ability to stabilize the required peptide bundle (G1V and W14A) or stabilize a persistent bundle that leads to a kinetically trapped hemifusion state (G1S). In addition, our results further suggest that the recently discovered leaky fusion mutant G13A, which is known to facilitate a pronounced leakage of the target membrane prior to lipid mixing, reduces the membrane integrity by forming a ‘super’ bundle. Our simulations offer a new interpretation for a number of experimentally observed features of the fusion reaction mediated by the prototypical fusion protein, influenza hemagglutinin, and might bring new insights into mechanisms of other viral fusion reactions. PMID:22761674

A visual analytic framework for data fusion in investigative intelligence

NASA Astrophysics Data System (ADS)

Cai, Guoray; Gross, Geoff; Llinas, James; Hall, David

2014-05-01

Intelligence analysis depends on data fusion systems to provide capabilities of detecting and tracking important objects, events, and their relationships in connection to an analytical situation. However, automated data fusion technologies are not mature enough to offer reliable and trustworthy information for situation awareness. Given the trend of increasing sophistication of data fusion algorithms and loss of transparency in data fusion process, analysts are left out of the data fusion process cycle with little to no control and confidence on the data fusion outcome. Following the recent rethinking of data fusion as human-centered process, this paper proposes a conceptual framework towards developing alternative data fusion architecture. This idea is inspired by the recent advances in our understanding of human cognitive systems, the science of visual analytics, and the latest thinking about human-centered data fusion. Our conceptual framework is supported by an analysis of the limitation of existing fully automated data fusion systems where the effectiveness of important algorithmic decisions depend on the availability of expert knowledge or the knowledge of the analyst's mental state in an investigation. The success of this effort will result in next generation data fusion systems that can be better trusted while maintaining high throughput.

Fusion of Enveloped Viruses in Endosomes

PubMed Central

White, Judith M.; Whittaker, Gary R.

2016-01-01

Ari Helenius launched the field of enveloped virus fusion in endosomes with a seminal paper in the Journal of Cell Biology in 1980. In the intervening years a great deal has been learned about the structures and mechanisms of viral membrane fusion proteins as well as about the endosomes in which different enveloped viruses fuse and the endosomal cues that trigger fusion. We now recognize three classes of viral membrane fusion proteins based on structural criteria and four mechanisms of fusion triggering. After reviewing general features of viral membrane fusion proteins and viral fusion in endosomes, we delve into three characterized mechanisms for viral fusion triggering in endosomes: by low pH, by receptor binding plus low pH, and by receptor binding plus the action of a protease. We end with a discussion of viruses that may employ novel endosomal fusion triggering mechanisms. A key take home message is that enveloped viruses that enter cells by fusing in endosomes traverse the endocytic pathway until they reach an endosome that has all of the environmental conditions (pH, proteases, ions, intracellular receptors, and lipid composition) to (if needed) prime and (in all cases) trigger the fusion protein and to support membrane fusion. PMID:26935856

Viral membrane fusion

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

2015-05-15

Membrane fusion is an essential step when enveloped viruses enter cells. Lipid bilayer fusion requires catalysis to overcome a high kinetic barrier; viral fusion proteins are the agents that fulfill this catalytic function. Despite a variety of molecular architectures, these proteins facilitate fusion by essentially the same generic mechanism. Stimulated by a signal associated with arrival at the cell to be infected (e.g., receptor or co-receptor binding, proton binding in an endosome), they undergo a series of conformational changes. A hydrophobic segment (a “fusion loop” or “fusion peptide”) engages the target-cell membrane and collapse of the bridging intermediate thus formedmore » 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.« less

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 Explanation of the JET n = 0 chirping mode Nucl. Fusion 46 S888-97 Urano H. et al 2006 Confinement degradation with beta for ELMy HH-mode plasmas in JT-60U tokamak Nucl. Fusion 46 781-7 Izzo V.A. et al 2006 A numerical investigation of the effects of impurity penetration depth on disruption mitigation by massive high-pressure gas jet Nucl. Fusion 46 541-7 Inagaki S. et al 2006 Comparison of transient electron heat transport in LHD helical and JT-60U tokamak plasmas Nucl. Fusion 46 133-41 Watanabe T.-H. et al 2006 Velocity-space structures of distribution function in toroidal ion temperature gradient turbulence Nucl. Fusion 46 24-32 2010 Nuclear Fusion Award nominees For the 2010 award, the papers published in the 2007 volume were assessed and the following papers were nominated, all of which are magnetic confinement experiments and theory. Rice J.E. et al 2007 Inter-machine comparison of intrinsic toroidal rotation in tokamaks Nucl. Fusion 47 1618-24 Lipschultz B. et al 2007 Plasma-surface interaction, scrape-off layer and divertor physics: implications for ITER Nucl. Fusion 47 1189-205 Loarer T. et al 2007 Gas balance and fuel retention in fusion devices Nucl. Fusion 47 1112-20 Garcia O.E et al 2007 Fluctuations and transport in the TCV scrape-off layer Nucl. Fusion 47 667-76 Zonca F. et al 2007 Electron fishbones: theory and experimental evidence Nucl. Fusion 47 1588-97 Maggi C.F. et al 2007 Characteristics of the H-mode pedestal in improved confinement scenarios in ASDEX Upgrade, DIII-D, JET and JT-60U Nucl. Fusion 47 535-51 Yoshida M. et al 2007 Momentum transport and plasma rotation profile in toroidal direction in JT-60U L-mode plasmas Nucl. Fusion 47 856-63 Zohm H. et al 2007 Control of MHD instabilities by ECCD: ASDEX Upgrade results and implications for ITER Nucl. Fusion 47 228-32 Snyder P.B. et al 2007 Stability and dynamics of the edge pedestal in the low collisionality regime: physics mechanisms for steady-state ELM-free operation Nucl. Fusion 47 961-8 Urano H. et al 2007 H-mode pedestal structure in the variation of toroidal rotation and toroidal field ripple in JT-60U Nucl. Fusion 47 706-13 Günter S. et al 2007 Interaction of energetic particles with large and small scale instabilities Nucl. Fusion 47 920-8

Fusion Materials Research at Oak Ridge National Laboratory in Fiscal Year 2014

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wiffen, Frederick W.; Noe, Susan P.; Snead, Lance Lewis

2014-10-01

The realization of fusion energy is a formidable challenge with significant achievements resulting from close integration of the plasma physics and applied technology disciplines. Presently, the most significant technological challenge for the near-term experiments such as ITER, and next generation fusion power systems, is the inability of current materials and components to withstand the harsh fusion nuclear environment. The overarching goal of the ORNL fusion materials program is to provide the applied materials science support and understanding to underpin the ongoing DOE Office of Science fusion energy program while developing materials for fusion power systems. In doing so the programmore » continues to be integrated both with the larger U.S. and international fusion materials communities, and with the international fusion design and technology communities.« less

Quantitative Analysis of Lipid Droplet Fusion: Inefficient Steady State Fusion but Rapid Stimulation by Chemical Fusogens

PubMed Central

Murphy, Samantha; Martin, Sally; Parton, Robert G.

2010-01-01

Lipid droplets (LDs) are dynamic cytoplasmic organelles containing neutral lipids and bounded by a phospholipid monolayer. Previous studies have suggested that LDs can undergo constitutive homotypic fusion, a process linked to the inhibitory effects of fatty acids on glucose transporter trafficking. Using strict quantitative criteria for LD fusion together with refined light microscopic methods and real-time analysis, we now show that LDs in diverse cell types show low constitutive fusogenic activity under normal growth conditions. To investigate the possible modulation of LD fusion, we screened for agents that can trigger fusion. A number of pharmacological agents caused homotypic fusion of lipid droplets in a variety of cell types. This provided a novel cell system to study rapid regulated fusion between homotypic phospholipid monolayers. LD fusion involved an initial step in which the two adjacent membranes became continuous (<10 s), followed by the slower merging (100 s) of the neutral lipid cores to produce a single spherical LD. These fusion events were accompanied by changes to the LD surface organization. Measurements of LDs undergoing homotypic fusion showed that fused LDs maintained their initial volume, with a corresponding decrease in surface area suggesting rapid removal of membrane from the fused LD. This study provides estimates for the level of constitutive LD fusion in cells and questions the role of LD fusion in vivo. In addition, it highlights the extent of LD restructuring which occurs when homotypic LD fusion is triggered in a variety of cell types. PMID:21203462

Fusion or confusion: knowledge or nonsense?

NASA Astrophysics Data System (ADS)

Rothman, Peter L.; Denton, Richard V.

1991-08-01

The terms 'data fusion,' 'sensor fusion,' multi-sensor integration,' and 'multi-source integration' have been used widely in the technical literature to refer to a variety of techniques, technologies, systems, and applications which employ and/or combine data derived from multiple information sources. Applications of data fusion range from real-time fusion of sensor information for the navigation of mobile robots to the off-line fusion of both human and technical strategic intelligence data. The Department of Defense Critical Technologies Plan lists data fusion in the highest priority group of critical technologies, but just what is data fusion? The DoD Critical Technologies Plan states that data fusion involves 'the acquisition, integration, filtering, correlation, and synthesis of useful data from diverse sources for the purposes of situation/environment assessment, planning, detecting, verifying, diagnosing problems, aiding tactical and strategic decisions, and improving system performance and utility.' More simply states, sensor fusion refers to the combination of data from multiple sources to provide enhanced information quality and availability over that which is available from any individual source alone. This paper presents a survey of the state-of-the- art in data fusion technologies, system components, and applications. A set of characteristics which can be utilized to classify data fusion systems is presented. Additionally, a unifying mathematical and conceptual framework within which to understand and organize fusion technologies is described. A discussion of often overlooked issues in the development of sensor fusion systems is also presented.

The ubiquitin–proteasome system regulates membrane fusion of yeast vacuoles

PubMed Central

Kleijnen, Maurits F; Kirkpatrick, Donald S; Gygi, Steven P

2007-01-01

Ubiquitination is known to regulate early stages of intracellular vesicular transport, without proteasomal involvement. We now show that, in yeast, ubiquitination regulates a late-stage, membrane fusion, with proteasomal involvement. A known proteasome mutant had a vacuolar fragmentation phenotype in vivo often associated with vacuolar membrane fusion defects, suggesting a proteasomal role in fusion. Inhibiting vacuolar proteasomes interfered with membrane fusion in vitro, showing that fusion cannot occur without proteasomal degradation. If so, one would expect to find ubiquitinated proteins on vacuolar membranes. We found a small number of these, identified the most prevalent one as Ypt7 and mapped its two major ubiquitination sites. Ubiquitinated Ypt7 was linked to the degradation event that is necessary for fusion: vacuolar Ypt7 and vacuolar proteasomes were interdependent, ubiquitinated Ypt7 became a proteasomal substrate during fusion, and proteasome inhibitors reduced fusion to greater degree when we decreased Ypt7 ubiquitination. The strongest model holds that fusion cannot proceed without proteasomal degradation of ubiquitinated Ypt7. As Ypt7 is one of many Rab GTPases, ubiquitin–proteasome regulation may be involved in membrane fusion elsewhere. PMID:17183369

Direct observation of intermediate states in model membrane fusion

PubMed Central

Keidel, Andrea; Bartsch, Tobias F.; Florin, Ernst-Ludwig

2016-01-01

We introduce a novel assay for membrane fusion of solid supported membranes on silica beads and on coverslips. Fusion of the lipid bilayers is induced by bringing an optically trapped bead in contact with the coverslip surface while observing the bead’s thermal motion with microsecond temporal and nanometer spatial resolution using a three-dimensional position detector. The probability of fusion is controlled by the membrane tension on the particle. We show that the progression of fusion can be monitored by changes in the three-dimensional position histograms of the bead and in its rate of diffusion. We were able to observe all fusion intermediates including transient fusion, formation of a stalk, hemifusion and the completion of a fusion pore. Fusion intermediates are characterized by axial but not lateral confinement of the motion of the bead and independently by the change of its rate of diffusion due to the additional drag from the stalk-like connection between the two membranes. The detailed information provided by this assay makes it ideally suited for studies of early events in pure lipid bilayer fusion or fusion assisted by fusogenic molecules. PMID:27029285

Fc-fusion Proteins in Therapy: An Updated View.

PubMed

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

2017-01-01

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

Multiscale Medical Image Fusion in Wavelet Domain

PubMed Central

Khare, Ashish

2013-01-01

Wavelet transforms have emerged as a powerful tool in image fusion. However, the study and analysis of medical image fusion is still a challenging area of research. Therefore, in this paper, we propose a multiscale fusion of multimodal medical images in wavelet domain. Fusion of medical images has been performed at multiple scales varying from minimum to maximum level using maximum selection rule which provides more flexibility and choice to select the relevant fused images. The experimental analysis of the proposed method has been performed with several sets of medical images. Fusion results have been evaluated subjectively and objectively with existing state-of-the-art fusion methods which include several pyramid- and wavelet-transform-based fusion methods and principal component analysis (PCA) fusion method. The comparative analysis of the fusion results has been performed with edge strength (Q), mutual information (MI), entropy (E), standard deviation (SD), blind structural similarity index metric (BSSIM), spatial frequency (SF), and average gradient (AG) metrics. The combined subjective and objective evaluations of the proposed fusion method at multiple scales showed the effectiveness and goodness of the proposed approach. PMID:24453868

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schowalter, Rachel M.; Wurth, Mark A.; Aguilar, Hector C.

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 ormore » 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.« less

Direct observation of intermediate states in model membrane fusion.

PubMed

Keidel, Andrea; Bartsch, Tobias F; Florin, Ernst-Ludwig

2016-03-31

We introduce a novel assay for membrane fusion of solid supported membranes on silica beads and on coverslips. Fusion of the lipid bilayers is induced by bringing an optically trapped bead in contact with the coverslip surface while observing the bead's thermal motion with microsecond temporal and nanometer spatial resolution using a three-dimensional position detector. The probability of fusion is controlled by the membrane tension on the particle. We show that the progression of fusion can be monitored by changes in the three-dimensional position histograms of the bead and in its rate of diffusion. We were able to observe all fusion intermediates including transient fusion, formation of a stalk, hemifusion and the completion of a fusion pore. Fusion intermediates are characterized by axial but not lateral confinement of the motion of the bead and independently by the change of its rate of diffusion due to the additional drag from the stalk-like connection between the two membranes. The detailed information provided by this assay makes it ideally suited for studies of early events in pure lipid bilayer fusion or fusion assisted by fusogenic molecules.

Outcomes of Posterolateral Fusion with and without Instrumentation and of Interbody Fusion for Isthmic Spondylolisthesis: A Prospective Study.

PubMed

Endler, Peter; Ekman, Per; Möller, Hans; Gerdhem, Paul

2017-05-03

Various methods for the treatment of isthmic spondylolisthesis are available. The aim of this study was to compare outcomes after posterolateral fusion without instrumentation, posterolateral fusion with instrumentation, and interbody fusion. The Swedish Spine Register was used to identify 765 patients who had been operated on for isthmic spondylolisthesis and had at least preoperative and 2-year outcome data; 586 of them had longer follow-up (a mean of 6.9 years). The outcome measures were a global assessment of leg and back pain, the Oswestry Disability Index (ODI), the EuroQol-5 Dimensions (EQ-5D) Questionnaire, the Short Form-36 (SF-36), a visual analog scale (VAS) for back and leg pain, and satisfaction with treatment. Data on additional lumbar spine surgery was searched for in the register, with the mean duration of follow-up for this variable being 10.6 years after the index procedure. Statistical analyses were performed with analysis of covariance or competing-risks proportional hazards regression, adjusted for baseline differences in the studied variables, smoking, employment status, and level of fusion. Posterolateral fusion without instrumentation was performed in 102 patients; posterolateral fusion with instrumentation, in 452; and interbody fusion, in 211. At 1 year, improvement was reported in the global assessment for back pain by 54% of the patients who had posterolateral fusion without instrumentation, 68% of those treated with posterolateral fusion with instrumentation, and 70% of those treated with interbody fusion (p = 0.009). The VAS for back pain and reported satisfaction with treatment showed similar patterns (p = 0.003 and p = 0.017, respectively), whereas other outcomes did not differ among the treatment groups at 1 year. At 2 years, the global assessment for back pain indicated improvement in 57% of the patients who had undergone posterolateral fusion without instrumentation, 70% of those who had posterolateral fusion with instrumentation, and 71% of those treated with interbody fusion (p = 0.022). There were no significant outcome differences at the mean 6.9-year follow-up interval. There was an increased hazard ratio for additional lumbar spine surgery after interbody fusion (4.34; 95% confidence interval [CI] = 1.71 to 11.03) and posterolateral fusion with instrumentation (2.56; 95% CI = 1.02 to 6.42) compared with after posterolateral fusion without instrumentation (1.00; reference). Fusion with instrumentation, with or without interbody fusion, was associated with more improvement in back pain scores and higher satisfaction with treatment compared with fusion without instrumentation at 1 year, but the difference was attenuated with longer follow-up. Fusion with instrumentation was associated with a significantly higher risk of additional spine surgery. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

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.

A novel framework of tissue membrane systems for image fusion.

PubMed

Zhang, Zulin; Yi, Xinzhong; Peng, Hong

2014-01-01

This paper proposes a tissue membrane system-based framework to deal with the optimal image fusion problem. A spatial domain fusion algorithm is given, and a tissue membrane system of multiple cells is used as its computing framework. Based on the multicellular structure and inherent communication mechanism of the tissue membrane system, an improved velocity-position model is developed. The performance of the fusion framework is studied with comparison of several traditional fusion methods as well as genetic algorithm (GA)-based and differential evolution (DE)-based spatial domain fusion methods. Experimental results show that the proposed fusion framework is superior or comparable to the other methods and can be efficiently used for image fusion.

Double patch clamp reveals that transient fusion (kiss-and-run) is a major mechanism of secretion in calf adrenal chromaffin cells: high calcium shifts the mechanism from kiss-and-run to complete fusion.

PubMed

Elhamdani, Abdeladim; Azizi, Fouad; Artalejo, Cristina R

2006-03-15

Transient fusion ("kiss-and-run") is accepted as a mode of transmitter release both in central neurons and neuroendocrine cells, but the prevalence of this mechanism compared with full fusion is still in doubt. Using a novel double patch-clamp method (whole cell/cell attached), permitting the recording of unitary capacitance events while stimulating under a variety of conditions including action potentials, we show that transient fusion is the predominant (>90%) mode of secretion in calf adrenal chromaffin cells. Raising intracellular Ca2+ concentration ([Ca]i) from 10 to 200 microM increases the incidence of full fusion events at the expense of transient fusion. Blocking rapid endocytosis that normally terminates transient fusion events also promotes full fusion events. Thus, [Ca]i controls the transition between transient and full fusion, each of which is coupled to different modes of endocytosis.

SCAR/WAVE and Arp2/3 are critical for cytoskeletal remodeling at the site of myoblast fusion

PubMed Central

Richardson, Brian E.; Beckett, Karen; Nowak, Scott J.; Baylies, Mary K.

2010-01-01

Summary Myoblast fusion is critical for formation and repair of skeletal muscle. Here we show that active remodeling of the actin cytoskeleton is essential for fusion in Drosophila. Using live imaging, we have identified a dynamic F-actin accumulation (actin focus) at the site of fusion. Dissolution of the actin focus directly precedes a fusion event. Whereas several known fusion components regulate these actin foci, others target additional behaviors required for fusion. Mutations in kette/Nap1, an actin polymerization regulator, lead to enlarged foci that do not dissolve, consistent with the observed block in fusion. Kette is required to positively regulate SCAR/WAVE, which in turn activates the Arp2/3 complex. Mutants in SCAR and Arp2/3 have a fusion block and foci phenotype, suggesting that Kette-SCAR-Arp2/3 participate in an actin polymerization event required for focus dissolution. Our data identify a new paradigm for understanding the mechanisms underlying fusion in myoblasts and other tissues. PMID:18003739

Remotely controlled fusion of selected vesicles and living cells: a key issue review

NASA Astrophysics Data System (ADS)

Bahadori, Azra; Moreno-Pescador, Guillermo; Oddershede, Lene B.; Bendix, Poul M.

2018-03-01

Remote control over fusion of single cells and vesicles has a great potential in biological and chemical research allowing both transfer of genetic material between cells and transfer of molecular content between vesicles. Membrane fusion is a critical process in biology that facilitates molecular transport and mixing of cellular cytoplasms with potential formation of hybrid cells. Cells precisely regulate internal membrane fusions with the aid of specialized fusion complexes that physically provide the energy necessary for mediating fusion. Physical factors like membrane curvature, tension and temperature, affect biological membrane fusion by lowering the associated energy barrier. This has inspired the development of physical approaches to harness the fusion process at a single cell level by using remotely controlled electromagnetic fields to trigger membrane fusion. Here, we critically review various approaches, based on lasers or electric pulses, to control fusion between individual cells or between individual lipid vesicles and discuss their potential and limitations for present and future applications within biochemistry, biology and soft matter.

Belief Function Based Decision Fusion for Decentralized Target Classification in Wireless Sensor Networks

PubMed Central

Zhang, Wenyu; Zhang, Zhenjiang

2015-01-01

Decision fusion in sensor networks enables sensors to improve classification accuracy while reducing the energy consumption and bandwidth demand for data transmission. In this paper, we focus on the decentralized multi-class classification fusion problem in wireless sensor networks (WSNs) and a new simple but effective decision fusion rule based on belief function theory is proposed. Unlike existing belief function based decision fusion schemes, the proposed approach is compatible with any type of classifier because the basic belief assignments (BBAs) of each sensor are constructed on the basis of the classifier’s training output confusion matrix and real-time observations. We also derive explicit global BBA in the fusion center under Dempster’s combinational rule, making the decision making operation in the fusion center greatly simplified. Also, sending the whole BBA structure to the fusion center is avoided. Experimental results demonstrate that the proposed fusion rule has better performance in fusion accuracy compared with the naïve Bayes rule and weighted majority voting rule. PMID:26295399

Line tension at lipid phase boundaries as driving force for HIV fusion peptide-mediated fusion

NASA Astrophysics Data System (ADS)

Yang, Sung-Tae; Kiessling, Volker; Tamm, Lukas K.

2016-04-01

Lipids and proteins are organized in cellular membranes in clusters, often called `lipid rafts'. Although raft-constituent ordered lipid domains are thought to be energetically unfavourable for membrane fusion, rafts have long been implicated in many biological fusion processes. For the case of HIV gp41-mediated membrane fusion, this apparent contradiction can be resolved by recognizing that the interfaces between ordered and disordered lipid domains are the predominant sites of fusion. Here we show that line tension at lipid domain boundaries contributes significant energy to drive gp41-fusion peptide-mediated fusion. This energy, which depends on the hydrophobic mismatch between ordered and disordered lipid domains, may contribute tens of kBT to fusion, that is, it is comparable to the energy required to form a lipid stalk intermediate. Line-active compounds such as vitamin E lower line tension in inhomogeneous membranes, thereby inhibit membrane fusion, and thus may be useful natural viral entry inhibitors.

ER-associated SNAREs and Sey1p mediate nuclear fusion at two distinct steps during yeast mating.

PubMed

Rogers, Jason V; Arlow, Tim; Inkellis, Elizabeth R; Koo, Timothy S; Rose, Mark D

2013-12-01

During yeast mating, two haploid nuclei fuse membranes to form a single diploid nucleus. However, the known proteins required for nuclear fusion are unlikely to function as direct fusogens (i.e., they are unlikely to directly catalyze lipid bilayer fusion) based on their predicted structure and localization. Therefore we screened known fusogens from vesicle trafficking (soluble N-ethylmaleimide-sensitive factor attachment protein receptors [SNAREs]) and homotypic endoplasmic reticulum (ER) fusion (Sey1p) for additional roles in nuclear fusion. Here we demonstrate that the ER-localized SNAREs Sec20p, Ufe1p, Use1p, and Bos1p are required for efficient nuclear fusion. In contrast, Sey1p is required indirectly for nuclear fusion; sey1Δ zygotes accumulate ER at the zone of cell fusion, causing a block in nuclear congression. However, double mutants of Sey1p and Sec20p, Ufe1p, or Use1p, but not Bos1p, display extreme ER morphology defects, worse than either single mutant, suggesting that retrograde SNAREs fuse ER in the absence of Sey1p. Together these data demonstrate that SNAREs mediate nuclear fusion, ER fusion after cell fusion is necessary to complete nuclear congression, and there exists a SNARE-mediated, Sey1p-independent ER fusion pathway.

Airborne Infrared and Visible Image Fusion Combined with Region Segmentation

PubMed Central

Zuo, Yujia; Liu, Jinghong; Bai, Guanbing; Wang, Xuan; Sun, Mingchao

2017-01-01

This paper proposes an infrared (IR) and visible image fusion method introducing region segmentation into the dual-tree complex wavelet transform (DTCWT) region. This method should effectively improve both the target indication and scene spectrum features of fusion images, and the target identification and tracking reliability of fusion system, on an airborne photoelectric platform. The method involves segmenting the region in an IR image by significance, and identifying the target region and the background region; then, fusing the low-frequency components in the DTCWT region according to the region segmentation result. For high-frequency components, the region weights need to be assigned by the information richness of region details to conduct fusion based on both weights and adaptive phases, and then introducing a shrinkage function to suppress noise; Finally, the fused low-frequency and high-frequency components are reconstructed to obtain the fusion image. The experimental results show that the proposed method can fully extract complementary information from the source images to obtain a fusion image with good target indication and rich information on scene details. They also give a fusion result superior to existing popular fusion methods, based on eithers subjective or objective evaluation. With good stability and high fusion accuracy, this method can meet the fusion requirements of IR-visible image fusion systems. PMID:28505137

Airborne Infrared and Visible Image Fusion Combined with Region Segmentation.

PubMed

Zuo, Yujia; Liu, Jinghong; Bai, Guanbing; Wang, Xuan; Sun, Mingchao

2017-05-15

This paper proposes an infrared (IR) and visible image fusion method introducing region segmentation into the dual-tree complex wavelet transform (DTCWT) region. This method should effectively improve both the target indication and scene spectrum features of fusion images, and the target identification and tracking reliability of fusion system, on an airborne photoelectric platform. The method involves segmenting the region in an IR image by significance, and identifying the target region and the background region; then, fusing the low-frequency components in the DTCWT region according to the region segmentation result. For high-frequency components, the region weights need to be assigned by the information richness of region details to conduct fusion based on both weights and adaptive phases, and then introducing a shrinkage function to suppress noise; Finally, the fused low-frequency and high-frequency components are reconstructed to obtain the fusion image. The experimental results show that the proposed method can fully extract complementary information from the source images to obtain a fusion image with good target indication and rich information on scene details. They also give a fusion result superior to existing popular fusion methods, based on eithers subjective or objective evaluation. With good stability and high fusion accuracy, this method can meet the fusion requirements of IR-visible image fusion systems.

The tumorigenic FGFR3-TACC3 gene fusion escapes miR-99a regulation in glioblastoma.

PubMed

Parker, Brittany C; Annala, Matti J; Cogdell, David E; Granberg, Kirsi J; Sun, Yan; Ji, Ping; Li, Xia; Gumin, Joy; Zheng, Hong; Hu, Limei; Yli-Harja, Olli; Haapasalo, Hannu; Visakorpi, Tapio; Liu, Xiuping; Liu, Chang-Gong; Sawaya, Raymond; Fuller, Gregory N; Chen, Kexin; Lang, Frederick F; Nykter, Matti; Zhang, Wei

2013-02-01

Fusion genes are chromosomal aberrations that are found in many cancers and can be used as prognostic markers and drug targets in clinical practice. Fusions can lead to production of oncogenic fusion proteins or to enhanced expression of oncogenes. Several recent studies have reported that some fusion genes can escape microRNA regulation via 3'-untranslated region (3'-UTR) deletion. We performed whole transcriptome sequencing to identify fusion genes in glioma and discovered FGFR3-TACC3 fusions in 4 of 48 glioblastoma samples from patients both of mixed European and of Asian descent, but not in any of 43 low-grade glioma samples tested. The fusion, caused by tandem duplication on 4p16.3, led to the loss of the 3'-UTR of FGFR3, blocking gene regulation of miR-99a and enhancing expression of the fusion gene. The fusion gene was mutually exclusive with EGFR, PDGFR, or MET amplification. Using cultured glioblastoma cells and a mouse xenograft model, we found that fusion protein expression promoted cell proliferation and tumor progression, while WT FGFR3 protein was not tumorigenic, even under forced overexpression. These results demonstrated that the FGFR3-TACC3 gene fusion is expressed in human cancer and generates an oncogenic protein that promotes tumorigenesis in glioblastoma.

confFuse: High-Confidence Fusion Gene Detection across Tumor Entities.

PubMed

Huang, Zhiqin; Jones, David T W; Wu, Yonghe; Lichter, Peter; Zapatka, Marc

2017-01-01

Background: Fusion genes play an important role in the tumorigenesis of many cancers. Next-generation sequencing (NGS) technologies have been successfully applied in fusion gene detection for the last several years, and a number of NGS-based tools have been developed for identifying fusion genes during this period. Most fusion gene detection tools based on RNA-seq data report a large number of candidates (mostly false positives), making it hard to prioritize candidates for experimental validation and further analysis. Selection of reliable fusion genes for downstream analysis becomes very important in cancer research. We therefore developed confFuse, a scoring algorithm to reliably select high-confidence fusion genes which are likely to be biologically relevant. Results: confFuse takes multiple parameters into account in order to assign each fusion candidate a confidence score, of which score ≥8 indicates high-confidence fusion gene predictions. These parameters were manually curated based on our experience and on certain structural motifs of fusion genes. Compared with alternative tools, based on 96 published RNA-seq samples from different tumor entities, our method can significantly reduce the number of fusion candidates (301 high-confidence from 8,083 total predicted fusion genes) and keep high detection accuracy (recovery rate 85.7%). Validation of 18 novel, high-confidence fusions detected in three breast tumor samples resulted in a 100% validation rate. Conclusions: confFuse is a novel downstream filtering method that allows selection of highly reliable fusion gene candidates for further downstream analysis and experimental validations. confFuse is available at https://github.com/Zhiqin-HUANG/confFuse.

Development and Verification of an RNA Sequencing (RNA-Seq) Assay for the Detection of Gene Fusions in Tumors.

PubMed

Winters, Jennifer L; Davila, Jaime I; McDonald, Amber M; Nair, Asha A; Fadra, Numrah; Wehrs, Rebecca N; Thomas, Brittany C; Balcom, Jessica R; Jin, Long; Wu, Xianglin; Voss, Jesse S; Klee, Eric W; Oliver, Gavin R; Graham, Rondell P; Neff, Jadee L; Rumilla, Kandelaria M; Aypar, Umut; Kipp, Benjamin R; Jenkins, Robert B; Jen, Jin; Halling, Kevin C

2018-06-13

We assessed the performance characteristics of an RNA sequencing (RNA-Seq) assay designed to detect gene fusions in 571 genes to help manage patients with cancer. Polyadenylated RNA was converted to cDNA, which was then used to prepare next-generation sequencing libraries that were sequenced on an Illumina HiSeq 2500 instrument and analyzed with an in-house developed bioinformatic pipeline. The assay identified 38 of 41 gene fusions detected by another method, such as fluorescence in situ hybridization or RT-PCR, for a sensitivity of 93%. No false-positive gene fusions were identified in 15 normal tissue specimens and 10 tumor specimens that were negative for fusions by RNA sequencing or Mate Pair NGS (100% specificity). The assay also identified 22 fusions in 17 tumor specimens that had not been detected by other methods. Eighteen of the 22 fusions had not previously been described. Good intra-assay and interassay reproducibility was observed with complete concordance for the presence or absence of gene fusions in replicates. The analytical sensitivity of the assay was tested by diluting RNA isolated from gene fusion-positive cases with fusion-negative RNA. Gene fusions were generally detectable down to 12.5% dilutions for most fusions and as little as 3% for some fusions. This assay can help identify fusions in patients with cancer; these patients may in turn benefit from both US Food and Drug Administration-approved and investigational targeted therapies. Copyright © 2018 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

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.

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.

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

Preventing Fusion Mass Shift Avoids Postoperative Distal Curve Adding-on in Adolescent Idiopathic Scoliosis.

PubMed

Shigematsu, Hideki; Cheung, Jason Pui Yin; Bruzzone, Mauro; Matsumori, Hiroaki; Mak, Kin-Cheung; Samartzis, Dino; Luk, Keith Dip Kei

2017-05-01

Surgery for adolescent idiopathic scoliosis (AIS) is only complete after achieving fusion to maintain the correction obtained intraoperatively. The instrumented or fused segments can be referred to as the "fusion mass". In patients with AIS, the ideal fusion mass strategy has been established based on fulcrum-bending radiographs for main thoracic curves. Ideally, the fusion mass should achieve parallel endplates of the upper and lower instrumented vertebra and correct any "shift" for truncal balance. Distal adding-on is an important element to consider in AIS surgery. This phenomenon represents a progressive increase in the number of vertebrae included distally in the primary curvature and it should be avoided as it is associated with unsatisfactory cosmesis and an increased risk of revision surgery. However, it remains unknown whether any fusion mass shift, or shift in the fusion mass or instrumented segments, affects global spinal balance and distal adding-on after curve correction surgery in patients with AIS. (1) To investigate the relationship among postoperative fusion mass shift, global balance, and distal adding-on phenomenon in patients with AIS; and (2) to identify a cutoff value of fusion mass shift that will lead to distal adding-on. This was a retrospective study of patients with AIS from a single institution. Between 2006 and 2011 we performed 69 selective thoracic fusions for patients with main thoracic AIS. All patients were evaluated preoperatively and at 2 years postoperatively. The Cobb angle between the cranial and caudal endplates of the fusion mass and the coronal shift between them, which was defined as "fusion mass shift", were measured. Patients with a fusion mass Cobb angle greater than 20° were excluded to specifically determine the effect of fusion mass shift on distal adding-on phenomenon. Fusion mass shift was empirically set as 20 mm for analysis. Therefore, of the 69 patients who underwent selective thoracic fusion, only 52 with a fusion mass Cobb angle of 20° or less were recruited for study. We defined patients with a fusion mass shift of 20 mm or less as the balanced group and those with a fusion mass shift greater than 20 mm as the unbalanced group. A receiver operating characteristic (ROC) curve was used to determine the cutoff point of fusion mass shift for adding-on. Of the 52 patients studied, fusion mass shift (> 20 mm) was noted in 11 (21%), and six of those patients had distal adding-on at final followup. Although global spinal balance did not differ significantly between patients with or without fusion mass shift, the occurrence of adding-on phenomenon was significantly higher in the unbalanced group (55% (six of 11 patients), odds ratio [OR], 8.6; 95% CI, 2-39; p < 0.002) than the balanced group (12% [five of 41 patients]). Based on the ROC curve analysis, a fusion mass shift more than 18 mm was observed as the cutoff point for distal adding-on phenomenon (area under the curve, 0.70; 95% CI, 0.5-0.9; likelihood ratio, 5.0; sensitivity, 0.64; specificity, 0.73; positive predictive value, 39% [seven of 18 patients]; negative predictive value, 88% [30 of 34 patients]; OR, 4.8; 95% CI, 1-20; p = 0.02). Our study illustrates the substantial utility of the fulcrum-bending radiograph in determining fusion levels that can avoid fusion mass shift; thereby, underlining its importance in designing personalized surgical strategies for patients with scoliosis. Preoperatively, determining fusion levels by fulcrum-bending radiographs to avoid residual fusion mass shift is imperative. Intraoperatively, any fusion mass shift should be corrected to avoid distal adding-on, reoperation, and elevated healthcare costs. Level II, prognostic study.

Estimating the melting point, entropy of fusion, and enthalpy of fusion of organic compounds via SPARC

EPA Science Inventory

The entropies of fusion, enthalies of fusion, and melting points of organic compounds can be estimated through three models developed using the SPARC (SPARC Performs Automated Reasoning in Chemistry) platform. The entropy of fusion is modeled through a combination of interaction ...

HEDP and new directions for fusion energy

NASA Astrophysics Data System (ADS)

Kirkpatrick, Ronald C.

2010-06-01

Magnetic-confinement fusion energy and inertia-confinement fusion energy (IFE) represent two extreme approaches to the quest for the application of thermonuclear fusion to electrical energy generation. Blind pursuit of these extreme approaches has long delayed the achievement of their common goal. We point out the possibility of an intermediate approach that promises cheaper, and consequently more rapid development of fusion energy. For example, magneto-inertial fusion appears to be possible over a broad range of parameter space. It is further argued that imposition of artificial constraints impedes the discovery of physics solutions for the fusion energy problem.

Review of fusion synfuels

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fillo, J.A.

1980-01-01

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

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

Sensor fusion III: 3-D perception and recognition; Proceedings of the Meeting, Boston, MA, Nov. 5-8, 1990

NASA Technical Reports Server (NTRS)

Schenker, Paul S. (Editor)

1991-01-01

The volume on data fusion from multiple sources discusses fusing multiple views, temporal analysis and 3D motion interpretation, sensor fusion and eye-to-hand coordination, and integration in human shape perception. Attention is given to surface reconstruction, statistical methods in sensor fusion, fusing sensor data with environmental knowledge, computational models for sensor fusion, and evaluation and selection of sensor fusion techniques. Topics addressed include the structure of a scene from two and three projections, optical flow techniques for moving target detection, tactical sensor-based exploration in a robotic environment, and the fusion of human and machine skills for remote robotic operations. Also discussed are K-nearest-neighbor concepts for sensor fusion, surface reconstruction with discontinuities, a sensor-knowledge-command fusion paradigm for man-machine systems, coordinating sensing and local navigation, and terrain map matching using multisensing techniques for applications to autonomous vehicle navigation.

Estimating the melting point, entropy of fusion, and enthalpy of fusion of organic compounds via SPARC.

PubMed

Whiteside, T S; Hilal, S H; Brenner, A; Carreira, L A

2016-08-01

The entropy of fusion, enthalpy of fusion, and melting point of organic compounds can be estimated through three models developed using the SPARC (SPARC Performs Automated Reasoning in Chemistry) platform. The entropy of fusion is modelled through a combination of interaction terms and physical descriptors. The enthalpy of fusion is modelled as a function of the entropy of fusion, boiling point, and flexibility of the molecule. The melting point model is the enthalpy of fusion divided by the entropy of fusion. These models were developed in part to improve SPARC's vapour pressure and solubility models. These models have been tested on 904 unique compounds. The entropy model has a RMS of 12.5 J mol(-1) K(-1). The enthalpy model has a RMS of 4.87 kJ mol(-1). The melting point model has a RMS of 54.4°C.

Novel cooperative neural fusion algorithms for image restoration and image fusion.

PubMed

Xia, Youshen; Kamel, Mohamed S

2007-02-01

To deal with the problem of restoring degraded images with non-Gaussian noise, this paper proposes a novel cooperative neural fusion regularization (CNFR) algorithm for image restoration. Compared with conventional regularization algorithms for image restoration, the proposed CNFR algorithm can relax need of the optimal regularization parameter to be estimated. Furthermore, to enhance the quality of restored images, this paper presents a cooperative neural fusion (CNF) algorithm for image fusion. Compared with existing signal-level image fusion algorithms, the proposed CNF algorithm can greatly reduce the loss of contrast information under blind Gaussian noise environments. The performance analysis shows that the proposed two neural fusion algorithms can converge globally to the robust and optimal image estimate. Simulation results confirm that in different noise environments, the proposed two neural fusion algorithms can obtain a better image estimate than several well known image restoration and image fusion methods.

Control of a laser inertial confinement fusion-fission power plant

DOEpatents

Moses, Edward I.; Latkowski, Jeffery F.; Kramer, Kevin J.

2015-10-27

A laser inertial-confinement fusion-fission energy power plant is described. The fusion-fission hybrid system uses inertial confinement fusion to produce neutrons from a fusion reaction of deuterium and tritium. The fusion neutrons drive a sub-critical blanket of fissile or fertile fuel. A coolant circulated through the fuel extracts heat from the fuel that is used to generate electricity. The inertial confinement fusion reaction can be implemented using central hot spot or fast ignition fusion, and direct or indirect drive. The fusion neutrons result in ultra-deep burn-up of the fuel in the fission blanket, thus enabling the burning of nuclear waste. Fuels include depleted uranium, natural uranium, enriched uranium, spent nuclear fuel, thorium, and weapons grade plutonium. LIFE engines can meet worldwide electricity needs in a safe and sustainable manner, while drastically shrinking the highly undesirable stockpiles of depleted uranium, spent nuclear fuel and excess weapons materials.

Arabidopsis HAP2/GCS1 is a gamete fusion protein homologous to somatic and viral fusogens

PubMed Central

Valansi, Clari; Moi, David; Leikina, Evgenia; Matveev, Elena; Chernomordik, Leonid V.

2017-01-01

Cell–cell fusion is inherent to sexual reproduction. Loss of HAPLESS 2/GENERATIVE CELL SPECIFIC 1 (HAP2/GCS1) proteins results in gamete fusion failure in diverse organisms, but their exact role is unclear. In this study, we show that Arabidopsis thaliana HAP2/GCS1 is sufficient to promote mammalian cell–cell fusion. Hemifusion and complete fusion depend on HAP2/GCS1 presence in both fusing cells. Furthermore, expression of HAP2 on the surface of pseudotyped vesicular stomatitis virus results in homotypic virus–cell fusion. We demonstrate that the Caenorhabditis elegans Epithelial Fusion Failure 1 (EFF-1) somatic cell fusogen can replace HAP2/GCS1 in one of the fusing membranes, indicating that HAP2/GCS1 and EFF-1 share a similar fusion mechanism. Structural modeling of the HAP2/GCS1 protein family predicts that they are homologous to EFF-1 and viral class II fusion proteins (e.g., Zika virus). We name this superfamily Fusexins: fusion proteins essential for sexual reproduction and exoplasmic merger of plasma membranes. We suggest a common origin and evolution of sexual reproduction, enveloped virus entry into cells, and somatic cell fusion. PMID:28137780

SNAREs support atlastin-mediated homotypic ER fusion in Saccharomyces cerevisiae

PubMed Central

Lee, Miriam; Ko, Young-Joon; Moon, Yeojin; Han, Minsoo; Kim, Hyung-Wook; Lee, Sung Haeng; Kang, KyeongJin

2015-01-01

Dynamin-like GTPases of the atlastin family are thought to mediate homotypic endoplasmic reticulum (ER) membrane fusion; however, the underlying mechanism remains largely unclear. Here, we developed a simple and quantitative in vitro assay using isolated yeast microsomes for measuring yeast atlastin Sey1p-dependent ER fusion. Using this assay, we found that the ER SNAREs Sec22p and Sec20p were required for Sey1p-mediated ER fusion. Consistently, ER fusion was significantly reduced by inhibition of Sec18p and Sec17p, which regulate SNARE-mediated membrane fusion. The involvement of SNAREs in Sey1p-dependent ER fusion was further supported by the physical interaction of Sey1p with Sec22p and Ufe1p, another ER SNARE. Furthermore, our estimation of the concentration of Sey1p on isolated microsomes, together with the lack of fusion between Sey1p proteoliposomes even with a 25-fold excess of the physiological concentration of Sey1p, suggests that Sey1p requires additional factors to support ER fusion in vivo. Collectively, our data strongly suggest that SNARE-mediated membrane fusion is involved in atlastin-initiated homotypic ER fusion. PMID:26216899

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

PubMed

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

2000-03-10

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

Mitochondrial fusion dynamics is robust in the heart and depends on calcium oscillations and contractile activity

PubMed Central

Eisner, Verónica; Gao, Erhe; Csordás, György; Slovinsky, William S.; Paillard, Melanie; Cheng, Lan; Ibetti, Jessica; Chen, S. R. Wayne; Chuprun, J. Kurt; Hoek, Jan B.; Koch, Walter J.; Hajnóczky, György

2017-01-01

Mitochondrial fusion is thought to be important for supporting cardiac contractility, but is hardly detectable in cultured cardiomyocytes and is difficult to directly evaluate in the heart. We overcame this obstacle through in vivo adenoviral transduction with matrix-targeted photoactivatable GFP and confocal microscopy. Imaging in whole rat hearts indicated mitochondrial network formation and fusion activity in ventricular cardiomyocytes. Promptly after isolation, cardiomyocytes showed extensive mitochondrial connectivity and fusion, which decayed in culture (at 24–48 h). Fusion manifested both as rapid content mixing events between adjacent organelles and slower events between both neighboring and distant mitochondria. Loss of fusion in culture likely results from the decline in calcium oscillations/contractile activity and mitofusin 1 (Mfn1), because (i) verapamil suppressed both contraction and mitochondrial fusion, (ii) after spontaneous contraction or short-term field stimulation fusion activity increased in cardiomyocytes, and (iii) ryanodine receptor-2–mediated calcium oscillations increased fusion activity in HEK293 cells and complementing changes occurred in Mfn1. Weakened cardiac contractility in vivo in alcoholic animals is also associated with depressed mitochondrial fusion. Thus, attenuated mitochondrial fusion might contribute to the pathogenesis of cardiomyopathy. PMID:28096338

Multi-focus image fusion using a guided-filter-based difference image.

PubMed

Yan, Xiang; Qin, Hanlin; Li, Jia; Zhou, Huixin; Yang, Tingwu

2016-03-20

The aim of multi-focus image fusion technology is to integrate different partially focused images into one all-focused image. To realize this goal, a new multi-focus image fusion method based on a guided filter is proposed and an efficient salient feature extraction method is presented in this paper. Furthermore, feature extraction is primarily the main objective of the present work. Based on salient feature extraction, the guided filter is first used to acquire the smoothing image containing the most sharpness regions. To obtain the initial fusion map, we compose a mixed focus measure by combining the variance of image intensities and the energy of the image gradient together. Then, the initial fusion map is further processed by a morphological filter to obtain a good reprocessed fusion map. Lastly, the final fusion map is determined via the reprocessed fusion map and is optimized by a guided filter. Experimental results demonstrate that the proposed method does markedly improve the fusion performance compared to previous fusion methods and can be competitive with or even outperform state-of-the-art fusion methods in terms of both subjective visual effects and objective quality metrics.

Multisensor Parallel Largest Ellipsoid Distributed Data Fusion with Unknown Cross-Covariances

PubMed Central

Liu, Baoyu; Zhan, Xingqun; Zhu, Zheng H.

2017-01-01

As the largest ellipsoid (LE) data fusion algorithm can only be applied to two-sensor system, in this contribution, parallel fusion structure is proposed to introduce the LE algorithm into a multisensor system with unknown cross-covariances, and three parallel fusion structures based on different estimate pairing methods are presented and analyzed. In order to assess the influence of fusion structure on fusion performance, two fusion performance assessment parameters are defined as Fusion Distance and Fusion Index. Moreover, the formula for calculating the upper bounds of actual fused error covariances of the presented multisensor LE fusers is also provided. Demonstrated with simulation examples, the Fusion Index indicates fuser’s actual fused accuracy and its sensitivity to the sensor orders, as well as its robustness to the accuracy of newly added sensors. Compared to the LE fuser with sequential structure, the LE fusers with proposed parallel structures not only significantly improve their properties in these aspects, but also embrace better performances in consistency and computation efficiency. The presented multisensor LE fusers generally have better accuracies than covariance intersection (CI) fusion algorithm and are consistent when the local estimates are weakly correlated. PMID:28661442

Effective donor cell fusion conditions for production of cloned dogs by somatic cell nuclear transfer.

PubMed

Park, JungEun; Oh, HyunJu; Hong, SoGun; Kim, MinJung; Kim, GeonA; Koo, OkJae; Kang, SungKeun; Jang, Goo; Lee, ByeongChun

2011-03-01

As shown by the birth of the first cloned dog 'Snuppy', a protocol to produce viable cloned dogs has been reported. In order to evaluate optimum fusion conditions for improving dog cloning efficiency, in vivo matured oocytes were reconstructed with adult somatic cells from a female Pekingese using different fusion conditions. Fusion with needle vs chamber methods, and with low vs high pulse strength was compared by evaluating fusion rate and in vivo development of canine cloned embryos. The fusion rates in the high voltage groups were significantly higher than in the low voltage groups regardless of fusion method (83.5 vs 66.1% for the needle fusion method, 67.4 vs 37.9% for the fusion chamber method). After embryo transfer, one each pregnancy was detected after using the needle fusion method with high and low voltage and in the chamber fusion method with high voltage, whereas no pregnancy was detected using the chamber method with low voltage. However, only the pregnancy from the needle fusion method with high voltage was maintained to term and one healthy puppy was delivered. The results of the present study demonstrated that two DC pulses of 3.8 to 4.0 kV/cm for 15 μsec using the needle fusion method were the most effective method for the production of cloned dogs under the conditions of this experiment. Copyright © 2011 Elsevier Inc. All rights reserved.

Failure analysis of knee arthrodesis with the WichitaFusion Nail.

PubMed

Parcel, Ted W; Levering, Melissa; Polikandriotis, John A; Gustke, Kenneth A; Bernasek, Thomas L

2013-11-01

Arthrodesis is a salvage procedure for failed total knee arthroplasty with the intent to create a stable, pain-free limb on which to ambulate or transfer. For many patients, the alternative to arthrodesis may be an above-knee amputation. Available techniques for knee arthrodesis include compression plating, external fixators, and intramedullary fixation. The purpose of this study was to report the knee fusion rate of consecutive patients at 1 institution using an intramedullary fusion nail and to identify patient risk factors for fusion failure. Between November 1998 and November 2008, twenty-eight patients undergoing knee arthrodesis with an average follow-up of 18 months (range, 3-64 months) were retrospectively studied. Demographic information, presence of fusion, clinical function, pain level, and bone defect data were collected and analyzed. Eighty-two percent (23/28) of patients had radiographic evidence of successful fusion with an average time to fusion of 21 weeks (range, 10-58 weeks). When examining patient variables that could correlate with fusion rates, patients with an Anderson Orthopaedic Research Institute type 3 femoral or type 3 tibial defect had a statistically significant lower fusion rate. The intramedullary fusion nail is an effective device for knee arthrodesis that offers ease of insertion through the knee wound with the advantages of initial bone compression and rigid fixation. Although the use of intramedullary fusion nails leads to a high fusion rate, significant bone deficiency limits successful fusion. Copyright 2013, SLACK Incorporated.

BRAF Fusion Analysis in Pilocytic Astrocytomas: KIAA1549-BRAF 15-9 Fusions Are More Frequent in the Midline Than Within the Cerebellum

PubMed Central

Faulkner, Claire; Ellis, Hayley Patricia; Shaw, Abigail; Penman, Catherine; Palmer, Abigail; Wragg, Christopher; Greenslade, Mark; Haynes, Harry Russell; Williams, Hannah; Lowis, Stephen; White, Paul; Williams, Maggie; Capper, David; Kurian, Kathreena Mary

2015-01-01

Abstract Pilocytic astrocytomas (PAs) are increasingly tested for KIAA1549-BRAF fusions. We used reverse transcription polymerase chain reaction for the 3 most common KIAA1549-BRAF fusions, together with BRAF V600E and histone H3.3 K27M analyses to identify relationships of these molecular characteristics with clinical features in a cohort of 32 PA patients. In this group, the overall BRAF fusion detection rate was 24 (75%). Ten (42%) of the 24 had the 16-9 fusion, 8 (33%) had only the 15-9 fusion, and 1 (4%) of the patients had only the 16-11 fusion. In the PAs with only the 15-9 fusion, 1 PA was in the cerebellum and 7 were centered in the midline outside of the cerebellum, that is, in the hypothalamus (n = 4), optic pathways (n = 2), and brainstem (n = 1). Tumors within the cerebellum were negatively associated with fusion 15-9. Seven (22%) of the 32 patients had tumor-related deaths and 25 of the patients (78%) were alive between 2 and 14 years after initial biopsy. Age, sex, tumor location, 16-9 fusion, and 15-9 fusion were not associated with overall survival. Thus, in this small cohort, 15-9 KIAA1549-BRAF fusion was associated with midline PAs located outside of the cerebellum; these tumors, which are generally difficult to resect, are prone to recurrence. PMID:26222501

Fusion Energy Division progress report, 1 January 1990--31 December 1991

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sheffield, J.; Baker, C.C.; Saltmarsh, M.J.

1994-03-01

The Fusion Program of the Oak Ridge National Laboratory (ORNL), a major part of the national fusion program, encompasses nearly all areas of magnetic fusion research. The program is directed toward the development of fusion as an economical and environmentally attractive energy source for the future. The program involves staff from ORNL, Martin Marietta Energy systems, Inc., private industry, the academic community, and other fusion laboratories, in the US and abroad. Achievements resulting from this collaboration are documented in this report, which is issued as the progress report of the ORNL Fusion Energy Division; it also contains information from componentsmore » for the Fusion Program that are external to the division (about 15% of the program effort). The areas addressed by the Fusion Program include the following: experimental and theoretical research on magnetic confinement concepts; engineering and physics of existing and planned devices, including remote handling; development and testing of diagnostic tools and techniques in support of experiments; assembly and distribution to the fusion community of databases on atomic physics and radiation effects; development and testing of technologies for heating and fueling fusion plasmas; development and testing of superconducting magnets for containing fusion plasmas; development and testing of materials for fusion devices; and exploration of opportunities to apply the unique skills, technology, and techniques developed in the course of this work to other areas (about 15% of the Division`s activities). Highlights from program activities during 1990 and 1991 are presented.« less

A Multiplexed Amplicon Approach for Detecting Gene Fusions by Next-Generation Sequencing.

PubMed

Beadling, Carol; Wald, Abigail I; Warrick, Andrea; Neff, Tanaya L; Zhong, Shan; Nikiforov, Yuri E; Corless, Christopher L; Nikiforova, Marina N

2016-03-01

Chromosomal rearrangements that result in oncogenic gene fusions are clinically important drivers of many cancer types. Rapid and sensitive methods are therefore needed to detect a broad range of gene fusions in clinical specimens that are often of limited quantity and quality. We describe a next-generation sequencing approach that uses a multiplex PCR-based amplicon panel to interrogate fusion transcripts that involve 19 driver genes and 94 partners implicated in solid tumors. The panel also includes control assays that evaluate the 3'/5' expression ratios of 12 oncogenic kinases, which might be used to infer gene fusion events when the partner is unknown or not included on the panel. There was good concordance between the solid tumor fusion gene panel and other methods, including fluorescence in situ hybridization, real-time PCR, Sanger sequencing, and other next-generation sequencing panels, because 40 specimens known to harbor gene fusions were correctly identified. No specific fusion reads were observed in 59 fusion-negative specimens. The 3'/5' expression ratio was informative for fusions that involved ALK, RET, and NTRK1 but not for BRAF or ROS1 fusions. However, among 37 ALK or RET fusion-negative specimens, four exhibited elevated 3'/5' expression ratios, indicating that fusions predicted solely by 3'/5' read ratios require confirmatory testing. Copyright © 2016 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

TMPRSS2-ERG gene fusion status in minute (minimal) prostatic adenocarcinoma.

PubMed

Albadine, Roula; Latour, Mathieu; Toubaji, Antoun; Haffner, Michael; Isaacs, William B; A Platz, Elizabeth; Meeker, Alan K; Demarzo, Angelo M; Epstein, Jonathan I; Netto, George J

2009-11-01

Minute prostatic adenocarcinomas are considered to be of insufficient virulence. Given recent suggestions of TMPRSS2-ERG gene fusion association with aggressive prostatic adenocarcinoma, we evaluated the incidence of TMPRSS2-ERG fusion in minute prostatic adenocarcinomas. A total of 45 consecutive prostatectomies with minute adenocarcinoma were used for tissue microarray construction. A total of 63 consecutive non-minimal, Gleason Score 6 tumors, from a separate PSA Era prostatectomy tissue microarray, were used for comparison. FISH was carried out using ERG break-apart probes. Tumors were assessed for fusion by deletion (Edel) or split (Esplit), duplicated fusions and low-level copy number gain in normal ERG gene locus. Minute adenocarcinomas: Fusion was evaluable in 32/45 tumors (71%). Fifteen out of 32 (47%) tumors were positive for fusion. Six (19%) were of the Edel class and 7 (22%) were classified as combined Edel+Esplit. Non-minute adenocarcinomas (pT2): Fusion was identified in 20/30 tumors (67%). Four (13%) were of Edel class and 5 (17%) were combined Edel+Esplit. Duplicated fusions were encountered in 5 (16%) tumors. Non-minute adenocarcinomas (pT3): Fusion was identified in 19/33 (58%). Fusion was due to a deletion in 6 (18%) tumors. Seven tumors (21%) were classified as combined Edel+Esplit. One tumor showed Esplit alone. Duplicated fusions were encountered in 3 (9%) cases. The incidence of duplicated fusions was higher in non-minute adenocarcinomas (13 vs 0%; P=0.03). A trend for higher incidence of low-level copy number gain in normal ERG gene locus without fusion was noted in non-minute adenocarcinomas (10 vs 0%; P=0.07). We found a TMPRSS2-ERG fusion rate of 47% in minute adenocarcinomas. The latter is not significantly different from that of grade matched non-minute adenocarcinomas. The incidence of duplicated fusion was higher in non-minute adenocarcinomas. Our finding of comparable rate of TMPRSS2-ERG fusion in minute adenocarcinomas may argue against its value as a marker of aggressive prostate carcinoma phenotype.

Five major controversial issues about fusion level selection in corrective surgery for adolescent idiopathic scoliosis: a narrative review.

PubMed

Lee, Choon Sung; Hwang, Chang Ju; Lee, Dong-Ho; Cho, Jae Hwan

2017-07-01

Shoulder imbalance, coronal decompensation, and adding-on phenomenon following corrective surgery in patients with adolescent idiopathic scoliosis are known to be related to the fusion level selected. Although many studies have assessed the appropriate selection of the proximal and distal fusion level, no definite conclusions have been drawn thus far. We aimed to assess the problems with fusion level selection for corrective surgery in patients with adolescent idiopathic scoliosis, and to enhance understanding about these problems. This study is a narrative review. We conducted a literature search of fusion level selection in corrective surgery for adolescent idiopathic scoliosis. Accordingly, we selected and reviewed five debatable topics related to fusion level selection: (1) selective thoracic fusion; (2) selective thoracolumbar-lumbar (TL-L) fusion; (3) adding-on phenomenon; (4) distal fusion level selection for major TL-L curves; and (5) proximal fusion level selection and shoulder imbalance. Selective fusion can be chosen in specific curve types, although there is a risk of coronal decompensation or adding-on phenomenon. Generally, wider indications for selective fusions are usually associated with more frequent complications. Despite the determination of several indications for selective fusion to avoid such complications, no clear guidelines have been established. Although authors have suggested various criteria to prevent the adding-on phenomenon, no consensus has been reached on the appropriate selection of lower instrumented vertebra. The fusion level selection for major TL-L curves primarily focuses on whether distal fusion can terminate at L3, a topic that remains unclear. Furthermore, because of the presence of several related factors and complications, proximal level selection and shoulder imbalance has been constantly debated and remains controversial from its etiology to its prevention. Although several difficult problems in the diagnosis and treatment of adolescent idiopathic scoliosis have been resolved by understanding its mechanism and via technical advancement, no definite guideline for fusion level selection has been established. A review of five major controversial issues about fusion level selection could provide better understanding of adolescent idiopathic scoliosis. We believe that a thorough validation study of the abovementioned controversial issues can help address them. Copyright © 2017 Elsevier Inc. All rights reserved.

Hendra virus fusion protein transmembrane domain contributes to pre-fusion protein stability

PubMed Central

Webb, Stacy; Nagy, Tamas; Moseley, Hunter; Fried, Michael; Dutch, Rebecca

2017-01-01

Enveloped viruses utilize fusion (F) proteins studding the surface of the virus to facilitate membrane fusion with a target cell membrane. Fusion of the viral envelope with a cellular membrane is required for release of viral genomic material, so the virus can ultimately reproduce and spread. To drive fusion, the F protein undergoes an irreversible conformational change, transitioning from a metastable pre-fusion conformation to a more thermodynamically stable post-fusion structure. Understanding the elements that control stability of the pre-fusion state and triggering to the post-fusion conformation is important for understanding F protein function. Mutations in F protein transmembrane (TM) domains implicated the TM domain in the fusion process, but the structural and molecular details in fusion remain unclear. Previously, analytical ultracentrifugation was utilized to demonstrate that isolated TM domains of Hendra virus F protein associate in a monomer-trimer equilibrium (Smith, E. C., Smith, S. E., Carter, J. R., Webb, S. R., Gibson, K. M., Hellman, L. M., Fried, M. G., and Dutch, R. E. (2013) J. Biol. Chem. 288, 35726–35735). To determine factors driving this association, 140 paramyxovirus F protein TM domain sequences were analyzed. A heptad repeat of β-branched residues was found, and analysis of the Hendra virus F TM domain revealed a heptad repeat leucine-isoleucine zipper motif (LIZ). Replacement of the LIZ with alanine resulted in dramatically reduced TM-TM association. Mutation of the LIZ in the whole protein resulted in decreased protein stability, including pre-fusion conformation stability. Together, our data suggest that the heptad repeat LIZ contributed to TM-TM association and is important for F protein function and pre-fusion stability. PMID:28213515

Hendra virus fusion protein transmembrane domain contributes to pre-fusion protein stability.

PubMed

Webb, Stacy; Nagy, Tamas; Moseley, Hunter; Fried, Michael; Dutch, Rebecca

2017-04-07

Enveloped viruses utilize fusion (F) proteins studding the surface of the virus to facilitate membrane fusion with a target cell membrane. Fusion of the viral envelope with a cellular membrane is required for release of viral genomic material, so the virus can ultimately reproduce and spread. To drive fusion, the F protein undergoes an irreversible conformational change, transitioning from a metastable pre-fusion conformation to a more thermodynamically stable post-fusion structure. Understanding the elements that control stability of the pre-fusion state and triggering to the post-fusion conformation is important for understanding F protein function. Mutations in F protein transmembrane (TM) domains implicated the TM domain in the fusion process, but the structural and molecular details in fusion remain unclear. Previously, analytical ultracentrifugation was utilized to demonstrate that isolated TM domains of Hendra virus F protein associate in a monomer-trimer equilibrium (Smith, E. C., Smith, S. E., Carter, J. R., Webb, S. R., Gibson, K. M., Hellman, L. M., Fried, M. G., and Dutch, R. E. (2013) J. Biol. Chem. 288, 35726-35735). To determine factors driving this association, 140 paramyxovirus F protein TM domain sequences were analyzed. A heptad repeat of β-branched residues was found, and analysis of the Hendra virus F TM domain revealed a heptad repeat leucine-isoleucine zipper motif (LIZ). Replacement of the LIZ with alanine resulted in dramatically reduced TM-TM association. Mutation of the LIZ in the whole protein resulted in decreased protein stability, including pre-fusion conformation stability. Together, our data suggest that the heptad repeat LIZ contributed to TM-TM association and is important for F protein function and pre-fusion stability. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

URREF Reliability Versus Credibility in Information Fusion

DTIC Science & Technology

2013-07-01

Fusion, Vol. 3, No. 2, December, 2008. [31] E. Blasch, J. Dezert, and P. Valin , “DSMT Applied to Seismic and Acoustic Sensor Fusion,” Proc. IEEE Nat...44] E. Blasch, P. Valin , E. Bossé, “Measures of Effectiveness for High- Level Fusion,” Int. Conference on Information Fusion, 2010. [45] X. Mei, H...and P. Valin , “Information Fusion Measures of Effectiveness (MOE) for Decision Support,” Proc. SPIE 8050, 2011. [49] Y. Zheng, W. Dong, and E

Commercial objectives, technology transfer, and systems analysis for fusion power development

NASA Astrophysics Data System (ADS)

Dean, Stephen O.

1988-03-01

Fusion is an essentially inexhaustible source of energy that has the potential for economically attractive commercial applications with excellent safety and environmental characteristics. The primary focus for the fusion-energy development program is the generation of centralstation electricity. Fusion has the potential, however, for many other applications. The fact that a large fraction of the energy released in a DT fusion reaction is carried by high-energy neutrons suggests potentially unique applications. These include breeding of fissile fuels, production of hydrogen and other chemical products, transmutation or “burning” of various nuclear or chemical wastes, radiation processing of materials, production of radioisotopes, food preservation, medical diagnosis and medical treatment, and space power and space propulsion. In addition, fusion R&D will lead to new products and new markets. Each fusion application must meet certain standards of economic and safety and environmental attractiveness. For this reason, economics on the one hand, and safety and environment and licensing on the other hand, are the two primary criteria for setting long-range commercial fusion objectives. A major function of systems analysis is to evaluate the potential of fusion against these objectives and to help guide the fusion R&D program toward practical applications. The transfer of fusion technology and skills from the national laboratories and universities to industry is the key to achieving the long-range objective of commercial fusion applications.

Distinct roles for key karyogamy proteins during yeast nuclear fusion.

PubMed

Melloy, Patricia; Shen, Shu; White, Erin; Rose, Mark D

2009-09-01

During yeast mating, cell fusion is followed by the congression and fusion of the two nuclei. Proteins required for nuclear fusion are found at the surface (Prm3p) and within the lumen (Kar2p, Kar5p, and Kar8p) of the nuclear envelope (NE). Electron tomography (ET) of zygotes revealed that mutations in these proteins block nuclear fusion with different morphologies, suggesting that they act in different steps of fusion. Specifically, prm3 zygotes were blocked before formation of membrane bridges, whereas kar2, kar5, and kar8 zygotes frequently contained them. Membrane bridges were significantly larger and occurred more frequently in kar2 and kar8, than in kar5 mutant zygotes. The kinetics of NE fusion in prm3, kar5, and kar8 mutants, measured by live-cell fluorescence microscopy, were well correlated with the size and frequency of bridges observed by ET. However the kar2 mutant was defective for transfer of NE lumenal GFP, but not diffusion within the lumen, suggesting that transfer was blocked at the NE fusion junction. These observations suggest that Prm3p acts before initiation of outer NE fusion, Kar5p may help dilation of the initial fusion pore, and Kar2p and Kar8p act after outer NE fusion, during inner NE fusion.

ER-associated SNAREs and Sey1p mediate nuclear fusion at two distinct steps during yeast mating

PubMed Central

Rogers, Jason V.; Arlow, Tim; Inkellis, Elizabeth R.; Koo, Timothy S.; Rose, Mark D.

