Fusion Plasma Performance and Confinement Studies on JT-60 and JT-60U

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

Kamada, Y.; Fujita, T.; Ishida, S.

2002-09-15

Fusion plasma performance and confinement studies on JT-60 and JT-60U are reviewed. With the main aim of providing a physics basis for ITER and the steady-state tokamak reactors, JT-60/JT-60U has been developing and optimizing the operational concepts, and extending the discharge regimes toward sustainment of high integrated performance in the reactor relevant parameter regime. In addition to achievement of high fusion plasma performances such as the equivalent breakeven condition (Q{sub DT}{sup eq} up to 1.25) and a high fusion triple product n{sub D}(0){tau}{sub E}T{sub i}(0) = 1.5 x 10{sup 21} m{sup -3}skeV, JT-60U has demonstrated the integrated performance of highmore » confinement, high {beta}{sub N}, full non-inductive current drive with a large fraction of bootstrap current. These favorable performances have been achieved in the two advanced operation regimes, the reversed magnetic shear (RS) and the weak magnetic shear (high-{beta}{sub p}) ELMy H modes characterized by both internal transport barriers (ITB) and edge transport barriers (ETB). The key factors in optimizing these plasmas towards high integrated performance are control of profiles of current, pressure, rotation, etc. utilizing a variety of heating, current drive, torque input, and particle control capabilities and high triangularity operation. As represented by discovery of ITBs (density ITB in the central pellet mode, ion temperature ITB in the high-{beta}{sub p} mode, and electron temperature ITB in the reversed shear mode), confinement studies in JT-60/JT-60U have been emphasizing freedom and also restriction of radial profiles of temperature and density. In addition to characterization of confinement and analyses of transport properties of the OH, the L-mode, the H-mode, the pellet mode, the high-{beta}{sub p} mode, and the RS mode, JT-60U has clarified formation conditions, spatial structures and dynamics of edge and internal transport barriers, and evaluated effects of repetitive MHD events on confinement such as sawteeth and ELMs. Through these studies, JT-60U has demonstrated applicability of the high confinement modes to ITER and the steady-state tokamak reactors.« less

Enhanced expression of cro-beta-galactosidase fusion proteins under the control of the PR promoter of bacteriophage lambda.

PubMed Central

Zabeau, M; Stanley, K K

1982-01-01

Hybrid plasmids carrying cro-lacZ gene fusions have been constructed by joining DNA segments carrying the PR promoter and the start of the cro gene of bacteriophage lambda to the lacZ gene fragment carried by plasmid pLG400 . Plasmids in which the translational reading frames of the cro and lacZ genes are joined in-register (type I) direct the synthesis of elevated levels of cro-beta-galactosidase fusion protein amounting to 30% of the total cellular protein, while plasmids in which the genes are fused out-of-register (type II) produce a low level of beta-galactosidase protein. Sequence rearrangements downstream of the cro initiator AUG were found to influence the efficiency of translation, and have been correlated with alterations in the RNA secondary structure of the ribosome-binding site. Plasmids which direct the synthesis of high levels of beta-galactosidase are conditionally lethal and can only be propagated when the PR promoter is repressed. Deletion of sequences downstream of the lacZ gene restored viability, indicating that this region of the plasmid encodes a function which inhibits the growth of the cells. The different applications of these plasmids for expression of cloned genes are discussed. Images Fig. 6. PMID:6327257

Binding Linkage in a Telomere DNA–Protein Complex at the Ends of Oxytricha nova Chromosomes

PubMed Central

Buczek, Pawel; Orr, Rochelle S.; Pyper, Sean R.; Shum, Mili; Ota, Emily Kimmel Irene; Gerum, Shawn E.; Horvath, Martin P.

2005-01-01

Alpha and beta protein subunits of the telomere end binding protein from Oxytricha nova (OnTEBP) combine with telomere single strand DNA to form a protective cap at the ends of chromosomes. We tested how protein–protein interactions seen in the co-crystal structure relate to DNA binding through use of fusion proteins engineered as different combinations of domains and subunits derived from OnTEBP. Joining alpha and beta resulted in a protein that bound single strand telomere DNA with high affinity (KD-DNA=1.4 nM). Another fusion protein, constructed without the C-terminal protein–protein interaction domain of alpha, bound DNA with 200-fold diminished affinity (KD-DNA=290 nM) even though the DNA-binding domains of alpha and beta were joined through a peptide linker. Adding back the alpha C-terminal domain as a separate protein restored high-affinity DNA binding. The binding behaviors of these fusion proteins and the native protein subunits are consistent with cooperative linkage between protein-association and DNA-binding equilibria. Linking DNA–protein stability to protein–protein contacts at a remote site may provide a trigger point for DNA–protein disassembly during telomere replication when the single strand telomere DNA must exchange between a very stable OnTEBP complex and telomerase. PMID:15967465

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

Lazarus, E; Peng, Yueng Kay Martin

Oak Ridge National Laboratory (ORNL) proposes to build the Spherical Torus Experiment (STX), a very low aspect ratio toroidal confinement device. This proposal concentrates on tokamak operation of the experiment; however, it can in principle be operated as a pinch or reversed-field pinch as well. As a tokamak, the spherical torus confines a plasma that is characterized by high toroidal beta, low poloidal beta, large natural elongation, high plasma current for a given edge q, and strong paramagnetism. These features combine to offer the possibility of a compact, low-field fusion device. The figure below shows that when compared to amore » conventional tokamak the spherical torus represents a major change in geometry. The primary goals of the experiment will be to demonstrate a capability for high beta (20%) in the first stability regime, to extend our knowledge of tokamak confinement scaling, and to test oscillating-field current drive. The experiment will operate in the high-beta, collisionless regime, which is achieved in STX at low temperatures because of the geometry. At a minimum, operation of STX will help to resolve fundamental questions regarding the scaling of beta and confinement in tokamaks. Complete success in this program would have a significant impact on toroidal fusion research in that it would demonstrate solutions to the problems of beta and steady-state operation in the tokamak. The proposed device has a major radius of 0.45 m, a toroidai field of 0.5 T, a plasma current of 900 kA, and heating by neutral beam injection. We estimate 30 months for design, construction, and assembly. The budget estimate, including contingency and escalation, is $6.8 million.« less

Impact of physics and technology innovations on compact tokamak fusion pilot plants

NASA Astrophysics Data System (ADS)

Menard, Jonathan

2016-10-01

For magnetic fusion to be economically attractive and have near-term impact on the world energy scene it is important to focus on key physics and technology innovations that could enable net electricity production at reduced size and cost. The tokamak is presently closest to achieving the fusion conditions necessary for net electricity at acceptable device size, although sustaining high-performance scenarios free of disruptions remains a significant challenge for the tokamak approach. Previous pilot plant studies have shown that electricity gain is proportional to the product of the fusion gain, blanket thermal conversion efficiency, and auxiliary heating wall-plug efficiency. In this work, the impact of several innovations is assessed with respect to maximizing fusion gain. At fixed bootstrap current fraction, fusion gain varies approximately as the square of the confinement multiplier, normalized beta, and major radius, and varies as the toroidal field and elongation both to the third power. For example, REBCO high-temperature superconductors (HTS) offer the potential to operate at much higher toroidal field than present fusion magnets, but HTS cables are also beginning to access winding pack current densities up to an order of magnitude higher than present technology, and smaller HTS TF magnet sizes make low-aspect-ratio HTS tokamaks potentially attractive by leveraging naturally higher normalized beta and elongation. Further, advances in kinetic stabilization and feedback control of resistive wall modes could also enable significant increases in normalized beta and fusion gain. Significant reductions in pilot plant size will also likely require increased plasma energy confinement, and control of turbulence and/or low edge recycling (for example using lithium walls) would have major impact on fusion gain. Reduced device size could also exacerbate divertor heat loads, and the impact of novel divertor solutions on pilot plant configurations is addressed. For missions including tritium breeding, high-thermal-efficiency liquid metal breeding blankets are attractive, and novel immersion blankets offer the potential for simplified fabrication and maintenance and reduced cost. Lastly, the optimal aspect ratio for a tokamak pilot plant is likely a function of the device mission and associated cost, with low aspect ratio favored for minimizing TF magnet mass and higher aspect ratio favored for minimizing blanket mass. The interplay between a range of physics and technology innovations for enabling compact pilot plants will be described. This work was supported by U.S. DOE Contract Number DE-AC02-09CH11466.

AE activity during transient beta drops in high poloidal beta discharges

NASA Astrophysics Data System (ADS)

Huang, J.; Gong, X. Z.; Ren, Q. L.; Ding, S. Y.; Qian, J. P.; Pan, C. K.; Li, G. Q.; Heidbrink, W. W.; Garofalo, A. M.; McClenaghan, J.

2016-10-01

Enhanced AE activity has been observed during transient beta drops in high poloidal beta DIII-D discharges with internal transport barriers (ITBs). These drops in beta are believed to be caused by n=1 external kink modes. In some discharges, beta recovers within 200 ms but, in others, beta stays suppressed. A typical discharge has βP 3, qmin 3, and q95 12. The drop in beta affects both fast ions and thermal particles, and a drop is also observed in the density and rotation. The enhanced AE activity follows the instability that causes the beta drop, is largest at the lowest beta, and subsides as beta recovers. MHD stability analysis is planned. A database study of the plasma conditions associated with the collapse will be also presented. Supported in part by the US Department of Energy under DE-FC02-04ER54698, DE-AC05-06OR23100, and by the National Natural Science Foundation of China 11575249, and the National Magnetic Confinement Fusion Program of China No. 2015GB110005.

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

Zhao Jincun; Wang Wei; Yuan Zhihong

The spike (S) protein of SARS coronavirus (SARS-CoV) is responsible for viral binding with ACE2 molecules. Its receptor-binding motif (S-RBM) is located between residues 424 and 494, which folds into 2 anti-parallel {beta}-sheets, {beta}5 and {beta}6. We have previously demonstrated that fragment 450-650 of the S protein (S450-650) is predominantly recognized by convalescent sera of SARS patients. The N-terminal 60 residues (450-510) of the S450-650 fragment covers the entire {beta}6 strand of S-RBM. In the present study, we demonstrate that patient sera predominantly recognized 2 linear epitopes outside the {beta}6 fragment, while the mouse antisera, induced by immunization of BALB/cmore » mice with recombinant S450-650, mainly recognized the {beta}6 strand-containing region. Unlike patient sera, however, the mouse antisera were unable to inhibit the infectivity of S protein-expressing (SARS-CoV-S) pseudovirus. Fusion protein between green fluorescence protein (GFP) and S450-650 (S450-650-GFP) was able to stain Vero E6 cells and deletion of the {beta}6 fragment rendered the fusion product (S511-650-GFP) unable to do so. Similarly, recombinant S450-650, but not S511-650, was able to block the infection of Vero E6 cells by the SARS-CoV-S pseudovirus. Co-precipitation experiments confirmed that S450-650 was able to specifically bind with ACE2 molecules in lysate of Vero E6 cells. However, the ability of S450-510, either alone or in fusion with GFP, to bind with ACE2 was significantly poorer compared with S450-650. Our data suggest a possibility that, although the {beta}6 strand alone is able to bind with ACE2 with relatively high affinity, residues outside the S-RBM could also assist the receptor binding of SARS-CoV-S protein.« less

Extension of high poloidal beta scenario in DIII-D to lower q95 for steady state fusion reactor

NASA Astrophysics Data System (ADS)

Huang, J.; Gong, X.; Qian, J.; Ding, S.; Ren, Q.; Guo, W.; Pan, C.; Li, G.; Xia, T.; Garofalo, A.; Lao, L.; Hyatt, A.; Ferron, J.; Collins, C.; Lin, D.; McKee, G.; Rhode, T.; McClenaghan, J.; Holcomb, C.; Cui, L.; Heidbrink, W.; Zhu, Y.; Diiid Team; East Team

2017-10-01

DIII-D/EAST joint experiments have improved the high poloidal beta scenario with sustained large-radius internal transport barrier (ITB) extended to high plasma current Ip 1MA with q95 6.0. Slight off-axis NBCD is applied to obtain broader current density profile, ITBs can now be sustained below the previously observed βp threshold with excellent confinement (H98y2 1.8). The scenario also exhibits a local negative shear appearing with q increased at rho 0.4, which helps ITB formation and sustainment. This confirms TGLF prediction that negative magnetic shear can help recover ITB and achieve high confinement with reduced q95. Detailed analysis shows that the Shafranov shift and q profile is critical in the ITB formation at high βp regime. Supported in part by National Magnetic Confinement Fusion Program of China 2015GB102000, 2015GB110005, and US Department of Energy under DE-FC02-04ER54698.

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.

Spherical torus fusion reactor

DOEpatents

Peng, Yueng-Kay M.

1989-04-04

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

Spherical torus fusion reactor

DOEpatents

Peng, Yueng-Kay M.

1989-01-01

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

Status of fusion research and implications for D/He-3 systems

NASA Technical Reports Server (NTRS)

Miley, George H.

1988-01-01

World wide programs in both magnetic confinement and inertial confinement fusion research have made steady progress towards the experimental demonstration of energy breakeven. However, after breakeven is achieved, considerable time and effort must still be expended to develop a usable power plant. The main program described is focused on Deuterium-Tritium devices. In magnetic confinement, three of the most promising high beta approaches with a reasonable experimental data base are the Field Reversed Configuration, the high field tokamak, and the dense Z-pinch. The situation is less clear in inertial confinement where the first step requires an experimental demonstration of D/T spark ignition. It appears that fusion research has reached a point in time where an R and D plan to develop a D/He-3 fusion reactor can be laid out with some confidence of success.

Analysis of Yersinia enterocolitica Effector Translocation into Host Cells Using Beta-lactamase Effector Fusions.

PubMed

Wolters, Manuel; Zobiak, Bernd; Nauth, Theresa; Aepfelbacher, Martin

2015-10-13

Many gram-negative bacteria including pathogenic Yersinia spp. employ type III secretion systems to translocate effector proteins into eukaryotic target cells. Inside the host cell the effector proteins manipulate cellular functions to the benefit of the bacteria. To better understand the control of type III secretion during host cell interaction, sensitive and accurate assays to measure translocation are required. We here describe the application of an assay based on the fusion of a Yersinia enterocolitica effector protein fragment (Yersinia outer protein; YopE) with TEM-1 beta-lactamase for quantitative analysis of translocation. The assay relies on cleavage of a cell permeant FRET dye (CCF4/AM) by translocated beta-lactamase fusion. After cleavage of the cephalosporin core of CCF4 by the beta-lactamase, FRET from coumarin to fluorescein is disrupted and excitation of the coumarin moiety leads to blue fluorescence emission. Different applications of this method have been described in the literature highlighting its versatility. The method allows for analysis of translocation in vitro and also in in vivo, e.g., in a mouse model. Detection of the fluorescence signals can be performed using plate readers, FACS analysis or fluorescence microscopy. In the setup described here, in vitro translocation of effector fusions into HeLa cells by different Yersinia mutants is monitored by laser scanning microscopy. Recording intracellular conversion of the FRET reporter by the beta-lactamase effector fusion in real-time provides robust quantitative results. We here show exemplary data, demonstrating increased translocation by a Y. enterocolitica YopE mutant compared to the wild type strain.

Transport modeling of the DIII-D high $${{\\beta}_{p}}$$ scenario and extrapolations to ITER steady-state operation

DOE PAGES

McClenaghan, Joseph; Garofalo, Andrea M.; Meneghini, Orso; ...

2017-08-03

In this study, transport modeling of a proposed ITER steady-state scenario based on DIII-D high poloidal-beta (more » $${{\\beta}_{p}}$$ ) discharges finds that ITB formation can occur with either sufficient rotation or a negative central shear q-profile. The high $${{\\beta}_{p}}$$ scenario is characterized by a large bootstrap current fraction (80%) which reduces the demands on the external current drive, and a large radius internal transport barrier which is associated with excellent normalized confinement. Modeling predictions of the electron transport in the high $${{\\beta}_{p}}$$ scenario improve as $${{q}_{95}}$$ approaches levels similar to typical existing models of ITER steady-state and the ion transport is turbulence dominated. Typical temperature and density profiles from the non-inductive high $${{\\beta}_{p}}$$ scenario on DIII-D are scaled according to 0D modeling predictions of the requirements for achieving a $Q=5$ steady-state fusion gain in ITER with 'day one' heating and current drive capabilities. Then, TGLF turbulence modeling is carried out under systematic variations of the toroidal rotation and the core q-profile. A high bootstrap fraction, high $${{\\beta}_{p}}$$ scenario is found to be near an ITB formation threshold, and either strong negative central magnetic shear or rotation in a high bootstrap fraction are found to successfully provide the turbulence suppression required to achieve $Q=5$.« less

Nuclear Fusion prize laudation Nuclear Fusion prize laudation

NASA Astrophysics Data System (ADS)

Burkart, W.

2011-01-01

Clean energy in abundance will be of critical importance to the pursuit of world peace and development. As part of the IAEA's activities to facilitate the dissemination of fusion related science and technology, the journal Nuclear Fusion is intended to contribute to the realization of such energy from fusion. In 2010, we celebrated the 50th anniversary of the IAEA journal. The excellence of research published in the journal is attested to by its high citation index. The IAEA recognizes excellence by means of an annual prize awarded to the authors of papers judged to have made the greatest impact. On the occasion of the 2010 IAEA Fusion Energy Conference in Daejeon, Republic of Korea at the welcome dinner hosted by the city of Daejeon, we celebrated the achievements of the 2009 and 2010 Nuclear Fusion prize winners. Steve Sabbagh, from the Department of Applied Physics and Applied Mathematics, Columbia University, New York is the winner of the 2009 award for his paper: 'Resistive wall stabilized operation in rotating high beta NSTX plasmas' [1]. This is a landmark paper which reports record parameters of beta in a large spherical torus plasma and presents a thorough investigation of the physics of resistive wall mode (RWM) instability. The paper makes a significant contribution to the critical topic of RWM stabilization. John Rice, from the Plasma Science and Fusion Center, MIT, Cambridge is the winner of the 2010 award for his paper: 'Inter-machine comparison of intrinsic toroidal rotation in tokamaks' [2]. The 2010 award is for a seminal paper that analyzes results across a range of machines in order to develop a universal scaling that can be used to predict intrinsic rotation. This paper has already triggered a wealth of experimental and theoretical work. I congratulate both authors and their colleagues on these exceptional papers. W. Burkart Deputy Director General Department of Nuclear Sciences and Applications International Atomic Energy Agency, Vienna, Austria References [1] Sabbagh S. et al 2006 Nucl. Fusion 46 635-44 [2] Rice J.E. et al 2007 Nucl. Fusion 47 1618-24

Interaction with beta-arrestin determines the difference in internalization behavor between beta1- and beta2-adrenergic receptors.

PubMed

Shiina, T; Kawasaki, A; Nagao, T; Kurose, H

2000-09-15

The beta(1)-adrenergic receptor (beta(1)AR) shows the resistance to agonist-induced internalization. As beta-arrestin is important for internalization, we examine the interaction of beta-arrestin with beta(1)AR with three different methods: intracellular trafficking of beta-arrestin, binding of in vitro translated beta-arrestin to intracellular domains of beta(1)- and beta(2)ARs, and inhibition of betaAR-stimulated adenylyl cyclase activities by beta-arrestin. The green fluorescent protein-tagged beta-arrestin 2 translocates to and stays at the plasma membrane by beta(2)AR stimulation. Although green fluorescent protein-tagged beta-arrestin 2 also translocates to the plasma membrane, it returns to the cytoplasm 10-30 min after beta(1)AR stimulation. The binding of in vitro translated beta-arrestin 1 and beta-arrestin 2 to the third intracellular loop and the carboxyl tail of beta(1)AR is lower than that of beta(2)AR. The fusion protein of beta-arrestin 1 with glutathione S-transferase inhibits the beta(1)- and beta(2)AR-stimulated adenylyl cyclase activities, although inhibition of the beta(1)AR-stimulated activity requires a higher concentration of the fusion protein than that of the beta(2)AR-stimulated activity. These results suggest that weak interaction of beta(1)AR with beta-arrestins explains the resistance to agonist-induced internalization. This is further supported by the finding that beta-arrestin can induce internalization of beta(1)AR when beta-arrestin 1 does not dissociate from beta(1)AR by fusing to the carboxyl tail of beta(1)AR.

Identification of functional domains within the alpha and beta subunits of beta-hexosaminidase A through the expression of alpha-beta fusion proteins.

PubMed

Tse, R; Wu, Y J; Vavougios, G; Hou, Y; Hinek, A; Mahuran, D J

1996-08-20

There are three human beta-hexosaminidase isozymes which are composed of all possible dimeric combinations of an alpha and/or a beta subunit; A (alpha beta), and B (beta beta), and S (alpha alpha). The amino acid sequences of the two subunits are 60% identical. The homology between the two chains varies with the middle > the carboxy-terminal > > the amino-terminal portions. Although dimerization is required for activity, each subunit contains its own active site and differs in its substrate specificity and thermal stability. The presence of the beta subunit in hexosaminidase A also influences the substrate specificity of the alpha subunit; e.g., in vivo only the A heterodimer can hydrolyze GM2 ganglioside. In this report, we localize functional regions in the two subunits by cellular expression of alpha/beta fusion proteins joined at adjacently aligned residues. First, a chimeric alpha/beta chain was made by replacing the least well-conserved amino-terminal section of the beta chain with the corresponding alpha section. The biochemical characteristics of this protein were nearly identical to hexosaminidase B. Therefore, the most dissimilar regions in the subunits are not responsible for their dissimilar biochemical properties. A second fusion protein was made that also included the more homologous middle section of the alpha chain. This protein expressed the substrate specificity unique to isozymes containing an alpha subunit (A and S). We conclude that the region responsible for the ability of the alpha subunit to bind negatively charged substrates is located within residues alpha 132-283. Interestingly, the remaining carboxy-terminal section from the beta chain, beta 316-556, was sufficient to allow this chimera to hydrolyze GM2 ganglioside with 10% the specific activity of heterodimeric hexosaminidase A. Thus, the carboxy-terminal section of each subunit is likely involved in subunit-subunit interactions.

Method for nondestructive fuel assay of laser fusion targets

DOEpatents

Farnum, Eugene H.; Fries, R. Jay

1976-01-01

A method for nondestructively determining the deuterium and tritium content of laser fusion targets by counting the x rays produced by the interaction of tritium beta particles with the walls of the microballoons used to contain the deuterium and tritium gas mixture under high pressure. The x rays provide a direct measure of the tritium content and a means for calculating the deuterium content using the initial known D-T ratio and the known deuterium and tritium diffusion rates.

Beta > 1 Plasmas

NASA Astrophysics Data System (ADS)

Jones, Robert

2017-10-01

I have suggested that fusion researchers should put more effort into the study of beta > 1 or wall confined plasmas. Magneto-Inertial Fusion and Magnetized Target Fusion projects at Los Alamos National Laboratory are recent examples of this sort of work. Unfortunately, theoretical studies of such systems may be employing overly optimistic models of the magnetic thermal insulation. One might well expect such systems to have stochastic field lines. If that is the case then we might want to employ turbulent thermal insulation as suggested in my papers: Current Science, pg 991, 1988 and Bull. Am. Phys. Soc., Nov. 4, 2009.

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

Ohara-Imaizumi, Mica; Aoyagi, Kyota; Nakamichi, Yoko

We simultaneously analyzed insulin granule fusion with insulin fused to green fluorescent protein and the subplasma membrane Ca{sup 2+} concentration ([Ca{sup 2+}]{sub PM}) with the Ca{sup 2+} indicator Fura Red in rat {beta} cells by dual-color total internal reflection fluorescence microscopy. We found that rapid and marked elevation in [Ca{sup 2+}]{sub PM} caused insulin granule fusion mostly from previously docked granules during the high KCl-evoked release and high glucose-evoked first phase release. In contrast, the slow and sustained elevation in [Ca{sup 2+}]{sub PM} induced fusion from newcomers translocated from the internal pool during the low KCl-evoked release and glucose-evoked secondmore » phase release. These data suggest that the pattern of the [Ca{sup 2+}]{sub PM} rise directly determines the types of fusing granules.« less

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

NASA Astrophysics Data System (ADS)

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

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

Is Deuterium Nuclear Fusion Catalyzed by Antineutrinos?

NASA Astrophysics Data System (ADS)

Shomer, Isaac

2010-02-01

The hypothesis of Fischbach and Jenkins that neutrinos emitted from the sun accelerate radioactive decay is noted. It is thought that neutrinos accelerate beta decay by reacting with neutron-rich nuclides to form a beta particle and a daughter product, with no antineutrino emitted. Conversely, it is proposed that antineutrinos can react with proton-rich nuclides to cause positron decay, with no neutrino emitted. It is also proposed that the nuclear fusion of the hydrogen bomb is triggered not only by the energy of the igniting fission bomb, but by the antineutrinos created by the rapid beta decay of the daughter products in the fission process. The contemplated mechanism for antineutrino initiated fusion is the following: 1. The antineutrinos from the fission daughter products cause positron decay of deuterium by the process outlined above. 2. In a later fusion step, these positrons subsequently react with neutrons in deuterium to create antineutrinos. Electrons are unavailable to annihilate positrons in the plasma of the hydrogen bomb. 3. These antineutrinos thereafter react with more deuterium to form positrons, thereby propagating a chain reaction. )

Cholesterol depletion by methyl-beta-cyclodextrin enhances myoblast fusion and induces the formation of myotubes with disorganized nuclei.

PubMed

Mermelstein, Cláudia S; Portilho, Débora M; Medeiros, Rommel B; Matos, Aline R; Einicker-Lamas, Marcelo; Tortelote, Giovane G; Vieyra, Adalberto; Costa, Manoel L

2005-02-01

The formation of a skeletal muscle fiber begins with the withdrawal of committed mononucleated precursors from the cell cycle. These myoblasts elongate while aligning with each other, guided by recognition between their membranes. This step is followed by cell fusion and the formation of long striated multinucleated myotubes. We used methyl-beta-cyclodextrin (MCD) in primary cultured chick skeletal muscle cells to deplete membrane cholesterol and investigate its role during myogenesis. MCD promoted a significant increase in the expression of troponin T, enhanced myoblast fusion, and induced the formation of large multinucleated myotubes with nuclei being clustered centrally and not aligned at the cell periphery. MCD myotubes were striated, as indicated by sarcomeric alpha-actinin staining, and microtubule and desmin filament distribution was not altered. Pre-fusion MCD-treated myoblasts formed large aggregates, with cadherin and beta-catenin being accumulated in cell adhesion contacts. We also found that the membrane microdomain marker GM1 was not present as clusters in the membrane of MCD-treated myoblasts. Our data demonstrate that cholesterol is involved in the early steps of skeletal muscle differentiation.

Membrane topology analysis of Escherichia coli K-12 Mtr permease by alkaline phosphatase and beta-galactosidase fusions.

PubMed

Sarsero, J P; Pittard, A J

1995-01-01

The mtr gene of Escherichia coli K-12 encodes an inner membrane protein which is responsible for the active transport of trypotophan into the cell. It has been proposed that the Mtr permease has a novel structure consisting of 11 hydrophobic transmembrane spans, with a cytoplasmically disposed amino terminus and a carboxyl terminus located in the periplasmic space (J.P. Sarsero, P. J. Wookey, P. Gollnick, C. Yanofsky, and A.J. Pittard, J. Bacteriol. 173:3231-3234, 1991). The validity of this model was examined by the construction of fusion proteins between the Mtr permease and alkaline phosphatase or beta-galactosidase. In addition to the conventional methods, in which the reporter enzyme replaces a carboxyl-terminal portion of the membrane protein, the recently developed alkaline phosphatase sandwich fusion technique was utilized, in which alkaline phosphatase is inserted into an otherwise intact membrane protein. A cluster of alkaline phosphatase fusions to the carboxyl-terminal end of the Mtr permease exhibited high levels of alkaline phosphatase activity, giving support to the proposition of a periplasmically located carboxyl terminus. The majority of fusion proteins produced enzymatic activities which were in agreement with the positions of the fusion sites on the proposed topological model of the permease. The synthesis of a small cluster of hybrid proteins, whose enzymatic activity did not agree with the location of their fusion sites within putative transmembrane span VIII or the preceding periplasmic loop, was not detected by immunological techniques and did not necessitate modification of the proposed model in this region. Slight alterations may need to be made in the positioning of the carboxyl-terminal end of transmembrane span X.

Enzyme-linked immunosorbent assay for Escherichia coli heat-stable enterotoxin type II.

PubMed Central

Handl, C; Rönnberg, B; Nilsson, B; Olsson, E; Jonsson, H; Flock, J I

1988-01-01

The gene for Escherichia coli heat-stable enterotoxin type II (STII) was fused to the genes for protein A from Staphylococcus aureus and beta-galactosidase in two different expression systems. Antibodies raised in rabbits against the protein A-STII fusion protein recognized the beta-galactosidase-STII fusion protein. The latter fusion protein was used as the immobilized antigen in an enzyme-linked immunosorbent assay (ELISA) for detection of STII. The correlation between the results of the ELISA and the intestinal loop test in piglets was 95%, suggesting that the ELISA can be used to reliably detect STII. Images PMID:3049659

Comparison of immune responses against foot-and-mouth disease virus induced by fusion proteins using the swine IgG heavy chain constant region or beta-galactosidase as a carrier of immunogenic epitopes.

PubMed

Li, Guangjin; Chen, Weizao; Yan, Weiyao; Zhao, Kai; Liu, Mingqiu; Zhang, Jun; Fei, Liang; Xu, Quanxing; Sheng, Zutian; Lu, Yonggan; Zheng, Zhaoxin

2004-10-25

Previously, we demonstrated that a fusion protein (Gal-FMDV) consisting of beta-galactosidase and an immunogenic peptide, amino acids (141-160)-(21-40)-(141-160), of foot-and-mouth disease virus (FMDV) VP1 protein induced protective immune responses in guinea pigs and swine. We now designed a new potential recombinant protein vaccine against FMDV in swine. The immunogenic peptide, amino acids (141-160)-(21-40)-(141-160) from the VP1 protein of serotype O FMDV, was fused to the carboxy terminus of a swine immunoglobulin G single heavy chain constant region and expressed in Escherichia coli. The expressed fusion protein (IgG-FMDV) was purified and emulsified with oil adjuvant. Vaccination twice at an interval of 3 weeks with the emulsified IgG-FMDV fusion protein induced an FMDV-specific spleen proliferative T-cell response in guinea pigs and elicited high levels of neutralizing antibody in guinea pigs and swine. All of the immunized animals were efficiently protected against FMDV challenge. There was no significant difference between IgG-FMDV and Gal-FMDV in eliciting immunity after vaccination twice in swine. However, when evaluating the efficacy of a single inoculation of the fusion proteins, we found that IgG-FMDV could elicit a protective immune response in swine, while Gal-FMDV only elicited a weak neutralizing activity and could not protect the swine against FMDV challenge. Our results suggest that the IgG-FMDV fusion protein is a promising vaccine candidate for FMD in swine.

Projecting High Beta Steady-State Scenarios from DIII-D Advanced Tokamk Discharges

NASA Astrophysics Data System (ADS)

Park, J. M.

2013-10-01

Fusion power plant studies based on steady-state tokamak operation suggest that normalized beta in the range of 4-6 is needed for economic viability. DIII-D is exploring a range of candidate high beta scenarios guided by FASTRAN modeling in a repeated cycle of experiment and modeling validation. FASTRAN is a new iterative numerical procedure coupled to the Integrated Plasma Simulator (IPS) that integrates models of core transport, heating and current drive, equilibrium and stability self-consistently to find steady state (d / dt = 0) solutions, and reproduces most features of DIII-D high beta discharges with a stationary current profile. Separately, modeling components such as core transport (TGLF) and off-axis neutral beam current drive (NUBEAM) show reasonable agreement with experiment. Projecting forward to scenarios possible on DIII-D with future upgrades, two self-consistent noninductive scenarios at βN > 4 are found: high qmin and high internal inductance li. Both have bootstrap current fraction fBS > 0 . 5 and rely on the planned addition of a second off-axis neutral beamline and increased electron cyclotron heating. The high qmin > 2 scenario achieves stable operation at βN as high as 5 by a very broad current density profile to improve the ideal-wall stabilization of low-n instabilities along with confinement enhancement from low magnetic shear. The li near 1 scenario does not depend on ideal-wall stabilization. Improved confinement from strong magnetic shear makes up for the lower pedestal needed to maintain li high. The tradeoff between increasing li and reduced edge pedestal determines the achievable βN (near 4) and fBS (near 0.5). This modeling identifies the necessary upgrades to achieve target scenarios and clarifies the pros and cons of particular scenarios to better inform the development of steady-state fusion. Supported by the US Department of Energy under DE-AC05-00OR22725 & DE-FC02-04ER54698.

Drp1 guarding of the mitochondrial network is important for glucose-stimulated insulin secretion in pancreatic beta cells

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

Reinhardt, Florian; Schultz, Julia; Waterstradt, Rica

Mitochondria form a tubular network in mammalian cells, and the mitochondrial life cycle is determined by fission, fusion and autophagy. Dynamin-related protein 1 (Drp1) has a pivotal role in these processes because it alone is able to constrict mitochondria. However, the regulation and function of Drp1 have been shown to vary between cell types. Mitochondrial morphology affects mitochondrial metabolism and function. In pancreatic beta cells mitochondrial metabolism is a key component of the glucose-induced cascade of insulin secretion. The goal of the present study was to investigate the action of Drp1 in pancreatic beta cells. For this purpose Drp1 wasmore » down-regulated by means of shDrp1 in insulin-secreting INS1 cells and mouse pancreatic islets. In INS1 cells reduced Drp1 expression resulted in diminished expression of proteins regulating mitochondrial fusion, namely mitofusin 1 and 2, and optic atrophy protein 1. Diminished mitochondrial dynamics can therefore be assumed. After down-regulation of Drp1 in INS1 cells and spread mouse islets the initially homogenous mitochondrial network characterised by a moderate level of interconnections shifted towards high heterogeneity with elongated, clustered and looped mitochondria. These morphological changes were found to correlate directly with functional alterations. Mitochondrial membrane potential and ATP generation were significantly reduced in INS1 cells after Drp1down-regulation. Finally, a significant loss of glucose-stimulated insulin secretion was demonstrated in INS1 cells and mouse pancreatic islets. In conclusion, Drp1 expression is important in pancreatic beta cells to maintain the regulation of insulin secretion. -- Highlights: •Down-regulation of Drp1 in INS1 cells reduces mitochondrial fusion protein expression. •Mitochondrial membrane potential in INS1 cells is diminished after Drp1 down-regulation. •Mitochondria become elongated after down-regulation of Drp1 in beta cells. •Down-regulation of Drp1 in islets evokes loss of glucose-stimulated insulin secretion.« less

Effects of sulfate concentrations on the expression of a soybean seed storage protein gene and its reversibility in transgenic Arabidopsis thaliana.

PubMed

Hirai, M Y; Fujiwara, T; Chino, M; Naito, S

1995-10-01

Transgenic expression of genes encoding the alpha' and beta subunits of beta-conglycinin, one of the major seed storage proteins of soybean (Glycine max [L.] Merr.), was analyzed in Arabidopsis thaliana (L.) Heynh. under conditions of sulfate deficiency. Temporal patterns of expression of both the intact beta subunit gene and the beta subunit gene promoter fused to the beta-glucuronidase (GUS) gene are similar in soil-less cultures using rockwool, suggesting that the response to sulfate deficiency is regulated mainly at the level of transcription. In hydroponic cultures with various concentrations of sulfate, expression of both the intact beta subunit gene and the beta subunit gene promoter-GUS fusion gene were negatively correlated to increased sulfate concentrations in the culture medium. Transfer of transgenic A. thaliana plants carrying the beta subunit gene promoter-GUS fusion from sulfate-deficient to sulfate-sufficient control medium caused GUS activity in developing siliques to be repressed within two days. A reverse shift, where the plants were transferred from the control to sulfate-deficient medium, caused GUS activity to become higher than that in seeds of the control plants within two days. These results indicate that the expression of the beta subunit gene promoter responds rapidly to changes of sulfate availability.

Modeling of Steady-state Scenarios for the Fusion Nuclear Science Facility, Advanced Tokamak Approach

NASA Astrophysics Data System (ADS)

Garofalo, A. M.; Chan, V. S.; Prater, R.; Smith, S. P.; St. John, H. E.; Meneghini, O.

2013-10-01

A Fusion National Science Facility (FNSF) would complement ITER in addressing the community identified science and technology gaps to a commercially attractive DEMO, including breeding tritium and completing the fuel cycle, qualifying nuclear materials for high fluence, developing suitable materials for the plasma-boundary interface, and demonstrating power extraction. Steady-state plasma operation is highly desirable to address the requirements for fusion nuclear technology testing [1]. The Advanced Tokamak (AT) is a strong candidate for an FNSF as a consequence of its mature physics base, capability to address the key issues with a more compact device, and the direct relevance to an attractive target power plant. Key features of AT are fully noninductive current drive, strong plasma cross section shaping, internal profiles consistent with high bootstrap fraction, and operation at high beta, typically above the free boundary limit, βN > 3 . Work supported by GA IR&D funding, DE-FC02-04ER54698, and DE-FG02-95ER43309.

Observation of finite-. beta. MHD phenomena in tokamaks

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

McGuire, K.M.

1984-09-01

Stable high-beta plasmas are required for the tokamak to attain an economical fusion reactor. Recently, intense neutral beam heating experiments in tokamaks have shown new effects on plasma stability and confinement associated with high beta plasmas. The observed spectrum of MHD fluctuations at high beta is clearly dominated by the n = 1 mode when the q = 1 surface is in the plasma. The m/n = 1/1 mode drives other n = 1 modes through toroidal coupling and n > 1 modes through nonlinear coupling. On PDX, with near perpendicular injection, a resonant interaction between the n = 1more » internal kink and the trapped fast ions results in loss of beam particles and heating power. Key parameters in the theory are the value of q/sub 0/ and the injection angle. High frequency broadband magnetic fluctuations have been observed on ISX-B and D-III and a correlation with the deterioration of plasma confinement was reported. During enhanced confinement (H-mode) discharges in divertor plasmas, two new edge instabilities were observed, both localized radially near the separatrix. By assembling results from the different tokamak experiments, it is found that the simple theoretical ideal MHD beta limit has not been exceeded. Whether this represents an ultimate tokamak limit or if beta optimized configurations (Dee- or bean-shaped plasmas) can exceed this limit and perhaps enter a second regime of stability remains to be clarified.« less

Structural and biological mimicry of protein surface recognition by [alpha/beta]-peptide foldamers

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

Horne, W. Seth; Johnson, Lisa M.; Ketas, Thomas J.

