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

Calculation of Formation and Decay of Heavy Compound Nuclei

NASA Astrophysics Data System (ADS)

Cherepanov, E. A.

2001-04-01

The report describes a method for calculating fusion and decay probabilities in reactions leading to the production of transfermium elements. The competition between quasi-fission and fussion is described on the basis of the Dinuclear System Concept (DNSC). The both competition between fusion and quasi-fission and statistical decay of heavy highly fissionable excited compound nuclei is described in an approach based on the Monte-Carlo method.

Systematic analysis of hot Yb* isotopes using the energy density formalism

NASA Astrophysics Data System (ADS)

Jain, Deepika; Sharma, Manoj K.; Rajni; Kumar, Raj; Gupta, Raj K.

2014-10-01

A systematic study of the spin-orbit density interaction potential is carried out, with spherical as well as deformed choices of nuclei, for a variety of near-symmetric and asymmetric colliding nuclei leading to various isotopes of the compound nucleus Yb*, using the semiclassical extended Thomas-Fermi formulation (ETF) of the Skyrme energy density formalism (SEDF). We observe that the spin-orbit density interaction barrier height ( and barrier position ( increase systematically with the increase in number of neutrons in both the projectile and target, for spherical systems. On allowing deformation effects with optimum orientations, the barrier-height increases by a large order of magnitude, as compared to the spherical case, in going from 156Yb* to 172Yb* nuclear systems formed via near-symmetric Ni+Mo or asymmetric O+Sm colliding nuclei, except that for the oblate-shaped nuclei, the is the highest and shifts towards a smaller (compact) interaction radius. The temperature does not change the behavior of spin-orbit density dependent ( and independent ( interaction potentials, except for some minor changes in the magnitude. The orientation degree of freedom also plays an important role in modifying the barrier characteristics and hence produces a large effect on the fusion cross section. The fusion excitation function of the compound nuclei 160, 164Yb* formed in different incoming channels, show clearly that the new forces GSkI and KDE0v1 respond better than the old SIII force. Among the first two, KDE0v1 seems to perform better. The fusion cross-sections are also predicted for a few other isotopes of Yb*.

Investigations on the system boron-carbon silicon

NASA Technical Reports Server (NTRS)

Kieffer, R.; Gugel, E.; Leimer, G.; Ettmayer, P.

1983-01-01

The above elements form with each other binary compounds which are very interesting from the point of view of their structure and their chemistry and which are important for technology. The present investigation is concerned with the three-component system and the behavior of the binary compounds occurring in it. Investigations employing various techniques, such as X-ray, chemical analysis, microscopy and fusion experiments showed that no ternary phase exists within the boundary of the ternary system. There is no compound with a higher abrasion capacity than boron carbide. The probable phase field divisions at two isothermic intersections and the fusion isotherms are indicated.

Strategies for enhancing bioluminescent bacterial sensor performance by promoter region manipulation

PubMed Central

Bilic, Benny; Belkin, Shimshon

2010-01-01

Genetically engineered microbial reporter strains are based upon the fusion of an inducible sensing element upstream of a reporting element, so that the construct emits a dose-dependent signal when exposed to the inducing compound(s) or stress factor(s). In this communication1 we described several general approaches undertaken in order to enhance the sensing performance of such promoter::reporter fusions. Significant improvements in detection sensitivity, response kinetics and signal intensity were achieved by modi fication of the length of the promoter-containing DNA fragment, by random or site-directed mutagenesis and by promoter duplication. The general nature of these genetics manipulations makes them applicable to other types of promoter::reporter fusions. PMID:21326942

Influence of laser power on microstructure and mechanical properties of laser welded-brazed Mg to Ni coated Ti alloys

NASA Astrophysics Data System (ADS)

Tan, Caiwang; Lu, Qingshuang; Chen, Bo; Song, Xiaoguo; Li, Liqun; Feng, Jicai; Wang, Yang

2017-03-01

AZ31B Magnesium (Mg) and Ti-6Al-4V titanium (Ti) alloys with Ni coating were joined by laser welding-brazing process using AZ92 Mg based filler. The influence of laser power on microstructure and mechanical properties were investigated. Ni coating was found to significantly promote good wetting-spreading ability of molten filler on the Ti sheet. Acceptable joints without obvious defects were obtained within a relatively wide processing window. In the process metallurgical bonding was achieved by the formation of Ti3Al phase at direct irradiation zone and Al-Ni phase followed by a layer of Mg-Al-Ni ternary compound adjacent to the fusion zone at the intermediate zone. The thickness of reaction layers increased slowly with the increasing laser power. The tensile-shear test indicated that joints produced at the laser power of 1300 W reached 2387 N fracture load, representing 88.5% joint efficiency with respect to the Mg base metal. The corresponding failure occurred in the fusion zone of the Mg base metal, while joints fractured at the interface at lower/higher laser power due to the crack or excessive intermetallic compound (IMC) formation along the interface.

An Efficient Procedure for Microscale Synthesis of Semicarbazones

ERIC Educational Resources Information Center

Pandita, Sangeeta; Goyal, Samta; Passey, Sarita

2004-01-01

A successful microscale fusion of semicarbazones, or transformation of carbonyl compounds into semicarbazones is performed through an effective grinding system. The donning of protective attire is advised to avoid the hazardous effects of semicarbazide hydrochloride during the fusion process.

Sub-barrier quasifission in heavy element formation reactions with deformed actinide target nuclei

NASA Astrophysics Data System (ADS)

Hinde, D. J.; Jeung, D. Y.; Prasad, E.; Wakhle, A.; Dasgupta, M.; Evers, M.; Luong, D. H.; du Rietz, R.; Simenel, C.; Simpson, E. C.; Williams, E.

2018-02-01

Background: The formation of superheavy elements (SHEs) by fusion of two massive nuclei is severely inhibited by the competing quasifission process. Low excitation energies favor SHE survival against fusion-fission competition. In "cold" fusion with spherical target nuclei near 208Pb, SHE yields are largest at beam energies significantly below the average capture barrier. In "hot" fusion with statically deformed actinide nuclei, this is not the case. Here the elongated deformation-aligned configurations in sub-barrier capture reactions inhibits fusion (formation of a compact compound nucleus), instead favoring rapid reseparation through quasifission. Purpose: To determine the probabilities of fast and slow quasifission in reactions with prolate statically deformed actinide nuclei, through measurement and quantitative analysis of the dependence of quasifission characteristics at beam energies spanning the average capture barrier energy. Methods: The Australian National University Heavy Ion Accelerator Facility and CUBE fission spectrometer have been used to measure fission and quasifission mass and angle distributions for reactions with projectiles from C to S, bombarding Th and U target nuclei. Results: Mass-asymmetric quasifission occurring on a fast time scale, associated with collisions with the tips of the prolate actinide nuclei, shows a rapid increase in probability with increasing projectile charge, the transition being centered around projectile atomic number ZP=14 . For mass-symmetric fission events, deviations of angular anisotropies from expectations for fusion fission, indicating a component of slower quasifission, suggest a similar transition, but centered around ZP˜8 . Conclusions: Collisions with the tips of statically deformed prolate actinide nuclei show evidence for two distinct quasifission processes of different time scales. Their probabilities both increase rapidly with the projectile charge. The probability of fusion can be severely suppressed by these two quasifission processes, since the sub-barrier heavy element yield is likely to be determined by the product of the probabilities of surviving each quasifission process.

In silico screening of small molecule libraries using the dengue virus envelope E protein has identified compounds with antiviral activity against multiple flaviviruses.

PubMed

Kampmann, Thorsten; Yennamalli, Ragothaman; Campbell, Phillipa; Stoermer, Martin J; Fairlie, David P; Kobe, Bostjan; Young, Paul R

2009-12-01

The flaviviruses comprise a large group of related viruses, many of which pose a significant global human health threat, most notably the dengue viruses (DENV), West Nile virus (WNV) and yellow fever virus (YFV). Flaviviruses enter host cells via fusion of the viral and cellular membranes, a process mediated by the major viral envelope protein E as it undergoes a low pH induced conformational change in the endosomal compartment of the host cell. This essential entry stage in the flavivirus life cycle provides an attractive target for the development of antiviral agents. We performed an in silico docking screen of the Maybridge chemical database within a previously described ligand binding pocket in the dengue E protein structure that is thought to play a key role in the conformational transitions that lead to membrane fusion. The biological activity of selected compounds identified from this screen revealed low micromolar antiviral potency against dengue virus for two of the compounds. Our results also provide the first evidence that compounds selected to bind to this ligand binding site on the flavivirus E protein abrogate fusion activity. Interestingly, one of these compounds also has antiviral activity against both WNV (kunjin strain) and YFV.

Fusing porphyrins with polycyclic aromatic hydrocarbons and heterocycles for optoelectronic applications

DOEpatents

Thompson, Mark E.; Diev, Viacheslav; Hanson, Kenneth; Forrest, Stephen R.

2015-08-18

A compound that can be used as a donor material in organic photovoltaic devices comprising a non-activated porphyrin fused with one or more non-activated polycyclic aromatic rings or one or more non-activated heterocyclic rings can be obtained by a thermal fusion process. The compounds can include structures of Formula I: ##STR00001## By heating the reaction mixture of non-activated porphyrins with non-activated polycyclic aromatic rings or heterocyclic rings to a fusion temperature and holding for a predetermined time, fusion of one or more polycyclic rings or heterocyclic rings to the non-activated porphyrin core in meso,.beta. fashion is achieved resulting in hybrid structures containing a distorted porphyrin ring with annulated aromatic rings. The porphyrin core can be olygoporphyrins.

Small Molecule Fluoride Toxicity Agonists

PubMed Central

Nelson1, James W.; Plummer, Mark S.; Blount, Kenneth F.; Ames, Tyler D.; Breaker, Ronald R.

2015-01-01

SUMMARY Fluoride is a ubiquitous anion that inhibits a wide variety of metabolic processes. Here we report the identification of a series of compounds that enhance fluoride toxicity in Escherichia coli and Streptococcus mutans. These molecules were isolated by using a high-throughput screen (HTS) for compounds that increase intracellular fluoride levels as determined via a fluoride riboswitch-reporter fusion construct. A series of derivatives were synthesized to examine structure-activity relationships, leading to the identification of compounds with improved activity. Thus, we demonstrate that small molecule fluoride toxicity agonists can be identified by HTS from existing chemical libraries by exploiting a natural fluoride riboswitch. In addition, our findings suggest that some molecules might be further optimized to function as binary antibacterial agents when combined with fluoride. PMID:25910244

Phase Transition Enthalpy Measurements of Organic and Organometallic Compounds. Sublimation, Vaporization and Fusion Enthalpies From 1880 to 2015. Part 1. C1 - C10

NASA Astrophysics Data System (ADS)

Acree, William; Chickos, James S.

2016-09-01

A compendium of phase change enthalpies published in 2010 is updated to include the period 1880-2015. Phase change enthalpies including fusion, vaporization, and sublimation enthalpies are included for organic, organometallic, and a few inorganic compounds. Part 1 of this compendium includes organic compounds from C1 to C10. Part 2 of this compendium, to be published separately, will include organic and organometallic compounds from C11 to C192. Sufficient data are presently available to permit thermodynamic cycles to be constructed as an independent means of evaluating the reliability of the data. Temperature adjustments of phase change enthalpies from the temperature of measurement to the standard reference temperature, T = 298.15 K, and a protocol for doing so are briefly discussed.

Fluoride salts as phase change materials for thermal energy storage in the temperature range 1000-1400 K

NASA Technical Reports Server (NTRS)

Misra, Ajay K.

1988-01-01

Eutectic compositions and congruently melting intermediate compounds in binary and ternary fluoride salt systems were characterized for potential use as latent heat of fusion phase change materials to store thermal energy in the temperature range 1000-1400 K. The melting points and eutectic compositions for many systems with published phase diagrams were experimentally verified and new eutectic compositions having melting points between 1000 and 1400 K were identified. Heats of fusion of several binary and ternary eutectics and congruently melting compounds were experimentally measured by differential scanning calorimetry. For a few systems in which heats of mixing in the melts have been measured, heats of fusion of the eutectics were calculated from thermodynamic considerations and good agreement was obtained between the measured and calculated values. Several combinations of salts with high heats of fusion per unit mass (greater than 0.7 kJ/g) have been identified for possible use as phase change materials in advanced solar dynamic space power applications.

High efficiency and brightness fluorescent organic light emitting diode by triplet-triplet fusion

DOEpatents

Forrest, Stephen; Zhang, Yifan

2015-02-10

A first device is provided. The first device further comprises an organic light emitting device. The organic light emitting device further comprises an anode, a cathode, and an emissive layer disposed between the anode and the cathode. The emissive layer may include an organic host compound and at least one organic emitting compound capable of fluorescent emission at room temperature. Various configurations are described for providing a range of current densities in which T-T fusion dominates over S-T annihilation, leading to very high efficiency fluorescent OLEDs.

A Fusion Protein of the p53 Transaction Domain and the p53-Binding Domain of the Oncoprotein MdmX as an Efficient System for High-Throughput Screening of MdmX Inhibitors.

PubMed

Chen, Rong; Zhou, Jingjing; Qin, Lingyun; Chen, Yao; Huang, Yongqi; Liu, Huili; Su, Zhengding

2017-06-27

In nearly half of cancers, the anticancer activity of p53 protein is often impaired by the overexpressed oncoprotein Mdm2 and its homologue, MdmX, demanding efficient therapeutics to disrupt the aberrant p53-MdmX/Mdm2 interactions to restore the p53 activity. While many potent Mdm2-specific inhibitors have already undergone clinical investigations, searching for MdmX-specific inhibitors has become very attractive, requiring a more efficient screening strategy for evaluating potential scaffolds or leads. In this work, considering that the intrinsic fluorescence residue Trp23 in the p53 transaction domain (p53p) plays an important role in determining the p53-MdmX/Mdm2 interactions, we constructed a fusion protein to utilize this intrinsic fluorescence signal to monitor high-throughput screening of a compound library. The fusion protein was composed of the p53p followed by the N-terminal domain of MdmX (N-MdmX) through a flexible amino acid linker, while the whole fusion protein contained a sole intrinsic fluorescence probe. The fusion protein was then evaluated using fluorescence spectroscopy against model compounds. Our results revealed that the variation of the fluorescence signal was highly correlated with the concentration of the ligand within 65 μM. The fusion protein was further evaluated with respect to its feasibility for use in high-throughput screening using a model compound library, including controls. We found that the imidazo-indole scaffold was a bona fide scaffold for template-based design of MdmX inhibitors. Thus, the p53p-N-MdmX fusion protein we designed provides a convenient and efficient tool for high-throughput screening of new MdmX inhibitors. The strategy described in this work should be applicable for other protein targets to accelerate drug discovery.

What perspectives for the synthesis of heavier superheavy nuclei? Results and comparison with models

NASA Astrophysics Data System (ADS)

Mandaglio, G.; Nasirov, A. K.; Curciarello, F.; De Leo, V.; Romaniuk, M.; Fazio, G.; Giardina, G.

2013-03-01

The possibility to synthesize heavier superheavy elements in massive nuclei reactions is strongly limited by the hindrance to complete fusion of reacting nuclei: due to the onset of the quasifission process in the entrance channel, which competes with complete fusion, and by strong increase of the fission yield along the de-excitation cascade of the compound nucleus in comparison to the evaporation residue formation. We present a wide and detailed procedure allowing us to describe the experimental results (evaporation residue nuclei and fissionlike products) in the mass asymmetric and symmetric reactions. Very reliable estimations and perspectives for the synthesis of superheavy elements in many massive nuclei reactions up to Z = 120 and eventually also for Z > 120 have been obtained.

/sup 18/O + /sup 12/C fusion-evaporation reaction

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

Heusch, B; Beck, C; Coffin, J P

1980-01-01

A study of the /sup 18/O + /sup 12/C fusion evaporation reaction has been undertaken for 2 reasons: to make a systematic study of the formation cross section for each individual evaporation residue over a broad excitation energy region in the compound nucleus /sup 30/Si:30 to 62 MeV; and to compare all results to fusion-evaporation calculations done in the framework of the Hauser-Feschbach statistical model.

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.

Combination of 2D/3D ligand-based similarity search in rapid virtual screening from multimillion compound repositories. Selection and biological evaluation of potential PDE4 and PDE5 inhibitors.

PubMed

Dobi, Krisztina; Hajdú, István; Flachner, Beáta; Fabó, Gabriella; Szaszkó, Mária; Bognár, Melinda; Magyar, Csaba; Simon, István; Szisz, Dániel; Lőrincz, Zsolt; Cseh, Sándor; Dormán, György

2014-05-28

Rapid in silico selection of target focused libraries from commercial repositories is an attractive and cost effective approach. If structures of active compounds are available rapid 2D similarity search can be performed on multimillion compound databases but the generated library requires further focusing by various 2D/3D chemoinformatics tools. We report here a combination of the 2D approach with a ligand-based 3D method (Screen3D) which applies flexible matching to align reference and target compounds in a dynamic manner and thus to assess their structural and conformational similarity. In the first case study we compared the 2D and 3D similarity scores on an existing dataset derived from the biological evaluation of a PDE5 focused library. Based on the obtained similarity metrices a fusion score was proposed. The fusion score was applied to refine the 2D similarity search in a second case study where we aimed at selecting and evaluating a PDE4B focused library. The application of this fused 2D/3D similarity measure led to an increase of the hit rate from 8.5% (1st round, 47% inhibition at 10 µM) to 28.5% (2nd round at 50% inhibition at 10 µM) and the best two hits had 53 nM inhibitory activities.

Small molecule fluoride toxicity agonists.

PubMed

Nelson, James W; Plummer, Mark S; Blount, Kenneth F; Ames, Tyler D; Breaker, Ronald R

2015-04-23

Fluoride is a ubiquitous anion that inhibits a wide variety of metabolic processes. Here, we report the identification of a series of compounds that enhance fluoride toxicity in Escherichia coli and Streptococcus mutans. These molecules were isolated by using a high-throughput screen (HTS) for compounds that increase intracellular fluoride levels as determined via a fluoride riboswitch reporter fusion construct. A series of derivatives were synthesized to examine structure-activity relationships, leading to the identification of compounds with improved activity. Thus, we demonstrate that small molecule fluoride toxicity agonists can be identified by HTS from existing chemical libraries by exploiting a natural fluoride riboswitch. In addition, our findings suggest that some molecules might be further optimized to function as binary antibacterial agents when combined with fluoride. Copyright © 2015 Elsevier Ltd. All rights reserved.

A novel in-cell ELISA method for screening of compounds inhibiting TRKA phosphorylation, using KM12 cell line harboring TRKA rearrangement.

PubMed

Pandre, Manoj Kumar; Shaik, Shama; Satya Pratap, Veera Venkata Valluri; Yadlapalli, Prasad; Yanamandra, Mahesh; Mitra, Sayan

2018-03-15

Tropomyosin-related kinase A (TRKA) fusion was originally detected in colorectal carcinoma that had resulted in expression of the oncogenic chimeric protein TPM3-TRKA. Lately, many more rearrangements in TRK family of kinases generating oncogenic fusion proteins have been identified. These genetic rearrangements usually result in fusion of cytoplasmic kinase domain of TRK to another gene of interest resulting in constitutive kinase activity. Estimation of TRK inhibitor potency in a cellular context is required for drug discovery programs and is measured by receptor phosphorylation levels upon compound administration. However, since a large chunk of the TRK protein is lost in this rearrangement, it's difficult to set up sandwich ELISA for detection of receptor phosphorylation in any cell assay harboring these fusion proteins. In order to address this issue, we developed a novel and robust in-cell ELISA method which quantifies the phosphorylation of TRK kinase (Tyr 674/675) within the KM12 cells. This cell based method is more versatile & economical than conventional ELISA using engineered overexpressing cell line and/or western blot methods. Performance reliability & robustness for the validated assay were determined by %CV and Z factor in assays with reference molecule larotrectinib. This in-cell ELISA method can be used with any TRKA rearranged oncogenic fusion cell type and can be extended to other TRK isoforms as well. We have used this assay to screen novel molecules in KM12 cells and to study pharmacodynamic properties of compounds in TRKA signaling. Copyright © 2018 Elsevier Inc. All rights reserved.

Phase Transition Enthalpy Measurements of Organic and Organometallic Compounds and Ionic Liquids. Sublimation, Vaporization, and Fusion Enthalpies from 1880 to 2015. Part 2. C11-C192

NASA Astrophysics Data System (ADS)

Acree, William; Chickos, James S.

2017-03-01

The second part of this compendium concludes with a collection of phase change enthalpies of organic molecules inclusive of C11-C192 reported over the period 1880-2015. Also included are phase change enthalpies including fusion, vaporization, and sublimation enthalpies for organometallic, ionic liquids, and a few inorganic compounds. Paper I of this compendium, published separately, includes organic compounds from C1 to C10 and describes a group additivity method for evaluating solid, liquid, and gas phase heat capacities as well as temperature adjustments of phase changes. Paper II of this compendium also includes an updated version of a group additivity method for evaluating total phase change entropies which together with the fusion temperature can be useful in estimating total phase change enthalpies. Other uses include application in identifying potential substances that either form liquid or plastic crystals or exhibit additional phase changes such as undetected solid-solid transitions or behave anisotropically in the liquid state.

Phase Transition Enthalpy Measurements of Organic and Organometallic Compounds. Sublimation, Vaporization and Fusion Enthalpies From 1880 to 2015. Part 1. C{sub 1} − C{sub 10}

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

Acree, William; Chickos, James S.

2016-09-15

A compendium of phase change enthalpies published in 2010 is updated to include the period 1880–2015. Phase change enthalpies including fusion, vaporization, and sublimation enthalpies are included for organic, organometallic, and a few inorganic compounds. Part 1 of this compendium includes organic compounds from C{sub 1} to C{sub 10}. Part 2 of this compendium, to be published separately, will include organic and organometallic compounds from C{sub 11} to C{sub 192}. Sufficient data are presently available to permit thermodynamic cycles to be constructed as an independent means of evaluating the reliability of the data. Temperature adjustments of phase change enthalpies frommore » the temperature of measurement to the standard reference temperature, T = 298.15 K, and a protocol for doing so are briefly discussed.« less

Near-barrier Fusion Evaporation and Fission of 28Si+174Yb and 32S+170Er

NASA Astrophysics Data System (ADS)

Wang, Dongxi; Lin, Chengjian; Jia, Huiming; Ma, Nanru; Sun, Lijie; Xu, Xinxing; Yang, Lei; Yang, Feng; Zhang, Huanqiao; Bao, Pengfei

2017-11-01

Fusion evaporation residues and fission fragments have been measured, respectively, at energies around the Coulomb barrier for the 28Si+174Yb and 32S+170Er systems forming the same compound nucleus 202Po. The excitation function of fusion evaporation, fission as well as capture reactions were deduced. Coupled-channels analyses reveal that couplings to the deformations of targets and the two-phonon states of projectiles contribute much to the enhancement of capture cross sections at sub-barrier energies. The mass and total kinetic energy of fission fragments were deduced by the time-difference method assuming full momentum transfer in a two-body kinematics. The mass-energy and mass-angle distributions were obtained and no obvious quasi-fission components were observed in this bombarding energy range. Further, mass distributions of fission fragments were fitted to extract their widths. Results show that the mass widths decrease monotonically with decreasing energy, but might start to increase when Ec.m./VB < 0.95 for both systems.

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

Beavin, P. Jr.

A previously published method for determining zirconium in antiperspirant aerosols was collaboratively studied by 7 laboratories. The method consists of 2 procedures: a rapid dilution procedure for soluble zirconium compounds or a lengthier fusion procedure for total zirconium followed by colorimetric determination. The collaborators were asked to perform the following: Spiking materials representing 4 levels of soluble zirconium were added to weighed portions of a zirconium-free cream base concentrate and the portions were assayed by the dilution procedure. Spiking materials representing 4 levels of zirconium in either the soluble or the insoluble form (or as a mixture) were also addedmore » to portions of the same concentrate and these portions were assayed by the fusion procedure. They were also asked to concentrate and assay, by both procedures, 2 cans each of 2 commercial aerosol antiperspirants containing zirconyl hydroxychloride. The average percent recoveries and standard deviations for spiked samples were 99.8-100.2 and 1.69-2.71, respectively, for soluble compounds determined by the dilution procedure, and 93.8-97.4 and 3.09-4.78, respectively, for soluble and/or insoluble compounds determined by the fusion procedure. The average perent zirconium found by the dilution procedure in the 2 commercial aerosol products was 0.751 and 0.792. Insufficient collaborative results were received for the fusion procedure for statistical evaluation. The dilution procedure has been adopted as official first action.« less

Situational awareness of a coordinated cyber attack

NASA Astrophysics Data System (ADS)

Sudit, Moises; Stotz, Adam; Holender, Michael

2005-03-01

As technology continues to advance, services and capabilities become computerized, and an ever increasing amount of business is conducted electronically the threat of cyber attacks gets compounded by the complexity of such attacks and the criticality of the information which must be secured. A new age of virtual warfare has dawned in which seconds can differentiate between the protection of vital information and/or services and a malicious attacker attaining their goal. In this paper we present a novel approach in the real-time detection of multistage coordinated cyber attacks and the promising initial testing results we have obtained. We introduce INFERD (INformation Fusion Engine for Real-time Decision-making), an adaptable information fusion engine which performs fusion at levels zero, one, and two to provide real-time situational assessment and its application to the cyber domain in the ECCARS (Event Correlation for Cyber Attack Recognition System) system. The advantages to our approach are fourfold: (1) The complexity of the attacks which we consider, (2) the level of abstraction in which the analyst interacts with the attack scenarios, (3) the speed at which the information fusion is presented and performed, and (4) our disregard for ad-hoc rules or a priori parameters.

Drug-Induced Trafficking of P-Glycoprotein in Human Brain Capillary Endothelial Cells as Demonstrated by Exposure to Mitomycin C

PubMed Central

Noack, Andreas; Noack, Sandra; Hoffmann, Andrea; Maalouf, Katia; Buettner, Manuela; Couraud, Pierre-Olivier; Romero, Ignacio A.; Weksler, Babette; Alms, Dana; Römermann, Kerstin; Naim, Hassan Y.; Löscher, Wolfgang

2014-01-01

P-glycoprotein (Pgp; ABCB1/MDR1) is a major efflux transporter at the blood-brain barrier (BBB), restricting the penetration of various compounds. In other tissues, trafficking of Pgp from subcellular stores to the cell surface has been demonstrated and may constitute a rapid way of the cell to respond to toxic compounds by functional membrane insertion of the transporter. It is not known whether drug-induced Pgp trafficking also occurs in brain capillary endothelial cells that form the BBB. In this study, trafficking of Pgp was investigated in human brain capillary endothelial cells (hCMEC/D3) that were stably transfected with a doxycycline-inducible MDR1-EGFP fusion plasmid. In the presence of doxycycline, these cells exhibited a 15-fold increase in Pgp-EGFP fusion protein expression, which was associated with an increased efflux of the Pgp substrate rhodamine 123 (Rho123). The chemotherapeutic agent mitomycin C (MMC) was used to study drug-induced trafficking of Pgp. Confocal fluorescence microscopy of single hCMEC/D3-MDR1-EGFP cells revealed that Pgp redistribution from intracellular pools to the cell surface occurred within 2 h of MMC exposure. Pgp-EGFP exhibited a punctuate pattern at the cell surface compatible with concentrated regions of the fusion protein in membrane microdomains, i.e., lipid rafts, which was confirmed by Western blot analysis of biotinylated cell surface proteins in Lubrol-resistant membranes. MMC exposure also increased the functionality of Pgp as assessed in three functional assays with Pgp substrates (Rho123, eFluxx-ID Gold, calcein-AM). However, this increase occurred with some delay after the increased Pgp expression and coincided with the release of Pgp from the Lubrol-resistant membrane complexes. Disrupting rafts by depleting the membrane of cholesterol increased the functionality of Pgp. Our data present the first direct evidence of drug-induced Pgp trafficking at the human BBB and indicate that Pgp has to be released from lipid rafts to gain its full functionality. PMID:24505408

Drug-induced trafficking of p-glycoprotein in human brain capillary endothelial cells as demonstrated by exposure to mitomycin C.

PubMed

Noack, Andreas; Noack, Sandra; Hoffmann, Andrea; Maalouf, Katia; Buettner, Manuela; Couraud, Pierre-Olivier; Romero, Ignacio A; Weksler, Babette; Alms, Dana; Römermann, Kerstin; Naim, Hassan Y; Löscher, Wolfgang

2014-01-01

P-glycoprotein (Pgp; ABCB1/MDR1) is a major efflux transporter at the blood-brain barrier (BBB), restricting the penetration of various compounds. In other tissues, trafficking of Pgp from subcellular stores to the cell surface has been demonstrated and may constitute a rapid way of the cell to respond to toxic compounds by functional membrane insertion of the transporter. It is not known whether drug-induced Pgp trafficking also occurs in brain capillary endothelial cells that form the BBB. In this study, trafficking of Pgp was investigated in human brain capillary endothelial cells (hCMEC/D3) that were stably transfected with a doxycycline-inducible MDR1-EGFP fusion plasmid. In the presence of doxycycline, these cells exhibited a 15-fold increase in Pgp-EGFP fusion protein expression, which was associated with an increased efflux of the Pgp substrate rhodamine 123 (Rho123). The chemotherapeutic agent mitomycin C (MMC) was used to study drug-induced trafficking of Pgp. Confocal fluorescence microscopy of single hCMEC/D3-MDR1-EGFP cells revealed that Pgp redistribution from intracellular pools to the cell surface occurred within 2 h of MMC exposure. Pgp-EGFP exhibited a punctuate pattern at the cell surface compatible with concentrated regions of the fusion protein in membrane microdomains, i.e., lipid rafts, which was confirmed by Western blot analysis of biotinylated cell surface proteins in Lubrol-resistant membranes. MMC exposure also increased the functionality of Pgp as assessed in three functional assays with Pgp substrates (Rho123, eFluxx-ID Gold, calcein-AM). However, this increase occurred with some delay after the increased Pgp expression and coincided with the release of Pgp from the Lubrol-resistant membrane complexes. Disrupting rafts by depleting the membrane of cholesterol increased the functionality of Pgp. Our data present the first direct evidence of drug-induced Pgp trafficking at the human BBB and indicate that Pgp has to be released from lipid rafts to gain its full functionality.

Production and characterization of active recombinant interleukin-12/eGFP fusion protein in stably-transfected DF1 chicken cells.

PubMed

Wu, Hsing Chieh; Chen, Yu San; Shen, Pin Chun; Shien, Jui Hung; Lee, Long Huw; Chiu, Hua Hsien

2015-01-01

The adjuvant activity of chicken interleukin-12 (chIL-12) protein has been described as similar to that of mammalian IL-12. Recombinant chIL-12 can be produced using several methods, but chIL-12 production in eukaryotic cells is lower than that in prokaryotic cells. Stimulating compounds, such as dimethyl sulfoxide (DMSO), can be added to animal cell cultures to overcome this drawback. In this study, we constructed a cell line, DF1/chIL-12 which stably expressed a fusion protein, chIL-12 and enhanced green fluorescent protein (eGFP) connected by a (G4 S)3 linker sequence. Fusion protein production was increased when cells were cultured in the presence of DMSO. When 1 × 10(6) DF1/chIL-12 cells were inoculated in a T-175 flask containing 30 mL of media, incubated for 15 h, and further cultivated in the presence of 4% DMSO for 48 h, the production of total fusion protein was mostly enhanced compared with the production of total fusion protein by using cell lysates induced with DMSO at other concentrations. The concentrations of the unpurified and purified total fusion proteins in cell lysates were 2,781 ± 2.72 ng mL(-1) and 2,207 ± 3.28 ng mL(-1) , respectively. The recovery rate was 79%. The fusion protein stimulated chicken splenocytes to produce IFN-γ, which was measured using an enzyme-linked immunosorbent assay, in the culture supernatant, indicating that treating DF1/chIL-12 cells with DMSO or producing chIL-12 in a fusion protein form does not have adverse effects on the bioactivity of chIL-12. © 2015 American Institute of Chemical Engineers.

Pre-compound emission in low-energy heavy-ion interactions

NASA Astrophysics Data System (ADS)

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

2017-11-01

Recent experimental studies have shown the presence of pre-compound emission component in heavy ion reactions at low projectile energy ranging from 4 to 7 MeV/nucleons. In earlier measurements strength of the pre-compound component has been estimated from the difference in forward-backward distributions of emitted particles. Present measurement is a part of an ongoing program on the study of reaction dynamics of heavy ion interactions at low energies aimed at investigating the effect of momentum transfer in compound, precompound, complete and incomplete fusion processes in heavy ion reactions. In the present work on the basis of momentum transfer the measurement of the recoil range distributions of heavy residues has been used to decipher the components of compound and pre-compound emission processes in the fusion of 16O projectile with 159Tb and 169Tm targets. The analysis of recoil range distribution measurements show two distinct linear momentum transfer components corresponding to pre-compound and compound nucleus processes are involved. In order to obtain the mean input angular momentum associated with compound and pre-compound emission processes, an online measurement of the spin distributions of the residues has been performed. The analysis of spin distribution indicate that the mean input angular momentum associated with pre-compound products is found to be relatively lower than that associated with compound nucleus process. The pre-compound components obtained from the present analysis are consistent with those obtained from the analysis of excitation functions.

Odd-Z Transactinide Compound Nucleus Reactions Including the Discovery of 260Bh

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

Nelson, Sarah L.

Several reactions producing odd-Z transactinide compound nuclei were studiedwith the 88-Inch Cyclotron and the Berkeley Gas-Filled Separator at the Lawrence Berkeley National Laboratory. The goal was to produce the same compound nucleus ator near the same excitation energy with similar values of angular momentum via differentnuclear reactions. In doing so, it can be determined if there is a preference in entrancechannel, because under these experimental conditions the survival portion of Swiatecki, Siwek-Wilcznska, and Wilczynski's"Fusion By Diffusion" model is nearly identical forthe two reactions. Additionally, because the same compound nucleus is produced, theexit channel is the same. Four compound nuclei were examined in this study: 258Db, 262Bh, 266Mt, and 272Rg. These nuclei were produced by using very similar heavy-ion induced-fusion reactions which differ only by one proton in the projectile or target nucleus (e.g.: 50Ti + 209Bi vs. 51V + 208Pb). Peak 1n exit channel cross sections were determined for each reaction in each pair, and three of the four pairs' cross sections were identical within statistical uncertainties. This indicates there is not an obvious preference of entrancechannel in these paired reactions. Charge equilibration immediately prior to fusionleading to a decreased fusion barrier is the likely cause of this phenomenon. In addition to this systematic study, the lightest isotope of element 107, bohrium, was discovered in the 209Bi( 52Cr,n) reaction. 260Bh was found to decay by emission of a 10.16 MeV alpha particle with a half-life of 35more » $$+19\\atop{-9}$$ ms. The cross section is 59 pb at an excitation energy of 15.0 MeV. The effect of the N = 152 shell is also seen in this isotope's alpha particle energy, the first evidence of such an effect in Bh. All reactions studied are also compared to model predictions by Swiatecki, Siwek-Wilcznska, and Wilczynski 's" Fusion By Diffusion " theory.« less

Dynamics of 28,30S i* compound nuclei formed at sub-barrier energies

NASA Astrophysics Data System (ADS)

Kaur, Manpreet; Singh, Bir Bikram; Kaur, Sarbjeet

2018-05-01

The decay of 28S i* and 30S i* compound nuclei (CN) formed at sub-barrier energies, in the reactions induced by stable projectile 16O and exotic projectile 18O, respectively, has been investigated within the quantum mechanical fragmentation theory based dynamical cluster-decay model (DCM). The collective potential energy surface shows that xα-type (x is an integer) clusters are minimized in the decay of 28S i* while in case of 30S i* in addition to xα-type clusters, np-xα (n, p are neutron and proton, respectively) type clusters are also minimized. These minimized fragments have more preformation probability P0, which is an important factor through which nuclear structure effects of decaying CN are probed, within DCM. The results show that light particles (LPs) are contributing mostly in the fusion cross-section, σfusion. In case of 30S i*, the contribution of 1n is highest and more compared to 4He in case of 28S i*, which seems to play an important role in fusion enhancement. The DCM calculated σfusion for both the CN formed with same Ec.m. = 7.0 MeV gives more value for σfusion of 30S i*, in agreement with the experimental data.

Sensor data fusion for spectroscopy-based detection of explosives

NASA Astrophysics Data System (ADS)

Shah, Pratik V.; Singh, Abhijeet; Agarwal, Sanjeev; Sedigh, Sahra; Ford, Alan; Waterbury, Robert

2009-05-01

In-situ trace detection of explosive compounds such as RDX, TNT, and ammonium nitrate, is an important problem for the detection of IEDs and IED precursors. Spectroscopic techniques such as LIBS and Raman have shown promise for the detection of residues of explosive compounds on surfaces from standoff distances. Individually, both LIBS and Raman techniques suffer from various limitations, e.g., their robustness and reliability suffers due to variations in peak strengths and locations. However, the orthogonal nature of the spectral and compositional information provided by these techniques makes them suitable candidates for the use of sensor fusion to improve the overall detection performance. In this paper, we utilize peak energies in a region by fitting Lorentzian or Gaussian peaks around the location of interest. The ratios of peak energies are used for discrimination, in order to normalize the effect of changes in overall signal strength. Two data fusion techniques are discussed in this paper. Multi-spot fusion is performed on a set of independent samples from the same region based on the maximum likelihood formulation. Furthermore, the results from LIBS and Raman sensors are fused using linear discriminators. Improved detection performance with significantly reduced false alarm rates is reported using fusion techniques on data collected for sponsor demonstration at Fort Leonard Wood.

The emissivities of liquid metals at their fusion temperatures.

NASA Technical Reports Server (NTRS)

Bonnell, D. W.; Treverton, J. A.; Valerga, A. J.; Margrave , J. L.

1972-01-01

The emissivities for several transition metals and various other metals and compounds in the liquid state at their fusion temperatures have been determined in this laboratory. The technique used involves electromagnetic levitation-induction heating of the materials in an inert atmosphere. The brightness temperature of the liquid phase of the material is measured as the material is heated through fusion. Given a reliable value of the fusion temperature, which is available for most pure substances, one may readily calculate an emissivity for the liquid phase at the fusion temperature. Even in cases where melting points are poorly known, the brightness temperatures are unique parameters, independent of the temperature scale and measured for a chemically defined system at a fixed point.

Unique intermetallic compounds prepared by shock wave synthesis

NASA Technical Reports Server (NTRS)

Otto, G.; Reece, O. Y.; Roy, U.

1971-01-01

Technique compresses fine ground metallic powder mixture beyond crystal fusion point. Absence of vapor pressure voids and elimination of incongruous effects permit application of technique to large scale fabrication of intermetallic compounds with specific characteristics, e.g., semiconduction, superconduction, or magnetic properties.

Synthesis, characterization and corrosion inhibition properties of benzamide-2-chloro-4-nitrobenzoic acid and anthranilic acid-2-chloro-4-nitrobenzoic acid for mild steel corrosion in acidic medium

NASA Astrophysics Data System (ADS)

Pandey, Archana; Verma, Chandrabhan; Singh, B.; Ebenso, Eno E.

2018-03-01

The present study deals with the synthesis of two new compounds namely, benzamide - 2-chloro-4-nitrobenzoic acid (BENCNBA) and anthranilic acid-2-chloro-4-nitrobenzoic acid (AACNBA) using solid phase reactions. The phase diagram studies revealed that formation of the investigated compounds occurs in 1:1 molar ratio. The synthesized compounds were characterized using several spectral techniques such as FT-IR, 1H and 13C NMR, UV-Vis, powder X-ray diffraction (PXRD). Single crystal XRD (SCXRD) study showed that both BENCNBA and AACNBA compounds crystallize in triclinic crystal system with P-1 space group. Further, the presence of intermolecular hydrogen bonding between the constituent components was also supported by single crystal X-ray diffraction (SCXRD) method. Heat of mixing, entropy of fusion, roughness parameter, interfacial energy and excess thermodynamic functions have also been computed using the enthalpy of fusion values derived from differential scanning calorimeter (DSC) study. The inhibition effect of BENCNBA and AACNBA on the mild steel corrosion in hydrochloric acid solution was tested using electrochemical methods. Electrochemical impedance spectroscopy (EIS) study revealed that both BENCNBA and AACNBA behaved as interface corrosion inhibitors and showed maximum inhibition efficiencies of 95.71% and 96.42%, respectively at 400 ppm (1.23 × 10-3 M) concentration. Potentiodynamic polarization (PDP) measurements suggested that BENCNBA and AACNBA acted as mixed type corrosion inhibitors. EIS and PDP results showed that BENCNBA and AACNBA act as efficient corrosion inhibitors for mild steel and their inhibition efficiencies enhances on increasing their concentrations.

Enhancement of Skin Penetration of Hydrophilic and Lipophilic Compounds by pH-sensitive Liposomes.

PubMed

Tokudome, Yoshihiro; Nakamura, Kaoru; Itaya, Yurina; Hashimoto, Fumie

2015-01-01

Enhance skin penetration of hydrophilic and lipophilic compounds using liposomes that are responsible to the pH of the skin surface. pH-sensitive liposomes were prepared by a thin layer and freeze-thaw method with dioleoyl phosphatidyl ethanolamine and cholesteryl hemisuccinate. Liposomal fusion with stratum corneum lipid liposomes was measured using fluorescence resonance energy transfer. Particle diameter and zeta potential of the liposomes after fusion were measured by dynamic light scattering and electrophoresis. Under neutral pH conditions, the diameter of the pH-sensitive liposomes was 130 nm and their zeta potential was -70 mV. In weakly acidic conditions, the diameter was larger than 3,000 nm and the zeta potential was -50 mV. In contrast, the particle diameter and the zeta potential of the non-pH-sensitive liposomes remained constant under various pH conditions. A skin penetration study was performed on hairless mice skin using vertical diffusion cells, showing that the fusion ability of pH-sensitive liposomes was higher than that of non-pH-sensitive liposomes. In the skin penetration study was carried out using hydrophilic (calcein) and lipophilic (N-(7-nitrobenz- 2-oxa-1,3-diazol-4yl)-PE) (NBD-PE) model compounds which were applied to the skin with pH-sensitive liposomes as carrier. The fluorescent compounds contained within the pH-sensitive liposomes permeated the skin more effectively than those within non-pH-sensitive liposomes, and this ability was further enhanced with the lipophilic compound. These studies suggest that pH-sensitive liposomes have potential as an important tool for delivery of compounds into the skin.

Rigid amphipathic fusion inhibitors demonstrate antiviral activity against African swine fever virus.

PubMed

Hakobyan, Astghik; Galindo, Inmaculada; Nañez, Almudena; Arabyan, Erik; Karalyan, Zaven; Chistov, Alexey A; Streshnev, Philipp P; Korshun, Vladimir A; Alonso, Covadonga; Zakaryan, Hovakim

2018-01-01

Rigid amphipathic fusion inhibitors (RAFIs) are a family of nucleoside derivatives that inhibit the infectivity of several enveloped viruses by interacting with virion envelope lipids and inhibiting fusion between viral and cellular membranes. Here we tested the antiviral activity of two RAFIs, 5-(Perylen-3-ylethynyl)-arabino-uridine (aUY11) and 5-(Perylen-3-ylethynyl)uracil-1-acetic acid (cm1UY11) against African swine fever virus (ASFV), for which no effective vaccine is available. Both compounds displayed a potent, dose-dependent inhibitory effect on ASFV infection in Vero cells. The major antiviral effect was observed when aUY11 and cm1UY11 were added at early stages of infection and maintained during the complete viral cycle. Furthermore, virucidal assay revealed a significant extracellular anti-ASFV activity for both compounds. We also found decrease in the synthesis of early and late viral proteins in Vero cells treated with cm1UY11. Finally, the inhibitory effect of aUY11 and cm1UY11 on ASFV infection in porcine alveolar macrophages was confirmed. Overall, our study has identified novel anti-ASFV compounds with potential for future therapeutic developments.

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.

Newly Engineered Magnetic Erythrocytes for Sustained and Targeted Delivery of Anti-Cancer Therapeutic Compounds

PubMed Central

Taranta, Monia; Naldi, Ilaria

2011-01-01

Cytotoxic chemotherapy of cancer is limited by serious, sometimes life-threatening, side effects that arise from toxicities to sensitive normal cells because the therapies are not selective for malignant cells. So how can they be selectively improved? Alternative pharmaceutical formulations of anti-cancer agents have been investigated in order to improve conventional chemotherapy treatment. These formulations are associated with problems like severe toxic side effects on healthy organs, drug resistance and limited access of the drug to the tumor sites suggested the need to focus on site-specific controlled drug delivery systems. In response to these concerns, we have developed a new drug delivery system based on magnetic erythrocytes engineered with a viral spike fusion protein. This new erythrocyte-based drug delivery system has the potential for magnetic-controlled site-specific localization and highly efficient fusion capability with the targeted cells. Here we show that the erythro-magneto-HA virosomes drug delivery system is able to attach and fuse with the target cells and to efficiently release therapeutic compounds inside the cells. The efficacy of the anti-cancer drug employed is increased and the dose required is 10 time less than that needed with conventional therapy. PMID:21373641

Potential of derived lunar volatiles for life support

NASA Technical Reports Server (NTRS)

Bula, R. J.; Wittenberg, L. J.; Tibbitts, T. W.; Kulcinski, G. L.

1992-01-01

The lunar regolith contains small quantities of solar wind implanted volatile compounds that have vital, basic uses for maintaining life support systems of lunar or space settlements. Recent proposals to utilize the helium-3 isotope (He-3) derived from the lunar regolith as a fuel for fusion reactors would result in the availability of large quantities of other lunar volatile compounds. The quantities obtained would provide the annual life support replacement requirements of 1150 to 23,000 inhabitants per ton of He-3 recovered, depending on the volatile compound. Utilization of the lunar volatile compounds for life support depends on the costs, in terms of materials and energy, associated with their extraction from the lunar regolith as compared to the delivery costs of these compounds from Earth resources. Considering today's conservative estimated transportation costs ($10,000 dollars per kilogram) and regolith mining costs ($5 dollars per ton), the life support replacement requirements could be more economically supplied by recovering the lunar volatile compounds than transporting these materials from Earth resources, even before He-3 will be utilized as a fusion fuel. In addition, availability of lunar volatile compounds could have a significant cost impact on maintaining the life support systems of the space station and a Mars base.

Inhibition of herpes simplex virus type 1 entry by chloride channel inhibitors tamoxifen and NPPB

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

Zheng, Kai; College of Life Science and Technology, Jinan University, Guangzhou; Chen, Maoyun

2014-04-18

Highlights: • We analyze the anti-HSV potential of chloride channel inhibitors. • Tamoxifen and NPPB show anti-HSV-1 and anti-ACV-resistant HSV-1 activities. • HSV-1 infection induces intracellular chloride concentration increasing. • Tamoxifen and NPPB inhibit HSV-1 early infection. • Tamoxifen and NPPB prevent the fusion process of HSV-1. - Abstract: Herpes simplex virus type 1 (HSV-1) infection is very common worldwide and can cause significant health problems from periodic skin and corneal lesions to encephalitis. Appearance of drug-resistant viruses in clinical therapy has made exploring novel antiviral agents emergent. Here we show that chloride channel inhibitors, including tamoxifen and 5-nitro-2-(3-phenyl-propylamino) benzoicmore » acid (NPPB), exhibited extensive antiviral activities toward HSV-1 and ACV-resistant HSV viruses. HSV-1 infection induced chloride ion influx while treatment with inhibitors reduced the increase of intracellular chloride ion concentration. Pretreatment or treatment of inhibitors at different time points during HSV-1 infection all suppressed viral RNA synthesis, protein expression and virus production. More detailed studies demonstrated that tamoxifen and NPPB acted as potent inhibitors of HSV-1 early entry step by preventing viral binding, penetration and nuclear translocation. Specifically the compounds appeared to affect viral fusion process by inhibiting virus binding to lipid rafts and interrupting calcium homeostasis. Taken together, the observation that tamoxifen and NPPB can block viral entry suggests a stronger potential for these compounds as well as other ion channel inhibitors in antiviral therapy against HSV-1, especially the compound tamoxifen is an immediately actionable drug that can be reused for treatment of HSV-1 infections.« less

Desorption behavior of sorbed flavor compounds from packaging films with ethanol solution.

PubMed

Hwang, Y H; Matsui, T; Hanada, T; Shimoda, M; Matsumoto, K; Osajima, Y

2000-09-01

Desorption behavior of sorbed flavor compounds such as ethyl esters, n-aldehydes, and n-alcohols from LDPE and PET films was investigated in 0 to 100% (v/v) ethanol solutions at 20 degrees C, 50 degrees C, and 60 degrees C. In both films, the desorption apparently increased with increasing ethanol concentration and treatment temperature, depending on the compatibility of the flavor compound with the solvent. Namely, the partition coefficient of ethyl esters, n-aldehydes, and n-alcohols in the LDPE film turned out to be approximately zero at >/=60%, >/=80%, and >/=40% (v/v) ethanol, respectively (for PET film, >/=80%, >/=80%, and >/=40% (v/v) ethanol concentrations were required for complete desorption, respectively). As for physical properties (heat of fusion, melting point, and tensile strength and elongation at break) of LDPE and PET films, there were no significant differences between intact film and the treated film with 60% (v/v) ethanol for 30 min at 60 degrees C. These results suggest that it is possible to apply a desorption solvent such as ethanol solution for desorption of sorbed flavor compounds from packaging films with no physical change in the film properties by this desorption treatment.

Comparing fusion techniques for the ImageCLEF 2013 medical case retrieval task.

PubMed

G Seco de Herrera, Alba; Schaer, Roger; Markonis, Dimitrios; Müller, Henning

2015-01-01

Retrieval systems can supply similar cases with a proven diagnosis to a new example case under observation to help clinicians during their work. The ImageCLEFmed evaluation campaign proposes a framework where research groups can compare case-based retrieval approaches. This paper focuses on the case-based task and adds results of the compound figure separation and modality classification tasks. Several fusion approaches are compared to identify the approaches best adapted to the heterogeneous data of the task. Fusion of visual and textual features is analyzed, demonstrating that the selection of the fusion strategy can improve the best performance on the case-based retrieval task. Copyright © 2014 Elsevier Ltd. All rights reserved.

Study of Chelyabinsk LL5 meteorite fragment with a light lithology and its fusion crust using Mössbauer spectroscopy with a high velocity resolution

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

Maksimova, Alevtina A.; Petrova, Evgeniya V.; Grokhovsky, Victor I.

2014-10-27

Study of Chelyabinsk LL5 ordinary chondrite fragment with a light lithology and its fusion crust, fallen on February 15, 2013, in Russian Federation, was carried out using Mössbauer spectroscopy with a high velocity resolution. The Mössbauer spectra of the internal matter and fusion crust were fitted and all components were related to iron-bearing phases such as olivine, pyroxene, troilite, Fe-Ni-Co alloy, and chromite in the internal matter and olivine, pyroxene, troilite, Fe-Ni-Co alloy, and magnesioferrite in the fusion crust. A comparison of the content of different phases in the internal matter and in the fusion crust of this fragment showedmore » that ferric compounds resulted from olivine, pyroxene, and troilite combustion in the atmosphere.« less

Synthesis reactions and radioactive properties of transactinoid elements

NASA Astrophysics Data System (ADS)

Oganessian, Yu. Ts.

1994-10-01

It is well known that the heaviest elements of the periodic table have been synthesized in the cold fusion of magic nuclei of Pb with Z less than 26 ions. Because of dynamic limitations for fusion under strong Coulomb interaction of nuclei, the cross-sections of cold fusion reactions diminish exponentially with growing compound nucleus atomic number. For element Z = 110 produced in the reaction Pb-208(Ni-62,n)(sub 271)110, the expected cross-section is 10(exp -36) sq cm. In still more asymmetric reactions, when isotopes of actinoid elements irradiated with relatively light ions (Z less than or equal 12) are used as the target material, the compound nuclei possess an excitation energy of approx. 50 MeV. At this energy the nuclear shell effects are strongly suppressed and, as a result, in the case of hot compound nuclei of transactinoid elements the fission barrier is practically absent. The transition of these nuclei into the ground state depends strongly on the dynamic properties of the system with respect to the fission degree of freedom. Experimental studies were going on in two directions: (1) determination of the fission time by measuring the prefission neutrons (of Cf-Fm nuclei) in a wide interval of excitation energies; (2) direct synthesis of known nuclides with Z = 102-105 in reactions with ions of Ne-22, Mg-26, Al-27 and P-31 when final nuclei are produced in the ground state after the evaporation of five or six neutrons from the excited compound nuclei (E(sub x) = 50-60 MeV). The dependence of the reaction cross-section (HI, 5-6n) on the atomic number of the compound nucleus in different target-ion combinations points to the possibility of synthesizing new elements in hot fusion reactions. The advantage of these reactions arises from the use of neutron-rich nuclei like Cm-248 and Cf-249 which allows us to synthesize nuclei close to the deformed shell N = 162, for which a considerable growth of stability against spontaneous fission is predicted. Experimental set-ups and methods of detecting rare events of formation and decay of transactinide nuclei are described.

The emissivities of liquid metals at their fusion temperatures

NASA Technical Reports Server (NTRS)

Bonnell, D. W.; Treverton, J. A.; Valerga, A. J.; Margrave, J. L.

1972-01-01

A survey of the literature through 1969 shows an almost total lack of experimental emissivity data for metals in the liquid state. The emissivities for several transition metals and various other metals and compounds in the liquid state at their fusion temperatures have been determined. The technique used involves electromagnetic levitation-induction heating of the materials in an inert atmosphere. The brightness temperature of the liquid phase of the material is measured as the material is heated through fusion. Given a reliable value of the fusion temperature, which is available for most pure substances, one may readily calculate an emissivity for the liquid phase at the fusion temperatures. Even in cases where melting points are poorly known, the brightness temperatures are unique parameters, independent of the temperature scale and measured for a chemically defined system at a fixed point. Better emissivities may be recalculated as better melting point data become available.

Pre-terrestrial origin of rust in the Nakhla meteorite

NASA Technical Reports Server (NTRS)

Wentworth, Susan J.; Gooding, James L.

1990-01-01

The authors present quantative elemental compositions and summarize textural evidence for the pre-terrestrial origin of rust on the Nakhla meteorite. The material in question is called 'rust' because its phase composition remains unknown. Compelling evidence for the pre-terrestrial origin of the rust is found in rust veins truncated by fusion crust and preserved as faults in sutured igneous crystals. Rust veins that approach the meteorite's fusion crust become discontinuous and exhibit vugs that suggest partial decrepitation; no veins that penetrate the fusion crust have been found. Because the rust probably contains volatile compounds, it is reasonable to expect that heating near the ablation surface (formed during atmospheric entry to Earth) would encourage devolatilization of the rust. Hence, the absence of rust veins in fusion crust and vugs in rust veins near fusion crust clearly imply that the rust existed in the meteorite before atmospheric entry.

Fugacity ratio estimations for high-melting rigid aromatic compounds.

PubMed

Van Noort, Paul C M

2004-07-01

Prediction of the environmental fate of organic compounds requires knowledge of their tendency to stay in the gas and water phase. Vapor pressure and aqueous solubility are commonly used descriptors for these processes. Depending on the type of distribution process, values for either the pure solid state or the (subcooled) liquid state have to be used. Values for the (subcooled) liquid state can be calculated from those for the solid state, and vice versa, using the fugacity ratio. Fugacity ratios are usually calculated from the entropy of fusion and the melting point. For polycyclic aromatic hydrocarbons, chlorobenzenes, chlorodibenzofuranes, and chlorodibenzo(p)dioxins, fugacity ratios calculated using experimental entropies of fusion were systematically less than those obtained from a thermodynamically more rigorous approach using heat capacity data. The deviation was more than 1 order of magnitude at the highest melting point. The use of a universal value for the entropy of fusion of 56 J/molK resulted in either over or underestimation by up to more than 1 order of magnitude. A simple correction factor, based on the melting point only, was derived. This correction factor allowed the fugacity ratios to be estimated from experimental entropies of fusion and melting point with an accuracy better than 0.1-0.2 log units. Copyright 2004 Elsevier Ltd.

The amalgamation stage of fusion reactions

NASA Astrophysics Data System (ADS)

Mouze, Genevieve

2005-04-01

There is no need of a repulsive potential in the amalgamation stage for explaining the small fusion cross sections. The repulsive potential proposed by A. Adamian et al.(1) can advantageously be replaced by the affinity of the reaction of re-dissociation of the compound nucleus into its entrance-channel configuration. This reaction, which occurs after the penetration of the Coulomb barrier, is an equilibrium between dual and compact form of the compound nucleus, and the energy Q released in the dissociation is equal to the energy required for amalgamating. The total energy of the confined system being equal to the height B of the Coulomb barrier, the intrinsic excitation energy of the compact nucleus is equal to (B - Q). In the reaction 82Se+ 138Ba (2), the dissociation of 220Th releases 180.524 MeV, and B= 196.08 MeV. With an intrinsic excitation energy of 15.56 MeV, the confined compact 220Th has enough energy for emitting two neutrons ( S(2n) = 13.85 MeV). Thus the favored xn channel of fusion reactions can be precisely predicted. This new, mass-data-based model of fusion is completely parameter-free. 1 G.G. Adamian et al., PRC 69 (2004) 044601. 2 K. Satou et al. PRC C 65(2002) 054602.

Engineering Styrene Monooxygenase for Biocatalysis: Reductase-Epoxidase Fusion Proteins.

PubMed

Heine, Thomas; Tucker, Kathryn; Okonkwo, Nonye; Assefa, Berhanegebriel; Conrad, Catleen; Scholtissek, Anika; Schlömann, Michael; Gassner, George; Tischler, Dirk

2017-04-01

The enantioselective epoxidation of styrene and related compounds by two-component styrene monooxygenases (SMOs) has targeted these enzymes for development as biocatalysts. In the present work, we prepare genetically engineered fusion proteins that join the C-terminus of the epoxidase (StyA) to the N-terminus of the reductase (StyB) through a linker peptide and demonstrate their utility as biocatalysts in the synthesis of Tyrain purple and other indigoid dyes. A single-vector expression system offers a simplified platform for transformation and expansion of the catalytic function of styrene monooxygenases, and the resulting fusion proteins are self-regulated and couple efficiently NADH oxidation to styrene epoxidation. We find that the reductase domain proceeds through a sequential ternary-complex mechanism at low FAD concentration and a double-displacement mechanism at higher concentrations of FAD. Single-turnover studies indicate an observed rate constant for FAD-to-FAD hydride transfer of ~8 s -1 . This step is rate limiting in the styrene epoxidation reaction and helps to ensure that flavin reduction and styrene epoxidation reactions proceed without wasteful side reactions. Comparison of the reductase activity of the fusion proteins with the naturally occurring reductase, SMOB, and N-terminally histidine-tagged reductase, NSMOB, suggests that the observed changes in catalytic mechanism are due in part to an increase in flavin-binding affinity associated with the N-terminal extension of the reductase.

UGT-29 protein expression and localization during bacterial infection in Caenorhabditis elegans

NASA Astrophysics Data System (ADS)

Wong, Rui-Rui; Lee, Song-Hua; Nathan, Sheila

2014-09-01

The nematode Caenorhabditis elegans is routinely used as an animal model to delineate complex molecular mechanisms involved in the host response to pathogen infection. Following up on an earlier study on host-pathogen interaction, we constructed a ugt-29::GFP transcriptional fusion transgenic worm strain to examine UGT-29 protein expression and localization upon bacterial infection. UGT-29 orthologs can be found in higher organisms including humans and is proposed as a member of the UDP-Glucoronosyl Transferase family of proteins which are involved in phase II detoxification of compounds detrimental to the host organism. Under uninfected conditions, UGT-29::GFP fusion protein was highly expressed in the C. elegans anterior pharynx and intestine, two major organs involved in detoxification. We further evaluated the localization of the enzyme in worms infected with the bacterial pathogen, Burkholderia pseudomallei. The infected ugt-29::GFP transgenic strain exhibited increased fluorescence in the pharynx and intestine with pronounced fluorescence also extending to body wall muscle. This transcriptional fusion GFP transgenic worm is a convenient and direct tool to provide information on UGT detoxification enzyme gene expression and could be a useful tool for a number of diverse applications.

Influence of Zn Interlayer on Interfacial Microstructure and Mechanical Properties of TIG Lap-Welded Mg/Al Joints

NASA Astrophysics Data System (ADS)

Gao, Qiong; Wang, Kehong

2016-03-01

This study explored 6061 Al alloy and AZ31B Mg alloy joined by TIG lap welding with Zn foils of varying thicknesses, with the additional Zn element being imported into the fusion zone to alloy the weld seam. The microstructures and chemical composition in the fusion zone near the Mg substrate were examined by SEM and EDS, and tensile shear strength tests were conducted to investigate the mechanical properties of the Al/Mg joints, as well as the fracture surfaces, and phase compositions. The results revealed that the introduction of an appropriate amount of Zn transition layer improves the microstructure of Mg/Al joints and effectively reduces the formation of Mg-Al intermetallic compounds (IMCs). The most common IMCs in the fusion zone near the Mg substrate were Mg-Zn and Mg-Al-Zn IMCs. The type and distribution of IMCs generated in the weld zone differed according to Zn additions; Zn interlayer thickness of 0.4 mm improved the sample's mechanical properties considerably compared to thicknesses of less than 0.4 mm; however, any further increase in Zn interlayer thickness of above 0.4 mm caused mechanical properties to deteriorate.

Solid and liquid heat capacities of n-alkyl para-aminobenzoates near the melting point.

PubMed

Neau, S H; Flynn, G L

1990-11-01

The expression that relates the ideal mole fraction solubility of a crystalline compound to physicochemical properties of the compound includes a term involving the difference in the heat capacities of the solid and liquid forms of the solute, delta Cp. There are two alternate conventions which are employed to eliminate this term. The first assumes that the term involving delta Cp, or delta Cp itself, is zero. The alternate assumption assigns the value of the entropy of fusion to the differential heat capacity. The relative validity of these two assumptions was evaluated using the straight-chain alkyl para-aminobenzoates as test compounds. The heat capacities of the solid and liquid forms of each of the para-aminobenzoates, near the respective melting point, were determined by differential scanning calorimetry. The data lead one to conclude that the assumption that the differential heat capacity is not usually negligible and is better approximated by the entropy of fusion.

Trust and Independence Aware Decision Fusion in Distributed Networks

DTIC Science & Technology

2013-01-01

evidence in order to derive a unified belief where conflicting evidence exists. However, neither DST nor TBM deals with misbehaving data sources and...about the target. The problem is compounded by the misbehaving nodes who supply false data in the network. This work aims at enhancing the accuracy of...derive a unified belief where conflicting evidence exists. However, neither DST nor TBM deals with misbehaving data sources and dependence of fusion

Protection of macaques from vaginal SHIV challenge by vaginally delivered inhibitors of virus-cell fusion.

PubMed

Veazey, Ronald S; Klasse, Per Johan; Schader, Susan M; Hu, Qinxue; Ketas, Thomas J; Lu, Min; Marx, Preston A; Dufour, Jason; Colonno, Richard J; Shattock, Robin J; Springer, Martin S; Moore, John P

2005-11-03

Human immunodeficiency virus type 1 (HIV-1) continues to spread, principally by heterosexual sex, but no vaccine is available. Hence, alternative prevention methods are needed to supplement educational and behavioural-modification programmes. One such approach is a vaginal microbicide: the application of inhibitory compounds before intercourse. Here, we have evaluated the microbicide concept using the rhesus macaque 'high dose' vaginal transmission model with a CCR5-receptor-using simian-human immunodeficiency virus (SHIV-162P3) and three compounds that inhibit different stages of the virus-cell attachment and entry process. These compounds are BMS-378806, a small molecule that binds the viral gp120 glycoprotein and prevents its attachment to the CD4 and CCR5 receptors, CMPD167, a small molecule that binds to CCR5 to inhibit gp120 association, and C52L, a bacterially expressed peptide inhibitor of gp41-mediated fusion. In vitro, all three compounds inhibit infection of T cells and cervical tissue explants, and C52L acts synergistically with CMPD167 or BMS-378806 to inhibit infection of cell lines. In vivo, significant protection was achieved using each compound alone and in combinations. CMPD167 and BMS-378806 were protective even when applied 6 h before challenge.

P2X1 Receptor Antagonists Inhibit HIV-1 Fusion by Blocking Virus-Coreceptor Interactions

PubMed Central

Giroud, Charline; Marin, Mariana; Hammonds, Jason; Spearman, Paul

2015-01-01

ABSTRACT HIV-1 Env glycoprotein-mediated fusion is initiated upon sequential binding of Env to CD4 and the coreceptor CXCR4 or CCR5. Whereas these interactions are thought to be necessary and sufficient to promote HIV-1 fusion, other host factors can modulate this process. Previous studies reported potent inhibition of HIV-1 fusion by selective P2X1 receptor antagonists, including NF279, and suggested that these receptors play a role in HIV-1 entry. Here we investigated the mechanism of antiviral activity of NF279 and found that this compound does not inhibit HIV-1 fusion by preventing the activation of P2X1 channels but effectively blocks the binding of the virus to CXCR4 or CCR5. The notion of an off-target effect of NF279 on HIV-1 fusion is supported by the lack of detectable expression of P2X1 receptors in cells used in fusion experiments and by the fact that the addition of ATP or the enzymatic depletion of ATP in culture medium does not modulate viral fusion. Importantly, NF279 fails to inhibit HIV-1 fusion with cell lines and primary macrophages when added at an intermediate stage downstream of Env-CD4-coreceptor engagement. Conversely, in the presence of NF279, HIV-1 fusion is arrested downstream of CD4 binding but prior to coreceptor engagement. NF279 also antagonizes the signaling function of CCR5, CXCR4, and another chemokine receptor, as evidenced by the suppression of calcium responses elicited by specific ligands and by recombinant gp120. Collectively, our results demonstrate that NF279 is a dual HIV-1 coreceptor inhibitor that interferes with the functional engagement of CCR5 and CXCR4 by Env. IMPORTANCE Inhibition of P2X receptor activity suppresses HIV-1 fusion and replication, suggesting that P2X signaling is involved in HIV-1 entry. However, mechanistic experiments conducted in this study imply that P2X1 receptor is not expressed in target cells or involved in viral fusion. Instead, we found that inhibition of HIV-1 fusion by a specific P2X1 receptor antagonist, NF279, is due to the blocking of virus interactions with both the CXCR4 and CCR5 coreceptors. The ability of NF279 to abrogate cellular calcium signaling induced by the respective chemokines showed that this compound acts as a dual-coreceptor antagonist. P2X1 receptor antagonists could thus represent a new class of dual-coreceptor inhibitors with a structure and a mechanism of action that are distinct from those of known HIV-1 coreceptor antagonists. PMID:26136569

P2X1 Receptor Antagonists Inhibit HIV-1 Fusion by Blocking Virus-Coreceptor Interactions.