2013-01-01

During yeast mating, two haploid nuclei fuse membranes to form a single diploid nucleus. However, the known proteins required for nuclear fusion are unlikely to function as direct fusogens (i.e., they are unlikely to directly catalyze lipid bilayer fusion) based on their predicted structure and localization. Therefore we screened known fusogens from vesicle trafficking (soluble N-ethylmaleimide–sensitive factor attachment protein receptors [SNAREs]) and homotypic endoplasmic reticulum (ER) fusion (Sey1p) for additional roles in nuclear fusion. Here we demonstrate that the ER-localized SNAREs Sec20p, Ufe1p, Use1p, and Bos1p are required for efficient nuclear fusion. In contrast, Sey1p is required indirectly for nuclear fusion; sey1Δ zygotes accumulate ER at the zone of cell fusion, causing a block in nuclear congression. However, double mutants of Sey1p and Sec20p, Ufe1p, or Use1p, but not Bos1p, display extreme ER morphology defects, worse than either single mutant, suggesting that retrograde SNAREs fuse ER in the absence of Sey1p. Together these data demonstrate that SNAREs mediate nuclear fusion, ER fusion after cell fusion is necessary to complete nuclear congression, and there exists a SNARE-mediated, Sey1p-independent ER fusion pathway. PMID:24152736

Binaural pitch fusion: Comparison of normal-hearing and hearing-impaired listenersa)

PubMed Central

Reiss, Lina A. J.; Shayman, Corey S.; Walker, Emily P.; Bennett, Keri O.; Fowler, Jennifer R.; Hartling, Curtis L.; Glickman, Bess; Lasarev, Michael R.; Oh, Yonghee

2017-01-01

Binaural pitch fusion is the fusion of dichotically presented tones that evoke different pitches between the ears. In normal-hearing (NH) listeners, the frequency range over which binaural pitch fusion occurs is usually <0.2 octaves. Recently, broad fusion ranges of 1–4 octaves were demonstrated in bimodal cochlear implant users. In the current study, it was hypothesized that hearing aid (HA) users would also exhibit broad fusion. Fusion ranges were measured in both NH and hearing-impaired (HI) listeners with hearing losses ranging from mild-moderate to severe-profound, and relationships of fusion range with demographic factors and with diplacusis were examined. Fusion ranges of NH and HI listeners averaged 0.17 ± 0.13 octaves and 1.7 ± 1.5 octaves, respectively. In HI listeners, fusion ranges were positively correlated with a principal component measure of the covarying factors of young age, early age of hearing loss onset, and long durations of hearing loss and HA use, but not with hearing threshold, amplification level, or diplacusis. In NH listeners, no correlations were observed with age, hearing threshold, or diplacusis. The association of broad fusion with early onset, long duration of hearing loss suggests a possible role of long-term experience with hearing loss and amplification in the development of broad fusion. PMID:28372056

The tumorigenic FGFR3-TACC3 gene fusion escapes miR-99a regulation in glioblastoma

PubMed Central

Parker, Brittany C.; Annala, Matti J.; Cogdell, David E.; Granberg, Kirsi J.; Sun, Yan; Ji, Ping; Li, Xia; Gumin, Joy; Zheng, Hong; Hu, Limei; Yli-Harja, Olli; Haapasalo, Hannu; Visakorpi, Tapio; Liu, Xiuping; Liu, Chang-gong; Sawaya, Raymond; Fuller, Gregory N.; Chen, Kexin; Lang, Frederick F.; Nykter, Matti; Zhang, Wei

2013-01-01

Fusion genes are chromosomal aberrations that are found in many cancers and can be used as prognostic markers and drug targets in clinical practice. Fusions can lead to production of oncogenic fusion proteins or to enhanced expression of oncogenes. Several recent studies have reported that some fusion genes can escape microRNA regulation via 3′–untranslated region (3′-UTR) deletion. We performed whole transcriptome sequencing to identify fusion genes in glioma and discovered FGFR3-TACC3 fusions in 4 of 48 glioblastoma samples from patients both of mixed European and of Asian descent, but not in any of 43 low-grade glioma samples tested. The fusion, caused by tandem duplication on 4p16.3, led to the loss of the 3′-UTR of FGFR3, blocking gene regulation of miR-99a and enhancing expression of the fusion gene. The fusion gene was mutually exclusive with EGFR, PDGFR, or MET amplification. Using cultured glioblastoma cells and a mouse xenograft model, we found that fusion protein expression promoted cell proliferation and tumor progression, while WT FGFR3 protein was not tumorigenic, even under forced overexpression. These results demonstrated that the FGFR3-TACC3 gene fusion is expressed in human cancer and generates an oncogenic protein that promotes tumorigenesis in glioblastoma. PMID:23298836

Design of a multisensor data fusion system for target detection

NASA Astrophysics Data System (ADS)

Thomopoulos, Stelios C.; Okello, Nickens N.; Kadar, Ivan; Lovas, Louis A.

1993-09-01

The objective of this paper is to discuss the issues that are involved in the design of a multisensor fusion system and provide a systematic analysis and synthesis methodology for the design of the fusion system. The system under consideration consists of multifrequency (similar) radar sensors. However, the fusion design must be flexible to accommodate additional dissimilar sensors such as IR, EO, ESM, and Ladar. The motivation for the system design is the proof of the fusion concept for enhancing the detectability of small targets in clutter. In the context of down-selecting the proper configuration for multisensor (similar and dissimilar, and centralized vs. distributed) data fusion, the issues of data modeling, fusion approaches, and fusion architectures need to be addressed for the particular application being considered. Although the study of different approaches may proceed in parallel, the interplay among them is crucial in selecting a fusion configuration for a given application. The natural sequence for addressing the three different issues is to begin from the data modeling, in order to determine the information content of the data. This information will dictate the appropriate fusion approach. This, in turn, will lead to a global fusion architecture. Both distributed and centralized fusion architectures are used to illustrate the design issues along with Monte-Carlo simulation performance comparison of a single sensor versus a multisensor centrally fused system.

Membrane Fusion Promoted by Increasing Surface Densities of the Paramyxovirus F and HN Proteins: Comparison of Fusion Reactions Mediated by Simian Virus 5 F, Human Parainfluenza Virus Type 3 F, and Influenza Virus HA

PubMed Central

Dutch, Rebecca Ellis; Joshi, Sangeeta Bagai; Lamb, Robert A.

1998-01-01

The membrane fusion reaction promoted by the paramyxovirus simian virus 5 (SV5) and human parainfluenza virus type 3 (HPIV-3) fusion (F) proteins and hemagglutinin-neuraminidase (HN) proteins was characterized when the surface densities of F and HN were varied. Using a quantitative content mixing assay, it was found that the extent of SV5 F-mediated fusion was dependent on the surface density of the SV5 F protein but independent of the density of SV5 HN protein, indicating that HN serves only a binding function in the reaction. However, the extent of HPIV-3 F protein promoted fusion reaction was found to be dependent on surface density of HPIV-3 HN protein, suggesting that the HPIV-3 HN protein is a direct participant in the fusion reaction. Analysis of the kinetics of lipid mixing demonstrated that both initial rates and final extents of fusion increased with rising SV5 F protein surface densities, suggesting that multiple fusion pores can be active during SV5 F protein-promoted membrane fusion. Initial rates and extent of lipid mixing were also found to increase with increasing influenza virus hemagglutinin protein surface density, suggesting parallels between the mechanism of fusion promoted by these two viral fusion proteins. PMID:9733810

Two heretical thoughts on fusion and climate

NASA Astrophysics Data System (ADS)

Manheimer, Wallace

2016-10-01

This presents and explores 2 heretical thoughts regarding controlled fusion and climate. First, the only way that fusion can contribute to midcentury power is by switching its goal from pure fusion, to fusion breeding. Fusion breeding makes many fewer demands on the fusion device than does pure fusion. Fusion breeding could lead to a sustainable, carbon free, environmentally and economically viable, midcentury infrastructure, with little or no proliferation risk, which could provide terawatts of power for the world. The second involves climate. We are all inundated by media warnings, not only of warming from CO2 in the atmosphere, but all sorts of other environmental disasters. For instance there will be more intense storms, rising sea levels, wild fires, retreating glaciers, droughts, loss of agricultural productivity... These assertions are very easy to check out. Such a search shows that we are nowhere near any sort of environmental crisis. The timing could be serendipitous; the time necessary to develop fusion breeding could well match up to the time when it is needed so as to avoid harm to the earth's climate and/or depletion of finite energy resources.

Statistical algorithms improve accuracy of gene fusion detection

PubMed Central

Hsieh, Gillian; Bierman, Rob; Szabo, Linda; Lee, Alex Gia; Freeman, Donald E.; Watson, Nathaniel; Sweet-Cordero, E. Alejandro

2017-01-01

Abstract Gene fusions are known to play critical roles in tumor pathogenesis. Yet, sensitive and specific algorithms to detect gene fusions in cancer do not currently exist. In this paper, we present a new statistical algorithm, MACHETE (Mismatched Alignment CHimEra Tracking Engine), which achieves highly sensitive and specific detection of gene fusions from RNA-Seq data, including the highest Positive Predictive Value (PPV) compared to the current state-of-the-art, as assessed in simulated data. We show that the best performing published algorithms either find large numbers of fusions in negative control data or suffer from low sensitivity detecting known driving fusions in gold standard settings, such as EWSR1-FLI1. As proof of principle that MACHETE discovers novel gene fusions with high accuracy in vivo, we mined public data to discover and subsequently PCR validate novel gene fusions missed by other algorithms in the ovarian cancer cell line OVCAR3. These results highlight the gains in accuracy achieved by introducing statistical models into fusion detection, and pave the way for unbiased discovery of potentially driving and druggable gene fusions in primary tumors. PMID:28541529

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liao Maofu; Kielian, Margaret

2005-02-05

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

FusionAnalyser: a new graphical, event-driven tool for fusion rearrangements discovery

PubMed Central

Piazza, Rocco; Pirola, Alessandra; Spinelli, Roberta; Valletta, Simona; Redaelli, Sara; Magistroni, Vera; Gambacorti-Passerini, Carlo

2012-01-01

Gene fusions are common driver events in leukaemias and solid tumours; here we present FusionAnalyser, a tool dedicated to the identification of driver fusion rearrangements in human cancer through the analysis of paired-end high-throughput transcriptome sequencing data. We initially tested FusionAnalyser by using a set of in silico randomly generated sequencing data from 20 known human translocations occurring in cancer and subsequently using transcriptome data from three chronic and three acute myeloid leukaemia samples. in all the cases our tool was invariably able to detect the presence of the correct driver fusion event(s) with high specificity. In one of the acute myeloid leukaemia samples, FusionAnalyser identified a novel, cryptic, in-frame ETS2–ERG fusion. A fully event-driven graphical interface and a flexible filtering system allow complex analyses to be run in the absence of any a priori programming or scripting knowledge. Therefore, we propose FusionAnalyser as an efficient and robust graphical tool for the identification of functional rearrangements in the context of high-throughput transcriptome sequencing data. PMID:22570408

FusionAnalyser: a new graphical, event-driven tool for fusion rearrangements discovery.

PubMed

Piazza, Rocco; Pirola, Alessandra; Spinelli, Roberta; Valletta, Simona; Redaelli, Sara; Magistroni, Vera; Gambacorti-Passerini, Carlo

2012-09-01

Gene fusions are common driver events in leukaemias and solid tumours; here we present FusionAnalyser, a tool dedicated to the identification of driver fusion rearrangements in human cancer through the analysis of paired-end high-throughput transcriptome sequencing data. We initially tested FusionAnalyser by using a set of in silico randomly generated sequencing data from 20 known human translocations occurring in cancer and subsequently using transcriptome data from three chronic and three acute myeloid leukaemia samples. in all the cases our tool was invariably able to detect the presence of the correct driver fusion event(s) with high specificity. In one of the acute myeloid leukaemia samples, FusionAnalyser identified a novel, cryptic, in-frame ETS2-ERG fusion. A fully event-driven graphical interface and a flexible filtering system allow complex analyses to be run in the absence of any a priori programming or scripting knowledge. Therefore, we propose FusionAnalyser as an efficient and robust graphical tool for the identification of functional rearrangements in the context of high-throughput transcriptome sequencing data.

Dual Split Protein-Based Fusion Assay Reveals that Mutations to Herpes Simplex Virus (HSV) Glycoprotein gB Alter the Kinetics of Cell-Cell Fusion Induced by HSV Entry Glycoproteins

PubMed Central

Atanasiu, Doina; Saw, Wan Ting; Gallagher, John R.; Hannah, Brian P.; Matsuda, Zene; Whitbeck, J. Charles; Cohen, Gary H.

2013-01-01

Herpes simplex virus (HSV) entry and cell-cell fusion require glycoproteins gD, gH/gL, and gB. We propose that receptor-activated changes to gD cause it to activate gH/gL, which then triggers gB into an active form. We employed a dual split-protein (DSP) assay to monitor the kinetics of HSV glycoprotein-induced cell-cell fusion. This assay measures content mixing between two cells, i.e., fusion, within the same cell population in real time (minutes to hours). Titration experiments suggest that both gD and gH/gL act in a catalytic fashion to trigger gB. In fact, fusion rates are governed by the amount of gB on the cell surface. We then used the DSP assay to focus on mutants in two functional regions (FRs) of gB, FR1 and FR3. FR1 contains the fusion loops (FL1 and FL2), and FR3 encompasses the crown at the trimer top. All FL mutants initiated fusion very slowly, if at all. However, the fusion rates caused by some FL2 mutants increased over time, so that total fusion by 8 h looked much like that of the WT. Two distinct kinetic patterns, “slow and fast,” emerged for mutants in the crown of gB (FR3), again showing differences in initiation and ongoing fusion. Of note are the fusion kinetics of the gB syn mutant (LL871/872AA). Although this mutant was originally included as an ongoing high-rate-of-fusion control, its initiation of fusion is so rapid that it appears to be on a “hair trigger.” Thus, the DSP assay affords a unique way to examine the dynamics of HSV glycoprotein-induced cell fusion. PMID:23946457

Minimally Invasive Transforaminal Lumbar Interbody Fusion: Meta-analysis of the Fusion Rates. What is the Optimal Graft Material?

PubMed

Parajón, Avelino; Alimi, Marjan; Navarro-Ramirez, Rodrigo; Christos, Paul; Torres-Campa, Jose M; Moriguchi, Yu; Lang, Gernot; Härtl, Roger

2017-12-01

Minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) is an increasingly popular procedure with several potential advantages over traditional open TLIF. The current study aimed to compare fusion rates of different graft materials used in MIS-TLIF, via meta-analysis of the published literature. A Medline search was performed and a database was created including patient's type of graft, clinical outcome, fusion rate, fusion assessment modality, and duration of follow-up. Meta-analysis of the fusion rate was performed using StatsDirect software (StatsDirect Ltd, Cheshire, United Kingdom). A total of 1533 patients from 40 series were included. Fusion rates were high, ranging from 91.8% to 99%. The imaging modalities used to assess fusion were computed tomography scans (30%) and X-rays (70%). Comparison of all recombinant human bone morphogenetic protein (rhBMP) series with all non-rhBMP series showed fusion rates of 96.6% and 92.5%, respectively. The lowest fusion rate was seen with isolated use of autologous local bone (91.8%). The highest fusion rate was observed with combination of autologous local bone with bone extender and rhBMP (99.1%). The highest fusion rate without the use of BMP was seen with autologous local bone + bone extender (93.1%). The reported complication rate ranged from 0% to 35.71%. Clinical improvement was observed in all studies. Fusion rates are generally high with MIS-TLIF regardless of the graft material used. Given the potential complications of iliac bone harvesting and rhBMP, use of other bone graft options for MIS-TLIF is reasonable. The highest fusion rate without the use of rhBMP was seen with autologous local bone plus bone extender (93.1%). Published by Oxford University Press on behalf of Congress of Neurological Surgeons 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Fusion Rates of Different Anterior Grafts in Thoracolumbar Fractures.

PubMed

Antoni, Maxime; Charles, Yann Philippe; Walter, Axel; Schuller, Sébastien; Steib, Jean-Paul

2015-11-01

Retrospective CT analysis of anterior fusion in thoracolumbar trauma. The aim of this study was to compare fusion rates of different bone grafts and to analyze risk factors for pseudarthrosis. Interbody fusion is indicated in anterior column defects. Different grafts are used: autologous iliac crest, titanium mesh cages filled with cancellous bone, and autologous ribs. It is not clear which graft offers the most reliable fusion. Radiologic data of 116 patients (71 men, 45 women) operated for type A2, A3, B, or C fractures were analyzed. The average age was 44.6 years (range, 16-75 y) and follow-up was 2.7 years (range, 1-9 y). All patients were treated by posterior instrumentation followed by an anterior graft: 53 cases with iliac crest, 43 cases with mesh cages, and 20 with rib grafts. Fusion was evaluated on CT and classified into complete fusion, partial fusion, unipolar pseudarthrosis, and bipolar pseudarthrosis. Iliac crest fused in 66%, cages in 98%, and rib grafts in 90%. The fusion rate of cages filled with bone was significantly higher as the iliac graft fusion rate (P=0.002). The same was applied to rib grafts compared with iliac crest (P=0.041). Additional bone formation around the main graft, bridging both vertebral bodies, was observed in 31 of the 53 iliac crests grafts. Pseudarthrosis occurred more often in smokers (P=0.042). A relationship between fracture or instrumentation types, sex, age, BMI, and fusion could not be determined. Tricortical iliac crest grafts showed an unexpected high pseudarthrosis rate in thoracolumbar injuries. Their cortical bone is dense and their fusion surface is small. Rib grafts led to a better fusion when used in combination with the cancellous bone from the fractured vertebral body. Titanium mesh cages filled with cancellous bone led to the highest fusion rate and built a complete bony bridge between vertebral bodies. Smoking seemed to influence fusion. Case control study, Level III.

Tensor functors between Morita duals of fusion categories

NASA Astrophysics Data System (ADS)

Galindo, César; Plavnik, Julia Yael

2017-03-01

Given a fusion category C and an indecomposable C -module category M , the fusion category C^*_{_{M}} of C-module endofunctors of M is called the (Morita) dual fusion category of C with respect to M . We describe tensor functors between two arbitrary duals C^*_{_{M}} and D^*_N in terms of data associated to C and D . We apply the results to G-equivariantizations of fusion categories and group-theoretical fusion categories. We describe the orbits of the action of the Brauer-Picard group on the set of module categories and we propose a categorification of the Rosenberg-Zelinsky sequence for fusion categories.

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.

Measuring time of flight of fusion products in an inertial electrostatic confinement fusion device for spatial profiling of fusion reactions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Donovan, D. C.; Boris, D. R.; Kulcinski, G. L.

2013-03-15

A new diagnostic has been developed that uses the time of flight (TOF) of the products from a nuclear fusion reaction to determine the location where the fusion reaction occurred. The TOF diagnostic uses charged particle detectors on opposing sides of the inertial electrostatic confinement (IEC) device that are coupled to high resolution timing electronics to measure the spatial profile of fusion reactions occurring between the two charged particle detectors. This diagnostic was constructed and tested by the University of Wisconsin-Madison Inertial Electrostatic Confinement Fusion Group in the IEC device, HOMER, which accelerates deuterium ions to fusion relevant energies inmore » a high voltage ({approx}100 kV), spherically symmetric, electrostatic potential well [J. F. Santarius, G. L. Kulcinski, R. P. Ashley, D. R. Boris, B. B. Cipiti, S. K. Murali, G. R. Piefer, R. F. Radel, T. E. Radel, and A. L. Wehmeyer, Fusion Sci. Technol. 47, 1238 (2005)]. The TOF diagnostic detects the products of D(d,p)T reactions and determines where along a chord through the device the fusion event occurred. The diagnostic is also capable of using charged particle spectroscopy to determine the Doppler shift imparted to the fusion products by the center of mass energy of the fusion reactants. The TOF diagnostic is thus able to collect spatial profiles of the fusion reaction density along a chord through the device, coupled with the center of mass energy of the reactions occurring at each location. This provides levels of diagnostic detail never before achieved on an IEC device.« less

Influence of Alendronate and Endplate Degeneration to Single Level Posterior Lumbar Spinal Interbody Fusion

PubMed Central

Rhee, Wootack; Ha, Seongil; Lim, Jae Hyeon; Jang, Il Tae

2014-01-01

Objective Using alendronate after spinal fusion is a controversial issue due to the inhibition of osteoclast mediated bone resorption. In addition, there are an increasing number of reports that the endplate degeneration influences the lumbar spinal fusion. The object of this retrospective controlled study was to evaluate how the endplate degeneration and the bisphosphonate medication influence the spinal fusion through radiographic evaluation. Methods In this study, 44 patients who underwent single-level posterior lumbar interbody fusion (PLIF) using cage were examined from April 2007 to March 2009. All patients had been diagnosed as osteoporosis and would be recommended for alendronate medication. Endplate degeneration is categorized by the Modic changes. The solid fusion is defined if there was bridging bone between the vertebral bodies, either within or external to the cage on the plain X-ray and if there is less than 5° of angular difference in dynamic X-ray. Results In alendronate group, fusion was achieved in 66.7% compared to 73.9% in control group (no medication). Alendronate did not influence the fusion rate of PLIF. However, there was the statistical difference of fusion rate between the endplate degeneration group and the group without endplate degeneration. A total of 52.4% of fusion rate was seen in the endplate degeneration group compared to 91.3% in the group without endplate degeneration. The endplate degeneration suppresses the fusion process of PLIF. Conclusion Alendronate does not influence the fusion process in osteoporotic patients. The endplate degeneration decreases the fusion rate. PMID:25620981

A Narrative Review of Lumbar Fusion Surgery With Relevance to Chiropractic Practice.

PubMed

Daniels, Clinton J; Wakefield, Pamela J; Bub, Glenn A; Toombs, James D

2016-12-01

The purpose of this narrative review was to describe the most common spinal fusion surgical procedures, address the clinical indications for lumbar fusion in degeneration cases, identify potential complications, and discuss their relevance to chiropractic management of patients after surgical fusion. The PubMed database was searched from the beginning of the record through March 31, 2015, for English language articles related to lumbar fusion or arthrodesis or both and their incidence, procedures, complications, and postoperative chiropractic cases. Articles were retrieved and evaluated for relevance. The bibliographies of selected articles were also reviewed. The most typical lumbar fusion procedures are posterior lumbar interbody fusion, anterior lumbar interbody fusion, transforaminal interbody fusion, and lateral lumbar interbody fusion. Fair level evidence supports lumbar fusion procedures for degenerative spondylolisthesis with instability and for intractable low back pain that has failed conservative care. Complications and development of chronic pain after surgery is common, and these patients frequently present to chiropractic physicians. Several reports describe the potential benefit of chiropractic management with spinal manipulation, flexion-distraction manipulation, and manipulation under anesthesia for postfusion low back pain. There are no published experimental studies related specifically to chiropractic care of postfusion low back pain. This article describes the indications for fusion, common surgical practice, potential complications, and relevant published chiropractic literature. This review includes 10 cases that showed positive benefits from chiropractic manipulation, flexion-distraction, and/or manipulation under anesthesia for postfusion lumbar pain. Chiropractic care may have a role in helping patients in pain who have undergone lumbar fusion surgery.

[Research progress of multi-model medical image fusion and recognition].

PubMed

Zhou, Tao; Lu, Huiling; Chen, Zhiqiang; Ma, Jingxian

2013-10-01

Medical image fusion and recognition has a wide range of applications, such as focal location, cancer staging and treatment effect assessment. Multi-model medical image fusion and recognition are analyzed and summarized in this paper. Firstly, the question of multi-model medical image fusion and recognition is discussed, and its advantage and key steps are discussed. Secondly, three fusion strategies are reviewed from the point of algorithm, and four fusion recognition structures are discussed. Thirdly, difficulties, challenges and possible future research direction are discussed.

PI(4,5)P2 regulates myoblast fusion through Arp2/3 regulator localization at the fusion site

PubMed Central

Bothe, Ingo; Deng, Su; Baylies, Mary

2014-01-01

Cell-cell fusion is a regulated process that requires merging of the opposing membranes and underlying cytoskeletons. However, the integration between membrane and cytoskeleton signaling during fusion is not known. Using Drosophila, we demonstrate that the membrane phosphoinositide PI(4,5)P2 is a crucial regulator of F-actin dynamics during myoblast fusion. PI(4,5)P2 is locally enriched and colocalizes spatially and temporally with the F-actin focus that defines the fusion site. PI(4,5)P2 enrichment depends on receptor engagement but is upstream or parallel to actin remodeling. Regulators of actin branching via Arp2/3 colocalize with PI(4,5)P2 in vivo and bind PI(4,5)P2 in vitro. Manipulation of PI(4,5)P2 availability leads to impaired fusion, with a reduction in the F-actin focus size and altered focus morphology. Mechanistically, the changes in the actin focus are due to a failure in the enrichment of actin regulators at the fusion site. Moreover, improper localization of these regulators hinders expansion of the fusion interface. Thus, PI(4,5)P2 enrichment at the fusion site encodes spatial and temporal information that regulates fusion progression through the localization of activators of actin polymerization. PMID:24821989

Gradient-based multiresolution image fusion.

PubMed

Petrović, Valdimir S; Xydeas, Costas S

2004-02-01

A novel approach to multiresolution signal-level image fusion is presented for accurately transferring visual information from any number of input image signals, into a single fused image without loss of information or the introduction of distortion. The proposed system uses a "fuse-then-decompose" technique realized through a novel, fusion/decomposition system architecture. In particular, information fusion is performed on a multiresolution gradient map representation domain of image signal information. At each resolution, input images are represented as gradient maps and combined to produce new, fused gradient maps. Fused gradient map signals are processed, using gradient filters derived from high-pass quadrature mirror filters to yield a fused multiresolution pyramid representation. The fused output image is obtained by applying, on the fused pyramid, a reconstruction process that is analogous to that of conventional discrete wavelet transform. This new gradient fusion significantly reduces the amount of distortion artefacts and the loss of contrast information usually observed in fused images obtained from conventional multiresolution fusion schemes. This is because fusion in the gradient map domain significantly improves the reliability of the feature selection and information fusion processes. Fusion performance is evaluated through informal visual inspection and subjective psychometric preference tests, as well as objective fusion performance measurements. Results clearly demonstrate the superiority of this new approach when compared to conventional fusion systems.

The "grep" command but not FusionMap, FusionFinder or ChimeraScan captures the CIC-DUX4 fusion gene from whole transcriptome sequencing data on a small round cell tumor with t(4;19)(q35;q13).

PubMed

Panagopoulos, Ioannis; Gorunova, Ludmila; Bjerkehagen, Bodil; Heim, Sverre

2014-01-01

Whole transcriptome sequencing was used to study a small round cell tumor in which a t(4;19)(q35;q13) was part of the complex karyotype but where the initial reverse transcriptase PCR (RT-PCR) examination did not detect a CIC-DUX4 fusion transcript previously described as the crucial gene-level outcome of this specific translocation. The RNA sequencing data were analysed using the FusionMap, FusionFinder, and ChimeraScan programs which are specifically designed to identify fusion genes. FusionMap, FusionFinder, and ChimeraScan identified 1017, 102, and 101 fusion transcripts, respectively, but CIC-DUX4 was not among them. Since the RNA sequencing data are in the fastq text-based format, we searched the files using the "grep" command-line utility. The "grep" command searches the text for specific expressions and displays, by default, the lines where matches occur. The "specific expression" was a sequence of 20 nucleotides from the coding part of the last exon 20 of CIC (Reference Sequence: NM_015125.3) chosen since all the so far reported CIC breakpoints have occurred here. Fifteen chimeric CIC-DUX4 cDNA sequences were captured and the fusion between the CIC and DUX4 genes was mapped precisely. New primer combinations were constructed based on these findings and were used together with a polymerase suitable for amplification of GC-rich DNA templates to amplify CIC-DUX4 cDNA fragments which had the same fusion point found with "grep". In conclusion, FusionMap, FusionFinder, and ChimeraScan generated a plethora of fusion transcripts but did not detect the biologically important CIC-DUX4 chimeric transcript; they are generally useful but evidently suffer from imperfect both sensitivity and specificity. The "grep" command is an excellent tool to capture chimeric transcripts from RNA sequencing data when the pathological and/or cytogenetic information strongly indicates the presence of a specific fusion gene.

Effects of a Commercial Insurance Policy Restriction on Lumbar Fusion in North Carolina and the Implications for National Adoption

PubMed Central

Deyo, Richard A.; Lurie, Jon D.; Carey, Timothy S.; Tosteson, Anna N.A.; Mirza, Sohail K.

2015-01-01

Study design Analysis of the State Inpatient Database of North Carolina, 2005–2012, and the Nationwide Inpatient Sample, including all inpatient lumbar fusion admissions from non-federal hospitals. Objective To examine the influence of a major commercial policy change that restricted lumbar fusion for certain indications, and to forecast the potential impact if the policy were adopted nationally. Summary of Background Data Few studies have examined the effects of recent changes in commercial coverage policies that restrict the use of lumbar fusion. Methods We included adults undergoing elective lumbar fusion or re-fusion operations in North Carolina. We aggregated data into a monthly time series to report changes in the rates and volume of lumbar fusion operations for disc herniation or degeneration, spinal stenosis, spondylolisthesis, or revision fusions. Time series regression models were used to test for significant changes in the use of fusion operation following a major commercial coverage policy change initiated on January 1st, 2011. Results There was a substantial decline in the use of lumbar fusion for disc herniation or degeneration following the policy change on January 1st, 2011. Overall rates of elective lumbar fusion operations in North Carolina (per 100,000 residents) increased from 103.2 in 2005 to 120.4 in 2009, before declining to 101.9 by 2012. The population rate (per 100,000 residents) of fusion among those under age 65 increased from 89.5 in 2005 to 101.2 in 2009, followed by a sharp decline to 76.8 by 2012. There was no acceleration in the already increasing rate of fusion for spinal stenosis, spondylolisthesis or revision procedures, but there was a coincident increase in decompression without fusion. Conclusions This commercial insurance policy change had its intended effect of reducing fusion operations for indications with less evidence of effectiveness without changing rates for other indications or resulting in an overall reduction in spine surgery. Nevertheless, broader adoption of the policy could significantly reduce the national rates of fusion operations and associated costs. PMID:26679877

Distributed data fusion across multiple hard and soft mobile sensor platforms

NASA Astrophysics Data System (ADS)

Sinsley, Gregory

One of the biggest challenges currently facing the robotics field is sensor data fusion. Unmanned robots carry many sophisticated sensors including visual and infrared cameras, radar, laser range finders, chemical sensors, accelerometers, gyros, and global positioning systems. By effectively fusing the data from these sensors, a robot would be able to form a coherent view of its world that could then be used to facilitate both autonomous and intelligent operation. Another distinct fusion problem is that of fusing data from teammates with data from onboard sensors. If an entire team of vehicles has the same worldview they will be able to cooperate much more effectively. Sharing worldviews is made even more difficult if the teammates have different sensor types. The final fusion challenge the robotics field faces is that of fusing data gathered by robots with data gathered by human teammates (soft sensors). Humans sense the world completely differently from robots, which makes this problem particularly difficult. The advantage of fusing data from humans is that it makes more information available to the entire team, thus helping each agent to make the best possible decisions. This thesis presents a system for fusing data from multiple unmanned aerial vehicles, unmanned ground vehicles, and human observers. The first issue this thesis addresses is that of centralized data fusion. This is a foundational data fusion issue, which has been very well studied. Important issues in centralized fusion include data association, classification, tracking, and robotics problems. Because these problems are so well studied, this thesis does not make any major contributions in this area, but does review it for completeness. The chapter on centralized fusion concludes with an example unmanned aerial vehicle surveillance problem that demonstrates many of the traditional fusion methods. The second problem this thesis addresses is that of distributed data fusion. Distributed data fusion is a younger field than centralized fusion. The main issues in distributed fusion that are addressed are distributed classification and distributed tracking. There are several well established methods for performing distributed fusion that are first reviewed. The chapter on distributed fusion concludes with a multiple unmanned vehicle collaborative test involving an unmanned aerial vehicle and an unmanned ground vehicle. The third issue this thesis addresses is that of soft sensor only data fusion. Soft-only fusion is a newer field than centralized or distributed hard sensor fusion. Because of the novelty of the field, the chapter on soft only fusion contains less background information and instead focuses on some new results in soft sensor data fusion. Specifically, it discusses a novel fuzzy logic based soft sensor data fusion method. This new method is tested using both simulations and field measurements. The biggest issue addressed in this thesis is that of combined hard and soft fusion. Fusion of hard and soft data is the newest area for research in the data fusion community; therefore, some of the largest theoretical contributions in this thesis are in the chapter on combined hard and soft fusion. This chapter presents a novel combined hard and soft data fusion method based on random set theory, which processes random set data using a particle filter. Furthermore, the particle filter is designed to be distributed across multiple robots and portable computers (used by human observers) so that there is no centralized failure point in the system. After laying out a theoretical groundwork for hard and soft sensor data fusion the thesis presents practical applications for hard and soft sensor data fusion in simulation. Through a series of three progressively more difficult simulations, some important hard and soft sensor data fusion capabilities are demonstrated. The first simulation demonstrates fusing data from a single soft sensor and a single hard sensor in order to track a car that could be driving normally or erratically. The second simulation adds the extra complication of classifying the type of target to the simulation. The third simulation uses multiple hard and soft sensors, with a limited field of view, to track a moving target and classify it as a friend, foe, or neutral. The final chapter builds on the work done in previous chapters by performing a field test of the algorithms for hard and soft sensor data fusion. The test utilizes an unmanned aerial vehicle, an unmanned ground vehicle, and a human observer with a laptop. The test is designed to mimic a collaborative human and robot search and rescue problem. This test makes some of the most important practical contributions of the thesis by showing that the algorithms that have been developed for hard and soft sensor data fusion are capable of running in real time on relatively simple hardware.

Engineering Considerations for the Self-Energizing Magnetoplasmadynamic (MPD)-Type Fusion Plasma Thruster

DTIC Science & Technology

1992-02-01

Feasibility studies Of dense plasma focus (DPF) device as a fusion propulsion thruster have been performed. Both conventional and spin-polarized D...uncertainties remain in the validity of scaling laws on capacitor mass at high current beyond 1 MA. Fusion Propulsion, Dense Plasma Focus , Magnetoplasmadynamic Thruster, Advanced Fuel, D-3He Fusion, Spin-Polarized Fusion.

A color fusion method of infrared and low-light-level images based on visual perception

NASA Astrophysics Data System (ADS)

Han, Jing; Yan, Minmin; Zhang, Yi; Bai, Lianfa

2014-11-01

The color fusion images can be obtained through the fusion of infrared and low-light-level images, which will contain both the information of the two. The fusion images can help observers to understand the multichannel images comprehensively. However, simple fusion may lose the target information due to inconspicuous targets in long-distance infrared and low-light-level images; and if targets extraction is adopted blindly, the perception of the scene information will be affected seriously. To solve this problem, a new fusion method based on visual perception is proposed in this paper. The extraction of the visual targets ("what" information) and parallel processing mechanism are applied in traditional color fusion methods. The infrared and low-light-level color fusion images are achieved based on efficient typical targets learning. Experimental results show the effectiveness of the proposed method. The fusion images achieved by our algorithm can not only improve the detection rate of targets, but also get rich natural information of the scenes.

Reanalysis of RNA-Sequencing Data Reveals Several Additional Fusion Genes with Multiple Isoforms

PubMed Central

Kangaspeska, Sara; Hultsch, Susanne; Edgren, Henrik; Nicorici, Daniel; Murumägi, Astrid; Kallioniemi, Olli

2012-01-01

RNA-sequencing and tailored bioinformatic methodologies have paved the way for identification of expressed fusion genes from the chaotic genomes of solid tumors. We have recently successfully exploited RNA-sequencing for the discovery of 24 novel fusion genes in breast cancer. Here, we demonstrate the importance of continuous optimization of the bioinformatic methodology for this purpose, and report the discovery and experimental validation of 13 additional fusion genes from the same samples. Integration of copy number profiling with the RNA-sequencing results revealed that the majority of the gene fusions were promoter-donating events that occurred at copy number transition points or involved high-level DNA-amplifications. Sequencing of genomic fusion break points confirmed that DNA-level rearrangements underlie selected fusion transcripts. Furthermore, a significant portion (>60%) of the fusion genes were alternatively spliced. This illustrates the importance of reanalyzing sequencing data as gene definitions change and bioinformatic methods improve, and highlights the previously unforeseen isoform diversity among fusion transcripts. PMID:23119097

Reanalysis of RNA-sequencing data reveals several additional fusion genes with multiple isoforms.

PubMed

Kangaspeska, Sara; Hultsch, Susanne; Edgren, Henrik; Nicorici, Daniel; Murumägi, Astrid; Kallioniemi, Olli

2012-01-01

RNA-sequencing and tailored bioinformatic methodologies have paved the way for identification of expressed fusion genes from the chaotic genomes of solid tumors. We have recently successfully exploited RNA-sequencing for the discovery of 24 novel fusion genes in breast cancer. Here, we demonstrate the importance of continuous optimization of the bioinformatic methodology for this purpose, and report the discovery and experimental validation of 13 additional fusion genes from the same samples. Integration of copy number profiling with the RNA-sequencing results revealed that the majority of the gene fusions were promoter-donating events that occurred at copy number transition points or involved high-level DNA-amplifications. Sequencing of genomic fusion break points confirmed that DNA-level rearrangements underlie selected fusion transcripts. Furthermore, a significant portion (>60%) of the fusion genes were alternatively spliced. This illustrates the importance of reanalyzing sequencing data as gene definitions change and bioinformatic methods improve, and highlights the previously unforeseen isoform diversity among fusion transcripts.

Feature level fusion of hand and face biometrics

NASA Astrophysics Data System (ADS)

Ross, Arun A.; Govindarajan, Rohin

2005-03-01

Multibiometric systems utilize the evidence presented by multiple biometric sources (e.g., face and fingerprint, multiple fingers of a user, multiple matchers, etc.) in order to determine or verify the identity of an individual. Information from multiple sources can be consolidated in several distinct levels, including the feature extraction level, match score level and decision level. While fusion at the match score and decision levels have been extensively studied in the literature, fusion at the feature level is a relatively understudied problem. In this paper we discuss fusion at the feature level in 3 different scenarios: (i) fusion of PCA and LDA coefficients of face; (ii) fusion of LDA coefficients corresponding to the R,G,B channels of a face image; (iii) fusion of face and hand modalities. Preliminary results are encouraging and help in highlighting the pros and cons of performing fusion at this level. The primary motivation of this work is to demonstrate the viability of such a fusion and to underscore the importance of pursuing further research in this direction.

Infrared and Visual Image Fusion through Fuzzy Measure and Alternating Operators

PubMed Central

Bai, Xiangzhi

2015-01-01

The crucial problem of infrared and visual image fusion is how to effectively extract the image features, including the image regions and details and combine these features into the final fusion result to produce a clear fused image. To obtain an effective fusion result with clear image details, an algorithm for infrared and visual image fusion through the fuzzy measure and alternating operators is proposed in this paper. Firstly, the alternating operators constructed using the opening and closing based toggle operator are analyzed. Secondly, two types of the constructed alternating operators are used to extract the multi-scale features of the original infrared and visual images for fusion. Thirdly, the extracted multi-scale features are combined through the fuzzy measure-based weight strategy to form the final fusion features. Finally, the final fusion features are incorporated with the original infrared and visual images using the contrast enlargement strategy. All the experimental results indicate that the proposed algorithm is effective for infrared and visual image fusion. PMID:26184229

Nuclear fusion during yeast mating occurs by a three-step pathway.

PubMed

Melloy, Patricia; Shen, Shu; White, Erin; McIntosh, J Richard; Rose, Mark D

2007-11-19

In Saccharomyces cerevisiae, mating culminates in nuclear fusion to produce a diploid zygote. Two models for nuclear fusion have been proposed: a one-step model in which the outer and inner nuclear membranes and the spindle pole bodies (SPBs) fuse simultaneously and a three-step model in which the three events occur separately. To differentiate between these models, we used electron tomography and time-lapse light microscopy of early stage wild-type zygotes. We observe two distinct SPBs in approximately 80% of zygotes that contain fused nuclei, whereas we only see fused or partially fused SPBs in zygotes in which the site of nuclear envelope (NE) fusion is already dilated. This demonstrates that SPB fusion occurs after NE fusion. Time-lapse microscopy of zygotes containing fluorescent protein tags that localize to either the NE lumen or the nucleoplasm demonstrates that outer membrane fusion precedes inner membrane fusion. We conclude that nuclear fusion occurs by a three-step pathway.

Proposal for a novel type of small scale aneutronic fusion reactor

NASA Astrophysics Data System (ADS)

Gruenwald, J.

2017-02-01

The aim of this work is to propose a novel scheme for a small scale aneutronic fusion reactor. This new reactor type makes use of the advantages of combining laser driven plasma acceleration and electrostatic confinement fusion. An intense laser beam is used to create a lithium-proton plasma with high density, which is then collimated and focused into the centre of the fusion reaction chamber. The basic concept presented here is based on the 7Li-proton fusion reaction. However, the physical and technological fundamentals may generally as well be applied to 11B-proton fusion. The former fusion reaction path offers higher energy yields while the latter has larger fusion cross sections. Within this paper a technological realisation of such a fusion device, which allows a steady state operation with highly energetic, well collimated ion beam, is presented. It will be demonstrated that the energetic break even can be reached with this device by using a combination of already existing technologies.

Infrared and Visual Image Fusion through Fuzzy Measure and Alternating Operators.

PubMed

Bai, Xiangzhi

2015-07-15

The crucial problem of infrared and visual image fusion is how to effectively extract the image features, including the image regions and details and combine these features into the final fusion result to produce a clear fused image. To obtain an effective fusion result with clear image details, an algorithm for infrared and visual image fusion through the fuzzy measure and alternating operators is proposed in this paper. Firstly, the alternating operators constructed using the opening and closing based toggle operator are analyzed. Secondly, two types of the constructed alternating operators are used to extract the multi-scale features of the original infrared and visual images for fusion. Thirdly, the extracted multi-scale features are combined through the fuzzy measure-based weight strategy to form the final fusion features. Finally, the final fusion features are incorporated with the original infrared and visual images using the contrast enlargement strategy. All the experimental results indicate that the proposed algorithm is effective for infrared and visual image fusion.

Vibrio effector protein VopQ inhibits fusion of V-ATPase–containing membranes

PubMed Central

Sreelatha, Anju; Bennett, Terry L.; Carpinone, Emily M.; O’Brien, Kevin M.; Jordan, Kamyron D.; Burdette, Dara L.; Orth, Kim; Starai, Vincent J.

2015-01-01

Vesicle fusion governs many important biological processes, and imbalances in the regulation of membrane fusion can lead to a variety of diseases such as diabetes and neurological disorders. Here we show that the Vibrio parahaemolyticus effector protein VopQ is a potent inhibitor of membrane fusion based on an in vitro yeast vacuole fusion model. Previously, we demonstrated that VopQ binds to the Vo domain of the conserved V-type H+-ATPase (V-ATPase) found on acidic compartments such as the yeast vacuole. VopQ forms a nonspecific, voltage-gated membrane channel of 18 Å resulting in neutralization of these compartments. We now present data showing that VopQ inhibits yeast vacuole fusion. Furthermore, we identified a unique mutation in VopQ that delineates its two functions, deacidification and inhibition of membrane fusion. The use of VopQ as a membrane fusion inhibitor in this manner now provides convincing evidence that vacuole fusion occurs independently of luminal acidification in vitro. PMID:25453092

Vibrio effector protein VopQ inhibits fusion of V-ATPase-containing membranes.

PubMed

Sreelatha, Anju; Bennett, Terry L; Carpinone, Emily M; O'Brien, Kevin M; Jordan, Kamyron D; Burdette, Dara L; Orth, Kim; Starai, Vincent J

2015-01-06

Vesicle fusion governs many important biological processes, and imbalances in the regulation of membrane fusion can lead to a variety of diseases such as diabetes and neurological disorders. Here we show that the Vibrio parahaemolyticus effector protein VopQ is a potent inhibitor of membrane fusion based on an in vitro yeast vacuole fusion model. Previously, we demonstrated that VopQ binds to the V(o) domain of the conserved V-type H(+)-ATPase (V-ATPase) found on acidic compartments such as the yeast vacuole. VopQ forms a nonspecific, voltage-gated membrane channel of 18 Å resulting in neutralization of these compartments. We now present data showing that VopQ inhibits yeast vacuole fusion. Furthermore, we identified a unique mutation in VopQ that delineates its two functions, deacidification and inhibition of membrane fusion. The use of VopQ as a membrane fusion inhibitor in this manner now provides convincing evidence that vacuole fusion occurs independently of luminal acidification in vitro.

Multi-focus image fusion based on window empirical mode decomposition

NASA Astrophysics Data System (ADS)

Qin, Xinqiang; Zheng, Jiaoyue; Hu, Gang; Wang, Jiao

2017-09-01

In order to improve multi-focus image fusion quality, a novel fusion algorithm based on window empirical mode decomposition (WEMD) is proposed. This WEMD is an improved form of bidimensional empirical mode decomposition (BEMD), due to its decomposition process using the adding window principle, effectively resolving the signal concealment problem. We used WEMD for multi-focus image fusion, and formulated different fusion rules for bidimensional intrinsic mode function (BIMF) components and the residue component. For fusion of the BIMF components, the concept of the Sum-modified-Laplacian was used and a scheme based on the visual feature contrast adopted; when choosing the residue coefficients, a pixel value based on the local visibility was selected. We carried out four groups of multi-focus image fusion experiments and compared objective evaluation criteria with other three fusion methods. The experimental results show that the proposed fusion approach is effective and performs better at fusing multi-focus images than some traditional methods.

Face-iris multimodal biometric scheme based on feature level fusion

NASA Astrophysics Data System (ADS)

Huo, Guang; Liu, Yuanning; Zhu, Xiaodong; Dong, Hongxing; He, Fei

2015-11-01

Unlike score level fusion, feature level fusion demands all the features extracted from unimodal traits with high distinguishability, as well as homogeneity and compatibility, which is difficult to achieve. Therefore, most multimodal biometric research focuses on score level fusion, whereas few investigate feature level fusion. We propose a face-iris recognition method based on feature level fusion. We build a special two-dimensional-Gabor filter bank to extract local texture features from face and iris images, and then transform them by histogram statistics into an energy-orientation variance histogram feature with lower dimensions and higher distinguishability. Finally, through a fusion-recognition strategy based on principal components analysis and support vector machine (FRSPS), feature level fusion and one-to-n identification are accomplished. The experimental results demonstrate that this method can not only effectively extract face and iris features but also provide higher recognition accuracy. Compared with some state-of-the-art fusion methods, the proposed method has a significant performance advantage.

La Crosse virus (LACV) Gc fusion peptide mutants have impaired growth and fusion phenotypes, but remain neurotoxic

DOE Office of Scientific and Technical Information (OSTI.GOV)

Soldan, Samantha S., E-mail: sssoldan@mail.med.upenn.ed; Hollidge, Bradley S.; Department of Neuroscience Graduate Group, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-4283

La Crosse virus is a leading cause of pediatric encephalitis in the Midwestern United States and an emerging pathogen in the American South. The LACV glycoprotein Gc plays a critical role in entry as the virus attachment protein. A 22 amino acid hydrophobic region within Gc (1066-1087) was recently identified as the LACV fusion peptide. To further define the role of Gc (1066-1087) in virus entry, fusion, and neuropathogenesis, a panel of recombinant LACV (rLACV) fusion peptide mutant viruses was generated. Replication of mutant rLACVs was significantly reduced. In addition, the fusion peptide mutants demonstrated decreased fusion phenotypes relative tomore » LACV-WT. Interestingly, these viruses maintained their ability to cause neuronal loss in culture, suggesting that the fusion peptide of LACV Gc is a determinant of properties associated with neuroinvasion (growth to high titer in muscle cells and a robust fusion phenotype), but not necessarily of neurovirulence.« less

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

PubMed

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

2013-10-01

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

Visualization and Sequencing of Membrane Remodeling Leading to Influenza Virus Fusion

PubMed Central

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

2016-01-01

ABSTRACT Protein-mediated membrane fusion is an essential step in many fundamental biological events, including enveloped virus infection. The nature of protein and membrane intermediates and the sequence of membrane remodeling during these essential processes remain poorly understood. Here we used cryo-electron tomography (cryo-ET) to image the interplay between influenza virus and vesicles with a range of lipid compositions. By following the population kinetics of membrane fusion intermediates imaged by cryo-ET, we found that membrane remodeling commenced with the hemagglutinin fusion protein spikes grappling onto the target membrane, followed by localized target membrane dimpling as local clusters of hemagglutinin started to undergo conformational refolding. The local dimples then transitioned to extended, tightly apposed contact zones where the two proximal membrane leaflets were in most cases indistinguishable from each other, suggesting significant dehydration and possible intermingling of the lipid head groups. Increasing the content of fusion-enhancing cholesterol or bis-monoacylglycerophosphate in the target membrane led to an increase in extended contact zone formation. Interestingly, hemifused intermediates were found to be extremely rare in the influenza virus fusion system studied here, most likely reflecting the instability of this state and its rapid conversion to postfusion complexes, which increased in population over time. By tracking the populations of fusion complexes over time, the architecture and sequence of membrane reorganization leading to efficient enveloped virus fusion were thus resolved. IMPORTANCE Enveloped viruses employ specialized surface proteins to mediate fusion of cellular and viral membranes that results in the formation of pores through which the viral genetic material is delivered to the cell. For influenza virus, the trimeric hemagglutinin (HA) glycoprotein spike mediates host cell attachment and membrane fusion. While structures of a subset of conformations and parts of the fusion machinery have been characterized, the nature and sequence of membrane deformations during fusion have largely eluded characterization. Building upon studies that focused on early stages of HA-mediated membrane remodeling, here cryo-electron tomography (cryo-ET) was used to image the three-dimensional organization of intact influenza virions at different stages of fusion with liposomes, leading all the way to completion of the fusion reaction. By monitoring the evolution of fusion intermediate populations over the course of acid-induced fusion, we identified the progression of membrane reorganization that leads to efficient fusion by an enveloped virus. PMID:27226364

Progress in understanding the neuronal SNARE function and its regulation.

PubMed

Yoon, T-Y; Shin, Y-K

2009-02-01

Vesicle budding and fusion underlies many essential biochemical deliveries in eukaryotic cells, and its core fusion machinery is thought to be built on one protein family named soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE). Recent technical advances based on site-directed fluorescence labelling and nano-scale detection down to the single-molecule level rapidly unveiled the protein and the lipid intermediates along the fusion pathway as well as the molecular actions of fusion effectors. Here we summarize these new exciting findings in context with a new mechanistic model that reconciles two existing fusion models: the proteinaceous pore model and the hemifusion model. Further, we attempt to locate the points of action for the fusion effectors along the fusion pathway and to delineate the energetic interplay between the SNARE complexes and the fusion effectors.

Membrane Fusion Involved in Neurotransmission: Glimpse from Electron Microscope and Molecular Simulation

PubMed Central

Yang, Zhiwei; Gou, Lu; Chen, Shuyu; Li, Na; Zhang, Shengli; Zhang, Lei

2017-01-01

Membrane fusion is one of the most fundamental physiological processes in eukaryotes for triggering the fusion of lipid and content, as well as the neurotransmission. However, the architecture features of neurotransmitter release machinery and interdependent mechanism of synaptic membrane fusion have not been extensively studied. This review article expounds the neuronal membrane fusion processes, discusses the fundamental steps in all fusion reactions (membrane aggregation, membrane association, lipid rearrangement and lipid and content mixing) and the probable mechanism coupling to the delivery of neurotransmitters. Subsequently, this work summarizes the research on the fusion process in synaptic transmission, using electron microscopy (EM) and molecular simulation approaches. Finally, we propose the future outlook for more exciting applications of membrane fusion involved in synaptic transmission, with the aid of stochastic optical reconstruction microscopy (STORM), cryo-EM (cryo-EM), and molecular simulations. PMID:28638320

Pedicle screw fixation for isthmic spondylolisthesis: does posterior lumbar interbody fusion improve outcome over posterolateral fusion?

PubMed

La Rosa, Giovanni; Conti, Alfredo; Cacciola, Fabio; Cardali, Salvatore; La Torre, Domenico; Gambadauro, Nicola Maria; Tomasello, Francesco

2003-09-01

Posterolateral fusion involving instrumentation-assisted segmental fixation represents a valid procedure in the treatment of lumbar instability. In cases of anterior column failure, such as in isthmic spondylolisthesis, supplemental posterior lumbar interbody fusion (PLIF) may improve the fusion rate and endurance of the construct. Posterior lumbar interbody fusion is, however, a more demanding procedure and increases costs and risks of the intervention. The advantages of this technique must, therefore, be weighed against those of a simple posterior lumbar fusion. Thirty-five consecutive patients underwent pedicle screw fixation for isthmic spondylolisthesis. In 18 patients posterior lumbar fusion was performed, and in 17 patients PLIF was added. Clinical, economic, functional, and radiographic data were assessed to determine differences in clinical and functional results and biomechanical properties. At 2-year follow-up examination, the correction of subluxation, disc height, and foraminal area were maintained in the group in which a PLIF procedure was performed, but not in the posterolateral fusion-only group (p < 0.05). Nevertheless, no statistical intergroup differences were demonstrated in terms of neurological improvement (p = 1), economic (p = 0.43), or functional (p = 0.95) outcome, nor in terms of fusion rate (p = 0.49). The authors' findings support the view that an interbody fusion confers superior mechanical strength to the spinal construct; when posterolateral fusion is the sole intervention, progressive loss of the extreme correction can be expected. Such mechanical insufficiency, however, did not influence clinical outcome.

LegC3, an Effector Protein from Legionella pneumophila, Inhibits Homotypic Yeast Vacuole Fusion In Vivo and In Vitro

PubMed Central

Bennett, Terry L.; Kraft, Shannon M.; Reaves, Barbara J.; Mima, Joji; O’Brien, Kevin M.; Starai, Vincent J.

2013-01-01

During infection, the intracellular pathogenic bacterium Legionella pneumophila causes an extensive remodeling of host membrane trafficking pathways, both in the construction of a replication-competent vacuole comprised of ER-derived vesicles and plasma membrane components, and in the inhibition of normal phagosome:endosome/lysosome fusion pathways. Here, we identify the LegC3 secreted effector protein from L. pneumophila as able to inhibit a SNARE- and Rab GTPase-dependent membrane fusion pathway in vitro, the homotypic fusion of yeast vacuoles (lysosomes). This vacuole fusion inhibition appeared to be specific, as similar secreted coiled-coiled domain containing proteins from L. pneumophila, LegC7/YlfA and LegC2/YlfB, did not inhibit vacuole fusion. The LegC3-mediated fusion inhibition was reversible by a yeast cytosolic extract, as well as by a purified soluble SNARE, Vam7p. LegC3 blocked the formation of trans-SNARE complexes during vacuole fusion, although we did not detect a direct interaction of LegC3 with the vacuolar SNARE protein complexes required for fusion. Additionally, LegC3 was incapable of inhibiting a defined synthetic model of vacuolar SNARE-driven membrane fusion, further suggesting that LegC3 does not directly inhibit the activity of vacuolar SNAREs, HOPS complex, or Sec17p/18p during membrane fusion. LegC3 is likely utilized by Legionella to modulate eukaryotic membrane fusion events during pathogenesis. PMID:23437241

The exocytotic fusion pore modeled as a lipidic pore.

PubMed Central

Nanavati, C; Markin, V S; Oberhauser, A F; Fernandez, J M

1992-01-01

Freeze-fracture electron micrographs from degranulating cells show that the lumen of the secretory granule is connected to the extracellular compartment via large (20 to 150 nm diameter) aqueous pores. These exocytotic fusion pores appear to be made up of a highly curved bilayer that spans the plasma and granule membranes. Conductance measurements, using the patch-clamp technique, have been used to study the fusion pore from the instant it conducts ions. These measurements reveal the presence of early fusion pores that are much smaller than those observed in electron micrographs. Early fusion pores open abruptly, fluctuate, and then either expand irreversibly or close. The molecular structure of these early fusion pores is unknown. In the simplest extremes, these early fusion pores could be either ion channel like protein pores or lipidic pores. Here, we explored the latter possibility, namely that of the early exocytotic fusion pore modeled as a lipid-lined pore whose free energy was composed of curvature elastic energy and work done by tension. Like early exocytotic fusion pores, we found that these lipidic pores could open abruptly, fluctuate, and expand irreversibly. Closure of these lipidic pores could be caused by slight changes in lipid composition. Conductance distributions for stable lipidic pores matched those of exocytotic fusion pores. These findings demonstrate that lipidic pores can exhibit the properties of exocytotic fusion pores, thus providing an alternate framework with which to understand and interpret exocytotic fusion pore data. PMID:1420930

[Detection of ALK, ROS1 and RET fusion genes in non-small cell lung cancer patients and its clinicopathologic correlation].

PubMed

Zhong, Shan; Zhang, Haiping; Bai, Dongyu; Gao, Dehong; Zheng, Jie; Ding, Yi

2015-09-01

To study the prevalence of ALK, ROS1 and RET fusion genes in non-small cell lung cancer (NSCLC), and its correlation with clinicopathologic features. Formalin-fixed and paraffin-embedded tissue sections from samples of 302 patients with NSCLC were screened for ALK, ROS1, RET fusions by real-time polymerase chain reaction (PCR). All of the cases were validated by Sanger DNA sequencing. The relationship between ALK, ROS1, RET fusion genes and clinicopathologic features were analyzed. In the cohort of 302 NSCLC samples, 3.97% (12/302) were found to contain ALK fusion genes, including 3 cases with E13; A20 gene fusion, 3 cases with E6; A20 gene fusion and 3 cases with E20; A20 gene fusion. There was no statistically significant difference in patient's gender, age, smoking history and histologic type. Moreover, in the 302 NSCLC samples studied, 3.97% (12/302) were found to contain ROS1 fusion genes, with CD74-ROS1 fusion identified in 9 cases. There was no statistically significant difference in patients' gender, age, smoking history and histologic type. One non-smoking elderly female patient with pulmonary adenocarcinoma had RET gene fusion. None of the cases studied had concurrent ALK, ROS1 and RET mutations. The ALK, ROS1 and RET fusion gene mutation rates in NSCLC are low, they represent some specific molecular subtypes of NSCLC. Genetic testing has significant meaning to guide clinical targeted therapy.

Arthroscopic partial wrist fusion.

PubMed

Ho, Pak-Cheong

2008-12-01

The wide intraarticular exposure of the wrist joint under arthroscopic view provides an excellent ground for various forms of partial wrist fusion. Combining with percutaneous fixation technique, arthroscopic partial wrist fusion can potentially generate the best possible functional outcome by preserving the maximal motion pertained with each type of partial wrist fusion because the effect of extraarticular adhesion associated with open surgery can be minimized. From November 1997 to May 2008, the author had performed 12 cases of arthroscopic partial wrist fusion, including scaphotrapeziotrapezoid fusion in 3, scaphoidectomy and 4-corner fusion in 4, radioscapholunate fusion in 3, radiolunate fusion in 1, and lunotriquetral fusion in 1 case. Through the radiocarpal or midcarpal joint, the corresponding articular surfaces were denuded of cartilage using arthroscopic burr and curette. Carpal bones involved in the fusion process were then transfixed with K wires percutaneously after alignment corrected and confirmed under fluoroscopic control. Autogenous cancellous bone graft or bone substitute were inserted and impacted to the fusion site through cannula under direct arthroscopic view. Final fixation could be by multiple K wires or cannulated screw system. Early mobilization was encouraged. Surgical complications were minor, including pin tract infection, skin burn, and delay union in 1 case. Uneventful radiologic union was obtained in 9 cases, stable fibrous union in 2, and nonunion in 1. The average follow-up period was 70 months. Symptom was resolved or improved, and functional motion was gained in all cases. All surgical scars were almost invisible, and aesthetic outcome was excellent.

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

PubMed Central

Koehler, Jeffrey W.; Smith, Jeffrey M.; Ripoll, Daniel R.; Spik, Kristin W.; Taylor, Shannon L.; Badger, Catherine V.; Grant, Rebecca J.; Ogg, Monica M.; Wallqvist, Anders; Guttieri, Mary C.; Garry, Robert F.; Schmaljohn, Connie S.

2013-01-01

For enveloped viruses, fusion of the viral envelope with a cellular membrane is critical for a productive infection to occur. This fusion process is mediated by at least three classes of fusion proteins (Class I, II, and III) based on the protein sequence and structure. For Rift Valley fever virus (RVFV), the glycoprotein Gc (Class II fusion protein) mediates this fusion event following entry into the endocytic pathway, allowing the viral genome access to the cell cytoplasm. Here, we show that peptides analogous to the RVFV Gc stem region inhibited RVFV infectivity in cell culture by inhibiting the fusion process. Further, we show that infectivity can be inhibited for diverse, unrelated RNA viruses that have Class I (Ebola virus), Class II (Andes virus), or Class III (vesicular stomatitis virus) fusion proteins using this single peptide. Our findings are consistent with an inhibition mechanism similar to that proposed for stem peptide fusion inhibitors of dengue virus in which the RVFV inhibitory peptide first binds to both the virion and cell membranes, allowing it to traffic with the virus into the endocytic pathway. Upon acidification and rearrangement of Gc, the peptide is then able to specifically bind to Gc and prevent fusion of the viral and endocytic membranes, thus inhibiting viral infection. These results could provide novel insights into conserved features among the three classes of viral fusion proteins and offer direction for the future development of broadly active fusion inhibitors. PMID:24069485

Comparison of posterolateral lumbar fusion rates of Grafton Putty and OP-1 Putty in an athymic rat model.

PubMed

Bomback, David A; Grauer, Jonathan N; Lugo, Roberto; Troiano, Nancy; Patel, Tushar Ch; Friedlaender, Gary E

2004-08-01

Posterolateral lumbar spine fusions in athymic rats. To compare spine fusion rates of two different osteoinductive products. Many osteoinductive bone graft alternatives are available. Grafton (a demineralized bone matrix [DBM]) and Osteogenic Protein-1 (OP-1, an individual recombinant bone morphogenetic protein) are two such alternatives. The relative efficacy of products from these two classes has not been previously studied. The athymic rat spine fusion model has been validated and demonstrated useful to minimize inflammatory responses to xenogeneic or differentially expressed proteins such as those presented by DBMs of human etiology. Single-level intertransverse process fusions were performed in 60 athymic nude rats with 2 cc/kg of Grafton or OP-1 Putty. Half of each study group was killed at 3 weeks and half at 6 weeks. Fusion masses were assessed by radiography, manual palpation, and histology. At 3 weeks, manual palpation revealed a 13% fusion rate with Grafton and a 100% fusion rate with OP-1 (P = 0.0001). At 6 weeks, manual palpation revealed a 39% fusion rate of with Grafton and a 100% fusion rate with OP-1 (P = 0.0007). Similar fusion rates were found by histology at 3 and 6 weeks. Of note, one or two adjacent levels were fused in all of the OP-1 animals and none of the Grafton animals. Significant differences between the ability of Grafton and OP-1 to induce bone formation in an athymic rat posterolateral lumbar spine fusion model were found.

A method based on IHS cylindrical transform model for quality assessment of image fusion

NASA Astrophysics Data System (ADS)

Zhu, Xiaokun; Jia, Yonghong

2005-10-01

Image fusion technique has been widely applied to remote sensing image analysis and processing, and methods for quality assessment of image fusion in remote sensing have also become the research issues at home and abroad. Traditional assessment methods combine calculation of quantitative indexes and visual interpretation to compare fused images quantificationally and qualitatively. However, in the existing assessment methods, there are two defects: on one hand, most imdexes lack the theoretic support to compare different fusion methods. On the hand, there is not a uniform preference for most of the quantitative assessment indexes when they are applied to estimate the fusion effects. That is, the spatial resolution and spectral feature could not be analyzed synchronously by these indexes and there is not a general method to unify the spatial and spectral feature assessment. So in this paper, on the basis of the approximate general model of four traditional fusion methods, including Intensity Hue Saturation(IHS) triangle transform fusion, High Pass Filter(HPF) fusion, Principal Component Analysis(PCA) fusion, Wavelet Transform(WT) fusion, a correlation coefficient assessment method based on IHS cylindrical transform is proposed. By experiments, this method can not only get the evaluation results of spatial and spectral features on the basis of uniform preference, but also can acquire the comparison between fusion image sources and fused images, and acquire differences among fusion methods. Compared with the traditional assessment methods, the new methods is more intuitionistic, and in accord with subjective estimation.

C-terminal tyrosine residues modulate the fusion activity of the Hendra virus fusion protein

PubMed Central

Popa, Andreea; Pager, Cara Teresia; Dutch, Rebecca Ellis

2011-01-01

The paramyxovirus family includes important human pathogens such as measles, mumps, respiratory syncytial virus and the recently emerged, highly pathogenic Hendra and Nipah viruses. The viral fusion (F) protein plays critical roles in infection, promoting both the viral-cell membrane fusion events needed for viral entry as well as cell-cell fusion events leading to syncytia formation. We describe the surprising finding that addition of the short epitope HA tag to the cytoplasmic tail (CT) of the Hendra virus F protein leads to a significant increase in cell-cell membrane fusion. This increase was not due to alterations in surface expression, cleavage state, or association with lipid microdomains. Addition of a Myc tag of similar length did not alter Hendra F fusion activity, indicating that the observed stimulation was not solely a result of lengthening the CT. Three tyrosine residues within the HA tag were critical for the increase in fusion, suggesting C-terminal tyrosines may modulate Hendra fusion activity. The effects of HA tag addition varied with other fusion proteins, as parainfluenza virus 5 F-HA showed decreased surface expression and no stimulation in fusion. These results indicate that additions to the C-terminal end of the F protein CT can modulate protein function in a sequence specific manner, reinforcing the need for careful analysis of epitope tagged glycoproteins. In addition, our results implicate C-terminal tyrosine residues in modulation of the membrane fusion reaction promoted by these viral glycoproteins. PMID:21175223

Prevalence and clinicopathological characteristics of ALK fusion subtypes in lung adenocarcinomas from Chinese populations.

PubMed

Zheng, Difan; Wang, Rui; Zhang, Yang; Pan, Yunjian; Cheng, Xinghua; Cheng, Chao; Zheng, Shanbo; Li, Hang; Gong, Ranxia; Li, Yuan; Shen, Xuxia; Sun, Yihua; Chen, Haiquan

2016-04-01

We performed this retrospective study to have a comprehensive investigation of the clinicopathological characteristics of ALK fusion-positive lung adenocarcinoma in Chinese populations. We screened 1407 patients with primary lung adenocarcinoma from October 2007 to May 2013. Quantitative real-time PCR (qRT-PCR), reverse transcriptase PCR (RT-PCR), and fluorescence in situ hybridization were performed to detect ALK fusion genes, with validation of positive results using immunohistochemistry. Clinicopathological characteristics were collected to assess prognosis in ALK fusion-positive patients. Of 1407 patients with lung adenocarcinoma, there were 74 (5.3 %) ALK fusion-positive patients. Patients harboring ALK fusion were significantly younger (56.0 years vs. 59.8 years p = 0.002) and were more likely to have advanced stages (stage III or stage IV) (OR 1.761; 95 % CI 1.10-2.82, p = 0.017). Lepidic predominant adenocarcinoma was rarely found in ALK fusion patients (2.7 vs. 13.5 % p = 0.025), while IMA (invasive mucinous adenocarcinoma) predominant adenocarcinoma was more frequently found (21.6 vs. 5.0 % p < 0.001). ALK fusion was neither a risk factor nor protective factor in relapse-free survival and overall survival. Male, current smoker, and EML4-ALK variant 3 indicated poor prognosis among ALK fusion-positive lung adenocarcinomas. ALK fusion was detected in 5.3 % (74/1407) of the Chinese patients with lung adenocarcinoma. ALK fusion defines a molecular subset of lung adenocarcinoma with unique clinicopathological characteristics. Different ALK fusion variants determine distinct prognoses.

pH-Sensitive Liposomes: Acid-Induced Liposome Fusion

NASA Astrophysics Data System (ADS)

Connor, Jerome; Yatvin, Milton B.; Huang, Leaf

1984-03-01

Sonicated unilamellar liposomes containing phosphatidylethanolamine and palmitoylhomocysteine fuse rapidly when the medium pH is lowered from 7 to 5. Liposome fusion was demonstrated by (i) mixing of the liposomal lipids as shown by resonance energy transfer, (ii) gel filtration, and (iii) electron microscopy. The pH-sensitive fusion of liposomes was observed only when palmitoylhomocysteine (>= 20 mol%) was present in the liposomes. The presence of phosphatidyl-ethanolamine in the liposomes greatly enhanced fusion whereas the presence of phosphatidylcholine inhibited fusion. During fusion of liposomes containing phosphatidylethanolamine and palmitoylhomocysteine (8:2, mol/mol), almost all of the encapsulated calcein was released. Inclusion of cholesterol (40 mol%) in the liposomes substantially decreased leakage without impairing fusion.

Review of the magnetic fusion program by the 1986 ERAB Fusion Panel

NASA Astrophysics Data System (ADS)

Davidson, Ronald C.

1987-09-01

The 1986 ERAB Fusion Panel finds that fusion energy continues to be an attractive energy source with great potential for the future, and that the magnetic fusion program continues to make substantial technical progress. In addition, fusion research advances plasma physics, a sophisticated and useful branch of applied science, as well as technologies important to industry and defense. These factors fully justify the substantial expenditures by the Department of Energy in fusion research and development (R&D). The Panel endorses the overall program direction, strategy, and plans, and recognizes the importance and timeliness of proceeding with a burning plasma experiment, such as the proposed Compact Ignition Tokamak (CIT) experiment.

Possible application of electromagnetic guns to impact fusion

NASA Astrophysics Data System (ADS)

Kostoff, R. N.; Peaslee, A. T., Jr.; Ribe, F. L.

1982-01-01

The possible application of electromagnetic guns to impact fusion for the generation of electric power is discussed, and advantages of impact fusion over the more conventional inertial confinement fusion concepts are examined. It is shown that impact fusion can achieve the necessary high yields, of the order of a few gigajoules, which are difficult to achieve with lasers except at unrealistically high target gains. The rail gun accelerator is well adapted to the delivery of some 10-100 megajoules of energy to the fusion target, and the electrical technology involved is relatively simple: inductive storage or rotating machinery and capacitors. It is concluded that the rail gun has the potential of developing into an impact fusion macroparticle accelerator.

Introduction to Nuclear Fusion Power and the Design of Fusion Reactors. An Issue-Oriented Module.