Unnatural oligomers that can mimic protein surfaces offer a potentially useful strategy for blocking biomedically important protein-protein interactions. Here we evaluate an approach based on combining {alpha}- and {beta}-amino acid residues in the context of a polypeptide sequence from the HIV protein gp41, which represents an excellent testbed because of the wealth of available structural and biological information. We show that {alpha}/{beta}-peptides can mimic structural and functional properties of a critical gp41 subunit. Physical studies in solution, crystallographic data, and results from cell-fusion and virus-infectivity assays collectively indicate that the gp41-mimetic {alpha}/{beta}-peptides effectively block HIV-cell fusion via a mechanism comparablemore » to that of gp41-derived {alpha}-peptides. An optimized {alpha}/{beta}-peptide is far less susceptible to proteolytic degradation than is an analogous {alpha}-peptide. Our findings show how a two-stage design approach, in which sequence-based {alpha} {yields} {beta} replacements are followed by site-specific backbone rigidification, can lead to physical and biological mimicry of a natural biorecognition process.« less

Compatibility of internal transport barrier with steady-state operation in the high bootstrap fraction regime on DIII-D

DOE PAGES

Garofalo, Andrea M.; Gong, Xianzu; Grierson, Brian A.; ...

2015-11-16

Recent EAST/DIII-D joint experiments on the high poloidal beta tokamak regime in DIII-D have demonstrated fully noninductive operation with an internal transport barrier (ITB) at large minor radius, at normalized fusion performance increased by ≥30% relative to earlier work. The advancement was enabled by improved understanding of the “relaxation oscillations”, previously attributed to repetitive ITB collapses, and of the fast ion behavior in this regime. It was found that the “relaxation oscillations” are coupled core-edge modes 2 amenable to wall-stabilization, and that fast ion losses which previously dictated a large plasma-wall separation to avoid wall over-heating, can be reduced tomore » classical levels with sufficient plasma density. By using optimized waveforms of the plasma-wall separation and plasma density, fully noninductive plasmas have been sustained for long durations with excellent energy confinement quality, bootstrap fraction ≥ 80%, β N ≤ 4 , β P ≥ 3 , and β T ≥ 2%. Finally, these results bolster the applicability of the high poloidal beta tokamak regime toward the realization of a steady-state fusion reactor.« less

Phenomenology of beam driven modes in the field reversed configuration

NASA Astrophysics Data System (ADS)

Magee, Richard; Bolte, Nathan; Clary, Ryan; Necas, Ales; Korepanov, Sergey; Smirnov, Artem; Thompson, Matthew; Tajima, Toshiki; THE TAE Team

2016-10-01

The C-2U experiment offers a unique plasma environment combining a high beta field reversed configuration (FRC) embedded in a low beta magnetic mirror with high power neutral beam injection. The beams are injected tangentially into a modest magnetic field so that the orbits of the resulting fast ions encircle the entire plasma. These large orbit particles sustain and stabilize the plasma and suppress turbulence. Measurements of magnetic fluctuations at the edge of the plasma reveal the presence of three coherent beam driven modes: a low frequency, chirping mode, a mode near the ion cyclotron frequency, and a high frequency compressional Alfven mode. Remarkably, none of these modes are observed to have a deleterious effect on global plasma confinement. In fact, the cyclotron mode has the beneficial effect of dramatically enhancing the DD fusion reaction rate by drawing a trail from the plasma ion energy distribution on a sub-collisional timescale. In this presentation, we experimentally characterize the beam driven modes in the C-2U FRC with data from multiple diagnostics including magnetics, spectroscopy, neutral particle analyzers and fusion product diagnostics. Results are compared to a particle-in-cell simulation in a simplified geometry.

Modular low aspect ratio-high beta torsatron

DOEpatents

Sheffield, George V.; Furth, Harold P.

1984-02-07

A fusion reactor device in which the toroidal magnetic field and at least a portion of the poloidal magnetic field are provided by a single set of modular coils. The coils are arranged on the surface of a low aspect ratio toroid in planes having the cylindrical coordinate relationship .phi.=.phi..sub.i +kz where k is a constant equal to each coil's pitch and .phi..sub.i is the toroidal angle at which the i'th coil intersects the z=o plane. The device may be described as a modular, high beta torsation whose screw symmetry is pointed along the systems major (z) axis. The toroid defined by the modular coils preferably has a racetrack minor cross section. When vertical field coils and preferably a toroidal plasma current are provided for magnetic field surface closure within the toroid, a vacuum magnetic field of racetrack shaped minor cross section with improved stability and beta valves is obtained.

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

Qian, Jinping P.; Garofalo, Andrea M.; Gong, Xianzu Z.

Recent EAST/DIII-D joint experiments on the high poloidal betamore » $${{\\beta}_{\\text{P}}}$$ regime in DIII-D have extended operation with internal transport barriers (ITBs) and excellent energy confinement (H 98y2 ~ 1.6) to higher plasma current, for lower q 95 ≤ 7.0, and more balanced neutral beam injection (NBI) (torque injection < 2 Nm), for lower plasma rotation than previous results. Transport analysis and experimental measurements at low toroidal rotation suggest that the E × B shear effect is not key to the ITB formation in these high $${{\\beta}_{\\text{P}}}$$ discharges. Experiments and TGLF modeling show that the Shafranov shift has a key stabilizing effect on turbulence. Extrapolation of the DIII-D results using a 0D model shows that with the improved confinement, the high bootstrap fraction regime could achieve fusion gain Q = 5 in ITER at $${{\\beta}_{\\text{N}}}$$ ~ 2.9 and q 95 ~ 7. With the optimization of q(0), the required improved confinement is achievable when using 1.5D TGLF-SAT1 for transport simulations. Furthermore, results reported in this paper suggest that the DIII-D high $${{\\beta}_{\\text{P}}}$$ scenario could be a candidate for ITER steady state operation.« less

Super H-mode: theoretical prediction and initial observations of a new high performance regime for tokamak operation

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

Snyder, Philip B.; Solomon, Wayne M.; Burrell, Keith H.

2015-07-21

A new “Super H-mode” regime is predicted, which enables pedestal height and predicted fusion performance substantially higher than for H-mode operation. This new regime is predicted to exist by the EPED pedestal model, which calculates criticality constraints for peeling-ballooning and kinetic ballooning modes, and combines them to predict the pedestal height and width. EPED usually predicts a single (“H-mode”) pedestal solution for each set of input parameters, however, in strongly shaped plasmas above a critical density, multiple pedestal solutions are found, including the standard “Hmode” solution, and a “Super H-Mode” solution at substantially larger pedestal height and width. The Supermore » H-mode regime is predicted to be accessible by controlling the trajectory of the density, and to increase fusion performance for ITER, as well as for DEMO designs with strong shaping. A set of experiments on DIII-D has identified the predicted Super H-mode regime, and finds pedestal height and width, and their variation with density, in good agreement with theoretical predictions from the EPED model. Finally, the very high pedestal enables operation at high global beta and high confinement, including the highest normalized beta achieved on DIII-D with a quiescent edge.« less

High performance advanced tokamak regimes in DIII-D for next-step experiments

NASA Astrophysics Data System (ADS)

Greenfield, C. M.; Murakami, M.; Ferron, J. R.; Wade, M. R.; Luce, T. C.; Petty, C. C.; Menard, J. E.; Petrie, T. W.; Allen, S. L.; Burrell, K. H.; Casper, T. A.; DeBoo, J. C.; Doyle, E. J.; Garofalo, A. M.; Gorelov, I. A.; Groebner, R. J.; Hobirk, J.; Hyatt, A. W.; Jayakumar, R. J.; Kessel, C. E.; La Haye, R. J.; Jackson, G. L.; Lohr, J.; Makowski, M. A.; Pinsker, R. I.; Politzer, P. A.; Prater, R.; Strait, E. J.; Taylor, T. S.; West, W. P.; DIII-D Team

2004-05-01

Advanced Tokamak (AT) research in DIII-D [K. H. Burrell for the DIII-D Team, in Proceedings of the 19th Fusion Energy Conference, Lyon, France, 2002 (International Atomic Energy Agency, Vienna, 2002) published on CD-ROM] seeks to provide a scientific basis for steady-state high performance operation in future devices. These regimes require high toroidal beta to maximize fusion output and poloidal beta to maximize the self-driven bootstrap current. Achieving these conditions requires integrated, simultaneous control of the current and pressure profiles, and active magnetohydrodynamic stability control. The building blocks for AT operation are in hand. Resistive wall mode stabilization via plasma rotation and active feedback with nonaxisymmetric coils allows routine operation above the no-wall beta limit. Neoclassical tearing modes are stabilized by active feedback control of localized electron cyclotron current drive (ECCD). Plasma shaping and profile control provide further improvements. Under these conditions, bootstrap supplies most of the current. Steady-state operation requires replacing the remaining Ohmic current, mostly located near the half radius, with noninductive external sources. In DIII-D this current is provided by ECCD, and nearly stationary AT discharges have been sustained with little remaining Ohmic current. Fast wave current drive is being developed to control the central magnetic shear. Density control, with divertor cryopumps, of AT discharges with edge localized moding H-mode edges facilitates high current drive efficiency at reactor relevant collisionalities. A sophisticated plasma control system allows integrated control of these elements. Close coupling between modeling and experiment is key to understanding the separate elements, their complex nonlinear interactions, and their integration into self-consistent high performance scenarios. Progress on this development, and its implications for next-step devices, will be illustrated by results of recent experiment and simulation efforts.

Creation of active TIM barrel enzymes through genetic fusion of half-barrel domain constructs derived from two distantly related glycosyl hydrolases.

PubMed

Sharma, Prerna; Kaila, Pallavi; Guptasarma, Purnananda

2016-12-01

Diverse unrelated enzymes that adopt the beta/alpha (or TIM) barrel topology display similar arrangements of beta/alpha units placed in a radial eight-fold symmetry around the barrel's axis. The TIM barrel was originally thought to be a single structural domain; however, it is now thought that TIM barrels arose from duplication and fusion of smaller half-barrels consisting of four beta/alpha units. We describe here the design, expression and purification, as well as characterization of folding, activity and stability, of chimeras of two TIM barrel glycosyl hydrolases, made by fusing different half-barrel domains derived from an endoglucanase from Clostridium cellulolyticum, CelCCA and a beta-glucosidase from Pyrococcus furiosus, CelB. We show that after refolding following purification from inclusion bodies, the two half-barrel fusion chimeras (CelCCACelB and CelBCelCCA) display catalytic activity although they assemble into large soluble oligomeric aggregated species containing chains of mixed beta and alpha structure. CelBCelCCA displays hyperthermophile-like structural stability as well as significant stability to chemical denaturation (C m of 2.6 m guanidinium hydrochloride), whereas CelCCACelB displays mesophile-like stability (T m of ~ 71 °C). The endoglucanase activities of both chimeras are an order of magnitude lower than those of CelB or CelCCA, whereas the beta-glucosidase activity of CelBCelCCA is about two orders of magnitude lower than that of CelB. The chimera CelCCACelB shows no beta-glucosidase activity. Our results demonstrate that half-barrel domains from unrelated sources can fold, assemble and function, with scope for improvement. Pyrococcus furiosus beta-glucosidase (CelB, EC: 3.2.1.21). Clostridium cellulolyticum endoglucanase A (CelCCA, EC: 3.2.1.4). © 2016 Federation of European Biochemical Societies.

Ten tandem repeats of {beta}-hCG 109-118 enhance immunogenicity and anti-tumor effects of {beta}-hCG C-terminal peptide carried by mycobacterial heat-shock protein HSP65

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

Zhang Yankai; Yan Rong; He Yi

2006-07-14

The {beta}-subunit of human chorionic gonadotropin ({beta}-hCG) is secreted by many kinds of tumors and it has been used as an ideal target antigen to develop vaccines against tumors. In view of the low immunogenicity of this self-peptide,we designed a method based on isocaudamer technique to repeat tandemly the 10-residue sequence X of {beta}-hCG (109-118), then 10 tandemly repeated copies of the 10-residue sequence combined with {beta}-hCG C-terminal 37 peptides were fused to mycobacterial heat-shock protein 65 to construct a fusion protein HSP65-X10-{beta}hCGCTP37 as an immunogen. In this study, we examined the effect of the tandem repeats of this 10-residuemore » sequence in eliciting an immune by comparing the immunogenicity and anti-tumor effects of the two immunogens, HSP65-X10-{beta}hCGCTP37 and HSP65-{beta}hCGCTP37 (without the 10 tandem repeats). Immunization of mice with the fusion protein HSP65-X10-{beta}hCGCTP37 elicited much higher levels of specific anti-{beta}-hCG antibodies and more effectively inhibited the growth of Lewis lung carcinoma (LLC) in vivo than with HSP65-{beta}hCGCTP37, which should suggest that HSP65-X10-{beta}hCGCTP37 may be an effective protein vaccine for the treatment of {beta}-hCG-dependent tumors and multiple tandem repeats of a certain epitope are an efficient method to overcome the low immunogenicity of self-peptide antigens.« less

Wnt/beta-catenin pathway activation and myogenic differentiation are induced by cholesterol depletion.

PubMed

Mermelstein, Cláudia S; Portilho, Débora M; Mendes, Fábio A; Costa, Manoel L; Abreu, José Garcia

2007-03-01

Myogenic differentiation is a multistep process that begins with the commitment of mononucleated precursors that withdraw from cell cycle. These myoblasts elongate while aligning to each other, guided by the recognition between their membranes. This step is followed by cell fusion and the formation of long and striated multinucleated myotubes. We have recently shown that cholesterol depletion by methyl-beta-cyclodextrin (MbetaCD) induces myogenic differentiation by enhancing myoblast recognition and fusion. Here, we further studied the signaling pathways responsible for early steps of myogenesis. As it is known that Wnt plays a role in muscle differentiation, we used the chemical MbetaCD to deplete membrane cholesterol and investigate the involvement of the Wnt/beta-catenin pathway during myogenesis. We show that cholesterol depletion promoted a significant increase in expression of beta-catenin, its nuclear translocation and activation of the Wnt pathway. Moreover, we show that the activation of the Wnt pathway after cholesterol depletion can be inhibited by the soluble protein Frzb-1. Our data suggest that membrane cholesterol is involved in Wnt/beta-catenin signaling in the early steps of myogenic differentiation.

Advances in the high bootstrap fraction regime on DIII-D towards the Q = 5 mission of ITER steady state

DOE PAGES

Qian, Jinping P.; Garofalo, Andrea M.; Gong, Xianzu Z.; ...

2017-03-20

Recent EAST/DIII-D joint experiments on the high poloidal betamore » $${{\\beta}_{\\text{P}}}$$ regime in DIII-D have extended operation with internal transport barriers (ITBs) and excellent energy confinement (H 98y2 ~ 1.6) to higher plasma current, for lower q 95 ≤ 7.0, and more balanced neutral beam injection (NBI) (torque injection < 2 Nm), for lower plasma rotation than previous results. Transport analysis and experimental measurements at low toroidal rotation suggest that the E × B shear effect is not key to the ITB formation in these high $${{\\beta}_{\\text{P}}}$$ discharges. Experiments and TGLF modeling show that the Shafranov shift has a key stabilizing effect on turbulence. Extrapolation of the DIII-D results using a 0D model shows that with the improved confinement, the high bootstrap fraction regime could achieve fusion gain Q = 5 in ITER at $${{\\beta}_{\\text{N}}}$$ ~ 2.9 and q 95 ~ 7. With the optimization of q(0), the required improved confinement is achievable when using 1.5D TGLF-SAT1 for transport simulations. Furthermore, results reported in this paper suggest that the DIII-D high $${{\\beta}_{\\text{P}}}$$ scenario could be a candidate for ITER steady state operation.« less

Isolation and characterization of a cDNA from Cuphea lanceolata encoding a beta-ketoacyl-ACP reductase.

PubMed

Klein, B; Pawlowski, K; Höricke-Grandpierre, C; Schell, J; Töpfer, R

1992-05-01

A cDNA encoding beta-ketoacyl-ACP reductase (EC 1.1.1.100), an integral part of the fatty acid synthase type II, was cloned from Cuphea lanceolata. This cDNA of 1276 bp codes for a polypeptide of 320 amino acids with 63 N-terminal residues presumably representing a transit peptide and 257 residues corresponding to the mature protein of 27 kDa. The encoded protein shows strong homology with the amino-terminal sequence and two tryptic peptides from avocado mesocarp beta-ketoacyl-ACP reductase, and its total amino acid composition is highly similar to those of the beta-ketoacyl-ACP reductases of avocado and spinach. Amino acid sequence homologies to polyketide synthase, beta-ketoreductases and short-chain alcohol dehydrogenases are discussed. An engineered fusion protein lacking most of the transit peptide, which was produced in Escherichia coli, was isolated and proved to possess beta-ketoacyl-ACP reductase activity. Hybridization studies revealed that in C. lanceolata beta-ketoacyl-ACP reductase is encoded by a small family of at least two genes and that members of this family are expressed in roots, leaves, flowers and seeds.

Expression of the Pasteurella haemolytica leukotoxin is inhibited by a locus that encodes an ATP-binding cassette homolog.

PubMed Central

Highlander, S K; Wickersham, E A; Garza, O; Weinstock, G M

1993-01-01

Multicopy and single-copy chromosomal fusions between the Pasteurella haemolytica leukotoxin regulatory region and the Escherichia coli beta-galactosidase gene have been constructed. These fusions were used as reporters to identify and isolate regulators of leukotoxin expression from a P. haemolytica cosmid library. A cosmid clone, which inhibited leukotoxin expression from multicopy and single-copy protein fusions, was isolated and found to contain the complete leukotoxin gene cluster plus additional upstream sequences. The locus responsible for inhibition of expression from leukotoxin-beta-galactosidase fusions was mapped within these upstream sequences, by transposon mutagenesis with Tn5, and its DNA sequence was determined. The inhibitory activity was found to be associated with a predicted 440-amino-acid reading frame (lapA) that lies within a four-gene arginine transport locus. LapA is predicted to be the nucleotide-binding component of this transport system and shares homology with the Clp family of proteases. Images PMID:8359916

Molecular cloning and characterization of beluga whale (Delphinapterus leucas) interleukin-1beta and tumor necrosis factor-alpha.

PubMed Central

Denis, F; Archambault, D

2001-01-01

Interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) are cytokines produced primarily by monocytes and macrophages with regulatory effects in inflammation and multiple aspects of the immune response. As yet, no molecular data have been reported for IL-1beta and TNF-alpha of the beluga whale. In this study, we cloned and determined the entire cDNA sequence encoding beluga whale IL-1beta and TNF-alpha. The genetic relationship of the cytokine sequences was then analyzed with those from several mammalian species, including the human and the pig. The homology of beluga whale IL-1beta nucleic acid and deduced amino acid sequences with those from these mammalian species ranged from 74.6 to 86.0% and 62.7 to 77.1%, respectively, whereas that of TNF-alpha varied from 79.3 to 90.8% and 75.3 to 87.7%, respectively. Phylogenetic analyses based on deduced amino acid sequences showed that the beluga whale IL-1beta and TNF-alpha were most closely related to those of the ruminant species (cattle, sheep, and deer). The beluga whale IL-1beta- and TNF-alpha-encoding sequences were thereafter successfully expressed in Escherichia coli as fusion proteins by using procaryotic expression vectors. The fusion proteins were used to produce beluga whale IL-1beta- and TNF-alpha-specific rabbit antisera. Images Figure 3. Figure 4. Figure 5. PMID:11768130

High Voltage, Fast-Switching Module for Active Control of Magnetic Fields and Edge Plasma Currents

NASA Astrophysics Data System (ADS)

Ziemba, Timothy; Miller, Kenneth; Prager, James; Slobodov, Ilia

2016-10-01

Fast, reliable, real-time control of plasma is critical to the success of magnetic fusion science. High voltage and current supplies are needed to mitigate instabilities in all experiments as well as disruption events in large scale tokamaks for steady-state operation. Silicon carbide (SiC) MOSFETs offer many advantages over IGBTs including lower drive energy requirements, lower conduction and switching losses, and higher switching frequency capabilities; however, these devices are limited to 1.2-1.7 kV devices. As fusion enters the long-pulse and burning plasma eras, efficiency of power switching will be important. Eagle Harbor Technologies (EHT), Inc. developing a high voltage SiC MOSFET module that operates at 10 kV. This switch module utilizes EHT gate drive technology, which has demonstrated the ability to increase SiC MOSFET switching efficiency. The module will allow more rapid development of high voltage switching power supplies at lower cost necessary for the next generation of fast plasma feedback and control. EHT is partnering with the High Beta Tokamak group at Columbia to develop detailed high voltage module specifications, to ensure that the final product meets the needs of the fusion science community.

HIV-1 virion fusion assay: uncoating not required and no effect of Nef on fusion

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

Cavrois, Marielle; Neidleman, Jason; Yonemoto, Wes

2004-10-15

We recently described a sensitive and specific assay that detects the fusion of HIV-1 virions to a broad range of target cells, including primary CD4 cells. This assay involves the use of virions containing {beta}-lactamase-Vpr (BlaM-Vpr) and the loading of target cells with CCF2, a fluorogenic substrate of {beta}-lactamase. Since Vpr strongly associates with the viral core, uncoating of the viral particle might be required for effective cleavage of CCF2 by BlaM-Vpr. Here, we show that BlaM-Vpr within mature viral cores effectively cleaves CCF2, indicating that this assay measures virion fusion independently of uncoating. We also show that wildtype andmore » Nef-deficient HIV-1 virions fuse with equivalent efficiency to HeLa-CD4 cells, SupT1 T cells, and primary CD4 T cells. Since Nef enhances cytoplasmic delivery of viral cores and increases viral infectivity, these findings indicate that Nef enhances an early post-fusion event in the multistep process of viral entry. Possible sites of Nef action include enlargement of the fusion pore, enhanced uncoating of viral particles, and more efficient passage of viral cores through the dense cortical actin network located immediately beneath the plasma membrane.« less

A heterologous hormone response element enhances expression of rat beta-casein promoter-driven chloramphenicol acetyltransferase fusion genes in the mammary gland of transgenic mice.

PubMed

Greenberg, N M; Reding, T V; Duffy, T; Rosen, J M

1991-10-01

Previous studies have demonstrated that the entire rat beta-casein (R beta C) gene and a -524/+490 R beta C fragment-chloramphenicol acetyltransferase (CAT) fusion gene are expressed preferentially in the mammary gland of transgenic mice in a developmentally regulated fashion. However, transgene expression was infrequent, less than 1% of that observed for the endogenous gene, and varied as much as 500-fold, presumably due to the site of chromosomal integration. To determine whether a heterologous hormone-responsive enhancer could be used to increase both the level and frequency of expression in the mammary gland, a fragment derived from the mouse mammary tumor virus long terminal repeat containing four hormone response elements (HREs) was inserted into the R beta C promoter at a site not known to contain transcriptional regulatory elements. Transgenic mice generated which carried HRE-enhanced R beta C-CAT fusion genes expressed CAT activity in the mammary glands of all founder lines examined at levels that were on average 13-fold greater than for lines generated with similar constructs not carrying HREs. In the highest expressing line, the level of HRE-enhanced transgene expression was found to be developmentally regulated, increasing 14-fold in the mammary gland from virgin to day 10 of lactation. In this line, expression was also observed in the thymus and spleen; however, the level of CAT activity was 4-fold lower than in the mammary gland and was not developmentally regulated. In adrenalectomized mice, the administration of dexamethasone stimulated CAT expression in the mammary gland but not in the thymus and spleen. These studies demonstrate that in the context of the R beta C promoter, the HRE functions in the mammary gland to increase both the frequency and level of transgene expression.

The Role of Combined ICRF and NBI Heating in JET Hybrid Plasmas in Quest for High D-T Fusion Yield

NASA Astrophysics Data System (ADS)

Mantsinen, Mervi; Challis, Clive; Frigione, Domenico; Graves, Jonathan; Hobirk, Joerg; Belonohy, Eva; Czarnecka, Agata; Eriksson, Jacob; Gallart, Dani; Goniche, Marc; Hellesen, Carl; Jacquet, Philippe; Joffrin, Emmanuel; King, Damian; Krawczyk, Natalia; Lennholm, Morten; Lerche, Ernesto; Pawelec, Ewa; Sips, George; Solano, Emilia R.; Tsalas, Maximos; Valisa, Marco

2017-10-01

Combined ICRF and NBI heating played a key role in achieving the world-record fusion yield in the first deuterium-tritium campaign at the JET tokamak in 1997. The current plans for JET include new experiments with deuterium-tritium (D-T) plasmas with more ITER-like conditions given the recently installed ITER-like wall (ILW). In the 2015-2016 campaigns, significant efforts have been devoted to the development of high-performance plasma scenarios compatible with ILW in preparation of the forthcoming D-T campaign. Good progress was made in both the inductive (baseline) and the hybrid scenario: a new record JET ILW fusion yield with a significantly extended duration of the high-performance phase was achieved. This paper reports on the progress with the hybrid scenario which is a candidate for ITER longpulse operation (˜1000 s) thanks to its improved normalized confinement, reduced plasma current and higher plasma beta with respect to the ITER reference baseline scenario. The combined NBI+ICRF power in the hybrid scenario was increased to 33 MW and the record fusion yield, averaged over 100 ms, to 2.9x1016 neutrons/s from the 2014 ILW fusion record of 2.3x1016 neutrons/s. Impurity control with ICRF waves was one of the key means for extending the duration of the high-performance phase. The main results are reviewed covering both key core and edge plasma issues.

Plasma Experiments on an Internal Coil Device with an High Temperature Superconductor

NASA Astrophysics Data System (ADS)

Yuichi, Ogawa; Junji, Morikawa; Kotaro, Ohkuni; Dan, Hori; Shigeo, Yamakosi; Nagato, Yanagi; Toshiyuki, Mito; Masataka, Iwakuma; Toshio, Uede

2003-10-01

An internal coil device would be expected for exploring high beta plasmas based on plasma relaxation process. Prof. A. Hasegawa proposed an advanced fusion reactor with a dipole configuration, and Mahajan and Yoshida developed a new high beta state based on two-fluid relaxation theory. To study these high beta plasmas, we have constructed an internal coil device with a high temperature superconductor. The major radius of the internal coil is 15 cm, and the coil current is 50 kA. Three different types of Ag-sheathed Bi-2223 tapes are employed; i.e., a high critical current tape with a low silver ratio for the main HTS coil, a 0.3wt3atprovided by a GM refrigerator and supplied to the coil through a check valve, and the coil current is directly excited with the external power supply through removable electrodes. It took about 11 hours to cool the coil down to 21 K from the room temperature, and the nominal cable current of 118 A (overall coil current: 50 kA) has been achieved. A decay time constant of the persistent current is a few tens of hours. Plasma experiments in a dipole configuration have been initiated.

Overview of LDX Results

NASA Astrophysics Data System (ADS)

Kesner, J.; Boxer, A. C.; Ellsworth, J. L.; Karim, I.; Garnier, D. T.; Hansen, A. K.; Mauel, M. E.; Ortiz, E. E.

2006-10-01

The levitated dipole experiment (LDX) is a new research facility that is investigating plasma confinement and stability in a dipole magnetic field configuration as a possible catalyzed DD fusion power source that would avoid the burning of tritium. We report the production of high beta plasma confined by a laboratory superconducting dipole using neutral gas fueling and electron cyclotron resonance heating (ECRH). The pressure results from a population of anisotropic energetic trapped electrons that is sustained by microwave heating provided sufficient neutral gas is supplied to the plasma. The trapped electron beta was observed to be limited by the hot electron interchange (HEI) instability, but when the neutral gas was programmed so as to maintain the deuterium gas pressure near 0.2 mPa, the fast electron pressure increased by more than a factor of ten and the resulting stable high beta plasma was maintained quasi-continuously for up to 14 seconds. Low frequency (<10 kHz) fluctuations are sometimes observed at low neutral base pressure.

Medium-{beta} free-boundary equilibria of a quasi-isodynamic stellarator

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

Mikhailov, M. I.; Drevlak, M.; Nuehrenberg, J.

Free-boundary MHD equilibria with magnetic surfaces in the vacuum region surrounding the plasma [E. Strumberger, Nucl. Fusion 37, 19 (1997); M. Drevlak, D. Monticello, and A. Reiman, Nucl. Fusion 45, 731 (2005)] are obtained for a quasi-isodynamic stellarator [A. A. Subbotin, M. I. Mikhailov, V. D. Shafranov et al., Nucl. Fusion 46, 921 (2006); M. I. Mikhailov, J. Nuhrenberg, and V. D. Shafranov, Plasma Phys. Rep. 35, 529 (2009)].

Production and study of high-beta plasma confined by a superconducting dipole magneta)

NASA Astrophysics Data System (ADS)

Garnier, D. T.; Hansen, A.; Mauel, M. E.; Ortiz, E.; Boxer, A. C.; Ellsworth, J.; Karim, I.; Kesner, J.; Mahar, S.; Roach, A.

2006-05-01

The Levitated Dipole Experiment (LDX) [J. Kesner et al., in Fusion Energy 1998, 1165 (1999)] is a new research facility that is exploring the confinement and stability of plasma created within the dipole field produced by a strong superconducting magnet. Unlike other configurations in which stability depends on curvature and magnetic shear, magnetohydrodynamic stability of a dipole derives from plasma compressibility. Theoretically, the dipole magnetic geometry can stabilize a centrally peaked plasma pressure that exceeds the local magnetic pressure (β>1), and the absence of magnetic shear allows particle and energy confinement to decouple. In initial experiments, long-pulse, quasi-steady-state microwave discharges lasting more than 10s have been produced that are consistent with equilibria having peak beta values of 20%. Detailed measurements have been made of discharge evolution, plasma dynamics and instability, and the roles of gas fueling, microwave power deposition profiles, and plasma boundary shape. In these initial experiments, the high-field superconducting floating coil was supported by three thin supports. The plasma is created by multifrequency electron cyclotron resonance heating at 2.45 and 6.4GHz, and a population of energetic electrons, with mean energies above 50keV, dominates the plasma pressure. Creation of high-pressure, high-beta plasma is possible only when intense hot electron interchange instabilities are stabilized by sufficiently high background plasma density. A dramatic transition from a low-density, low-beta regime to a more quiescent, high-beta regime is observed when the plasma fueling rate and confinement time become sufficiently large.

EDITORIAL: The Nuclear Fusion Award The Nuclear Fusion Award

NASA Astrophysics Data System (ADS)

Kikuchi, M.

2011-01-01

The Nuclear Fusion Award ceremony for 2009 and 2010 award winners was held during the 23rd IAEA Fusion Energy Conference in Daejeon. This time, both 2009 and 2010 award winners were celebrated by the IAEA and the participants of the 23rd IAEA Fusion Energy Conference. The Nuclear Fusion Award is a paper prize to acknowledge the best distinguished paper among the published papers in a particular volume of the Nuclear Fusion journal. Among the top-cited and highly-recommended papers chosen by the Editorial Board, excluding overview and review papers, and by analyzing self-citation and non-self-citation with an emphasis on non-self-citation, the Editorial Board confidentially selects ten distinguished papers as nominees for the Nuclear Fusion Award. Certificates are given to the leading authors of the Nuclear Fusion Award nominees. The final winner is selected among the ten nominees by the Nuclear Fusion Editorial Board voting confidentially. 2009 Nuclear Fusion Award nominees For the 2009 award, the papers published in the 2006 volume were assessed and the following papers were nominated, most of which are magnetic confinement experiments, theory and modeling, while one addresses inertial confinement. Sabbagh S.A. et al 2006 Resistive wall stabilized operation in rotating high beta NSTX plasmas Nucl. Fusion 46 635-44 La Haye R.J. et al 2006 Cross-machine benchmarking for ITER of neoclassical tearing mode stabilization by electron cyclotron current drive Nucl. Fusion 46 451-61 Honrubia J.J. et al 2006 Three-dimensional fast electron transport for ignition-scale inertial fusion capsules Nucl. Fusion 46 L25-8 Ido T. et al 2006 Observation of the interaction between the geodesic acoustic mode and ambient fluctuation in the JFT-2M tokamak Nucl. Fusion 46 512-20 Plyusnin V.V. et al 2006 Study of runaway electron generation during major disruptions in JET Nucl. Fusion 46 277-84 Pitts R.A. et al 2006 Far SOL ELM ion energies in JET Nucl. Fusion 46 82-98 Berk H.L. et al 2006 Explanation of the JET n = 0 chirping mode Nucl. Fusion 46 S888-97 Urano H. et al 2006 Confinement degradation with beta for ELMy HH-mode plasmas in JT-60U tokamak Nucl. Fusion 46 781-7 Izzo V.A. et al 2006 A numerical investigation of the effects of impurity penetration depth on disruption mitigation by massive high-pressure gas jet Nucl. Fusion 46 541-7 Inagaki S. et al 2006 Comparison of transient electron heat transport in LHD helical and JT-60U tokamak plasmas Nucl. Fusion 46 133-41 Watanabe T.-H. et al 2006 Velocity-space structures of distribution function in toroidal ion temperature gradient turbulence Nucl. Fusion 46 24-32 2010 Nuclear Fusion Award nominees For the 2010 award, the papers published in the 2007 volume were assessed and the following papers were nominated, all of which are magnetic confinement experiments and theory. Rice J.E. et al 2007 Inter-machine comparison of intrinsic toroidal rotation in tokamaks Nucl. Fusion 47 1618-24 Lipschultz B. et al 2007 Plasma-surface interaction, scrape-off layer and divertor physics: implications for ITER Nucl. Fusion 47 1189-205 Loarer T. et al 2007 Gas balance and fuel retention in fusion devices Nucl. Fusion 47 1112-20 Garcia O.E et al 2007 Fluctuations and transport in the TCV scrape-off layer Nucl. Fusion 47 667-76 Zonca F. et al 2007 Electron fishbones: theory and experimental evidence Nucl. Fusion 47 1588-97 Maggi C.F. et al 2007 Characteristics of the H-mode pedestal in improved confinement scenarios in ASDEX Upgrade, DIII-D, JET and JT-60U Nucl. Fusion 47 535-51 Yoshida M. et al 2007 Momentum transport and plasma rotation profile in toroidal direction in JT-60U L-mode plasmas Nucl. Fusion 47 856-63 Zohm H. et al 2007 Control of MHD instabilities by ECCD: ASDEX Upgrade results and implications for ITER Nucl. Fusion 47 228-32 Snyder P.B. et al 2007 Stability and dynamics of the edge pedestal in the low collisionality regime: physics mechanisms for steady-state ELM-free operation Nucl. Fusion 47 961-8 Urano H. et al 2007 H-mode pedestal structure in the variation of toroidal rotation and toroidal field ripple in JT-60U Nucl. Fusion 47 706-13 Günter S. et al 2007 Interaction of energetic particles with large and small scale instabilities Nucl. Fusion 47 920-8

A GDT-based fusion neutron source for academic and industrial applications

NASA Astrophysics Data System (ADS)

Anderson, J. K.; Forest, C. B.; Mirnov, V. V.; Peterson, E. E.; Waleffe, R.; Wallace, J.; Harvey, R. W.

2017-10-01

The design of a fusion neutron source based on the gas dynamic trap (GDT) configuration is underway. The motivation is both the ends and the means. There are immediate applications for neutrons including medical isotope production and actinide burners. Taking the next step in the magnetic mirror path will leverage advances in high-temperature superconducting magnets and additive manufacturing in confining a fusion plasma, and both the technological and physics bases exist. Recent breakthrough results at the GDT facility in Russia demonstrate stable confinement of a beta 60% mirror plasma at high Te ( 1 keV). These scale readily to a fusion neutron source with an increase in magnetic field, mirror ratio, and ion energy. Studies of a next-step compact device focus on calculations of MHD equilibrium and stability, and Fokker-Planck modeling to optimize the heating scenario. The conceptualized device uses off-the-shelf MRI magnets for a 1 T central field, REBCO superconducting mirror coils (which can currently produce fields in excess of 30T), and existing 75 keV NBI and 140 GHz ECRH. High harmonic fast wave injection is damped on beam ions, dramatically increasing the fusion reactivity for an incremental bump in input power. MHD stability is achieved with the vortex confinement scheme, where a biasing profile imposes optimal ExB rotation of the plasma. Liquid metal divertors are being considered in the end cells. Work supported by the Wisconsin Alumni Research Foundation.

Modeling the excitation of global Alfven modes by an external antenna in the Joint European Torus (JET)

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

Huysmans, G.T.A.; Kerner, W.; Borba, D.

1995-05-01

The active excitation of global Alfven modes using the saddle coils in the Joint European Torus (JET) [{ital Plasma} {ital Physics} {ital and} {ital Controlled} {ital Nuclear} {ital Fusion} {ital Research} 1984, Proceedings of the 10th International Conference, London (International Atomic Energy Agency, Vienna, 1985), Vol. 1, p. 11] as the external antenna, will provide information on the damping of global modes without the need to drive the modes unstable. For the modeling of the Alfven mode excitation, the toroidal resistive magnetohydrodynamics (MHD) code CASTOR (Complex Alfven Spectrum in TORoidal geometry) [18{ital th} {ital EPS} {ital Conference} {ital On} {italmore » Controlled} {ital Fusion} {ital and} {ital Plasma} {ital Physics}, Berlin, 1991, edited by P. Bachmann and D. C. Robinson (The European Physical Society, Petit-Lancy, 1991), Vol. 15, Part IV, p. 89] has been extended to calculate the response to an external antenna. The excitation of a high-performance, high beta JET discharge is studied numerically. In particular, the influence of a finite pressure is investigated. Weakly damped low-{ital n} global modes do exist in the gaps in the continuous spectrum at high beta. A pressure-driven global mode is found due to the interaction of Alfven and slow modes. Its frequency scales solely with the plasma temperature, not like a pure Alfven mode with a density and magnetic field.« less

Interallelic complementation of mutations in propionic acidemia by microinjection of mutant cDNAs into fibroblasts of affected patients

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

Loyer, M.; Leclerc, D.; Gravel, R.A.

1994-09-01

Propionic acidemia is a rare autosomal recessive disorder resulting from defects of the {alpha} or {beta} subunit of biotin-dependent propionyl-CoA carboxylase (PCC). Mutations are assigned to defects of the PCCA ({alpha} subunit) or PCCB ({beta} subunit) gene through complementation studies after somatic fusion of patient cell lines. About two-thirds of patients with {beta} subunit defects (complementation group pccBC) show interallelic complementation in cell fusion experiments (subgroups pccB and pccC), monitored by the PCC-dependent metabolisms of {sup 14}C-propionate. Most patient cell lines are heteroallelic for two different mutations, leaving ambiguous the identity of the mutation participating in interallelic complementation. To identifymore » the complementing mutations, we have expressed {beta}-subunit cDNAs containing individual mutations by microinjection of the cDNAs in recipient cells from patients with {beta} subunit defects. Correction of the PCC defect was monitored by autoradiography of {sup 14}C-propionate incorporation. In some experiments, cDNAs were co-injected with a plasmid expressing the E. coli lacZ gene as a positive control for successful injection. Two mutations from the pccB subgroup showed complementation when injected into pccC cells; dupKICK140-143 and Pro228Leu. Similarly, two mutations from the pccC subgroup complemented after injection into pccB cells; {Delta}Ile408 and Arg410Trp. No mutation complemented with mutation of the pccBC group which are classified as non-complementing in cell fusion experiments. The results show that the complementing pccB mutations are found in the N-terminal half of the {beta} subunit, while the complementing pccC mutations cluxter at a site in the C-terminal half. The latter site is a candidate for the propionyl-CoA binding site based on sequence identity with a region of transcarboxylase from Propionibacterium shermanii.« less

Helium Catalyzed D-D Fusion in a Levitated Dipole

NASA Astrophysics Data System (ADS)

Kesner, J.; Bromberg, L.; Garnier, D. T.; Hansen, A.; Mauel, M. E.