PubMed

Giroud, Charline; Marin, Mariana; Hammonds, Jason; Spearman, Paul; Melikyan, Gregory B

2015-09-01

HIV-1 Env glycoprotein-mediated fusion is initiated upon sequential binding of Env to CD4 and the coreceptor CXCR4 or CCR5. Whereas these interactions are thought to be necessary and sufficient to promote HIV-1 fusion, other host factors can modulate this process. Previous studies reported potent inhibition of HIV-1 fusion by selective P2X1 receptor antagonists, including NF279, and suggested that these receptors play a role in HIV-1 entry. Here we investigated the mechanism of antiviral activity of NF279 and found that this compound does not inhibit HIV-1 fusion by preventing the activation of P2X1 channels but effectively blocks the binding of the virus to CXCR4 or CCR5. The notion of an off-target effect of NF279 on HIV-1 fusion is supported by the lack of detectable expression of P2X1 receptors in cells used in fusion experiments and by the fact that the addition of ATP or the enzymatic depletion of ATP in culture medium does not modulate viral fusion. Importantly, NF279 fails to inhibit HIV-1 fusion with cell lines and primary macrophages when added at an intermediate stage downstream of Env-CD4-coreceptor engagement. Conversely, in the presence of NF279, HIV-1 fusion is arrested downstream of CD4 binding but prior to coreceptor engagement. NF279 also antagonizes the signaling function of CCR5, CXCR4, and another chemokine receptor, as evidenced by the suppression of calcium responses elicited by specific ligands and by recombinant gp120. Collectively, our results demonstrate that NF279 is a dual HIV-1 coreceptor inhibitor that interferes with the functional engagement of CCR5 and CXCR4 by Env. Inhibition of P2X receptor activity suppresses HIV-1 fusion and replication, suggesting that P2X signaling is involved in HIV-1 entry. However, mechanistic experiments conducted in this study imply that P2X1 receptor is not expressed in target cells or involved in viral fusion. Instead, we found that inhibition of HIV-1 fusion by a specific P2X1 receptor antagonist, NF279, is due to the blocking of virus interactions with both the CXCR4 and CCR5 coreceptors. The ability of NF279 to abrogate cellular calcium signaling induced by the respective chemokines showed that this compound acts as a dual-coreceptor antagonist. P2X1 receptor antagonists could thus represent a new class of dual-coreceptor inhibitors with a structure and a mechanism of action that are distinct from those of known HIV-1 coreceptor antagonists. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

5-(Perylen-3-yl)Ethynyl-arabino-Uridine (aUY11), an Arabino-Based Rigid Amphipathic Fusion Inhibitor, Targets Virion Envelope Lipids To Inhibit Fusion of Influenza Virus, Hepatitis C Virus, and Other Enveloped Viruses

PubMed Central

Colpitts, Che C.; Ustinov, Alexey V.; Epand, Raquel F.; Epand, Richard M.; Korshun, Vladimir A.

2013-01-01

Entry of enveloped viruses requires fusion of viral and cellular membranes. Fusion requires the formation of an intermediate stalk structure, in which only the outer leaflets are fused. The stalk structure, in turn, requires the lipid bilayer of the envelope to bend into negative curvature. This process is inhibited by enrichment in the outer leaflet of lipids with larger polar headgroups, which favor positive curvature. Accordingly, phospholipids with such shape inhibit viral fusion. We previously identified a compound, 5-(perylen-3-yl)ethynyl-2′-deoxy-uridine (dUY11), with overall shape and amphipathicity similar to those of these phospholipids. dUY11 inhibited the formation of the negative curvature necessary for stalk formation and the fusion of a model enveloped virus, vesicular stomatitis virus (VSV). We proposed that dUY11 acted by biophysical mechanisms as a result of its shape and amphipathicity. To test this model, we have now characterized the mechanisms against influenza virus and HCV of 5-(perylen-3-yl)ethynyl-arabino-uridine (aUY11), which has shape and amphipathicity similar to those of dUY11 but contains an arabino-nucleoside. aUY11 interacted with envelope lipids to inhibit the infectivity of influenza virus, hepatitis C virus (HCV), herpes simplex virus 1 and 2 (HSV-1/2), and other enveloped viruses. It specifically inhibited the fusion of influenza virus, HCV, VSV, and even protein-free liposomes to cells. Furthermore, aUY11 inhibited the formation of negative curvature in model lipid bilayers. In summary, the arabino-derived aUY11 and the deoxy-derived dUY11 act by the same antiviral mechanisms against several enveloped but otherwise unrelated viruses. Therefore, chemically unrelated compounds of appropriate shape and amphipathicity target virion envelope lipids to inhibit formation of the negative curvature required for fusion, inhibiting infectivity by biophysical, not biochemical, mechanisms. PMID:23283943

A novel fission-independent role of dynamin-related protein 1 in cardiac mitochondrial respiration

PubMed Central

Zhang, Huiliang; Wang, Pei; Bisetto, Sara; Yoon, Yisang; Chen, Quan; Sheu, Shey-Shing; Wang, Wang

2017-01-01

Aims Mitochondria in adult cardiomyocytes exhibit static morphology and infrequent dynamic changes, despite the high abundance of fission and fusion regulatory proteins in the heart. Previous reports have indicated that fusion proteins may bear functions beyond morphology regulation. Here, we investigated the role of fission protein, dynamin-related protein 1 (DRP1), on mitochondrial respiration regulation in adult cardiomyocytes. Methods and results By using genetic or pharmacological approaches, we manipulated the activity or protein level of fission and fusion proteins and found they mildly influenced mitochondrial morphology in adult rodent cardiomyocytes, which is in contrast to their significant effect in H9C2 cardiac myoblasts. Intriguingly, inhibiting endogenous DRP1 by dominant-negative DRP1 mutation (K38A), shRNA, or Mdivi-1 suppressed maximal respiration and respiratory control ratio in isolated mitochondria from adult mouse heart or in adult cardiomyocytes from rat. Meanwhile, basal respiration was increased due to increased proton leak. Facilitating mitofusin-mediated fusion by S3 compound, however, failed to inhibit mitochondrial respiration in adult cardiomyocytes. Mechanistically, DRP1 inhibition did not affect the maximal activity of individual respiratory chain complexes or the assembly of supercomplexes. Knocking out cyclophilin D, a regulator of mitochondrial permeability transition pore (mPTP), abolished the effect of DRP1 inhibition on respiration. Finally, DRP1 inhibition decreased transient mPTP-mediated mitochondrial flashes, delayed laser-induced mPTP opening and suppressed mitochondrial reactive oxygen species (ROS). Conclusion These results uncover a novel non-canonical function of the fission protein, DRP1 in maintaining or positively stimulating mitochondrial respiration, bioenergetics and ROS signalling in adult cardiomyocyte, which is likely independent of morphological changes. PMID:27794519

A novel fission-independent role of dynamin-related protein 1 in cardiac mitochondrial respiration.

PubMed

Zhang, Huiliang; Wang, Pei; Bisetto, Sara; Yoon, Yisang; Chen, Quan; Sheu, Shey-Shing; Wang, Wang

2017-02-01

Mitochondria in adult cardiomyocytes exhibit static morphology and infrequent dynamic changes, despite the high abundance of fission and fusion regulatory proteins in the heart. Previous reports have indicated that fusion proteins may bear functions beyond morphology regulation. Here, we investigated the role of fission protein, dynamin-related protein 1 (DRP1), on mitochondrial respiration regulation in adult cardiomyocytes. By using genetic or pharmacological approaches, we manipulated the activity or protein level of fission and fusion proteins and found they mildly influenced mitochondrial morphology in adult rodent cardiomyocytes, which is in contrast to their significant effect in H9C2 cardiac myoblasts. Intriguingly, inhibiting endogenous DRP1 by dominant-negative DRP1 mutation (K38A), shRNA, or Mdivi-1 suppressed maximal respiration and respiratory control ratio in isolated mitochondria from adult mouse heart or in adult cardiomyocytes from rat. Meanwhile, basal respiration was increased due to increased proton leak. Facilitating mitofusin-mediated fusion by S3 compound, however, failed to inhibit mitochondrial respiration in adult cardiomyocytes. Mechanistically, DRP1 inhibition did not affect the maximal activity of individual respiratory chain complexes or the assembly of supercomplexes. Knocking out cyclophilin D, a regulator of mitochondrial permeability transition pore (mPTP), abolished the effect of DRP1 inhibition on respiration. Finally, DRP1 inhibition decreased transient mPTP-mediated mitochondrial flashes, delayed laser-induced mPTP opening and suppressed mitochondrial reactive oxygen species (ROS). These results uncover a novel non-canonical function of the fission protein, DRP1 in maintaining or positively stimulating mitochondrial respiration, bioenergetics and ROS signalling in adult cardiomyocyte, which is likely independent of morphological changes. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For Permissions, please email: journals.permissions@oup.com.

Spin distributions and cross sections of evaporation residues in the 28Si+176Yb reaction

NASA Astrophysics Data System (ADS)

Sudarshan, K.; Tripathi, R.; Sodaye, S.; Sharma, S. K.; Pujari, P. K.; Gehlot, J.; Madhavan, N.; Nath, S.; Mohanto, G.; Mukul, I.; Jhingan, A.; Mazumdar, I.

2017-02-01

Background: Non-compound-nucleus fission in the preactinide region has been an active area of investigation in the recent past. Based on the measurements of fission-fragment mass distributions in the fission of 202Po, populated by reactions with varying entrance channel mass asymmetry, the onset of non-compound-nucleus fission was proposed to be around ZpZt˜1000 [Phys. Rev. C 77, 024606 (2008), 10.1103/PhysRevC.77.024606], where Zp and Zt are the projectile and target proton numbers, respectively. Purpose: The present paper is aimed at the measurement of cross sections and spin distributions of evaporation residues in the 28Si+176Yb reaction (ZpZt=980 ) to investigate the fusion hindrance which, in turn, would give information about the contribution from non-compound-nucleus fission in this reaction. Method: Evaporation-residue cross sections were measured in the beam energy range of 129-166 MeV using the hybrid recoil mass analyzer (HYRA) operated in the gas-filled mode. Evaporation-residue cross sections were also measured by the recoil catcher technique followed by off-line γ -ray spectrometry at few intermediate energies. γ -ray multiplicities of evaporation residues were measured to infer about their spin distribution. The measurements were carried out using NaI(Tl) detector-based 4π-spin spectrometer from the Tata Institute of Fundamental Research, Mumbai, coupled to the HYRA. Results: Evaporation-residue cross sections were significantly lower compared to those calculated using the statistical model code pace2 [Phys. Rev. C 21, 230 (1980), 10.1103/PhysRevC.21.230] with the coupled-channel fusion model code ccfus [Comput. Phys. Commun. 46, 187 (1987), 10.1016/0010-4655(87)90045-2] at beam energies close to the entrance channel Coulomb barrier. At higher beam energies, experimental cross sections were close to those predicted by the model. Average γ -ray multiplicities or angular momentum values of evaporation residues were in agreement with the calculations of the code ccfus + pace2 within the experimental uncertainties at all the beam energies. Conclusions: Deviation of evaporation-residue cross sections from the "fusion + statistical model" predictions at beam energies close to the entrance channel Coulomb barrier indicates fusion hindrance at these beam energies which would lead to non-compound-nucleus fission. However, reasonable agreement of average angular momentum values of evaporation residues at these beam energies with those calculated using the coupled-channel fusion model with the statistical model codes ccfus + pace2 suggests that fusion suppression at beam energies close to the entrance channel Coulomb barrier where populated l waves are low is not l dependent.

Determining the thermodynamic melting parameters of sulfamethoxazole, trimethoprim, urea, nicodin, and their double eutectics by differential scanning calorimetry

NASA Astrophysics Data System (ADS)

Agafonova, E. V.; Moshchenskii, Yu. V.; Tkachenko, M. L.

2013-08-01

The literature data on the thermodynamic melting characteristics of sulfamethoxazole, urea, trimethoprim, and nicodin are analyzed for individual compounds. Their enthalpies and melting points, either individually or in the composition of eutectics, are found by means of DSC. The entropies of fusion and the cryoscopic constants of individual compounds are calculated.

Measles Virus Fusion Protein: Structure, Function and Inhibition

PubMed Central

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

2016-01-01

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

Measles Virus Fusion Protein: Structure, Function and Inhibition.

PubMed

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

2016-04-21

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

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

Entropy-functional-based online adaptive decision fusion framework with application to wildfire detection in video.

PubMed

Gunay, Osman; Toreyin, Behçet Ugur; Kose, Kivanc; Cetin, A Enis

2012-05-01

In this paper, an entropy-functional-based online adaptive decision fusion (EADF) framework is developed for image analysis and computer vision applications. In this framework, it is assumed that the compound algorithm consists of several subalgorithms, each of which yields its own decision as a real number centered around zero, representing the confidence level of that particular subalgorithm. Decision values are linearly combined with weights that are updated online according to an active fusion method based on performing entropic projections onto convex sets describing subalgorithms. It is assumed that there is an oracle, who is usually a human operator, providing feedback to the decision fusion method. A video-based wildfire detection system was developed to evaluate the performance of the decision fusion algorithm. In this case, image data arrive sequentially, and the oracle is the security guard of the forest lookout tower, verifying the decision of the combined algorithm. The simulation results are presented.

Double differential light charged particle emission cross sections for some structural fusion materials

NASA Astrophysics Data System (ADS)

Sarpün, Ismail Hakki; n, Abdullah Aydı; Tel, Eyyup

2017-09-01

In fusion reactors, neutron induced radioactivity strongly depends on the irradiated material. So, a proper selection of structural materials will have been limited the radioactive inventory in a fusion reactor. First-wall and blanket components have high radioactivity concentration due to being the most flux-exposed structures. The main objective of fusion structural material research is the development and selection of materials for reactor components with good thermo-mechanical and physical properties, coupled with low-activation characteristics. Double differential light charged particle emission cross section, which is a fundamental data to determine nuclear heating and material damages in structural fusion material research, for some elements target nuclei have been calculated by the TALYS 1.8 nuclear reaction code at 14-15 MeV neutron incident energy and compared with available experimental data in EXFOR library. Direct, compound and pre-equilibrium reaction contribution have been theoretically calculated and dominant contribution have been determined for each emission of proton, deuteron and alpha particle.

Role of wave packet width in quantum molecular dynamics in fusion reactions near barrier

NASA Astrophysics Data System (ADS)

Cao, X. G.; Ma, Y. G.; Zhang, G. Q.; Wang, H. W.; Anastasi, A.; Curciarello, F.; De Leo, V.

2014-05-01

The dynamical fusion process of 48Ca + 144Sm with different impact parameters near barrier is studied by an extended quantum molecular dynamics (EQMD) model, where width of wavepacket is dynamically treated based on variational principle. The time evolution of different energy components such as potential energy, kinetic energy, Coulomb energy and Pauli potential are analyzed when dynamical or fixed width is assumed in calculation. It is found that the dynamical wavepacket width can enhance the dissipation of incident energy and the fluctuations, which are important to form compound nuclei. Moreover, we compare the fusion barrier dependence on the incident energy when it is determined by both dynamical and fixed wavepacket width.

The production of copper phthalocyanine and/or its derivatives

NASA Technical Reports Server (NTRS)

Segawa, T.; Matsuzaki, K.; Sawada, H.; Ninomiya, R.; Suyama, M.

1984-01-01

This document discusses the production of copper phthalocyanine and/or its derivatives, which are useful for dye pigments. The method described uses urea, a copper compound and/or a catalyst which have been suspended in an inert reaction medium. The copper compound, catalyst and urea fused and the reaction is performed by using the obtained fusion. The advantages of the invention are listed.

Survival Mediated Heavy Element Capture Cross Sections

NASA Astrophysics Data System (ADS)

Loveland, Walter; Yao, Larry

2017-11-01

Formally, the cross section for producing a heavy evaporation residue, σEVR, in a fusion reaction can be written as where E is the center of mass energy, and T is the probability of the colliding nuclei to overcome the potential barrier in the entrance channel and reach the contact point. PCN is the probability that the projectile-target system will evolve from the contact point to the compound nucleus. Wsur is the probability that the compound nucleus will decay to produce an evaporation residue rather than fissioning. However, one must remember that the Wsur term effectively sets the allowed values of the spin, which in turn, restricts the values of the capture and fusion cross sections. We point out the implications of this fact for capture cross sections for heavy element formation reactions.

Can Baird's and Clar's Rules Combined Explain Triplet State Energies of Polycyclic Conjugated Hydrocarbons with Fused 4nπ- and (4n + 2)π-Rings?

PubMed

Ayub, Rabia; Bakouri, Ouissam El; Jorner, Kjell; Solà, Miquel; Ottosson, Henrik

2017-06-16

Compounds that can be labeled as "aromatic chameleons" are π-conjugated compounds that are able to adjust their π-electron distributions so as to comply with the different rules of aromaticity in different electronic states. We used quantum chemical calculations to explore how the fusion of benzene rings onto aromatic chameleonic units represented by biphenylene, dibenzocyclooctatetraene, and dibenzo[a,e]pentalene modifies the first triplet excited states (T 1 ) of the compounds. Decreases in T 1 energies are observed when going from isomers with linear connectivity of the fused benzene rings to those with cis- or trans-bent connectivities. The T 1 energies decreased down to those of the parent (isolated) 4nπ-electron units. Simultaneously, we observe an increased influence of triplet state aromaticity of the central 4n ring as given by Baird's rule and evidenced by geometric, magnetic, and electron density based aromaticity indices (HOMA, NICS-XY, ACID, and FLU). Because of an influence of triplet state aromaticity in the central 4nπ-electron units, the most stabilized compounds retain the triplet excitation in Baird π-quartets or octets, enabling the outer benzene rings to adapt closed-shell singlet Clar π-sextet character. Interestingly, the T 1 energies go down as the total number of aromatic cycles within a molecule in the T 1 state increases.

Influence of fusion dynamics on fission observables: A multidimensional analysis

NASA Astrophysics Data System (ADS)

Schmitt, C.; Mazurek, K.; Nadtochy, P. N.

2018-01-01

An attempt to unfold the respective influence of the fusion and fission stages on typical fission observables, and namely the neutron prescission multiplicity, is proposed. A four-dimensional dynamical stochastic Langevin model is used to calculate the decay by fission of excited compound nuclei produced in a wide set of heavy-ion collisions. The comparison of the results from such a calculation and experimental data is discussed, guided by predictions of the dynamical deterministic HICOL code for the compound-nucleus formation time. While the dependence of the latter on the entrance-channel properties can straigthforwardly explain some observations, a complex interplay between the various parameters of the reaction is found to occur in other cases. A multidimensional analysis of the respective role of these parameters, including entrance-channel asymmetry, bombarding energy, compound-nucleus fissility, angular momentum, and excitation energy, is proposed. It is shown that, depending on the size of the system, apparent inconsistencies may be deduced when projecting onto specific ordering parameters. The work suggests the possibility of delicate compensation effects in governing the measured fission observables, thereby highlighting the necessity of a multidimensional discussion.

A novel microfluidic system for the mass production of Inertial Fusion Energy shells

NASA Astrophysics Data System (ADS)

Inoue, N. T.

2016-04-01

A system which can mass produce millimetre sized spherical polymer shells economically and with high precision will be a great step towards the Inertial Fusion Energy goal. Microfluidics has shown itself to be a disruptive technology, where a rapid and continuous production of compound emulsions can be processed into such shells. Planar emulsion generators co-flow-focus in one step (COFON) and cascaded co-flow- focus (COFUS) enable millimetre compound emulsions to be produced using a one or two step formation process respectively. The co-flow-focus geometry uses symmetric and curved carrier fluid entrance walls to create a focusing orifice-minima and a carrier flow which aids movement and shaping of the dispersed fluid(s) towards the outlet, whilst maintaining operation in the dripping regime. Precision concentric alignment of these compound emulsions remains one of the greatest challenges. However steps to solve this passively using curved channel modulation to perturbate the emulsion have shown that rapid alignment can be achieved. Issues with satellite droplet formation, repeatability of the emulsion generation and cost are also addressed.

UV-visible-DAD and 1H-NMR spectroscopy data fusion for studying the photodegradation process of azo-dyes using MCR-ALS.

PubMed

Fernández, Cristina; Pilar Callao, M; Larrechi, M Soledad

2013-12-15

The photodegradation process of three azo-dyes - Acid Orange 61, Acid Red 97 and Acid Brown 425 - was monitored simultaneously by ultraviolet-visible spectroscopy with diode array detector (UV-vis-DAD) and (1)H-nuclear magnetic resonance ((1)H-NMR). Multivariate curve resolution-alternating least squares (MCR-ALS) was applied to obtain the concentration and spectral profile of the chemical compounds involved in the process. The analysis of the H-NMR data suggests there are more intermediate compounds than those obtained with the UV-vis-DAD data. The fusion of UV-vis-DAD and the (1)H-NMR signal before the multivariate analysis provides better results than when only one of the two detector signals was used. It was concluded that three degradation products were present in the medium when the three azo-dyes had practically degraded. This study is the first application of UV-vis-DAD and (1)H-NMR spectroscopy data fusion in this field and illustrates its potential as a quick method for evaluating the evolution of the azo-dye photodegradation process. © 2013 Elsevier B.V. All rights reserved.

Use of the Aspergillus oryzae actin gene promoter in a novel reporter system for exploring antifungal compounds and their target genes.

PubMed

Marui, Junichiro; Yoshimi, Akira; Hagiwara, Daisuke; Fujii-Watanabe, Yoshimi; Oda, Ken; Koike, Hideaki; Tamano, Koichi; Ishii, Tomoko; Sano, Motoaki; Machida, Masayuki; Abe, Keietsu

2010-08-01

Demand for novel antifungal drugs for medical and agricultural uses has been increasing because of the diversity of pathogenic fungi and the emergence of drug-resistant strains. Genomic resources for various living species, including pathogenic fungi, can be utilized to develop novel and effective antifungal compounds. We used Aspergillus oryzae as a model to construct a reporter system for exploring novel antifungal compounds and their target genes. The comprehensive gene expression analysis showed that the actin-encoding actB gene was transcriptionally highly induced by benomyl treatment. We therefore used the actB gene to construct a novel reporter system for monitoring responses to cytoskeletal stress in A. oryzae by introducing the actB promoter::EGFP fusion gene. Distinct fluorescence was observed in the reporter strain with minimum background noise in response to not only benomyl but also compounds inhibiting lipid metabolism that is closely related to cell membrane integrity. The fluorescent responses indicated that the reporter strain can be used to screen for lead compounds affecting fungal microtubule and cell membrane integrity, both of which are attractive antifungal targets. Furthermore, the reporter strain was shown to be technically applicable for identifying novel target genes of antifungal drugs triggering perturbation of fungal microtubules or membrane integrity.

Enhanced Neuroplasticity by the Metabolic Enhancer Piracetam Associated with Improved Mitochondrial Dynamics and Altered Permeability Transition Pore Function.

PubMed

Stockburger, Carola; Miano, Davide; Pallas, Thea; Friedland, Kristina; Müller, Walter E

2016-01-01

The mitochondrial cascade hypothesis of dementia assumes mitochondrial dysfunction leading to reduced energy supply, impaired neuroplasticity, and finally cell death as one major pathomechanism underlying the continuum from brain aging over mild cognitive impairment to initial and advanced late onset Alzheimer's disease. Accordingly, improving mitochondrial function has become an important strategy to treat the early stages of this continuum. The metabolic enhancer piracetam has been proposed as possible prototype for those compounds by increasing impaired mitochondrial function and related aspects like mechanisms of neuroplasticity. We here report that piracetam at therapeutically relevant concentrations improves neuritogenesis in the human cell line SH-SY5Y over conditions mirroring the whole spectrum of age-associated cognitive decline. These effects go parallel with improvement of impaired mitochondrial dynamics shifting back fission and fusion balance to the energetically more favorable fusion site. Impaired fission and fusion balance can also be induced by a reduction of the mitochondrial permeability transition pore (mPTP) function as atractyloside which indicates the mPTP has similar effects on mitochondrial dynamics. These changes are also reduced by piracetam. These findings suggest the mPTP as an important target for the beneficial effects of piracetam on mitochondrial function.

Enhanced Neuroplasticity by the Metabolic Enhancer Piracetam Associated with Improved Mitochondrial Dynamics and Altered Permeability Transition Pore Function

PubMed Central

Stockburger, Carola; Miano, Davide; Pallas, Thea; Müller, Walter E.

2016-01-01

The mitochondrial cascade hypothesis of dementia assumes mitochondrial dysfunction leading to reduced energy supply, impaired neuroplasticity, and finally cell death as one major pathomechanism underlying the continuum from brain aging over mild cognitive impairment to initial and advanced late onset Alzheimer's disease. Accordingly, improving mitochondrial function has become an important strategy to treat the early stages of this continuum. The metabolic enhancer piracetam has been proposed as possible prototype for those compounds by increasing impaired mitochondrial function and related aspects like mechanisms of neuroplasticity. We here report that piracetam at therapeutically relevant concentrations improves neuritogenesis in the human cell line SH-SY5Y over conditions mirroring the whole spectrum of age-associated cognitive decline. These effects go parallel with improvement of impaired mitochondrial dynamics shifting back fission and fusion balance to the energetically more favorable fusion site. Impaired fission and fusion balance can also be induced by a reduction of the mitochondrial permeability transition pore (mPTP) function as atractyloside which indicates the mPTP has similar effects on mitochondrial dynamics. These changes are also reduced by piracetam. These findings suggest the mPTP as an important target for the beneficial effects of piracetam on mitochondrial function. PMID:27747106

The biosynthetic gene cluster for the cyanogenic glucoside dhurrin in Sorghum bicolor contains its co-expressed vacuolar MATE transporter

PubMed Central

Darbani, Behrooz; Motawia, Mohammed Saddik; Olsen, Carl Erik; Nour-Eldin, Hussam H.; Møller, Birger Lindberg; Rook, Fred

2016-01-01

Genomic gene clusters for the biosynthesis of chemical defence compounds are increasingly identified in plant genomes. We previously reported the independent evolution of biosynthetic gene clusters for cyanogenic glucoside biosynthesis in three plant lineages. Here we report that the gene cluster for the cyanogenic glucoside dhurrin in Sorghum bicolor additionally contains a gene, SbMATE2, encoding a transporter of the multidrug and toxic compound extrusion (MATE) family, which is co-expressed with the biosynthetic genes. The predicted localisation of SbMATE2 to the vacuolar membrane was demonstrated experimentally by transient expression of a SbMATE2-YFP fusion protein and confocal microscopy. Transport studies in Xenopus laevis oocytes demonstrate that SbMATE2 is able to transport dhurrin. In addition, SbMATE2 was able to transport non-endogenous cyanogenic glucosides, but not the anthocyanin cyanidin 3-O-glucoside or the glucosinolate indol-3-yl-methyl glucosinolate. The genomic co-localisation of a transporter gene with the biosynthetic genes producing the transported compound is discussed in relation to the role self-toxicity of chemical defence compounds may play in the formation of gene clusters. PMID:27841372

Sensor fusion in identified visual interneurons.

PubMed

Parsons, Matthew M; Krapp, Holger G; Laughlin, Simon B

2010-04-13

Animal locomotion often depends upon stabilization reflexes that use sensory feedback to maintain trajectories and orientation. Such stabilizing reflexes are critically important for the blowfly, whose aerodynamic instability permits outstanding maneuverability but increases the demands placed on flight control. Flies use several sensory systems to drive reflex responses, and recent studies have provided access to the circuitry responsible for combining and employing these sensory inputs. We report that lobula plate VS neurons combine inputs from two optical sensors, the ocelli and the compound eyes. Both systems deliver essential information on in-flight rotations, but our neuronal recordings reveal that the ocelli encode this information in three axes, whereas the compound eyes encode in nine. The difference in dimensionality is reconciled by tuning each VS neuron to the ocellar axis closest to its compound eye axis. We suggest that this simple projection combines the speed of the ocelli with the accuracy of the compound eyes without compromising either. Our findings also support the suggestion that the coordinates of sensory information processing are aligned with axes controlling the natural modes of the fly's flight to improve the efficiency with which sensory signals are transformed into appropriate motor commands.

Conversion of radioactive ferrocyanide compounds to immobile glasses

DOEpatents

Schulz, Wallace W.; Dressen, A. Louise

1977-04-26

Complex radioactive ferrocyanide compounds result from the scavenging of cesium from waste products produced in the chemical reprocessing of nuclear fuel. These ferrocyanides, in accordance with this process, are converted to an immobile glass, resistant to leaching by water, by fusion together with sodium carbonate and a mixture of (a) basalt and boron trioxide (B.sub.2 O.sub.3) or (b) silica (SiO.sub.2) and lime (CaO).

Generation of a strong core centering force in a submillimeter compound droplet system

NASA Technical Reports Server (NTRS)

Lee, M. C.; Feng, I. A.; Elleman, D. D.; Wang, T. G.; Young, A. T.

1982-01-01

By amplitude-modulating the driving voltage of an acoustic levitating apparatus, a strong core centering force was generated in a submillimeter compound droplet system suspended by the radiation pressure in a gaseous medium. Depending on the acoustic characteristics of the droplet system, it was found that the technique can be utilized advantageously in the multiple-layer coating of an inertial confinement fusion pellet.

Nuclear science experiments with a bright neutron source from fusion reactions on the OMEGA Laser System

NASA Astrophysics Data System (ADS)

Forrest, C. J.; Knauer, J. P.; Schroeder, W. U.; Glebov, V. Yu.; Radha, P. B.; Regan, S. P.; Sangster, T. C.; Sickles, M.; Stoeckl, C.; Szczepanski, J.

2018-04-01

Subnanosecond impulses of 1013 to 1014 neutrons, produced in direct-drive laser inertial confinement fusion implosions, have been used to irradiate deuterated targets at the OMEGA Laser System (Boehly et al., 1997). The target compounds include heavy water (D2O) and deuterated benzene (C6D6). Yields and energy spectra of neutrons from D(n,2n)p to study the breakup reaction have been measured at a forward angle of θlab = 3 .5∘ ± 3.5° with a sensitive, high-dynamic-range neutron time-of-flight spectrometer to infer the double-differential breakup cross section d2 σ/dE d Ω for 14-MeV D-T fusion neutrons.

Mass and angular distributions of the reaction products in heavy ion collisions

NASA Astrophysics Data System (ADS)

Nasirov, A. K.; Giardina, G.; Mandaglio, G.; Kayumov, B. M.; Tashkhodjaev, R. B.

2018-05-01

The optimal reactions and beam energies leading to synthesize superheavy elements is searched by studying mass and angular distributions of fission-like products in heavy-ion collisions since the evaporation residue cross section consists an ignorable small part of the fusion cross section. The intensity of the yield of fission-like products allows us to estimate the probability of the complete fusion of the interacting nuclei. The overlap of the mass and angular distributions of the fusion-fission and quasifission products causes difficulty at estimation of the correct value of the probability of the compound nucleus formation. A study of the mass and angular distributions of the reaction products is suitable key to understand the interaction mechanism of heavy ion collisions.

The discovery of 1,2,3,9b-tetrahydro-5H-imidazo[2,1-a]isoindol-5-ones as a new class of respiratory syncytial virus (RSV) fusion inhibitors. Part 1.

PubMed

Bond, Silas; Draffan, Alistair G; Fenner, Jennifer E; Lambert, John; Lim, Chin Yu; Lin, Bo; Luttick, Angela; Mitchell, Jeffrey P; Morton, Craig J; Nearn, Roland H; Sanford, Vanessa; Stanislawski, Pauline C; Tucker, Simon P

2015-02-15

Respiratory syncytial virus (RSV) is a major cause of respiratory tract infections in infants, young children and adults. Compound 1a (9b-(4-chlorophenyl)-1-(4-fluorobenzoyl)-1,2,3,9b-tetrahydro-5H-imidazo[2,1-a]isoindol-5-one) was identified as an inhibitor of A and B strains of RSV targeting the fusion glycoprotein. SAR was developed by systematic exploration of the phenyl (R(1)) and benzoyl (R(2)) groups. Furthermore, introduction of a nitrogen at the 8-position of the tricyclic core resulted in active analogues with improved properties (aqueous solubility, protein binding and logD) and excellent rat pharmacokinetics (e.g., rat oral bioavailability of 89% for compound 17). Copyright © 2014 Elsevier Ltd. All rights reserved.

Precipitation behavior of σ phase in fusion zone of dissimilar stainless steel welds during multi-pass GTAW process

NASA Astrophysics Data System (ADS)

Hsieh, Chih-Chun; Chang, Tao-Chih; Lin, Dong-Yih; Chen, Ming-Che; Wu, Weite

2007-10-01

The purpose of this study is to investigate the precipitation characteristics of σ phase in the fusion zone of stainless steel welds at various welding passes during a tungsten are welding (GTAW) process. The morphology, quantity, and chemical composition of the δ-ferrite and σ phase were analyzed using optical microscopy (OM), a ferritscope (FS), a X-ray diffractometer (XRD), scanning electron microscopy (SEM), an electron probe micro-analyzer (EPMA), and a wavelength dispersive spectrometer (WDS), respectively. Massive δ-ferrite was observed in the fusion zone of the first pass welds during welding of dissimilar stainless steels. The σ phase precipitated at the inner δ-ferrite particles and decreased δ-ferrite content during the third pass welding. The σ and δ phases can be stabilized by Si element, which promoted the phase transformation of σ→ϱ+λ2 in the fusion zone of the third pass welds. It was found that the σ phase was a Fe-Cr-Si intermetallic compound found in the fusion zone of the third pass welds during multi-pass welding.

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

A sensitive assay using a native protein substrate for screening HIV-1 maturation inhibitors targeting the protease cleavage site between the matrix and capsid.

PubMed

Lee, Sook-Kyung; Cheng, Nancy; Hull-Ryde, Emily; Potempa, Marc; Schiffer, Celia A; Janzen, William; Swanstrom, Ronald

2013-07-23

The matrix/capsid processing site in the HIV-1 Gag precursor is likely the most sensitive target to inhibit HIV-1 replication. We have previously shown that modest incomplete processing at the site leads to a complete loss of virion infectivity. In the study presented here, a sensitive assay based on fluorescence polarization that can monitor cleavage at the MA/CA site in the context of the folded protein substrate is described. The substrate, an MA/CA fusion protein, was labeled with the fluorescein-based FlAsH (fluorescein arsenical hairpin) reagent that binds to a tetracysteine motif (CCGPCC) that was introduced within the N-terminal domain of CA. By limiting the size of CA and increasing the size of MA (with an N-terminal GST fusion), we were able to measure significant differences in polarization values as a function of HIV-1 protease cleavage. The sensitivity of the assay was tested in the presence of increasing amounts of an HIV-1 protease inhibitor, which resulted in a gradual decrease in the fluorescence polarization values demonstrating that the assay is sensitive in discerning changes in protease processing. The high-throughput screening assay validation in 384-well plates showed that the assay is reproducible and robust with an average Z' value of 0.79 and average coefficient of variation values of <3%. The robustness and reproducibility of the assay were further validated using the LOPAC(1280) compound library, demonstrating that the assay provides a sensitive high-throughput screening platform that can be used with large compound libraries for identifying novel maturation inhibitors targeting the MA/CA site of the HIV-1 Gag polyprotein.

Zirconium vanadium chromium alloy

DOEpatents

Mendelsohn, M.H.; Gruen, D.M.

1980-10-14

A ternary intermetallic compound having the formula Zr(V/sub 1-x/Cr/sub x/)/sub 2/ where x is in the range of 0.01 to 0.90 is capable of reversibly sorbing hydrogen at temperatures ranging from room temperature to 200/sup 0/C, at pressures down to 10/sup -6/ torr. The compound is suitable for use as a hydrogen getter in low pressure, high temperature applications such as magnetic confinement fusion devices.

The mixture of "ecstasy" and its metabolites impairs mitochondrial fusion/fission equilibrium and trafficking in hippocampal neurons, at in vivo relevant concentrations.

PubMed

Barbosa, Daniel José; Serrat, Romàn; Mirra, Serena; Quevedo, Martí; de Barreda, Elena Goméz; Àvila, Jesús; Ferreira, Luísa Maria; Branco, Paula Sério; Fernandes, Eduarda; Lourdes Bastos, Maria de; Capela, João Paulo; Soriano, Eduardo; Carvalho, Félix

2014-06-01

3,4-Methylenedioxymethamphetamine (MDMA; "ecstasy") is a potentially neurotoxic recreational drug of abuse. Though the mechanisms involved are still not completely understood, formation of reactive metabolites and mitochondrial dysfunction contribute to MDMA-related neurotoxicity. Neuronal mitochondrial trafficking, and their targeting to synapses, is essential for proper neuronal function and survival, rendering neurons particularly vulnerable to mitochondrial dysfunction. Indeed, MDMA-associated disruption of Ca(2+) homeostasis and ATP depletion have been described in neurons, thus suggesting possible MDMA interference on mitochondrial dynamics. In this study, we performed real-time functional experiments of mitochondrial trafficking to explore the role of in situ mitochondrial dysfunction in MDMA's neurotoxic actions. We show that the mixture of MDMA and six of its major in vivo metabolites, each compound at 10μM, impaired mitochondrial trafficking and increased the fragmentation of axonal mitochondria in cultured hippocampal neurons. Furthermore, the overexpression of mitofusin 2 (Mfn2) or dynamin-related protein 1 (Drp1) K38A constructs almost completely rescued the trafficking deficits caused by this mixture. Finally, in hippocampal neurons overexpressing a Mfn2 mutant, Mfn2 R94Q, with impaired fusion and transport properties, it was confirmed that a dysregulation of mitochondrial fission/fusion events greatly contributed to the reported trafficking phenotype. In conclusion, our study demonstrated, for the first time, that the mixture of MDMA and its metabolites, at concentrations relevant to the in vivo scenario, impaired mitochondrial trafficking and increased mitochondrial fragmentation in hippocampal neurons, thus providing a new insight in the context of "ecstasy"-induced neuronal injury.

Functional imaging: monitoring heme oxygenase-1 gene expression in vivo

NASA Astrophysics Data System (ADS)

Zhang, Weisheng; Reilly-Contag, Pamela; Stevenson, David K.; Contag, Christopher H.

1999-07-01

The regulation of genetic elements can be monitored in living animals using photoproteins as reporters. Heme oxygenase (HO) is the key catabolic enzyme in the heme degradation pathway. Here, HO expression serves as a model for in vivo functional imaging of transcriptional regulation of a clinically relevant gene. HO enzymatic activity is inhibited by heme analogs, metalloporphyrins, but many members of this family of compounds also activate transcription of the HO-1 promoter. The degree of transcriptional activation by twelve metalloporphyrins, differing at the central metal and porphyrin ring substituents, was evaluated in both NIH 3T3 stable lines and transgenic animals containing HO-1 promoter-luciferase gene fusions. In the correlative cell culture assays, the metalloporphyrins increased transcription form the full length HO promoter fusion to varying degrees, but none increased transcription from a truncated HO-1 promoter. These results suggested that one or both of the two distal enhancer elements located at -4 and -10 Kb upstream from transcriptional start are required for HO-1 induction by heme and its analogs. The full-length HO-1-luc fusion was then evaluated as a transgene in mice. It was possible to monitor the effects of the metalloporphyrins, SnMP and ZnPP, in living animals over time. This spatiotemporal analyses of gene expression in vivo implied that alterations in porphyrin ring substituents and the central metal may affect the extent of gene activation. These data further indicate that using photoprotein reporters, subtle differences in gene expression can be monitored in living animals.

Oxygen stabilized zirconium-vanadium-iron alloy

DOEpatents

Mendelsohn, Marshall H.; Gruen, Dieter M.

1982-01-01

An oxygen stabilized intermetallic compound having the formula (Zr.sub.1-x Ti.sub.x).sub.2-u (V.sub.1-y Fe.sub.y)O.sub.z where x=0.0 to 0.9, y=0.01 to 0.9, z=0.25 to 0.5 and u=0 to 1. The compound is capable of reversibly sorbing hydrogen at temperatures from -196.degree. C. to 200.degree. C. at pressures down to 10.sup.-6 torr. The compound is suitable for use as a hydrogen getter in low pressure, high temperature applications such as magnetic confinement fusion devices.

Oxygen-stabilized zirconium-vanadium-iron alloy

DOEpatents

Mendelsohn, M.H.; Gruen, D.M.

1981-06-16

An oxygen stabilized intermetallic compound is described which has the formula (Zr/sub 1-x/Ti/sub x/)/sub 2-u/(V/sub 1-y/Fe/sub y/)O/sub z/ where x = 0.0 to 0.9, y = 0.01 to 0.9, z = 0.25 to 0.5 and u = 0 to 1. The compound is capable of reversibly sorbing hydrogen at temperatures from -196/sup 0/C to 200/sup 0/C at pressures down to 10/sup -6/ torr. The compound is suitable for use as a hydrogen getter in low pressure, high temperature applications such as magnetic confinement fusion devices.

Development of Laser Based Plasma Diagnostics for Fusion Research on NSTX-U

NASA Astrophysics Data System (ADS)

Barchfeld, Robert Adam

Worldwide demand for power, and in particular electricity, is growing. Increasing population, expanding dependence on electrical devices, as well as the development of emerging nations, has created significant challenges for the power production. Compounding the issue are concerns over pollution, natural resource supplies, and political obstacles in troubled parts of the world. Many believe that investment in renewable energy will solve the expected energy crisis; however, renewable energy has many shortfalls. Consequently, additional sources of energy should be explored to provide the best options for the future. Electricity from fusion power offers many advantages over competing technologies. It can potentially produce large amounts of clean energy, without the serious concerns of fission power plant safety and nuclear waste. Fuel supplies for fusion are plentiful. Fusion power plants can be operated as needed, without dependence on location, or local conditions. However, there are significant challenges before fusion can be realized. Many factors currently limit the effectiveness of fusion power, which prevents a commercial power plant from being feasible. Scientists in many countries have built, and operate, experimental fusion plants to study the fusion process. The leading examples are magnetic confinement reactors known as tokamaks. At present, reactor gain is near unity, where the fusion power output is nearly the same as the power required to operate the reactor. A tenfold increase in gain is what reactors such as ITER hope to achieve, where 50 MW will be used for plasma heating, magnetic fields, and so forth, with a power output of 500 MW. Before this can happen, further research is required. Loss of particle and energy confinement is a principal cause of low performance; therefore, increasing confinement time is key. There are many causes of thermal and particle transport that are being researched, and the prime tools for conducting this research are plasma diagnostics. Plasma diagnostics collect data from fusion reactors in a number of different ways. Among these are far infrared (FIR) laser based systems. By probing a fusion plasma with FIR lasers, many properties can be measured, such as density and density fluctuations. This dissertation discusses the theory and design of two laser based diagnostic instruments: 1) the Far Infrared Tangential Interferometer and Polarimeter (FIReTIP) systems, and 2) the High-ktheta Scattering System. Both of these systems have been designed and fabricated at UC Davis for use on the National Spherical Torus Experiment - Upgrade (NSTX-U), located at Princeton Plasma Physics Laboratory (PPPL). These systems will aid PPPL scientists in fusion research. The FIReTIP system uses 119 ?m methanol lasers to pass through the plasma core to measure a chord averaged plasma density through interferometry. It can also measure the toroidal magnetic field strength by the way of polarimetery. The High-ktheta Scattering System uses a 693 GHz formic acid laser to measure electron scale turbulence. Through collective Thomson scattering, as the probe beam passes through the plasma, collective electron motion will scatter power to a receiver with the angle determined by the turbulence wavenumber. This diagnostic will measure ktheta from 7 to 40 cm-1 with a 4-channel receiver array. The High-ktheta Scattering system was designed to facilitate research on electron temperature gradient (ETG) modes, which are believed to be a major contributor to anomalous transport on NSTX-U. The design and testing of these plasma diagnostics are described in detail. There are a broad range of components detailed including: optically pumped gas FIR lasers, overmoded low loss waveguide, launching and receiving optical designs, quasi-optical mixers, electronics, and monitoring and control systems. Additionally, details are provided for laser maintenance, alignment techniques, and the fundamentals of nano-CNC-machining.

Fusion-fission and quasifission of superheavy systems with Z =110 -116 formed in 48Ca-induced reactions

NASA Astrophysics Data System (ADS)

Kozulin, E. M.; Knyazheva, G. N.; Itkis, I. M.; Itkis, M. G.; Bogachev, A. A.; Chernysheva, E. V.; Krupa, L.; Hanappe, F.; Dorvaux, O.; Stuttgé, L.; Trzaska, W. H.; Schmitt, C.; Chubarian, G.

2014-11-01

Background: In heavy-ion-induced reactions the mechanism leading to the formation of the compound nucleus and the role of quasifission is still not clear. Purpose: Investigation of the quasifission process of superheavy composite systems with Z =110 -116 and comparison with properties of fusion-fission and quasifission of lighter composite systems. Method: Mass and energy distributions of fissionlike fragments formed in the reactions 48Ca+232Th, 238U , 244Pu , and 248Cm at energies near the Coulomb barrier have been measured using the double-arm time-of-flight spectrometer CORSET at the U-400 cyclotron of the FLNR JINR. Results: The most probable fragment masses as well as total kinetic energies and their dispersions in dependence on the interaction energies and ion-target combinations have been studied for asymmetric and symmetric fragments formed in the reactions. The capture cross sections were obtained for the reactions 48Ca+244Pu and 248Cm . The lower limits for fission barriers of 283 -286Cn , 289 -292Fl , and 293 -296Lv compound nuclei were estimated. Conclusions: Analysis of the properties of symmetric fragments has shown that a significant part of these fragments may be attributed to fusion-fission process for the reactions 48Ca +238U , 244Pu , and 248Cm .

Engineering Herbicide Metabolism in Tobacco and Arabidopsis with CYP76B1, a Cytochrome P450 Enzyme from Jerusalem Artichoke1

PubMed Central

Didierjean, Luc; Gondet, Laurence; Perkins, Roberta; Lau, Sze-Mei Cindy; Schaller, Hubert; O'Keefe, Daniel P.; Werck-Reichhart, Danièle

2002-01-01

The Jerusalem artichoke (Helianthus tuberosus) xenobiotic inducible cytochrome P450, CYP76B1, catalyzes rapid oxidative dealkylation of various phenylurea herbicides to yield nonphytotoxic metabolites. We have found that increased herbicide metabolism and tolerance can be achieved by ectopic constitutive expression of CYP76B1 in tobacco (Nicotiana tabacum) and Arabidopsis. Transformation with CYP76B1 conferred on tobacco and Arabidopsis a 20-fold increase in tolerance to linuron, a compound detoxified by a single dealkylation, and a 10-fold increase in tolerance to isoproturon or chlortoluron, which need successive catalytic steps for detoxification. Two constructs for expression of translational fusions of CYP76B1 with P450 reductase were prepared to test if they would yield even greater herbicide tolerance. Plants expressing these constructs had lower herbicide tolerance than CYP76B1 alone, which is apparently a consequence of reduced stability of the fusion proteins. In all cases, increased herbicide tolerance results from more extensive metabolism, as demonstrated with exogenously fed phenylurea. Beside increased herbicide tolerance, expression of CYP76B1 has no other visible phenotype in the transgenic plants. Our data indicate that CYP76B1 can function as a selectable marker for plant transformation, allowing efficient selection in vitro and in soil-grown plants. Plants expressing CYP76B1 may also be a potential tool for phytoremediation of contaminated sites. PMID:12226498

Dissection of the Role of the Stable Signal Peptide of the Arenavirus Envelope Glycoprotein in Membrane Fusion

PubMed Central

Messina, Emily L.; York, Joanne

2012-01-01

The arenavirus envelope glycoprotein (GPC) retains a stable signal peptide (SSP) as an essential subunit in the mature complex. The 58-amino-acid residue SSP comprises two membrane-spanning hydrophobic regions separated by a short ectodomain loop that interacts with the G2 fusion subunit to promote pH-dependent membrane fusion. Small-molecule compounds that target this unique SSP-G2 interaction prevent arenavirus entry and infection. The interaction between SSP and G2 is sensitive to the phylogenetic distance between New World (Junín) and Old World (Lassa) arenaviruses. For example, heterotypic GPC complexes are unable to support virion entry. In this report, we demonstrate that the hybrid GPC complexes are properly assembled, proteolytically cleaved, and transported to the cell surface but are specifically defective in their membrane fusion activity. Chimeric SSP constructs reveal that this incompatibility is localized to the first transmembrane segment of SSP (TM1). Genetic changes in TM1 also affect sensitivity to small-molecule fusion inhibitors, generating resistance in some cases and inhibitor dependence in others. Our studies suggest that interactions of SSP TM1 with the transmembrane domain of G2 may be important for GPC-mediated membrane fusion and its inhibition. PMID:22438561

Anomalous anisotropies of fission fragments in near- and sub-barrier fusion-fussion reactions

NASA Astrophysics Data System (ADS)

Huanqiao, Zhang; Zuhua, Liu; Jincheng, Xu; Jun, Lu; Ming, Ruan; Kan, Xu

1992-03-01

Fission cross sections and angular distributions have been measured for the reactions of 16O + 232Th and238U, and19F + 208Pb and232Th at near- and sub-barrier energies. The fission excitation functions are rather well reproduced on the basis of Wong model or coupled channels theory. However, the models which reproduce the sub-barrier fusion cross sections fail to account for the experimental anisotropies of fission fragments. It is found that the observed anisotropies are much larger than expected. For the first time it has been observed that the anisotropies as a function of the center-of-mass energy show a peak centered near 4.5 MeV below the fusion barrier for several reaction systems. The present approaches fail to explain these anomalies. For 19F + 208Pb systems, our results confirm the prediction of an approximately constant value for the mean square spin of the compound nucleus produced in far sub-barrier fusion reaction.

Novel Design Strategy for Checkpoint Kinase 2 Inhibitors Using Pharmacophore Modeling, Combinatorial Fusion, and Virtual Screening

PubMed Central

Wang, Yen-Ling

2014-01-01

Checkpoint kinase 2 (Chk2) has a great effect on DNA-damage and plays an important role in response to DNA double-strand breaks and related lesions. In this study, we will concentrate on Chk2 and the purpose is to find the potential inhibitors by the pharmacophore hypotheses (PhModels), combinatorial fusion, and virtual screening techniques. Applying combinatorial fusion into PhModels and virtual screening techniques is a novel design strategy for drug design. We used combinatorial fusion to analyze the prediction results and then obtained the best correlation coefficient of the testing set (r test) with the value 0.816 by combining the BesttrainBesttest and FasttrainFasttest prediction results. The potential inhibitors were selected from NCI database by screening according to BesttrainBesttest + FasttrainFasttest prediction results and molecular docking with CDOCKER docking program. Finally, the selected compounds have high interaction energy between a ligand and a receptor. Through these approaches, 23 potential inhibitors for Chk2 are retrieved for further study. PMID:24864236

Dynamics of 17F + 58Ni reaction via complete and incomplete fusion processes at above barrier energies

NASA Astrophysics Data System (ADS)

Grover, Neha; Sandhu, Kirandeep; Sharma, Manoj K.

2018-06-01

The dynamics of 17F + 58Ni reaction induced via a loosely bound projectile (17F) is examined using the collective clusterization approach of the dynamical cluster decay model (DCM) with respect to the recent experimental data available at beam energies Ebeam = 54.1 and 58.5 MeV. The calculations are done for quadrupole deformations of fragments using the optimum orientation approach. In view of the loosely bound nature of 17F, the main focus of the present work is on the comparison of complete and incomplete fusion. It is studied using various components such as fragmentation potential, mass distribution, and barrier modification. Different decay modes (ER, IMF, HMF, and fission) are also compared to determine the complete fusion and incomplete fusion paths. Additionally, the decay paths of the nucleus formed from loosely bound (17F) and tightly bound (16O) projectiles are compared. Furthermore, the role of temperature-dependent pairing strength is analyzed in terms of the binary fragmentation of the compound system formed.

Technology of welding aluminum alloys-IV

NASA Technical Reports Server (NTRS)

Ginez, R.; Lewis, J. R.; Millett, A. U.; Saenger, K. A.; Skelly, J. K.; Standiford, V. E.; Whiteman, J. O.

1978-01-01

Skate-weld carriage and track assembly were developed for controlled fusion welding on compound-curvature surfaces. Unlike fixed-position carriage used for vertical, horizontal, and circumferential welding, carriage has suspension system that permits angular positioning of weld head on carriage. It also has carriage-and-drive track mechanism capable of traveling over compound curvatures. Carriage is designed with universal mounting platform so that slim tools, weld heads, or X-ray units can be interchanged without need for realinement.

Method of gettering hydrogen under conditions of low pressure

DOEpatents

Mendelsohn, M.H.; Gruen, D.M.

1983-08-09

A ternary intermetallic compound having the formula Zr(V[sub 1[minus]x]Cr[sub x])[sub 2] where x is in the range of 0.01 to 0.90 is capable of reversibly sorbing hydrogen at temperatures ranging from room temperature to 200 C, at pressures down to 10[sup [minus]6] Torr. The compound is suitable for use as a hydrogen getter in low pressure, high temperature applications such as magnetic confinement fusion devices. 3 figs.

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

Virginia Finley

The results of the 1999 environmental surveillance and monitoring program for the Princeton Plasma Physics Laboratory (PPPL) are presented and discussed. The purpose of this report is to provide the U.S. Department of Energy and the public with information on the level of radioactive and non-radioactive pollutants (if any) that are added to the environment as a result of PPPL's operations. The report also summarizes environmental initiatives, assessments, and programs that were undertaken in 1999. The Princeton Plasma Physics Laboratory has engaged in fusion energy research since 1951. The long-range goal of the U.S. Magnetic Fusion Energy Research Program ismore » to create innovations to make fusion power a practical reality--an alternative energy source. 1999 marked the first year of National Spherical Torus Experiment (NSTX) operations and Tokamak Fusion Test Reactor (TFTR) dismantlement and deconstruction activities. A collaboration among fourteen national laboratories, universities, and research institutions, the NSTX is a major element in the U.S. Fusion Energy Sciences Program. It has been designed to test the physics principles of spherical torus (ST) plasmas. The ST concept could play an important role in the development of smaller, more economical fusion reactors. With its completion within budget and ahead of its target schedule, NSTX first plasma occurred on February 12, 1999. The 1999 performance of the Princeton Plasma Physics Laboratory was rated ''outstanding'' by the U.S. Department of Energy in the Laboratory Appraisal report issued early in 2000. The report cited the Laboratory's consistently excellent scientific and technological achievements, its successful management practices, and included high marks in a host of other areas including environmental management, employee health and safety, human resources administration, science education, and communications. Groundwater investigations continued under a voluntary agreement with the New Jersey Department of Environmental Protection. PPPL monitored for the presence of non-radiological contaminants, mainly volatile organic compounds (components of degreasing solvents). Monitoring revealed the presence of low levels of volatile organic compounds in an area adjacent to PPPL. Also, PPPL's radiological monitoring program characterized the ambient, background levels of tritium in the environment and from the TFTR stack; the data are presented in this report.« less

Experimental Solubility Approach to Determine PDMS-Water Partition Constants and PDMS Activity Coefficients.

PubMed

Grant, Sharon; Schacht, Veronika J; Escher, Beate I; Hawker, Darryl W; Gaus, Caroline

2016-03-15

Freely dissolved aqueous concentration and chemical activity are important determinants of contaminant transport, fate, and toxic potential. Both parameters are commonly quantified using Solid Phase Micro-Extraction (SPME) based on a sorptive polymer such as polydimethylsiloxane (PDMS). This method requires the PDMS-water partition constants, KPDMSw, or activity coefficient to be known. For superhydrophobic contaminants (log KOW >6), application of existing methods to measure these parameters is challenging, and independent measures to validate KPDMSw values would be beneficial. We developed a simple, rapid method to directly measure PDMS solubilities of solid contaminants, SPDMS(S), which together with literature thermodynamic properties was then used to estimate KPDMSw and activity coefficients in PDMS. PDMS solubility for the test compounds (log KOW 7.2-8.3) ranged over 3 orders of magnitude (4.1-5700 μM), and was dependent on compound class. For polychlorinated biphenyls (PCBs) and polychlorinated dibenzo-p-dioxins (PCDDs), solubility-derived KPDMSw increased linearly with hydrophobicity, consistent with trends previously reported for less chlorinated congeners. In contrast, subcooled liquid PDMS solubilities, SPDMS(L), were approximately constant within a compound class. SPDMS(S) and KPDMSw can therefore be predicted for a compound class with reasonable robustness based solely on the class-specific SPDMS(L) and a particular congener's entropy of fusion, melting point, and aqueous solubility.

Comparison of the resulting error in data fusion techniques when used with remote sensing, earth observation, and in-situ data sets for water quality applications

NASA Astrophysics Data System (ADS)

Ziemba, Alexander; El Serafy, Ghada

2016-04-01

Ecological modeling and water quality investigations are complex processes which can require a high level of parameterization and a multitude of varying data sets in order to properly execute the model in question. Since models are generally complex, their calibration and validation can benefit from the application of data and information fusion techniques. The data applied to ecological models comes from a wide range of sources such as remote sensing, earth observation, and in-situ measurements, resulting in a high variability in the temporal and spatial resolution of the various data sets available to water quality investigators. It is proposed that effective fusion into a comprehensive singular set will provide a more complete and robust data resource with which models can be calibrated, validated, and driven by. Each individual product contains a unique valuation of error resulting from the method of measurement and application of pre-processing techniques. The uncertainty and error is further compounded when the data being fused is of varying temporal and spatial resolution. In order to have a reliable fusion based model and data set, the uncertainty of the results and confidence interval of the data being reported must be effectively communicated to those who would utilize the data product or model outputs in a decision making process[2]. Here we review an array of data fusion techniques applied to various remote sensing, earth observation, and in-situ data sets whose domains' are varied in spatial and temporal resolution. The data sets examined are combined in a manner so that the various classifications, complementary, redundant, and cooperative, of data are all assessed to determine classification's impact on the propagation and compounding of error. In order to assess the error of the fused data products, a comparison is conducted with data sets containing a known confidence interval and quality rating. We conclude with a quantification of the performance of the data fusion techniques and a recommendation on the feasibility of applying of the fused products in operating forecast systems and modeling scenarios. The error bands and confidence intervals derived can be used in order to clarify the error and confidence of water quality variables produced by prediction and forecasting models. References [1] F. Castanedo, "A Review of Data Fusion Techniques", The Scientific World Journal, vol. 2013, pp. 1-19, 2013. [2] T. Keenan, M. Carbone, M. Reichstein and A. Richardson, "The model-data fusion pitfall: assuming certainty in an uncertain world", Oecologia, vol. 167, no. 3, pp. 587-597, 2011.

Exposure to monomethylarsonous acid (MMA(III)) leads to altered selenoprotein synthesis in a primary human lung cell model.

PubMed

Meno, Sarah R; Nelson, Rebecca; Hintze, Korry J; Self, William T

2009-09-01

Monomethylarsonous acid (MMA(III)), a trivalent metabolite of arsenic, is highly cytotoxic and recent cell culture studies suggest that it might act as a carcinogen. The general consensus of studies indicates that the cytotoxicity of MMA(III) is a result of increased levels of reactive oxygen species (ROS). A longstanding relationship between arsenic and selenium metabolism has led to the use of selenium as a supplement in arsenic exposed populations, however the impact of organic arsenicals (methylated metabolites) on selenium metabolism is still poorly understood. In this study we determined the impact of exposure to MMA(III) on the regulation of expression of TrxR1 and its activity using a primary lung fibroblast line, WI-38. The promoter region of the gene encoding the selenoprotein thioredoxin reductase 1 (TrxR1) contains an antioxidant responsive element (ARE) that has been shown to be activated in the presence of electrophilic compounds. Results from radiolabeled selenoproteins indicate that exposure to low concentrations of MMA(III) resulted in increased synthesis of TrxR1 in WI-38 cells, and lower incorporation of selenium into other selenoproteins. MMA(III) treatment led to increased mRNA encoding TrxR1 in WI-38 cells, while lower levels of mRNA coding for cellular glutathione peroxidase (cGpx) were detected in exposed cells. Luciferase activity of TrxR1 promoter fusions increased with addition of MMA(III), as did expression of a rat quinone reductase (QR) promoter fusion construct. However, MMA(III) induction of the TRX1 promoter fusion was abrogated when the ARE was mutated, suggesting that this regulation is mediated via the ARE. These results indicate that MMA(III) alters the expression of selenoproteins based on a selective induction of TrxR1, and this response to exposure to organic arsenicals that requires the ARE element.

Excess cholesterol inhibits glucose-stimulated fusion pore dynamics in insulin exocytosis.

PubMed

Xu, Yingke; Toomre, Derek K; Bogan, Jonathan S; Hao, Mingming

2017-11-01

Type 2 diabetes is caused by defects in both insulin sensitivity and insulin secretion. Glucose triggers insulin secretion by causing exocytosis of insulin granules from pancreatic β-cells. High circulating cholesterol levels and a diminished capacity of serum to remove cholesterol from β-cells are observed in diabetic individuals. Both of these effects can lead to cholesterol accumulation in β-cells and contribute to β-cell dysfunction. However, the molecular mechanisms by which cholesterol accumulation impairs β-cell function remain largely unknown. Here, we used total internal reflection fluorescence microscopy to address, at the single-granule level, the role of cholesterol in regulating fusion pore dynamics during insulin exocytosis. We focused particularly on the effects of cholesterol overload, which is relevant to type 2 diabetes. We show that excess cholesterol reduced the number of glucose-stimulated fusion events, and modulated the proportion of full fusion and kiss-and-run fusion events. Analysis of single exocytic events revealed distinct fusion kinetics, with more clustered and compound exocytosis observed in cholesterol-overloaded β-cells. We provide evidence for the involvement of the GTPase dynamin, which is regulated in part by cholesterol-induced phosphatidylinositol 4,5-bisphosphate enrichment in the plasma membrane, in the switch between full fusion and kiss-and-run fusion. Characterization of insulin exocytosis offers insights into the role that elevated cholesterol may play in the development of type 2 diabetes. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Melting properties of Pt and its transport coefficients in liquid states under high pressures

NASA Astrophysics Data System (ADS)

Wang, Pan-Pan; Shao, Ju-Xiang; Cao, Qi-Long

2016-11-01

Molecular dynamics (MD) simulations of the melting and transport properties in liquid states of platinum for the pressure range (50-200 GPa) are reported. The melting curve of platinum is consistent with previous ab initio MD simulation results and the first-principles melting curve. Calculated results for the pressure dependence of fusion entropy and fusion volume show that the fusion entropy and the fusion volume decrease with increasing pressure, and the ratio of the fusion volume to fusion entropy roughly reproduces the melting slope, which has a moderate decrease along the melting line. The Arrhenius law well describes the temperature dependence of self-diffusion coefficients and viscosity under high pressure, and the diffusion activation energy decreases with increasing pressure, while the viscosity activation energy increases with increasing pressure. In addition, the entropy-scaling law, proposed by Rosenfeld under ambient pressure, still holds well for liquid Pt under high pressure conditions.

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

Statistical and dynamical modeling of heavy-ion fusion-fission reactions

NASA Astrophysics Data System (ADS)

Eslamizadeh, H.; Razazzadeh, H.

2018-02-01

A modified statistical model and a four dimensional dynamical model based on Langevin equations have been used to simulate the fission process of the excited compound nuclei 207At and 216Ra produced in the fusion 19F + 188Os and 19F + 197Au reactions. The evaporation residue cross section, the fission cross section, the pre-scission neutron, proton and alpha multiplicities and the anisotropy of fission fragments angular distribution have been calculated for the excited compound nuclei 207At and 216Ra. In the modified statistical model the effects of spin K about the symmetry axis and temperature have been considered in calculations of the fission widths and the potential energy surfaces. It was shown that the modified statistical model can reproduce the above mentioned experimental data by using appropriate values of the temperature coefficient of the effective potential equal to λ = 0.0180 ± 0.0055, 0.0080 ± 0.0030 MeV-2 and the scaling factor of the fission barrier height equal to rs = 1.0015 ± 0.0025, 1.0040 ± 0.0020 for the compound nuclei 207At and 216Ra, respectively. Three collective shape coordinates plus the projection of total spin of the compound nucleus on the symmetry axis, K, were considered in the four dimensional dynamical model. In the dynamical calculations, dissipation was generated through the chaos weighted wall and window friction formula. Comparison of the theoretical results with the experimental data showed that two models make it possible to reproduce satisfactorily the above mentioned experimental data for the excited compound nuclei 207At and 216Ra.

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

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

Disruption of the Flnb gene in mice phenocopies the human disease spondylocarpotarsal synostosis syndrome.

PubMed

Farrington-Rock, Claire; Kirilova, Veneta; Dillard-Telm, Lisa; Borowsky, Alexander D; Chalk, Sara; Rock, Matthew J; Cohn, Daniel H; Krakow, Deborah

2008-03-01

Spondylocarpotarsal synostosis syndrome (SCT) is an autosomal recessive disease that is characterized by short stature, and fusions of the vertebrae and carpal and tarsal bones. SCT results from homozygosity or compound heterozygosity for nonsense mutations in FLNB. FLNB encodes filamin B, a multifunctional cytoplasmic protein that plays a critical role in skeletal development. Protein extracts derived from cells of SCT patients with nonsense mutations in FLNB did not contain filamin B, demonstrating that SCT results from absence of filamin B. To understand the role of filamin B in skeletal development, an Flnb-/- mouse model was generated. The Flnb-/- mice were phenotypically similar to individuals with SCT as they exhibited short stature and similar skeletal abnormalities. Newborn Flnb-/- mice had fusions between the neural arches of the vertebrae in the cervical and thoracic spine. At postnatal day 60, the vertebral fusions were more widespread and involved the vertebral bodies as well as the neural arches. In addition, fusions were seen in sternum and carpal bones. Analysis of the Flnb-/- mice phenotype showed that an absence of filamin B causes progressive vertebral fusions, which is contrary to the previous hypothesis that SCT results from failure of normal spinal segmentation. These findings suggest that spinal segmentation can occur normally in the absence of filamin B, but the protein is required for maintenance of intervertebral, carpal and sternal joints, and the joint fusion process commences antenatally.

Computation of Electron Impact Ionization Cross sections of Iron Hydrogen Clusters - Relevance in Fusion Plasmas

NASA Astrophysics Data System (ADS)

Patel, Umang; Joshipura, K. N.

2017-04-01

Plasma-wall interaction (PWI) is one of the key issues in nuclear fusion research. In nuclear fusion devices, such as the JET tokamak or the ITER, first-wall materials will be directly exposed to plasma components. Erosion of first-wall materials is a consequence of the impact of hydrogen and its isotopes as main constituents of the hot plasma. Besides the formation of gas-phase atomic species in various charge states, di- and polyatomic molecular species are expected to be formed via PWI processes. These compounds may profoundly disturb the fusion plasma, may lead to unfavorable re-deposition of materials and composites in other areas of the vessel. Interaction between atoms, molecules as well transport of impurities are of interest for modelling of fusion plasma. Qion by electron impact are such process also important in low temperature plasma processing, astrophysics etc. We reported electron impact Qionfor iron hydrogen clusters, FeHn (n = 1 to 10) from ionization threshold to 2000 eV. A semi empirical approach called Complex Scattering Potential - Ionization Contribution (CSP-ic) has been employed for the reported calculation. In context of fusion relevant species Qion were reported for beryllium and its hydrides, tungsten and its oxides and cluster of beryllium-tungsten by Huber et al.. Iron hydrogen clusters are another such species whose Qion were calculated through DM and BEB formalisms, same has been compared with present calculations.

Effect of zoledronic acid in an L6-L7 rabbit spine fusion model.