ERIC Educational Resources Information Center

Fillo, J. A.

This three-part module focuses on the principles of nuclear fusion and on the likely nature and components of a controlled-fusion power reactor. The physical conditions for a net energy release from fusion and two approaches (magnetic and inertial confinement) which are being developed to achieve this goal are described. Safety issues associated…

Spin distribution of evaporation residues formed in complete and incomplete fusion in 16O+154Sm system

NASA Astrophysics Data System (ADS)

Singh, D.; Linda, Sneha B.; Giri, Pankaj K.; Mahato, Amritraj; Tripathi, R.; Kumar, Harish; Afzal Ansari, M.; Sathik, N. P. M.; Ali, Rahbar; Kumar, Rakesh; Muralithar, S.; Singh, R. P.

2017-11-01

Spin distributions for several evaporation residues populated in the 16O+154Sm system have been measured at projectile energy ≈ 6.2 MeV/A by using the charged particle-γ-coincidence technique. The measured spin distributions of the evaporation residues populated through incomplete fusion associated with 'fast' α and 2α-emission channels are found to be entirely different from fusion-evaporation channels. It is observed that the mean input angular momentum for the evaporation residues formed in incomplete fusion channel is relatively higher than that observed for evaporation residues in complete fusion channels. The feeding intensity profile of evaporation residues populated through complete fusion and incomplete fusion have also been studied. The incomplete fusion channels are found to have narrow range feeding only for high spin states, while complete fusion channels are strongly fed over a broad spin range and widely populated. Comparison of present results with earlier data suggests that the mean input angular momentum values are relatively smaller for spherical target than that of deformed target using the same projectile and incident energy highlighting the role of target deformation in incomplete fusion dynamics.

Applying design principles to fusion reactor configurations for propulsion in space

NASA Technical Reports Server (NTRS)

Carpenter, Scott A.; Deveny, Marc E.; Schulze, Norman R.

1993-01-01

The application of fusion power to space propulsion requires rethinking the engineering-design solution to controlled-fusion energy. Whereas the unit cost of electricity (COE) drives the engineering-design solution for utility-based fusion reactor configurations; initial mass to low earth orbit (IMLEO), specific jet power (kW(thrust)/kg(engine)), and reusability drive the engineering-design solution for successful application of fusion power to space propulsion. We applied three design principles (DP's) to adapt and optimize three candidate-terrestrial-fusion-reactor configurations for propulsion in space. The three design principles are: provide maximum direct access to space for waste radiation, operate components as passive radiators to minimize cooling-system mass, and optimize the plasma fuel, fuel mix, and temperature for best specific jet power. The three candidate terrestrial fusion reactor configurations are: the thermal barrier tandem mirror (TBTM), field reversed mirror (FRM), and levitated dipole field (LDF). The resulting three candidate space fusion propulsion systems have their IMLEO minimized and their specific jet power and reusability maximized. We performed a preliminary rating of these configurations and concluded that the leading engineering-design solution to space fusion propulsion is a modified TBTM that we call the Mirror Fusion Propulsion System (MFPS).

Membrane fusion activity of vesicular stomatitis virus glycoprotein G is induced by low pH but not by heat or denaturant.

PubMed

Yao, Yi; Ghosh, Kakoli; Epand, Raquel F; Epand, Richard M; Ghosh, Hara P

2003-06-05

The fusogenic envelope glycoprotein G of the rhabdovirus vesicular stomatitis virus (VSV) induces membrane fusion at acidic pH. At acidic pH the G protein undergoes a major structural reorganization leading to the fusogenic conformation. However, unlike other viral fusion proteins, the low-pH-induced conformational change of VSV G is completely reversible. As well, the presence of an alpha-helical coiled-coil motif required for fusion by a number of viral and cellular fusion proteins was not predicted in VSV G protein by using a number of algorithms. Results of pH dependence of the thermal stability of G protein as determined by intrinsic Trp fluorescence and circular dichroism (CD) spectroscopy show that the G protein is equally stable at neutral or acidic pH. Destabilization of G structure at neutral pH with either heat or urea did not induce membrane fusion or conformational change(s) leading to membrane fusion. Taken together, these data suggest that the mechanism of VSV G-induced fusion is distinct from the fusion mechanism of fusion proteins that involve a coiled-coil motif.

Membrane fusion and exocytosis.

PubMed

Jahn, R; Südhof, T C

1999-01-01

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

Comprehensive characterization of RSPO fusions in colorectal traditional serrated adenomas.

PubMed

Sekine, Shigeki; Ogawa, Reiko; Hashimoto, Taiki; Motohiro, Kojima; Yoshida, Hiroshi; Taniguchi, Hirokazu; Saito, Yutaka; Yasuhiro, Ohno; Ochiai, Atsushi; Hiraoka, Nobuyoshi

2017-10-01

Traditional serrated adenoma (TSA) is a rare but distinct type of colorectal polyp. Our previous study showed that PTPRK-RSPO3 fusions are frequent and characteristic genetic alterations in TSAs. This study aimed to characterize comprehensively the prevalence and variability of RSPO fusions in colorectal TSAs. We examined RSPO expression and explored novel RSPO fusions in 129 TSAs, including 66 lesions analysed previously for WNT pathway gene mutations. Quantitative polymerase chain reaction (qPCR) analyses identified three and 43 TSAs overexpressing RSPO2 and RSPO3, respectively, whereas the expression of RSPO1 and RSPO4 was marginal or undetectable in all cases. RSPO overexpression was always mutually exclusive with other WNT pathway gene mutations. Known PTPRK-RSPO3 fusions were detected in 37 TSAs, all but one of which overexpressed RSPO3. In addition, rapid amplification of cDNA ends revealed three novel RSPO fusion transcripts, an NRIP1-RSPO2 fusion and two PTPRK-RSPO3 fusion isoforms, in six TSAs. Overall, 43 TSAs had RSPO fusions (33%), whereas four TSAs (3%) overexpressed RSPO in the absence of RSPO fusions. TSAs with RSPO fusions showed several clinicopathological features, including distal localization (P = 0.0063), larger size (P = 0.0055), prominent ectopic crypt foci (P = 8.4 × 10 -4 ), association of a high-grade component (P = 1.1 × 10 -4 ), and the presence of KRAS mutations (P = 4.5 × 10 -5 ). The present study identified RSPO fusion transcripts, including three novel transcripts, in one-third of colorectal TSAs and showed that PTPRK-RSPO3 fusions were the predominant cause of RSPO overexpression in colorectal TSA. © 2017 John Wiley & Sons Ltd.

RSPO fusion transcripts in colorectal cancer in Japanese population.

PubMed

Shinmura, Kazuya; Kahyo, Tomoaki; Kato, Hisami; Igarashi, Hisaki; Matsuura, Shun; Nakamura, Satoki; Kurachi, Kiyotaka; Nakamura, Toshio; Ogawa, Hiroshi; Funai, Kazuhito; Tanahashi, Masayuki; Niwa, Hiroshi; Sugimura, Haruhiko

2014-08-01

R-spondin (RSPO) gene fusions have recently been discovered in a subset of human colorectal cancer (CRC) in the U.S. population; however, whether the fusion is recurrent in CRC arising in patients from the other demographic areas and whether it is specific for CRC remain uncertain. In this study, we examined 75 primary CRCs and 121 primary lung cancers in the Japanese population for EIF3E-RSPO2 and PTPRK-RSPO3 fusion transcripts using RT-PCR and subsequent sequencing analyses. Although the expression of EIF3E-RSPO2 and PTPRK-RSPO3 was not detected in any of the lung carcinomas, RSPO fusions were detected in three (4%) of the 75 CRCs. Two CRCs contained EIF3E-RSPO2 fusion transcripts, and another CRC contained PTPRK-RSPO3 fusion transcripts. Interestingly, in one of the two EIF3E-RSPO2 fusion-positive CRCs, a novel fusion variant form of EIF3E-RSPO2 was identified: exon 1 of EIF3E was connected to exon 2 of RSPO2 by a 351-bp insertion. A quantitative RT-PCR analysis revealed that RSPO mRNA expression was upregulated in the three CRCs containing RSPO fusion transcripts, while it was downregulated in nearly all of the other CRCs. An immunohistochemical analysis and a mutational analysis revealed that the RSPO fusion-containing CRC had a CDX2 cell lineage, was positive for mismatch repair protein expression, and had the wild-type APC allele. Finally, the forced expression of RSPO fusion proteins were shown to endow colorectal cells with an increased growth ability. These results suggest that the expression of RSPO fusion transcripts is related to a subset of CRCs arising in the Japanese population.

Adaptive fusion of infrared and visible images in dynamic scene

NASA Astrophysics Data System (ADS)

Yang, Guang; Yin, Yafeng; Man, Hong; Desai, Sachi

2011-11-01

Multiple modalities sensor fusion has been widely employed in various surveillance and military applications. A variety of image fusion techniques including PCA, wavelet, curvelet and HSV has been proposed in recent years to improve human visual perception for object detection. One of the main challenges for visible and infrared image fusion is to automatically determine an optimal fusion strategy for different input scenes along with an acceptable computational cost. This paper, we propose a fast and adaptive feature selection based image fusion method to obtain high a contrast image from visible and infrared sensors for targets detection. At first, fuzzy c-means clustering is applied on the infrared image to highlight possible hotspot regions, which will be considered as potential targets' locations. After that, the region surrounding the target area is segmented as the background regions. Then image fusion is locally applied on the selected target and background regions by computing different linear combination of color components from registered visible and infrared images. After obtaining different fused images, histogram distributions are computed on these local fusion images as the fusion feature set. The variance ratio which is based on Linear Discriminative Analysis (LDA) measure is employed to sort the feature set and the most discriminative one is selected for the whole image fusion. As the feature selection is performed over time, the process will dynamically determine the most suitable feature for the image fusion in different scenes. Experiment is conducted on the OSU Color-Thermal database, and TNO Human Factor dataset. The fusion results indicate that our proposed method achieved a competitive performance compared with other fusion algorithms at a relatively low computational cost.

FT-MIR and NIR spectral data fusion: a synergetic strategy for the geographical traceability of Panax notoginseng.

PubMed

Li, Yun; Zhang, Jin-Yu; Wang, Yuan-Zhong

2018-01-01

Three data fusion strategies (low-llevel, mid-llevel, and high-llevel) combined with a multivariate classification algorithm (random forest, RF) were applied to authenticate the geographical origins of Panax notoginseng collected from five regions of Yunnan province in China. In low-level fusion, the original data from two spectra (Fourier transform mid-IR spectrum and near-IR spectrum) were directly concatenated into a new matrix, which then was applied for the classification. Mid-level fusion was the strategy that inputted variables extracted from the spectral data into an RF classification model. The extracted variables were processed by iterate variable selection of the RF model and principal component analysis. The use of high-level fusion combined the decision making of each spectroscopic technique and resulted in an ensemble decision. The results showed that the mid-level and high-level data fusion take advantage of the information synergy from two spectroscopic techniques and had better classification performance than that of independent decision making. High-level data fusion is the most effective strategy since the classification results are better than those of the other fusion strategies: accuracy rates ranged between 93% and 96% for the low-level data fusion, between 95% and 98% for the mid-level data fusion, and between 98% and 100% for the high-level data fusion. In conclusion, the high-level data fusion strategy for Fourier transform mid-IR and near-IR spectra can be used as a reliable tool for correct geographical identification of P. notoginseng. Graphical abstract The analytical steps of Fourier transform mid-IR and near-IR spectral data fusion for the geographical traceability of Panax notoginseng.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Neilson, Hutch

Nuclear fusion — the process that powers the sun — offers an environmentally benign, intrinsically safe energy source with an abundant supply of low-cost fuel. It is the focus of an international research program, including the ITER fusion collaboration, which involves seven parties representing half the world’s population. The realization of fusion power would change the economics and ecology of energy production as profoundly as petroleum exploitation did two centuries ago. The 21st century finds fusion research in a transformed landscape. The worldwide fusion community broadly agrees that the science has advanced to the point where an aggressive action plan,more » aimed at the remaining barriers to practical fusion energy, is warranted. At the same time, and largely because of its scientific advance, the program faces new challenges; above all it is challenged to demonstrate the timeliness of its promised benefits. In response to this changed landscape, the Office of Fusion Energy Sciences (OFES) in the US Department of Energy commissioned a number of community-based studies of the key scientific and technical foci of magnetic fusion research. The Research Needs Workshop (ReNeW) for Magnetic Fusion Energy Sciences is a capstone to these studies. In the context of magnetic fusion energy, ReNeW surveyed the issues identified in previous studies, and used them as a starting point to define and characterize the research activities that the advance of fusion as a practical energy source will require. Thus, ReNeW’s task was to identify (1) the scientific and technological research frontiers of the fusion program, and, especially, (2) a set of activities that will most effectively advance those frontiers. (Note that ReNeW was not charged with developing a strategic plan or timeline for the implementation of fusion power.)« less

Adjacent level effects of bi level disc replacement, bi level fusion and disc replacement plus fusion in cervical spine--a finite element based study.

PubMed

Faizan, Ahmad; Goel, Vijay K; Biyani, Ashok; Garfin, Steven R; Bono, Christopher M

2012-03-01

Studies delineating the adjacent level effect of single level disc replacement systems have been reported in literature. The aim of this study was to compare the adjacent level biomechanics of bi-level disc replacement, bi-level fusion and a construct having adjoining level disc replacement and fusion system. In total, biomechanics of four models- intact, bi level disc replacement, bi level fusion and fusion plus disc replacement at adjoining levels- was studied to gain insight into the effects of various instrumentation systems on cranial and caudal adjacent levels using finite element analysis (73.6N+varying moment). The bi-level fusion models are more than twice as stiff as compared to the intact model during flexion-extension, lateral bending and axial rotation. Bi-level disc replacement model required moments lower than intact model (1.5Nm). Fusion plus disc replacement model required moment 10-25% more than intact model, except in extension. Adjacent level motions, facet loads and endplate stresses increased substantially in the bi-level fusion model. On the other hand, adjacent level motions, facet loads and endplate stresses were similar to intact for the bi-level disc replacement model. For the fusion plus disc replacement model, adjacent level motions, facet loads and endplate stresses were closer to intact model rather than the bi-level fusion model, except in extension. Based on our finite element analysis, fusion plus disc replacement procedure has less severe biomechanical effects on adjacent levels when compared to bi-level fusion procedure. Bi-level disc replacement procedure did not have any adverse mechanical effects on adjacent levels. Copyright © 2011 Elsevier Ltd. All rights reserved.

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

PubMed

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

2007-07-15

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

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

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

2015-03-01

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. © 2015. Published by The Company of Biologists Ltd.

Increased efficiency of mammalian somatic cell hybrid production under microgravity conditions during ballistic rocket flight

NASA Technical Reports Server (NTRS)

Schnettler, R.; Gessner, P.; Zimmermann, U.; Neil, G. A.; Urnovitz, H. B.

1989-01-01

The electrofusion of hybridoma cell lines under short-duration microgravity during a flight of the TEXUS 18 Black Brand ballistic sounding rocket at Kiruna, Sweden is reported. The fusion partners, growth medium, cell fusion medium, cell fusion, cell viability in the fusion medium, and postfusion cell culture are described, and the rocket, cell fusion chamber, apparatus, and module are examined. The experimental timeline, the effects of fusion medium and incubation time on cell viability and hybrid yields, and the effect of microgravity on hybrid yields are considered.

[Research Progress of Multi-Model Medical Image Fusion at Feature Level].

PubMed

Zhang, Junjie; Zhou, Tao; Lu, Huiling; Wang, Huiqun

2016-04-01

Medical image fusion realizes advantage integration of functional images and anatomical images.This article discusses the research progress of multi-model medical image fusion at feature level.We firstly describe the principle of medical image fusion at feature level.Then we analyze and summarize fuzzy sets,rough sets,D-S evidence theory,artificial neural network,principal component analysis and other fusion methods’ applications in medical image fusion and get summery.Lastly,we in this article indicate present problems and the research direction of multi-model medical images in the future.

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.

Warthin-like Mucoepidermoid Carcinoma: A Combined Study of Fluorescence In Situ Hybridization and Whole-slide Imaging.

PubMed

Ishibashi, Kenichiro; Ito, Yohei; Masaki, Ayako; Fujii, Kana; Beppu, Shintaro; Sakakibara, Takeo; Takino, Hisashi; Takase, Hiroshi; Ijichi, Kei; Shimozato, Kazuo; Inagaki, Hiroshi

2015-11-01

There has been some debate as to whether a subset of metaplastic Warthin tumors (mWTs) harbor the mucoepidermoid carcinoma (MEC)-associated CRTC1-MAML2 fusion. We analyzed 15 tumors originally diagnosed as mWT (mWT-like tumors), 2 of which had concurrent MECs. We looked for the CRTC1/3-MAML2 fusion transcripts and performed immunohistochemistry for p63 and fluorescence in situ hybridization (FISH) for the MAML2 split. To localize MAML2 split-positive cells at the cellular level, whole tumor tissue sections were digitalized (whole-slide imaging [WSI]). The CRTC1-MAML2, but not CRTC3-MAML2 was detected in 5/15 mWT-like tumors. FISH-WSI results showed that all epithelial cells harbored the MAML2 split in fusion-positive mWT-like tumors and were totally negative in fusion-negative mWT-like tumors. A review of the hematoxylin and eosin-stained slides showed that morphology of the "metaplastic" epithelium was virtually indistinguishable between fusion-positive and fusion-negative tumors. However, oncocytic bilayered tumor epithelium, characteristic to typical WT, was always found somewhere in the fusion-negative tumors but not in the fusion-positive tumors. This distinguishing histologic finding enabled 5 pathologists to easily differentiate the 2 tumor groups with 100% accuracy. The age and sex distribution of fusion-positive mWT-like tumor cases was similar to that of fusion-positive MEC cases and significantly different from those of fusion-negative mWT-like tumor and typical WT cases. In addition, only fusion-positive mWT-like tumors possessed concurrent low-grade MECs. In conclusion, a subset of mWT-like tumors were positive for the CRTC1-MAML2 fusion and had many features that are more in accord with MEC than with WT. The term Warthin-like MEC should be considered for fusion-positive mWT-like tumors.

Inhibition of Sendai virus fusion with phospholipid vesicles and human erythrocyte membranes by hydrophobic peptides

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kelsey, D.R.; Flanagan, T.D.; Young, J.E.

1991-06-01

Hydrophobic di- and tripeptides which are capable of inhibiting enveloped virus infection of cells are also capable of inhibiting at least three different types of membrane fusion events. Large unilamellar vesicles (LUV) of N-methyl dioleoylphosphatidylethanolamine (N-methyl DOPE), containing encapsulated 1-aminonaphthalene-3,6,8-trisulfonic acid (ANTS) and/or p-xylene bis(pyridinium bromide) (DPX), were formed by extrusion. Vesicle fusion and leakage were then monitored with the ANTS/DPX fluorescence assay. Sendai virus fusion with lipid vesicles and Sendai virus fusion with human erythrocyte membranes were measured by following the relief of fluorescence quenching of virus labeled with octadecylrhodamine B chloride (R18). This study found that the effectivenessmore » of the peptides carbobenzoxy-L-Phe-L-Phe (Z-L-Phe-L-Phe), Z-L-Phe, Z-D-Phe, and Z-Gly-L-Phe-L-Phe in inhibiting N-methyl DOPE LUV fusion or fusion of virus with N-methyl DOPE LUV also paralleled their reported ability to block viral infectivity. Furthermore, Z-D-Phe-L-PheGly and Z-Gly-L-Phe inhibited Sendai virus fusion with human erythrocyte membranes with the same relative potency with which they inhibited vesicle-vesicle and virus-vesicle fusion. The evidence suggests a mechanism by which these peptides exert their inhibition of plaque formation by enveloped viruses. This class of inhibitors apparently acts by inhibiting fusion of the viral envelope with the target cell membrane, thereby preventing viral infection. The physical pathway by which these peptides inhibit membrane fusion was investigated. {sup 31}P nuclear magnetic resonance (NMR) of proposed intermediates in the pathway for membrane fusion in LUV revealed that the potent fusion inhibitor Z-D-Phe-L-PheGly selectively altered the structure (or dynamics) of the hypothesized fusion intermediates and that the poor inhibitor Z-Gly-L-Phe did not.« less

Influence of incomplete fusion on complete fusion at energies above the Coulomb barrier

NASA Astrophysics Data System (ADS)

Shuaib, Mohd; Sharma, Vijay R.; Yadav, Abhishek; Sharma, Manoj Kumar; Singh, Pushpendra P.; Singh, Devendra P.; Kumar, R.; Singh, R. P.; Muralithar, S.; Singh, B. P.; Prasad, R.

2017-10-01

In the present work, excitation functions of several reaction residues in the system 19F+169Tm, populated via the complete and incomplete fusion processes, have been measured using off-line γ-ray spectroscopy. The analysis of excitation functions has been done within the framework of statistical model code pace4. The excitation functions of residues populated via xn and pxn channels are found to be in good agreement with those estimated by the theoretical model code, which confirms the production of these residues solely via complete fusion process. However, a significant enhancement has been observed in the cross-sections of residues involving α-emitting channels as compared to the theoretical predictions. The observed enhancement in the cross-sections has been attributed to the incomplete fusion processes. In order to have a better insight into the onset and strength of incomplete fusion, the incomplete fusion strength function has been deduced. At present, there is no theoretical model available which can satisfactorily explain the incomplete fusion reaction data at energies ≈4-6 MeV/nucleon. In the present work, the influence of incomplete fusion on complete fusion in the 19F+169Tm system has also been studied. The measured cross-section data may be important for the development of reactor technology as well. It has been found that the incomplete fusion strength function strongly depends on the α-Q value of the projectile, which is found to be in good agreement with the existing literature data. The analysis strongly supports the projectile-dependent mass-asymmetry systematics. In order to study the influence of Coulomb effect ({Z}{{P}}{Z}{{T}}) on incomplete fusion, the deduced strength function for the present work is compared with the nearby projectile-target combinations. The incomplete fusion strength function is found to increase linearly with {Z}{{P}}{Z}{{T}}, indicating a strong influence of Coulomb effect in the incomplete fusion reactions.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yu, Qianlong; Blissard, Gary W.; Liu, Tong-Xian

The Autographa californica multiple nucleopolyhedrovirus GP64 is a class III viral fusion protein. Although the post-fusion structure of GP64 has been solved, its pre-fusion structure and the detailed mechanism of conformational change are unknown. In GP64, domain V is predicted to interact with two domain I segments that flank fusion loop 2. To evaluate the significance of the amino acids involved in these interactions, we examined 24 amino acid positions that represent interacting and conserved residues within domains I and V. In several cases, substitution of a single amino acid involved in a predicted interaction disrupted membrane fusion activity, butmore » no single amino acid pair appears to be absolutely required. We identified 4 critical residues in domain V (G438, W439, T452, and T456) that are important for membrane fusion, and two residues (G438 and W439) that appear to be important for formation or stability of the pre-fusion conformation of GP64. - Highlights: • The baculovirus envelope glycoprotein GP64 is a class III viral fusion protein. • The detailed mechanism of conformational change of GP64 is unknown. • We analyzed 24 positions that might stabilize the post-fusion structure of GP64. • We identified 4 residues in domain V that were critical for membrane fusion. • Two residues are critical for formation of the pre-fusion conformation of GP64.« less

A mechanism of protein-mediated fusion: coupling between refolding of the influenza hemagglutinin and lipid rearrangements.

PubMed Central

Kozlov, M M; Chernomordik, L V

1998-01-01

Although membrane fusion mediated by influenza virus hemagglutinin (HA) is the best characterized example of ubiquitous protein-mediated fusion, it is still not known how the low-pH-induced refolding of HA trimers causes fusion. This refolding involves 1) repositioning of the hydrophobic N-terminal sequence of the HA2 subunit of HA ("fusion peptide"), and 2) the recruitment of additional residues to the alpha-helical coiled coil of a rigid central rod of the trimer. We propose here a mechanism by which these conformational changes can cause local bending of the viral membrane, priming it for fusion. In this model fusion is triggered by incorporation of fusion peptides into viral membrane. Refolding of a central rod exerts forces that pull the fusion peptides, tending to bend the membrane around HA trimer into a saddle-like shape. Elastic energy drives self-assembly of these HA-containing membrane elements in the plane of the membrane into a ring-like cluster. Bulging of the viral membrane within such cluster yields a dimple growing toward the bound target membrane. Bending stresses in the lipidic top of the dimple facilitate membrane fusion. We analyze the energetics of this proposed sequence of membrane rearrangements, and demonstrate that this simple mechanism may explain some of the known phenomenological features of fusion. PMID:9726939

Recurrent EML4-NTRK3 fusions in infantile fibrosarcoma and congenital mesoblastic nephroma suggest a revised testing strategy.

PubMed

Church, Alanna J; Calicchio, Monica L; Nardi, Valentina; Skalova, Alena; Pinto, Andre; Dillon, Deborah A; Gomez-Fernandez, Carmen R; Manoj, Namitha; Haimes, Josh D; Stahl, Joshua A; Dela Cruz, Filemon S; Tannenbaum-Dvir, Sarah; Glade-Bender, Julia L; Kung, Andrew L; DuBois, Steven G; Kozakewich, Harry P; Janeway, Katherine A; Perez-Atayde, Antonio R; Harris, Marian H

2018-03-01

Infantile fibrosarcoma and congenital mesoblastic nephroma are tumors of infancy traditionally associated with the ETV6-NTRK3 gene fusion. However, a number of case reports have identified variant fusions in these tumors. In order to assess the frequency of variant NTRK3 fusions, and in particular whether the recently identified EML4-NTRK3 fusion is recurrent, 63 archival cases of infantile fibrosarcoma, congenital mesoblastic nephroma, mammary analog secretory carcinoma and secretory breast carcinoma (tumor types that are known to carry recurrent ETV6-NTRK3 fusions) were tested with NTRK3 break-apart FISH, EML4-NTRK3 dual fusion FISH, and targeted RNA sequencing. The EML4-NTRK3 fusion was identified in two cases of infantile fibrosarcoma (one of which was previously described), and in one case of congenital mesoblastic nephroma, demonstrating that the EML4-NTRK3 fusion is a recurrent genetic event in these related tumors. The growing spectrum of gene fusions associated with infantile fibrosarcoma and congenital mesoblastic nephroma along with the recent availability of targeted therapies directed toward inhibition of NTRK signaling argue for alternate testing strategies beyond ETV6 break-apart FISH. The use of either NTRK3 FISH or next-generation sequencing will expand the number of cases in which an oncogenic fusion is identified and facilitate optimal diagnosis and treatment for patients.

A local approach for focussed Bayesian fusion

NASA Astrophysics Data System (ADS)

Sander, Jennifer; Heizmann, Michael; Goussev, Igor; Beyerer, Jürgen

2009-04-01

Local Bayesian fusion approaches aim to reduce high storage and computational costs of Bayesian fusion which is separated from fixed modeling assumptions. Using the small world formalism, we argue why this proceeding is conform with Bayesian theory. Then, we concentrate on the realization of local Bayesian fusion by focussing the fusion process solely on local regions that are task relevant with a high probability. The resulting local models correspond then to restricted versions of the original one. In a previous publication, we used bounds for the probability of misleading evidence to show the validity of the pre-evaluation of task specific knowledge and prior information which we perform to build local models. In this paper, we prove the validity of this proceeding using information theoretic arguments. For additional efficiency, local Bayesian fusion can be realized in a distributed manner. Here, several local Bayesian fusion tasks are evaluated and unified after the actual fusion process. For the practical realization of distributed local Bayesian fusion, software agents are predestinated. There is a natural analogy between the resulting agent based architecture and criminal investigations in real life. We show how this analogy can be used to improve the efficiency of distributed local Bayesian fusion additionally. Using a landscape model, we present an experimental study of distributed local Bayesian fusion in the field of reconnaissance, which highlights its high potential.

Effects of ROCK inhibitor Y-27632 on cell fusion through a microslit.

PubMed

Wada, Ken-Ichi; Hosokawa, Kazuo; Ito, Yoshihiro; Maeda, Mizuo

2015-11-01

We previously reported a direct cytoplasmic transfer method using a microfluidic device, in which cell fusion was induced through a microslit (slit-through-fusion) by the Sendai virus envelope (HVJ-E) to prevent nuclear mixing. However, the method was impractical due to low efficiency of slit-through-fusion formation and insufficient prevention of nuclear mixing. The purpose of this study was to establish an efficient method for inducing slit-through-fusion without nuclear mixing. We hypothesized that modulation of cytoskeletal component can decrease nuclear migration through the microslit considering its functions. Here we report that supplementation with Y-27632, a specific ROCK inhibitor, significantly enhances cell fusion induction and prevention of nuclear mixing. Supplementation with Y-27632 increased the formation of slit-through-fusion efficiency by more than twofold. Disruption of F-actin by Y-27632 prevented nuclear migration between fused cells through the microslit. These two effects of Y-27632 led to promotion of the slit-through-fusion without nuclear mixing with a 16.5-fold higher frequency compared to our previous method (i.e., cell fusion induction by HVJ-E without supplementation with Y-27632). We also confirmed that mitochondria were successfully transferred to the fusion partner under conditions of Y-27632 supplementation. These findings demonstrate the practicality of our cell fusion system in producing direct cytoplasmic transfer between live cells. © 2015 Wiley Periodicals, Inc.

Salvage of infected total knee fusion: the last option.

PubMed

Wiedel, Jerome D

2002-11-01

Currently the most common indication for an arthrodesis of the knee is a failed infected total knee prosthesis. Other causes of a failed total knee replacement that might necessitate a knee fusion include aseptic loosening, deficient extensor mechanism, poor soft tissues, and Charcot joint. Techniques available for achieving a knee fusion are external fixation and internal fixation methods. The external fixation compression devices have been the most widely used for knee fusion and have been successful until the indications for fusion changed to mostly failed prosthetic knee replacement. With failed total knee replacement, the problem of severe bone loss became an issue, and the external fixation compression devices, even including the biplane external fixators, have been the least successful method reported for gaining fusion. The Ilizarov technique has been shown to achieve rigid fixation despite this bone loss, and a review of reports are showing high fusion rates using this method. Internal fixation methods including plate fixation and intramedullary nails have had the best success in gaining fusion in the face of this bone loss and have replaced external fixation methods as the technique of choice for knee fusion when severe bone loss is present. A review of the literature and a discussion of different fusion techniques are presented including a discussion of the influence that infection has on the success of fusion.

Y fuse? Sex chromosome fusions in fishes and reptiles.

PubMed

Pennell, Matthew W; Kirkpatrick, Mark; Otto, Sarah P; Vamosi, Jana C; Peichel, Catherine L; Valenzuela, Nicole; Kitano, Jun

2015-05-01

Chromosomal fusion plays a recurring role in the evolution of adaptations and reproductive isolation among species, yet little is known of the evolutionary drivers of chromosomal fusions. Because sex chromosomes (X and Y in male heterogametic systems, Z and W in female heterogametic systems) differ in their selective, mutational, and demographic environments, those differences provide a unique opportunity to dissect the evolutionary forces that drive chromosomal fusions. We estimate the rate at which fusions between sex chromosomes and autosomes become established across the phylogenies of both fishes and squamate reptiles. Both the incidence among extant species and the establishment rate of Y-autosome fusions is much higher than for X-autosome, Z-autosome, or W-autosome fusions. Using population genetic models, we show that this pattern cannot be reconciled with many standard explanations for the spread of fusions. In particular, direct selection acting on fusions or sexually antagonistic selection cannot, on their own, account for the predominance of Y-autosome fusions. The most plausible explanation for the observed data seems to be (a) that fusions are slightly deleterious, and (b) that the mutation rate is male-biased or the reproductive sex ratio is female-biased. We identify other combinations of evolutionary forces that might in principle account for the data although they appear less likely. Our results shed light on the processes that drive structural changes throughout the genome.

Y Fuse? Sex Chromosome Fusions in Fishes and Reptiles

PubMed Central

Vamosi, Jana C.; Peichel, Catherine L.; Valenzuela, Nicole; Kitano, Jun

2015-01-01

Chromosomal fusion plays a recurring role in the evolution of adaptations and reproductive isolation among species, yet little is known of the evolutionary drivers of chromosomal fusions. Because sex chromosomes (X and Y in male heterogametic systems, Z and W in female heterogametic systems) differ in their selective, mutational, and demographic environments, those differences provide a unique opportunity to dissect the evolutionary forces that drive chromosomal fusions. We estimate the rate at which fusions between sex chromosomes and autosomes become established across the phylogenies of both fishes and squamate reptiles. Both the incidence among extant species and the establishment rate of Y-autosome fusions is much higher than for X-autosome, Z-autosome, or W-autosome fusions. Using population genetic models, we show that this pattern cannot be reconciled with many standard explanations for the spread of fusions. In particular, direct selection acting on fusions or sexually antagonistic selection cannot, on their own, account for the predominance of Y-autosome fusions. The most plausible explanation for the observed data seems to be (a) that fusions are slightly deleterious, and (b) that the mutation rate is male-biased or the reproductive sex ratio is female-biased. We identify other combinations of evolutionary forces that might in principle account for the data although they appear less likely. Our results shed light on the processes that drive structural changes throughout the genome. PMID:25993542

Binaural Pitch Fusion in Bilateral Cochlear Implant Users.

PubMed

Reiss, Lina A J; Fowler, Jennifer R; Hartling, Curtis L; Oh, Yonghee

Binaural pitch fusion is the fusion of stimuli that evoke different pitches between the ears into a single auditory image. Individuals who use hearing aids or bimodal cochlear implants (CIs) experience abnormally broad binaural pitch fusion, such that sounds differing in pitch by as much as 3-4 octaves are fused across ears, leading to spectral averaging and speech perception interference. The goal of this study was to determine if adult bilateral CI users also experience broad binaural pitch fusion. Stimuli were pulse trains delivered to individual electrodes. Fusion ranges were measured using simultaneous, dichotic presentation of reference and comparison stimuli in opposite ears, and varying the comparison stimulus to find the range that fused with the reference stimulus. Bilateral CI listeners had binaural pitch fusion ranges varying from 0 to 12 mm (average 6.1 ± 3.9 mm), where 12 mm indicates fusion over all electrodes in the array. No significant correlations of fusion range were observed with any subject factors related to age, hearing loss history, or hearing device history, or with any electrode factors including interaural electrode pitch mismatch, pitch match bandwidth, or within-ear electrode discrimination abilities. Bilateral CI listeners have abnormally broad fusion, similar to hearing aid and bimodal CI listeners. This broad fusion may explain the variability of binaural benefits for speech perception in quiet and in noise in bilateral CI users.

Mutagenesis of the La Crosse Virus glycoprotein supports a role for Gc (1066-1087) as the fusion peptide

DOE Office of Scientific and Technical Information (OSTI.GOV)

Plassmeyer, Matthew L.; Graduate Group Molecular and Cell Biology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6058; Soldan, Samantha S.

The La Crosse Virus (LACV) M segment encodes two glycoproteins (Gn and Gc), and plays a critical role in the neuropathogenesis of LACV infection as the primary determinant of neuroinvasion. A recent study from our group demonstrated that the region comprising the membrane proximal two-thirds of Gc, amino acids 860-1442, is critical in mediating LACV fusion and entry. Furthermore, computational analysis identified structural similarities between a portion of this region, amino acids 970-1350, and the E1 fusion protein of two alphaviruses: Sindbis virus and Semliki Forrest virus (SFV). Within the region 970-1350, a 22-amino-acid hydrophobic segment (1066-1087) is predicted tomore » correlate structurally with the fusion peptides of class II fusion proteins. We performed site-directed mutagenesis of key amino acids in this 22-amino acid segment and determined the functional consequences of these mutations on fusion and entry. Several mutations within this hydrophobic domain affected glycoprotein expression to some extent, but all mutations either shifted the pH threshold of fusion below that of the wild-type protein, reduced fusion efficiency, or abrogated cell-to-cell fusion and pseudotype entry altogether. These results, coupled with the aforementioned computational modeling, suggest that the LACV Gc functions as a class II fusion protein and support a role for the region Gc 1066-1087 as a fusion peptide.« less

Treating Traumatic Lumbosacral Spondylolisthesis Using Posterior Lumbar Interbody Fusion with three years follow up

PubMed Central

Tang, Shujie

2014-01-01

Objective: To analyze the surgical outcome of traumatic lumbosacral spondylolisthesis treated using posterior lumbar interbody fusion, and help spine surgeons to determine the treatment strategy. Methods: We reviewed retrospectively five cases of traumatic lumbosacral spondylolisthesis treated in our hospital from May 2005 to May 2010. There were four male and one female patient, treated surgically using posterior lumbar interbody fusion. The patients’ data including age, neurological status, operation time, blood loss, follow-up periods, X- radiographs and fusion status were collected. Results: All the cases were treated using posterior lumbar interbody fusion to realize decompression, reduction and fusion. Solid arthrodesis was found at the 12-month follow-up. No shift or breakage of the instrumentation was found, and all the patients were symptom-free at the last follow-up. Conclusion: Traumatic lumbosacral spondylolisthesis can be treated using posterior lumbar interbody fusion to realize the perfect reduction, decompression, fixation and fusion. PMID:25225542

Estimating the melting point, entropy of fusion, and enthalpy of ...

EPA Pesticide Factsheets

The entropies of fusion, enthalies of fusion, and melting points of organic compounds can be estimated through three models developed using the SPARC (SPARC Performs Automated Reasoning in Chemistry) platform. The entropy of fusion is modeled through a combination of interaction terms and physical descriptors. The enthalpy of fusion is modeled as a function of the entropy of fusion, boiling point, and fexibility of the molecule. The melting point model is the enthlapy of fusion divided by the entropy of fusion. These models were developed in part to improve SPARC's vapor pressure and solubility models. These models have been tested on 904 unique compounds. The entropy model has a RMS of 12.5 J mol-1K-1. The enthalpy model has a RMS of 4.87 kJ mol-1. The melting point model has a RMS of 54.4°C. Published in the journal, SAR and QSAR in Environmental Research

Paramyxovirus Glycoproteins and the Membrane Fusion Process.

PubMed

Aguilar, Hector C; Henderson, Bryce A; Zamora, J Lizbeth; Johnston, Gunner P

2016-09-01

The family Paramyxoviridae includes many viruses that significantly affect human and animal health. An essential step in the paramyxovirus life cycle is viral entry into host cells, mediated by virus-cell membrane fusion. Upon viral entry, infection results in expression of the paramyxoviral glycoproteins on the infected cell surface. This can lead to cell-cell fusion (syncytia formation), often linked to pathogenesis. Thus membrane fusion is essential for both viral entry and cell-cell fusion and an attractive target for therapeutic development. While there are important differences between viral-cell and cell-cell membrane fusion, many aspects are conserved. The paramyxoviruses generally utilize two envelope glycoproteins to orchestrate membrane fusion. Here, we discuss the roles of these glycoproteins in distinct steps of the membrane fusion process. These findings can offer insights into evolutionary relationships among Paramyxoviridae genera and offer future targets for prophylactic and therapeutic development.

Paramyxovirus Glycoproteins and the Membrane Fusion Process

PubMed Central

Aguilar, Hector C.; Henderson, Bryce A.; Zamora, J. Lizbeth; Johnston, Gunner P.

2016-01-01

The family Paramyxoviridae includes many viruses that significantly affect human and animal health. An essential step in the paramyxovirus life cycle is viral entry into host cells, mediated by virus-cell membrane fusion. Upon viral entry, infection results in expression of the paramyxoviral glycoproteins on the infected cell surface. This can lead to cell-cell fusion (syncytia formation), often linked to pathogenesis. Thus membrane fusion is essential for both viral entry and cell-cell fusion and an attractive target for therapeutic development. While there are important differences between viral-cell and cell-cell membrane fusion, many aspects are conserved. The paramyxoviruses generally utilize two envelope glycoproteins to orchestrate membrane fusion. Here, we discuss the roles of these glycoproteins in distinct steps of the membrane fusion process. These findings can offer insights into evolutionary relationships among Paramyxoviridae genera and offer future targets for prophylactic and therapeutic development. PMID:28138419

Future Directions for Fusion Propulsion Research at NASA

NASA Technical Reports Server (NTRS)

Adams, Robert B.; Cassibry, Jason T.

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. Arguments for fusion propulsion are presented, along with fusion enabled mission examples, fusion technology trade space, and a proposed outline for future efforts.

Exo-endo cellulase fusion protein

DOEpatents

Bower, Benjamin S [Palo Alto, CA; Larenas, Edmund A [Palo Alto, CA; Mitchinson, Colin [Palo Alto, CA

2012-01-17

The present invention relates to a heterologous exo-endo cellulase fusion construct, which encodes a fusion protein having cellulolytic activity comprising a catalytic domain derived from a fungal exo-cellobiohydrolase and a catalytic domain derived from an endoglucanase. The invention also relates to vectors and fungal host cells comprising the heterologous exo-endo cellulase fusion construct as well as methods for producing a cellulase fusion protein and enzymatic cellulase compositions.

A review of data fusion techniques.

PubMed

Castanedo, Federico

2013-01-01

The integration of data and knowledge from several sources is known as data fusion. This paper summarizes the state of the data fusion field and describes the most relevant studies. We first enumerate and explain different classification schemes for data fusion. Then, the most common algorithms are reviewed. These methods and algorithms are presented using three different categories: (i) data association, (ii) state estimation, and (iii) decision fusion.

Two Strategic Decisions Facing Fusion

NASA Astrophysics Data System (ADS)

Baldwin, D. E.

1998-06-01

Two strategic decisions facing the U.S. fusion program are described. The first decision deals with the role and rationale of the tokamak within the U. S. fusion program, and it underlies the debate over our continuing role in the evolving ITER collaboration (mid-1998). The second decision concerns how to include Inertial Fusion Energy (IFE) as a viable part of the national effort to harness fusion energy.

Novel spinal instrumentation to enhance osteogenesis and fusion: a preliminary study.

PubMed

MacEwan, Matthew R; Talcott, Michael R; Moran, Daniel W; Leuthardt, Eric C

2016-09-01

OBJECTIVE Instrumented spinal fusion continues to exhibit high failure rates in patients undergoing multilevel lumbar fusion or pseudarthrosis revision; with Grade II or higher spondylolisthesis; or in those possessing risk factors such as obesity, tobacco use, or metabolic disorders. Direct current (DC) electrical stimulation of bone growth represents a unique surgical adjunct in vertebral fusion procedures, yet existing spinal fusion stimulators are not optimized to enhance interbody fusion. To develop an advanced method of applying DC electrical stimulation to promote interbody fusion, a novel osteogenic spinal system capable of routing DC through rigid instrumentation and into the vertebral bodies was fabricated. A pilot study was designed to assess the feasibility of osteogenic instrumentation and compare the ability of osteogenic instrumentation to promote successful interbody fusion in vivo to standard spinal instrumentation with autograft. METHODS Instrumented, single-level, posterior lumbar interbody fusion (PLIF) with autologous graft was performed at L4-5 in adult Toggenburg/Alpine goats, using both osteogenic spinal instrumentation (plus electrical stimulation) and standard spinal instrumentation (no electrical stimulation). At terminal time points (3 months, 6 months), animals were killed and lumbar spines were explanted for radiographic analysis using a SOMATOM Dual Source Definition CT Scanner and high-resolution Microcat II CT Scanner. Trabecular continuity, radiodensity within the fusion mass, and regional bone formation were examined to determine successful spinal fusion. RESULTS Quantitative analysis of average bone density in pedicle screw beds confirmed that electroactive pedicle screws used in the osteogenic spinal system focally enhanced bone density in instrumented vertebral bodies. Qualitative and quantitative analysis of high-resolution CT scans of explanted lumbar spines further demonstrated that the osteogenic spinal system induced solid bony fusion across the L4-5 disc space as early as 6 weeks postoperatively. In comparison, inactive spinal instrumentation with autograft was unable to promote successful interbody fusion by 6 months postoperatively. CONCLUSIONS Results of this study demonstrate that novel osteogenic spinal instrumentation supports interbody fusion through the focal delivery of DC electrical stimulation. With further technical development and scientific/clinical validation, osteogenic spinal instrumentation may offer a unique alternative to biological scaffolds and pharmaceutical adjuncts used in spinal fusion procedures.

[Clinical utility of real-time fluorescent PCR for combined detection of anaplastic lymphoma kinase and c-ros oncogene 1 receptor tyrosine kinase in non-small cell lung cancer].

PubMed

Bai, D Y; Zhang, H P; Zhong, S; Suo, W H; Gao, D H; Ding, Y; Tu, J H

2016-12-23

Objective: To investigate the clinical application value of combined detection of ALK fusion gene and c-ros oncogene 1 receptor tyrosine kinase (ROS1) fusion gene in non-small cell lung cancer (NSCLC) using real-time fluorescent PCR. Methods: A kit for combined detection of ALK fusion gene and ROS1 fusion gene based on fluorescent PCR was used to simultaneously detect the two fusion genes in 302 cases of NSCLC specimens. The results were validated through Sanger sequencing. The consistency of the two detection methods was analyzed. Results: All 302 cases of NSCLC specimens were successfully analyzed through fluorescent PCR (302/302). 12 cases (4.0%) were found to contain ALK fusion gene, including 3 cases with ALK-M1, 3 with ALK-M2, 3 with ALK-M3, 1 with ALK-M4, and 2 with ALK-M6 fusion gene.12 cases (4.0%) were found to contain ROS1 fusion gene, including 1 case with ROS1-M7, 8 cases with ROS1-M8, 1 case with ROS1-M12, 1 case with ROS1-M14, and 1 case with double-positive ROS1-M3 and ROS1-M8 fusion genes. The total detection rate of ALK fusion gene and ROS1 fusion gene was 7.9% (24/302) and 278 cases showed to be negative for ALK fusion gene and ROS1 fusion gene. The successful detection rates for Sanger DNA sequencing were also 100%. The positive, negative and total coincidence rates obtained by real-time fluorescent PCR and by Sanger DNA sequencing were all 100%. Conclusions: The results of Sanger DNA sequencing demonstrate that the real-time fluorescent PCR assay is equally effective in detecting ALK and ROS1 fusion genes in NSCLC tissues. Furthermore, real-time fluorescent PCR assay can be used to detect trace ALK and ROS1 fusion gene simultaneously in tiny samples, and can save time and avoid repeated sampling. It is worthy of recommendation as a rapid and reliable detection technique.

Radiographic and Clinical Outcome of Silicate-substituted Calcium Phosphate (Si-CaP) Ceramic Bone Graft in Spinal Fusion Procedures.

PubMed

Alimi, Marjan; Navarro-Ramirez, Rodrigo; Parikh, Karishma; Njoku, Innocent; Hofstetter, Christoph P; Tsiouris, Apostolos J; Härtl, Roger

2017-07-01

Retrospective cohort study. To evaluate the radiographic and clinical outcome of silicate-substituted calcium phosphate (Si-CaP), utilized as a graft substance in spinal fusion procedures. Specific properties of Si-CaP provide the graft with negative surface charge that can result in a positive effect on the osteoblast activity and neovascularization of the bone. This study included those patients who underwent spinal fusion procedures between 2007 and 2011 in which Si-CaP was used as the only bone graft substance. Fusion was evaluated on follow-up CT scans. Clinical outcome was assessed using Oswestry Disability Index, Neck Disability Index, and the visual analogue scale (VAS) for back, leg, neck, and arm pain. A total of 234 patients (516 spinal fusion levels) were studied. Surgical procedures consisted of 57 transforaminal lumbar interbody fusion, 49 anterior cervical discectomy and fusion, 44 extreme lateral interbody fusion, 30 posterior cervical fusions, 19 thoracic fusion surgeries, 17 axial lumbar interbody fusions, 16 combined anterior and posterior cervical fusions, and 2 anterior lumbar interbody fusion. At a mean radiographic follow-up of 14.2±4.3 months, fusion was found to be present in 82.9% of patients and 86.8% of levels. The highest fusion rate was observed in the cervical region. At the latest clinical follow-up of 21.7±14.2 months, all clinical outcome parameters showed significant improvement. The Oswestry Disability Index improved from 45.6 to 13.3 points, Neck Disability Index from 40.6 to 29.3, VAS back from 6.1 to 3.5, VAS leg from 5.6 to 2.4, VAS neck from 4.7 to 2.7, and VAS arm from 4.1 to 1.7. Of 7 cases with secondary surgical procedure at the index level, the indication for surgery was nonunion in 3 patients. Si-CaP is an effective bone graft substitute. At the latest follow-up, favorable radiographic and clinical outcome was observed in the majority of patients. Level-III.

3D Neutronic Analysis in MHD Calculations at ARIES-ST Fusion Reactors Systems

NASA Astrophysics Data System (ADS)

Hançerliogulları, Aybaba; Cini, Mesut

2013-10-01

In this study, we developed new models for liquid wall (FW) state at ARIES-ST fusion reactor systems. ARIES-ST is a 1,000 MWe fusion reactor system based on a low aspect ratio ST plasma. In this article, we analyzed the characteristic properties of magnetohydrodynamics (MHD) and heat transfer conditions by using Monte-Carlo simulation methods (ARIES Team et al. in Fusion Eng Des 49-50:689-695, 2000; Tillack et al. in Fusion Eng Des 65:215-261, 2003) . In fusion applications, liquid metals are traditionally considered to be the best working fluids. The working liquid must be a lithium-containing medium in order to provide adequate tritium that the plasma is self-sustained and that the fusion is a renewable energy source. As for Flibe free surface flows, the MHD effects caused by interaction with the mean flow is negligible, while a fairly uniform flow of thick can be maintained throughout the reactor based on 3-D MHD calculations. In this study, neutronic parameters, that is to say, energy multiplication factor radiation, heat flux and fissile fuel breeding were researched for fusion reactor with various thorium and uranium molten salts. Sufficient tritium amount is needed for the reactor to work itself. In the tritium breeding ratio (TBR) >1.05 ARIES-ST fusion model TBR is >1.1 so that tritium self-sufficiency is maintained for DT fusion systems (Starke et al. in Fusion Energ Des 84:1794-1798, 2009; Najmabadi et al. in Fusion Energ Des 80:3-23, 2006).

Influenza Virus-Mediated Membrane Fusion: Determinants of Hemagglutinin Fusogenic Activity and Experimental Approaches for Assessing Virus Fusion

PubMed Central

Hamilton, Brian S.; Whittaker, Gary R.; Daniel, Susan

2012-01-01

Hemagglutinin (HA) is the viral protein that facilitates the entry of influenza viruses into host cells. This protein controls two critical aspects of entry: virus binding and membrane fusion. In order for HA to carry out these functions, it must first undergo a priming step, proteolytic cleavage, which renders it fusion competent. Membrane fusion commences from inside the endosome after a drop in lumenal pH and an ensuing conformational change in HA that leads to the hemifusion of the outer membrane leaflets of the virus and endosome, the formation of a stalk between them, followed by pore formation. Thus, the fusion machinery is an excellent target for antiviral compounds, especially those that target the conserved stem region of the protein. However, traditional ensemble fusion assays provide a somewhat limited ability to directly quantify fusion partly due to the inherent averaging of individual fusion events resulting from experimental constraints. Inspired by the gains achieved by single molecule experiments and analysis of stochastic events, recently-developed individual virion imaging techniques and analysis of single fusion events has provided critical information about individual virion behavior, discriminated intermediate fusion steps within a single virion, and allowed the study of the overall population dynamics without the loss of discrete, individual information. In this article, we first start by reviewing the determinants of HA fusogenic activity and the viral entry process, highlight some open questions, and then describe the experimental approaches for assaying fusion that will be useful in developing the most effective therapies in the future. PMID:22852045

Task toward a Realization of Commercial Tokamak Fusion Plants in 2050 -The Role of ITER and the Succeeding Developments- 5.Challenge to Innovative Technologies and the Expected Market Appeal

NASA Astrophysics Data System (ADS)

Tobita, Kenji; Konishi, Satoshi; Tokimatsu, Koji; Nishio, Satoshi; Hiwatari, Ryoji

This section describes the future of fusion energy in terms of its impact on the global energy supply and global warming mitigation, the possible entry scenarios of fusion into future energy market, and innovative technologies for deploying and expanding fusion's share in the market. Section 5.1 shows that fusion energy can contribute to the stabilization of atmospheric CO2 concentration if fusion is introduced into the future energy market at a competitive price. Considerations regarding fusion's entry scenarios into the energy market are presented in Sec. 5.2, suggesting that fusion should replace fossil energy sources and thus contribute to global warming mitigation. In this sense, first generation fusion power plants should be a viable energy source with global appeal and be so attractive as to be employed in developing countries rather than in developed countries. Favorable factors lending to this purpose are fusion's stability as a power source, and its security, safety, and environmental frendliness as well as its cost-of-electricity. The requirements for core plasma to expand the share of fusion in the market in the latter half of this century are given in Sec.5.3, pointing out the importance of high beta access with low aspect ratio and plasma profile control. From this same point of view, innovative fusion technologies worthy of further development are commented on in Sec. 5.4, addressing the high temperature blanket, hydrogen production, high temperature superconductors, and hot cell maintenance.

Low-intensity pulsed ultrasound enhances healing of laminectomy chip bone grafts on spinal fusion: a model of posterolateral intertransverse fusion in rabbits.

PubMed

Liao, Jen-Chung; Chen, Wen-Jer; Chen, Lih-Hui; Lai, Po-Liang; Keorochana, Gun

2011-04-01

Laminectomy-derived chip bone graft was usually used in spinal fusion; however, the result of this kind of local bone used in lumbar posterolateral fusion is uncertain. This study tested the hypotheses that low-intensity pulsed ultrasound (LIPU) can accelerate the healing process of laminectomy bone chips in a spinal fusion and enhance the union rate. Forty-eight rabbits were randomly divided into three groups for the spinal unilateral uninstrumented posterolateral fusion of L5-L6: autologous iliac bone graft (AIBG), laminectomy chip bone graft (LCBG), LCBG plus LIPU (LCBG + LIPU). Each group was subdivided into 6-week and 12-week subgroups. All rabbits were subjected to radiographic examination and manual testing. All successful spinal fusion specimens received biomechanical testing and a histologic examination. The LCBG + LIPU group had the highest successful fusion rate at 6-week and 12-week examination (75% and 100%, respectively). At 6 weeks, the average maximum toque at failure values of the fusion masses for the LCBG + LIPU group was significantly higher than that for the LCBG group (p = 0.034). The average maximum torque of the 12-week LCBG + LIPU group was significantly higher than those of the 12-week AIBG and 12-week LCBG groups (p = 0.040 and p = 0.026, respectively). This study suggested that LIPU can enhance bone healing. With augmentation by LIPU, laminectomy chip bone used in lumbar posterolateral fusion can achieve a similar fusion rate and stronger fusion mass than those of an AIBG.

Engineering and Functional Characterization of Fusion Genes Identifies Novel Oncogenic Drivers of Cancer.

PubMed

Lu, Hengyu; Villafane, Nicole; Dogruluk, Turgut; Grzeskowiak, Caitlin L; Kong, Kathleen; Tsang, Yiu Huen; Zagorodna, Oksana; Pantazi, Angeliki; Yang, Lixing; Neill, Nicholas J; Kim, Young Won; Creighton, Chad J; Verhaak, Roel G; Mills, Gordon B; Park, Peter J; Kucherlapati, Raju; Scott, Kenneth L

2017-07-01

Oncogenic gene fusions drive many human cancers, but tools to more quickly unravel their functional contributions are needed. Here we describe methodology permitting fusion gene construction for functional evaluation. Using this strategy, we engineered the known fusion oncogenes, BCR-ABL1, EML4-ALK , and ETV6-NTRK3, as well as 20 previously uncharacterized fusion genes identified in The Cancer Genome Atlas datasets. In addition to confirming oncogenic activity of the known fusion oncogenes engineered by our construction strategy, we validated five novel fusion genes involving MET, NTRK2 , and BRAF kinases that exhibited potent transforming activity and conferred sensitivity to FDA-approved kinase inhibitors. Our fusion construction strategy also enabled domain-function studies of BRAF fusion genes. Our results confirmed other reports that the transforming activity of BRAF fusions results from truncation-mediated loss of inhibitory domains within the N-terminus of the BRAF protein. BRAF mutations residing within this inhibitory region may provide a means for BRAF activation in cancer, therefore we leveraged the modular design of our fusion gene construction methodology to screen N-terminal domain mutations discovered in tumors that are wild-type at the BRAF mutation hotspot, V600. We identified an oncogenic mutation, F247L, whose expression robustly activated the MAPK pathway and sensitized cells to BRAF and MEK inhibitors. When applied broadly, these tools will facilitate rapid fusion gene construction for subsequent functional characterization and translation into personalized treatment strategies. Cancer Res; 77(13); 3502-12. ©2017 AACR . ©2017 American Association for Cancer Research.

A testbed for architecture and fidelity trade studies in the Bayesian decision-level fusion of ATR products

NASA Astrophysics Data System (ADS)

Erickson, Kyle J.; Ross, Timothy D.

2007-04-01

Decision-level fusion is an appealing extension to automatic/assisted target recognition (ATR) as it is a low-bandwidth technique bolstered by a strong theoretical foundation that requires no modification of the source algorithms. Despite the relative simplicity of decision-level fusion, there are many options for fusion application and fusion algorithm specifications. This paper describes a tool that allows trade studies and optimizations across these many options, by feeding an actual fusion algorithm via models of the system environment. Models and fusion algorithms can be specified and then exercised many times, with accumulated results used to compute performance metrics such as probability of correct identification. Performance differences between the best of the contributing sources and the fused result constitute examples of "gain." The tool, constructed as part of the Fusion for Identifying Targets Experiment (FITE) within the Air Force Research Laboratory (AFRL) Sensors Directorate ATR Thrust, finds its main use in examining the relationships among conditions affecting the target, prior information, fusion algorithm complexity, and fusion gain. ATR as an unsolved problem provides the main challenges to fusion in its high cost and relative scarcity of training data, its variability in application, the inability to produce truly random samples, and its sensitivity to context. This paper summarizes the mathematics underlying decision-level fusion in the ATR domain and describes a MATLAB-based architecture for exploring the trade space thus defined. Specific dimensions within this trade space are delineated, providing the raw material necessary to define experiments suitable for multi-look and multi-sensor ATR systems.

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

Fusion breeder

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moir, R.W.

1982-02-22

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

Fusion breeder

DOE Office of Scientific and Technical Information (OSTI.GOV)

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 outlinemore » specific research and development goals so that the fusion breeder will be developed in time to meet fissile fuel needs.« less

[Construction and expression of the targeting super-antigen EGF-SEA fusion gene].

PubMed

Xie, Yang; Peng, Shaoping; Liao, Zhiying; Liu, Jiafeng; Liu, Xuemei; Chen, Weifeng

2014-05-01

To construct expression vector for the SEA-EGF fusion gene. Clone the SEA gene and the EGF gene segment with PCR and RT-PCR independently, and connect this two genes by the bridge PCR. Insert the fusion gene EGF-SEA into the expression vector PET-44. Induced the secretion of the fusion protein SEA-EGF by the antileptic. The gene fragment encoding EGF and SEA mature peptide was successfully cloned. The fusion gene EGF-SEA was successfully constructed and was inserted into expression vector. The new recombinant expression vector for fusion gene EGF-SEA is specific for head and neck cancer, laid the foundation for the further study of fusion protein SEA-EGF targeting immune therapy in head and neck tumors.

Dicentric breakage at telomere fusions

PubMed Central

Pobiega, Sabrina; Marcand, Stéphane

2010-01-01

Nonhomologous end-joining (NHEJ) inhibition at telomeres ensures that native chromosome ends do not fuse together. But the occurrence and consequences of rare telomere fusions are not well understood. It is notably unclear whether a telomere fusion could be processed to restore telomere ends. Here we address the behavior of individual dicentrics formed by telomere fusion in the yeast Saccharomyces cerevisiae. Our approach was to first stabilize and amplify fusions between two chromosomes by temporarily inactivating one centromere. Next we analyzed dicentric breakage following centromere reactivation. Unexpectedly, dicentrics often break at the telomere fusions during progression through mitosis, a process that restores the parental chromosomes. This unforeseen result suggests a rescue pathway able to process telomere fusions and to back up NHEJ inhibition at telomeres. PMID:20360388

Records for conversion of laser energy to nuclear energy in exploding nanostructures

NASA Astrophysics Data System (ADS)

Jortner, Joshua; Last, Isidore

2017-09-01

Table-top nuclear fusion reactions in the chemical physics laboratory can be driven by high-energy dynamics of Coulomb exploding, multicharged, deuterium containing nanostructures generated by ultraintense, femtosecond, near-infrared laser pulses. Theoretical-computational studies of table-top laser-driven nuclear fusion of high-energy (up to 15 MeV) deuterons with 7Li, 6Li and D nuclei demonstrate the attainment of high fusion yields within a source-target reaction design, which constitutes the highest table-top fusion efficiencies obtained up to date. The conversion efficiency of laser energy to nuclear energy (0.1-1.0%) for table-top fusion is comparable to that for DT fusion currently accomplished for 'big science' inertial fusion setups.

Scientific and technological advancements in inertial fusion energy

DOE PAGES

Hinkel, D. E.

2013-09-26

Scientific advancements in inertial fusion energy (IFE) were reported on at the IAEA Fusion Energy Conference, October 2012. Results presented transect the different ways to assemble the fuel, different scenarios for igniting the fuel, and progress in IFE technologies. The achievements of the National Ignition Campaign within the USA, using the National Ignition Facility (NIF) to indirectly drive laser fusion, have found beneficial the achievements in other IFE arenas such as directly driven laser fusion and target fabrication. Moreover, the successes at NIF have pay-off to alternative scenarios such as fast ignition, shock ignition, and heavy-ion fusion as well asmore » to directly driven laser fusion. As a result, this synergy is summarized here, and future scientific studies are detailed.« less

Identification of Protein-Protein Interactions with Glutathione-S-Transferase (GST) Fusion Proteins.

PubMed

Einarson, Margret B; Pugacheva, Elena N; Orlinick, Jason R

2007-08-01

INTRODUCTIONGlutathione-S-transferase (GST) fusion proteins have had a wide range of applications since their introduction as tools for synthesis of recombinant proteins in bacteria. GST was originally selected as a fusion moiety because of several desirable properties. First and foremost, when expressed in bacteria alone, or as a fusion, GST is not sequestered in inclusion bodies (in contrast to previous fusion protein systems). Second, GST can be affinity-purified without denaturation because it binds to immobilized glutathione, which provides the basis for simple purification. Consequently, GST fusion proteins are routinely used for antibody generation and purification, protein-protein interaction studies, and biochemical analysis. This article describes the use of GST fusion proteins as probes for the identification of protein-protein interactions.

A phorbol ester-binding protein is required downstream of Rab5 in endosome fusion.

PubMed

Aballay, A; Barbieri, M A; Colombo, M I; Arenas, G N; Stahl, P D; Mayorga, L S

1998-12-28

Previous observations indicate that a zinc and phorbol ester binding factor is necessary for endosome fusion. To further characterize the role of this factor in the process, we used an in vitro endosome fusion assay supplemented with recombinant Rab5 proteins. Both zinc depletion and addition of calphostin C, an inhibitor of protein kinase C, inhibited endosome fusion in the presence of active Rab5. Addition of the phorbol ester PMA (phorbol 12-myristate 13-acetate) reversed the inhibition of endosome fusion caused by a Rab5 negative mutant. Moreover, PMA stimulated fusion in the presence of Rab5 immunodepleted cytosol. These results suggest that the phorbol ester binding protein is acting downstream of Rab5 in endosome fusion.

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)

Magnetized Target Fusion in Advanced Propulsion Research

NASA Technical Reports Server (NTRS)

Cylar, Rashad

2003-01-01

The Magnetized Target Fusion (MTF) Propulsion lab at NASA Marshall Space Flight Center in Huntsville, Alabama has a program in place that has adopted to attempt to create a faster, lower cost and more reliable deep space transportation system. In this deep space travel the physics and development of high velocity plasma jets must be understood. The MTF Propulsion lab is also in attempt to open up the solar system for human exploration and commercial use. Fusion, as compared to fission, is just the opposite. Fusion involves the light atomic nuclei combination to produce denser nuclei. In the process, the energy is created by destroying the mass according to the distinguished equation: E = mc2 . Fusion energy development is being pursued worldwide as a very sustainable form of energy that is environmentally friendly. For the purposes of space exploration fusion reactions considered include the isotopes of hydrogen-deuterium (D2) and tritium (T3). Nuclei have an electrostatic repulsion between them and in order for the nuclei to fuse this repulsion must be overcome. One technique to bypass repulsion is to heat the nuclei to very high temperatures. The temperatures vary according to the type of reactions. For D-D reactions, one billion degrees Celsius is required, and for D-T reactions, one hundred million degrees is sufficient. There has to be energy input for useful output to be obtained form the fusion To make fusion propulsion practical, the mass, the volume, and the cost of the equipment to produce the reactions (generally called the reactor) need to be reduced by an order of magnitude or two from the state-of-the-art fusion machines. Innovations in fusion schemes are therefore required, especially for obtaining thrust for propulsive applications. Magnetized target fusion (MTF) is one of the innovative fusion concepts that have emerged over the last several years. MSFC is working with Los Alamos National Laboratory and other research groups in studying the underlying principles involved in MTF. Magnetized Target Fusion is an attempt to combine MCF (magnetic confinement fusion) for energy confinement and ICF (inertial confinement fusion) for efficient compression heating and wall free containment of the fusing plasma. It also seeks to combine the best features to these two main commonplace approaches to fusion.

[The dependence of the range of fusion on some selected functions of the visual system. Part II: Accommodation and dominance].

PubMed

Adamek, Bogdan; Karczewicz, Danuta

2006-01-01

This present study is the continuation of Part I of the research into the range of fusion in which the difference between both eyeballs as far as convergent fusion is concerned was described. The phenomenon was called "visual unevenness of the range of convergent fusion". This part of the study is devoted to the analysis of the relationship between the unevenness of the fusion, ocular dominance and accommodation. A lower range of convergent fusion was observed in the dominant eye with the higher accommodation, In contrast, a higher range of fusion was observed in the not dominant eye with lower accommodation. The authors think that the phenomenon of ocular unevenness of the range of convergent fusion does not depend on the peripheral part of visual organ. In fact, it does seem to point out to a cortical process. The authors suggest that quantitative tests on amplitude of fusion should be carried out first on the first eye and then on the other. The results obtained from both eyes should be compared with each other.

Auto-fusion and the shaping of neurons and tubes

PubMed Central

Soulavie, Fabien; Sundaram, Meera V.

2016-01-01

Cells adopt specific shapes that are necessary for specific functions. For example, some neurons extend elaborate arborized dendrites that can contact multiple targets. Epithelial and endothelial cells can form tiny seamless unicellular tubes with an intracellular lumen. Recent advances showed that cells can auto-fuse to acquire those specific shapes. During auto-fusion, a cell merges two parts of its own plasma membrane. In contrast to cell-cell fusion or macropinocytic fission, which result in the merging or formation of two separate membrane bound compartments, auto-fusion preserves one compartment, but changes its shape. The discovery of auto-fusion in C. elegans was enabled by identification of specific protein fusogens, EFF-1 and AFF-1, that mediate cell-cell fusion. Phenotypic characterization of eff-1 and aff-1 mutants revealed that fusogen-mediated fusion of two parts of the same cell can be used to sculpt dendritic arbors, reconnect two parts of an axon after injury, or form a hollow unicellular tube. Similar auto-fusion events recently were detected in vertebrate cells, suggesting that auto-fusion could be a widely used mechanism for shaping neurons and tubes. PMID:27436685

Premature activation of the paramyxovirus fusion protein before target cell attachment with corruption of the viral fusion machinery.

PubMed

Farzan, Shohreh F; Palermo, Laura M; Yokoyama, Christine C; Orefice, Gianmarco; Fornabaio, Micaela; Sarkar, Aurijit; Kellogg, Glen E; Greengard, Olga; Porotto, Matteo; Moscona, Anne

2011-11-04

Paramyxoviruses, including the childhood pathogen human parainfluenza virus type 3, enter host cells by fusion of the viral and target cell membranes. This fusion results from the concerted action of its two envelope glycoproteins, the hemagglutinin-neuraminidase (HN) and the fusion protein (F). The receptor-bound HN triggers F to undergo conformational changes that render it competent to mediate fusion of the viral and cellular membranes. We proposed that, if the fusion process could be activated prematurely before the virion reaches the target host cell, infection could be prevented. We identified a small molecule that inhibits paramyxovirus entry into target cells and prevents infection. We show here that this compound works by an interaction with HN that results in F-activation prior to receptor binding. The fusion process is thereby prematurely activated, preventing fusion of the viral membrane with target cells and precluding viral entry. This first evidence that activation of a paramyxovirus F can be specifically induced before the virus contacts its target cell suggests a new strategy with broad implications for the design of antiviral agents.