2003-10-01

Fusion research has focused on the goal of deuterium and tritium (D-T) fusion power because the reaction rate is large compared with the other fusion fuels: D-D or D-He3. Furthermore, the D-D cycle is difficult in traditional confinement devices, such as tokamaks, because good energy confinement is accompanied by good particle confinement which leads to an accumulation of ash. Fusion reactors based on the D-D reaction would be advantageous to D-T based reactors since they do not require the breeding of tritium and can reduce the flux of energetic neutrons that cause material damage. We propose a fusion power source based on the levitated dipole fusion concept that uses a "helium catalyzed D-D" fuel cycle, where rapid circulation of plasma allows the removal of tritium and the re-injection of the He3 decay product, eliminating the need for a massive blanket and shield. Stable dipole confinement derives from plasma compressibility instead of the magnetic shear and average good curvature. As a result, a dipole magnetic field can stabilize plasma at high beta while allowing large-scale adiabatic particle circulation. These properties may make the levitated dipole uniquely capable of achieving good energy confinement with low particle confinement. We find that a dipole based D-D power source can provide better utilization of magnetic field energy with a comparable mass power density to a D-T based tokamak power source.

Integrated Scenario Modeling of NSTX Advanced Plasma Configurations

NASA Astrophysics Data System (ADS)

Kessel, Charles; Synakowski, Edward

2003-10-01

The Spherical Torus will provide an attractive fusion energy source if it can demonstrate the following major features: high elongation and triangularity, 100% non-inductive current with a credible path to high bootstrap fractions, non-solenoidal startup and current rampup, high beta with stabilization of RWM instabilities, and sufficiently high energy confinement. NSTX has specific experimental milestones to examine these features, and integrated scenario modeling is helping to understand how these configurations might be produced and what tools are needed to access this operating space. Simulations with the Tokamak Simulation Code (TSC), CURRAY, and JSOLVER/BALMSC/PEST2 have identified fully non-inductively sustained, high beta plasmas that rely on strong plasma shaping accomplished with a PF coil modification, off-axis current drive from Electron Bernstein Waves (EBW), flexible on-axis heating and CD from High Harmonic Fast Wave (HHFW) and Neutral Beam Injection (NBI), and density control. Ideal MHD stability shows that with wall stabilization through plasma rotation and/or RWM feedback coils, a beta of 40% is achievable, with 100% non-inductive current sustained for 4 current diffusion times. Experimental data and theory are combined to produce a best extrapolation to these regimes, which is continuously improved as the discharges approach these parameters, and theoretical/computational methods expand. Further investigations and development for integrated scenario modeling on NSTX is discussed.

Assignment of the structural gene for human beta glucuronidase to chromosome 7 and tetrameric association of subunits in the enzyme molecule.

PubMed Central

Chern, C J; Croce, C M

1976-01-01

The structural locus for human beta glucuronidase is assigned to chromosome 7, a localization based upon concordant segregation of the expression of the human enzyme and the presence of human chromosome 7 in somatic cell hybrid clones derived independently from fusions of different human and mouse cells. Hybrid clones containing only human chromosome 7 are included in this study. Electrophoresis of beta glucuronidase also has revealed that human beta glucuronidase has a tetrametric structure. Images Fig. 1 Fig. 2 Fig. 3 PMID:941902

Method of oocyte activation affects cloning efficiency in pigs.

PubMed

Whitworth, Kristin M; Li, Rongfeng; Spate, Lee D; Wax, David M; Rieke, August; Whyte, Jeffrey J; Manandhar, Gaurishankar; Sutovsky, Miriam; Green, Jonathan A; Sutovsky, Peter; Prather, Randall S

2009-05-01

The following experiments compared the efficiency of three fusion/activation protocols following somatic cell nuclear transfer (SCNT) with porcine somatic cells transfected with enhanced green fluorescent protein driven by the chicken beta-actin/rabbit beta-globin hybrid promoter (pCAGG-EGFP). The three protocols included electrical fusion/activation (NT1), electrical fusion/activation followed by treatment with a reversible proteasomal inhibitor MG132 (NT2) and electrical fusion in low Ca(2+) followed by chemical activation with thimerosal/dithiothreitol (NT3). Data were collected at Days 6, 12, 14, 30, and 114 of gestation. Fusion rates, blastocyst-stage mean cell numbers, recovery rates, and pregnancy rates were calculated and compared between protocols. Fusion rates were significantly higher for NT1 and NT2 compared to NT3 (P < 0.05). There was no significant difference in mean nuclear number. Pregnancy rate for NT2 was 100% (n = 19) at all stages collected and was significantly higher than NT1 (71.4%, n = 28; P < 0.05), but was not significantly higher than NT3 (82.6%, n = 23; P < 0.15). Recovery rates were calculated based on the number of embryos, conceptuses, fetuses, or piglets present at the time of collection, divided by the number of embryos transferred to the recipient gilts. Recovery rates between the three groups were not significantly different at any of the stages collected (P > 0.05). All fusion/activation treatments produced live, pCAGG-EGFP positive piglets from SCNT. Treatment with MG132 after fusion/activation of reconstructed porcine embryos was the most effective method when comparing the overall pregnancy rates. The beneficial effect of NT2 protocol may be due to the stimulation of proteasomes that infiltrate donor cell nucleus shortly after nuclear transfer. (c) 2008 Wiley-Liss, Inc.

Improved H mode with flat central q profile on EAST

NASA Astrophysics Data System (ADS)

Liu, Haiqing; Yang, Yao; Gao, Xiang; Zeng, Long; Qian, Jinping; Gong, Xianzu; Wan, Baonian; Ding, Weixing; Brower, David Lyn; EAST Team

2017-10-01

High betaN ( 1.8) plasma with good confinement (H98y2 1.1) on EAST tokamak has been reported recently. These ELMy H-mode plasmas with Bt = 1.6T, Ip = 400 kA and q95 4.5 were heated by lower hybrid wave and neutral beam injection. The internal transport barrier (ITB) and edge transport barrier (ETB) are both observed with m/n =1/1 fishbone, which were identified to clamp central q at values close to unity. Implying an improved H-mode with flat central q profile and absence of sawteeth, like other devices. Accurate q profile, key profile for developing scenarios aim at high performance H mode, were derived by Polarimeter-interferometer (POINT) measurement as constraint. Base on the optimized current profile, better confinement (H98y2 1.4) with an electron ITB was obtained also with flat central q profile and absence of sawteeth at high betaP ( 2) regime with Bt = 2.5T, Ip = 400 kA. Both high betaN regime and high betaP regime H mode, are characterized by a stationary flat central q profile q0 >=1, but typically close to 1, absence of sawteeth, H98(y,2) >1 and simultaneously, with ITB. This work is supported by the National Magnetic Confinement Fusion Program of China with Contract No. 2014GB106002 and partly supported by the US D.O.E. contract DESC0010469.

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

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

Filone, Claire Marie; Heise, Mark; Doms, Robert W.

2006-12-20

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

The conceptual design of a robust, compact, modular tokamak reactor based on high-field superconductors

NASA Astrophysics Data System (ADS)

Whyte, D. G.; Bonoli, P.; Barnard, H.; Haakonsen, C.; Hartwig, Z.; Kasten, C.; Palmer, T.; Sung, C.; Sutherland, D.; Bromberg, L.; Mangiarotti, F.; Goh, J.; Sorbom, B.; Sierchio, J.; Ball, J.; Greenwald, M.; Olynyk, G.; Minervini, J.

2012-10-01

Two of the greatest challenges to tokamak reactors are 1) large single-unit cost of each reactor's construction and 2) their susceptibility to disruptions from operation at or above operational limits. We present an attractive tokamak reactor design that substantially lessens these issues by exploiting recent advancements in superconductor (SC) tapes allowing peak field on SC coil > 20 Tesla. A R˜3.3 m, B˜9.2 T, ˜ 500 MW fusion power tokamak provides high fusion gain while avoiding all disruptive operating boundaries (no-wall beta, kink, and density limits). Robust steady-state core scenarios are obtained by exploiting the synergy of high field, compact size and ideal efficiency current drive using high-field side launch of Lower Hybrid waves. The design features a completely modular replacement of internal solid components enabled by the demountability of the coils/tapes and the use of an immersion liquid blanket. This modularity opens up the possibility of using the device as a nuclear component test facility.

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.

Stabilization and cytoskeletal-association of LDL receptor mRNA are mediated by distinct domains in its 3' untranslated region.

PubMed

Wilson, G M; Vasa, M Z; Deeley, R G

1998-05-01

The mRNA encoding the human low density lipoprotein (LDL) receptor is transiently stabilized after phorbol ester treatment of HepG2 cells and has been shown to associate with components of the cytoskeleton in this cell line (G. M. Wilson, E. A. Roberts, and R. G. Deeley, J. Lipid Res. 1997. 38: 437-446). Using an episomal expression system, fragments of the 3' untranslated region (3'UTR) of LDL receptor mRNA were transcribed in fusion with the coding region of beta-globin mRNA in HepG2 cells. Analyses of the decay kinetics of these beta-globin-LDL receptor fusion mRNA deletion mutants showed that sequences in the proximal 3'UTR of LDL receptor mRNA including several AU-rich elements (AREs) were sufficient to confer short constitutive mRNA half-life in the heterologous system. Stabilization of LDL receptor mRNA in the presence of PMA required sequences in the distal 3'UTR, at or near three Alu-like repetitive elements. Furthermore, the 3'UTR of LDL receptor mRNA conferred cytoskeletal association on the otherwise unassociated beta-globin mRNA, by a mechanism involving at least two distinct RNA elements. Comparisons of decay kinetics and subcellular localization of endogenous LDL receptor mRNA and beta-globin-LDL receptor mRNA fusions in HepG2 cells have demonstrated that several cis-acting elements in the receptor 3'UTR contribute to post-transcriptional regulation of receptor expression, and provide further support for involvement of the cytoskeleton in the regulation of LDL receptor mRNA turnover.

Extending the validation of multi-mode model for anomalous transport to high beta poloidal tokamak scenario in DIII-D

NASA Astrophysics Data System (ADS)

Pankin, A. Y.; Kritz, A. H.; Rafiq, T.; Garofalo, A. M.; Holod, I.; Weiland, J.

2018-05-01

The Multi-Mode Model (MMM7.1) for anomalous transport is tested in predictive modeling of temperature profiles of a high beta poloidal DIII-D discharge. This new H-mode plasma regime, with high beta poloidal and high bootstrap currents, has been studied in DIII-D tokamak discharges [A. Garofalo et al., Nucl. Fusion 55, 123025 (2015)]. The role of instabilities that can drive the anomalous transport described by MMM7.1 is investigated. The temperature profiles for a high beta poloidal DIII-D discharge are computed using the NCLASS model for the neoclassical transport and the Weiland and Electron Temperature Gradient (ETG) components of the MMM7.1 model for the anomalous transport. The neoclassical transport is found to be the main contributor to the ion thermal transport in the plasma core. The contributions from the ion temperature gradient driven modes are found to be important only outside of the internal transport barrier. The magnitudes of the predicted temperature profiles are found to be in a reasonable agreement with experimental profiles. The simulation results approximately reproduce the internal transport barrier in the ion temperature profile but not in the electron temperature profile due to a weak dependence of the ETG driven transport on the Shafranov shift in the ETG component of MMM7.1. Possible effects that can contribute to stabilization of these modes, for example, effects associated with the large beta poloidal such as the Shafranov shift stabilization in the MMM7.1 model, are discussed. It is demonstrated that the E × B flow shear has a relatively small effect in the formation of the internal transport barrier in the high beta poloidal DIII-D discharge 154406. The Shafranov shift (alpha stabilization) and small or reversed magnetic shear profiles are found to be the primary reasons for quenched anomalous transport in this discharge.

Joint DIII-D/EAST Experiments Toward Steady State AT Demonstration

NASA Astrophysics Data System (ADS)

Garofalo, A. M.; Meneghini, O.; Staebler, G. M.; van Zeeland, M. A.; Gong, X.; Ding, S.; Qian, J.; Ren, Q.; Xu, G.; Grierson, B. A.; Solomon, W. M.; Holcomb, C. T.

2015-11-01

Joint DIII-D/EAST experiments on fully noninductive operation at high poloidal beta have demonstrated several attractive features of this regime for a steady-state fusion reactor. Very large bootstrap fraction (>80 %) is desirable because it reduces the demands on external noninductive current drive. High bootstrap fraction with an H-mode edge results in a broad current profile and internal transport barriers (ITBs) at large minor radius, leading to high normalized energy confinement and high MHD stability limits. The ITB radius expands with higher normalized beta, further improving both stability and confinement. Electron density ITB and large Shafranov shift lead to low AE activity in the plasma core and low anomalous fast ion losses. Both the ITB and the current profile show remarkable robustness against perturbations, without external control. Supported by US DOE under DE-FC02-04ER54698, DE-AC02-09CH11466 & DE-AC52-07NA27344 & by NMCFSP under contracts 2015GB102000 and 2015GB110001.

Eliciting an antibody response against a recombinant TSH containing fusion protein.

PubMed

Mard-Soltani, Maysam; Rasaee, Mohamad Javad; Sheikhi, AbdolKarim; Hedayati, Mehdi

2017-01-01

Designing novel antigens to rise specific antibodies for Thyroid Stimulating Hormone (TSH) detection is of great significance. A novel fusion protein consisting of the C termini sequence of TSH beta subunit and a fusion sequence was designed and produced for rabbit immunization. Thereafter, the produced antibodies were purified and characterized for TSH detection. Our results indicate that the produced antibody is capable of sensitive and specific detection of TSH with low cross reactivity. This study underscores the applicability of designed fusion protein for specific and sensitive polyclonal antibody production and the importance of selecting an amenable region of the TSH for immunization.

Repetitively Pulsed High Power RF Solid-State System

NASA Astrophysics Data System (ADS)

Bowman, Chris; Ziemba, Timothy; Miller, Kenneth E.; Prager, James; Quinley, Morgan

2017-10-01

Eagle Harbor Technologies, Inc. (EHT) is developing a low-cost, fully solid-state architecture for the generation of the RF frequencies and power levels necessary for plasma heating and diagnostic systems at validation platform experiments within the fusion science community. In Year 1 of this program, EHT has developed a solid-state RF system that combines an inductive adder, nonlinear transmission line (NLTL), and antenna into a single system that can be deployed at fusion science experiments. EHT has designed and optimized a lumped-element NLTL that will be suitable RF generation near the lower-hybrid frequency at the High Beta Tokamak (HBT) located at Columbia University. In Year 2, EHT will test this system at the Helicity Injected Torus at the University of Washington and HBT at Columbia. EHT will present results from Year 1 testing and optimization of the NLTL-based RF system. With support of DOE SBIR.

Alternate fusion fuels workshop

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

Not Available

1981-06-01

The workshop was organized to focus on a specific confinement scheme: the tokamak. The workshop was divided into two parts: systems and physics. The topics discussed in the systems session were narrowly focused on systems and engineering considerations in the tokamak geometry. The workshop participants reviewed the status of system studies, trade-offs between d-t and d-d based reactors and engineering problems associated with the design of a high-temperature, high-field reactor utilizing advanced fuels. In the physics session issues were discussed dealing with high-beta stability, synchrotron losses and transport in alternate fuel systems. The agenda for the workshop is attached.

The diagnostic performance of recombinant Trypanosoma cruzi ribosomal P2beta protein is influenced by its expression system.

PubMed

Marcipar, Iván S; Olivares, María Laura; Robles, Lucía; Dekanty, Andrés; Marcipar, Alberto; Silber, Ariel M

2004-03-01

In the present work, we have determined the effect of expression vectors and their corresponding host bacteria on the antigenic performance of Trypanosoma cruzi P2beta (TcP2beta) full-length recombinant protein. The gene encoding the TcP2beta ribosomal protein was cloned in pMAL-c2 and pET-32a vectors that allow the expression of high levels of soluble fusion proteins. A panel of 32 positive and 32 negative sera was assayed with the purified proteins expressed using pMal-c2 (TcP2beta-MBP) and pET-32a (TcP2beta-TRX) vectors and with MBP and TRX purified from pMAL-c2 and pET-32a vectors, respectively. The antigenic behavior of each TcP2beta recombinant protein differed in the diagnostic performance in terms of DI(+) (93.7 for TcP2beta-MBP vs 100% for TcP2beta-TRX), in DI(-) (90.5 for TcP2beta-MBP vs 100% for TcP2beta-TRX) and in cross-reaction with negative sera. To determine if the higher reactivity of expressed pMAL-c2 protein was due to folding during protein expression or to a steric effect related to the protein adsorption at the titration plate, the reactivity of sera against soluble proteins was assessed by ELISA inhibition assays. As each soluble protein preserved its level of reactivity, we concluded that differences in reactivity were due to intrinsic characteristics of the proteins and not to differences in patterns of adsorption to the plates.

ITER-FEAT operation

NASA Astrophysics Data System (ADS)

Shimomura, Y.; Aymar, R.; Chuyanov, V. A.; Huguet, M.; Matsumoto, H.; Mizoguchi, T.; Murakami, Y.; Polevoi, A. R.; Shimada, M.; ITER Joint Central Team; ITER Home Teams

2001-03-01

ITER is planned to be the first fusion experimental reactor in the world operating for research in physics and engineering. The first ten years of operation will be devoted primarily to physics issues at low neutron fluence and the following ten years of operation to engineering testing at higher fluence. ITER can accommodate various plasma configurations and plasma operation modes, such as inductive high Q modes, long pulse hybrid modes and non-inductive steady state modes, with large ranges of plasma current, density, beta and fusion power, and with various heating and current drive methods. This flexibility will provide an advantage for coping with uncertainties in the physics database, in studying burning plasmas, in introducing advanced features and in optimizing the plasma performance for the different programme objectives. Remote sites will be able to participate in the ITER experiment. This concept will provide an advantage not only in operating ITER for 24 hours a day but also in involving the worldwide fusion community and in promoting scientific competition among the ITER Parties.

Recombinant fusion protein and DNA vaccines against foot and mouth disease virus infection in guinea pig and swine.

PubMed

Huang, H; Yang, Z; Xu, Q; Sheng, Z; Xie, Y; Yan, W; You, Y; Sun, L; Zheng, Z

1999-01-01

In this study, we provide evidence that a recombinant fusion protein containing beta-galactosidase and a tandem repeat peptide of immunogenic dominant epitope of foot-and-mouth disease virus (FMDV) VP1 protein elicits high levels of neutralizing antibody and protects both guinea pigs and swine against infection. Vaccination with this fusion protein induced a FMDV-specific proliferative T-cell response and a neutralizing antibody response. The immunized guinea pigs and swine were protected against FMD type O virus infection. Two DNA plasmids expressing genes of foot-and-mouth disease were constructed. Both plasmids pBO1 and pCO1 contain a signal sequence of the swine immunoglobulin G (IgG) gene and fusion protein gene of pXZ84. The signal sequence and fusion protein gene were under the control of a metallothionein promoter in the case of the pBO1 plasmid and under the control of a cytomegalovirus immediate early promoter in the case of pCO1 plasmid. When pBO1 and pCO1 were inoculated intramuscularly into guinea pigs, both plasmids elicited a neutralizing antibody response and spleen cell proliferation increased following stimulation with FMDV antigen, but animals were not protected from viral challenge.

Multi-Wavelength Imaging of Solar Plasma - High-Beta Disruption Model of Solar Flares -

NASA Astrophysics Data System (ADS)

Shibasaki, Kiyoto

Solar atmosphere is filled with plasma and magnetic field. Activities in the atmosphere are due to plasma instabilities in the magnetic field. To understand the physical mechanisms of activities / instabilities, it is necessary to know the physical conditions of magnetized plasma, such as temperature, density, magnetic field, and their spatial structures and temporal developments. Multi-wavelength imaging is essential for this purpose. Imaging observations of the Sun at microwave, X-ray, EUV and optical ranges are routinely going on. Due to free exchange of original data among solar physics and related field communities, we can easily combine images covering wide range of spectrum. Even under such circumstances, we still do not understand the cause of activities in the solar atmosphere well. The current standard model of solar activities is based on magnetic reconnection: release of stored magnetic energy by reconnection is the cause of solar activities on the Sun such as solar flares. However, recent X-ray, EUV and microwave observations with high spatial and temporal resolution show that dense plasma is involved in activities from the beginning. Based on these observations, I propose a high-beta model of solar activities, which is very similar to high-beta disruptions in magnetically confined fusion experiments.

Gibbs free energy difference between the undercooled liquid and the beta phase of a Ti-Cr alloy

NASA Technical Reports Server (NTRS)

Ohsaka, K.; Trinh, E. H.; Holzer, J. C.; Johnson, W. L.

1992-01-01

The heat of fusion and the specific heats of the solid and liquid have been experimentally determined for a Ti60Cr40 alloy. The data are used to evaluate the Gibbs free energy difference, delta-G, between the liquid and the beta phase as a function of temperature to verify a reported spontaneous vitrification (SV) of the beta phase in Ti-Cr alloys. The results show that SV of an undistorted beta phase in the Ti60Cr40 alloy at 873 K is not feasible because delta-G is positive at the temperature. However, delta-G may become negative with additional excess free energy to the beta phase in the form of defects.

MHD Stability in Compact Stellarators

NASA Astrophysics Data System (ADS)

Fu, Guoyong

1999-11-01

A key issue for current carrying compact stellarators(S.P. Hirshman et al., "Physics of compact stellarators", Phys. Plasmas 6, 1858 (1999).) is the stability of ideal MHD modes. We present recent stability results of external kink modes, ballooning mode, and vertical modes in Quasi-axisymmetric Stellarators (QAS)( A. Reiman et al, "Physics issue in the design of a high beta Quasi-Axisymmetric Stellarator" the 17th IAEA Fusion Energy conference, (Yokohama, Japan, October 1998), Paper ICP/06.) as well as Quasi-Omnigeneous Stellarators (QOS)^2. The 3D stability code Terpsichore(W. A. Cooper et al., Phys. Plasmas 3, 275 (1996)) is used in this study. The vertical stability in a current carrying stellarator is studied for the first time. The vertical mode is found to be stabilized by externally generated poloidal flux(G.Y. Fu et al., "Stability of vertical mode in a current carrying stellarator"., to be submitted). Physically, this is because the external poloidal flux enhances the field line bending energy relative to the current drive term in the MHD energy principle, δ W. A simple stability criteria is derived in the limit of large aspect ratio and constant current density. For wall at infinite distance from the plasma, the amount of external flux needed for stabilization is given by f=(κ^2-κ)/(κ^2+1) where κ is the axisymmetric elongation and f is the fraction of the external rotational transform at the plasma edge. A systematic parameter study shows that the external kink in QAS can be stabilized at high beta ( ~ 5%) without a conducting wall by combination of edge magnetic shear and 3D shaping(G. Y. Fu et al., "MHD stability calculations of high-beta Quasi-Axisymmetric Stellarators", the 17th IAEA Fusion Energy conference, (Yokohama, Japan, October 1998), paper THP1/07.). The optimal shaping is obtained by using an optimizer with kink stability included in its objective function. The physics mechanism for the kink modes is studied by examining relative contributions of individual terms in δ W. It is found the external kinks are mainly driven by the parallel current. The pressure contributes significantly to the overall drive through the curvature term and the Pfirsch-Schluter current. These results demonstrate potential of QAS and QOS for disruption-free operations at high-beta without a close-fitting conducting wall and feedback stabilization.

Stability analysis of the high poloidal bet scenario on DIII-Dtowards operation athigher plasma current

NASA Astrophysics Data System (ADS)

Guo, W. F.; Gong, X. Z.; Huang, J.; Ren, Q. L.; Qian, J. P.; Ding, S. Y.; Pan, C. K.; Li, G. Q.; Xia, T. Y.; Garofalo, A. M.; Lao, L.; Hyatt, A.; Ferron, J.; Meneghini, O.; Liu, Y. Q.; McClenaghan, J.; Holcomb, C. T.

2017-10-01

The high poloidal beta scenario with plasma current IP 600 kA and large-radius internal transport barrier (ITB) on DIII-D is subject to n =1 MHD kink modes when the current profile becomes very broad at internal inductance values li 0.5-0.6. It is desirable to extend this scenario to higer plasma current ( 1 MA) for highernormalized fusionperformance. However, higher current at constant normalized beta, ?N 3, would reducethe poloidal bet, ?P, below the threshold for ITB sustainment, observed at ?P 1.9. Thus, to avoid loss of the IT, ?N?? must be increased together with IP while avoiding the kink instability. MHD analysis is presented that explains possible paths to high ?N stability limit for the kink mode in tis scenario. Work supported by National Magnetic Confinement Fusion Program of Chin under 2015GB110001 and 2015GB102000 - National Natural Science Foundation of China under Grant No. 1147521 and by US DOE under DE-FC02-04ER54698.

Rock-salt structure lithium deuteride formation in liquid lithium with high-concentrations of deuterium: a first-principles molecular dynamics study

DOE PAGES

Chen, Mohan; Abrams, T.; Jaworski, M. A.; ...

2015-12-17

Because of lithium's possible use as a first wall material in a fusion reactor, a fundamental understanding of the interactions between liquid lithium (Li) and deuterium (D) is important. Here, we predict structural and dynamical properties of liquid Li samples with high concentrations of D, as derived from first-principles molecular dynamics simulations. Liquid Li samples with four concentrations of inserted D atoms (LiDmore » $$_{\\beta}$$ , $$\\beta =0.25$$ , 0.50, 0.75, and 1.00) are studied at temperatures ranging from 470 to 1143 K. Densities, diffusivities, pair distribution functions, bond angle distribution functions, geometries, and charge transfer between Li and D atoms are calculated and analyzed. The analysis suggests liquid–solid phase transitions can occur at some concentrations and temperatures, forming rock-salt LiD within liquid Li. Finally, we observed the formation of some D 2 molecules at high D concentrations.« less

Deuterium-Tritium Beta-Layering Within a National Ignition Facility Scale Polymer Target in the LANL Cryogenic Pressure Loader

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

Ebey, Peter S.; Dole, James M.; Geller, Drew A.

2005-11-15

Beta-layering, the process of beta-decay heat-driven mass redistribution, has been demonstrated in a deuterium-tritium (D-T)-filled polymer sphere of the type required for fusion ignition experiments at the National Ignition Facility. This is the first report, to the best of the authors' knowledge, of a D-T layer formed in a permeation-filled sphere. The 2-mm-diam sphere was filled with D-T by permeation; cooled to cryogenic temperatures while in the high-pressure permeation vessel; and, while cold, removed to an optical axis where the D-T was frozen, melted, and beta-layered in a series of experiments over several weeks' time. This work was performed inmore » the Los Alamos National Laboratory cryogenic pressure loader system. The beta-layering time constant was 24.0 {+-} 2.5 min, less than the theoretical value of 26.8 min, and not showing the significant increase due to build-up of {sup 3}He often observed in beta-layered samples. Supercooling of the liquid D-T was observed. Neither the polymer target nor its tenting material showed visual signs of degradation after 5 weeks of exposure to D-T. Small external thermal gradients were used to shift the D-T material back and forth within the sphere.« less

Recent progress in understanding electron thermal transport in NSTX

DOE PAGES

Ren, Y.; Belova, E.; Gorelenkov, N.; ...

2017-03-10

The anomalous level of electron thermal transport inferred in magnetically confined configurations is one of the most challenging problems for the ultimate realization of fusion power using toroidal devices: tokamaks, spherical tori and stellarators. It is generally believed that plasma instabilities driven by the abundant free energy in fusion plasmas are responsible for the electron thermal transport. The National Spherical Torus eXperiment (NSTX) (Ono et al 2000 Nucl. Fusion 40 557) provides a unique laboratory for studying plasma instabilities and their relation to electron thermal transport due to its low toroidal field, high plasma beta, low aspect ratio and largemore » ExB flow shear. Recent findings on NSTX have shown that multiple instabilities are required to explain observed electron thermal transport, given the wide range of equilibrium parameters due to different operational scenarios and radial regions in fusion plasmas. Here we review the recent progresses in understanding anomalous electron thermal transport in NSTX and focus on mechanisms that could drive electron thermal transport in the core region. The synergy between experiment and theoretical/ numerical modeling is essential to achieving these progresses. The plans for newly commissioned NSTX-Upgrade will also be discussed.« less

Translational regulation of sigma 32 synthesis: requirement for an internal control element.

PubMed Central

Kamath-Loeb, A S; Gross, C A

1991-01-01

We have investigated the sequence requirements for the translational regulation of sigma 32 by examining the behavior of a new rpoH-lacZ protein fusion containing a short N-terminal fragment of sigma 32 fused to beta-galactosidase. Although the fusion retains rpoH translational initiation signals, it lacks translational regulation, implicating coding sequences within rpoH in this regulatory process. Images PMID:2050641

Adenovirus fibre shaft sequences fold into the native triple beta-spiral fold when N-terminally fused to the bacteriophage T4 fibritin foldon trimerisation motif.

PubMed

Papanikolopoulou, Katerina; Teixeira, Susana; Belrhali, Hassan; Forsyth, V Trevor; Mitraki, Anna; van Raaij, Mark J

2004-09-03

Adenovirus fibres are trimeric proteins that consist of a globular C-terminal domain, a central fibrous shaft and an N-terminal part that attaches to the viral capsid. In the presence of the globular C-terminal domain, which is necessary for correct trimerisation, the shaft segment adopts a triple beta-spiral conformation. We have replaced the head of the fibre by the trimerisation domain of the bacteriophage T4 fibritin, the foldon. Two different fusion constructs were made and crystallised, one with an eight amino acid residue linker and one with a linker of only two residues. X-ray crystallographic studies of both fusion proteins shows that residues 319-391 of the adenovirus type 2 fibre shaft fold into a triple beta-spiral fold indistinguishable from the native structure, although this is now resolved at a higher resolution of 1.9 A. The foldon residues 458-483 also adopt their natural structure. The intervening linkers are not well ordered in the crystal structures. This work shows that the shaft sequences retain their capacity to fold into their native beta-spiral fibrous fold when fused to a foreign C-terminal trimerisation motif. It provides a structural basis to artificially trimerise longer adenovirus shaft segments and segments from other trimeric beta-structured fibre proteins. Such artificial fibrous constructs, amenable to crystallisation and solution studies, can offer tractable model systems for the study of beta-fibrous structure. They can also prove useful for gene therapy and fibre engineering applications.

Targeting expression of a transforming growth factor beta 1 transgene to the pregnant mammary gland inhibits alveolar development and lactation.

PubMed Central

Jhappan, C; Geiser, A G; Kordon, E C; Bagheri, D; Hennighausen, L; Roberts, A B; Smith, G H; Merlino, G

1993-01-01

Transforming growth factor-beta 1 (TGF-beta 1) possesses highly potent, diverse and often opposing cell-specific activities, and has been implicated in the regulation of a variety of physiologic and developmental processes. To determine the effects of in vivo overexpression of TGF-beta 1 on mammary gland function, transgenic mice were generated harboring a fusion gene consisting of the porcine TGF-beta 1 cDNA placed under the control of regulatory elements of the pregnancy-responsive mouse whey-acidic protein (WAP) gene. Females from two of four transgenic lines were unable to lactate due to inhibition of the formation of lobuloalveolar structures and suppression of production of endogenous milk protein. In contrast, ductal development of the mammary glands was not overtly impaired. There was a complete concordance in transgenic mice between manifestation of the lactation-deficient phenotype and expression of RNA from the WAP/TGF-beta 1 transgene, which was present at low levels in the virgin gland, but was greatly induced at mid-pregnancy. TGF-beta 1 was localized to numerous alveoli and to the periductal extracellular matrix in the mammary gland of transgenic females late in pregnancy by immunohistochemical analysis. Glands reconstituted from cultured transgenic mammary epithelial cells duplicated the inhibition of lobuloalveolar development observed in situ in the mammary glands of pregnant transgenic mice. Results from this transgenic model strongly support the hypothesis that TGF-beta 1 plays an important in vivo role in regulating the development and function of the mammary gland. Images PMID:8491177

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

A. Brooks; A.H. Reiman; G.H. Neilson

High-beta, low-aspect-ratio (compact) stellarators are promising solutions to the problem of developing a magnetic plasma configuration for magnetic fusion power plants that can be sustained in steady-state without disrupting. These concepts combine features of stellarators and advanced tokamaks and have aspect ratios similar to those of tokamaks (2-4). They are based on computed plasma configurations that are shaped in three dimensions to provide desired stability and transport properties. Experiments are planned as part of a program to develop this concept. A beta = 4% quasi-axisymmetric plasma configuration has been evaluated for the National Compact Stellarator Experiment (NCSX). It has amore » substantial bootstrap current and is shaped to stabilize ballooning, external kink, vertical, and neoclassical tearing modes without feedback or close-fitting conductors. Quasi-omnigeneous plasma configurations stable to ballooning modes at beta = 4% have been evaluated for the Quasi-Omnigeneous Stellarator (QOS) experiment. These equilibria have relatively low bootstrap currents and are insensitive to changes in beta. Coil configurations have been calculated that reconstruct these plasma configurations, preserving their important physics properties. Theory- and experiment-based confinement analyses are used to evaluate the technical capabilities needed to reach target plasma conditions. The physics basis for these complementary experiments is described.« less

Formation of highly stable chimeric trimers by fusion of an adenovirus fiber shaft fragment with the foldon domain of bacteriophage t4 fibritin.

PubMed

Papanikolopoulou, Katerina; Forge, Vincent; Goeltz, Pierrette; Mitraki, Anna

2004-03-05

The folding of beta-structured, fibrous proteins is a largely unexplored area. A class of such proteins is used by viruses as adhesins, and recent studies revealed novel beta-structured motifs for them. We have been studying the folding and assembly of adenovirus fibers that consist of a globular C-terminal domain, a central fibrous shaft, and an N-terminal part that attaches to the viral capsid. The globular C-terminal, or "head" domain, has been postulated to be necessary for the trimerization of the fiber and might act as a registration signal that directs its correct folding and assembly. In this work, we replaced the head of the fiber by the trimerization domain of the bacteriophage T4 fibritin, termed "foldon." Two chimeric proteins, comprising the foldon domain connected at the C-terminal end of four fiber shaft repeats with or without the use of a natural linker sequence, fold into highly stable, SDS-resistant trimers. The structural signatures of the chimeric proteins as seen by CD and infrared spectroscopy are reported. The results suggest that the foldon domain can successfully replace the fiber head domain in ensuring correct trimerization of the shaft sequences. Biological implications and implications for engineering highly stable, beta-structured nanorods are discussed.

Immunogenicity of a recombinant fusion protein of tandem repeat epitopes of foot-and-mouth disease virus type Asia 1 for guinea pigs.

PubMed

Zhang, Q; Yang, Y Q; Zhang, Z Y; Li, L; Yan, W Y; Jiang, W J; Xin, A G; Lei, C X; Zheng, Z X

2002-01-01

In this study, the sequences of capsid protein VPI regions of YNAs1.1 and YNAs1.2 isolates of foot-and-mouth disease virus (FMDV) were analyzed and a peptide containing amino acids (aa) 133-158 of VP1 and aa 20-34 of VP4 of FMDV type Asia I was assumed to contain B and T cell epitopes, because it is hypervariable and includes a cell attachment site RGD located in the G-H loop. The DNA fragments encoding aa 133-158 of VP1 and aa 20-34 of VP4 of FMDV type Asia 1 were chemically synthesized and ligated into a tandem repeat of aa 133-158-20 approximately 34-133-158. In order to enhance its immunogenicity, the tandem repeat was inserted downstream of the beta-galactosidase gene in the expression vector pWR590. This insertion yielded a recombinant expression vector pAS1 encoding the fusion protein. The latter reacted with sera from FMDV type Asia 1-infected animals in vitro and elicited high levels of neutralizing antibodies in guinea pigs. The T cell proliferation in immunized animals increased following stimulation with the fusion protein. It is reported for the first time that a recombinant fusion protein vaccine was produced using B and T cell epitopes of FMDV type Asia 1 and that this fusion protein was immunogenic. The fusion protein reported here can serve as a candidate of fusion epitopes for design of a vaccine against FMDV type Asia 1.

The High Field Ultra Low Aspect Ratio Tokamak (HF-ULART)

NASA Astrophysics Data System (ADS)

Ribeiro, Celso

2017-10-01

Recently, a medium-size HF-ULART has been proposed. The major objective is to explore the high beta and pressure under the high toroidal field, using present day technology. This might be one of pathway scenarios for a potential ultra-compact pulsed neutron source (UCP-NS) based on the spherical tokamak (ST) concept, which may lead to more steady-state NS or even to a fusion reactor, via realistic design scaling. The HF-ULART pulsed mode operation is created by quasi-simultaneous adiabatic compression (AC) in both minor and major radius of a very high beta plasma, possibly with further help of passive-wall stabilization, as envisaged in the RULART concept. This may help the revival of the studies of the AC technique in tokamaks, alongside the less compact and more complex ST-40 device, currently under construction. In addition, by similarities, studies in HF-ULART as a UCP-NS may also help to test the feasibility of the compact NS via the spheromak concept, which also uses the AC technique. Simulations of AC in HF-ULART plasmas will be presented.

Drift kinetic effects on plasma response in high beta spherical tokamak experiments

NASA Astrophysics Data System (ADS)

Wang, Zhirui; Park, Jong-Kyu; Menard, Jonathan E.; Liu, Yueqiang; Kaye, Stanley M.; Gerhardt, Stefan

2018-01-01

The high β plasma response to rotating n=1 external magnetic perturbations is numerically studied and compared with the National Spherical Torus Experiment (NSTX). The hybrid magnetohydrodynamic(MHD)-kinetic modeling shows that drift kinetic effects are important in resolving the disagreement of plasma response between the ideal MHD prediction and the NSTX experimental observation when plasma pressure reaches and exceeds the no-wall limit (Troyon et al 1984 Plasma Phys. Control. Fusion 26 209). Since the external rotating fields and high plasma rotation are presented in the NSTX experiments, the importance of the resistive wall effect and plasma rotation in determining the plasma response is also identified, where the resistive wall suppresses the plasma response through the wall eddy current. The inertial energy due to plasma rotation destabilizes the plasma. The complexity of the plasma response in this study indicates that MHD modeling, including comprehensive physics, e.g. the drift kinetic effects, resistive wall and plasma rotation, are essential in order to reliably predict the plasma behavior in a high beta spherical tokamak device.