PubMed

Bransford, Rick; Goergens, Elisabeth; Briody, Julie; Amanat, Negin; Cree, Andrew; Little, David

2007-04-01

Previous studies have shown that zoledronic acid administration can increase mineral content and strength in distraction osteogenesis. Of the few studies that have examined the use of bisphosphonates in spinal arthrodesis, none have assessed the effect of single dose treatment. The objective of this study was to evaluate the feasibility of enhancing spinal fusion rate using single dose zoledronic acid (ZA) to increase fusion-mass size and mineral density. Forty-eight New Zealand white rabbits underwent an L6-L7 intertransverse process fusion. The L6-L7 model is more challenging than the more commonly used level of L5-L6. Animals were randomly allocated to one of three groups, one received iliac crest bone graft alone, one group received iliac crest bone graft with locally administered zoledronic acid, 20 microg, and one group received iliac crest bone graft with a single dose of systemically administered zoledronic acid, 0.1 mg/kg. ZA doses were administered at the time of surgery. Twenty-four rabbits were culled at 6 weeks and 24 rabbits were culled at 12 weeks. Success of spinal fusion was determined by manual palpation. Specimens were evaluated radiographically, underwent quantitative computerised tomography analysis and were tested biomechanically in flexion and extension. In the six-week group, only five of the 24 spines fused with no noticeable trend with respect to treatment. In the 12-week group there was a trend toward increased fusion in the systemically administered ZA group (63%) versus the other two groups (25%) but was not statistically significant (p = 0.15). Radiographically, the local ZA treatment group showed a delay in remodelling with the presence of unremodelled bone chips. The 12-week systemic ZA group exhibited an 86% increase in BMC, a 31% increase in vBMD and a 41% increase in the volume of the fusion-mass (p < 0.05). The 12-week local ZA group also showed significant increases in BMC (69%), vBMD (31%) and total fusion-mass volume (29%) (p < 0.05). Biomechanical testing showed that the range of motion in flexion decreased to 4.5 (+/-2.5) degrees and 4.8 (+/-4.7) degrees for the local and systemic groups respectively compared to 9.6 (+/-4.9) degrees for the control group (p < 0.05). This study has shown that zoledronic acid increased fusion-mass size and bone mineral content. Systemic ZA led to an increased fusion rate; however the fusion rate remained below 100%. We suggest that bisphosphonate treatment may require an anabolic conjunctive therapy to ensure enhanced successful fusion.

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.

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.

Spine surgery in geriatric patients: Sometimes unnecessary, too much, or too little

PubMed Central

Epstein, Nancy E.

2011-01-01

Background: Although the frequency of spinal surgical procedures has been increasing, particularly in patients of age 65 and over (geriatric), multiple overlapping comorbidities increase their risk/complication rates. Nevertheless, sometimes these high-risk geriatric patients are considered for “unnecessary”, too much (instrumented fusions), or too little [minimally invasive surgery (MIS)] spine surgery. Methods: In a review of the literature and reanalysis of data from prior studies, attention was focused on the increasing number of operations offered to geriatric patients, their increased comorbidities, and the offers for “unnecessary” spine fusions, including both major open and MIS procedures. Results: In the literature, the frequency of spine operations, particularly instrumented fusions, has markedly increased in patients of age 65 and older. Specifically, in a 2010 report, a 28-fold increase in anterior discectomy and fusion was observed for geriatric patients. Geriatric patients with more comorbid factors, including diabetes, hypertension, coronary artery disease (prior procedures), depression, and obesity, experience higher postoperative complication rates and costs. Sometimes “unnecessary”, too much (instrumented fusions), and too little (MIS spine) surgeries were offered to geriatric patients, which increased the morbidity. One study observed a 10% complication rate for decompression alone (average age 76.4), a 40% complication rate for decompression/limited fusion (average age 70.4), and a 56% complication rate for full curve fusions (average age 62.5). Conclusions: Increasingly, spine operations in geriatric patients with multiple comorbidities are sometimes “unnecessary”, offer too much surgery (instrumentation), or too little surgery (MIS). PMID:22276241

Novel design strategy for checkpoint kinase 2 inhibitors using pharmacophore modeling, combinatorial fusion, and virtual screening.

PubMed

Lin, Chun-Yuan; Wang, Yen-Ling

2014-01-01

Checkpoint kinase 2 (Chk2) has a great effect on DNA-damage and plays an important role in response to DNA double-strand breaks and related lesions. In this study, we will concentrate on Chk2 and the purpose is to find the potential inhibitors by the pharmacophore hypotheses (PhModels), combinatorial fusion, and virtual screening techniques. Applying combinatorial fusion into PhModels and virtual screening techniques is a novel design strategy for drug design. We used combinatorial fusion to analyze the prediction results and then obtained the best correlation coefficient of the testing set (r test) with the value 0.816 by combining the Best(train)Best(test) and Fast(train)Fast(test) prediction results. The potential inhibitors were selected from NCI database by screening according to Best(train)Best(test) + Fast(train)Fast(test) prediction results and molecular docking with CDOCKER docking program. Finally, the selected compounds have high interaction energy between a ligand and a receptor. Through these approaches, 23 potential inhibitors for Chk2 are retrieved for further study.

Structures of the prefusion form of measles virus fusion protein in complex with inhibitors.

PubMed

Hashiguchi, Takao; Fukuda, Yoshinari; Matsuoka, Rei; Kuroda, Daisuke; Kubota, Marie; Shirogane, Yuta; Watanabe, Shumpei; Tsumoto, Kouhei; Kohda, Daisuke; Plemper, Richard Karl; Yanagi, Yusuke

2018-03-06

Measles virus (MeV), a major cause of childhood morbidity and mortality, is highly immunotropic and one of the most contagious pathogens. MeV may establish, albeit rarely, persistent infection in the central nervous system, causing fatal and intractable neurodegenerative diseases such as subacute sclerosing panencephalitis and measles inclusion body encephalitis. Recent studies have suggested that particular substitutions in the MeV fusion (F) protein are involved in the pathogenesis by destabilizing the F protein and endowing it with hyperfusogenicity. Here we show the crystal structures of the prefusion MeV-F alone and in complex with the small compound AS-48 or a fusion inhibitor peptide. Notably, these independently developed inhibitors bind the same hydrophobic pocket located at the region connecting the head and stalk of MeV-F, where a number of substitutions in MeV isolates from neurodegenerative diseases are also localized. Since these inhibitors could suppress membrane fusion mediated by most of the hyperfusogenic MeV-F mutants, the development of more effective inhibitors based on the structures may be warranted to treat MeV-induced neurodegenerative diseases.

In Silico target fishing: addressing a "Big Data" problem by ligand-based similarity rankings with data fusion.

PubMed

Liu, Xian; Xu, Yuan; Li, Shanshan; Wang, Yulan; Peng, Jianlong; Luo, Cheng; Luo, Xiaomin; Zheng, Mingyue; Chen, Kaixian; Jiang, Hualiang

2014-01-01

Ligand-based in silico target fishing can be used to identify the potential interacting target of bioactive ligands, which is useful for understanding the polypharmacology and safety profile of existing drugs. The underlying principle of the approach is that known bioactive ligands can be used as reference to predict the targets for a new compound. We tested a pipeline enabling large-scale target fishing and drug repositioning, based on simple fingerprint similarity rankings with data fusion. A large library containing 533 drug relevant targets with 179,807 active ligands was compiled, where each target was defined by its ligand set. For a given query molecule, its target profile is generated by similarity searching against the ligand sets assigned to each target, for which individual searches utilizing multiple reference structures are then fused into a single ranking list representing the potential target interaction profile of the query compound. The proposed approach was validated by 10-fold cross validation and two external tests using data from DrugBank and Therapeutic Target Database (TTD). The use of the approach was further demonstrated with some examples concerning the drug repositioning and drug side-effects prediction. The promising results suggest that the proposed method is useful for not only finding promiscuous drugs for their new usages, but also predicting some important toxic liabilities. With the rapid increasing volume and diversity of data concerning drug related targets and their ligands, the simple ligand-based target fishing approach would play an important role in assisting future drug design and discovery.

Exploiting the synergistic effect of concurrent data signals: Low-level fusion of liquid chromatographic with dual detection data.

PubMed

Teglia, Carla M; Azcarate, Silvana M; Alcaráz, Mirta R; Goicoechea, Héctor C; Culzoni, María J

2018-08-15

A low-level data fusion strategy was developed and implemented for data processing of second-order liquid chromatographic data with dual detection, i.e. absorbance and fluorescence monitoring. The synergistic effect of coupling individual information provided by two different detectors was evaluated by analyzing the results gathered after the application of a series of data preprocessing steps and chemometric resolution. The chemometric modeling involved data analysis by MCR-ALS, PARAFAC and N-PLS. Their ability to handle the new data block was assessed through the estimation of the analytical figures of merits achieved in the prediction of a validation set containing fifteen fluorescent and non-fluorescent veterinary active ingredients that can be found in poultry litter. Eventually, the feasibility of the application of the fusion strategy to real poultry litter samples containing the studied compounds was verified. Copyright © 2018 Elsevier B.V. All rights reserved.

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

Muth, Thomas R; Yamamoto, Yukinori; Frederick, David Alan

ORNL undertook an investigation using gas tungsten arc (GTA) welding on consolidated powder metallurgy (PM) titanium (Ti) plate, to identify the causal factors behind observed porosity in fusion welding. Tramp element compounds of sodium and magnesium, residual from the metallothermic reduction of titanium chloride used to produce the titanium, were remnant in the starting powder and were identified as gas forming species. PM-titanium made from revert scrap where sodium and magnesium were absent, showed fusion weld porosity, although to a lesser degree. We show that porosity was attributable to hydrogen from adsorbed water on the surface of the powders priormore » to consolidation. The removal / minimization of both adsorbed water on the surface of titanium powder and the residues from the reduction process prior to consolidation of titanium powders, are critical to achieve equivalent fusion welding success similar to that seen in wrought titanium produced via the Kroll process.« less

Causal Factors of Weld Porosity in Gas Tungsten Arc Welding of Powder-Metallurgy-Produced Titanium Alloys

NASA Astrophysics Data System (ADS)

Muth, T. R.; Yamamoto, Y.; Frederick, D. A.; Contescu, C. I.; Chen, W.; Lim, Y. C.; Peter, W. H.; Feng, Z.

2013-05-01

An investigation was undertaken using gas tungsten arc (GTA) welding on consolidated powder metallurgy (PM) titanium (Ti) plate to identify the causal factors behind observed porosity in fusion welding. Tramp element compounds of sodium and magnesium, residual from the metallothermic reduction of titanium chloride used to produce the titanium, were remnant in the starting powder and were identified as gas-forming species. PM-titanium made from revert scrap, where sodium and magnesium were absent, showed fusion weld porosity, although to a lesser degree. We show that porosity was attributable to hydrogen from adsorbed water on the surface of the powders prior to consolidation. The removal and minimization of both adsorbed water on the surface of titanium powder and the residues from the reduction process prior to consolidation of titanium powders are critical for achieving equivalent fusion welding success similar to that seen in wrought titanium produced via the Kroll process.

Systematic study of the isotopic dependence of fusion dynamics for neutron- and proton-rich nuclei using a proximity formalism

NASA Astrophysics Data System (ADS)

Ghodsi, O. N.; Gharaei, R.; Lari, F.

2012-08-01

The behaviors of barrier characteristics and fusion cross sections are analyzed by changing neutrons over a wide range of colliding systems. For this purpose, we have extended our previous study [Ghodsi and Gharaei, Eur. Phys. J. AEPJAFV1434-600110.1140/epja/i2012-12021-x 48, 21 (2012), it is devoted to the colliding systems with neutron-rich nuclei] to 125 isotopic systems with the condition of 0.5⩽N/Z⩽1.6 for their compound nuclei. The AW 95, Bass 80, Denisov DP, and Prox. 2010 potentials are used to calculate the nuclear part of the interacting potential. The obtained results show that the trend of barrier heights VB and positions RB as well as nuclear VN and Coulomb VC potentials (at R=RB) as a function of (N/Z-1) quantity are nonlinear (second order) whereas the fusion cross sections follow a linear dependence.

Strength and Persistence of Energy-Based Vessel Seals Rely on Tissue Water and Glycosaminoglycan Content.

PubMed

Kramer, Eric A; Cezo, James D; Fankell, Douglas P; Taylor, Kenneth D; Rentschler, Mark E; Ferguson, Virginia L

2016-11-01

Vessel ligation using energy-based surgical devices is steadily replacing conventional closure methods during minimally invasive and open procedures. In exploring the molecular nature of thermally-induced tissue bonds, novel applications for surgical resection and repair may be revealed. This work presents an analysis of the influence of unbound water and hydrophilic glycosaminoglycans on the formation and resilience of vascular seals via: (a) changes in pre-fusion tissue hydration, (b) the enzymatic digestion of glycosaminoglycans (GAGs) prior to fusion and (c) the rehydration of vascular seals following fusion. An 11% increase in pre-fusion unbound water led to an 84% rise in vascular seal strength. The digestion of GAGs prior to fusion led to increases of up to 82% in seal strength, while the rehydration of native and GAG-digested vascular seals decreased strengths by 41 and 44%, respectively. The effects of increased unbound water content prior to fusion combined with the effects of seal rehydration after fusion suggest that the heat-induced displacement of tissue water is a major contributor to tissue adhesion during energy-based vessel sealing. The effects of pre-fusion GAG-digestion on seal integrity indicate that GAGs are inhibitory to the bond formation process during thermal ligation. GAG digestion may allow for increased water transport and protein interaction during the fusion process, leading to the formation of stronger bonds. These findings provide insight into the physiochemical nature of the fusion bond, its potential for optimization in vascular closure and its application to novel strategies for vascular resection and repair.

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

Mitochondrial fusion increases the mitochondrial DNA copy number in budding yeast.

PubMed

Hori, Akiko; Yoshida, Minoru; Ling, Feng

2011-05-01

Mitochondrial fusion plays an important role in mitochondrial DNA (mtDNA) maintenance, although the underlying mechanisms are unclear. In budding yeast, certain levels of reactive oxygen species (ROS) can promote recombination-mediated mtDNA replication, and mtDNA maintenance depends on the homologous DNA pairing protein Mhr1. Here, we show that the fusion of isolated yeast mitochondria, which can be monitored by the bimolecular fluorescence complementation-derived green fluorescent protein (GFP) fluorescence, increases the mtDNA copy number in a manner dependent on Mhr1. The fusion event, accompanied by the degradation of dissociated electron transport chain complex IV and transient reductions in the complex IV subunits by the inner membrane AAA proteases such as Yme1, increases ROS levels. Analysis of the initial stage of mitochondrial fusion in early log-phase cells produced similar results. Moreover, higher ROS levels in mitochondrial fusion-deficient mutant cells increased the amount of newly synthesized mtDNA, resulting in increases in the mtDNA copy number. In contrast, reducing ROS levels in yme1 null mutant cells significantly decreased the mtDNA copy number, leading to an increase in cells lacking mtDNA. Our results indicate that mitochondrial fusion induces mtDNA synthesis by facilitating ROS-triggered, recombination-mediated replication and thereby prevents the generation of mitochondria lacking DNA. © 2011 The Authors. Journal compilation © 2011 by the Molecular Biology Society of Japan/Blackwell Publishing Ltd.

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

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.

Study on reaction mechanism by analysis of kinetic energy spectra of light particles and formation of final products

NASA Astrophysics Data System (ADS)

Giardina, G.; Mandaglio, G.; Nasirov, A. K.; Anastasi, A.; Curciarello, F.; Fazio, G.

2018-05-01

The sensitivity of reaction mechanism in the formation of compound nucleus (CN) by the analysis of kinetic energy spectra of light particles and of reaction products are shown. The dependence of the P CN fusion probability of reactants and W sur survival probability of CN against fission at its deexcitation on the mass and charge symmetries in the entrance channel of heavy-ion collisions, as well as on the neutron numbers is discussed. The possibility of conducting a complex program of investigations of the complete fusion by reliable ways depends on the detailed and refined methods of experimental and theoretical analyses.

Nuclear Fusion Rate Study of a Muonic Molecule via Nuclear Threshold Resonances

NASA Astrophysics Data System (ADS)

Faghihi, F.; Eskandari, M. R.

This work follows our previous calculations of the ground state binding energy, size, and the effective nuclear charge of the muonic T3 molecule, using the Born-Oppenheimer adiabatic approximation. In our past articles, we showed that the system possesses two minimum positions, the first one at the muonic distance and the second at the atomic distance. Also, the symmetric planner vibrational model assumed between the two minima and the approximated potential were calculated. Following from the previous studies, we now calculate the fusion rate of the T3 muonic molecule according to the overlap integral of the resonance nuclear compound nucleus and the molecular wave functions.

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

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

Surface preparation effects on GTA weld shape in JBK-75 stainless steel

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

Campbell, R.D.; Robertson, A.M.; Heiple, C.R.

1993-02-01

The results of a study are reported here on the effects of surface preparation on the shape of autogenous gas tungsten arc (GTA) welds in JBK-75, an austenitic precipitation hardenable stainless steel similar to A286. Minor changes in surface preparation produced substantial changes in the fusion zone shape and welding behavior of this alloy. Increased and more consistent depth of fusion (higher d/w ratios) along with improved arc stability and less arc wander resulted from wire brushing and other abrasive surface preparations, although chemical and machining methods did not produce any increase in depth of fusion. Abrasive treatments roughen themore » surface, increase the surface area, increase the surface oxide thickness, and entrap oxide. The increased weld d/w ratio is attributed to oxygen added to the weld pool from the surface oxide on the base metal. The added oxygen alters the surface-tension-driven fluid flow pattern in the weld pool. Increased depth of fusion in wire-fed U-groove weld joints also resulted when welding wire with a greater surface oxide thickness was used. Increasing the amount of wire brushing produced even deeper welds. However, a maximum in depth of fusion was observed with further wire brushing, beyond which weld fusion depth decreased.« less

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

Virginia L. Finley

The results of the 2000 environmental surveillance and monitoring program for the Princeton Plasma Physics Laboratory (PPPL) are presented and discussed. The purpose of this report is to provide the U.S. Department of Energy and the public with information on the level of radioactive and nonradioactive pollutants (if any) that are added to the environment as a result of PPPL's operations. The report also summarizes environmental initiatives, assessments, and programs that were undertaken in 2000. The Princeton Plasma Physics Laboratory has engaged in fusion energy research since 1951. The long-range goal of the U.S. Magnetic Fusion Energy Research Program ismore » to create innovations to make fusion power a practical reality -- an alternative energy source. The year 2000 marked the second year of National Spherical Torus Experiment (NSTX) operations and Tokamak Fusion Test Reactor (TFTR) dismantlement and deconstruction activities. A collaboration among fourteen national laboratories, universities, and research institutions, the NSTX is a major element in the U.S. Fusion Energy Sciences Program. It has been designed to test the physics principles of spherical torus (ST) plasmas. The ST concept could play an important role in the development of smaller, more economical fusion power plants. With its completion within budget and ahead of its target schedule, NSTX first plasma occurred on February 12, 1999. In 2000, PPPL's radiological environmental monitoring program measured tritium in the air at on-site and off-site sampling stations. PPPL is capable of detecting small changes in the ambient levels of tritium by using highly sensitive monitors. The operation of an in-stack monitor located on D-site is a requirement of the National Emission Standard for Hazardous Air Pollutants (NESHAPs) regulations with limits set by the Environmental Protection Agency (EPA). Also included in PPPL's radiological environmental monitoring program, are precipitation, surface, ground, a nd waste water monitoring. Groundwater investigations continued under a voluntary agreement with the New Jersey Department of Environmental Protection. PPPL monitored for the presence of nonradiological contaminants, mainly volatile organic compounds (components of degreasing solvents). Monitoring revealed the presence of low levels of volatile organic compounds in an area adjacent to PPPL. Also, PPPL's radiological monitoring program characterized the ambient, background levels of tritium in the environment and from the D-site stack; the data are presented in this report.« less

Discovery of imidazopyridine derivatives as highly potent respiratory syncytial virus fusion inhibitors.

PubMed

Feng, Song; Hong, Di; Wang, Baoxia; Zheng, Xiufang; Miao, Kun; Wang, Lisha; Yun, Hongying; Gao, Lu; Zhao, Shuhai; Shen, Hong C

2015-03-12

A series of imidazolepyridine derivatives were designed and synthesized according to the established docking studies. The imidazopyridine derivatives were found to have good potency and physical-chemical properties. Several highly potent compounds such as 8ji, 8jl, and 8jm were identified with single nanomolar activities. The most potent compound 8jm showed an IC50 of 3 nM, lower microsome clearance and no CYP inhibition. The profile of 8jm appeared to be superior to BMS433771, and supported further optimization.

Discovery of Imidazopyridine Derivatives as Highly Potent Respiratory Syncytial Virus Fusion Inhibitors

PubMed Central

2015-01-01

A series of imidazolepyridine derivatives were designed and synthesized according to the established docking studies. The imidazopyridine derivatives were found to have good potency and physical-chemical properties. Several highly potent compounds such as 8ji, 8jl, and 8jm were identified with single nanomolar activities. The most potent compound 8jm showed an IC50 of 3 nM, lower microsome clearance and no CYP inhibition. The profile of 8jm appeared to be superior to BMS433771, and supported further optimization. PMID:25941547

Phenotypic and genotypic characterization of influenza virus mutants selected with the sialidase fusion protein DAS181

PubMed Central

Triana-Baltzer, Gallen B.; Sanders, Rebecca L.; Hedlund, Maria; Jensen, Kellie A.; Aschenbrenner, Laura M.; Larson, Jeffrey L.; Fang, Fang

2011-01-01

Background Influenza viruses (IFVs) frequently achieve resistance to antiviral drugs, necessitating the development of compounds with novel mechanisms of action. DAS181 (Fludase®), a sialidase fusion protein, may have a reduced potential for generating drug resistance due to its novel host-targeting mechanism of action. Methods IFV strains B/Maryland/1/59 and A/Victoria/3/75 (H3N2) were subjected to >30 passages under increasing selective pressure with DAS181. The DAS181-selected IFV isolates were characterized in vitro and in mice. Results Despite extensive passaging, DAS181-selected viruses exhibited a very low level of resistance to DAS181, which ranged between 3- and 18-fold increase in EC50. DAS181-selected viruses displayed an attenuated phenotype in vitro, as exhibited by slower growth, smaller plaque size and increased particle to pfu ratios relative to wild-type virus. Further, the DAS181 resistance phenotype was unstable and was substantially reversed over time upon DAS181 withdrawal. In mice, the DAS181-selected viruses exhibited no greater virulence than their wild-type counterparts. Genotypic and phenotypic analysis of DAS181-selected viruses revealed mutations in the haemagglutinin (HA) and neuraminidase (NA) molecules and also changes in HA and NA function. Conclusions Results indicate that resistance to DAS181 is minimal and unstable. The DAS181-selected IFV isolates exhibit reduced fitness in vitro, likely due to altered HA and NA functions. PMID:21097900

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.

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.

Development of an inducible platform for intercellular protein delivery.

PubMed

Siller, Richard; Dufour, Eric; Lycke, Max; Wilmut, Ian; Jung, Yong-Wook; Park, In Hyun; Sullivan, Gareth J

2017-04-30

A challenge to protein based therapies is the ability to produce biologically active proteins and their ensured delivery. Various approaches have been utilised including fusion of protein transduction domains with a protein or biomolecule of interest. A compounding issue is lack of specificity, efficiency and indeed whether the protein fusions are actually translocated into the cell and not merely an artefact of the fixation process. Here we present a novel platform, allowing the inducible export and uptake of a protein of interest. The system utilises a combination of the Tetracyline repressor system, combined with a fusion protein containing the N-terminal signal peptide from human chorionic gonadotropin beta-subunit, and a C-terminal poly-arginine domain for efficient uptake by target cells. This novel platform was validated using enhanced green fluorescent protein as the gene of interest. Doxycycline efficiently induced expression of the fusion protein. The human chorionic gonadotropin beta-subunit facilitated the export of the fusion protein into the cell culture media. Finally, the fusion protein was able to efficiently enter into neighbouring cells (target cells), mediated by the poly-arginine cell penetrating peptide. Importantly we have addressed the issue of whether the observed uptake is an artefact of the fixation process or indeed genuine translocation. In addition this platform provides a number of potential applications in diverse areas such as stem cell biology, immune therapy and cancer targeting therapies. Copyright © 2017 Elsevier B.V. All rights reserved.

Water consumption and biomass production of protoplast fusion lines of poplar hybrids under drought stress

PubMed Central

Hennig, Anne; Kleinschmit, Jörg R. G.; Schoneberg, Sebastian; Löffler, Sonja; Janßen, Alwin; Polle, Andrea

2015-01-01

Woody crops such as poplars (Populus) can contribute to meet the increasing energy demand of a growing human population and can therefore enhance the security of energy supply. Using energy from biomass increases ecological sustainability as biomass is considered to play a pivotal role in abating climate change. Because areas for establishing poplar plantations are often confined to marginal sites drought tolerance is one important trait for poplar genotypes cultivated in short rotation coppice. We tested 9-month-old plants of four tetraploid Populus tremula (L.) × P. tremuloides (Michx.) lines that were generated by protoplast fusion and their diploid counterpart for water consumption and drought stress responses in a greenhouse experiment. The fusion lines showed equivalent or decreased height growth, stem biomass and total leaf area compared to the diploid line. The relative height increment of the fusion lines was not reduced compared to the diploid line when the plants were exposed to drought. The fusion lines were distinguished from the diploid counterpart by stomatal characteristics such as increased size and lower density. The changes in the stomatal apparatus did not affect the stomatal conductance. When exposed to drought the carbohydrate concentrations increased more strongly in the fusion lines than in the diploid line. Two fusion lines consumed significantly less water with regard to height growth, producing equivalent or increased relative stem biomass under drought compared to their diploid relative. Therefore, these tetraploid fusion lines are interesting candidates for short rotation biomass plantation on dry sites. PMID:26042130

National Trends in Demographics and Outcomes Following Cervical Fusion for Cervical Spondylotic Myelopathy

PubMed Central

Vonck, Caroline E.; Tanenbaum, Joseph E.; Smith, Gabriel A.; Benzel, Edward C.; Mroz, Thomas E.; Steinmetz, Michael P.

2017-01-01

Study Design: Retrospective trends analysis. Objectives: Cervical fusion is a common adjunctive surgical modality used in the treatment of cervical spondylotic myelopathy (CSM). The purpose of this study was to quantify national trends in patient demographics, hospital characteristics, and outcomes in the surgical management of CSM. Methods: This was a retrospective study that used the National Inpatient Sample. The sample included all patients over 18 years of age with a diagnosis of CSM who underwent cervical fusion from 2003 to 2013. The outcome measures were in-hospital mortality, length of stay, and hospital charges. Chi-square tests were performed to compare categorical variables. Independent t tests were performed to compare continuous variables. Results: We identified 62 970 patients with CSM who underwent cervical fusion from 2003 to 2013. The number of fusions performed per year in the treatment of CSM increased from 3879 to 8181. The average age of all fusion patients increased from 58.2 to 60.6 years (P < .001). Length of stay did not change significantly from a mean of 3.7 days. In-hospital mortality decreased from 0.6% to 0.3% (P < .01). Hospital charges increased from $49 445 to $92 040 (P < .001). Conclusions: This study showed a dramatic increase in cervical fusions to treat CSM from 2003 to 2013 concomitant with increasing age of the patient population. Despite increases in average age and number of comorbidities, length of stay remained constant and a decrease in mortality was seen across the study period. However, hospital charges increased dramatically.

A Small Molecule Inhibitor of ETV1, YK-4-279, Prevents Prostate Cancer Growth and Metastasis in a Mouse Xenograft Model

PubMed Central

Rahim, Said; Minas, Tsion; Hong, Sung-Hyeok; Justvig, Sarah; Çelik, Haydar; Kont, Yasemin Saygideger; Han, Jenny; Kallarakal, Abraham T.; Kong, Yali; Rudek, Michelle A.; Brown, Milton L.; Kallakury, Bhaskar; Toretsky, Jeffrey A.; Üren, Aykut

2014-01-01

Background The erythroblastosis virus E26 transforming sequences (ETS) family of transcription factors consists of a highly conserved group of genes that play important roles in cellular proliferation, differentiation, migration and invasion. Chromosomal translocations fusing ETS factors to promoters of androgen responsive genes have been found in prostate cancers, including the most clinically aggressive forms. ERG and ETV1 are the most commonly translocated ETS proteins. Over-expression of these proteins in prostate cancer cells results in a more invasive phenotype. Inhibition of ETS activity by small molecule inhibitors may provide a novel method for the treatment of prostate cancer. Methods and Findings We recently demonstrated that the small molecule YK-4-279 inhibits biological activity of ETV1 in fusion-positive prostate cancer cells leading to decreased motility and invasion in-vitro. Here, we present data from an in-vivo mouse xenograft model. SCID-beige mice were subcutaneously implanted with fusion-positive LNCaP-luc-M6 and fusion-negative PC-3M-luc-C6 tumors. Animals were treated with YK-4-279, and its effects on primary tumor growth and lung metastasis were evaluated. YK-4-279 treatment resulted in decreased growth of the primary tumor only in LNCaP-luc-M6 cohort. When primary tumors were grown to comparable sizes, YK-4-279 inhibited tumor metastasis to the lungs. Expression of ETV1 target genes MMP7, FKBP10 and GLYATL2 were reduced in YK-4-279 treated animals. ETS fusion-negative PC-3M-luc-C6 xenografts were unresponsive to the compound. Furthermore, YK-4-279 is a chiral molecule that exists as a racemic mixture of R and S enantiomers. We established that (S)-YK-4-279 is the active enantiomer in prostate cancer cells. Conclusion Our results demonstrate that YK-4-279 is a potent inhibitor of ETV1 and inhibits both the primary tumor growth and metastasis of fusion positive prostate cancer xenografts. Therefore, YK-4-279 or similar compounds may be evaluated as a potential therapeutic tool for treatment of human prostate cancer at different stages. PMID:25479232

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

Finley, V.L. and Levine, J.D.

The results of the 1997 environmental surveillance and monitoring program for the Princeton Plasma Physics Laboratory (PPPL) are presented and discussed. The purpose of this report is to provide the U.S. Department of Energy and the public with information on the level of radioactive and non-radioactive pollutants, if any, that are added to the environment as a result of PPPL's operations. During Calendar Year 1997, PPPL's Tokamak Fusion Test Reactor (TFTR) completed fifteen years of fusion experiments begun in 1982. Over the course of three and half years of deuterium-tritium (D-T) plasma experiments, PPPL set a world record of 10.7more » million watts of controlled fusion power, more than 700 tritium shots pulsed into the reactor vessel generating more than 5.6 x 10 20 neutron and 1.6 gigajoules of fusion energy and researchers studied plasma science experimental data, which included "enhanced reverse shear techniques." As TFTR was completing its historic operations, PPPL participated with the Oak Ridge National Laboratory, Columbia University, and the University of Washington (Seattle) in a collaboration effort to design the National Spherical Torus Experiment (NSTX). This next device, NSTX, is located in the former TFTR Hot Cell on D site, and it is designed to be a smaller and more economical torus fusion reactor. Construction of this device began in late 1997, and first plasma in scheduled for early 1999. For 1997, the U.S. Department of Energy in its Laboratory Appraisal report rated the overall performance of Princeton Plasma Physics Laboratory as "excellent." The report cited the Laboratory's consistently excellent scientific and technological achievements and its successful management practices, which included high marks for environmental management, employee health and safety, human resources administration, science education, and communications. Groundwater investigations continued under a voluntary agreement with the New Jersey Department of Environmental Protection. PPPL monitored the presence of non-radiological contaminants, mainly volatile organic compounds (components of degreasing solvents). Monitoring revealed the presence of low levels of volatile organic compounds in an adjacent area to PPPL. Also, PPPL's radiological monitoring program characterized the ambient, background levels of tritium in the environment and from the TFTR stack; the data are presented in this report.« less

Effect of lordosis angle change after lumbar/lumbosacral fusion on sacrum angular displacement: a finite element study.

PubMed

Mao, Ningfang; Shi, Jian; He, Dawei; Xie, Yang; Bai, Yushu; Wei, Xianzhao; Shi, Zhicai; Li, Ming

2014-11-01

To assess and characterize the sacrum angular displacements in response to lumbar lordosis after lumbar/lumbosacral fusion. A finite element model of the lower lumbar spine-pelvis was established and used to simulate the posterior fusion at L3-L5 and L4-S1. The lordosis angle in the fusion segments was set to five different conditions with respect to the intact model: 10° less than intact, 5° less than intact, same as intact, 5° more than intact, and 10° more than intact. Variations of the sacrum angular displacements with lordosis changes were analyzed under loading setting of axial compression, flexion, extension, lateral bending, and axial rotation. Compared with the intact lordosis, both increased and decreased lumbar lordosis angles caused the sacrum angular displacements to be increased. The lordosis angle increased by 10° induced the most substantial increase in sacrum angular displacements. In addition, the sacrum angular displacements of the L4-S1 fusion model at different lordosis angles were higher than those of the L3-L5 fusion model. The sacrum angular displacements occur as a result of the fusion surgery (L4-S1) and the changes in lumbar lordosis.

Light charged particle multiplicities in fusion and quasifission reactions

NASA Astrophysics Data System (ADS)

Kalandarov, Sh. A.; Adamian, G. G.; Antonenko, N. V.; Lacroix, D.; Wieleczko, J. P.

2018-01-01

The light charged particle evaporation from the compound nucleus and from the complex fragments in the reactions 32S+100Mo, 121Sb+27Al, 40Ar+164Dy, and 40Ar+ nat Ag is studied within the dinuclear system model. The possibility to distinguish the reaction products from different reaction mechanisms is discussed.

Teaching the Evolution of the Angiosperm Carpel.

ERIC Educational Resources Information Center

Laferriere, Joseph E.

1992-01-01

The carpel is a highly modified leaf enclosing the ovules. This article describes methods for teaching about the evolution of the carpel and the nature of carpel fusion. Presents an illustration of the evolution of the most common types of compound pistil arrangement from the ancestral single-carpel marginal type of placentation. (PR)

Anti-HIV drugs: 25 compounds approved within 25 years after the discovery of HIV.

PubMed

De Clercq, Erik

2009-04-01

In 2008, 25 years after the human immunodeficiency virus (HIV) was discovered as the then tentative aetiological agent of acquired immune deficiency syndrome (AIDS), exactly 25 anti-HIV compounds have been formally approved for clinical use in the treatment of AIDS. These compounds fall into six categories: nucleoside reverse transcriptase inhibitors (NRTIs: zidovudine, didanosine, zalcitabine, stavudine, lamivudine, abacavir and emtricitabine); nucleotide reverse transcriptase inhibitors (NtRTIs: tenofovir); non-nucleoside reverse transcriptase inhibitors (NNRTIs: nevirapine, delavirdine, efavirenz and etravirine); protease inhibitors (PIs: saquinavir, ritonavir, indinavir, nelfinavir, amprenavir, lopinavir, atazanavir, fosamprenavir, tipranavir and darunavir); cell entry inhibitors [fusion inhibitors (FIs: enfuvirtide) and co-receptor inhibitors (CRIs: maraviroc)]; and integrase inhibitors (INIs: raltegravir). These compounds should be used in drug combination regimens to achieve the highest possible benefit, tolerability and compliance and to diminish the risk of resistance development.

Volatile organic compound and semivolatile organic compound outgassing rates for ethylene propylene diene monomer and fluoropolymer seals

NASA Astrophysics Data System (ADS)

Pecault, Isabelle Tovena

2017-11-01

High-power laser facilities, such as Laser MegaJoule, are currently being operated for inertial confinement fusion experiments. Emission of volatile organic compounds (VOC) and moreover semivolatile organic compounds (SVOCs) from seals in laser environment is of tremendous importance for the optics lifetime and laser performance. That is why all the seals were screening in the same conditions: 48 h at 30°C and three successive cycle of 1.5 h at 50°C. This paper focuses on the qualification test performed on three seals: two ethylene propylene diene monomer (EPDM) and one fluoropolymer (FPM). It is shown that the molded and the extruded EPDM do not outgas the same amount neither the same molecules whereas EPDM and FPM outgas nearly the same level of phthalates.

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

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.

IgG-Paraoxonase-1 Fusion Protein for Targeted Drug Delivery Across the Human Blood-Brain Barrier

PubMed Central

Boado, Ruben J.; Zhang, Yun; Zhang, Yufeng; Wang, Yuntao; Pardridge, William M.

2009-01-01

Paraoxonase (PON)-1 is the most potent human protein with organophosphatase activity against organophosphate (OP) toxins. OP compounds readily cross the blood-brain barrier (BBB), and have lethal mechanisms of action within the brain. The production of a brain penetrating form of human PON1, which crosses the BBB, is possible with the re-engineering of the enzyme as a fusion protein with a monoclonal antibody (MAb) against the human insulin receptor (HIR). The HIRMAb crosses the BBB via the endogenous insulin receptor, and acts as a molecular Trojan horse to ferry the PON1 into brain. The human PON1 was fused to the carboxyl terminus of the heavy chain of the chimeric HIRMAb. COS cells were dual transfected with the heavy chain gene and the light chain gene, and the HIRMAb-PON1 fusion protein was affinity purified with protein A chromatography. Western blotting with antibodies to human IgG or human PON1 showed the heavy chain of the HIRMAb-PON1 fusion protein was 40 kDa larger than the heavy chain of the chimeric HIRMAb. The ED50 of binding to the HIR extracellular domain was 0.55 ± 0.07 nM and 1.1 ±0.1 nM, respectively, for the chimeric HIRMAb and the HIRMAb-PON1 fusion protein. The PON1 enzyme activity of the fusion protein was approximately 25% of the enzyme activity in human plasma, based on a fluorometric enzymatic assay. In conclusion, human PON1 has been re-engineered as an IgG-organophosphatase fusion protein that penetrates the human BBB. PMID:19434854

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

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.

New eutectic alloys and their heats of transformation

NASA Technical Reports Server (NTRS)

Farkas, D.; Birchenall, C. E.

1985-01-01

Eutectic compositions and congruently melting intermetallic compounds in binary and multicomponent systems among common elements such as Al, Ca, Cu, Mg, P, Si, and Zn may be useful for high temperature heat storage. In this work, heats of fusion of new multicomponent eutectics and intermetallic phases are reported, some of which are competitive with molten salts in heat storage density at high temperatures. The method used to determine unknown eutectic compositions combined results of differential thermal analysis, metallography, and microprobe analysis. The method allows determination of eutectic compositions in no more than three steps. The heats of fusion of the alloys were measured using commercial calorimeters, a differential thermal analyzer, and a differential scanning calorimeter.

Development and growth of compound tooth plates in Callorhinchus milii (chondrichthyes, holocephali).

PubMed

Didier, D A; Stahl, B J; Zangerl, R

1994-10-01

The chimaeroid holocephalian fishes are distinguished among extant chondrichthyans by the possession of three pairs of tooth plates, evergrowing and partially hypermineralized, that are not shed and replaced like the teeth of living elasmobranchs. Although derivation of the chimaeroid tooth plate from the fusion of members of a plesiomorphic chondrichthyan tooth family has been proposed, evidence for this hypothesis has been lacking. A new analysis of the development and structure of the tooth plates in Callorhinchus milii (Holocephali, Chimaeriformes) reveals the compound nature of the tooth plates in a chimaeroid fish. Each tooth plate consists of an oral and aboral territory that form independently in the embryo and maintain separate growth surfaces through life. The descending lamina on the aboral surface of the tooth plate demarcates the growth surface of the aboral territory. Comparison with the tooth plates of Chimaera monstrosa indicates that compound tooth plates may be a feature of all chimaeroids in which a descending lamina is present. The tooth plates in these fishes represent the fusion of two members of a reduced tooth family. The condition of the tooth plates in C. milii is plesiomorphic for chimaeroids and is of evolutionary significance in that it provides further evidence to support a lyodont dentition in chimaeroid fishes similar to that found in other chondrichthyans. © 1994 Wiley-Liss, Inc. Copyright © 1994 Wiley-Liss, Inc.

A Biomimetic Sensor for the Classification of Honeys of Different Floral Origin and the Detection of Adulteration

PubMed Central

Zakaria, Ammar; Shakaff, Ali Yeon Md; Masnan, Maz Jamilah; Ahmad, Mohd Noor; Adom, Abdul Hamid; Jaafar, Mahmad Nor; Ghani, Supri A.; Abdullah, Abu Hassan; Aziz, Abdul Hallis Abdul; Kamarudin, Latifah Munirah; Subari, Norazian; Fikri, Nazifah Ahmad

2011-01-01

The major compounds in honey are carbohydrates such as monosaccharides and disaccharides. The same compounds are found in cane-sugar concentrates. Unfortunately when sugar concentrate is added to honey, laboratory assessments are found to be ineffective in detecting this adulteration. Unlike tracing heavy metals in honey, sugar adulterated honey is much trickier and harder to detect, and traditionally it has been very challenging to come up with a suitable method to prove the presence of adulterants in honey products. This paper proposes a combination of array sensing and multi-modality sensor fusion that can effectively discriminate the samples not only based on the compounds present in the sample but also mimic the way humans perceive flavours and aromas. Conversely, analytical instruments are based on chemical separations which may alter the properties of the volatiles or flavours of a particular honey. The present work is focused on classifying 18 samples of different honeys, sugar syrups and adulterated samples using data fusion of electronic nose (e-nose) and electronic tongue (e-tongue) measurements. Each group of samples was evaluated separately by the e-nose and e-tongue. Principal Component Analysis (PCA) and Linear Discriminant Analysis (LDA) were able to separately discriminate monofloral honey from sugar syrup, and polyfloral honey from sugar and adulterated samples using the e-nose and e-tongue. The e-nose was observed to give better separation compared to e-tongue assessment, particularly when LDA was applied. However, when all samples were combined in one classification analysis, neither PCA nor LDA were able to discriminate between honeys of different floral origins, sugar syrup and adulterated samples. By applying a sensor fusion technique, the classification for the 18 different samples was improved. Significant improvement was observed using PCA, while LDA not only improved the discrimination but also gave better classification. An improvement in performance was also observed using a Probabilistic Neural Network classifier when the e-nose and e-tongue data were fused. PMID:22164046

A biomimetic sensor for the classification of honeys of different floral origin and the detection of adulteration.

PubMed

Zakaria, Ammar; Shakaff, Ali Yeon Md; Masnan, Maz Jamilah; Ahmad, Mohd Noor; Adom, Abdul Hamid; Jaafar, Mahmad Nor; Ghani, Supri A; Abdullah, Abu Hassan; Aziz, Abdul Hallis Abdul; Kamarudin, Latifah Munirah; Subari, Norazian; Fikri, Nazifah Ahmad

2011-01-01

The major compounds in honey are carbohydrates such as monosaccharides and disaccharides. The same compounds are found in cane-sugar concentrates. Unfortunately when sugar concentrate is added to honey, laboratory assessments are found to be ineffective in detecting this adulteration. Unlike tracing heavy metals in honey, sugar adulterated honey is much trickier and harder to detect, and traditionally it has been very challenging to come up with a suitable method to prove the presence of adulterants in honey products. This paper proposes a combination of array sensing and multi-modality sensor fusion that can effectively discriminate the samples not only based on the compounds present in the sample but also mimic the way humans perceive flavours and aromas. Conversely, analytical instruments are based on chemical separations which may alter the properties of the volatiles or flavours of a particular honey. The present work is focused on classifying 18 samples of different honeys, sugar syrups and adulterated samples using data fusion of electronic nose (e-nose) and electronic tongue (e-tongue) measurements. Each group of samples was evaluated separately by the e-nose and e-tongue. Principal Component Analysis (PCA) and Linear Discriminant Analysis (LDA) were able to separately discriminate monofloral honey from sugar syrup, and polyfloral honey from sugar and adulterated samples using the e-nose and e-tongue. The e-nose was observed to give better separation compared to e-tongue assessment, particularly when LDA was applied. However, when all samples were combined in one classification analysis, neither PCA nor LDA were able to discriminate between honeys of different floral origins, sugar syrup and adulterated samples. By applying a sensor fusion technique, the classification for the 18 different samples was improved. Significant improvement was observed using PCA, while LDA not only improved the discrimination but also gave better classification. An improvement in performance was also observed using a Probabilistic Neural Network classifier when the e-nose and e-tongue data were fused.

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.

Carbon-containing compounds on fusion-related surfaces: Thermal and ion-induced formation and erosion

NASA Astrophysics Data System (ADS)

Linsmeier, Christian

2004-12-01

The deposition of carbon on metals is the unavoidable consequence of the application of different wall materials in present and future fusion experiments like ITER. Presently used and prospected materials besides carbon (CFC materials in high heat load areas) are tungsten and beryllium. The simultaneous application of different materials leads to the formation of surface compounds due to the erosion, transport and re-deposition of material during plasma operations. The formation and erosion processes are governed by widely varying surface temperatures and kinetic energies as well as the spectrum of impinging particles from the plasma. The knowledge of the dependence on these parameters is crucial for the understanding and prediction of the compound formation on wall materials. The formation of surface layers is of great importance, since they not only determine erosion rates, but also influence the ability of the first wall for hydrogen isotope inventory accumulation and release. Surface compound formation, diffusion and erosion phenomena are studied under well-controlled ultra-high vacuum conditions using in-situ X-ray photoelectron spectroscopy (XPS) and ion beam analysis techniques available at a 3 MV tandem accelerator. XPS provides chemical information and allows distinguishing elemental and carbidic phases with high surface sensitivity. Accelerator-based spectroscopies provide quantitative compositional analysis and sensitivity for deuterium in the surface layers. Using these techniques, the formation of carbidic layers on metals is studied from room temperature up to 1700 K. The formation of an interfacial carbide of several monolayers thickness is not only observed for metals with exothermic carbide formation enthalpies, but also in the cases of Ni and Fe which form endothermic carbides. Additional carbon deposited at 300 K remains elemental. Depending on the substrate, carbon diffusion into the bulk starts at elevated temperatures together with additional carbide formation. Depending on the bond nature in the carbide (metallic in the transition metal carbides, ionic e.g. in Be2C), the surface carbide layer is dissolved upon further increased temperatures or remains stable. Carbide formation can also be initiated by ion bombardment, both of chemically inert noble gas ions or C+ or CO+ ions. In the latter case, a deposition-erosion equilibrium develops which leads to a ternary surface layer of constant thickness. A chemical erosion channel is also discussed for the enhanced erosion of thin carbon films on metals by deuterium ions.

Atomistic simulation of the influence of Cr on the mobility of the edge dislocation in Fe(Cr) alloys

NASA Astrophysics Data System (ADS)

Hafez Haghighat, S. M.; Terentyev, D.; Schäublin, R.

2011-10-01

In this work Fe-Cr compounds, as model alloys for the ferritic base steels that are considered as main candidates for the structural materials of the future fusion reactors, are studied using molecular dynamics simulations. The Cr or so-called α' precipitates, which are obstacles to dislocations, affect mechanical properties, leading to hardening and loss of ductility. The flow stress to move an edge dislocation in a Cr solid solution in pure Fe is studied as a function of Cr content. The strength of a nanometric Cr precipitate as obstacle to an edge dislocation in pure Fe is investigated as a function of its Cr content. Results show that with increasing Cr content the precipitate obstacle strength increases, with a strong sensitivity to the local atomic order. Temperature induces a monotonic decrease of the flow stress of the Cr solid solution and of the Cr precipitate obstacle strength.

Quest for consistent modelling of statistical decay of the compound nucleus

NASA Astrophysics Data System (ADS)

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

2018-01-01

A statistical model description of heavy ion induced fusion-fission reactions is presented where shell effects, collective enhancement of level density, tilting away effect of compound nuclear spin and dissipation are included. It is shown that the inclusion of all these effects provides a consistent picture of fission where fission hindrance is required to explain the experimental values of both pre-scission neutron multiplicities and evaporation residue cross-sections in contrast to some of the earlier works where a fission hindrance is required for pre-scission neutrons but a fission enhancement for evaporation residue cross-sections.

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

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.

Surface Density of the Hendra G Protein Modulates Hendra F Protein-Promoted Membrane Fusion: Role for Hendra G Protein Trafficking and Degradation

PubMed Central

Whitman, Shannon D.; Dutch, Rebecca Ellis

2007-01-01

Hendra virus, like most paramyxoviruses, requires both a fusion (F) and attachment (G) protein for promotion of cell-cell fusion. Recent studies determined that Hendra F is proteolytically processed by the cellular protease cathepsin L after endocytosis. This unique cathepsin L processing results in a small percentage of Hendra F on the cell surface. To determine how the surface densities of the two Hendra glycoproteins affect fusion promotion, we performed experiments that varied the levels of glycoproteins expressed in transfected cells. Using two different fusion assays, we found a marked increase in fusion when expression of the Hendra G protein was increased, with a 1:1 molar ratio of Hendra F:G on the cell surface resulting in optimal membrane fusion. Our results also showed that Hendra G protein levels are modulated by both more rapid protein turnover and slower protein trafficking than is seen for Hendra F. PMID:17328935

TEST FUSION IN ADULT FORAMINIFERA: A REVIEW WITH NEW OBSERVATIONS OF AN EARLY EOCENE NUMMULITES SPECIMEN

PubMed Central

Ferràndez-Cañadell, Carles; Briguglio, Antonino; Hohenegger, Johann; Wöger, Julia

2015-01-01

In foraminifera, so-called “double tests” usually arise due to abnormal growth originating mainly from twinning, but may also be caused by irregularities in the early chambers and by regeneration after test injury that modifies the direction of growth. A fourth cause of double tests has only rarely been reported: the fusion of the tests of two adult individuals. We studied an early Eocene Nummulites double test consisting of two adult individuals that fused after an extended period of independent growth. The specimen was studied using computed tomography with micrometric resolution (micro-CT) that allowed bi- and three-dimensional visualization of the internal structure. Before fusion each individual test had 30–36 chambers, which, by comparison with growth rates in recent nummulitids, implies at least three months of independent growth. After fusion, the compound test grew in two spirals that fused after about one whorl and then continued in a single spiral. To fuse their tests, either adult individuals have to be forced to do so or the allorecognition (ability to distinguish between self and another individual) mechanisms must fail. A possible explanation for the merged Nummulites tests in this study is forced fusion in attached individuals after surviving ingestion and digestion by a metazoan. Alternatively, environmental stress could lead to a failure of allorecognition mechanisms and/or foraminiferal motility. Once fused, subsequent growth seems to be determined mainly by the relative orientation of individual tests. In any case, the frequency in which adult fusion occurs remains unknown. PMID:26166916

Fusion and quasifission studies for the 40Ca+186W,192Os reactions

NASA Astrophysics Data System (ADS)

Prasad, E.; Hinde, D. J.; Williams, E.; Dasgupta, M.; Carter, I. P.; Cook, K. J.; Jeung, D. Y.; Luong, D. H.; Palshetkar, C. S.; Rafferty, D. C.; Ramachandran, K.; Simenel, C.; Wakhle, A.

2017-09-01

Background: All elements above atomic number 113 have been synthesized using hot fusion reactions with calcium beams on statically deformed actinide target nuclei. Quasifission and fusion-fission are the two major mechanisms responsible for the very low production cross sections of superheavy elements. Purpose: To achieve a quantitative measurement of capture and quasifission characteristics as a function of beam energy in reactions forming heavy compound systems using calcium beams as projectiles. Methods: Fission fragment mass-angle distributions were measured for the two reactions 40Ca+186W and 40C+192Os, populating 226Pu and 232Cm compound nuclei, respectively, using the Heavy Ion Accelerator Facility and CUBE spectrometer at the Australian National University. Mass ratio distributions, angular distributions, and total fission cross sections were obtained from the experimental data. Simulations to match the features of the experimental mass-angle distributions were performed using a classical phenomenological approach. Results: Both 40Ca+186W and 40C+192Os reactions show strong mass-angle correlations at all energies measured. A maximum fusion probability of 60 -70 % is estimated for the two reactions in the energy range of the present study. Coupled-channels calculations assuming standard Woods-Saxon potential parameters overpredict the capture cross sections. Large nuclear potential diffuseness parameters ˜1.5 fm are required to fit the total capture cross sections. The presence of a weak mass-asymmetric quasifission component attributed to the higher angular momentum events can be reproduced with a shorter average sticking time but longer mass-equilibration time constant. Conclusions: The deduced above-barrier capture cross sections suggest that the dissipative processes are already occurring outside the capture barrier. The mass-angle correlations indicate that a compact shape is not achieved for deformation aligned collisions with lower capture barriers. The average sticking time of fast quasifission events is 10-20 s.

Ultra-High-Throughput Screening of an In Vitro-Synthesized Horseradish Peroxidase Displayed on Microbeads Using Cell Sorter

PubMed Central

Zhu, Bo; Mizoguchi, Takuro; Kojima, Takaaki; Nakano, Hideo

2015-01-01

The C1a isoenzyme of horseradish peroxidase (HRP) is an industrially important heme-containing enzyme that utilizes hydrogen peroxide to oxidize a wide variety of inorganic and organic compounds for practical applications, including synthesis of fine chemicals, medical diagnostics, and bioremediation. To develop a ultra-high-throughput screening system for HRP, we successfully produced active HRP in an Escherichia coli cell-free protein synthesis system, by adding disulfide bond isomerase DsbC and optimizing the concentrations of hemin and calcium ions and the temperature. The biosynthesized HRP was fused with a single-chain Cro (scCro) DNA-binding tag at its N-terminal and C-terminal sites. The addition of the scCro-tag at both ends increased the solubility of the protein. Next, HRP and its fusion proteins were successfully synthesized in a water droplet emulsion by using hexadecane as the oil phase and SunSoft No. 818SK as the surfactant. HRP fusion proteins were displayed on microbeads attached with double-stranded DNA (containing the scCro binding sequence) via scCro-DNA interactions. The activities of the immobilized HRP fusion proteins were detected with a tyramide-based fluorogenic assay using flow cytometry. Moreover, a model microbead library containing wild type hrp (WT) and inactive mutant (MUT) genes was screened using fluorescence-activated cell-sorting, thus efficiently enriching the WT gene from the 1:100 (WT:MUT) library. The technique described here could serve as a novel platform for the ultra-high-throughput discovery of more useful HRP mutants and other heme-containing peroxidases. PMID:25993095

Novel push-pull fluorescent dyes - 7-(diethylamino)furo- and thieno[3,2-c]coumarins derivatives: structure, electronic spectra and TD-DFT study

NASA Astrophysics Data System (ADS)

Akchurin, Igor O.; Yakhutina, Anna I.; Bochkov, Andrei Y.; Solovjova, Natalya P.; Medvedev, Michael G.; Traven, Valerii F.

2018-05-01

Novel push-pull fluorescent dyes - 7-(diethylamino)furo- and 7-(diethylamino)thieno[3,2-c]coumarins derivatives have been synthesized using formyl derivatives of furo- and thieno[3,2-c]coumarins as starting materials. Electron absorption and fluorescent spectra of the dyes have been recorded in different solvents. Structure and solvent effects on the dyes spectral characteristics were analyzed. The fusion of five-membered heterocycle to coumarin provides a definite increase of Stokes shifts in all solvents and results in higher quantum yields of fluorescence. The absorption and emission bands of thieno[3,2-c] coumarin derivatives are definitely shifted to the red region (3-30 nm) compared to similar derivatives of furo[3,2-c]coumarin. TD-DFT calculations of some of the studied compounds have shown that hybrid DFT functionals and adequate representation of molecular environment are essential for obtaining accurate UV-Vis absorption spectra for the dyes with extended π-system. The longest-wave electron transitions in the studied compounds were computationally shown to be of push-pull nature.

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.

Morphological changes in vesicles and release of an encapsulated compound triggered by a photoresponsive Malachite Green leuconitrile derivative.

PubMed

Uda, Ryoko M; Hiraishi, Eri; Ohnishi, Ryo; Nakahara, Yoshio; Kimura, Keiichi

2010-04-20

Photoinduced morphological changes in phosphatidylcholine vesicles are triggered by a Malachite Green leuconitrile derivative dissolved in the lipidic membrane, and are observed at Malachite Green derivative/lipid ratios <5 mol %. This Malachite Green derivative is a photoresponsive compound that undergoes ionization to afford a positive charge on the molecule by UV irradiation. The Malachite Green derivative exhibits amphiphilicity when ionized photochemically, whereas it behaves as a lipophilic compound under dark conditions. Cryo-transmission electron microscopy was used to determine vesicle morphology. The effects of the Malachite Green derivative on vesicles were studied by dynamic light scattering and fluorescence resonance energy transfer. Irradiation of vesicles containing the Malachite Green derivative induces nonspherical vesicle morphology, fusion of vesicles, and membrane solubilization, depending on conditions. Furthermore, irradiation of the Malachite Green derivative induces the release of a vesicle-encapsulated compound.

The section TiInSe/sub 2/-TiSbSe/sub 2/ of the system Ti-In-Sb-Se

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

Guseinov, G.D.; Chapanova, L.M.; Mal'sagov, A.U.

1985-09-01

The ternary compounds A /SUP I/ B /SUP III/ C/sub 2/ /SUP VI/ (A /SUP I/ is univalent Ti; B /SUP III/ is Ga or In; and C /SUP VI/ is S, Se or Te) form a class of semiconductors with a large number of different gap widths. The compounds crystallize in the chalcopyrite structure. Solid solutions based on these compounds, which permit varying smoothly the gap width and other physical parameters over wide limits, are of great interest. The authors synthesized the compounds TiInSe/sub 2/ and TiSbSe/sub 2/ from the starting materials Ti-000, In-000, Sb-000 and Se-OSCh-17-4 by directmore » fusion of the components, taken in a stoichiometric ratio, in quartz ampules evacuated to 1.3 X 10/sup -3/ Pa and sealed.« less

Biomechanics of coupled motion in the cervical spine during simulated whiplash in patients with pre-existing cervical or lumbar spinal fusion

PubMed Central

Huang, H.; Nightingale, R. W.

2018-01-01

Objectives Loss of motion following spine segment fusion results in increased strain in the adjacent motion segments. However, to date, studies on the biomechanics of the cervical spine have not assessed the role of coupled motions in the lumbar spine. Accordingly, we investigated the biomechanics of the cervical spine following cervical fusion and lumbar fusion during simulated whiplash using a whole-human finite element (FE) model to simulate coupled motions of the spine. Methods A previously validated FE model of the human body in the driver-occupant position was used to investigate cervical hyperextension injury. The cervical spine was subjected to simulated whiplash exposure in accordance with Euro NCAP (the European New Car Assessment Programme) testing using the whole human FE model. The coupled motions between the cervical spine and lumbar spine were assessed by evaluating the biomechanical effects of simulated cervical fusion and lumbar fusion. Results Peak anterior longitudinal ligament (ALL) strain ranged from 0.106 to 0.382 in a normal spine, and from 0.116 to 0.399 in a fused cervical spine. Strain increased from cranial to caudal levels. The mean strain increase in the motion segment immediately adjacent to the site of fusion from C2-C3 through C5-C6 was 26.1% and 50.8% following single- and two-level cervical fusion, respectively (p = 0.03, unpaired two-way t-test). Peak cervical strains following various lumbar-fusion procedures were 1.0% less than those seen in a healthy spine (p = 0.61, two-way ANOVA). Conclusion Cervical arthrodesis increases peak ALL strain in the adjacent motion segments. C3-4 experiences greater changes in strain than C6-7. Lumbar fusion did not have a significant effect on cervical spine strain. Cite this article: H. Huang, R. W. Nightingale, A. B. C. Dang. Biomechanics of coupled motion in the cervical spine during simulated whiplash in patients with pre-existing cervical or lumbar spinal fusion: A Finite Element Study. Bone Joint Res 2018;7:28–35. DOI: 10.1302/2046-3758.71.BJR-2017-0100.R1. PMID:29330341

Biomechanics of coupled motion in the cervical spine during simulated whiplash in patients with pre-existing cervical or lumbar spinal fusion: A Finite Element Study.

PubMed

Huang, H; Nightingale, R W; Dang, A B C

2018-01-01

Loss of motion following spine segment fusion results in increased strain in the adjacent motion segments. However, to date, studies on the biomechanics of the cervical spine have not assessed the role of coupled motions in the lumbar spine. Accordingly, we investigated the biomechanics of the cervical spine following cervical fusion and lumbar fusion during simulated whiplash using a whole-human finite element (FE) model to simulate coupled motions of the spine. A previously validated FE model of the human body in the driver-occupant position was used to investigate cervical hyperextension injury. The cervical spine was subjected to simulated whiplash exposure in accordance with Euro NCAP (the European New Car Assessment Programme) testing using the whole human FE model. The coupled motions between the cervical spine and lumbar spine were assessed by evaluating the biomechanical effects of simulated cervical fusion and lumbar fusion. Peak anterior longitudinal ligament (ALL) strain ranged from 0.106 to 0.382 in a normal spine, and from 0.116 to 0.399 in a fused cervical spine. Strain increased from cranial to caudal levels. The mean strain increase in the motion segment immediately adjacent to the site of fusion from C2-C3 through C5-C6 was 26.1% and 50.8% following single- and two-level cervical fusion, respectively (p = 0.03, unpaired two-way t -test). Peak cervical strains following various lumbar-fusion procedures were 1.0% less than those seen in a healthy spine (p = 0.61, two-way ANOVA). Cervical arthrodesis increases peak ALL strain in the adjacent motion segments. C3-4 experiences greater changes in strain than C6-7. Lumbar fusion did not have a significant effect on cervical spine strain. Cite this article : H. Huang, R. W. Nightingale, A. B. C. Dang. Biomechanics of coupled motion in the cervical spine during simulated whiplash in patients with pre-existing cervical or lumbar spinal fusion: A Finite Element Study. Bone Joint Res 2018;7:28-35. DOI: 10.1302/2046-3758.71.BJR-2017-0100.R1. © 2018 Huang et al.

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.

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

A protein disulfide isomerase gene fusion expression system that increases the extracellular productivity of Bacillus brevis.

PubMed

Kajino, T; Ohto, C; Muramatsu, M; Obata, S; Udaka, S; Yamada, Y; Takahashi, H

2000-02-01

We have developed a versatile Bacillus brevis expression and secretion system based on the use of fungal protein disulfide isomerase (PDI) as a gene fusion partner. Fusion with PDI increased the extracellular production of heterologous proteins (light chain of immunoglobulin G, 8-fold; geranylgeranyl pyrophosphate synthase, 12-fold). Linkage to PDI prevented the aggregation of the secreted proteins, resulting in high-level accumulation of fusion proteins in soluble and biologically active forms. We also show that the disulfide isomerase activity of PDI in a fusion protein is responsible for the suppression of the aggregation of the protein with intradisulfide, whereas aggregation of the protein without intradisulfide was prevented even when the protein was fused to a mutant PDI whose two active sites were disrupted, suggesting that another PDI function, such as chaperone-like activity, synergistically prevented the aggregation of heterologous proteins in the PDI fusion expression system.

An Approach to Automated Fusion System Design and Adaptation

PubMed Central

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

2017-01-01

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

T-type α1H Ca2+ channels are involved in Ca2+ signaling during terminal differentiation (fusion) of human myoblasts

PubMed Central

Bijlenga, Philippe; Liu, Jian-Hui; Espinos, Estelle; Haenggeli, Charles-Antoine; Fischer-Lougheed, Jacqueline; Bader, Charles R.; Bernheim, Laurent

2000-01-01

Mechanisms underlying Ca2+ signaling during human myoblast terminal differentiation were studied using cell cultures. We found that T-type Ca2+ channels (T-channels) are expressed in myoblasts just before fusion. Their inhibition by amiloride or Ni2+ suppresses fusion and prevents an intracellular Ca2+ concentration increase normally observed at the onset of fusion. The use of antisense oligonucleotides indicates that the functional T-channels are formed by α1H subunits. At hyperpolarized potentials, these channels allow a window current sufficient to increase [Ca2+]i. As hyperpolarization is a prerequisite to myoblast fusion, we conclude that the Ca2+ signal required for fusion is produced when the resting potential enters the T-channel window. A similar mechanism could operate in other cell types of which differentiation implicates membrane hyperpolarization. PMID:10861024

An Approach to Automated Fusion System Design and Adaptation.

PubMed

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

2017-03-16

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

A Protein Disulfide Isomerase Gene Fusion Expression System That Increases the Extracellular Productivity of Bacillus brevis

PubMed Central

Kajino, Tsutomu; Ohto, Chikara; Muramatsu, Masayoshi; Obata, Shusei; Udaka, Shigezo; Yamada, Yukio; Takahashi, Haruo

2000-01-01

We have developed a versatile Bacillus brevis expression and secretion system based on the use of fungal protein disulfide isomerase (PDI) as a gene fusion partner. Fusion with PDI increased the extracellular production of heterologous proteins (light chain of immunoglobulin G, 8-fold; geranylgeranyl pyrophosphate synthase, 12-fold). Linkage to PDI prevented the aggregation of the secreted proteins, resulting in high-level accumulation of fusion proteins in soluble and biologically active forms. We also show that the disulfide isomerase activity of PDI in a fusion protein is responsible for the suppression of the aggregation of the protein with intradisulfide, whereas aggregation of the protein without intradisulfide was prevented even when the protein was fused to a mutant PDI whose two active sites were disrupted, suggesting that another PDI function, such as chaperone-like activity, synergistically prevented the aggregation of heterologous proteins in the PDI fusion expression system. PMID:10653729

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

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

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.

Unveiling the identity of distant targets through advanced Raman-laser-induced breakdown spectroscopy data fusion strategies.

PubMed

Moros, Javier; Javier Laserna, J

2015-03-01

Data fusion is the process of combining data gathered from two or more sensors to produce a more specific, comprehensive and unified dataset of the inspected target. On this basis, much has been said about the possible benefits resulting from the use of molecular and atomic information for the detection of explosives. The orthogonal nature of the spectral and compositional information provided by Raman spectroscopy and laser-induced breakdown spectroscopy (LIBS) makes them suitable candidates for an optimal combination of their data, thus achieving inferences that are not feasible using a single sensor. The present manuscript evaluates several architectures for the combination of spectral outputs from these two sensors in order to compare the benefits and drawbacks of data fusion for improving the overall identification performance. From the simple assembling (concatenation or addition) of Raman and LIBS spectra to signals' processing on the basis of linear algebra (either the outer product or the outer sum), different identification patterns of several compounds (explosives, potential confusants and supports) have been built. The efficiency on target differentiation by using each of the architectures has been evaluated by comparing the identification yield obtained for all the inspected targets from correlation and similarity measurements. Additionally, a specific code integrated by several of these patterns to identify each compound has also been evaluated. This approach permits to obtain a better knowledge about the identity of an interrogated target, mainly in those decisive cases in which LIBS or Raman cannot be effective separately to reach a decision. Copyright © 2014 Elsevier B.V. All rights reserved.

Bioactive benzopyrone derivatives from new recombinant fusant of marine Streptomyces.

PubMed

El-Gendy, Mervat M A; Shaaban, M; El-Bondkly, A M; Shaaban, K A

2008-07-01

In our searching program for bioactive secondary metabolites from marine Streptomycetes, three microbial benzopyrone derivatives (1-3), 7-methylcoumarin (1) and two flavonoides, rhamnazin (2) and cirsimaritin (3), were obtained during the working up of the ethyl acetate fraction of a marine Streptomyces fusant obtained from protoplast fusion between Streptomyces strains Merv 1996 and Merv 7409. The structures of the three compounds (1-3) were established by nuclear magnetic resonance, mass, UV spectra, and by comparison with literature data. Marine Streptomyces strains were identified based on their phenotypic and chemotypic characteristics as two different bioactive strains of the genus Streptomyces. We described here the fermentation, isolation, as well as the biological activity of these bioactive compounds. The isolated compounds (1-3) are reported here as microbial products for the first time.

Two-level noncontiguous versus three-level anterior cervical discectomy and fusion: a biomechanical comparison.