Comprehensive Analysis of CBFβ-MYH11 Fusion Transcripts in Acute Myeloid Leukemia by RT-PCR Analysis

PubMed Central

Kadkol, ShriHari S.; Bruno, Annette; Dodge, Carol; Lindgren, Valerie; Ravandi, Farhad

2004-01-01

CBFβ-MYH11 fusion transcripts are expressed in acute myeloid leukemias of the M4Eo subtype. Patients who express CBFβ-MYH11 fusion transcripts respond favorably to high-dose chemotherapy and are generally spared allogeneic bone marrow transplantation. Hence it is important to identify this fusion in all patients with acute myeloid leukemia M4Eo leukemia. The fusion can be detected by cytogenetics, fluorescence in-situ hybridization (FISH), or by molecular analysis with RT-PCR. Multiple fusion transcripts arising as a result of various breakpoints in the CBFβ and MYH11 have been identified. In this report we describe a comprehensive RT-PCR assay to identify all known fusion transcripts and provide an algorithm for molecular analysis of CBFβ-MYH11 fusions from patient specimens. Further, identification of the fusion transcript by such an assay would help in the diagnosis and follow up of patients with cryptic inversion 16 translocations (such as patient 2 in this report) not detected by standard cytogenetics or FISH and for rational design of probes for quantitative analysis by real-time PCR. PMID:14736823

Positional effects of fusion partners on the yield and solubility of MBP fusion proteins.

PubMed

Raran-Kurussi, Sreejith; Keefe, Karina; Waugh, David S

2015-06-01

Escherichia coli maltose-binding protein (MBP) is exceptionally effective at promoting the solubility of its fusion partners. However, there are conflicting reports in the literature claiming that (1) MBP is an effective solubility enhancer only when it is joined to the N-terminus of an aggregation-prone passenger protein, and (2) MBP is equally effective when fused to either end of the passenger. Here, we endeavor to resolve this controversy by comparing the solubility of a diverse set of MBP fusion proteins that, unlike those analyzed in previous studies, are identical in every way except for the order of the two domains. The results indicate that fusion proteins with an N-terminal MBP provide an excellent solubility advantage along with more robust expression when compared to analogous fusions in which MBP is the C-terminal fusion partner. We find that only intrinsically soluble passenger proteins (i.e., those not requiring a solubility enhancer) are produced as soluble fusions when they precede MBP. We also report that even subtle differences in inter-domain linker sequences can influence the solubility of fusion proteins. Published by Elsevier Inc.

Positional effects of fusion partners on the yield and solubility of MBP fusion proteins

PubMed Central

Raran-Kurussi, Sreejith; Keefe, Karina; Waugh, David S.

2015-01-01

Escherichia coli maltose-binding protein (MBP) is exceptionally effective at promoting the solubility of its fusion partners. However, there are conflicting reports in the literature claiming that 1) MBP is an effective solubility enhancer only when it is joined to the N-terminus of an aggregation-prone passenger protein, and 2) MBP is equally effective when fused to either end of the passenger. Here, we endeavor to resolve this controversy by comparing the solubility of a diverse set of MBP fusion proteins that, unlike those analyzed in previous studies, are identical in every way except for the order of the two domains. The results indicate that fusion proteins with an N-terminal MBP provide an excellent solubility advantage along with more robust expression when compared to analogous fusions in which MBP is the C-terminal fusion partner. We find that only intrinsically soluble passenger proteins (i.e., those not requiring a solubility enhancer) are produced as soluble fusions when they precede MBP. We also report that even subtle differences in inter-domain linker sequences can influence the solubility of fusion proteins. PMID:25782741

Laser-induced fast fusion of gold nanoparticle-modified polyelectrolyte microcapsules.

PubMed

Wu, Yingjie; Frueh, Johannes; Si, Tieyan; Möhwald, Helmuth; He, Qiang

2015-02-07

In this study we investigated the effect of laser-induced membrane fusion of polyelectrolyte multilayer (PEM) based microcapsules bearing surface-attached gold nanoparticles (AuNPs) in aqueous media. We demonstrate that a dense coating of the capsules with AuNPs leads to enhanced light absorption, causing an increase of local temperature. This enhances the migration of polyelectrolytes within the PEMs and thus enables a complete fusion of two or more capsules. The encapsulated substances can achieve complete merging upon short-term laser irradiation (30 s, 30 mW @ 650 nm). The whole fusion process is followed by optical microscopy and scanning electron microscopy. In control experiments, microcapsules without AuNPs do not show a significant capsule fusion upon irradiation. It was also found that the duration of capsule fusion is affected by the density of AuNPs on the shell - the higher the density of AuNPs the shorter the fusion time. All these findings confirm that laser-induced microcapsule fusion is a new type of membrane fusion. This effect helps to study the interior exchange reactions of functional microcapsules, micro-reactors and drug transport across multilayers.

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

PubMed

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

2006-03-03

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

Telomeres and mechanisms of Robertsonian fusion.

PubMed

Slijepcevic, P

1998-05-01

The Robertsonian (Rb) fusion, a chromosome rearrangement involving centric fusion of two acro-(telo)centric chromosomes to form a single metacentric, is one of the most frequent events in mammalian karyotype evolution. Since one of the functions of telomeres is to preserve chromosome integrity, a prerequisite for the formation of Rb fusions should be either telomere loss or telomere inactivation. Possible mechanisms underlying the formation of various types of Rb fusion are discussed here. For example, Rb fusion in wild mice involves complete loss of p-arm telomeres by chromosome breakage within minor satellite sequences. By contrast, interstitial telomeric sites are found in the pericentromeric regions of chromosomes originating from a number of vertebrate species, suggesting the occurrence of Rb-like fusion without loss of telomeres, a possibility consistent with some form of telomere inactivation. Finally, a recent study suggests that telomere shortening induced by the deletion of the telomerase RNA gene in the mouse germ-line leads to telomere loss and high frequencies of Rb fusion in mouse somatic cells. Thus, at least three mechanisms in mammalian cells lead to the formation of Rb fusions.

a Comparative Analysis of Spatiotemporal Data Fusion Models for Landsat and Modis Data

NASA Astrophysics Data System (ADS)

Hazaymeh, K.; Almagbile, A.

2018-04-01

In this study, three documented spatiotemporal data fusion models were applied to Landsat-7 and MODIS surface reflectance, and NDVI. The algorithms included the spatial and temporal adaptive reflectance fusion model (STARFM), sparse representation based on a spatiotemporal reflectance fusion model (SPSTFM), and spatiotemporal image-fusion model (STI-FM). The objectives of this study were to (i) compare the performance of these three fusion models using a one Landsat-MODIS spectral reflectance image pairs using time-series datasets from the Coleambally irrigation area in Australia, and (ii) quantitatively evaluate the accuracy of the synthetic images generated from each fusion model using statistical measurements. Results showed that the three fusion models predicted the synthetic Landsat-7 image with adequate agreements. The STI-FM produced more accurate reconstructions of both Landsat-7 spectral bands and NDVI. Furthermore, it produced surface reflectance images having the highest correlation with the actual Landsat-7 images. This study indicated that STI-FM would be more suitable for spatiotemporal data fusion applications such as vegetation monitoring, drought monitoring, and evapotranspiration.

Fusion Safety Program annual report, fiscal year 1994

NASA Astrophysics Data System (ADS)

Longhurst, Glen R.; Cadwallader, Lee C.; Dolan, Thomas J.; Herring, J. Stephen; McCarthy, Kathryn A.; Merrill, Brad J.; Motloch, Chester C.; Petti, David A.

1995-03-01

This report summarizes the major activities of the Fusion Safety Program in fiscal year 1994. The Idaho National Engineering Laboratory (INEL) is the designated lead laboratory and Lockheed Idaho Technologies Company is the prime contractor for this program. The Fusion Safety Program was initiated in 1979. Activities are conducted at the INEL, at other DOE laboratories, and at other institutions, including the University of Wisconsin. The technical areas covered in this report include tritium safety, beryllium safety, chemical reactions and activation product release, safety aspects of fusion magnet systems, plasma disruptions, risk assessment failure rate data base development, and thermalhydraulics code development and their application to fusion safety issues. Much of this work has been done in support of the International Thermonuclear Experimental Reactor (ITER). Also included in the report are summaries of the safety and environmental studies performed by the Fusion Safety Program for the Tokamak Physics Experiment and the Tokamak Fusion Test Reactor and of the technical support for commercial fusion facility conceptual design studies. A major activity this year has been work to develop a DOE Technical Standard for the safety of fusion test facilities.

Distinct features of multivesicular body-lysosome fusion revealed by a new cell-free content-mixing assay.

PubMed

Karim, Mahmoud Abdul; Samyn, Dieter Ronny; Mattie, Sevan; Brett, Christopher Leonard

2018-02-01

When marked for degradation, surface receptor and transporter proteins are internalized and delivered to endosomes where they are packaged into intralumenal vesicles (ILVs). Many rounds of ILV formation create multivesicular bodies (MVBs) that fuse with lysosomes exposing ILVs to hydrolases for catabolism. Despite being critical for protein degradation, the molecular underpinnings of MVB-lysosome fusion remain unclear, although machinery underlying other lysosome fusion events is implicated. But how then is specificity conferred? And how is MVB maturation and fusion coordinated for efficient protein degradation? To address these questions, we developed a cell-free MVB-lysosome fusion assay using Saccharomyces cerevisiae as a model. After confirming that the Rab7 ortholog Ypt7 and the multisubunit tethering complex HOPS (homotypic fusion and vacuole protein sorting complex) are required, we found that the Qa-SNARE Pep12 distinguishes this event from homotypic lysosome fusion. Mutations that impair MVB maturation block fusion by preventing Ypt7 activation, confirming that a Rab-cascade mechanism harmonizes MVB maturation with lysosome fusion. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A Summary of the NASA Fusion Propulsion Workshop 2000

NASA Technical Reports Server (NTRS)

Thio, Y. C. Francis; Turchi, Peter J.; Santarius, John F.; Schafer, Charles (Technical Monitor)

2001-01-01

A NASA Fusion Propulsion Workshop was held on Nov. 8 and 9, 2000 at Marshall Space Flight Center (MSFC) in Huntsville, Alabama. A total of 43 papers were presented at the Workshop orally or by posters, covering a broad spectrum of issues related to applying fusion to propulsion. The status of fusion research was reported at the Workshop showing the outstanding scientific research that has been accomplished worldwide in the fusion energy research program. The international fusion research community has demonstrated the scientific principles of fusion creating plasmas with conditions for fusion burn with a gain of order unity: 0.25 in Princeton TFTR, 0.65 in the Joint European Torus, and a Q-equivalent of 1.25 in Japan's JT-60. This research has developed an impressive range of physics and technological capabilities that may be applied effectively to the research of possibly new propulsion-oriented fusion schemes. The pertinent physics capabilities include the plasma computational tools, the experimental plasma facilities, the diagnostics techniques, and the theoretical understanding. The enabling technologies include the various plasma heating, acceleration, and the pulsed power technologies.

Engineered three-dimensional multicellular culture model to recapitulate morphogenetic fusion using human cells

EPA Science Inventory

Tissue fusion during early mammalian development requires crosstalk between multiple cell types. For example, paracrine signaling between palatal epithelial cells and palatal mesenchyme mediates the fusion of opposing palatal shelves during embryonic development. Fusion events in...

A Review of Data Fusion Techniques

PubMed Central

2013-01-01

The integration of data and knowledge from several sources is known as data fusion. This paper summarizes the state of the data fusion field and describes the most relevant studies. We first enumerate and explain different classification schemes for data fusion. Then, the most common algorithms are reviewed. These methods and algorithms are presented using three different categories: (i) data association, (ii) state estimation, and (iii) decision fusion. PMID:24288502

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hazeltine, Richard D.

The mission of the Institute for Fusion Studies has been to serve as a national center for theoretical fusion and plasma physics research. As an independent scientific group of critical size, its objectives were to conduct research on fundamental phenomena important to fusion; to serve as a center for fusion theory exchange activities with other countries; to exchange scientific developments with other academic disciplines; and to train students and postdoctoral fellows in fusion and plasma physics research.

Laser-induced fusion of human embryonic stem cells with optical tweezers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen Shuxun; Wang Xiaolin; Sun Dong

2013-07-15

We report a study on the laser-induced fusion of human embryonic stem cells (hESCs) at the single-cell level. Cells were manipulated by optical tweezers and fused under irradiation with pulsed UV laser at 355 nm. Successful fusion was indicated by green fluorescence protein transfer. The influence of laser pulse energy on the fusion efficiency was investigated. The fused products were viable as gauged by live cell staining. Successful fusion of hESCs with somatic cells was also demonstrated. The reported fusion outcome may facilitate studies of cell differentiation, maturation, and reprogramming.

Objective quality assessment for multiexposure multifocus image fusion.

PubMed

Hassen, Rania; Wang, Zhou; Salama, Magdy M A

2015-09-01

There has been a growing interest in image fusion technologies, but how to objectively evaluate the quality of fused images has not been fully understood. Here, we propose a method for objective quality assessment of multiexposure multifocus image fusion based on the evaluation of three key factors of fused image quality: 1) contrast preservation; 2) sharpness; and 3) structure preservation. Subjective experiments are conducted to create an image fusion database, based on which, performance evaluation shows that the proposed fusion quality index correlates well with subjective scores, and gives a significant improvement over the existing fusion quality measures.

A small molecule fusion inhibitor of dengue virus.

PubMed

Poh, Mee Kian; Yip, Andy; Zhang, Summer; Priestle, John P; Ma, Ngai Ling; Smit, Jolanda M; Wilschut, Jan; Shi, Pei-Yong; Wenk, Markus R; Schul, Wouter

2009-12-01

The dengue virus envelope protein plays an essential role in viral entry by mediating fusion between the viral and host membranes. The crystal structure of the envelope protein shows a pocket (located at a "hinge" between Domains I and II) that can be occupied by ligand n-octyl-beta-D-glucoside (betaOG). Compounds blocking the betaOG pocket are thought to interfere with conformational changes in the envelope protein that are essential for fusion. Two fusion assays were developed to examine the anti-fusion activities of compounds. The first assay measures the cellular internalization of propidium iodide upon membrane fusion. The second assay measures the protease activity of trypsin upon fusion between dengue virions and trypsin-containing liposomes. We performed an in silico virtual screening for small molecules that can potentially bind to the betaOG pocket and tested these candidate molecules in the two fusion assays. We identified one compound that inhibits dengue fusion in both assays with an IC(50) of 6.8 microM and reduces viral titers with an EC(50) of 9.8 microM. Time-of-addition experiments showed that the compound was only active when present during viral infection but not when added 1h later, in agreement with a mechanism of action through fusion inhibition.

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.

ChimerDB 3.0: an enhanced database for fusion genes from cancer transcriptome and literature data mining.

PubMed

Lee, Myunggyo; Lee, Kyubum; Yu, Namhee; Jang, Insu; Choi, Ikjung; Kim, Pora; Jang, Ye Eun; Kim, Byounggun; Kim, Sunkyu; Lee, Byungwook; Kang, Jaewoo; Lee, Sanghyuk

2017-01-04

Fusion gene is an important class of therapeutic targets and prognostic markers in cancer. ChimerDB is a comprehensive database of fusion genes encompassing analysis of deep sequencing data and manual curations. In this update, the database coverage was enhanced considerably by adding two new modules of The Cancer Genome Atlas (TCGA) RNA-Seq analysis and PubMed abstract mining. ChimerDB 3.0 is composed of three modules of ChimerKB, ChimerPub and ChimerSeq. ChimerKB represents a knowledgebase including 1066 fusion genes with manual curation that were compiled from public resources of fusion genes with experimental evidences. ChimerPub includes 2767 fusion genes obtained from text mining of PubMed abstracts. ChimerSeq module is designed to archive the fusion candidates from deep sequencing data. Importantly, we have analyzed RNA-Seq data of the TCGA project covering 4569 patients in 23 cancer types using two reliable programs of FusionScan and TopHat-Fusion. The new user interface supports diverse search options and graphic representation of fusion gene structure. ChimerDB 3.0 is available at http://ercsb.ewha.ac.kr/fusiongene/. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Homeland security application of the Army Soft Target Exploitation and Fusion (STEF) system

NASA Astrophysics Data System (ADS)

Antony, Richard T.; Karakowski, Joseph A.

2010-04-01

A fusion system that accommodates both text-based extracted information along with more conventional sensor-derived input has been developed and demonstrated in a terrorist attack scenario as part of the Empire Challenge (EC) 09 Exercise. Although the fusion system was developed to support Army military analysts, the system, based on a set of foundational fusion principles, has direct applicability to department of homeland security (DHS) & defense, law enforcement, and other applications. Several novel fusion technologies and applications were demonstrated in EC09. One such technology is location normalization that accommodates both fuzzy semantic expressions such as behind Library A, across the street from the market place, as well as traditional spatial representations. Additionally, the fusion system provides a range of fusion products not supported by traditional fusion algorithms. Many of these additional capabilities have direct applicability to DHS. A formal test of the fusion system was performed during the EC09 exercise. The system demonstrated that it was able to (1) automatically form tracks, (2) help analysts visualize behavior of individuals over time, (3) link key individuals based on both explicit message-based information as well as discovered (fusion-derived) implicit relationships, and (4) suggest possible individuals of interest based on their association with High Value Individuals (HVI) and user-defined key locations.

Membrane Fusion Induced by Small Molecules and Ions

PubMed Central

Mondal Roy, Sutapa; Sarkar, Munna

2011-01-01

Membrane fusion is a key event in many biological processes. These processes are controlled by various fusogenic agents of which proteins and peptides from the principal group. The fusion process is characterized by three major steps, namely, inter membrane contact, lipid mixing forming the intermediate step, pore opening and finally mixing of inner contents of the cells/vesicles. These steps are governed by energy barriers, which need to be overcome to complete fusion. Structural reorganization of big molecules like proteins/peptides, supplies the required driving force to overcome the energy barrier of the different intermediate steps. Small molecules/ions do not share this advantage. Hence fusion induced by small molecules/ions is expected to be different from that induced by proteins/peptides. Although several reviews exist on membrane fusion, no recent review is devoted solely to small moleculs/ions induced membrane fusion. Here we intend to present, how a variety of small molecules/ions act as independent fusogens. The detailed mechanism of some are well understood but for many it is still an unanswered question. Clearer understanding of how a particular small molecule can control fusion will open up a vista to use these moleucles instead of proteins/peptides to induce fusion both in vivo and in vitro fusion processes. PMID:21660306

Direct transfer of learned behaviour via cell fusion in non-neural organisms

PubMed Central

Vogel, David

2016-01-01

Cell fusion is a fundamental phenomenon observed in all eukaryotes. Cells can exchange resources such as molecules or organelles during fusion. In this paper, we ask whether a cell can also transfer an adaptive response to a fusion partner. We addressed this question in the unicellular slime mould Physarum polycephalum, in which cell–cell fusion is extremely common. Slime moulds are capable of habituation, a simple form of learning, when repeatedly exposed to an innocuous repellent, despite lacking neurons and comprising only a single cell. In this paper, we present a set of experiments demonstrating that slime moulds habituated to a repellent can transfer this adaptive response by cell fusion to individuals that have never encountered the repellent. In addition, we show that a slime mould resulting from the fusion of a minority of habituated slime moulds and a majority of unhabituated ones still shows an adaptive response to the repellent. Finally, we further reveal that fusion must last a certain time to ensure an effective transfer of the behavioural adaptation between slime moulds. Our results provide strong experimental evidence that slime moulds exhibit transfer of learned behaviour during cell fusion and raise the possibility that similar phenomena may occur in other cell–cell fusion systems. PMID:28003457

Cell fusion in the liver, revisited

PubMed Central

Lizier, Michela; Castelli, Alessandra; Montagna, Cristina; Lucchini, Franco; Vezzoni, Paolo; Faggioli, Francesca

2018-01-01

There is wide agreement that cell fusion is a physiological process in cells in mammalian bone, muscle and placenta. In other organs, such as the cerebellum, cell fusion is controversial. The liver contains a considerable number of polyploid cells: They are commonly believed to originate by genome endoreplication, although the contribution of cell fusion to polyploidization has not been excluded. Here, we address the topic of cell fusion in the liver from a historical point of view. We discuss experimental evidence clearly supporting the hypothesis that cell fusion occurs in the liver, specifically when bone marrow cells were injected into mice and shown to rescue genetic hepatic degenerative defects. Those experiments-carried out in the latter half of the last century-were initially interpreted to show “transdifferentiation”, but are now believed to demonstrate fusion between donor macrophages and host hepatocytes, raising the possibility that physiologically polyploid cells, such as hepatocytes, could originate, at least partially, through homotypic cell fusion. In support of the homotypic cell fusion hypothesis, we present new data generated using a chimera-based model, a much simpler model than those previously used. Cell fusion as a road to polyploidization in the liver has not been extensively investigated, and its contribution to a variety of conditions, such as viral infections, carcinogenesis and aging, remains unclear. PMID:29527257

Real-time sensor validation and fusion for distributed autonomous sensors

NASA Astrophysics Data System (ADS)

Yuan, Xiaojing; Li, Xiangshang; Buckles, Bill P.

2004-04-01

Multi-sensor data fusion has found widespread applications in industrial and research sectors. The purpose of real time multi-sensor data fusion is to dynamically estimate an improved system model from a set of different data sources, i.e., sensors. This paper presented a systematic and unified real time sensor validation and fusion framework (RTSVFF) based on distributed autonomous sensors. The RTSVFF is an open architecture which consists of four layers - the transaction layer, the process fusion layer, the control layer, and the planning layer. This paradigm facilitates distribution of intelligence to the sensor level and sharing of information among sensors, controllers, and other devices in the system. The openness of the architecture also provides a platform to test different sensor validation and fusion algorithms and thus facilitates the selection of near optimal algorithms for specific sensor fusion application. In the version of the model presented in this paper, confidence weighted averaging is employed to address the dynamic system state issue noted above. The state is computed using an adaptive estimator and dynamic validation curve for numeric data fusion and a robust diagnostic map for decision level qualitative fusion. The framework is then applied to automatic monitoring of a gas-turbine engine, including a performance comparison of the proposed real-time sensor fusion algorithms and a traditional numerical weighted average.

Regulation of Herpes Simplex Virus Glycoprotein-Induced Cascade of Events Governing Cell-Cell Fusion

PubMed Central

Saw, Wan Ting; Eisenberg, Roselyn J.; Cohen, Gary H.

2016-01-01

ABSTRACT Receptor-dependent herpes simplex virus (HSV)-induced cell-cell fusion requires glycoproteins gD, gH/gL, and gB. Our current model posits that during fusion, receptor-activated conformational changes in gD activate gH/gL, which subsequently triggers the transformation of the prefusion form of gB into a fusogenic state. To examine the role of each glycoprotein in receptor-dependent cell-cell fusion, we took advantage of our discovery that fusion by wild-type herpes simplex virus 2 (HSV-2) glycoproteins occurs twice as fast as that achieved by HSV-1 glycoproteins. By sequentially swapping each glycoprotein between the two serotypes, we established that fusion speed was governed by gH/gL, with gH being the main contributor. While the mutant forms of gB fuse at distinct rates that are dictated by their molecular structure, these restrictions can be overcome by gH/gL of HSV-2 (gH2/gL2), thereby enhancing their activity. We also found that deregulated forms of gD of HSV-1 (gD1) and gH2/gL2 can alter the fusogenic potential of gB, promoting cell fusion in the absence of a cellular receptor, and that deregulated forms of gB can drive the fusion machinery to even higher levels. Low pH enhanced fusion by affecting the structure of both gB and gH/gL mutants. Together, our data highlight the complexity of the fusion machinery, the impact of the activation state of each glycoprotein on the fusion process, and the critical role of gH/gL in regulating HSV-induced fusion. IMPORTANCE Cell-cell fusion mediated by HSV glycoproteins requires gD, gH/gL, gB, and a gD receptor. Here, we show that fusion by wild-type HSV-2 glycoproteins occurs twice as fast as that achieved by HSV-1 glycoproteins. By sequentially swapping each glycoprotein between the two serotypes, we found that the fusion process was controlled by gH/gL. Restrictions imposed on the gB structure by mutations could be overcome by gH2/gL2, enhancing the activity of the mutants. Under low-pH conditions or when using deregulated forms of gD1 and gH2/gL2, the fusogenic potential of gB could only be increased in the absence of receptor, underlining the exquisite regulation that occurs in the presence of receptor. Our data highlight the complexity of the fusion machinery, the impact of the activation state of each glycoprotein on the fusion process, and the critical role of gH/gL in regulating HSV-induced fusion. PMID:27630245

Disc replacement adjacent to cervical fusion: a biomechanical comparison of hybrid construct versus two-level fusion.

PubMed

Lee, Michael J; Dumonski, Mark; Phillips, Frank M; Voronov, Leonard I; Renner, Susan M; Carandang, Gerard; Havey, Robert M; Patwardhan, Avinash G

2011-11-01

A cadaveric biomechanical study. To investigate the biomechanical behavior of the cervical spine after cervical total disc replacement (TDR) adjacent to a fusion as compared to a two-level fusion. There are concerns regarding the biomechanical effects of cervical fusion on the mobile motion segments. Although previous biomechanical studies have demonstrated that cervical disc replacement normalizes adjacent segment motion, there is a little information regarding the function of a cervical disc replacement adjacent to an anterior cervical decompression and fusion, a potentially common clinical application. Nine cadaveric cervical spines (C3-T1, age: 60.2 ± 3.5 years) were tested under load- and displacement-control testing. After intact testing, a simulated fusion was performed at C4-C5, followed by C6-C7. The simulated fusion was then reversed, and the response of TDR at C5-C6 was measured. A hybrid construct was then tested with the TDR either below or above a single-level fusion and contrasted with a simulated two-level fusion (C4-C6 and C5-C7). The external fixator device used to simulate fusion significantly reduced range of motion (ROM) at C4-C5 and C6-C7 by 74.7 ± 8.1% and 78.1 ± 11.5%, respectively (P < 0.05). Removal of the fusion construct restored the motion response of the spinal segments to their intact state. Arthroplasty performed at C5-C6 using the porous-coated motion disc prosthesis maintained the total flexion-extension ROM to the level of the intact controls when used as a stand-alone procedure or when implanted adjacent to a single-level fusion (P > 0.05). The location of the single-level fusion, whether above or below the arthroplasty, did not significantly affect the motion response of the arthroplasty in the hybrid construct. Performing a two-level fusion significantly increased the motion demands on the nonoperated segments as compared to a hybrid TDR-plus fusion construct when the spine was required to reach the same motion end points. The spine with a hybrid construct required significantly less extension moment than the spine with a two-level fusion to reach the same extension end point. The porous-coated motion cervical prosthesis restored the ROM of the treated level to the intact state. When the porous-coated motion prosthesis was used in a hybrid construct, the TDR response was not adversely affected. A hybrid construct seems to offer significant biomechanical advantages over two-level fusion in terms of reducing compensatory adjacent-level hypermobility and also loads required to achieve a predetermined ROM.

Lumbar spinal fusion. Outcome in relation to surgical methods, choice of implant and postoperative rehabilitation.

PubMed

Christensen, Finn Bjarke

2004-10-01

Chronic low back pain (CLBP) has become one of the most common causes of disability in adults under 45 years of age and is consequently one of the most common reasons for early retirement in industrialised societies. Accordingly, CLBP represents an expensive drain on society's resources and is a very challenging area for which a consensus for rational therapy is yet to be established. The spinal fusion procedure was introduced as a treatment option for CLBP more than 70 years ago. However, few areas of spinal surgery have caused so much controversy as spinal fusion. The literature reveals divergent opinions about when fusion is indicated and how it should be performed. Furthermore, the significance of the role of postoperative rehabilitation following spinal fusion may be underestimated. There exists no consensus on the design of a program specific for rehabilitation. Ideally, for any given surgical procedure, it should be possible to identify not only possible complications relative to a surgical procedure, but also what symptoms may be expected, and what pain behaviour may be expected of a particular patient. The overall aims of the current studies were: 1) to introduce patient-based functional outcome evaluation into spinal fusion treatment; 2) to evaluate radiological assessment of different spinal fusion procedures; 3) to investigate the effect of titanium versus stainless steel pedicle screws on mechanical fixation and bone ingrowth in lumbar spinal fusion; 4) to analyse the clinical and radiological outcome of different lumbar spinal fusion techniques; 5) to evaluate complications and re-operation rates following different surgical procedures; and 6) to analyse the effect of different rehabilitation strategies for lumbar spinal fusion patients. The present thesis comprises 9 studies: 2 clinical retrospective studies, 1 clinical prospective case/reference study, 5 clinical randomised prospective studies and 1 animal study (Mini-pigs). In total, 594 patients were included in the investigation from 1979 to 1999. Each had prior to inclusion at least 2 years of CLBP and had therefore been subjected to most of the conservative treatment leg pain, due to localized isthmic spondylolisthesis grades I-II or primary or secondary degeneration. PATIENT-BASED FUNCTIONAL OUTCOME: Patients' self-reported parameters should include the impact of CLBP on daily activity, work and leisure time activities, anxiety/depression, social interests and intensity of back and leg pain. Between 1993 and 2003 approximately 1400 lumbar spinal fusion patients completed the Dallas Pain Questionnaire under prospective design studies. In 1996, the Low Back Pain Rating scale was added to the standard questionnaire packet distributed among spinal fusion patients. In our experience, these tools are valid instruments for clinical assessment of candidates for spinal fusion procedures. It is extremely difficult to interpret radiographs of both lumbar posterolateral fusion and anterior interbody fusion. Plain radiographs are clearly not the perfect media for analysis of spinal fusion, but until new and better diagnostic methods are available for clinical use, radiographs will remain the golden standard. Therefore, the development of a detailed reliable radiographic classification system is highly desirable. The classification used in the present thesis for the evaluation of posteroalteral spinal fusion, both with and without instrumentation, demonstrated good interobserver and intraobserver agreement. The classification showed acceptable reliability and may be one way to improve interstudy and intrastudy correlation of radiologic outcomes after posterolateral spinal fusion. Radiology-based evaluation of anterior lumbar interbody fusion is further complicated when cages are employed. The use of different cage designs and materials makes it almost impossible to establish a standard radiological classification system for anterior fusions. BONE-SCREW INTERFACE: Mechanical binding at the bone-screw interface was significantly greater for titanium pedicle screws than it was for stainless steel. This could be explained by the fact that the titanium screws had superior bone on-growth. There was no correlation between screw removal torques and pull-out strength. Clinically, the use of titanium and titanium-alloy pedicle screws may be preferable for osteoporotic patients and those with decreased osteogenesis. The present series of studies observed significant long-term functional improvement for approximately 70% of patients who had undergone lumbar spinal fusion procedure. Solid fusion as determined from radiographs ranged from 52% to 92% depending on the choice of surgical procedure. The choice of surgical procedure should relate to the diagnosis, as patients with isthmic spondylolisthesis (Grades I and II) are best served with posterolateral fusion without instrumentation, and patients with disc degeneration seem to gain most from instrumented posterolateral fusion or circumferential fusion. The number of perioperative complications increased with the use of pedicle screw systems to support posterolateral fusions and increased further with the use of circumferential fusions. There was no significant association between outcome result and perioperative complications. The risk of reoperation within 2 years after the spinal fusion procedure was, however, significantly lower for those who had received circumferential fusion in comparison to posterolateral fusion with instrumentation. Furthermore, the risk of non-union was found to be significantly lower for patients who had received circumferential fusion as compared to posterolateral fusion with and without instrumentation. The complications of sexual dysfunction and fusion at non-intended levels were found to be significant but without influence on the overall outcome. The patients in the Back-café group performed a succession of many daily tasks significantly better and moreover had less pain compared with both the Video and Training groups 2 years after lumbar spinal fusion. The Video group had significantly greater treatment demands outside the hospital system. This study demonstrates the importance of the inclusion of coping schemes and questions the role of intensive exercises in a rehabilitation program for spinal fusion patients.

Induction of cell-cell fusion by ectromelia virus is not inhibited by its fusion inhibitory complex.

PubMed

Erez, Noam; Paran, Nir; Maik-Rachline, Galia; Politi, Boaz; Israely, Tomer; Schnider, Paula; Fuchs, Pinhas; Melamed, Sharon; Lustig, Shlomo

2009-09-29

Ectromelia virus, a member of the Orthopox genus, is the causative agent of the highly infectious mousepox disease. Previous studies have shown that different poxviruses induce cell-cell fusion which is manifested by the formation of multinucleated-giant cells (polykaryocytes). This phenomenon has been widely studied with vaccinia virus in conditions which require artificial acidification of the medium. We show that Ectromelia virus induces cell-cell fusion under neutral pH conditions and requires the presence of a sufficient amount of viral particles on the plasma membrane of infected cells. This could be achieved by infection with a replicating virus and its propagation in infected cells (fusion "from within") or by infection with a high amount of virus particles per cell (fusion "from without"). Inhibition of virus maturation or inhibition of virus transport on microtubules towards the plasma membrane resulted in a complete inhibition of syncytia formation. We show that in contrast to vaccinia virus, Ectromelia virus induces cell-cell fusion irrespectively of its hemagglutination properties and cell-surface expression of the orthologs of the fusion inhibitory complex, A56 and K2. Additionally, cell-cell fusion was also detected in mice lungs following lethal respiratory infection. Ectromelia virus induces spontaneous cell-cell fusion in-vitro and in-vivo although expressing an A56/K2 fusion inhibitory complex. This syncytia formation property cannot be attributed to the 37 amino acid deletion in ECTV A56.

Embedding the results of focussed Bayesian fusion into a global context

NASA Astrophysics Data System (ADS)

Sander, Jennifer; Heizmann, Michael

2014-05-01

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

The transition zone above a lumbosacral fusion.

PubMed

Hambly, M F; Wiltse, L L; Raghavan, N; Schneiderman, G; Koenig, C

1998-08-15

The clinical and radiographic effect of a lumbar or lumbosacral fusion was studied in 42 patients who had undergone a posterolateral fusion with an average follow-up of 22.6 years. To examine the long-term effects of posterolateral lumbar or lumbosacral fusion on the cephalad two motion segments (transition zone). It is commonly held that accelerated degeneration occurs in the motion segments adjacent to a fusion. Most studies are of short-term, anecdotal, uncontrolled reports that pay particular attention only to the first motion segment immediately cephalad to the fusion. Forty-two patients who had previously undergone a posterolateral lumbar or lumbosacral fusion underwent radiographic and clinical evaluation. Rate of fusion, range of motion, osteophytes, degenerative spondylolisthesis, retrolisthesis, facet arthrosis, disc ossification, dynamic instability, and disc space height were all studied and statistically compared with an age- and gender-matched control group. The patient's self-reported clinical outcome was also recorded. Degenerative changes occurred at the second level above the fused levels with a frequency equal to those occurring in the first level. There was no statistical difference between the study group and the cohort group in the presence of radiographic changes within the transition zone. In those patients undergoing fusion for degenerative processes, 75% reported a good to excellent outcome, whereas 84% of those undergoing fusion for spondylolysis or spondylolisthesis reported a good to excellent outcome. Radiographic changes occur within the transition zone cephalad to a lumbar or lumbosacral fusion. However, these changes are also seen in control subjects who have had no surgery.

Feasibility study on sensor data fusion for the CP-140 aircraft: fusion architecture analyses

NASA Astrophysics Data System (ADS)

Shahbazian, Elisa

1995-09-01

Loral Canada completed (May 1995) a Department of National Defense (DND) Chief of Research and Development (CRAD) contract, to study the feasibility of implementing a multi- sensor data fusion (MSDF) system onboard the CP-140 Aurora aircraft. This system is expected to fuse data from: (a) attributed measurement oriented sensors (ESM, IFF, etc.); (b) imaging sensors (FLIR, SAR, etc.); (c) tracking sensors (radar, acoustics, etc.); (d) data from remote platforms (data links); and (e) non-sensor data (intelligence reports, environmental data, visual sightings, encyclopedic data, etc.). Based on purely theoretical considerations a central-level fusion architecture will lead to a higher performance fusion system. However, there are a number of systems and fusion architecture issues involving fusion of such dissimilar data: (1) the currently existing sensors are not designed to provide the type of data required by a fusion system; (2) the different types (attribute, imaging, tracking, etc.) of data may require different degree of processing, before they can be used within a fusion system efficiently; (3) the data quality from different sensors, and more importantly from remote platforms via the data links must be taken into account before fusing; and (4) the non-sensor data may impose specific requirements on the fusion architecture (e.g. variable weight/priority for the data from different sensors). This paper presents the analyses performed for the selection of the fusion architecture for the enhanced sensor suite planned for the CP-140 aircraft in the context of the mission requirements and environmental conditions.

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

EPA Science Inventory

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

A model for explaining fusion suppression using classical trajectory method

NASA Astrophysics Data System (ADS)

Phookan, C. K.; Kalita, K.

2015-01-01

We adopt a semi-classical approach for explanation of projectile breakup and above barrier fusion suppression for the reactions 6Li+152Sm and 6Li+144Sm. The cut-off impact parameter for fusion is determined by employing quantum mechanical ideas. Within this cut-off impact parameter for fusion, the fraction of projectiles undergoing breakup is determined using the method of classical trajectory in two-dimensions. For obtaining the initial conditions of the equations of motion, a simplified model of the 6Li nucleus has been proposed. We introduce a simple formula for explanation of fusion suppression. We find excellent agreement between the experimental and calculated fusion cross section. A slight modification of the above formula for fusion suppression is also proposed for a three-dimensional model.

Extracellular annexins and dynamin are important for sequential steps in myoblast fusion

PubMed Central

Leikina, Evgenia; Melikov, Kamran; Sanyal, Sarmistha; Verma, Santosh K.; Eun, Bokkee; Gebert, Claudia; Pfeifer, Karl; Lizunov, Vladimir A.; Kozlov, Michael M.

2013-01-01

Myoblast fusion into multinucleated myotubes is a crucial step in skeletal muscle development and regeneration. Here, we accumulated murine myoblasts at the ready-to-fuse stage by blocking formation of early fusion intermediates with lysophosphatidylcholine. Lifting the block allowed us to explore a largely synchronized fusion. We found that initial merger of two cell membranes detected as lipid mixing involved extracellular annexins A1 and A5 acting in a functionally redundant manner. Subsequent stages of myoblast fusion depended on dynamin activity, phosphatidylinositol(4,5)bisphosphate content, and cell metabolism. Uncoupling fusion from preceding stages of myogenesis will help in the analysis of the interplay between protein machines that initiate and complete cell unification and in the identification of additional protein players controlling different fusion stages. PMID:23277424

Fusion cross sections for reactions involving medium and heavy nucleus-nucleus systems

NASA Astrophysics Data System (ADS)

Atta, Debasis; Basu, D. N.

2014-12-01

Existing data on near-barrier fusion excitation functions of medium and heavy nucleus-nucleus systems have been analyzed by using a simple diffused-barrier formula derived assuming the Gaussian shape of the barrier-height distributions. The fusion cross section is obtained by folding the Gaussian barrier distribution with the classical expression for the fusion cross section for a fixed barrier. The energy dependence of the fusion cross section, thus obtained, provides good description to the existing data on near-barrier fusion and capture excitation functions for medium and heavy nucleus-nucleus systems. The theoretical values for the parameters of the barrier distribution are estimated which can be used for fusion or capture cross-section predictions that are especially important for planning experiments for synthesizing new superheavy elements.

NASA-NIAC 2001 Phase I Research Grant on Aneutronic Fusion Spacecraft Architecture

NASA Technical Reports Server (NTRS)

Tarditi, Alfonso G. (Principal Investigator); Scott, John H.; Miley, George H.

2012-01-01

This study was developed because the recognized need of defining of a new spacecraft architecture suitable for aneutronic fusion and featuring game-changing space travel capabilities. The core of this architecture is the definition of a new kind of fusion-based space propulsion system. This research is not about exploring a new fusion energy concept, it actually assumes the availability of an aneutronic fusion energy reactor. The focus is on providing the best (most efficient) utilization of fusion energy for propulsion purposes. The rationale is that without a proper architecture design even the utilization of a fusion reactor as a prime energy source for spacecraft propulsion is not going to provide the required performances for achieving a substantial change of current space travel capabilities.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Henderson, Ian M.; Collins, Aaron M.; Quintana, Hope A.

In this study, we develop a quantitative dye dequenching technique for the measurement of polymersome fusion, using it to characterize the salt mediated, mechanically-induced fusion of polymersomes with polymer, lipid, and so-called stealth lipid vesicles. While dye dequenching has been used to quantitatively explore liposome fusion in the past, this is the first use of dye dequenching to measure polymersome fusion of which we are aware. In addition to providing quantitative results, dye dequenching is ideal for detecting fusion in instances where DLS results would be ambiguous, such as low yield levels and size ranges outside the capabilities of DLS.more » The dye chosen for this study was a cyanine derivative, 1,1'-dioctadecyl-3,3,3',3'-tetramethylindotricarbocyanine iodide (DiR), which proved to provide excellent data on the extent of polymersome fusion. Using this technique, we have shown the limited fusion capabilities of polymersome/liposome heterofusion, notably DOPC vesicles fusing with polymersomes at half the efficiency of polymersome homofusion and DPPC vesicles showing virtually no fusion. In addition to these key heterofusion experiments, we determined the broad applicability of dye dequenching in measuring kinetic rates of polymersome fusion; and showed that even at elevated temperatures or over multiple weeks' time, no polymersome fusion occurred without agitation. Stealth liposomes formed from DPPC and PEO-functionalized lipid, however, fused with polymersomes and stealth liposomes with relatively high efficiency, lending support to our hypothesis that the response of the PEO corona to salt is a key factor in the fusion process. This last finding suggests that although the conjugation of PEO to lipids increases vesicle biocompatibility and enables their longer circulation times, it also renders the vesicles subject to destabilization under high salt and shear (e.g. in the circulatory system) that may lead to, in this case, fusion.« less

Tyrosine kinase fusion genes in pediatric BCR-ABL1-like acute lymphoblastic leukemia

PubMed Central

Boer, Judith M.; Steeghs, Elisabeth M.P.; Marchante, João R.M.; Boeree, Aurélie; Beaudoin, James J.; Berna Beverloo, H.; Kuiper, Roland P.; Escherich, Gabriele; van der Velden, Vincent H.J.; van der Schoot, C. Ellen; de Groot-Kruseman, Hester A.; Pieters, Rob; den Boer, Monique L.

2017-01-01

Approximately 15% of pediatric B cell precursor acute lymphoblastic leukemia (BCP-ALL) is characterized by gene expression similar to that of BCR-ABL1-positive disease and unfavorable prognosis. This BCR-ABL1-like subtype shows a high frequency of B-cell development gene aberrations and tyrosine kinase-activating lesions. To evaluate the clinical significance of tyrosine kinase gene fusions in children with BCP-ALL, we studied the frequency of recently identified tyrosine kinase fusions, associated genetic features, and prognosis in a representative Dutch/German cohort. We identified 14 tyrosine kinase fusions among 77 BCR-ABL1-like cases (18%) and none among 76 non-BCR-ABL1-like B-other cases. Novel exon fusions were identified for RCSD1-ABL2 and TERF2-JAK2. JAK2 mutation was mutually exclusive with tyrosine kinase fusions and only occurred in cases with high CRLF2 expression. The non/late response rate and levels of minimal residual disease in the fusion-positive BCR-ABL1-like group were higher than in the non-BCR-ABL1-like B-others (p<0.01), and also higher, albeit not statistically significant, compared with the fusion-negative BCR-ABL1-like group. The 8-year cumulative incidence of relapse in the fusion-positive BCR-ABL1-like group (35%) was comparable with that in the fusion-negative BCR-ABL1-like group (35%), and worse than in the non-BCR-ABL1-like B-other group (17%, p=0.07). IKZF1 deletions, predominantly other than the dominant-negative isoform and full deletion, co-occurred with tyrosine kinase fusions. This study shows that tyrosine kinase fusion-positive cases are a high-risk subtype of BCP-ALL, which warrants further studies with specific kinase inhibitors to improve outcome. PMID:27894077

Changes in ranging and agonistic behavior of vervet monkeys (Cercopithecus aethiops) after predator-induced group fusion.

PubMed

Jaffe, Karin Enstam; Isbell, Lynne A

2010-06-01

Socio-ecological theory predicts that group fusion in female-philopatric primate species will be rare because females experience increased costs by associating with non-relatives. Indeed, fusion has been reported only 14 times in only 4 female-philopatric cercopithecines despite many years of observation. Here, we describe changes in ranging and agonistic behavior of vervet monkeys (Cercopithecus aethiops) after the fusion of two groups, the sole group fusion during 11 years of observation, induced by a brief but intense period of apparent leopard predation. Before fusion, both groups made few incursions into the other group's territory and spent most of the time in their own territories. After the fusion, the amalgamated group shifted its activities and used both territories in similar proportion. Rates of female agonism increased after fusion, particularly in the 2 weeks following fusion, and the small group females assumed the lowest ranks in the female dominance hierarchy. Rates of agonism returned to prefusion rates a month later. Although rates of high-intensity interactions (i.e., chases) did not increase after fusion, small group females were more likely to be the recipients of, and lose, agonistic interactions than large group females; a small group female and her infant were attacked and wounded by a coalition of large group females shortly after the fusion. The observations presented here reveal that the circumstances surrounding group fusions are more variable than previously realized, but are still in accordance with expectations from socio-ecological theory that predation can favor the formation of larger groups. In this case, under threat of severe predation, individuals may have surrendered group autonomy for the greater security of larger numbers. (c) 2010 Wiley-Liss, Inc.

The effect of excision of the posterior arch of C1 on C1/C2 fusion using transarticular screws.

PubMed

Chang, K C; Samartzis, D; Fuego, S M; Dhatt, S S; Wong, Y W; Cheung, W Y; Luk, K D K; Cheung, K M C

2013-07-01

Transarticular screw fixation with autograft is an established procedure for the surgical treatment of atlantoaxial instability. Removal of the posterior arch of C1 may affect the rate of fusion. This study assessed the rate of atlantoaxial fusion using transarticular screws with or without removal of the posterior arch of C1. We reviewed 30 consecutive patients who underwent atlantoaxial fusion with a minimum follow-up of two years. In 25 patients (group A) the posterior arch of C1 was not excised (group A) and in five it was (group B). Fusion was assessed on static and dynamic radiographs. In selected patients CT imaging was also used to assess fusion and the position of the screws. There were 15 men and 15 women with a mean age of 51.2 years (23 to 77) and a mean follow-up of 7.7 years (2 to 11.6). Stable union with a solid fusion or a stable fibrous union was achieved in 29 patients (97%). In Group A, 20 patients (80%) achieved a solid fusion, four (16%) a stable fibrous union and one (4%) a nonunion. In Group B, stable union was achieved in all patients, three having a solid fusion and two a stable fibrous union. There was no statistically significant difference between the status of fusion in the two groups. Complications were noted in 12 patients (40%); these were mainly related to the screws, and included malpositioning and breakage. The presence of an intact or removed posterior arch of C1 did not affect the rate of fusion in patients with atlantoaxial instability undergoing C1/C2 fusion using transarticular screws and autograft.

FGFR1/3 tyrosine kinase fusions define a unique molecular subtype of non-small cell lung cancer.

PubMed

Wang, Rui; Wang, Lei; Li, Yuan; Hu, Haichuan; Shen, Lei; Shen, Xuxia; Pan, Yunjian; Ye, Ting; Zhang, Yang; Luo, Xiaoyang; Zhang, Yiliang; Pan, Bin; Li, Bin; Li, Hang; Zhang, Jie; Pao, William; Ji, Hongbin; Sun, Yihua; Chen, Haiquan

2014-08-01

The fibroblast growth factor receptor (FGFR)-3 fusion genes have been recently demonstrated in a subset of non-small cell lung cancer (NSCLC). To aid in identification and treatment of these patients, we examined the frequency, clinicopathologic characteristics, and treatment outcomes of patients who had NSCLC with or without FGFR fusions. Fourteen known FGFR fusion variants, including FGFR1, FGFR2, and FGFR3, were detected by RT-PCR and verified by direct sequencing in 1,328 patients with NSCLC. All patients were also analyzed for mutations in EGFR, KRAS, HER2, BRAF, ALK, RET, and ROS1. Clinical characteristics, including age, sex, smoking status, stage, subtypes of lung adenocarcinoma, relapse-free survival, and overall survival, were collected. Of 1,328 tumors screened, two (0.2%) were BAG4-FGFR1 fusion and 15 (1.1%) were FGFR3-TACC3 fusion. Six of 1,016 patients with lung adenocarcinoma were FGFR3-TACC3 fusions and 11 of 312 lung squamous cell carcinoma harbored BAG4-FGFR1 or FGFR3-TACC3 fusions. Compared with the FGFR fusion-negative group, patients with FGFR fusions were more likely to be smokers (94.1%, 16 of 17 patients, P < 0.001), significantly associated with larger tumor (>3 cm; 88.2%, 15 of 17 patients, P < 0.001) and with a tendency to be more poorly differentiated (53.9%, nine of 17 patients, P = 0.095). FGFR fusions define a molecular subset of NSCLC with distinct clinical characteristics. FGFR is a druggable target and patients with FGFR fusions may benefit from FGFR-targeted therapy, which needs further clinical investigation. ©2014 American Association for Cancer Research.

Hybrid Biosynthetic Autograft Extender for Use in Posterior Lumbar Interbody Fusion: Safety and Clinical Effectiveness.

PubMed

Chedid, Mokbel K; Tundo, Kelly M; Block, Jon E; Muir, Jeffrey M

2015-01-01

Autologous iliac crest bone graft is the preferred option for spinal fusion, but the morbidity associated with bone harvest and the need for graft augmentation in more demanding cases necessitates combining local bone with bone substitutes. The purpose of this study was to document the clinical effectiveness and safety of a novel hybrid biosynthetic scaffold material consisting of poly(D,L-lactide-co-glycolide) (PLGA, 75:25) combined by lyophilization with unmodified high molecular weight hyaluronic acid (10-12% wt:wt) as an extender for a broad range of spinal fusion procedures. We retrospectively evaluated all patients undergoing single- and multi-level posterior lumbar interbody fusion at an academic medical center over a 3-year period. A total of 108 patients underwent 109 procedures (245 individual vertebral levels). Patient-related outcomes included pain measured on a Visual Analog Scale. Radiographic outcomes were assessed at 6 weeks, 3-6 months, and 1 year postoperatively. Radiographic fusion or progression of fusion was documented in 221 of 236 index levels (93.6%) at a mean (±SD) time to fusion of 10.2+4.1 months. Single and multi-level fusions were not associated with significantly different success rates. Mean pain scores (+SD) for all patients improved from 6.8+2.5 at baseline to 3.6+2.9 at approximately 12 months. Improvements in VAS were greatest in patients undergoing one- or two-level fusion, with patients undergoing multi-level fusion demonstrating lesser but still statistically significant improvements. Overall, stable fusion was observed in 64.8% of vertebral levels; partial fusion was demonstrated in 28.8% of vertebral levels. Only 15 of 236 levels (6.4%) were non-fused at final follow-up.

The Formin Diaphanous Regulates Myoblast Fusion through Actin Polymerization and Arp2/3 Regulation

PubMed Central

Deng, Su; Bothe, Ingo; Baylies, Mary K.

2015-01-01

The formation of multinucleated muscle cells through cell-cell fusion is a conserved process from fruit flies to humans. Numerous studies have shown the importance of Arp2/3, its regulators, and branched actin for the formation of an actin structure, the F-actin focus, at the fusion site. This F-actin focus forms the core of an invasive podosome-like structure that is required for myoblast fusion. In this study, we find that the formin Diaphanous (Dia), which nucleates and facilitates the elongation of actin filaments, is essential for Drosophila myoblast fusion. Following cell recognition and adhesion, Dia is enriched at the myoblast fusion site, concomitant with, and having the same dynamics as, the F-actin focus. Through analysis of Dia loss-of-function conditions using mutant alleles but particularly a dominant negative Dia transgene, we demonstrate that reduction in Dia activity in myoblasts leads to a fusion block. Significantly, no actin focus is detected, and neither branched actin regulators, SCAR or WASp, accumulate at the fusion site when Dia levels are reduced. Expression of constitutively active Dia also causes a fusion block that is associated with an increase in highly dynamic filopodia, altered actin turnover rates and F-actin distribution, and mislocalization of SCAR and WASp at the fusion site. Together our data indicate that Dia plays two roles during invasive podosome formation at the fusion site: it dictates the level of linear F-actin polymerization, and it is required for appropriate branched actin polymerization via localization of SCAR and WASp. These studies provide new insight to the mechanisms of cell-cell fusion, the relationship between different regulators of actin polymerization, and invasive podosome formation that occurs in normal development and in disease. PMID:26295716

Spring-Loaded Model Revisited: Paramyxovirus Fusion Requires Engagement of a Receptor Binding Protein beyond Initial Triggering of the Fusion Protein▿

PubMed Central

Porotto, Matteo; DeVito, Ilaria; Palmer, Samantha G.; Jurgens, Eric M.; Yee, Jia L.; Yokoyama, Christine C.; Pessi, Antonello; Moscona, Anne

2011-01-01

During paramyxovirus entry into a host cell, receptor engagement by a specialized binding protein triggers conformational changes in the adjacent fusion protein (F), leading to fusion between the viral and cell membranes. According to the existing paradigm of paramyxovirus membrane fusion, the initial activation of F by the receptor binding protein sets off a spring-loaded mechanism whereby the F protein progresses independently through the subsequent steps in the fusion process, ending in membrane merger. For human parainfluenza virus type 3 (HPIV3), the receptor binding protein (hemagglutinin-neuraminidase [HN]) has three functions: receptor binding, receptor cleaving, and activating F. We report that continuous receptor engagement by HN activates F to advance through the series of structural rearrangements required for fusion. In contrast to the prevailing model, the role of HN-receptor engagement in the fusion process is required beyond an initiating step, i.e., it is still required even after the insertion of the fusion peptide into the target cell membrane, enabling F to mediate membrane merger. We also report that for Nipah virus, whose receptor binding protein has no receptor-cleaving activity, the continuous stimulation of the F protein by a receptor-engaged binding protein is key for fusion. We suggest a general model for paramyxovirus fusion activation in which receptor engagement plays an active role in F activation, and the continued engagement of the receptor binding protein is essential to F protein function until the onset of membrane merger. This model has broad implications for the mechanism of paramyxovirus fusion and for strategies to prevent viral entry. PMID:21976650

Spring-loaded model revisited: paramyxovirus fusion requires engagement of a receptor binding protein beyond initial triggering of the fusion protein.

PubMed

Porotto, Matteo; Devito, Ilaria; Palmer, Samantha G; Jurgens, Eric M; Yee, Jia L; Yokoyama, Christine C; Pessi, Antonello; Moscona, Anne

2011-12-01

During paramyxovirus entry into a host cell, receptor engagement by a specialized binding protein triggers conformational changes in the adjacent fusion protein (F), leading to fusion between the viral and cell membranes. According to the existing paradigm of paramyxovirus membrane fusion, the initial activation of F by the receptor binding protein sets off a spring-loaded mechanism whereby the F protein progresses independently through the subsequent steps in the fusion process, ending in membrane merger. For human parainfluenza virus type 3 (HPIV3), the receptor binding protein (hemagglutinin-neuraminidase [HN]) has three functions: receptor binding, receptor cleaving, and activating F. We report that continuous receptor engagement by HN activates F to advance through the series of structural rearrangements required for fusion. In contrast to the prevailing model, the role of HN-receptor engagement in the fusion process is required beyond an initiating step, i.e., it is still required even after the insertion of the fusion peptide into the target cell membrane, enabling F to mediate membrane merger. We also report that for Nipah virus, whose receptor binding protein has no receptor-cleaving activity, the continuous stimulation of the F protein by a receptor-engaged binding protein is key for fusion. We suggest a general model for paramyxovirus fusion activation in which receptor engagement plays an active role in F activation, and the continued engagement of the receptor binding protein is essential to F protein function until the onset of membrane merger. This model has broad implications for the mechanism of paramyxovirus fusion and for strategies to prevent viral entry.

Strong FGFR3 staining is a marker for FGFR3 fusions in diffuse gliomas

PubMed Central

Annala, Matti; Lehtinen, Birgitta; Kesseli, Juha; Haapasalo, Joonas; Ruusuvuori, Pekka; Yli-Harja, Olli; Visakorpi, Tapio; Haapasalo, Hannu; Nykter, Matti; Zhang, Wei

2017-01-01

Abstract Background Inhibitors of fibroblast growth factor receptors (FGFRs) have recently arisen as a promising treatment option for patients with FGFR alterations. Gene fusions involving FGFR3 and transforming acidic coiled-coil protein 3 (TACC3) have been detected in diffuse gliomas and other malignancies, and fusion-positive cases have responded well to FGFR inhibition. As high FGFR3 expression has been detected in fusion-positive tumors, we sought to determine the clinical significance of FGFR3 protein expression level as well as its potential for indicating FGFR3 fusions. Methods We performed FGFR3 immunohistochemistry on tissue microarrays containing 676 grades II–IV astrocytomas and 116 grades II–III oligodendroglial tumor specimens. Fifty-one cases were further analyzed using targeted sequencing. Results Moderate to strong FGFR3 staining was detected in gliomas of all grades, was more common in females, and was associated with poor survival in diffuse astrocytomas. Targeted sequencing identified FGFR3-TACC3 fusions and an FGFR3-CAMK2A fusion in 10 of 15 strongly stained cases, whereas no fusions were found in 36 negatively to moderately stained cases. Fusion-positive cases were predominantly female and negative for IDH and EGFR/PDGFRA/MET alterations. These and moderately stained cases show lower MIB-1 proliferation index than negatively to weakly stained cases. Furthermore, stronger FGFR3 expression was commonly observed in malignant tissue regions of lower cellularity in fusion-negative cases. Importantly, subregional negative FGFR3 staining was also observed in a few fusion-positive cases. Conclusions Strong FGFR3 protein expression is indicative of FGFR3 fusions and may serve as a clinically applicable predictive marker for treatment regimens based on FGFR inhibitors. PMID:28379477

Highly specific targeting of the TMPRSS2/ERG fusion gene using liposomal nanovectors

PubMed Central

Shao, Longjiang; Tekedereli, Ibrahim; Wang, Jianghua; Yuca, Erkan; Tsang, Susan; Sood, Anil; Lopez-Berestein, Gabriel; Ozpolat, Bulent; Ittmann, Michael

2012-01-01

Purpose The TMPRSS2/ERG (T/E) fusion gene is present in half of all prostate cancer (PCa) tumors. Fusion of the oncogenic ERG gene with the androgen-regulated TMPRSS2 gene promoter results in expression of fusion mRNAs in PCa cells. The junction of theTMPRSS2 and ERG derived portions of the fusion mRNA constitutes a cancer specific target in cells containing the T/E fusion gene. Targeting the most common alternatively spliced fusion gene mRNA junctional isoforms in vivo using siRNAs in liposomal nanovectors may potentially be a novel, low toxicity treatment for PCa. Experimental Design We designed and optimized siRNAs targeting the two most common T/E fusion gene mRNA junctional isoforms (Type III or Type VI). Specificity of siRNAs was assessed by transient co-transfection in vitro. To test their ability to inhibit growth of PCa cells expressing these fusion gene isoforms in vivo, specific siRNAs in liposomal nanovectors were used to treat mice bearing orthotopic or subcutaneous xenograft tumors expressing the targeted fusion isoforms. Results The targeting siRNAs were both potent and highly specific in vitro. In vivo they significantly inhibited tumor growth. The degree of growth inhibition was variable and was correlated with the extent of fusion gene knockdown. The growth inhibition was associated with marked inhibition of angiogenesis and, to a lesser degree, proliferation and a marked increase in apoptosis of tumor cells. No toxicity was observed. Conclusions Targeting the T/E fusion junction in vivo with specific siRNAs delivered via liposomal nanovectors is a promising therapy for men with PCa. PMID:23052253

Highly specific targeting of the TMPRSS2/ERG fusion gene using liposomal nanovectors.

PubMed

Shao, Longjiang; Tekedereli, Ibrahim; Wang, Jianghua; Yuca, Erkan; Tsang, Susan; Sood, Anil; Lopez-Berestein, Gabriel; Ozpolat, Bulent; Ittmann, Michael

2012-12-15

The TMPRSS2/ERG (T/E) fusion gene is present in half of all prostate cancer tumors. Fusion of the oncogenic ERG gene with the androgen-regulated TMPRSS2 gene promoter results in expression of fusion mRNAs in prostate cancer cells. The junction of theTMPRSS2- and ERG-derived portions of the fusion mRNA constitutes a cancer-specific target in cells containing the T/E fusion gene. Targeting the most common alternatively spliced fusion gene mRNA junctional isoforms in vivo using siRNAs in liposomal nanovectors may potentially be a novel, low-toxicity treatment for prostate cancer. We designed and optimized siRNAs targeting the two most common T/E fusion gene mRNA junctional isoforms (type III or type VI). Specificity of siRNAs was assessed by transient co-transfection in vitro. To test their ability to inhibit growth of prostate cancer cells expressing these fusion gene isoforms in vivo, specific siRNAs in liposomal nanovectors were used to treat mice bearing orthotopic or subcutaneous xenograft tumors expressing the targeted fusion isoforms. The targeting siRNAs were both potent and highly specific in vitro. In vivo they significantly inhibited tumor growth. The degree of growth inhibition was variable and was correlated with the extent of fusion gene knockdown. The growth inhibition was associated with marked inhibition of angiogenesis and, to a lesser degree, proliferation and a marked increase in apoptosis of tumor cells. No toxicity was observed. Targeting the T/E fusion junction in vivo with specific siRNAs delivered via liposomal nanovectors is a promising therapy for men with prostate cancer. ©2012 AACR.

Magnetized Target Fusion Driven by Plasma Liners

NASA Technical Reports Server (NTRS)

Thio, Y. C. Francis; Kirkpatrick, Ronald C.; Knapp, Charles E.; Rodgers, Stephen L. (Technical Monitor)

2002-01-01

Magnetized target fusion is an emerging, relatively unexplored approach to fusion for electrical power and propulsion application. The physical principles of the concept are founded upon both inertial confinement fusion (ICF) and magnetic confinement fusion (MCF). It attempts to combine the favorable attributes of both these orthogonal approaches to fusion, but at the same time, avoiding the extreme technical challenges of both by exploiting a fusion regime intermediate between them. It uses a material liner to compress, heat and contain the fusion reacting plasma (the target plasma) mentally. By doing so, the fusion burn could be made to occur at plasma densities as high as six orders of magnitude higher than conventional MCF such as tokamak, thus leading to an approximately three orders of magnitude reduction in the plasma energy required for ignition. It also uses a transient magnetic field, compressed to extremely high intensity (100's T to 1000T) in the target plasma, to slow down the heat transport to the liner and to increase the energy deposition of charged-particle fusion products. This has several compounding beneficial effects. It leads to longer energy confinement time compared with conventional ICF without magnetized target, and thus permits the use of much lower plasma density to produce reasonable burn-up fraction. The compounding effects of lower plasma density and the magneto-insulation of the target lead to greatly reduced compressional heating power on the target. The increased energy deposition rate of charged-particle fusion products also helps to lower the energy threshold required for ignition and increasing the burn-up fraction. The reduction in ignition energy and the compressional power compound to lead to reduced system size, mass and R&D cost. It is a fusion approach that has an affordable R&D pathway, and appears attractive for propulsion application in the nearer term.

Z-Pinch Fusion for Energy Applications

DOE Office of Scientific and Technical Information (OSTI.GOV)

SPIELMAN,RICK B.

2000-01-01

Z pinches, the oldest fusion concept, have recently been revisited in light of significant advances in the fields of plasma physics and pulsed power engineering. The possibility exists for z-pinch fusion to play a role in commercial energy applications. We report on work to develop z-pinch fusion concepts, the result of an extensive literature search, and the output for a congressionally-mandated workshop on fusion energy held in Snowmass, Co July 11-23,1999.

Engineering and Functional Characterization of Fusion Genes Identifies Novel Oncogenic Drivers of Cancer. | Office of Cancer Genomics

Cancer.gov

Oncogenic gene fusions drive many human cancers, but tools to more quickly unravel their functional contributions are needed. Here we describe methodology permitting fusion gene construction for functional evaluation. Using this strategy, we engineered the known fusion oncogenes, BCR-ABL1, EML4-ALK, and ETV6-NTRK3, as well as 20 previously uncharacterized fusion genes identified in TCGA datasets.

Alternative approaches to fusion. [reactor design and reactor physics for Tokamak fusion reactors

NASA Technical Reports Server (NTRS)

Roth, R. J.

1976-01-01

The limitations of the Tokamak fusion reactor concept are discussed and various other fusion reactor concepts are considered that employ the containment of thermonuclear plasmas by magnetic fields (i.e., stellarators). Progress made in the containment of plasmas in toroidal devices is reported. Reactor design concepts are illustrated. The possibility of using fusion reactors as a power source in interplanetary space travel and electric power plants is briefly examined.

Directed Energy HPM, PP, & PPS Efforts: Magnetized Target Fusion - Field Reversed Configuration

DTIC Science & Technology

2006-08-04

interior. 15. SUBJECT TERMS Magnetized Target Fusion (MTF), Field-Reversed Configuration (FRC), Alternative Confinement Concepts, Fusion Energy 16...research, the Department of Energy’s Office of Fusion Energy Studies (DOE OFES). Sections 2 through 4, which follow, describe in detail SAIC’s, FabTek’s...the plasma physics areas (FRCs and fusion energy ) in which we are working. The conference paper was submitted at this time, as well, and will

ALIF and total disc replacement versus 2-level circumferential fusion with TLIF: a prospective, randomized, clinical and radiological trial.

PubMed

Hoff, Eike K; Strube, Patrick; Pumberger, Matthias; Zahn, Robert K; Putzier, Michael

2016-05-01

Prospective, randomized trial. The treatment of degenerative disc disease (DDD) with two-level fusion has been associated with a reasonable rate of complications. The aim of the present study was to compare (Hybrid) stand-alone anterior lumbar interbody fusion (ALIF) at L5/S1 with total disc replacement at L4/5 (TDR) as an alternative surgical strategy to (Fusion) 2-level circumferential fusion employing transforaminal lumbar interbody fusion (TLIF) with transpedicular stabilization at L4-S1. A total of 62 patients with symptomatic DDD of segments L5/S1 (Modic ≥2°) and L4/5 (Modic ≤2°; positive discography) were enrolled; 31 were treated with Hybrid and 31 with Fusion. Preoperatively, at 0, 12, and a mean follow-up of 37 months, clinical (ODI, VAS) and radiological evaluations (plain/extension-flexion radiographs evaluated for implant failure, fusion, global and segmental lordosis, and ROM) were performed. In 26 of 31 Hybrid and 24 of 31 Fusion patients available at the final follow-up, we found a significant clinical improvement compared to preoperatively. Hybrid patients had significantly lower VAS scores immediately postoperatively and at follow-up compared to Fusion patients. The complication rates were low and similar between the groups. Lumbar lordosis increased in both groups. The increase was mainly located at L4-S1 in the Hybrid group and at L1-L4 in the Fusion group. Hybrid patients presented with increased ROM at L4/5 and L3/4, and Fusion patients presented with increased ROM at L3/4, with significantly greater ROM at L3/4 compared to Hybrid patients at follow-up. Hybrid surgery is a viable surgical alternative for the presented indication. Approach-related inferior trauma and the balanced restoration of lumbar lordosis resulted in superior clinical outcomes compared to two-level circumferential fusion with TLIF.

Lights on: Dye dequenching reveals polymersome fusion with polymer, lipid and stealth lipid vesicles

DOE PAGES

Henderson, Ian M.; Collins, Aaron M.; Quintana, Hope A.; ...