Nuclear Fusion Award 2009 speech Nuclear Fusion Award 2009 speech

NASA Astrophysics Data System (ADS)

Sabbagh, Steven Anthony

2011-01-01

This is an exceptional moment in my career, and so I want to thank all of my teachers, colleagues and mentors who have made this possible. From my co-authors and myself, many thanks to the International Atomic Energy Agency, IOP Publishing, the Nuclear Fusion journal team, and the selection committee for the great honor of receiving this award. Also gratitude to Kikuchi-sensei, not only for the inventive and visionary creation of this award, but also for being a key mentor dating back to his efforts in producing high neutron output in JT-60U. It was also a great honor to receive the award directly from IAEA Deputy Director General Burkart during the 23rd IAEA Fusion Energy Conference in Daejeon. Receiving the award at this venue is particularly exciting as Daejeon is home to the new, next-generation KSTAR tokamak device that will lead key magnetic fusion research areas going forward. I would also like to thank the mayor of Daejeon, Dr Yum Hong-Chul, and all of the meeting organizers for giving us all a truly spectacular and singular welcoming event during which the award was presented. The research leading to the award would not have been possible without the support of the US Department of Energy, and I thank the Department for the continued funding of this research. Special mention must be made to a valuable co-author who is no longer with us, Professor A. Bondeson, who was a significant pioneer in resistive wall mode (RWM) research. I would like to thank my wife, Mary, for her infinite patience and encouragement. Finally, I would like to personally thank all of you that have approached and congratulated me directly. There are no units to measure how important your words have been in this regard. When notified that our paper had been shortlisted for the 2009 Nuclear Fusion Award, my co-authors responded echoing how I felt—honored to be included in such a fine collection of research by colleagues. It was unfathomable—would this paper follow the brilliant work of Dr Todd Evans, another significant mentor of mine, as winner of this prestigious award? Then, it happened. The paper covers several key topics related to high beta tokamak physics. For me, the greatest satisfaction in receiving this award is because it was the first Nuclear Fusion Award to recognize research on the National Spherical Torus Experiment (NSTX) located at the Princeton Plasma Physics Laboratory. The achievement of record stability parameters in a mega-Ampere class spherical torus (ST) device reported in the paper represents a multi-year effort, contributed to by the entire research team. Research to maintain such plasmas for an indefinite period continues today. Understanding RWM stabilization physics is crucial for this goal, and leveraging the high beta ST operating space uniquely tests theory for application to future STs and to tokamaks in general, including advanced operational scenarios of ITER. For instance, the RWM was found to have significant amplitude in components with the toroidal mode number greater than unity. This has important implications for general active RWM control. Evidence that the RWM passive stabilization physics and marginal stability criterion are indeed more complex than originally thought was shown in this paper. Present work shows the greater complexity has a direct impact on how we should extrapolate RWM stabilization to future devices. The paper also reported the qualitative observation of neoclassical toroidal viscosity (NTV), followed by a companion paper by our group in 2006 reporting the quantitative observation of this effect and comparison to theory. The physics of this interesting and important phenomenon was introduced to me by Professor J. Callen (who has given an overview talk at this conference including this subject) and Professor Kerchung Shaing of the University of Wisconsin, to whom I am quite indebted. The paper also reported the first measurement of resonant field amplification at high beta in the NSTX, following work of the Columbia University group at DIII-D during that period. My greatest hope in our stability physics research effort is that our insight in this portion of the much larger research effort, of which we all partake, to make fusion reactors a practical reality, will give new and future researchers the input and motivation to amplify our work and create realities that we had thought were just out of reach. Receiving the 2009 IAEA Nuclear Fusion Award is a substantial honor that greatly motivates me to continue to support the international nuclear fusion research effort at the highest level possible. So, please allow me to raise this beautiful trophy high, here today, to best remember this fine honor. Thank you. Steven Anthony Sabbagh 2009 Nuclear Fusion Award winner Columbia University, New York, NY, USA

[Prokaryotic expression and immunogenicity analysis of the chimeric HBcAg containing APP beta cleavage site peptide and Aβ(1-15);].

PubMed

Feng, Gai-feng; Wang, Jun-yang; Jin, Hui; Wang, Wei-xi; Qian, Yi-hua; Yang, Wei-na; Wang, Quan-ying; Yang, Guang-xiao

2011-11-01

To construct the recombinant prokaryotic expression plasmid pET/c-ABCSP-Aβ(15-c);, and evaluate the immunogenicity of the fusion protein expressed in E.coli. The gene fragment HBc88-144 was amplified by PCR and subcloned to pUC19. The APP beta cleavage site peptide(ABCSP) and Aβ(1-15); gene(ABCSP-Aβ(15);) was amplified by PCR and inserted downstream of HBc1-71 in pGEMEX/c1-71. After restriction enzyme digestion, c1-17-ABCSP-Aβ(15); were connected with HBc88-144, yielding the recombinant gene c-ABCSP-Aβ(15-c);. c-ABCSP-Aβ(15-c); gene was subcloned into pET-28a(+).The fusion protein expressed in transformed E.coli BL21 was induced with IPTG and analyzed by SDS-PAGE. The virus-like particles (VLP) formed by fusion protein was observed with Transmission Electron Microscope (TEM). 4 Kunming (KM) mice received intraperitoneal injection (i.p) of fusion protein VLP. The antibody was detected by indirect ELISA. The recombinant gene was confirmed by restriction enzyme digestion and DNA sequencing. After IPTG induction, fusion protein was expressed and mainly existed in the sediment of the bacterial lysate. The expression level was 40% of all the proteins in the sediment. The fusion protein could form VLP. After 5 times of immunization, the titer of anti-ABCSP and anti-Aβantibody in sera of KM mice reached up to 1:5 000 and 1:10 000 respectively, while the anti-HBc antibody was undetectable. Recombinant c-ABCSP-Aβ(15-c); gene can be expressed in E.coli. The expressed protein could form VLP and has a strong immunogenicity. This study lays the foundation for the study of AD genetic engineering vaccine.

Modular low-aspect-ratio high-beta torsatron

DOEpatents

Sheffield, G.V.

1982-04-01

A fusion-reactor device is described which the toroidal magnetic field and at least a portion of the poloidal magnetic field are provided by a single set of modular coils. The coils are arranged on the surface of a low-aspect-ratio toroid in planed having the cylindrical coordinate relationship phi = phi/sub i/ + kz, where k is a constant equal to each coil's pitch and phi/sub i/ is the toroidal angle at which the i'th coil intersects the z = o plane. The toroid defined by the modular coils preferably has a race track minor cross section. When vertical field coils and, preferably, a toroidal plasma current are provided for magnetic-field-surface closure within the toroid, a vacuum magnetic field of racetrack-shaped minor cross section with improved stability and beta valves is obtained.

An overview of optical diagnostics developed for the Lockheed Martin compact fusion reactor

NASA Astrophysics Data System (ADS)

Sommers, Bradley; Raymond, Anthony; Gucker, Sarah; Lockheed Martin Compact Fusion Reactor Team

2017-10-01

The T4B experiment is a linear, encapsulated ring cusp confinement device, designed to develop a physics and technology basis for a follow-on high beta machine as part of the compact fusion reactor program. Toward this end, a collection of non-invasive optical diagnostics have been developed to investigate confinement, neutral beam heating, and source behavior on the T4B device. These diagnostics include: (1) a multipoint Thomson scattering system employing a 532 nm Nd:YAG laser and high throughput spectrometer to measure 1D profiles of electron density and temperature, (2) a dispersion interferometer utilizing a continuous-wave CO2 laser (10.6 μm) to measure time resolved, line-integrated electron density, and (3) a bolometer suite utilizing four AXUV photodiodes with 64 lines of sight to generate 2D reconstructions of total radiative power and soft x-ray emission (via beryllium filters). An overview of design methods, including laser systems, detection schemes, and data analysis techniques is presented as well as results to date.

HNF1(beta) is required for mesoderm induction in the Xenopus embryo.

PubMed

Vignali, R; Poggi, L; Madeddu, F; Barsacchi, G

2000-04-01

XHNF1(&bgr;) is a homeobox-containing gene initially expressed at the blastula stage in the vegetal part of the Xenopus embryo. We investigated its early role by functional ablation, through mRNA injection of an XHNF1(beta)/engrailed repressor fusion construct (XHNF1(beta)/EngR). Dorsal injections of XHNF1(beta)/EngR mRNA abolish dorsal mesoderm formation, leading to axial deficiencies; ventral injections disrupt ventral mesoderm formation without affecting axial development. XHNF1(beta)/EngR phenotypic effects specifically depend on the DNA-binding activity of its homeodomain and are fully rescued by coinjection of XHNF1(beta) mRNA. Vegetal injection of XHNF1(beta)/EngR mRNA blocks the mesoderm-inducing ability of vegetal explants. Both B-Vg1 and VegT maternal determinants trigger XHNF1(beta) expression in animal caps. XHNF1(beta)/EngR mRNA blocks B-Vg1-mediated, but not by eFGF-mediated, mesoderm induction in animals caps. However, wild-type XHNF1(beta) mRNA does not trigger Xbra expression in animal caps. We conclude that XHNF1(beta) function is essential, though not sufficient, for mesoderm induction in the Xenopus embryo.

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

Ozawa, Tatsuhiko; Horii, Masae; Kobayashi, Eiji

Highlights: Black-Right-Pointing-Pointer A novel soluble TCR composed of TCR V and C regions with Ig Fc region is generated. Black-Right-Pointing-Pointer TCR-Fc protein immobilized by an anti-C{beta} antibody bound to a p/MHC tetramer. Black-Right-Pointing-Pointer Binding affinity of TCR-Fc was markedly increased by binding with anti-C{beta} antibody. -- Abstract: The identification and cloning of tumor antigen-specific T cell receptors (TCRs) and the production of the soluble form of the TCR (sTCR) contributed to the development of diagnostic and therapeutic tools for cancer. Recently, several groups have reported the development of technologies for the production of sTCRs. The native sTCR has a verymore » low binding affinity for the antigenic peptide/MHC (p/MHC) complex. In this study, we established a technology to produce high affinity, functional sTCRs. We generated a novel sTCR-Fc fusion protein composed of the TCR V and C regions of the TCR linked to the immunoglobulin (Ig) Fc region. A Western blot analysis revealed that the molecular weight of the fusion protein was approximately 60 kDa under reducing conditions and approximately 100-200 kDa under non-reducing conditions. ELISAs using various antibodies showed that the structure of each domain of the TCR-Fc protein was intact. The TCR-Fc protein immobilized by an anti-C{beta} antibody effectively bound to a p/MHC tetramer. An SPR analysis showed that the TCR-Fc protein had a low binding affinity (KD; 1.1 Multiplication-Sign 10{sup -5} M) to the p/MHC monomer. Interestingly, when the TCR-Fc protein was pre-incubated with an anti-C{beta} antibody, its binding affinity for p/MHC increased by 5-fold (2.2 Multiplication-Sign 10{sup -6} M). We demonstrated a novel method for constructing a functional soluble TCR using the Ig Fc region and showed that the binding affinity of the functional sTCR-Fc was markedly increased by an anti-C{beta} antibody, which is probably due to the stabilization of the V{alpha}/V{beta} region of the TCR. These findings provide new insights into the binding of sTCRs to p/MHCs and will hopefully be instrumental in establishing functional sTCR as a diagnostic and therapeutic tool for cancer.« less

D-He-3 spherical torus fusion reactor system study

NASA Astrophysics Data System (ADS)

Macon, William A., Jr.

1992-04-01

This system study extrapolates present physics knowledge and technology to predict the anticipated characteristics of D-He3 spherical torus fusion reactors and their sensitivity to uncertainties in important parameters. Reference cases for steady-state 1000 MWe reactors operating in H-mode in both the 1st stability regime and the 2nd stability regime were developed and assessed quantitatively. These devices would a very small aspect ratio (A=1,2), a major radius of about 2.0 m, an on-axis magnetic field less than 2 T, a large plasma current (80-120 MA) dominated by the bootstrap effect, and high plasma beta (greater than O.6). The estimated cost of electricity is in the range of 60-90 mills/kW-hr, assuming the use of a direct energy conversion system. The inherent safety and environmental advantages of D-He3 fusion indicate that this reactor concept could be competitive with advanced fission breeder reactors and large-scale solar electric plants by the end of the 21st century if research and development can produce the anticipated physics and technology advances.

Two modes of control of pilA, the gene encoding type 1 pilin in Escherichia coli.

PubMed Central

Orndorff, P E; Spears, P A; Schauer, D; Falkow, S

1985-01-01

Type 1 piliation in Escherichia coli is subject to metastable regulation at the transcriptional level (B. I. Eisenstein, Science 214:337-339, 1981). However, the genes controlling in this fashion are not known. We present evidence that the pilA gene, encoding the structural subunit of type 1 pili, is subject to metastable transcriptional regulation. A pilA'-lacZ fusion, constructed in vitro on a recombinant plasmid, was used in conjunction with a recBC sbcB mutant of E. coli K-12 to introduce the fusion into the chromosomal region encoding Pil. This fusion was found to be subject to metastable transcriptional control. The rate of switching from the Lac+ to the Lac- phenotype was 4 X 10(-4) per cell per generation and 6.2 X 10(-4) in the opposite direction. A ca. 10-fold difference in beta-galactosidase activity was observed between phenotypically "ON" (Lac+) and "OFF" (Lac-) populations. P1 transduction experiments showed that the element determining the ON or OFF phenotype was tightly linked to pilA. In addition to the metastable regulation of pilA, a second type of transcriptional regulation was effected by the product of a gene, hyp, adjacent to pilA. By using a recombinant plasmid containing just a pilA'-lacZ fusion and the putative pilA promoter, we found that a lesion in hyp conferred a beta-galactosidase activity about fivefold higher than that of a strain possessing the parental hyp gene. Mutants constructed to have a pilA'-lacZ fusion and a hyp::Tn5-132 mutation in the chromosome exhibited a frequency of switching from Lac+ to Lac- and vice versa indistinguishable from that of the parental strain. However, in the ON mode, hyp::Tn5-132 mutants showed a twofold-higher beta-galactosidase activity. Thus, hyp does not appear to affect metastable variation but does affect the level of transcription of the pilA gene in the ON (transcribed) mode. Images PMID:3930469

Detection of anticentromere antibodies using cloned autoantigen CENP-B.

PubMed

Rothfield, N; Whitaker, D; Bordwell, B; Weiner, E; Senecal, J L; Earnshaw, W

1987-12-01

A solid-phase enzyme-linked immunosorbent assay has been established using a cloned fusion protein, CtermCENP-B [beta-gal], as antigen. The fusion protein carries the major epitope of CENP-B, the major centromeric autoantigen. The enzyme-linked immunosorbent assay was more sensitive than immunofluorescence techniques in detecting anticentromere antibodies in patients with scleroderma or Raynaud's disease, and was weakly positive in 3% of normal controls and in 3% of 70 patients with other connective tissue diseases.

Molecular dynamics analysis of conformational change of paramyxovirus F protein during the initial steps of membrane fusion

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

Martin-Garcia, Fernando; Mendieta-Moreno, Jesus Ignacio; Mendieta, Jesus

2012-03-30

Highlights: Black-Right-Pointing-Pointer Initial conformational change of paramyxovirus F protein is caused only by mechanical forces. Black-Right-Pointing-Pointer HRA region undergoes a structural change from a beta + alpha conformation to an extended coil and then to an all-alpha conformation. Black-Right-Pointing-Pointer HRS domains of F protein form three single {alpha}-helices prior to generation of the coiled coil. -- Abstract: The fusion of paramyxovirus to the cell membrane is mediated by fusion protein (F protein) present in the virus envelope, which undergoes a dramatic conformational change during the process. Unlike hemagglutinin in orthomyxovirus, this change is not mediated by an alteration of environmentalmore » pH, and its cause remains unknown. Steered molecular dynamics analysis leads us to suggest that the conformational modification is mediated only by stretching mechanical forces once the transmembrane fusion peptide of the protein is anchored to the cell membrane. Such elongating forces will generate major secondary structure rearrangement in the heptad repeat A region of the F protein; from {beta}-sheet conformation to an elongated coil and then spontaneously to an {alpha}-helix. In addition, it is proposed that the heptad repeat A region adopts a final three-helix coiled coil and that this structure appears after the formation of individual helices in each monomer.« less

E-cadherin suppression accelerates squamous cell carcinoma progression in three-dimensional, human tissue constructs.

PubMed

Margulis, Alexander; Zhang, Weitian; Alt-Holland, Addy; Crawford, Howard C; Fusenig, Norbert E; Garlick, Jonathan A

2005-03-01

We studied the link between loss of E-cadherin-mediated adhesion and acquisition of malignant properties in three-dimensional, human tissue constructs that mimicked the initial stages of squamous cell cancer progression. Suppression of E-cadherin expression in early-stage, skin-derived tumor cells (HaCaT-II-4) was induced by cytoplasmic sequestration of beta-catenin upon stable expression of a dominant-negative E-cadherin fusion protein (H-2Kd-Ecad). In monolayer cultures, expression of H-2Kd-Ecad resulted in decreased levels of E-cadherin, redistribution of beta-catenin to the cytoplasm, and complete loss of intercellular adhesion when compared with control II-4 cells. This was accompanied by a 7-fold decrease in beta-catenin-mediated transcription and a 12-fold increase in cell migration. In three-dimensional constructs, E-cadherin-deficient tissues showed disruption of architecture, loss of adherens junctional proteins from cell contacts, and focal tumor cell invasion. Invasion was linked to activation of matrix metalloproteinase (MMP)-mediated degradation of basement membrane in H-2Kd-Ecad-expressing tissue constructs that was blocked by MMP inhibition (GM6001). Quantitative reverse transcription-PCR showed a 2.5-fold increase in MMP-2 and an 8-fold increase in MMP-9 in cells expressing the H-2Kd-Ecad fusion protein when compared with controls, and gel zymography showed increased MMP protein levels. Following surface transplantation of three-dimensional tissues, suppression of E-cadherin expression greatly accelerated tumorigenesis in vivo by inducing a switch to high-grade carcinomas that resulted in a 5-fold increase in tumor size after 4 weeks. Suppression of E-cadherin expression and loss of its function fundamentally modified squamous cell carcinoma progression by activating a highly invasive, aggressive tumor phenotype, whereas maintenance of E-cadherin prevented invasion in vitro and limited tumor progression in vivo.

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

A role for the precuneus in thought-action fusion: evidence from participants with significant obsessive-compulsive symptoms.

PubMed

Jones, Rhiannon; Bhattacharya, Joydeep

2014-01-01

Likelihood thought-action fusion (TAF-L) refers to a cognitive bias in which individuals believe that the mere thought of a negative event increases its likelihood of occurring in reality. TAF-L is most commonly associated with obsessive-compulsive disorder (OCD) but is also present in depression, generalized anxiety disorder and psychosis. We induced TAF-L in individuals with high (High-OC, N = 23) and low (Low-OC, N = 24) levels of OC traits, and used low resolution electromagnetic tomography (LORETA) to localise the accompanying electrical brain activity patterns. The results showed greater TAF-L in the High-OC than in the Low-OC group (p < .005), which was accompanied by significantly greater upper beta frequency (19-30 Hz) activity in the precuneus (p < .05). Further, the precuneus activity was positively correlated with self-reported magnitude of TAF-L (p < .01), suggesting a specific role of this region in this cognitive bias. Results are discussed with reference to self-referential processing and the default-mode network.

A role for the precuneus in thought–action fusion: Evidence from participants with significant obsessive–compulsive symptoms☆

PubMed Central

Jones, Rhiannon; Bhattacharya, Joydeep

2013-01-01

Likelihood thought–action fusion (TAF-L) refers to a cognitive bias in which individuals believe that the mere thought of a negative event increases its likelihood of occurring in reality. TAF-L is most commonly associated with obsessive–compulsive disorder (OCD) but is also present in depression, generalized anxiety disorder and psychosis. We induced TAF-L in individuals with high (High-OC, N = 23) and low (Low-OC, N = 24) levels of OC traits, and used low resolution electromagnetic tomography (LORETA) to localise the accompanying electrical brain activity patterns. The results showed greater TAF-L in the High-OC than in the Low-OC group (p < .005), which was accompanied by significantly greater upper beta frequency (19–30 Hz) activity in the precuneus (p < .05). Further, the precuneus activity was positively correlated with self-reported magnitude of TAF-L (p < .01), suggesting a specific role of this region in this cognitive bias. Results are discussed with reference to self-referential processing and the default-mode network. PMID:24371793

Characterization of the Rana grylio virus 3{beta}-hydroxysteroid dehydrogenase and its novel role in suppressing virus-induced cytopathic effect

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

Sun Wei; Huang Youhua; Zhao Zhe

2006-12-08

The 3{beta}-hydroxysteroid dehydrogenase (3{beta}-HSD) isoenzymes play a key role in cellular steroid hormone synthesis. Here, a 3{beta}-HSD gene homolog was cloned from Rana grylio virus (RGV), a member of family Iridoviridae. RGV 3{beta}-HSD gene has 1068 bp, encoding a 355 aa predicted protein. Transcription analyses showed that RGV 3{beta}-HSD gene was transcribed immediate-early during infection from an initiation site 19 nucleotides upstream of the translation start site. Confocal microscopy revealed that the 3{beta}-HSD-EGFP fusion protein was exclusively colocalized with the mitochondria marker (pDsRed2-Mito) in EPC cells. Upon morphological observation and MTT assay, it was revealed that overexpression of RGV 3{beta}-HSDmore » in EPC cells could apparently suppress RGV-induced cytopathic effect (CPE). The present studies indicate that the RGV immediate-early 3{beta}-HSD gene encodes a mitochondria-localized protein, which has a novel role in suppressing virus-induced CPE. All these suggest that RGV 3{beta}-HSD might be a protein involved in host-virus interaction.« less

Recent Progress on Spherical Torus Research

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

Ono, Masayuki; Kaita, Robert

2014-01-01

The spherical torus or spherical tokamak (ST) is a member of the tokamak family with its aspect ratio (A = R0/a) reduced to A ~ 1.5, well below the normal tokamak operating range of A ≥ 2.5. As the aspect ratio is reduced, the ideal tokamak beta β (radio of plasma to magnetic pressure) stability limit increases rapidly, approximately as β ~ 1/A. The plasma current it can sustain for a given edge safety factor q-95 also increases rapidly. Because of the above, as well as the natural elongation κ, which makes its plasma shape appear spherical, the ST configurationmore » can yield exceptionally high tokamak performance in a compact geometry. Due to its compactness and high performance, the ST configuration has various near term applications, including a compact fusion neutron source with low tritium consumption, in addition to its longer term goal of attractive fusion energy power source. Since the start of the two megaampere class ST facilities in 2000, National Spherical Torus Experiment (NSTX) in the US and Mega Ampere Spherical Tokamak (MAST) in UK, active ST research has been conducted worldwide. More than sixteen ST research facilities operating during this period have achieved remarkable advances in all of fusion science areas, involving fundamental fusion energy science as well as innovation. These results suggest exciting future prospects for ST research both near term and longer term. The present paper reviews the scientific progress made by the worldwide ST research community during this new mega-ampere-ST era.« less

Crystal Structure of Menin Reveals Binding Site for Mixed Lineage Leukemia (MLL) Protein

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

Murai, Marcelo J.; Chruszcz, Maksymilian; Reddy, Gireesh

2014-10-02

Menin is a tumor suppressor protein that is encoded by the MEN1 (multiple endocrine neoplasia 1) gene and controls cell growth in endocrine tissues. Importantly, menin also serves as a critical oncogenic cofactor of MLL (mixed lineage leukemia) fusion proteins in acute leukemias. Direct association of menin with MLL fusion proteins is required for MLL fusion protein-mediated leukemogenesis in vivo, and this interaction has been validated as a new potential therapeutic target for development of novel anti-leukemia agents. Here, we report the first crystal structure of menin homolog from Nematostella vectensis. Due to a very high sequence similarity, the Nematostellamore » menin is a close homolog of human menin, and these two proteins likely have very similar structures. Menin is predominantly an {alpha}-helical protein with the protein core comprising three tetratricopeptide motifs that are flanked by two {alpha}-helical bundles and covered by a {beta}-sheet motif. A very interesting feature of menin structure is the presence of a large central cavity that is highly conserved between Nematostella and human menin. By employing site-directed mutagenesis, we have demonstrated that this cavity constitutes the binding site for MLL. Our data provide a structural basis for understanding the role of menin as a tumor suppressor protein and as an oncogenic co-factor of MLL fusion proteins. It also provides essential structural information for development of inhibitors targeting the menin-MLL interaction as a novel therapeutic strategy in MLL-related leukemias.« less

Advanced ECCD based NTM control in closed-loop operation at ASDEX Upgrade (AUG)

NASA Astrophysics Data System (ADS)

Reich, Matthias; Barrera-Orte, Laura; Behler, Karl; Bock, Alexander; Giannone, Louis; Maraschek, Marc; Poli, Emanuele; Rapson, Chris; Stober, Jörg; Treutterer, Wolfgang

2012-10-01

In high performance plasmas, Neoclassical Tearing Modes (NTMs) are regularly observed at reactor-grade beta-values. They limit the achievable normalized beta, which is undesirable because fusion performance scales as beta squared. The method of choice for controlling and avoiding NTMs at AUG is the deposition of ECCD inside the magnetic island for stabilization in real-time (rt). Our approach to tackling such complex control problems using real-time diagnostics allows rigorous optimization of all subsystems. Recent progress in rt-equilibrium reconstruction (< 3.5 ms), rt-localization of NTMs (< 8 ms) and rt beam tracing (< 25 ms) allows closed-loop feedback operation using multiple movable mirrors as the ECCD deposition actuator. The rt-equilibrium uses function parametrization or a fast Grad-Shafranov solver with an option to include rt-MSE measurements. The island localization is based on a correlation of ECE and filtered Mirnov signals. The rt beam-tracing module provides deposition locations and their derivative versus actuator position of multiple gyrotrons. The ``MHD controller'' finally drives the actuators. Results utilizing closed-loop operation with multiple gyrotrons and their effect on NTMs are shown.

Z-membranes: artificial organelles for overexpressing recombinant integral membrane proteins.

PubMed Central

Gong, F C; Giddings, T H; Meehl, J B; Staehelin, L A; Galbraith, D W

1996-01-01

We have expressed a fusion protein formed between the avian infectious bronchitis virus M protein and the bacterial enzyme beta-glucuronidase in transgenic tobacco cells. Electron microscope images of such cells demonstrate that overexpression of this fusion protein gives rise to a type of endoplasmic reticulum membrane domain in which adjacent membranes become zippered together apparently as a consequence of the oligomerizing action of beta-glucuronidase. These zippered (Z-) membranes lack markers of the endoplasmic reticulum (NADH cytochrome c reductase and ribosomes) and accumulate in the cells in the form of multilayered scroll-like structures (up to 2 micrometers in diameter; 20-50 per cell) without affecting plant growth. The discovery of Z-membranes has broad implications for biology and biotechnology in that they provide a means for accumulating large quantities of recombinant membrane proteins within discrete domains of native membranes. Images Fig. 1 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 PMID:8700911

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

Moroz, P.E.

A new stellarator configuration, the Double-Helix Stellarator (DHS), is introduced. This novel configuration features a double-helix center post as the only helical element of the stellarator coil system. The DHS configuration has many unique characteristics. One of them is the extreme low plasma aspect ratio, A {approx} 1--1.2. Other advantages include a high enclosed volume, appreciable rotational transform, and a possibility of extreme-high-{beta} MHD equilibria. Moreover, the DHS features improved transport characteristics caused by the absence of the magnetic field ripple on the outboard of the torus. Compactness, simplicity and modularity of the coil system add to the DHS advantagesmore » for fusion applications.« less

Assessing the relative stabilities of engineered hemoglobins using electrospray mass spectrometry.

PubMed

Apostol, I

1999-07-15

An ion trap mass spectrometer equipped with an electrospray source was used to examine the relative thermodynamic stabilities of various hemoglobins with respect to both tetramer dissociation and hemin dissociation. The results demonstrated that the stability of hemoglobin molecules can be differentiated by the amount of applied collision-induced dissociation (CID) energy necessary to break up the intact tetramer into its constituent globins. The stability of the intact tetramer was affected by single mutations in the beta-globins. The stabilities of the constituent hologlobins were assessed via trap CID of selected ions. The results demonstrated the importance of the contributions of the hologlobin components to the stability of the intact tetramer. Genetic fusion of two alpha-globins, through the introduction of a single glycine residue between the C-terminus of one alpha-chain and the N-terminus of the second, significantly increased the stability of the hemoglobin pseudo-tetramer. Chemical crosslinking of the beta-globins in addition to genetic fusion of alpha-globins further stabilized the hemoglobin molecule. A dihemoglobin molecule produced by the genetic fusion of two di-alpha-globins with a flexible linker demonstrated a decreased stability relative to the corresponding monohemoglobin. Copyright 1999 Academic Press.

Recent Progress on Spherical Torus Research and Implications for Fusion Energy Development Path

NASA Astrophysics Data System (ADS)

Ono, Masayuki

2014-10-01

The spherical torus or spherical tokamak (ST) is a member of the tokamak family with its aspect ratio (A =R0 / a) reduced to A near 1.5, well below the normal tokamak operating range of A equal to 2.5 or greater. As the aspect ratio is reduced, the ideal tokamak beta (radio of plasma to magnetic pressure) stability limit increases rapidly, approximately as 1/A. The plasma current it can sustain for a given edge safety factor q-95 also increases rapidly. Because of the above, as well as the natural plasma elongation which makes its plasma shape appear spherical, the ST configuration can yield exceptionally high tokamak performance in a compact geometry. Due to its compactness and high performance, the ST configuration has various near term applications, including a compact fusion neutron source with low tritium consumption, in addition to the longer term goal of an attractive fusion energy power source. Since the start of the two mega-ampere class ST facilities in 2000, the National Spherical Torus Experiment (NSTX) in the US and Mega Ampere Spherical Tokamak (MAST) in the UK, active ST research has been conducted worldwide. More than sixteen ST research facilities operating during this period have achieved remarkable advances in all areas of fusion research, including fundamental fusion energy science as well as technological innovation. These results suggest exciting future prospects for ST research in both the near and longer term. The talk will summarize the key physics results from worldwide ST experiments, and describe ST community plans to provide the database for FNSF design while improving predictive capabilities for ITER and beyond. This work supported by DoE Contract No. DE-AC02-09CH11466.

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

PubMed

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

2007-03-01

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

Microstructure formation in partially melted zone during gas tungsten arc welding of AZ91 Mg cast alloy

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

Zhu Tianping; Chen, Zhan W.; Gao Wei

2008-11-15

During gas tungsten arc (GTA) welding of AZ91 Mg cast alloy, constitutional liquid forms locally in the original interdendritic regions in the partially melted zone (PMZ). The PMZ re-solidification behaviour has not been well understood. In this study, the gradual change of the re-solidification microstructure within PMZ from base metal side to weld metal side was characterised. High cooling rate experiments using Gleeble thermal simulator were also conducted to understand the morphological change of the {alpha}-Mg/{beta}-Mg{sub 17}Al{sub 12} phase interface formed during re-solidification after partial melting. It was found that the original partially divorced eutectic structure has become a moremore » regular eutectic phase in most of the PMZ, although close to the fusion boundary the re-solidified eutectic is again a divorced one. Proceeding the eutectic re-solidification, if the degree of partial melting is sufficiently high, {alpha}-Mg re-solidified with a cellular growth, resulting in a serrated interface between {alpha}-Mg and {alpha}-Mg/{beta}-Mg{sub 17}Al{sub 12} in the weld sample and between {alpha}-Mg and {beta}-Mg{sub 17}Al{sub 12} (fully divorced eutectic) in Gleeble samples. The morphological changes affected by the peak temperature and cooling rate are also explained.« less

Axial-Current Matrix Elements in Light Nuclei from Lattice QCD

NASA Astrophysics Data System (ADS)

Savage, M.; Beane, S.; Chang, E.; Davoudi, Z.; Detmold, W.; Orginos, K.; Shanahan, P.; Tiburzi, B.; Wagman, M.; Winter, F.; Nplqcd Collaboration

I present results from the first lattice QCD calculations of axial-current matrix elements in light nuclei, performed by the NPLQCD collaboration. Precision calculations of these matrix elements, and the subsequent extraction of multi-nucleon axial-current operators, are essential in refining theoretical predictions of the proton-proton fusion cross section, neutrino-nucleus cross sections and $\\beta\\beta$-decay rates of nuclei. In addition, they are expected to shed light on the phenomenological quenching of $g_A$ that is required in nuclear many-body calculations.

Final Report: Levitated Dipole Experiment

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

Kesner, Jay; Mauel, Michael

2013-03-10

Since the very first experiments with the LDX, research progress was rapid and significant. Initial experiments were conducted with the high-field superconducting coil suspended by three thin rods. These experiments produced long-pulse, quasi-steady-state microwave discharges, lasting more than 10 s, having peak beta values of 20% [Garnier et al., Physics of Plasmas, 13 (2006) 056111]. High- beta, near steady-state discharges have been maintained in LDX for more than 20 seconds, and this capability made LDX the longest pulse fusion confinement experiment operating in the U.S. fusion program. A significant measure of progress in the LDX research program was the routinemore » investigation of plasma confinement with a magnetically-levitated dipole and the resulting observations of confinement improvement. In both supported and levitated configurations, detailed measurements were made of discharge evolution, plasma dynamics and instability, and the roles of gas fueling, microwave power deposition profiles, and plasma boundary shape. High-temperature plasma was created by multi frequency electron cyclotron resonance heating at 2.45 GHz, 6.4 GHz, 10.5 GHz and 28 GHz allowing control of heating profiles. Depending upon neutral fueling rates, the LDX discharges contain a fraction of energetic electrons, with mean energies above 50 keV. Depending on whether or not the superconducting dipole was levitated or supported, the peak thermal electron temperature was estimated to exceed 500 eV and peak densities to approach 1e18 m -3. We have found that levitation causes a strong inwards density pinch [Boxer et al., Nature Physics, 6 (2010) 207] and we have observed the central plasma density increase dramatically indicating a significant improvement in the confinement of a thermal plasma species.« less

Truncated presequences of mitochondrial F1-ATPase beta subunit from Nicotiana plumbaginifolia transport CAT and GUS proteins into mitochondria of transgenic tobacco.

PubMed

Chaumont, F; Silva Filho, M de C; Thomas, D; Leterme, S; Boutry, M

1994-02-01

The mitochondrial F1-ATPase beta subunit (ATPase-beta) of Nicotiana plumbaginifolia is nucleus-encoded as a precursor containing an NH2-terminal extension. By sequencing the mature N. tabacum ATPase-beta, we determined the length of the presequence, viz. 54 residues. To define the essential regions of this presequence, we produced a series of 3' deletions in the sequence coding for the 90 NH2-terminal residues of ATPase-beta. The truncated sequences were fused with the chloramphenicol acetyl transferase (cat) and beta-glucuronidase (gus) genes and introduced into tobacco plants. From the observed distribution of CAT and GUS activity in the plant cells, we conclude that the first 23 amino-acid residues of ATPase-beta remain capable of specifically targeting reporter proteins into mitochondria. Immunodetection in transgenic plants and in vitro import experiments with various CAT fusion proteins show that the precursors are processed at the expected cleavage site but also at a cryptic site located in the linker region between the presequence and the first methionine of native CAT.

Cross-immunoreactivity between the LH1 antibody and cytokeratin epitopes in the differentiating epidermis of embryos of the grass snake Natrix natrix L. during the end stages of embryogenesis.

PubMed

Swadźba, Elwira; Rupik, Weronika

2012-01-01

The monoclonal anti-cytokeratin 1/10 (LH1) antibody recognizing K1/K10 keratin epitopes that characterizes a keratinized epidermis of mammals cross-reacts with the beta and Oberhäutchen layers covering the scales and gastrosteges of grass snake embryos during the final period of epidermis differentiation. The immunolocalization of the anti-cytokeratin 1/10 (LH1) antibody appears in the beta layer of the epidermis, covering the outer surface of the gastrosteges at the beginning of developmental stage XI, and in the beta layer of the epidermis, covering the outer surface of the scales at the end of developmental stage XI. This antibody cross-reacts with the Oberhäutchen layers in the epidermis covering the outer surface of both scales and gastrosteges at developmental stages XI and XII just before its fusion with the beta layers. After fusion of the Oberhäutchen and beta layers, LH1 immunolabeling is weaker than before. This might suggest that alpha-keratins in these layers of the epidermis are masked by beta-keratins, modified, or degraded. The anti-cytokeratin 1/10 (LH1) antibody stains the Oberhäutchen layer in the epidermis covering the inner surface of the gastrosteges and the hinge regions between gastrosteges at the end of developmental stage XI. However, the Oberhäutchen of the epidermis covering the inner surfaces of the scales and the hinge regions between scales does not show cytokeratin 1/10 (LH1) immunolabeling until hatching. This cross-reactivity suggests that the beta and Oberhäutchen layers probably contain some alpha-keratins that react with the LH1 antibody. It is possible that these alpha-keratins create specific scaffolding for the latest beta-keratin deposition. It is also possible that the LH1 antibody cross-reacts with other epidermal proteins such as filament-associated proteins, i.e., filaggrin-like. The anti-cytokeratin 1/10 (LH1) antibody does not stain the alpha and mesos layers until hatching. We suppose that the differentiation of these layers will begin just after the first postnatal sloughing.

High-Q plasmas in the TFTR tokamak

NASA Astrophysics Data System (ADS)

Jassby, D. L.; Barnes, C. W.; Bell, M. G.; Bitter, M.; Boivin, R.; Bretz, N. L.; Budny, R. V.; Bush, C. E.; Dylla, H. F.; Efthimion, P. C.; Fredrickson, E. D.; Hawryluk, R. J.; Hill, K. W.; Hosea, J.; Hsuan, H.; Janos, A. C.; Jobes, F. C.; Johnson, D. W.; Johnson, L. C.; Kamperschroer, J.; Kieras-Phillips, C.; Kilpatrick, S. J.; LaMarche, P. H.; LeBlanc, B.; Mansfield, D. K.; Marmar, E. S.; McCune, D. C.; McGuire, K. M.; Meade, D. M.; Medley, S. S.; Mikkelsen, D. R.; Mueller, D.; Owens, D. K.; Park, H. K.; Paul, S. F.; Pitcher, S.; Ramsey, A. T.; Redi, M. H.; Sabbagh, S. A.; Scott, S. D.; Snipes, J.; Stevens, J.; Strachan, J. D.; Stratton, B. C.; Synakowski, E. J.; Taylor, G.; Terry, J. L.; Timberlake, J. R.; Towner, H. H.; Ulrickson, M.; von Goeler, S.; Wieland, R. M.; Williams, M.; Wilson, J. R.; Wong, K.-L.; Young, K. M.; Zarnstorff, M. C.; Zweben, S. J.

1991-08-01

In the Tokamak Fusion Test Reactor (TFTR) [Plasma Phys. Controlled Fusion 26, 11 (1984)], the highest neutron source strength Sn and D-D fusion power gain QDD are realized in the neutral-beam-fueled and heated ``supershot'' regime that occurs after extensive wall conditioning to minimize recycling. For the best supershots, Sn increases approximately as P1.8b. The highest-Q shots are characterized by high Te (up to 12 keV), Ti (up to 34 keV), and stored energy (up to 4.7 MJ), highly peaked density profiles, broad Te profiles, and lower Zeff. Replacement of critical areas of the graphite limiter tiles with carbon-fiber composite tiles and improved alignment with the plasma have mitigated the ``carbon bloom.'' Wall conditioning by lithium pellet injection prior to the beam pulse reduces carbon influx and particle recycling. Empirically, QDD increases with decreasing pre-injection carbon radiation, and increases strongly with density peakedness [ne(0)/] during the beam pulse. To date, the best fusion results are Sn=5×1016 n/sec, QDD=1.85×10-3, and neutron yield=4.0×1016 n/pulse, obtained at Ip=1.6-1.9 MA and beam energy Eb=95-103 keV, with nearly balanced co- and counter-injected beam power. Computer simulations of supershot plasmas show that typically 50%-60% of Sn arises from beam-target reactions, with the remainder divided between beam-beam and thermonuclear reactions, the thermonuclear fraction increasing with Pb. The simulations predict that QDT=0.3-0.4 would be obtained for the best present plasma conditions, if half the deuterium neutral beams were to be replaced by tritium beams. Somewhat higher values are calculated if D beams are injected into a predominantly tritium target plasma. The projected central beta of fusion alphas is 0.4%-0.6%, a level sufficient for the study of alpha-induced collective effects.