PubMed

Finn, Michael A; Samuelson, Mical M; Bishop, Frank; Bachus, Kent N; Brodke, Darrel S

2011-03-15

Biomechanical study. To determine biomechanical forces exerted on intermediate and adjacent segments after two- or three-level fusion for treatment of noncontiguous levels. Increased motion adjacent to fused spinal segments is postulated to be a driving force in adjacent segment degeneration. Occasionally, a patient requires treatment of noncontiguous levels on either side of a normal level. The biomechanical forces exerted on the intermediate and adjacent levels are unknown. Seven intact human cadaveric cervical spines (C3-T1) were mounted in a custom seven-axis spine simulator equipped with a follower load apparatus and OptoTRAK three-dimensional tracking system. Each intact specimen underwent five cycles each of flexion/extension, lateral bending, and axial rotation under a ± 1.5 Nm moment and a 100-Nm axial follower load. Applied torque and motion data in each axis of motion and level were recorded. Testing was repeated under the same parameters after C4-C5 and C6-C7 diskectomies were performed and fused with rigid cervical plates and interbody spacers and again after a three-level fusion from C4 to C7. Range of motion was modestly increased (35%) in the intermediate and adjacent levels in the skip fusion construct. A significant or nearly significant difference was reached in seven of nine moments. With the three-level fusion construct, motion at the infra- and supra-adjacent levels was significantly or nearly significantly increased in all applied moments over the intact and the two-level noncontiguous construct. The magnitude of this change was substantial (72%). Infra- and supra-adjacent levels experienced a marked increase in strain in all moments with a three-level fusion, whereas the intermediate, supra-, and infra-adjacent segments of a two-level fusion experienced modest strain moments relative to intact. It would be appropriate to consider noncontiguous fusions instead of a three-level fusion when confronted with nonadjacent disease.

Construction of hybrid peptide synthetases by module and domain fusions

PubMed Central

Mootz, Henning D.; Schwarzer, Dirk; Marahiel, Mohamed A.

2000-01-01

Nonribosomal peptide synthetases are modular enzymes that assemble peptides of diverse structures and important biological activities. Their modular organization provides a great potential for the rational design of novel compounds by recombination of the biosynthetic genes. Here we describe the extension of a dimodular system to trimodular ones based on whole-module fusion. The recombinant hybrid enzymes were purified to monitor product assembly in vitro. We started from the first two modules of tyrocidine synthetase, which catalyze the formation of the dipeptide dPhe-Pro, to construct such hybrid systems. Fusion of the second, proline-specific module with the ninth and tenth modules of the tyrocidine synthetases, specific for ornithine and leucine, respectively, resulted in dimodular hybrid enzymes exhibiting the combined substrate specificities. The thioesterase domain was fused to the terminal module. Upon incubation of these dimodular enzymes with the first tyrocidine module, TycA, incorporating dPhe, the predicted tripeptides dPhe-Pro-Orn and dPhe-Pro-Leu were obtained at rates of 0.15 min-1 and 2.1 min-1. The internal thioesterase domain was necessary and sufficient to release the products from the hybrid enzymes and thereby facilitate a catalytic turnover. Our approach of whole-module fusion is based on an improved definition of the fusion sites and overcomes the recently discovered editing function of the intrinsic condensation domains. The stepwise construction of hybrid peptide synthetases from catalytic subunits reinforces the inherent potential for the synthesis of novel, designed peptides. PMID:10811885

Construction of hybrid peptide synthetases by module and domain fusions.

PubMed

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

2000-05-23

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

Multivalent dendrimeric compounds containing carbohydrates expressed on immune cells inhibit infection by primary isolates of HIV-1

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

Rosa Borges, Andrew; Wieczorek, Lindsay; Johnson, Benitra

2010-12-05

Specific glycosphingolipids (GSL), found on the surface of target immune cells, are recognized as alternate cell surface receptors by the human immunodeficiency virus type 1 (HIV-1) external envelope glycoprotein. In this study, the globotriose and 3'-sialyllactose carbohydrate head groups found on two GSL were covalently attached to a dendrimer core to produce two types of unique multivalent carbohydrates (MVC). These MVC inhibited HIV-1 infection of T cell lines and primary peripheral blood mononuclear cells (PBMC) by T cell line-adapted viruses or primary isolates, with IC{sub 50}s ranging from 0.1 to 7.4 {mu}g/ml. Inhibition of Env-mediated membrane fusion by MVC wasmore » also observed using a dye-transfer assay. These carbohydrate compounds warrant further investigation as a potential new class of HIV-1 entry inhibitors. The data presented also shed light on the role of carbohydrate moieties in HIV-1 virus-host cell interactions. -- Research Highlights: {yields}Multivalent carbohydrates (MVCs) inhibited infection of PBMCs by HIV-1. {yields}MVCs inhibited infection by T cell line-adapted viruses. {yields}MVCs inhibited infection by primary isolates of HIV-1. {yields}MVCs inhibited Env-mediated membrane fusion.« less

Prediction of poly(ethylene) glycol-drug eutectic compositions using an index based on the van't Hoff equation.

PubMed

Law, Devalina; Wang, Weili; Schmitt, Eric A; Long, Michelle A

2002-03-01

To define an index based on the van't Hoff equation that can be used as a screening tool for predicting poly(ethylene) glycol (PEG)-drug eutectic composition. Phase diagrams of PEG with ritonavir, ibuprofen, fenofibrate. naproxen, and griseofulvin were constructed using differential scanning calorimetry, hot stage microscopy and powder X-ray diftractometry. Previously reported phase diagrams were also used to test the predictive capability of the index. This work shows that a modified van't Hoff equation can be used to model the drug liquidus line of these phase diagrams. The slope of the liquidus line depends on the melting point (T(f)d) and heat of fusion (deltaH(f)d) of the drug and describes the initial rate at which the eutectic or monotectic point is approached. Based on this finding, a dimensionless index Ic was defined. The index can be calculated from the melting points of the pure components and heat of fusion of the drug. In addition to the compounds listed above, the index was found to predict the eutectic composition for flurbiprofen, temazepam and indomethacin. These compounds range over 150 degrees C in T(f)d, and from 25-65 kJ/mole in deltaH(f)d. Using Ic the approximate eutectic composition for eight different compounds was predicted. The index provides a useful screening tool for assessing the maximum drug loading in a drug-polymer eutectic/monotectic formulation.

Targeted Cell Fusion Facilitates Stable Heterokaryon Generation In Vitro and In Vivo

PubMed Central

Long, Michael A.; Rossi, Fabio M. V.

2011-01-01

Induced cell fusion has enabled several important discoveries, including the phenomenon of nuclear reprogramming and may yet be applied as a novel therapy for degenerative diseases. However, existing fusogens lack the efficiency required to enable investigation of the epigenetic modifications underlying nuclear reprogramming and the specificity required for clinical application. Here we present a chimeric measles hemagglutinin, Hα7, which specifically and efficiently mediates the fusion of diverse cell types with skeletal muscle both in vitro and in vivo. When compared directly to polyethylene glycol, Hα7 consistently generated a substantial increase in heterokaryon yield and exhibited insignificant levels of toxicity. Moreover, this increased fusion efficiency enabled detection of chromatin modifications associated with nuclear reprogramming following Hα7-mediated fusion of human fibroblasts and mouse myotubes. Finally, Hα7 was also capable of increasing the contribution of transplanted fibroblasts to skeletal muscle repair in vivo, suggesting that this strategy could be used for therapeutic gene delivery. PMID:22039476

Electron beam-induced radiation damage: the bubbling response in amorphous dried sodium phosphate buffer.

PubMed

Massover, William H

2010-06-01

Irradiation of an amorphous layer of dried sodium phosphate buffer (pH = 7.0) by transmission electron microscopy (100-120 kV) causes rapid formation of numerous small spherical bubbles [10-100 A (= 1-10 nm)] containing an unknown gas. Bubbling is detected even with the first low-dose exposure. In a thin layer (ca. 100-150 A), bubbling typically goes through nucleation, growth, possible fusion, and end-state, after which further changes are not apparent; co-irradiated adjacent areas having a slightly smaller thickness never develop bubbles. In moderately thicker regions (ca. over 200 A), there is no end-state. Instead, a complex sequence of microstructural changes is elicited during continued intermittent high-dose irradiation: nucleation, growth, early simple fusions, a second round of extensive multiple fusions, general reduction of matrix thickness (producing flattening and expansion of larger bubbles, occasional bubble fission, and formation of very large irregularly-shaped bubbles by a third round of compound fusion events), and slow shrinkage of all bubbles. The ongoing lighter appearance of bubble lumens, maintenance of their rounded shape, and extensive changes in size and form indicate that gas content continues throughout their surprisingly long lifetime; the thin dense boundary layer surrounding all bubbles is proposed to be the main mechanism for their long lifetime.

Alternative Affinity Ligands for Immunoglobulins.

PubMed

Kruljec, Nika; Bratkovič, Tomaž

2017-08-16

The demand for recombinant therapeutic antibodies and Fc-fusion proteins is expected to increase in the years to come. Hence, extensive efforts are concentrated on improving the downstream processing. In particular, the development of better-affinity chromatography matrices, supporting robust time- and cost-effective antibody purification, is warranted. With the advances in molecular design and high-throughput screening approaches from chemical and biological combinatorial libraries, novel affinity ligands representing alternatives to bacterial immunoglobulin (Ig)-binding proteins have entered the scene. Here, we review the design, development, and properties of diverse classes of alternative antibody-binding ligands, ranging from engineered versions of Ig-binding proteins, to artificial binding proteins, peptides, aptamers, and synthetic small-molecular-weight compounds. We also provide examples of applications for the novel affinity matrices in chromatography and beyond.

Application of cellular mechanisms to growth and development of food producing animals.

PubMed

Chung, K Y; Johnson, B J

2008-04-01

Postnatal skeletal muscle growth is a result of hypertrophy of existing skeletal muscle fibers in food producing animals. Accumulation of additional nuclei, as a source of DNA, to the multinucleated skeletal muscle fiber aids in fiber hypertrophy during periods of rapid skeletal muscle growth. Muscle satellite cells are recognized as the source of nuclei to support muscle hypertrophy. Exogenous growth-enhancing compounds have been used to modulate growth rate and efficiency in meat animals for over a half century. In cattle, these compounds enhance efficiency of growth by preferentially stimulating skeletal muscle growth compared with adipose tissue. There are 2 main classes of compounds approved for use in cattle in the United States, anabolic steroids and beta-adrenergic agonists (beta-AA). Administration of both trenbolone acetate and estradiol-17beta, as implants, increased carcass protein accumulation 8 to 10% in yearling steers. Muscle satellite cells isolated from steers implanted with trenbolone acetate/ estradiol-17beta had a shorter lag phase in culture compared with satellite cells isolated from control steers. Collectively, these data indicate that activation, increased proliferation, and subsequent fusion of satellite cells in muscles of implanted cattle may be an important mechanism by which anabolic steroids enhance muscle hypertrophy. Oral administration of beta-AA to ruminants does not alter DNA accumulation in skeletal muscle over a typical feeding period (28 to 42 d). Enhanced muscle hypertrophy observed due to beta-AA feeding occurs by direct, receptor-mediated changes in protein synthesis and degradation rates of skeletal muscle tissue. Proper timing of anabolic steroid administration when coupled with beta-AA feeding could result in a synergistic response in skeletal muscle growth due to the effects of anabolic steroids at increasing satellite cell activity, which then can support the rapid hypertrophic changes of the muscle fiber when exposed to beta-AA. At the same time each of these classes of compounds are stimulating lean tissue deposition, they appear to repress adipogenesis in meat animals. Increased knowledge of the mechanism by which growth promoters regulate lean tissue deposition and adipogenesis in meat animals will allow for effective application of these techniques to optimize lean tissue growth and minimize the negative effects on meat quality.

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

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

Virginia L. Finley

The purpose of this report is to provide the U.S. Department of Energy (DOE) and the public with information on the level of radioactive and nonradioactive pollutants (if any) that are added to the environment as a result of the Princeton Plasma Physics Laboratory's (PPPL) operations. The results of the 2001 environmental surveillance and monitoring program for PPPL are presented and discussed. The report also summarizes environmental initiatives, assessments, and programs that were undertaken in 2001. PPPL has engaged in fusion energy research since 1951. The vision of the Laboratory is to create innovations to make fusion power a practicalmore » reality--a clean, alternative energy source. The Year 2001 marked the third year of National Spherical Torus Experiment (NSTX) operations and Tokamak Fusion Test Reactor (TFTR) dismantlement and deconstruction activities. A collaboration among fourteen national laboratories, universities, and research institutions, the NSTX is a major element in the U.S. Fusion Energy Sciences Program. It has been designed to test the physics principles of spherical torus (ST) plasmas. The ST concept could play an important role in the development of smaller, more economical fusion reactors. In 2001, PPPL's radiological environmental monitoring program measured tritium in the air at on- and off-site sampling stations. PPPL is capable of detecting small changes in the ambient levels of tritium by using highly sensitive monitors. The operation of an in-stack monitor located on D-site is a requirement of the National Emission Standard for Hazardous Air Pollutants (NESHAPs) regulations; also included in PPPL's radiological environmental monitoring program, are water monitoring--precipitation, ground-, surface-, and waste-waters. PPPL's radiological monitoring program characterized the ambient, background levels of tritium in the environment and from the D-site stack; the data are presented in this report. Groundwater monitoring continue d under a voluntary agreement with the New Jersey Department of Environmental Protection. PPPL monitored for the presence of nonradiological contaminants, mainly volatile organic compounds (components of degreasing solvents). Monitoring revealed the low levels of volatile organic compounds in an area adjacent to PPPL. In 2001, PPPL was in compliance with its permit limits for surface and sanitary discharges and had no reportable releases. Additionally, as part of DOE's program for the purchase of recycled content and other environmentally preferred products, PPPL has ranked in the excellent category of 80 to 90% of the goal.« less

Molecular basis of abnormal red-green color vision: a family with three types of color vision defects.

PubMed Central

Drummond-Borg, M; Deeb, S; Motulsky, A G

1988-01-01

The molecular nature of three different types of X-linked color-vision defects, protanomaly, deuteranomaly, and protanopia, in a large 3-generation family was determined. In the protanomalous and protanopic males the normal red pigment gene was replaced by a 5' red-3' green fusion gene. The protanomalous male had more red pigment DNA in his fusion gene than did the more severely affected protanopic individual. The deuteranomalous individual had four green pigment genes and one 5' green-3' red fusion gene. These results extend those of Nathans et al., who proposed that most red-green color-vision defects arise as a result of unequal crossing-over between the red and green pigment genes. The various data suggest that differences in severity of color-vision defects associated with fusion genes are caused by differences in crossover sites between the red and green pigment genes. Currently used molecular methodology is not sufficiently sensitive to define these fusion points accurately, and the specific color-vision defect within the deutan or protan class cannot be predicted. The DNA patterns for color-vision genes of female heterozygotes have not previously been described. Patterns of heterozygotes may not be distinguishable from those of normals. However, a definite assignment of the various color pigment gene arrays could be carried out by family study. Two compound heterozygotes for color-vision defects who tested as normal by anomaloscopy were found to carry abnormal fusion genes. In addition, a normal red pigment gene was present on one chromosome and at least one normal green pigment gene was present on the other.(ABSTRACT TRUNCATED AT 250 WORDS) Images Figure 3 PMID:2847528

Phosphatidylinositol 4,5-bisphosphate optical uncaging potentiates exocytosis

PubMed Central

Wierda, Keimpe DB; Pinheiro, Paulo S; Nadler, André; McCarthy, Anthony W; Ziomkiewicz, Iwona; Kruse, Martin; Reither, Gregor; Rettig, Jens; Lehmann, Martin; Haucke, Volker; Hille, Bertil

2017-01-01

Phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2] is essential for exocytosis. Classical ways of manipulating PI(4,5)P2 levels are slower than its metabolism, making it difficult to distinguish effects of PI(4,5)P2 from those of its metabolites. We developed a membrane-permeant, photoactivatable PI(4,5)P2, which is loaded into cells in an inactive form and activated by light, allowing sub-second increases in PI(4,5)P2 levels. By combining this compound with electrophysiological measurements in mouse adrenal chromaffin cells, we show that PI(4,5)P2 uncaging potentiates exocytosis and identify synaptotagmin-1 (the Ca2+ sensor for exocytosis) and Munc13-2 (a vesicle priming protein) as the relevant effector proteins. PI(4,5)P2 activation of exocytosis did not depend on the PI(4,5)P2-binding CAPS-proteins, suggesting that PI(4,5)P2 uncaging may bypass CAPS-function. Finally, PI(4,5)P2 uncaging triggered the rapid fusion of a subset of readily-releasable vesicles, revealing a rapid role of PI(4,5)P2 in fusion triggering. Thus, optical uncaging of signaling lipids can uncover their rapid effects on cellular processes and identify lipid effectors. PMID:29068313

Quantitative high throughput screening identifies inhibitors of anthrax-induced cell death

PubMed Central

Zhu, Ping Jun; Hobson, Peyton; Southall, Noel; Qiu, Cunping; Thomas, Craig J.; Lu, Jiamo; Inglese, James; Zheng, Wei; Leppla, Stephen H.; Bugge, Thomas H.; Austin, Christopher P.; Liu, Shihui

2009-01-01

Here, we report the results of a quantitative high-throughput screen (qHTS) measuring the endocytosis and translocation of a β-lactamase-fused-lethal factor and the identification of small molecules capable of obstructing the process of anthrax toxin internalization. Several small molecules protect RAW264.7 macrophages and CHO cells from anthrax lethal toxin and protected cells from an LF-Pseudomonas exotoxin fusion protein and diphtheria toxin. Further efforts demonstrated that these compounds impaired the PA heptamer pre-pore to pore conversion in cells expressing the CMG2 receptor, but not the related TEM8 receptor, indicating that these compounds likely interfere with toxin internalization. PMID:19540764

Kinetics of Cell Fusion Induced by a Syncytia-Producing Mutant of Herpes Simplex Virus Type I

PubMed Central

Person, Stanley; Knowles, Robert W.; Read, G. Sullivan; Warner, Susan C.; Bond, Vincent C.

1976-01-01

We have isolated a number of plaque-morphology mutants from a strain of herpes simplex virus type I which, unlike the wild type, cause extensive cell fusion during a productive viral infection. After the onset of fusion, there is an exponential decrease in the number of single cells as a function of time after infection. At a multiplicity of infection (MOI) of 3.8 plaque-forming units per cell, fusion begins 5.3 h after infection with the number of single cells decreasing to 10% of the original number 10.2 h after infection. As the MOI is gradually increased from 0.4 to 8, the onset of fusion occurs earlier during infection. However, when the MOI is increased from 8 to 86, the onset of fusion does not occur any earlier. The rate of fusion is independent of the MOI for an MOI greater than 1. The rate of fusion varies linearly with initial cell density up to 3.5 × 104 cells/cm2 and is independent of initial cell density at higher cell concentrations. To assay cell fusion we have developed a simple quantitative assay using a Coulter counter to measure the number of single cells as a function of time after infection. Data obtained using a Coulter counter are similar to those obtained with a microscope assay. PMID:173881

Atomic Force Microscope Studies of the Fusion of Floating Lipid Bilayers

PubMed Central

Abdulreda, Midhat H.; Moy, Vincent T.

2007-01-01

This study investigated the fusion of apposing floating bilayers of egg L-α-phosphatidylcholine (egg PC) or 1,2-dimyristoyl-sn-glycero-3-phosphocholine. Atomic force microscope measurements of fusion forces under different compression rates were acquired to reveal the energy landscape of the fusion process under varied lipid composition and temperature. Between compression rates of ∼1000 and ∼100,000 pN/s, applied forces in the range from ∼100 to ∼500 pN resulted in fusion of floating bilayers. Our atomic force microscope measurements indicated that one main energy barrier dominated the fusion process. The acquired dynamic force spectra were fit with a simple model based on the transition state theory with the assumption that the fusion activation potential is linear. A significant shift in the energy landscape was observed when bilayer fluidity and composition were modified, respectively, by temperature and different cholesterol concentrations (15% ≤ chol ≤ 25%). Such modifications resulted in a more than twofold increase in the width of the fusion energy barrier for egg PC and 1,2-dimyristoyl-sn-glycero-3-phosphocholine floating bilayers. The addition of 25% cholesterol to egg PC bilayers increased the activation energy by ∼1.0 kBT compared with that of bilayers with egg PC alone. These results reveal that widening of the energy barrier and consequently reduction in its slope facilitated membrane fusion. PMID:17400691

Atomic force microscope studies of the fusion of floating lipid bilayers.

PubMed

Abdulreda, Midhat H; Moy, Vincent T

2007-06-15

This study investigated the fusion of apposing floating bilayers of egg L-alpha-phosphatidylcholine (egg PC) or 1,2-dimyristoyl-sn-glycero-3-phosphocholine. Atomic force microscope measurements of fusion forces under different compression rates were acquired to reveal the energy landscape of the fusion process under varied lipid composition and temperature. Between compression rates of approximately 1000 and approximately 100,000 pN/s, applied forces in the range from approximately 100 to approximately 500 pN resulted in fusion of floating bilayers. Our atomic force microscope measurements indicated that one main energy barrier dominated the fusion process. The acquired dynamic force spectra were fit with a simple model based on the transition state theory with the assumption that the fusion activation potential is linear. A significant shift in the energy landscape was observed when bilayer fluidity and composition were modified, respectively, by temperature and different cholesterol concentrations (15% < or = chol < or = 25%). Such modifications resulted in a more than twofold increase in the width of the fusion energy barrier for egg PC and 1,2-dimyristoyl-sn-glycero-3-phosphocholine floating bilayers. The addition of 25% cholesterol to egg PC bilayers increased the activation energy by approximately 1.0 k(B)T compared with that of bilayers with egg PC alone. These results reveal that widening of the energy barrier and consequently reduction in its slope facilitated membrane fusion.

The Fusion Model of Intelligent Transportation Systems Based on the Urban Traffic Ontology

NASA Astrophysics Data System (ADS)

Yang, Wang-Dong; Wang, Tao

On these issues unified representation of urban transport information using urban transport ontology, it defines the statute and the algebraic operations of semantic fusion in ontology level in order to achieve the fusion of urban traffic information in the semantic completeness and consistency. Thus this paper takes advantage of the semantic completeness of the ontology to build urban traffic ontology model with which we resolve the problems as ontology mergence and equivalence verification in semantic fusion of traffic information integration. Information integration in urban transport can increase the function of semantic fusion, and reduce the amount of data integration of urban traffic information as well enhance the efficiency and integrity of traffic information query for the help, through the practical application of intelligent traffic information integration platform of Changde city, the paper has practically proved that the semantic fusion based on ontology increases the effect and efficiency of the urban traffic information integration, reduces the storage quantity, and improve query efficiency and information completeness.

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.

Pairwise diversity ranking of polychotomous features for ensemble physiological signal classifiers.

PubMed

Gupta, Lalit; Kota, Srinivas; Molfese, Dennis L; Vaidyanathan, Ravi

2013-06-01

It is well known that fusion classifiers for physiological signal classification with diverse components (classifiers or data sets) outperform those with less diverse components. Determining component diversity, therefore, is of the utmost importance in the design of fusion classifiers that are often employed in clinical diagnostic and numerous other pattern recognition problems. In this article, a new pairwise diversity-based ranking strategy is introduced to select a subset of ensemble components, which when combined will be more diverse than any other component subset of the same size. The strategy is unified in the sense that the components can be classifiers or data sets. Moreover, the classifiers and data sets can be polychotomous. Classifier-fusion and data-fusion systems are formulated based on the diversity-based selection strategy, and the application of the two fusion strategies are demonstrated through the classification of multichannel event-related potentials. It is observed that for both classifier and data fusion, the classification accuracy tends to increase/decrease when the diversity of the component ensemble increases/decreases. For the four sets of 14-channel event-related potentials considered, it is shown that data fusion outperforms classifier fusion. Furthermore, it is demonstrated that the combination of data components that yield the best performance, in a relative sense, can be determined through the diversity-based selection strategy.

Phosphatidylinositol 4,5-bisphosphate regulates SNARE-dependent membrane fusion.

PubMed

James, Declan J; Khodthong, Chuenchanok; Kowalchyk, Judith A; Martin, Thomas F J

2008-07-28

Phosphatidylinositol 4,5-bisphosphate (PI 4,5-P(2)) on the plasma membrane is essential for vesicle exocytosis but its role in membrane fusion has not been determined. Here, we quantify the concentration of PI 4,5-P(2) as approximately 6 mol% in the cytoplasmic leaflet of plasma membrane microdomains at sites of docked vesicles. At this concentration of PI 4,5-P(2) soluble NSF attachment protein receptor (SNARE)-dependent liposome fusion is inhibited. Inhibition by PI 4,5-P(2) likely results from its intrinsic positive curvature-promoting properties that inhibit formation of high negative curvature membrane fusion intermediates. Mutation of juxtamembrane basic residues in the plasma membrane SNARE syntaxin-1 increase inhibition by PI 4,5-P(2), suggesting that syntaxin sequesters PI 4,5-P(2) to alleviate inhibition. To define an essential rather than inhibitory role for PI 4,5-P(2), we test a PI 4,5-P(2)-binding priming factor required for vesicle exocytosis. Ca(2+)-dependent activator protein for secretion promotes increased rates of SNARE-dependent fusion that are PI 4,5-P(2) dependent. These results indicate that PI 4,5-P(2) regulates fusion both as a fusion restraint that syntaxin-1 alleviates and as an essential cofactor that recruits protein priming factors to facilitate SNARE-dependent fusion.

Simulated Radioscapholunate Fusion Alters Carpal Kinematics While Preserving Dart-Thrower's Motion

PubMed Central

Calfee, Ryan P.; Leventhal, Evan L.; Wilkerson, Jim; Moore, Douglas C.; Akelman, Edward; Crisco, Joseph J.

2014-01-01

Purpose Midcarpal degeneration is well documented after radioscapholunate fusion. This study tested the hypothesis that radioscapholunate fusion alters the kinematic behavior of the remaining lunotriquetral and midcarpal joints, with specific focus on the dart-thrower's motion. Methods Simulated radioscapholunate fusions were performed on 6 cadaveric wrists in an anatomically neutral posture. Two 0.060-in. carbon fiber pins were placed from proximal to distal across the radiolunate and radioscaphoid joints, respectively. The wrists were passively positioned in a custom jig toward a full range of motion along the orthogonal axes as well as oblique motions, with additional intermediate positions along the dart-thrower's path. Using a computed tomography– based markerless bone registration technique, each carpal bone's three-dimensional rotation was defined as a function of wrist flexion/extension from the pinned neutral position. Kinematic data was analyzed against data collected on the same wrist prior to fixation using hierarchical linear regression analysis and paired Student's t-tests. Results After simulated fusion, wrist motion was restricted to an average flexion-extension arc of 48°, reduced from 77°, and radial-ulnar deviation arc of 19°, reduced from 33°. The remaining motion was maximally preserved along the dart-thrower's path from radial-extension toward ulnar-flexion. The simulated fusion significantly increased rotation through the scaphotrapezial joint, scaphocapitate joint, triquetrohamate joint, and lunotriquetral joint. For example, in the pinned wrist, the rotation of the hamate relative to the triquetrum increased 85%. Therefore, during every 10° of total wrist motion, the hamate rotated an average of nearly 8° relative to the triquetrum after pinning versus 4° in the normal state. Conclusions Simulated radioscapholunate fusion altered midcarpal and lunotriquetral kinematics. The increased rotations across these remaining joints provide one potential explanation for midcarpal degeneration after radioscapholunate fusion. Additionally, this fusion model confirms the dart-thrower's hypothesis, as wrist motion after simulated radioscapholunate fusion was primarily preserved from radial-extension toward ulnar-flexion. PMID:18406953

Multi-Sensor Fusion with Interaction Multiple Model and Chi-Square Test Tolerant Filter.

PubMed

Yang, Chun; Mohammadi, Arash; Chen, Qing-Wei

2016-11-02

Motivated by the key importance of multi-sensor information fusion algorithms in the state-of-the-art integrated navigation systems due to recent advancements in sensor technologies, telecommunication, and navigation systems, the paper proposes an improved and innovative fault-tolerant fusion framework. An integrated navigation system is considered consisting of four sensory sub-systems, i.e., Strap-down Inertial Navigation System (SINS), Global Navigation System (GPS), the Bei-Dou2 (BD2) and Celestial Navigation System (CNS) navigation sensors. In such multi-sensor applications, on the one hand, the design of an efficient fusion methodology is extremely constrained specially when no information regarding the system's error characteristics is available. On the other hand, the development of an accurate fault detection and integrity monitoring solution is both challenging and critical. The paper addresses the sensitivity issues of conventional fault detection solutions and the unavailability of a precisely known system model by jointly designing fault detection and information fusion algorithms. In particular, by using ideas from Interacting Multiple Model (IMM) filters, the uncertainty of the system will be adjusted adaptively by model probabilities and using the proposed fuzzy-based fusion framework. The paper also addresses the problem of using corrupted measurements for fault detection purposes by designing a two state propagator chi-square test jointly with the fusion algorithm. Two IMM predictors, running in parallel, are used and alternatively reactivated based on the received information form the fusion filter to increase the reliability and accuracy of the proposed detection solution. With the combination of the IMM and the proposed fusion method, we increase the failure sensitivity of the detection system and, thereby, significantly increase the overall reliability and accuracy of the integrated navigation system. Simulation results indicate that the proposed fault tolerant fusion framework provides superior performance over its traditional counterparts.

Multi-Sensor Fusion with Interaction Multiple Model and Chi-Square Test Tolerant Filter

PubMed Central

Yang, Chun; Mohammadi, Arash; Chen, Qing-Wei

2016-01-01

Motivated by the key importance of multi-sensor information fusion algorithms in the state-of-the-art integrated navigation systems due to recent advancements in sensor technologies, telecommunication, and navigation systems, the paper proposes an improved and innovative fault-tolerant fusion framework. An integrated navigation system is considered consisting of four sensory sub-systems, i.e., Strap-down Inertial Navigation System (SINS), Global Navigation System (GPS), the Bei-Dou2 (BD2) and Celestial Navigation System (CNS) navigation sensors. In such multi-sensor applications, on the one hand, the design of an efficient fusion methodology is extremely constrained specially when no information regarding the system’s error characteristics is available. On the other hand, the development of an accurate fault detection and integrity monitoring solution is both challenging and critical. The paper addresses the sensitivity issues of conventional fault detection solutions and the unavailability of a precisely known system model by jointly designing fault detection and information fusion algorithms. In particular, by using ideas from Interacting Multiple Model (IMM) filters, the uncertainty of the system will be adjusted adaptively by model probabilities and using the proposed fuzzy-based fusion framework. The paper also addresses the problem of using corrupted measurements for fault detection purposes by designing a two state propagator chi-square test jointly with the fusion algorithm. Two IMM predictors, running in parallel, are used and alternatively reactivated based on the received information form the fusion filter to increase the reliability and accuracy of the proposed detection solution. With the combination of the IMM and the proposed fusion method, we increase the failure sensitivity of the detection system and, thereby, significantly increase the overall reliability and accuracy of the integrated navigation system. Simulation results indicate that the proposed fault tolerant fusion framework provides superior performance over its traditional counterparts. PMID:27827832

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

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.

CXCR2 inverse agonism detected by arrestin redistribution.

PubMed

Kredel, Simone; Wolff, Michael; Wiedenmann, Jörg; Moepps, Barbara; Nienhaus, G Ulrich; Gierschik, Peter; Kistler, Barbara; Heilker, Ralf

2009-10-01

To study CXCR2 modulated arrestin redistribution, the authors employed arrestin as a fusion protein containing either the Aequorea victoria-derived enhanced green fluorescent protein (EGFP) or a recently developed mutant of eqFP611, a red fluorescent protein derived from Entacmaea quadricolor. This mutant, referred to as RFP611, had earlier been found to assume a dimeric quarternary structure. It was therefore employed in this work as a "tandem" (td) construct for pseudo-monomeric fusion protein labeling. Both arrestin fusion proteins, containing either td-RFP611 (Arr-td-RFP611) or enhanced green fluorescent protein (EGFP; Arr-EGFP), were found to colocalize with internalized fluorescently labeled Gro-alpha a few minutes after Gro-alpha addition. Intriguingly, however, Arr-td-RFP611 and Arr-EGFP displayed distinct cellular distribution patterns in the absence of any CXCR2-activating ligand. Under these conditions, Arr-td-RFP611 showed a largely homogeneous cytosolic distribution, whereas Arr-EGFP segregated, to a large degree, into granular spots. These observations indicate a higher sensitivity of Arr EGFP to the constitutive activity of CXCR2 and, accordingly, an increased arrestin redistribution to coated pits and endocytic vesicles. In support of this interpretation, the authors found the known CXCR2 antagonist Sch527123 to act as an inverse agonist with respect to Arr-EGFP redistribution. The inverse agonistic properties of Sch527123 were confirmed in vitro in a guanine nucleotide binding assay, revealing an IC(50) value similar to that observed for Arr-EGFP redistribution. Thus, the redistribution assay, when based on Arr-EGFP, enables the profiling of antagonistic test compounds with respect to inverse agonism. When based on Arr-td-RFP611, the assay may be employed to study CXCR2 agonism or neutral antagonism.

Low-intensity pulsed ultrasound promotes spinal fusion and enhances migration and proliferation of MG63s through sonic hedgehog signaling pathway.

PubMed

Zhou, Xiao-Yi; Xu, Xi-Ming; Wu, Sui-Yi; Zhang, Zi-Cheng; Wang, Fei; Yang, Yi-Lin; Li, Ming; Wei, Xian-Zhao

2018-05-01

Low-intensity pulsed ultrasound (LIPUS) has been found to accelerate the healing process of spinal fusion via a process closely related to osteoblast differentiation and migration. Sonic hedgehog (Shh) signaling plays an important role in development and homeostasis, including a critical function in bone formation. However, its role in spinal fusion during LIPUS treatment is still unknown. This study showed that LIPUS treatment after spinal fusion surgery increased bone formation. The increased bone mass under LIPUS treatment appeared to result from the increased migration and proliferation of osteoblasts, resulting from upregulation of the Shh signaling pathway. In contrast, inhibition of Shh reduced the migratory and proliferative ability of osteoblast-like MG63 cells and blocked the efficacy of LIPUS treatment. Copyright © 2018 Elsevier Inc. All rights reserved.

An Examination of the Phase Transition Thermodynamics of (S)- and (RS)-Naproxen as a Basis for the Design of Enantioselective Crystallization Processes.

PubMed

Buchholz, Hannes; Emel'yanenko, Vladimir N; Lorenz, Heike; Verevkin, Sergey P

2016-05-01

A detailed experimental analysis of the phase transition thermodynamics of (S)-naproxen and (RS)-naproxen is reported. Vapor pressures were determined experimentally via the transpiration method. Sublimation enthalpies were obtained from the vapor pressures and from independent TGA measurements. Thermodynamics of fusion which have been well-studied in the literature were systematically remeasured by DSC. Both sublimation and fusion enthalpies were adjusted to one reference temperature, T = 298 K, using measured heat capacities of the solid and the melt phase by DSC. Average values from the measurements and from literature data were suggested for the sublimation and fusion enthalpies. In order to prove consistency of the proposed values the vaporization enthalpies obtained by combination of both were compared to vaporization enthalpies obtained by the group-additivity method and the correlation-gas chromatography method. The importance of reliable and precise phase transition data for thermochemical calculations such as the prediction of solid/liquid phase behaviour of chiral compounds is highlighted. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Fusion Leadership: Unlocking the Subtle Forces that Change People and Organizations.

ERIC Educational Resources Information Center

Daft, Richard L.; Lengel, Robert H.

Fusion leadership is a metaphor for a certain style of management where partnerships are created, barriers reduced, conversation increased, and joint responsibility enhanced. Ways in which an organization can implement this type of leadership are presented. The book details various characteristics of fusion leadership, describing the forces that…

Characterisation of Weibel-Palade body fusion by amperometry in endothelial cells reveals fusion pore dynamics and the effect of cholesterol on exocytosis.

PubMed

Cookson, Emma A; Conte, Ianina L; Dempster, John; Hannah, Matthew J; Carter, Tom

2013-12-01

Regulated secretion from endothelial cells is mediated by Weibel-Palade body (WPB) exocytosis. Plasma membrane cholesterol is implicated in regulating secretory granule exocytosis and fusion pore dynamics; however, its role in modulating WPB exocytosis is not clear. To address this we combined high-resolution electrochemical analysis of WPB fusion pore dynamics, by amperometry, with high-speed optical imaging of WPB exocytosis following cholesterol depletion or supplementation in human umbilical vein endothelial cells. We identified serotonin (5-HT) immunoreactivity in WPBs, and VMAT1 expression allowing detection of secreted 5-HT as discrete current spikes during exocytosis. A high proportion of spikes (∼75%) had pre-spike foot signals, indicating that WPB fusion proceeds via an initial narrow pore. Cholesterol depletion significantly reduced pre-spike foot signal duration and increased the rate of fusion pore expansion, whereas cholesterol supplementation had broadly the reverse effect. Cholesterol depletion slowed the onset of hormone-evoked WPB exocytosis, whereas its supplementation increased the rate of WPB exocytosis and hormone-evoked proregion secretion. Our results provide the first analysis of WPB fusion pore dynamics and highlight an important role for cholesterol in the regulation of WPB exocytosis.

Study on polarization image methods in turbid medium

NASA Astrophysics Data System (ADS)

Fu, Qiang; Mo, Chunhe; Liu, Boyu; Duan, Jin; Zhang, Su; Zhu, Yong

2014-11-01

Polarization imaging detection technology in addition to the traditional imaging information, also can get polarization multi-dimensional information, thus improve the probability of target detection and recognition.Image fusion in turbid medium target polarization image research, is helpful to obtain high quality images. Based on visible light wavelength of light wavelength of laser polarization imaging, through the rotation Angle of polaroid get corresponding linear polarized light intensity, respectively to obtain the concentration range from 5% to 10% of turbid medium target stocks of polarization parameters, introduces the processing of image fusion technology, main research on access to the polarization of the image by using different polarization image fusion methods for image processing, discusses several kinds of turbid medium has superior performance of polarization image fusion method, and gives the treatment effect and analysis of data tables. Then use pixel level, feature level and decision level fusion algorithm on three levels of information fusion, DOLP polarization image fusion, the results show that: with the increase of the polarization Angle, polarization image will be more and more fuzzy, quality worse and worse. Than a single fused image contrast of the image be improved obviously, the finally analysis on reasons of the increase the image contrast and polarized light.

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

Anderson, J.L.; Jenkins, E.M.; Walthers, C.R.

Compound cryopumps have been added to the Tritium Systems Test Assembly (TSTA) integrated fusion fuel loop. Operations have been performed which closely simulate an actual fusion reactor pumping scenario. In addition, performance data have been taken that support the concept of using coconut charcoal as a sorbent at 4K for pumping helium. Later tests show that coconut charcoal may be used to co-pump D,T and He mixtures on a single 4K panel. Rotary spiral pumps have been used successfully in several applications at TSTA and have acquired more than 9000 hours of maintenance-free operation. Metal bellows pumps have been usedmore » to back the spiral pumps and have been relatively trouble free in loop operations. Bellows pumps also have more than 9000 hours of maintenance-free operation. 5 refs., 6 figs.« less

Solid State Research

DTIC Science & Technology

1990-05-15

reference to indicate the exact time of the transmitted pulse. The returned pulses are detected using a four - quadrant photomultiplie tube, and each quadrant ...1990) Nondegencrate Four -Wave Mixing K.B. Nichols DTIC AD-A221419 in AlGaAs Waveguides W.D. Goodhue Wafer Fusion: A Novel Technique Z.L. Liau Appl...Annealing H.J. Zeiger (1990) of Etched Compound Semiconductor Structures: Theoretical Modeling and Experimental Confirmation Programmable, Four -Channel

National Biocontainment Training Center

DTIC Science & Technology

2015-02-01

develop novel diagnostic platforms to detect drug resistant TB and identification of novel antimicrobial compounds with antibacterial activity against...rCCHFV rescue work in BSL-4. Figure 6. Schematic of the CCHFV M segment fusion with Nanoluc. (a) insert the Nanoluc after the signal peptide , (b...in Dallas, Texas. Trainers: Vickie Jones and Jason Hardcastle. Food and Drug Administration (FDA-CBER) – BSL3 training was provided for faculty and

Applications of the Aqueous Self-Cooled Blanket concept

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

Steiner, D.; Embrechts, M.J.; Varsamis, G.

1986-11-01

In this paper a novel water-cooled blanket concept is examined. This concept, designated the Aqueous Self-Cooled Blanket (ASCB), employs water with small amounts of dissolved fertile compounds as both the coolant and the breeding medium. The ASCB concept is reviewed and its application in three different contexts is examined: (1) power reactors; (2) near-term devices such as NET; and (3) fusion-fission hybrids.

Overview of Fusion Tags for Recombinant Proteins.

PubMed

Kosobokova, E N; Skrypnik, K A; Kosorukov, V S

2016-03-01

Virtually all recombinant proteins are now prepared using fusion domains also known as "tags". The use of tags helps to solve some serious problems: to simplify procedures of protein isolation, to increase expression and solubility of the desired protein, to simplify protein refolding and increase its efficiency, and to prevent proteolysis. In this review, advantages and disadvantages of such fusion tags are analyzed and data on both well-known and new tags are generalized. The authors own data are also presented.

Synthesis, Spectral Characterization, Thermal and Optical Studies of Novel Complexes: 4-(Dimethylamino)benzylidene-4-acetamideaniline and 4-(Dimethylamino)benzylidene-4-nitroaniline.

PubMed

Neupane, Umesh; Rai, R N

2017-11-01

The phase diagram representing solid-liquid equilibrium of entire range of composition and thermodynamic studies of two binary organic systems of 4-dimethylaminobenzaldehyde (DMAB) with two NLO active compounds, p-aminoacetanilide (PAA) and p-nitroaniline (PNA), have been studied by solid state synthetic route. Both systems are independently forming a new entity called intermolecular complex (IMC) and two eutectics on either side of intermolecular complexes. The various thermodynamic parameters such as heat of mixing, entropy of fusion, roughness parameter, interfacial energy and excess thermodynamic functions of IMCs and eutectics were calculated using the heat of fusion values. The TGA and DTA studies were performed to understand the physico-chemical, thermal behavior and unique identity of newly synthesized organic complexes, 4-(dimethylamino)benzylidene-4-acetamideaniline (DMABPAA) and 4-(dimethylamino)benzylidene-4-nitroaniline (DMABPNA), and their respective enthalpy of fusion values were found to be 30.01 and 37.26 kJ mol - 1 . The higher melting point of both the novel complexes than their parent's compounds reveal the strong molecular interaction between parent components to yield the complex. The FTIR spectral analysis predicts the disappearance of aldehyde peaks of DMAB and NH 2 peaks of PAA and PNA while the appearance of entirely new peaks than that of parent's compounds are the supportive for the formation of new molecular entities. These findings are further supported by FTNMR spectrum studies by observation of disappearance of proton peak of aldehyde of DMAB and amine peaks of PAA and PNA rather formation of new imine proton peak or peaks were observed. The appearance of new peaks in Powder XRD of complexes than those of parent components is further indicative for the formation of complexes. The absorption spectrum of DMABPAA and DMABPNA showed intra-molecular charge-transfer (ICT) excited state absorption at 258 and 241 nm, respectively. Both the IMCs, DMABPAA and DMABPNA, show strong fluorescence with quantum yield 0.66 and 0.93, respectively, in methanol solution.

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.

Influence of the asymmetry parameter and dissipation coefficient of the K coordinate on different aspects of fission of excited compound nuclei

NASA Astrophysics Data System (ADS)

Eslamizadeh, H.; Abdollahi, N.

2018-02-01

The dynamics of fission of the excited compound nuclei 256Fm, 215Fr, 187Ir, 172Yb, 162Yb, and 142Ce produced in fusion reactions with 158.8 MeV 18O has been studied by solving three- and four-dimensional Langevin equations with dissipation generated through the chaos weighted wall and window friction formula. The constant dissipation coefficients of K , γK=0.077 (MeVzs ) -1 /2 , γK=0.2 (MeVzs ) -1 /2 and a nonconstant dissipation coefficient of K have been used to reproduce the experimental data for both symmetric and asymmetric splitting of the fissioning systems. The average kinetic energies of fission fragments, the pre-scission neutron multiplicities, the fission time, and the variances of the mass and kinetic energy of fission fragments are calculated for the excited compound nuclei 256Fm, 215Fr, 187Ir, 172Yb, 162Yb, 142Ce, and results of the calculations are compared with each other and with the experimental data. Comparison of the theoretical results with the experimental data calculated by using different values of γK shows that the difference is small between the results of calculations for symmetric and asymmetric simulations of the fission process of excited intermediate nuclei, whereas for heavy compound nuclei the difference is slightly high. In other words, the effect of the asymmetry parameter on the fission process of intermediate nuclei is smaller than the effect on heavy nuclei. Furthermore, we show that the pre-scission neutron multiplicity decreases rapidly with increasing fragment asymmetry.

Laser-induced tissue fluorescence in radiofrequency tissue-fusion characterization.

PubMed

Su, Lei; Fonseca, Martina B; Arya, Shobhit; Kudo, Hiromi; Goldin, Robert; Hanna, George B; Elson, Daniel S

2014-01-01

Heat-induced tissue fusion is an important procedure in modern surgery and can greatly reduce trauma, complications, and mortality during minimally invasive surgical blood vessel anastomosis, but it may also have further benefits if applied to other tissue types such as small and large intestine anastomoses. We present a tissue-fusion characterization technology using laser-induced fluorescence spectroscopy, which provides further insight into tissue constituent variations at the molecular level. In particular, an increase of fluorescence intensity in 450- to 550-nm range for 375- and 405-nm excitation suggests that the collagen cross-linking in fused tissues increased. Our experimental and statistical analyses showed that, by using fluorescence spectral data, good fusion could be differentiated from other cases with an accuracy of more than 95%. This suggests that the fluorescence spectroscopy could be potentially used as a feedback control method in online tissue-fusion monitoring.

Thermonuclear plasma with autocatalytic thermomagnetic current amplification by nuclear reactions from fusion neutrons

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

Winterberg, F.

2006-03-15

It is proposed to use the neutrons released from a deuterium-tritium or deuterium-deuterium fusion reaction to drive thermomagnetic currents in a plasma corona surrounding the fusion plasma through the heating of the corona with nuclear reactions by the neutrons released in the fusion reaction. Because the neutron reaction cross sections are larger for slow neutrons, it is proposed to slow them down in a moderator separated from the hot plasma of the corona, giving the configuration a striking similarity to a heterogeneous nuclear fission reactor. While in a fission reactor the separation makes possible a growing neutron chain reaction, itmore » here makes possible the autocatalytic amplification of the thermomagnetic currents by an increase of the fusion reaction rate through a rise of the plasma pressure by the magnetic pressure of the thermomagnetic currents. This is expected to substantially increase the n{tau} product over its Lawson value.« less

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.

Systematic study of probable projectile-target combinations for the synthesis of the superheavy nucleus 302120

NASA Astrophysics Data System (ADS)

Santhosh, K. P.; Safoora, V.

2016-08-01

Probable projectile-target combinations for the synthesis of the superheavy element 302120 have been studied taking the Coulomb and proximity potential as the interaction barrier. The probabilities of the compound nucleus formation PCN for the projectile-target combinations found in the cold reaction valley of 302120 are estimated. At energies near and above the Coulomb barrier, we have calculated the capture, fusion, and evaporation residue cross sections for the reactions of all probable projectile-target combinations so as to predict the most promising projectile-target combinations for the synthesis of the superheavy element 302120 in heavy-ion fusion reactions. The calculated fusion and evaporation cross sections for the more asymmetric ("hotter") projectile-target combination is found to be higher than the less asymmetric ("colder") combination. It can be seen from the nature of the quasifission barrier height, mass asymmetry, the probability of compound nucleus formation, survival probability, and excitation energy, the systems 44Ar+258No , 46Ar+256No , 48Ca+254Fm , 50Ca+252Fm , 54Ti+248Cf , and 58Cr+244Cm in deep region I of the cold reaction valley and the systems 62Fe+240Pu , 64Fe+238Pu , 68Ni+234U , 70Ni+232U , 72Ni+230U , and 74Zn+228Th in the other cold valleys are identified as the better projectile-target combinations for the synthesis of 302120. Our predictions on the synthesis of 302120 superheavy nuclei using the combinations 54Cr+248Cm , 58Fe+244Pu , 64Ni+238U , and 50Ti+249Cf are compared with available experimental data and other theoretical predictions.

Mitofusin-2 protects against cold stress-induced cell injury in HEK293 cells

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

Zhang, Wenbin; Chen, Yaomin; Yang, Qun

2010-06-25

Mitochondrial impairment is hypothesized to contribute to cell injury during cold stress. Mitochondria fission and fusion are closely related in the function of the mitochondria, but the precise mechanisms whereby these processes regulate cell injury during cold stress remain to be determined. HEK293 cells were cultured in a cold environment (4.0 {+-} 0.1 {sup o}C) for 2, 4, 8, or 12 h. Western blot analyses showed that these cells expressed decreased fission-related protein Drp1 and increased fusion-related protein Mfn2 at 4 h; meanwhile, electron microscopy analysis revealed large and long mitochondrial morphology within these cells, indicating increased mitochondrial fusion. Withmore » silencing of Mfn2 but not of Mfn1 by siRNA promoted cold-stress-induced cell death with decreased ATP production in HEK293 cells. Our results show that increased expression of Mfn2 and mitochondrial fusion are important for mitochondrial function as well as cell survival during cold stress. These findings have important implications for understanding the mechanisms of mitochondrial fusion and fission in cold-stress-induced cell injury.« less

Tisseel utilized as hemostatic in spine surgery impacts time to drain removal and length of stay.

PubMed

Epstein, Nancy E

2014-01-01

Although fibrin sealants (FSs) and fibrin glues (FGs) are predominantly utilized to strengthen repairs of cerebrospinal fluid (CSF) fistulas (deliberate/traumatic) during spinal surgery, they are also increasingly utilized to achieve hemostasis. Here, we investigated whether adding Tisseel (Baxter International Inc., Westlake Village, CA, USA), utilized to address increased bleeding during multilevel lumbar laminectomies with non-instrumented fusions, would reduce or equalize the time to drain removal and length of stay (LOS) without contributing to infections or prolonging time to fusion. Prospectively, 39 patients underwent multilevel laminectomies and 1-2 level non-instrumented (in situ) fusions to address stenosis/olisthesis; 22 who demonstrated increased intraoperative bleeding received Tisseel, while 17 without such bleeding did not. The 22 receiving versus 17 not receiving Tisseel, with similar clinical parameters, underwent comparable average multilevel laminectomies (4.36 and 4.25) and 1-2 level fusions (1.4 vs. 1.29 levels). As anticipated, for those receiving Tisseel, the average intraoperative estimated blood loss (EBL), total postoperative blood loss, and total perioperative transfusion requirements [red blood cells (RBC), fresh frozen plasma (FFP), platelets] were higher. However, Tisseel had the added benefit of equalizing the time to postoperative drain removal [e.g. 3.41 days (with) vs. 3.38 days (without)] and LOS [e.g. 5.86 days (with) vs. 5.82 days (without)] without increasing the infection rates (e.g. one superficial infection per group) or average times to fusion (e.g. 5.9 vs. 5.5 months). Adding Tisseel for increased bleeding during multilevel laminectomies/in situ fusions contributed to hemostasis by equalizing the average times to drain removal/LOS compared to patients without increased bleeding and not requiring Tisseel.

Granule mobility, fusion frequency and insulin secretion are differentially affected by insulinotropic stimuli.

PubMed

Schumacher, Kirstin; Matz, Magnus; Brüning, Dennis; Baumann, Knut; Rustenbeck, Ingo

2015-05-01

The pre-exocytotic behavior of insulin granules was studied against the background of the entirety of submembrane granules in MIN6 cells, and the characteristics were compared with the macroscopic secretion pattern and the cytosolic Ca(2+) concentration of MIN6 pseudo-islets at 22°C, 32°C and 37°C. The mobility of granules labeled by insulin-EGFP and the fusion events were assessed by TIRF microscopy utilizing an observer-independent algorithm. In the z-dimension, 40 mm K(+) or 30 mm glucose increased the granule turnover. The effect of high K(+) was quickly reversible. The increase by glucose was more sustained and modified the efficacy of a subsequent K(+) stimulus. The effect size of glucose increased with physiological temperature whereas that of high K(+) did not. The mobility in the x/y-dimension and the fusion rates were little affected by the stimuli, in contrast to secretion. Fusion and secretion, however, had the same temperature dependence. Granules that appeared and fused within one image sequence had significantly larger caging diameters than pre-existent granules that underwent fusion. These in turn had a different mobility than residence-matched non-fusing granules. In conclusion, delivery to the membrane, tethering and fusion of granules are differently affected by insulinotropic stimuli. Fusion rates and secretion do not appear to be tightly coupled. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A Flavonoid Compound Promotes Neuronal Differentiation of Embryonic Stem Cells via PPAR-β Modulating Mitochondrial Energy Metabolism.

PubMed

Mei, Yu-Qin; Pan, Zong-Fu; Chen, Wen-Teng; Xu, Min-Hua; Zhu, Dan-Yan; Yu, Yong-Ping; Lou, Yi-Jia

2016-01-01

Relatively little is known regarding mitochondrial metabolism in neuronal differentiation of embryonic stem (ES) cells. By using a small molecule, present research has investigated the pattern of cellular energy metabolism in neural progenitor cells derived from mouse ES cells. Flavonoid compound 4a faithfully facilitated ES cells to differentiate into neurons morphologically and functionally. The expression and localization of peroxisome proliferator-activated receptors (PPARs) were examined in neural progenitor cells. PPAR-β expression showed robust upregulation compared to solvent control. Treatment with PPAR-β agonist L165041 alone or together with compound 4a significantly promoted neuronal differentiation, while antagonist GSK0660 blocked the neurogenesis-promoting effect of compound 4a. Consistently, knockdown of PPAR-β in ES cells abolished compound 4a-induced neuronal differentiation. Interestingly, we found that mitochondrial fusion protein Mfn2 was also abolished by sh-PPAR-β, resulting in abnormal mitochondrial Ca2+ ([Ca2+]M) transients as well as impaired mitochondrial bioenergetics. In conclusion, we demonstrated that by modulating mitochondrial energy metabolism through Mfn2 and mitochondrial Ca2+, PPAR-β took an important role in neuronal differentiation induced by flavonoid compound 4a.

A Flavonoid Compound Promotes Neuronal Differentiation of Embryonic Stem Cells via PPAR-β Modulating Mitochondrial Energy Metabolism

PubMed Central

Mei, Yu-qin; Pan, Zong-fu; Chen, Wen-teng; Xu, Min-hua; Zhu, Dan-yan; Yu, Yong-ping; Lou, Yi-jia

2016-01-01

Relatively little is known regarding mitochondrial metabolism in neuronal differentiation of embryonic stem (ES) cells. By using a small molecule, present research has investigated the pattern of cellular energy metabolism in neural progenitor cells derived from mouse ES cells. Flavonoid compound 4a faithfully facilitated ES cells to differentiate into neurons morphologically and functionally. The expression and localization of peroxisome proliferator-activated receptors (PPARs) were examined in neural progenitor cells. PPAR-β expression showed robust upregulation compared to solvent control. Treatment with PPAR-β agonist L165041 alone or together with compound 4a significantly promoted neuronal differentiation, while antagonist GSK0660 blocked the neurogenesis-promoting effect of compound 4a. Consistently, knockdown of PPAR-β in ES cells abolished compound 4a-induced neuronal differentiation. Interestingly, we found that mitochondrial fusion protein Mfn2 was also abolished by sh-PPAR-β, resulting in abnormal mitochondrial Ca2+ ([Ca2+]M) transients as well as impaired mitochondrial bioenergetics. In conclusion, we demonstrated that by modulating mitochondrial energy metabolism through Mfn2 and mitochondrial Ca2+, PPAR-β took an important role in neuronal differentiation induced by flavonoid compound 4a. PMID:27315062

Epidemiologic and Economic Burden Attributable to First Spinal Fusion Surgery: Analysis From an Italian Administrative Database.

PubMed

Cortesi, Paolo A; Assietti, Roberto; Cuzzocrea, Fabrizio; Prestamburgo, Domenico; Pluderi, Mauro; Cozzolino, Paolo; Tito, Patrizia; Vanelli, Roberto; Cecconi, Davide; Borsa, Stefano; Cesana, Giancarlo; Mantovani, Lorenzo G

2017-09-15

Retrospective large population based-study. Assessment of the epidemiologic trends and economic burden of first spinal fusions. No adequate data are available regarding the epidemiology of spinal fusion surgery and its economic impact in Europe. The study population was identified through a data warehouse (DENALI), which matches clinical and economic data of different Healthcare Administrative databases of the Italian Lombardy Region. The study population consisted of all subjects, resident in Lombardy, who, during the period January 2001 to December 2010, underwent spinal fusion surgery (ICD-9-CM codes: 81.04, 81.05, 81.06, 81.07, and 81.08). The first procedure was used as the index event. We estimated the incidence of first spinal fusion surgery, the population and surgery characteristics and the healthcare costs from the National Health Service's perspective. The analysis was performed for the entire population and divided into the main groups of diagnosis. The analysis identified 17,772 [mean age (SD): 54.6 (14.5) years, 55.3% females] spinal fusion surgeries. Almost 67% of the patients suffered from a lumbar degenerative disease. The incidence rate of interventions increased from 11.5 to 18.5 per 100,000 person-year between 2001 and 2006, and was above 20.0 per 100,000 person-year in the last 4 years. The patients' mean age increased during the observational time period from 48.1 to 55.9 years; whereas the median hospital length of stay reported for the index event decreased. The average cost of the spinal fusion surgery increased during the observational period, from &OV0556; 4726 up to &OV0556; 9388. The study showed an increasing incidence of spinal fusion surgery and costs from 2001 to 2010. These results can be used to better understand the epidemiological and economic burden of these interventions, and help to optimize the resources available considering the different clinical approaches accessible today. 4.

Viral entry mechanisms: the increasing diversity of paramyxovirus entry

PubMed Central

Smith, Everett Clinton; Popa, Andreea; Chang, Andres; Masante, Cyril; Dutch, Rebecca Ellis

2009-01-01

The paramyxovirus family contains established human pathogens such as measles virus and human respiratory syncytial virus, and emerging pathogens including the Hendra and Nipah viruses and the recently identified human metapneumovirus. Two major envelope glycoproteins, the attachment protein and the fusion protein, promote the processes of viral attachment and virus-cell membrane fusion required for entry. While common mechanisms of fusion protein proteolytic activation and the mechanism of membrane fusion promotion have been shown in recent years, considerable diversity exists in the family related to receptor binding and the potential mechanisms of fusion triggering. PMID:19878307

Investigation on the quasifission process by theoretical analysis of experimental data of fissionlike reaction products

NASA Astrophysics Data System (ADS)

Giardina, G.; Nasirov, A. K.; Mandaglio, G.; Curciarello, F.; De Leo, V.; Fazio, G.; Manganaro, M.; Romaniuk, M.; Saccá, C.

2011-02-01

The hindrance to complete fusion is a phenomenon presenting in the most part of the capture events in reactions with massive nuclei. This phenomenon is due to the onset of the quasifission process which competes with complete fusion during the evolution of the composed system formed at capture stage. The branching ratio between quasifission and complete fusion strongly depends from different characteristics of reacting nuclei in the entrance channel. The experimental and theoretical investigations of reaction dynamics connected with the formation of composed system is nowadays the main subject of the nuclear reactions. There is ambiguity in establishment of the reaction mechanism leading to the observed binary fissionlike fragments. The correct estimation of the fusion probability is important in planning experiments for the synthesis of superheavy elements. The experimental determination of evaporation residues only is not enough to restore the true reaction dynamics. The experimental observation of fissionlike fragments only cannot assure the correct distinguishing of products of the quasifission, fast fission, and fusion-fission processes which have overlapping in the mass (angular, kinetic energy) distributions of fragments. In this paper we consider a wide set of reactions (with different mass asymmetry and mass symmetry parameters) with the aim to explain the role played by many quantities on the reaction mechanisms. We also present the results of study of the 48Ca+249Bk reaction used to synthesize superheavy nuclei with Z = 117 by the determination of the evaporation residue cross sections and the effective fission barriers < Bf > of excited nuclei formed along the de-excitation cascade of the compound nucleus.

Cloning of a methanol-inducible moxF promoter and its analysis in moxB mutants of Methylobacterium extorquens AM1rif.

PubMed Central

Morris, C J; Lidstrom, M E

1992-01-01

In Methylobacterium extorquens AM1, gene encoding methanol dehydrogenase polypeptides are transcriptionally regulated in response to C1 compounds, including methanol (M. E. Lidstrom and D. I. Stirling, Annu. Rev. Microbiol. 44:27-57, 1990). In order to study this regulation, a transcriptional fusion has been constructed between a beta-galactosidase reporter gene and a 1.55-kb XhoI-SalI fragment of M. extorquens AM1rif DNA encoding the N terminus of the methanol dehydrogenase large subunit (moxF) and 1,289 bp of upstream DNA. The fusion exhibited orientation-specific promoter activity in M. extorquens AM1rif but was expressed constitutively when the transcriptional fusion was located on the plasmid. However, correct regulation was restored when the construction was inserted in the M. extorquens AM1rif chromosome. This DNA fragment was shown to contain both the moxFJGI promoter and the sequences necessary in cis for its transcriptional regulation by methanol. Transcription from this promoter was studied in the M. extorquens AM1rif moxB mutant strains UV4rif and UV25rif, which have a pleiotropic phenotype with regard to the components of methanol oxidation. In these mutants, beta-galactosidase activity from the fusion was reduced to a level equal to that of the vector background when the fusion was present in both plasmid and chromosomal locations. Since both constitutive and methanol-inducible promoter activities were lost in the mutants, moxB appears to be required for transcription of the genes encoding the methanol dehydrogenase polypeptides. Images PMID:1624436

Long-term Clinical and Radiographic Outcomes of Pedicle Subtraction Osteotomy for Fixed Sagittal Imbalance: Does Level of Proximal Fusion Affect the Outcome? Minimum 5-Year Follow-up.

PubMed

Yagi, Mitsuru; King, Akilah B; Cunningham, Matthew E; Boachie-Adjei, Oheneba

2013-03-01

Retrospective case series of surgically treated adult patients with fixed sagittal imbalance. To assess clinical and radiographic changes after pedicle subtraction osteotomy (PSO) to treat adult fixed sagittal imbalance. Although recent reports have shown favorable clinical outcomes for PSO, few reports have published long-term follow-up outcomes. It is also unknown whether long-term outcomes are correlated with the level of proximal fusion and the radiographic changes that are observed after PSO. We reviewed the charts, X-rays, and postoperative SRS-22 and Oswestry Disability Index (ODI) scores of 32 adult patients who presented with fixed sagittal imbalance and were treated with lumbar PSO. Long fusions were defined as those proximal to T6, and short fusions were defined as those below T8. Measured radiographic parameters included thoracic kyphosis, lumbar lordosis (LL), sacral slope, pelvic incidence, and sagittal balance (SVA). Statistical analysis included Student t test and chi-square test. A p value of < .05 and a confidence interval of 95% were considered statistically significant. Among the reviewed cases were 23 women and 9 men, with a mean age of 50.9 years (range, 33-76 years) and a mean follow-up 8.6 years (range, 5-16 years). The LL increased from -16.0° preoperatively to -52.1° postoperatively. This metric decreased to -51.0° at final follow-up. The SVA decreased from 10.4 cm preoperatively to 3.6 cm postoperatively. The SVA increased to 5.4 cm at the final follow-up visit. There were 17 long fusions and 15 short fusions. The SRS scores at the final follow-up time point were: total, 3.63; function, 3.59; pain, 3.68; self-image, 3.46; mental health, 3.56; satisfaction, 4.26. A total of 16 patients exhibited minimal disability, 11 exhibited moderate disability, and 2 exhibited severe disability in ODI scores at the final follow-up visit (average, 28.2%). The SRS and ODI scores were not significantly different between groups (p = .64 for SRS; p = .59 for ODI). We observed no significant differences between groups with respect to the LL, sacral slope, or pelvic incidence. The observed increase in SVA at the final follow-up visit was significantly larger in the short fusion group compared with the increase we observed in the long fusion group (p = .03). The thoracic kyphosis (T5-T12) and proximal junctional angle at the final follow-up visit also significantly increased in patients who underwent a short fusion (p < .001). A total of 14 major complications occurred in 12 patients (8 in the short fusion group and 6 in the long fusion group) (p = .43). Eight patients required additional surgery to treat these complications. In a group of adults presenting with fixed sagittal imbalance, PSO provided good sagittal balance and maintained favorable clinical outcomes in both the short and long fusion groups despite a slight decrease in the SVA and a high complication rate. The data suggest that the loss of sagittal balance may be attributed to increase global and junctional kyphosis in short fusion groups, and should be monitored for long-term outcomes. Particular attention should be paid to the long-term deterioration of the SVA in adults who present with fixed sagittal imbalance after PSO. Copyright © 2013 Scoliosis Research Society. Published by Elsevier Inc. All rights reserved.

Probing the mechanism of fusion in a two-dimensional computer simulation.

PubMed Central

Chanturiya, Alexandr; Scaria, Puthurapamil; Kuksenok, Oleksandr; Woodle, Martin C

2002-01-01

A two-dimensional (2D) model of lipid bilayers was developed and used to investigate a possible role of membrane lateral tension in membrane fusion. We found that an increase of lateral tension in contacting monolayers of 2D analogs of liposomes and planar membranes could cause not only hemifusion, but also complete fusion when internal pressure is introduced in the model. With a certain set of model parameters it was possible to induce hemifusion-like structural changes by a tension increase in only one of the two contacting bilayers. The effect of lysolipids was modeled as an insertion of a small number of extra molecules into the cis or trans side of the interacting bilayers at different stages of simulation. It was found that cis insertion arrests fusion and trans insertion has no inhibitory effect on fusion. The possibility of protein participation in tension-driven fusion was tested in simulation, with one of two model liposomes containing a number of structures capable of reducing the area occupied by them in the outer monolayer. It was found that condensation of these structures was sufficient to produce membrane reorganization similar to that observed in simulations with "protein-free" bilayers. These data support the hypothesis that changes in membrane lateral tension may be responsible for fusion in both model phospholipid membranes and in biological protein-mediated fusion. PMID:12023230

A Data Fusion Method in Wireless Sensor Networks

PubMed Central

Izadi, Davood; Abawajy, Jemal H.; Ghanavati, Sara; Herawan, Tutut

2015-01-01

The success of a Wireless Sensor Network (WSN) deployment strongly depends on the quality of service (QoS) it provides regarding issues such as data accuracy, data aggregation delays and network lifetime maximisation. This is especially challenging in data fusion mechanisms, where a small fraction of low quality data in the fusion input may negatively impact the overall fusion result. In this paper, we present a fuzzy-based data fusion approach for WSN with the aim of increasing the QoS whilst reducing the energy consumption of the sensor network. The proposed approach is able to distinguish and aggregate only true values of the collected data as such, thus reducing the burden of processing the entire data at the base station (BS). It is also able to eliminate redundant data and consequently reduce energy consumption thus increasing the network lifetime. We studied the effectiveness of the proposed data fusion approach experimentally and compared it with two baseline approaches in terms of data collection, number of transferred data packets and energy consumption. The results of the experiments show that the proposed approach achieves better results than the baseline approaches. PMID:25635417

Optical biosensor for environmental on-line monitoring of naphthalene and salicylate bioavailability with an immobilized bioluminescent catabolic reporter bacterium.