2015-12-13

In this study, we develop a quantitative dye dequenching technique for the measurement of polymersome fusion, using it to characterize the salt mediated, mechanically-induced fusion of polymersomes with polymer, lipid, and so-called stealth lipid vesicles. While dye dequenching has been used to quantitatively explore liposome fusion in the past, this is the first use of dye dequenching to measure polymersome fusion of which we are aware. In addition to providing quantitative results, dye dequenching is ideal for detecting fusion in instances where DLS results would be ambiguous, such as low yield levels and size ranges outside the capabilities of DLS.more » The dye chosen for this study was a cyanine derivative, 1,1'-dioctadecyl-3,3,3',3'-tetramethylindotricarbocyanine iodide (DiR), which proved to provide excellent data on the extent of polymersome fusion. Using this technique, we have shown the limited fusion capabilities of polymersome/liposome heterofusion, notably DOPC vesicles fusing with polymersomes at half the efficiency of polymersome homofusion and DPPC vesicles showing virtually no fusion. In addition to these key heterofusion experiments, we determined the broad applicability of dye dequenching in measuring kinetic rates of polymersome fusion; and showed that even at elevated temperatures or over multiple weeks' time, no polymersome fusion occurred without agitation. Stealth liposomes formed from DPPC and PEO-functionalized lipid, however, fused with polymersomes and stealth liposomes with relatively high efficiency, lending support to our hypothesis that the response of the PEO corona to salt is a key factor in the fusion process. This last finding suggests that although the conjugation of PEO to lipids increases vesicle biocompatibility and enables their longer circulation times, it also renders the vesicles subject to destabilization under high salt and shear (e.g. in the circulatory system) that may lead to, in this case, fusion.« less

Full-Length Trimeric Influenza Virus Hemagglutinin II Membrane Fusion Protein and Shorter Constructs Lacking the Fusion Peptide or Transmembrane Domain: Hyperthermostability of the Full-Length Protein and the Soluble Ectodomain and Fusion Peptide Make Significant Contributions to Fusion of Membrane Vesicles†

PubMed Central

Ratnayake, Punsisi U.; Ekanayaka, E. A. Prabodha; Komanduru, Sweta S.; Weliky, David P.

2015-01-01

Influenza virus is a Class I enveloped virus which is initially endocytosed into a host respiratory epithelial cell. Subsequent reduction of the pH to the 5–6 range triggers a structural change of the viral hemagglutinin II (HA2) protein, fusion of the viral and endosomal membranes, and release of the viral nucleocapsid into the cytoplasm. HA2 contains fusion peptide (FP), soluble ectodomain (SE), transmembrane (TM), and intraviral domains with respective lengths of ~25, ~160, ~25, and ~10 residues. The present work provides a straightforward protocol for producing and purifying mg quantities of full-length HA2 from expression in bacteria. Biophysical and structural comparisons are made between full-length HA2 and shorter constructs including SHA2 ≡ SE, FHA2 ≡ FP + SE, and SHA2-TM ≡ SE + TM constructs. The constructs are helical in detergent at pH 7.4 and the dominant trimer species. The proteins are highly thermostable in decylmaltoside detergent with Tm > 90 °C for HA2 with stabilization provided by the SE, FP, and TM domains. The proteins are likely in a trimer-of-hairpins structure, the final protein state during fusion. All constructs induce fusion of negatively-charged vesicles at pH 5.0 with much less fusion at pH 7.4. Attractive protein/vesicle electrostatics play a role in fusion, as the proteins are positively-charged at pH 5.0 and negatively-charged at pH 7.4 and the pH-dependence of fusion is reversed for positively-charged vesicles. Comparison of fusion between constructs supports significant contributions to fusion from the SE and the FP with little effect from the TM. PMID:26297995

Effects of combined teriparatide and zoledronic acid on posterior lumbar vertebral fusion in an aged ovariectomized rat model of osteopenia.

PubMed

Yishake, Mumingjiang; Yasen, Miersalijiang; Jiang, Libo; Liu, Wangmi; Xing, Rong; Chen, Qian; Lin, Hong; Dong, Jian

2018-03-01

There has been no study regarding the effect of a combination of teriparatide (TPTD) and zoledronic acid (ZA) on vertebral fusion. In this study, we investigate the effect of single and combined TPTD and ZA treatment on lumbar vertebral fusion in aged ovariectomized (OVX) rats. Sixty two-month-old female Sprague-Dawley rats were ovariectomized and underwent bilateral L4-L5 posterolateral intertransverse fusion after 10 months. The OVX rats received vehicle (control) treatment, or ZA (100 µg/kg, once), or TPTD (60 µg/kg/2 d for 42 d), or ZA + TPTD until they were euthanized at 6 weeks following lumbar vertebral fusion. The lumbar spine was harvested. Bone mineral density (BMD), bone fusion, bone volume (BV), and bone formation rate (BFR)were analyzed by dual-energy X-ray absorptiometry (DXA), radiography, micro-computed tomography, and histomorphometry. Compared with vehicle (control) treatment, ZA and TPTD monotherapy increased bone volume (BV) at fusion site, and ZA + TPTD combined therapy had an additive effect. Treatment with TPTD and ZA + TPTD increased the bone fusion rate when compared with the control group. ZA monotherapy did not alter the rate of bone fusion. The TPTD and ZA + TPTD treatment groups had increased mineral apposition rate (MAR), mineralizing surfaces/bone surface ((MS/BS), and BFR/BS compared with the OVX group. Our experiment confirm that the monotherapy with TPTD and combination therapy with ZA + TPTD in an OVX rat model of osteopenia following lumbar vertebral fusion surgery increased bone fusion mass and bone fusion rate, and ZA + TPTD combined therapy had an additive effect on bone fusion mass. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:937-944, 2018. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Effect of Surgical Approach on Pulmonary Function in Adolescent Idiopathic Scoliosis Patients: A Systemic Review and Meta-analysis.

PubMed

Lee, Andy C H; Feger, Mark A; Singla, Anuj; Abel, Mark F

2016-11-15

Systemic review and meta-analysis. To analyze the effect of spinal fusion and instrumentation for adolescent idiopathic scoliosis (AIS) on absolute pulmonary function test (PFTs). Pulmonary function is correlated with severity of deformity in AIS patients and studies that have analyzed the effect of spinal fusion and instrumentation on PFTs for AIS have reported inconsistent results. There is a need to analyze the effect of spinal fusion on PFTs with stratification by surgical approach. Our analysis included 22 studies. Cohen's d effect sizes were calculated for absolute PFT outcome measures with 95% confidence intervals (CI). Meta-analyses were performed at each postoperative time frame for six homogeneous surgical approaches: (i) combined anterior release and posterior fusion with instrumentation; (ii) combined video assisted anterior release and posterior fusion with instrumentation without thoracoplasty; (iii) posterior fusion with instrumentation without thoracoplasty; (iv) anterior fusion with instrumentation and without thoracoplasty; (v) video assisted anterior fusion with instrumentation without thoracoplasty; and (vi) any scoliosis surgery with additional thoracoplasty. Anterior spinal fusion with instrumentation, any scoliosis surgery with concomitant thoracoplasty, or video-assisted anterior fusion with instrumentation for AIS had similar absolute PFTs at their 2 year postoperative follow up compared with their preoperative PFTs (effect sizes ranging from -0.2-0.2 with all CI crossing "0"). Posterior spinal fusion with instrumentation (with or without an anterior release) demonstrated small to moderate increases in PFTs 2 years postoperatively (effect sizes ranging from 0.35-0.65 with all CI not crossing "0"). Anterior fusion with instrumentation, regardless of the approach, and any scoliosis surgery with concomitant thoracoplasty do not lead to significant change in pulmonary functions 2 year after surgery. Posterior spinal fusion with instrumentation (with or without an anterior release) resulted in small to moderate increases in PFTs. N/A.

Lumbar interbody fusion: techniques, indications and comparison of interbody fusion options including PLIF, TLIF, MI-TLIF, OLIF/ATP, LLIF and ALIF

PubMed Central

Phan, Kevin; Malham, Greg; Seex, Kevin; Rao, Prashanth J.

2015-01-01

Degenerative disc and facet joint disease of the lumbar spine is common in the ageing population, and is one of the most frequent causes of disability. Lumbar spondylosis may result in mechanical back pain, radicular and claudicant symptoms, reduced mobility and poor quality of life. Surgical interbody fusion of degenerative levels is an effective treatment option to stabilize the painful motion segment, and may provide indirect decompression of the neural elements, restore lordosis and correct deformity. The surgical options for interbody fusion of the lumbar spine include: posterior lumbar interbody fusion (PLIF), transforaminal lumbar interbody fusion (TLIF), minimally invasive transforaminal lumbar interbody fusion (MI-TLIF), oblique lumbar interbody fusion/anterior to psoas (OLIF/ATP), lateral lumbar interbody fusion (LLIF) and anterior lumbar interbody fusion (ALIF). The indications may include: discogenic/facetogenic low back pain, neurogenic claudication, radiculopathy due to foraminal stenosis, lumbar degenerative spinal deformity including symptomatic spondylolisthesis and degenerative scoliosis. In general, traditional posterior approaches are frequently used with acceptable fusion rates and low complication rates, however they are limited by thecal sac and nerve root retraction, along with iatrogenic injury to the paraspinal musculature and disruption of the posterior tension band. Minimally invasive (MIS) posterior approaches have evolved in an attempt to reduce approach related complications. Anterior approaches avoid the spinal canal, cauda equina and nerve roots, however have issues with approach related abdominal and vascular complications. In addition, lateral and OLIF techniques have potential risks to the lumbar plexus and psoas muscle. The present study aims firstly to comprehensively review the available literature and evidence for different lumbar interbody fusion (LIF) techniques. Secondly, we propose a set of recommendations and guidelines for the indications for interbody fusion options. Thirdly, this article provides a description of each approach, and illustrates the potential benefits and disadvantages of each technique with reference to indication and spine level performed. PMID:27683674

Analysis of decision fusion algorithms in handling uncertainties for integrated health monitoring systems

NASA Astrophysics Data System (ADS)

Zein-Sabatto, Saleh; Mikhail, Maged; Bodruzzaman, Mohammad; DeSimio, Martin; Derriso, Mark; Behbahani, Alireza

2012-06-01

It has been widely accepted that data fusion and information fusion methods can improve the accuracy and robustness of decision-making in structural health monitoring systems. It is arguably true nonetheless, that decision-level is equally beneficial when applied to integrated health monitoring systems. Several decisions at low-levels of abstraction may be produced by different decision-makers; however, decision-level fusion is required at the final stage of the process to provide accurate assessment about the health of the monitored system as a whole. An example of such integrated systems with complex decision-making scenarios is the integrated health monitoring of aircraft. Thorough understanding of the characteristics of the decision-fusion methodologies is a crucial step for successful implementation of such decision-fusion systems. In this paper, we have presented the major information fusion methodologies reported in the literature, i.e., probabilistic, evidential, and artificial intelligent based methods. The theoretical basis and characteristics of these methodologies are explained and their performances are analyzed. Second, candidate methods from the above fusion methodologies, i.e., Bayesian, Dempster-Shafer, and fuzzy logic algorithms are selected and their applications are extended to decisions fusion. Finally, fusion algorithms are developed based on the selected fusion methods and their performance are tested on decisions generated from synthetic data and from experimental data. Also in this paper, a modeling methodology, i.e. cloud model, for generating synthetic decisions is presented and used. Using the cloud model, both types of uncertainties; randomness and fuzziness, involved in real decision-making are modeled. Synthetic decisions are generated with an unbiased process and varying interaction complexities among decisions to provide for fair performance comparison of the selected decision-fusion algorithms. For verification purposes, implementation results of the developed fusion algorithms on structural health monitoring data collected from experimental tests are reported in this paper.

Transmembrane Domains of Highly Pathogenic Viral Fusion Proteins Exhibit Trimeric Association In Vitro

PubMed Central

Webb, Stacy R.; Smith, Stacy E.; Fried, Michael G.

2018-01-01

ABSTRACT Enveloped viruses require viral fusion proteins to promote fusion of the viral envelope with a target cell membrane. To drive fusion, these proteins undergo large conformational changes that must occur at the right place and at the right time. Understanding the elements which control the stability of the prefusion state and the initiation of conformational changes is key to understanding the function of these important proteins. The construction of mutations in the fusion protein transmembrane domains (TMDs) or the replacement of these domains with lipid anchors has implicated the TMD in the fusion process. However, the structural and molecular details of the role of the TMD in these fusion events remain unclear. Previously, we demonstrated that isolated paramyxovirus fusion protein TMDs associate in a monomer-trimer equilibrium, using sedimentation equilibrium analytical ultracentrifugation. Using a similar approach, the work presented here indicates that trimeric interactions also occur between the fusion protein TMDs of Ebola virus, influenza virus, severe acute respiratory syndrome coronavirus (SARS CoV), and rabies virus. Our results suggest that TM-TM interactions are important in the fusion protein function of diverse viral families. IMPORTANCE Many important human pathogens are enveloped viruses that utilize membrane-bound glycoproteins to mediate viral entry. Factors that contribute to the stability of these glycoproteins have been identified in the ectodomain of several viral fusion proteins, including residues within the soluble ectodomain. Although it is often thought to simply act as an anchor, the transmembrane domain of viral fusion proteins has been implicated in protein stability and function as well. Here, using a biophysical approach, we demonstrated that the fusion protein transmembrane domains of several deadly pathogens—Ebola virus, influenza virus, SARS CoV, and rabies virus—self-associate. This observation across various viral families suggests that transmembrane domain interactions may be broadly relevant and serve as a new target for therapeutic development. PMID:29669880

Full-length trimeric influenza virus hemagglutinin II membrane fusion protein and shorter constructs lacking the fusion peptide or transmembrane domain: Hyperthermostability of the full-length protein and the soluble ectodomain and fusion peptide make significant contributions to fusion of membrane vesicles.

PubMed

Ratnayake, Punsisi U; Prabodha Ekanayaka, E A; Komanduru, Sweta S; Weliky, David P

2016-01-01

Influenza virus is a class I enveloped virus which is initially endocytosed into a host respiratory epithelial cell. Subsequent reduction of the pH to the 5-6 range triggers a structural change of the viral hemagglutinin II (HA2) protein, fusion of the viral and endosomal membranes, and release of the viral nucleocapsid into the cytoplasm. HA2 contains fusion peptide (FP), soluble ectodomain (SE), transmembrane (TM), and intraviral domains with respective lengths of ∼ 25, ∼ 160, ∼ 25, and ∼ 10 residues. The present work provides a straightforward protocol for producing and purifying mg quantities of full-length HA2 from expression in bacteria. Biophysical and structural comparisons are made between full-length HA2 and shorter constructs including SHA2 ≡ SE, FHA2 ≡ FP+SE, and SHA2-TM ≡ SE+TM constructs. The constructs are helical in detergent at pH 7.4 and the dominant trimer species. The proteins are highly thermostable in decylmaltoside detergent with Tm>90 °C for HA2 with stabilization provided by the SE, FP, and TM domains. The proteins are likely in a trimer-of-hairpins structure, the final protein state during fusion. All constructs induce fusion of negatively-charged vesicles at pH 5.0 with much less fusion at pH 7.4. Attractive protein/vesicle electrostatics play a role in fusion, as the proteins are positively-charged at pH 5.0 and negatively-charged at pH 7.4 and the pH-dependence of fusion is reversed for positively-charged vesicles. Comparison of fusion between constructs supports significant contributions to fusion from the SE and the FP with little effect from the TM. Copyright © 2015 Elsevier Inc. All rights reserved.

Green fluorescence protein-based content-mixing assay of SNARE-driven membrane fusion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Heo, Paul; Kong, Byoungjae; Jung, Young-Hun

Soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins mediate intracellular membrane fusion by forming a ternary SNARE complex. A minimalist approach utilizing proteoliposomes with reconstituted SNARE proteins yielded a wealth of information pinpointing the molecular mechanism of SNARE-mediated fusion and its regulation by accessory proteins. Two important attributes of a membrane fusion are lipid-mixing and the formation of an aqueous passage between apposing membranes. These two attributes are typically observed by using various fluorescent dyes. Currently available in vitro assay systems for observing fusion pore opening have several weaknesses such as cargo-bleeding, incomplete removal of unencapsulated dyes, and inadequate information regardingmore » the size of the fusion pore, limiting measurements of the final stage of membrane fusion. In the present study, we used a biotinylated green fluorescence protein and streptavidin conjugated with Dylight 594 (DyStrp) as a Föster resonance energy transfer (FRET) donor and acceptor, respectively. This FRET pair encapsulated in each v-vesicle containing synaptobrevin and t-vesicle containing a binary acceptor complex of syntaxin 1a and synaptosomal-associated protein 25 revealed the opening of a large fusion pore of more than 5 nm, without the unwanted signals from unencapsulated dyes or leakage. This system enabled determination of the stoichiometry of the merging vesicles because the FRET efficiency of the FRET pair depended on the molar ratio between dyes. Here, we report a robust and informative assay for SNARE-mediated fusion pore opening. - Highlights: • SNARE proteins drive membrane fusion and open a pore for cargo release. • Biotinylated GFP and DyStrp was used as the reporter pair of fusion pore opening. • Procedure for efficient SNARE reconstitution and reporter encapsulation was established. • The FRET pair reported opening of a large fusion pore bigger than 5 nm. • The assay was robust and provided information of stoichiometry of vesicle fusion.« less

Pre-fusion RSV F strongly boosts pre-fusion specific neutralizing responses in cattle pre-exposed to bovine RSV.

PubMed

Steff, Ann-Muriel; Monroe, James; Friedrich, Kristian; Chandramouli, Sumana; Nguyen, Thi Lien-Anh; Tian, Sai; Vandepaer, Sarah; Toussaint, Jean-François; Carfi, Andrea

2017-10-20

Human respiratory syncytial virus (hRSV) is responsible for serious lower respiratory tract disease in infants and in older adults, and remains an important vaccine need. RSV fusion (F) glycoprotein is a key target for neutralizing antibodies. RSV F stabilized in its pre-fusion conformation (DS-Cav1 F) induces high neutralizing antibody titers in naïve animals, but it remains unknown to what extent pre-fusion F can boost pre-existing neutralizing responses in RSV seropositive adults. We here assess DS-Cav1 F immunogenicity in seropositive cattle pre-exposed to bovine RSV, a virus closely related to hRSV. A single immunization with non-adjuvanted DS-Cav1 F strongly boosts RSV neutralizing responses, directed towards pre-fusion F-specific epitopes, whereas a post-fusion F is unable to do so. Vaccination with pre-fusion F thus represents a promising strategy for maternal immunization and for other RSV vaccine target populations such as older adults.

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.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cheng, De-Chun; Zhong, Guo-Cai; Su, Ju-Xiang

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 potentialmore » 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.« less

Irradiation-induced fusion between giant vesicles and photoresponsive large unilamellar vesicles containing malachite green derivative.

PubMed

Uda, Ryoko M; Yoshikawa, Yuki; Kitaba, Moe; Nishimoto, Noriko

2018-07-01

Light-initiated fusion between vesicles has attracted much attention in the research community. In particular, fusion between photoresponsive and non-photoresponsive vesicles has been of much interest in the development of systems for the delivery of therapeutic agents to cells. We have performed fusion between giant vesicles (GVs) and photoresponsive smaller vesicles containing malachite green (MG) derivative, which undergoes ionization to afford a positive charge on the molecule by irradiation. The fusion proceeds as the concentration of GV lipid increases toward equimolarity with the lipid of the smaller vesicle. It is also dependent on the molar percentage of photoionized MG in the lipid of the smaller vesicle. On the other hand, the fusion is hardly affected by the anionic component of the GV. The photoinduced fusion was characterized by two methods, involving the mixing of lipid membranes and of aqueous contents. Fluorescence microscopy revealed that irradiation triggered the fusion of a single GV with the smaller vesicles containing MG. Copyright © 2018 Elsevier B.V. All rights reserved.

Structure of the Newcastle disease virus F protein in the post-fusion conformation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Swanson, Kurt; Wen, Xiaolin; Leser, George P.

2010-11-17

The paramyxovirus F protein is a class I viral membrane fusion protein which undergoes a significant refolding transition during virus entry. Previous studies of the Newcastle disease virus, human parainfluenza virus 3 and parainfluenza virus 5 F proteins revealed differences in the pre- and post-fusion structures. The NDV Queensland (Q) F structure lacked structural elements observed in the other two structures, which are key to the refolding and fusogenic activity of F. Here we present the NDV Australia-Victoria (AV) F protein post-fusion structure and provide EM evidence for its folding to a pre-fusion form. The NDV AV F structure containsmore » heptad repeat elements missing in the previous NDV Q F structure, forming a post-fusion six-helix bundle (6HB) similar to the post-fusion hPIV3 F structure. Electrostatic and temperature factor analysis of the F structures points to regions of these proteins that may be functionally important in their membrane fusion activity.« less

Amphiphilic gold nanoparticles as modulators of lipid membrane fusion

NASA Astrophysics Data System (ADS)

Tahir, Mukarram; Alexander-Katz, Alfredo

The fusion of lipid membranes is central to biological functions like inter-cellular transport and signaling and is coordinated by proteins of the soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) superfamily. We utilize molecular dynamics simulations to demonstrate that gold nanoparticles functionalized with a mixed-monolayer of hydrophobic and hydrophilic alkanethiol ligands can act as synthetic analogues of these fusion proteins and mediate lipid membrane fusion by catalyzing the formation of a toroidal stalk between adjacent membranes and enabling the formation of a fusion pore upon influx of Ca2+ into the exterior solvent. The fusion pathway enabled by these synthetic nanostructures is analogous to the regulated fast fusion pathway observed during synaptic vesicle fusion; it therefore provides novel physical insights into this important biological process while also being relevant in a number of single-cell therapeutic applications. Computational resources from NSF XSEDE contract TG-DMR130042. Financial support from DOE CSGF fellowship DE-FG02-97ER25308.

Integrative Multi-Spectral Sensor Device for Far-Infrared and Visible Light Fusion

NASA Astrophysics Data System (ADS)

Qiao, Tiezhu; Chen, Lulu; Pang, Yusong; Yan, Gaowei

2018-06-01

Infrared and visible light image fusion technology is a hot spot in the research of multi-sensor fusion technology in recent years. Existing infrared and visible light fusion technologies need to register before fusion because of using two cameras. However, the application effect of the registration technology has yet to be improved. Hence, a novel integrative multi-spectral sensor device is proposed for infrared and visible light fusion, and by using the beam splitter prism, the coaxial light incident from the same lens is projected to the infrared charge coupled device (CCD) and visible light CCD, respectively. In this paper, the imaging mechanism of the proposed sensor device is studied with the process of the signals acquisition and fusion. The simulation experiment, which involves the entire process of the optic system, signal acquisition, and signal fusion, is constructed based on imaging effect model. Additionally, the quality evaluation index is adopted to analyze the simulation result. The experimental results demonstrate that the proposed sensor device is effective and feasible.

SAFE Software and FED Database to Uncover Protein-Protein Interactions using Gene Fusion Analysis.

PubMed

Tsagrasoulis, Dimosthenis; Danos, Vasilis; Kissa, Maria; Trimpalis, Philip; Koumandou, V Lila; Karagouni, Amalia D; Tsakalidis, Athanasios; Kossida, Sophia

2012-01-01

Domain Fusion Analysis takes advantage of the fact that certain proteins in a given proteome A, are found to have statistically significant similarity with two separate proteins in another proteome B. In other words, the result of a fusion event between two separate proteins in proteome B is a specific full-length protein in proteome A. In such a case, it can be safely concluded that the protein pair has a common biological function or even interacts physically. In this paper, we present the Fusion Events Database (FED), a database for the maintenance and retrieval of fusion data both in prokaryotic and eukaryotic organisms and the Software for the Analysis of Fusion Events (SAFE), a computational platform implemented for the automated detection, filtering and visualization of fusion events (both available at: http://www.bioacademy.gr/bioinformatics/projects/ProteinFusion/index.htm). Finally, we analyze the proteomes of three microorganisms using these tools in order to demonstrate their functionality.

SAFE Software and FED Database to Uncover Protein-Protein Interactions using Gene Fusion Analysis

PubMed Central

Tsagrasoulis, Dimosthenis; Danos, Vasilis; Kissa, Maria; Trimpalis, Philip; Koumandou, V. Lila; Karagouni, Amalia D.; Tsakalidis, Athanasios; Kossida, Sophia

2012-01-01

Domain Fusion Analysis takes advantage of the fact that certain proteins in a given proteome A, are found to have statistically significant similarity with two separate proteins in another proteome B. In other words, the result of a fusion event between two separate proteins in proteome B is a specific full-length protein in proteome A. In such a case, it can be safely concluded that the protein pair has a common biological function or even interacts physically. In this paper, we present the Fusion Events Database (FED), a database for the maintenance and retrieval of fusion data both in prokaryotic and eukaryotic organisms and the Software for the Analysis of Fusion Events (SAFE), a computational platform implemented for the automated detection, filtering and visualization of fusion events (both available at: http://www.bioacademy.gr/bioinformatics/projects/ProteinFusion/index.htm). Finally, we analyze the proteomes of three microorganisms using these tools in order to demonstrate their functionality. PMID:22267904

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, Claire Y.-H., E-mail: CHuang1@cdc.go; Butrapet, Siritorn; Moss, Kelly J.

The flaviviral envelope (E) protein directs virus-mediated membrane fusion. To investigate membrane fusion as a requirement for virus growth, we introduced 27 unique mutations into the fusion peptide of an infectious cDNA clone of dengue 2 virus and recovered seven stable mutant viruses. The fusion efficiency of the mutants was impaired, demonstrating for the first time the requirement for specific FP AAs in optimal fusion. Mutant viruses exhibited different growth kinetics and/or genetic stabilities in different cell types and adult mosquitoes. Virus particles could be recovered following RNA transfection of cells with four lethal mutants; however, recovered viruses could notmore » re-infect cells. These viruses could enter cells, but internalized virus appeared to be retained in endosomal compartments of infected cells, thus suggesting a fusion blockade. Mutations of the FP also resulted in reduced virus reactivity with flavivirus group-reactive antibodies, confirming earlier reports using virus-like particles.« less

[An improved medical image fusion algorithm and quality evaluation].

PubMed

Chen, Meiling; Tao, Ling; Qian, Zhiyu

2009-08-01

Medical image fusion is of very important value for application in medical image analysis and diagnosis. In this paper, the conventional method of wavelet fusion is improved,so a new algorithm of medical image fusion is presented and the high frequency and low frequency coefficients are studied respectively. When high frequency coefficients are chosen, the regional edge intensities of each sub-image are calculated to realize adaptive fusion. The choice of low frequency coefficient is based on the edges of images, so that the fused image preserves all useful information and appears more distinctly. We apply the conventional and the improved fusion algorithms based on wavelet transform to fuse two images of human body and also evaluate the fusion results through a quality evaluation method. Experimental results show that this algorithm can effectively retain the details of information on original images and enhance their edge and texture features. This new algorithm is better than the conventional fusion algorithm based on wavelet transform.

An Overview of INEL Fusion Safety R&D Facilities

NASA Astrophysics Data System (ADS)

McCarthy, K. A.; Smolik, G. R.; Anderl, R. A.; Carmack, W. J.; Longhurst, G. R.

1997-06-01

The Fusion Safety Program at the Idaho National Engineering Laboratory has the lead for fusion safety work in the United States. Over the years, we have developed several experimental facilities to provide data for fusion reactor safety analyses. We now have four major experimental facilities that provide data for use in safety assessments. The Steam-Reactivity Measurement System measures hydrogen generation rates and tritium mobilization rates in high-temperature (up to 1200°C) fusion relevant materials exposed to steam. The Volatilization of Activation Product Oxides Reactor Facility provides information on mobilization and transport and chemical reactivity of fusion relevant materials at high temperature (up to 1200°C) in an oxidizing environment (air or steam). The Fusion Aerosol Source Test Facility is a scaled-up version of VAPOR. The ion-implanta-tion/thermal-desorption system is dedicated to research into processes and phenomena associated with the interaction of hydrogen isotopes with fusion materials. In this paper we describe the capabilities of these facilities.

Constancy and diversity in the flavivirus fusion peptide.

PubMed

Seligman, Stephen J

2008-02-14

Flaviviruses include the mosquito-borne dengue, Japanese encephalitis, yellow fever and West Nile and the tick-borne encephalitis viruses. They are responsible for considerable world-wide morbidity and mortality. Viral entry is mediated by a conserved fusion peptide containing 16 amino acids located in domain II of the envelope protein E. Highly orchestrated conformational changes initiated by exposure to acidic pH accompany the fusion process and are important factors limiting amino acid changes in the fusion peptide that still permit fusion with host cell membranes in both arthropod and vertebrate hosts. The cell-fusing related agents, growing only in mosquitoes or insect cell lines, possess a different homologous peptide. Analysis of 46 named flaviviruses deposited in the Entrez Nucleotides database extended the constancy in the canonical fusion peptide sequences of mosquito-borne, tick-borne and viruses with no known vector to include more recently-sequenced viruses. The mosquito-borne signature amino acid, G104, was also found in flaviviruses with no known vector and with the cell-fusion related viruses. Despite the constancy in the canonical sequences in pathogenic flaviviruses, mutations were surprisingly frequent with a 27% prevalence of nonsynonymous mutations in yellow fever virus fusion peptide sequences, and 0 to 7.4% prevalence in the others. Six of seven yellow fever patients whose virus had fusion peptide mutations died. In the cell-fusing related agents, not enough sequences have been deposited to estimate reliably the prevalence of fusion peptide mutations. However, the canonical sequences homologous to the fusion peptide and the pattern of disulfide linkages in protein E differed significantly from the other flaviviruses. The constancy of the canonical fusion peptide sequences in the arthropod-borne flaviviruses contrasts with the high prevalence of mutations in most individual viruses. The discrepancy may be the result of a survival advantage accompanying sequence diversity (quasispecies) involving the fusion peptide. Limited clinical data with yellow fever virus suggest that the presence of fusion peptide mutants is not associated with a decreased case fatality rate. The cell-fusing related agents may have substantial differences from other flaviviruses in their mechanism of viral entry into the host cell.

Prevalence of Abelson murine leukemia viral oncogene homolog-breakpoint cluster region fusions and correlation with peripheral blood parameters in chronic myelogenous leukemia patients in Lorestan Province, Iran.

PubMed

Kiani, Ali Asghar; Shahsavar, Farhad; Gorji, Mojtaba; Ahmadi, Kolsoum; Nazarabad, Vahideh Heydari; Bahmani, Banafsheh

2016-01-01

Chronic myelogenous leukemia (CML) is a chronic malignancy of myeloid linage associated with a significant increase in granulocytes in bone marrow and peripheral blood. CML diagnosis is based on detection of Philadelphia chromosome and "Abelson murine leukemia viral oncogene homolog" (ABL)-"breakpoint cluster region protein" fusions (ABL-BCR fusions). In this study, patients with CML morphology were studied according to ABL-BCR fusions and the relationship between the fusions and peripheral blood cell changes was examined. All patients suspected to chronic myeloproliferative disorders in Lorestan Province visiting subspecialist hematology clinics who were confirmed by oncologist were studied over a period of 5 years. After completing basic data questionnaire, blood samples were obtained with informed consent from the patients. Blood cell count and morphology were investigated and RNA was extracted from blood samples. cDNA was synthesized from RNA and ABL-BCR fusions including b3a2 and b2a2 (protein 210 kd or p210), e1a2 (protein 190 kdor p190), and e19a2 (protein 230 kdor p230) were studied by multiplex reverse transcription polymerase chain reaction method. Coexistence of e1a2 and b2a2 (p210/p190) fusions was also studied. The prevalence of mutations and their correlation with the blood parameters were statistically analyzed. Of 58 patients positive for ABL-BCR fusion, 18 (30.5%) had b2a2 fusion, 37 (62.71%) had b3a2 fusion and three (3.08%) had e1a2 fusion. Coexistence of e1a2 and b2a2 (p210/p190) was not observed. There was no significant correlation between ABL-BCR fusions and white blood cell count, platelet count, and hemoglobin concentration. The ABL-BCR fusions in Lorestan Province were similar to other studies in Iran, and b3a2 fusion had the highest prevalence in the studied patients studied.

Tracking fusion of human mesenchymal stem cells after transplantation to the heart.

PubMed

Freeman, Brian T; Kouris, Nicholas A; Ogle, Brenda M

2015-06-01

Evidence suggests that transplanted mesenchymal stem cells (MSCs) can aid recovery of damaged myocardium caused by myocardial infarction. One possible mechanism for MSC-mediated recovery is reprogramming after cell fusion between transplanted MSCs and recipient cardiac cells. We used a Cre/LoxP-based luciferase reporter system coupled to biophotonic imaging to detect fusion of transplanted human pluripotent stem cell-derived MSCs to cells of organs of living mice. Human MSCs, with transient expression of a viral fusogen, were delivered to the murine heart via a collagen patch. At 2 days and 1 week later, living mice were probed for bioluminescence indicative of cell fusion. Cell fusion was detected at the site of delivery (heart) and in distal tissues (i.e., stomach, small intestine, liver). Fusion was confirmed at the cellular scale via fluorescence in situ hybridization for human-specific and mouse-specific centromeres. Human cells in organs distal to the heart were typically located near the vasculature, suggesting MSCs and perhaps MSC fusion products have the ability to migrate via the circulatory system to distal organs and engraft with local cells. The present study reveals previously unknown migratory patterns of delivered human MSCs and associated fusion products in the healthy murine heart. The study also sets the stage for follow-on studies to determine the functional effects of cell fusion in a model of myocardial damage or disease. Mesenchymal stem cells (MSCs) are transplanted to the heart, cartilage, and other tissues to recover lost function or at least limit overactive immune responses. Analysis of tissues after MSC transplantation shows evidence of fusion between MSCs and the cells of the recipient. To date, the biologic implications of cell fusion remain unclear. A newly developed in vivo tracking system was used to identify MSC fusion products in living mice. The migratory patterns of fusion products were determined both in the target organ (i.e., the heart) and in distal organs. This study shows, for the first time, evidence of fusion products at sites distal from the target organ and data to suggest that migration occurs via the vasculature. These results will inform and improve future, MSC-based therapeutics. ©AlphaMed Press.

Fusion enhancement at near and sub-barrier energies in 19O + 12C

DOE PAGES

Singh, Varinderjit; Vadas, J.; Steinbach, T. K.; ...

2016-12-12

Measuring the fusion excitation function for an isotopic chain of projectile nuclei provides a stringent test of a microscopic description of fusion. We report the first measurement of the fusion excitation function at near-barrier energies for the 19O+ 12C system. The measured excitation function is compared with the fusion excitation function of 18O+ 12C. A significant enhancement in the fusion probability of 19O ions with a 12C target as compared to 18O ions is observed. As a result, the experimental cross-sections observed at near-barrier energies are compared with a state-of-the-art microscopic model.

Preparation of GST Fusion Proteins.

PubMed

Einarson, Margret B; Pugacheva, Elena N; Orlinick, Jason R

2007-04-01

INTRODUCTIONThis protocol describes the preparation of glutathione-S-transferase (GST) fusion proteins, which have had a wide range of applications since their introduction as tools for synthesis of recombinant proteins in bacteria. GST was originally selected as a fusion moiety because of several desirable properties. First and foremost, when expressed in bacteria alone, or as a fusion, GST is not sequestered in inclusion bodies (in contrast to previous fusion protein systems). Second, GST can be affinity-purified without denaturation because it binds to immobilized glutathione, which provides the basis for simple purification. Consequently, GST fusion proteins are routinely used for antibody generation and purification, protein-protein interaction studies, and biochemical analysis.

Review of 3d GIS Data Fusion Methods and Progress

NASA Astrophysics Data System (ADS)

Hua, Wei; Hou, Miaole; Hu, Yungang

2018-04-01

3D data fusion is a research hotspot in the field of computer vision and fine mapping, and plays an important role in fine measurement, risk monitoring, data display and other processes. At present, the research of 3D data fusion in the field of Surveying and mapping focuses on the 3D model fusion of terrain and ground objects. This paper summarizes the basic methods of 3D data fusion of terrain and ground objects in recent years, and classified the data structure and the establishment method of 3D model, and some of the most widely used fusion methods are analysed and commented.

Overexpression of an archaeal geranylgeranyl diphosphate synthase in Escherichia coli cells.

PubMed

Ohto, C; Nakane, H; Hemmi, H; Ohnuma, S; Obata, S; Nishino, T

1998-06-01

An archaeal geranylgeranyl diphosphate synthase was overexpressed in Escherichia coli cells as fusion proteins. These fusion proteins retained their thermostability and had higher specific activity than did a partially purified native enzyme Previously reported. We purified 24.3 mg of MBP (maltose-binding protein)-fusion protein and 5.4 mg of GST (glutathione S-transferase)-fusion protein from a one-liter culture of E. coli. The MBP-fusion proteins existed in dimer, tetramer, octamer, or dodecamer form, and their product specificities were altered according to the oligomerization. The MBP-fusion protein has protease-sensitive sites in the portion corresponding to geranylgeranyl diphosphate synthase.

The continuum fusion theory of signal detection applied to a bi-modal fusion problem

NASA Astrophysics Data System (ADS)

Schaum, A.

2011-05-01

A new formalism has been developed that produces detection algorithms for model-based problems, in which one or more parameter values is unknown. Continuum Fusion can be used to generate different flavors of algorithm for any composite hypothesis testing problem. The methodology is defined by a fusion logic that can be translated into max/min conditions. Here it is applied to a simple sensor fusion model, but one for which the generalized likelihood ratio test is intractable. By contrast, a fusion-based response to the same problem can be devised that is solvable in closed form and represents a good approximation to the GLR test.

Application of the JDL data fusion process model for cyber security

NASA Astrophysics Data System (ADS)

Giacobe, Nicklaus A.

2010-04-01

A number of cyber security technologies have proposed the use of data fusion to enhance the defensive capabilities of the network and aid in the development of situational awareness for the security analyst. While there have been advances in fusion technologies and the application of fusion in intrusion detection systems (IDSs), in particular, additional progress can be made by gaining a better understanding of a variety of data fusion processes and applying them to the cyber security application domain. This research explores the underlying processes identified in the Joint Directors of Laboratories (JDL) data fusion process model and further describes them in a cyber security context.

Auto-fusion and the shaping of neurons and tubes.

PubMed

Soulavie, Fabien; Sundaram, Meera V

2016-12-01

Cells adopt specific shapes that are necessary for specific functions. For example, some neurons extend elaborate arborized dendrites that can contact multiple targets. Epithelial and endothelial cells can form tiny seamless unicellular tubes with an intracellular lumen. Recent advances showed that cells can auto-fuse to acquire those specific shapes. During auto-fusion, a cell merges two parts of its own plasma membrane. In contrast to cell-cell fusion or macropinocytic fission, which result in the merging or formation of two separate membrane bound compartments, auto-fusion preserves one compartment, but changes its shape. The discovery of auto-fusion in C. elegans was enabled by identification of specific protein fusogens, EFF-1 and AFF-1, that mediate cell-cell fusion. Phenotypic characterization of eff-1 and aff-1 mutants revealed that fusogen-mediated fusion of two parts of the same cell can be used to sculpt dendritic arbors, reconnect two parts of an axon after injury, or form a hollow unicellular tube. Similar auto-fusion events recently were detected in vertebrate cells, suggesting that auto-fusion could be a widely used mechanism for shaping neurons and tubes. Copyright © 2016 Elsevier Ltd. All rights reserved.

Towards a programme of testing and qualification for structural and plasma-facing materials in ‘fusion neutron’ environments

NASA Astrophysics Data System (ADS)

Stork, D.; Heidinger, R.; Muroga, T.; Zinkle, S. J.; Moeslang, A.; Porton, M.; Boutard, J.-L.; Gonzalez, S.; Ibarra, A.

2017-09-01

Materials damage by 14.1MeV neutrons from deuterium-tritium (D-T) fusion reactions can only be characterised definitively by subjecting a relevant configuration of test materials to high-intensity ‘fusion-neutron spectrum sources’, i.e. those simulating closely D-T fusion-neutron spectra. This provides major challenges to programmes to design and construct a demonstration fusion reactor prior to having a large-scale, high-intensity source of such neutrons. In this paper, we discuss the different aspects related to these ‘relevant configuration’ tests, including: • generic issues in materials qualification/validation, comparing safety requirements against those of investment protection; • lessons learned from the fission programme, enabling a reduced fusion materials testing programme; • the use and limitations of presently available possible irradiation sources to optimise a fusion neutron testing program including fission-neutron irradiation of isotopically and chemically tailored steels, ion damage by high-energy helium ions and self-ion beams, or irradiation studies with neutron sources of non-fusion spectra; and • the different potential sources of simulated fusion neutron spectra and the choice using stripping reactions from deuterium-beam ions incident on light-element targets.

Hybrid indirect-drive/direct-drive target for inertial confinement fusion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Perkins, Lindsay John

A hybrid indirect-drive/direct drive for inertial confinement fusion utilizing laser beams from a first direction and laser beams from a second direction including a central fusion fuel component; a first portion of a shell surrounding said central fusion fuel component, said first portion of a shell having a first thickness; a second portion of a shell surrounding said fusion fuel component, said second portion of a shell having a second thickness that is greater than said thickness of said first portion of a shell; and a hohlraum containing at least a portion of said fusion fuel component and at leastmore » a portion of said first portion of a shell; wherein said hohlraum is in a position relative to said first laser beam and to receive said first laser beam and produce X-rays that are directed to said first portion of a shell and said fusion fuel component; and wherein said fusion fuel component and said second portion of a shell are in a position relative to said second laser beam such that said second portion of a shell and said fusion fuel component receive said second laser beam.« less

Fusion Power measurement at ITER

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bertalot, L.; Barnsley, R.; Krasilnikov, V.

2015-07-01

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

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.

Multiscale image fusion using the undecimated wavelet transform with spectral factorization and nonorthogonal filter banks.

PubMed

Ellmauthaler, Andreas; Pagliari, Carla L; da Silva, Eduardo A B

2013-03-01

Multiscale transforms are among the most popular techniques in the field of pixel-level image fusion. However, the fusion performance of these methods often deteriorates for images derived from different sensor modalities. In this paper, we demonstrate that for such images, results can be improved using a novel undecimated wavelet transform (UWT)-based fusion scheme, which splits the image decomposition process into two successive filtering operations using spectral factorization of the analysis filters. The actual fusion takes place after convolution with the first filter pair. Its significantly smaller support size leads to the minimization of the unwanted spreading of coefficient values around overlapping image singularities. This usually complicates the feature selection process and may lead to the introduction of reconstruction errors in the fused image. Moreover, we will show that the nonsubsampled nature of the UWT allows the design of nonorthogonal filter banks, which are more robust to artifacts introduced during fusion, additionally improving the obtained results. The combination of these techniques leads to a fusion framework, which provides clear advantages over traditional multiscale fusion approaches, independent of the underlying fusion rule, and reduces unwanted side effects such as ringing artifacts in the fused reconstruction.

Multispectral medical image fusion in Contourlet domain for computer based diagnosis of Alzheimer's disease.

PubMed

Bhateja, Vikrant; Moin, Aisha; Srivastava, Anuja; Bao, Le Nguyen; Lay-Ekuakille, Aimé; Le, Dac-Nhuong

2016-07-01

Computer based diagnosis of Alzheimer's disease can be performed by dint of the analysis of the functional and structural changes in the brain. Multispectral image fusion deliberates upon fusion of the complementary information while discarding the surplus information to achieve a solitary image which encloses both spatial and spectral details. This paper presents a Non-Sub-sampled Contourlet Transform (NSCT) based multispectral image fusion model for computer-aided diagnosis of Alzheimer's disease. The proposed fusion methodology involves color transformation of the input multispectral image. The multispectral image in YIQ color space is decomposed using NSCT followed by dimensionality reduction using modified Principal Component Analysis algorithm on the low frequency coefficients. Further, the high frequency coefficients are enhanced using non-linear enhancement function. Two different fusion rules are then applied to the low-pass and high-pass sub-bands: Phase congruency is applied to low frequency coefficients and a combination of directive contrast and normalized Shannon entropy is applied to high frequency coefficients. The superiority of the fusion response is depicted by the comparisons made with the other state-of-the-art fusion approaches (in terms of various fusion metrics).

Multispectral medical image fusion in Contourlet domain for computer based diagnosis of Alzheimer’s disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bhateja, Vikrant, E-mail: bhateja.vikrant@gmail.com, E-mail: nhuongld@hus.edu.vn; Moin, Aisha; Srivastava, Anuja

Computer based diagnosis of Alzheimer’s disease can be performed by dint of the analysis of the functional and structural changes in the brain. Multispectral image fusion deliberates upon fusion of the complementary information while discarding the surplus information to achieve a solitary image which encloses both spatial and spectral details. This paper presents a Non-Sub-sampled Contourlet Transform (NSCT) based multispectral image fusion model for computer-aided diagnosis of Alzheimer’s disease. The proposed fusion methodology involves color transformation of the input multispectral image. The multispectral image in YIQ color space is decomposed using NSCT followed by dimensionality reduction using modified Principal Componentmore » Analysis algorithm on the low frequency coefficients. Further, the high frequency coefficients are enhanced using non-linear enhancement function. Two different fusion rules are then applied to the low-pass and high-pass sub-bands: Phase congruency is applied to low frequency coefficients and a combination of directive contrast and normalized Shannon entropy is applied to high frequency coefficients. The superiority of the fusion response is depicted by the comparisons made with the other state-of-the-art fusion approaches (in terms of various fusion metrics).« less

Association of insurance status and spinal fusion usage in the United States during two decades.

PubMed

John, Jason; Mirahmadizadeh, Alireza; Seifi, Ali

2018-05-01

This study examined the distribution of spinal fusion usage among payer groups in the United States. Using the National Inpatient Sample (NIS) database, total discharges, length of stay, and mean hospital charges of patients who underwent spinal fusion from 1997 to 2014 in the United States were determined and analyzed. 5,715,625 total discharges with spinal fusion were reported. Among them, 2,875,188 (50.3%) were covered by private insurance, 1,710,182 by Medicare (29.9%), 342,638 (6.0%) by Medicaid, and 91,990 (1.6%) were uninsured. A statistically significant increase in spinal fusion usage occurred within each payer group over the study period (P < 0.001). For every year of the study period, private insurance patients had the most number and uninsured patients had the least number of total discharges with spinal fusion. Furthermore, annual growth in spinal fusion usage was greatest among private insurance patients, and smallest among uninsured patients. Total discharges with spinal fusion increased significantly across all payer groups between 1997 and 2014, but not equally. Further inquiry is indicated to determine the etiology of spinal fusion usage discrepancies between payer groups. Copyright © 2018 Elsevier Ltd. All rights reserved.

Myogenin, AP2β, NOS-1, and HMGA2 are surrogate markers of fusion status in rhabdomyosarcoma: a report from the soft tissue sarcoma committee of the children's oncology group.

PubMed

Rudzinski, Erin R; Anderson, James R; Lyden, Elizabeth R; Bridge, Julia A; Barr, Frederic G; Gastier-Foster, Julie M; Bachmeyer, Karen; Skapek, Stephen X; Hawkins, Douglas S; Teot, Lisa A; Parham, David M

2014-05-01

Pediatric rhabdomyosarcoma (RMS) is traditionally classified on the basis of the histologic appearance into alveolar (ARMS) and embryonal (ERMS) subtypes. The majority of ARMS contain a PAX3-FOXO1 or PAX7-FOXO1 gene fusion, but about 20% do not. Intergroup Rhabdomyosarcoma Study stage-matched and group-matched ARMS typically behaves more aggressively than ERMS, but recent studies have shown that it is, in fact, the fusion status that drives the outcome for RMS. Gene expression microarray data indicate that several genes discriminate between fusion-positive and fusion-negative RMS with high specificity. Using tissue microarrays containing a series of both ARMS and ERMS, we identified a panel of 4 immunohistochemical markers-myogenin, AP2β, NOS-1, and HMGA2-which can be used as surrogate markers of fusion status in RMS. These antibodies provide an alternative to molecular methods for identification of fusion-positive RMS, particularly in cases in which there is scant or poor-quality material. In addition, these antibodies may be useful in fusion-negative ARMS as an indicator that a variant gene fusion may be present.

A Cell-Cell Fusion Assay to Assess Arenavirus Envelope Glycoprotein Membrane-Fusion Activity.

PubMed

York, Joanne; Nunberg, Jack H

2018-01-01

For many viruses that enter their target cells through pH-dependent fusion of the viral and endosomal membranes, cell-cell fusion assays can provide an experimental platform for investigating the structure-function relationships that promote envelope glycoprotein membrane-fusion activity. Typically, these assays employ effector cells expressing the recombinant envelope glycoprotein on the cell surface and target cells engineered to quantitatively report fusion with the effector cell. In the protocol described here, Vero cells are transfected with a plasmid encoding the arenavirus envelope glycoprotein complex GPC and infected with the vTF7-3 vaccinia virus expressing the bacteriophage T7 RNA polymerase. These effector cells are mixed with target cells infected with the vCB21R-lacZ vaccinia virus encoding a β-galactosidase reporter under the control of the T7 promoter. Cell-cell fusion is induced upon exposure to low-pH medium (pH 5.0), and the resultant expression of the β-galactosidase reporter is quantitated using a chemiluminescent substrate. We have utilized this robust microplate cell-cell fusion assay extensively to study arenavirus entry and its inhibition by small-molecule fusion inhibitors.

Performance Evaluation of Fusing Protected Fingerprint Minutiae Templates on the Decision Level

PubMed Central

Yang, Bian; Busch, Christoph; de Groot, Koen; Xu, Haiyun; Veldhuis, Raymond N. J.

2012-01-01

In a biometric authentication system using protected templates, a pseudonymous identifier is the part of a protected template that can be directly compared. Each compared pair of pseudonymous identifiers results in a decision testing whether both identifiers are derived from the same biometric characteristic. Compared to an unprotected system, most existing biometric template protection methods cause to a certain extent degradation in biometric performance. Fusion is therefore a promising way to enhance the biometric performance in template-protected biometric systems. Compared to feature level fusion and score level fusion, decision level fusion has not only the least fusion complexity, but also the maximum interoperability across different biometric features, template protection and recognition algorithms, templates formats, and comparison score rules. However, performance improvement via decision level fusion is not obvious. It is influenced by both the dependency and the performance gap among the conducted tests for fusion. We investigate in this paper several fusion scenarios (multi-sample, multi-instance, multi-sensor, multi-algorithm, and their combinations) on the binary decision level, and evaluate their biometric performance and fusion efficiency on a multi-sensor fingerprint database with 71,994 samples. PMID:22778583

Studies of Ebola Virus Glycoprotein-Mediated Entry and Fusion by Using Pseudotyped Human Immunodeficiency Virus Type 1 Virions: Involvement of Cytoskeletal Proteins and Enhancement by Tumor Necrosis Factor Alpha

PubMed Central

Yonezawa, Akihito; Cavrois, Marielle; Greene, Warner C.

2005-01-01

The Ebola filoviruses are aggressive pathogens that cause severe and often lethal hemorrhagic fever syndromes in humans and nonhuman primates. To date, no effective therapies have been identified. To analyze the entry and fusion properties of Ebola virus, we adapted a human immunodeficiency virus type 1 (HIV-1) virion-based fusion assay by substituting Ebola virus glycoprotein (GP) for the HIV-1 envelope. Fusion was detected by cleavage of the fluorogenic substrate CCF2 by β-lactamase-Vpr incorporated into virions and released as a result of virion fusion. Entry and fusion induced by the Ebola virus GP occurred with much slower kinetics than with vesicular stomatitis virus G protein (VSV-G) and were blocked by depletion of membrane cholesterol and by inhibition of vesicular acidification with bafilomycin A1. These properties confirmed earlier studies and validated the assay for exploring other properties of Ebola virus GP-mediated entry and fusion. Entry and fusion of Ebola virus GP pseudotypes, but not VSV-G or HIV-1 Env pseudotypes, were impaired in the presence of the microtubule-disrupting agent nocodazole but were enhanced in the presence of the microtubule-stabilizing agent paclitaxel (Taxol). Agents that impaired microfilament function, including cytochalasin B, cytochalasin D, latrunculin A, and jasplakinolide, also inhibited Ebola virus GP-mediated entry and fusion. Together, these findings suggest that both microtubules and microfilaments may play a role in the effective trafficking of vesicles containing Ebola virions from the cell surface to the appropriate acidified vesicular compartment where fusion occurs. In terms of Ebola virus GP-mediated entry and fusion to various target cells, primary macrophages proved highly sensitive, while monocytes from the same donors displayed greatly reduced levels of entry and fusion. We further observed that tumor necrosis factor alpha, which is released by Ebola virus-infected monocytes/macrophages, enhanced Ebola virus GP-mediated entry and fusion to human umbilical vein endothelial cells. Thus, Ebola virus infection of one target cell may induce biological changes that facilitate infection of secondary target cells that play a key role in filovirus pathogenesis. Finally, these studies indicate that pseudotyping in the HIV-1 virion-based fusion assay may be a valuable approach to the study of entry and fusion properties mediated through the envelopes of other viral pathogens. PMID:15613320

Frontier of Fusion Research: Path to the Steady State Fusion Reactor by Large Helical Device

NASA Astrophysics Data System (ADS)

Motojima, Osamu

2006-12-01

The ITER, the International Thermonuclear Experimental Reactor, which will be built in Cadarache in France, has finally started this year, 2006. Since the thermal energy produced by fusion reactions divided by the external heating power, i.e., the Q value, will be larger than 10, this is a big step of the fusion research for half a century trying to tame the nuclear fusion for the 6.5 Billion people on the Earth. The source of the Sun's power is lasting steadily and safely for 8 Billion years. As a potentially safe environmentally friendly and economically competitive energy source, fusion should provide a sustainable future energy supply for all mankind for ten thousands of years. At the frontier of fusion research important milestones are recently marked on a long road toward a true prototype fusion reactor. In its own merits, research into harnessing turbulent burning plasmas and thereby controlling fusion reaction, is one of the grand challenges of complex systems science. After a brief overview of a status of world fusion projects, a focus is given on fusion research at the National Institute for Fusion Science (NIFS) in Japan, which is playing a role of the Inter University Institute, the coordinating Center of Excellence for academic fusion research and by the Large Helical Device (LHD), the world's largest superconducting heliotron device, as a National Users' facility. The current status of LHD project is presented focusing on the experimental program and the recent achievements in basic parameters and in steady state operations. Since, its start in a year 1998, a remarkable progress has presently resulted in the temperature of 140 Million degree, the highest density of 500 Thousand Billion/cc with the internal density barrier (IDB) and the highest steady average beta of 4.5% in helical plasma devices and the largest total input energy of 1.6 GJ, in all magnetic confinement fusion devices. Finally, a perspective is given of the ITER Broad Approach program as an integrated part of ITER and Development of Fusion Energy project Agreement. Moreover, the relationship with the NIFS' new parent organization the National Institutes of Natural Sciences and with foreign research institutions is briefly explained.

The Role of Ion Selectivity of the Fusion Pore on Transmission and the Exocytosis of Neurotransmitters and Hormones

NASA Astrophysics Data System (ADS)

Delacruz, Joannalyn Bongar

Healthy nervous system function depends on proper transmission. Synaptic transmission occurs by the release of transmitters from vesicles that fuse to the plasma membrane of a pre-synaptic cell. Regulated release of neurotransmitters, neuropeptides, and hormones occurs by exocytosis, initiated by the formation of the fusion pore. The initial fusion pore has molecular dimensions with a diameter of 1-2 nm and a rapid lifetime on the millisecond time scale. It connects the vesicular lumen and extracellular space, serving as an important step for regulating the release of charged transmitters. Comprehending the molecular structure and biophysical properties of the fusion pore is essential for a mechanistic understanding of vesicle-plasma membrane fusion and transmitter release. Release of charged transmitter molecules such as glutamate, acetylcholine, dopamine, or noradrenaline through a narrow fusion pore requires compensation of change in charge. Transmitter release through the fusion pore is therefore an electrodiffusion process. If the fusion pore is selective for specific ions, then its selectivity will affect the rate of transmitter release via the voltage gradient that develops across the fusion pore. The elucidation of these mechanisms can lead to a better understanding of nervous system cell biology, neural and endocrine signaling, learning, memory, motor control, sensory function and integration, and in particular synaptic transmission. This investigation can advance our understanding of neurological disorders in which noradrenergic and dopaminergic exocytosis is disturbed, leading to neurological consequences of developmental disorders, epilepsy, Parkinson's disease, and other neurodegenerative diseases. Ultimately, understanding the role of selectivity in the fusion pore and its effects on exocytosis can contribute to the development of more effective therapies. This study investigates the selectivity of the fusion pore by observing the effects of ion influx and efflux through the fusion pore. The experiments reveal negatively charged transmitter release can occur through a fusion pore at larger conductance values, past a threshold range. Narrow fusion pores with lower conductance values favor cation selectivity, which would accelerate the release of positively charged transmitters such as acetylcholine in the neuromuscular junction. However, release of negatively charged neurotransmitters such as glutamate can occur if an expanded fusion pore mediates release of this fast major excitatory transmitter. The intention of this research is to expand our understanding of the nervous system, which can contribute to healthy shifts in our clinical and educational interventions that are commonly delivered.

Calcium-Dependent Rubella Virus Fusion Occurs in Early Endosomes.

PubMed

Dubé, Mathieu; Etienne, Loïc; Fels, Maximilian; Kielian, Margaret

2016-07-15

The E1 membrane protein of rubella virus (RuV) is a class II membrane fusion protein structurally related to the fusion proteins of the alphaviruses, flaviviruses, and phleboviruses. Virus entry is mediated by a low pH-dependent fusion reaction through E1's insertion into the cell membrane and refolding to a stable homotrimer. Unlike the other described class II proteins, RuV E1 contains 2 fusion loops, which complex a metal ion between them by interactions with residues N88 and D136. Insertion of the E1 protein into the target membrane, fusion, and infection require calcium and are blocked by alanine substitution of N88 or D136. Here we addressed the requirements of E1 for calcium binding and the intracellular location of the calcium requirement during virus entry. Our results demonstrated that N88 and D136 are optimally configured to support RuV fusion and are strongly selected for during the virus life cycle. While E1 has some similarities with cellular proteins that bind calcium and anionic lipids, RuV binding to the membrane was independent of anionic lipids. Virus fusion occurred within early endosomes, and chelation of intracellular calcium showed that calcium within the early endosome was required for virus fusion and infection. Calcium triggered the reversible insertion of E1 into the target membrane at neutral pH, but E1 homotrimer formation and fusion required a low pH. Thus, RuV E1, unlike other known class II fusion proteins, has distinct triggers for membrane insertion and fusion protein refolding mediated, respectively, by endosomal calcium and low pH. Rubella virus causes a mild disease of childhood, but infection of pregnant women frequently results in miscarriage or severe birth defects. In spite of an effective vaccine, RuV disease remains a serious problem in many developing countries. RuV infection of host cells involves endocytic uptake and low pH-triggered membrane fusion and is unusual in its requirement for calcium binding by the membrane fusion protein. Here we addressed the mechanism of the calcium requirement and the required location of calcium during virus entry. Both calcium and low pH were essential during the virus fusion reaction, which was shown to occur in the early endosome compartment. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Calcium-Dependent Rubella Virus Fusion Occurs in Early Endosomes

PubMed Central

Dubé, Mathieu; Etienne, Loïc; Fels, Maximilian

2016-01-01

ABSTRACT The E1 membrane protein of rubella virus (RuV) is a class II membrane fusion protein structurally related to the fusion proteins of the alphaviruses, flaviviruses, and phleboviruses. Virus entry is mediated by a low pH-dependent fusion reaction through E1's insertion into the cell membrane and refolding to a stable homotrimer. Unlike the other described class II proteins, RuV E1 contains 2 fusion loops, which complex a metal ion between them by interactions with residues N88 and D136. Insertion of the E1 protein into the target membrane, fusion, and infection require calcium and are blocked by alanine substitution of N88 or D136. Here we addressed the requirements of E1 for calcium binding and the intracellular location of the calcium requirement during virus entry. Our results demonstrated that N88 and D136 are optimally configured to support RuV fusion and are strongly selected for during the virus life cycle. While E1 has some similarities with cellular proteins that bind calcium and anionic lipids, RuV binding to the membrane was independent of anionic lipids. Virus fusion occurred within early endosomes, and chelation of intracellular calcium showed that calcium within the early endosome was required for virus fusion and infection. Calcium triggered the reversible insertion of E1 into the target membrane at neutral pH, but E1 homotrimer formation and fusion required a low pH. Thus, RuV E1, unlike other known class II fusion proteins, has distinct triggers for membrane insertion and fusion protein refolding mediated, respectively, by endosomal calcium and low pH. IMPORTANCE Rubella virus causes a mild disease of childhood, but infection of pregnant women frequently results in miscarriage or severe birth defects. In spite of an effective vaccine, RuV disease remains a serious problem in many developing countries. RuV infection of host cells involves endocytic uptake and low pH-triggered membrane fusion and is unusual in its requirement for calcium binding by the membrane fusion protein. Here we addressed the mechanism of the calcium requirement and the required location of calcium during virus entry. Both calcium and low pH were essential during the virus fusion reaction, which was shown to occur in the early endosome compartment. PMID:27122589

Allogeneic mesenchymal precursor cells (MPCs) combined with an osteoconductive scaffold to promote lumbar interbody spine fusion in an ovine model.

PubMed

Wheeler, Donna L; Fredericks, Douglas C; Dryer, Randall F; Bae, Hyun W

2016-03-01

Advances in immunomagnetic cell sorting have enabled isolation and purification of pleuripotent stem cells from marrow aspirates and have expanded stem cell therapies to include allogeneic sources. This study aimed to determine the safety and efficacy of allogeneic mesenchymal precursor cells (MPCs) combined with an osteoconductive scaffold in lumbar interbody spinal fusion using an ovine model. Thirty-two skeletally mature ewes underwent a single-level interbody fusion procedure using a Polyetheretherketone fusion cage supplemented with either iliac crest autograft (AG) or an osteconductive scaffold (Mastergraft Matrix, Medtronic, Memphis, TN, USA) with 2.5×10(6) MPCs, 6.25×10(6) MPCs, or 12.5×10(6) MPCs. Plain radiographs and computed tomography scans were scored for bridging bone at multiple points during healing and at necropsy. The biomechanical competency of fusion was scored by manual palpation and quantified using functional radiographs at necropsy. Postnecropsy histopathology and histomorphometric analysis assessed the local response to MPC treatment and quantified the volume and connectivity of newly formed bridging bone. Safety was assessed by serum biochemistry, hematology, and organ histopathology. Mesenchymal precursor cell treatment caused no adverse systemic or local tissue responses. All analyses indicated MPCs combined with an osteoconductive scaffold achieved similar or better fusion success as AG treatment after 16 weeks, and increasing the MPC dose did not enhance fusion. Manual palpation of the fusion site indicated more than 75% of MPC-treated and 65% of AG-treated animals achieved rigid fusion, which was corroborated with functional radiography. Computed tomography fusion scores indicated all animals in the MPC- and AG-treatment groups were fused at 16 weeks, yet X-ray scores indicated only 67% of the AG-treated animals were fused. Histomorphometry analyses showed equivalent outcomes for fusion connectivity and bony fusion area for MPC- and AG-treated groups. Approximately 6% residual graft material remained in the MPC-treated fusion sites at 16 weeks. Adult allogeneic MPCs delivered using an osteoconductive scaffold were both safe and efficacious in this ovine spine interbody fusion model. These results support the use ofallogeneic MPCs as an alternative to AG for lumbar interbody spinal fusion procedures. Copyright © 2016 Elsevier Inc. All rights reserved.

Case Study: Organotypic human in vitro models of embryonic morphogenetic fusion

EPA Science Inventory

Morphogenetic fusion of tissues is a common event in embryonic development and disruption of fusion is associated with birth defects of the eye, heart, neural tube, phallus, palate, and other organ systems. Embryonic tissue fusion requires precise regulation of cell-cell and cell...

Data fusion for CD metrology: heterogeneous hybridization of scatterometry, CDSEM, and AFM data

NASA Astrophysics Data System (ADS)

Hazart, J.; Chesneau, N.; Evin, G.; Largent, A.; Derville, A.; Thérèse, R.; Bos, S.; Bouyssou, R.; Dezauzier, C.; Foucher, J.

2014-04-01

The manufacturing of next generation semiconductor devices forces metrology tool providers for an exceptional effort in order to meet the requirements for precision, accuracy and throughput stated in the ITRS. In the past years hybrid metrology (based on data fusion theories) has been investigated as a new methodology for advanced metrology [1][2][3]. This paper provides a new point of view of data fusion for metrology through some experiments and simulations. The techniques are presented concretely in terms of equations to be solved. The first point of view is High Level Fusion which is the use of simple numbers with their associated uncertainty postprocessed by tools. In this paper, it is divided into two stages: one for calibration to reach accuracy, the second to reach precision thanks to Bayesian Fusion. From our perspective, the first stage is mandatory before applying the second stage which is commonly presented [1]. However a reference metrology system is necessary for this fusion. So, precision can be improved if and only if the tools to be fused are perfectly matched at least for some parameters. We provide a methodology similar to a multidimensional TMU able to perform this matching exercise. It is demonstrated on a 28 nm node backend lithography case. The second point of view is Deep Level Fusion which works on the contrary with raw data and their combination. In the approach presented here, the analysis of each raw data is based on a parametric model and connections between the parameters of each tool. In order to allow OCD/SEM Deep Level Fusion, a SEM Compact Model derived from [4] has been developed and compared to AFM. As far as we know, this is the first time such techniques have been coupled at Deep Level. A numerical study on the case of a simple stack for lithography is performed. We show strict equivalence of Deep Level Fusion and High Level Fusion when tools are sensitive and models are perfect. When one of the tools can be considered as a reference and the second is biased, High Level Fusion is far superior to standard Deep Level Fusion. Otherwise, only the second stage of High Level Fusion is possible (Bayesian Fusion) and do not provide substantial advantage. Finally, when OCD is equipped with methods for bias detection [5], Deep Level Fusion outclasses the two-stage High Level Fusion and will benefit to the industry for most advanced nodes production.

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

PubMed Central

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

2002-01-01

Envelope glycoproteins (Env) of retroviruses are trimers of SU (surface) and TM (transmembrane) heterodimers and are expressed on virions in fusion-competent forms that are likely to be metastable. Activation of the viral receptor-binding domain (RBD) via its interaction with a cell surface receptor is thought to initiate a cascade of events that lead to refolding of the Env glycoprotein into its stable fusion-active conformation. While the fusion-active conformation of the TM subunit has been described in detail for several retroviruses, little is known about the fusion-competent structure of the retroviral glycoproteins or the molecular events that mediate the transition between the two conformations. By characterizing Env chimeras between the ecotropic and amphotropic murine leukemia virus (MLV) SUs as well as a set of point mutants, we show that alterations of the conformation of the SU glycoprotein strongly elevate Env fusogenicity by disrupting the stability of the Env complex. Compensatory mutations that restored both Env stability and fusion control were also identified, allowing definition of interactions within the Env complex that maintain the stability of the native Env complex. We show that, in the receptor-unbound form, structural interactions between the N terminus of the viral RBD (NTR domain), the proline-rich region (PRR), and the distal part of the C-terminal domain of the SU subunit maintain a conformation of the glycoprotein that is fusion inhibitory. Additionally, we identified mutations that disrupt this fusion-inhibitory conformation and allow fusion activation in the absence of viral receptors, provided that receptor-activated RBD fragments are added in trans during infection. Other mutations were identified that allow fusion activation in the absence of receptors for both the viral glycoprotein and the trans-acting RBD. Finally, we found mutations of the SU that bypass in cis the requirement for the NTR domain in fusion activation. All these different mutations call for a critical role of the PRR in mediating conformational changes of the Env glycoprotein during fusion activation. Our results suggest a model of MLV Env fusion activation in which unlocking of the fusion-inhibitory conformation is initiated by receptor binding of the viral RBD, which, upon disruption of the PRR, allows the NTR domain to promote further events in Env fusion activation. This involves a second type of interaction, in cis or in trans, between the receptor-activated RBD and a median segment of the freed C-terminal domain. PMID:12208946

Circumferential fusion is dominant over posterolateral fusion in a long-term perspective: cost-utility evaluation of a randomized controlled trial in severe, chronic low back pain.