Identification of beta-2 as a key cell adhesion molecule in PCa cell neurotropic behavior: a novel ex vivo and biophysical approach.

PubMed

Jansson, Keith H; Castillo, Deborah G; Morris, Joseph W; Boggs, Mary E; Czymmek, Kirk J; Adams, Elizabeth L; Schramm, Lawrence P; Sikes, Robert A

2014-01-01

Prostate cancer (PCa) is believed to metastasize through the blood/lymphatics systems; however, PCa may utilize the extensive innervation of the prostate for glandular egress. The interaction of PCa and its nerve fibers is observed in 80% of PCa and is termed perineural invasion (PNI). PCa cells have been observed traveling through the endoneurium of nerves, although the underlying mechanisms have not been elucidated. Voltage sensitive sodium channels (VSSC) are multimeric transmembrane protein complexes comprised of a pore-forming α subunit and one or two auxiliary beta (β) subunits with inherent cell adhesion molecule (CAM) functions. The beta-2 isoform (gene SCN2B) interacts with several neural CAMs, while interacting putatively with other prominent neural CAMs. Furthermore, beta-2 exhibits elevated mRNA and protein levels in highly metastatic and castrate-resistant PCa. When overexpressed in weakly aggressive LNCaP cells (2BECFP), beta-2 alters LNCaP cell morphology and enhances LNCaP cell metastasis associated behavior in vitro. We hypothesize that PCa cells use beta-2 as a CAM during PNI and subsequent PCa metastasis. The objective of this study was to determine the effect of beta-2 expression on PCa cell neurotropic metastasis associated behavior. We overexpressed beta-2 as a fusion protein with enhanced cyan fluorescence protein (ECFP) in weakly aggressive LNCaP cells and observed neurotropic effects utilizing our novel ex vivo organotypic spinal cord co-culture model, and performed functional assays with neural matrices and atomic force microscopy. With increased beta-2 expression, PCa cells display a trend of enhanced association with nerve axons. On laminin, a neural CAM, overexpression of beta-2 enhances PCa cell migration, invasion, and growth. 2BECFP cells exhibit marked binding affinity to laminin relative to LNECFP controls, and recombinant beta-2 ectodomain elicits more binding events to laminin than BSA control. Functional overexpression of VSSC beta subunits in PCa may mediate PCa metastatic behavior through association with neural matrices.

CK2(beta)tes gene encodes a testis-specific isoform of the regulatory subunit of casein kinase 2 in Drosophila melanogaster.

PubMed

Kalmykova, Alla I; Shevelyov, Yuri Y; Polesskaya, Oksana O; Dobritsa, Anna A; Evstafieva, Alexandra G; Boldyreff, Brigitte; Issinger, Olaf-Georg; Gvozdev, Vladimir A

2002-03-01

An earlier described CK2(beta)tes gene of Drosophila melanogaster is shown to encode a male germline specific isoform of regulatory beta subunit of casein kinase 2. Western-analysis using anti-CK2(beta)tes Ig revealed CK2(beta)tes protein in Drosophila testes extract. Expression of a CK2(beta)tes-beta-galactosidase fusion protein driven by the CK2(beta)tes promoter was found in transgenic flies at postmitotic stages of spermatogenesis. Examination of biochemical characteristics of a recombinant CK2(beta)tes protein expressed in Escherichia coli revealed properties similar to those of CK2beta: (a) CK2(beta)tes protein stimulates CK2alpha catalytic activity toward synthetic peptide; (b) it inhibits phosphorylation of calmodulin and mediates stimulation of CK2alpha by polylysine; (c) it is able to form (CK2(beta)tes)2 dimers, as well as (CK2alpha)2(CK2(beta)tes)2 tetramers. Using the yeast two-hybrid system and coimmunoprecipitation analysis of protein extract from Drosophila testes, we demonstrated an association between CK2(beta)tes and CK2alpha. Northern-analysis has shown that another regulatory (beta') subunit found recently in D. melanogaster genome is also testis-specific. Thus, we describe the first example of two tissue-specific regulatory subunits of CK2 which might serve to provide CK2 substrate recognition during spermatogenesis.

Beta-hydroxy-beta-methylbutyrate (HMB) stimulates myogenic cell proliferation, differentiation and survival via the MAPK/ERK and PI3K/Akt pathways.

PubMed

Kornasio, Reut; Riederer, Ingo; Butler-Browne, Gillian; Mouly, Vincent; Uni, Zehava; Halevy, Orna

2009-05-01

Beta-hydroxy-beta-methylbutyrate (HMB), a leucine catabolite, has been shown to prevent exercise-induced protein degradation and muscle damage. We hypothesized that HMB would directly regulate muscle-cell proliferation and differentiation and would attenuate apoptosis, the latter presumably underlying satellite-cell depletion during muscle degradation or atrophy. Adding various concentrations of HMB to serum-starved myoblasts induced cell proliferation and MyoD expression as well as the phosphorylation of MAPK/ERK. HMB induced differentiation-specific markers, increased IGF-I mRNA levels and accelerated cell fusion. Its inhibition of serum-starvation- or staurosporine-induced apoptosis was reflected by less apoptotic cells, reduced BAX expression and increased levels of Bcl-2 and Bcl-X. Annexin V staining and flow cytometry analysis showed reduced staurosporine-induced apoptosis in human myoblasts in response to HMB. HMB enhanced the association of the p85 subunit of PI3K with tyrosine-phosphorylated proteins. HMB elevated Akt phosphorylation on Thr308 and Ser473 and this was inhibited by Wortmannin, suggesting that HMB acts via Class I PI3K. Blocking of the PI3K/Akt pathway with specific inhibitors revealed its requirement in mediating the promotive effects of HMB on muscle cell differentiation and fusion. These direct effects of HMB on myoblast differentiation and survival resembling those of IGF-I, at least in culture, suggest its positive influence in preventing muscle wasting.

Physics Basis for the Advanced Tokamak Fusion Power Plant ARIES-AT

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

S.C. Jardin; C.E. Kessel; T.K. Mau

2003-10-07

The advanced tokamak is considered as the basis for a fusion power plant. The ARIES-AT design has an aspect ratio of A always equal to R/a = 4.0, an elongation and triangularity of kappa = 2.20, delta = 0.90 (evaluated at the separatrix surface), a toroidal beta of beta = 9.1% (normalized to the vacuum toroidal field at the plasma center), which corresponds to a normalized beta of bN * 100 x b/(I(sub)P(MA)/a(m)B(T)) = 5.4. These beta values are chosen to be 10% below the ideal-MHD stability limit. The bootstrap-current fraction is fBS * I(sub)BS/I(sub)P = 0.91. This leads tomore » a design with total plasma current I(sub)P = 12.8 MA, and toroidal field of 11.1 T (at the coil edge) and 5.8 T (at the plasma center). The major and minor radii are 5.2 and 1.3 m, respectively. The effects of H-mode edge gradients and the stability of this configuration to non-ideal modes is analyzed. The current-drive system consists of ICRF/FW for on-axis current drive and a lower-hybrid system for off-axis. Tran sport projections are presented using the drift-wave based GLF23 model. The approach to power and particle exhaust using both plasma core and scrape-off-layer radiation is presented.« less

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.

In vivo marking of spontaneous or vaccine-induced fibrosarcomas in the domestic house cat, using an adenoviral vector containing a bifunctional fusion protein, GAL-TEK.

PubMed

Marini, F C; Cannon, J P; Belmont, J W; Shillitoe, E J; Lapeyre, J N

1995-09-01

We evaluated the ability of a replication-deficient, recombinant adenoviral vector to transfer the bifunctional gene GAL-TEK, which expresses a marking/therapeutic gene product, to naturally occurring cat fibrosarcomas in situ. GAL-TEK contains an in-frame fusion of the bacterial LacZ gene for histochemical marking of tumors with beta-galactosidase (beta-Gal) and the HSV tk gene for enzyme-prodrug activation of the prodrug ganciclovir (GCV) to induce selective tumor cell killing. GAL-TEK bifunctional marking and cell killing activities were tested in vitro after adenoviral vector infection of HT1080 human fibrosarcoma cells. The tk activity of GAL-TEK is shown to be almost as potent as HSV tk to catalyze conversion of GCV to GCV nucleotides and promote selective cell killing. Using 8 cats with recurring 2.5-cm2 fibrosarcomas that either arose spontaneously or were induced by vaccine, we determined experimentally the administration routes and times required for optimum GAL-TEK gene transfer by beta-Gal histological staining and reverse transcriptase polymerase chain reaction to the multiple compartments of the growing fibrosarcomas consonant with minimizing collateral infection of neighboring tissues and other unwanted side effects.

Exploration of high harmonic fast wave heating on the National Spherical Torus Experiment

NASA Astrophysics Data System (ADS)

Wilson, J. R.; Bell, R. E.; Bernabei, S.; Bitter, M.; Bonoli, P.; Gates, D.; Hosea, J.; LeBlanc, B.; Mau, T. K.; Medley, S.; Menard, J.; Mueller, D.; Ono, M.; Phillips, C. K.; Pinsker, R. I.; Raman, R.; Rosenberg, A.; Ryan, P.; Sabbagh, S.; Stutman, D.; Swain, D.; Takase, Y.; Wilgen, J.

2003-05-01

High harmonic fast wave (HHFW) heating has been proposed as a particularly attractive means for plasma heating and current drive in the high beta plasmas that are achievable in spherical torus (ST) devices. The National Spherical Torus Experiment (NSTX) [M. Ono, S. M. Kaye, S. Neumeyer et al., in Proceedings of the 18th IEEE/NPSS Symposium on Fusion Engineering, Albuquerque, 1999 (IEEE, Piscataway, NJ, 1999), p. 53] is such a device. An rf heating system has been installed on the NSTX to explore the physics of HHFW heating, current drive via rf waves and for use as a tool to demonstrate the attractiveness of the ST concept as a fusion device. To date, experiments have demonstrated many of the theoretical predictions for HHFW. In particular, strong wave absorption on electrons over a wide range of plasma parameters and wave parallel phase velocities, wave acceleration of energetic ions, and indications of current drive for directed wave spectra have been observed. In addition HHFW heating has been used to explore the energy transport properties of NSTX plasmas, to create H-mode discharges with a large fraction of bootstrap current and to control the plasma current profile during the early stages of the discharge.

Axial-Current Matrix Elements in Light Nuclei from Lattice QCD

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

Savage, Martin; Shanahan, Phiala E.; Tiburzi, Brian C.

2016-12-01

I present results from the first lattice QCD calculations of axial-current matrix elements in light nuclei, performed by the NPLQCD collaboration. Precision calculations of these matrix elements, and the subsequent extraction of multi-nucleon axial-current operators, are essential in refining theoretical predictions of the proton-proton fusion cross section, neutrino-nucleus cross sections andmore » $$\\beta\\beta$$-decay rates of nuclei. In addition, they are expected to shed light on the phenomenological quenching of $$g_A$$ that is required in nuclear many-body calculations.« less

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

Peng, Y.K.M.; Strickler, D.J.

The spherical torus is a very small aspect ratio (A < 2) confinement concept obtained by retaining only the indispensable components inboard to the plasma torus. MHD equilibrium calculations show that spherical torus plasmas with safety factor q > 2 are characterized by high toroidal beta (..beta../sub t/ > 0.2), low poloidal beta (..beta../sub p/ < 0.3), naturally large elongation (kappa greater than or equal to 2), large plasma current with I/sub p//(aB/sub t0/) up to about 7 MA/mT, strong paramagnetism (B/sub t//B/sub t0/ > 1.5), and strong plasma helicity (F comparable to THETA). A large near-omnigeneous region is seenmore » at the large-major-radius, bad-curvature region of the plasma in comparison with the conventional tokamaks. These features combine to engender the spherical torus plasma in a unique physics regime which permits compact fusion at low field and modest cost. Because of its strong paramagnetism and helicity, the spherical torus plasma shares some of the desirable features of spheromak and reversed-field pinch (RFP) plasmas, but with tokamak-like confinement and safety factor q. The general class of spherical tori, which includes the spherical tokamak (q > 1), the spherical pinch (1 > q > O), and the spherical RFP (q < O), have magnetic field configurations unique in comparison with conventional tokamaks and RFPs. 22 refs., 12 figs.« less

Cloning, expression, and characterization of a peculiar choline-binding beta-galactosidase from Streptococcus mitis.

PubMed

Campuzano, Susana; Serra, Beatriz; Llull, Daniel; García, José L; García, Pedro

2009-09-01

A Streptococcus mitis genomic DNA fragment carrying the SMT1224 gene encoding a putative beta-galactosidase was identified, cloned, and expressed in Escherichia coli. This gene encodes a protein 2,411 amino acids long with a predicted molecular mass of 268 kDa. The deduced protein contains an N-terminal signal peptide and a C-terminal choline-binding domain consisting of five consensus repeats, which facilitates the anchoring of the secreted enzyme to the cell wall. The choline-binding capacity of the protein facilitates its purification using DEAE-cellulose affinity chromatography, although its complete purification was achieved by constructing a His-tagged fusion protein. The recombinant protein was characterized as a monomeric beta-galactosidase showing a specific activity of around 2,500 U/mg of protein, with optimum temperature and pH ranges of 30 to 40 degrees C and 6.0 to 6.5, respectively. Enzyme activity is not inhibited by glucose, even at 200 mM, and remains highly stable in solution or immobilized at room temperature in the absence of protein stabilizers. In S. mitis, the enzyme was located attached to the cell surface, but a significant activity was also detected in the culture medium. This novel enzyme represents the first beta-galactosidase having a modular structure with a choline-binding domain, a peculiar property that can also be useful for some biotechnological applications.

Tumor suppression function of the Big-h3 gene in radiation carcinogenesis

NASA Astrophysics Data System (ADS)

Zhao, Y.; Piao, C.; Hei, T.

Interaction between cell and extracellular matrix (ECM) plays a crucial role in tumor invasiveness and metastasis. Using an immortalized human bronchial epithelial (BEP2D) cell model, we show here that expression of Big-h3 gene, a secreted adhesion molecule induced by transforming growth factor- beta (TGF-beta ), is markedly decreased in independently generated, high LET radiation-induced tumor cell lines (TL1-TL5) relative to parental BEP2D cells. Expression of this gene was restored to control level in fusion cell lines between the tumorigenic and parental BEP2D cells that were no longer tumorigenic in nude mice. Transfection of Big-h3 gene into tumor cells resulted in a significant reduction of tumor growth. While integrin receptor alpha 5/beta 1 was overexpressed in tumor cells, its expression was corrected to the level of control BEP2D cells after Big-h3 transfection. These data suggest that Big-h3 is involved in tumor progression by regulating integrin receptor alpha 5/beta 1. . WWee We further show that down regulation of Big-h3 results from loss of expression of TGFbeta1 in tumor cells. The findings provide strong evidence that the Big-h3 gene has tumor suppressor function in radiation induced tumorigenic human bronchial epithelial cells and suggest a potential target for interventional therapy.

Application of very high harmonic fast waves for off-axis current drive in the DIII-D and FNSF-AT tokamaks

DOE PAGES

Prater, Ronald; Moeller, Charles P.; Pinsker, Robert I.; ...

2014-06-26

Fast waves at frequencies far above the ion cyclotron frequency and approaching the lower hybrid frequency (also called “helicons” or “whistlers”) have application to off-axis current drive in tokamaks with high electron beta. The high frequency causes the whistler-like behavior of the wave power nearly following field lines, but with a small radial component, so the waves spiral slowly toward the plasma center. The high frequency also contributes to strong damping. Modeling predicts robust off-axis current drive with good efficiency compared to alternatives in high performance discharges in DIII-D and Fusion Nuclear Science Facility (FNSF) when the electron beta ismore » above about 1.8%. Detailed analysis of ray behavior shows that ray trajectories and damping are deterministic (that is, not strongly affected by plasma profiles or initial ray conditions), unlike the chaotic ray behavior in lower frequency fast wave experiments. Current drive was found to not be sensitive to the launched value of the parallel index of refraction n||, so wave accessibility issues can be reduced. Finally, use of a traveling wave antenna provides a very narrow n|| spectrum, which also helps avoid accessibility problems.« less

Analysis of the L1 gene product of human papillomavirus type 16 by expression in a vaccinia virus recombinant.

PubMed

Browne, H M; Churcher, M J; Stanley, M A; Smith, G L; Minson, A C

1988-06-01

The L1 open reading frame of human papillomavirus type 16 (HPV16) has been expressed in vaccinia virus under the control of both the 7.5K early and late promoter, and the 4b major late promoter. Antibodies to a beta-galactosidase fusion protein containing a C-terminal portion of the HPV16 L1 gene product were used to compare the levels of L1 expression in the two recombinants, and showed that greater levels of expression were obtained when the gene was placed under the control of the 4b late promoter. Immunofluorescence studies revealed a nuclear location of the L1 gene product when expressed in vaccinia virus. Antibodies to the beta-galactosidase fusion protein detected a major polypeptide species of 57K and a minor species of 64K in Western blots of recombinant-infected cell lysates. The 64K species was not detected when cells were infected in the presence of tunicamycin, indicating that the primary translation product of the HPV16 L1 open reading frame is modified by N-linked glycosylation when expressed in vaccinia virus. Whereas antibodies to HPV16 L1 fusion proteins and to a peptide containing amino acids from the C terminus of HPV16 L1 reacted well in Western blots with the HPV16 L1 target expressed in vaccinia virus, no reactivity was observed with antibodies to bovine papillomavirus type 1 particles or to a HPV6b fusion protein.

Lymphotoxin beta receptor (Lt betaR): dual roles in demyelination and remyelination and successful therapeutic intervention using Lt betaR-Ig protein.

PubMed

Plant, Sheila R; Iocca, Heather A; Wang, Ying; Thrash, J Cameron; O'Connor, Brian P; Arnett, Heather A; Fu, Yang-Xin; Carson, Monica J; Ting, Jenny P-Y

2007-07-11

Inflammation mediated by macrophages is increasingly found to play a central role in diseases and disorders that affect a myriad of organs, prominent among these are diseases of the CNS. The neurotoxicant-induced, cuprizone model of demyelination is ideally suited for the analysis of inflammatory events. Demyelination on exposure to cuprizone is accompanied by predictable microglial activation and astrogliosis, and, after cuprizone withdrawal, this activation reproducibly diminishes during remyelination. This study demonstrates enhanced expression of lymphotoxin beta receptor (Lt betaR) during the demyelination phase of this model, and Lt betaR is found in areas enriched with microglial and astroglial cells. Deletion of the Lt betaR gene (Lt betaR-/-) resulted in a significant delay in demyelination but also a slight delay in remyelination. Inhibition of Lt betaR signaling by an Lt betaR-Ig fusion decoy protein successfully delayed demyelination in wild-type mice. Unexpectedly, this Lt betaR-Ig decoy protein dramatically accelerated the rate of remyelination, even after the maximal pathological disease state had been reached. This strongly indicates the beneficial role of Lt betaR-Ig in the delay of demyelination and the acceleration of remyelination. The discrepancy between remyelination rates in these systems could be attributed to developmental abnormalities in the immune systems of Lt betaR-/- mice. These findings bode well for the use of an inhibitory Lt betaR-Ig as a candidate biological therapy in demyelinating disorders, because it is beneficial during both demyelination and remyelination.

Characterization of Phospholipids in Insulin Secretory Granules and Mitochondria in Pancreatic Beta Cells and Their Changes with Glucose Stimulation*

PubMed Central

MacDonald, Michael J.; Ade, Lacmbouh; Ntambi, James M.; Ansari, Israr-Ul H.; Stoker, Scott W.

2015-01-01

The lipid composition of insulin secretory granules (ISG) has never previously been thoroughly characterized. We characterized the phospholipid composition of ISG and mitochondria in pancreatic beta cells without and with glucose stimulation. The phospholipid/protein ratios of most phospholipids containing unsaturated fatty acids were higher in ISG than in whole cells and in mitochondria. The concentrations of negatively charged phospholipids, phosphatidylserine, and phosphatidylinositol in ISG were 5-fold higher than in the whole cell. In ISG phosphatidylserine, phosphatidylinositol, phosphatidylethanolamine, and sphingomyelin, fatty acids 12:0 and 14:0 were high, as were phosphatidylserine and phosphatidylinositol containing 18-carbon unsaturated FA. With glucose stimulation, the concentration of many ISG phosphatidylserines and phosphatidylinositols increased; unsaturated fatty acids in phosphatidylserine increased; and most phosphatidylethanolamines, phosphatidylcholines, sphingomyelins, and lysophosphatidylcholines were unchanged. Unsaturation and shorter fatty acid length in phospholipids facilitate curvature and fluidity of membranes, which favors fusion of membranes. Recent evidence suggests that negatively charged phospholipids, such as phosphatidylserine, act as coupling factors enhancing the interaction of positively charged regions in SNARE proteins in synaptic or secretory vesicle membrane lipid bilayers with positively charged regions in SNARE proteins in the plasma membrane lipid bilayer to facilitate docking of vesicles to the plasma membrane during exocytosis. The results indicate that ISG phospholipids are in a dynamic state and are consistent with the idea that changes in ISG phospholipids facilitate fusion of ISG with the plasma membrane-enhancing glucose-stimulated insulin exocytosis. PMID:25762724

Anaplastic lymphoma kinase is expressed in different subtypes of human breast cancer

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

Perez-Pinera, Pablo; Chang, Y.; Astudillo, A.

2007-06-29

Pleiotrophin (PTN, Ptn) is an 18 kDa cytokine expressed in human breast cancers. Since inappropriate expression of Ptn stimulates progression of breast cancer in transgenic mice and a dominant negative PTN reverses the transformed phenotype of human breast cancer cells that inappropriately express Ptn, it is suggested that constitutive PTN signaling in breast cancer cells that inappropriately express Ptn activates pathways that promote a more aggressive breast cancer phenotype. Pleiotrophin signals by inactivating its receptor, the receptor protein tyrosine phosphatase (RPTP){beta}/{zeta}, and, recently, PTN was found to activate anaplastic lymphoma kinase (ALK) through the PTN/RPTP{beta}/{zeta} signaling pathway in PTN-stimulated cells,more » not through a direct interaction of PTN with ALK and thus not through the PTN-enforced dimerization of ALK. Since full-length ALK is activated in different malignant cancers and activated ALK is a potent oncogenic protein, we examined human breast cancers to test the possibility that ALK may be expressed in breast cancers and potentially activated through the PTN/RPTP{beta}/{zeta} signaling pathway; we now demonstrate that ALK is strongly expressed in different histological subtypes of human breast cancer; furthermore, ALK is expressed in both nuclei and cytoplasm and, in the 'dotted' pattern characteristic of ALK fusion proteins in anaplastic large cell lymphoma. This study thus supports the possibility that activated ALK may be important in human breast cancers and potentially activated either through the PTN/RPTP{beta}/{zeta} signaling pathway, or, alternatively, as an activated fusion protein to stimulate progression of breast cancer in humans.« less

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.

Exploration of High Harmonic Fast Wave Heating on the National Spherical Torus Experiment

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

J.R. Wilson; R.E. Bell; S. Bernabei

2003-02-11

High Harmonic Fast Wave (HHFW) heating has been proposed as a particularly attractive means for plasma heating and current drive in the high-beta plasmas that are achievable in spherical torus (ST) devices. The National Spherical Torus Experiment (NSTX) [Ono, M., Kaye, S.M., Neumeyer, S., et al., Proceedings, 18th IEEE/NPSS Symposium on Fusion Engineering, Albuquerque, 1999, (IEEE, Piscataway, NJ (1999), p. 53.)] is such a device. An radio-frequency (rf) heating system has been installed on NSTX to explore the physics of HHFW heating, current drive via rf waves and for use as a tool to demonstrate the attractiveness of the STmore » concept as a fusion device. To date, experiments have demonstrated many of the theoretical predictions for HHFW. In particular, strong wave absorption on electrons over a wide range of plasma parameters and wave parallel phase velocities, wave acceleration of energetic ions, and indications of current drive for directed wave spectra have been observed. In addition HHFW heating has been used to explore the energy transport properties of NSTX plasmas, to create H-mode (high-confinement mode) discharges with a large fraction of bootstrap current and to control the plasma current profile during the early stages of the discharge.« less

Imaging of laboratory magnetospheric plasmas using coherence imaging technique

NASA Astrophysics Data System (ADS)

Nishiura, Masaki; Takahashi, Noriki; Yoshida, Zensho; Nakamura, Kaori; Kawazura, Yohei; Kenmochi, Naoki; Nakatsuka, Masataka; Sugata, Tetsuya; Katsura, Shotaro; Howard, John

2017-10-01

The ring trap 1 (RT-1) device creates a laboratory magnetosphere for the studies on plasma physics and advanced nuclear fusion. A levitated superconducting coil produces magnetic dipole fields that realize a high beta plasma confinement that is motivated by self-organized plasmas in planetary magnetospheres. The electron cyclotron resonance heating (ECRH) with 8.2 GHz and 50 kW produces the plasmas with hot electrons in a few ten keV range. The electrons contribute to the local electron beta that exceeded 1 in RT-1. For the ion heating, ion cyclotron range of frequencies (ICRF) heating with 2-4 MHz and 10 kW has been performed in RT-1. The radial profile of ion temperature by a spectroscopic measurement indicates the signature of ion heating. In the holistic point of view, a coherence imaging system has been implemented for imaging the entire ion dynamics in the laboratory magnetosphere. The diagnostic system and obtained results will be presented.

Learning Activity Package, Physical Science. LAP Numbers 8, 9, 10, and 11.

ERIC Educational Resources Information Center

Williams, G. J.

These four units of the Learning Activity Packages (LAPs) for individualized instruction in physical science cover nuclear reactions, alpha and beta particles, atomic radiation, medical use of nuclear energy, fission, fusion, simple machines, Newton's laws of motion, electricity, currents, electromagnetism, Oersted's experiment, sound, light,…

Crystal Structures of Beta- and Gammaretrovirus Fusion Proteins Reveal a Role for Electrostatic Stapling in Viral Entry

PubMed Central

Aydin, Halil; Cook, Jonathan D.

2014-01-01

Membrane fusion is a key step in the life cycle of all envelope viruses, but this process is energetically unfavorable; the transmembrane fusion subunit (TM) of the virion-attached glycoprotein actively catalyzes the membrane merger process. Retroviral glycoproteins are the prototypical system to study pH-independent viral entry. In this study, we determined crystal structures of extramembrane regions of the TMs from Mason-Pfizer monkey virus (MPMV) and xenotropic murine leukemia virus-related virus (XMRV) at 1.7-Å and 2.2-Å resolution, respectively. The structures are comprised of a trimer of hairpins that is characteristic of class I viral fusion proteins and now completes a structural library of retroviral fusion proteins. Our results allowed us to identify a series of intra- and interchain electrostatic interactions in the heptad repeat and chain reversal regions. Mutagenesis reveals that charge-neutralizing salt bridge mutations significantly destabilize the postfusion six-helix bundle and abrogate retroviral infection, demonstrating that electrostatic stapling of the fusion subunit is essential for viral entry. Our data indicate that salt bridges are a major stabilizing force on the MPMV and XMRV retroviral TMs and likely provide the key energetics for viral and host membrane fusion. PMID:24131724

Identification of a new membrane-associated polypeptide specified by the coronavirus infectious bronchitis virus.

PubMed

Smith, A R; Boursnell, M E; Binns, M M; Brown, T D; Inglis, S C

1990-01-01

Nucleotide sequences from the third open reading frame of mRNA D (D3) of infectious bronchitis virus (IBV) were expressed in bacteria as part of a fusion protein with beta-galactosidase. Antiserum raised in rabbits against this fusion protein immunoprecipitated from IBV-infected chick kidney or Vero cells a polypeptide of 12.4K, the size expected for a D3-encoded product. The D3 polypeptide is apparently non-glycosylated, and appears to be associated with the membrane fraction of infected cells, as judged by cell fractionation and immunofluorescence.

Analysis of Snail1 function and regulation by Twist1 in palatal fusion.

PubMed

Yu, Wenli; Zhang, Yanping; Ruest, L Bruno; Svoboda, Kathy K H

2013-01-01

Palatal fusion is a tightly controlled process which comprises multiple cellular events, including cell movement and differentiation. Midline epithelial seam (MES) degradation is essential to palatal fusion. In this study, we analyzed the function of Snail1 during the degradation of the MES. We also analyzed the mechanism regulating the expression of the Snail1 gene in palatal shelves. Palatal explants treated with Snail1 siRNA did not degrade the MES and E-cadherin was not repressed leading to failure of palatal fusion. Transforming growth factor beta 3 (Tgfβ3) regulated Snail1 mRNA, as Snail1 expression decreased in response to Tgfβ3 neutralizing antibody and a PI-3 kinase (PI3K) inhibitor. Twist1, in collaboration with E2A factors, regulated the expression of Snail1. Twist1/E47 dimers bond to the Snail1 promoter to activate expression. Without E47, Twist1 repressed Snail1 expression. These results support the hypothesis that Tgfβ3 may signal through Twist1 and then Snail1 to downregulate E-cadherin expression during palatal fusion.

Numerical study of the Columbia high-beta device: Torus-II

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

Izzo, R.

1981-01-01

The ionization, heating and subsequent long-time-scale behavior of the helium plasma in the Columbia fusion device, Torus-II, is studied. The purpose of this work is to perform numerical simulations while maintaining a high level of interaction with experimentalists. The device is operated as a toroidal z-pinch to prepare the gas for heating. This ionization of helium is studied using a zero-dimensional, two-fluid code. It is essentially an energy balance calculation that follows the development of the various charge states of the helium and any impurities (primarily silicon and oxygen) that are present. The code is an atomic physics model ofmore » Torus-II. In addition to ionization, we include three-body and radiative recombination processes.« less

Isolation and characterization of an Arabidopsis biotin carboxylase gene and its promoter.

PubMed

Bao, X; Shorrosh, B S; Ohlrogge, J B

1997-11-01

In the plastids of most plants, acetyl-CoA carboxylase (ACCase; EC 6.4.1.2) is a multisubunit complex consisting of biotin carboxylase (BC), biotin-carboxyl carrier protien (BCCP), and carboxytransferase (alpha-CT, beta-CT) subunits. To better understand the regulation of this enzyme, we have isolated and sequenced a BC genomic clone from Arabidopsis and partially characterized its promoter. Fifteen introns were identified. The deduced amino acid sequence of the mature BC protein is highly conserved between Arabidopsis and tobacco (92.6% identity). BC expression was evaluated using northern blots and BC/GUS fusion constructs in transgenic Arabidopsis. GUS activity in the BC/GUS transgenics as well as transcript level of the native gene were both found to be higher in silique and flower than in root and leaf. Analysis of tobacco suspension cells transformed with truncated BC promoter/GUS gene fusions indicated the region from -140 to +147 contained necessary promoter elements which supported basal gene expression. A positive regulatory region was found to be located between -2100 and -140, whereas a negative element was possibly located in the first intron. In addition, several conserved regulatory elements were identified in the BC promoter. Surprisingly, although BC is a low-abundance protein, the expression of BC/GUS fusion constructs was similar to 35S/GUS constructs.

Final Report: Levitated Dipole Experiment

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

Kesner, Jay; Mauel, Michael

2013-03-10

Since the very first experiments with the LDX, research progress was rapid and significant. Initial experiments were conducted with the high-field superconducting coil suspended by three thin rods. These experiments produced long-pulse, quasi-steady-state microwave discharges, lasting more than 10 s, having peak beta values of 20% [Garnier, Phys. Plasmas, v13, p. 056111, 2006]. High-beta, near steady-state discharges have been maintained in LDX for more than 20 seconds, and this capability makes LDX the longest pulse fusion confinement experiment now operating in the U.S. fusion program. In both supported and levitated configurations, detailed measurements are made of discharge evolution, plasma dynamicsmore » and instability, and the roles of gas fueling, microwave power deposition profiles, and plasma boundary shape. High-temperature plasma is created by multifrequency electron cyclotron resonance heating allowing control of heating profiles. Depending upon neutral fueling rates, the LDX discharges contain a fraction of energetic electrons, with mean energies above 50 keV. Depending on whether or not the superconducting dipole is levitated or supported, the peak thermal electron temperature is estimated to exceed 500 eV and peak densities reach 1.0E18 (1/m3). Several significant discoveries resulted from the routine investigation of plasma confinement with a magnetically-levitated dipole. For the first time, toroidal plasma with pressure approaching the pressure of the confining magnetic field was well-confined in steady-state without a toroidal magnetic field. Magnetic levitation proved to be reliable and is now routine. The dipole's cryostat allows up to three hours of "float time" between re-cooling with liquid helium and providing scientists unprecedented access to the physics of magnetizd plasma. Levitation eliminates field-aligned particle sources and sinks and results in a toroidal, magnetically-confined plasma where profiles are determined by cross-field transport. We find levitation causes the central plasma density to increase dramatically and to significantly improve the confinement of thermal plasma [Boxer, Nature-Physics, v8, p. 949, 2010]. Several diagnostic systems have been used to measure plasma fluctuations, and these appear to represent low-frequency convection that may lead to adiabatic heating and strongly peaked pressure profiles. These experiments are remarkable, and the motivate wide-ranging studies of plasma found in space and confined for fusion energy. In the following report, we describe: (i) observations of the centrally-peaked density profile that appears naturally as a consequence of a strong turbulent pinch, (ii) observations of overall density and pressure increases that suggest large improvements to the thermal electron confinement time result occur during levitation, and (iii) the remarkable properties of low-frequency plasma fluctuations that cause magnetized plasma to "self-organize" into well-confined, centrally-peaked profiles that are relative to fusion and to space.« less

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

PubMed

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

2016-07-01

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

High beta effects and nonlinear evolution of the TAE instability

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

Spong, D.A.

1992-12-31

The toroidal Alfven eigenmode has recently been observed experimentally on DIII-D and TFTR when neutral beams are injected near the Alfven velocity. This instability is also of concern for future high {beta} D-T devices where fusion by-product alpha populations will generally be super-Alfvenic. We have developed a gyrofluid model (with Landau closure) of the TAE mode which can include most of the relevant damping mechanisms (continuum damping, ion and electron damping, ion FLR and collisional trapped electron damping) as well as reproducing analytically predicted undamped growth rates relatively accurately. An important consideration in predicting future unstable TAE regimes is themore » effect of finite beta in the background plasma. Due to the Shafranov shift and distortion of the flux surfaces, the location of the stable TAE root and the continuum will shift with increasing {beta}. The net effect of this is to generally enhance continuum damping and stabilize the TAF instability. Also, as the pressure gradient drive from the background becomes increasingly important, coupling between TAE and background driven modes can alter the TAE mode. A further application of our gyrofluid model which will be discussed is the nonlinear evolution of the TAE instability. Gyrofluid models offer a convenient reduced description which is more amenable to computational nonlinear modeling than full kinetic particle models. Our results demonstrate the rise and crash phases of TAE activity similar to experimental observations. The saturation is caused by generation of m=0 n=0 components through nonlinear beatings of the n > 1 modes; these cause modifications to the original equilibrium profiles in such a direction as to decrease the instability drive. This is the gyrofluid analog of direct particle losses. The peak magnetic fluctuation level increases with increasing energetic species beta, resulting in non-resonant stochastization of magnetic field lines.« less

High beta effects and nonlinear evolution of the TAE instability

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

Spong, D.A.

1992-01-01

The toroidal Alfven eigenmode has recently been observed experimentally on DIII-D and TFTR when neutral beams are injected near the Alfven velocity. This instability is also of concern for future high [beta] D-T devices where fusion by-product alpha populations will generally be super-Alfvenic. We have developed a gyrofluid model (with Landau closure) of the TAE mode which can include most of the relevant damping mechanisms (continuum damping, ion and electron damping, ion FLR and collisional trapped electron damping) as well as reproducing analytically predicted undamped growth rates relatively accurately. An important consideration in predicting future unstable TAE regimes is themore » effect of finite beta in the background plasma. Due to the Shafranov shift and distortion of the flux surfaces, the location of the stable TAE root and the continuum will shift with increasing [beta]. The net effect of this is to generally enhance continuum damping and stabilize the TAF instability. Also, as the pressure gradient drive from the background becomes increasingly important, coupling between TAE and background driven modes can alter the TAE mode. A further application of our gyrofluid model which will be discussed is the nonlinear evolution of the TAE instability. Gyrofluid models offer a convenient reduced description which is more amenable to computational nonlinear modeling than full kinetic particle models. Our results demonstrate the rise and crash phases of TAE activity similar to experimental observations. The saturation is caused by generation of m=0 n=0 components through nonlinear beatings of the n > 1 modes; these cause modifications to the original equilibrium profiles in such a direction as to decrease the instability drive. This is the gyrofluid analog of direct particle losses. The peak magnetic fluctuation level increases with increasing energetic species beta, resulting in non-resonant stochastization of magnetic field lines.« less

Epidermal differentiation during ontogeny and after hatching in the snake Liasis fuscus (Pythonidae, Serpentes, Reptilia), with emphasis on the formation of the shedding complex.

PubMed

Alibardi, L; Thompson, M B

2003-04-01

Differentiation and localization of keratin in the epidermis during embryonic development and up to 3 months posthatching in the Australian water python, Liasis fuscus, was studied by ultrastructural and immunocytochemical methods. Scales arise from dome-like folds in the skin that produce tightly imbricating scales. The dermis of these scales is completely differentiated before any epidermal differentiation begins, with a loose dermis made of mesenchymal cells beneath the differentiating outer scale surface. At this stage (33) the embryo is still unpigmented and two layers of suprabasal cells contain abundant glycogen. At Stage 34 (beginning of pigmentation) the first layers of cells beneath the bilayered periderm (presumptive clear and oberhautchen layers) have not yet formed a shedding complex, within which prehatching shedding takes place. At Stage 35 the shedding complex, consisting of the clear and oberhautchen layers, is discernible. The clear layer contains a fine fibrous network that faces the underlying oberhautchen, where the spinulae initially contain a core of fibrous material and small beta-keratin packets. Differentiation continues at Stage 36 when the beta-layer forms and beta-keratin packets are deposited both on the fibrous core of the oberhautchen and within beta-cells. Mesos cells are produced from the germinal layer but remain undifferentiated. At Stage 37, before hatching, the beta-layer is compact, the mesos layer contains mesos granules, and cells of the alpha-layer are present but are not yet keratinized. They are still only partially differentiated a few hours after hatching, when a new shedding complex is forming underneath. Using antibodies against chick scale beta-keratin resolved at high magnification with immunofluorescent or immunogold conjugates, we offer the first molecular confirmation that in snakes only the oberhautchen component of the shedding complex and the underlying beta cells contain beta-keratin. Initially, there is little immunoreactivity in the small beta-packets of the oberhautchen, but it increases after fusion with the underlying cells to produce the syncytial beta layer. The beta-keratin packets coalesce with the tonofilaments, including those attached to desmosomes, which rapidly disappear in both oberhautchen and beta-cells as differentiation progresses. The labeling is low to absent in forming mesos-cells beneath the beta-layer. This study further supports the hypothesis that the shedding complex in lepidosaurian reptiles evolved after there was a segregation between alpha-keratogenic cells from beta-keratogenic cells during epidermal renewal. Copyright 2003 Wiley-Liss, Inc.