PubMed Central

Heitzer, A; Malachowsky, K; Thonnard, J E; Bienkowski, P R; White, D C; Sayler, G S

1994-01-01

An optical whole-cell biosensor based on a genetically engineered bioluminescent catabolic reporter bacterium was developed for continuous on-line monitoring of naphthalene and salicylate bioavailability and microbial catabolic activity potential in waste streams. The bioluminescent reporter bacterium, Pseudomonas fluorescens HK44, carries a transcriptional nahG-luxCDABE fusion for naphthalene and salicylate catabolism. Exposure to either compound resulted in inducible bioluminescence. The reporter culture was immobilized onto the surface of an optical light guide by using strontium alginate. This biosensor probe was then inserted into a measurement cell which simultaneously received the waste stream solution and a maintenance medium. Exposure under defined conditions to both naphthalene and salicylate resulted in a rapid increase in bioluminescence. The magnitude of the response and the response time were concentration dependent. Good reproducibility of the response was observed during repetitive perturbations with either naphthalene or salicylate. Exposure to other compounds, such as glucose and complex nutrient medium or toluene, resulted in either minor bioluminescence increases after significantly longer response times compared with naphthalene or no response, respectively. The environmental utility of the biosensor was tested by using real pollutant mixtures. A specific bioluminescence response was obtained after exposure to either an aqueous solution saturated with JP-4 jet fuel or an aqueous leachate from a manufactured-gas plant soil, since naphthalene was present in both pollutant mixtures. PMID:8017932

α versus non-α cluster decays of the excited compound nucleus *124Ce using various formulations of the nuclear proximity potential

NASA Astrophysics Data System (ADS)

Kaur, Arshdeep; Chopra, Sahila; Gupta, Raj K.

2015-06-01

The earlier study of *124Ce formed in the 32S+92Mo reaction at an above barrier beam energy of 150 MeV, using the pocket formula of Blocki et al. for the nuclear proximity potential in the dynamical cluster-decay model (DCM), is extended to the use of other nuclear interaction potentials derived from the Skyrme energy density functional (SEDF) based on the semiclassical extended Thomas Fermi (ETF) approach under the frozen density approximation. The Skyrme forces used are the old SII, SIII, SIV, SKa, SkM, and SLy4 and new GSkI and KDE0(v1), given for both normal and isospin-rich nuclei. It is found that the α -nucleus structure, over the non-α nucleus structure, is preferred for only two Skyrme forces, the SIII and KDE0(v1). An extended intermediate mass fragments (IMFs) window, along with the new decay region of heavy mass fragments (HMFs) and the near-symmetric and symmetric fission fragments which, on adding the complementary heavy fragments, corresponds to (A /2 )±12 mass region of the fusion-fission (ff) process, are predicted by considering cross sections of orders observed in the experiment under study. For the predicted (total) fusion cross section, the survival probability Psurv of the compound nucleus (CN) against fission is shown to be very small because of the very large predicted ff component. On the other hand, the CN formation probability PCN is found to be nearly equal to 1, and hence the decay under study is a pure CN decay for all the nuclear potentials considered, since the estimated noncompound nucleus (nCN) content is almost negligible. We have also applied the extended-Wong model of Gupta and collaborators, and find that the ℓmax values and total fusion cross sections are of the same order as for the DCM. Thus, the extended-Wong model, which describes only the total fusion cross section in terms of the barrier characteristics of the entrance channel nuclei, could be useful for initial experimental studies to be fully treated using the DCM for all the observed decay products.

Decay analysis of compound nuclei formed in reactions with exotic neutron-rich 9Li projectile and the synthesis of 217At* within the dynamical cluster-decay model

NASA Astrophysics Data System (ADS)

Kaur, Arshdeep; Kaushal, Pooja; Hemdeep; Gupta, Raj K.

2018-01-01

The decay of various compound nuclei formed via exotic neutron-rich 9Li projectile is studied within the dynamical cluster-decay model (DCM). Following the earlier work of one of us (RKG) and collaborators (M. Kaur et al. (2015) [1]), for an empirically fixed neck-length parameter ΔRemp, the only parameter in the DCM, at a given incident laboratory energy ELab, we are able to fit almost exactly the (total) fusion cross section σfus =∑x=16σxn for 9Li projectile on 208Pb and other targets, with σfus depending strongly on the target mass of the most abundant isotope and its (magic) shell structure. This result shows the predictable nature of the DCM. The neck-length parameter ΔRemp is fixed empirically for the decay of 217At* formed in 9Li + 208Pb reaction at a fixed laboratory energy ELab, and then the total fusion cross section σfus calculated for all other reactions using 9Li as a projectile on different targets. Apparently, this procedure could be used to predict σfus for 9Li-induced reactions where experimental data are not available. Furthermore, optimum choice of "cold" target-projectile combinations, forming "hot" compact configurations, are predicted for the synthesis of compound nucleus 217At* with 8Li + 209Pb as one of the target-projectile combination, or another (t , p) combination 48Ca + 169Tb, with a doubly magic 48Ca, as the best possibility.

Cell-Based Small-Molecule Compound Screen Identifies Fenretinide as Potential Therapeutic for Translocation-Positive Rhabdomyosarcoma

PubMed Central

Herrero Martín, David; Boro, Aleksandar; Schäfer, Beat W.

2013-01-01

A subset of paediatric sarcomas are characterized by chromosomal translocations encoding specific oncogenic transcription factors. Such fusion proteins represent tumor specific therapeutic targets although so far it has not been possible to directly inhibit their activity by small-molecule compounds. In this study, we hypothesized that screening a small-molecule library might identify already existing drugs that are able to modulate the transcriptional activity of PAX3/FOXO1, the fusion protein specifically found in the pediatric tumor alveolar rhabdomyosarcoma (aRMS). Towards this end, we established a reporter cell line based on the well characterized PAX3/FOXO1 target gene AP2ß. A library enriched in mostly FDA approved drugs was screened using specific luciferase activity as read-out and normalized for cell viability. The most effective inhibitor identified from this screen was Fenretinide. Treatment with this compound resulted in down-regulation of PAX3/FOXO1 mRNA and protein levels as well as in reduced expression of several of its direct target genes, but not of wild-type FOXO1, in a dose- and time-dependent manner. Moreover, fenretinide induced reactive oxygen species and apoptosis as shown by caspase 9 and PARP cleavage and upregulated miR-9. Importantly, it demonstrated a significant anti-tumor effect in vivo. These results are similar to earlier reports for two other pediatric tumors, namely neuroblastoma and Ewing sarcoma, where fenretinide is under clinical development. Our results suggest that fenretinide might represent a novel treatment option also for translocation-positive rhabdomyosarcoma. PMID:23372815

Integrating multiple aspects of mitochondrial dynamics in neurons: Age-related differences and dynamic changes in a chronic rotenone model

PubMed Central

Arnold, Beth; Cassady, Steven J.; Van Laar, Victor S.; Berman, Sarah B.

2010-01-01

Changes in dynamic properties of mitochondria are increasingly implicated in neurodegenerative diseases, particularly Parkinson’s disease (PD). Static changes in mitochondrial morphology, often under acutely toxic conditions, are commonly utilized as indicators of changes in mitochondrial fission and fusion. However, in neurons, mitochondrial fission and fusion occur in a dynamic system of axonal/dendritic transport, biogenesis and degradation, and thus, likely interact and change over time. We sought to explore this using a chronic neuronal model (nonlethal low-concentration rotenone over several weeks), examining distal neurites, which may give insight into the earliest changes occurring in PD. Using this model, in live primary neurons, we directly quantified mitochondrial fission, fusion, and transport over time and integrated multiple aspects of mitochondrial dynamics, including morphology and growth/mitophagy. We found that rates of mitochondrial fission and fusion change as neurons age. In addition, we found that chronic rotenone exposure initially increased the ratio of fusion to fission, but later, this was reversed. Surprisingly, despite changes in rates of fission and fusion, mitochondrial morphology was minimally affected, demonstrating that morphology can be an inaccurate indicator of fission/fusion changes. In addition, we found evidence of subcellular compartmentalization of compensatory changes, as mitochondrial density increased in distal neurites first, which may be important in PD, where pathology may begin distally. We propose that rotenone-induced early changes such as in mitochondrial fusion are compensatory, accompanied later by detrimental fission. As evidence, in a dopaminergic neuronal model, in which chronic rotenone caused loss of neurites before cell death (like PD pathology), inhibiting fission protected against the neurite loss. This suggests that aberrant mitochondrial dynamics may contribute to the earliest neuropathologic mechanisms in PD. These data also emphasize that mitochondrial fission and fusion do not occur in isolation, and highlight the importance of analysis and integration of multiple mitochondrial dynamic functions in neurons. PMID:20850532

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.

Fission and quasifission of composite systems with Z =108 -120 : Transition from heavy-ion reactions involving S and Ca to Ti and Ni ions

NASA Astrophysics Data System (ADS)

Kozulin, E. M.; Knyazheva, G. N.; Novikov, K. V.; Itkis, I. M.; Itkis, M. G.; Dmitriev, S. N.; Oganessian, Yu. Ts.; Bogachev, A. A.; Kozulina, N. I.; Harca, I.; Trzaska, W. H.; Ghosh, T. K.

2016-11-01

Background: Suppression of compound nucleus formation in the reactions with heavy ions by a quasifission process in dependence on the reaction entrance channel. Purpose: Investigation of fission and quasifission processes in the reactions 36S,48Ca,48Ti , and 64Ni+238U at energies around the Coulomb barrier. Methods: Mass-energy distributions of fissionlike fragments formed in the reaction 48Ti+238U at energies of 247, 258, and 271 MeV have been measured using the double-arm time-of-flight spectrometer CORSET at the U400 cyclotron of the Flerov Laboratory of Nuclear Reactions and compared with mass-energy distributions for the reactions 36S,48Ca,64Ni+238U . Results: The most probable fragment masses as well as total kinetic energies and their dispersions in dependence on the interaction energies have been investigated for asymmetric and symmetric fragments for the studied reactions. The fusion probabilities have been deduced from the analysis of mass-energy distributions. Conclusion: The estimated fusion probability for the reactions S, Ca, Ti, and Ni ions with actinide nuclei shows that it depends exponentially on the mean fissility parameter of the system. For the reactions with actinide nuclei leading to the formation of superheavy elements the fusion probabilities are of several orders of magnitude higher than in the case of cold fusion reactions.

Welcome Back: Responses of Female Bonobos (Pan paniscus) to Fusions.

PubMed

Moscovice, Liza R; Deschner, Tobias; Hohmann, Gottfried

2015-01-01

In species with a high degree of fission-fusion social dynamics, fusions may trigger social conflict and thus provide an opportunity to identify sources of social tension and mechanisms related to its alleviation. We characterized behavioral and endocrine responses of captive female bonobos (Pan paniscus) to fusions within a zoo facility designed to simulate naturalistic fission-fusion social dynamics. We compared urinary cortisol levels and frequencies of aggression, grooming and socio-sexual interactions between female bonobos while in stable sub-groups and when one "joiner" was reunited with the "residents" of another sub-group. We hypothesized that fusions would trigger increases in aggression and cortisol levels among reunited joiners and resident females. We further predicted that females who face more uncertainty in their social interactions following fusions may use grooming and/or socio-sexual behavior to reduce social tension and aggression. The only aggression on reunion days occurred between reunited females, but frequencies of aggression remained low across non-reunion and reunion days, and there was no effect of fusions on cortisol levels. Fusions did not influence patterns of grooming, but there were increases in socio-sexual solicitations and socio-sexual interactions between joiners and resident females. Joiners who had been separated from residents for longer received the most solicitations, but were also more selective in their acceptance of solicitations and preferred to have socio-sexual interactions with higher-ranking residents. Our results suggest that socio-sexual interactions play a role in reintegrating female bonobos into social groups following fusions. In addition, females who receive a high number of solicitations are able to gain more control over their socio-sexual interactions and may use socio-sexual interactions for other purposes, such as to enhance their social standing.

Welcome Back: Responses of Female Bonobos (Pan paniscus) to Fusions

PubMed Central

Moscovice, Liza R.; Deschner, Tobias; Hohmann, Gottfried

2015-01-01

In species with a high degree of fission-fusion social dynamics, fusions may trigger social conflict and thus provide an opportunity to identify sources of social tension and mechanisms related to its alleviation. We characterized behavioral and endocrine responses of captive female bonobos (Pan paniscus) to fusions within a zoo facility designed to simulate naturalistic fission-fusion social dynamics. We compared urinary cortisol levels and frequencies of aggression, grooming and socio-sexual interactions between female bonobos while in stable sub-groups and when one “joiner” was reunited with the “residents” of another sub-group. We hypothesized that fusions would trigger increases in aggression and cortisol levels among reunited joiners and resident females. We further predicted that females who face more uncertainty in their social interactions following fusions may use grooming and/or socio-sexual behavior to reduce social tension and aggression. The only aggression on reunion days occurred between reunited females, but frequencies of aggression remained low across non-reunion and reunion days, and there was no effect of fusions on cortisol levels. Fusions did not influence patterns of grooming, but there were increases in socio-sexual solicitations and socio-sexual interactions between joiners and resident females. Joiners who had been separated from residents for longer received the most solicitations, but were also more selective in their acceptance of solicitations and preferred to have socio-sexual interactions with higher-ranking residents. Our results suggest that socio-sexual interactions play a role in reintegrating female bonobos into social groups following fusions. In addition, females who receive a high number of solicitations are able to gain more control over their socio-sexual interactions and may use socio-sexual interactions for other purposes, such as to enhance their social standing. PMID:25996476

Effective enrichment strategy for EML4-ALK fusion gene screening in patients with non-small cell lung cancer.

PubMed

Kobayashi, Makoto; Sakakibara, Tomohiro; Inoue, Akira; Fukuhara, Tatsuro; Sasano, Hironobu; Ichinose, Masakazu; Nukiwa, Toshihiro

2014-01-01

A novel fusion gene that comprises the echinoderm microtubule-associated protein-like 4 (EML4) and anaplastic lymphoma kinase (ALK) genes was recently identified in non-small cell lung cancer (NSCLC), particularly in adenocarcinoma. A specific ALK inhibitor has been shown to exert anti-tumor effects in NSCLC with the EML4-ALK fusion gene. Previous reports suggested an EML4-ALK incidence of approximately 5% in a pan-NSCLC population, with an increased frequency in younger patients, but an appropriate strategy for further selecting patients with the EML4-ALK fusion gene remains unknown. Patients, 55 years of age or younger, who were diagnosed with NSCLC without typical squamous cell carcinoma features at our institute were retrospectively evaluated. The tumor specimens were examined by immunohistochemistry for the EML4-ALK fusion gene and by polymerase chain reaction for epidermal growth factor receptor (EGFR) mutations. Between January 2004 and September 2011, the EML4-ALK fusion gene was detected in 19.6% (9/46) of patients. The fusion gene incidence increased to 31% (9/29) when patients with EGFR mutations were excluded. The EML4-ALK fusion gene was further detected in 2 cases of undifferentiated cell carcinoma. EML4-ALK fusion gene examinations could be more effectively performed by selecting young NSCLC patients without EGFR mutations, whereas selection on the basis of a non-smoking or adenocarcinoma history, as reported in previous studies, may not correctly identify the patient groups with potential EML4-ALK fusion gene. Copyright © 2013 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

The effects of local insulin application to lumbar spinal fusions in a rat model.

PubMed

Koerner, John D; Yalamanchili, Praveen; Munoz, William; Uko, Linda; Chaudhary, Saad B; Lin, Sheldon S; Vives, Michael J

2013-01-01

The rates of pseudoarthrosis after a single-level spinal fusion have been reported up to 35%, and the agents that increase the rate of fusion have an important role in decreasing pseudoarthrosis after spinal fusion. Previous studies have analyzed the effects of local insulin application to an autograft in a rat segmental defect model. Defects treated with a time-released insulin implant had significantly more new bone formation and greater quality of bone compared with controls based on histology and histomorphometry. A time-released insulin implant may have similar effects when applied in a lumbar spinal fusion model. This study analyzes the effects of a local time-released insulin implant applied to the fusion bed in a rat posterolateral lumbar spinal fusion model. Our hypothesis was twofold: first, a time-released insulin implant applied to the autograft bed in a rat posterolateral lumbar fusion will increase the rate of successful fusion and second, will alter the local environment of the fusion site by increasing the levels of local growth factors. Animal model (Institutional Animal Care and Use Committee approved) using 40 adult male Sprague-Dawley rats. Forty skeletally mature Sprague-Dawley rats weighing approximately 500 g each underwent posterolateral intertransverse lumbar fusions with iliac crest autograft from L4 to L5 using a Wiltse-type approach. After exposure of the transverse processes and high-speed burr decortication, a Linplant (Linshin Canada, Inc., ON, Canada) consisting of 95% microrecrystalized palmitic acid and 5% bovine insulin (experimental group) or a sham implant consisting of only palmitic acid (control group) was implanted on the fusion bed with iliac crest autograft. As per the manufacturer, the Linplant has a release rate of 2 U/day for a minimum of 40 days. The transverse processes and autograft beds of 10 animals from the experimental and 10 from the control group were harvested at Day 4 and analyzed for growth factors. The remaining 20 spines were harvested at 8 weeks and underwent a radiographic examination, manual palpation, and microcomputed tomographic (micro-CT) examination. One of the 8-week control animals died on postoperative Day 1, likely due to anesthesia. In the groups sacrificed at Day 4, there was a significant increase in insulinlike growth factor-I (IGF-I) in the insulin treatment group compared with the controls (0.185 vs. 0.129; p=.001). No significant differences were demonstrated in the levels of transforming growth factor beta-1, platelet-derived growth factor-AB, and vascular endothelial growth factor between the groups (p=.461, .452, and .767 respectively). Based on the radiographs, 1 of 9 controls had a solid bilateral fusion mass, 2 of 9 had unilateral fusion mass, 3 of 9 had small fusion mass bilaterally, and 3 of 9 had graft resorption. The treatment group had solid bilateral fusion mass in 6 of 10 and unilateral fusion mass in 4 of 10, whereas a small bilateral fusion mass and graft resorption were not observed. The difference between the groups was significant (p=.0067). Based on manual palpation, only 1 of 9 controls was considered fused, 4 of 9 were partially fused, and 4 of 9 were not fused. In the treatment group, there were 6 of 10 fusions, 3 of 10 partial fusions, and 1 of 10 were not fused. The difference between the groups was significant (p=.0084). Based on the micro-CT, the mean bone volume of the control group was 126.7 mm(3) and 203.8 mm(3) in the insulin treatment group. The difference between the groups was significant (p=.0007). This study demonstrates the potential role of a time-released insulin implant as a bone graft enhancer using a rat posterolateral intertransverse lumbar fusion model. The insulin-treatment group had significantly higher fusion rates based on the radiographs and manual palpation and had significantly higher levels of IGF-I and significantly more bone volume on micro-CT. Copyright © 2013 Elsevier Inc. All rights reserved.

Arginine and proline applied as food additives stimulate high freeze tolerance in larvae of Drosophila melanogaster.

PubMed

Koštál, Vladimír; Korbelová, Jaroslava; Poupardin, Rodolphe; Moos, Martin; Šimek, Petr

2016-08-01

The fruit fly Drosophila melanogaster is an insect of tropical origin. Its larval stage is evolutionarily adapted for rapid growth and development under warm conditions and shows high sensitivity to cold. In this study, we further developed an optimal acclimation and freezing protocol that significantly improves larval freeze tolerance (an ability to survive at -5°C when most of the freezable fraction of water is converted to ice). Using the optimal protocol, freeze survival to adult stage increased from 0.7% to 12.6% in the larvae fed standard diet (agar, sugar, yeast, cornmeal). Next, we fed the larvae diets augmented with 31 different amino compounds, administered in different concentrations, and observed their effects on larval metabolomic composition, viability, rate of development and freeze tolerance. While some diet additives were toxic, others showed positive effects on freeze tolerance. Statistical correlation revealed tight association between high freeze tolerance and high levels of amino compounds involved in arginine and proline metabolism. Proline- and arginine-augmented diets showed the highest potential, improving freeze survival to 42.1% and 50.6%, respectively. Two plausible mechanisms by which high concentrations of proline and arginine might stimulate high freeze tolerance are discussed: (i) proline, probably in combination with trehalose, could reduce partial unfolding of proteins and prevent membrane fusions in the larvae exposed to thermal stress (prior to freezing) or during freeze dehydration; (ii) both arginine and proline are exceptional among amino compounds in their ability to form supramolecular aggregates which probably bind partially unfolded proteins and inhibit their aggregation under increasing freeze dehydration. © 2016. Published by The Company of Biologists Ltd.

Identification of a Specific Isoform of Tomato Lipoxygenase (TomloxC) Involved in the Generation of Fatty Acid-Derived Flavor Compounds1

PubMed Central

Chen, Guoping; Hackett, Rachel; Walker, David; Taylor, Andy; Lin, Zhefeng; Grierson, Donald

2004-01-01

There are at least five lipoxygenases (TomloxA, TomloxB, TomloxC, TomloxD, and TomloxE) present in tomato (Lycopersicon esculentum Mill.) fruit, but their role in generation of fruit flavor volatiles has been unclear. To assess the physiological role of TomloxC in the generation of volatile C6 aldehyde and alcohol flavor compounds, we produced transgenic tomato plants with greatly reduced TomloxC using sense and antisense constructs under control of the cauliflower mosaic virus 35S promoter. The expression level of the TomloxC mRNA in some transgenic plants was selectively reduced by gene silencing or antisense inhibition to between 1% and 5% of the wild-type controls, but the expression levels of mRNAs for the four other isoforms were unaffected. The specific depletion of TomloxC in transgenic tomatoes led to a marked reduction in the levels of known flavor volatiles, including hexanal, hexenal, and hexenol, to as little as 1.5% of those of wild-type controls following maceration of ripening fruit. Addition of linoleic or linolenic acid to fruit homogenates significantly increased the levels of flavor volatiles, but the increase with the TomloxC-depleted transgenic fruit extracts was much lower than with the wild-type control. Confocal imaging of tobacco (Nicotiana tabacum) leaf cells expressing a TomloxC-GFP fusion confirmed a chloroplast localization of the protein. Together, these results suggest that TomloxC is a chloroplast-targeted lipoxygenase isoform that can use both linoleic and linolenic acids as substrates to generate volatile C6 flavor compounds. The roles of the other lipoxygenase isoforms are discussed. PMID:15347800

Hybridization and Polyploidization of Saccharomyces cerevisiae Strains by Transformation-Associated Cell Fusion

PubMed Central

Takagi, Atsuko; Harashima, Satoshi; Oshima, Yasuji

1985-01-01

Hybrid or polyploid clones of Saccharomyces cerevisiae produced by protoplast fusion were easily isolated by selecting transformants with the plasmid phenotype because the transformation was directly associated with cell fusion. When haploid cells were used as the original strain, the transformants were mostly diploids with a significant fraction of polyploids (triploids or tetraploids). Repeated transformation after curing the plasmid gave rise to clones with higher ploidy, but the frequency of cell fusion was severely reduced as ploidy increased. Images PMID:16346702

Effects of selective fusion on the thermal history of the Moon, Mars, and Venus

USGS Publications Warehouse

Lee, W.H.K.

1968-01-01

A comparative study on the thermal history of the Moon, Mars, and Venus was made by numerical solutions of the heat equation including and excluding selective fusion of silicates. Selective fusion was approximated by melting in a multicomponent system and redistribution of radioactive elements. Effects on selective fusion on the thermal models are (1) lowering (by several hundred degrees centigrade) and stabilizing the internal temperature distribution, and (2) increasing the surface heat-flow. ?? 1968.

Cadherin-11 Regulation of Fibrosis through Modulation of Epithelial-to-Mesenchymal Transition: Implications for Pulmonary Fibrosis in Scleroderma

DTIC Science & Technology

2013-10-01

4A, TGFbeta decreased E- cadherin expression and increase Col1a1 expression in MLE12 cells. Soluble Cad11 Fc fusion protein inhibited EMT induced by...TGFbeta as noted my higher E-cadherin levels and a significant reduction in Col1a1 mRNA. In contrast, when Cad11 Fc fusion protein was immobilized...Fc fusion protein alone was able to induce Col1a1 expression at the 50 ug/ml concentration, although E-cadherin expression was also increased. In

Excitation energy dependence of fragment-mass distributions from fission of 180,190Hg formed in fusion reactions of 36Ar + 144,154Sm

DOE PAGES

Nishio, K.; Andreyev, A. N.; Chapman, R.; ...

2015-06-30

Mass distributions of fission fragments from the compound nuclei 180Hg and 190 Hg formed in fusion reactions 36Ar + 144 Smand 36Ar + 154Sm, respectively, were measured at initial excitation energies of E*( 180Hg) = 33-66 MeV and E*( 190Hg) = 48-71 MeV. In the fission of 180Hg, the mass spectra were well reproduced by assuming only an asymmetric-mass division, with most probable light and heavy fragment masses more » $$\\overline{A}_L$$/ $$\\overline{A}_H$$ = 79/101. The mass asymmetry for 180Hg agrees well with that obtained in the low-energy β +/EC-delayed fission of 180Tl, from our earlier ISOLDE(CERN) experiment. Fission of 190Hg is found to proceed in a similar way, delivering the mass asymmetry of $$\\overline{A}_L$$/ $$\\overline{A}_H$$ = 83/107, throughout the measured excitation energy range. The persistence as a function of excitation energy of the mass-asymmetric fission for both proton-rich Hg isotopes gives strong evidence for the survival of microscopic effects up to effective excitation energies of compound nuclei as high as 40 MeV. In conclusion, this behavior is different from fission of actinide nuclei and heavier mercury isotope 198Hg.« less

Mitochondrial remodeling following fission inhibition by 15d-PGJ2 involves molecular changes in mitochondrial fusion protein OPA1

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

Kar, Rekha; Department of Biochemistry, UT Health Science Center at San Antonio, San Antonio, TX 78229; Mishra, Nandita

2010-09-03

Research highlights: {yields} Chemical inhibition of fission protein Drp1 leads to mitochondrial fusion. {yields} Increased fusion stimulates molecular changes in mitochondrial fusion protein OPA1. {yields} Proteolysis of larger isoforms, new synthesis and ubiquitination of OPA1 occur. {yields} Loss of mitochondrial tubular rigidity and disorganization of cristae. {yields} Generation of large swollen dysfunctional mitochondria. -- Abstract: We showed earlier that 15 deoxy {Delta}{sup 12,14} prostaglandin J2 (15d-PGJ2) inactivates Drp1 and induces mitochondrial fusion . However, prolonged incubation of cells with 15d-PGJ2 resulted in remodeling of fused mitochondria into large swollen mitochondria with irregular cristae structure. While initial fusion of mitochondria bymore » 15d-PGJ2 required the presence of both outer (Mfn1 and Mfn2) and inner (OPA1) mitochondrial membrane fusion proteins, later mitochondrial changes involved increased degradation of the fusion protein OPA1 and ubiquitination of newly synthesized OPA1 along with decreased expression of Mfn1 and Mfn2, which likely contributed to the loss of tubular rigidity, disorganization of cristae, and formation of large swollen degenerated dysfunctional mitochondria. Similar to inhibition of Drp1 by 15d-PGJ2, decreased expression of fission protein Drp1 by siRNA also resulted in the loss of fusion proteins. Prevention of 15d-PGJ2 induced mitochondrial elongation by thiol antioxidants prevented not only loss of OPA1 isoforms but also its ubiquitination. These findings provide novel insights into unforeseen complexity of molecular events that modulate mitochondrial plasticity.« less

Development of a keratinocyte-based screening model for antipsoriatic drugs using green fluorescent protein under the control of an endogenous promoter.

PubMed

Pol, Arno; van Ruissen, Fred; Schalkwijk, Joost

2002-08-01

Inflamed epidermis (psoriasis, wound healing, ultraviolet-irradiated skin) harbors keratinocytes that are hyperproliferative and display an abnormal differentiation program. A distinct feature of this so-called regenerative maturation pathway is the expression of proteins such as the cytokeratins CK6, CK16, and CK17 and the antiinflammatory protein SKALP/elafin. These proteins are absent in normal skin but highly induced in lesional psoriatic skin. Expression of these genes can be used as a surrogate marker for psoriasis in drug-screening procedures of large compound libraries. The aim of this study was to develop a keratinocyte cell line that contained a reporter gene under the control of a psoriasis-associated endogenous promoter and demonstrate its use in an assay suitable for screening. We generated a stably transfected keratinocyte cell line that expresses enhanced green fluorescent protein (EGFP), under the control of a 0.8-kb fragment derived from the promoter of the SKALP/elafin gene, which confers high levels of tissue-specific expression at the mRNA level. Induction of the SKALP promoter by tumor necrosis factor-alpha resulted in increased expression levels of the secreted SKALP-EGFP fusion protein as assessed by direct readout of fluorescence and fluorescence polarization in 96-well cell culture plates. The fold stimulation of the reporter gene was comparable to that of the endogenous SKALP gene as assessed by enzyme-linked immunosorbent assay. Although the dynamic range of the screening system is limited, the small standard deviation yields a Z factor of 0.49. This indicates that the assay is suitable as a high-throughput screen, and provides proof of the concept that a secreted EGFP fusion protein under the control of a physiologically relevant endogenous promoter can be used as a fluorescence-based high-throughput screen for differentiation-modifying or antiinflammatory compounds that act via the keratinocyte.

Experimental Test in a Tokamak of Fusion with Spin-Polarized D and 3He

NASA Astrophysics Data System (ADS)

Honig, Arnold; Sandorfi, Andrew

2007-06-01

An experiment to test polarization retention of highly polarized D and 3He fusion fuels prior to their fusion reactions in a tTokamak is in preparation. The fusion reaction rate with 100% vector polarized reactants is expected from simple theory to increase by a factor of 1.5. With presently available polarizations, fusion reaction enhancements of ˜15% are achievable and of significant interest, while several avenues for obtaining higher polarizations are open. The potential for survival of initial fusion fuel polarizations at ˜108 K plasma core temperatures (˜5KeV) throughout the time interval preceding fusion burn was addressed in a seminal paper in 1982. While the positive conclusion from those calculations suggests that reaction enhancements are indeed feasible, this crucial factor has never been tested in a high temperature plasma core because of difficulties in preparation and injection of sufficiently polarized fusion fuels into a high temperature reactorfusion plasma. Our solution to these problems employs a new source of highly polarized D in the form of solid HD which has been developed and used in our laboratories. Solid HD is compatible with fusion physics in view of its simplicity of elemental composition and very long (weeks) relaxation times at 4K temperature, allowing efficient polarization-preserving cold-transfer operations. Containment and polarization of the HD within polymer capsules, similar to those used in inertial confinement fusion (ICF), is an innovation which simplifies the cold-transfer of polarized fuel from the dilution refrigerator polarization-production apparatus to other liquid helium temperature cryostats, for storage, transport and placement into the barrel of a cryogenic pellet gun for firing at high velocity into the reactor. The other polarized fuel partner, 3He, has been prepared as a polarized gas for applications including high-energy polarized targets and magnetic resonance imaging (MRI) scans. It will be introduced into the reactor by loading at high pressure into a thick-walled ICF-type polymer shell for injection into the plasma core with a room temperature injection gun. Based on current experience, polarizations of both D and 3He of ˜55% are projected, producing a fusion yield increase of about 15%. A collaboration is being developed for implementing this experiment at the DIII-D Ttokamak experiment at San Diego, operated by General Atomics for the U.S. Department of Energy. Calculations indicate a 10% fusion yield increase in the 14.6 MeV protons from the D-3He reaction will provide a statistically significant test of polarization retention in the plasma. Injection of the polarized fuels into a 4He or 1H plasma improves the discrimination of the effects of polarized fuels. Details of the HD fuel preparation, of the polarization processes, and of the injection into the plasma will beare presented. If the expected fusion reaction yield increase indicative of polarization retention is detected, a route to significantly improved second generation D-3He fusion would be established, as well as confidence to undertake the more difficult polarization of tritium, which would offer important cost savings and improved prospects of ignition in the ITER program.

Study of near-stability nuclei populated as fission fragments in heavy-ion fusion reactions

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

Fotiadis, Nikolaos; Nelson, Ronald O; Devlin, Matthew

2010-01-01

Examples are presented to illustrate the power of prompt {gamma}-ray spectroscopy of fission fragments from compound nuclei with A {approx} 200 formed in fusion-evaporation reactions in experiments using the Gammasphere Ge-detector array. Complementary methods, such as Coulomb excitation and deep-inelastic processes, are also discussed. In other cases (n, xn{gamma}) reactions on stable isotopes have been used to establish neutron excitation functions for {gamma}-rays using a pulsed 'white'-neutron source, coupled to a high-energy-resolution germanium-detector array. The excitation functions can unambiguously assign {gamma}-rays to a specific reaction product. Results from all these methods bridge the gaps in the systematics of high-spin statesmore » between the neutron-deficient and neutron-rich nuclei. Results near shell closures should motivate new shell model calculations.« less

Nuclear science experiments with a bright neutron source from fusion reactions on the OMEGA Laser System

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

Forrest, C. J.; Knauer, J. P.; Schroeder, W. U.

Subnanosecond impulses of 10 13 to 10 14 neutrons, produced in direct-drive laser inertial confinement fusion implosions, have been used to irradiate deuterated targets at the OMEGA Laser System [T. R. Boehly et al., Opt. Commun. 133, 495 (1997)]. The target compounds include heavy water (D 2O) and deuterated benzene (C 6D 6). Yields and energy spectra of neutrons from D(n,2n)p to study the breakup reaction have been measured at a forward angle of θlab = 3.5 degrees plus/minus 3.5 degrees with a sensitive, high-dynamic-range neutron time-of-flight spectrometer to infer the double-differential breakup cross section d2sigma/dEdomega for 14-MeV D–T fusionmore » neutrons.« less

Nuclear science experiments with a bright neutron source from fusion reactions on the OMEGA Laser System

DOE PAGES

Forrest, C. J.; Knauer, J. P.; Schroeder, W. U.; ...

2018-01-31

Subnanosecond impulses of 10 13 to 10 14 neutrons, produced in direct-drive laser inertial confinement fusion implosions, have been used to irradiate deuterated targets at the OMEGA Laser System [T. R. Boehly et al., Opt. Commun. 133, 495 (1997)]. The target compounds include heavy water (D 2O) and deuterated benzene (C 6D 6). Yields and energy spectra of neutrons from D(n,2n)p to study the breakup reaction have been measured at a forward angle of θlab = 3.5 degrees plus/minus 3.5 degrees with a sensitive, high-dynamic-range neutron time-of-flight spectrometer to infer the double-differential breakup cross section d2sigma/dEdomega for 14-MeV D–T fusionmore » neutrons.« 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.

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.

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.

Hybrid testing of lumbar CHARITE discs versus fusions.

PubMed

Panjabi, Manohar; Malcolmson, George; Teng, Edward; Tominaga, Yasuhiro; Henderson, Gweneth; Serhan, Hassan

2007-04-20

An in vitro human cadaveric biomechanical study. To quantify effects on operated and other levels, including adjacent levels, due to CHARITE disc implantations versus simulated fusions, using follower load and the new hybrid test method in flexion-extension and bilateral torsion. Spinal fusion has been associated with long-term accelerated degeneration at adjacent levels. As opposed to the fusion, artificial discs are designed to preserve motion and diminish the adjacent-level effects. Five fresh human cadaveric lumbar specimens (T12-S1) underwent multidirectional testing in flexion-extension and bilateral torsion with 400 N follower load. Intact specimen total ranges of motion were determined with +/-10 Nm unconstrained pure moments. The intact range of motion was used as input for the hybrid tests of 5 constructs: 1) CHARITE disc at L5-S1; 2) fusion at L5-S1; 3) CHARITE discs at L4-L5 and L5-S1; 4) CHARITE disc at L4-L5 and fusion at L5-S1; and 5) 2-level fusion at L4-L5-S1. Using repeated-measures single factor analysis of variance and Bonferroni statistical tests (P < 0.05), intervertebral motion redistribution of each construct was compared with the intact. In flexion-extension, 1-level CHARITE disc preserved motion at the operated and other levels, while 2-level CHARITE showed some amount of other-level effects. In contrast, 1- and 2-level fusions increased other-level motions (average, 21.0% and 61.9%, respectively). In torsion, both 1- and 2-level discs preserved motions at all levels. The 2-level simulated fusion increased motions at proximal levels (22.9%), while the 1-level fusion produced no significant changes. In general, CHARITE discs preserved operated- and other-level motions. Fusion simulations affected motion redistribution at other levels, including adjacent levels.

Productivity benefits of minimally invasive surgery in patients with chronic sacroiliac joint dysfunction.

PubMed

Saavoss, Josh D; Koenig, Lane; Cher, Daniel J

2016-01-01

Sacroiliac joint (SIJ) dysfunction is associated with a marked decrease in quality of life. Increasing evidence supports minimally invasive SIJ fusion as a safe and effective procedure for the treatment of chronic SIJ dysfunction. The impact of SIJ fusion on worker productivity is not known. Regression modeling using data from the National Health Interview Survey was applied to determine the relationship between responses to selected interview questions related to function and economic outcomes. Regression coefficients were then applied to prospectively collected, individual patient data in a randomized trial of SIJ fusion (INSITE, NCT01681004) to estimate expected differences in economic outcomes across treatments. Patients who receive SIJ fusion using iFuse Implant System(®) have an expected increase in the probability of working of 16% (95% confidence interval [CI] 11%-21%) relative to nonsurgical patients. The expected change in earnings across groups was US $3,128 (not statistically significant). Combining the two metrics, the annual increase in worker productivity given surgical vs nonsurgical care was $6,924 (95% CI $1,890-$11,945). For employees with chronic, severe SIJ dysfunction, minimally invasive SIJ fusion may improve worker productivity compared to nonsurgical treatment.

Dilation of fusion pores by crowding of SNARE proteins

PubMed Central

Wu, Zhenyong; Bello, Oscar D; Thiyagarajan, Sathish; Auclair, Sarah Marie; Vennekate, Wensi; Krishnakumar, Shyam S; O'Shaughnessy, Ben; Karatekin, Erdem

2017-01-01

Hormones and neurotransmitters are released through fluctuating exocytotic fusion pores that can flicker open and shut multiple times. Cargo release and vesicle recycling depend on the fate of the pore, which may reseal or dilate irreversibly. Pore nucleation requires zippering between vesicle-associated v-SNAREs and target membrane t-SNAREs, but the mechanisms governing the subsequent pore dilation are not understood. Here, we probed the dilation of single fusion pores using v-SNARE-reconstituted ~23-nm-diameter discoidal nanolipoprotein particles (vNLPs) as fusion partners with cells ectopically expressing cognate, 'flipped' t-SNAREs. Pore nucleation required a minimum of two v-SNAREs per NLP face, and further increases in v-SNARE copy numbers did not affect nucleation rate. By contrast, the probability of pore dilation increased with increasing v-SNARE copies and was far from saturating at 15 v-SNARE copies per face, the NLP capacity. Our experimental and computational results suggest that SNARE availability may be pivotal in determining whether neurotransmitters or hormones are released through a transient ('kiss and run') or an irreversibly dilating pore (full fusion). DOI: http://dx.doi.org/10.7554/eLife.22964.001 PMID:28346138

Apparatus and method for extracting power from energetic ions produced in nuclear fusion

DOEpatents

Fisch, N.J.; Rax, J.M.

1994-12-20

An apparatus and method of extracting power from energetic ions produced by nuclear fusion in a toroidal plasma to enhance respectively the toroidal plasma current and fusion reactivity. By injecting waves of predetermined frequency and phase traveling substantially in a selected poloidal direction within the plasma, the energetic ions become diffused in energy and space such that the energetic ions lose energy and amplify the waves. The amplified waves are further adapted to travel substantially in a selected toroidal direction to increase preferentially the energy of electrons traveling in one toroidal direction which, in turn, enhances or generates a toroidal plasma current. In an further adaptation, the amplified waves can be made to preferentially increase the energy of fuel ions within the plasma to enhance the fusion reactivity of the fuel ions. The described direct, or in situ, conversion of the energetic ion energy provides an efficient and economical means of delivering power to a fusion reactor. 4 figures.

Spatial resolution enhancement of satellite image data using fusion approach

NASA Astrophysics Data System (ADS)

Lestiana, H.; Sukristiyanti

2018-02-01

Object identification using remote sensing data has a problem when the spatial resolution is not in accordance with the object. The fusion approach is one of methods to solve the problem, to improve the object recognition and to increase the objects information by combining data from multiple sensors. The application of fusion image can be used to estimate the environmental component that is needed to monitor in multiple views, such as evapotranspiration estimation, 3D ground-based characterisation, smart city application, urban environments, terrestrial mapping, and water vegetation. Based on fusion application method, the visible object in land area has been easily recognized using the method. The variety of object information in land area has increased the variation of environmental component estimation. The difficulties in recognizing the invisible object like Submarine Groundwater Discharge (SGD), especially in tropical area, might be decreased by the fusion method. The less variation of the object in the sea surface temperature is a challenge to be solved.

Apparatus and method for extracting power from energetic ions produced in nuclear fusion

DOEpatents

Fisch, Nathaniel J.; Rax, Jean M.

1994-01-01

An apparatus and method of extracting power from energetic ions produced by nuclear fusion in a toroidal plasma to enhance respectively the toroidal plasma current and fusion reactivity. By injecting waves of predetermined frequency and phase traveling substantially in a selected poloidal direction within the plasma, the energetic ions become diffused in energy and space such that the energetic ions lose energy and amplify the waves. The amplified waves are further adapted to travel substantially in a selected toroidal direction to increase preferentially the energy of electrons traveling in one toroidal direction which, in turn, enhances or generates a toroidal plasma current. In an further adaptation, the amplified waves can be made to preferentially increase the energy of fuel ions within the plasma to enhance the fusion reactivity of the fuel ions. The described direct, or in situ, conversion of the energetic ion energy provides an efficient and economical means of delivering power to a fusion reactor.

Role of Mediator and Effects of Temperature on ortho-C-N Bond Fusion Reactions of Aniline Using Ruthenium Templates: Isolation and Characterization of New Ruthenium Complexes of the in-Situ-Generated Ligands.

PubMed

Roy, Suman K; Sengupta, Debabrata; Rath, Santi Prasad; Saha, Tanushri; Samanta, Subhas; Goswami, Sreebrata

2017-05-01

In this work, ortho-C-N bond fusion reactions of aniline are followed by the use of two different ruthenium mediators. Reaction of aniline with [Ru III (terpy)Cl 3 ] (terpy = 2,2':6',2″-terpyridine) resulted in a trans bis-aniline ruthenium(II) complex [1] + which upon oxidation with H 2 O 2 produced compound [2] + of a bidentate ligand, N-phenyl-1,2-benzoquinonediimine, due to an oxidative ortho-C-N bond fusion reaction. Complex [1] + and aniline (neat) at 185 °C produced a bis-chelated ruthenium complex (3). A previously reported complex [Ru II (N-phenyl-1,2-benzoquinonediimine)(aniline) 2 (Cl) 2 ] (5) undergoes similar oxidation by air at 185 °C to produce complex [3]. A separate chemical reaction between aniline and strongly oxidizing tetra-n-propylammonium perruthenate [(n-pr) 4 N] + [RuO 4 ] - in air produced a ruthenium complex [4] of a N 4 -tetraamidophenylmacrocycle ligand via multiple ortho-C-N bond fusion reaction. Notably, the yield of this product is low (5%) at 100 °C but increases to 25% in refluxing aniline. All these complexes are characterized fully by their physicochemical characterizations and X-ray structure determination. From their structural parameters and other spectroscopic studies, complex [2] + is assigned as [Ru II (terpy)(N-phenyl-1,2-benzoquinonediimine)(Cl)] + whereas complex [4] is described as a ruthenium(VI) complex comprised of a reduced deprotonated N-phenyl-1,2-diamidobenzene and N 4 -tetraamidophenylmacrocyclic ligand. Complex [2] + exhibits one reversible oxidation at 1.32 V and one reversible reduction at -0.75 V vs Ag/AgCl reference electrode. EPR of the electrogenerated complexes has revealed that the oxidized complex is a ruthenium(III) complex with an axial EPR spectrum at g av = 2.06. The reduced complex [2], on the other hand, shows a single-line EPR signal at g av = 1.998. In contrast, complex [4] shows two successive one-electron oxidation waves at 0.5 and 0.8 V and an irreversible reduction wave at -0.9 V. EPR studies of the oxidized complexes [4] + and [4] 2+ reveal that oxidations are ligand centered. DFT calculations were employed to elucidate the electronic structures as well as the redox processes associated with the above complexes. Aerial ortho-C-N bond fusion reactions of aniline using two different mediators, viz. [Ru III (terpy)Cl 3 ] and [(n-pr) 4 N] + [RuO 4 ] - , have been followed. It is found that in the case of oxidizable Ru(III) mediator complex, C-N bond fusion is limited only to dimerization reaction whereas the high-valent Ru(VII) salt mediates multiple C-N bond fusion reactions leading to the formation of a novel tetradentate N 4 -tetraamidophenylmacrocyclic ligand. Valence ambiguity in the complexes of the resultant redox-active ligands is scrutinized.

An Investigation for Ground State Features of Some Structural Fusion Materials

NASA Astrophysics Data System (ADS)

Aytekin, H.; Tel, E.; Baldik, R.; Aydin, A.

2011-02-01

Environmental concerns associated with fossil fuels are creating increased interest in alternative non-fossil energy sources. Nuclear fusion can be one of the most attractive sources of energy from the viewpoint of safety and minimal environmental impact. When considered in all energy systems, the requirements for performance of structural materials in a fusion reactor first wall, blanket or diverter, are arguably more demanding or difficult than for other energy system. The development of fusion materials for the safety of fusion power systems and understanding nuclear properties is important. In this paper, ground state properties for some structural fusion materials as 27Al, 51V, 52Cr, 55Mn, and 56Fe are investigated using Skyrme-Hartree-Fock method. The obtained results have been discussed and compared with the available experimental data.

Method of controlling fusion reaction rates

DOEpatents

Kulsrud, Russell M.; Furth, Harold P.; Valeo, Ernest J.; Goldhaber, Maurice

1988-01-01

A method of controlling the reaction rates of the fuel atoms in a fusion reactor comprises the step of polarizing the nuclei of the fuel atoms in a particular direction relative to the plasma confining magnetic field. Fusion reaction rates can be increased or decreased, and the direction of emission of the reaction products can be controlled, depending on the choice of polarization direction.

Method of controlling fusion reaction rates

DOEpatents

Kulsrud, Russell M.; Furth, Harold P.; Valeo, Ernest J.; Goldhaber, Maurice

1988-03-01

A method of controlling the reaction rates of the fuel atoms in a fusion reactor comprises the step of polarizing the nuclei of the fuel atoms in a particular direction relative to the plasma confining magnetic field. Fusion reaction rates can be increased or decreased, and the direction of emission of the reaction products can be controlled, depending on the choice of polarization direction.

Structural and kinetic analysis of the unnatural fusion protein 4-coumaroyl-CoA ligase::stilbene synthase

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

Wang, Yechun; Yi, Hankuil; Wang, Melissa

2012-10-24

To increase the biochemical efficiency of biosynthetic systems, metabolic engineers have explored different approaches for organizing enzymes, including the generation of unnatural fusion proteins. Previous work aimed at improving the biosynthesis of resveratrol, a stilbene associated a range of health-promoting activities, in yeast used an unnatural engineered fusion protein of Arabidopsis thaliana (thale cress) 4-coumaroyl-CoA ligase (At4CL1) and Vitis vinifera (grape) stilbene synthase (VvSTS) to increase resveratrol levels 15-fold relative to yeast expressing the individual enzymes. Here we present the crystallographic and biochemical analysis of the 4CL::STS fusion protein. Determination of the X-ray crystal structure of 4CL::STS provides the firstmore » molecular view of an artificial didomain adenylation/ketosynthase fusion protein. Comparison of the steady-state kinetic properties of At4CL1, VvSTS, and 4CL::STS demonstrates that the fusion protein improves catalytic efficiency of either reaction less than 3-fold. Structural and kinetic analysis suggests that colocalization of the two enzyme active sites within 70 {angstrom} of each other provides the basis for enhanced in vivo synthesis of resveratrol.« less

Fusion partners can increase the expression of recombinant interleukins via transient transfection in 2936E cells

PubMed Central

Carter, Jane; Zhang, Jue; Dang, Thien-Lan; Hasegawa, Haruki; Cheng, Janet D; Gianan, Irene; O'Neill, Jason W; Wolfson, Martin; Siu, Sophia; Qu, Sheldon; Meininger, David; Kim, Helen; Delaney, John; Mehlin, Christopher

2010-01-01

The expression levels of five secreted target interleukins (IL-11, 15, 17B, 32, and IL23 p19 subunit) were tested with three different fusion partners in 2936E cells. When fused to the N-terminus, human serum albumin (HSA) was found to enhance the expression of both IL-17B and IL-15, cytokines which did not express at measurable levels on their own. Although the crystallizable fragment of an antibody (Fc) was also an effective fusion partner for IL-17B, Fc did not increase expression of IL-15. Fc was superior to HSA for the expression of the p19 subunit of IL-23, but no partner led to measurable levels of IL-32γ secretion. Glutathione S-transferase (GST) did not enhance the expression of any target and suppressed the production of IL-11, a cytokine which expressed robustly both on its own and when fused to HSA or Fc. Cleavage of the fusion partner was not always possible. The use of HSA or Fc as N-terminal fusions can be an effective technique to express difficult proteins, especially for applications in which the fusion partner need not be removed. PMID:20014434

Design and Analysis of a Data Fusion Scheme in Mobile Wireless Sensor Networks Based on Multi-Protocol Mobile Agents

PubMed Central

Wu, Chunxue; Wu, Wenliang; Wan, Caihua

2017-01-01

Sensors are increasingly used in mobile environments with wireless network connections. Multiple sensor types measure distinct aspects of the same event. Their measurements are then combined to produce integrated, reliable results. As the number of sensors in networks increases, low energy requirements and changing network connections complicate event detection and measurement. We present a data fusion scheme for use in mobile wireless sensor networks with high energy efficiency and low network delays, that still produces reliable results. In the first phase, we used a network simulation where mobile agents dynamically select the next hop migration node based on the stability parameter of the link, and perform the data fusion at the migration node. Agents use the fusion results to decide if it should return the fusion results to the processing center or continue to collect more data. In the second phase. The feasibility of data fusion at the node level is confirmed by an experimental design where fused data from color sensors show near-identical results to actual physical temperatures. These results are potentially important for new large-scale sensor network applications. PMID:29099793

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.

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

Introgression of Swertia mussotii gene into Bupleurum scorzonerifolium via somatic hybridization

PubMed Central

2011-01-01

Background The wild herb Swertia mussotii is a source of the anti-hepatitis compounds swertiamarin, mangiferin and gentiopicroside. Its over-exploitation has raised the priority of producing these compounds heterologously. Somatic hybridization represents a novel approach for introgressing Swertia mussotii genes into a less endangered species. Results Protoplasts derived from calli of Bupleurum scorzonerifolium and S. mussotii were fused to produce 194 putative hybrid cell lines, of which three (all derived from fusions where the S. mussotii protoplasts were pre-treated for 30 s with UV light) later differentiated into green plants. The hybridity of the calli was confirmed by a combination of isozyme, RAPD and chromosomal analysis. The hybrid calli genomes were predominantly B. scorzonerifolium. GISH analysis of mitotic chromosomes confirmed that the irradiation of donor protoplasts increased the frequency of chromosome elimination and fragmentation. RFLP analysis of organellar DNA revealed that mitochondrial and chloroplast DNA of both parents coexisted and recombined in some hybrid cell lines. Some of the hybrid calli contained SmG10H from donor, and produced swertiamarin, mangiferin and certain volatile compounds characteristic of S. mussotii. The expression of SmG10H (geraniol 10-hydroxylase) was associated with the heterologous accumulation of swertiamarin. Conclusions Somatic hybrids between B. scorzonerifolium and S. mussotii were obtained, hybrids selected all contained introgressed nuclear and cytoplasmic DNA from S. mussotii; and some produced more mangiferin than the donor itself. The introgression of SmG10H was necessary for the accumulation of swertiamarin. PMID:21513581

A novel osteogenic oxysterol compound for therapeutic development to promote bone growth: activation of hedgehog signaling and osteogenesis through smoothened binding.

PubMed

Montgomery, Scott R; Nargizyan, Taya; Meliton, Vicente; Nachtergaele, Sigrid; Rohatgi, Rajat; Stappenbeck, Frank; Jung, Michael E; Johnson, Jared S; Aghdasi, Bayan; Tian, Haijun; Weintraub, Gil; Inoue, Hirokazu; Atti, Elisa; Tetradis, Sotirios; Pereira, Renata C; Hokugo, Akishige; Alobaidaan, Raed; Tan, Yanlin; Hahn, Theodor J; Wang, Jeffrey C; Parhami, Farhad

2014-08-01

Osteogenic factors are often used in orthopedics to promote bone growth, improve fracture healing, and induce spine fusion. Osteogenic oxysterols are naturally occurring molecules that were shown to induce osteogenic differentiation in vitro and promote spine fusion in vivo. The purpose of this study was to identify an osteogenic oxysterol more suitable for clinical development than those previously reported, and evaluate its ability to promote osteogenesis in vitro and spine fusion in rats in vivo. Among more than 100 oxysterol analogues synthesized, Oxy133 induced significant expression of osteogenic markers Runx2, osterix (OSX), alkaline phosphatase (ALP), bone sialoprotein (BSP), and osteocalcin (OCN) in C3H10T1/2 mouse embryonic fibroblasts and in M2-10B4 mouse marrow stromal cells. Oxy133-induced activation of an 8X-Gli luciferase reporter, its direct binding to Smoothened, and the inhibition of Oxy133-induced osteogenic effects by the Hedgehog (Hh) pathway inhibitor, cyclopamine, demonstrated the role of Hh pathway in mediating osteogenic responses to Oxy133. Oxy133 did not stimulate osteogenesis via BMP or Wnt signaling. Oxy133 induced the expression of OSX, BSP, and OCN, and stimulated robust mineralization in primary human mesenchymal stem cells. In vivo, bilateral spine fusion occurred through endochondral ossification and was observed in animals treated with Oxy133 at the fusion site on X-ray after 4 weeks and confirmed with manual assessment, micro-CT (µCT), and histology after 8 weeks, with equal efficiency to recombinant human bone morphogenetic protein-2 (rhBMP-2). Unlike rhBMP-2, Oxy133 did not induce adipogenesis in the fusion mass and resulted in denser bone evidenced by greater bone volume/tissue volume (BV/TV) ratio and smaller trabecular separation. Findings here suggest that Oxy133 has significant potential as an osteogenic molecule with greater ease of synthesis and improved time to fusion compared to previously studied oxysterols. Small molecule osteogenic oxysterols may serve as the next generation of bone anabolic agents for therapeutic development. © 2014 American Society for Bone and Mineral Research.

A Novel Osteogenic Oxysterol Compound for Therapeutic Development to Promote Bone Growth: Activation of Hedgehog Signaling and Osteogenesis through Smoothened Binding

PubMed Central

Montgomery, Scott R.; Nargizyan, Taya; Meliton, Vicente; Nachtergaele, Sigrid; Rohatgi, Rajat; Stappenbeck, Frank; Jung, Michael E.; Johnson, Jared S.; Aghdasi, Bayan; Tian, Haijun; Weintraub, Gil; Inoue, Hirokazu; Atti, Elisa; Tetradis, Sotirios; Pereira, Renata C; Hokugo, Akishige; Alobaidaan, Raed; Tan, Yanlin; Hahn, Theodor J.; Wang, Jeffrey C; Parhami, Farhad

2015-01-01

Osteogenic factors are often used in orthopedics to promote bone growth, improve fracture healing, and induce spine fusion. Osteogenic oxysterols are naturally occurring molecules that were shown to induce osteogenic differentiation in vitro and promote spine fusion in vivo. The purpose of this study was to identify an osteogenic oxysterol more suitable for clinical development than those previously reported, and evaluate its ability to promote osteogenesis in vitro and spine fusion in rats in vivo. Among more than 100 oxysterol analogues synthesized, Oxy133 induced significant expression of osteogenic markers Runx2, osterix (OSX), alkaline phosphatase (ALP), bone sialoprotein (BSP), and osteocalcin (OCN) in C3H10T1/2 mouse embryonic fibroblasts and in M2-10B4 mouse marrow stromal cells. Oxy133-induced activation of an 8×-Gli luciferase reporter, its direct binding to Smoothened, and the inhibition of Oxy133-induced osteogenic effects by the Hedgehog (Hh) pathway inhibitor, cyclopamine, demonstrated the role of Hh pathway in mediating osteogenic responses to Oxy133. Oxy133 did not stimulate osteogenesis via BMP or Wnt signaling. Oxy133 induced the expression of OSX, BSP, and OCN and stimulated robust mineralization in primary human mesenchymal stem cells. In vivo, bilateral spine fusion occurred through endochondral ossification and was observed in animals treated with Oxy133 at the fusion site on xray after 4 weeks and confirmed with manual assessment, micro CT (μCT), and histology after 8 weeks, with equal efficiency to recombinant human bone morphogenetic protein-2 (rhBMP-2). Unlike rhBMP-2, Oxy133 did not induce adipogenesis in the fusion mass and resulted in denser bone evidenced by greater BV/TV ratio and smaller trabecular separation. Findings here suggest that Oxy133 has significant potential as an osteogenic molecule with greater ease of synthesis and improved time to fusion compared to previously studied oxysterols. Small molecule osteogenic oxysterols may serve as the next generation of bone anabolic agents for therapeutic development. PMID:24591126

Identification and Partial Characterization of a Novel UDP-N-Acetylenolpyruvoylglucosamine Reductase/UDP-N-Acetylmuramate:l-Alanine Ligase Fusion Enzyme from Verrucomicrobium spinosum DSM 4136(T).

PubMed

Naqvi, Kubra F; Patin, Delphine; Wheatley, Matthew S; Savka, Michael A; Dobson, Renwick C J; Gan, Han Ming; Barreteau, Hélène; Blanot, Didier; Mengin-Lecreulx, Dominique; Hudson, André O

2016-01-01

The enzymes involved in synthesizing the bacterial cell wall are attractive targets for the design of antibacterial compounds, since this pathway is essential for bacteria and is absent in animals, particularly humans. A survey of the genome of a bacterium that belongs to the phylum Verrucomicrobia, the closest free-living relative to bacteria from the Chlamydiales phylum, shows genetic evidence that Verrucomicrobium spinosum possesses a novel fusion open reading frame (ORF) annotated by the locus tag (VspiD_010100018130). The ORF, which is predicted to encode the enzymes UDP-N-acetylenolpyruvoylglucosamine reductase (MurB) and UDP-N-acetylmuramate:l-alanine ligase (MurC) that are involved in the cytoplasmic steps of peptidoglycan biosynthesis, was cloned. In vivo analyses using functional complementation showed that the fusion gene was able to complement Escherichia coli murB and murC temperature sensitive mutants. The purified recombinant fusion enzyme (MurB/C Vs ) was shown to be endowed with UDP-N-acetylmuramate:l-alanine ligase activity. In vitro analyses demonstrated that the latter enzyme had a pH optimum of 9.0, a magnesium optimum of 10 mM and a temperature optimum of 44-46°C. Its apparent K m values for ATP, UDP-MurNAc, and l-alanine were 470, 90, and 25 μM, respectively. However, all attempts to demonstrate an in vitro UDP-N-acetylenolpyruvoylglucosamine reductase (MurB) activity were unsuccessful. Lastly, Hidden Markov Model-based similarity search and phylogenetic analysis revealed that this fusion enzyme could only be identified in specific lineages within the Verrucomicrobia phylum.

Identification and Partial Characterization of a Novel UDP-N-Acetylenolpyruvoylglucosamine Reductase/UDP-N-Acetylmuramate:l-Alanine Ligase Fusion Enzyme from Verrucomicrobium spinosum DSM 4136T

PubMed Central

Naqvi, Kubra F.; Patin, Delphine; Wheatley, Matthew S.; Savka, Michael A.; Dobson, Renwick C. J.; Gan, Han Ming; Barreteau, Hélène; Blanot, Didier; Mengin-Lecreulx, Dominique; Hudson, André O.

2016-01-01

The enzymes involved in synthesizing the bacterial cell wall are attractive targets for the design of antibacterial compounds, since this pathway is essential for bacteria and is absent in animals, particularly humans. A survey of the genome of a bacterium that belongs to the phylum Verrucomicrobia, the closest free-living relative to bacteria from the Chlamydiales phylum, shows genetic evidence that Verrucomicrobium spinosum possesses a novel fusion open reading frame (ORF) annotated by the locus tag (VspiD_010100018130). The ORF, which is predicted to encode the enzymes UDP-N-acetylenolpyruvoylglucosamine reductase (MurB) and UDP-N-acetylmuramate:l-alanine ligase (MurC) that are involved in the cytoplasmic steps of peptidoglycan biosynthesis, was cloned. In vivo analyses using functional complementation showed that the fusion gene was able to complement Escherichia coli murB and murC temperature sensitive mutants. The purified recombinant fusion enzyme (MurB/CVs) was shown to be endowed with UDP-N-acetylmuramate:l-alanine ligase activity. In vitro analyses demonstrated that the latter enzyme had a pH optimum of 9.0, a magnesium optimum of 10 mM and a temperature optimum of 44–46°C. Its apparent Km values for ATP, UDP-MurNAc, and l-alanine were 470, 90, and 25 μM, respectively. However, all attempts to demonstrate an in vitro UDP-N-acetylenolpyruvoylglucosamine reductase (MurB) activity were unsuccessful. Lastly, Hidden Markov Model-based similarity search and phylogenetic analysis revealed that this fusion enzyme could only be identified in specific lineages within the Verrucomicrobia phylum. PMID:27047475

Preservation or Restoration of Segmental and Regional Spinal Lordosis Using Minimally Invasive Interbody Fusion Techniques in Degenerative Lumbar Conditions: A Literature Review.

PubMed

Uribe, Juan S; Myhre, Sue Lynn; Youssef, Jim A

2016-04-01

A literature review. The purpose of this study was to review lumbar segmental and regional alignment changes following treatment with a variety of minimally invasive surgery (MIS) interbody fusion procedures for short-segment, degenerative conditions. An increasing number of lumbar fusions are being performed with minimally invasive exposures, despite a perception that minimally invasive lumbar interbody fusion procedures are unable to affect segmental and regional lordosis. Through a MEDLINE and Google Scholar search, a total of 23 articles were identified that reported alignment following minimally invasive lumbar fusion for degenerative (nondeformity) lumbar spinal conditions to examine aggregate changes in postoperative alignment. Of the 23 studies identified, 28 study cohorts were included in the analysis. Procedural cohorts included MIS ALIF (two), extreme lateral interbody fusion (XLIF) (16), and MIS posterior/transforaminal lumbar interbody fusion (P/TLIF) (11). Across 19 study cohorts and 720 patients, weighted average of lumbar lordosis preoperatively for all procedures was 43.5° (range 28.4°-52.5°) and increased 3.4° (9%) (range -2° to 7.4°) postoperatively (P < 0.001). Segmental lordosis increased, on average, by 4° from a weighted average of 8.3° preoperatively (range -0.8° to 15.8°) to 11.2° at postoperative time points (range -0.2° to 22.8°) (P < 0.001) in 1182 patient from 24 study cohorts. Simple linear regression revealed a significant relationship between preoperative lumbar lordosis and change in lumbar lordosis (r = 0.413; P = 0.003), wherein lower preoperative lumbar lordosis predicted a greater increase in postoperative lumbar lordosis. Significant gains in both weighted average lumbar lordosis and segmental lordosis were seen following MIS interbody fusion. None of the segmental lordosis cohorts and only two of the 19 lumbar lordosis cohorts showed decreases in lordosis postoperatively. These results suggest that MIS approaches are able to impact regional and local segmental alignment and that preoperative patient factors can impact the extent of correction gained (preserving vs. restoring alignment). 4.

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

Direct Drive Fusion Energy Shock Ignition Designs for Sub-MJ Lasers

DTIC Science & Technology

2008-09-01

FUSION ENERGY SHOCK IGNITION DESIGNS FOR SUB-MJ LASERS Andrew J. Schmitt, J. W. Bates, S. P. Obenschain, and S. T. Zalesak Plasma Physics Division, Naval Research Laboratory, Washington DC 20375 andrew.schmitt@nrl.navy.mil D. E. Fyfe LCP&FD, Naval Research Laboratory, Washington DC 20375 R. Betti Fusion Science Center and Laboratory for Laser Energetics, University of Rochester, Rochester NY New approaches in target design have increased the pos- sibility that useful fusion power can be generated with sub-MJ lasers. We have performed many 1D and 2D

Biomechanical effects of fusion levels on the risk of proximal junctional failure and kyphosis in lumbar spinal fusion surgery.

PubMed

Park, Won Man; Choi, Dae Kyung; Kim, Kyungsoo; Kim, Yongjung J; Kim, Yoon Hyuk

2015-12-01

Spinal fusion surgery is a widely used surgical procedure for sagittal realignment. Clinical studies have reported that spinal fusion may cause proximal junctional kyphosis and failure with disc failure, vertebral fracture, and/or failure at the implant-bone interface. However, the biomechanical injury mechanisms of proximal junctional kyphosis and failure remain unclear. A finite element model of the thoracolumbar spine was used. Nine fusion models with pedicle screw systems implanted at the L2-L3, L3-L4, L4-L5, L5-S1, L2-L4, L3-L5, L4-S1, L2-L5, and L3-S1 levels were developed based on the respective surgical protocols. The developed models simulated flexion-extension using hybrid testing protocol. When spinal fusion was performed at more distal levels, particularly at the L5-S1 level, the following biomechanical properties increased during flexion-extension: range of motion, stress on the annulus fibrosus fibers and vertebra at the adjacent motion segment, and the magnitude of axial forces on the pedicle screw at the uppermost instrumented vertebra. The results of this study demonstrate that more distal fusion levels, particularly in spinal fusion including the L5-S1 level, lead to greater increases in the risk of proximal junctional kyphosis and failure, as evidenced by larger ranges of motion, higher stresses on fibers of the annulus fibrosus and vertebra at the adjacent segment, and higher axial forces on the screw at the uppermost instrumented vertebra in flexion-extension. Therefore, fusion levels should be carefully selected to avoid proximal junctional kyphosis and failure. Copyright © 2015 Elsevier Ltd. All rights reserved.

Adaptive multifocus image fusion using block compressed sensing with smoothed projected Landweber integration in the wavelet domain.