PubMed

Soegaard, Rikke; Bünger, Cody E; Christiansen, Terkel; Høy, Kristian; Eiskjaer, Søren P; Christensen, Finn B

2007-10-15

Cost-utility evaluation of a randomized, controlled trial with a 4- to 8-year follow-up. To investigate the incremental cost per quality-adjusted-life-year (QALY) when comparing circumferential fusion to posterolateral fusion in a long-term, societal perspective. The cost-effectiveness of circumferential fusion in a long-term perspective is uncertain but nonetheless highly relevant as the ISSLS prize winner 2006 in clinical studies reported the effect of circumferential fusion superior to the effect of posterolateral fusion. A recent trial found no significant difference between posterolateral and circumferential fusion reporting cost-effectiveness from a 2-year viewpoint. A total of 146 patients were randomized to posterolateral or circumferential fusion and followed 4 to 8 years after surgery. The mean age of the cohort was 46 years (range, 20-65 years); 61% were females, 49% were smokers, 30% had primary diagnosis of isthmic spondylolisthesis, 35% had disc degeneration and no previous surgery, and 35% had disc degeneration and previous surgery. Eighty-two percent of patients have had symptoms for more than 2 years and 50% were out of the labor market due to sickness. The EQ-5D instrument was applied for the measurement of health-related quality of life and costs (2004 U.S. dollars) were measured in a full-scale societal perspective. Productivity costs were valued by the Friction Cost method, and both costs and effects were discounted. Arithmetic means and 95% bias-corrected, bootstrapped confidence intervals were reported. Nonparametric statistics were used for tests of statistical significance. Comprehensive sensitivity analysis was conducted and reported using cost-effectiveness acceptability curves. The circumferential group demonstrated clinical superiority over the posterolateral fusion group in functional outcome (P < 0.01), fusion rate (P < 0.04), and number of reoperations (P < 0.01) among others. Cost-utility analysis demonstrated circumferential fusion dominant over posterolateral fusion, that is, for each QALY gained performing circumferential fusion, the incremental saving was estimated at U.S. $49,306 (95% confidence interval, $27,183-$2,735,712). Results proved to be strong to various sensitivity analyses; only a differentiated underestimation of patients' need for postoperative household help against the circumferential approach could alter the dominance; however, still the probability of cost-effectiveness was >0.85 given a threshold for willingness to pay of U.S. $50,000 per QALY. Circumferential fusion is dominant over instrumented posterolateral fusion, that is, both being significantly cheaper and significantly better in a long-term, societal perspective.

Chimeric Amino Acid Rearrangements as Immune Targets in Prostate Cancer

DTIC Science & Technology

2016-05-01

plot showing gene fusions between exon boundaries Figure 3. Lum (PC141070) A B Figure 4. Recurrent fusion genes present in the TCGA intermediate and...class I restricted epitopes in 6 out of 50 patient tumors. One recurrent gene fusion encoded by the TMPRSS2:ERG type VI fusion was detected in 3...found to have high-affinity (IEDB score អ nM) MHC class I predicted epitopes. Recurrent fusions In a comparative analysis across the patient

Revisiting the JDL Model for Information Exploitation

DTIC Science & Technology

2013-07-01

High-Level Information Fusion Management and Systems Design, Artech House, Norwood, MA, 2012. [10] E. Blasch, D. A. Lambert, P. Valin , M. M. Kokar...Fusion – Fusion2012 Panel Discussion,” Int. Conf. on Info Fusion, 2012. [29] E. P. Blasch, P. Valin , A-L. Jousselme, et al., “Top Ten Trends in High...P. Valin , E. Bosse, M. Nilsson, J. Van Laere, et al., “Implication of Culture: User Roles in Information Fusion for Enhanced Situational

Preface to the Special Issue: Strategic Opportunities for Fusion Energy

DOE PAGES

Mauel, M. E.; Greenwald, Martin; Ryutov, Dmitri D.; ...

2016-01-23

Here, the Journal of Fusion Energy provides a forum for discussion of broader policy and planning issues that play a crucial role in energy fusion programs. In keeping with this purpose and in response to several recent strategic planning efforts worldwide, this Special Issue on Strategic Opportunities was launched with the goal to invite fusion scientists and engineers to record viewpoints of the scientific opportunities and policy issues that can drive continued advancements in fusion energy research.

Outcome of transforaminal lumbar interbody fusion in spondylolisthesis-A clinico-radiological correlation.

PubMed

Balasubramanian, Vijay Anand; Douraiswami, Balaji; Subramani, Suresh

2018-06-01

Lumbar spondylolisthesis is a common cause of morbidity in middle aged individuals. Spinal fusion with instrumentation has become the gold standard for lumbar segmental instability. Studies which correlate the improvement in radiology postoperatively with functional outcome show contrasting reports. This study is aimed at finding the correlation between clinical and radiological outcomes after surgery with transforaminal lumbar interbody fusion. A retrospective study in 35 patients who underwent transforaminal lumbar interbody fusion in a period of 1 year was done. Preoperative pain (VAS Score), functional ability (ODI), radiological parameters (slip angle, slip grade, disc height, foraminal height, lumbar lordosis) were compared with postoperative recordings at the last followup. Functional improvement (Macnab's criteria) and fusion (Lee's fusion criteria) were assessed. Statistical analysis was done with student's paired t -test and Pearson's correlation coefficient. VAS score, ODI improved from 8 to 2 and 70 to 15 respectively. Slip angle improved from 23°to 5° on an average. 80% patients showed fusion and 85% showed good clinical outcome at 1 year followup. Analyzing with Pearson correlation coefficient showed no significant relation between pain scores and radiological parameters. But there was statistically significant relation between radiological fusion and the final clinical outcome. TLIF produces spinal fusion in most individuals. Strong spinal fusion is essential for good clinical outcome in spondylolisthesis patients who undergo TLIF. Reduction in slip is not necessary for all patients with listhesis.

Vegetative hyphal fusion and subsequent nuclear behavior in Epichloë grass endophytes.

PubMed

Shoji, Jun-Ya; Charlton, Nikki D; Yi, Mihwa; Young, Carolyn A; Craven, Kelly D

2015-01-01

Epichloë species (including the former genus Neotyphodium) are fungal symbionts of many agronomically important forage grasses, and provide their grass hosts with protection from a wide range of biotic and abiotic stresses. Epichloë species include many interspecific hybrids with allodiploid-like genomes, which may provide the potential for combined traits or recombination to generate new traits. Though circumstantial evidence suggests that such interspecific hybrids might have arisen from nuclear fusion events following vegetative hyphal fusion between different Epichloë strains, this hypothesis has not been addressed empirically. Here, we investigated vegetative hyphal fusion and subsequent nuclear behavior in Epichloë species. A majority of Epichloë strains, especially those having a sexual stage, underwent self vegetative hyphal fusion. Vegetative fusion also occurred between two hyphae from different Epichloë strains. Though Epichloë spp. are uninucleate fungi, hyphal fusion resulted in two nuclei stably sharing the same cytoplasm, which might ultimately lead to nuclear fusion. In addition, protoplast fusion experiments gave rise to uninucleate putative hybrids, which apparently had two markers, one from each parent within the same nucleus. These results are consistent with the notion that interspecific hybrids arise from vegetative hyphal fusion. However, we also discuss additional factors, such as post-hybridization selection, that may be important to explain the recognized prevalence of hybrids in Epichloë species.

Vegetative Hyphal Fusion and Subsequent Nuclear Behavior in Epichloë Grass Endophytes

PubMed Central

Shoji, Jun-ya; Charlton, Nikki D.; Yi, Mihwa; Young, Carolyn A.; Craven, Kelly D.

2015-01-01

Epichloë species (including the former genus Neotyphodium) are fungal symbionts of many agronomically important forage grasses, and provide their grass hosts with protection from a wide range of biotic and abiotic stresses. Epichloë species include many interspecific hybrids with allodiploid-like genomes, which may provide the potential for combined traits or recombination to generate new traits. Though circumstantial evidence suggests that such interspecific hybrids might have arisen from nuclear fusion events following vegetative hyphal fusion between different Epichloë strains, this hypothesis has not been addressed empirically. Here, we investigated vegetative hyphal fusion and subsequent nuclear behavior in Epichloë species. A majority of Epichloë strains, especially those having a sexual stage, underwent self vegetative hyphal fusion. Vegetative fusion also occurred between two hyphae from different Epichloë strains. Though Epichloë spp. are uninucleate fungi, hyphal fusion resulted in two nuclei stably sharing the same cytoplasm, which might ultimately lead to nuclear fusion. In addition, protoplast fusion experiments gave rise to uninucleate putative hybrids, which apparently had two markers, one from each parent within the same nucleus. These results are consistent with the notion that interspecific hybrids arise from vegetative hyphal fusion. However, we also discuss additional factors, such as post-hybridization selection, that may be important to explain the recognized prevalence of hybrids in Epichloë species. PMID:25837972

Electrostatic Architecture of the Infectious Salmon Anemia Virus (ISAV) Core Fusion Protein Illustrates a Carboxyl-Carboxylate pH Sensor.

PubMed

Cook, Jonathan D; Soto-Montoya, Hazel; Korpela, Markus K; Lee, Jeffrey E

2015-07-24

Segment 5, ORF 1 of the infectious salmon anemia virus (ISAV) genome, encodes for the ISAV F protein, which is responsible for viral-host endosomal membrane fusion during a productive ISAV infection. The entry machinery of ISAV is composed of a complex of the ISAV F and ISAV hemagglutinin esterase (HE) proteins in an unknown stoichiometry prior to receptor engagement by ISAV HE. Following binding of the receptor to ISAV HE, dissociation of the ISAV F protein from HE, and subsequent endocytosis, the ISAV F protein resolves into a fusion-competent oligomeric state. Here, we present a 2.1 Å crystal structure of the fusion core of the ISAV F protein determined at low pH. This structure has allowed us to unambiguously demonstrate that the ISAV entry machinery exhibits typical class I viral fusion protein architecture. Furthermore, we have determined stabilizing factors that accommodate the pH-dependent mode of ISAV transmission, and our structure has allowed the identification of a central coil that is conserved across numerous and varied post-fusion viral glycoprotein structures. We then discuss a mechanistic model of ISAV fusion that parallels the paramyxoviral class I fusion strategy wherein attachment and fusion are relegated to separate proteins in a similar fashion to ISAV fusion. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

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

PubMed Central

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

2014-01-01

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

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

PubMed

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

2014-11-26

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

Feature-Motivated Simplified Adaptive PCNN-Based Medical Image Fusion Algorithm in NSST Domain.

PubMed

Ganasala, Padma; Kumar, Vinod

2016-02-01

Multimodality medical image fusion plays a vital role in diagnosis, treatment planning, and follow-up studies of various diseases. It provides a composite image containing critical information of source images required for better localization and definition of different organs and lesions. In the state-of-the-art image fusion methods based on nonsubsampled shearlet transform (NSST) and pulse-coupled neural network (PCNN), authors have used normalized coefficient value to motivate the PCNN-processing both low-frequency (LF) and high-frequency (HF) sub-bands. This makes the fused image blurred and decreases its contrast. The main objective of this work is to design an image fusion method that gives the fused image with better contrast, more detail information, and suitable for clinical use. We propose a novel image fusion method utilizing feature-motivated adaptive PCNN in NSST domain for fusion of anatomical images. The basic PCNN model is simplified, and adaptive-linking strength is used. Different features are used to motivate the PCNN-processing LF and HF sub-bands. The proposed method is extended for fusion of functional image with an anatomical image in improved nonlinear intensity hue and saturation (INIHS) color model. Extensive fusion experiments have been performed on CT-MRI and SPECT-MRI datasets. Visual and quantitative analysis of experimental results proved that the proposed method provides satisfactory fusion outcome compared to other image fusion methods.

An Oncogenic NTRK Fusion in a Patient with Soft-Tissue Sarcoma with Response to the Tropomyosin-Related Kinase Inhibitor LOXO-101.

PubMed

Doebele, Robert C; Davis, Lara E; Vaishnavi, Aria; Le, Anh T; Estrada-Bernal, Adriana; Keysar, Stephen; Jimeno, Antonio; Varella-Garcia, Marileila; Aisner, Dara L; Li, Yali; Stephens, Philip J; Morosini, Deborah; Tuch, Brian B; Fernandes, Michele; Nanda, Nisha; Low, Jennifer A

2015-10-01

Oncogenic TRK fusions induce cancer cell proliferation and engage critical cancer-related downstream signaling pathways. These TRK fusions occur rarely, but in a diverse spectrum of tumor histologies. LOXO-101 is an orally administered inhibitor of the TRK kinase and is highly selective only for the TRK family of receptors. Preclinical models of LOXO-101 using TRK-fusion-bearing human-derived cancer cell lines demonstrate inhibition of the fusion oncoprotein and cellular proliferation in vitro, and tumor growth in vivo. The tumor of a 41-year-old woman with soft-tissue sarcoma metastatic to the lung was found to harbor an LMNA-NTRK1 gene fusion encoding a functional LMNA-TRKA fusion oncoprotein as determined by an in situ proximity ligation assay. In a phase I study of LOXO-101 (ClinicalTrials.gov no. NCT02122913), this patient's tumors underwent rapid and substantial tumor regression, with an accompanying improvement in pulmonary dyspnea, oxygen saturation, and plasma tumor markers. TRK fusions have been deemed putative oncogenic drivers, but their clinical significance remained unclear. A patient with a metastatic soft-tissue sarcoma with an LMNA-NTRK1 fusion had rapid and substantial tumor regression with a novel, highly selective TRK inhibitor, LOXO-101, providing the first clinical evidence of benefit from inhibiting TRK fusions. ©2015 American Association for Cancer Research.

Independent evolutionary origins of functional polyamine biosynthetic enzyme fusions catalyzing de novo diamine to triamine formation

PubMed Central

Green, Robert; Hanfrey, Colin C.; Elliott, Katherine A.; McCloskey, Diane E.; Wang, Xiaojing; Kanugula, Sreenivas; Pegg, Anthony E.; Michael, Anthony J.

2011-01-01

Summary We have identified gene fusions of polyamine biosynthetic enzymes S-adenosylmethionine decarboxylase (AdoMetDC, speD) and aminopropyltransferase (speE) orthologues in diverse bacterial phyla. Both domains are functionally active and we demonstrate the novel de novo synthesis of the triamine spermidine from the diamine putrescine by fusion enzymes from β-proteobacterium Delftia acidovorans and δ-proteobacterium Syntrophus aciditrophicus, in a ΔspeDE gene deletion strain of Salmonella enterica sv. Typhimurium. Fusion proteins from marine α-proteobacterium Candidatus Pelagibacter ubique, actinobacterium Nocardia farcinica, chlorobi species Chloroherpeton thalassium, and β-proteobacterium Delftia acidovorans each produce a different profile of non-native polyamines including sym-norspermidine when expressed in Escherichia coli. The different aminopropyltransferase activities together with phylogenetic analysis confirm independent evolutionary origins for some fusions. Comparative genomic analysis strongly indicates that gene fusions arose by merger of adjacent open reading frames. Independent fusion events, and horizontal and vertical gene transfer contributed to the scattered phyletic distribution of the gene fusions. Surprisingly, expression of fusion genes in E. coli and S. Typhimurium revealed novel latent spermidine catabolic activity producing non-native 1,3-diaminopropane in these species. We have also identified fusions of polyamine biosynthetic enzymes agmatine deiminase and N-carbamoylputrescine amidohydrolase in archaea, and of S-adenosylmethionine decarboxylase and ornithine decarboxylase in the single-celled green alga Micromonas. PMID:21762220

A tethering complex drives the terminal stage of SNARE-dependent membrane fusion

NASA Astrophysics Data System (ADS)

D'Agostino, Massimo; Risselada, Herre Jelger; Lürick, Anna; Ungermann, Christian; Mayer, Andreas

2017-11-01

Membrane fusion in eukaryotic cells mediates the biogenesis of organelles, vesicular traffic between them, and exo- and endocytosis of important signalling molecules, such as hormones and neurotransmitters. Distinct tasks in intracellular membrane fusion have been assigned to conserved protein systems. Tethering proteins mediate the initial recognition and attachment of membranes, whereas SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) protein complexes are considered as the core fusion engine. SNARE complexes provide mechanical energy to distort membranes and drive them through a hemifusion intermediate towards the formation of a fusion pore. This last step is highly energy-demanding. Here we combine the in vivo and in vitro fusion of yeast vacuoles with molecular simulations to show that tethering proteins are critical for overcoming the final energy barrier to fusion pore formation. SNAREs alone drive vacuoles only into the hemifused state. Tethering proteins greatly increase the volume of SNARE complexes and deform the site of hemifusion, which lowers the energy barrier for pore opening and provides the driving force. Thereby, tethering proteins assume a crucial mechanical role in the terminal stage of membrane fusion that is likely to be conserved at multiple steps of vesicular traffic. We therefore propose that SNAREs and tethering proteins should be considered as a single, non-dissociable device that drives fusion. The core fusion machinery may then be larger and more complex than previously thought.

Kinetic analysis of thermal stability of human low density lipoproteins: a model for LDL fusion in atherogenesis[S

PubMed Central

Lu, Mengxiao; Gantz, Donald L.; Herscovitz, Haya; Gursky, Olga

2012-01-01

Fusion of modified LDL in the arterial wall promotes atherogenesis. Earlier we showed that thermal denaturation mimics LDL remodeling and fusion, and revealed kinetic origin of LDL stability. Here we report the first quantitative analysis of LDL thermal stability. Turbidity data show sigmoidal kinetics of LDL heat denaturation, which is unique among lipoproteins, suggesting that fusion is preceded by other structural changes. High activation energy of denaturation, Ea = 100 ± 8 kcal/mol, indicates disruption of extensive packing interactions in LDL. Size-exclusion chromatography, nondenaturing gel electrophoresis, and negative-stain electron microscopy suggest that LDL dimerization is an early step in thermally induced fusion. Monoclonal antibody binding suggests possible involvement of apoB N-terminal domain in early stages of LDL fusion. LDL fusion accelerates at pH < 7, which may contribute to LDL retention in acidic atherosclerotic lesions. Fusion also accelerates upon increasing LDL concentration in near-physiologic range, which likely contributes to atherogenesis. Thermal stability of LDL decreases with increasing particle size, indicating that the pro-atherogenic properties of small dense LDL do not result from their enhanced fusion. Our work provides the first kinetic approach to measuring LDL stability and suggests that lipid-lowering therapies that reduce LDL concentration but increase the particle size may have opposite effects on LDL fusion. PMID:22855737

Active inhibition of herpes simplex virus type 1-induced cell fusion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bzik, D.J.; Person, S.; Read, G.S.

1982-01-01

Previous studies have demonstrated that syn mutant-infected cells fuse less well with nonsyncytial virus-infected cells than with uninfected cells, a phenomenon defined as function inhibition. The present study characterizes the kinetics as well as the requirements for expression of fusion inhibition. Initially, the capacity of sparse syn mutant-infected cells to fuse with uninfected surrounding cells was determined throughout infection. Of seven syn mutants examined, including representatives with alterations in two different viral genes that affect cell fusion, all showed an increase in fusion capacity up to 12 hr after infection and a decrease at later times. Fusion inhibition was examinedmore » in experiments employing sparse syn20-infected cells which had been incubated to a maximum fusion capacity; it was shown that surrounding cells infected with KOS, the parent of syn20, began to inhibit fusion by the syn20-infected cells at about 4 hr after infection, and that the maximum ability to inhibit fusion was attained at about 6 hr after infection. The metabolic blocking agents actinomycin D (RNA), cycloheximide (protein), 2-deoxyglucose, and tunicamycin (glycoslyation of glycoproteins) all showed the ability to inhibit the expression of fusion inhibition by KOS-infected cells if added shortly after infection. It is concluded that fusion inhibition is an active process that requires the synthesis of RNA, proteins, and glycoproteins. 17 references, 3 figures, 2 tables.« less

Generation of fusion protein EGFRvIII-HBcAg and its anti-tumor effect in vivo

PubMed Central

Duan, Xiao-yi; Han, Dong-gang; Zhang, Ming-xin; Wang, Jian-sheng

2009-01-01

The epidermal growth factor receptor variant III (EGFRvIII) is the most common variation of EGFR. Because it shows a high frequency in several different types of tumor and has not been detected in normal tissues, it is an ideal target for tumor specific therapy. In this study, we prepared EGFRvIII-HBcAg fusion protein. After immunization with fusion protein, HBcAg or PBS, the titers of antibody in BALB/c mice immunized with fusion protein reached 2.75 × 105. Western blot analysis demonstrated that the fusion protein had specific antigenicity against anti-EGFRvIII antibody. Further observation showed fusion protein induced a high frequency of IFN-γ-secreting lymphocytes. CD4+T cells rather than CD8+T cells were associated with the production of IFN-γ. Using Renca-vIII(+) cell as specific stimulator, we observed remarkable cytotoxic activity in splenocytes from mice immunized with fusion protein. Mice were challenged with Renca-vIII(+) cells after five times immunization. In fusion protein group, three of ten mice failed to develop tumor and all survived at the end of the research. The weight of tumors in fusion protein were obviously lighter than that in other two groups (t = 4.73, P = 0.044;t = 6.89, P = 0.040). These findings demonstrated that EGFRvIII-HBcAg fusion protein triggered protective responses against tumor expressing EGFRvIII. PMID:19788747

Kinetic analysis of thermal stability of human low density lipoproteins: a model for LDL fusion in atherogenesis.

PubMed

Lu, Mengxiao; Gantz, Donald L; Herscovitz, Haya; Gursky, Olga

2012-10-01

Fusion of modified LDL in the arterial wall promotes atherogenesis. Earlier we showed that thermal denaturation mimics LDL remodeling and fusion, and revealed kinetic origin of LDL stability. Here we report the first quantitative analysis of LDL thermal stability. Turbidity data show sigmoidal kinetics of LDL heat denaturation, which is unique among lipoproteins, suggesting that fusion is preceded by other structural changes. High activation energy of denaturation, E(a) = 100 ± 8 kcal/mol, indicates disruption of extensive packing interactions in LDL. Size-exclusion chromatography, nondenaturing gel electrophoresis, and negative-stain electron microscopy suggest that LDL dimerization is an early step in thermally induced fusion. Monoclonal antibody binding suggests possible involvement of apoB N-terminal domain in early stages of LDL fusion. LDL fusion accelerates at pH < 7, which may contribute to LDL retention in acidic atherosclerotic lesions. Fusion also accelerates upon increasing LDL concentration in near-physiologic range, which likely contributes to atherogenesis. Thermal stability of LDL decreases with increasing particle size, indicating that the pro-atherogenic properties of small dense LDL do not result from their enhanced fusion. Our work provides the first kinetic approach to measuring LDL stability and suggests that lipid-lowering therapies that reduce LDL concentration but increase the particle size may have opposite effects on LDL fusion.

Paclitaxel stimulates chromosomal fusion and instability in cells with dysfunctional telomeres: Implication in multinucleation and chemosensitization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, Jeong-Eun; Woo, Seon Rang; Department of Biochemistry, College of Medicine, Korea University, Seoul 136-705

Research highlights: {yields} Paclitaxel serves as a stimulator of chromosomal fusion in cells in which telomeres are dysfunctional. {yields} Typical fusions involve p-arms, but paclitaxel-induced fusions occur between both q- and p-arms. {yields} Paclitaxel-stimulated fusions in cells in which telomeres are dysfunctional evoke prolonged G2/M cell cycle arrest and delay multinucleation. {yields} Upon telomere erosion, paclitaxel promotes chromosomal instability and subsequent apoptosis. {yields} Chromosomal fusion enhances paclitaxel chemosensitivity under telomere dysfunction. -- Abstract: The anticancer effect of paclitaxel is attributable principally to irreversible promotion of microtubule stabilization and is hampered upon development of chemoresistance by tumor cells. Telomere shortening, andmore » eventual telomere erosion, evoke chromosomal instability, resulting in particular cellular responses. Using telomerase-deficient cells derived from mTREC-/-p53-/- mice, here we show that, upon telomere erosion, paclitaxel propagates chromosomal instability by stimulating chromosomal end-to-end fusions and delaying the development of multinucleation. The end-to-end fusions involve both the p- and q-arms in cells in which telomeres are dysfunctional. Paclitaxel-induced chromosomal fusions were accompanied by prolonged G2/M cell cycle arrest, delayed multinucleation, and apoptosis. Telomere dysfunctional cells with mutlinucleation eventually underwent apoptosis. Thus, as telomere erosion proceeds, paclitaxel stimulates chromosomal fusion and instability, and both apoptosis and chemosensitization eventually develop.« less

[MRI/TRUS fusion-guided prostate biopsy : Value in the context of focal therapy].

PubMed

Franz, T; von Hardenberg, J; Blana, A; Cash, H; Baumunk, D; Salomon, G; Hadaschik, B; Henkel, T; Herrmann, J; Kahmann, F; Köhrmann, K-U; Köllermann, J; Kruck, S; Liehr, U-B; Machtens, S; Peters, I; Radtke, J P; Roosen, A; Schlemmer, H-P; Sentker, L; Wendler, J J; Witzsch, U; Stolzenburg, J-U; Schostak, M; Ganzer, R

2017-02-01

Several systems for MRI/TRUS fusion-guided biopsy of the prostate are commercially available. Many studies have shown superiority of fusion systems for tumor detection and diagnostic quality compared to random biopsy. The benefit of fusion systems in focal therapy of prostate cancer (PC) is less clear. Critical considerations of fusion systems for planning and monitoring of focal therapy of PC were investigated. A systematic literature review of available fusion systems for the period 2013-5/2016 was performed. A checklist of technical details, suitability for special anatomic situations and suitability for focal therapy was established by the German working group for focal therapy (Arbeitskreis fokale und Mikrotherapie). Eight fusion systems were considered (Artemis™, BioJet, BiopSee®, iSR´obot™ Mona Lisa, Hitachi HI-RVS, UroNav and Urostation®). Differences were found for biopsy mode (transrectal, perineal, both), fusion mode (elastic or rigid), navigation (image-based, electromagnetic sensor-based or mechanical sensor-based) and space requirements. Several consensus groups recommend fusion systems for focal therapy. Useful features are "needle tracking" and compatibility between fusion system and treatment device (available for Artemis™, BiopSee® and Urostation® with Focal One®; BiopSee®, Hitachi HI-RVS with NanoKnife®; BioJet, BiopSee® with cryoablation, brachytherapy). There are a few studies for treatment planning. However, studies on treatment monitoring after focal therapy are missing.

Establishment of a new method to quantitatively evaluate hyphal fusion ability in Aspergillus oryzae.

PubMed

Tsukasaki, Wakako; Maruyama, Jun-Ichi; Kitamoto, Katsuhiko

2014-01-01

Hyphal fusion is involved in the formation of an interconnected colony in filamentous fungi, and it is the first process in sexual/parasexual reproduction. However, it was difficult to evaluate hyphal fusion efficiency due to the low frequency in Aspergillus oryzae in spite of its industrial significance. Here, we established a method to quantitatively evaluate the hyphal fusion ability of A. oryzae with mixed culture of two different auxotrophic strains, where the ratio of heterokaryotic conidia growing without the auxotrophic requirements reflects the hyphal fusion efficiency. By employing this method, it was demonstrated that AoSO and AoFus3 are required for hyphal fusion, and that hyphal fusion efficiency of A. oryzae was increased by depleting nitrogen source, including large amounts of carbon source, and adjusting pH to 7.0.

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.

Decision Fusion with Channel Errors in Distributed Decode-Then-Fuse Sensor Networks

PubMed Central

Yan, Yongsheng; Wang, Haiyan; Shen, Xiaohong; Zhong, Xionghu

2015-01-01

Decision fusion for distributed detection in sensor networks under non-ideal channels is investigated in this paper. Usually, the local decisions are transmitted to the fusion center (FC) and decoded, and a fusion rule is then applied to achieve a global decision. We propose an optimal likelihood ratio test (LRT)-based fusion rule to take the uncertainty of the decoded binary data due to modulation, reception mode and communication channel into account. The average bit error rate (BER) is employed to characterize such an uncertainty. Further, the detection performance is analyzed under both non-identical and identical local detection performance indices. In addition, the performance of the proposed method is compared with the existing optimal and suboptimal LRT fusion rules. The results show that the proposed fusion rule is more robust compared to these existing ones. PMID:26251908

Importance of lifetime effects in breakup and suppression of complete fusion in reactions of weakly bound nuclei

NASA Astrophysics Data System (ADS)

Cook, K. J.; Simpson, E. C.; Luong, D. H.; Kalkal, Sunil; Dasgupta, M.; Hinde, D. J.

2016-06-01

Background: Complete fusion cross sections in collisions of light weakly bound nuclei and high-Z targets show suppression of complete fusion at above-barrier energies. This has been interpreted as resulting from the breakup of the weakly bound nucleus prior to reaching the fusion barrier, reducing the probability of complete charge capture. Below-barrier studies of reactions of 9Be have found that the breakup of 8Be formed by neutron stripping dominates over direct breakup and that transfer-triggered breakup may account for the observed suppression of complete fusion. Purpose: This paper investigates how the above conclusions are affected by lifetimes of the resonant states that are populated prior to breakup. If the mean life of a populated resonance (above the breakup threshold) is much longer than the fusion time scale, then its breakup (decay) cannot suppress complete fusion. For short-lived resonances, the situation is more complex. This work explicitly includes the mean life of the short-lived 2+ resonance in 8Be in classical dynamical model calculations to determine its effect on energy and angular correlations of the breakup fragments and on model predictions of suppression of cross sections for complete fusion at above-barrier energies. Method: Previously performed coincidence measurements of breakup fragments produced in reactions of 9Be with 144Sm, 168Er, 186W, 196Pt, 208Pb, and 209Bi at energies below the barrier have been reanalyzed using an improved efficiency determination of the BALiN detector array. Predictions of breakup observables and of complete and incomplete fusion at energies above the fusion barrier are then made using the classical dynamical simulation code platypus, modified to include the effect of lifetimes of resonant states. Results: The agreement of the breakup observables is much improved when lifetime effects are included explicitly. Sensitivity to subzeptosecond lifetime is observed. The predicted suppression of complete fusion owing to breakup is nearly independent of Z and has an average value of ˜9 % . This is below the experimentally determined fusion suppression, which is typically ˜30 % in these systems. Conclusions: Inclusion of resonance lifetimes is essential to correctly reproduce breakup observables. This results in a larger fraction of nuclei remaining intact at the fusion-barrier radius compared with calculations that do not explicitly include lifetime effects. The more realistic treatment of breakup followed in this work leads to the conclusion that the suppression of complete fusion cannot be fully explained by breakup prior to reaching the fusion barrier. Only one-third of the observed fusion suppression can be attributed to the competing process of breakup. Other mechanisms that can suppress complete fusion must therefore be investigated. One of the possible candidates is cluster transfer that produces the same heavy targetlike nuclei as those formed by incomplete fusion.

Macrophage Fusion Is Controlled by the Cytoplasmic Protein Tyrosine Phosphatase PTP-PEST/PTPN12

PubMed Central

Rhee, Inmoo; Davidson, Dominique; Souza, Cleiton Martins; Vacher, Jean

2013-01-01

Macrophages can undergo cell-cell fusion, leading to the formation of multinucleated giant cells and osteoclasts. This process is believed to promote the proteolytic activity of macrophages toward pathogens, foreign bodies, and extracellular matrices. Here, we examined the role of PTP-PEST (PTPN12), a cytoplasmic protein tyrosine phosphatase, in macrophage fusion. Using a macrophage-targeted PTP-PEST-deficient mouse, we determined that PTP-PEST was not needed for macrophage differentiation or cytokine production. However, it was necessary for interleukin-4-induced macrophage fusion into multinucleated giant cells in vitro. It was also needed for macrophage fusion following implantation of a foreign body in vivo. Moreover, in the RAW264.7 macrophage cell line, PTP-PEST was required for receptor activator of nuclear factor kappa-B ligand (RANKL)-triggered macrophage fusion into osteoclasts. PTP-PEST had no impact on expression of fusion mediators such as β-integrins, E-cadherin, and CD47, which enable macrophages to become fusion competent. However, it was needed for polarization of macrophages, migration induced by the chemokine CC chemokine ligand 2 (CCL2), and integrin-induced spreading, three key events in the fusion process. PTP-PEST deficiency resulted in specific hyperphosphorylation of the protein tyrosine kinase Pyk2 and the adaptor paxillin. Moreover, a fusion defect was induced upon treatment of normal macrophages with a Pyk2 inhibitor. Together, these data argue that macrophage fusion is critically dependent on PTP-PEST. This function is seemingly due to the ability of PTP-PEST to control phosphorylation of Pyk2 and paxillin, thereby regulating cell polarization, migration, and spreading. PMID:23589331

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kirkpatrick, R. C.

Nuclear fusion was discovered experimentally in 1933-34 and other charged particle nuclear reactions were documented shortly thereafter. Work in earnest on the fusion ignition problem began with Edward Teller's group at Los Alamos during the war years. His group quantified all the important basic atomic and nuclear processes and summarized their interactions. A few years later, the success of the early theory developed at Los Alamos led to very successful thermonuclear weapons, but also to decades of unsuccessful attempts to harness fusion as an energy source of the future. The reasons for this history are many, but it seems appropriatemore » to review some of the basics with the objective of identifying what is essential for success and what is not. This tutorial discusses only the conditions required for ignition in small fusion targets and how the target design impacts driver requirements. Generally speaking, the driver must meet the energy, power and power density requirements needed by the fusion target. The most relevant parameters for ignition of the fusion fuel are the minimum temperature and areal density (rhoR), but these parameters set secondary conditions that must be achieved, namely an implosion velocity, target size and pressure, which are interrelated. Despite the apparent simplicity of inertial fusion targets, there is not a single mode of fusion ignition, and the necessary combination of minimum temperature and areal density depends on the mode of ignition. However, by providing a magnetic field of sufficient strength, the conditions needed for fusion ignition can be drastically altered. Magnetized target fusion potentially opens up a vast parameter space between the extremes of magnetic and inertial fusion.« less

Distinct Requirements for HIV-Cell Fusion and HIV-mediated Cell-Cell Fusion*

PubMed Central

Kondo, Naoyuki; Marin, Mariana; Kim, Jeong Hwa; Desai, Tanay M.; Melikyan, Gregory B.

2015-01-01

Whether HIV-1 enters cells by fusing with the plasma membrane or with endosomes is a subject of active debate. The ability of HIV-1 to mediate fusion between adjacent cells, a process referred to as “fusion-from-without” (FFWO), shows that this virus can fuse with the plasma membrane. To compare FFWO occurring at the cell surface with HIV-cell fusion through a conventional entry route, we designed an experimental approach that enabled the measurements of both processes in the same sample. The following key differences were observed. First, a very small fraction of viruses fusing with target cells participated in FFWO. Second, whereas HIV-1 fusion with adherent cells was insensitive to actin inhibitors, post-CD4/coreceptor binding steps during FFWO were abrogated. A partial dependence of HIV-cell fusion on actin remodeling was observed in CD4+ T cells, but this effect appeared to be due to the actin dependence of virus uptake. Third, deletion of the cytoplasmic tail of HIV-1 gp41 dramatically enhanced the ability of the virus to promote FFWO, while having a modest effect on virus-cell fusion. Distinct efficiencies and actin dependences of FFWO versus HIV-cell fusion are consistent with the notion that, except for a minor fraction of particles that mediate fusion between the plasma membranes of adjacent cells, HIV-1 enters through an endocytic pathway. We surmise, however, that cell-cell contacts enabling HIV-1 fusion with the plasma membrane could be favored at the sites of high density of target cells, such as lymph nodes. PMID:25589785

Macrophage fusion is controlled by the cytoplasmic protein tyrosine phosphatase PTP-PEST/PTPN12.

PubMed

Rhee, Inmoo; Davidson, Dominique; Souza, Cleiton Martins; Vacher, Jean; Veillette, André

2013-06-01

Macrophages can undergo cell-cell fusion, leading to the formation of multinucleated giant cells and osteoclasts. This process is believed to promote the proteolytic activity of macrophages toward pathogens, foreign bodies, and extracellular matrices. Here, we examined the role of PTP-PEST (PTPN12), a cytoplasmic protein tyrosine phosphatase, in macrophage fusion. Using a macrophage-targeted PTP-PEST-deficient mouse, we determined that PTP-PEST was not needed for macrophage differentiation or cytokine production. However, it was necessary for interleukin-4-induced macrophage fusion into multinucleated giant cells in vitro. It was also needed for macrophage fusion following implantation of a foreign body in vivo. Moreover, in the RAW264.7 macrophage cell line, PTP-PEST was required for receptor activator of nuclear factor kappa-B ligand (RANKL)-triggered macrophage fusion into osteoclasts. PTP-PEST had no impact on expression of fusion mediators such as β-integrins, E-cadherin, and CD47, which enable macrophages to become fusion competent. However, it was needed for polarization of macrophages, migration induced by the chemokine CC chemokine ligand 2 (CCL2), and integrin-induced spreading, three key events in the fusion process. PTP-PEST deficiency resulted in specific hyperphosphorylation of the protein tyrosine kinase Pyk2 and the adaptor paxillin. Moreover, a fusion defect was induced upon treatment of normal macrophages with a Pyk2 inhibitor. Together, these data argue that macrophage fusion is critically dependent on PTP-PEST. This function is seemingly due to the ability of PTP-PEST to control phosphorylation of Pyk2 and paxillin, thereby regulating cell polarization, migration, and spreading.

Hybrid Image Fusion for Sharpness Enhancement of Multi-Spectral Lunar Images

NASA Astrophysics Data System (ADS)

Awumah, Anna; Mahanti, Prasun; Robinson, Mark

2016-10-01

Image fusion enhances the sharpness of a multi-spectral (MS) image by incorporating spatial details from a higher-resolution panchromatic (Pan) image [1,2]. Known applications of image fusion for planetary images are rare, although image fusion is well-known for its applications to Earth-based remote sensing. In a recent work [3], six different image fusion algorithms were implemented and their performances were verified with images from the Lunar Reconnaissance Orbiter (LRO) Camera. The image fusion procedure obtained a high-resolution multi-spectral (HRMS) product from the LRO Narrow Angle Camera (used as Pan) and LRO Wide Angle Camera (used as MS) images. The results showed that the Intensity-Hue-Saturation (IHS) algorithm results in a high-spatial quality product while the Wavelet-based image fusion algorithm best preserves spectral quality among all the algorithms. In this work we show the results of a hybrid IHS-Wavelet image fusion algorithm when applied to LROC MS images. The hybrid method provides the best HRMS product - both in terms of spatial resolution and preservation of spectral details. Results from hybrid image fusion can enable new science and increase the science return from existing LROC images.[1] Pohl, Cle, and John L. Van Genderen. "Review article multisensor image fusion in remote sensing: concepts, methods and applications." International journal of remote sensing 19.5 (1998): 823-854.[2] Zhang, Yun. "Understanding image fusion." Photogramm. Eng. Remote Sens 70.6 (2004): 657-661.[3] Mahanti, Prasun et al. "Enhancement of spatial resolution of the LROC Wide Angle Camera images." Archives, XXIII ISPRS Congress Archives (2016).

Study on ( n,t) Reactions of Zr, Nb and Ta Nuclei

NASA Astrophysics Data System (ADS)

Tel, E.; Yiğit, M.; Tanır, G.

2012-04-01

The world faces serious energy shortages in the near future. To meet the world energy demand, the nuclear fusion with safety, environmentally acceptability and economic is the best suited. Fusion is attractive as an energy source because of the virtually inexhaustible supply of fuel, the promise of minimal adverse environmental impact, and its inherent safety. Fusion will not produce CO2 or SO2 and thus will not contribute to global warming or acid rain. Furthermore, there are not radioactive nuclear waste problems in the fusion reactors. Although there have been significant research and development studies on the inertial and magnetic fusion reactor technology, there is still a long way to go to penetrate commercial fusion reactors to the energy market. Because, tritium self-sufficiency must be maintained for a commercial power plant. For self-sustaining (D-T) fusion driver tritium breeding ratio should be greater than 1.05. And also, the success of fusion power system is dependent on performance of the first wall, blanket or divertor systems. So, the performance of structural materials for fusion power systems, understanding nuclear properties systematic and working out of ( n,t) reaction cross sections are very important. Zirconium (Zr), Niobium (Nb) and Tantal (Ta) containing alloys are important structural materials for fusion reactors, accelerator-driven systems, and many other fields. In this study, ( n,t) reactions for some structural fusion materials such as 88,90,92,94,96Zr, 93,94,95Nb and 179,181Ta have been investigated. The calculated results are discussed andcompared with the experimental data taken from the literature.

Comparison of interbody fusion approaches for disabling low back pain.

PubMed

Hacker, R J

1997-03-15

This is a study comparing two groups of patients surgically treated for disabling low back pain. One group was treated with lumbar anteroposterior fusion (360 degrees fusion), the other with posterior lumbar interbody fusion and an interbody fixation device. To determine which approach provided the best and most cost-effective outcome using similar patient selection criteria. Others have shown that certain patients with disabling low back pain benefit from lumbar fusion. Although rarely reported, the costs of different surgical treatments appear to vary significantly, whereas the patient outcome may vary little. Since 1991, 75 patients have been treated Starting in 1993, posterior lumbar interbody fusion BAK was offered to patients as an alternative to 360 degrees fusion. The treating surgeon reviewed the cases. The interbody fixation device used (BAK; Spine-Tech, Inc., Minneapolis, MN) was part of a Food and Drug Administration study. Patient selection criteria included examination, response to conservative therapy, imaging, psychological profile, and discography. North American Spine Society outcome questionnaires, BAK investigation data radiographs, chart entries, billing records and patient interviews were the basis for assessment. Age, sex compensable injury history and history of previous surgery were similar. Operative time; blood loss, hospitalization time, and total costs were significantly different. There was a quicker return to work and closure of workers compensation claims for the posterior lumbar interbody fusion-BAK group. Patient satisfaction was comparable at last follow-up. Posterior lumbar interbody fusion-BAK achieves equal patient satisfaction but fiscally surpasses the 360 degrees fusion approach. Today's environment of regulated medical practice requires the surgeon to consider cost effectiveness when performing fusion for low back pain.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Palomo, Concepción; Mas, Vicente; Vázquez, Mónica

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

Epidural Abscess: A Propensity Analysis of Surgical Treatment Strategies.

PubMed

Chaker, Anisse N; Bhimani, Abhiraj D; Esfahani, Darian R; Rosinski, Clayton L; Geever, Brett W; Patel, Akash S; Hobbs, Jonathan G; Burch, Taylor G; Patel, Saavan; Mehta, Ankit I

2018-06-18

Observational analysis of retrospectively collected data. A retrospective study was performed in order to compare the surgical profile of risk factors and perioperative complications for laminectomy and laminectomy with fusion procedures in the treatment of SEA. Spinal epidural abscess (SEA) is a highly morbid condition typically presenting with back pain, fever, and neurologic deficits. Posterior fusion has been used to supplement traditional laminectomy of SEA to improve spinal stability. At present, the ideal surgical strategy - laminectomy with or without fusion - remains elusive. 30-day outcomes such as reoperation and readmission following laminectomy and laminectomy with fusion in patients with SEA were investigated utilizing the American College of Surgeons National Quality Improvement Program database. Demographics and clinical risk factors were collected, and propensity matching was performed to account for differences in risk profiles between the groups. 738 patients were studied (608 laminectomy alone, 130 fusion). The fusion population was in worse health. The fusion population experienced significantly greater rate of return to the operating room (odds ratio (OR) 1.892), with the difference primarily accounted for by cervical spine operations. Additionally, fusion patients had significantly greater rates of blood transfusion. Infection was the most common reason for reoperation in both populations. Both laminectomy and laminectomy with fusion effectively treat SEA, but addition of fusion is associated with significantly higher rates of transfusion and perioperative return to the operating room. In operative situations where either procedure is reasonable, surgeons should consider that fusion nearly doubles the odds of reoperation in the short-term, and weigh this risk against the benefit of added stability. 3.

Entropic forces drive self-organization and membrane fusion by SNARE proteins

PubMed Central

Stratton, Benjamin S.; Warner, Jason M.; Rothman, James E.; O’Shaughnessy, Ben

2017-01-01

SNARE proteins are the core of the cell’s fusion machinery and mediate virtually all known intracellular membrane fusion reactions on which exocytosis and trafficking depend. Fusion is catalyzed when vesicle-associated v-SNAREs form trans-SNARE complexes (“SNAREpins”) with target membrane-associated t-SNAREs, a zippering-like process releasing ∼65 kT per SNAREpin. Fusion requires several SNAREpins, but how they cooperate is unknown and reports of the number required vary widely. To capture the collective behavior on the long timescales of fusion, we developed a highly coarse-grained model that retains key biophysical SNARE properties such as the zippering energy landscape and the surface charge distribution. In simulations the ∼65-kT zippering energy was almost entirely dissipated, with fully assembled SNARE motifs but uncomplexed linker domains. The SNAREpins self-organized into a circular cluster at the fusion site, driven by entropic forces that originate in steric–electrostatic interactions among SNAREpins and membranes. Cooperative entropic forces expanded the cluster and pulled the membranes together at the center point with high force. We find that there is no critical number of SNAREs required for fusion, but instead the fusion rate increases rapidly with the number of SNAREpins due to increasing entropic forces. We hypothesize that this principle finds physiological use to boost fusion rates to meet the demanding timescales of neurotransmission, exploiting the large number of v-SNAREs available in synaptic vesicles. Once in an unfettered cluster, we estimate ≥15 SNAREpins are required for fusion within the ∼1-ms timescale of neurotransmitter release. PMID:28490503

Comparative evaluation of three-dimensional Gd-EOB-DTPA-enhanced MR fusion imaging with CT fusion imaging in the assessment of treatment effect of radiofrequency ablation of hepatocellular carcinoma.

PubMed

Makino, Yuki; Imai, Yasuharu; Igura, Takumi; Hori, Masatoshi; Fukuda, Kazuto; Sawai, Yoshiyuki; Kogita, Sachiyo; Fujita, Norihiko; Takehara, Tetsuo; Murakami, Takamichi

2015-01-01

To assess the feasibility of fusion of pre- and post-ablation gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (Gd-EOB-DTPA-MRI) to evaluate the effects of radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC), compared with similarly fused CT images This retrospective study included 67 patients with 92 HCCs treated with RFA. Fusion images of pre- and post-RFA dynamic CT, and pre- and post-RFA Gd-EOB-DTPA-MRI were created, using a rigid registration method. The minimal ablative margin measured on fusion imaging was categorized into three groups: (1) tumor protruding outside the ablation zone boundary, (2) ablative margin 0-<5.0 mm beyond the tumor boundary, and (3) ablative margin ≥5.0 mm beyond the tumor boundary. The categorization of minimal ablative margins was compared between CT and MR fusion images. In 57 (62.0%) HCCs, treatment evaluation was possible both on CT and MR fusion images, and the overall agreement between them for the categorization of minimal ablative margin was good (κ coefficient = 0.676, P < 0.01). MR fusion imaging enabled treatment evaluation in a significantly larger number of HCCs than CT fusion imaging (86/92 [93.5%] vs. 62/92 [67.4%], P < 0.05). Fusion of pre- and post-ablation Gd-EOB-DTPA-MRI is feasible for treatment evaluation after RFA. It may enable accurate treatment evaluation in cases where CT fusion imaging is not helpful.

Development of motor fusion in patients with a history of strabismic amblyopia who are treated part-time with Bangerter foils.

PubMed

Abrams, Michael S; Duncan, Candace L; McMurtrey, Ryan

2011-04-01

To document the development of motor fusion when patients with a history of strabismic amblyopia are treated part-time with Bangerter foils. This was a prospective interventional outcome study of consecutive patients with a history of strabismic amblyopia, horizontal strabismus (only) ≤20(∆), visual acuity of 20/60 or better in the nonfixating eye, and no motor fusion (as indicated by the absence of prism vergence) for 1 year before entry into the study. Subjects wore a 0.1 density Bangerter foil for 3-4 hours daily. Data on visual acuity, alignment, and motor fusion status were collected for a minimum of 2 years. Patients with motor fusion were then followed for a minimum of 18 months to assess the stability of their motor fusion status after the Bangerter foil was discontinued. Of the 46 patients meeting entry criteria (mean age, 5.3 ± 1.7 years) who completed follow-up, 28 (61%) developed motor fusion. Motor fusion was retained in all 17 patients who were followed after their foils were discontinued for a mean of 13.3 months. A child's motor fusion status is generally believed to be established during an early formative period of visual development. The development of motor fusion in many of our patients during the course of part-time Bangerter foil treatment suggests that improvements in motor fusion status can occur at a later age than previously believed. Copyright © 2011 American Association for Pediatric Ophthalmology and Strabismus. Published by Mosby, Inc. All rights reserved.

21 CFR 886.1880 - Fusion and stereoscopic target.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Fusion and stereoscopic target. 886.1880 Section... (CONTINUED) MEDICAL DEVICES OPHTHALMIC DEVICES Diagnostic Devices § 886.1880 Fusion and stereoscopic target. (a) Identification. A fusion and stereoscopic target is a device intended for use as a viewing object...

21 CFR 886.1880 - Fusion and stereoscopic target.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Fusion and stereoscopic target. 886.1880 Section... (CONTINUED) MEDICAL DEVICES OPHTHALMIC DEVICES Diagnostic Devices § 886.1880 Fusion and stereoscopic target. (a) Identification. A fusion and stereoscopic target is a device intended for use as a viewing object...

Magneto-Inertial Fusion

DOE PAGES

Wurden, G. A.; Hsu, S. C.; Intrator, T. P.; ...

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). Furthermore, the status of MIF research in North America at multiple institutions is summarized including recent progress, research opportunities, and future plans.

DOE Office of Scientific and Technical Information (OSTI.GOV)

None

Nuclear fusion - the process that powers the sun - offers an environmentally benign, intrinsically safe energy source with an abundant supply of low-cost fuel. It is the focus of an international research program, including the ITE R fusion collaboration, which involves seven parties representing half the world's population. The realization of fusion power would change the economics and ecology of energy production as profoundly as petroleum exploitation did two centuries ago. The 21st century finds fusion research in a transformed landscape. The worldwide fusion community broadly agrees that the science has advanced to the point where an aggressive actionmore » plan, aimed at the remaining barriers to practical fusion energy, is warranted. At the same time, and largely because of its scientific advance, the program faces new challenges; above all it is challenged to demonstrate the timeliness of its promised benefits. In response to this changed landscape, the Office of Fusion Energy Sciences (OFES ) in the US Department of Energy commissioned a number of community-based studies of the key scientific and technical foci of magnetic fusion research. The Research Needs Workshop (ReNeW) for Magnetic Fusion Energy Sciences is a capstone to these studies. In the context of magnetic fusion energy, ReNeW surveyed the issues identified in previous studies, and used them as a starting point to define and characterize the research activities that the advance of fusion as a practical energy source will require. Thus, ReNeW's task was to identify (1) the scientific and technological research frontiers of the fusion program, and, especially, (2) a set of activities that will most effectively advance those frontiers. (Note that ReNeW was not charged with developing a strategic plan or timeline for the implementation of fusion power.) This Report presents a portfolio of research activities for US research in magnetic fusion for the next two decades. It is intended to provide a strategic framework for realizing practical fusion energy. The portfolio is the product of ten months of fusion-community study and discussion, culminating in a Workshop held in Bethesda, Maryland, from June 8 to June 12, 2009. The Workshop involved some 200 scientists from Universities, National Laboratories and private industry, including several scientists from outside the US. Largely following the Basic Research Needs model established by the Office of Basic Energy Sciences (BES ), the Report presents a collection of discrete research activities, here called 'thrusts.' Each thrust is based on an explicitly identified question, or coherent set of questions, on the frontier of fusion science. It presents a strategy to find the needed answers, combining the necessary intellectual and hardware tools, experimental facilities, and computational resources into an integrated, focused program. The thrusts should be viewed as building blocks for a fusion program plan whose overall structure will be developed by OFES , using whatever additional community input it requests. Part I of the Report reviews the issues identified in previous fusion-community studies, which systematically identified the key research issues and described them in considerable detail. It then considers in some detail the scientific and technical means that can be used to address these is sues. It ends by showing how these various research requirements are organized into a set of eighteen thrusts. Part II presents a detailed and self-contained discussion of each thrust, including the goals, required facilities and tools for each. This Executive Summary focuses on a survey of the ReNeW thrusts. The following brief review of fusion science is intended to provide context for that survey. A more detailed discussion of fusion science can be found in an Appendix to this Summary, entitled 'A Fusion Primer.'« less

External Heat Transfer Coefficient Measurements on a Surrogate Indirect Inertial Confinement Fusion Target

DOE PAGES

Miles, Robin; Havstad, Mark; LeBlanc, Mary; ...

2015-09-15

External heat transfer coefficients were measured around a surrogate Indirect inertial confinement fusion (ICF) based on the Laser Inertial Fusion Energy (LIFE) design target to validate thermal models of the LIFE target during flight through a fusion chamber. Results indicate that heat transfer coefficients for this target 25-50 W/m 2∙K are consistent with theoretically derived heat transfer coefficients and valid for use in calculation of target heating during flight through a fusion chamber.

An overview of near-barrier fusion studies with stable beams

NASA Astrophysics Data System (ADS)

Trotta, M.; Stefanini, A. M.; Beghini, S.; Behera, B. R.; Corradi, L.; Fioretto, E.; Gadea, A.; Itkis, M. G.; Knyazheva, G. N.; Kondratiev, N. A.; Kozulin, E. M.; Mărginean, N.; Mason, P.; Montagnoli, G.; Pokrovsky, I. V.; Sagaidak, R. N.; Scarlassara, F.; Silvestri, R.; Szilner, S.

2007-05-01

An overview of results in fusion studies with stable beams spanning different mass regions and energy ranges is presented. The advantages offered by studying channel coupling effects, involving low-lying excited states of the colliding nuclei, as well as the difficulties in understanding the influence of transfer couplings on fusion, are firstly remarked. The competition of fusion with quasi-fission in heavy systems and the unexpected steep falloff of fusion cross sections at far sub-barrier energies are finally discussed.

Investigation of Phenomena Related to D2O Electrolysis at a Palladium Cathode

DTIC Science & Technology

1990-10-30

L. Lawson, J. Shoemaker, F. Cheng and J. C. Wass, Manuscript submitted to J. Fusion Energy . 15. D. Albolgi, R. Ballinger, V. C, moroto, X. Chen, R...submitted to the Journal of Fusion Energy . 16. P. Clark Souers, Hydrogen Properties for Fusion , Energy , University of California, Berkely 1986. 17. P. L...Hagelstein, Proc. of the Cold Fusion Workshop, J. Fusion Energy , in press. 18. J. Rafelski, M. Gaide, D. Harley and S. E. Jones, unpublished results

Scalloped Hibachi and Vacuum-Pressure Foil for Electra: Electron Beam Pumped KrF Laser

DTIC Science & Technology

2007-06-01

confinement fusion energy (IFE) applications [1-8]. The foils are a critical part of this durability and efficiency. The electron beam, generated in a high...and A. W. Maschke, “Design descriptions of the Prometheus- L and -H inertial fusion energy drivers,” Fusion Engineering and Design, vol. 25, pp...inertial fusion energy ,” Fusion Engineering and Design, vol. 44, pp. 371-375, March 1999. [4] I. Okuda, e. Takahashi, and Y. Owadano, “A

Human Myoblast Fusion Requires Expression of Functional Inward Rectifier Kir2.1 Channels

PubMed Central

Fischer-Lougheed, Jacqueline; Liu, Jian-Hui; Espinos, Estelle; Mordasini, David; Bader, Charles R.; Belin, Dominique; Bernheim, Laurent

2001-01-01

Myoblast fusion is essential to skeletal muscle development and repair. We have demonstrated previously that human myoblasts hyperpolarize, before fusion, through the sequential expression of two K+ channels: an ether-à-go-go and an inward rectifier. This hyperpolarization is a prerequisite for fusion, as it sets the resting membrane potential in a range at which Ca2+ can enter myoblasts and thereby trigger fusion via a window current through α1H T channels. PMID:11352930

The surgical treatment of vertebral deformities in achondroplastic dwarfism.

PubMed

Parisini, P; Greggi, T; Casadei, R; Martini, A; De Zerbi, M; Campanacci, L; Perozzi, M

1996-01-01

The authors analyzed 15 patients affected with achondroplastic dwarfism with vertebral deformity treated surgically between 1976 and 1994. The forms represented were: achondroplasia; diastrophic dwarfism; spondyloepiphyseal achondroplasia. The types of vertebral deformity were: kyphosis: 12 (angular: 6; regular: 6); scoliosis: 1; kyphoscoliosis: 2. Neurological symptoms were present in 10 patients. Treatment was as follows: laminectomy: 8; posterior fusion with instrumentation: 2; anterior fusion: 2; anterior fusion with laminectomy and posterior fusion: 3. There were postoperative neurological complications in 4 cases (27%). Fusion must be performed early in angular kyphosis in the adult in order to prevent neurological symptoms. Wide laminectomies do not require associated fusion because they do not cause late vertebral instability.

Enhanced image fusion using directional contrast rules in fuzzy transform domain.

PubMed

Nandal, Amita; Rosales, Hamurabi Gamboa

2016-01-01

In this paper a novel image fusion algorithm based on directional contrast in fuzzy transform (FTR) domain is proposed. Input images to be fused are first divided into several non-overlapping blocks. The components of these sub-blocks are fused using directional contrast based fuzzy fusion rule in FTR domain. The fused sub-blocks are then transformed into original size blocks using inverse-FTR. Further, these inverse transformed blocks are fused according to select maximum based fusion rule for reconstructing the final fused image. The proposed fusion algorithm is both visually and quantitatively compared with other standard and recent fusion algorithms. Experimental results demonstrate that the proposed method generates better results than the other methods.

FuzzyFusion: an application architecture for multisource information fusion

NASA Astrophysics Data System (ADS)

Fox, Kevin L.; Henning, Ronda R.

2009-04-01

The correlation of information from disparate sources has long been an issue in data fusion research. Traditional data fusion addresses the correlation of information from sources as diverse as single-purpose sensors to all-source multi-media information. Information system vulnerability information is similar in its diversity of sources and content, and in the desire to draw a meaningful conclusion, namely, the security posture of the system under inspection. FuzzyFusionTM, A data fusion model that is being applied to the computer network operations domain is presented. This model has been successfully prototyped in an applied research environment and represents a next generation assurance tool for system and network security.

Control of muscle formation by the fusogenic micropeptide myomixer

PubMed Central

Bi, Pengpeng; Ramirez-Martinez, Andres; Li, Hui; Cannavino, Jessica; McAnally, John R.; Shelton, John M.; Sánchez-Ortiz, Efrain; Bassel-Duby, Rhonda; Olson, Eric N.

2017-01-01

Skeletal muscle formation occurs through fusion of myoblasts to form multinucleated myofibers. From a genome-wide clustered regularly interspaced short palindromic repeats (CRISPR) loss-of-function screen for genes required for myoblast fusion and myogenesis, we discovered an 84–amino acid muscle-specific peptide that we call Myomixer. Myomixer expression coincides with myoblast differentiation and is essential for fusion and skeletal muscle formation during embryogenesis. Myomixer localizes to the plasma membrane, where it promotes myoblast fusion and associates with Myomaker, a fusogenic membrane protein. Myomixer together with Myomaker can also induce fibroblast-fibroblast fusion and fibroblast-myoblast fusion. We conclude that the Myomixer-Myomaker pair controls the critical step in myofiber formation during muscle development. PMID:28386024

Lunar Helium-3 and Fusion Power

NASA Technical Reports Server (NTRS)

1988-01-01

The NASA Office of Exploration sponsored the NASA Lunar Helium-3 and Fusion Power Workshop. The meeting was held to understand the potential of using He-3 from the moon for terrestrial fusion power production. It provided an overview, two parallel working sessions, a review of sessions, and discussions. The lunar mining session concluded that mining, beneficiation, separation, and return of He-3 from the moon would be possible but that a large scale operation and improved technology is required. The fusion power session concluded that: (1) that He-3 offers significant, possibly compelling, advantages over fusion of tritium, principally increased reactor life, reduced radioactive wastes, and high efficiency conversion, (2) that detailed assessment of the potential of the D/He-3 fuel cycle requires more information, and (3) D/He-3 fusion may be best for commercial purposes, although D/T fusion is more near term.

AxiaLIF system: minimally invasive device for presacral lumbar interbody spinal fusion

PubMed Central

Rapp, Steven M; Miller, Larry E; Block, Jon E

2011-01-01

Lumbar fusion is commonly performed to alleviate chronic low back and leg pain secondary to disc degeneration, spondylolisthesis with or without concomitant lumbar spinal stenosis, or chronic lumbar instability. However, the risk of iatrogenic injury during traditional anterior, posterior, and transforaminal open fusion surgery is significant. The axial lumbar interbody fusion (AxiaLIF) system is a minimally invasive fusion device that accesses the lumbar (L4–S1) intervertebral disc spaces via a reproducible presacral approach that avoids critical neurovascular and musculoligamentous structures. Since the AxiaLIF system received marketing clearance from the US Food and Drug Administration in 2004, clinical studies of this device have reported high fusion rates without implant subsidence, significant improvements in pain and function, and low complication rates. This paper describes the design and approach of this lumbar fusion system, details the indications for use, and summarizes the clinical experience with the AxiaLIF system to date. PMID:22915939

AxiaLIF system: minimally invasive device for presacral lumbar interbody spinal fusion.

PubMed

Rapp, Steven M; Miller, Larry E; Block, Jon E

2011-01-01

Lumbar fusion is commonly performed to alleviate chronic low back and leg pain secondary to disc degeneration, spondylolisthesis with or without concomitant lumbar spinal stenosis, or chronic lumbar instability. However, the risk of iatrogenic injury during traditional anterior, posterior, and transforaminal open fusion surgery is significant. The axial lumbar interbody fusion (AxiaLIF) system is a minimally invasive fusion device that accesses the lumbar (L4-S1) intervertebral disc spaces via a reproducible presacral approach that avoids critical neurovascular and musculoligamentous structures. Since the AxiaLIF system received marketing clearance from the US Food and Drug Administration in 2004, clinical studies of this device have reported high fusion rates without implant subsidence, significant improvements in pain and function, and low complication rates. This paper describes the design and approach of this lumbar fusion system, details the indications for use, and summarizes the clinical experience with the AxiaLIF system to date.

History of Nuclear Fusion Research in Japan

NASA Astrophysics Data System (ADS)

Iguchi, Harukazu; Matsuoka, Keisuke; Kimura, Kazue; Namba, Chusei; Matsuda, Shinzaburo

In the late 1950s just after the atomic energy research was opened worldwide, there was a lively discussion among scientists on the strategy of nuclear fusion research in Japan. Finally, decision was made that fusion research should be started from the basic, namely, research on plasma physics and from cultivation of human resources at universities under the Ministry of Education, Science and Culture (MOE). However, an endorsement was given that construction of an experimental device for fusion research would be approved sooner or later. Studies on toroidal plasma confinement started at Japan Atomic Energy Research Institute (JAERI) under the Science and Technology Agency (STA) in the mid-1960s. Dualistic fusion research framework in Japan was established. This structure has lasted until now. Fusion research activities over the last 50 years are described by the use of a flowchart, which is convenient to glance the historical development of fusion research in Japan.

Design of multivalent complexes using the barnase*barstar module.

PubMed

Deyev, Sergey M; Waibel, Robert; Lebedenko, Ekaterina N; Schubiger, August P; Plückthun, Andreas

2003-12-01

The ribonuclease barnase (12 kDa) and its inhibitor barstar (10 kDa) form a very tight complex in which all N and C termini are accessible for fusion. Here we exploit this system to create modular targeting molecules based on antibody scFv fragment fusions to barnase, to two barnase molecules in series and to barstar. We describe the construction, production and purification of defined dimeric and trimeric complexes. Immobilized barnase fusions are used to capture barstar fusions from crude extracts to yield homogeneous, heterodimeric fusion proteins. These proteins are stable, soluble and resistant to proteolysis. Using fusions with anti-p185(HER2-ECD) 4D5 scFv, we show that the anticipated gain in avidity from monomer to dimer to trimer is obtained and that favorable tumor targeting properties are achieved. Many permutations of engineered multispecific fusion proteins become accessible with this technology of quasi-covalent heterodimers.

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.

chimeraviz: a tool for visualizing chimeric RNA.

PubMed

Lågstad, Stian; Zhao, Sen; Hoff, Andreas M; Johannessen, Bjarne; Lingjærde, Ole Christian; Skotheim, Rolf I

2017-09-15

Advances in high-throughput RNA sequencing have enabled more efficient detection of fusion transcripts, but the technology and associated software used for fusion detection from sequencing data often yield a high false discovery rate. Good prioritization of the results is important, and this can be helped by a visualization framework that automatically integrates RNA data with known genomic features. Here we present chimeraviz , a Bioconductor package that automates the creation of chimeric RNA visualizations. The package supports input from nine different fusion-finder tools: deFuse, EricScript, InFusion, JAFFA, FusionCatcher, FusionMap, PRADA, SOAPfuse and STAR-FUSION. chimeraviz is an R package available via Bioconductor ( https://bioconductor.org/packages/release/bioc/html/chimeraviz.html ) under Artistic-2.0. Source code and support is available at GitHub ( https://github.com/stianlagstad/chimeraviz ). rolf.i.skotheim@rr-research.no. Supplementary data are available at Bioinformatics online. © The Author(s) 2017. Published by Oxford University Press.

Advances in multi-sensor data fusion: algorithms and applications.

PubMed

Dong, Jiang; Zhuang, Dafang; Huang, Yaohuan; Fu, Jingying

2009-01-01

With the development of satellite and remote sensing techniques, more and more image data from airborne/satellite sensors have become available. Multi-sensor image fusion seeks to combine information from different images to obtain more inferences than can be derived from a single sensor. In image-based application fields, image fusion has emerged as a promising research area since the end of the last century. The paper presents an overview of recent advances in multi-sensor satellite image fusion. Firstly, the most popular existing fusion algorithms are introduced, with emphasis on their recent improvements. Advances in main applications fields in remote sensing, including object identification, classification, change detection and maneuvering targets tracking, are described. Both advantages and limitations of those applications are then discussed. Recommendations are addressed, including: (1) Improvements of fusion algorithms; (2) Development of "algorithm fusion" methods; (3) Establishment of an automatic quality assessment scheme.

Role of partial linear momentum transfer on incomplete fusion reaction

NASA Astrophysics Data System (ADS)

Ali, Sabir; Ahmad, Tauseef; Kumar, Kamal; Gull, Muntazir; Rizvi, I. A.; Agarwal, Avinash; Ghugre, S. S.; Sinha, A. K.; Chaubey, A. K.

2018-04-01

Measurements of forward recoil range distributions (FRRDs) of the evaporation residues, populated in the 20Ne+51V reaction at E_{lab}≈ 145 MeV, have been carried out using the offline characteristic γ-ray detection method. The observation does corroborate the presence of complete fusion (CF) process in the population of p xn channel residues and both complete as well as incomplete fusion (ICF) processes in the population of α emitting channel residues. The FRRDs of p xn channel residues comprise single peak only, whereas α emitting channel residues have multiple peaks in their FRRDs. CF cross section data were used to extract the fusion functions. Extracted fusion functions were found to be suppressed with respect to the universal fusion function which is used as a uniform standard reference. The observed contribution arising from the ICF process in the population of α emitting channel residues is explained in terms of breakup fusion model.

Multispectral image fusion for target detection

NASA Astrophysics Data System (ADS)

Leviner, Marom; Maltz, Masha

2009-09-01

Various different methods to perform multi-spectral image fusion have been suggested, mostly on the pixel level. However, the jury is still out on the benefits of a fused image compared to its source images. We present here a new multi-spectral image fusion method, multi-spectral segmentation fusion (MSSF), which uses a feature level processing paradigm. To test our method, we compared human observer performance in an experiment using MSSF against two established methods: Averaging and Principle Components Analysis (PCA), and against its two source bands, visible and infrared. The task that we studied was: target detection in the cluttered environment. MSSF proved superior to the other fusion methods. Based on these findings, current speculation about the circumstances in which multi-spectral image fusion in general and specific fusion methods in particular would be superior to using the original image sources can be further addressed.

Inertial-confinement fusion with lasers

NASA Astrophysics Data System (ADS)

Betti, R.; Hurricane, O. A.

2016-05-01

The quest for controlled fusion energy has been ongoing for over a half century. The demonstration of ignition and energy gain from thermonuclear fuels in the laboratory has been a major goal of fusion research for decades. Thermonuclear ignition is widely considered a milestone in the development of fusion energy, as well as a major scientific achievement with important applications in national security and basic sciences. The US is arguably the world leader in the inertial confinement approach to fusion and has invested in large facilities to pursue it, with the objective of establishing the science related to the safety and reliability of the stockpile of nuclear weapons. Although significant progress has been made in recent years, major challenges still remain in the quest for thermonuclear ignition via laser fusion. Here, we review the current state of the art in inertial confinement fusion research and describe the underlying physical principles.