The FAST (FRC Acceleration Space Thruster) Experiment

NASA Technical Reports Server (NTRS)

Martin, Adam; Eskridge, R.; Lee, M.; Richeson, J.; Smith, J.; Thio, Y. C. F.; Slough, J.; Rodgers, Stephen L. (Technical Monitor)

2001-01-01

The Field Reverse Configuration (FRC) is a magnetized plasmoid that has been developed for use in magnetic confinement fusion. Several of its properties suggest that it may also be useful as a thruster for in-space propulsion. The FRC is a compact toroid that has only poloidal field, and is characterized by a high plasma beta = (P)/(B (sup 2) /2Mu0), the ratio of plasma pressure to magnetic field pressure, so that it makes efficient use of magnetic field to confine a plasma. In an FRC thruster, plasmoids would be repetitively formed and accelerated to high velocity; velocities of = 250 km/s (Isp = 25,000s) have already been achieved in fusion experiments. The FRC is inductively formed and accelerated, and so is not subject to the problem of electrode erosion. As the plasmoid may be accelerated over an extended length, it can in principle be made very efficient. And the achievable jet powers should be scalable to the MW range. A 10 kW thruster experiment - FAST (FRC Acceleration Space Thruster) has just started at the Marshall Space Flight Center. The design of FAST and the status of construction and operation will be presented.

A quantitative study of skeletofusimotor innervation in the cat peroneus tertius muscle.

PubMed Central

Jami, L; Murthy, K S; Petit, J

1982-01-01

1. Physiological tests were used to identify skeletofusimotor or beta axons to the cat peroneus tertius muscle in order to assess the proportion of beta axons in the motor supply to this muscle. 2. Static beta axons (beta S) were identified by: (a) observation of a delay between the complete block of extrafusal contraction and the failure of spindle activation upon prolonged stimulation, (b) increase of spindle excitation with stimulation frequencies above that eliciting maximal extrafusal contraction, (c) observation of 'unfused' frequencygram of spindle primary afferent discharge during stimulation of the axon at frequencies above that eliciting complete fusion of extrafusal contraction and (d) static action exerted on the response of the spindle afferent to ramp stretch. 3. Dynamic beta axons (beta D) were identified by the persistence of spindle activation after selective block of extrafusal neuromuscular junctions and by their dynamic action on spindle primary endings. 4. The actions of 116 motor axons (conduction velocity 56-104 m/sec) on ninety-five spindle afferents (fifty-seven from primary and thirty-eight from secondary endings) were examined in ten experiments. Thirty-six beta axons (31% of the total sample) were identified: twenty-four beta S (conduction velocity 69-104 m/sec) and twelve beta D (conduction velocity 56-91 m/sec). 5. Twenty (35%) primary endings were activated by a beta S and sixteen (28%) by a beta D axon. Nineteen (45%) secondary endings were activated by a beta S and five (13%) by a beta D axon. Convergence of beta D and beta S axons on the same spindle occurred in 10% of instances. beta-innervated spindles were also supplied by gamma axons. 6. Most of the beta S motor units were of the fast-fatigue resistant (FR) type, with a few units of the fast-fatigable (FF) type, and nearly all the beta D motor units were of the slow (S) type. PMID:6213764

Protein- protein interaction detection system using fluorescent protein microdomains

DOEpatents

Waldo, Geoffrey S.; Cabantous, Stephanie

2010-02-23

The invention provides a protein labeling and interaction detection system based on engineered fragments of fluorescent and chromophoric proteins that require fused interacting polypeptides to drive the association of the fragments, and further are soluble and stable, and do not change the solubility of polypeptides to which they are fused. In one embodiment, a test protein X is fused to a sixteen amino acid fragment of GFP (.beta.-strand 10, amino acids 198-214), engineered to not perturb fusion protein solubility. A second test protein Y is fused to a sixteen amino acid fragment of GFP (.beta.-strand 11, amino acids 215-230), engineered to not perturb fusion protein solubility. When X and Y interact, they bring the GFP strands into proximity, and are detected by complementation with a third GFP fragment consisting of GFP amino acids 1-198 (strands 1-9). When GFP strands 10 and 11 are held together by interaction of protein X and Y, they spontaneous association with GFP strands 1-9, resulting in structural complementation, folding, and concomitant GFP fluorescence.

Imaging exocytosis of single glucagon-like peptide-1 containing granules in a murine enteroendocrine cell line with total internal reflection fluorescent microscopy

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

Ohara-Imaizumi, Mica; Aoyagi, Kyota; Akimoto, Yoshihiro

To analyze the exocytosis of glucagon-like peptide-1 (GLP-1) granules, we imaged the motion of GLP-1 granules labeled with enhanced yellow fluorescent protein (Venus) fused to human growth hormone (hGH-Venus) in an enteroendocrine cell line, STC-1 cells, by total internal reflection fluorescent (TIRF) microscopy. We found glucose stimulation caused biphasic GLP-1 granule exocytosis: during the first phase, fusion events occurred from two types of granules (previously docked granules and newcomers), and thereafter continuous fusion was observed mostly from newcomers during the second phase. Closely similar to the insulin granule fusion from pancreatic {beta} cells, the regulated biphasic exocytosis from two typesmore » of granules may be a common mechanism in glucose-evoked hormone release from endocrine cells.« less

Sequence-specific interaction between the disintegrin domain of mouse ADAM 3 and murine eggs: role of beta1 integrin-associated proteins CD9, CD81, and CD98.

PubMed

Takahashi, Y; Bigler, D; Ito, Y; White, J M

2001-04-01

ADAM 3 is a sperm surface glycoprotein that has been implicated in sperm-egg adhesion. Because little is known about the adhesive activity of ADAMs, we investigated the interaction of ADAM 3 disintegrin domains, made in bacteria and in insect cells, with murine eggs. Both recombinant proteins inhibited sperm-egg binding and fusion with potencies similar to that which we recently reported for the ADAM 2 disintegrin domain. Alanine scanning mutagenesis revealed a critical importance for the glutamine at position 7 of the disintegrin loop. Fluorescent beads coated with the ADAM 3 disintegrin domain bound to the egg surface. Bead binding was inhibited by an authentic, but not by a scrambled, peptide analog of the disintegrin loop. Bead binding was also inhibited by the function-blocking anti-alpha6 monoclonal antibody (mAb) GoH3, but not by a nonfunction blocking anti-alpha6 mAb, or by mAbs against either the alphav or beta3 integrin subunits. We also present evidence that in addition to the tetraspanin CD9, two other beta1-integrin-associated proteins, the tetraspanin CD81 as well as the single pass transmembrane protein CD98 are expressed on murine eggs. Antibodies to CD9 and CD98 inhibited in vitro fertilization and binding of the ADAM 3 disintegrin domain. Our findings are discussed in terms of the involvement of multiple sperm ADAMs and multiple egg beta1 integrin-associated proteins in sperm-egg binding and fusion. We propose that an egg surface "tetraspan web" facilitates fertilization and that it may do so by fostering ADAM-integrin interactions.

Ultraviolet-induced movement of the human DNA repair protein, xeroderma pigmentosum type G, in the nucleus

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

Park, M.S.; Knauf, J.A.; Pendergrass, S.H.

1996-08-06

Xeroderma pigmentosum type G (XPG) is a human genetic disease exhibiting extreme sensitivity to sunlight. XPG patients are defective XPG endonuclease, which is an enzyme essential for DNA repair of the major kinds of solar ultraviolet (UV)-induced DNA damages. Here we describe a novel dynamics of this protein within the cell nucleus after UV irradiation of human cells. USing confocal microscopy, we have localized the immunofluorescent, antigenic signal of XPG protein to foci throughout the cell nucleus. Our biochemical studies also established that XPG protein forms a tight association with nuclear structure(s). In human skin fibroblast cells, the number ofmore » XPG foci decreased within 2 h after UV irradiation, whereas total nuclear XPG fluorescence intensity remained constant, suggesting redistribution of XPG from a limited number of nuclear foci to the nucleus overall. Within 8 h after UV, most XPG antigenic signal was found as foci. Using {beta}-galactosidase-XPG fusion constructs ({beta}-gal-XPG) transfected into HeLa cells, we have identified a single region of XPG that is evidently responsible both for foci formation and for the UV dynamic response. The fusion protein carrying the C terminus of XPG (amino acids 1146-1185) localized {beta}-gal specific antigenic signal to foci and to the nucleolus regions. After UV irradiation, antigenic {beta}-gal translocated reversibly from the subnuclear structures to the whole nucleus with kinetics very similar to the movements of XPG protein. These findings lead us to propose a model in which distribution of XPG protein may regulate the rate of DNA repair within transcriptionally active and inactive compartments of the cell nucleus. 50 refs., 5 figs., 1 tab.« less

Development of the Los Alamos National Laboratory Cryogenic Pressure Loader

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

Ebey, Peter S.; Dole, James M.; Hoffer, James K.

2003-05-15

Targets for inertial fusion research and ignition at OMEGA, the National Ignition Facility, LMJ, and future facilities rely on beta-radiation-driven layering of spherical cryogenic DT ice layers contained within plastic or metal shells. Plastic shells will be permeation filled at room temperature then cooled to cryogenic temperatures before removal of the overpressure. The cryogenic pressure loader (CPL) was recently developed at Los Alamos National Laboratory as a testbed for studying the filling and layering of plastic target shells with DT. A technical description of the CPL is provided. The CPL consists of a cryostat, which contains a high-pressure permeation cell,more » and has optical access for investigating beta layering. The cryostat is housed within a tritium glovebox that contains manifolds for supplying high-pressure DT. The CPL shares some design elements with the cryogenic target handling system at the OMEGA facility to allow testing of tritium issues related to that system. The CPL has the capability to fill plastic targets by permeation to pressures up to 100 MPa and to cool them to 15 K. The CPL will accommodate a range of targets and may be modified for future experiments.« less

Fusion nuclear science facilities and pilot plants based on the spherical tokamak

NASA Astrophysics Data System (ADS)

Menard, J. E.; Brown, T.; El-Guebaly, L.; Boyer, M.; Canik, J.; Colling, B.; Raman, R.; Wang, Z.; Zhai, Y.; Buxton, P.; Covele, B.; D'Angelo, C.; Davis, A.; Gerhardt, S.; Gryaznevich, M.; Harb, M.; Hender, T. C.; Kaye, S.; Kingham, D.; Kotschenreuther, M.; Mahajan, S.; Maingi, R.; Marriott, E.; Meier, E. T.; Mynsberge, L.; Neumeyer, C.; Ono, M.; Park, J.-K.; Sabbagh, S. A.; Soukhanovskii, V.; Valanju, P.; Woolley, R.

2016-10-01

A fusion nuclear science facility (FNSF) could play an important role in the development of fusion energy by providing the nuclear environment needed to develop fusion materials and components. The spherical torus/tokamak (ST) is a leading candidate for an FNSF due to its potentially high neutron wall loading and modular configuration. A key consideration for the choice of FNSF configuration is the range of achievable missions as a function of device size. Possible missions include: providing high neutron wall loading and fluence, demonstrating tritium self-sufficiency, and demonstrating electrical self-sufficiency. All of these missions must also be compatible with a viable divertor, first-wall, and blanket solution. ST-FNSF configurations have been developed simultaneously incorporating for the first time: (1) a blanket system capable of tritium breeding ratio TBR  ≈  1, (2) a poloidal field coil set supporting high elongation and triangularity for a range of internal inductance and normalized beta values consistent with NSTX/NSTX-U previous/planned operation, (3) a long-legged divertor analogous to the MAST-U divertor which substantially reduces projected peak divertor heat-flux and has all outboard poloidal field coils outside the vacuum chamber and superconducting to reduce power consumption, and (4) a vertical maintenance scheme in which blanket structures and the centerstack can be removed independently. Progress in these ST-FNSF missions versus configuration studies including dependence on plasma major radius R 0 for a range 1 m-2.2 m are described. In particular, it is found the threshold major radius for TBR  =  1 is {{R}0}≥slant 1.7 m, and a smaller R 0  =  1 m ST device has TBR  ≈  0.9 which is below unity but substantially reduces T consumption relative to not breeding. Calculations of neutral beam heating and current drive for non-inductive ramp-up and sustainment are described. An A  =  2, R 0  =  3 m device incorporating high-temperature superconductor toroidal field coil magnets capable of high neutron fluence and both tritium and electrical self-sufficiency is also presented following systematic aspect ratio studies.

Fusion nuclear science facilities and pilot plants based on the spherical tokamak

DOE PAGES

Menard, J. E.; Brown, T.; El-Guebaly, L.; ...

2016-08-16

Here, a fusion nuclear science facility (FNSF) could play an important role in the development of fusion energy by providing the nuclear environment needed to develop fusion materials and components. The spherical torus/tokamak (ST) is a leading candidate for an FNSF due to its potentially high neutron wall loading and modular configuration. A key consideration for the choice of FNSF configuration is the range of achievable missions as a function of device size. Possible missions include: providing high neutron wall loading and fluence, demonstrating tritium self-sufficiency, and demonstrating electrical self-sufficiency. All of these missions must also be compatible with a viable divertor, first-wall, and blanket solution. ST-FNSF configurations have been developed simultaneously incorporating for the first time: (1) a blanket system capable of tritium breeding ratio TBR ≈ 1, (2) a poloidal field coil set supporting high elongation and triangularity for a range of internal inductance and normalized beta values consistent with NSTX/NSTX-U previous/planned operation, (3) a long-legged divertor analogous to the MAST-U divertor which substantially reduces projected peak divertor heat-flux and has all outboard poloidal field coils outside the vacuum chamber and superconducting to reduce power consumption, and (4) a vertical maintenance scheme in which blanket structures and the centerstack can be removed independently. Progress in these ST-FNSF missions versus configuration studies including dependence on plasma major radius R 0 for a range 1 m–2.2 m are described. In particular, it is found the threshold major radius for TBR = 1 ismore » $${{R}_{0}}\\geqslant 1.7$$ m, and a smaller R 0 = 1 m ST device has TBR ≈ 0.9 which is below unity but substantially reduces T consumption relative to not breeding. Calculations of neutral beam heating and current drive for non-inductive ramp-up and sustainment are described. An A = 2, R = 3 m device incorporating high-temperature superconductor toroidal field coil magnets capable of high neutron fluence and both tritium and electrical self-sufficiency is also presented following systematic aspect ratio studies.« less

Access to high beta advanced inductive plasmas at low injected torque

NASA Astrophysics Data System (ADS)

Solomon, W. M.; Politzer, P. A.; Buttery, R. J.; Holcomb, C. T.; Ferron, J. R.; Garofalo, A. M.; Grierson, B. A.; Hanson, J. M.; In, Y.; Jackson, G. L.; Kinsey, J. E.; La Haye, R. J.; Lanctot, M. J.; Luce, T. C.; Okabayashi, M.; Petty, C. C.; Turco, F.; Welander, A. S.

2013-09-01

Recent experiments on DIII-D demonstrate that advanced inductive (AI) discharges with high equivalent normalized fusion gain can be accessed and sustained with very low amounts (∼1 N m) of externally injected torque, a level of torque that is anticipated to drive a similar amount of rotation as the beams on ITER, via simple consideration of the scaling of the moment of inertia and confinement time. The AI regime is typically characterized by high confinement, and high βN, allowing the possibility for high performance, high gain operation at reduced plasma current. Discharges achieved βN ∼ 3.1 with H98(y,2) ∼ 1 at q95 ∼ 4, and are sustained for the maximum duration of the counter neutral beams (NBs). In addition, plasmas using zero net NB torque from the startup all the way through to the high βN phase have been created. AI discharges are found to become increasingly susceptible to m/n = 2/1 neoclassical tearing modes as the torque is decreased, which if left unmitigated, generally slow and lock, terminating the high performance phase of the discharge. Access is not notably different whether one ramps the torque down at high βN, or ramps βN up at low torque. The use of electron cyclotron heating (ECH) and current drive proved to be an effective method of avoiding such modes, enabling stable operation at high beta and low torque, a portion of phase space that has otherwise been inaccessible. Thermal confinement is significantly reduced at low rotation, a result that is reproduced using the TGLF transport model. Although it is thought that stiffness is increased in regions of low magnetic shear, in these AI plasmas, the reduced confinement occurs at radii outside the low shear, and in fact, higher temperature gradients can be found in the low shear region at low rotation. Momentum transport is also larger at low rotation, but a significant intrinsic torque is measured that is consistent with a previous scaling considering the role of the turbulent Reynolds stress and thermal ion orbit loss. Although high normalized fusion performance has been achieved in these discharges, more detailed projections suggest that enhancement in the confinement needs to be realized in order to obtain a low current solution consistent with ITER Q = 10 performance, and this remains a future research challenge.

Characterization of phospholipids in insulin secretory granules and mitochondria in pancreatic beta cells and their changes with glucose stimulation.

PubMed

MacDonald, Michael J; Ade, Lacmbouh; Ntambi, James M; Ansari, Israr-Ul H; Stoker, Scott W

2015-04-24

The lipid composition of insulin secretory granules (ISG) has never previously been thoroughly characterized. We characterized the phospholipid composition of ISG and mitochondria in pancreatic beta cells without and with glucose stimulation. The phospholipid/protein ratios of most phospholipids containing unsaturated fatty acids were higher in ISG than in whole cells and in mitochondria. The concentrations of negatively charged phospholipids, phosphatidylserine, and phosphatidylinositol in ISG were 5-fold higher than in the whole cell. In ISG phosphatidylserine, phosphatidylinositol, phosphatidylethanolamine, and sphingomyelin, fatty acids 12:0 and 14:0 were high, as were phosphatidylserine and phosphatidylinositol containing 18-carbon unsaturated FA. With glucose stimulation, the concentration of many ISG phosphatidylserines and phosphatidylinositols increased; unsaturated fatty acids in phosphatidylserine increased; and most phosphatidylethanolamines, phosphatidylcholines, sphingomyelins, and lysophosphatidylcholines were unchanged. Unsaturation and shorter fatty acid length in phospholipids facilitate curvature and fluidity of membranes, which favors fusion of membranes. Recent evidence suggests that negatively charged phospholipids, such as phosphatidylserine, act as coupling factors enhancing the interaction of positively charged regions in SNARE proteins in synaptic or secretory vesicle membrane lipid bilayers with positively charged regions in SNARE proteins in the plasma membrane lipid bilayer to facilitate docking of vesicles to the plasma membrane during exocytosis. The results indicate that ISG phospholipids are in a dynamic state and are consistent with the idea that changes in ISG phospholipids facilitate fusion of ISG with the plasma membrane-enhancing glucose-stimulated insulin exocytosis. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

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

PubMed

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

2006-09-01

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

Impact of ideal MHD stability limits on high-beta hybrid operation

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

Piovesan, Paolo; Igochine, V.; Turco, F.

Here, the hybrid scenario is a candidate for stationary high-fusion gain tokamak operation in ITER and DEMO. To obtain such performance, the energy confinement and the normalized pressuremore » $${{\\beta}_{N}}$$ must be maximized, which requires operating near or above ideal MHD no-wall limits. New experimental findings show how these limits can affect hybrid operation. Even if hybrids are mainly limited by tearing modes, proximity to the no-wall limit leads to 3D field amplification that affects plasma profiles, e.g. rotation braking is observed in ASDEX Upgrade throughout the plasma and peaks in the core. As a result, even the small ASDEX Upgrade error fields are amplified and their effects become visible. To quantify such effects, ASDEX Upgrade measured the response to 3D fields applied by $$8\\times 2$$ non-axisymmetric coils as $${{\\beta}_{N}}$$ approaches the no-wall limit. The full n = 1 response profile and poloidal structure were measured by a suite of diagnostics and compared with linear MHD simulations, revealing a characteristic feature of hybrids: the n = 1 response is due to a global, marginally-stable n = 1 kink characterized by a large m = 1, n = 1 core harmonic due to q min being just above 1. A helical core distortion of a few cm forms and affects various core quantities, including plasma rotation, electron and ion temperature, and intrinsic W density. In similar experiments, DIII-D also measured the effect of this helical core on the internal current profile, providing information useful to understanding of the physics of magnetic flux pumping, i.e. anomalous current redistribution by MHD modes that keeps $${{q}_{\\text{min}}}>1$$ . Thanks to flux pumping, a broad current profile is maintained in DIII-D even with large on-axis current drive, enabling fully non-inductive operation at high $${{\\beta}_{N}}$$ up to 3.5–4.« less

Impact of ideal MHD stability limits on high-beta hybrid operation

DOE PAGES

Piovesan, Paolo; Igochine, V.; Turco, F.; ...

2016-10-27

Here, the hybrid scenario is a candidate for stationary high-fusion gain tokamak operation in ITER and DEMO. To obtain such performance, the energy confinement and the normalized pressuremore » $${{\\beta}_{N}}$$ must be maximized, which requires operating near or above ideal MHD no-wall limits. New experimental findings show how these limits can affect hybrid operation. Even if hybrids are mainly limited by tearing modes, proximity to the no-wall limit leads to 3D field amplification that affects plasma profiles, e.g. rotation braking is observed in ASDEX Upgrade throughout the plasma and peaks in the core. As a result, even the small ASDEX Upgrade error fields are amplified and their effects become visible. To quantify such effects, ASDEX Upgrade measured the response to 3D fields applied by $$8\\times 2$$ non-axisymmetric coils as $${{\\beta}_{N}}$$ approaches the no-wall limit. The full n = 1 response profile and poloidal structure were measured by a suite of diagnostics and compared with linear MHD simulations, revealing a characteristic feature of hybrids: the n = 1 response is due to a global, marginally-stable n = 1 kink characterized by a large m = 1, n = 1 core harmonic due to q min being just above 1. A helical core distortion of a few cm forms and affects various core quantities, including plasma rotation, electron and ion temperature, and intrinsic W density. In similar experiments, DIII-D also measured the effect of this helical core on the internal current profile, providing information useful to understanding of the physics of magnetic flux pumping, i.e. anomalous current redistribution by MHD modes that keeps $${{q}_{\\text{min}}}>1$$ . Thanks to flux pumping, a broad current profile is maintained in DIII-D even with large on-axis current drive, enabling fully non-inductive operation at high $${{\\beta}_{N}}$$ up to 3.5–4.« less

Design and installation of a ferromagnetic wall in tokamak geometry

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

Hughes, P. E., E-mail: peh2109@columbia.edu; Levesque, J. P.; Rivera, N.

Low-activation ferritic steels are leading material candidates for use in next-generation fusion development experiments such as a prospective component test facility and DEMO power reactor. Understanding the interaction of plasmas with a ferromagnetic wall will provide crucial physics for these facilities. In order to study ferromagnetic effects in toroidal geometry, a ferritic wall upgrade was designed and installed in the High Beta Tokamak–Extended Pulse (HBT-EP). Several material options were investigated based on conductivity, magnetic permeability, vacuum compatibility, and other criteria, and the material of choice (high-cobalt steel) is characterized. Installation was accomplished quickly, with minimal impact on existing diagnostics andmore » overall machine performance, and initial results demonstrate the effects of the ferritic wall on plasma stability.« less

Isotope and fast ions turbulence suppression effects: Consequences for high-β ITER plasmas

NASA Astrophysics Data System (ADS)

Garcia, J.; Görler, T.; Jenko, F.

2018-05-01

The impact of isotope effects and fast ions on microturbulence is analyzed by means of non-linear gyrokinetic simulations for an ITER hybrid scenario at high beta obtained from previous integrated modelling simulations with simplified assumptions. Simulations show that ITER might work very close to threshold, and in these conditions, significant turbulence suppression is found from DD to DT plasmas. Electromagnetic effects are shown to play an important role in the onset of this isotope effect. Additionally, even external ExB flow shear, which is expected to be low in ITER, has a stronger impact on DT than on DD. The fast ions generated by fusion reactions can additionally reduce turbulence even more although the impact in ITER seems weaker than in present-day tokamaks.

Predicting the sensitivity of the beryllium/scintillator layer neutron detector using Monte Carlo and experimental response functions.

PubMed

Styron, J D; Cooper, G W; Ruiz, C L; Hahn, K D; Chandler, G A; Nelson, A J; Torres, J A; McWatters, B R; Carpenter, Ken; Bonura, M A

2014-11-01

A methodology for obtaining empirical curves relating absolute measured scintillation light output to beta energy deposited is presented. Output signals were measured from thin plastic scintillator using NIST traceable beta and gamma sources and MCNP5 was used to model the energy deposition from each source. Combining the experimental and calculated results gives the desired empirical relationships. To validate, the sensitivity of a beryllium/scintillator-layer neutron activation detector was predicted and then exposed to a known neutron fluence from a Deuterium-Deuterium fusion plasma (DD). The predicted and the measured sensitivity were in statistical agreement.

Purification and characterization of a GH43 β-xylosidase from Enterobacter sp. identified and cloned from forest soil bacteria.

PubMed

Campos, Eleonora; Negro Alvarez, María José; Sabarís di Lorenzo, Gonzalo; Gonzalez, Sergio; Rorig, Marcela; Talia, Paola; Grasso, Daniel H; Sáez, Felicia; Manzanares Secades, Paloma; Ballesteros Perdices, Mercedes; Cataldi, Angel A

2014-01-01

The use of lignocellulosic biomass for second generation biofuels requires optimization of enzymatic breakdown of plant cell walls. In this work, cellulolytic bacteria were isolated from a native and two cultivated forest soil samples. Amplification of glycosyl hydrolases was attempted by using a low stringency-degenerate primer PCR strategy, using total soil DNA and bulk DNA pooled from positive colonies as template. A set of primers was designed based on Acidothermus cellulolyticus genome, by search of conserved domains of glycosyl hydrolases (GH) families of interest. Using this approach, a fragment containing an open reading frame (ORF) with 98% identity to a putative GH43 beta-xylosidase coding gene from Enterobacter cloacae was amplified and cloned. The full protein was expressed in Escherichia coli as N-terminal or C-terminal His-tagged fusions and purified under native conditions. Only N-terminal fusion protein, His-Xyl43, presented beta-xylosidase activity. On pNPX, optimal activity was achieved at pH 6 and 40 °C and Km and Kcat values were 2.92 mM and 1.32 seg(-1), respectively. Activity was also demonstrated on xylobiose (X2), with Km 17.8 mM and Kcat 380 s(-1). These results demonstrated that Xyl43 is a functional beta-xylosidase and it is the first evidence of this activity for Enterobacter sp. Copyright © 2013 Elsevier GmbH. All rights reserved.

An Imposed Dynamo Current Drive Experiment: Demonstration of Confinement

NASA Astrophysics Data System (ADS)

Jarboe, Thomas; Hansen, Chris; Hossack, Aaron; Marklin, George; Morgan, Kyle; Nelson, Brian; Sutherland, Derek; Victor, Brian

2014-10-01

An experiment for studying and developing the efficient sustainment of a spheromak with sufficient confinement (current-drive power heats the plasma to its stability β-limit) and in the keV temperature range is discussed. A high- β spheromak sustained by imposed dynamo current drive (IDCD) is justified because: previous transient experiments showed sufficient confinement in the keV range with no external toroidal field coil; recent results on HIT-SI show sustainment with sufficient confinement at low temperature; the potential of IDCD of solving other fusion issues; a very attractive reactor concept; and the general need for efficient current drive in magnetic fusion. The design of a 0.55 m minor radius machine with the required density control, wall loading, and neutral shielding for a 2 s pulse is presented. Peak temperatures of 1 keV and toroidal currents of 1.35 MA and 16% wall-normalized plasma beta are envisioned. The experiment is large enough to address the key issues yet small enough for rapid modification and for extended MHD modeling of startup and code validation.

Novel t(5;11)(q32;q13.4) with NUMA1-PDGFRB fusion in a myeloid neoplasm with eosinophilia with response to imatinib mesylate.

PubMed

Zou, Ying S; Hoppman, Nicole L; Singh, Zeba N; Sawhney, Sameer; Kotiah, Sandy D; Baer, Maria R

2017-04-01

We report a NUMA1-PDGFRB fusion in a myeloproliferative neoplasm with eosinophilia in a 61-year old man, with response to imatinib mesylate therapy. A t(5;11) chromosome translocation involving bands 5q32 and 11q13.4 was identified by metaphase chromosome analysis, and rearrangement of the platelet-derived growth factor receptor beta (PDGFRB) gene on 5q32 was demonstrated by FISH using a PDGFRB break-apart probe set. Bacterial artificial chromosome (BAC) FISH mapping of the PDGFRB fusion partner gene narrowed the breakpoint at 11q13.4 to a 150 kb genomic region containing three genes, including NUMA1. Mate pair sequencing analysis demonstrated NUMA1-PDGFRB fusion. The fusion protein includes coiled-coil domains of nuclear mitotic apparatus protein 1 (NuMA1, involved in protein homodimerization and heteroassociation) and tyrosine kinase domains of PDGFRB. Diverse rearrangements involving the PDGFRB gene have been identified in myeloid and lymphoid neoplasms with eosinophilia, but rearrangement of the nuclear mitotic apparatus protein 1 (NUMA1) gene has previously been reported in a human malignancy in only one instance, a NUMA1-RARA fusion caused by a t(11;17) translocation in a patient with acute promyelocytic leukemia. The NUMA1-PDGFRB fusion is the second instance of rearrangement of NUMA1, encoding an element of the mitotic apparatus, in human cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

Advances in the high bootstrap fraction regime on DIII-D towards the Q  =  5 mission of ITER steady state

NASA Astrophysics Data System (ADS)

Qian, J. P.; Garofalo, A. M.; Gong, X. Z.; Ren, Q. L.; Ding, S. Y.; Solomon, W. M.; Xu, G. S.; Grierson, B. A.; Guo, W. F.; Holcomb, C. T.; McClenaghan, J.; McKee, G. R.; Pan, C. K.; Huang, J.; Staebler, G. M.; Wan, B. N.

2017-05-01

Recent EAST/DIII-D joint experiments on the high poloidal beta {β\\text{P}} regime in DIII-D have extended operation with internal transport barriers (ITBs) and excellent energy confinement (H 98y2 ~ 1.6) to higher plasma current, for lower q 95  ⩽  7.0, and more balanced neutral beam injection (NBI) (torque injection  <  2 Nm), for lower plasma rotation than previous results (Garofalo et al, IAEA 2014, Gong et al 2014 IAEA Int. Conf. on Fusion Energy). Transport analysis and experimental measurements at low toroidal rotation suggest that the E  ×  B shear effect is not key to the ITB formation in these high {β\\text{P}} discharges. Experiments and TGLF modeling show that the Shafranov shift has a key stabilizing effect on turbulence. Extrapolation of the DIII-D results using a 0D model shows that with the improved confinement, the high bootstrap fraction regime could achieve fusion gain Q  =  5 in ITER at {β\\text{N}} ~ 2.9 and q 95 ~ 7. With the optimization of q(0), the required improved confinement is achievable when using 1.5D TGLF-SAT1 for transport simulations. Results reported in this paper suggest that the DIII-D high {β\\text{P}} scenario could be a candidate for ITER steady state operation.

Runaway Geneeration In Disruptions Of Plasmas In TFTR

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

Fredrickson, E. D.; Bell, M. G.; Taylor, G.

2014-03-31

Many disruptions in the Tokamak Fusion Test Reactor (TFTR) [D. Meade and the TFTR Group, in Proceedings of the International Conference on Plasma Physics and Controlled Nuclear Fusion, Washington, DC, 1990 (International Atomic Energy Agency, Vienna, 1991), Vol. 1, pp. 9-24] produced populations of runaway electrons which carried a significant fraction of the original plasma current. In this paper, we describe experiments where, following a disruption of a low-beta, reversed shear plasma, currents of up to 1 MA carried mainly by runaway electrons were controlled and then ramped down to near zero using the ohmic transformer. In the longer lastingmore » runaway plasmas, Parail-Pogutse instabilities were observed.« less

A series of vectors to construct lacZ fusions for the study of gene expression in Schizosaccharomyces pombe.

PubMed

Lafuente, M J; Petit, T; Gancedo, C

1997-12-22

We have constructed a series of plasmids to facilitate the fusion of promoters with or without coding regions of genes of Schizosaccharomyces pombe to the lacZ gene of Escherichia coli. These vectors carry a multiple cloning region in which fission yeast DNA may be inserted in three different reading frames with respect to the coding region of lacZ. The plasmids were constructed with the ura4+ or the his3+ marker of S. pombe. Functionality of the plasmids was tested measuring in parallel the expression of fructose 1,6-bisphosphatase and beta-galactosidase under the control of the fbp1+ promoter in different conditions.

High β produced by neutral beam injection in the START (Small Tight Aspect Ratio Tokamak) spherical tokamak

NASA Astrophysics Data System (ADS)

Sykes, Alan

1997-05-01

The world's first high-power auxiliary heating experiments in a tight aspect ratio (or spherical) tokamak have been performed on the Small Tight Aspect Ratio Tokomak (START) device [Sykes et al., Nucl. Fusion 32, 694 (1992)] at Culham Laboratory, using the 40 keV, 0.5 MW Neutral Beam Injector loaned by the Oak Ridge National Laboratory. Injection has been mainly of hydrogen into hydrogen or deuterium target plasmas, with a one-day campaign to explore D→D operation. In each case injection provides a combination of higher density operation and effective heating of both ions and electrons. The highest β values achieved to date in START are volume average βT˜11.5% and central beta βO˜50%. Already high, these values are expected to increase further with the use of higher beam power.

A fully human anti-Ep-CAM scFv-beta-glucuronidase fusion protein for selective chemotherapy with a glucuronide prodrug

PubMed Central

de Graaf, M; Boven, E; Oosterhoff, D; van der Meulen-Muileman, I H; Huls, G A; Gerritsen, W R; Haisma, H J; Pinedo, H M

2002-01-01

Monoclonal antibodies against tumour-associated antigens could be useful to deliver enzymes selectively to the site of a tumour for activation of a non-toxic prodrug. A completely human fusion protein may be advantageous for repeated administration, as host immune responses may be avoided. We have constructed a fusion protein consisting of a human single chain Fv antibody, C28, against the epithelial cell adhesion molecule and the human enzyme β-glucuronidase. The sequences encoding C28 and human enzyme β-glucuronidase were joined by a sequence encoding a flexible linker, and were preceded by the IgGκ signal sequence for secretion of the fusion protein. A CHO cell line was engineered to secrete C28-β-glucuronidase fusion protein. Antibody specificity and enzyme activity were retained in the secreted fusion protein that had an apparent molecular mass of 100 kDa under denaturing conditions. The fusion protein was able to convert a non-toxic prodrug of doxorubicin, N-[4-doxorubicin-N-carbonyl(oxymethyl)phenyl]-O-β-glucuronyl carbamate to doxorubicin, resulting in cytotoxicity. A bystander effect was demonstrated, as doxorubicin was detected in all cells after N-[4-doxorubicin-N-carbonyl(oxymethyl)phenyl]-O-β-glucuronyl carbamate administration when only 10% of the cells expressed the fusion protein. This is the first fully human and functional fusion protein consisting of an scFv against epithelial cell adhesion molecule and human enzyme β-glucuronidase for future use in tumour-specific activation of a non-toxic glucuronide prodrug. British Journal of Cancer (2002) 86, 811–818. DOI: 10.1038/sj/bjc/6600143 www.bjcancer.com © 2002 Cancer Research UK PMID:11875747

Localization and characterization of the calsequestrin-binding domain of triadin 1. Evidence for a charged beta-strand in mediating the protein-protein interaction.

PubMed

Kobayashi, Y M; Alseikhan, B A; Jones, L R

2000-06-09

Triadin is an integral membrane protein of the junctional sarcoplasmic reticulum that binds to the high capacity Ca(2+)-binding protein calsequestrin and anchors it to the ryanodine receptor. The lumenal domain of triadin contains multiple repeats of alternating lysine and glutamic acid residues, which have been defined as KEKE motifs and have been proposed to promote protein associations. Here we identified the specific residues of triadin responsible for binding to calsequestrin by mutational analysis of triadin 1, the major cardiac isoform. A series of deletional fusion proteins of triadin 1 was generated, and by using metabolically labeled calsequestrin in filter-overlay assays, the calsequestrin-binding domain of triadin 1 was localized to a single KEKE motif comprised of 25 amino acids. Alanine mutagenesis within this motif demonstrated that the critical amino acids of triadin binding to calsequestrin are the even-numbered residues Lys(210), Lys(212), Glu(214), Lys(216), Gly(218), Gln(220), Lys(222), and Lys(224). Replacement of the odd-numbered residues within this motif by alanine had no effect on calsequestrin binding to triadin. The results suggest a model in which residues 210-224 of triadin form a beta-strand, with the even-numbered residues in the strand interacting with charged residues of calsequestrin, stabilizing a "polar zipper" that links the two proteins together. This small, highly charged beta-strand of triadin may tether calsequestrin to the junctional face membrane, allowing calsequestrin to sequester Ca(2+) in the vicinity of the ryanodine receptor during Ca(2+) uptake and Ca(2+) release.

Isolation of Erwinia chrysanthemi kduD mutants altered in pectin degradation.

PubMed Central

Condemine, G; Hugouvieux-Cotte-Pattat, N; Robert-Baudouy, J

1986-01-01

Mutants of Erwinia chrysanthemi impaired in pectin degradation were isolated by chemical and Mu d(Ap lac) insertion mutagenesis. A mutation in the kduD gene coding for 2-keto-3-deoxygluconate oxidoreductase prevented the growth of the bacteria on polygalacturonate as the sole carbon source. Analysis of the kduD::Mu d(Ap lac) insertions indicated that kduD is either an isolated gene or the last gene of a polycistronic operon. Some of the Mu d(Ap lac) insertions were kduD-lac fusions in which beta-galactosidase synthesis reflected kduD gene expression. In all these fusions, beta-galactosidase activity was shown to be sensitive to catabolite repression by glucose and to be inducible by polygalacturonate, galacturonate, and other intermediates of polygalacturonate catabolism. Galacturonate-mediated induction was prevented by a mutation which blocked its metabolism to 2-keto-3-deoxygluconate. 2-Keto-3-deoxygluconate appeared to be the true inducer of kduD expression resulting from galacturonate degradation. 5-Keto-4-deoxyuronate or 2,5-diketo-3-deoxygluconate were the true inducers, originating from polygalacturonate cleavage. These three intermediates also appeared to induce pectate lyases, oligogalacturonate lyase, and 5-keto-4-deoxyuronate isomerase synthesis. PMID:3949717

Single Null Negative Triangularity Tokamak for Power Handling

NASA Astrophysics Data System (ADS)

Kikuchi, Mitsuru; Medvedev, S.; Takizuka, T.; Sauter, O.; Merle, A.; Coda, S.; Chen, D.; Li, J. X.