PubMed

V S, Unni; Mishra, Deepak; Subrahmanyam, G R K S

2016-12-01

The need for image fusion in current image processing systems is increasing mainly due to the increased number and variety of image acquisition techniques. Image fusion is the process of combining substantial information from several sensors using mathematical techniques in order to create a single composite image that will be more comprehensive and thus more useful for a human operator or other computer vision tasks. This paper presents a new approach to multifocus image fusion based on sparse signal representation. Block-based compressive sensing integrated with a projection-driven compressive sensing (CS) recovery that encourages sparsity in the wavelet domain is used as a method to get the focused image from a set of out-of-focus images. Compression is achieved during the image acquisition process using a block compressive sensing method. An adaptive thresholding technique within the smoothed projected Landweber recovery process reconstructs high-resolution focused images from low-dimensional CS measurements of out-of-focus images. Discrete wavelet transform and dual-tree complex wavelet transform are used as the sparsifying basis for the proposed fusion. The main finding lies in the fact that sparsification enables a better selection of the fusion coefficients and hence better fusion. A Laplacian mixture model fit is done in the wavelet domain and estimation of the probability density function (pdf) parameters by expectation maximization leads us to the proper selection of the coefficients of the fused image. Using the proposed method compared with the fusion scheme without employing the projected Landweber (PL) scheme and the other existing CS-based fusion approaches, it is observed that with fewer samples itself, the proposed method outperforms other approaches.

Processes in massive nuclei reactions and the way to complete fusion of reactants. What perspectives for the synthesis of heavier superheavy elements?

NASA Astrophysics Data System (ADS)

Mandaglio, G.; Nasirov, A. K.; Curciarello, F.; De Leo, V.; Romaniuk, M.; Fazio, G.; Giardina, G.

2012-12-01

By using the dinuclear system (DNS) model we determine the capture of reactants at the first stage of reaction, the competition between the DNS decay by the quasifission (QF) and the complete fusion (CF) process up to formation of the compound nucleus (CN) having compact shape. Further evolution of the CN is considered as its fission into two fragments or formation of evaporation residues (ER) by its cooling after emission of neutrons or/and charged light particles. Disappearance of the CN fission barrier due to its fast rotation leads to the fast fission (FF) by formation of fissionlike fragments. The results of calculations for the mass symmetric 136Xe+136Xe reaction, almost mass symmetric 108Mo+144Ba reaction, and mass asymmetric like 24Mg+238U and 34S+248Cm reactions are discussed. The fusion probability PCN calculated for many massive nuclei reactions leading to formation of superheavy nuclei have been analyzed. The reactions which can lead in perspective to the synthesis of superheavy elements in the Z = 120 - 126 range and, eventually, also to heaviest nuclei, are discussed.

Exocytosis and Endocytosis: Modes, Functions, and Coupling Mechanisms*

PubMed Central

Wu, Ling-Gang; Hamid, Edaeni; Shin, Wonchul; Chiang, Hsueh-Cheng

2016-01-01

Vesicle exocytosis releases content to mediate many biological events, including synaptic transmission essential for brain functions. Following exocytosis, endocytosis is initiated to retrieve exocytosed vesicles within seconds to minutes. Decades of studies in secretory cells reveal three exocytosis modes coupled to three endocytosis modes: (a) full-collapse fusion, in which vesicles collapse into the plasma membrane, followed by classical endocytosis involving membrane invagination and vesicle reformation; (b) kiss-and-run, in which the fusion pore opens and closes; and (c) compound exocytosis, which involves exocytosis of giant vesicles formed via vesicle-vesicle fusion, followed by bulk endocytosis that retrieves giant vesicles. Here we review these exo- and endocytosis modes and their roles in regulating quantal size and synaptic strength, generating synaptic plasticity, maintaining exocytosis, and clearing release sites for vesicle replenishment. Furthermore, we highlight recent progress in understanding how vesicle endocytosis is initiated and is thus coupled to exocytosis. The emerging model is that calcium influx via voltage-dependent calcium channels at the calcium microdomain triggers endocytosis and controls endocytosis rate; calmodulin and synaptotagmin are the calcium sensors; and the exocytosis machinery, including SNARE proteins (synaptobrevin, SNAP25, and syntaxin), is needed to coinitiate endocytosis, likely to control the amount of endocytosis. PMID:24274740

Thermodynamic and structural aspects of novel 1,2,4-thiadiazoles in solid and biological mediums.

PubMed

Perlovich, German L; Proshin, Alexey N; Volkova, Tatyana V; Bui, Cong Trinh; Bachurin, Sergey O

2011-10-03

Novel 1,2,4-thiadiazoles were synthesized. Crystal structures of these compounds were solved by X-ray diffraction experiments, and comparative analysis of packing architecture and hydrogen bond networks was carried out. Thermodynamic aspects of sublimation processes of the compounds under study were analyzed using temperature dependencies of vapor pressure. Thermophysical characteristics of the molecular crystals were obtained and compared with the sublimation and structural parameters. The melting points correlate with sublimation Gibbs energies. Moreover, an increase of donor-acceptor interactions in crystal structures leads to growth of Gibbs energy values. Relationships between the melting points and the fragmental contributions to the packing energies were established: R(1)-R(4) fragmental interactions are responsible for the fusion processes of this class of compounds. Solubility and solvation processes of 1,2,4-thiadiazoles in buffer, n-hexane and n-octanol were studied within a wide range of temperature intervals, and their thermodynamic functions were calculated. Specific and nonspecific interactions of molecules resolved in crystals and solvents were estimated and compared. It was found that the melting points correlate with sublimation Gibbs energies. Distribution processes of compounds in buffer/n-octanol and buffer/n-hexane systems (describing different types of membranes) were investigated. Transfer processes of the studied molecules from the buffer to n-octanol/n-hexane phases were analyzed by the diagram method with evaluation of the enthalpic and entropic terms. This approach allowed us to design drug molecules with optimal passive transport properties. Calcium-blocking properties of the substances were evaluated. The trend between the ability to inhibit Glu-Ca uptake and the distribution coefficients in buffer/hexane system was observed.

Enhanced Vaccine-Induced CD8+ T Cell Responses to Malaria Antigen ME-TRAP by Fusion to MHC Class II Invariant Chain

PubMed Central

Spencer, Alexandra J.; Cottingham, Matthew G.; Jenks, Jennifer A.; Longley, Rhea J.; Capone, Stefania; Colloca, Stefano; Folgori, Antonella; Cortese, Riccardo; Nicosia, Alfredo; Bregu, Migena; Hill, Adrian V. S.

2014-01-01

The orthodox role of the invariant chain (CD74; Ii) is in antigen presentation to CD4+ T cells, but enhanced CD8+ T cells responses have been reported after vaccination with vectored viral vaccines encoding a fusion of Ii to the antigen of interest. In this study we assessed whether fusion of the malarial antigen, ME-TRAP, to Ii could increase the vaccine-induced CD8+ T cell response. Following single or heterologous prime-boost vaccination of mice with a recombinant chimpanzee adenovirus vector, ChAd63, or recombinant modified vaccinia virus Ankara (MVA), higher frequencies of antigen-specific CD4+ and CD8+ T cells were observed, with the largest increases observed following a ChAd63-MVA heterologous prime-boost regimen. Studies in non-human primates confirmed the ability of Ii-fusion to augment the T cell response, where a 4-fold increase was maintained up to 11 weeks after the MVA boost. Of the numerous different approaches explored to increase vectored vaccine induced immunogenicity over the years, fusion to the invariant chain showed a consistent enhancement in CD8+ T cell responses across different animal species and may therefore find application in the development of vaccines against human malaria and other diseases where high levels of cell-mediated immunity are required. PMID:24945248

Preventing droplet deformation during dielectrophoretic centering of a compound emulsion droplet

NASA Astrophysics Data System (ADS)

Randall, Greg; Blue, Brent

2012-11-01

Compound droplets, or droplets-within-droplets, are traditionally key components in applications ranging from drug delivery to the food industry. Presently, millimeter-sized compound droplets are precursors for shell targets in inertial fusion energy work. However, a key constraint in target fabrication is a uniform shell wall thickness, which in turn requires a centered core droplet in the compound droplet precursor. Previously, Bei et al. (2009, 2010) have shown that compound droplets could be centered in a static fluid using an electric field of 0.7 kV/cm at 20 MHz. Randall et al. (2012) developed a process to center the core of a moving compound droplet, though the ~kV/cm field induced small (< 5%) but undesirable droplet stretching. This work shows that by using macromolecular emulsifiers to strengthen the droplet's interfaces, (proteins, tunable peptides, or biotinylated streptavidin) droplet stretching can be greatly inhibited. Proof-of-principle experiments are performed in either a stagnant density-matched aquarium or a vertical channel of buoyancy-driven droplets in a ~kV/cm electric field. A scaling analysis is given from a fluid mechanics and interfacial rheology perspective and we discuss the effective interfacial charge from an emulsifier and its impact on centering. Work funded by General Atomics Internal R&D.

Improving Echo-Guided Procedures Using an Ultrasound-CT Image Fusion System.

PubMed

Diana, Michele; Halvax, Peter; Mertz, Damien; Legner, Andras; Brulé, Jean-Marcel; Robinet, Eric; Mutter, Didier; Pessaux, Patrick; Marescaux, Jacques

2015-06-01

Image fusion between ultrasound (US) and computed tomography (CT) scan or magnetic resonance can increase operator accuracy in targeting liver lesions, particularly when those are undetectable with US alone. We have developed a modular gel to simulate hepatic solid lesions for educational purposes in imaging and minimally invasive ablation techniques. We aimed to assess the impact of image fusion in targeting artificial hepatic lesions during the hands-on part of 2 courses (basic and advanced) in hepatobiliary surgery. Under US guidance, 10 fake tumors of various sizes were created in the livers of 2 pigs, by percutaneous injection of a biocompatible gel engineered to be hyperdense on CT scanning and barely detectable on US. A CT scan was obtained and a CT-US image fusion was performed using the ACUSON S3000 US system (Siemens Healthcare, Germany). A total of 12 blinded course attendants, were asked in turn to perform a 10-minute liver scan with US alone followed by a 10-minute scan using image fusion. Using US alone, the expert managed to identify all lesions successfully. The true positive rate for course attendants with US alone was 14/36 and 2/24 in the advanced and basic courses, respectively. The total number of false positives identified was 26. With image fusion, the rate of true positives significantly increased to 31/36 (P < .001) in the advanced group and 16/24 in the basic group (P < .001). The total number of false positives, considering all participants, decreased to 4 (P < .001). Image fusion significantly increases accuracy in targeting hepatic lesions and might improve echo-guided procedures. © The Author(s) 2015.

Sacroiliac Joint Fusion Minimally Affects Adjacent Lumbar Segment Motion: A Finite Element Study

PubMed Central

Kiapour, Ali; Yerby, Scott A.; Goel, Vijay K.

2015-01-01

Background Adjacent segment disease is a recognized consequence of fusion in the spinal column. Fusion of the sacroiliac joint is an effective method of pain reduction. Although effective, the consequences of sacroiliac joint fusion and the potential for adjacent segment disease for the adjacent lumbar spinal levels is unknown. The objective of this study was to quantify the change in range of motion of the sacroiliac joint and the adjacent lumbar spinal motion segments due to sacroiliac joint fusion and compare these changes to previous literature to assess the potential for adjacent segment disease in the lumbar spine. Methods An experimentally validated finite element model of the lumbar spine and pelvis was used to simulate a fusion of the sacroiliac joint using three laterally placed triangular implants (iFuse Implant System, SI-BONE, Inc., San Jose, CA). The range of motion of the sacroiliac joint and the adjacent lumbar spinal motion segments were calculated using a hybrid loading protocol and compared with the intact range of motion in flexion, extension, lateral bending, and axial rotation. Results The range of motions of the treated sacroiliac joints were reduced in flexion, extension, lateral bending, and axial rotation, by 56.6%, 59.5%, 27.8%, and 53.3%, respectively when compared with the intact condition. The stiffening of the sacroiliac joint resulted in increases at the adjacent lumbar motion segment (L5-S1) for flexion, extension, lateral bending, and axial rotation, of 3.0%, 3.7%, 1.1%, and 4.6%, respectively. Conclusions Fusion of the sacroiliac joint resulted in substantial (> 50%) reductions in flexion, extension, and axial rotation of the sacroiliac joint with minimal (< 5%) increases in range of motion in the lumbar spine. Although the predicted increases in lumbar range of motion are minimal after sacroiliac joint fusion, the long-term clinical results remain to be investigated. PMID:26767156

Sacroiliac Joint Fusion Minimally Affects Adjacent Lumbar Segment Motion: A Finite Element Study.

PubMed

Lindsey, Derek P; Kiapour, Ali; Yerby, Scott A; Goel, Vijay K

2015-01-01

Adjacent segment disease is a recognized consequence of fusion in the spinal column. Fusion of the sacroiliac joint is an effective method of pain reduction. Although effective, the consequences of sacroiliac joint fusion and the potential for adjacent segment disease for the adjacent lumbar spinal levels is unknown. The objective of this study was to quantify the change in range of motion of the sacroiliac joint and the adjacent lumbar spinal motion segments due to sacroiliac joint fusion and compare these changes to previous literature to assess the potential for adjacent segment disease in the lumbar spine. An experimentally validated finite element model of the lumbar spine and pelvis was used to simulate a fusion of the sacroiliac joint using three laterally placed triangular implants (iFuse Implant System, SI-BONE, Inc., San Jose, CA). The range of motion of the sacroiliac joint and the adjacent lumbar spinal motion segments were calculated using a hybrid loading protocol and compared with the intact range of motion in flexion, extension, lateral bending, and axial rotation. The range of motions of the treated sacroiliac joints were reduced in flexion, extension, lateral bending, and axial rotation, by 56.6%, 59.5%, 27.8%, and 53.3%, respectively when compared with the intact condition. The stiffening of the sacroiliac joint resulted in increases at the adjacent lumbar motion segment (L5-S1) for flexion, extension, lateral bending, and axial rotation, of 3.0%, 3.7%, 1.1%, and 4.6%, respectively. Fusion of the sacroiliac joint resulted in substantial (> 50%) reductions in flexion, extension, and axial rotation of the sacroiliac joint with minimal (< 5%) increases in range of motion in the lumbar spine. Although the predicted increases in lumbar range of motion are minimal after sacroiliac joint fusion, the long-term clinical results remain to be investigated.

A Single Amino Acid Substitution in the Core Protein of West Nile Virus Increases Resistance to Acidotropic Compounds

PubMed Central

Martín-Acebes, Miguel A.; Blázquez, Ana-Belén; de Oya, Nereida Jiménez; Escribano-Romero, Estela; Shi, Pei-Yong; Saiz, Juan-Carlos

2013-01-01

West Nile virus (WNV) is a worldwide distributed mosquito-borne flavivirus that naturally cycles between birds and mosquitoes, although it can infect multiple vertebrate hosts including horses and humans. This virus is responsible for recurrent epidemics of febrile illness and encephalitis, and has recently become a global concern. WNV requires to transit through intracellular acidic compartments at two different steps to complete its infectious cycle. These include fusion between the viral envelope and the membrane of endosomes during viral entry, and virus maturation in the trans-Golgi network. In this study, we followed a genetic approach to study the connections between viral components and acidic pH. A WNV mutant with increased resistance to the acidotropic compound NH4Cl, which blocks organelle acidification and inhibits WNV infection, was selected. Nucleotide sequencing revealed that this mutant displayed a single amino acid substitution (Lys 3 to Glu) on the highly basic internal capsid or core (C) protein. The functional role of this replacement was confirmed by its introduction into a WNV infectious clone. This single amino acid substitution also increased resistance to other acidification inhibitor (concanamycin A) and induced a reduction of the neurovirulence in mice. Interestingly, a naturally occurring accompanying mutation found on prM protein abolished the resistant phenotype, supporting the idea of a genetic crosstalk between the internal C protein and the external glycoproteins of the virion. The findings here reported unveil a non-previously assessed connection between the C viral protein and the acidic pH necessary for entry and proper exit of flaviviruses. PMID:23874963

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.

Early repositioning through compound set enrichment analysis: a knowledge-recycling strategy.

PubMed

Temesi, Gergely; Bolgár, Bence; Arany, Adám; Szalai, Csaba; Antal, Péter; Mátyus, Péter

2014-04-01

Despite famous serendipitous drug repositioning success stories, systematic projects have not yet delivered the expected results. However, repositioning technologies are gaining ground in different phases of routine drug development, together with new adaptive strategies. We demonstrate the power of the compound information pool, the ever-growing heterogeneous information repertoire of approved drugs and candidates as an invaluable catalyzer in this transition. Systematic, computational utilization of this information pool for candidates in early phases is an open research problem; we propose a novel application of the enrichment analysis statistical framework for fusion of this information pool, specifically for the prediction of indications. Pharmaceutical consequences are formulated for a systematic and continuous knowledge recycling strategy, utilizing this information pool throughout the drug-discovery pipeline.

Glycoprotein interactions in paramyxovirus fusion

PubMed Central

Iorio, Ronald M; Melanson, Vanessa R; Mahon, Paul J

2009-01-01

The Paramyxoviridae are enveloped, negative-stranded RNA viruses, some of which recognize sialic acid-containing receptors, while others recognize specific proteinaceous receptors. The major cytopathic effect of paramyxovirus infection is membrane fusion-induced syncytium formation. Paramyxoviruses are unusual in that the receptor-binding and fusion-promoting activities reside on two different spike structures, the attachment and fusion glycoproteins, respectively. For most paramyxoviruses, this distribution of functions requires a mechanism by which the two processes can be linked for the promotion of fusion. This is accomplished by a virus-specific interaction between the two proteins. An increasing body of evidence supports the notion that members of this family of viruses utilize this glycoprotein interaction in different ways in order to mediate the regulation of the fusion protein activation, depending on the type of receptor utilized by the virus. PMID:20161127

Effects of selective fusion on the thermal history of the earth's mantle

USGS Publications Warehouse

Lee, W.H.K.

1968-01-01

A comparative study on the thermal history of the earth's mantle was made by numerical solutions of the heat equation including and excluding selective fusion of silicates. Selective fusion was approximated by melting in a multicomponent system and redistribution of radioactive elements. Effects of selective fusion on the thermal models are (1) lowering (by several hundred degrees centigrade) and stabilizing the internal temperature distribution, and (2) increasing the surface heat-flow. It was found that models with selective fusion gave results more compatible with observations of both present temperature and surface heat-flow. The results therefore suggest continuous differentiation of the earth's mantle throughout geologic time, and support the hypothesis that the earth's atmosphere, oceans, and crust have been accumulated throughout the earth's history by degassing and selective fusion of the mantle. ?? 1968.

QuantFusion: Novel Unified Methodology for Enhanced Coverage and Precision in Quantifying Global Proteomic Changes in Whole Tissues.

PubMed

Gunawardena, Harsha P; O'Brien, Jonathon; Wrobel, John A; Xie, Ling; Davies, Sherri R; Li, Shunqiang; Ellis, Matthew J; Qaqish, Bahjat F; Chen, Xian

2016-02-01

Single quantitative platforms such as label-based or label-free quantitation (LFQ) present compromises in accuracy, precision, protein sequence coverage, and speed of quantifiable proteomic measurements. To maximize the quantitative precision and the number of quantifiable proteins or the quantifiable coverage of tissue proteomes, we have developed a unified approach, termed QuantFusion, that combines the quantitative ratios of all peptides measured by both LFQ and label-based methodologies. Here, we demonstrate the use of QuantFusion in determining the proteins differentially expressed in a pair of patient-derived tumor xenografts (PDXs) representing two major breast cancer (BC) subtypes, basal and luminal. Label-based in-spectra quantitative peptides derived from amino acid-coded tagging (AACT, also known as SILAC) of a non-malignant mammary cell line were uniformly added to each xenograft with a constant predefined ratio, from which Ratio-of-Ratio estimates were obtained for the label-free peptides paired with AACT peptides in each PDX tumor. A mixed model statistical analysis was used to determine global differential protein expression by combining complementary quantifiable peptide ratios measured by LFQ and Ratio-of-Ratios, respectively. With minimum number of replicates required for obtaining the statistically significant ratios, QuantFusion uses the distinct mechanisms to "rescue" the missing data inherent to both LFQ and label-based quantitation. Combined quantifiable peptide data from both quantitative schemes increased the overall number of peptide level measurements and protein level estimates. In our analysis of the PDX tumor proteomes, QuantFusion increased the number of distinct peptide ratios by 65%, representing differentially expressed proteins between the BC subtypes. This quantifiable coverage improvement, in turn, not only increased the number of measurable protein fold-changes by 8% but also increased the average precision of quantitative estimates by 181% so that some BC subtypically expressed proteins were rescued by QuantFusion. Thus, incorporating data from multiple quantitative approaches while accounting for measurement variability at both the peptide and global protein levels make QuantFusion unique for obtaining increased coverage and quantitative precision for tissue proteomes. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Computational assessment of several hydrogen-free high energy compounds.

PubMed

Tan, Bisheng; Huang, Ming; Long, Xinping; Li, Jinshan; Fan, Guijuan

2016-01-01

Tetrazino-tetrazine-tetraoxide (TTTO) is an attractive high energy compound, but unfortunately, it is not yet experimentally synthesized so far. Isomerization of TTTO leads to its five isomers, bond-separation energies were empolyed to compare the global stability of six compounds, it is found that isomer 1 has the highest bond-separation energy (1204.6kJ/mol), compared with TTTO (1151.2kJ/mol); thermodynamic properties of six compounds were theoretically calculated, including standard formation enthalpies (solid and gaseous), standard fusion enthalpies, standard vaporation enthalpies, standard sublimation enthalpies, lattice energies and normal melting points, normal boiling points; their detonation performances were also computed, including detonation heat (Q, cal/g), detonation velocity (D, km/s), detonation pressure (P, GPa) and impact sensitivity (h50, cm), compared with TTTO (Q=1311.01J/g, D=9.228km/s, P=40.556GPa, h50=12.7cm), isomer 5 exhibites better detonation performances (Q=1523.74J/g, D=9.389km/s, P=41.329GPa, h50= 28.4cm). Copyright © 2015 Elsevier Inc. All rights reserved.

Study of incomplete fusion reaction dynamics in 13C +165 Ho system and its dependence on various entrance channel parameters

NASA Astrophysics Data System (ADS)

Tali, Suhail A.; Kumar, Harish; Ansari, M. Afzal; Ali, Asif; Singh, D.; Ali, Rahbar; Giri, Pankaj K.; Linda, Sneha B.; Parashari, Siddharth; Kumar, R.; Singh, R. P.; Muralithar, S.

2018-02-01

The excitation functions for the evaporation residues populated in the interaction of 13C +165 Ho system have been measured at projectile energies ≈ 4-7 MeV/nucleon. Stacked foil activation technique followed by off-line γ-ray spectroscopy have been employed in the present work. The experimentally measured cross-sections are analyzed in the frame work of statistical model code PACE4, which takes into account only the complete fusion reaction cross-sections. The evaporation residues populated via xn and pxn channels were found to be in good agreement with the PACE4 predictions, while a significant enhancement in the measured cross-sections over PACE4 predictions is observed in case of α-emitting channels, which may be attributed to the incomplete fusion process. For the better understanding of incomplete fusion dynamics, the incomplete fusion fraction has also been deduced and its sensitivity with various entrance channel parameters like: projectile energy, mass-asymmetry, projectile structure in terms of Qα-value and Coulomb effect has been studied in the present work. The incomplete fusion fraction is found to increase with increasing the projectile energy and a strong projectile structure dependent mass-asymmetry systematic is also observed. The incomplete fusion fraction is also found to be small for more negative Qα-value projectile (13C) induced reactions as compared to less negative Qα-value projectiles (12C, 16O and 20Ne) induced reactions with the same target nucleus 165Ho. An interesting trend is obtained on further investigation of incomplete fusion dependence on Coulomb effect (ZPZT).

Identification and Characterization of LFD-2, a Predicted Fringe Protein Required for Membrane Integrity during Cell Fusion in Neurospora crassa

PubMed Central

Palma-Guerrero, Javier; Zhao, Jiuhai; Gonçalves, A. Pedro; Starr, Trevor L.

2015-01-01

The molecular mechanisms of membrane merger during somatic cell fusion in eukaryotic species are poorly understood. In the filamentous fungus Neurospora crassa, somatic cell fusion occurs between genetically identical germinated asexual spores (germlings) and between hyphae to form the interconnected network characteristic of a filamentous fungal colony. In N. crassa, two proteins have been identified to function at the step of membrane fusion during somatic cell fusion: PRM1 and LFD-1. The absence of either one of these two proteins results in an increase of germling pairs arrested during cell fusion with tightly appressed plasma membranes and an increase in the frequency of cell lysis of adhered germlings. The level of cell lysis in ΔPrm1 or Δlfd-1 germlings is dependent on the extracellular calcium concentration. An available transcriptional profile data set was used to identify genes encoding predicted transmembrane proteins that showed reduced expression levels in germlings cultured in the absence of extracellular calcium. From these analyses, we identified a mutant (lfd-2, for late fusion defect-2) that showed a calcium-dependent cell lysis phenotype. lfd-2 encodes a protein with a Fringe domain and showed endoplasmic reticulum and Golgi membrane localization. The deletion of an additional gene predicted to encode a low-affinity calcium transporter, fig1, also resulted in a strain that showed a calcium-dependent cell lysis phenotype. Genetic analyses showed that LFD-2 and FIG1 likely function in separate pathways to regulate aspects of membrane merger and repair during cell fusion. PMID:25595444

Evaporation residue cross-section measurements for 48Ti-induced reactions

NASA Astrophysics Data System (ADS)

Sharma, Priya; Behera, B. R.; Mahajan, Ruchi; Thakur, Meenu; Kaur, Gurpreet; Kapoor, Kushal; Rani, Kavita; Madhavan, N.; Nath, S.; Gehlot, J.; Dubey, R.; Mazumdar, I.; Patel, S. M.; Dhibar, M.; Hosamani, M. M.; Khushboo, Kumar, Neeraj; Shamlath, A.; Mohanto, G.; Pal, Santanu

2017-09-01

Background: A significant research effort is currently aimed at understanding the synthesis of heavy elements. For this purpose, heavy ion induced fusion reactions are used and various experimental observations have indicated the influence of shell and deformation effects in the compound nucleus (CN) formation. There is a need to understand these two effects. Purpose: To investigate the effect of proton shell closure and deformation through the comparison of evaporation residue (ER) cross sections for the systems involving heavy compound nuclei around the ZCN=82 region. Methods: A systematic study of ER cross-section measurements was carried out for the 48Ti+Nd,150142 , 144Sm systems in the energy range of 140 -205 MeV . The measurement has been performed using the gas-filled mode of the hybrid recoil mass analyzer present at the Inter University Accelerator Centre (IUAC), New Delhi. Theoretical calculations based on a statistical model were carried out incorporating an adjustable barrier scaling factor to fit the experimental ER cross section. Coupled-channel calculations were also performed using the ccfull code to obtain the spin distribution of the CN, which was used as an input in the calculations. Results: Experimental ER cross sections for 48Ti+Nd,150142 were found to be considerably smaller than the statistical model predictions whereas experimental and statistical model predictions for 48Ti+144Sm were of comparable magnitudes. Conclusion: Though comparison of experimental ER cross sections with statistical model predictions indicate considerable non-compound-nuclear processes for 48Ti+Nd,150142 reactions, no such evidence is found for the 48Ti+144Sm system. Further investigations are required to understand the difference in fusion probabilities of 48Ti+142Nd and 48Ti+144Sm systems.

Compound kinetochores of the Indian muntjac. Evolution by linear fusion of unit kinetochores.

PubMed

Brinkley, B R; Valdivia, M M; Tousson, A; Brenner, S L

1984-01-01

The chromosomes of the Indian muntjac (Muntiacus muntjak vaginalis) are unique among mammals due to their low diploid number (2N = 6 female, 7 male) and large size. It has been proposed that the karyotype of this small Asiatic deer evolved from a related deer the Chinese muntjac (Muntiacus reevesi) with a diploid chromosome number of 2n = 46 consisting of small telocentric chromosomes. In this study we utilized a kinetochore-specific antiserum derived from human patients with the autoimmune disease scleroderma CREST as an immunofluorescent probe to examine kinetochores of the two muntjac species. Since CREST antiserum binds to kinetochores of mitotic chromosomes as well as prekinetochores in interphase nuclei, it was possible to identify and compare kinetochore morphology throughout the cell cycle. Our observations indicated that the kinetochores of the Indian muntjac are composed of a linear beadlike array of smaller subunits that become revealed during interphase. The kinetochores of the Chinese muntjac consisted of minute fluorescent dots located at the tips of the 46 telocentric chromosomes. During interphase, however, the kinetochores of the Chinese muntjac clustered into small aggregates reminiscent of the beadlike arrays seen in the Indian muntjac. Morphometric measurements of fluorescence indicated an equivalent amount of stained material in the two species. Our observations indicate that the kinetochores of the Indian muntjac are compound structures composed of linear arrays of smaller units the size of the individual kinetochores seen on metaphase chromosomes of the Chinese muntjac. Our study supports the notion that the kinetochores of the Indian muntjac evolved by linear fusion of unit kinetochores of the Chinese muntjac. Moreover, it is concluded that the evolution of compound kinetochores may have been facilitated by the non-random aggregation of interphase kinetochores in the nuclei of the ancestral species.

Biomechanical Analysis of Cervical Disc Replacement and Fusion Using Single Level, Two Level, and Hybrid Constructs.

PubMed

Gandhi, Anup A; Kode, Swathi; DeVries, Nicole A; Grosland, Nicole M; Smucker, Joseph D; Fredericks, Douglas C

2015-10-15

A biomechanical study comparing arthroplasty with fusion using human cadaveric C2-T1 spines. To compare the kinematics of the cervical spine after arthroplasty and fusion using single level, 2 level and hybrid constructs. Previous studies have shown that spinal levels adjacent to a fusion experience increased motion and higher stress which may lead to adjacent segment disc degeneration. Cervical arthroplasty achieves similar decompression but preserves the motion at the operated level, potentially decreasing the occurrence of adjacent segment disc degeneration. 11 specimens (C2-T1) were divided into 2 groups (BRYAN and PRESTIGE LP). The specimens were tested in the following order; intact, single level total disc replacement (TDR) at C5-C6, 2-level TDR at C5-C6-C7, fusion at C5-C6 and TDR at C6-C7 (Hybrid construct), and lastly a 2-level fusion. The intact specimens were tested up to a moment of 2.0 Nm. After each surgical intervention, the specimens were loaded until the primary motion (C2-T1) matched the motion of the respective intact state (hybrid control). An arthroplasty preserved motion at the implanted level and maintained normal motion at the nonoperative levels. Arthrodesis resulted in a significant decrease in motion at the fused level and an increase in motion at the unfused levels. In the hybrid construct, the TDR adjacent to fusion preserved motion at the arthroplasty level, thereby reducing the demand on the other levels. Cervical disc arthroplasty with both the BRYAN and PRESTIGE LP discs not only preserved the motion at the operated level, but also maintained the normal motion at the adjacent levels. Under simulated physiologic loading, the motion patterns of the spine with the BRYAN or PRESTIGE LP disc were very similar and were closer than fusion to the intact motion pattern. An adjacent segment disc replacement is biomechanically favorable to a fusion in the presence of a pre-existing fusion.

Effects of large-angle Coulomb collisions on inertial confinement fusion plasmas.

PubMed

Turrell, A E; Sherlock, M; Rose, S J

2014-06-20

Large-angle Coulomb collisions affect the rates of energy and momentum exchange in a plasma, and it is expected that their effects will be important in many plasmas of current research interest, including in inertial confinement fusion. Their inclusion is a long-standing problem, and the first fully self-consistent method for calculating their effects is presented. This method is applied to "burn" in the hot fuel in inertial confinement fusion capsules and finds that the yield increases due to an increase in the rate of temperature equilibration between electrons and ions which is not predicted by small-angle collision theories. The equilibration rate increases are 50%-100% for number densities of 10(30)  m(-3) and temperatures around 1 keV.

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.

The Effect of Iliac Crest Autograft on the Outcome of Fusion in the Setting of Degenerative Spondylolisthesis

PubMed Central

Radcliff, Kristen; Hwang, Raymond; Hilibrand, Alan; Smith, Harvey E.; Gruskay, Jordan; Lurie, Jon D.; Zhao, Wenyan; Albert, Todd; Weinstein, James

2012-01-01

Background: There is considerable controversy about the long-term morbidity associated with the use of posterior autologous iliac crest bone graft for lumbar spine fusion procedures compared with the use of bone-graft substitutes. The hypothesis of this study was that there is no long-term difference in outcome for patients who had posterior lumbar fusion with or without iliac crest autograft. Methods: The study population includes patients enrolled in the degenerative spondylolisthesis cohort of the Spine Patient Outcomes Research Trial who underwent lumbar spinal fusion. Patients were divided according to whether they had or had not received posterior autologous iliac crest bone graft. Results: There were 108 patients who had fusion with iliac crest autograft and 246 who had fusion without iliac crest autograft. There were no baseline differences between groups in demographic characteristics, comorbidities, or baseline clinical scores. At baseline, the group that received iliac crest bone graft had an increased percentage of patients who had multilevel fusions (32% versus 21%; p = 0.033) and L5-S1 surgery (37% versus 26%; p = 0.031) compared with the group without iliac crest autograft. Operative time was higher in the iliac crest bone-graft group (233.4 versus 200.9 minutes; p < 0.001), and there was a trend toward increased blood loss (686.9 versus 582.3; p = 0.057). There were no significant differences in postoperative complications, including infection or reoperation rates, between the groups. On the basis of the numbers available, no significant differences were detected between the groups treated with or without iliac crest bone graft with regard to the scores on Short Form-36, Oswestry Disability Index, Stenosis Bothersomeness Index, and Low Back Pain Bothersomeness Scale or the percent of patient satisfaction with symptoms averaged over the study period. Conclusions: The outcome scores associated with the use of posterior iliac crest bone graft for lumbar spinal fusion were not significantly lower than those after fusion without iliac crest autograft. Conversely, iliac crest bone-grafting was not associated with an increase in the complication rates or rates of reoperation. On the basis of these results, surgeons may choose to use iliac crest bone graft on a case-by-case basis for lumbar spinal fusion. Level of Evidence: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence. PMID:22878599

Interaction of cord factor (alpha, alpha'-trehalose-6,6'-dimycolate) with phospholipids.

PubMed

Crowe, L M; Spargo, B J; Ioneda, T; Beaman, B L; Crowe, J H

1994-08-24

We previously reported that cord factor (alpha,alpha'-trehalose-6,6'-dimycolate) isolated from Nocardia asteroides strain GUH-2 strongly inhibits fusion between unilamellar vesicles containing acidic phospholipid. We chose to study the effects of this molecule on liposome fusion since the presence of N. asteroides GUH-2 in the phagosomes of mouse macrophages had been shown to prevent phagosomal acidification and inhibit phagosome-lysosome fusion. A virtually non-virulent strain, N. asteroides 10905, does not prevent acidification or phagosome-lysosome fusion and, further, contains only trace amounts of cord factor. In the present paper, we have investigated the effects of cord factor on phospholipid bilayers that could be responsible for the inhibition of fusion. We show that cord factor increases molecular area, measured by isothermal compression of a monolayer film, in a mixed monolayer more than would be expected based in its individual contribution to molecular area. Cord factor, as well as other glycolipids investigated, increased the overall hydration of bilayers of dipalmitoylphosphatidylcholine by 50%, as estimated from the unfrozen water fraction measured by differential scanning calorimetry. The effect of calcium on this increased molecular area and headgroup hydration was measured by fluorescence anisotropy and FTIR spectroscopy of phosphatidylserine liposomes. Both techniques showed that cord factor, incorporated at 10 mol%, increased acyl chain disorder over controls in the presence of Ca2+. However, FTIR showed that cord factor did not prevent headgroup dehydration by the Ca2+. The other glycolipids tested did not prevent either the Ca(2+)-induced chain crystallization or headgroup dehydration of phosphatidylserine bilayers. These data point to a possible role of the bulky mycolic acids of cord factor in preventing Ca(2+)-induced fusion of liposomes containing acidic phospholipids.

Sagittal alignment after lumbar interbody fusion: comparing anterior, lateral, and transforaminal approaches.

PubMed

Watkins, Robert G; Hanna, Robert; Chang, David; Watkins, Robert G

2014-07-01

Retrospective radiographic analysis. To determine which lumbar interbody technique is most effective for restoring lordosis, increasing disk height, and reducing spondylolisthesis. Lumbar interbody fusions are performed in hopes of increasing fusion potential, correcting deformity, and indirectly decompressing nerve roots. No published study has directly compared anterior, lateral, and transforaminal lumber interbody fusions in terms of ability to restore lordosis, increase disk height, and reduce spondylolisthesis. Lumbar interbody fusion techniques were retrospectively compared in terms of improvement of lordosis, disk height, and spondylolisthesis between preoperative and follow-up lateral radiographs. A total of 220 consecutive patients with 309 operative levels were compared by surgery type: anterior (184 levels), lateral (86 levels), and transforaminal (39 levels). Average follow-up was 19.2 months (range, 1-56 mo), with no statistical difference between the groups. Intragroup analysis showed that the anterior (4.5 degrees) and lateral (2.2 degrees) groups significantly improved lordosis from preoperative to follow-up, whereas the transforaminal (0.8 degrees) group did not. Intergroup analysis showed that the anterior group significantly improved lordosis more than both the lateral and transforaminal groups. The anterior (2.2 mm) and lateral (2.0 mm) groups both significantly improved disk height more than the transforaminal (0.5 mm) group. All 3 groups significantly reduced spondylolisthesis, with no difference between the groups. After lumbar interbody fusion, improvement of lordosis was significant for both the anterior and lateral groups, but not the transforaminal group. Intergroup analysis showed the anterior group had significantly improved lordosis compared to both the other groups. The anterior and lateral groups had significantly increased disk height compared to the transforaminal group. All the 3 groups significantly reduced spondylolisthesis, with no difference between the groups.

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

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.

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

U-Groove aluminum weld strength improvement

NASA Technical Reports Server (NTRS)

Verderaime, V.; Vaughan, R.

1996-01-01

Though butt-welds are among the most preferred joining methods in aerostructures, their strength dependence on inelastic mechanics is generally the least understood. This study investigated experimental strain distributions across a thick aluminum U-grooved weld and identified two weld process considerations for improving the multipass weld strength. The extreme thermal expansion and contraction gradient of the fusion heat input across the groove tab thickness produces severe peaking, which induces bending under uniaxial loading. The filler strain-hardening decreased with increasing filler pass sequence, producing the weakest welds on the last pass side. Current welding schedules unknowingly compound these effects which reduce the weld strength. A depeaking index model was developed to select filler pass thicknesses, pass numbers, and sequences to improve depeaking in the welding process. The intent is to combine the strongest weld pass side with the peaking induced bending tension to provide a more uniform stress and stronger weld under axial tensile loading.

Electron spin resonance study of CuGa1-xMnxSe2 magnetic semiconducting compounds

NASA Astrophysics Data System (ADS)

Fermin, José R.; Nava, Alexander; Durante-Rincón, C. A.; Castro, Jaime; Silva, Pedro J.

2013-02-01

We report on the magnetic properties of the diluted magnetic semiconductor CuGa1-xMnxSe2. For this, Electron spin resonance (ESR) experiments in the temperature range 70 K

Development and Applications of Photo-triggered Theranostic Agents

PubMed Central

Rai, Prakash; Mallidi, Srivallesha; Zheng, Xiang; Rahmanzadeh, Ramtin; Mir, Youssef; Elrington, Stefan; Khurshid, Ahmat; Hasan, Tayyaba

2010-01-01

Theranostics, the fusion of therapy and diagnostics for optimizing efficacy and safety of therapeutic regimes, is a growing field that is paving the way towards the goal of personalized medicine for the benefit of patients. The use of light as a remote-activation mechanism for drug delivery has received increased attention due to its advantages in highly specific spatial and temporal control of compound release. Photo-triggered theranostic constructs could facilitate an entirely new category of clinical solutions which permit early recognition of the disease by enhancing contrast in various imaging modalities followed by the tailored guidance of therapy. Finally, such theranostic agents could aid imaging modalities in monitoring response to therapy. This article reviews recent developments in the use of light-triggered theranostic agents for simultaneous imaging and photoactivation of therapeutic agents. Specifically, we discuss recent developments in the use of theranostic agents for photodynamic-, photothermal- or photo-triggered chemo-therapy for several diseases. PMID:20858520

Theoretical Considerations of the Prigogine-Defay Ration with Regard to the Glass-Forming Ability of Drugs from Undercooled Melts

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

Wyttenbach, Nicole; Kirchmeyer, Wiebke; Alsenz, Jochem

Drug behavior in undercooled melts is highly important for pharmaceutics with regard to amorphous solid dispersions, and therefore, categories were recently introduced that differentiate glass formers (GFs) from other drugs that are nonglass formers (nGFs). The present study is based on the assumption that molecular properties relevant for the so-called Prigogine–Defay (PD) ratio would be indicative of a drug’s glass-forming ability. The PD ratio depends in theory on the entropy of fusion and molar volume. Experimental data were gathered from a broad set of pharmaceutical compounds (n = 54) using differential scanning calorimetry. The obtained entropy of fusion and molarmore » volume were indeed found to significantly discriminate GFs from nGFs. In a next step, the entropy of fusion was predicted by different in silico methods. A first group contribution method provided rather unreliable estimates for the entropy of fusion, while an alternative in silico approach seemed more promising for drug categorization. Thus, a significant discrimination model employed molar volume, a so-called effective hydrogen bond number, and effective number of torsional bonds (or torsional units) to categorize GFs and nGFs (p ≤ 0.0000). The results led to new insights into drug vitrification and to practical rules of thumb. The latter may serve as guidance in pharmaceutical profiling and early formulation development with respect to amorphous drug formulations.« less

Munc13-4 functions as a Ca2+ sensor for homotypic secretory granule fusion to generate endosomal exocytic vacuoles

PubMed Central

Woo, Sang Su; James, Declan J.; Martin, Thomas F. J.

2017-01-01

Munc13-4 is a Ca2+-dependent SNARE (soluble N-ethylmaleimide–sensitive factor attachment protein receptor)- and phospholipid-binding protein that localizes to and primes secretory granules (SGs) for Ca2+-evoked secretion in various secretory cells. Studies in mast cell–like RBL-2H3 cells provide direct evidence that Munc13–4 with its two Ca2+-binding C2 domains functions as a Ca2+ sensor for SG exocytosis. Unexpectedly, Ca2+ stimulation also generated large (>2.4 μm in diameter) Munc13-4+/Rab7+/Rab11+ endosomal vacuoles. Vacuole generation involved the homotypic fusion of Munc13-4+/Rab7+ SGs, followed by a merge with Rab11+ endosomes, and depended on Ca2+ binding to Munc13-4. Munc13-4 promoted the Ca2+-stimulated fusion of VAMP8-containing liposomes with liposomes containing exocytic or endosomal Q-SNAREs and directly interacted with late endosomal SNARE complexes. Thus Munc13-4 is a tethering/priming factor and Ca2+ sensor for both heterotypic SG-plasma membrane and homotypic SG-SG fusion. Total internal reflection fluorescence microscopy imaging revealed that vacuoles were exocytic and mediated secretion of β-hexosaminidase and cytokines accompanied by Munc13-4 diffusion onto the plasma membrane. The results provide new molecular insights into the mechanism of multigranular compound exocytosis commonly observed in various secretory cells. PMID:28100639

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.

Potent peptidic fusion inhibitors of influenza virus

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

Kadam, Rameshwar U.; Juraszek, Jarek; Brandenburg, Boerries

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

Fused cerebral organoids model interactions between brain regions.

PubMed

Bagley, Joshua A; Reumann, Daniel; Bian, Shan; Lévi-Strauss, Julie; Knoblich, Juergen A

2017-07-01

Human brain development involves complex interactions between different regions, including long-distance neuronal migration or formation of major axonal tracts. Different brain regions can be cultured in vitro within 3D cerebral organoids, but the random arrangement of regional identities limits the reliable analysis of complex phenotypes. Here, we describe a coculture method combining brain regions of choice within one organoid tissue. By fusing organoids of dorsal and ventral forebrain identities, we generate a dorsal-ventral axis. Using fluorescent reporters, we demonstrate CXCR4-dependent GABAergic interneuron migration from ventral to dorsal forebrain and describe methodology for time-lapse imaging of human interneuron migration. Our results demonstrate that cerebral organoid fusion cultures can model complex interactions between different brain regions. Combined with reprogramming technology, fusions should offer researchers the possibility to analyze complex neurodevelopmental defects using cells from neurological disease patients and to test potential therapeutic compounds.

Stabilin-2 modulates the efficiency of myoblast fusion during myogenic differentiation and muscle regeneration

PubMed Central

Park, Seung-Yoon; Yun, Youngeun; Lim, Jung-Suk; Kim, Mi-Jin; Kim, Sang-Yeob; Kim, Jung-Eun; Kim, In-San

2016-01-01

Myoblast fusion is essential for the formation of skeletal muscle myofibres. Studies have shown that phosphatidylserine is necessary for myoblast fusion, but the underlying mechanism is not known. Here we show that the phosphatidylserine receptor stabilin-2 acts as a membrane protein for myoblast fusion during myogenic differentiation and muscle regeneration. Stabilin-2 expression is induced during myogenic differentiation, and is regulated by calcineurin/NFAT signalling in myoblasts. Forced expression of stabilin-2 in myoblasts is associated with increased myotube formation, whereas deficiency of stabilin-2 results in the formation of small, thin myotubes. Stab2-deficient mice have myofibres with small cross-sectional area and few myonuclei and impaired muscle regeneration after injury. Importantly, myoblasts lacking stabilin-2 have reduced phosphatidylserine-dependent fusion. Collectively, our results show that stabilin-2 contributes to phosphatidylserine-dependent myoblast fusion and provide new insights into the molecular mechanism by which phosphatidylserine mediates myoblast fusion during muscle growth and regeneration. PMID:26972991

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.

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

Effective World Modeling: Multisensor Data Fusion Methodology for Automated Driving

PubMed Central

Elfring, Jos; Appeldoorn, Rein; van den Dries, Sjoerd; Kwakkernaat, Maurice

2016-01-01

The number of perception sensors on automated vehicles increases due to the increasing number of advanced driver assistance system functions and their increasing complexity. Furthermore, fail-safe systems require redundancy, thereby increasing the number of sensors even further. A one-size-fits-all multisensor data fusion architecture is not realistic due to the enormous diversity in vehicles, sensors and applications. As an alternative, this work presents a methodology that can be used to effectively come up with an implementation to build a consistent model of a vehicle’s surroundings. The methodology is accompanied by a software architecture. This combination minimizes the effort required to update the multisensor data fusion system whenever sensors or applications are added or replaced. A series of real-world experiments involving different sensors and algorithms demonstrates the methodology and the software architecture. PMID:27727171

A Study of Primary Collision Dynamics in Inverse-Kinematics Reaction of 78Kr on 40Ca at a Bombarding Energy of 10 MeV per Nucleon

NASA Astrophysics Data System (ADS)

Henry, Eric M.

The CHIMERA multi-detector array at LNS Catania has been used to study the inverse-kinematics reaction of 78Kr + 40Ca at a bombarding energy of 10 A MeV. The multi-detector is capable of detecting individual products of the collision essential for the reconstruction of the collision dynamics. This is the first time CHIMERA has been used at low-energy, which offered a unique challenge for the calibration and interpretation of experimental data. Initial interrogation of the calibrated data revealed a class of selected events characterized by two coincident heavy fragments (atomic number Z>3) that together account for the majority of the total mass of the colliding system. These events are consistent with the complete fusion and subsequent binary split (fission) of a composite nucleus. The observed fission fragments are characterized by a broad A, Z distribution and are centered about symmetric fission while exhibiting relative velocities significantly higher than given by Viola systematics. Additional analysis of the kinematic relationship between the fission fragments was performed. Of note, is that the center-of-mass angular distribution (dsigma/dtheta) of the fission fragments exhibits an unexpected anisotropy inconsistent with a compound-nucleus reaction. This anisotropy is indicative of a dynamic fusion/fission-like process. The observed angular distribution features a forward-backward anisotropy most prevalent for mass-asymmetric events. Furthermore, the more massive fragment of mass-asymmetric events appears to emerge preferentially in the forward direction, along the beam axis. Analysis of the angular distribution of alpha particles emitted from these fission fragments suggests the events are associated mostly with central collisions. The observations associated with this subset of events are similar to those reported for dynamic fragmentation of projectile-like fragments, but have not before been observed for a fusion/fission-like process. Comparisons to dynamic and statistical reaction model predictions are inconsistent with known phenomena, but suggest a peculiar dynamics-driven scenario. A plausible explanation of the experimental results is the existence of a phenomenon similar to a "fusion window", or a range of impact parameters in which complete fusion cannot be achieved. In this scenario, the system must absorb all the relative motion and convert it to vibrational energy or heat. As the energy increases the system may not be able to accommodate this conversion of energy without breaking apart.

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

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

Corey, Elizabeth A.; Iorio, Ronald M.; Program in Immunology and Virology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655

2009-01-05

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

Pixel-level multisensor image fusion based on matrix completion and robust principal component analysis

NASA Astrophysics Data System (ADS)

Wang, Zhuozheng; Deller, J. R.; Fleet, Blair D.

2016-01-01

Acquired digital images are often corrupted by a lack of camera focus, faulty illumination, or missing data. An algorithm is presented for fusion of multiple corrupted images of a scene using the lifting wavelet transform. The method employs adaptive fusion arithmetic based on matrix completion and self-adaptive regional variance estimation. Characteristics of the wavelet coefficients are used to adaptively select fusion rules. Robust principal component analysis is applied to low-frequency image components, and regional variance estimation is applied to high-frequency components. Experiments reveal that the method is effective for multifocus, visible-light, and infrared image fusion. Compared with traditional algorithms, the new algorithm not only increases the amount of preserved information and clarity but also improves robustness.

Melting curves and entropy of fusion of body-centered cubic tungsten under pressure

NASA Astrophysics Data System (ADS)

Liu, Chun-Mei; Chen, Xiang-Rong; Xu, Chao; Cai, Ling-Cang; Jing, Fu-Qian

2012-07-01

The melting curves and entropy of fusion of body-centered cubic (bcc) tungsten (W) under pressure are investigated via molecular dynamics (MD) simulations with extended Finnis-Sinclair (EFS) potential. The zero pressure melting point obtained is better than other theoretical results by MD simulations with the embedded-atom-method (EAM), Finnis-Sinclair (FS) and modified EAM potentials, and by ab initio MD simulations. Our radial distribution function and running coordination number analyses indicate that apart from the expected increase in disorder, the main change on going from solid to liquid is thus a slight decrease in coordination number. Our entropy of fusion of W during melting, ΔS, at zero pressure, 7.619 J/mol.K, is in good agreement with the experimental and other theoretical data. We found that, with the increasing pressure, the entropy of fusion ΔS decreases fast first and then oscillates with pressure; when the pressure is higher than 100 GPa, the entropy of fusion ΔS is about 6.575 ± 0.086 J/mol.K, which shows less pressure effect.

Translocations in epithelial cancers

PubMed Central

Chad Brenner, J.; Chinnaiyan, Arul M.

2009-01-01

Genomic translocations leading to the expression of chimeric transcripts characterize several hematologic, mesenchymal and epithelial malignancies. While several gene fusions have been linked to essential molecular events in hematologic malignancies, the identification and characterization of recurrent chimeric transcripts in epithelial cancers has been limited. However, the recent discovery of the recurrent gene fusions in prostate cancer has sparked a revitalization of the quest to identify novel rearrangements in epithelial malignancies. Here, the molecular mechanisms of gene fusions that drive several epithelial cancers and the recent technological advances that increase the speed and reliability of recurrent gene fusion discovery are explored. PMID:19406209

Effects of interval between fusion and activation, cytochalasin B treatment, and number of transferred embryos, on cloning efficiency in goats.

PubMed

Liu, J; Li, L L; Du, S; Bai, X Y; Zhang, H D; Tang, S; Zhao, M T; Ma, B H; Quan, F S; Zhao, X E; Zhang, Y

2011-10-01

To improve the efficiency of somatic cell nuclear transfer (SCNT) in goats, we evaluated the effects of the interval between fusion and activation (1 to 5 h), cytochalasin B (CB) treatment after electrofusion, and the number of transferred embryos on the in vivo and in vitro development of cloned caprine embryos. The majority of the reconstructed embryos had condensed chromosomes and metaphase-like chromosomes at 2 and 3 h after fusion; cleavage and blastocyst rates from those two groups were higher (P < 0.05) than those of embryos activated 1, 4, or 5 h after fusion. Treatment with CB between fusion and activation improved in vitro and in vivo development of nuclear transfer (NT) goat embryos by reducing the fragmentation rate (P < 0.05). Although there were no significant differences in NT efficiency, pregnancy rate and kids born per recipient were increased by transfer of 20 or 30 embryos per recipient compared with 10 embryos. We concluded that CB treatment for 2 to 3 h between fusion and activation was an efficient method for generating cloned goats by somatic cell NT. In addition, increasing the number of embryos transferred to each recipient resulted in more live offspring from fewer recipients. Copyright © 2011 Elsevier Inc. All rights reserved.

Effect of Interbody Fusion on the Remaining Discs of the Lumbar Spine in Subjects with Disc Degeneration.

PubMed

Ryu, Robert; Techy, Fernando; Varadarajan, Ravikumar; Amirouche, Farid

2016-02-01

To study effects (stress loads) of lumbar fusion on the remaining segments (adjacent or not) of the lumbar spine in the setting of degenerated adjacent discs. A lumbar spine finite element model was built and validated. The full model of the lumbar spine was a parametric finite element model of segments L 1-5 . Numerous hypothetical combinations of one-level lumbar spine fusion and one-level disc degeneration were created. These models were subjected to 10 Nm flexion and extension moments and the stresses on the endplates and consequently on the intervertebral lumbar discs measured. These values were compared to the stresses on healthy lumbar spine discs under the same load and fusion scenarios. Increased stress at endplates was observed only in the settings of L4-5 fusion and L3-4 disc degeneration (8% stress elevation at L2,3 in flexion or extension, and 25% elevation at L3,4 in flexion only). All other combinations showed less endplate stress than did the control model. For fusion at L3-4 and degeneration at L4-5 , the stresses in the endplates at the adjacent level inferior to the fused disc decreased for both loading disc height reductions. Stresses in flexion decreased after fusion by 29.5% and 25.8% for degeneration I and II, respectively. Results for extension were similar. For fusion at L2-3 and degeneration at L4-5 , stresses in the endplates decreased more markedly at the degenerated (30%), than at the fused level (14%) in the presence of 25% disc height reduction and 10 Nm flexion, whereas in extension stresses decreased more at the fused (24.3%) than the degenerated level (5.86%). For fusion at L3-4 and degeneration at L2-3 , there were no increases in endplate stress in any scenario. For fusion at L4-5 and degeneration at L3-4 , progression of degeneration from I to II had a significant effect only in flexion. A dramatic increase in stress was noted in the endplates of the degenerated disc (L3-4 ) in flexion for degeneration II. Stresses are greater in flexion at the endplates of L3-4 and in flexion and extension at L2-3 in the presence of L3-4 disc disease and L4-5 fusion than in the control group. In all other combinations of fusion and disc disease, endplate stress was less for all levels tested than in the control model. © 2016 Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.

P20A inhibits HIV-1 fusion through its electrostatic interaction with the distal region of the gp41 fusion core.

PubMed

Fu, Shushu; Tong, Pei; Tan, Yue; Zhu, Yun; Chen, Ying-Hua

2015-09-01

We previously identified an HIV-1 fusion inhibitor P20A targeting HIV-1 gp41 6-HB fusion core. Using alanine scanning mutagenesis, we investigated the effect of 6-HB surface residue mutations on the binding affinity between P20A and 6-HB. Substitution of positively or negatively charged residues in the distal region of 6-HB with alanines resulted in significant decrease or increase of its binding affinity to P20A, respectively. The 6-HB with E630K, D632K, or E634K mutation exhibited enhanced binding affinity with P20A, suggesting that P20A blocks HIV-1 fusion through electrostatic interaction with the positively charged residues in the distal region of the gp41 fusion core. Copyright © 2015 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Annexin A2-S100A10 heterotetramer is upregulated by PML/RARα fusion protein and promotes plasminogen-dependent fibrinolysis and matrix invasion in acute promyelocytic leukemia.

PubMed

Huang, Dan; Yang, Yan; Sun, Jian; Dong, Xiaorong; Wang, Jiao; Liu, Hongchen; Lu, Chengquan; Chen, Xueyu; Shao, Jing; Yan, Jinsong

2017-09-01

Aberrant expression of annexin A2-S100A10 heterotetramer (AIIt) associated with PML/RARα fusion protein causes lethal hyperfibrinolysis in acute promyelocytic leukemia (APL), but the mechanism is unclear. To facilitate the investigation of regulatory association between ANXA2 and promyelocytic leukemia/retinoic acid receptor a (PML/RARα) fusion protein, this work was performed to determine the transcription start site of ANXA2 promoter with rapid amplification of 5'-cDNA ends analysis. Zinc-induced U937/PR9 cells expressed PML/RARα fusion protein, and resultant increases in ANXA2 transcripts and translational expressions of both ANXA2 and S100A10, while S100A10 transcripts remained constitutive. The transactivation of ANXA2 promoter by PML/RARα fusion protein was 3.29 ± 0.13 fold higher than that by control pSG5 vector or wild-type RARα. The overexpression of ANXA2 in U937 transfected with full-length ANXA2 cDNA was associated with increased S100A10 subunit, although S100A10 transcripts remained constitutive. The tPA-dependent initial rate of plasmin generation (IRPG) in zinc-treated U937/PR9 increased by 2.13-fold, and cell invasiveness increased by 27.6%. Antibodies against ANXA2, S100A10, or combination of both all remarkably inhibited the IRPG and invasiveness in U937/PR9 and NB4. Treatment of zinc-induced U937/PR9 or circulating APL blasts with all-trans retinoic acid (ATRA) significantly reduced cell surface ANXA2 and S100A10 and associated reductions in IRPG and invasiveness. Thus, PML/RARα fusion protein transactivated the ANXA2 promoter to upregulate ANXA2 and accumulate S100A10. Increased AIIt promoted IRPG and invasiveness, both of which were partly abolished by antibodies against ANXA2 and S100A10 or by ATRA.

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

PubMed

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

2002-12-01

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

Methods of increasing secretion of polypeptides having biological activity

DOEpatents

Merino, Sandra

2014-05-27

The present invention relates to methods for producing a secreted polypeptide having biological activity, comprising: (a) transforming a fungal host cell with a fusion protein construct encoding a fusion protein, which comprises: (i) a first polynucleotide encoding a signal peptide; (ii) a second polynucleotide encoding at least a catalytic domain of an endoglucanase or a portion thereof; and (iii) a third polynucleotide encoding at least a catalytic domain of a polypeptide having biological activity; wherein the signal peptide and at least the catalytic domain of the endoglucanase increases secretion of the polypeptide having biological activity compared to the absence of at least the catalytic domain of the endoglucanase; (b) cultivating the transformed fungal host cell under conditions suitable for production of the fusion protein; and (c) recovering the fusion protein, a component thereof, or a combination thereof, having biological activity, from the cultivation medium.

Methods of increasing secretion of polypeptides having biological activity

DOEpatents

Merino, Sandra

2014-10-28

The present invention relates to methods for producing a secreted polypeptide having biological activity, comprising: (a) transforming a fungal host cell with a fusion protein construct encoding a fusion protein, which comprises: (i) a first polynucleotide encoding a signal peptide; (ii) a second polynucleotide encoding at least a catalytic domain of an endoglucanase or a portion thereof; and (iii) a third polynucleotide encoding at least a catalytic domain of a polypeptide having biological activity; wherein the signal peptide and at least the catalytic domain of the endoglucanase increases secretion of the polypeptide having biological activity compared to the absence of at least the catalytic domain of the endoglucanase; (b) cultivating the transformed fungal host cell under conditions suitable for production of the fusion protein; and (c) recovering the fusion protein, a component thereof, or a combination thereof, having biological activity, from the cultivation medium.

Methods of increasing secretion of polypeptides having biological activity

DOEpatents

Merino, Sandra

2015-04-14

The present invention relates to methods for producing a secreted polypeptide having biological activity, comprising: (a) transforming a fungal host cell with a fusion protein construct encoding a fusion protein, which comprises: (i) a first polynucleotide encoding a signal peptide; (ii) a second polynucleotide encoding at least a catalytic domain of an endoglucanase or a portion thereof; and (iii) a third polynucleotide encoding at least a catalytic domain of a polypeptide having biological activity; wherein the signal peptide and at least the catalytic domain of the endoglucanase increases secretion of the polypeptide having biological activity compared to the absence of at least the catalytic domain of the endoglucanase; (b) cultivating the transformed fungal host cell under conditions suitable for production of the fusion protein; and (c) recovering the fusion protein, a component thereof, or a combination thereof, having biological activity, from the cultivation medium.

Methods of increasing secretion of polypeptides having biological activity

DOEpatents

Merino, Sandra

2013-10-01

The present invention relates to methods for producing a secreted polypeptide having biological activity, comprising: (a) transforming a fungal host cell with a fusion protein construct encoding a fusion protein, which comprises: (i) a first polynucleotide encoding a signal peptide; (ii) a second polynucleotide encoding at least a catalytic domain of an endoglucanase or a portion thereof; and (iii) a third polynucleotide encoding at least a catalytic domain of a polypeptide having biological activity; wherein the signal peptide and at least the catalytic domain of the endoglucanase increases secretion of the polypeptide having biological activity compared to the absence of at least the catalytic domain of the endoglucanase; (b) cultivating the transformed fungal host cell under conditions suitable for production of the fusion protein; and (c) recovering the fusion protein, a component thereof, or a combination thereof, having biological activity, from the cultivation medium.

CED-9 and mitochondrial homeostasis in C. elegans muscle

PubMed Central

Tan, Frederick J.; Husain, Michelle; Manlandro, Cara Marie; Koppenol, Marijke; Fire, Andrew Z.; Hill, R. Blake

2009-01-01

Summary Mitochondrial homeostasis reflects a dynamic balance between membrane fission and fusion events thought essential for mitochondrial function. We report here that altered expression of the C. elegans BCL2 homolog CED-9 affects both mitochondrial fission and fusion. Although striated muscle cells lacking CED-9 have no alteration in mitochondrial size or ultrastructure, these cells appear more sensitive to mitochondrial fragmentation. By contrast, increased CED-9 expression in these cells produces highly interconnected mitochondria. This mitochondrial phenotype is partially suppressed by increased expression of the dynamin-related GTPase DRP-1, with suppression dependent on the BH3 binding pocket of CED-9. This suppression suggests that CED-9 directly regulates DRP-1, a model supported by our finding that CED-9 activates the GTPase activity of human DRP1. Thus, CED-9 is capable of regulating the mitochondrial fission-fusion cycle but is not essential for either fission or fusion. PMID:18827010

Fusion neutron irradiation of Ni-Si alloys at high temperature*1

NASA Astrophysics Data System (ADS)

Huang, J. S.; Guinan, M. W.; Hahn, P. A.

1988-07-01

Two Ni-4% Si alloys, with different cold work levels, have been irradiated with 14-MeV fusion neutrons at 623 K, and their Curie temperatures have been monitored during irradiation. The results are compared to those of an identical alloy irradiated by 2-MeV electrons. The results show that increasing dislocation density increases the Curie temperature change rate. At the same damage rate, the Curie temperature change rate for the alloy irradiated by 14-MeV fusion neutrons is only 6-7% of that for an identical alloy irradiated by 2-MeV electrons. It is well known that the migration of radiation induced defects contributes to segregation of silicon atoms at sinks in this alloy, causing the Curie temperature changes. The current results imply that the relative free defect production efficiency decreases from one for the electron irradiated sample to 6-7% for the fusion neutron irradiated sample.

Detection of antistaphylococcal and toxic compounds by biological assay systems developed with a reporter Staphylococcus aureus strain harboring a heat inducible promoter - lacZ transcriptional fusion.

PubMed

Chanda, Palas Kumar; Ganguly, Tridib; Das, Malabika; Lee, Chia Yen; Luong, Thanh T; Sau, Subrata

2007-11-30

Previously it was reported that promoter of groES-groEL operon of Staphylococcus aureus is induced by various cell-wall active antibiotics. In order to exploit the above promoter for identifying novel antistaphylococcal drugs, we have cloned the promoter containing region (P(g)) of groES-groEL operon of S. aureus Newman and found that the above promoter is induced by sublethal concentrations of many antibiotics including cell-wall active antibiotics. A reporter S. aureus RN4220 strain (designated SAU006) was constructed by inserting the P(g)-lacZ transcriptional fusion into its chromosome. Agarose-based assay developed with SAU006 shows that P(g) in single-copy is also induced distinctly by different classes of antibiotics. Data indicate that ciprofloxacin, rifampicin, ampicillin, and cephalothin are strong inducers, whereas, tetracycline, streptomycin and vancomycin induce the above promoter weakly. Sublethal concentrations of ciprofloxacin and ampicilin even have induced P(g) efficiently in microtiter plate grown SAU006. Additional studies show for the first time that above promoter is also induced weakly by arsenate salt and hydrogen peroxide. Taken together, we suggest that our simple and sensitive assay systems with SAU006 could be utilized for screening and detecting not only novel antistaphylococcal compounds but also different toxic chemicals.

EARLY ONSET OF CRANIOSYNOSTOSIS IN AN APERT MOUSE MODEL REVEALS CRITICAL FEATURES OF THIS PATHOLOGY

PubMed Central

Holmes, Greg; Rothschild, Gerson; Roy, Upal Basu; Deng, Chu-Xia; Mansukhani, Alka; Basilico, Claudio

2009-01-01

Activating mutations of FGFRs1–3 cause craniosynostosis (CS), the premature fusion of cranial bones, in man and mouse. The mechanisms by which such mutations lead to CS have been variously ascribed to increased osteoblast proliferation, differentiation, and apoptosis, but it is not always clear how these disturbances relate to the process of suture fusion. We have reassessed coronal suture fusion in an Apert Fgfr2 (S252W) mouse model. We find that the critical event of CS is the early loss of basal sutural mesenchyme as the osteogenic fronts, expressing activated Fgfr2, unite to form a contiguous skeletogenic membrane. A mild increase in osteoprogenitor proliferation precedes but does not accompany this event, and apoptosis is insignificant. On the other hand, the more apical coronal suture initially forms appropriately but then undergoes fusion, albeit at a slower rate, accompanied by a significant decrease in osteoprogenitor proliferation, and increased osteoblast maturation. Apoptosis now accompanies fusion, but is restricted to bone fronts in contact with one another. We correlated these in vivo observations with the intrinsic effects of the activated Fgfr2 S252W mutation in primary osteoblasts in culture, which show an increased capacity for both proliferation and differentiation. Our studies suggest that the major determinant of Fgfr2-induced craniosynostosis is the failure to respond to signals that would halt the recruitment or the advancement of osteoprogenitor cells at the sites where sutures should normally form. PMID:19389359

Binaural fusion and listening effort in children who use bilateral cochlear implants: a psychoacoustic and pupillometric study.