Fusion of multi-spectral and panchromatic images based on 2D-PWVD and SSIM

NASA Astrophysics Data System (ADS)

Tan, Dongjie; Liu, Yi; Hou, Ruonan; Xue, Bindang

2016-03-01

A combined method using 2D pseudo Wigner-Ville distribution (2D-PWVD) and structural similarity(SSIM) index is proposed for fusion of low resolution multi-spectral (MS) image and high resolution panchromatic (PAN) image. First, the intensity component of multi-spectral image is extracted with generalized IHS transform. Then, the spectrum diagrams of the intensity components of multi-spectral image and panchromatic image are obtained with 2D-PWVD. Different fusion rules are designed for different frequency information of the spectrum diagrams. SSIM index is used to evaluate the high frequency information of the spectrum diagrams for assigning the weights in the fusion processing adaptively. After the new spectrum diagram is achieved according to the fusion rule, the final fusion image can be obtained by inverse 2D-PWVD and inverse GIHS transform. Experimental results show that, the proposed method can obtain high quality fusion images.

Versatile fusion source integrator AFSI for fast ion and neutron studies in fusion devices

NASA Astrophysics Data System (ADS)

Sirén, Paula; Varje, Jari; Äkäslompolo, Simppa; Asunta, Otto; Giroud, Carine; Kurki-Suonio, Taina; Weisen, Henri; JET Contributors, The

2018-01-01

ASCOT Fusion Source Integrator AFSI, an efficient tool for calculating fusion reaction rates and characterizing the fusion products, based on arbitrary reactant distributions, has been developed and is reported in this paper. Calculation of reactor-relevant D-D, D-T and D-3He fusion reactions has been implemented based on the Bosch-Hale fusion cross sections. The reactions can be calculated between arbitrary particle populations, including Maxwellian thermal particles and minority energetic particles. Reaction rate profiles, energy spectra and full 4D phase space distributions can be calculated for the non-isotropic reaction products. The code is especially suitable for integrated modelling in self-consistent plasma physics simulations as well as in the Serpent neutronics calculation chain. Validation of the model has been performed for neutron measurements at the JET tokamak and the code has been applied to predictive simulations in ITER.

Background: Energy's holy grail. [The quest for controlled fusion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

This article presents a brief history of the pursuit and development of fusion as a power source. Starting with the 1950s through the present, the research efforts of the US and other countries is highlighted, including a chronology of hey developments. Other topics discussed include cold fusion and magnetic versus inertial fusion issues.

49 CFR 192.281 - Plastic pipe.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Plastic pipe. (a) General. A plastic pipe joint that is joined by solvent cement, adhesive, or heat fusion..., see § 192.7). (3) The joint may not be heated to accelerate the setting of the cement. (c) Heat-fusion joints. Each heat-fusion joint on plastic pipe must comply with the following: (1) A butt heat-fusion...

49 CFR 192.281 - Plastic pipe.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Plastic pipe. (a) General. A plastic pipe joint that is joined by solvent cement, adhesive, or heat fusion..., see § 192.7). (3) The joint may not be heated to accelerate the setting of the cement. (c) Heat-fusion joints. Each heat-fusion joint on plastic pipe must comply with the following: (1) A butt heat-fusion...

49 CFR 192.281 - Plastic pipe.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Plastic pipe. (a) General. A plastic pipe joint that is joined by solvent cement, adhesive, or heat fusion..., see § 192.7). (3) The joint may not be heated to accelerate the setting of the cement. (c) Heat-fusion joints. Each heat-fusion joint on plastic pipe must comply with the following: (1) A butt heat-fusion...

49 CFR 192.281 - Plastic pipe.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Plastic pipe. (a) General. A plastic pipe joint that is joined by solvent cement, adhesive, or heat fusion..., see § 192.7). (3) The joint may not be heated to accelerate the setting of the cement. (c) Heat-fusion joints. Each heat-fusion joint on plastic pipe must comply with the following: (1) A butt heat-fusion...

Fast retrieval and autonomous regulation of single spontaneously recycling synaptic vesicles

PubMed Central

Leitz, Jeremy; Kavalali, Ege T

2014-01-01

Presynaptic terminals release neurotransmitters spontaneously in a manner that can be regulated by Ca2+. However, the mechanisms underlying this regulation are poorly understood because the inherent stochasticity and low probability of spontaneous fusion events has curtailed their visualization at individual release sites. Here, using pH-sensitive optical probes targeted to synaptic vesicles, we visualized single spontaneous fusion events and found that they are retrieved extremely rapidly with faster re-acidification kinetics than their action potential-evoked counterparts. These fusion events were coupled to postsynaptic NMDA receptor-driven Ca2+ signals, and at elevated Ca2+ concentrations there was an increase in the number of vesicles that would undergo fusion. Furthermore, spontaneous vesicle fusion propensity in a synapse was Ca2+-dependent but regulated autonomously: independent of evoked fusion probability at the same synapse. Taken together, these results expand classical quantal analysis to incorporate endocytic and exocytic phases of single fusion events and uncover autonomous regulation of spontaneous fusion. DOI: http://dx.doi.org/10.7554/eLife.03658.001 PMID:25415052

Molecular and cellular aspects of rhabdovirus entry.

PubMed

Albertini, Aurélie A V; Baquero, Eduard; Ferlin, Anna; Gaudin, Yves

2012-01-01

Rhabdoviruses enter the cell via the endocytic pathway and subsequently fuse with a cellular membrane within the acidic environment of the endosome. Both receptor recognition and membrane fusion are mediated by a single transmembrane viral glycoprotein (G). Fusion is triggered via a low-pH induced structural rearrangement. G is an atypical fusion protein as there is a pH-dependent equilibrium between its pre- and post-fusion conformations. The elucidation of the atomic structures of these two conformations for the vesicular stomatitis virus (VSV) G has revealed that it is different from the previously characterized class I and class II fusion proteins. In this review, the pre- and post-fusion VSV G structures are presented in detail demonstrating that G combines the features of the class I and class II fusion proteins. In addition to these similarities, these G structures also reveal some particularities that expand our understanding of the working of fusion machineries. Combined with data from recent studies that revealed the cellular aspects of the initial stages of rhabdovirus infection, all these data give an integrated view of the entry pathway of rhabdoviruses into their host cell.

Molecular and Cellular Aspects of Rhabdovirus Entry

PubMed Central

Albertini, Aurélie A. V.; Baquero, Eduard; Ferlin, Anna; Gaudin, Yves

2012-01-01

Rhabdoviruses enter the cell via the endocytic pathway and subsequently fuse with a cellular membrane within the acidic environment of the endosome. Both receptor recognition and membrane fusion are mediated by a single transmembrane viral glycoprotein (G). Fusion is triggered via a low-pH induced structural rearrangement. G is an atypical fusion protein as there is a pH-dependent equilibrium between its pre- and post-fusion conformations. The elucidation of the atomic structures of these two conformations for the vesicular stomatitis virus (VSV) G has revealed that it is different from the previously characterized class I and class II fusion proteins. In this review, the pre- and post-fusion VSV G structures are presented in detail demonstrating that G combines the features of the class I and class II fusion proteins. In addition to these similarities, these G structures also reveal some particularities that expand our understanding of the working of fusion machineries. Combined with data from recent studies that revealed the cellular aspects of the initial stages of rhabdovirus infection, all these data give an integrated view of the entry pathway of rhabdoviruses into their host cell. PMID:22355455

Fusion Simulation Project Workshop Report

NASA Astrophysics Data System (ADS)

Kritz, Arnold; Keyes, David

2009-03-01

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

Identity fusion predicts endorsement of pro-group behaviours targeting nationality, religion, or football in Brazilian samples.

PubMed

Bortolini, Tiago; Newson, Martha; Natividade, Jean Carlos; Vázquez, Alexandra; Gómez, Ángel

2018-04-01

A visceral feeling of oneness with a group - identity fusion - has proven to be a stronger predictor of pro-group behaviours than other measures of group bonding, such as group identification. However, the relationship between identity fusion, other group alignment measures and their different roles in predicting pro-group behaviour is still controversial. Here, we test whether identity fusion is related to, but different from, unidimensional and multidimensional measures of group identification. We also show that identity fusion explains further variance of the endorsement of pro-group behaviour than these alternative measures and examine the structural and discriminant properties of identity fusion and group identification measures in three different contexts: nationality, religion, and football fandom. Finally, we extend the fusion literature to a new culture: Brazil. To the best of our knowledge, this is the first research explicitly addressing a comparison between these two forms of group alignment, identity fusion and identification with a group, and their role in predicting pro-group behaviours. © 2018 The British Psychological Society.

Multi-Sensor Optimal Data Fusion Based on the Adaptive Fading Unscented Kalman Filter

PubMed Central

Gao, Bingbing; Hu, Gaoge; Gao, Shesheng; Gu, Chengfan

2018-01-01

This paper presents a new optimal data fusion methodology based on the adaptive fading unscented Kalman filter for multi-sensor nonlinear stochastic systems. This methodology has a two-level fusion structure: at the bottom level, an adaptive fading unscented Kalman filter based on the Mahalanobis distance is developed and serves as local filters to improve the adaptability and robustness of local state estimations against process-modeling error; at the top level, an unscented transformation-based multi-sensor optimal data fusion for the case of N local filters is established according to the principle of linear minimum variance to calculate globally optimal state estimation by fusion of local estimations. The proposed methodology effectively refrains from the influence of process-modeling error on the fusion solution, leading to improved adaptability and robustness of data fusion for multi-sensor nonlinear stochastic systems. It also achieves globally optimal fusion results based on the principle of linear minimum variance. Simulation and experimental results demonstrate the efficacy of the proposed methodology for INS/GNSS/CNS (inertial navigation system/global navigation satellite system/celestial navigation system) integrated navigation. PMID:29415509

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

PubMed

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

2013-08-01

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

The defects and microstructure in the fusion zone of multipass laser welded joints with Inconel 52M filler wire for nuclear power plants

NASA Astrophysics Data System (ADS)

Li, Gang; Lu, Xiaofeng; Zhu, Xiaolei; Huang, Jian; Liu, Luwei; Wu, Yixiong

2017-09-01

The defects and microstructure in the fusion zone of multipass laser welded joints with Inconel 52M filler wire are investigated for nuclear power plants. Experimental results indicate that the incomplete fusion forms as the deposited metals do not completely cover the groove during multipass laser welding. The dendritic morphologies are observed on the inner surface of the porosity in the fusion zone. Many small cellular are found in the zones near the fusion boundary. With solidification preceding, cellular gradually turn into columnar dendrites and symmetrical columnar dendrites are exhibited in the weld center of the fusion zone. The fine equiaxed grains form and columnar dendrites disappear in the remelted zone of two passes. The dendrite arm spacing in the fusion zone becomes widened with increasing welding heat input. Nb-rich carbides/carbonitrides are preferentially precipitated in the fusion zone of multipass laser welded joints. In respect to high cooling rate during multipass laser welding, element segregation could be insufficient to achieve the component of Laves phase.

Multi-Sensor Optimal Data Fusion Based on the Adaptive Fading Unscented Kalman Filter.

PubMed

Gao, Bingbing; Hu, Gaoge; Gao, Shesheng; Zhong, Yongmin; Gu, Chengfan

2018-02-06

This paper presents a new optimal data fusion methodology based on the adaptive fading unscented Kalman filter for multi-sensor nonlinear stochastic systems. This methodology has a two-level fusion structure: at the bottom level, an adaptive fading unscented Kalman filter based on the Mahalanobis distance is developed and serves as local filters to improve the adaptability and robustness of local state estimations against process-modeling error; at the top level, an unscented transformation-based multi-sensor optimal data fusion for the case of N local filters is established according to the principle of linear minimum variance to calculate globally optimal state estimation by fusion of local estimations. The proposed methodology effectively refrains from the influence of process-modeling error on the fusion solution, leading to improved adaptability and robustness of data fusion for multi-sensor nonlinear stochastic systems. It also achieves globally optimal fusion results based on the principle of linear minimum variance. Simulation and experimental results demonstrate the efficacy of the proposed methodology for INS/GNSS/CNS (inertial navigation system/global navigation satellite system/celestial navigation system) integrated navigation.

A Hierarchical Convolutional Neural Network for vesicle fusion event classification.

PubMed

Li, Haohan; Mao, Yunxiang; Yin, Zhaozheng; Xu, Yingke

2017-09-01

Quantitative analysis of vesicle exocytosis and classification of different modes of vesicle fusion from the fluorescence microscopy are of primary importance for biomedical researches. In this paper, we propose a novel Hierarchical Convolutional Neural Network (HCNN) method to automatically identify vesicle fusion events in time-lapse Total Internal Reflection Fluorescence Microscopy (TIRFM) image sequences. Firstly, a detection and tracking method is developed to extract image patch sequences containing potential fusion events. Then, a Gaussian Mixture Model (GMM) is applied on each image patch of the patch sequence with outliers rejected for robust Gaussian fitting. By utilizing the high-level time-series intensity change features introduced by GMM and the visual appearance features embedded in some key moments of the fusion process, the proposed HCNN architecture is able to classify each candidate patch sequence into three classes: full fusion event, partial fusion event and non-fusion event. Finally, we validate the performance of our method on 9 challenging datasets that have been annotated by cell biologists, and our method achieves better performances when comparing with three previous methods. Copyright © 2017 Elsevier Ltd. All rights reserved.

A Ratiometric Two-Photon Fluorescent Probe for Tracking the Lysosomal ATP Level: Direct in cellulo Observation of Lysosomal Membrane Fusion Processes.

PubMed

Jun, Yong Woong; Wang, Taejun; Hwang, Sekyu; Kim, Dokyoung; Ma, Donghee; Kim, Ki Hean; Kim, Sungjee; Jung, Junyang; Ahn, Kyo Han

2018-06-05

Vesicles exchange its contents through membrane fusion processes-kiss-and-run and full-collapse fusion. Indirect observation of these fusion processes using artificial vesicles enhanced our understanding on the molecular mechanisms involved. Direct observation of the fusion processes in a real biological system, however, remains a challenge owing to many technical obstacles. We disclose a ratiometric two-photon probe offering real-time tracking of lysosomal ATP with quantitative information for the first time. By applying the probe to two-photon live-cell imaging technique, lysosomal membrane fusion process in cells has been directly observed along with the concentration of its content-lysosomal ATP. Results show that the kiss-and-run process between lysosomes proceeds through repeating transient interactions with gradual content mixing, whereas the full-fusion process occurs at once. Furthermore, it is confirmed that both the fusion processes proceed with conservation of the content. Such a small-molecule probe exerts minimal disturbance and hence has potential for studying various biological processes associated with lysosomal ATP. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Beyond ALK-RET, ROS1 and other oncogene fusions in lung cancer

PubMed Central

Nakaoku, Takashi; Tsuta, Koji; Tsuchihara, Katsuya; Matsumoto, Shingo; Yoh, Kiyotaka; Goto, Koichi

2015-01-01

Fusions of the RET and ROS1 protein tyrosine kinase oncogenes with several partner genes were recently identified as new targetable genetic aberrations in cases of non-small cell lung cancer (NSCLC) lacking activating EGFR, KRAS, ALK, BRAF, or HER2 oncogene aberrations. RET and ROS1 fusion-positive tumors are mainly observed in young, female, and/or never smoking patients. Studies based on in vitro and in vivo (i.e., mouse) models and studies of several fusion-positive patients indicate that inhibiting the kinase activity of the RET and ROS1 fusion proteins is a promising therapeutic strategy. Accordingly, there are several ongoing clinical trials aimed at examining the efficacy of tyrosine kinase inhibitors (TKIs) against RET and ROS1 proteins in patients with fusion-positive lung cancer. Other gene fusions (NTRK1, NRG1, and FGFR1/2/3) that are targetable by existing TKIs have also been identified in NSCLCs. Options for personalized lung cancer therapy will be increased with the help of multiplex diagnosis systems able to detect multiple druggable gene fusions. PMID:25870798

A measurement fusion method for nonlinear system identification using a cooperative learning algorithm.

PubMed

Xia, Youshen; Kamel, Mohamed S

2007-06-01

Identification of a general nonlinear noisy system viewed as an estimation of a predictor function is studied in this article. A measurement fusion method for the predictor function estimate is proposed. In the proposed scheme, observed data are first fused by using an optimal fusion technique, and then the optimal fused data are incorporated in a nonlinear function estimator based on a robust least squares support vector machine (LS-SVM). A cooperative learning algorithm is proposed to implement the proposed measurement fusion method. Compared with related identification methods, the proposed method can minimize both the approximation error and the noise error. The performance analysis shows that the proposed optimal measurement fusion function estimate has a smaller mean square error than the LS-SVM function estimate. Moreover, the proposed cooperative learning algorithm can converge globally to the optimal measurement fusion function estimate. Finally, the proposed measurement fusion method is applied to ARMA signal and spatial temporal signal modeling. Experimental results show that the proposed measurement fusion method can provide a more accurate model.

MFN1 deacetylation activates adaptive mitochondrial fusion and protects metabolically challenged mitochondria.

PubMed

Lee, Joo-Yong; Kapur, Meghan; Li, Ming; Choi, Moon-Chang; Choi, Sujin; Kim, Hak-June; Kim, Inhye; Lee, Eunji; Taylor, J Paul; Yao, Tso-Pang

2014-11-15

Fasting and glucose shortage activate a metabolic switch that shifts more energy production to mitochondria. This metabolic adaptation ensures energy supply, but also elevates the risk of mitochondrial oxidative damage. Here, we present evidence that metabolically challenged mitochondria undergo active fusion to suppress oxidative stress. In response to glucose starvation, mitofusin 1 (MFN1) becomes associated with the protein deacetylase HDAC6. This interaction leads to MFN1 deacetylation and activation, promoting mitochondrial fusion. Deficiency in HDAC6 or MFN1 prevents mitochondrial fusion induced by glucose deprivation. Unexpectedly, failure to undergo fusion does not acutely affect mitochondrial adaptive energy production; instead, it causes excessive production of mitochondrial reactive oxygen species and oxidative damage, a defect suppressed by an acetylation-resistant MFN1 mutant. In mice subjected to fasting, skeletal muscle mitochondria undergo dramatic fusion. Remarkably, fasting-induced mitochondrial fusion is abrogated in HDAC6-knockout mice, resulting in extensive mitochondrial degeneration. These findings show that adaptive mitochondrial fusion protects metabolically challenged mitochondria. © 2014. Published by The Company of Biologists Ltd.

Fusomorphogenesis: cell fusion in organ formation.

PubMed

Shemer, G; Podbilewicz, B

2000-05-01

Cell fusion is a universal process that occurs during fertilization and in the formation of organs such as muscles, placenta, and bones. Very little is known about the molecular and cellular mechanisms of cell fusion during pattern formation. Here we review the dynamic anatomy of all cell fusions during embryonic and postembryonic development in an organism. Nearly all the cell fates and cell lineages are invariant in the nematode C. elegans and one third of the cells that are born fuse to form 44 syncytia in a reproducible and stereotyped way. To explain the function of cell fusion in organ formation we propose the fusomorphogenetic model as a simple cellular mechanism to efficiently redistribute membranes using a combination of cell fusion and polarized membrane recycling during morphogenesis. Thus, regulated intercellular and intracellular membrane fusion processes may drive elongation of the embryo as well as postembryonic organ formation in C. elegans. Finally, we use the fusomorphogenetic hypothesis to explain the role of cell fusion in the formation of organs like muscles, bones, and placenta in mammals and other species and to speculate on how the intracellular machinery that drive fusomorphogenesis may have evolved.

Status and problems of fusion reactor development.

PubMed

Schumacher, U

2001-03-01

Thermonuclear fusion of deuterium and tritium constitutes an enormous potential for a safe, environmentally compatible and sustainable energy supply. The fuel source is practically inexhaustible. Further, the safety prospects of a fusion reactor are quite favourable due to the inherently self-limiting fusion process, the limited radiologic toxicity and the passive cooling property. Among a small number of approaches, the concept of toroidal magnetic confinement of fusion plasmas has achieved most impressive scientific and technical progress towards energy release by thermonuclear burn of deuterium-tritium fuels. The status of thermonuclear fusion research activity world-wide is reviewed and present solutions to the complicated physical and technological problems are presented. These problems comprise plasma heating, confinement and exhaust of energy and particles, plasma stability, alpha particle heating, fusion reactor materials, reactor safety and environmental compatibility. The results and the high scientific level of this international research activity provide a sound basis for the realisation of the International Thermonuclear Experimental Reactor (ITER), whose goal is to demonstrate the scientific and technological feasibility of a fusion energy source for peaceful purposes.

CAPS drives trans-SNARE complex formation and membrane fusion through syntaxin interactions.

PubMed

James, Declan J; Kowalchyk, Judith; Daily, Neil; Petrie, Matt; Martin, Thomas F J

2009-10-13

Ca(2+)-dependent activator protein for secretion (CAPS) is an essential factor for regulated vesicle exocytosis that functions in priming reactions before Ca(2+)-triggered fusion of vesicles with the plasma membrane. However, the precise events that CAPS regulates to promote vesicle fusion are unclear. In the current work, we reconstituted CAPS function in a SNARE-dependent liposome fusion assay using VAMP2-containing donor and syntaxin-1/SNAP-25-containing acceptor liposomes. The CAPS stimulation of fusion required PI(4,5)P(2) in acceptor liposomes and was independent of Ca(2+), but Ca(2+) dependence was restored by inclusion of synaptotagmin. CAPS stimulated trans-SNARE complex formation concomitant with the stimulation of full membrane fusion at physiological SNARE densities. CAPS bound syntaxin-1, and CAPS truncations that competitively inhibited syntaxin-1 binding also inhibited CAPS-dependent fusion. The results revealed an unexpected activity of a priming protein to accelerate fusion by efficiently promoting trans-SNARE complex formation. CAPS may function in priming by organizing SNARE complexes on the plasma membrane.

[Rumination and cognitive fusion in dementia family caregivers].

PubMed

Romero-Moreno, Rosa; Márquez-González, María; Losada, Andrés; Fernández-Fernández, Virginia; Nogales-González, Celia

2015-01-01

Rumination has been described as a dysfunctional coping strategy related to emotional distress. Recently, it has been highlighted from the Acceptance and Commitment Therapy therapeutic approach, the negative role that cognitive fusion (the extent to which we are psychologically tangled with and dominated by the form or content of our thoughts) has on the explanation of distress. The aim of this study is to simultaneously analyze the role of rumination and cognitive fusion in the caregiving stress process. The sample of 176 dementia caregivers was divided in four groups, taking into account their levels of rumination and cognitive fusion: HRHF=high rumination+high cognitive fusion; HRLF=high rumination+low cognitive fusion; LRHF= low rumination+high cognitive fusion; and LRLC=low rumination and low cognitive fusion. Caregiver stress factors, frequency of pleasant events, experiential avoidance, coherence and satisfaction with personal values, depression, anxiety and satisfaction with life, were measured. The HRHF group showed higher levels of depression, anxiety, experiential avoidance and lower levels of satisfaction with life, frequency of pleasant events, coherence and satisfaction with personal values, than the other three groups. Considering simultaneously rumination and cognitive fusion may contribute to a better understanding of caregiver coping and distress. Copyright © 2014 SEGG. Published by Elsevier Espana. All rights reserved.

Nanoparticle delivery of miR-223 to attenuate macrophage fusion

PubMed Central

Moore, Laura Beth; Sawyer, Andrew J.; Saucier-Sawyer, Jennifer; Saltzman, W. Mark; Kyriakides, Themis R.

2016-01-01

The foreign body response (FBR) begins with injury acquired during implantation of a biomaterial (BM) and is detrimental due to the eventual encapsulation of the implant. Fusion of macrophages to form foreign body giant cells (FBGC), a hallmark of the FBR, is the consequence of a multistep mechanism induced by interleukin (IL)-4 that includes the acquisition of a fusion competent state and subsequent cytoskeletal rearrangements. However, the precise mechanism, regulation, and interplay among molecular mediators to generate FBGCs are insufficiently understood. Seeking novel mediators of fusion that might be regulated at the post-transcriptional level, we examined the role of microRNAs (miRs) in this process. A miR microarray was screened and identified miR-223 as a negative regulator of macrophage fusion. In addition, transfection of primary macrophages with a mir-223 mimic attenuated IL-4-induced fusion. Furthermore, miR-223 KO mice and mir-223 deficient cells displayed increased fusion in vivo and in vitro, respectively. Finally, we developed a method for in vivo delivery of miR-223 mimic utilizing PLGA nanoparticles, which inhibited FBGC formation in a biomaterial implant model. Our results identify miR-223 as a negative regulator of fusion and demonstrate miR-223 mimic-loaded nanoparticles as a therapeutic inhibitor of macrophage fusion. PMID:26967647

Reprogramming of somatic cells induced by fusion of embryonic stem cells using hemagglutinating virus of Japan envelope (HVJ-E)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yue, Xiao-shan; Department of Biomolecular Engineering, Graduate School of Bioscience and Technology, Tokyo Institute of Technology, Nagatsuta-cho, Midori-ku, Yokohama-shi, Kanagawa 226-8501; Fujishiro, Masako

In this research, hemagglutinating virus of Japan envelope (HVJ-E) was used to reprogram somatic cells by fusion with mouse embryonic stem (ES) cells. Neomycin-resistant mouse embryonic fibroblasts (MEFs) were used as somatic cells. Nanog-overexpressing puromycin-resistant EB3 cells were used as mouse ES cells. These two cells were fused by exposing to HVJ-E and the generated fusion cells were selected by puromycin and G418 to get the stable fusion cell line. The fusion cells form colonies in feeder-free culture system. Microsatellite analysis of the fusion cells showed that they possessed genes from both ES cells and fibroblasts. The fusion cells weremore » tetraploid, had alkali phosphatase activity, and expressed stem cell marker genes such as Pou5f1, Nanog, and Sox2, but not the fibroblast cell marker genes such as Col1a1 and Col1a2. The pluripotency of fusion cells was confirmed by their expression of marker genes for all the three germ layers after differentiation induction, and by their ability to form teratoma which contained all the three primary layers. Our results show that HVJ-E can be used as a fusion reagent for reprogramming of somatic cells.« less

Revisions to the JDL data fusion model

NASA Astrophysics Data System (ADS)

Steinberg, Alan N.; Bowman, Christopher L.; White, Franklin E.

1999-03-01

The Data Fusion Model maintained by the Joint Directors of Laboratories (JDL) Data Fusion Group is the most widely-used method for categorizing data fusion-related functions. This paper discusses the current effort to revise the expand this model to facilitate the cost-effective development, acquisition, integration and operation of multi- sensor/multi-source systems. Data fusion involves combining information - in the broadest sense - to estimate or predict the state of some aspect of the universe. These may be represented in terms of attributive and relational states. If the job is to estimate the state of a people, it can be useful to include consideration of informational and perceptual states in addition to the physical state. Developing cost-effective multi-source information systems requires a method for specifying data fusion processing and control functions, interfaces, and associate databases. The lack of common engineering standards for data fusion systems has been a major impediment to integration and re-use of available technology: current developments do not lend themselves to objective evaluation, comparison or re-use. This paper reports on proposed revisions and expansions of the JDL Data FUsion model to remedy some of these deficiencies. This involves broadening the functional model and related taxonomy beyond the original military focus, and integrating the Data Fusion Tree Architecture model for system description, design and development.

Sensitivity Changes over the Course of Infection Increases the Likelihood of Resistance Against Fusion but Not CCR5 Receptor Blockers

PubMed Central

Chatziandreou, Nikolaos; Arauz, Ana Belen; Freitas, Ines; Nyein, Phyu Hninn; Fenton, Gregory; Mehta, Shruti H.; Kirk, Gregory D.

2012-01-01

Abstract As HIV-1 evolves over the course of infection, resistance against antiretrovirals may arise in the absence of drug pressure, especially against receptor and fusion blockers because of the extensive changes observed in the envelope glycoprotein. Here we show that viruses from the chronic phase of disease are significantly less sensitive to CCR5 receptor and fusion blockers compared to early infection variants. Differences in susceptibility to CCR5 antagonists were observed in spite of no demonstrable CXCR4 receptor utilization. No significant sensitivity differences were observed to another entry blocker, soluble CD4, or to reverse transcriptase, protease, or integrase inhibitors. Chronic as compared to early phase variants demonstrated greater replication when passaged in the presence of subinhibitory concentrations of fusion but not CCR5 receptor inhibitors. Fusion antagonist resistance, however, emerged from only one chronic phase virus culture. Because sensitivity to receptor and fusion antagonists is correlated with receptor affinity and fusion capacity, respectively, changes that occur in the envelope glycoprotein over the course of infection confer greater ability to use the CCR5 receptor and increased fusion ability. Our in vitro passage studies suggest that these evolving phenotypes increase the likelihood of resistance against fusion but not CCR5 receptor blockers. PMID:22650962

Radiotherapy treatment planning: benefits of CT-MR image registration and fusion in tumor volume delineation.

PubMed

Djan, Igor; Petrović, Borislava; Erak, Marko; Nikolić, Ivan; Lucić, Silvija

2013-08-01

Development of imaging techniques, computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET), made great impact on radiotherapy treatment planning by improving the localization of target volumes. Improved localization allows better local control of tumor volumes, but also minimizes geographical misses. Mutual information is obtained by registration and fusion of images achieved manually or automatically. The aim of this study was to validate the CT-MRI image fusion method and compare delineation obtained by CT versus CT-MRI image fusion. The image fusion software (XIO CMS 4.50.0) was applied to delineate 16 patients. The patients were scanned on CT and MRI in the treatment position within an immobilization device before the initial treatment. The gross tumor volume (GTV) and clinical target volume (CTV) were delineated on CT alone and on CT+MRI images consecutively and image fusion was obtained. Image fusion showed that CTV delineated on a CT image study set is mainly inadequate for treatment planning, in comparison with CTV delineated on CT-MRI fused image study set. Fusion of different modalities enables the most accurate target volume delineation. This study shows that registration and image fusion allows precise target localization in terms of GTV and CTV and local disease control.

Femtosecond laser-induced fusion of nonadherent cells and two-cell porcine embryos.

PubMed

Kuetemeyer, Kai; Lucas-Hahn, Andrea; Petersen, Bjoern; Niemann, Heiner; Heisterkamp, Alexander

2011-08-01

Cell fusion is a fundamental biological process that can be artificially induced by different methods. Although femtosecond (fs) lasers have been successfully employed for cell fusion over the past few years, the underlying mechanisms are still unknown. In our experimental study, we investigated the correlation between fs laser-induced cell fusion and membrane perforation, and the influence of laser parameters on the fusion efficiency of nonadherent HL-60 cells. We found that shorter exposure times resulted in higher fusion efficiencies with a maximum of 21% at 10 ms and 100 mJ/cm(2) (190 mW). Successful cell fusion was indicated by the formation of a long-lasting vapor bubble in the irradiated area with an average diameter much larger than in cell perforation experiments. With this knowledge, we demonstrated, for the first time, the fusion of very large parthenogenetic two-cell porcine embryos with high efficiencies of 55% at 20 ms and 360 mJ/cm(2) (670 mW). Long-term viability of fused embryos was proven by successful development up to the blastocyst stage in 70% of cases with no significant difference to controls. In contrast to previous studies, our results indicate that fs laser-induced cell fusion occurs when the membrane pore size exceeds a critical value, preventing immediate membrane resealing.

ATG14 controls SNARE-mediated autophagosome fusion with a lysosome.

PubMed

Liu, Rong; Zhi, Xiaoyong; Zhong, Qing

2015-01-01

Autophagosome fusion with a lysosome constitutes the last barrier for autophagic degradation. It is speculated that this fusion process is precisely and tightly regulated. Recent genetic evidence suggests that a set of SNARE proteins, including STX17, SNAP29, and VAMP8, are essential for the fusion between autophagosomes and lysosomes. However, it remains unclear whether these SNAREs are fusion competent and how their fusogenic activity is specifically regulated during autophagy. Using a combination of biochemical, cell biology, and genetic approaches, we demonstrated that fusogenic activity of the autophagic SNARE complex is temporally and spatially controlled by ATG14/Barkor/Atg14L, an essential autophagy-specific regulator of the class III phosphatidylinositol 3-kinase complex (PtdIns3K). ATG14 directly binds to the STX17-SNAP29 binary complex on autophagosomes and promotes STX17-SNAP29-VAMP8-mediated autophagosome fusion with lysosomes. ATG14 homo-oligomerization is required for SNARE binding and fusion promotion, but is dispensable for PtdIns3K stimulation and autophagosome biogenesis. Consequently, ATG14 homo-oligomerization is required for autophagosome fusion with a lysosome, but is dispensable for autophagosome biogenesis. These data support a key role of ATG14 in controlling autophagosome fusion with a lysosome.

Study on Latent Heat of Fusion of Ice in Aqueous Solutions

NASA Astrophysics Data System (ADS)

Kumano, Hiroyuki; Asaoka, Tatsunori; Saito, Akio; Okawa, Seiji

In this study, latent heat of fusion of ice in aqueous solutions was measured to understand latent heat of fusion of ice slurries. Propylene glycol, ethylene glycol, ethanol, NaCl and NaNO3 solutions were examined as the aqueous solutions. In the measurement, pure ice was put into the solution, and the temperature variation of the solution due to the melting of the ice was measured. Then, the effective latent heat of fusion was calculated from energy balance equation. When ice melts in solution, the concentration of the solution varies due to the melting of the ice, and dilution heat must be considered. Therefore, the latent heat of fusion of ice in aqueous solutions was predicted by considering the effects of dilution and freezing-point depression. The latent heat of fusion was also measured by differential scanning calorimetry(DSC) to compare the results obtained from the experiments with that obtained by DSC. As the result, it was found that the effective latent heat of fusion of ice decreased with the increase of the concentration of solution, and the effective latent heat of fusion was calculated from latent heat of fusion of pure ice and the effects of freezing-point depression and the dilution heat.

Design Considerations for Clean QED Fusion Propulsion Systems

NASA Astrophysics Data System (ADS)

Bussard, Robert W.; Jameson, Lorin W.

1994-07-01

The direct production of electric power appears possible from fusion reactions between fuels whose products consist solely of charged particles and thus do not present radiation hazards from energetic neutron production, as do reactions involving deuteron-bearing fuels. Among these are the fuels p, 11B, 3He, and 6Li. All of these can be ``burned'' in inertial-electrostatic-fusion (IEF) devices to power QED fusion-electric rocket engines. These IEF sources provide direct-converted electrical power at high voltage (MeV) to drive e-beams for efficient propellant heating to extreme temperatures, with resulting high specific impulse performance capabilities. IEF/QED engine systems using p11B can outperform all other advanced concepts for controlled fusion propulsion by 2-3 orders of magnitude, while 6Li6Li fusion yields one order of magnitude less advance. Either of these fusion rocket propulsion systems can provide very rapid transit for solar system missions, with high payload fractions in single-stage vehicles. The 3He3He reaction can not be used practically for direct electric conversion because of the wide spread in energy of its fusion products. However, it may eventually prove useful for thermal/electrical power generation in central station power plants, or for direct-fusion-product (DFP) propellant heatingin advanced deep-space rocket engines.

Spatiotemporal regulation of cell fusion by JNK and JAK/STAT signaling during Drosophila wound healing.

PubMed

Lee, Ji-Hyun; Lee, Chan-Wool; Park, Si-Hyoung; Choe, Kwang-Min

2017-06-01

Cell-cell fusion is widely observed during development and disease, and imposes a dramatic change on participating cells. Cell fusion should be tightly controlled, but the underlying mechanism is poorly understood. Here, we found that the JAK/STAT pathway suppressed cell fusion during wound healing in the Drosophila larval epidermis, restricting cell fusion to the vicinity of the wound. In the absence of JAK/STAT signaling, a large syncytium containing a 3-fold higher number of nuclei than observed in wild-type tissue formed in wounded epidermis. The JAK/STAT ligand-encoding genes upd2 and upd3 were transcriptionally induced by wounding, and were required for suppressing excess cell fusion. JNK (also known as Basket in flies) was activated in the wound vicinity and activity peaked at ∼8 h after injury, whereas JAK/STAT signaling was activated in an adjoining concentric ring and activity peaked at a later stage. Cell fusion occurred primarily in the wound vicinity, where JAK/STAT activation was suppressed by fusion-inducing JNK signaling. JAK/STAT signaling was both necessary and sufficient for the induction of βPS integrin (also known as Myospheroid) expression, suggesting that the suppression of cell fusion was mediated at least in part by integrin protein. © 2017. Published by The Company of Biologists Ltd.

Enhancement of fusion at near-barrier energies for neutron-rich light nuclei: 19O +12 C

NASA Astrophysics Data System (ADS)

Singh, Varinderjit; Vadas, J.; Steinbach, T. K.; Wiggins, B. B.; Hudan, S.; Desouza, R. T.; Baby, L. T.; Kuvin, S. A.; Tripathi, Vandana; Wiedenhover, I.; Umar, A. S.

2017-01-01

Measuring the fusion excitation function for an isotopic chain of projectile nuclei provides a sensitive test of a microscopic description of fusion. To investigate the theoretically predicted fusion enhancement for neutron-rich light nuclei, an experiment was performed to measure the fusion excitation functions for 19 O +12 C and 18 O +12 C . Using the 18O(d,p) reaction and the RESOLUT mass spectrometer at Florida State University, a beam of 19O was produced with an intensity of 2-4 x 103 p/s. This beam bombarded a 100 μg/cm2 carbon target. Using an approach optimized for the measurement of fusion with a low-intensity beam, evaporation residues (ERs) resulting from the de-excitation of the fusion product were measured. The ERs were identified by measuring their energy and time-of-flight. At near-barrier energies, an enhancement of fusion by a factor of three has been observed for 19 O +12 C in comparison to 18 O +12 C . Comparison of the experimental results with the predictions of a density constrained time-dependent Hartree-Fock (DC-TDHF) model provide evidence for the importance of pairing in the fusion process. Supported by the US DOE under Grant No. DEFG02-88ER-40404.

Stalk model of membrane fusion: solution of energy crisis.

PubMed Central

Kozlovsky, Yonathan; Kozlov, Michael M

2002-01-01

Membrane fusion proceeds via formation of intermediate nonbilayer structures. The stalk model of fusion intermediate is commonly recognized to account for the major phenomenology of the fusion process. However, in its current form, the stalk model poses a challenge. On one hand, it is able to describe qualitatively the modulation of the fusion reaction by the lipid composition of the membranes. On the other, it predicts very large values of the stalk energy, so that the related energy barrier for fusion cannot be overcome by membranes within a biologically reasonable span of time. We suggest a new structure for the fusion stalk, which resolves the energy crisis of the model. Our approach is based on a combined deformation of the stalk membrane including bending of the membrane surface and tilt of the hydrocarbon chains of lipid molecules. We demonstrate that the energy of the fusion stalk is a few times smaller than those predicted previously and the stalks are feasible in real systems. We account quantitatively for the experimental results on dependence of the fusion reaction on the lipid composition of different membrane monolayers. We analyze the dependence of the stalk energy on the distance between the fusing membranes and provide the experimentally testable predictions for the structural features of the stalk intermediates. PMID:11806930

The Fusion of Membranes and Vesicles: Pathway and Energy Barriers from Dissipative Particle Dynamics

PubMed Central

Grafmüller, Andrea; Shillcock, Julian; Lipowsky, Reinhard

2009-01-01

The fusion of lipid bilayers is studied with dissipative particle dynamics simulations. First, to achieve control over membrane properties, the effects of individual simulation parameters are studied and optimized. Then, a large number of fusion events for a vesicle and a planar bilayer are simulated using the optimized parameter set. In the observed fusion pathway, configurations of individual lipids play an important role. Fusion starts with individual lipids assuming a splayed tail configuration with one tail inserted in each membrane. To determine the corresponding energy barrier, we measure the average work for interbilayer flips of a lipid tail, i.e., the average work to displace one lipid tail from one bilayer to the other. This energy barrier is found to depend strongly on a certain dissipative particle dynamics parameter, and, thus, can be adjusted in the simulations. Overall, three subprocesses have been identified in the fusion pathway. Their energy barriers are estimated to lie in the range 8–15 kBT. The fusion probability is found to possess a maximum at intermediate tension values. As one decreases the tension, the fusion probability seems to vanish before the tensionless membrane state is attained. This would imply that the tension has to exceed a certain threshold value to induce fusion. PMID:19348749

The national ignition facility and atomic data

NASA Astrophysics Data System (ADS)

Crandall, David H.

1998-07-01

The National Ignition Facility (NIF) is under construction, capping over 25 years of development of the inertial confinement fusion concept by providing the facility to obtain fusion ignition in the laboratory for the first time. The NIF is a 192 beam glass laser to provide energy controlled in space and time so that a millimeter-scale capsule containing deuterium and tritium can be compressed to fusion conditions. Light transport, conversion of light in frequency, interaction of light with matter in solid and plasma forms, and diagnostics of extreme material conditions on small scale all use atomic data in preparing for use of the NIF. The NIF will provide opportunity to make measurements of atomic data in extreme physical environments related to fusion energy, nuclear weapon detonation, and astrophysics. The first laser beams of NIF should be operational in 2001 and the full facility completed at the end of 2003. NIF is to provide 1.8 megajoule of blue light on fusion targets and is intended to achieve fusion ignition by about the end of 2007. Today's inertial fusion development activities use atomic data to design and predict fusion capsule performance and in non-fusion applications to analyze radiation transport and radiation effects on matter. Conditions investigated involve radiation temperature of hundreds of eV, pressures up to gigabars and time scales of femptoseconds.

The pharmacological efficacy of the anti-IL17 scFv and sTNFR1 bispecific fusion protein in inflammation mouse stimulated by LPS.

PubMed

Yang, Yongbi; Zhang, Teng; Cao, Hongxue; Yu, Dan; Zhang, Tong; Zhao, Shaojuan; Jing, Xiaohui; Song, Liying; Liu, Yunye; Che, Ruixiang; Liu, Xin; Li, Deshan; Ren, Guiping

2017-08-01

Acute lung injury (ALI) is still a leading cause of morbidity and mortality in critically ill patients. Recently, our study found that a bispecific fusion protein treatment can ameliorate the lung injury induced by LPS. However, the molecular mechanisms which bispecific fusion protein ameliorates acute lung injury remain unclear. In this study, we found that the bispecific fusion protein treatment inhibited the nuclear transcription of NF-κB in confocal laser scanning fluorescence microscopy, the bispecific fusion protein exert protective effects in the cell model of ALI induced by lipopolysaccharide (LPS) via inhibiting the nuclear factor κB (NF-κB) signaling pathway and mediate inflammation. Moreover, the treatment of the bispecific fusion protein show its efficacy in animal models stimulated by LPS, the results of real-time PCR and ELISA demonstrate that bispecific fusion protein treatment effectively inhibited the over-expression of inflammatory cytokines(tumor necrosis factor α, interleukin 1β and interleukin 17). In addition, LPS-challenged mice exhibited significant lung injury characterized by the deterioration of histopathology, which was meliorated by bispecific fusion protein treatment. Collectively, these results demonstrate that bispecific fusion protein treatment ameliorates LPS-induced ALI through reducing inflammatory cytokines and lung inflammation, which may be associated with the decreased the nuclear transcription of NF-κB. The bispecific fusion protein may be useful as a novel therapy to treat ALI. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Detection of EML4-ALK fusion gene and features associated with EGFR mutations in Chinese patients with non-small-cell lung cancer.

PubMed

Wen, Miaomiao; Wang, Xuejiao; Sun, Ying; Xia, Jinghua; Fan, Liangbo; Xing, Hao; Zhang, Zhipei; Li, Xiaofei

2016-01-01

Echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) and epidermal growth factor receptor (EGFR) define specific molecular subsets of lung cancer with distinct clinical features. We aimed at revealing the clinical features of EML4-ALK fusion gene and EGFR mutation in non-small-cell lung cancer (NSCLC). We enrolled 694 Chinese patients with NSCLC for analysis. EML4-ALK fusion gene was analyzed by real-time polymerase chain reaction, and EGFR mutations were analyzed by amplified refractory mutation system. Among the 694 patients, 60 (8.65%) patients had EML4-ALK fusions. In continuity correction χ (2) test analysis, EML4-ALK fusion gene was correlated with sex, age, smoking status, and histology, but no significant association was observed between EML4-ALK fusion gene and clinical stage. A total of 147 (21.18%) patients had EGFR mutations. In concordance with previous reports, EGFR mutation was correlated with age, smoking status, histology, and clinical stage, whereas patient age was not significantly associated with EGFR mutation. Meanwhile, to our surprise, six (0.86%) patients had coexisting EML4-ALK fusions and EGFR mutations. EML4-ALK fusion gene defines a new molecular subset in patients with NSCLC. Six patients who harbored both EML4-ALK fusion genes and EGFR mutations were identified in our study. The EGFR mutations and the EML4-ALK fusion genes are coexistent.

Rubella virus: first calcium-requiring viral fusion protein.

PubMed

Dubé, Mathieu; Rey, Felix A; Kielian, Margaret

2014-12-01

Rubella virus (RuV) infection of pregnant women can cause fetal death, miscarriage, or severe fetal malformations, and remains a significant health problem in much of the underdeveloped world. RuV is a small enveloped RNA virus that infects target cells by receptor-mediated endocytosis and low pH-dependent membrane fusion. The structure of the RuV E1 fusion protein was recently solved in its postfusion conformation. RuV E1 is a member of the class II fusion proteins and is structurally related to the alphavirus and flavivirus fusion proteins. Unlike the other known class II fusion proteins, however, RuV E1 contains two fusion loops, with a metal ion complexed between them by the polar residues N88 and D136. Here we demonstrated that RuV infection specifically requires Ca(2+) during virus entry. Other tested cations did not substitute. Ca(2+) was not required for virus binding to cell surface receptors, endocytic uptake, or formation of the low pH-dependent E1 homotrimer. However, Ca(2+) was required for low pH-triggered E1 liposome insertion, virus fusion and infection. Alanine substitution of N88 or D136 was lethal. While the mutant viruses were efficiently assembled and endocytosed by host cells, E1-membrane insertion and fusion were specifically blocked. Together our data indicate that RuV E1 is the first example of a Ca(2+)-dependent viral fusion protein and has a unique membrane interaction mechanism.

PAX3/7-FOXO1 fusion status in older rhabdomyosarcoma patient population by fluorescent in situ hybridization.

PubMed

Dumont, Sarah N; Lazar, Alexander J; Bridge, Julia A; Benjamin, Robert S; Trent, Jonathan C

2012-02-01

In pediatric alveolar rhabdomyosarcoma, the PAX3-FOXO1 and PAX7-FOXO1 gene fusions are prognostic indicators, while little is known concerning this disease in older patients. To determine whether PAX3/7-FOXO1 fusion gene status correlates with outcome in adolescent, young adult, and adult rhabdomyosarcoma patients, the histological, immunohistochemical, and clinical characteristics of 105 patients followed at The University of Texas MD Anderson Cancer Center from 1957 to 2001 were evaluated. The samples were assembled into a tissue microarray, and fusion gene status was determined by fluorescence in situ hybridization using PAX3, PAX7, and FOXO1 loci-specific probes. The disease characteristics and specific gene fusion were correlated with patient outcomes using the log-rank test. Fifty-two percent of the samples exhibited a PAX3-FOXO1 fusion, 15% the PAX7-FOXO1 fusion, and 33% were negative for a rearrangement of these loci. The presence of PAX3/7-FOXO1 translocation was significantly associated with a higher frequency of metastatic disease. Although a statistically significant correlation between the PAX3/7-FOXO1 fusion gene status and overall survival was not identified, there was a trend toward better outcomes for patients with fusion-negative RMS. Therefore, identification of a FOXO1 fusion appears to be an interesting tool for predicting outcomes in older rhabdomyosarcoma patients and is worth further investigations in this rare subgroup of RMS population.

Detection of EML4-ALK fusion gene and features associated with EGFR mutations in Chinese patients with non-small-cell lung cancer

PubMed Central

Wen, Miaomiao; Wang, Xuejiao; Sun, Ying; Xia, Jinghua; Fan, Liangbo; Xing, Hao; Zhang, Zhipei; Li, Xiaofei

2016-01-01

Purpose Echinoderm microtubule-associated protein-like 4–anaplastic lymphoma kinase (EML4-ALK) and epidermal growth factor receptor (EGFR) define specific molecular subsets of lung cancer with distinct clinical features. We aimed at revealing the clinical features of EML4-ALK fusion gene and EGFR mutation in non-small-cell lung cancer (NSCLC). Methods We enrolled 694 Chinese patients with NSCLC for analysis. EML4-ALK fusion gene was analyzed by real-time polymerase chain reaction, and EGFR mutations were analyzed by amplified refractory mutation system. Results Among the 694 patients, 60 (8.65%) patients had EML4-ALK fusions. In continuity correction χ2 test analysis, EML4-ALK fusion gene was correlated with sex, age, smoking status, and histology, but no significant association was observed between EML4-ALK fusion gene and clinical stage. A total of 147 (21.18%) patients had EGFR mutations. In concordance with previous reports, EGFR mutation was correlated with age, smoking status, histology, and clinical stage, whereas patient age was not significantly associated with EGFR mutation. Meanwhile, to our surprise, six (0.86%) patients had coexisting EML4-ALK fusions and EGFR mutations. Conclusion EML4-ALK fusion gene defines a new molecular subset in patients with NSCLC. Six patients who harbored both EML4-ALK fusion genes and EGFR mutations were identified in our study. The EGFR mutations and the EML4-ALK fusion genes are coexistent. PMID:27103824

Efficacy of different bone volume expanders for augmenting lumbar fusions.

PubMed

Epstein, Nancy E

2008-01-01

A wide variety of bone volume expanders are being used in performing posterolateral lumbar noninstrumented and instrumented lumbar fusions. This article presents a review of their efficacy based on fusion rates, complications, and outcomes. Lumbar noninstrumented and instrumented fusions frequently use laminar autografts and different bone graft expanders. This review presents the utility of multiple forms/ratios of DBMs containing allografts. It also discusses the efficacy of artificial bone graft substitutes, including HA and B-TCP. Dynamic x-ray and/or CT examinations were used to document fusion in most series. Outcomes were variously assessed using Odom's criteria or different outcome questionnaires (Oswestry Questionnaire, SF-36, Dallas Pain Questionnaire, and/or Low Back Pain Rating Scale). Performing noninstrumented and instrumented lumbar posterolateral fusions resulted in comparable fusion rates in many series. Similar outcomes were also documented based on Odom's criteria or the multiple patient-based questionnaires. However, in some studies, the addition of spinal instrumentation increased the reoperation rate, operative time, blood loss, and cost. Various forms of DBMs, applied in different ratios to autografts, effectively supplemented spinal fusions in animal models and patient series. beta-Tricalcium phosphate, which is used to augment autograft fusions addressing idiopathic scoliosis or lumbar disease, also proved to be effective. Different types of bone volume expanders, including various forms of allograft-based DBMs, and artificial bone graft substitutes (HA and B-TCP) effectively promote posterolateral lumbar noninstrumented and instrumented fusions when added to autografts.

Preventive antitumor activity against hepatocellular carcinoma (HCC) induced by immunization with fusions of dendritic cells and HCC cells in mice.

PubMed

Homma, S; Toda, G; Gong, J; Kufe, D; Ohno, T

2001-11-01

The prevention of recurrence of hepatocellular carcinoma (HCC) after treatment is very important for improvement of the prognosis of HCC patients. Dendritic cells (DCs) are potent antigen-presenting cells that can prime naive T cells to induce a primary immune response. We attempted to induce preventive antitumor immunity against HCC by immunizing BALB/c mice with fusions of DCs and HCC cells. Murine bone marrow-derived DCs and a murine HCC cell line. BNL cells, were fused by treatment with 50% polyethyleneglvcol (PEG). Fusion efficacy was assessed by the analysis of fusions of BNL cells stained with red fluorescent dye and DCs stained with green fluorescent dye. Mice injected intravenously with DC/BNL fusions were challenged by BNL cell inoculation. About 30% of the PEG-treated non-adherent cells with both fluorescences were considered to be fusion cells. The cell fraction of DC/BNL fusions showed phenotypes of DCs, MHC class II, CD80, CD86, and intercellular adhesion molecule (ICAM)-1, which were not expressed on BNL cells. Mice immunized with the fusions were protected against the inoculation of BNL tumor cells, whereas injection with a mixture of DCs and BNL cells not treated with PEG did not provide significant resistance against BNL cell inoculation. Splenocytes from DC/BNL fusion-immunized mice showed lytic activity against BNL cells. These results demonstrate that immunization with fusions of DCs and HCC cells is capable of inducing preventive antitumor immunity against HCC.

Remodeling of the notochord during development of vertebral fusions in Atlantic salmon (Salmo salar).

PubMed

Ytteborg, Elisabeth; Torgersen, Jacob Seilø; Pedersen, Mona E; Baeverfjord, Grete; Hannesson, Kirsten O; Takle, Harald

2010-12-01

Histological characterization of spinal fusions in Atlantic salmon (Salmo salar) has demonstrated shape alterations of vertebral body endplates, a reduced intervertebral space, and replacement of intervertebral cells by ectopic bone. However, the significance of the notochord during the fusion process has not been addressed. We have therefore investigated structural and cellular events in the notochord during the development of vertebral fusions. In order to induce vertebral fusions, Atlantic salmon were exposed to elevated temperatures from fertilization until they attained a size of 15g. Based on results from radiography, intermediate and terminal stages of the fusion process were investigated by immunohistochemistry and real-time quantitative polymerase chain reaction. Examination of structural extracellular matrix proteins such as Perlecan, Aggrecan, Elastin, and Laminin revealed reduced activity and reorganization at early stages in the pathology. Staining for elastic fibers visualized a thinner elastic membrane surrounding the notochord of developing fusions, and immunohistochemistry for Perlecan showed that the notochordal sheath was stretched during fusion. These findings in the outer notochord correlated with the loss of Aggrecan- and Substance-P-positive signals and the further loss of vacuoles from the chordocytes in the central notochord. At more progressed stages of fusion, chordocytes condensed, and the expression of Aggrecan and Substance P reappeared. The hyperdense regions seem to be of importance for the formation of notochordal tissue into bone. Thus, the remodeling of notochord integrity by reduced elasticity, structural alterations, and cellular changes is probably involved in the development of vertebral fusions.

Development of fusogenic glass surfaces that impart spatiotemporal control over macrophage fusion: Direct visualization of multinucleated giant cell formation

PubMed Central

Faust, James J.; Christenson, Wayne; Doudrick, Kyle; Ros, Robert

2017-01-01

Implantation of synthetic material, including vascular grafts, pacemakers, etc. results in the foreign body reaction and the formation of multinucleated giant cells (MGCs) at the exterior surface of the implant. Despite the long-standing premise that fusion of mononucleated macrophages results in the formation of MGCs, to date, no published study has shown fusion in context with living specimens. This is due to the fact that optical-quality glass, which is required for the majority of live imaging techniques, does not promote macrophage fusion. Consequently, the morphological changes that macrophages undergo during fusion as well as the mechanisms that govern this process remain ill-defined. In this study, we serendipitously identified a highly fusogenic glass surface and discovered that the capacity to promote fusion was due to oleamide contamination. When adsorbed on glass, oleamide and other molecules that contain long-chain hydrocarbons promoted high levels of macrophage fusion. Adhesion, an essential step for macrophage fusion, was apparently mediated by Mac-1 integrin (CD11b/CD18, αMβ2) as determined by single cell force spectroscopy and adhesion assays. Micropatterned glass further increased fusion and enabled a remarkable degree of spatiotemporal control over MGC formation. Using these surfaces, we reveal the kinetics that govern MGC formation in vitro. We anticipate that the spatiotemporal control afforded by these surfaces will expedite studies designed to identify the mechanism(s) of macrophage fusion and MGC formation with implication for the design of novel biomaterials. PMID:28340410

Purification and Crystallization Reveal Two Types of Interactions of the Fusion Protein Homotrimer of Semliki Forest Virus

PubMed Central

Gibbons, Don L.; Reilly, Brigid; Ahn, Anna; Vaney, Marie-Christine; Vigouroux, Armelle; Rey, Felix A.; Kielian, Margaret

2004-01-01

The fusion proteins of the alphaviruses and flaviviruses have a similar native structure and convert to a highly stable homotrimer conformation during the fusion of the viral and target membranes. The properties of the alpha- and flavivirus fusion proteins distinguish them from the class I viral fusion proteins, such as influenza virus hemagglutinin, and establish them as the first members of the class II fusion proteins. Understanding how this new class carries out membrane fusion will require analysis of the structural basis for both the interaction of the protein subunits within the homotrimer and their interaction with the viral and target membranes. To this end we report a purification method for the E1 ectodomain homotrimer from the alphavirus Semliki Forest virus. The purified protein is trimeric, detergent soluble, retains the characteristic stability of the starting homotrimer, and is free of lipid and other contaminants. In contrast to the postfusion structures that have been determined for the class I proteins, the E1 homotrimer contains the fusion peptide region responsible for interaction with target membranes. This E1 trimer preparation is an excellent candidate for structural studies of the class II viral fusion proteins, and we report conditions that generate three-dimensional crystals suitable for analysis by X-ray diffraction. Determination of the structure will provide our first high-resolution views of both the low-pH-induced trimeric conformation and the target membrane-interacting region of the alphavirus fusion protein. PMID:15016874

Fusion Materials Research at Oak Ridge National Laboratory in Fiscal Year 2015

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wiffen, F. W.; Katoh, Yutai; Melton, Stephanie G.

The realization of fusion energy is a formidable challenge with significant achievements resulting from close integration of the plasma physics and applied technology disciplines. Presently, the most significant technological challenge for the near-term experiments such as ITER, and next generation fusion power systems, is the inability of current materials and components to withstand the harsh fusion nuclear environment. The overarching goal of the Oak Ridge National Laboratory (ORNL) fusion materials program is to provide the applied materials science support and understanding to underpin the ongoing Department of Energy (DOE) Office of Science fusion energy program while developing materials for fusionmore » power systems. In doing so the program continues to be integrated both with the larger United States (US) and international fusion materials communities, and with the international fusion design and technology communities.This document provides a summary of Fiscal Year (FY) 2015 activities supporting the Office of Science, Office of Fusion Energy Sciences Materials Research for Magnetic Fusion Energy (AT-60-20-10-0) carried out by ORNL. The organization of this report is mainly by material type, with sections on specific technical activities. Four projects selected in the Funding Opportunity Announcement (FOA) solicitation of late 2011 and funded in FY2012-FY2014 are identified by “FOA” in the titles. This report includes the final funded work of these projects, although ORNL plans to continue some of this work within the base program.« less

Condorcet and borda count fusion method for ligand-based virtual screening.

PubMed

Ahmed, Ali; Saeed, Faisal; Salim, Naomie; Abdo, Ammar

2014-01-01

It is known that any individual similarity measure will not always give the best recall of active molecule structure for all types of activity classes. Recently, the effectiveness of ligand-based virtual screening approaches can be enhanced by using data fusion. Data fusion can be implemented using two different approaches: group fusion and similarity fusion. Similarity fusion involves searching using multiple similarity measures. The similarity scores, or ranking, for each similarity measure are combined to obtain the final ranking of the compounds in the database. The Condorcet fusion method was examined. This approach combines the outputs of similarity searches from eleven association and distance similarity coefficients, and then the winner measure for each class of molecules, based on Condorcet fusion, was chosen to be the best method of searching. The recall of retrieved active molecules at top 5% and significant test are used to evaluate our proposed method. The MDL drug data report (MDDR), maximum unbiased validation (MUV) and Directory of Useful Decoys (DUD) data sets were used for experiments and were represented by 2D fingerprints. Simulated virtual screening experiments with the standard two data sets show that the use of Condorcet fusion provides a very simple way of improving the ligand-based virtual screening, especially when the active molecules being sought have a lowest degree of structural heterogeneity. However, the effectiveness of the Condorcet fusion was increased slightly when structural sets of high diversity activities were being sought.

Condorcet and borda count fusion method for ligand-based virtual screening

PubMed Central

2014-01-01

Background It is known that any individual similarity measure will not always give the best recall of active molecule structure for all types of activity classes. Recently, the effectiveness of ligand-based virtual screening approaches can be enhanced by using data fusion. Data fusion can be implemented using two different approaches: group fusion and similarity fusion. Similarity fusion involves searching using multiple similarity measures. The similarity scores, or ranking, for each similarity measure are combined to obtain the final ranking of the compounds in the database. Results The Condorcet fusion method was examined. This approach combines the outputs of similarity searches from eleven association and distance similarity coefficients, and then the winner measure for each class of molecules, based on Condorcet fusion, was chosen to be the best method of searching. The recall of retrieved active molecules at top 5% and significant test are used to evaluate our proposed method. The MDL drug data report (MDDR), maximum unbiased validation (MUV) and Directory of Useful Decoys (DUD) data sets were used for experiments and were represented by 2D fingerprints. Conclusions Simulated virtual screening experiments with the standard two data sets show that the use of Condorcet fusion provides a very simple way of improving the ligand-based virtual screening, especially when the active molecules being sought have a lowest degree of structural heterogeneity. However, the effectiveness of the Condorcet fusion was increased slightly when structural sets of high diversity activities were being sought. PMID:24883114

Barrier distributions and signatures of transfer channels in the Ca40+Ni58,64 fusion reactions at energies around and below the Coulomb barrier

NASA Astrophysics Data System (ADS)

Bourgin, D.; Courtin, S.; Haas, F.; Stefanini, A. M.; Montagnoli, G.; Goasduff, A.; Montanari, D.; Corradi, L.; Fioretto, E.; Huiming, J.; Scarlassara, F.; Rowley, N.; Szilner, S.; Mijatović, T.

2014-10-01

Background: The nuclear structure of colliding nuclei is known to influence the fusion process. Couplings of the relative motion to nuclear shape deformations and vibrations lead to an enhancement of the sub-barrier fusion cross section in comparison with the predictions of one-dimensional barrier penetration models. This enhancement is explained by coupled-channels calculations including these couplings. The sub-barrier fusion cross section is also affected by nucleon transfer channels between the colliding nuclei. Purpose: The aim of the present experiment is to investigate the influence of the projectile and target nuclear structures on the fusion cross sections in the Ca40+Ni58 and Ca40+Ni64 systems. Methods: The experimental and theoretical fusion excitation functions as well as the barrier distributions were compared for these two systems. Coupled-channels calculations were performed using the ccfull code. Results: Good agreement was found between the measured and calculated fusion cross sections for the Ca40+Ni58 system. The situation is different for the Ca40+Ni64 system where the coupled-channels calculations with no nucleon transfer clearly underestimate the fusion cross sections below the Coulomb barrier. The fusion excitation function was, however, well reproduced at low and high energies by including the coupling to the neutron pair-transfer channel in the calculations. Conclusions: The nuclear structure of the colliding nuclei influences the fusion cross sections below the Coulomb barrier for both Ca40+Ni58,64 systems. Moreover, we highlighted the effect of the neutron pair-transfer channel on the fusion cross sections in Ca40+Ni64.

Expanding the molecular signature of ossifying fibromyxoid tumors with two novel gene fusions: CREBBP-BCORL1 and KDM2A-WWTR1.

PubMed

Kao, Yu-Chien; Sung, Yun-Shao; Zhang, Lei; Chen, Chun-Liang; Huang, Shih-Chiang; Antonescu, Cristina R

2017-01-01

Ossifying fibromyxoid tumor (OFMT) is an uncommon mesenchymal neoplasm of uncertain differentiation and intermediate malignant potential. Recurrent gene fusions involving either PHF1 or BCOR have been found in 85% of OFMT, including typical and malignant examples. As a subset of OFMT still lack known genetic abnormalities, we identified two OFMTs negative for PHF1 and BCOR rearrangements, which were subjected to transcriptome analysis for fusion discovery. The RNA sequencing found a novel CREBBP-BCORL1 fusion candidate in an axillary mass of a 51 year-old male and a KDM2A-WWTR1 in a thigh mass of a 36 year-old male. The gene fusions were validated by RT-PCR and FISH in the index cases and then screened by FISH on 4 additional OFMTs lacking known fusions. An identical CREBBP-BCORL1 fusion was found in an elbow tumor from a 30 year-old male. Both OFMTs with CREBBP-BCORL1 fusions had areas of typical OFMT morphology, exhibiting uniform round to epithelioid cells arranged in cords or nesting pattern in a fibromyxoid stroma. The OFMT with KDM2A-WWTR1 fusion involved dermis and superficial subcutis, being composed of ovoid cells in a fibromyxoid background with hyalinized giant rosettes. The S100 immunoreactivity ranged from very focal to absent. Similar to other known fusion genes in OFMT, BCORL1, CREBBP and KDM2A are also involved in histone modification. In summary, we expand the spectrum of molecular abnormalities in OFMT with 2 novel fusions, CREBBP-BCORL1 and KDM2A-WWTR1, further implicating the epigenetic deregulation as the leading pathogenetic mechanism in OFMT. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Expanding the Molecular Signature of Ossifying Fibromyxoid Tumors with 2 Novel Gene Fusions: CREBBP-BCORL1 and KDM2A-WWTR1

PubMed Central

Kao, Yu-Chien; Sung, Yun-Shao; Zhang, Lei; Chen, Chun-Liang; Huang, Shih-Chiang; Antonescu, Cristina R.

2017-01-01

Ossifying fibromyxoid tumor (OFMT) is an uncommon mesenchymal neoplasm of uncertain differentiation and intermediate malignant potential. Recurrent gene fusions involving either PHF1 or BCOR have been found in 85% of OFMT, including typical and malignant examples. As a subset of OFMT still lack known genetic abnormalities, we identified two OFMTs negative for PHF1 and BCOR rearrangements, which were subjected to transcriptome analysis for fusion discovery. The RNA sequencing found a novel CREBBP-BCORL1 fusion candidate in an axillary mass of a 51 year-old male and a KDM2A-WWTR1 in a thigh mass of a 36 year-old male. The gene fusions were validated by RT-PCR and FISH in the index cases and then screened by FISH on 4 additional OFMTs lacking known fusions. An identical CREBBP-BCORL1 fusion was found in an elbow tumor from a 30 year-old male. Both OFMTs with CREBBP-BCORL1 fusions had areas of typical OFMT morphology, exhibiting uniform round to epithelioid cells arranged in cords or nesting pattern in a fibromyxoid stroma. The OFMT with KDM2A-WWTR1 fusion involved dermis and superficial subcutis, being composed of ovoid cells in a fibromyxoid background with hyalinized giant rosettes. The S100 immunoreactivity ranged from very focal to absent. Similar to other known fusion genes in OFMT, BCORL1, CREBBP and KDM2A are also involved in histone modification. In summary, we expand the spectrum of molecular abnormalities in OFMT with 2 novel fusions, CREBBP-BCORL1 and KDM2A-WWTR1, further implicating the epigenetic deregulation as the leading pathogenetic mechanism in OFMT. PMID:27537276

Role of lipid phase separations and membrane hydration in phospholipid vesicle fusion.

PubMed

Hoekstra, D

1982-06-08

The relationship between lipid phase separation and fusion of small unilamellar phosphatidylserine-containing vesicles was investigated. The kinetics of phase separation were monitored by following the increase of self-quenching of the fluorescent phospholipid analogue N-(7-nitro-2,1,3-benzoxadiazol-4-yl)phosphatidylethanolamine, which occurs when the local concentration of the probe increases upon Ca2+-induced phase separation in phosphatidylserine (PS) bilayers [Hoekstra, D. (1982) Biochemistry 21, 1055-1061]. Fusion was determined by using the resonance energy transfer fusion assay [Struck, D. K., Hoekstra, D., & Pagano, R. E. (1981) Biochemistry 20, 4093-4099], which monitors the mixing of fluorescent lipid donor and acceptor molecules, resulting in an increase in energy transfer efficiency. The results show that in the presence of Ca2+, fusion proceeds much more rapidly (t 1/2 less than 5 s) than the process of phase separation (T 1/2 congruent to 1 min). Mg2+ also induced fusion, albeit at higher concentrations than Ca2+. Mg2+-induced phase separation were not detected, however. Subthreshold concentrations of Ca2+ (0.5 mM) or Mg2+ (2 mM) induced extensive fusion of PS-containing vesicles in poly(ethylene glycol) containing media. This effect did not appear to be a poly(ethylene glycol)-facilitated enhancement of cation binding to the bilayer, and consequently Ca2+-induced phase separation was not observed. The results suggest that macroscopic phase separation may facilitate but does not induced the fusion process and is therefore, not directly involved in the actual fusion mechanism. The fusion experiments performed in the presence of poly(ethylene glycol) suggest that the degree of bilayer dehydration and the creation of "point defects" in the bilayer without rigorous structural rearrangements in the membrane are dominant factors in the initial fusion events.