2017-10-01

Power and particle control in fusion reactor is challenge and we proposed the negative triangularity tokamak (NTT) to eliminate ELM by operating L-mode edge with improved core confinement. The SN configuration has more flexibility in shaping by adopting rectangular-shaped TF coils. The limiting normalized beta is 3.56 with wall stabilization and 3.14 without wall. The vertical stability is assured under a reasonable control system. The wetted area on the divertor plates becomes wider in proportion to the larger major radius at the divertor strike points due to the NT configuration. In addition to the major-radius effect, the ``Flux Tune Expansion (FTE)'' is adopted to further reduce the heat load on the divertor plate by factor of 2.6 with a coil current 3 MA. L-mode edge also allows further increase in wetted area. The fusion power of 3 GW is deliverable only at normalized beta 2.1. Therefore this reactor may be operable stably against the serious MHD activities. The CD power for SS operation is 175 MW at Q = 17. AC operation is also possible option. A required HH factor is relatively modest H = 1.12.

Activation of IKKalpha and IKKbeta through their fusion with HTLV-I tax protein.

PubMed

Xiao, G; Sun, S C

2000-10-26

Human T-cell leukemia virus type I (HTLV-I) Tax protein persistently stimulates the activity of IkappaB kinase (IKK), resulting in constitutive activation of the transcription factor NF-kappaB. Tax activation of IKK requires physical interaction of this viral protein with the IKK regulatory subunit, IKKgamma. The Tax/IKKgamma interaction allows Tax to engage the IKK catalytic subunits, IKKalpha and IKKbeta, although it remains unclear whether this linker function of IKKgamma is sufficient for supporting the Tax-specific IKK activation. To address this question, we have examined the sequences of IKKgamma required for modulating the Tax/IKK signaling. We demonstrate that when fused to Tax, a small N-terminal fragment of IKKgamma, containing its minimal IKKalpha/beta-binding domain, is sufficient for bringing Tax to and activating the IKK catalytic subunits. Disruption of the IKKalpha/beta-binding activity of this domain abolishes its function in modulating the Tax/IKK signaling. We further demonstrate that direct fusion of Tax to IKKalpha and IKKbeta leads to activation of these kinases. These findings suggest that the IKKgamma-directed Tax/IKK association serves as a molecular trigger for IKK activation.

Overlapping reading frames at the LYS5 locus in the yeast Yarrowia lipolytica.

PubMed Central

Xuan, J W; Fournier, P; Declerck, N; Chasles, M; Gaillardin, C

1990-01-01

Mutants affected at the LYS5 locus of Yarrowia lipolytica lack detectable dehydrogenase (SDH) activity. The LYS5 gene has previously been cloned, and we present here the sequence of the 2.5-kilobase-pair (kb) DNA fragment complementing the lys5 mutation. Two large antiparallel open reading frames (ORF1 and ORF2) were observed, flanked by potential transcription signals. Both ORFs appear to be transcribed, but several lines of evidence suggest that only ORF2 is translated and encodes SDH. (i) The global amino acid compositions of Saccharomyces cerevisiae SDH and of the putative ORF2 product are similar and that of ORF1 is dissimilar. (ii) An in-frame translational fusion of ORF2 with the Escherichia coli lacZ gene was introduced into yeast cells and resulted in a beta-galactosidase activity regulated similarly to SDH; no beta-galactosidase activity was obtained with an in-frame fusion of ORF1 with lacZ. (iii) The introduction of a stop codon at the beginning of ORF2 prevented SDH expression in yeast cells, whereas no phenotypic effect was observed when ORF1 translation was blocked. Images PMID:2388625

The Apollo 5' exonuclease functions together with TRF2 to protect telomeres from DNA repair.

PubMed

Lenain, Christelle; Bauwens, Serge; Amiard, Simon; Brunori, Michele; Giraud-Panis, Marie-Josèphe; Gilson, Eric

2006-07-11

A major issue in telomere research is to understand how the integrity of chromosome ends is preserved . The human telomeric protein TRF2 coordinates several pathways that prevent checkpoint activation and chromosome fusions. In this work, we identified hSNM1B, here named Apollo, as a novel TRF2-interacting factor. Interestingly, the N-terminal domain of Apollo is closely related to that of Artemis, a factor involved in V(D)J recombination and DNA repair. Both proteins belong to the beta-CASP metallo-beta-lactamase family of DNA caretaker proteins. Apollo appears preferentially localized at telomeres in a TRF2-dependent manner. Reduced levels of Apollo exacerbate the sensitivity of cells to TRF2 inhibition, resulting in severe growth defects and an increased number of telomere-induced DNA-damage foci and telomere fusions. Purified Apollo protein exhibits a 5'-to-3' DNA exonuclease activity. We conclude that Apollo is a novel component of the human telomeric complex and works together with TRF2 to protect chromosome termini from being recognized and processed as DNA damage. These findings unveil a previously undescribed telomere-protection mechanism involving a DNA 5'-to-3' exonuclease.

[Optimization of prokaryotic expression conditions of Leptospira interrogans trigeminy genus-specific protein antigen based on surface response analysis].

PubMed

Wang, Jiang; Luo, Dongjiao; Sun, Aihua; Yan, Jie

2008-07-01

Lipoproteins LipL32 and LipL21 and transmembrane protein OMPL1 have been confirmed as the superficial genus-specific antigens of Leptospira interrogans, which can be used as antigens for developing a universal genetic engineering vaccine. In order to obtain high expression of an artificial fusion gene lipL32/1-lipL21-ompL1/2, we optimized prokaryotic expression conditions. We used surface response analysis based on the central composite design to optimize culture conditions of a new antigen protein by recombinant Escherichia coli DE3.The culture conditions included initial pH, induction start time, post-induction time, Isopropyl beta-D-thiogalactopyranoside (IPTG) concentration, and temperature. The maximal production of antigen protein was 37.78 mg/l. The optimal culture conditions for high recombinant fusion protein was determined: initial pH 7.9, induction start time 2.5 h, a post-induction time of 5.38 h, 0.20 mM IPTG, and a post-induction temperature of 31 degrees C. Surface response analysis based on CCD increased the target production. This statistical method reduced the number of experiments required for optimization and enabled rapid identification and integration of the key culture condition parameters for optimizing recombinant protein expression.

Non-inductively driven tokamak plasmas at near-unity βt in the Pegasus toroidal experiment

NASA Astrophysics Data System (ADS)

Reusch, J. A.; Bodner, G. M.; Bongard, M. W.; Burke, M. G.; Fonck, R. J.; Pachicano, J. L.; Perry, J. M.; Pierren, C.; Rhodes, A. T.; Richner, N. J.; Rodriguez Sanchez, C.; Schlossberg, D. J.; Weberski, J. D.

2018-05-01

A major goal of the spherical tokamak (ST) research program is accessing a state of low internal inductance ℓi, high elongation κ, and high toroidal and normalized beta ( βt and βN) without solenoidal current drive. Local helicity injection (LHI) in the Pegasus ST [Garstka et al., Nucl. Fusion 46, S603 (2006)] provides non-solenoidally driven plasmas that exhibit these characteristics. LHI utilizes compact, edge-localized current sources for plasma startup and sustainment. It results in hollow current density profiles with low ℓi. The low aspect ratio ( R0/a ˜1.2 ) of Pegasus allows access to high κ and high normalized plasma currents ( IN=Ip/a BT>14 ). Magnetic reconnection during LHI provides auxiliary ion heating. Together, these features provide access to very high βt plasmas. Equilibrium analyses indicate that βt up to ˜100% is achieved. These high βt discharges disrupt at the ideal no-wall β limit at βN˜7.

MHD Effects of a Ferritic Wall on Tokamak Plasmas

NASA Astrophysics Data System (ADS)

Hughes, Paul E.

It has been recognized for some time that the very high fluence of fast (14.1MeV) neutrons produced by deuterium-tritium fusion will represent a major materials challenge for the development of next-generation fusion energy projects such as a fusion component test facility and demonstration fusion power reactor. The best-understood and most promising solutions presently available are a family of low-activation steels originally developed for use in fission reactors, but the ferromagnetic properties of these steels represent a danger to plasma confinement through enhancement of magnetohydrodynamic instabilities and increased susceptibility to error fields. At present, experimental research into the effects of ferromagnetic materials on MHD stability in toroidal geometry has been confined to demonstrating that it is still possible to operate an advanced tokamak in the presence of ferromagnetic components. In order to better quantify the effects of ferromagnetic materials on tokamak plasma stability, a new ferritic wall has been installated in the High Beta Tokamak---Extended Pulse (HBT-EP) device. The development, assembly, installation, and testing of this wall as a modular upgrade is described, and the effect of the wall on machine performance is characterized. Comparative studies of plasma dynamics with the ferritic wall close-fitting against similar plasmas with the ferritic wall retracted demonstrate substantial effects on plasma stability. Resonant magnetic perturbations (RMPs) are applied, demonstrating a 50% increase in n = 1 plasma response amplitude when the ferritic wall is near the plasma. Susceptibility of plasmas to disruption events increases by a factor of 2 or more with the ferritic wall inserted, as disruptions are observed earlier with greater frequency. Growth rates of external kink instabilities are observed to be twice as large in the presence of a close-fitting ferritic wall. Initial studies are made of the influence of mode rotation frequency on the ferritic effect, as well as observations of the effect of the ferritic wall on disruption halo currents.

Translational autocontrol of the Escherichia coli ribosomal protein S15.

PubMed

Portier, C; Dondon, L; Grunberg-Manago, M

1990-01-20

When rpsO, the gene encoding the ribosomal protein S15 in Escherichia coli, is carried by a multicopy plasmid, the mRNA synthesis rate of S15 increases with the gene dosage but the rate of synthesis of S15 does not rise. A translational fusion between S15 and beta-galactosidase was introduced on the chromosome in a delta lac strain and the expression of beta-galactosidase studied under different conditions. The presence of S15 in trans represses the beta-galactosidase level five- to sixfold, while the synthesis rate of the S15-beta-galactosidase mRNA decreases by only 30 to 50%. These data indicate that S15 is subject to autogenous translational control. Derepressed mutants were isolated and sequenced. All the point mutations map in the second codon of S15, suggesting a location for the operator site that is very near to the translation initiation codon. However, the creation of deletion mutations shows that the operator extends into the 5' non-coding part of the message, thus overlapping the ribosome loading site.

Docking is not a prerequisite but a temporal constraint for fusion of secretory granules.

PubMed

Kasai, Kazuo; Fujita, Takuji; Gomi, Hiroshi; Izumi, Tetsuro

2008-07-01

We examined secretory granule dynamics using total internal reflection fluorescence microscopy in normal pancreatic beta cells and their mutants devoid of Rab27a and/or its effector, granuphilin, which play critical roles in the docking and recruitment of insulin granules to the plasma membrane. In the early phase of glucose stimulation in wild-type cells, we observed marked fusion of granules recruited from a relatively distant area, in parallel with that from granules located underneath the plasma membrane. Furthermore, despite a lack of granules directly attached to the plasma membrane, both spontaneous and evoked fusion was increased in granuphilin-null cells. In addition to these granuphilin-null phenotypes, Rab27a/granuphilin doubly deficient cells showed the decreases in granules located next to the docked area and in fusion from granules near the plasma membrane in the early phase of glucose-stimulated secretion, similar to Rab27a-mutated cells. Thus, the two proteins play nonoverlapping roles in insulin exocytosis: granuphilin acts on the granules underneath the plasma membrane, whereas Rab27a acts on those in a more distal area. These findings demonstrate that, in contrast to our conventional understanding, stable attachment of secretory granules to the plasma membrane is not prerequisite but temporally inhibitory for both spontaneous and evoked fusion.

Expression of the leukemia-associated CBF{beta}/SMMHC chimeric gene causes transformation of 3T3 cells

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

Hajra, A.; Liu, P.; Collins, E.S.

1994-09-01

A pericentric inversion of chromosome 16 (inv(16)(p13;q22)) is consistently seen in acute myeloid leukemia of the M4Eo subtype. This inversion fuses almost the entire coding region of the gene encoding of the {beta} subunit of the heterodimeric transcription factor CBF/PEBP2 to the region of the MYH11 gene encoding the rod domain for the smooth muscle myosin heavy chain (SMMHC). To investigate the biological properties of the CBF{beta}/SMMHC fusion protein, we have generated 3T3 cell lines that stably express the CBF{beta}/SMMHC chimeric cDNA or the normal, nonchimeric CBF{beta} and SMMHC cDNAs. 3T3 cells expressing CBF{beta}/SMMHC acquire a transformed phenotype, as indicatedmore » by altered cell morphology, formation of foci, and growth in soft agar. Cells constitutively overexpressing the normal CBF{beta} cDNA or the rod region of SMMHC remain nontransformed. Western blot analysis using antibodies to CBF{beta} and the SMMHC rod demonstrates that stably transfected cells express the appropriate chimeric or normal protein. Electrophoretic mobility shift assays reveal that cells transformed by the chimeric cDNA do not have a CBF-DNA complex of the expected mobility, but instead contain a large complex with CBF DNA-binding activity that fails to migrate out of the gel wells. In order to define the regions of CBF{beta}/SMMHC necessary for 3T3 transformation, we have stably transfected cells with mutant CBF{beta}/SMMHC cDNAs containing various deletions of the coding region. Analysis of these cell lines indicates that the transformation property of CBF{beta}/SMMHC requires regions of CBF{beta} known to be necessary for association with the DNA-binding CBF{alpha} subunit, and also requires an intact SMMHC carboxyl terminus, which is necessary for formation of the coiled coil domain of the myosin rod.« less

Vesicle-associated membrane protein 2 mediates trafficking of {alpha}5{beta}1 integrin to the plasma membrane

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

Hasan, Nazarul; Hu, Chuan, E-mail: chuan.hu@louisville.edu

2010-01-01

Integrins are major receptors for cell adhesion to the extracellular matrix (ECM). As transmembrane proteins, the levels of integrins at the plasma membrane or the cell surface are ultimately determined by the balance between two vesicle trafficking events: endocytosis of integrins at the plasma membrane and exocytosis of the vesicles that transport integrins. Here, we report that vesicle-associated membrane protein 2 (VAMP2), a SNARE protein that mediates vesicle fusion with the plasma membrane, is involved in the trafficking of {alpha}5{beta}1 integrin. VAMP2 was present on vesicles containing endocytosed {beta}1 integrin. Small interfering RNA (siRNA) silencing of VAMP2 markedly reduced cellmore » surface {alpha}5{beta}1 and inhibited cell adhesion and chemotactic migration to fibronectin, the ECM ligand of {alpha}5{beta}1, without altering cell surface expression of {alpha}2{beta}1 integrin or {alpha}3{beta}1 integrin. By contrast, silencing of VAMP8, another SNARE protein, had no effect on cell surface expression of the integrins or cell adhesion to fibronectin. In addition, VAMP2-mediated trafficking is involved in cell adhesion to collagen but not to laminin. Consistent with disruption of integrin functions in cell proliferation and survival, VAMP2 silencing diminished proliferation and triggered apoptosis. Collectively, these data indicate that VAMP2 mediates the trafficking of {alpha}5{beta}1 integrin to the plasma membrane and VAMP2-dependent integrin trafficking is critical in cell adhesion, migration and survival.« less

The 87-kD A gamma-globin enhancer-binding protein is a product of the HOXB2(HOX2H) locus.

PubMed

Sengupta, P K; Lavelle, D E; DeSimone, J

1994-03-01

Developmental regulation of globin gene expression may be controlled by developmental stage-specific nuclear proteins that influence interactions between the locus control region and local regulatory sequences near individual globin genes. We previously isolated an 87-kD nuclear protein from K562 cells that bound to DNA sequences in the beta-globin locus control region, gamma-globin promoter, and A gamma-globin enhancer. The presence of this protein in fetal globin-expressing cells and its absence in adult globin-expressing cells suggested that it may be a developmental stage-specific factor. A lambda gt11 K562 cDNA clone encoding a portion of the HOXB2 (formerly HOX2H) homeobox gene was isolated on the basis of the ability of its beta-galactosidase fusion protein to bind to the same DNA sequences as the 87-kD K562 protein. Because no other relationship had been established between the 87-kD K562 protein and the HOXB2 protein other than their ability to bind ot the same DNA sequences, we have investigated whether the two proteins are related antigenically. Our data show that antisera produced against the HOXB2-beta-gal fusion protein and a synthetic HOXB2 decapeptide react specifically with an 87-kD protein from K562 nuclear extract, showing that the 87-kD K562 nuclear protein is a product of the HOXB2 locus, and is the first demonstration of cellular HOXB2 protein.

Search for additional neutral MSSM Higgs bosons in the $$\\tau\\tau$$ final state in proton-proton collisions at $$\\sqrt{s}=$$ 13 TeV

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

Sirunyan, Albert M; et al.

A search is presented for additional neutral Higgs bosons in themore » $$\\tau\\tau$$ final state in proton-proton collisions at the LHC. The search is performed in the context of the minimal supersymmetric extension of the standard model (MSSM), using the data collected with the CMS detector in 2016 at a center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 35.9 fb$$^{-1}$$. To enhance the sensitivity to neutral MSSM Higgs bosons, the search includes production of the Higgs boson in association with b quarks. No significant deviation above the expected background is observed. Model-independent limits at 95% confidence level (CL) are set on the product of the branching fraction for the decay into $$\\tau$$ leptons and the cross section for the production via gluon fusion or in association with b quarks. These limits range from 18 pb at 90 GeV to 3.5 fb at 3.2 TeV for gluon fusion and from 15 pb (at 90 GeV) to 2.5 fb (at 3.2 TeV) for production in association with b quarks. In the m$$_{\\text{h}}^{\\text{mod+}}$$ scenario these limits translate into a 95% CL exclusion of $$\\tan\\beta>$$ 6 for neutral Higgs boson masses below 250 GeV, where $$\\tan\\beta$$ is the ratio of the vacuum expectation values of the neutral components of the two Higgs doublets. The 95% CL exclusion contour reaches 1.6 TeV for $$\\tan\\beta=$$ 60.« less

Performance of ITER as a burning plasma experiment

NASA Astrophysics Data System (ADS)

Shimada, M.; Mukhovatov, V.; Federici, G.; Gribov, Y.; Kukushkin, A.; Murakami, Y.; Polevoi, A.; Pustovitov, V.; Sengoku, S.; Sugihara, M.

2004-02-01

Recent performance analysis has improved confidence in achieving Q (= fusion power/auxiliary heating power)geq 10 in inductive operation in ITER. Performance analysis based on empirical scalings shows the feasibility of achieving Q geq 10 in inductive operation, particularly with improved modelling of helium exhaust. Analysis has also indicated the possibility that ITER can potentially demonstrate Q ~ 50, enabling studies of self-heated plasmas. Theory-based core modelling indicates the need for a high pedestal temperature (3.2-5.3 keV) to achieve Q geq 10, which is in the range of projections with presently available pedestal scalings. Pellet injection from the high-field side would be useful in enhancing Q and reducing edge localized mode (ELM) heat load in high plasma current operation. If the ELM heat load is not acceptable, it could be made tolerable by further tilting the target plate. Steady state operation scenarios at Q = 5 have been developed with modest requirements on confinement improvement and beta (HH98(y,2) geq 1.3 and bgrN geq 2.6). Stabilization of the resistive wall modes (RWMs), required in such regimes, is feasible with the present saddle coils and power supplies with double-wall structures taken into account. Recent analysis shows a potential of high power steady state operation with a fusion power of 0.7 GW at Q ~ 8. Achievement of the required bgrN ~ 3.6 by RWM stabilization is a possibility. Further analysis is also needed on reduction of the divertor target heat load.

The molecular biology of the group VIA Ca2+-independent phospholipase A2.

PubMed

Ma, Z; Turk, J

2001-01-01

The group VIA PLA2 is a member of the PLA2 superfamily. This enzyme, which is cytosolic and Ca2+-independent, has been designated iPLA2beta to distinguish it from another recently cloned Ca2+-independent PLA2. Features of iPLA2beta molecular structure offer some insight into possible cellular functions of the enzyme. At least two catalytically active iPLA2beta isoforms and additionalsplicing variants are derived from a single gene that consists of at least 17 exons located on human chromosome 22q13.1. Potential tumor suppressor genes also reside at or near this locus. Structural analyses reveal that iPLA2beta contains unique structural features that include a serine lipase consensus motif (GXSXG), a putative ATP-binding domain, an ankyrin-repeat domain, a caspase-3 cleavage motif DVTD138Y/N, a bipartite nuclear localization signal sequence, and a proline-rich region in the human long isoform. iPLA2beta is widely expressed among mammalian tissues, with highest expression in testis and brain. iPLA2beta prefers to hydrolyze fatty acid at the sn-2 fatty acid substituent but also exhibits phospholipase A1, lysophospholipase, PAF acetylhydrolase, and transacylase activities. iPLA2beta may participate in signaling, apoptosis, membrane phospholipid remodeling, membrane homeostasis, arachidonate release, and exocytotic membrane fusion. Structural features and the existence of multiple splicing variants of iPLA2beta suggest that iPLA2beta may be subject to complex regulatory mechanisms that differ among cell types. Further study of its regulation and interaction with other proteins may yield insight into how its structural features are related to its function.

Inactivated Recombinant Rabies Viruses Displaying Canine Distemper Virus Glycoproteins Induce Protective Immunity against Both Pathogens

PubMed Central

da Fontoura Budaszewski, Renata; Hudacek, Andrew; Sawatsky, Bevan; Krämer, Beate; Yin, Xiangping

2017-01-01

ABSTRACT The development of multivalent vaccines is an attractive methodology for the simultaneous prevention of several infectious diseases in vulnerable populations. Both canine distemper virus (CDV) and rabies virus (RABV) cause lethal disease in wild and domestic carnivores. While RABV vaccines are inactivated, the live-attenuated CDV vaccines retain residual virulence for highly susceptible wildlife species. In this study, we developed recombinant bivalent vaccine candidates based on recombinant vaccine strain rabies virus particles, which concurrently display the protective CDV and RABV glycoprotein antigens. The recombinant viruses replicated to near-wild-type titers, and the heterologous glycoproteins were efficiently expressed and incorporated in the viral particles. Immunization of ferrets with beta-propiolactone-inactivated recombinant virus particles elicited protective RABV antibody titers, and animals immunized with a combination of CDV attachment protein- and fusion protein-expressing recombinant viruses were protected from lethal CDV challenge. However, animals that were immunized with only a RABV expressing the attachment protein of CDV vaccine strain Onderstepoort succumbed to infection with a more recent wild-type strain, indicating that immune responses to the more conserved fusion protein contribute to protection against heterologous CDV strains. IMPORTANCE Rabies virus and canine distemper virus (CDV) cause high mortality rates and death in many carnivores. While rabies vaccines are inactivated and thus have an excellent safety profile and high stability, live-attenuated CDV vaccines can retain residual virulence in highly susceptible species. Here we generated recombinant inactivated rabies viruses that carry one of the CDV glycoproteins on their surface. Ferrets immunized twice with a mix of recombinant rabies viruses carrying the CDV fusion and attachment glycoproteins were protected from lethal CDV challenge, whereas all animals that received recombinant rabies viruses carrying only the CDV attachment protein according to the same immunization scheme died. Irrespective of the CDV antigens used, all animals developed protective titers against rabies virus, illustrating that a bivalent rabies virus-based vaccine against CDV induces protective immune responses against both pathogens. PMID:28148801

Princeton Plasma Physics Laboratory: Annual report, October 1, 1986--September 30, 1987

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

Not Available

1987-01-01

This report contains papers on the following topics: Principle Parameters Achieved in Experimental Devices (FY87); Tokamak Fusion Test Reactor; Princeton Beta Experiment-Modification; S-1 Spheromak; Current-Drive Experiment; X-Ray Laser Studies; Theoretical Division; Tokamak Modeling; Compact Ignition Tokamak; Engineering Department; Project Planning and Safety Office; Quality Assurance and Reliability; Administrative Operations; and PPPL Patent Invention Disclosures (FY87).

Stable Spheromaks Sustained by Neutral Beam Injection

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

Fowler, T K; Jayakumar, R; McLean, H S

It is shown that spheromak equilibria, stable at zero-beta but departing from the Taylor state, could be sustained by non-inductive current drive at acceptable power levels. Stability to both ideal MHD and tearing modes is verified using the NIMROD code for linear stability analysis. Non-linear NIMROD calculations with non-inductive current drive and pressure effects could point the way to improved fusion reactors.

[Expression optimization and characterization of Tenebrio molitor antimicrobiol peptides TmAMP1m in Escherichia coli].

PubMed

Alimu, Reyihanguli; Mao, Xinfang; Liu, Zhongyuan

2013-06-01

To improve the expression level of tmAMP1m gene from Tenebrio molitor in Escherichia coli, we studied the effects of expression level and activity of the fusion protein HIS-TmAMP1m by conditions, such as culture temperature, inducing time and the final concentration of inductor Isopropyl beta-D-thiogalactopyranoside (IPTG). We analyzed the optimum expression conditions by Tricine-SDS-PAGE electrophoresis, meanwhile, detected its antibacterial activity by using agarose cavity diffusion method. The results suggest that when inducing the recombinant plasmid with a final IPTG concentration of 0.1 mmol/L at 37 degrees C for 4 h, there was the highest expression level of fusion protein HIS-TmAMP1m in Escherichia coli. Under these conditions, the expression of fusion protein accounted for 40% of the total cell lysate with the best antibacterial activity. We purified the fusion protein HIS-TmAMPlm with nickel-nitrilotriacetic acid (Ni-NTA) metal-affinity chromatography matrices. Western blotting analysis indicates that the His monoclonal antibody could be specifically bound to fusion protein HIS-TmAMPlm. After expression by inducing, the fusion protein could inhibit the growth of host cell transformed by pET30a-tmAMP1m. The fusion protein HIS-TmAMP1m had better stability and remained higher antibacterial activities when incubated at 100 degrees C for 10 h, repeated freeze thawing at -20 degrees C, dissolved in strong acid and alkali, or treated by organic solvents and protease. Moreover, the minimum inhibitory concentration results demonstrated that the fusion protein HIS-TmAMP1m has a good antibacterial activity against Staphylococcus aureus, Staphylococcus sp., Corynebacterium glutamicum, Bacillus thuringiensis, Corynebacterium sp. This study laid the foundation to promote the application of insect antimicrobial peptides and further research.

The carboxyl-terminal region of ahnak provides a link between cardiac L-type Ca2+ channels and the actin-based cytoskeleton.

PubMed

Hohaus, Annette; Person, Veronika; Behlke, Joachim; Schaper, Jutta; Morano, Ingo; Haase, Hannelore

2002-08-01

Ahnak is a ubiquitously expressed giant protein of 5643 amino acids implicated in cell differentiation and signal transduction. In a recent study, we demonstrated the association of ahnak with the regulatory beta2 subunit of the cardiac L-type Ca2+ channel. Here we identify the most carboxyl-terminal ahnak region (aa 5262-5643) to interact with recombinant beta2a as well as with beta2 and beta1a isoforms of native muscle Ca2+ channels using a panel of GST fusion proteins. Equilibrium sedimentation analysis revealed Kd values of 55 +/- 11 nM and 328 +/- 24 nM for carboxyl-terminal (aa 195-606) and amino-terminal (aa 1-200) truncates of the beta2a subunit, respectively. The same carboxyl-terminal ahnak region (aa 5262-5643) bound to G-actin and cosedimented with F-actin. Confocal microscopy of human left ventricular tissue localized the carboxyl-terminal ahnak portion to the sarcolemma including the T-tubular system and the intercalated disks of cardiomyocytes. These results suggest that ahnak provides a structural basis for the subsarcolemmal cytoarchitecture and confers the regulatory role of the actin-based cytoskeleton to the L-type Ca2+ channel.

Fast ion beta limit measurements by collimated neutron detection in MST plasmas

NASA Astrophysics Data System (ADS)

Capecchi, William; Anderson, Jay; Bonofiglo, Phillip; Kim, Jungha; Sears, Stephanie

2015-11-01

Fast ion orbits in the reversed field pinch (RFP) are well ordered and classically confined despite magnetic field stochasticity generated by multiple tearing modes. Classical TRANSP modeling of a 1MW tangentially injected hydrogen neutral beam in MST deuterium plasmas predicts a core-localized fast ion density that can be up to 25% of the electron density and a fast ion beta of many times the local thermal beta. However, neutral particle analysis of an NBI-driven mode (presumably driven by a fast ion pressure gradient) shows mode-induced transport of core-localized fast ions and a saturated fast ion density. The TRANSP modeling is presumed valid until the onset of the beam-driven mode and gives an initial estimate of the volume-averaged fast ion beta of 1-2% (local core value up to 10%). A collimated neutron detector for fusion product profile measurements will be used to determine the spatial distribution of fast ions, allowing for a first measurement of the critical fast-ion pressure gradient required for mode destabilization. Testing/calibration data and initial fast-ion profiles will be presented. Characterization of both the local and global fast ion beta will be done for deuterium beam injection into deuterium plasmas for comparison to TRANSP predictions. Work supported by US DOE.

Overexpression of the VSSC-associated CAM, β-2, enhances LNCaP cell metastasis associated behavior.

PubMed

Jansson, Keith H; Lynch, Jill E; Lepori-Bui, Nadia; Czymmek, Kirk J; Duncan, Randall L; Sikes, Robert A

2012-07-01

Prostate cancer (PCa) is the second-leading cause of cancer death in American men. This is due largely to the "silent" nature of the disease until it has progressed to a highly metastatic and castrate resistant state. Voltage sensitive sodium channels (VSSCs) are multimeric transmembrane protein complexes comprised of a pore-forming α subunit and one or two β subunits. The β-subunits modulate surface expression and gating kinetics of the channels but also have inherent cell adhesion molecule (CAM) functions. We hypothesize that PCa cells use VSSC β-subunits as CAMs during PCa progression and metastasis. We overexpressed the beta-2 isoform as a C-terminal fusion protein with enhanced cyan fluorescence protein (ECFP) in the weakly metastatic LNCaP cells. The effect of beta-2 overexpression on cell morphology was examined using confocal microscopy while metastasis-associated behavior was tested by performing several in vitro metastatic functional assays and in vivo subcutaneous tumor studies. We found that cells overexpressing beta-2 (2BECFP) converted to a bipolar fibroblastic morphology. 2BECFP cells were more adhesive than control (ECFP) to vitronectin (twofold) and Matrigel® (1.3-fold), more invasive through Matrigel® (3.6-fold in 72 hr), and had enhanced migration (2.1-fold in 96 hr) independent of proliferation in wound-healing assays. In contrast, 2BECFP cells have a reduced tumor-take and tumor volume in vivo even though the overexpression of beta-2 was maintained. Functional overexpression of VSSC β-subunits in PCa may be one mechanism leading to increased metastatic behavior while decreasing the ability to form localized tumor masses. Copyright © 2011 Wiley Periodicals, Inc.

Kinetics of the formation of chromosome aberrations in X-irradiated human lymphocytes: analysis by premature chromosome condensation with delayed fusion.

PubMed

Greinert, R; Detzler, E; Volkmer, B; Harder, D

1995-11-01

Human lymphocytes irradiated with graded doses of up to 5 Gy of 150 kV X rays were fused with mitotic CHO cells after delay times ranging from 0 to 14 h after irradiation. The yields of dicentrics seen under PCC conditions, using C-banding for centromere detection, and of excess acentric fragments observed in the PCC experiment were determined by image analysis. At 4 Gy the time course of the yield of dicentrics shows an early plateau for delay times up to 2 h, then an S-shaped rise and a final plateau which is reached after a delay time of about 8 to 10 h. Whereas the dose-yield curve measured at zero delay time is strictly linear, the shape of the curve obtained for 8 h delay time is linear-quadratic. The linear yield component, alpha D, is formed entirely in the fast process manifested in the early plateau, while component beta D2 is developed slowly in the subsequent hours. Analysis of the kinetics of the rise of the S-shaped curve for yield as a function of time leads to the postulate of an "intermediate product" of pairwise DNA lesion interaction, still fragile when subjected to the stress of PCC, but gradually processed into a stable dicentric chromosome. It is concluded that the observed difference in the kinetics of the alpha and beta components explains a number of earlier results, especially the disappearance of the beta component at high LET, and opens possibilities for chemical and physical modification of the beta component during the extended formation process after irradiation observed here.

Alpha or beta human chorionic gonadotropin knockdown decrease BeWo cell fusion by down-regulating PKA and CREB activation

PubMed Central

Saryu Malhotra, Sudha; Suman, Pankaj; Kumar Gupta, Satish

2015-01-01

The aim of the present study is to delineate the role of human chorionic gonadotropin (hCG) in trophoblast fusion. In this direction, using shRNA lentiviral particles, α- and β-hCG silenced ‘BeWo’ cell lines were generated. Treatment of both α- and β-hCG silenced BeWo cells with either forskolin or exogenous hCG showed a significant reduction in cell fusion as compared with control shRNA treated cells. Studies by qRT-PCR, Western blotting and immunofluorescence revealed down-regulation of fusion-associated proteins such as syncytin-1 and syndecan-1 in the α- and β-hCG silenced cells. Delineation of downstream signaling pathways revealed that phosphorylation of PKA and CREB were compromised in the silenced cells whereas, no significant changes in p38MAPK and ERK1/2 phosphorylation were observed. Moreover, β-catenin activation was unaffected by either α- or β-hCG silencing. Further, inhibition of PKA by H89 inhibitor led to a significant decrease in BeWo cell fusion but had no effect on β-catenin activation suggesting the absence of non-canonical β-catenin stabilization via PKA. Interestingly, canonical activation of β-catenin was associated with the up-regulation of Wnt 10b expression. In summary, this study establishes the significance of hCG in the fusion of trophoblastic BeWo cells, but there may be additional factors involved in this process. PMID:26053549

Evidence that electrostatic interactions between vesicle-associated membrane protein 2 and acidic phospholipids may modulate the fusion of transport vesicles with the plasma membrane.

PubMed

Williams, Dumaine; Vicôgne, Jérome; Zaitseva, Irina; McLaughlin, Stuart; Pessin, Jeffrey E

2009-12-01

The juxtamembrane domain of vesicle-associated membrane protein (VAMP) 2 (also known as synaptobrevin2) contains a conserved cluster of basic/hydrophobic residues that may play an important role in membrane fusion. Our measurements on peptides corresponding to this domain determine the electrostatic and hydrophobic energies by which this domain of VAMP2 could bind to the adjacent lipid bilayer in an insulin granule or other transport vesicle. Mutation of residues within the juxtamembrane domain that reduce the VAMP2 net positive charge, and thus its interaction with membranes, inhibits secretion of insulin granules in beta cells. Increasing salt concentration in permeabilized cells, which reduces electrostatic interactions, also results in an inhibition of insulin secretion. Similarly, amphipathic weak bases (e.g., sphingosine) that reverse the negative electrostatic surface potential of a bilayer reverse membrane binding of the positively charged juxtamembrane domain of a reconstituted VAMP2 protein and inhibit membrane fusion. We propose a model in which the positively charged VAMP and syntaxin juxtamembrane regions facilitate fusion by bridging the negatively charged vesicle and plasma membrane leaflets.

Nonlinear Burn Control and Operating Point Optimization in ITER

NASA Astrophysics Data System (ADS)

Boyer, Mark; Schuster, Eugenio

2013-10-01

Control of the fusion power through regulation of the plasma density and temperature will be essential for achieving and maintaining desired operating points in fusion reactors and burning plasma experiments like ITER. In this work, a volume averaged model for the evolution of the density of energy, deuterium and tritium fuel ions, alpha-particles, and impurity ions is used to synthesize a multi-input multi-output nonlinear feedback controller for stabilizing and modulating the burn condition. Adaptive control techniques are used to account for uncertainty in model parameters, including particle confinement times and recycling rates. The control approach makes use of the different possible methods for altering the fusion power, including adjusting the temperature through auxiliary heating, modulating the density and isotopic mix through fueling, and altering the impurity density through impurity injection. Furthermore, a model-based optimization scheme is proposed to drive the system as close as possible to desired fusion power and temperature references. Constraints are considered in the optimization scheme to ensure that, for example, density and beta limits are avoided, and that optimal operation is achieved even when actuators reach saturation. Supported by the NSF CAREER award program (ECCS-0645086).

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

NASA Astrophysics Data System (ADS)

Motojima, Osamu

2006-12-01

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

HIT-SI Injector Voltage Measurements Using Injector Langmuir Probes

NASA Astrophysics Data System (ADS)

Aboul Hosn, Rabih; Smith, Roger; Jarboe, Thomas

2006-10-01

A pair of Langmuir probe arrays have been designed and built to measure floating potentials of the plasma at the injector mouth of the HIT-SI device. The Helicity Injected Torus using Steady Inductive Helicity Injection (HIT-SI) [1,2] is a ``bow tie'' spheromak using an electrodeless formation and sustainment concept. HIT-SI is powered by two inductive helicity injectors operated in quadrature to maintain a constant helicity injection rate. The electric probes consist of an array of four floating potential Langmuir probes measuring the voltage distribution in each injector from the shell to midpoint of the injector mouth. The probe measurements combine to determine the part of the injector loop voltage driving the n = 0 spheromak equilibrium region. Preliminary data suggest the spheromak voltage is the loop voltage minus the nearly constant injector voltage of 150-180 volts. These probe data will be used to calculate the helicity decay time of the spheromak. [1] T. R. Jarboe. Steady inductive helicity injection and its application to a high-beta spheromak. Fusion Technology, 36(1):85--91, July 1999. [2] P.E.Sieck et al., ``Demonstration of Steady Inductive Helicity Injection'', Nuc. Fusion, in press (2006).

Roles of mono-ubiquitinated Smad4 in the formation of Smad transcriptional complexes

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

Wang Bei; Suzuki, Hiroyuki; Kato, Mitsuyasu

2008-11-14

TGF-{beta} activates receptor-regulated Smad (R-Smad) through phosphorylation by type I receptors. Activated R-Smad binds to Smad4 and the complex translocates into the nucleus and stimulates the transcription of target genes through association with co-activators including p300. It is not clear, however, how activated Smad complexes are removed from target genes. In this study, we show that TGF-{beta} enhances the mono-ubiquitination of Smad4. Smad4 mono-ubiquitination was promoted by p300 and suppressed by the c-Ski co-repressor. Smad4 mono-ubiquitination disrupted the interaction with Smad2 in the presence of constitutively active TGF-{beta} type I receptor. Furthermore, mono-ubiquitinated Smad4 was not found in DNA-binding Smadmore » complexes. A Smad4-Ubiquitin fusion protein, which mimics mono-ubiquitinated Smad4, enhanced localization to the cytoplasm. These results suggest that mono-ubiquitination of Smad4 occurs in the transcriptional activator complex and facilitates the turnover of Smad complexes at target genes.« less

Roles of mono-ubiquitinated Smad4 in the formation of Smad transcriptional complexes.

PubMed

Wang, Bei; Suzuki, Hiroyuki; Kato, Mitsuyasu

2008-11-14

TGF-beta activates receptor-regulated Smad (R-Smad) through phosphorylation by type I receptors. Activated R-Smad binds to Smad4 and the complex translocates into the nucleus and stimulates the transcription of target genes through association with co-activators including p300. It is not clear, however, how activated Smad complexes are removed from target genes. In this study, we show that TGF-beta enhances the mono-ubiquitination of Smad4. Smad4 mono-ubiquitination was promoted by p300 and suppressed by the c-Ski co-repressor. Smad4 mono-ubiquitination disrupted the interaction with Smad2 in the presence of constitutively active TGF-beta type I receptor. Furthermore, mono-ubiquitinated Smad4 was not found in DNA-binding Smad complexes. A Smad4-Ubiquitin fusion protein, which mimics mono-ubiquitinated Smad4, enhanced localization to the cytoplasm. These results suggest that mono-ubiquitination of Smad4 occurs in the transcriptional activator complex and facilitates the turnover of Smad complexes at target genes.