PubMed

Steel, Morrison M; Papsin, Blake C; Gordon, Karen A

2015-01-01

Bilateral cochlear implants aim to provide hearing to both ears for children who are deaf and promote binaural/spatial hearing. Benefits are limited by mismatched devices and unilaterally-driven development which could compromise the normal integration of left and right ear input. We thus asked whether children hear a fused image (ie. 1 vs 2 sounds) from their bilateral implants and if this "binaural fusion" reduces listening effort. Binaural fusion was assessed by asking 25 deaf children with cochlear implants and 24 peers with normal hearing whether they heard one or two sounds when listening to bilaterally presented acoustic click-trains/electric pulses (250 Hz trains of 36 ms presented at 1 Hz). Reaction times and pupillary changes were recorded simultaneously to measure listening effort. Bilaterally implanted children heard one image of bilateral input less frequently than normal hearing peers, particularly when intensity levels on each side were balanced. Binaural fusion declined as brainstem asymmetries increased and age at implantation decreased. Children implanted later had access to acoustic input prior to implantation due to progressive deterioration of hearing. Increases in both pupil diameter and reaction time occurred as perception of binaural fusion decreased. Results indicate that, without binaural level cues, children have difficulty fusing input from their bilateral implants to perceive one sound which costs them increased listening effort. Brainstem asymmetries exacerbate this issue. By contrast, later implantation, reflecting longer access to bilateral acoustic hearing, may have supported development of auditory pathways underlying binaural fusion. Improved integration of bilateral cochlear implant signals for children is required to improve their binaural hearing.

Fusion imaging of contrast-enhanced ultrasound and contrast-enhanced CT or MRI before radiofrequency ablation for liver cancers.

PubMed

Bo, Xiao-Wan; Xu, Hui-Xiong; Wang, Dan; Guo, Le-Hang; Sun, Li-Ping; Li, Xiao-Long; Zhao, Chong-Ke; He, Ya-Ping; Liu, Bo-Ji; Li, Dan-Dan; Zhang, Kun

2016-11-01

To investigate the usefulness of fusion imaging of contrast-enhanced ultrasound (CEUS) and CECT/CEMRI before percutaneous ultrasound-guided radiofrequency ablation (RFA) for liver cancers. 45 consecutive patients with 70 liver lesions were included between March 2013 and October 2015, and all the lesions were identified on CEMRI/CECT prior to inclusion in the study. Planning ultrasound for percutaneous RFA was performed using conventional ultrasound, ultrasound-CECT/CEMRI and CEUS and CECT/CEMRI fusion imaging during the same session. The numbers of the conspicuous lesions on ultrasound and fusion imaging were recorded. RFA was performed according to the results of fusion imaging. Complete response (CR) rate was calculated and the complications were recorded. On conventional ultrasound, 25 (35.7%) of the 70 lesions were conspicuous, whereas 45 (64.3%) were inconspicuous. Ultrasound-CECT/CEMRI fusion imaging detected additional 24 lesions thus increased the number of the conspicuous lesions to 49 (70.0%) (70.0% vs 35.7%; p < 0.001 in comparison with conventional ultrasound). With the use of CEUS and CECT/CEMRI fusion imaging, the number of the conspicuous lesions further increased to 67 (95.7%, 67/70) (95.7% vs 70.0%, 95.7% vs 35.7%; both p < 0.001 in comparison with ultrasound and ultrasound-CECT/CEMRI fusion imaging, respectively). With the assistance of CEUS and CECT/CEMRI fusion imaging, the confidence level of the operator for performing RFA improved significantly with regard to visualization of the target lesions (p = 0.001). The CR rate for RFA was 97.0% (64/66) in accordance to the CECT/CEMRI results 1 month later. No procedure-related deaths and major complications occurred during and after RFA. Fusion of CEUS and CECT/CEMRI improves the visualization of those inconspicuous lesions on conventional ultrasound. It also facilitates improvement in the RFA operators' confidence and CR of RFA. Advances in knowledge: CEUS and CECT/CEMRI fusion imaging is better than both conventional ultrasound and ultrasound-CECT/CEMRI fusion imaging for lesion visualization and improves the operator confidence, thus it should be recommended to be used as a routine in ultrasound-guided percutaneous RFA procedures for liver cancer.

Fusion imaging of contrast-enhanced ultrasound and contrast-enhanced CT or MRI before radiofrequency ablation for liver cancers

PubMed Central

Bo, Xiao-Wan; Wang, Dan; Guo, Le-Hang; Sun, Li-Ping; Li, Xiao-Long; Zhao, Chong-Ke; He, Ya-Ping; Liu, Bo-Ji; Li, Dan-Dan; Zhang, Kun

2016-01-01

Objective: To investigate the usefulness of fusion imaging of contrast-enhanced ultrasound (CEUS) and CECT/CEMRI before percutaneous ultrasound-guided radiofrequency ablation (RFA) for liver cancers. Methods: 45 consecutive patients with 70 liver lesions were included between March 2013 and October 2015, and all the lesions were identified on CEMRI/CECT prior to inclusion in the study. Planning ultrasound for percutaneous RFA was performed using conventional ultrasound, ultrasound-CECT/CEMRI and CEUS and CECT/CEMRI fusion imaging during the same session. The numbers of the conspicuous lesions on ultrasound and fusion imaging were recorded. RFA was performed according to the results of fusion imaging. Complete response (CR) rate was calculated and the complications were recorded. Results: On conventional ultrasound, 25 (35.7%) of the 70 lesions were conspicuous, whereas 45 (64.3%) were inconspicuous. Ultrasound-CECT/CEMRI fusion imaging detected additional 24 lesions thus increased the number of the conspicuous lesions to 49 (70.0%) (70.0% vs 35.7%; p < 0.001 in comparison with conventional ultrasound). With the use of CEUS and CECT/CEMRI fusion imaging, the number of the conspicuous lesions further increased to 67 (95.7%, 67/70) (95.7% vs 70.0%, 95.7% vs 35.7%; both p < 0.001 in comparison with ultrasound and ultrasound-CECT/CEMRI fusion imaging, respectively). With the assistance of CEUS and CECT/CEMRI fusion imaging, the confidence level of the operator for performing RFA improved significantly with regard to visualization of the target lesions (p = 0.001). The CR rate for RFA was 97.0% (64/66) in accordance to the CECT/CEMRI results 1 month later. No procedure-related deaths and major complications occurred during and after RFA. Conclusion: Fusion of CEUS and CECT/CEMRI improves the visualization of those inconspicuous lesions on conventional ultrasound. It also facilitates improvement in the RFA operators' confidence and CR of RFA. Advances in knowledge: CEUS and CECT/CEMRI fusion imaging is better than both conventional ultrasound and ultrasound-CECT/CEMRI fusion imaging for lesion visualization and improves the operator confidence, thus it should be recommended to be used as a routine in ultrasound-guided percutaneous RFA procedures for liver cancer. PMID:27626506

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.

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

Fusion tags for protein solubility, purification and immunogenicity in Escherichia coli: the novel Fh8 system

PubMed Central

Costa, Sofia; Almeida, André; Castro, António; Domingues, Lucília

2014-01-01

Proteins are now widely produced in diverse microbial cell factories. The Escherichia coli is still the dominant host for recombinant protein production but, as a bacterial cell, it also has its issues: the aggregation of foreign proteins into insoluble inclusion bodies is perhaps the main limiting factor of the E. coli expression system. Conversely, E. coli benefits of cost, ease of use and scale make it essential to design new approaches directed for improved recombinant protein production in this host cell. With the aid of genetic and protein engineering novel tailored-made strategies can be designed to suit user or process requirements. Gene fusion technology has been widely used for the improvement of soluble protein production and/or purification in E. coli, and for increasing peptide’s immunogenicity as well. New fusion partners are constantly emerging and complementing the traditional solutions, as for instance, the Fh8 fusion tag that has been recently studied and ranked among the best solubility enhancer partners. In this review, we provide an overview of current strategies to improve recombinant protein production in E. coli, including the key factors for successful protein production, highlighting soluble protein production, and a comprehensive summary of the latest available and traditionally used gene fusion technologies. A special emphasis is given to the recently discovered Fh8 fusion system that can be used for soluble protein production, purification, and immunogenicity in E. coli. The number of existing fusion tags will probably increase in the next few years, and efforts should be taken to better understand how fusion tags act in E. coli. This knowledge will undoubtedly drive the development of new tailored-made tools for protein production in this bacterial system. PMID:24600443

Histology, fusion status, and outcome in metastatic rhabdomyosarcoma: A report from the Children's Oncology Group.

PubMed

Rudzinski, Erin R; Anderson, James R; Chi, Yueh-Yun; Gastier-Foster, Julie M; Astbury, Caroline; Barr, Frederic G; Skapek, Stephen X; Hawkins, Douglas S; Weigel, Brenda J; Pappo, Alberto; Meyer, William H; Arnold, Michael A; Teot, Lisa A; Parham, David M

2017-12-01

Distinguishing alveolar rhabdomyosarcoma (ARMS) from embryonal rhabdomyosarcoma (ERMS) has historically been of prognostic and therapeutic importance. However, classification has been complicated by shifting histologic criteria required for an ARMS diagnosis. Children's Oncology Group (COG) studies after IRS-IV, which included the height of this diagnostic shift, showed both an increased number of ARMS and an increase in the proportion of fusion-negative ARMS. Following diagnostic standardization and histologic re-review of ARMS cases enrolled during this era, analysis of low-risk (D9602) and intermediate-risk (D9803) rhabdomyosarcoma (RMS) studies showed that fusion status rather than histology best predicts prognosis for patients with RMS. This analysis remains to be completed for patients with high-risk RMS. We re-reviewed cases on high-risk COG studies D9802 and ARST0431 with an enrollment diagnosis of ARMS. We compared the event-free survival (EFS) and overall survival by histology, PAX-FOXO1 fusion, and clinical risk factors (Oberlin score) for patients with metastatic RMS using the log-rank test. Histology re-review resulted in reclassification as ERMS for 12% of D9802 cases and 5% of ARST0431 cases. Fusion-negative RMS had a superior EFS to fusion-positive RMS; however, poorer outcome for metastatic RMS was most related to clinical risk factors including age, primary site, and number of metastatic sites. In contrast to low- or intermediate-risk RMS, in metastatic RMS, clinical risk factors have the most impact on patient outcome. PAX-FOXO1 fusion is more common in patients with a high Oberlin score, but fusion status is not an independent biomarker of prognosis. © 2017 Wiley Periodicals, Inc.

Skyrme forces and decay of the Rf266*104 nucleus synthesized via different incoming channels

NASA Astrophysics Data System (ADS)

Niyti, Deep, Aman; Kharab, Rajesh; Chopra, Sahila; Gupta, Raj K.

2017-03-01

The excitation functions for the production of 262Rf, 261Rf, and 260Rf isotopes via 4 n -, 5 n -, and 6 n -decay channels from the *266Rf compound nucleus are studied within the dynamical cluster-decay model (DCM), including deformations β2 i and so-called hot-optimum orientations θi which support symmetric fission, in agreement with experiments. The data are available for 18O+248Cm and 22Ne+244Pu reactions, respectively, at the energy ranges of Elab=88.2 to 101.3 and 109.0 to 124.8 MeV. For the nuclear interaction potentials, we use the Skyrme energy density functional (SEDF) based on semiclassical extended Thomas Fermi (ETF) approach, which means an extension of the earlier study of excitation functions of *266Rf formed in 18O+248Cm reaction, based on the DCM using the pocket formula for nuclear proximity potential, showing interaction dependence. The Skyrme forces used here are the old SIII and SIV and new GSkI and KDE0(v1) given for both normal and isospin-rich nuclei, with densities added in frozen density approximation. Interestingly, the DCM gives an excellent fit to the measured data on fusion evaporation residue (ER) for both the incoming channels (18O+248Cm and 22Ne+244Pu ) at the energy range Elab=88.2 to 124.8 MeV, independent of the entrance channel and Skyrme force used. The possible fusion-fission (ff) and quasifission (qf) mass regions of fragments on DCM are also predicted. The DCM with Skyrme forces is further used to look for all the possible target-projectile (t-p) combinations forming the cold compound nucleus (CN) *266Rf at the CN excitation energy of Elab for hot compact configurations. The fusion evaporation residue cross sections, for the proposed new reactions in synthesizing the CN *266Rf, are also estimated for the future experiments, and role of mass asymmetry of nuclei is indicated.

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.

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.

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

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.

Effects of magnetization on fusion product trapping and secondary neutron spectraa)

NASA Astrophysics Data System (ADS)

Knapp, P. F.; Schmit, P. F.; Hansen, S. B.; Gomez, M. R.; Hahn, K. D.; Sinars, D. B.; Peterson, K. J.; Slutz, S. A.; Sefkow, A. B.; Awe, T. J.; Harding, E.; Jennings, C. A.; Desjarlais, M. P.; Chandler, G. A.; Cooper, G. W.; Cuneo, M. E.; Geissel, M.; Harvey-Thompson, A. J.; Porter, J. L.; Rochau, G. A.; Rovang, D. C.; Ruiz, C. L.; Savage, M. E.; Smith, I. C.; Stygar, W. A.; Herrmann, M. C.

2015-05-01

By magnetizing the fusion fuel in inertial confinement fusion (ICF) systems, the required stagnation pressure and density can be relaxed dramatically. This happens because the magnetic field insulates the hot fuel from the cold pusher and traps the charged fusion burn products. This trapping allows the burn products to deposit their energy in the fuel, facilitating plasma self-heating. Here, we report on a comprehensive theory of this trapping in a cylindrical DD plasma magnetized with a purely axial magnetic field. Using this theory, we are able to show that the secondary fusion reactions can be used to infer the magnetic field-radius product, BR, during fusion burn. This parameter, not ρR, is the primary confinement parameter in magnetized ICF. Using this method, we analyze data from recent Magnetized Liner Inertial Fusion experiments conducted on the Z machine at Sandia National Laboratories. We show that in these experiments BR ≈ 0.34(+0.14/-0.06) MG . cm, a ˜ 14× increase in BR from the initial value, and confirming that the DD-fusion tritons are magnetized at stagnation. This is the first experimental verification of charged burn product magnetization facilitated by compression of an initial seed magnetic flux.

SARS-CoV fusion peptides induce membrane surface ordering and curvature.

PubMed

Basso, Luis G M; Vicente, Eduardo F; Crusca, Edson; Cilli, Eduardo M; Costa-Filho, Antonio J

2016-11-28

Viral membrane fusion is an orchestrated process triggered by membrane-anchored viral fusion glycoproteins. The S2 subunit of the spike glycoprotein from severe acute respiratory syndrome (SARS) coronavirus (CoV) contains internal domains called fusion peptides (FP) that play essential roles in virus entry. Although membrane fusion has been broadly studied, there are still major gaps in the molecular details of lipid rearrangements in the bilayer during fusion peptide-membrane interactions. Here we employed differential scanning calorimetry (DSC) and electron spin resonance (ESR) to gather information on the membrane fusion mechanism promoted by two putative SARS FPs. DSC data showed the peptides strongly perturb the structural integrity of anionic vesicles and support the hypothesis that the peptides generate opposing curvature stresses on phosphatidylethanolamine membranes. ESR showed that both FPs increase lipid packing and head group ordering as well as reduce the intramembrane water content for anionic membranes. Therefore, bending moment in the bilayer could be generated, promoting negative curvature. The significance of the ordering effect, membrane dehydration, changes in the curvature properties and the possible role of negatively charged phospholipids in helping to overcome the high kinetic barrier involved in the different stages of the SARS-CoV-mediated membrane fusion are discussed.

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.

Effect of age on the perioperative and radiographic complications of multilevel cervicothoracic spinal fusions.

PubMed

Cloyd, Jordan M; Acosta, Frank L; Ames, Christopher P

2008-12-15

Retrospective review. To investigate the effect of age on the perioperative and radiographic complications associated with multilevel (>or=5) fusion of the cervicothoracic spine. Although the elderly comprise a substantial proportion of patients presenting with complex spinal pathology necessitating multilevel procedures across the cervical and cervicothoracic spine, the risk of perioperative and radiographic complications after these procedures is unknown. Between 2000 and 2007, 58 patients 65 years of age or older at a single institution underwent instrumented cervicothoracic spinal fusion of at least 5 levels. Fifty-eight patients under the age of 65 from the same time period served as a control group. A retrospective review of all hospital records, operative reports, radiographs, and clinic notes was conducted. Complications were classified as intraoperative, major and minor postoperative, and need for revision surgery. Flexion-extension radiographs were examined at discharge, 1.5, 6, 12 months, and then yearly, thereafter to evaluate fusion status and instrumentation-related complications. Principal diagnoses included spondylostenosis, malignancy, vertebral fracture, and osteomyelitis. Both groups were similar in number of levels fused (elderly, 6.7 +/- 2.1; control, 6.3 +/- 1.7) and circumferential procedures (27 vs. 28), respectively. There were no significant differences in operative time, blood loss, or length of hospital stay. Rates of intraoperative (5.2% vs. 3.4%), major (20.7% vs. 17.2%) and minor postoperative complications (27.6% vs. 22.4%), and reoperation (8.6% vs. 8.6%) were similar between the 2 groups. Utilization of a combined anterior-posterior fusion was associated with increased perioperative complications in the elderly on univariate but not multivariate analyses. Radiographic evidence of fusion was also comparable between the 2 groups. Perioperative complication rates of multilevel (>or=5) cervicothoracic spinal fusion in the elderly are high but not significantly different from those of younger patients. The use of a circumferential fusion procedure may increase the risk of a perioperative complication in older patients. Fusion rates are similar between the 2 groups.

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

Dahlburg, Jill; Corones, James; Batchelor, Donald

Fusion is potentially an inexhaustible energy source whose exploitation requires a basic understanding of high-temperature plasmas. The development of a science-based predictive capability for fusion-relevant plasmas is a challenge central to fusion energy science, in which numerical modeling has played a vital role for more than four decades. A combination of the very wide range in temporal and spatial scales, extreme anisotropy, the importance of geometric detail, and the requirement of causality which makes it impossible to parallelize over time, makes this problem one of the most challenging in computational physics. Sophisticated computational models are under development for many individualmore » features of magnetically confined plasmas and increases in the scope and reliability of feasible simulations have been enabled by increased scientific understanding and improvements in computer technology. However, full predictive modeling of fusion plasmas will require qualitative improvements and innovations to enable cross coupling of a wider variety of physical processes and to allow solution over a larger range of space and time scales. The exponential growth of computer speed, coupled with the high cost of large-scale experimental facilities, makes an integrated fusion simulation initiative a timely and cost-effective opportunity. Worldwide progress in laboratory fusion experiments provides the basis for a recent FESAC recommendation to proceed with a burning plasma experiment (see FESAC Review of Burning Plasma Physics Report, September 2001). Such an experiment, at the frontier of the physics of complex systems, would be a huge step in establishing the potential of magnetic fusion energy to contribute to the world’s energy security. An integrated simulation capability would dramatically enhance the utilization of such a facility and lead to optimization of toroidal fusion plasmas in general. This science-based predictive capability, which was cited in the FESAC integrated planning document (IPPA, 2000), represents a significant opportunity for the DOE Office of Science to further the understanding of fusion plasmas to a level unparalleled worldwide.« less

Cell fusion contributes to the rescue of apoptotic cardiomyocytes by bone marrow cells

PubMed Central

Yang, Wei-Jian; Li, Shu-Hong; Weisel, Richard D; Liu, Shi-Ming; Li, Ren-Ke

2012-01-01

Cardiomyocyte apoptosis is an important contributor to the progressive cardiac dysfunction that culminates in congestive heart failure. Bone marrow cells (BMCs) restore cardiac function following ischaemia, and transplanted BMCs have been reported to fuse with cells of diverse tissues. We previously demonstrated that the myogenic conversion of bone marrow stromal cells increased nearly twofold when the cells were co-cultured with apoptotic (TNF-α treated) cardiomyocytes. We therefore hypothesized that cell fusion may be a major mechanism by which BMCs rescue cardiomyocytes from apoptosis. We induced cellular apoptosis in neonatal rat cardiomyocytes by treatment with hydrogen peroxide (H2O2). The TUNEL assay demonstrated an increase in apoptosis from 4.5 ± 1.3% in non-treated cells to 19.0 ± 4.4% (P < 0.05) in treated cells. We subsequently co-cultured the apoptotic cardiomyocytes with BMCs and assessed cell fusion using flow cytometry. Fusion was rare in the non-treated control cardiomyocytes (0.3%), whereas H2O2 treatment led to significantly higher fusion rates than the control group (P < 0.05), with the highest rate of 7.9 ± 0.3% occurring at 25 μM H2O2. We found an inverse correlation between cell fusion and completion of cardiomyocyte apoptosis (R2 = 0.9863). An in vivo mouse model provided evidence of cell fusion in the infarcted myocardium following the injection of BMCs. The percentage of cells undergoing fusion was significantly higher in mice injected with BMCs following infarction (8.8 ± 1.3%) compared to mice that did not undergo infarction (4.6 ± 0.6%, P < 0.05). Enhancing cell fusion may be one method to preserve cardiomyocytes following myocardial infarction, and this new approach may provide a novel target for cardiac regenerative therapies. PMID:22805279

Targeting RSV with Vaccines and Small Molecule Drugs

PubMed Central

Costello, Heather M.; Ray, William C.; Chaiwatpongsakorn, Supranee; Peeples, Mark E.

2012-01-01

Respiratory syncytial virus (RSV) is the most significant cause of pediatric respiratory infections. Palivizumab (Synagis®), a humanized monoclonal antibody, has been used successfully for a number of years to prevent severe RSV disease in at-risk infants. However, despite intense efforts, there is no approved vaccine or small molecule drug for RSV. As an enveloped virus, RSV must fuse its envelope with the host cell membrane, which is accomplished through the actions of the fusion (F) glycoprotein, with attachment help from the G glycoprotein. Because of their integral role in initiation of infection and their accessibility outside the lipid bilayer, these proteins have been popular targets in the discovery and development of antiviral compounds and vaccines against RSV. This review examines advances in the development of antiviral compounds and vaccine candidates. PMID:22335496

[Effect of lumbar hybrid instrumentation and rigid fusion on the treated and the adjacent segments. A biomechanical study].

PubMed

Wiedenhöfer, B; Akbar, M; Fürstenberg, C H; Carstens, C; Hemmer, S; Schilling, C

2011-02-01

Degeneration of the upper adjacent segment after operative treatment of degenerative spinal diseases of the lumbar spine (degenerative disc disease DDD) is an unsolved problem. There is also no consensus on whether a rigid or dynamic treatment of DDD should be carried out to protect the segments. This study was carried out to evaluate the effect of bisegmental rigid 360° fusion and bisegmental hybrid fusion on the treated segment as well as on the upper adjacent segment under the aspect of segment protection. A total of six human spinal column preparations (L2-5) were tested under native conditions (NAT), with bisegmental rigid fusion (RIG 360°) and with hybrid fusion (Hybrid) in all three movement directions under physical load and with an preload. The range of motion (ROM) and neutral zone (NZ) were evaluated. The intradiscal pressure (IDP) was measured in the upper adjacent segment (OAS). The RIG 360° led to a significant reduction in movement in all directions compared to NAT but Hybrid only in lateral bending (LB). In the OAS the NZ was showed a much greater increase than the ROM. The RIG 360° showed an increase of the NZ in flexion-extension of 86.8% and in LB of 49.6% as well as a significant increase in axial rotation of 52.5%. The increase in the Hybrid was not significant compared to NAT in all directions. Pressure measurements in OAS showed no significant differences for RIG 360° and for Hybrid compared to NAT for both load scenarios. The range of motion of the treated segments for Hybrid were close to NAT in comparison to RIG 360° indicating a segment-protective effect. The hypothesis that rigid fusion has a significant effect on intersegmental mobility and the increase in intradiscal pressure in the upper adjacent segment could not be confirmed. The data indicate that the primary effect of fusion on the adjacent segment is very low but the fusion-linked increased frequency of extreme loads of the OAS falling within the significance level leads to degeneration. Even if the NZ values for Hybrid and RIG 360° do not significantly differ from NAT, the NZ alterations between the instrumentations tend to be strongly shifted in favor of Hybrid. The data confirm that the clear and sometimes significant alterations of the NZ can be an essential factor for development of adjacent segment degeneration. A dynamic conclusion of instrumentation in the sense of a topping-off would appear to be useful if pathoanatomical indications for an intervertebral disc prosthesis are present.

Laparoscopic bone dowel fusions of the lumbar spine.

PubMed

Silcox, D H

1998-10-01

Studies that show laparoscopic lumbar fusion to decrease cost or time of hospitalization or to increase the speed or incidence of return to activities are not currently available. Laparoscopic fusion of the lumbar spine appears to be a potentially attractive approach to treating axial back pain secondary to different causes. Although the technique is attractive because of its minimally invasive nature and marketing allure, it has yet to be established as to what the true clinical efficacy of this procedure will be. Further clinical study of these techniques with longer follow-up, and case-controlled studies should help clinicians to know the best fusion technique to offer patients.

Study of impurity effects on CFETR steady-state scenario by self-consistent integrated modeling

NASA Astrophysics Data System (ADS)

Shi, Nan; Chan, Vincent S.; Jian, Xiang; Li, Guoqiang; Chen, Jiale; Gao, Xiang; Shi, Shengyu; Kong, Defeng; Liu, Xiaoju; Mao, Shifeng; Xu, Guoliang

2017-12-01

Impurity effects on fusion performance of China fusion engineering test reactor (CFETR) due to extrinsic seeding are investigated. An integrated 1.5D modeling workflow evolves plasma equilibrium and all transport channels to steady state. The one modeling framework for integrated tasks framework is used to couple the transport solver, MHD equilibrium solver, and source and sink calculations. A self-consistent impurity profile constructed using a steady-state background plasma, which satisfies quasi-neutrality and true steady state, is presented for the first time. Studies are performed based on an optimized fully non-inductive scenario with varying concentrations of Argon (Ar) seeding. It is found that fusion performance improves before dropping off with increasing {{Z}\\text{eff}} , while the confinement remains at high level. Further analysis of transport for these plasmas shows that low-k ion temperature gradient modes dominate the turbulence. The decrease in linear growth rate and resultant fluxes of all channels with increasing {{Z}\\text{eff}} can be traced to impurity profile change by transport. The improvement in confinement levels off at higher {{Z}\\text{eff}} . Over the regime of study there is a competition between the suppressed transport and increasing radiation that leads to a peak in the fusion performance at {{Z}\\text{eff}} (~2.78 for CFETR). Extrinsic impurity seeding to control divertor heat load will need to be optimized around this value for best fusion performance.

Biomechanical study of tarsometatarsal joint fusion using finite element analysis.

PubMed

Wang, Yan; Li, Zengyong; Zhang, Ming

2014-11-01

Complications of surgeries in foot and ankle bring patients with severe sufferings. Sufficient understanding of the internal biomechanical information such as stress distribution, contact pressure, and deformation is critical to estimate the effectiveness of surgical treatments and avoid complications. Foot and ankle is an intricate and synergetic system, and localized intervention may alter the functions to the adjacent components. The aim of this study was to estimate biomechanical effects of the TMT joint fusion using comprehensive finite element (FE) analysis. A foot and ankle model consists of 28 bones, 72 ligaments, and plantar fascia with soft tissues embracing all the segments. Kinematic information and ground reaction force during gait were obtained from motion analysis. Three gait instants namely the first peak, second peak and mid-stance were simulated in a normal foot and a foot with TMT joint fusion. It was found that contact pressure on plantar foot increased by 0.42%, 19% and 37%, respectively after TMT fusion compared with normal foot walking. Navico-cuneiform and fifth meta-cuboid joints sustained 27% and 40% increase in contact pressure at second peak, implying potential risk of joint problems such as arthritis. Von Mises stress in the second metatarsal bone increased by 22% at midstance, making it susceptible to stress fracture. This study provides biomechanical information for understanding the possible consequences of TMT joint fusion. Copyright © 2014 IPEM. Published by Elsevier Ltd. All rights reserved.

Fusion-activated cation entry (FACE) via P2X₄ couples surfactant secretion and alveolar fluid transport.

PubMed

Thompson, Kristin E; Korbmacher, Jonas P; Hecht, Elena; Hobi, Nina; Wittekindt, Oliver H; Dietl, Paul; Kranz, Christine; Frick, Manfred

2013-04-01

Two fundamental mechanisms within alveoli are essential for lung function: regulated fluid transport and secretion of surfactant. Surfactant is secreted via exocytosis of lamellar bodies (LBs) in alveolar type II (ATII) cells. We recently reported that LB exocytosis results in fusion-activated cation entry (FACE) via P2X₄ receptors on LBs. We propose that FACE, in addition to facilitating surfactant secretion, modulates alveolar fluid transport. Correlative fluorescence and atomic force microscopy revealed that FACE-dependent water influx correlated with individual fusion events in rat primary ATII cells. Moreover, ATII cell monolayers grown at air-liquid interface exhibited increases in short-circuit current (Isc) on stimulation with ATP or UTP. Both are potent agonists for LB exocytosis, but only ATP activates FACE. ATP, not UTP, elicited additional fusion-dependent increases in Isc. Overexpressing dominant-negative P2X₄ abrogated this effect by ∼50%, whereas potentiating P2X4 lead to ∼80% increase in Isc. Finally, we monitored changes in alveolar surface liquid (ASL) on ATII monolayers by confocal microscopy. Only stimulation with ATP, not UTP, led to a significant, fusion-dependent, 20% decrease in ASL, indicating apical-to-basolateral fluid transport across ATII monolayers. Our data support the first direct link between LB exocytosis, regulation of surfactant secretion, and transalveolar fluid resorption via FACE.

SU-D-304-07: Application of Proton Boron Fusion Reaction to Radiation Therapy

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

Jung, J; Yoon, D; Shin, H

Purpose: we present the introduction of a therapy method using the proton boron fusion reaction. The purpose of this study is to verify the theoretical validity of proton boron fusion therapy using Monte Carlo simulations. Methods: After boron is accumulated in the tumor region, the emitted from outside the body proton can react with the boron in the tumor region. An increase of the proton’s maximum dose level is caused by the boron and only the tumor cell is damaged more critically. In addition, a prompt gamma ray is emitted from the proton boron reaction point. Here we show thatmore » the effectiveness of the proton boron fusion therapy (PBFT) was verified using Monte Carlo simulations. Results: We found that a dramatic increase by more than half of the proton’s maximum dose level was induced by the boron in the tumor region. This increase occurred only when the proton’s maximum dose point was located within the boron uptake region (BUR). In addition, the 719 keV prompt gamma ray peak produced by the proton boron fusion reaction was positively detected. Conclusion: This therapy method features the advantages such as the application of Bragg-peak to the therapy, the accurate targeting of tumor, improved therapy effects, and the monitoring of the therapy region during treatment.« less

Low-energy nuclear reaction of the 14N+169Tm system: Incomplete fusion

NASA Astrophysics Data System (ADS)

Kumar, R.; Sharma, Vijay R.; Yadav, Abhishek; Singh, Pushpendra P.; Agarwal, Avinash; Appannababu, S.; Mukherjee, S.; Singh, B. P.; Ali, R.; Bhowmik, R. K.

2017-11-01

Excitation functions of reaction residues produced in the 14N+169Tm system have been measured to high precision at energies above the fusion barrier, ranging from 1.04 VB to 1.30 VB , and analyzed in the framework of the statistical model code pace4. Analysis of α -emitting channels points toward the onset of incomplete fusion even at slightly above-barrier energies where complete fusion is supposed to be one of the dominant processes. The onset and strength of incomplete fusion have been deduced and studied in terms of various entrance channel parameters. Present results together with the reanalysis of existing data for various projectile-target combinations conclusively suggest strong influence of projectile structure on the onset of incomplete fusion. Also, a strong dependence on the Coulomb effect (ZPZT) has been observed for the present system along with different projectile-target combinations available in the literature. It is concluded that the fraction of incomplete fusion linearly increases with ZPZT and is found to be more for larger ZPZT values, indicating significantly important linear systematics.

Dynamin-related protein-1 controls fusion pore dynamics during platelet granule exocytosis.

PubMed

Koseoglu, Secil; Dilks, James R; Peters, Christian G; Fitch-Tewfik, Jennifer L; Fadel, Nathalie A; Jasuja, Reema; Italiano, Joseph E; Haynes, Christy L; Flaumenhaft, Robert

2013-03-01

Platelet granule exocytosis serves a central role in hemostasis and thrombosis. Recently, single-cell amperometry has shown that platelet membrane fusion during granule exocytosis results in the formation of a fusion pore that subsequently expands to enable the extrusion of granule contents. However, the molecular mechanisms that control platelet fusion pore expansion and collapse are not known. We identified dynamin-related protein-1 (Drp1) in platelets and found that an inhibitor of Drp1, mdivi-1, blocked exocytosis of both platelet dense and α-granules. We used single-cell amperometry to monitor serotonin release from individual dense granules and, thereby, measured the effect of Drp1 inhibition on fusion pore dynamics. Inhibition of Drp1 increased spike width and decreased prespike foot events, indicating that Drp1 influences fusion pore formation and expansion. Platelet-mediated thrombus formation in vivo after laser-induced injury of mouse cremaster arterioles was impaired after infusion of mdivi-1. These results demonstrate that inhibition of Drp1 disrupts platelet fusion pore dynamics and indicate that Drp1 can be targeted to control thrombus formation in vivo.

Fusion with stem cell makes the hepatocellular carcinoma cells similar to liver tumor-initiating cells.

PubMed

Wang, Ran; Chen, Shuxun; Li, Changxian; Ng, Kevin Tak Pan; Kong, Chi-wing; Cheng, Jinping; Cheng, Shuk Han; Li, Ronald A; Lo, Chung Mau; Man, Kwan; Sun, Dong

2016-02-04

Cell fusion is a fast and highly efficient technique for cells to acquire new properties. The fusion of somatic cells with stem cells can reprogram somatic cells to a pluripotent state. Our research on the fusion of stem cells and cancer cells demonstrates that the fused cells can exhibit stemness and cancer cell-like characteristics. Thus, tumor-initiating cell-like cells are generated. We employed laser-induced single-cell fusion technique to fuse the hepatocellular carcinoma cells and human embryonic stem cells (hESC). Real-time RT-PCR, flow cytometry and in vivo tumorigenicity assay were adopted to identify the gene expression difference. We successfully produced a fused cell line that coalesces the gene expression information of hepatocellular carcinoma cells and stem cells. Experimental results showed that the fused cells expressed cancer and stemness markers as well as exhibited increased resistance to drug treatment and enhanced tumorigenesis. Fusion with stem cells transforms liver cancer cells into tumor initiating-like cells. Results indicate that fusion between cancer cell and stem cell may generate tumor initiating-like cells.

Influence of collective nonideal shielding on fusion reaction in partially ionized classical nonideal plasmas

NASA Astrophysics Data System (ADS)

Lee, Myoung-Jae; Jung, Young-Dae

2017-04-01

The collective nonideal effects on the nuclear fusion reaction process are investigated in partially ionized classical nonideal hydrogen plasmas. The effective pseudopotential model taking into account the collective and plasma shielding effects is applied to describe the interaction potential in nonideal plasmas. The analytic expressions of the Sommerfeld parameter, the fusion penetration factor, and the cross section for the nuclear fusion reaction in nonideal plasmas are obtained as functions of the nonideality parameter, Debye length, and relative kinetic energy. It is found that the Sommerfeld parameter is suppressed due to the influence of collective nonideal shielding. However, the collective nonideal shielding is found to enhance the fusion penetration factor in partially ionized classical nonideal plasmas. It is also found that the fusion penetration factors in nonideal plasmas represented by the pseudopotential model are always greater than those in ideal plasmas represented by the Debye-Hückel model. In addition, it is shown that the collective nonideal shielding effect on the fusion penetration factor decreases with an increase of the kinetic energy.

Nuclear fusion of advanced fuels using converging focused ion beams

NASA Astrophysics Data System (ADS)

Egle, Brian James

The Six Ion Gun Fusion Experiment (SIGFE) was designed and built to investigate a possible avenue to increase the reaction rate efficiency of the D-D and D-3He nuclear fusion reactions in Inertial Electrostatic Confinement (IEC) devices to the levels required for several non-electric applications of nuclear fusion. The SIGFE is based on the seminal IEC experiment published by Hirsch in 1967, and is the first experiment to recreate the results and unique features of the Hirsch device. The SIGFE used six identical ion beams to focus and converge deuterium and helium-3 ions into a sphere of less than 2 mm at nearly mono-energetic ion energies up to 150 keV. With improved ion optics and diagnostics, the SIGFE concluded that within the investigated parameter space, the region where the ion beams converged accounted for less than 0.2% of the total D-D fusion reactions. The maximum D-D fusion rates were observed when the ion beams were intentionally defocused to strike the inside surface of the cathode lenses. In this defocused state, the total D-D fusion rate increased when the chamber pressure was decreased. The maximum D-D fusion rate was 4.3 x 107 neutrons per second at a cathode voltage of -130 kV, a total cathode current of 10 mA, and a chamber pressure of 27 mPa. The D and 3He ion beams were produced in six self-contained ion gun modules. The modules were each capable of at least 4 mA of ion current while maintaining a main chamber pressure as low as 13 mPa. The theoretically calculated extractable ion current agreed with the experiment within a factor of 2. A concept was also developed and evaluated for the production of radioisotopes from the 14.7 MeV D-3He fusion protons produced in an IEC device. Monte Carlo simulations of this concept determined that a D-3He fusion rate on the order of 1011 s-1 would be required for an IEC device to produce 1 mCi of the 11C radioisotope.

The Energy Maintenance Theory of Aging: Maintaining Energy Metabolism to Allow Longevity.

PubMed

Chaudhari, Snehal N; Kipreos, Edward T

2018-06-14

Fused, elongated mitochondria are more efficient in generating ATP than fragmented mitochondria. In diverse C. elegans longevity pathways, increased levels of fused mitochondria are associated with lifespan extension. Blocking mitochondrial fusion in these animals abolishes their extended longevity. The long-lived C. elegans vhl-1 mutant is an exception that does not have increased fused mitochondria, and is not dependent on fusion for longevity. Loss of mammalian VHL upregulates alternate energy generating pathways. This suggests that mitochondrial fusion facilitates longevity in C. elegans by increasing energy metabolism. In diverse animals, ATP levels broadly decreases with age. Substantial evidence supports the theory that increasing or maintaining energy metabolism promotes the survival of older animals. Increased ATP levels in older animals allow energy-intensive repair and homeostatic mechanisms such as proteostasis that act to prevent cellular aging. These observations support the emerging paradigm that maintaining energy metabolism promotes the survival of older animals. © 2018 WILEY Periodicals, Inc.

Theoretical Study of the Effects of Di-Muonic Molecules on Muon-Catalyzed Fusion

DTIC Science & Technology

2012-03-01

For example, synthetic zeolites could be used to separate molecular isotopes of hydrogen [12; 10] as could thermal diffusion and gas chromatography... thermal muon flux is large (see Chapter 8). Reactions which have the potential of increasing the muon-catalyzed fusion rate and reactions that could...the remainder of this document. Changes to the muon-catalyzed fusion cycle, that are expected to occur when the thermal muon flux is high, are

Decomposition of banten ilmenite by caustic fusion process for TiO2 photocatalytic applications

NASA Astrophysics Data System (ADS)

Aristanti, Y.; Supriyatna, Y. I.; Masduki, N. P.; Soepriyanto, S.

2018-01-01

Decomposition of Banten ilmenite by caustic fusion process for TiO2 photocatalytic applications has been done. Caustic fusion process using NaOH to obtain sodium titanate compound which is soluble in sulfuric acid (H2SO4) to produces TiOSO4 as a precursor. Synthesis of TiO2 from TiOSO4 precursors by variations of pH hydrolysis are 1.0 (TiO2 A), 1.5 (TiO2 B) and 2.0 (TiO2 C). XRD pattern identified TiO2 structures crystals are anatase phase and traces α-Fe2O3 as an impurity. Presence of Fe2O3 as an impurities give positive effect on TiO2 photocatalytic activity that is to narrower the band gap energy thus facilitates of electrons excitation from valence band to conduction band and enlarge the specific surface area thus reaction between Rhodamin B solution and TiO2 surface can be faster. TiO2 A, TiO2 B and TiO2 C was compared to TiO2 M (commercial TiO2) in Rhodamin B solution for the photocatalytic activity where the maximum TiO2 degradation efficiency was obtained at TiO2 C 80.0 % while TiO2 M 59.8 %.

Projection parameters for zirconia-alumina-ceria coatings made by flame spraying from results of numerical simulation

NASA Astrophysics Data System (ADS)

Rodríguez, L.; Ferrer, M.; Vargas, F.; Peña, G.

2017-12-01

A numerical simulation was performed with the software Jets et Poudres, the results let choose the parameters to deposit zirconia-alumina-ceria coatings of different composition on substrates of red clay, by thermal spraying with the oxyacetylene flame to obtain homogeneous coatings with good adhesion to the substrate. The effect of the projection distance (7, 10 and 12cm) between the substrate and the torch, the fusion percentage of particles and the K-Sommerfeld number was determined. This number is dimensionless and is affected by the projection distance and by the chemical composition of the particles. For a projection distance of 9cm, the fusion percentage of the particles varies between 83.8% and 100%, and the K-Sommerfeld number between 47.3 and 50 for the different compounds. This makes possible to obtain uniform coatings with good wettability, therefore, good adhesion to the substrate, while for the distance of 7cm the fusion percentage varies between 22% and 38%, due to the short time of the particles in the flame which causes low adhesion, when the projection distance is 12cm the particles do not have sufficient kinetic energy to reach the substrate and therefore the coating is not deposited.

The cross sections of fusion-evaporation reactions: the most promising route to superheavy elements beyond Z=118

NASA Astrophysics Data System (ADS)

Jadambaa, Khuyagbaatar

2017-11-01

The synthesis of superheavy elements beyond oganesson (Og), which has atomic number Z = 118, is currently one of the main topics in nuclear physics. An absence of sufficient amounts of target material with atomic numbers heavier than californium (Z = 98) forces the use of projectiles heavier than 48Ca (Z = 20), which has been successfully used for the discoveries of elements with Z = 114 - 118 in complete fusion reactions. Experimental cross sections of 48Ca with actinide targets behave very differently to "cold" and "hot" fusion-evaporation reactions, where doubly-magic lead and deformed actinides are used as targets, respectively. The known cross sections of these reactions have been analysed compared to calculated fission barriers. It has been suggested that observed discrepancies between the cross sections of 48Ca-induced and other fusionevaporation reactions originate from the shell structure of the compound nucleus, which lies in the island of the stability. Besides scarcely known data on other reactions involving heavier projectiles, the most promising projectile for the synthesis of the elements beyond Og seems to be 50Ti. However, detailed studies of 50Ti, 54Cr, 58Fe and 64Ni-induced reactions are necessary to be performed in order to fully understand the complexities of superheavy element formation.

Biomechanics of Artificial Disc Replacements Adjacent to a 2-Level Fusion in 4-Level Hybrid Constructs: An In Vitro Investigation

PubMed Central

Liao, Zhenhua; Fogel, Guy R.; Wei, Na; Gu, Hongsheng; Liu, Weiqiang

2015-01-01

Background The ideal procedure for multilevel cervical degenerative disc diseases remains controversial. Recent studies on hybrid surgery combining anterior cervical discectomy and fusion (ACDF) and artificial cervical disc replacement (ACDR) for 2-level and 3-level constructs have been reported in the literature. The purpose of this study was to estimate the biomechanics of 3 kinds of 4-level hybrid constructs, which are more likely to be used clinically compared to 4-level arthrodesis. Material/Methods Eighteen human cadaveric spines (C2–T1) were evaluated in different testing conditions: intact, with 3 kinds of 4-level hybrid constructs (hybrid C3–4 ACDR+C4–6 ACDF+C6–7ACDR; hybrid C3–5ACDF+C5–6ACDR+C6–7ACDR; hybrid C3–4ACDR+C4–5ACDR+C5–7ACDF); and 4-level fusion. Results Four-level fusion resulted in significant decrease in the C3–C7 ROM compared with the intact spine. The 3 different 4-level hybrid treatment groups caused only slight change at the instrumented levels compared to intact except for flexion. At the adjacent levels, 4-level fusion resulted in significant increase of contribution of both upper and lower adjacent levels. However, for the 3 hybrid constructs, significant changes of motion increase far lower than 4P at adjacent levels were only noted in partial loading conditions. No destabilizing effect or hypermobility were observed in any 4-level hybrid construct. Conclusions Four-level fusion significantly eliminated motion within the construct and increased motion at the adjacent segments. For all 3 different 4-level hybrid constructs, ACDR normalized motion of the index segment and adjacent segments with no significant hypermobility. Compared with the 4-level ACDF condition, the artificial discs in 4-level hybrid constructs had biomechanical advantages compared to fusion in normalizing adjacent level motion. PMID:26694835

Biomechanics of Artificial Disc Replacements Adjacent to a 2-Level Fusion in 4-Level Hybrid Constructs: An In Vitro Investigation.

PubMed

Liao, Zhenhua; Fogel, Guy R; Wei, Na; Gu, Hongsheng; Liu, Weiqiang

2015-12-23

BACKGROUND The ideal procedure for multilevel cervical degenerative disc diseases remains controversial. Recent studies on hybrid surgery combining anterior cervical discectomy and fusion (ACDF) and artificial cervical disc replacement (ACDR) for 2-level and 3-level constructs have been reported in the literature. The purpose of this study was to estimate the biomechanics of 3 kinds of 4-level hybrid constructs, which are more likely to be used clinically compared to 4-level arthrodesis. MATERIAL AND METHODS Eighteen human cadaveric spines (C2-T1) were evaluated in different testing conditions: intact, with 3 kinds of 4-level hybrid constructs (hybrid C3-4 ACDR+C4-6 ACDF+C6-7ACDR; hybrid C3-5ACDF+C5-6ACDR+C6-7ACDR; hybrid C3-4ACDR+C4-5ACDR+C5-7ACDF); and 4-level fusion. RESULTS Four-level fusion resulted in significant decrease in the C3-C7 ROM compared with the intact spine. The 3 different 4-level hybrid treatment groups caused only slight change at the instrumented levels compared to intact except for flexion. At the adjacent levels, 4-level fusion resulted in significant increase of contribution of both upper and lower adjacent levels. However, for the 3 hybrid constructs, significant changes of motion increase far lower than 4P at adjacent levels were only noted in partial loading conditions. No destabilizing effect or hypermobility were observed in any 4-level hybrid construct. CONCLUSIONS Four-level fusion significantly eliminated motion within the construct and increased motion at the adjacent segments. For all 3 different 4-level hybrid constructs, ACDR normalized motion of the index segment and adjacent segments with no significant hypermobility. Compared with the 4-level ACDF condition, the artificial discs in 4-level hybrid constructs had biomechanical advantages compared to fusion in normalizing adjacent level motion.

Arginine supplementation induces myoblast fusion via augmentation of nitric oxide production.

PubMed

Long, Jodi H D; Lira, Vitor A; Soltow, Quinlyn A; Betters, Jenna L; Sellman, Jeff E; Criswell, David S

2006-01-01

The semi-essential amino acid, L-arginine (L-Arg), is the substrate for endogenous synthesis of nitric oxide, a molecule that is involved in myoblast proliferation and fusion. Since L-Arg supply may limit nitric oxide synthase (NOS) activity in endothelial cells, we examined L-Arg supplementation in differentiating mouse myoblasts and tested the hypothesis that L-Arg exerts direct effects on myoblast fusion via augmentation of endogenous nitric oxide production. C(2)C(12) myoblasts in differentiation media received one of the following treatments for 120 h: 1 mM L-Arg, 0.1 mM N-nitro-L-arginine methyl ester (L-NAME), L-Arg + L-NAME, 10 mM L-Lysine, or no supplement (Control). Cultures were fixed and stained with hematoxylin and eosin for microphotometric image analysis of myotube density, nuclear density, and fusion index (% of total nuclei in myotubes). Endogenous production of nitric oxide during the treatment period peaked between 24 and 48 h. L-Arg amplified nitric oxide production between 0 and 24 h and increased myotube density, total nuclei number, and nuclear fusion index. These L-Arg effects were prevented by the NOS inhibitor, L-NAME. Further, L-Lysine, a competitive inhibitor of L-Arg uptake, repressed nitric oxide production and reduced myotube density and fusion index. In summary, L-Arg augments myotube formation and increases nitric oxide production in a process limited by cellular L-Arg uptake.

Signaling networks in TMPRSS2-ERG positive prostate cancers: Do we need a Pied Piper or sharpshooter to deal with "at large" fused oncoprotein.

PubMed

Lin, X; Qureshi, M Z; Romero, M A; Yaylim, I; Arif, S; Ucak, I; Fayyaz, S; Farooqi, A A; Mansoor, Q; Ismail, M

2017-02-28

Overwhelmingly increasing scientific evidence has provided near complete resolution of prostate cancer landscape and it is now more understandable that wide ranging factors underlies its development and progression. Increasingly it is being realized that genetic/epigenetic factors, Intra-tumoral and inter-tumoral heterogeneity, loss of apoptosis, dysregulations of spatio-temporally controlled signaling cascades, Darwinian evolution in response to therapeutic pressures play instrumental role in prostate carcinogenesis. Moreover, multi-directional patterns of spread between primary tumors and metastatic sites have also been studied extensively in prostate cancer. Research over the years has gradually and systematically revealed closer association between tumor phenotype and type of gene fusion. Latest developments in deep sequencing technologies have shown that gene fusions originate in a non-random, cell type dependent manner and are much more frequent than previously surmised. These findings enabled sub-classification and categorization of seemingly identical diseases. Furthermore, research methodologies have shown that many gene fusions inform us about risk stratification and many chimeric proteins encoded by the fused genes are being studied as drug target/s. We partition this multi-component review into the molecular basis of formation of fusion transcripts, how protein network is regulated in fusion positive prostate cancer cells and therapeutic strategies which are currently being investigated to efficiently target fusion transcript and its protein product.

Agile Thermal Management STT-RX: Themophysical Properties of Lithium Nitrate Trihydrate from - 20 degrees C to 80 degrees C (Preprint)

DTIC Science & Technology

2011-12-01

of interest as a thermal energy storage material, due to its large specific and volumetric heats of fusion and its low melting temperature. Here, we...compound to water and octadecane, two other potential thermal energy storage materials. Furthermore, we examine the lithium nitrate-water phase diagram and...lithium nitrate trihydrate-lithium nitrate eutectic point (Hfus = 264 ± 2 J·g-1, Tm = 28.3 °C). 15. SUBJECT TERMS salt hydrate, thermal energy

Development of Lead Compounds as Fusion Inhibitors for Dengue Virus

DTIC Science & Technology

2009-08-01

19a. NAME OF RESPONSIBLE PERSON USAMRMC a. REPORT U b . ABSTRACT U c. THIS PAGE U UU 61 19b. TELEPHONE NUMBER (include area code...and III (blue). B ) Structural alignment of E2 protein monomer in the absence and presence of βOG (pdbIDs 1OAN and 1OKE respectively), with the kl-β...hairpin loop colored as follows: prefusion state (yellow), intermediate βOG-E2 complex (blue), secondary structure colored by B -factor from blue

Methods for Effective Virtual Screening and Scaffold-Hopping in Chemical Compounds

DTIC Science & Technology

2007-04-04

contains color images. 14. ABSTRACT 15. SUBJECT TERMS 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 12 19a...Opterons with 4 GB of memory . We used the descriptor- spaces GF, ECZ3, and ErG (described in Section 4) for the evaluating the methods introduced in...screening: Use of data fusion and machine learning to enchance the effectiveness of sim- ilarity searching. J. Chem. Info. Model., (46):462–470, 2006. [18] J

Spinal fusion limits upper body range of motion during gait without inducing compensatory mechanisms in adolescent idiopathic scoliosis patients.

PubMed

Holewijn, R M; Kingma, I; de Kleuver, M; Schimmel, J J P; Keijsers, N L W

2017-09-01

Previous studies show a limited alteration of gait at normal walking speed after spinal fusion surgery for adolescent idiopathic scoliosis (AIS), despite the presumed essential role of spinal mobility during gait. This study analyses how spinal fusion affects gait at more challenging walking speeds. More specifically, we investigated whether thoracic-pelvic rotations are reduced to a larger extent at higher gait speeds and whether compensatory mechanisms above and below the stiffened spine are present. 18 AIS patients underwent gait analysis at increasing walking speeds (0.45 to 2.22m/s) before and after spinal fusion. The range of motion (ROM) of the upper (thorax, thoracic-pelvic and pelvis) and lower body (hip, knee and ankle) was determined in all three planes. Spatiotemporal parameters of interest were stride length and cadence. Spinal fusion diminished transverse plane thoracic-pelvic ROM and this difference was more explicit at higher walking speeds. Transversal pelvis ROM was also decreased but this effect was not affected by speed. Lower body ROM, step length and cadence remained unaffected. Despite the reduction of upper body ROM after spine surgery during high speed gait, no altered spatiotemporal parameters or increased compensatory ROM above or below the fusion (i.e. in the shoulder girdle or lower extremities) was identified. Thus, it remains unclear how patients can cope so well with such major surgery. Future studies should focus on analyzing the kinematics of individual spinal levels above and below the fusion during gait to investigate possible compensatory mechanisms within the spine. Copyright © 2017 Elsevier B.V. All rights reserved.

Normal myoblast fusion requires myoferlin

PubMed Central

Doherty, Katherine R.; Cave, Andrew; Davis, Dawn Belt; Delmonte, Anthony J.; Posey, Avery; Earley, Judy U.; Hadhazy, Michele; McNally, Elizabeth M.

2014-01-01

Summary Muscle growth occurs during embryonic development and continues in adult life as regeneration. During embryonic muscle growth and regeneration in mature muscle, singly nucleated myoblasts fuse to each other to form myotubes. In muscle growth, singly nucleated myoblasts can also fuse to existing large, syncytial myofibers as a mechanism of increasing muscle mass without increasing myofiber number. Myoblast fusion requires the alignment and fusion of two apposed lipid bilayers. The repair of muscle plasma membrane disruptions also relies on the fusion of two apposed lipid bilayers. The protein dysferlin, the product of the Limb Girdle Muscular Dystrophy type 2 locus, has been shown to be necessary for efficient, calcium-sensitive, membrane resealing. We now show that the related protein myoferlin is highly expressed in myoblasts undergoing fusion, and is expressed at the site of myoblasts fusing to myotubes. Like dysferlin, we found that myoferlin binds phospholipids in a calcium-sensitive manner that requires the first C2A domain. We generated mice with a null allele of myoferlin. Myoferlin null myoblasts undergo initial fusion events, but they form large myotubes less efficiently in vitro, consistent with a defect in a later stage of myogenesis. In vivo, myoferlin null mice have smaller muscles than controls do, and myoferlin null muscle lacks large diameter myofibers. Additionally, myoferlin null muscle does not regenerate as well as wild-type muscle does, and instead displays a dystrophic phenotype. These data support a role for myoferlin in the maturation of myotubes and the formation of large myotubes that arise from the fusion of myoblasts to multinucleate myotubes. PMID:16280346

Socioeconomic and regional differences in the treatment of cervical spondylotic myelopathy

PubMed Central

Palejwala, Sheri K.; Rughani, Anand I.; Lemole, G. Michael; Dumont, Travis M.

2017-01-01

Background: Cervical spondylotic myelopathy (CSM) is the leading cause of spinal cord dysfunction in the world. Surgical treatment is both medically and economically advantageous, and can be achieved through multiple approaches, with or without fusion. We used the Nationwide Inpatient Sample (NIS) database to better elucidate regional and socioeconomic variances in the treatment of CSM. Methods: The NIS database was queried for elective admissions with a primary diagnosis of CSM (ICD-9 721.1). This was evaluated for patients who also carried a diagnosis of anterior (ICD-9 81.02) or posterior cervical fusion (ICD-9 81.03), posterior cervical laminectomy (ICD 03.09), or a combination. We then investigated variances including regional trends and disparities according to hospital and insurance types. Results: During 2002–2012, 50605 patients were electively admitted with a diagnosis of CSM. Anterior fusions were more common in Midwestern states and in nonteaching hospitals. Fusion procedures were used more frequently than other treatments in private hospitals and with private insurance. Median hospital charges were also expectedly higher for fusion procedures and combined surgical approaches. Combined approaches were found to be significantly greater in patients with concurrent diagnoses of ossification of the posterior longitudinal ligament (OPLL) and CSM. Ultimately, there has been an increased utilization of fusion procedures versus nonfusion treatments, over the past decade, for patients with cervical myelopathy. Conclusions: Fusion surgery is being increasingly used for the treatment of CSM. Expensive procedures are being performed more frequently in both private hospitals and for those with private insurance, whereas the most economical procedure, posterior cervical laminectomy, was underutilized. PMID:28607826

Low energy measurements of the 10B(p ,α )7Be reaction

NASA Astrophysics Data System (ADS)

Wiescher, M.; deBoer, R. J.; Görres, J.; Azuma, R. E.

2017-04-01

Background: The 11B(p,2 α ) 4He reaction is being discussed as a prime candidate for advanced aneutronic fusion fuel systems. Particular interest in this reaction has recently emerged for laser driven plasma systems for energy generation and jet-propulsion systems. The lack of long-lived radioactive reaction products has been suggested as the main advantage of proton-boron fusion fuel. However, 19% of natural boron is 10B, with the 10B(p ,α )7Be fusion reaction producing long-lived 7Be as a side product. Purpose: A detailed measurement of the 10B(p ,α )7Be reaction over the critical energy range of hot fusion plasma environments will help to determine the amount of 7Be radioactivity being produced. This information can be used in turn to monitor the actual fusion temperature by offline measurement of the extracted 7Be activity. The goal of the here presented experiment is to expand on the results of earlier experiments, covering a wider energy range of interest for aneutronic plasma fusion applications, including also both 10B(p ,α0)7Be and the 10B(p ,α1)7Be reaction channels. Method: The reaction cross section was measured over a wide energy range from Ep=400 to 1000 keV using particle detection and from Ep=80 to 1440 keV using γ -ray spectroscopic techniques. Reaction α particles were measured at different angles to obtain angular distribution information. The results are discussed in terms of an R -matrix analysis. Results: The cross section data cover a wider energy range than previously investigated and bridge a gap in the previously available data sets. The cross sections show good agreement with previous results in the low energy region and show that the 10B(p ,α0)7Be channel is considerably larger than that of the 10B(p ,α1)7Be channel up to Ep≈1 MeV . Conclusions: The new reaction data provides important new information about the reaction cross section over the entire energy range of plasma fusion facilities. This data, when coupled with previous measurement of the competing 10B(p ,γ )11C reaction, will provide the opportunity for an extensive R -matrix analysis of the rather complex level structure in the 11C compound nucleus system.

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

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

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.

Confined ion energy >200 keV and increased fusion yield in a DPF with monolithic tungsten electrodes and pre-ionization

NASA Astrophysics Data System (ADS)

Lerner, Eric J.; Hassan, Syed M.; Karamitsos, Ivana; Von Roessel, Fred

2017-10-01

To reduce impurities in the dense plasma focus FF-1 device, we used monolithic tungsten electrodes with pre-ionization. With this new set-up, we demonstrated a three-fold reduction of impurities by mass and a ten-fold reduction by ion number. FF-1 produced a 50% increase in fusion yield over our previous copper electrodes, both for a single shot and for a mean of ten consecutive shots with the same conditions. These results represent a doubling of fusion yield as compared with any other plasma focus device with the same 60 kJ energy input. In addition, FF-1 produced a new single-shot record of 240 ± 20 keV for mean ion energy, a record for any confined fusion plasma, using any device, and a 50% improvement in ten-shot mean ion energy. With a deuterium-nitrogen mix and corona-discharge pre-ionization, we were also able to reduce the standard deviation in the fusion yield to about 15%, a four-fold reduction over the copper-electrode results. We intend to further reduce impurities with new experiments using microwave treatment of tungsten electrodes, followed by the use of beryllium electrodes.

Anterior Cervical Corpectomy with free vascularized fibular graft versus multilevel discectomy and grafting for Cervical Spondylotic Myelopathy

PubMed Central

Addosooki, Ahmad I; El-deen, Mohamed Alam

2015-01-01

Purpose A retrospective study to compare the radiologic and clinical outcomes of 2 different anterior approaches, multilevel anterior cervical discectomy with fusion (ACDF) using autologus ticortical bone graft versus anterior cervical corpectomy with fusion (ACCF) using free vascularized fibular graft (FVFG) for the management of cervical spondylotic myelopathy(CSM). Methods A total of 15 patients who underwent ACDF or ACCF using FVFG for multilevel CSM were divided into two groups. Group A (n = 7) underwent ACDF and group B (n = 8) ACCF. Clinical outcomes using Japanese Orthopaedic Association (JOA) score, perioperative parameters including operation time and hospital stay, radiological parameters including fusion rate and cervical lordosis, and complications were compared. Results Both group A and group B demonstrated significant increases in JOA scores. Patients who underwent ACDF experienced significantly shorter operation times and hospital stay. Both groups showed significant increases in postoperative cervical lordosis and achieved the same fusion rate (100 %). No major complications were encountered in both groups. Conclusion Both ACDF and ACCF using FVFG provide satisfactory clinical outcomes and fusion rates for multilevel CSM. However, multilevel ACDF is associated with better radiologic parameters, shorter hospital stay and shorter operative times. PMID:26767152

Membrane fusion between baculovirus budded virus-enveloped particles and giant liposomes generated using a droplet-transfer method for the incorporation of recombinant membrane proteins.

PubMed

Nishigami, Misako; Mori, Takaaki; Tomita, Masahiro; Takiguchi, Kingo; Tsumoto, Kanta

2017-07-01

Giant proteoliposomes are generally useful as artificial cell membranes in biochemical and biophysical studies, and various procedures for their preparation have been reported. We present here a novel preparation technique that involves the combination of i) cell-sized lipid vesicles (giant unilamellar vesicles, GUVs) that are generated using the droplet-transfer method, where lipid monolayer-coated water-in-oil microemulsion droplets interact with oil/water interfaces to form enclosed bilayer vesicles, and ii) budded viruses (BVs) of baculovirus (Autographa californica nucleopolyhedrovirus) that express recombinant transmembrane proteins on their envelopes. GP64, a fusogenic glycoprotein on viral envelopes, is activated by weak acids and is thought to cause membrane fusion with liposomes. Using confocal laser scanning microscopy (CLSM), we observed that the single giant liposomes fused with octadecyl rhodamine B chloride (R18)-labeled wild-type BV envelopes with moderate leakage of entrapped soluble compounds (calcein), and the fusion profile depended on the pH of the exterior solution: membrane fusion occurred at pH ∼4-5. We further demonstrated that recombinant transmembrane proteins, a red fluorescent protein (RFP)-tagged GPCR (corticotropin-releasing hormone receptor 1, CRHR1) and envelope protein GP64 could be partly incorporated into membranes of the individual giant liposomes with a reduction of the pH value, though there were also some immobile fluorescent spots observed on their circumferences. This combination may be useful for preparing giant proteoliposomes containing the desired membranes and inner phases. Copyright © 2017 Elsevier B.V. All rights reserved.

Breakup fusion theory of nuclear reactions

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

Mastroleo, R.C.

1987-01-01

Continuum spectra of particles emitted in incomplete fusion reactions are one of the major interests in current nuclear reaction studies. Based on an idea of the so-called breakup fusion (BF) reaction, several authors derived closed formulas for the singles cross section of the particles that are emitted. There have been presented, however, two conflicting cross section formulas for the same BF reaction. For convenience, we shall call one of them the IAV (Ichimura, Austern and Vincent) and the other UT (Udagawa and Tamura) cross section formulas. In this work, the formulation of the UT cross section formula (prior-form) is presented,more » and the post-form version of the IAV cross section formula is evaluted for a few {alpha}- and d-induced reactions based on the exact finite range method. It is shown that the values thus calculated are larger by an order of magnitude as compared with the experimental cross sections for the {alpha}-induced reactions, while they are comparable with the experimental cross sections for the d-induced reactions. A possible origin of why such a large cross section is resulted in the case of {alpha}-induced reactions is also discussed. Polarization of the residual compound nucleus produced in breakup fusion reactions are calculated and compared with experiments. It is shown that the polarization is rather sensitive to the deflection angles of the strongly absortive partial waves and to obtain a good fit with the experimental data a l-dependent potential in the incident channel is needed in order to stress the lower partial waves.« less

A high throughput Cre–lox activated viral membrane fusion assay identifies pharmacological inhibitors of HIV entry

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

Esposito, Anthony M.; Cheung, Pamela; Swartz, Talia H.

Enveloped virus entry occurs when viral and cellular membranes fuse releasing particle contents into the target cell. Human immunodeficiency virus (HIV) entry occurs by cell-free virus or virus transferred between infected and uninfected cells through structures called virological synapses. We developed a high-throughput cell-based assay to identify small molecule inhibitors of cell-free or virological synapse-mediated entry. An HIV clone carrying Cre recombinase as a Gag-internal gene fusion releases active Cre into cells upon viral entry activating a recombinatorial gene switch changing dsRed to GFP-expression. A screen of a 1998 known-biological profile small molecule library identified pharmacological HIV entry inhibitors thatmore » block both cell-free and cell-to-cell infection. Many top hits were noted as HIV inhibitors in prior studies, but not previously recognized as entry antagonists. Modest therapeutic indices for simvastatin and nigericin were observed in confirmatory HIV infection assays. This robust assay is adaptable to study HIV and heterologous viral pseudotypes. - Highlights: • Cre recombinase viral fusion assay screens cell-free or cell–cell entry inhibitors. • This Gag-iCre based assay is specific for the entry step of HIV replication. • Screened a library of known pharmacologic compounds for HIV fusion antagonists. • Many top hits were previously noted as HIV inhibitors, but here are classified as entry antagonists. Many top hits were previously noted as HIV inhibitors, but not as entry antagonists. • The assay is compatible with pseudotyping with HIV and heterologous viruses.« less

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).

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.

Intraspecific protoplast fusion of Brettanomyces anomalus for improved production of an extracellular β-glucosidase.

PubMed

Wu, Peng; Zhao, Xihong; Pan, Siyi

2014-09-03

Improvement of production of an extracellular β-glucosidase with high activity by Brettanomyces anomalus PSY-001 was performed by using recursive protoplast fusion in a genome-shuffling format. The initial population was generated by ultraviolet irradiation, ultrasonic mutagenesis and, then, subjected to recursive protoplast fusion. Mutant strains exhibiting significantly higher β-glucosidase activities in liquid media were isolated. The best mutant strain showed increased cell growth in a flask culture, as well as increased β-glucosidase production. A recombinant strain, F3-25, was obtained after three rounds of genome shuffling and its production of β-glucosidase activity reached 4790 U L -1 , which was a nearly eightfold increase compared to the original strain B. anomalus PSY-001. The subculture experiments indicated that F3-25 was genetically stable.

Intraspecific protoplast fusion of Brettanomyces anomalus for improved production of an extracellular β-glucosidase

PubMed Central

Wu, Peng; Zhao, Xihong; Pan, Siyi

2014-01-01

Improvement of production of an extracellular β-glucosidase with high activity by Brettanomyces anomalus PSY-001 was performed by using recursive protoplast fusion in a genome-shuffling format. The initial population was generated by ultraviolet irradiation, ultrasonic mutagenesis and, then, subjected to recursive protoplast fusion. Mutant strains exhibiting significantly higher β-glucosidase activities in liquid media were isolated. The best mutant strain showed increased cell growth in a flask culture, as well as increased β-glucosidase production. A recombinant strain, F3-25, was obtained after three rounds of genome shuffling and its production of β-glucosidase activity reached 4790 U L−1, which was a nearly eightfold increase compared to the original strain B. anomalus PSY-001. The subculture experiments indicated that F3-25 was genetically stable. PMID:26019572

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.

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

Bacteroides fragilis Enterotoxin Induces Formation of Autophagosomes in Endothelial Cells but Interferes with Fusion with Lysosomes for Complete Autophagic Flux through a Mitogen-Activated Protein Kinase-, AP-1-, and C/EBP Homologous Protein-Dependent Pathway.