Investigation of fusion gene expression in HCT116 cells.

PubMed

Zhang, Yanmei; Ren, Juan; Fang, Mengdie; Wang, Xiaoju

2017-12-01

Colon cancer is the most common type of gastrointestinal cancer. A number of specific and sensitive biomarkers facilitate the diagnosis and monitoring of patients with colon cancer. Fusion genes are typically identified in cancer and a majority of the newly identified fusion genes are oncogenic in nature. Therefore, fusion genes are potential biomarkers and/or therapy targets in cancer. In the present study, the regulation of specific candidate fusion genes were investigated using Brother of the Regulator of Imprinted Sites (BORIS) in the HCT116 colon cancer cell line, which is a paralog of the fusion gene regulator CCCTC-binding factor (CTCF). The copy number of BORIS increased correspondingly to the progression of colorectal carcinoma from the M0 to the M1a stage. It was identified that EIF3E(e1)-RSPO2(e2) , EIF3E(e1)-RSPO2(e3) , PTPRK(e1)-RSPO3(e2) , PTPRK(e7)-RSPO3(e2), TADA2A-MEF2B and MED13L-CD4 are fusion transcripts present in the transcriptome of the HCT116 colon cancer cell line. CDC42SE2-KIAAO146 is a genomic fusion transcript, which originates from DNA arrangement in HCT116 cells. BORIS suppresses the expression of EIF3E , RSPO2 , PTPRK , RSPO3 , TADA2A and CD4 to inhibit the expression of fusion transcripts in HCT116 cells. It was hypothesized that the fusion transcripts investigated in the present study may not be oncogenic in HCT116 cells. As BORIS is not colorectal carcinoma-specific, the fusion genes investigated may be a biomarker assemblage for monitoring the progression of colorectal carcinoma.

Investigation of fusion gene expression in HCT116 cells

PubMed Central

Zhang, Yanmei; Ren, Juan; Fang, Mengdie; Wang, Xiaoju

2017-01-01

Colon cancer is the most common type of gastrointestinal cancer. A number of specific and sensitive biomarkers facilitate the diagnosis and monitoring of patients with colon cancer. Fusion genes are typically identified in cancer and a majority of the newly identified fusion genes are oncogenic in nature. Therefore, fusion genes are potential biomarkers and/or therapy targets in cancer. In the present study, the regulation of specific candidate fusion genes were investigated using Brother of the Regulator of Imprinted Sites (BORIS) in the HCT116 colon cancer cell line, which is a paralog of the fusion gene regulator CCCTC-binding factor (CTCF). The copy number of BORIS increased correspondingly to the progression of colorectal carcinoma from the M0 to the M1a stage. It was identified that EIF3E(e1)-RSPO2(e2), EIF3E(e1)-RSPO2(e3), PTPRK(e1)-RSPO3(e2), PTPRK(e7)-RSPO3(e2), TADA2A-MEF2B and MED13L-CD4 are fusion transcripts present in the transcriptome of the HCT116 colon cancer cell line. CDC42SE2-KIAAO146 is a genomic fusion transcript, which originates from DNA arrangement in HCT116 cells. BORIS suppresses the expression of EIF3E, RSPO2, PTPRK, RSPO3, TADA2A and CD4 to inhibit the expression of fusion transcripts in HCT116 cells. It was hypothesized that the fusion transcripts investigated in the present study may not be oncogenic in HCT116 cells. As BORIS is not colorectal carcinoma-specific, the fusion genes investigated may be a biomarker assemblage for monitoring the progression of colorectal carcinoma. PMID:29181107

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

PubMed

Cai, Lifeng; Gochin, Miriam; Liu, Keliang

2011-12-01

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

Co-fuse: a new class discovery analysis tool to identify and prioritize recurrent fusion genes from RNA-sequencing data.

PubMed

Paisitkriangkrai, Sakrapee; Quek, Kelly; Nievergall, Eva; Jabbour, Anissa; Zannettino, Andrew; Kok, Chung Hoow

2018-06-07

Recurrent oncogenic fusion genes play a critical role in the development of various cancers and diseases and provide, in some cases, excellent therapeutic targets. To date, analysis tools that can identify and compare recurrent fusion genes across multiple samples have not been available to researchers. To address this deficiency, we developed Co-occurrence Fusion (Co-fuse), a new and easy to use software tool that enables biologists to merge RNA-seq information, allowing them to identify recurrent fusion genes, without the need for exhaustive data processing. Notably, Co-fuse is based on pattern mining and statistical analysis which enables the identification of hidden patterns of recurrent fusion genes. In this report, we show that Co-fuse can be used to identify 2 distinct groups within a set of 49 leukemic cell lines based on their recurrent fusion genes: a multiple myeloma (MM) samples-enriched cluster and an acute myeloid leukemia (AML) samples-enriched cluster. Our experimental results further demonstrate that Co-fuse can identify known driver fusion genes (e.g., IGH-MYC, IGH-WHSC1) in MM, when compared to AML samples, indicating the potential of Co-fuse to aid the discovery of yet unknown driver fusion genes through cohort comparisons. Additionally, using a 272 primary glioma sample RNA-seq dataset, Co-fuse was able to validate recurrent fusion genes, further demonstrating the power of this analysis tool to identify recurrent fusion genes. Taken together, Co-fuse is a powerful new analysis tool that can be readily applied to large RNA-seq datasets, and may lead to the discovery of new disease subgroups and potentially new driver genes, for which, targeted therapies could be developed. The Co-fuse R source code is publicly available at https://github.com/sakrapee/co-fuse .

Comprehensive analysis of the MYB-NFIB gene fusion in salivary adenoid cystic carcinoma: Incidence, variability, and clinicopathologic significance.

PubMed

Mitani, Yoshitsugu; Li, Jie; Rao, Pulivarthi H; Zhao, Yi-Jue; Bell, Diana; Lippman, Scott M; Weber, Randal S; Caulin, Carlos; El-Naggar, Adel K

2010-10-01

The objectives of this study were to determine the incidence of the MYB-NFIB fusion in salivary adenoid cystic carcinoma (ACC), to establish the clinicopathologic significance of the fusion, and to analyze the expression of MYB in ACCs in the context of the MYB-NFIB fusion. We did an extensive analysis involving 123 cancers of the salivary gland, including primary and metastatic ACCs, and non-ACC salivary carcinomas. MYB-NFIB fusions were identified by reverse transcriptase-PCR (RT-PCR) and sequencing of the RT-PCR products, and confirmed by fluorescence in situ hybridization. MYB RNA expression was determined by quantitative RT-PCR and protein expression was analyzed by immunohistochemistry. The MYB-NFIB fusion was detected in 28% primary and 35% metastatic ACCs, but not in any of the non-ACC salivary carcinomas analyzed. Different exons in both the MYB and NFIB genes were involved in the fusions, resulting in expression of multiple chimeric variants. Notably, MYB was overexpressed in the vast majority of the ACCs, although MYB expression was significantly higher in tumors carrying the MYB-NFIB fusion. The presence of the MYB-NFIB fusion was significantly associated (P = 0.03) with patients older than 50 years of age. No correlation with other clinicopathologic markers, factors, and survival was found. We conclude that the MYB-NFIB fusion characterizes a subset of ACCs and contributes to MYB overexpression. Additional mechanisms may be involved in MYB overexpression in ACCs lacking the MYB-NFIB fusion. These findings suggest that MYB may be a specific novel target for tumor intervention in patients with ACC. ©2010 AACR.

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

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Filone, Claire Marie; Heise, Mark; Doms, Robert W.

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 expressionmore » 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.« less

Fusion Rate and Clinical Outcomes in Two-Level Posterior Lumbar Interbody Fusion.

PubMed

Aono, Hiroyuki; Takenaka, Shota; Nagamoto, Yukitaka; Tobimatsu, Hidekazu; Yamashita, Tomoya; Furuya, Masayuki; Iwasaki, Motoki

2018-04-01

Posterior lumbar interbody fusion (PLIF) has become a general surgical method for degenerative lumbar diseases. Although many reports have focused on single-level PLIF, few have focused on 2-level PLIF, and no report has covered the fusion status of 2-level PLIF. The purpose of this study is to investigate clinical outcomes and fusion for 2-level PLIF by using a combination of dynamic radiographs and multiplanar-reconstruction computed tomography scans. This study consisted of 48 consecutive patients who underwent 2-level PLIF for degenerative lumbar diseases. We assessed surgery duration, estimated blood loss, complications, clinical outcomes as measured by the Japanese Orthopaedic Association score, lumbar sagittal alignment as measured on standing lateral radiographs, and fusion status as measured by dynamic radiographs and multiplanar-reconstruction computed tomography. Patients were examined at a follow-up point of 4.8 ± 2.2 years after surgery. Thirty-eight patients who did not undergo lumbosacral fusion comprised the lumbolumbar group, and 10 patients who underwent lumbosacral fusion comprised the lumbosacral group. The mean Japanese Orthopaedic Association score improved from 12.1 to 22.4 points by the final follow-up examination. Sagittal alignment also was improved. All patients had fusion in the cranial level. Seven patients had nonunion in the caudal level, and the lumbosacral group (40%) had a significantly poorer fusion rate than the lumbolumbar group (97%) did. Surgical outcomes of 2-level PLIF were satisfactory. The fusion rate at both levels was 85%. All nonunion was observed at the caudal level and concentrated at L5-S level in L4-5-S PLIF. Copyright © 2018 Elsevier Inc. All rights reserved.

Techniques of lumbar-sacral spine fusion in spondylosis: systematic literature review and meta-analysis of randomized clinical trials.

PubMed

Umeta, Ricardo S G; Avanzi, Osmar

2011-07-01

Spine fusions can be performed through different techniques and are used to treat a number of vertebral pathologies. However, there seems to be no consensus regarding which technique of fusion is best suited to treat each distinct spinal disease or group of diseases. To study the effectiveness and complications of the different techniques used for spinal fusion in patients with lumbar spondylosis. Systematic literature review and meta-analysis. Randomized clinical studies comparing the most commonly performed surgical techniques for spine fusion in lumbar-sacral spondylosis, as well as those reporting patient outcome were selected. Identify which technique, if any, presents the best clinical, functional, and radiographic outcome. Systematic literature review and meta-analysis based on scientific articles published and indexed to the following databases: PubMed (1966-2009), Cochrane Collaboration-CENTRAL, EMBASE (1980-2009), and LILACS (1982-2009). The general search strategy focused on the surgical treatment of patients with lumbar-sacral spondylosis. Eight studies met the inclusion criteria and were selected with a total of 1,136 patients. Meta-analysis showed that patients who underwent interbody fusion presented a significantly smaller blood loss (p=.001) and a greater rate of bone fusion (p=.02). Patients submitted to fusion using the posterolateral approach had a significantly shorter operative time (p=.007) and less perioperative complications (p=.03). No statistically significant difference was found for the other studied variables (pain, functional impairment, and return to work). The most commonly used techniques for lumbar spine fusion in patients with spondylosis were interbody fusion and posterolateral approach. Both techniques were comparable in final outcome, but the former presented better rates of fusion and the latter the less complications. Copyright © 2011 Elsevier Inc. All rights reserved.

SNARE-mediated Fusion of Single Proteoliposomes with Tethered Supported Bilayers in a Microfluidic Flow Cell Monitored by Polarized TIRF Microscopy

PubMed Central

Nikolaus, Joerg; Karatekin, Erdem

2016-01-01

In the ubiquitous process of membrane fusion the opening of a fusion pore establishes the first connection between two formerly separate compartments. During neurotransmitter or hormone release via exocytosis, the fusion pore can transiently open and close repeatedly, regulating cargo release kinetics. Pore dynamics also determine the mode of vesicle recycling; irreversible resealing results in transient, "kiss-and-run" fusion, whereas dilation leads to full fusion. To better understand what factors govern pore dynamics, we developed an assay to monitor membrane fusion using polarized total internal reflection fluorescence (TIRF) microscopy with single molecule sensitivity and ~15 msec time resolution in a biochemically well-defined in vitro system. Fusion of fluorescently labeled small unilamellar vesicles containing v-SNARE proteins (v-SUVs) with a planar bilayer bearing t-SNAREs, supported on a soft polymer cushion (t-SBL, t-supported bilayer), is monitored. The assay uses microfluidic flow channels that ensure minimal sample consumption while supplying a constant density of SUVs. Exploiting the rapid signal enhancement upon transfer of lipid labels from the SUV to the SBL during fusion, kinetics of lipid dye transfer is monitored. The sensitivity of TIRF microscopy allows tracking single fluorescent lipid labels, from which lipid diffusivity and SUV size can be deduced for every fusion event. Lipid dye release times can be much longer than expected for unimpeded passage through permanently open pores. Using a model that assumes retardation of lipid release is due to pore flickering, a pore "openness", the fraction of time the pore remains open during fusion, can be estimated. A soluble marker can be encapsulated in the SUVs for simultaneous monitoring of lipid and soluble cargo release. Such measurements indicate some pores may reseal after losing a fraction of the soluble cargo. PMID:27585113

Conserved Glycine Residues in the Fusion Peptide of the Paramyxovirus Fusion Protein Regulate Activation of the Native State

PubMed Central

Russell, Charles J.; Jardetzky, Theodore S.; Lamb, Robert A.

2004-01-01

Hydrophobic fusion peptides (FPs) are the most highly conserved regions of class I viral fusion-mediating glycoproteins (vFGPs). FPs often contain conserved glycine residues thought to be critical for forming structures that destabilize target membranes. Unexpectedly, a mutation of glycine residues in the FP of the fusion (F) protein from the paramyxovirus simian parainfluenza virus 5 (SV5) resulted in mutant F proteins with hyperactive fusion phenotypes (C. M. Horvath and R. A. Lamb, J. Virol. 66:2443-2455, 1992). Here, we constructed G3A and G7A mutations into the F proteins of SV5 (W3A and WR isolates), Newcastle disease virus (NDV), and human parainfluenza virus type 3 (HPIV3). All of the mutant F proteins, except NDV G7A, caused increased cell-cell fusion despite having slight to moderate reductions in cell surface expression compared to those of wild-type F proteins. The G3A and G7A mutations cause SV5 WR F, but not NDV F or HPIV3 F, to be triggered to cause fusion in the absence of coexpression of its homotypic receptor-binding protein hemagglutinin-neuraminidase (HN), suggesting that NDV and HPIV3 F have stricter requirements for homotypic HN for fusion activation. Dye transfer assays show that the G3A and G7A mutations decrease the energy required to activate F at a step in the fusion cascade preceding prehairpin intermediate formation and hemifusion. Conserved glycine residues in the FP of paramyxovirus F appear to have a primary role in regulating the activation of the metastable native form of F. Glycine residues in the FPs of other class I vFGPs may also regulate fusion activation. PMID:15564482

Effects of Local Administration of Boric Acid on Posterolateral Spinal Fusion with Autogenous Bone Grafting in a Rodent Model.

PubMed

Kömürcü, Erkam; Özyalvaçlı, Gülzade; Kaymaz, Burak; Gölge, Umut Hatay; Göksel, Ferdi; Cevizci, Sibel; Adam, Gürhan; Ozden, Raif

2015-09-01

Spinal fusion is among the most frequently applied spinal surgical procedures. The goal of the present study was to evaluate whether the local administration of boric acid (BA) improves spinal fusion in an experimental spinal fusion model in rats. Currently, there is no published data that evaluates the possible positive effects if the local administration of BA on posterolateral spinal fusion. Thirty-two rats were randomly divided into four independent groups: no material was added at the fusion area for group 1; an autogenous morselized corticocancellous bone graft was used for group 2; an autogenous morselized corticocancellous bone graft with boric acid (8.7 mg/kg) for group 3; and only boric acid was placed into the fusion area for group 4. The L4-L6 spinal segments were collected at week 6, and the assessments included radiography, manual palpation, and histomorphometry. A statistically significant difference was determined between the groups with regard to the mean histopathological scores (p = 0.002), and a paired comparison was made with the Mann-Whitney U test to detect the group/groups from which the difference originated. It was determined that only the graft + BA practice increased the histopathological score significantly with regard to the control group (p = 0.002). Whereas, there was no statistically significant difference between the groups in terms of the manual assessment of fusion and radiographic analysis (respectively p = 0.328 and p = 0.196). This preliminary study suggests that BA may clearly be useful as a therapeutic agent in spinal fusion. However, further research is required to show the most effective dosage of BA on spinal fusion, and should indicate whether BA effects spinal fusion in the human body.

The Effects of Ketorolac Injected via Patient Controlled Analgesia Postoperatively on Spinal Fusion

PubMed Central

Park, Si-Young; Moon, Seong-Hwan; Park, Moon-Soo; Oh, Kyung-Soo

2005-01-01

Lumbar spinal fusions have been performed for spinal stability, pain relief and improved function in spinal stenosis, scoliosis, spinal fractures, infectious conditions and other lumbar spinal problems. The success of lumbar spinal fusion depends on multifactors, such as types of bone graft materials, levels and numbers of fusion, spinal instrumentation, electrical stimulation, smoking and some drugs such as nonsteroidal anti-inflammatory drugs (NSAIDs). From January 2000 to December 2001, 88 consecutive patients, who were diagnosed with spinal stenosis or spondylolisthesis, were retrospectively enrolled in this study. One surgeon performed all 88 posterolateral spinal fusions with instrumentation and autoiliac bone graft. The patients were divided into two groups. The first group (n=30) was infused with ketorolac and fentanyl intravenously via patient controlled analgesia (PCA) postoperatively and the second group (n=58) was infused only with fentanyl. The spinal fusion rates and clinical outcomes of the two groups were compared. The incidence of incomplete union or nonunion was much higher in the ketorolac group, and the relative risk was approximately 6 times higher than control group (odds ratio: 5.64). The clinical outcomes, which were checked at least 1 year after surgery, showed strong correlations with the spinal fusion status. The control group (93.1%) showed significantly better clinical results than the ketorolac group (77.6%). Smoking had no effect on the spinal fusion outcome in this study. Even though the use of ketorolac after spinal fusion can reduce the need for morphine, thereby decreasing morphine related complications, ketorolac used via PCA at the immediate postoperative state inhibits spinal fusion resulting in a poorer clinical outcome. Therefore, NSAIDs such as ketorolac, should be avoided after posterolateral spinal fusion. PMID:15861498

Pharmacokinetics and brain uptake of an IgG-TNF decoy receptor fusion protein following intravenous, intraperitoneal, and subcutaneous administration in mice.

PubMed

Sumbria, Rachita K; Zhou, Qing-Hui; Hui, Eric Ka-Wai; Lu, Jeff Zhiqiang; Boado, Ruben J; Pardridge, William M

2013-04-01

Tumor necrosis factor (TNF)-α is a proinflammatory cytokine active in the brain. Etanercept, the TNF decoy receptor (TNFR), does not cross the blood-brain barrier (BBB). The TNFR was re-engineered for BBB penetration as a fusion protein with a chimeric monoclonal antibody (mAb) against the mouse transferrin receptor (TfR), and this fusion protein is designated cTfRMAb-TNFR. The cTfRMAb domain of the fusion protein acts as a molecular Trojan horse and mediates transport via the endogenous BBB TfR. To support future chronic treatment of mouse models of neural disease with daily administration of the cTfRMAb-TNFR fusion protein, a series of pharmacokinetics and brain uptake studies in the mouse was performed. The cTfRMAb-TNFR fusion protein was radiolabeled and injected into mice via the intravenous, intraperitoneal (IP), or subcutaneous (SQ) routes of administration at doses ranging from 0.35 to 10 mg/kg. The distribution of the fusion protein into plasma following the IP or SQ routes was enhanced by increasing the injection dose from 3 to 10 mg/kg. The fusion protein demonstrated long circulation times with high metabolic stability following the IP or SQ routes of injection. The IP or SQ routes produced concentrations of the cTfRMAb-TNFR fusion protein in the brain that exceed by 20- to 50-fold the concentration of TNFα in pathologic conditions of the brain. The SQ injection is the preferred route of administration, as the level of cTfRMAb fusion protein produced in the brain is comparable to that generated with intravenous injection, and at a much lower plasma area under the concentration curve of the fusion protein as compared to IP administration.

High Cholesterol Obviates a Prolonged Hemifusion Intermediate in Fast SNARE-Mediated Membrane Fusion

PubMed Central

Kreutzberger, Alex J.B.; Kiessling, Volker; Tamm, Lukas K.

2015-01-01

Cholesterol is essential for exocytosis in secretory cells, but the exact molecular mechanism by which it facilitates exocytosis is largely unknown. Distinguishing contributions from the lateral organization and dynamics of membrane proteins to vesicle docking and fusion and the promotion of fusion pores by negative intrinsic spontaneous curvature and other mechanical effects of cholesterol have been elusive. To shed more light on this process, we examined the effect of cholesterol on SNARE-mediated membrane fusion in a single-vesicle assay that is capable of resolving docking and elementary steps of fusion with millisecond time resolution. The effect of cholesterol on fusion pore formation between synaptobrevin-2 (VAMP-2)-containing proteoliposomes and acceptor t-SNARE complex-containing planar supported bilayers was examined using both membrane and content fluorescent markers. This approach revealed that increasing cholesterol in either the t-SNARE or the v-SNARE membrane favors a mechanism of direct fusion pore opening, whereas low cholesterol favors a mechanism leading to a long-lived (>5 s) hemifusion state. The amount of cholesterol in the target membrane had no significant effect on docking of synaptobrevin vesicles. Comparative studies with α-tocopherol (vitamin E) show that the negative intrinsic spontaneous curvature of cholesterol and its presumed promotion of a very short-lived (<50 ms) lipid stalk intermediate is the main factor that favors rapid fusion pore opening at high cholesterol. This study also shows that this single-vesicle fusion assay can distinguish between hemifusion and full fusion with only a single lipid dye, thereby freeing up a fluorescence channel for the simultaneous measurement of another parameter in fast time-resolved fusion assays. PMID:26200867

Tumor necrosis factor-{alpha} enhanced fusions between oral squamous cell carcinoma cells and endothelial cells via VCAM-1/VLA-4 pathway

DOE Office of Scientific and Technical Information (OSTI.GOV)

Song, Kai; Zhu, Fei; Zhang, Han-zhong

Fusion between cancer cells and host cells, including endothelial cells, may strongly modulate the biological behavior of tumors. However, no one is sure about the driving factors and underlying mechanism involved in such fusion. We hypothesized in this study that inflammation, one of the main characteristics in tumor microenvironment, serves as a prominent catalyst for fusion events. Our results showed that oral cancer cells can fuse spontaneously with endothelial cells in co-culture and inflammatory cytokine tumor necrosis factor-{alpha} (TNF-{alpha}) increased fusion of human umbilical vein endothelium cells and oral cancer cells by up to 3-fold in vitro. Additionally, human oralmore » squamous cell carcinoma cell lines and 35 out of 50 (70%) oral squamous carcinoma specimens express VLA-4, an integrin, previously implicated in fusions between human peripheral blood CD34-positive cells and murine cardiomyocytes. Expression of VCAM-1, a ligand for VLA-4, was evident on vascular endothelium of oral squamous cell carcinoma. Moreover, immunocytochemistry and flow cytometry analysis revealed that expression of VCAM-1 increased obviously in TNF-{alpha}-stimulated endothelial cells. Anti-VLA-4 or anti-VCAM-1 treatment can decrease significantly cancer-endothelial adhesion and block such fusion. Collectively, our results suggested that TNF-{alpha} could enhance cancer-endothelial cell adhesion and fusion through VCAM-1/VLA-4 pathway. This study provides insights into regulatory mechanism of cancer-endothelial cell fusion, and has important implications for the development of novel therapeutic strategies for prevention of metastasis. -- Highlights: Black-Right-Pointing-Pointer Spontaneous oral cancer-endothelial cell fusion. Black-Right-Pointing-Pointer TNF-{alpha} enhanced cell fusions. Black-Right-Pointing-Pointer VCAM-1/VLA-4 expressed in oral cancer. Black-Right-Pointing-Pointer TNF-{alpha} increased expression of VCAM-1 on endothelial cells. Black-Right-Pointing-Pointer VCAM-1/VLA-4 mediated TNF-{alpha}-enhanced cell fusions.« less

The Relationship between Serum Vitamin D Levels and Spinal Fusion Success: A Quantitative Analysis

PubMed Central

Metzger, Melodie F.; Kanim, Linda E.; Zhao, Li; Robinson, Samuel T.; Delamarter, Rick B.

2015-01-01

Study Design An in vivo dosing study of vitamin D in a rat posterolateral spinal fusion model with autogenous bone grafting. Rats randomized to four levels of Vitamin D adjusted rat chow, longitudinal serum validation, surgeons/observers blinded to dietary conditions, and rats followed prospectively for fusion endpoint. Objective To assess the impact of dietary and serum levels of Vitamin D on fusion success, consolidation of fusion mass, and biomechanical stiffness after posterolateral spinal fusion procedure. Summary of Background Data Metabolic risk factors, including vitamin D insufficiency, are often overlooked by spine surgeons. Currently there are no published data on the causal effect of insufficient or deficient vitamin D levels on the success of establishing solid bony union after a spinal fusion procedure. Methods 50 rats were randomized to four experimentally controlled rat chow diets: normal control, vitamin D-deficient, vitamin-D insufficient, and a non-toxic high dose of vitamin D, four weeks prior to surgery and maintained post-surgery until sacrifice. Serum levels of 25(OH)D were determined at surgery and sacrifice using radioimmunoassay. Posterolateral fusion surgery with tail autograft was performed. Rats were sacrificed 12 weeks post-operatively and fusion was evaluated via manual palpation, high resolution radiographs, μCT, and biomechanical testing. Results Serum 25(OH)D and calcium levels were significantly correlated with vitamin-D adjusted chow (p<0.001). There was a dose dependent relationship between vitamin D adjusted chow and manual palpation fusion with greatest differences found in measures of radiographic density between high and deficient vitamin D (p<0.05). Adequate levels of vitamin D (high and normal control) yielded stiffer fusion than inadequate levels (insufficient and deficient) (p<0.05). Conclusions Manual palpation fusion rates increased with supplementation of dietary vitamin D. Biomechanical stiffness, bone volume and density were also positively-related to vitamin D, and calcium. PMID:25627287

Complications with axial presacral lumbar interbody fusion: A 5-year postmarketing surveillance experience

PubMed Central

Gundanna, Mukund I.; Miller, Larry E.; Block, Jon E.

2011-01-01

Background Open and minimally invasive lumbar fusion procedures have inherent procedural risks, with posterior and transforaminal approaches resulting in significant soft-tissue injury and the anterior approach endangering organs and major blood vessels. An alternative lumbar fusion technique uses a small paracoccygeal incision and a presacral approach to the L5-S1 intervertebral space, which avoids critical structures and may result in a favorable safety profile versus open and other minimally invasive fusion techniques. The purpose of this study was to evaluate complications associated with axial interbody lumbar fusion procedures using the Axial Lumbar Interbody Fusion (AxiaLIF) System (TranS1, Wilmington, North Carolina) in the postmarketing period. Methods Between March 2005 and March 2010, 9,152 patients underwent interbody fusion with the AxiaLIF System through an axial presacral approach. A single-level L5-S1 fusion was performed in 8,034 patients (88%), and a 2-level (L4-S1) fusion was used in 1,118 (12%). A predefined database was designed to record device- or procedure-related complaints via spontaneous reporting. The complications that were recorded included bowel injury, superficial wound and systemic infections, transient intraoperative hypotension, migration, subsidence, presacral hematoma, sacral fracture, vascular injury, nerve injury, and ureter injury. Results Complications were reported in 120 of 9,152 patients (1.3%). The most commonly reported complications were bowel injury (n = 59, 0.6%) and transient intraoperative hypotension (n = 20, 0.2%). The overall complication rate was similar between single-level (n = 102, 1.3%) and 2-level (n = 18, 1.6%) fusion procedures, with no significant differences noted for any single complication. Conclusions The 5-year postmarketing surveillance experience with the AxiaLIF System suggests that axial interbody lumbar fusion through the presacral approach is associated with a low incidence of complications. The overall complication rates observed in our evaluation compare favorably with those reported in trials of open and minimally invasive lumbar fusion surgery. PMID:25802673

Chemotropism and Cell Fusion in Neurospora crassa Relies on the Formation of Distinct Protein Complexes by HAM-5 and a Novel Protein HAM-14

PubMed Central

Jonkers, Wilfried; Fischer, Monika S.; Do, Hung P.; Starr, Trevor L.; Glass, N. Louise

2016-01-01

In filamentous fungi, communication is essential for the formation of an interconnected, multinucleate, syncytial network, which is constructed via hyphal fusion or fusion of germinated asexual spores (germlings). Anastomosis in filamentous fungi is comparable to other somatic cell fusion events resulting in syncytia, including myoblast fusion during muscle differentiation, macrophage fusion, and fusion of trophoblasts during placental development. In Neurospora crassa, fusion of genetically identical germlings is a highly dynamic and regulated process that requires components of a MAP kinase signal transduction pathway. The kinase pathway components (NRC-1, MEK-2 and MAK-2) and the scaffold protein HAM-5 are recruited to hyphae and germling tips undergoing chemotropic interactions. The MAK-2/HAM-5 protein complex shows dynamic oscillation to hyphae/germling tips during chemotropic interactions, and which is out-of-phase to the dynamic localization of SOFT, which is a scaffold protein for components of the cell wall integrity MAP kinase pathway. In this study, we functionally characterize HAM-5 by generating ham-5 truncation constructs and show that the N-terminal half of HAM-5 was essential for function. This region is required for MAK-2 and MEK-2 interaction and for correct cellular localization of HAM-5 to “fusion puncta.” The localization of HAM-5 to puncta was not perturbed in 21 different fusion mutants, nor did these puncta colocalize with components of the secretory pathway. We also identified HAM-14 as a novel member of the HAM-5/MAK-2 pathway by mining MAK-2 phosphoproteomics data. HAM-14 was essential for germling fusion, but not for hyphal fusion. Colocalization and coimmunoprecipitation data indicate that HAM-14 interacts with MAK-2 and MEK-2 and may be involved in recruiting MAK-2 (and MEK-2) to complexes containing HAM-5. PMID:27029735

Chemotropism and Cell Fusion in Neurospora crassa Relies on the Formation of Distinct Protein Complexes by HAM-5 and a Novel Protein HAM-14.

PubMed

Jonkers, Wilfried; Fischer, Monika S; Do, Hung P; Starr, Trevor L; Glass, N Louise

2016-05-01

In filamentous fungi, communication is essential for the formation of an interconnected, multinucleate, syncytial network, which is constructed via hyphal fusion or fusion of germinated asexual spores (germlings). Anastomosis in filamentous fungi is comparable to other somatic cell fusion events resulting in syncytia, including myoblast fusion during muscle differentiation, macrophage fusion, and fusion of trophoblasts during placental development. In Neurospora crassa, fusion of genetically identical germlings is a highly dynamic and regulated process that requires components of a MAP kinase signal transduction pathway. The kinase pathway components (NRC-1, MEK-2 and MAK-2) and the scaffold protein HAM-5 are recruited to hyphae and germling tips undergoing chemotropic interactions. The MAK-2/HAM-5 protein complex shows dynamic oscillation to hyphae/germling tips during chemotropic interactions, and which is out-of-phase to the dynamic localization of SOFT, which is a scaffold protein for components of the cell wall integrity MAP kinase pathway. In this study, we functionally characterize HAM-5 by generating ham-5 truncation constructs and show that the N-terminal half of HAM-5 was essential for function. This region is required for MAK-2 and MEK-2 interaction and for correct cellular localization of HAM-5 to "fusion puncta." The localization of HAM-5 to puncta was not perturbed in 21 different fusion mutants, nor did these puncta colocalize with components of the secretory pathway. We also identified HAM-14 as a novel member of the HAM-5/MAK-2 pathway by mining MAK-2 phosphoproteomics data. HAM-14 was essential for germling fusion, but not for hyphal fusion. Colocalization and coimmunoprecipitation data indicate that HAM-14 interacts with MAK-2 and MEK-2 and may be involved in recruiting MAK-2 (and MEK-2) to complexes containing HAM-5. Copyright © 2016 by the Genetics Society of America.

Surgical and Functional Outcomes After Multilevel Cervical Fusion for Degenerative Disc Disease Compared With Fusion for Radiculopathy: A Study of Workers' Compensation Population.

PubMed

Faour, Mhamad; Anderson, Joshua T; Haas, Arnold R; Percy, Rick; Woods, Stephen T; Ahn, Uri M; Ahn, Nicholas U

2017-05-01

Retrospective cohort comparative study. To evaluate presurgical and surgical factors that affect return to work (RTW) status after multilevel cervical fusion, and to compare outcomes after multilevel cervical fusion for degenerative disc disease (DDD) versus radiculopathy. Cervical fusion provides more than 90% of symptomatic relief for radiculopathy and myelopathy. However, cervical fusion for DDD without radiculopathy is considered controversial. In addition, multilevel fusion is associated with poorer surgical outcomes with increased levels fused. Data of cervical comorbidities was collected from Ohio Bureau of Workers' Compensation for subjects with work-related injuries. The study population included subjects who underwent multilevel cervical fusion. Patients with radiculopathy or DDD were identified. Multivariate logistic regression was performed to identify factors that affect RTW status. Surgical and functional outcomes were compared between groups. Stable RTW status within 3 years after multilevel cervical fusion was negatively affected by: fusion for DDD, age > 55 years, preoperative opioid use, initial psychological evaluation before surgery, injury-to-surgery > 2 years and instrumentation.DDD group had lower rate of achieving stable RTW status (P= 0.0001) and RTW within 1 year of surgery (P= 0.0003) compared with radiculopathy group. DDD patients were less likely to have a stable RTW status [odds ratio, OR = 0.63 (0.50-0.79)] or RTW within 1 year after surgery [OR = 0.65 (0.52-0.82)].DDD group had higher rate of opioid use (P= 0.001), and higher rate of disability after surgery (P= 0.002). Multiple detriments affect stable RTW status after multilevel cervical fusion including DDD. DDD without radiculopathy was associated with lower RTW rates, less likelihood to return to work, higher disability, and higher opioid use after surgery. Multilevel cervical fusion for DDD may be counterproductive. Future studies should investigate further treatment options of DDD, and optimize patient selection criteria for surgical intervention. 3.

Analysis of clinicopathological features of the echinoderm microtubule-associated protein-like-4-anaplastic lymphoma kinase fusion gene in Chinese patients with advanced non-small-cell lung cancer

PubMed Central

Liu, Yu-Tao; Shi, Yuan-Kai; Hao, Xue-Zhi; Wang, Lin; Li, Jun-Ling; Han, Xiao-Hong; Li, Dan; Zhou, Yu-Jie; Tang, Le

2014-01-01

Background The echinoderm microtubule-associated protein-like-4-anaplastic lymphoma kinase (EML4-ALK) fusion gene defines a novel molecular subset of non-small-cell lung cancer (NSCLC). However, the clinicopathological features of patients with the EML4-ALK fusion gene have not been defined completely. Methods Clinicopathological data of 200 Chinese patients with advanced NSCLC were analyzed retrospectively to explore their possible correlations with EML4-ALK fusions. Results The EML4-ALK fusion gene was detected in 56 (28.0%) of the 200 NSCLC patients, and undetected in 22 (11.0%) patients because of an insufficient amount of pathological tissue. The median age of the patients with positive and negative EML4-ALK was 48 and 55 years, respectively. Patients with the EML4-ALK fusion gene were significantly younger (P< 0.001). The detection rate of the EML4-ALK fusion gene in patients who received primary tumor or metastatic lymph node resection was significantly higher than in patients who received fine-needle biopsy (P= 0.003). The detection rate of the EML4-ALK fusion gene in patients with a time lag from obtainment of the pathological tissue to EML4-ALK fusion gene detection ≤48 months was significantly higher than in patients >48 months (P= 0.020). The occurrence of the EML4-ALK fusion gene in patients with wild-type epidermal growth factor receptor (EGFR) was significantly higher than in patients with mutant-type EGFR (42.5% [37/87] vs. 6.3% [1/16], P= 0.005). Conclusions Younger age and wild-type EGFR were identified as clinicopathological characteristics of patients with advanced NSCLC who harbored the EML4-ALK fusion gene. The optimal time lag from the obtainment of the pathological tissue to the time of EML4-ALK fusion gene detection is ≤48 months. PMID:26767009

Quantifying the kinetics and morphological changes of the fusion of spheroid building blocks.

PubMed

Susienka, Michael J; Wilks, Benjamin T; Morgan, Jeffrey R

2016-10-10

Tissue fusion, whereby two or more spheroids coalesce, is a process that is fundamental to biofabrication. We have designed a quantitative, high-throughput platform to investigate the fusion of multicellular spheroids using agarose micro-molds. Spheroids of primary human chondrocytes (HCH) or human breast cancer cells (MCF-7) were self-assembled for 24 h and then brought together to form an array comprised of two spheroids (one doublet) per well. To quantify spheroid fusogenicity, we developed two assays: (1) an initial tack assay, defined as the minimum amount of time for two spheroids to form a mechanically stable tissue complex or doublet, and (2) a fusion assay, in which we defined and tracked key morphological parameters of the doublets as a function of time using wide-field fluorescence microscopy over a 24 h time-lapse. The initial tack of spheroid fusion was measured by inverting the micro-molds and centrifuging doublets at various time points to assess their connectedness. We found that the initial tack between two spheroids forms rapidly, with the majority of doublets remaining intact after centrifugation following just 30 min of fusion. Over the course of 24 h of fusion, several morphological changes occurred, which were quantified using a custom image analysis pipeline. End-to-end doublet lengths decreased over time, doublet widths decreased for chondrocytes and increased for MCF-7, contact lengths increased over time, and chondrocyte doublets exhibited higher intersphere angles at the end of fusion. We also assessed fusion by measuring the fluorescence intensity at the plane of fusion, which increased over time for both cell types. Interestingly, we observed that doublets moved and rotated in the micro-wells during fusion and this rotation was inhibited by ROCK inhibitor Y-27632 and myosin II inhibitor blebbistatin. Understanding and optimizing tissue fusion is essential for creating larger tissues, organs, or other structures using individual microtissues as building parts.

A dual-channel fusion system of visual and infrared images based on color transfer

NASA Astrophysics Data System (ADS)

Pei, Chuang; Jiang, Xiao-yu; Zhang, Peng-wei; Liang, Hao-cong

2013-09-01

A dual-channel fusion system of visual and infrared images based on color transfer The increasing availability and deployment of imaging sensors operating in multiple spectrums has led to a large research effort in image fusion, resulting in a plethora of pixel-level image fusion algorithms. However, most of these algorithms have gray or false color fusion results which are not adapt to human vision. Transfer color from a day-time reference image to get natural color fusion result is an effective way to solve this problem, but the computation cost of color transfer is expensive and can't meet the request of real-time image processing. We developed a dual-channel infrared and visual images fusion system based on TMS320DM642 digital signal processing chip. The system is divided into image acquisition and registration unit, image fusion processing unit, system control unit and image fusion result out-put unit. The image registration of dual-channel images is realized by combining hardware and software methods in the system. False color image fusion algorithm in RGB color space is used to get R-G fused image, then the system chooses a reference image to transfer color to the fusion result. A color lookup table based on statistical properties of images is proposed to solve the complexity computation problem in color transfer. The mapping calculation between the standard lookup table and the improved color lookup table is simple and only once for a fixed scene. The real-time fusion and natural colorization of infrared and visual images are realized by this system. The experimental result shows that the color-transferred images have a natural color perception to human eyes, and can highlight the targets effectively with clear background details. Human observers with this system will be able to interpret the image better and faster, thereby improving situational awareness and reducing target detection time.

Effect of Dietary Calcium on Spinal Bone Fusion in an Ovariectomized Rat Model

PubMed Central

Cho, Jae-Hoon; Cho, Dae-Chul; Yu, Song-Hee; Jeon, Young-Hoon; Sung, Joo-Kyung

2012-01-01

Objective To evaluate the effect of calcium supplementation on spinal bone fusion in ovariectomized (OVX) rats. Methods Sixteen female Sprague Dawley rats underwent bilateral ovariectomy at 12 weeks of age to induce osteoporosis and were randomly assigned to two groups : control group (n=8) and calcium-supplemented group (OVX-Ca, n=8). Autologous spinal bone fusion surgery was performed on both groups 8 weeks later. After fusion surgery, the OVX-Ca group was supplemented with calcium in drinking water for 8 weeks. Blood was obtained 4 and 8 weeks after fusion surgery. Eight weeks after fusion surgery, the rats were euthanized and the L4-5 spine removed. Bone fusion status and fusion volume were evaluated by manual palpation and three-dimensional computed tomography. Results The mean fusion volume in the L4-5 spine was significantly greater in the OVX-Ca group (71.80±8.06 mm3) than in controls (35.34±8.24 mm3) (p<0.01). The level of osteocalcin, a bone formation marker, was higher in OVX-Ca rats than in controls 4 weeks (610.08±10.41 vs. 551.61±12.34 ng/mL) and 8 weeks (552.05±19.67 vs. 502.98±22.76 ng/mL) after fusion surgery (p<0.05). The level of C-terminal telopeptide fragment of type I collagen, a bone resorption marker, was significantly lower in OVX-Ca rats than in controls 4 weeks (77.07±12.57 vs. 101.75±7.20 ng/mL) and 8 weeks (69.58±2.45 vs. 77.15±4.10 ng/mL) after fusion surgery (p<0.05). A mechanical strength test showed that the L4-5 vertebrae in the OVX-Ca group withstood a 50% higher maximal load compared with the controls (p<0.01). Conclusion Dietary calcium given to OVX rats after lumbar fusion surgery improved fusion volume and mechanical strength in an ovariectomized rat model. PMID:23133713

Matched Comparison of Fusion Rates between Hydroxyapatite Demineralized Bone Matrix and Autograft in Lumbar Interbody Fusion.

PubMed

Kim, Dae Hwan; Lee, Nam; Shin, Dong Ah; Yi, Seong; Kim, Keung Nyun; Ha, Yoon

2016-07-01

To compare the fusion rate of a hydroxyapatite demineralized bone matrix (DBM) with post-laminectomy acquired autograft in lumbar interbody fusion surgery and to evaluate the correlation between fusion rate and clinical outcome. From January 2013 to April 2014, 98 patients underwent lumbar interbody fusion surgery with hydroxyapatite DBM (HA-DBM group) in our institute. Of those patients, 65 received complete CT scans for 12 months postoperatively in order to evaluate fusion status. For comparison with autograft, we selected another 65 patients who underwent lumbar interbody fusion surgery with post-laminectomy acquired autograft (Autograft group) during the same period. Both fusion material groups were matched in terms of age, sex, body mass index (BMI), and bone mineral density (BMD). To evaluate the clinical outcomes, we analyzed the results of visual analogue scale (VAS), Oswestry Disability Index (ODI), and Short Form Health Survey (SF-36). We reviewed the CT scans of 149 fusion levels in 130 patients (HA-DBM group, 75 levels/65 patients; Autograft group, 74 levels/65 patients). Age, sex, BMI, and BMD were not significantly different between the groups (p=0.528, p=0.848, p=0.527, and p=0.610, respectively). The HA-DBM group showed 39 of 75 fused levels (52%), and the Autograft group showed 46 of 74 fused levels (62.2%). This difference was not statistically significant (p=0.21). In the HA-DBM group, older age and low BMD were significantly associated with non-fusion (61.24 vs. 66.68, p=0.027; -1.63 vs. -2.29, p=0.015, respectively). VAS and ODI showed significant improvement after surgery when fusion was successfully achieved in both groups (p=0.004, p=0.002, HA-DBM group; p=0.012, p=0.03, Autograft group). The fusion rates of the hydroxyapatite DBM and Autograft groups were not significantly different. In addition, clinical outcomes were similar between the groups. However, older age and low BMD are risk factors that might induce non-union after surgery with hydroxyapatite DBM.

Safety and Environment aspects of Tokamak- type Fusion Power Reactor- An Overview

NASA Astrophysics Data System (ADS)

Doshi, Bharat; Reddy, D. Chenna

2017-04-01

Naturally occurring thermonuclear fusion reaction (of light atoms to form a heavier nucleus) in the sun and every star in the universe, releases incredible amounts of energy. Demonstrating the controlled and sustained reaction of deuterium-tritium plasma should enable the development of fusion as an energy source here on Earth. The promising fusion power reactors could be operated on the deuterium-tritium fuel cycle with fuel self-sufficiency. The potential impact of fusion power on the environment and the possible risks associated with operating large-scale fusion power plants is being studied by different countries. The results show that fusion can be a very safe and sustainable energy source. A fusion power plant possesses not only intrinsic advantages with respect to safety compared to other sources of energy, but also a negligible long term impact on the environment provided certain precautions are taken in its design. One of the important considerations is in the selection of low activation structural materials for reactor vessel. Selection of the materials for first wall and breeding blanket components is also important from safety issues. It is possible to fully benefit from the advantages of fusion energy if safety and environmental concerns are taken into account when considering the conceptual studies of a reactor design. The significant safety hazards are due to the tritium inventory and energetic neutron fluence induced activity in the reactor vessel, first wall components, blanket system etc. The potential of release of radioactivity under operational and accident conditions needs attention while designing the fusion reactor. Appropriate safety analysis for the quantification of the risk shall be done following different methods such as FFMEA (Functional Failure Modes and Effects Analysis) and HAZOP (Hazards and operability). Level of safety and safety classification such as nuclear safety and non-nuclear safety is very important for the FPR (Fusion Power Reactor). This paper describes an overview of safety and environmental merits of fusion power reactor, issues and design considerations and need for R&D on safety and environmental aspects of Tokamak type fusion reactor.

Ultrasound fusion image error correction using subject-specific liver motion model and automatic image registration.

PubMed

Yang, Minglei; Ding, Hui; Zhu, Lei; Wang, Guangzhi

2016-12-01

Ultrasound fusion imaging is an emerging tool and benefits a variety of clinical applications, such as image-guided diagnosis and treatment of hepatocellular carcinoma and unresectable liver metastases. However, respiratory liver motion-induced misalignment of multimodal images (i.e., fusion error) compromises the effectiveness and practicability of this method. The purpose of this paper is to develop a subject-specific liver motion model and automatic registration-based method to correct the fusion error. An online-built subject-specific motion model and automatic image registration method for 2D ultrasound-3D magnetic resonance (MR) images were combined to compensate for the respiratory liver motion. The key steps included: 1) Build a subject-specific liver motion model for current subject online and perform the initial registration of pre-acquired 3D MR and intra-operative ultrasound images; 2) During fusion imaging, compensate for liver motion first using the motion model, and then using an automatic registration method to further correct the respiratory fusion error. Evaluation experiments were conducted on liver phantom and five subjects. In the phantom study, the fusion error (superior-inferior axis) was reduced from 13.90±2.38mm to 4.26±0.78mm by using the motion model only. The fusion error further decreased to 0.63±0.53mm by using the registration method. The registration method also decreased the rotation error from 7.06±0.21° to 1.18±0.66°. In the clinical study, the fusion error was reduced from 12.90±9.58mm to 6.12±2.90mm by using the motion model alone. Moreover, the fusion error decreased to 1.96±0.33mm by using the registration method. The proposed method can effectively correct the respiration-induced fusion error to improve the fusion image quality. This method can also reduce the error correction dependency on the initial registration of ultrasound and MR images. Overall, the proposed method can improve the clinical practicability of ultrasound fusion imaging. Copyright © 2016 Elsevier Ltd. All rights reserved.

Matched Comparison of Fusion Rates between Hydroxyapatite Demineralized Bone Matrix and Autograft in Lumbar Interbody Fusion

PubMed Central

Kim, Dae Hwan; Lee, Nam; Shin, Dong Ah; Yi, Seong; Kim, Keung Nyun

2016-01-01

Objective To compare the fusion rate of a hydroxyapatite demineralized bone matrix (DBM) with post-laminectomy acquired autograft in lumbar interbody fusion surgery and to evaluate the correlation between fusion rate and clinical outcome. Methods From January 2013 to April 2014, 98 patients underwent lumbar interbody fusion surgery with hydroxyapatite DBM (HA-DBM group) in our institute. Of those patients, 65 received complete CT scans for 12 months postoperatively in order to evaluate fusion status. For comparison with autograft, we selected another 65 patients who underwent lumbar interbody fusion surgery with post-laminectomy acquired autograft (Autograft group) during the same period. Both fusion material groups were matched in terms of age, sex, body mass index (BMI), and bone mineral density (BMD). To evaluate the clinical outcomes, we analyzed the results of visual analogue scale (VAS), Oswestry Disability Index (ODI), and Short Form Health Survey (SF-36). Results We reviewed the CT scans of 149 fusion levels in 130 patients (HA-DBM group, 75 levels/65 patients; Autograft group, 74 levels/65 patients). Age, sex, BMI, and BMD were not significantly different between the groups (p=0.528, p=0.848, p=0.527, and p=0.610, respectively). The HA-DBM group showed 39 of 75 fused levels (52%), and the Autograft group showed 46 of 74 fused levels (62.2%). This difference was not statistically significant (p=0.21). In the HA-DBM group, older age and low BMD were significantly associated with non-fusion (61.24 vs. 66.68, p=0.027; -1.63 vs. -2.29, p=0.015, respectively). VAS and ODI showed significant improvement after surgery when fusion was successfully achieved in both groups (p=0.004, p=0.002, HA-DBM group; p=0.012, p=0.03, Autograft group). Conclusion The fusion rates of the hydroxyapatite DBM and Autograft groups were not significantly different. In addition, clinical outcomes were similar between the groups. However, older age and low BMD are risk factors that might induce non-union after surgery with hydroxyapatite DBM. PMID:27446517

The importance of proximal fusion level selection for outcomes of multi-level lumbar posterolateral fusion.

PubMed

Nam, Woo Dong; Cho, Jae Hwan

2015-03-01

There are few studies about risk factors for poor outcomes from multi-level lumbar posterolateral fusion limited to three or four level lumbar posterolateral fusions. The purpose of this study was to analyze the outcomes of multi-level lumbar posterolateral fusion and to search for possible risk factors for poor surgical outcomes. We retrospectively analyzed 37 consecutive patients who underwent multi-level lumbar or lumbosacral posterolateral fusion with posterior instrumentation. The outcomes were deemed either 'good' or 'bad' based on clinical and radiological results. Many demographic and radiological factors were analyzed to examine potential risk factors for poor outcomes. Student t-test, Fisher exact test, and the chi-square test were used based on the nature of the variables. Multiple logistic regression analysis was used to exclude confounding factors. Twenty cases showed a good outcome (group A, 54.1%) and 17 cases showed a bad outcome (group B, 45.9%). The overall fusion rate was 70.3%. The revision procedures (group A: 1/20, 5.0%; group B: 4/17, 23.5%), proximal fusion to L2 (group A: 5/20, 25.0%; group B: 10/17, 58.8%), and severity of stenosis (group A: 12/19, 63.3%; group B: 3/11, 27.3%) were adopted as possible related factors to the outcome in univariate analysis. Multiple logistic regression analysis revealed that only the proximal fusion level (superior instrumented vertebra, SIV) was a significant risk factor. The cases in which SIV was L2 showed inferior outcomes than those in which SIV was L3. The odds ratio was 6.562 (95% confidence interval, 1.259 to 34.203). The overall outcome of multi-level lumbar or lumbosacral posterolateral fusion was not as high as we had hoped it would be. Whether the SIV was L2 or L3 was the only significant risk factor identified for poor outcomes in multi-level lumbar or lumbosacral posterolateral fusion in the current study. Thus, the authors recommend that proximal fusion levels be carefully determined when multi-level lumbar fusions are considered.

The Importance of Proximal Fusion Level Selection for Outcomes of Multi-Level Lumbar Posterolateral Fusion

PubMed Central

Nam, Woo Dong

2015-01-01

Background There are few studies about risk factors for poor outcomes from multi-level lumbar posterolateral fusion limited to three or four level lumbar posterolateral fusions. The purpose of this study was to analyze the outcomes of multi-level lumbar posterolateral fusion and to search for possible risk factors for poor surgical outcomes. Methods We retrospectively analyzed 37 consecutive patients who underwent multi-level lumbar or lumbosacral posterolateral fusion with posterior instrumentation. The outcomes were deemed either 'good' or 'bad' based on clinical and radiological results. Many demographic and radiological factors were analyzed to examine potential risk factors for poor outcomes. Student t-test, Fisher exact test, and the chi-square test were used based on the nature of the variables. Multiple logistic regression analysis was used to exclude confounding factors. Results Twenty cases showed a good outcome (group A, 54.1%) and 17 cases showed a bad outcome (group B, 45.9%). The overall fusion rate was 70.3%. The revision procedures (group A: 1/20, 5.0%; group B: 4/17, 23.5%), proximal fusion to L2 (group A: 5/20, 25.0%; group B: 10/17, 58.8%), and severity of stenosis (group A: 12/19, 63.3%; group B: 3/11, 27.3%) were adopted as possible related factors to the outcome in univariate analysis. Multiple logistic regression analysis revealed that only the proximal fusion level (superior instrumented vertebra, SIV) was a significant risk factor. The cases in which SIV was L2 showed inferior outcomes than those in which SIV was L3. The odds ratio was 6.562 (95% confidence interval, 1.259 to 34.203). Conclusions The overall outcome of multi-level lumbar or lumbosacral posterolateral fusion was not as high as we had hoped it would be. Whether the SIV was L2 or L3 was the only significant risk factor identified for poor outcomes in multi-level lumbar or lumbosacral posterolateral fusion in the current study. Thus, the authors recommend that proximal fusion levels be carefully determined when multi-level lumbar fusions are considered. PMID:25729522

The impact of preoperative epidural injections on postoperative infection in lumbar fusion surgery.

PubMed

Singla, Anuj; Yang, Scott; Werner, Brian C; Cancienne, Jourdan M; Nourbakhsh, Ali; Shimer, Adam L; Hassanzadeh, Hamid; Shen, Francis H

2017-05-01

OBJECTIVE Lumbar epidural steroid injections (LESIs) are performed for both diagnostic and therapeutic purposes for a variety of indications, including low-back pain, the leading cause of disability and expense due to work-related conditions in the US. The steroid agent used in epidural injections is reported to relieve nerve root inflammation, local ischemia, and resultant pain, but the injection may also have an adverse impact on spinal surgery performed thereafter. In particular, the possibility that preoperative epidural injections may increase the risk of surgical site infection after lumbar spinal fusion has been reported but has not been studied in detail. The goal of the present study was to use a large national insurance database to analyze the association of preoperative LESIs with surgical site infection after lumbar spinal fusion. METHODS A nationwide insurance database of patient records was used for this retrospective analysis. Current Procedural Terminology codes were used to query the database for patients who had undergone LESI and 1- or 2-level lumbar posterior spinal fusion procedures. The rate of postoperative infection after 1- or 2-level posterior spinal fusion was analyzed. These study patients were then divided into 3 separate cohorts: 1) lumbar spinal fusion performed within 1 month after LESI, 2) fusion performed between 1 and 3 months after LESI, and 3) fusion performed between 3 and 6 months after LESI. The study patients were compared with a control cohort of patients who underwent lumbar fusion without previous LESI. RESULTS The overall 3-month infection rate after lumbar spinal fusion procedure was 1.6% (1411 of 88,540 patients). The infection risk increased in patients who received LESI within 1 month (OR 2.6, p < 0.0001) or 1-3 months (OR 1.4, p = 0.0002) prior to surgery compared with controls. The infection risk was not significantly different from controls in patients who underwent lumbar fusion more than 3 months after LESI. CONCLUSIONS Lumbar spinal fusion performed within 3 months after LESI may be associated with an increased rate of postoperative infection. This association was not found when lumbar fusion was performed more than 3 months after LESI.

Enhanced bactericidal potency of nanoliposomes by modification of the fusion activity between liposomes and bacterium.

PubMed

Ma, Yufan; Wang, Zhao; Zhao, Wen; Lu, Tingli; Wang, Rutao; Mei, Qibing; Chen, Tao

2013-01-01

Pseudomonas aeruginosa represents a good model of antibiotic resistance. These organisms have an outer membrane with a low level of permeability to drugs that is often combined with multidrug efflux pumps, enzymatic inactivation of the drug, or alteration of its molecular target. The acute and growing problem of antibiotic resistance of Pseudomonas to conventional antibiotics made it imperative to develop new liposome formulations to overcome these mechanisms, and investigate the fusion between liposome and bacterium. The rigidity, stability and charge properties of phospholipid vesicles were modified by varying the cholesterol, 1,2-dioleoyl-sn-glycero-3-phosphatidylethanolamine (DOPE), and negatively charged lipids 1,2-dimyristoyl-sn-glycero-3-phosphoglycerol sodium salt (DMPG), 1,2-dimyristoyl-sn-glycero-3-phopho-L-serine sodium salt (DMPS), 1,2-dimyristoyl-sn-glycero-3-phosphate monosodium salt (DMPA), nature phosphatidylserine sodium salt from brain and nature phosphatidylinositol sodium salt from soybean concentrations in liposomes. Liposomal fusion with intact bacteria was monitored using a lipid-mixing assay. It was discovered that the fluid liposomes-bacterium fusion is not dependent on liposomal size and lamellarity. A similar degree of fusion was observed for liposomes with a particle size from 100 to 800 nm. The fluidity of liposomes is an essential pre-request for liposomes fusion with bacteria. Fusion was almost completely inhibited by incorporation of cholesterol into fluid liposomes. The increase in the amount of negative charges in fluid liposomes reduces fluid liposomes-bacteria fusion when tested without calcium cations due to electric repulsion, but addition of calcium cations brings the fusion level of fluid liposomes to similar or higher levels. Among the negative phospholipids examined, DMPA gave the highest degree of fusion, DMPS and DMPG had intermediate fusion levels, and PI resulted in the lowest degree of fusion. Furthermore, the fluid liposomal encapsulated tobramycin was prepared, and the bactericidal effect occurred more quickly when bacteria were cultured with liposomal encapsulated tobramycin. The bactericidal potency of fluid liposomes is dramatically enhanced with respect to fusion ability when the fusogenic lipid, DOPE, is included. Regardless of changes in liposome composition, fluid liposomes-bacterium fusion is universally enhanced by calcium ions. The information obtained in this study will increase our understanding of fluid liposomal action mechanisms, and help in optimizing the new generation of fluid liposomal formulations for the treatment of pulmonary bacterial infections.

CONFERENCE REPORT: Summary of the 8th IAEA Technical Meeting on Fusion Power Plant Safety

NASA Astrophysics Data System (ADS)

Girard, J. Ph.; Gulden, W.; Kolbasov, B.; Louzeiro-Malaquias, A.-J.; Petti, D.; Rodriguez-Rodrigo, L.

2008-01-01

Reports were presented covering a selection of topics on the safety of fusion power plants. These included a review on licensing studies developed for ITER site preparation surveying common and non-common issues (i.e. site dependent) as lessons to a broader approach for fusion power plant safety. Several fusion power plant models, spanning from accessible technology to more advanced-materials based concepts, were discussed. On the topic related to fusion-specific technology, safety studies were reported on different concepts of breeding blanket modules, tritium handling and auxiliary systems under normal and accident scenarios' operation. The testing of power plant relevant technology in ITER was also assessed in terms of normal operation and accident scenarios, and occupational doses and radioactive releases under these testings have been determined. Other specific safety issues for fusion have also been discussed such as availability and reliability of fusion power plants, dust and tritium inventories and component failure databases. This study reveals that the environmental impact of fusion power plants can be minimized through a proper selection of low activation materials and using recycling technology helping to reduce waste volume and potentially open the route for its reutilization for the nuclear sector or even its clearance into the commercial circuit. Computational codes for fusion safety have been presented in support of the many studies reported. The on-going work on establishing validation approaches aiming at improving the prediction capability of fusion codes has been supported by experimental results and new directions for development have been identified. Fusion standards are not available and fission experience is mostly used as the framework basis for licensing and target design for safe operation and occupational and environmental constraints. It has been argued that fusion can benefit if a specific fusion approach is implemented, in particular for materials selection which will have a large impact on waste disposal and recycling and in the real limits of radiation releases if indexed to the real impact on individuals and the environment given the differences in the types of radiation emitted by tritium when compared with the fission products. Round table sessions resulted in some common recommendations. The discussions also created the awareness of the need for a larger involvement of the IAEA in support of fusion safety standards development.

Enhanced bactericidal potency of nanoliposomes by modification of the fusion activity between liposomes and bacterium

PubMed Central

Ma, Yufan; Wang, Zhao; Zhao, Wen; Lu, Tingli; Wang, Rutao; Mei, Qibing; Chen, Tao

2013-01-01

Background Pseudomonas aeruginosa represents a good model of antibiotic resistance. These organisms have an outer membrane with a low level of permeability to drugs that is often combined with multidrug efflux pumps, enzymatic inactivation of the drug, or alteration of its molecular target. The acute and growing problem of antibiotic resistance of Pseudomonas to conventional antibiotics made it imperative to develop new liposome formulations to overcome these mechanisms, and investigate the fusion between liposome and bacterium. Methods The rigidity, stability and charge properties of phospholipid vesicles were modified by varying the cholesterol, 1,2-dioleoyl-sn-glycero-3-phosphatidylethanolamine (DOPE), and negatively charged lipids 1,2-dimyristoyl-sn-glycero-3-phosphoglycerol sodium salt (DMPG), 1,2-dimyristoyl-sn-glycero-3-phopho-L-serine sodium salt (DMPS), 1,2-dimyristoyl-sn-glycero-3-phosphate monosodium salt (DMPA), nature phosphatidylserine sodium salt from brain and nature phosphatidylinositol sodium salt from soybean concentrations in liposomes. Liposomal fusion with intact bacteria was monitored using a lipid-mixing assay. Results It was discovered that the fluid liposomes-bacterium fusion is not dependent on liposomal size and lamellarity. A similar degree of fusion was observed for liposomes with a particle size from 100 to 800 nm. The fluidity of liposomes is an essential pre-request for liposomes fusion with bacteria. Fusion was almost completely inhibited by incorporation of cholesterol into fluid liposomes. The increase in the amount of negative charges in fluid liposomes reduces fluid liposomes-bacteria fusion when tested without calcium cations due to electric repulsion, but addition of calcium cations brings the fusion level of fluid liposomes to similar or higher levels. Among the negative phospholipids examined, DMPA gave the highest degree of fusion, DMPS and DMPG had intermediate fusion levels, and PI resulted in the lowest degree of fusion. Furthermore, the fluid liposomal encapsulated tobramycin was prepared, and the bactericidal effect occurred more quickly when bacteria were cultured with liposomal encapsulated tobramycin. Conclusion The bactericidal potency of fluid liposomes is dramatically enhanced with respect to fusion ability when the fusogenic lipid, DOPE, is included. Regardless of changes in liposome composition, fluid liposomes-bacterium fusion is universally enhanced by calcium ions. The information obtained in this study will increase our understanding of fluid liposomal action mechanisms, and help in optimizing the new generation of fluid liposomal formulations for the treatment of pulmonary bacterial infections. PMID:23847417

Comparison of a Novel Oxysterol Molecule and rhBMP2 Fusion Rates in a Rabbit Posterolateral Lumbar Spine Model

PubMed Central

Scott, Trevor P.; Phan, Kevin H.; Tian, Haijun; Suzuki, Akinobu; Montgomery, Scott R.; Johnson, Jared S.; Atti, Elisa; Tetratis, Sotirios; Pereira, Renata C.; Wang, Jeffrey C.; Daubs, Michael D.; Stappenbeck, Frank; Parhami, Farhad

2015-01-01

Background Context The non-union rate following lumbar spinal fusion is as high as 25%. Bone morphogenetic protein-2 (rhBMP2) has been used as a biological adjunct to promote bony fusion. However, recently there have been concerns about BMP2. Oxysterol 133 (Oxy133) has been shown to promote excellent fusion rates in rodent lumbar spine models and offers a potential alternative to rhBMP2. Purpose The purpose of this study was to compare the fusion rate of rhBMP2 and Oxy133 in a randomized controlled trial using a posterolateral lumbar rabbit spinal fusion model. Study Design This was a randomized control animal study. Methods Twenty-four male adult white New Zealand rabbits (3–3.5kg) underwent bilateral posterolateral lumbar spinal fusion at L4–L5. Rabbits were divided into 4 groups: control (A), 30 µg rhBMP2 (B), 20 mg Oxy133 (C), and 60 mg Oxy133 (D). At 4 weeks, fusion was evaluated by fluoroscopy, and at 8 weeks the rabbits were sacrificed and fusion was evaluated radiographically, by manual palpation, and with microCT. Dr. Parhami is a founder and Dr. Stappenbeck is the Director of Chemistry at MAX BioPharma, which has licensed the rights to Oxy133 from UCLA, both have financial interests in the technology presented here. UCLA holds equity in MAX BioPharma. All other authors have no conflicts of interest. Studies reported here were supported in part by the NIH/NIAMS grant RO1AR059794 and in part by MAX BioPharma that purchased the rabbits and provided Oxy133. Results Fusion rates by radiographic analysis at 8 weeks were: group A 40.0%, group B 91.7%, group C 91.7%, and group D 100%. Evaluation of fusion masses by manual palpation of excised spines after sacrifice showed the following fusion rates: group A 0%, group B 83.3%, group C 83.3%, and group D 90%. MicroCT scanning confirmed these findings. Conclusions These findings in a rabbit model demonstrate that both 20 mg dose and 60 mg dose Oxy133 promote fusion that is equivalent to fusion induced by 30 µg rhBMP2 and significantly greater than the control group. The present findings confirm that Oxy133 is a promising candidate for therapeutic development as an alternative to rhBMP2 to promote spinal fusion. PMID:25450659

The efficacy of routine use of recombinant human bone morphogenetic protein-2 in occipitocervical and atlantoaxial fusions of the pediatric spine: a minimum of 12 months' follow-up with computed tomography.

PubMed

Sayama, Christina; Hadley, Caroline; Monaco, Gina N; Sen, Anish; Brayton, Alison; Briceño, Valentina; Tran, Brandon H; Ryan, Sheila L; Luerssen, Thomas G; Fulkerson, Daniel; Jea, Andrew

2015-07-01

OBJECT The purpose of this study focusing on fusion rate was to determine the efficacy of recombinant human bone morphogenetic protein-2 (rhBMP-2) use in posterior instrumented fusions of the craniocervical junction in the pediatric population. The authors previously reported the short-term (mean follow-up 11 months) safety and efficacy of rhBMP-2 use in the pediatric age group. The present study reports on their long-term results (minimum of 12 months' follow-up) and focuses on efficacy. METHODS The authors performed a retrospective review of 83 consecutive pediatric patients who had undergone posterior occipitocervical or atlantoaxial spine fusion at Texas Children's Hospital or Riley Children's Hospital during the period from October 2007 to October 2012. Forty-nine patients were excluded from further analysis because of death, loss to follow-up, or lack of CT evaluation of fusion at 12 or more months after surgery. Fusion was determined by postoperative CT scan at a minimum of 12 months after surgery. The fusion was graded and classified by a board-certified fellowship-trained pediatric neuroradiologist. Other factors, such as patient age, diagnosis, number of vertebral levels fused, use of allograft or autograft, dosage of bone morphogenetic protein (BMP), and use of postoperative orthosis, were recorded. RESULTS Thirty-four patients had a CT scan at least 12 months after surgery. The average age of the patients at surgery was 8 years, 1 month (range 10 months-17 years). The mean follow-up was 27.7 months (range 12-81 months). There were 37 fusion procedures in 34 patients. Solid fusion (CT Grade 4 or 4-) was achieved in 89.2% of attempts (33 of 37), while incomplete fusion or failure of fusion was seen in 10.8%. Based on logistic regression analysis, there was no significant association between solid fusion and age, sex, BMP dose, type of graft material, use of postoperative orthosis, or number of levels fused. Three of 34 patients (8.8%) required revision surgery. CONCLUSIONS Despite the large number of adult studies reporting positive effects of BMP on bone fusion, our long-term outcomes using rhBMP-2 in the pediatric population suggest that rates of fusion failure are higher than observed in contemporary adult and pediatric reports of occipitocervical and atlantoaxial spine fusions.