PubMed

Ko, Su Hyuk; Jeon, Jong Ik; Myung, Hyun Soo; Kim, Young-Jeon; Kim, Jung Mogg

2017-10-01

Bacteroides fragilis enterotoxin (BFT), a virulence factor of enterotoxigenic B. fragilis (ETBF), plays an essential role in mucosal inflammation. Although autophagy contributes to the pathogenesis of diverse infectious diseases, little is known about autophagy in ETBF infection. This study was conducted to investigate the role of BFT in the autophagic process in endothelial cells (ECs). Stimulation of human umbilical vein ECs (HUVECs) with BFT increased light chain 3 protein II (LC3-II) conversion from LC3-I and protein expression of p62, Atg5, and Atg12. In addition, BFT-exposed ECs showed increased indices of autophagosomal fusion with lysosomes such as LC3-lysosome-associated protein 2 (LAMP2) colocalization and the percentage of red vesicles monitored by the expression of dual-tagged LC3B. BFT also upregulated expression of C/EBP homologous protein (CHOP), and inhibition of CHOP significantly increased indices of autophagosomal fusion with lysosomes. BFT activated an AP-1 transcription factor, in which suppression of AP-1 activity significantly downregulated CHOP and augmented autophagosomal fusion with lysosomes. Furthermore, suppression of Jun N-terminal protein kinase (JNK) mitogen-activated protein kinase (MAPK) significantly inhibited the AP-1 and CHOP signals, leading to an increase in autophagosomal fusion with lysosomes in BFT-stimulated ECs. These results suggest that BFT induced accumulation of autophagosomes in ECs, but activation of a signaling pathway involving JNK, AP-1, and CHOP may interfere with complete autophagy. Copyright © 2017 American Society for Microbiology.

High fusion performance at high T i/ T e in JET-ILW baseline plasmas with high NBI heating power and low gas puffing

DOE PAGES

Kim, Hyun-Tae; Sips, A. C. C.; Romanelli, M.; ...

2018-02-01

This article presents the transport analysis of high density baseline discharges in the 2016 experimental campaign of the Joint European Torus with the ITER-Like Wall (JET-ILW), where a significant increase in the deuterium–deuterium (D–D) fusion neutron rate (~2.8 × 10 16 s -1) was achieved with stable high neutral beam injection (NBI) powers of up to 28 MW and low gas puffing. Increase in T i exceeding T e were produced for the first time in baseline discharges despite the high electron density; this enabled a significant increase in the thermal fusion reaction rate. As a result, the new achievedmore » record in fusion performance was much higher than the previous record in the same heating power baseline discharges, where T i = T e. In addition to the decreases in collisionality and the increases in ion heating fraction in the discharges with high NBI power, T i > T e can also be attributed to positive feedback between the high T i/T e ratio and stabilisation of the turbulent heat flux resulting from the ion temperature gradient driven mode. The high T i/T e ratio was correlated with high rotation frequency. Among the discharges with identical beam heating power, higher rotation frequencies were observed when particle fuelling was provided by low gas puffing and pellet injection. Lastly, this reveals that particle fuelling played a key role for achieving high T i/T e, and the improved fusion performance.« less

High fusion performance at high T i/ T e in JET-ILW baseline plasmas with high NBI heating power and low gas puffing

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

Kim, Hyun-Tae; Sips, A. C. C.; Romanelli, M.

This article presents the transport analysis of high density baseline discharges in the 2016 experimental campaign of the Joint European Torus with the ITER-Like Wall (JET-ILW), where a significant increase in the deuterium–deuterium (D–D) fusion neutron rate (~2.8 × 10 16 s -1) was achieved with stable high neutral beam injection (NBI) powers of up to 28 MW and low gas puffing. Increase in T i exceeding T e were produced for the first time in baseline discharges despite the high electron density; this enabled a significant increase in the thermal fusion reaction rate. As a result, the new achievedmore » record in fusion performance was much higher than the previous record in the same heating power baseline discharges, where T i = T e. In addition to the decreases in collisionality and the increases in ion heating fraction in the discharges with high NBI power, T i > T e can also be attributed to positive feedback between the high T i/T e ratio and stabilisation of the turbulent heat flux resulting from the ion temperature gradient driven mode. The high T i/T e ratio was correlated with high rotation frequency. Among the discharges with identical beam heating power, higher rotation frequencies were observed when particle fuelling was provided by low gas puffing and pellet injection. Lastly, this reveals that particle fuelling played a key role for achieving high T i/T e, and the improved fusion performance.« less

High fusion performance at high T i/T e in JET-ILW baseline plasmas with high NBI heating power and low gas puffing

NASA Astrophysics Data System (ADS)

Kim, Hyun-Tae; Sips, A. C. C.; Romanelli, M.; Challis, C. D.; Rimini, F.; Garzotti, L.; Lerche, E.; Buchanan, J.; Yuan, X.; Kaye, S.; contributors, JET

2018-03-01

This paper presents the transport analysis of high density baseline discharges in the 2016 experimental campaign of the Joint European Torus with the ITER-Like Wall (JET-ILW), where a significant increase in the deuterium-deuterium (D-D) fusion neutron rate (~2.8  ×  1016 s-1) was achieved with stable high neutral beam injection (NBI) powers of up to 28 MW and low gas puffing. Increase in T i exceeding T e were produced for the first time in baseline discharges despite the high electron density; this enabled a significant increase in the thermal fusion reaction rate. As a result, the new achieved record in fusion performance was much higher than the previous record in the same heating power baseline discharges, where T i  =  T e. In addition to the decreases in collisionality and the increases in ion heating fraction in the discharges with high NBI power, T i  >  T e can also be attributed to positive feedback between the high T i/T e ratio and stabilisation of the turbulent heat flux resulting from the ion temperature gradient driven mode. The high T i/T e ratio was correlated with high rotation frequency. Among the discharges with identical beam heating power, higher rotation frequencies were observed when particle fuelling was provided by low gas puffing and pellet injection. This reveals that particle fuelling played a key role for achieving high T i/T e, and the improved fusion performance.

Calcium-dependent regulation of SNARE-mediated membrane fusion by calmodulin.

PubMed

Di Giovanni, Jerome; Iborra, Cécile; Maulet, Yves; Lévêque, Christian; El Far, Oussama; Seagar, Michael

2010-07-30

Neuroexocytosis requires SNARE proteins, which assemble into trans complexes at the synaptic vesicle/plasma membrane interface and mediate bilayer fusion. Ca(2+) sensitivity is thought to be conferred by synaptotagmin, although the ubiquitous Ca(2+)-effector calmodulin has also been implicated in SNARE-dependent membrane fusion. To examine the molecular mechanisms involved, we examined the direct action of calmodulin and synaptotagmin in vitro, using fluorescence resonance energy transfer to assay lipid mixing between target- and vesicle-SNARE liposomes. Ca(2+)/calmodulin inhibited SNARE assembly and membrane fusion by binding to two distinct motifs located in the membrane-proximal regions of VAMP2 (K(D) = 500 nm) and syntaxin 1 (K(D) = 2 microm). In contrast, fusion was increased by full-length synaptotagmin 1 anchored in vesicle-SNARE liposomes. When synaptotagmin and calmodulin were combined, synaptotagmin overcame the inhibitory effects of calmodulin. Furthermore, synaptotagmin displaced calmodulin binding to target-SNAREs. These findings suggest that two distinct Ca(2+) sensors act antagonistically in SNARE-mediated fusion.

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

Garcia, Natalie K.; Guttman, Miklos; Ebner, Jamie L.

Influenza hemagglutinin (HA) mediates virus attachment to host cells and fusion of the viral and endosomal membranes during entry. While high-resolution structures are available for the pre-fusion HA ectodomain and the post-fusion HA2 subunit, the sequence of conformational changes during HA activation has eluded structural characterization. In this paper, we apply hydrogen-deuterium exchange with mass spectrometry to examine changes in structural dynamics of the HA ectodomain at various stages of activation, and compare the soluble ectodomain with intact HA on virions. At pH conditions approaching activation (pH 6.0–5.5) HA exhibits increased dynamics at the fusion peptide and neighboring regions, whilemore » the interface between receptor binding subunits (HA1) becomes stabilized. In contrast to many activation models, these data suggest that HA responds to endosomal acidification by releasing the fusion peptide prior to HA1 uncaging and the spring-loaded refolding of HA2. Finally, this staged process may facilitate efficient HA-mediated fusion.« less

Reliability of Measured Data for pH Sensor Arrays with Fault Diagnosis and Data Fusion Based on LabVIEW

PubMed Central

Liao, Yi-Hung; Chou, Jung-Chuan; Lin, Chin-Yi

2013-01-01

Fault diagnosis (FD) and data fusion (DF) technologies implemented in the LabVIEW program were used for a ruthenium dioxide pH sensor array. The purpose of the fault diagnosis and data fusion technologies is to increase the reliability of measured data. Data fusion is a very useful statistical method used for sensor arrays in many fields. Fault diagnosis is used to avoid sensor faults and to measure errors in the electrochemical measurement system, therefore, in this study, we use fault diagnosis to remove any faulty sensors in advance, and then proceed with data fusion in the sensor array. The average, self-adaptive and coefficient of variance data fusion methods are used in this study. The pH electrode is fabricated with ruthenium dioxide (RuO2) sensing membrane using a sputtering system to deposit it onto a silicon substrate, and eight RuO2 pH electrodes are fabricated to form a sensor array for this study. PMID:24351636

Reliability of measured data for pH sensor arrays with fault diagnosis and data fusion based on LabVIEW.

PubMed

Liao, Yi-Hung; Chou, Jung-Chuan; Lin, Chin-Yi

2013-12-13

Fault diagnosis (FD) and data fusion (DF) technologies implemented in the LabVIEW program were used for a ruthenium dioxide pH sensor array. The purpose of the fault diagnosis and data fusion technologies is to increase the reliability of measured data. Data fusion is a very useful statistical method used for sensor arrays in many fields. Fault diagnosis is used to avoid sensor faults and to measure errors in the electrochemical measurement system, therefore, in this study, we use fault diagnosis to remove any faulty sensors in advance, and then proceed with data fusion in the sensor array. The average, self-adaptive and coefficient of variance data fusion methods are used in this study. The pH electrode is fabricated with ruthenium dioxide (RuO2) sensing membrane using a sputtering system to deposit it onto a silicon substrate, and eight RuO2 pH electrodes are fabricated to form a sensor array for this study.

Dynamic changes during acid-induced activation of influenza hemagglutinin

DOE PAGES

Garcia, Natalie K.; Guttman, Miklos; Ebner, Jamie L.; ...

2015-03-12

Influenza hemagglutinin (HA) mediates virus attachment to host cells and fusion of the viral and endosomal membranes during entry. While high-resolution structures are available for the pre-fusion HA ectodomain and the post-fusion HA2 subunit, the sequence of conformational changes during HA activation has eluded structural characterization. In this paper, we apply hydrogen-deuterium exchange with mass spectrometry to examine changes in structural dynamics of the HA ectodomain at various stages of activation, and compare the soluble ectodomain with intact HA on virions. At pH conditions approaching activation (pH 6.0–5.5) HA exhibits increased dynamics at the fusion peptide and neighboring regions, whilemore » the interface between receptor binding subunits (HA1) becomes stabilized. In contrast to many activation models, these data suggest that HA responds to endosomal acidification by releasing the fusion peptide prior to HA1 uncaging and the spring-loaded refolding of HA2. Finally, this staged process may facilitate efficient HA-mediated fusion.« less

Requirement of myomaker-mediated stem cell fusion for skeletal muscle hypertrophy.

PubMed

Goh, Qingnian; Millay, Douglas P

2017-02-10

Fusion of skeletal muscle stem/progenitor cells is required for proper development and regeneration, however the significance of this process during adult muscle hypertrophy has not been explored. In response to muscle overload after synergist ablation in mice, we show that myomaker, a muscle specific membrane protein essential for myoblast fusion, is activated mainly in muscle progenitors and not myofibers. We rendered muscle progenitors fusion-incompetent through genetic deletion of myomaker in muscle stem cells and observed a complete reduction of overload-induced hypertrophy. This blunted hypertrophic response was associated with a reduction in Akt and p70s6k signaling and protein synthesis, suggesting a link between myonuclear accretion and activation of pro-hypertrophic pathways. Furthermore, fusion-incompetent muscle exhibited increased fibrosis after muscle overload, indicating a protective role for normal stem cell activity in reducing myofiber strain associated with hypertrophy. These findings reveal an essential contribution of myomaker-mediated stem cell fusion during physiological adult muscle hypertrophy.

Pretargeting with bispecific fusion proteins facilitates delivery of nanoparticles to tumor cells with distinct surface antigens.

PubMed

Yang, Qi; Parker, Christina L; Lin, Yukang; Press, Oliver W; Park, Steven I; Lai, Samuel K

2017-06-10

Tumor heterogeneity, which describes the genetically and phenotypically distinct subpopulations of tumor cells present within the same tumor or patient, presents a major challenge to targeted delivery of diagnostic and/or therapeutic agents. An ideal targeting strategy should deliver a given nanocarrier to the full diversity of cancer cells, which is difficult to achieve with conventional ligand-conjugated nanoparticles. We evaluated pretargeting (i.e., multistep targeting) as a strategy to facilitate nanoparticle delivery to multiple target cells by measuring the uptake of biotinylated nanoparticles by lymphoma cells with distinct surface antigens pretreated with different bispecific streptavidin-scFv fusion proteins. Fusion proteins targeting CD20 or tumor-associated glycoprotein 72 (TAG-72) mediated the specific in vitro uptake of 100nm biotin-functionalized nanoparticles by Raji and Jurkat lymphoma cells (CD20-positive and TAG-72-positive cells, respectively). Greater uptake was observed for pretargeted nanoparticles with increasing amounts of surface biotin, with 6- to 18-fold higher uptake vs. non-biotinylated nanoparticle and fusion protein controls. Fully biotin-modified particles remained resistant to cultured macrophage cell uptake, although they were still quickly cleared from systemic circulation in vivo (t 1/2 <1h). For single Raji tumor-bearing mice, pretargeting with CD20-specific FP significantly increased nanoparticle tumor targeting. In mice bearing both Raji and Jurkat tumors, pretargeting with both fusion proteins markedly increased nanoparticle targeting to both tumor types, compared to animals dosed with nanoparticles alone. These in vitro and in vivo observations support further evaluations of pretargeting fusion protein cocktails as a strategy to enhance nanoparticle delivery to a diverse array of molecularly distinct target cells. Copyright © 2017 Elsevier B.V. All rights reserved.

Disassembly time of deuterium-cluster-fusion plasma irradiated by an intense laser pulse.

PubMed

Bang, W

2015-07-01

Energetic deuterium ions from large deuterium clusters (>10nm diameter) irradiated by an intense laser pulse (>10(16)W/cm(2)) produce DD fusion neutrons for a time interval determined by the geometry of the resulting fusion plasma. We present an analytical solution of this time interval, the plasma disassembly time, for deuterium plasmas that are cylindrical in shape. Assuming a symmetrically expanding deuterium plasma, we calculate the expected fusion neutron yield and compare with an independent calculation of the yield using the concept of a finite confinement time at a fixed plasma density. The calculated neutron yields agree quantitatively with the available experimental data. Our one-dimensional simulations indicate that one could expect a tenfold increase in total neutron yield by magnetically confining a 10-keV deuterium fusion plasma for 10ns.

Post-fusion treatment with MG132 increases transcription factor expression in somatic cell nuclear transfer embryos in pigs.

PubMed

You, Jinyoung; Lee, Joohyeong; Kim, Jinyoung; Park, Junhong; Lee, Eunsong

2010-02-01

The objective of this study was to examine the effect of post-fusion treatment of somatic cell nuclear transfer (SCNT) oocytes with the proteasomal inhibitor MG132 on maturation promoting factor (MPF) activity, nuclear remodeling, embryonic development, and gene expression of cloned pig embryos. Immediately after electrofusion, SCNT oocytes were treated with MG132 and/or caffeine for 2 hr, vanadate for 0.5 hr, or vanadate for 0.5 hr followed by MG132 for 1.5 hr. Of the MG132 concentrations tested (0-5 microM), the 1 microM concentration showed a higher rate of blastocyst formation (25.9%) than 0 (14.2%), 0.5 (16.9%), and 5 microM (16.9%). Post-fusion treatment with MG132, caffeine, and both MG132 and caffeine improved blastocyst formation (22.1%, 21.4%, and 24.4%, respectively), whereas vanadate treatment inhibited blastocyst formation (6.5%) compared to the control (11.1%). When examined 2 hr after fusion and 1 hr after activation, MPF activity remained at a higher (P < 0.05) level in SCNT oocytes that were treated post-fusion with caffeine and/or MG132, but it was decreased by vanadate. The rate of oocytes showing premature chromosome condensation was not altered by MG132 but was decreased by vanadate treatment. In addition, formation of single pronuclei was increased by MG132 compared to control and vanadate treatment. MG132-treated embryos showed increased expression of POU5F1, DPPA2, DPPA3, DPPA5, and NDP52l1 genes compared to control embryos. Our results demonstrate that post-fusion treatment of SCNT oocytes with MG132 prevents MPF degradation and increases expression of transcription factors in SCNT embryos, which are necessary for normal development of SCNT embryos. (c) 2009 Wiley-Liss, Inc.

Resveratrol stimulates mitochondrial fusion by a mechanism requiring mitofusin-2.

PubMed

Robb, Ellen L; Moradi, Fereshteh; Maddalena, Lucas A; Valente, Andrew J F; Fonseca, Joao; Stuart, Jeffrey A

2017-04-01

Resveratrol (RES) is a plant-derived stilbene associated with a wide range of health benefits. Mitochondria are a key downstream target of RES, and in some cell types RES promotes mitochondrial biogenesis, altered cellular redox status, and a shift toward oxidative metabolism. Mitochondria exist as a dynamic network that continually remodels via fusion and fission processes, and the extent of fusion is related to cellular redox status and metabolism. We investigated RES's effects on mitochondrial network morphology in several cell lines using a quantitative approach to measure the extent of network fusion. 48 h continuous treatment with 10-20 μM RES stimulated mitochondrial fusion in C2C12 myoblasts, PC3 cancer cells, and mouse embryonic fibroblasts stimulated significant increases in fusion in all instances, resulting in larger and more highly branched mitochondrial networks. Mitofusin-2 (Mfn2) is a key protein facilitating mitochondrial fusion, and its expression was also stimulated by RES. Using Mfn2-null cells we demonstrated that RES's effects on mitochondrial fusion, cellular respiration rates, and cell growth are all dependent upon the presence of Mfn2. Taken together, these results demonstrate that Mfn2 and mitochondrial fusion are affected by RES in ways that appear to relate to RES's known effects on cellular metabolism and growth. Copyright © 2017 Elsevier Inc. All rights reserved.

SARS-CoV fusion peptides induce membrane surface ordering and curvature

PubMed Central

Basso, Luis G. M.; Vicente, Eduardo F.; Crusca Jr., Edson; Cilli, Eduardo M.; Costa-Filho, Antonio J.

2016-01-01

Viral membrane fusion is an orchestrated process triggered by membrane-anchored viral fusion glycoproteins. The S2 subunit of the spike glycoprotein from severe acute respiratory syndrome (SARS) coronavirus (CoV) contains internal domains called fusion peptides (FP) that play essential roles in virus entry. Although membrane fusion has been broadly studied, there are still major gaps in the molecular details of lipid rearrangements in the bilayer during fusion peptide-membrane interactions. Here we employed differential scanning calorimetry (DSC) and electron spin resonance (ESR) to gather information on the membrane fusion mechanism promoted by two putative SARS FPs. DSC data showed the peptides strongly perturb the structural integrity of anionic vesicles and support the hypothesis that the peptides generate opposing curvature stresses on phosphatidylethanolamine membranes. ESR showed that both FPs increase lipid packing and head group ordering as well as reduce the intramembrane water content for anionic membranes. Therefore, bending moment in the bilayer could be generated, promoting negative curvature. The significance of the ordering effect, membrane dehydration, changes in the curvature properties and the possible role of negatively charged phospholipids in helping to overcome the high kinetic barrier involved in the different stages of the SARS-CoV-mediated membrane fusion are discussed. PMID:27892522

Inner membrane fusion mediates spatial distribution of axonal mitochondria

PubMed Central

Yu, Yiyi; Lee, Hao-Chih; Chen, Kuan-Chieh; Suhan, Joseph; Qiu, Minhua; Ba, Qinle; Yang, Ge

2016-01-01

In eukaryotic cells, mitochondria form a dynamic interconnected network to respond to changing needs at different subcellular locations. A fundamental yet unanswered question regarding this network is whether, and if so how, local fusion and fission of individual mitochondria affect their global distribution. To address this question, we developed high-resolution computational image analysis techniques to examine the relations between mitochondrial fusion/fission and spatial distribution within the axon of Drosophila larval neurons. We found that stationary and moving mitochondria underwent fusion and fission regularly but followed different spatial distribution patterns and exhibited different morphology. Disruption of inner membrane fusion by knockdown of dOpa1, Drosophila Optic Atrophy 1, not only increased the spatial density of stationary and moving mitochondria but also changed their spatial distributions and morphology differentially. Knockdown of dOpa1 also impaired axonal transport of mitochondria. But the changed spatial distributions of mitochondria resulted primarily from disruption of inner membrane fusion because knockdown of Milton, a mitochondrial kinesin-1 adapter, caused similar transport velocity impairment but different spatial distributions. Together, our data reveals that stationary mitochondria within the axon interconnect with moving mitochondria through fusion and fission and that local inner membrane fusion between individual mitochondria mediates their global distribution. PMID:26742817

Fusion of agarase and neoagarobiose hydrolase for mono-sugar production from agar.

PubMed

Alkotaini, Bassam; Han, Nam Soo; Kim, Beom Soo

2017-02-01

In enzymatic saccharification of agar, endo- and exo-agarases together with neoagarobiose hydrolase (NABH) are important key enzymes for the sequential hydrolysis reactions. In this study, a bifunctional endo/exo-agarase was fused with NABH for production of mono-sugars (D-galactose and 3,6-anhydro-L-galactose) from agar using only one fusion enzyme. Two fusion enzymes with either bifunctional agarase (Sco3476) or NABH (Zg4663) at the N-terminus, Sco3476-Zg4663 (SZ) and Zg4663-Sco3476 (ZS), were constructed. Both fusion enzymes exhibited their optimal agarase and NABH activities at 40 and 35 °C, respectively. Fusions SZ and ZS enhanced the thermostability of the NABH activity, while only fusion SZ showed a slight enhancement in the NABH catalytic efficiency (K cat /K M ) from 14.8 (mg/mL) -1  s -1 to 15.8 (mg/mL) -1  s -1 . Saccharification of agar using fusion SZ resulted in 2-fold higher mono-sugar production and 3-fold lower neoagarobiose accumulation when compared to the physical mixture of Sco3476 and Zg4663. Therefore, this fusion has the potential to reduce enzyme production cost, decrease intermediate accumulation, and increase mono-sugar yield in agar saccharification.

Effects of magnetization on fusion product trapping and secondary neutron spectra

DOE PAGES

Knapp, Patrick F.; Schmit, Paul F.; Hansen, Stephanie B.; ...

2015-05-14

In magnetizing the fusion fuel in inertial confinement fusion (ICF) systems, we found that the required stagnation pressure and density can be relaxed dramatically. This happens because the magnetic field insulates the hot fuel from the cold pusher and traps the charged fusion burn products. This trapping allows the burn products to deposit their energy in the fuel, facilitating plasma self-heating. Here, we report on a comprehensive theory of this trapping in a cylindrical DD plasma magnetized with a purely axial magnetic field. Using this theory, we are able to show that the secondary fusion reactions can be used tomore » infer the magnetic field-radius product, BR, during fusion burn. This parameter, not ρR, is the primary confinement parameter in magnetized ICF. Using this method, we analyze data from recent Magnetized Liner InertialFusion experiments conducted on the Z machine at Sandia National Laboratories. Furthermore, we show that in these experiments BR ≈ 0.34(+0.14/-0.06) MG · cm, a ~ 14× increase in BR from the initial value, and confirming that the DD-fusion tritons are magnetized at stagnation. Lastly, this is the first experimental verification of charged burn product magnetization facilitated by compression of an initial seed magnetic flux.« less

Inertial-Electrostatic Confinement (IEC) Fusion for Space Propulsion

NASA Technical Reports Server (NTRS)

Nadler, Jon

1999-01-01

An Inertial-Electrostatic Confinement (IEC) device was assembled at the Marshall Space Flight Center (MSFC) Propulsion Research Center (PRC) to study the possibility of using EEC technology for deep space propulsion and power. Inertial-Electrostatic Confinement is capable of containing a nuclear fusion plasma in a series of virtual potential wells. These wells would substantially increase plasma confinement, possibly leading towards a high-gain, breakthrough fusion device. A one-foot in diameter IEC vessel was borrowed from the Fusion Studies Laboratory at the University of Illinois@Urbana-Champaign for the summer. This device was used in initial parameterization studies in order to design a larger, actively cooled device for permanent use at the PRC.

Inertial-Electrostatic Confinement (IEC) Fusion For Space Propulsion

NASA Technical Reports Server (NTRS)

Nadler, Jon

1999-01-01

An Inertial-Electrostatic Confinement (IEC) device was assembled at the Marshall Space Flight Center (MSFC) Propulsion Research Center (PRC) to study the possibility of using IEC technology for deep space propulsion and power. Inertial-Electrostatic Confinement is capable of containing a nuclear fusion plasma in a series of virtual potential wells. These wells would substantially increase plasma confinement, possibly leading towards a high-gain, breakthrough fusion device. A one-foot in diameter IEC vessel was borrowed from the Fusion Studies Laboratory at the University of Illinois @ Urbana-Champaign for the summer. This device was used in initial parameterization studies in order to design a larger, actively cooled device for permanent use at the PRC.

Phylogenetic ecology at world scale, a new fusion between ecology and evolution.

PubMed

Westoby, Mark

2006-07-01

One fusion between ecology and evolution is well established, under the title of population biology. The years 2006-2020 will see a new fusion, likely to prove equally creative. Inputs from ecology to this second fusion will be worldwide data sets for ecological traits across many species. Inputs from evolution will be phylogenetic trees with well-resolved topology and with increasingly tight geological dates for each branch point. There will be unification of two aims: first to explain the spread of different ways of making a living, across the range of present-day species; and second, to narrate the evolutionary history that has led up to present-day ecology.

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.

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

Information Fusion and Visualisation in Anti Asymmetric Warfare

DTIC Science & Technology

2006-12-01

thermal detectors (e.g. bolometers). They used the MWIR and LWIR part of the IR spectrum. Quantum detectors realize an image rate of over 100Hz while... panorama image by image fusion of several sensors components. EO designators are distinguished through their agility and increased resolution

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

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.

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

Strain on intervertebral discs after anterior cervical decompression and fusion.

PubMed

Matsunaga, S; Kabayama, S; Yamamoto, T; Yone, K; Sakou, T; Nakanishi, K

1999-04-01

An analysis of the change in strain distribution of intervertebral discs present after anterior cervical decompression and fusion by an original method. The analytical results were compared to occurrence of herniation of the intervertebral disc on magnetic resonance imaging. To elucidate the influence of anterior cervical decompression and fusion on the unfused segments of the spine. There is no consensus regarding the exact significance of the biomechanical change in the unfused segment present after surgery. Ninety-six patients subjected to anterior cervical decompression and fusion for herniation of intervertebral discs were examined. Shear strain and longitudinal strain of intervertebral discs were analyzed on pre- and postoperative lateral dynamic routine radiography of the cervical spine. Thirty of the 96 patients were examined by magnetic resonance imaging before and after surgery, and the relation between alteration in strains and postsurgical occurrence of disc herniation was examined. In the cases of double- or triple-level fusion, shear strain of adjacent segments had increased 20% on average 1 year after surgery. Thirteen intervertebral discs that had an abnormally high degree of strain showed an increase in longitudinal strain after surgery. Eleven (85%) of the 13 discs that showed an abnormal increase in longitudinal strain had herniation in the same intervertebral discs with compression of the spinal cord during the follow-up period. Relief of symptoms was significantly poor in the patients with recent herniation. Close attention should be paid to long-term biomechanical changes in the unfused segment.

Multilevel lumbar fusion and postoperative physiotherapy rehabilitation in a patient with persistent pain.

PubMed

Pons, Tracey; Shipton, Edward A

2011-04-01

There are no comparative randomised controlled trials of physiotherapy modalities for chronic low back and radicular pain associated with multilevel fusion. Physiotherapy-based rehabilitation to control pain and improve activation levels for persistent pain following multilevel fusion can be challenging. This is a case report of a 68-year-old man who was referred for physiotherapy intervention 10 months after a multilevel spinal fusion for spinal stenosis. He reported high levels of persistent postoperative pain with minimal activity as a consequence of his pain following the surgery. The physiotherapy interventions consisted of three phases of rehabilitation starting with pool exercise that progressed to land-based walking. These were all combined with transcutaneous electrical nerve stimulation (TENS) that was used consistently for up to 8 hours per day. As outcome measures, daily pain levels and walking distances were charted once the pool programme was completed (in the third phase). Phase progression was determined by shuttle test results. The pain level was correlated with the distance walked using linear regression over a 5-day average. Over a 5-day moving average, the pain level reduced and walking distance increased. The chart of recorded pain level and walking distance showed a trend toward decreased pain with the increased distance walked. In a patient undergoing multilevel lumbar fusion, the combined use of TENS and a progressive walking programme (from pool to land) reduced pain and increased walking distance. This improvement was despite poor medication compliance and a reported high level of postsurgical pain.

Mechanical Coupling via the Membrane Fusion SNARE Protein Syntaxin 1A: A Molecular Dynamics Study

PubMed Central

Knecht, Volker; Grubmüller, Helmut

2003-01-01

SNARE trans complexes between membranes likely promote membrane fusion. For the t-SNARE syntaxin 1A involved in synaptic transmission, the secondary structure and bending stiffness of the five-residue juxtamembrane linker is assumed to determine the required mechanical energy transfer from the cytosolic core complex to the membrane. These properties have here been studied by molecular dynamics and annealing simulations for the wild-type and a C-terminal-prolongated mutant within a neutral and an acidic bilayer, suggesting linker stiffnesses above 1.7 but below 50 × 10−3 kcal mol−1 deg−2. The transmembrane helix was found to be tilted by 15° and tightly anchored within the membrane with a stiffness of 4–5 kcal mol−1 Å−2. The linker turned out to be marginally helical and strongly influenced by its lipid environment. Charged lipids increased the helicity and H3 helix tilt stiffness. For the wild type, the linker was seen embedded deeply within the polar region of the bilayer, whereas the prolongation shifted the linker outward. This reduced its helicity and increased its average tilt, thereby presumably reducing fusion efficiency. Our results suggest that partially unstructured linkers provide considerable mechanical coupling; the energy transduced cooperatively by the linkers in a native fusion event is thus estimated to be 3–8 kcal/mol, implying a two-to-five orders of magnitude fusion rate increase. PMID:12609859

Gallium arsenide-gallium nitride wafer fusion and the n-aluminum gallium arsenide/p-gallium arsenide/n-gallium nitride double heterojunction bipolar transistor

NASA Astrophysics Data System (ADS)

Estrada, Sarah M.

This dissertation describes the n-AlGaAs/p-GaAs/n-GaN heterojunction bipolar transistor (HBT), the first transistor formed via wafer fusion. The fusion process was developed as a way to combine lattice-mismatched materials for high-performance electronic devices, not obtainable via conventional all-epitaxial formation methods. Despite the many challenges of wafer fusion, successful transistors were demonstrated and improved, via the optimization of material structure and fusion process conditions. Thus, this project demonstrated the integration of disparate device materials, chosen for their optimal electronic properties, unrestricted by the conventional (and very limiting) requirement of lattice-matching. By combining an AlGaAs-GaAs emitter-base with a GaN collector, the HBT benefited from the high breakdown voltage of GaN, and from the high emitter injection efficiency and low base transit time of AlGaAs-GaAs. Because the GaAs-GaN lattice mismatch precluded an all-epitaxial formation of the HBT, the GaAs-GaN heterostructure was formed via fusion. This project began with the development of a fusion process that formed mechanically robust and electrically active GaAs-GaN heterojunctions. During the correlation of device electrical performance with a systematic variation of fusion conditions over a wide range (500--750°C, 0.5--2hours), a mid-range fusion temperature was found to induce optimal HBT electrical performance. Transmission electron microscopy (TEM) and secondary ion mass spectrometry (SIMS) were used to assess possible reasons for the variations observed in device electrical performance. Fusion process conditions were correlated with electrical (I-V), structural (TEM), and chemical (SIMS) analyses of the resulting heterojunctions, in order to investigate the trade-off between increased interfacial disorder (TEM) with low fusion temperature and increased diffusion (SIMS) with high fusion temperature. The best do device results (IC ˜ 2.9 kA/cm2 and beta ˜ 3.5, at VCE = 20V and IB = 10mA) were obtained with an HBT formed via fusion at 600°C for 1 hour, with an optimized base-collector design. This was quite an improvement, as compared to an HBT with a simpler base-collector structure, also fused at 600°C for 1 hour (IC ˜ 0.83 kA/cm2 and beta ˜ 0.89, at VCE = 20V and IB = 10mA). Fused AlGaAs-GaAs-GaAs HBTs were compared to fused AlGaAs-GaAs-GaN HBTs, demonstrating that the use of a wider bandgap collector (Eg,GaN > Eg,GaAs) did indeed improve HBT performance at high applied voltages, as desired for high-power applications.

Characterization of ergocalciferol loaded solid lipid nanoparticles.

PubMed

Patel, Mandar R; San Martin-Gonzalez, M Fernanda

2012-01-01

The use of solid lipid nanoparticles (SLNs) is a technique that has been widely used in the pharmaceutical industry for the last 2 decades and has become of increasing interest to food scientists due to its potential for encapsulation and controlled release. Ergocalciferol (vitamin D₂) is a bioactive compound whose deficiency may lead to rickets in children and osteomalacia in adults. In this study, ergocalciferol was encapsulated in tripalmitin SLNs stabilized by polysorbate 20 (Tween 20). SLN dispersions (5% w/w) were prepared by hot homogenization technique using a nozzle-type high-pressure homogenizer. Ergocalciferol at 0%, 5%, 10%, 15%, and 20% (w/w of lipid) was dissolved in the molten lipid at 80 °C, mixed with a 5% (w/w) aqueous solution of polysorbate 20 and homogenized at 138 MPa at 80 °C. Particle size, thermal properties, and microstructure were evaluated by dynamic light scattering (DLS), differential scanning calorimetry (DSC), and transmission electron microscopy (TEM) respectively. As the proportion of ergocalciferol in the SLN increased from 0% to 20%, the Z-average values of the particles gradually decreased (P≤ 0.05) from approximately 120 nm to approximately 65 nm. DSC analysis of freeze dried SLN samples showed gradual decrease in enthalpies of fusion and crystallization for stable β-subcell whereas for SLN dispersions, the enthalpy of fusion of unstable α-subcell crystal increased with increased ergocalciferol loading. The TEM images of the ergocalciferol loaded SLN samples showed the presence of spherical as well as rod-shaped nanoparticles. It was also observed that the turbidity of the SLN dispersions reduced noticeably with increased ergocalciferol loading. This finding could be useful in terms of fortification of clear juices with ergocalciferol. Solid lipid nanoparticles (SLNs) were used in this study to encapsulate vitamin D₂, a vitamin important for bone health. It was found that as the concentration of vitamin D₂ increased in the lipid phase of SLN dispersion, the clarity of the dispersion increased. Also, with increased vitamin D₂ concentration, the stability of lipid crystal structure was affected in a way that indicates higher capacity of lipid to incorporate the vitamin molecules and hence to protect them better from oxygen and light. This vitamin loaded SLNs may offer alternatives to milk and margarine as a source of vitamin D. © 2011 Institute of Food Technologists®

TRAIL-CM4 fusion protein shows in vitro antibacterial activity and a stronger antitumor activity than solo TRAIL protein.

PubMed

Sang, Ming; Zhang, Jiaxin; Li, Bin; Chen, Yuqing

2016-06-01

A TRAIL-CM4 fusion protein in soluble form with tumor selective apoptosis and antibacterial functions was expressed in the Escherichia coli expression system and isolated through dialysis refolding and histidine-tag Nickel-affinity purification. Fresh Jurkat cells were treated with the TRAIL-CM4 fusion protein. Trypan blue staining and MTT analyses showed that, similar to a TRAIL positive control, Jurkat cell proliferation was significantly inhibited. Flow cytometry analyses using Annexin V-fluorescein revealed that Jurkat cells treated with the TRAIL-CM4 fusion protein exhibited increased apoptosis. Laser confocal microscopy showed that APB-CM4 and the fusion protein TRAIL-CM4 can bind to Jurkat cell membranes and initiate their destruction. ABP-CM4 enhances the antitumor activity of TRAIL by targeting and damaging the tumor cell membrane. In antibacterial experiments, agar well diffusion and bacterial growth inhibition curve assays revealed concentration-dependent TRAIL-CM4 antibacterial activity against Escherichia coli K12D31. The expressed TRAIL-CM4 fusion protein exhibited enhanced antitumor and antibacterial activities. Fusion protein expression allowed the two different proteins to function in combination. Copyright © 2016 Elsevier Inc. All rights reserved.

[Contrast-enhanced ultrasound (CEUS) and image fusion for procedures of liver interventions].

PubMed

Jung, E M; Clevert, D A

2018-06-01

Contrast-enhanced ultrasound (CEUS) is becoming increasingly important for the detection and characterization of malignant liver lesions and allows percutaneous treatment when surgery is not possible. Contrast-enhanced ultrasound image fusion with computed tomography (CT) and magnetic resonance imaging (MRI) opens up further options for the targeted investigation of a modified tumor treatment. Ultrasound image fusion offers the potential for real-time imaging and can be combined with other cross-sectional imaging techniques as well as CEUS. With the implementation of ultrasound contrast agents and image fusion, ultrasound has been improved in the detection and characterization of liver lesions in comparison to other cross-sectional imaging techniques. In addition, this method can also be used for intervention procedures. The success rate of fusion-guided biopsies or CEUS-guided tumor ablation lies between 80 and 100% in the literature. Ultrasound-guided image fusion using CT or MRI data, in combination with CEUS, can facilitate diagnosis and therapy follow-up after liver interventions. In addition to the primary applications of image fusion in the diagnosis and treatment of liver lesions, further useful indications can be integrated into daily work. These include, for example, intraoperative and vascular applications as well applications in other organ systems.

Will fusion be ready to meet the energy challenge for the 21st century?

NASA Astrophysics Data System (ADS)

Bréchet, Yves; Massard, Thierry

2016-05-01

Finite amount of fossil fuel, global warming, increasing demand of energies in emerging countries tend to promote new sources of energies to meet the needs of the coming centuries. Despite their attractiveness, renewable energies will not be sufficient both because of intermittency but also because of the pressure they would put on conventional materials. Thus nuclear energy with both fission and fusion reactors remain the main potential source of clean energy for the coming centuries. France has made a strong commitment to fusion reactor through ITER program. But following and sharing Euratom vision on fusion, France supports the academic program on Inertial Fusion Confinement with direct drive and especially the shock ignition scheme which is heavily studied among the French academic community. LMJ a defense facility for nuclear deterrence is also open to academic community along with a unique PW class laser PETAL. Research on fusion at LMJ-PETAL is one of the designated topics for experiments on the facility. Pairing with other smaller European facilities such as Orion, PALS or LULI2000, LMJ-PETAL will bring new and exciting results and contribution in fusion science in the coming years.

Time-Lapse Cinemicrographic Studies of X-Irradiated HeLa S3 Cells

PubMed Central

Hurwitz, Camilla; Tolmach, L. J.

1969-01-01

Analysis of time-lapse cinemicrographs of X-irradiated HeLa S3 cells has shown that the incidence of cell fusion was increased from 0.9% (following 1267 divisions) in control cells to an average of 22% (following 655 divisions) in cells irradiated with 500 rad doses of 220 kv X-rays. The incidence depended on the stage of the generation cycle at which the parent cells were irradiated. It was nearly constant in the first three postirradiation generations. Fusion occurred at all stages of the generation cycle, but preferentially during the first 20%. Cells undergoing fusion progressed more slowly through the generation cycle and had a higher probability of disintegrating than did irradiated cells that did not fuse. The occurrence of fusion was clonally distributed in the population. It took place only between sister (or closely related) cells. Protoplasmic bridges were often visible between sister cells prior to fusion. Giant cells arose only as a result of fusion. The incidence of multipolar divisions, though higher than in unirradiated cells, was only 5.5% in cultures irradiated with 500 rads. Fusion occurred following 85% of the multipolar divisions and was often followed by a multipolar division. ImagesFigure 1 PMID:5807221

Development of fusogenic glass surfaces that impart spatiotemporal control over macrophage fusion: Direct visualization of multinucleated giant cell formation.

PubMed

Faust, James J; Christenson, Wayne; Doudrick, Kyle; Ros, Robert; Ugarova, Tatiana P

2017-06-01

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, α M β 2 ) 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. Copyright © 2017 Elsevier Ltd. All rights reserved.

Percutaneous Thermal Ablation with Ultrasound Guidance. Fusion Imaging Guidance to Improve Conspicuity of Liver Metastasis

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

Hakime, Antoine, E-mail: thakime@yahoo.com; Yevich, Steven; Tselikas, Lambros

PurposeTo assess whether fusion imaging-guided percutaneous microwave ablation (MWA) can improve visibility and targeting of liver metastasis that were deemed inconspicuous on ultrasound (US).Materials and MethodsMWA of liver metastasis not judged conspicuous enough on US was performed under CT/US fusion imaging guidance. The conspicuity before and after the fusion imaging was graded on a five-point scale, and significance was assessed by Wilcoxon test. Technical success, procedure time, and procedure-related complications were evaluated.ResultsA total of 35 patients with 40 liver metastases (mean size 1.3 ± 0.4 cm) were enrolled. Image fusion improved conspicuity sufficiently to allow fusion-targeted MWA in 33 patients. The time requiredmore » for image fusion processing and tumors’ identification averaged 10 ± 2.1 min (range 5–14). Initial conspicuity on US by inclusion criteria was 1.2 ± 0.4 (range 0–2), while conspicuity after localization on fusion imaging was 3.5 ± 1 (range 1–5, p < 0.001). Technical success rate was 83% (33/40) in intention-to-treat analysis and 100% in analysis of treated tumors. There were no major procedure-related complications.ConclusionsFusion imaging broadens the scope of US-guided MWA to metastasis lacking adequate conspicuity on conventional US. Fusion imaging is an effective tool to increase the conspicuity of liver metastases that were initially deemed non visualizable on conventional US imaging.« less

Advances in Multi-Sensor Information Fusion: Theory and Applications 2017.

PubMed

Jin, Xue-Bo; Sun, Shuli; Wei, Hong; Yang, Feng-Bao

2018-04-11

The information fusion technique can integrate a large amount of data and knowledge representing the same real-world object and obtain a consistent, accurate, and useful representation of that object. The data may be independent or redundant, and can be obtained by different sensors at the same time or at different times. A suitable combination of investigative methods can substantially increase the profit of information in comparison with that from a single sensor. Multi-sensor information fusion has been a key issue in sensor research since the 1970s, and it has been applied in many fields. For example, manufacturing and process control industries can generate a lot of data, which have real, actionable business value. The fusion of these data can greatly improve productivity through digitization. The goal of this special issue is to report innovative ideas and solutions for multi-sensor information fusion in the emerging applications era, focusing on development, adoption, and applications.

Kinase gene fusions in defined subsets of melanoma.

PubMed

Turner, Jacqueline; Couts, Kasey; Sheren, Jamie; Saichaemchan, Siriwimon; Ariyawutyakorn, Witthawat; Avolio, Izabela; Cabral, Ethan; Glogowska, Magdelena; Amato, Carol; Robinson, Steven; Hintzsche, Jennifer; Applegate, Allison; Seelenfreund, Eric; Gonzalez, Rita; Wells, Keith; Bagby, Stacey; Tentler, John; Tan, Aik-Choon; Wisell, Joshua; Varella-Garcia, Marileila; Robinson, William

2017-01-01

Genomic rearrangements resulting in activating kinase fusions have been increasingly described in a number of cancers including malignant melanoma, but their frequency in specific melanoma subtypes has not been reported. We used break-apart fluorescence in situ hybridization (FISH) to identify genomic rearrangements in tissues from 59 patients with various types of malignant melanoma including acral lentiginous, mucosal, superficial spreading, and nodular. We identified four genomic rearrangements involving the genes BRAF, RET, and ROS1. Of these, three were confirmed by Immunohistochemistry (IHC) or sequencing and one was found to be an ARMC10-BRAF fusion that has not been previously reported in melanoma. These fusions occurred in different subtypes of melanoma but all in tumors lacking known driver mutations. Our data suggest gene fusions are more common than previously thought and should be further explored particularly in melanomas lacking known driver mutations. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Identification of syncytial mutations in a clinical isolate of herpes simplex virus 2

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

Muggeridge, Martin I.; Grantham, Michael L.; Center for Molecular and Tumor Virology, Louisiana State University Health Sciences Center, Shreveport, LA 71130

2004-10-25

Small polykaryocytes resulting from cell fusion are found in herpes simplex virus (HSV) lesions in patients, but their significance for viral spread and pathogenesis is unclear. Although syncytial variants causing extensive fusion in tissue culture can be readily isolated from laboratory strains, they are rarely found in clinical isolates, suggesting that extensive cell fusion may be deleterious in vivo. Syncytial mutations have previously been identified for several laboratory strains, but not for clinical isolates of HSV type 2. To address this deficiency, we studied a recent syncytial clinical isolate, finding it to be a mixture of two syncytial and onemore » nonsyncytial strain. The two syncytial strains have novel mutations in glycoprotein B, and in vitro cell fusion assays confirmed that they are responsible for syncytium formation. This panel of clinical strains may be ideal for examining the effect of increased cell fusion on pathogenesis.« less

From Data Acquisition to Data Fusion: A Comprehensive Review and a Roadmap for the Identification of Activities of Daily Living Using Mobile Devices

PubMed Central

Pires, Ivan Miguel; Garcia, Nuno M.; Pombo, Nuno; Flórez-Revuelta, Francisco

2016-01-01

This paper focuses on the research on the state of the art for sensor fusion techniques, applied to the sensors embedded in mobile devices, as a means to help identify the mobile device user’s daily activities. Sensor data fusion techniques are used to consolidate the data collected from several sensors, increasing the reliability of the algorithms for the identification of the different activities. However, mobile devices have several constraints, e.g., low memory, low battery life and low processing power, and some data fusion techniques are not suited to this scenario. The main purpose of this paper is to present an overview of the state of the art to identify examples of sensor data fusion techniques that can be applied to the sensors available in mobile devices aiming to identify activities of daily living (ADLs). PMID:26848664

Disassembly time of deuterium-cluster-fusion plasma irradiated by an intense laser pulse

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

Bang, W.

Energetic deuterium ions from large deuterium clusters (>10 nm diameter) irradiated by an intense laser pulse (>10¹⁶ W/cm²) produce DD fusion neutrons for a time interval determined by the geometry of the resulting fusion plasma. We show an analytical solution of this time interval, the plasma disassembly time, for deuterium plasmas that are cylindrical in shape. Assuming a symmetrically expanding deuterium plasma, we calculate the expected fusion neutron yield and compare with an independent calculation of the yield using the concept of a finite confinement time at a fixed plasma density. The calculated neutron yields agree quantitatively with the availablemore » experimental data. Our one-dimensional simulations indicate that one could expect a tenfold increase in total neutron yield by magnetically confining a 10 - keV deuterium fusion plasma for 10 ns.« less

Kinase Gene Fusions in Defined Subsets of Melanoma

PubMed Central

Turner, Jacqueline; Couts, Kasey; Sheren, Jamie; Saichaemchan, Siriwimon; Ariyawutyakorn, Witthawat; Avolio, Izabela; Cabral, Ethan; Glogowska, Magdelena; Amato, Carol; Robinson, Steven; Hintzsche, Jennifer; Applegate, Allison; Seelenfreund, Eric; Gonzalez, Rita; Wells, Keith; Bagby, Stacey; Tentler, John; Tan, Aik-Choon; Wisell, Joshua; Varella-Garcia, Marileila; Robinson, William

2017-01-01

Summary Genomic rearrangements resulting in activating kinase fusions have been increasingly described in a number of cancers including malignant melanoma, but their frequency in specific melanoma subtypes has not been reported. We used break-apart fluorescence in-situ hybridization (FISH) to identify genomic rearrangements in tissues from 59 patients with various types of malignant melanoma including acral lentiginous, mucosal, superficial spreading, and nodular. We identified four genomic rearrangements involving the genes BRAF, RET, and ROS1. Of these, three were confirmed by IHC or sequencing and one was found to be an ARMC10-BRAF fusion that has not been previously reported in melanoma. These fusions occurred in different subtypes of melanoma but all in tumors lacking known driver mutations. Our data suggest gene fusions are more common than previously thought-and should be further explored particularly in melanomas lacking known driver mutations. PMID:27864876

Disassembly time of deuterium-cluster-fusion plasma irradiated by an intense laser pulse

DOE PAGES

Bang, W.

2015-07-02

Energetic deuterium ions from large deuterium clusters (>10 nm diameter) irradiated by an intense laser pulse (>10¹⁶ W/cm²) produce DD fusion neutrons for a time interval determined by the geometry of the resulting fusion plasma. We show an analytical solution of this time interval, the plasma disassembly time, for deuterium plasmas that are cylindrical in shape. Assuming a symmetrically expanding deuterium plasma, we calculate the expected fusion neutron yield and compare with an independent calculation of the yield using the concept of a finite confinement time at a fixed plasma density. The calculated neutron yields agree quantitatively with the availablemore » experimental data. Our one-dimensional simulations indicate that one could expect a tenfold increase in total neutron yield by magnetically confining a 10 - keV deuterium fusion plasma for 10 ns.« less

Superior serum half life of albumin tagged TNF ligands

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

Mueller, Nicole; Schneider, Britta; Pfizenmaier, Klaus

2010-06-11

Due to their immune stimulating and apoptosis inducing properties, ligands of the TNF family attract increasing interest as therapeutic proteins. A general limitation of in vivo applications of recombinant soluble TNF ligands is their notoriously rapid clearance from circulation. To improve the serum half life of the TNF family members TNF, TWEAK and TRAIL, we genetically fused soluble variants of these molecules to human serum albumin (HSA). The serum albumin-TNF ligand fusion proteins were found to be of similar bioactivity as the corresponding HSA-less counterparts. Upon intravenous injection (i.v.), serum half life of HSA-TNF ligand fusion proteins, as determined bymore » ELISA, was around 15 h as compared to approximately 1 h for all of the recombinant control TNF ligands without HSA domain. Moreover, serum samples collected 6 or 24 h after i.v. injection still contained high TNF ligand bioactivity, demonstrating that there is only limited degradation/inactivation of circulating HSA-TNF ligand fusion proteins in vivo. In a xenotransplantation model, significantly less of the HSA-TRAIL fusion protein compared to the respective control TRAIL protein was required to achieve inhibition of tumor growth indicating that the increased half life of HSA-TNF ligand fusion proteins translates into better therapeutic action in vivo. In conclusion, our data suggest that genetic fusion to serum albumin is a powerful and generally applicable mean to improve bioavailability and in vivo activity of TNF ligands.« less

Protective efficacy of a Treponema pallidum Gpd DNA vaccine vectored by chitosan nanoparticles and fused with interleukin-2.

PubMed

Zhao, Feijun; Wang, Shiping; Zhang, Xiaohong; Gu, Weiming; Yu, Jian; Liu, Shuangquan; Zeng, Tiebing; Zhang, Yuejun; Wu, Yimou

2012-02-01

In the present study, immunomodulatory responses of a DNA vaccine constructed by fusing Treponema pallidum (Tp) glycerophosphodiester phosphodiesterase (Gpd) to interleukin-2 (IL-2) and using chitosan (CS) nanoparticles as vectors were investigated. New Zealand white rabbits were immunized by intramuscular inoculation of control DNAs, Tp Gpd DNA vaccine, or Gpd-IL-2 fusion DNA vaccine, which were vectored by CS nanoparticles. Levels of the anti-Gpd antibodies and levels of IL-2 and interferon-γ in rabbits were increased upon inoculation of Gpd-IL-2 fusion DNA vaccine, when compared with the inoculation with Gpd DNA vaccine, with CS vectoring increasing the effects. The Gpd-IL-2 fusion DNA vaccine efficiently enhanced the antigen-specific lymphocyte proliferative response. When the rabbits were challenged intradermally with 10(5) Tp (Nichols) spirochetes, the Gpd-IL-2 fusion DNA vaccine conferred better protection than the Gpd DNA vaccine (P < 0.05), as characterized by lower detectable amounts of dark field positive lesions (17.5%), lower ulcerative lesion scores (15%), and faster recovery. Individuals treated with the Tp Gpd-IL-2 fusion DNA vaccine vectored by CS nanoparticles had the lowest amounts of dark field positive lesions (10%) and ulcerations (5%) observed and the fastest recovery (42 days). These results indicate that the Gpd-IL-2 fusion DNA vaccine vectored by CS nanoparticles can efficiently induce Th1-dominant immune responses, improve protective efficacy against Tp spirochete infection, and effectively attenuate development of syphilitic lesions.

Fusion mutants of Newcastle disease virus selected with monoclonal antibodies to the hemagglutinin-neuraminidase.

PubMed Central

Iorio, R M; Glickman, R L

1992-01-01

The Australia-Victoria (AV) isolate of Newcastle disease virus (NDV) induces fusion from within but not fusion from without. L1, a neuraminidase (NA)-deficient virus derived from AV, has the opposite fusion phenotype from the wild-type virus. It fails to induce the former mode of fusion, but has gained a limited ability to promote the latter. Monoclonal antibodies to antigenic site 23 on the hemagglutinin-neuraminidase (HN) glycoprotein have previously been shown to select variants of the AV isolate that have altered NA activity or receptor-binding affinity. By using an antibody to this site, variants of L1 have been selected. Three of the variants have gained an increased affinity for sialic acid-containing receptors, as evidenced by the resistance of their hemagglutinating activity to the presence of reduced amounts of sialic acid on the surface of chicken erythrocytes. All four variants still have very low levels of NA activity, comparable to that of the parent virus, L1. The alteration in receptor-binding affinity results in a decreased potential for elution from cellular receptors and correlates with an increased ability to promote both modes of fusion. A single amino acid substitution in the HN protein of each variant, responsible for its escape from neutralization, has been identified. These studies identify two HN residues, 193 and 203, at which monoclonal antibody-selected substitution influences the receptor recognition properties of NDV and may influence its ability to promote syncytium formation. Images PMID:1404607

SU-F-T-140: Assessment of the Proton Boron Fusion Reaction for Practical Radiation Therapy Applications Using MCNP6

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

Adam, D; Bednarz, B

Purpose: The proton boron fusion reaction is a reaction that describes the creation of three alpha particles as the result of the interaction of a proton incident upon a 11B target. Theoretically, the proton boron fusion reaction is a desirable reaction for radiation therapy applications in that, with the appropriate boron delivery agent, it could potentially combine the localized dose delivery protons exhibit (Bragg peak) and the local deposition of high LET alpha particles in cancerous sites. Previous efforts have shown significant dose enhancement using the proton boron fusion reaction; the overarching purpose of this work is an attempt tomore » validate previous Monte Carlo results of the proton boron fusion reaction. Methods: The proton boron fusion reaction, 11B(p, 3α), is investigated using MCNP6 to assess the viability for potential use in radiation therapy. Simple simulations of a proton pencil beam incident upon both a water phantom and a water phantom with an axial region containing 100ppm boron were modeled using MCNP6 in order to determine the extent of the impact boron had upon the calculated energy deposition. Results: The maximum dose increase calculated was 0.026% for the incident 250 MeV proton beam scenario. The MCNP simulations performed demonstrated that the proton boron fusion reaction rate at clinically relevant boron concentrations was too small in order to have any measurable impact on the absorbed dose. Conclusion: For all MCNP6 simulations conducted, the increase of absorbed dose of a simple water phantom due to the 11B(p, 3α) reaction was found to be inconsequential. In addition, it was determined that there are no good evaluations of the 11B(p, 3α) reaction for use in MCNPX/6 and further work should be conducted in cross section evaluations in order to definitively evaluate the feasibility of the proton boron fusion reaction for use in radiation therapy applications.« less

Assembly of Four Diverse Heterocyclic Libraries Enabled by Prins Cyclization, Au-Catalyzed Enyne Cycloisomerization, and Automated Amide Synthesis

PubMed Central

Cui, Jiayue; Chai, David I.; Miller, Christopher; Hao, Jason; Thomas, Christopher; Wang, JingQi; Scheidt, Karl A.; Kozmin, Sergey A.

2013-01-01

We describe a unified synthetic strategy for efficient assembly of four new heterocyclic libraries. The synthesis began by creating a range of structurally diverse pyrrolidinones or piperidinones. Such compounds were obtained in a simple one-flask operation starting with readily available amines, ketoesters, and unsaturated anhydrides. The use of tetrahydropyran-containing ketoesters, which were rapidly assembled by our Prins cyclization protocol, enabled efficient fusion of pyran and piperidinone cores. A newly developed Au(I)-catalyzed cycloisomerization of alkyne-containing enamides further expanded heterocyclic diversity by providing rapid entry into a wide range of bicyclic and tricyclic dienamides. The final stage of the process entailed diversification of each of the initially produced carboxylic acids using a fully automated platform for amide synthesis, which delivered 1872 compounds in high diastereomeric and chemical purity. PMID:22860634

Uncertainties and understanding of experimental and theoretical results regarding reactions forming heavy and superheavy nuclei

NASA Astrophysics Data System (ADS)

Giardina, G.; Mandaglio, G.; Nasirov, A. K.; Anastasi, A.; Curciarello, F.; Fazio, G.

2018-02-01

Experimental and theoretical results of the PCN fusion probability of reactants in the entrance channel and the Wsur survival probability against fission at deexcitation of the compound nucleus formed in heavy-ion collisions are discussed. The theoretical results for a set of nuclear reactions leading to formation of compound nuclei (CNs) with the charge number Z = 102- 122 reveal a strong sensitivity of PCN to the characteristics of colliding nuclei in the entrance channel, dynamics of the reaction mechanism, and excitation energy of the system. We discuss the validity of assumptions and procedures for analysis of experimental data, and also the limits of validity of theoretical results obtained by the use of phenomenological models. The comparison of results obtained in many investigated reactions reveals serious limits of validity of the data analysis and calculation procedures.

The influence of Sc addition on the welding microstructure of Zr-based bulk metallic glass: The stability of the amorphous phase

NASA Astrophysics Data System (ADS)

Wang, Shing Hoa; Kuo, Pei Hung; Tsang, Hsiao Tsung; Jeng, Rong Ruey; Lin, Yu Lon

2007-10-01

Pulsed direct current autogeneous tungsten inert gas arc welding was conducted on rods of bulk metallic glasses (BMGs) Zr55Cu30Ni5Al10 and (Zr55Cu30Ni5Al10)99.98Sc0.02 under two different cooling conditions. The crystalline precipitates in the fusion zone of BMG Zr55Cu30Ni5Al10 were confirmed by microfocused x-ray diffraction pattern analysis as Zr2Ni and Zr2(Cu,Al) intermetallic compounds. In contrast, BMG with Sc addition (Zr55Cu30Ni5Al10)99.98Sc0.02 shows an excellent stable glass forming ability. The fusion zone of BMG (Zr55Cu30Ni5Al10)99.98Sc0.02 remains in the same amorphous state as that of the amorphous base metal when the weld is cooled with accelerated cooling.

Improved adaptive splitting and selection: the hybrid training method of a classifier based on a feature space partitioning.

PubMed

Jackowski, Konrad; Krawczyk, Bartosz; Woźniak, Michał

2014-05-01

Currently, methods of combined classification are the focus of intense research. A properly designed group of combined classifiers exploiting knowledge gathered in a pool of elementary classifiers can successfully outperform a single classifier. There are two essential issues to consider when creating combined classifiers: how to establish the most comprehensive pool and how to design a fusion model that allows for taking full advantage of the collected knowledge. In this work, we address the issues and propose an AdaSS+, training algorithm dedicated for the compound classifier system that effectively exploits local specialization of the elementary classifiers. An effective training procedure consists of two phases. The first phase detects the classifier competencies and adjusts the respective fusion parameters. The second phase boosts classification accuracy by elevating the degree of local specialization. The quality of the proposed algorithms are evaluated on the basis of a wide range of computer experiments that show that AdaSS+ can outperform the original method and several reference classifiers.

Synthesis, crystal growth, structural and physicochemical studies of novel binary organic complex: 4-chloroaniline-3-hydroxy-4-methoxybenzaldehyde

NASA Astrophysics Data System (ADS)

Sharma, K. P.; Reddi, R. S. B.; Bhattacharya, S.; Rai, R. N.

2012-06-01

The solid-state reaction, which is solvent free and green synthesis, has been adopted to explore the novel compound. The phase diagram of 4-chloroaniline (CA) and 3-hydroxy-4-methoxybenzaldehyde (HMB) system shows the formation of a novel 1:1 molecular complex, and two eutectics on either sides of complex. Thermochemical studies of complex and eutectics have been carried out for various properties such as heat of fusion, entropy of fusion, Jackson's parameters, interfacial energy and excess thermodynamic functions. The formation of molecular complex was also studied by IR, NMR, elemental analysis and UV-Vis absorption spectra. The single crystal of molecular complex was grown and its XRD study confirms the formation of complex and identifies the crystal structure and atomic packing of crystal of complex. Transmission spectra of grown crystal of the complex show 70% transmittance efficiency with cut off wavelength 412 nm. The band gap and refractive index of the crystal of complex have also been studied.

Fluoride salts and container materials for thermal energy storage applications in the temperature range 973 to 1400 K

NASA Technical Reports Server (NTRS)

Misra, Ajay K.; Whittenberger, J. Daniel

1987-01-01

Multicomponent fluoride salt mixtures were characterized for use as latent heat of fusion heat storage materials in advanced solar dynamic space power systems with operating temperatures in the range of 973 to 1400 K. The melting points and eutectic composition for many systems with published phase diagrams were verified, and several new eutectic compositions were identified. Additionally, the heats of fusion of several binary and ternary eutectics and congruently melting intermediate compounds were measured by differential scanning calorimetry. The extent of corrosion of various metals by fluoride melts was estimated from thermodynamic considerations, and equilibrium conditions inside a containment vessel were calculated as functions of the initial moisture content of the salt and free volume above the molten salt. Preliminary experimental data on the corrosion of commercial, high-temperature alloys in LiF-19.5CaF2 and NaF-27CaF2-36MgF2 melts are presented and compared to the thermodynamic predictions.

Fluoride salts and container materials for thermal energy storage applications in the temperature range 973 - 1400 K

NASA Technical Reports Server (NTRS)

Misra, Ajay K.; Whittenberger, J. Daniel

1987-01-01

Multicomponent fluoride salt mixtures were characterized for use as latent heat of fusion heat storage materials in advanced solar dynamic space power systems with operating temperatures in the range of 973 to 1400 K. The melting points and eutectic composition for many systems with published phase diagrams were verified, and several new eutectic compositions were identified. Additionally, the heats of fusion of several binary and ternary eutectics and congruently melting intermediate compounds were measured by differential scanning calorimetry. The extent of corrosion of various metals by fluoride melts was estimated from thermodynamic considerations, and equilibrium conditions inside a containment vessel were calculated as functions of the initial moisture content of the salt and free volume above the molten salt. Preliminary experimental data on the corrosion of commercial, high-temperature alloys in LiF-19.5CaF2 and NaF-27CaF2-36MgF2 melts are presented and compared to the thermodynamic predictions.

Antiviral mechanism of polyanionic carbosilane dendrimers against HIV-1

PubMed Central

Vacas-Córdoba, Enrique; Maly, Marek; De la Mata, Francisco J; Gómez, Rafael; Pion, Marjorie; Muñoz-Fernández, Mª Ángeles

2016-01-01

Nanotechnology-derived platforms, such as dendrimers, are very attractive in several biological applications. In the case of human immunodeficiency virus (HIV) infection, polyanionic carbosilane dendrimers have shown great potential as antiviral agents in the development of novel microbicides to prevent the sexual transmission of HIV-1. In this work, we studied the mechanism of two sulfated and naphthylsulfonated functionalized carbosilane dendrimers, G3-S16 and G2-NF16. They are able to inhibit viral infection at fusion and thus at the entry step. Both compounds impede the binding of viral particles to target cell surface and membrane fusion through the blockage of gp120–CD4 interaction. In addition, and for the first time, we demonstrate that dendrimers can inhibit cell-to-cell HIV transmission and difficult infectious synapse formation. Thus, carbosilane dendrimers’ mode of action is a multifactorial process targeting several proteins from viral envelope and from host cells that could block HIV infection at different stages during the first step of infection. PMID:27103798

Antimetastatic effects of cordycepin mediated by the inhibition of mitochondrial activity and estrogen-related receptor α in human ovarian carcinoma cells

PubMed Central

Wang, Chia-Woei; Hsu, Wei-Hsuan; Tai, Chen-Jei

2017-01-01

Cordycepin (3′-deoxyadenosine) is a compound for antitumor, which has been found to exert antiangiogenic, antimetastatic, and antiproliferative effects, as well as inducing apoptosis. However, the association between cancer metastasis and mitochondrial activity in cordycepin-treated ovarian carcinoma cells remains unclear. The 50 and 100 μM of cordycepin inhibits mitochondrial fusion and induces mitochondrial fission, respectively. These suggested that cordycepin showed the down-regulation of mitochondrial function and limitation of energy production. Because of activation of mitochondria and generation of energy are needed in cancer cell migration/invasion. After 24 h treatment, cordycepin suppresses epithelial–mesenchymal transition and migration in ovarian carcinoma cells through inhibiting estrogen-related receptor (ERR)-α. The ERRα is a co-transcription factor for gene expressions associated with mitochondrial fusion. Our results indicate that cordycepin suppresses metastasis and migration of ovarian carcinoma cells via inhibiting mitochondrial activity in non-toxic concentrations, and cordycepin has potential benefits in ovarian cancer therapy. PMID:27966445

Production of geranylgeraniol on overexpression of a prenyl diphosphate synthase fusion gene in Saccharomyces cerevisiae.

PubMed

Ohto, Chikara; Muramatsu, Masayoshi; Obata, Shusei; Sakuradani, Eiji; Shimizu, Sakayu

2010-07-01

An acyclic diterpene alcohol, (E,E,E)-geranylgeraniol (GGOH), is one of the important compounds used as perfume and pharmacological agents. A deficiency of squalene (SQ) synthase activity allows yeasts to accumulate an acyclic sesquiterpene alcohol, (E,E)-farnesol, in their cells. Since sterols are essential for the growth of yeasts, a deficiency of SQ synthase activity makes the addition of supplemental sterols to the culture media necessary. To develop a GGOH production method not requiring any supplemental sterols, we overexpressed HMG1 encoding hydroxymethylglutaryl-CoA reductase and the genes of two prenyl diphosphate synthases, ERG20 and BTS1, in Saccharomyces cerevisiae. A prototrophic diploid coexpressing HMG1 and the ERG20-BTS1 fusion accumulated GGOH with neither disruption of the SQ synthase gene nor the addition of any supplemental sterols. The GGOH content on the diploid cultivation in a 5-l jar fermenter reached 138.8 mg/l under optimal conditions.