Protein design on computers. Five new proteins: Shpilka, Grendel, Fingerclasp, Leather, and Aida.

PubMed

Sander, C; Vriend, G; Bazan, F; Horovitz, A; Nakamura, H; Ribas, L; Finkelstein, A V; Lockhart, A; Merkl, R; Perry, L J

1992-02-01

What is the current state of the art in protein design? This question was approached in a recent two-week protein design workshop sponsored by EMBO and held at the EMBL in Heidelberg. The goals were to test available design tools and to explore new design strategies. Five novel proteins were designed: Shpilka, a sandwich of two four-stranded beta-sheets, a scaffold on which to explore variations in loop topology; Grendel, a four-helical membrane anchor, ready for fusion to water-soluble functional domains; Finger-clasp, a dimer of interdigitating beta-beta-alpha units, the simplest variant of the "handshake" structural class; Aida, an antibody binding surface intended to be specific for flavodoxin; Leather--a minimal NAD binding domain, extracted from a larger protein. Each design is available as a set of three-dimensional coordinates, the corresponding amino acid sequence and a set of analytical results. The designs are placed in the public domain for scrutiny, improvement, and possible experimental verification.

Beta 1D integrin displaces the beta 1A isoform in striated muscles: localization at junctional structures and signaling potential in nonmuscle cells.

PubMed

Belkin, A M; Zhidkova, N I; Balzac, F; Altruda, F; Tomatis, D; Maier, A; Tarone, G; Koteliansky, V E; Burridge, K

1996-01-01

The cytoplasmic domains of integrins provide attachment of these extracellular matrix receptors to the cytoskeleton and play a critical role in integrin-mediated signal transduction. In this report we describe the identification, expression, localization, and initial functional characterization of a novel form of beta 1 integrin, termed beta 1D. This isoform contains a unique alternatively spliced cytoplasmic domain of 50 amino acids, with the last 24 amino acids encoded by an additional exon. Of these 24 amino acids, 11 are conserved when compared to the beta 1A isoform, but 13 are unique (Zhidkova, N. I., A. M. Belkin, and R. Mayne. 1995. Biochem. Biophys. Res. Commun. 214:279-285; van der Flier, A., I. Kuikman, C. Baudoin, R, van der Neuf, and A. Sonnenberg. 1995. FEBS Lett. 369:340-344). Using an anti-peptide antibody against the beta 1D integrin subunit, we demonstrated that the beta 1D isoform is synthesized only in skeletal and cardiac muscles, while very low amounts of beta 1A were detected by immunoblot in striated muscles. Whereas beta 1A could not be detected in adult skeletal muscle fibers and cardiomyocytes by immunofluorescence, beta 1D was localized to the sarcolemma of both cell types. In skeletal muscle, beta 1D was concentrated in costameres, myotendinous, and neuromuscular junctions. In cardiac muscle this beta 1 isoform was found in costamers and intercalated discs. beta 1D was associated with alpha 7A and alpha 7B in adult skeletal muscle. In cardiomyocytes of adult heart, alpha 7B was the major partner for the beta 1D isoform. beta 1D could not be detected in proliferating C2C12 myoblasts, but it appeared immediately after myoblast fusion and its amount continued to rise during myotube growth and maturation. In contrast, expression of the beta 1A isoform was downregulated during myodifferentiation in culture and it was completely displaced by beta 1D in mature differentiated myotubes. We also analyzed some functional properties of the beta 1D integrin subunit. Expression of human beta 1D in CHO cells led to its localization at focal adhesions. Clustering of this integrin isoform on the cell surface stimulated tyrosine phosphorylation of pp125FAK (focal adhesion kinase) and caused transient activation of mitogen-activated protein (MAP) kinases. These data indicate that beta 1D and beta 1A integrin isoforms are functionally similar with regard to integrin-mediated signaling.

Expression of amyloid-beta 1-40 and 1-42 peptides in Capsicum annum var. angulosum for oral immunization.

PubMed

Szabó, Beáta; Hori, Koichi; Nakajima, Akiko; Sasagawa, Noboru; Watanabe, Yuichiro; Ishiura, Shoichi

2004-08-01

Alzheimer's disease (AD), the leading cause of dementia in the elderly population, still remains without an effective treatment. The accumulation and deposition of the amyloid-beta peptide (Abeta) in the brain is thought to be a key event in the pathogenesis of AD. Recently, a novel exciting technology has been investigated to combat AD: new immunotherapeutic approaches have been described that are based on vaccination with the Abeta peptide itself, and this has been shown to induce functionally beneficial anti-Abeta antibody responses in different transgenic animal models of AD. Here we report the high level expression of GFP-Abeta1-40 and 1-42 peptides in Capsicum annum var. angulosum (green pepper) using a new tomato mosaic tobamovirus-based hybrid replication vector. After preinoculation of Nicotiana benthamiana plants with the in vitro transcript of the vector, the isolated virions were used to inoculate green pepper, which accumulated the GFPAbeta1-40 or 1-42 fusion proteins to a level of 100 microg/g of leaves 7 days after inoculation. These results make it possible to test whether oral immunization by feeding plant samples could stimulate antibody production against Abeta peptides.

Amyloid-linked cellular toxicity triggered by bacterial inclusion bodies

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

Gonzalez-Montalban, Nuria; Departament de Genetica i de Microbiologia, Universitat Autonoma de Barcelona, Bellaterra, 08193 Barcelona; Ciber de Bioingenieria, Biomateriales y Nanomedicina

The aggregation of proteins in the form of amyloid fibrils and plaques is the characteristic feature of some pathological conditions ranging from neurodegenerative disorders to systemic amyloidoses. The mechanisms by which the aggregation processes result in cell damage are under intense investigation but recent data indicate that prefibrillar aggregates are the most proximate mediators of toxicity rather than mature fibrils. Since it has been shown that prefibrillar forms of the nondisease-related misfolded proteins are highly toxic to cultured mammalian cells we have studied the cytoxicity associated to bacterial inclusion bodies that have been recently described as protein deposits presenting amyloid-likemore » structures. We have proved that bacterial inclusion bodies composed by a misfolding-prone {beta}-galactosidase fusion protein are clearly toxic for mammalian cells but the {beta}-galactosidase wild type enzyme forming more structured thermal aggregates does not impair cell viability, despite it also binds and enter into the cells. These results are in the line that the most cytotoxic aggregates are early prefibrilar assemblies but discard the hypothesis that the membrane destabilization is Key event to subsequent disruption of cellular processes, such as ion balance, oxidative state and the eventually cell death.« less

Quantitative visualization of synchronized insulin secretion from 3D-cultured cells

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

Suzuki, Takahiro; Kanamori, Takao; Inouye, Satoshi

Quantitative visualization of synchronized insulin secretion was performed in an isolated rat pancreatic islet and a spheroid of rat pancreatic beta cell line using a method of video-rate bioluminescence imaging. Video-rate images of insulin secretion from 3D-cultured cells were obtained by expressing the fusion protein of insulin and Gaussia luciferase (Insulin-GLase). A subclonal rat INS-1E cell line stably expressing Insulin-GLase, named iGL, was established and a cluster of iGL cells showed oscillatory insulin secretion that was completely synchronized in response to high glucose. Furthermore, we demonstrated the effect of an antidiabetic drug, glibenclamide, on synchronized insulin secretion from 2D- andmore » 3D-cultured iGL cells. The amount of secreted Insulin-GLase from iGL cells was also determined by a luminometer. Thus, our bioluminescence imaging method could generally be used for investigating protein secretion from living 3D-cultured cells. In addition, iGL cell line would be valuable for evaluating antidiabetic drugs. - Highlights: • An imaging method for protein secretion from 3D-cultured cells was established. • The fused protein of insulin to GLase, Insulin-GLase, was used as a reporter. • Synchronous insulin secretion was visualized in rat islets and spheroidal beta cells. • A rat beta cell line stably expressing Insulin-GLase, named iGL, was established. • Effect of an antidiabetic drug on insulin secretion was visualized in iGL cells.« less

Characterization of two trpE genes encoding anthranilate synthase {alpha}-subunit in Azospirillum brasilense

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

Ge Shimei; Xie Baoen; Chen Sanfeng

2006-03-10

The previous report from our laboratory has recently identified a new trpE gene (termed trpE {sub 2}) which exists independently in Azospirillum brasilense Yu62. In this study, amplification of trpE(G) (termed trpE {sub 1}(G) here) confirmed that there are two copies of trpE gene, one trpE being fused into trpG while the other trpE existed independently. This is First report to suggest that two copies of the trpE gene exist in this bacterium. Comparison of the nucleotide sequence demonstrated that putative leader peptide, terminator, and anti-terminator were found upstream of trpE {sub 1}(G) while these sequence features did not existmore » in front of trpE {sub 2}. The {beta}-galactosidase activity of an A. brasilense strain carrying a trpE {sub 2}-lacZ fusion remained constant at different tryptophan concentrations, but the {beta}-galactosidase activity of the same strain carrying a trpE {sub 1}(G)-lacZ fusion decreased as the tryptophan concentration increased. These data suggest that the expression of trpE {sub 1}(G) is regulated at the transcriptional level by attenuation while trpE {sub 2} is constantly expressed. The anthranilate synthase assays with trpE {sub 1}(G){sup -} and trpE {sub 2} {sup -} mutants demonstrated that TrpE{sub 1}(G) fusion protein is feedback inhibited by tryptophan while TrpE{sub 2} protein is not. We also found that both trpE {sub 1}(G) and trpE {sub 2} gene products were involved in IAA synthesis.« less

Fluorescence fluctuation analysis of BACE1-GFP fusion protein in cultured HEK293 cells

NASA Astrophysics Data System (ADS)

Gardeen, Spencer; Johnson, Joseph L.; Heikal, Ahmed A.

2016-10-01

Beta-site APP cleaving enzyme 1 (BACE1) is a type I transmembrane aspartyl protease. In the amyloidogenic pathway, BACE1 provides β-secretase activity that cleaves the amyloid precursor protein (APP) that leads to amyloid beta (Aβ) peptides. The aggregation of these Aβ will ultimately results in amyloid plaque formation, a hallmark of Alzheimer's disease (AD). Amyloid aggregation leads to progressive memory impairment and neural loss. Recent detergent protein extraction studies suggest that the untreated BACE1 protein forms a dimer that has significantly higher catalytic activity than its monomeric counterpart. Here, we examine the dimerization hypothesis of BACE1 in cultured HEK293 cells using fluorescence correlation spectroscopy (FCS). Cells were transfected with a BACE1-EGFP fusion protein construct and imaged using confocal and DIC microscopy to monitor labeled BACE1 localization and distribution within the cell. Our one-photon fluorescence fluctuation autocorrelation of BACE1- EGFP on the plasma membrane of HEK cells is modeled using two diffusing species on the plasma membrane with estimated diffusion coefficients of 1.39 x 10-7 cm2/sec and 2.8 x 10-8 cm2/sec under resting conditions and STA-200 inhibition, respectively. Anomalous diffusion model also provided adequate description of the observed autocorrelation function of BACE1- EGFP on the plasma membrane with an estimate exponent (α) of 0.8 and 0.5 for resting and STA-200 treated cells, respectively. The corresponding hydrodynamic radius of this transmembrane fusion protein was estimated using the measured diffusion coefficients assuming both Stokes-Einstein and Saffman-Delbruck models. Our results suggest a complex diffusion pattern of BACE1-EGFP on the plasma membrane of HEK cells with the possibility for dimer formation, especially under STA-200 inhibition.

Extracellular matrix and hormones transcriptionally regulate bovine. beta. -casein 5 prime sequences in stably transfected mouse mammary cells

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

Schmidhauser, C. Bissell, M.J.; Myers, C.A.; Casperson, G.F.

1990-12-01

Milk protein regulation involves synergistic action of lactogenic hormones and extracellular matrix (ECM). It is well established that substratum has a dramatic effect on morphology and function of mammary cells. The molecular mechanisms that regulate the ECM- and hormone-dependent gene expression, however, have not been resolved. To address this question, a subpopulation (designated CID 9) of the mouse mammary epithelial cell strain COMMA-2D has been developed in which more than 35% of the cells express {beta}-casein, form alveoli-like structures when plated onto a reconstituted basement membrane, and secrete {beta}-casein undirectionally into a lumen. These cells were stably transfected with amore » series of chloramphenicol acetyltransferase (CAT) fusion genes to study transcriptional regulation of the bovine {beta}-casein gene. The expression of CAT in these lines demonstrated a striking matrix and hormone dependency. This regulation occurered primarily at the transcriptional level and was dependent on the length of the 5{prime} flanking region of the {beta}-casein promotor. Both matrix and hormonal control of transcription occurred within at least the first 1790 base pairs upstream and/or 42 base pairs downstream of the transcriptional initiation site. The ECM effect was independent of glucocorticoid stimulation. However, prolactin was essential and hydrocortisone further increased CAT expression. Endogenous {beta}-casein expression in these lines was similar to that of the parent CID 9 cells. Our data indicate the existence of matrix-dependent elements that regulate transcription.« less

Expression of cholera toxin B-proinsulin fusion protein in lettuce and tobacco chloroplasts--oral administration protects against development of insulitis in non-obese diabetic mice.

PubMed

Ruhlman, Tracey; Ahangari, Raheleh; Devine, Andrew; Samsam, Mohtahsem; Daniell, Henry

2007-07-01

Lettuce and tobacco chloroplast transgenic lines expressing the cholera toxin B subunit-human proinsulin (CTB-Pins) fusion protein were generated. CTB-Pins accumulated up to ~16% of total soluble protein (TSP) in tobacco and up to ~2.5% of TSP in lettuce. Eight milligrams of powdered tobacco leaf material expressing CTB-Pins or, as negative controls, CTB-green fluorescent protein (CTB-GFP) or interferon-GFP (IFN-GFP), or untransformed leaf, were administered orally, each week for 7 weeks, to 5-week-old female non-obese diabetic (NOD) mice. The pancreas of CTB-Pins-treated mice showed decreased infiltration of cells characteristic of lymphocytes (insulitis); insulin-producing beta-cells in the pancreatic islets of CTB-Pins-treated mice were significantly preserved, with lower blood or urine glucose levels, by contrast with the few beta-cells remaining in the pancreatic islets of the negative controls. Increased expression of immunosuppressive cytokines, such as interleukin-4 and interleukin-10 (IL-4 and IL-10), was observed in the pancreas of CTB-Pins-treated NOD mice. Serum levels of immunoglobulin G1 (IgG1), but not IgG2a, were elevated in CTB-Pins-treated mice. Taken together, T-helper 2 (Th2) lymphocyte-mediated oral tolerance is a likely mechanism for the prevention of pancreatic insulitis and the preservation of insulin-producing beta-cells. This is the first report of expression of a therapeutic protein in transgenic chloroplasts of an edible crop. Transplastomic lettuce plants expressing CTB-Pins grew normally and transgenes were maternally inherited in T(1) progeny. This opens up the possibility for the low-cost production and delivery of human therapeutic proteins, and a strategy for the treatment of various other autoimmune diseases.

Non-inductively driven tokamak plasmas at near-unity β t in the Pegasus toroidal experiment

DOE PAGES

Reusch, Joshua A.; Bodner, Grant M.; Bongard, Michael W.; ...

2018-03-14

Amore » major goal of the spherical tokamak (ST) research program is accessing a state of low internal inductance ℓ i , high elongation κ , and high toroidal and normalized beta ( β t and β N ) without solenoidal current drive. Local helicity injection (LHI) in the Pegasus ST [Garstka et al., Nucl. Fusion 46, S603 (2006)] provides non-solenoidally driven plasmas that exhibit these characteristics. LHI utilizes compact, edge-localized current sources for plasma startup and sustainment. It results in hollow current density profiles with low ℓ i . The low aspect ratio ( R 0 / a ~ 1.2 ) of Pegasus allows access to high κ and high normalized plasma currents I N = I p / a B T > 14 ). Magnetic reconnection during LHI provides auxiliary ion heating. Together, these features provide access to very high β t plasmas. Equilibrium analyses indicate that β t up to ~100% is achieved. Finally, these high β t discharges disrupt at the ideal no-wall β limit at β N ~ 7. « less

Non-inductively driven tokamak plasmas at near-unity β t in the Pegasus toroidal experiment

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

Reusch, Joshua A.; Bodner, Grant M.; Bongard, Michael W.

Amore » major goal of the spherical tokamak (ST) research program is accessing a state of low internal inductance ℓ i , high elongation κ , and high toroidal and normalized beta ( β t and β N ) without solenoidal current drive. Local helicity injection (LHI) in the Pegasus ST [Garstka et al., Nucl. Fusion 46, S603 (2006)] provides non-solenoidally driven plasmas that exhibit these characteristics. LHI utilizes compact, edge-localized current sources for plasma startup and sustainment. It results in hollow current density profiles with low ℓ i . The low aspect ratio ( R 0 / a ~ 1.2 ) of Pegasus allows access to high κ and high normalized plasma currents I N = I p / a B T > 14 ). Magnetic reconnection during LHI provides auxiliary ion heating. Together, these features provide access to very high β t plasmas. Equilibrium analyses indicate that β t up to ~100% is achieved. Finally, these high β t discharges disrupt at the ideal no-wall β limit at β N ~ 7. « less

A high performance field-reversed configuration

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

Binderbauer, M. W.; Tajima, T.; Steinhauer, L. C.

2015-05-15

Conventional field-reversed configurations (FRCs), high-beta, prolate compact toroids embedded in poloidal magnetic fields, face notable stability and confinement concerns. These can be ameliorated by various control techniques, such as introducing a significant fast ion population. Indeed, adding neutral beam injection into the FRC over the past half-decade has contributed to striking improvements in confinement and stability. Further, the addition of electrically biased plasma guns at the ends, magnetic end plugs, and advanced surface conditioning led to dramatic reductions in turbulence-driven losses and greatly improved stability. Together, these enabled the build-up of a well-confined and dominant fast-ion population. Under such conditions,more » highly reproducible, macroscopically stable hot FRCs (with total plasma temperature of ∼1 keV) with record lifetimes were achieved. These accomplishments point to the prospect of advanced, beam-driven FRCs as an intriguing path toward fusion reactors. This paper reviews key results and presents context for further interpretation.« less

Regulation of expression and biochemical characterization of a beta-class carbonic anhydrase from the plant growth-promoting rhizobacterium, Azospirillum brasilense Sp7.

PubMed

Kaur, Simarjot; Mishra, Mukti Nath; Tripathi, Anil K

2009-10-01

Carbonic anhydrase (CA; [EC 4.2.1.1]) is a ubiquitous enzyme catalysing the reversible hydration of CO(2) to bicarbonate, a reaction that supports various biochemical and physiological functions. Genome analysis of Azospirillum brasilense, a nonphotosynthetic, nitrogen-fixing, rhizobacterium, revealed an ORF with homology to beta-class carbonic anhydrases (CAs). Biochemical characteristics of the beta-class CA of A. brasilense, analysed after cloning the gene (designated as bca), overexpressing in Escherichia coli and purifying the protein by affinity purification, revealed that the native recombinant enzyme is a homotetramer, inhibited by the known CA inhibitors. CA activity in A. brasilense cell extracts, reverse transcriptase (RT)-PCR and Western blot analyses showed that bca was constitutively expressed under aerobic conditions. Lower beta-galactosidase activity in A. brasilense cells harbouring bca promoter: lacZ fusion during the stationary phase or during growth on 3% CO(2) enriched air or at acidic pH indicated that the transcription of bca was downregulated by the stationary phase, elevated CO(2) levels and acidic pH conditions. These observations were also supported by RT-PCR analysis. Thus, beta-CA in A. brasilense seems to be required for scavenging CO(2) from the ambient air and the requirement of CO(2) hydration seems to be higher for the cultures growing exponentially at neutral to alkaline pH.

Bridging the gap between protein carboxyl methylation and phospholipid methylation to understand glucose-stimulated insulin secretion from the pancreatic beta cell.

PubMed

Kowluru, Anjaneyulu

2008-01-15

Recent findings have implicated post-translational modifications at C-terminal cysteines [e.g., methylation] of specific proteins [e.g., G-proteins] in glucose-stimulated insulin secretion [GSIS]. Furthermore, methylation at the C-terminal leucine of the catalytic subunit of protein phosphatase 2A [PP2Ac] has also been shown to be relevant for GSIS. In addition to these two classes of protein methyl transferases, a novel class of glucose-activated phospholipid methyl transferases have also been identified in the beta cell. These enzymes catalyze three successive methylations of phosphatidylethanolamine to yield phosphatidylcholine. The "newly formed" phosphatidylcholine is felt to induce alterations in the membrane fluidity, which might favor vesicular fusion with the plasma membrane for the exocytosis of insulin. The objectives of this commentary are to: (i) review the existing evidence on the regulation, by glucose and other insulin secretagogues, of post-translational carboxylmethylation [CML] of specific proteins in the beta cell; (ii) discuss the experimental evidence, which implicates regulation, by glucose and other insulin secretagogues, of phosphatidylethanolamine methylation in the islet beta cell; (iii) propose a model for potential cross-talk between the protein and lipid methylation pathways in the regulation of GSIS and (iv) highlight potential avenues for future research, including the development of specific pharmacological inhibitors to further decipher regulatory roles for these methylation reactions in islet beta cell function.

A liver X receptor (LXR)-{beta} alternative splicing variant (LXRBSV) acts as an RNA co-activator of LXR-{beta}

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

Hashimoto, Koshi, E-mail: khashi@med.gunma-u.ac.jp; Ishida, Emi; Matsumoto, Shunichi

2009-12-25

We report the isolation and functional characterization of a novel transcriptional co-activator, termed LXRBSV. LXRBSV is an alternative splicing variant of liver X receptor (LXR)-{beta} LXRBSV has an intronic sequence between exons 2 and 3 in the mouse LXR-{beta} gene. The LXRBSV gene is expressed in various tissues including the liver and brain. We sub-cloned LXRBSV into pSG5, a mammalian expression vector, and LXRBSV in pSG5 augmented human Sterol Response Element Binding Protein (SREBP)-1c promoter activity in HepG2 cells in a ligand (TO901317) dependent manner. The transactivation mediated by LXRBSV is selective for LXR-{beta}. The LXRBSV protein was deduced tomore » be 64 amino acids in length; however, a GAL4-LXRBSV fusion protein was not able to induce transactivation. Serial deletion constructs of LXRBSV demonstrated that the intronic sequence inserted in LXRBSV is required for its transactivation activity. An ATG mutant of LXRBSV was able to induce transactivation as wild type. Furthermore, LXRBSV functions in the presence of cycloheximide. Taken together, we have concluded that LXRBSV acts as an RNA transcript not as a protein. In the current study, we have demonstrated for the first time that an alternative splicing variant of a nuclear receptor acts as an RNA co-activator.« less

VAMP-2 and cellubrevin are expressed in pancreatic beta-cells and are essential for Ca(2+)-but not for GTP gamma S-induced insulin secretion.

PubMed Central

Regazzi, R; Wollheim, C B; Lang, J; Theler, J M; Rossetto, O; Montecucco, C; Sadoul, K; Weller, U; Palmer, M; Thorens, B

1995-01-01

VAMP proteins are important components of the machinery controlling docking and/or fusion of secretory vesicles with their target membrane. We investigated the expression of VAMP proteins in pancreatic beta-cells and their implication in the exocytosis of insulin. cDNA cloning revealed that VAMP-2 and cellubrevin, but not VAMP-1, are expressed in rat pancreatic islets and that their sequence is identical to that isolated from rat brain. Pancreatic beta-cells contain secretory granules that store and secrete insulin as well as synaptic-like microvesicles carrying gamma-aminobutyric acid. After subcellular fractionation on continuous sucrose gradients, VAMP-2 and cellubrevin were found to be associated with both types of secretory vesicle. The association of VAMP-2 with insulin-containing granules was confirmed by confocal microscopy of primary cultures of rat pancreatic beta-cells. Pretreatment of streptolysin-O permeabilized insulin-secreting cells with tetanus and botulinum B neurotoxins selectively cleaved VAMP-2 and cellubrevin and abolished Ca(2+)-induced insulin release (IC50 approximately 15 nM). By contrast, the pretreatment with tetanus and botulinum B neurotoxins did not prevent GTP gamma S-stimulated insulin secretion. Taken together, our results show that pancreatic beta-cells express VAMP-2 and cellubrevin and that one or both of these proteins selectively control Ca(2+)-mediated insulin secretion. Images PMID:7796801

Incorporating priors on expert performance parameters for segmentation validation and label fusion: a maximum a posteriori STAPLE

PubMed Central

Commowick, Olivier; Warfield, Simon K

2010-01-01

In order to evaluate the quality of segmentations of an image and assess intra- and inter-expert variability in segmentation performance, an Expectation Maximization (EM) algorithm for Simultaneous Truth And Performance Level Estimation (STAPLE) was recently developed. This algorithm, originally presented for segmentation validation, has since been used for many applications, such as atlas construction and decision fusion. However, the manual delineation of structures of interest is a very time consuming and burdensome task. Further, as the time required and burden of manual delineation increase, the accuracy of the delineation is decreased. Therefore, it may be desirable to ask the experts to delineate only a reduced number of structures or the segmentation of all structures by all experts may simply not be achieved. Fusion from data with some structures not segmented by each expert should be carried out in a manner that accounts for the missing information. In other applications, locally inconsistent segmentations may drive the STAPLE algorithm into an undesirable local optimum, leading to misclassifications or misleading experts performance parameters. We present a new algorithm that allows fusion with partial delineation and which can avoid convergence to undesirable local optima in the presence of strongly inconsistent segmentations. The algorithm extends STAPLE by incorporating prior probabilities for the expert performance parameters. This is achieved through a Maximum A Posteriori formulation, where the prior probabilities for the performance parameters are modeled by a beta distribution. We demonstrate that this new algorithm enables dramatically improved fusion from data with partial delineation by each expert in comparison to fusion with STAPLE. PMID:20879379

Incorporating priors on expert performance parameters for segmentation validation and label fusion: a maximum a posteriori STAPLE.

PubMed

Commowick, Olivier; Warfield, Simon K

2010-01-01

In order to evaluate the quality of segmentations of an image and assess intra- and inter-expert variability in segmentation performance, an Expectation Maximization (EM) algorithm for Simultaneous Truth And Performance Level Estimation (STAPLE) was recently developed. This algorithm, originally presented for segmentation validation, has since been used for many applications, such as atlas construction and decision fusion. However, the manual delineation of structures of interest is a very time consuming and burdensome task. Further, as the time required and burden of manual delineation increase, the accuracy of the delineation is decreased. Therefore, it may be desirable to ask the experts to delineate only a reduced number of structures or the segmentation of all structures by all experts may simply not be achieved. Fusion from data with some structures not segmented by each expert should be carried out in a manner that accounts for the missing information. In other applications, locally inconsistent segmentations may drive the STAPLE algorithm into an undesirable local optimum, leading to misclassifications or misleading experts performance parameters. We present a new algorithm that allows fusion with partial delineation and which can avoid convergence to undesirable local optima in the presence of strongly inconsistent segmentations. The algorithm extends STAPLE by incorporating prior probabilities for the expert performance parameters. This is achieved through a Maximum A Posteriori formulation, where the prior probabilities for the performance parameters are modeled by a beta distribution. We demonstrate that this new algorithm enables dramatically improved fusion from data with partial delineation by each expert in comparison to fusion with STAPLE.

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

Stencel, J.R.; Finley, V.L.

This report gives the results of the environmental activities and monitoring programs at the Princeton Plasma Physics Laboratory for CY90. The report is prepared to provide the US Department of Energy (DOE) and the public with information on the level of radioactive and nonradioactive pollutants, if any, added to the environment as a result of PPPL operations, as well as environmental initiatives, assessments, and programs. The objective of the Annual Site Environmental Report is to document evidence that DOE facility environmental protection programs adequately protect the environment and the public health. The PPPL has engaged in fusion energy research sincemore » 1951 and in 1990 had one of its two large tokamak devices in operation: namely, the Tokamak Fusion Test Reactor. The Princeton Beta Experiment-Modification is undergoing new modifications and upgrades for future operation. A new machine, the Burning Plasma Experiment -- formerly called the Compact Ignition Tokamak -- is under conceptual design, and it is awaiting the approval of its draft Environmental Assessment report by DOE Headquarters. This report is required under the National Environmental Policy Act. The long-range goal of the US Magnetic Fusion Energy Research Program is to develop and demonstrate the practical application of fusion power as an alternate energy source. 59 refs., 39 figs., 45 tabs.« less

Capturing Neutrinos from a Star's Final Hours

NASA Astrophysics Data System (ADS)

Hensley, Kerry

2018-04-01

What happens on the last day of a massive stars life? In the hours before the star collapses and explodes as a supernova, the rapid evolution of material in its core creates swarms of neutrinos. Observing these neutrinos may help us understand the final stages of a massive stars life but theyve never been detected.A view of some of the 1,520 phototubes within the MiniBooNE neutrino detector. Observations from this and other detectors are helping to illuminate the nature of the mysterious neutrino. [Fred Ullrich/FNAL]Silent Signposts of Stellar EvolutionThe nuclear fusion that powers stars generates tremendous amounts of energy. Much of this energy is emitted as photons, but a curious and elusive particle the neutrino carries away most of the energy in the late stages of stellar evolution.Stellar neutrinos can be created through two processes: thermal processesand beta processes. Thermal processes e.g.,pair production, in which a particle/antiparticle pair are created depend on the temperature and pressure of the stellar core. Beta processes i.e.,when a proton converts to a neutron, or vice versa are instead linked to the isotopic makeup of the stars core. This means that, if we can observe them, beta-process neutrinos may be able to tell us about the last steps of stellar nucleosynthesis in a dying star.But observing these neutrinos is not so easilydone. Neutrinos arenearly massless, neutral particles that interact only feebly with matter; out of the whopping 1060neutrinos released in a supernova explosion, even the most sensitive detectors only record the passage of just a few. Do we have a chance of detectingthe beta-process neutrinos that are released in the final few hours of a stars life, beforethe collapse?Neutrino luminosities leading up to core collapse. Shortly before collapse, the luminosity of beta-process neutrinos outshines that of any other neutrino flavor or origin. [Adapted from Patton et al. 2017]Modeling Stellar CoresTo answer this question, Kelly Patton (University of Washington) and collaborators first used a stellar evolution model to explore neutrino production in massive stars. They modeled the evolution of two massive stars 15 and 30 times the mass of our Sun from the onset of nuclear fusion to the moment of collapse.The authors found that in the last few hours before collapse, during which the material in the stars cores is rapidly upcycled into heavier elements, the flux from beta-process neutrinos rivals that of thermal neutrinos and even exceeds it at high energies. So now we know there are many beta-process neutrinos but can we spot them?Neutrino and antineutrino fluxes at Earth from the last 2 hours of a 30-solar-mass stars life compared to the flux from background sources. The rows represent calculations using two different neutrino mass hierarchies. Click to enlarge. [Patton et al. 2017]Observing Elusive NeutrinosFor an imminent supernova at a distance of 1 kiloparsec, the authors find that the presupernova electron neutrino flux rises above the background noise from the Sun, nuclear reactors, and radioactive decay within the Earth in the final two hours before collapse.Based on these calculations, current and future neutrino observatories should be able to detect tens of neutrinos from a supernova within 1 kiloparsec, about 30% of which would be beta-process neutrinos. As the distance to the star increases, the time and energy window within which neutrinos can be observed gradually narrows, until it closes for stars at a distance of about 30 kiloparsecs.Are there any nearby supergiants soon to go supernova so these predictions can be tested? At a distance of only 650 light-years, the red supergiant star Betelgeuse should produce detectable neutrinos when it explodes an exciting opportunity for astronomers in the far future!CitationKelly M. Patton et al 2017ApJ8516. doi:10.3847/1538-4357/aa95c4

Expression in Bacillus subtilis of the Bacillus thuringiensis cryIIIA toxin gene is not dependent on a sporulation-specific sigma factor and is increased in a spo0A mutant.

PubMed

Agaisse, H; Lereclus, D

1994-08-01

Expression of the Bacillus thuringiensis cryIIIA gene encoding a Coleoptera-specific toxin is weak during vegetative growth and is activated at the onset of the stationary phase. cryIIIA'-'lacZ fusions and primer extension analysis show that the regulation of cryIIIA expression is similar in Bacillus subtilis and in B. thuringiensis. Activation of cryIIIA expression was not altered in B. subtilis mutant strains deficient for the sigma H and sigma E sporulation-specific sigma factors or for minor sigma factors such as sigma B, sigma D, or sigma L. This result and the nucleotide sequence of the -35 and -10 regions of the cryIIIA promoter suggest that cryIIIA expression might be directed by the E sigma A form of RNA polymerase. Expression of the cryIIIA'-'lacZ fusion is shut off after t2 (2 h after time zero) of sporulation in the B. subtilis wild-type strain grown on nutrient broth sporulation medium. However, no decrease in cryIIIA-directed beta-galactosidase activity occurred in sigma H, kinA, or spo0A mutant strains. Moreover, beta-galactosidase activity was higher and remained elevated after t2 in the spo0A mutant strain. beta-Galactosidase activity was weak in abrB and spo0A abrB mutant strains, suggesting that AbrB is responsible for the higher level of cryIIIA expression observed in a spo0A mutant. However, both in spo0A and spo0A abrB mutant strains, beta-galactosidase activity remained elevated after t2, suggesting that even in the absence of AbrB, cryIIIA expression is controlled through modulation of the phosphorylated form of Spo0A. When the cryIIIA gene is expressed in a B. subtilis spo0A mutant strain or in the 168 wild-type strain, large amounts of toxins are produced and accumulate to form a flat rectangular crystal characteristic of the coleopteran-specific B. thuringiensis strains.

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

PubMed

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

2017-01-01

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

Analysis of Rheb in the cellular slime mold Dictyostelium discoideum: cellular localization, spatial expression and overexpression.

PubMed

Swer, Pynskhem Bok; Bhadoriya, Pooja; Saran, Shweta

2014-03-01

Dictyostelium discoideum encodes a single Rheb protein showing sequence similarity to human homologues of Rheb. The DdRheb protein shares 52 percent identity and 100 percent similarity with the human Rheb1 protein. Fluorescence of Rheb yellow fluorescent protein fusion was detected in the D. discoideum cytoplasm. Reverse transcription-polymerase chain reaction and whole-mount in situ hybridization analyses showed that rheb is expressed at all stages of development and in prestalk cells in the multicellular structures developed. When the expression of rheb as a fusion with lacZ was driven under its own promoter, the beta-galactosidase activity was seen in the prestalk cells. D. discoideum overexpressing Rheb shows an increase in the size of the cell. Treatment of the overexpressing Rheb cells with rapamycin confirms its involvement in the TOR signalling pathway.

Repression of choline kinase by inositol and choline in Saccharomyces cerevisiae.

PubMed Central

Hosaka, K; Murakami, T; Kodaki, T; Nikawa, J; Yamashita, S

1990-01-01

The regulation of choline kinase (EC 2.7.1.32), the initial enzyme in the CDP-choline pathway, was examined in Saccharomyces cerevisiae. The addition of myo-inositol to a culture of wild-type cells resulted in a significant decrease in choline kinase activity. Additional supplementation of choline caused a further reduction in the activity. The coding frame of the choline kinase gene, CK1, was joined to the carboxyl terminus of lacZ and expressed in Escherichia coli as a fusion protein, which was then used to prepare an anti-choline kinase antibody. Upon Western (immuno-) and Northern (RNA) blot analyses using the antibody and a CK1 probe, respectively, the decrease in the enzyme activity was found to be correlated with decreases in the enzyme amount and mRNA abundance. The molecular mass of the enzyme was estimated to be 66 kilodaltons, in agreement with the value predicted previously from the nucleotide sequence of the gene. The coding region of CK1 was replaced with that of lacZ, and CK1 expression was measured by assaying beta-galactosidase. The expression of beta-galactosidase from this fusion was repressed by myo-inositol and choline and derepressed in a time-dependent manner upon their removal. The present findings indicate that yeast choline kinase is regulated by myo-inositol and choline at the level of mRNA abundance. Images FIG. 3 FIG. 4 PMID:2156807

Molecular recognition of parathyroid hormone by its G protein-coupled receptor

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

Pioszak, Augen A.; Xu, H. Eric

Parathyroid hormone (PTH) is central to calcium homeostasis and bone maintenance in vertebrates, and as such it has been used for treating osteoporosis. It acts primarily by binding to its receptor, PTH1R, a member of the class B G protein-coupled receptor (GPCR) family that also includes receptors for glucagon, calcitonin, and other therapeutically important peptide hormones. Despite considerable interest and much research, determining the structure of the receptor-hormone complex has been hindered by difficulties in purifying the receptor and obtaining diffraction-quality crystals. Here, we present a method for expression and purification of the extracellular domain (ECD) of human PTH1R engineeredmore » as a maltose-binding protein (MBP) fusion that readily crystallizes. The 1.95-{angstrom} structure of PTH bound to the MBP-PTH1R-ECD fusion reveals that PTH docks as an amphipathic helix into a central hydrophobic groove formed by a three-layer {alpha}-{beta}-{beta}{alpha} fold of the PTH1R ECD, resembling a hot dog in a bun. Conservation in the ECD scaffold and the helical structure of peptide hormones emphasizes this hot dog model as a general mechanism of hormone recognition common to class B GPCRs. Our findings reveal critical insights into PTH actions and provide a rational template for drug design that targets this hormone signaling pathway.« less

Beer Law Constants and Vapor Pressures of HgI2 over HgI2(s,l)

NASA Technical Reports Server (NTRS)

Su, Ching-Hua; Zhu, Shen; Ramachandran, N.; Burger, A.

2002-01-01

Optical absorption spectra of the vapor phase over HgI2(s,l) were measured at sample temperatures between 349 and 610 K for wavelengths between 200 and 600 nm. The spectra show the samples sublimed congruently into HGI2 without any observed Hg or I2 absorption spectra. The Beer's Law constants for 15 wavelengths between 200 and 440 nm were derived. From these constants the vapor pressure of HgI2, P, was found to be a function of temperature for the liquid and the solid beta-phases: ln P(atm) = -7700/T(K) + 12.462 (liquid phase) and ln P(atm) = -10150/T(K) + 17.026 (beta-phase). The expressions match the enthalpies of vaporization and sublimation of 15.30 and 20.17 kcal/mole respectively, for the liquid and the beta-phase HgI2. The difference in the enthalpies gives an enthalpy of fusion of 4.87 kcal/mole, and the intersection of the two expressions gives a melting point of 537 K.

Inactivated Recombinant Rabies Viruses Displaying Canine Distemper Virus Glycoproteins Induce Protective Immunity against Both Pathogens.

PubMed

da Fontoura Budaszewski, Renata; Hudacek, Andrew; Sawatsky, Bevan; Krämer, Beate; Yin, Xiangping; Schnell, Matthias J; von Messling, Veronika

2017-04-15

The development of multivalent vaccines is an attractive methodology for the simultaneous prevention of several infectious diseases in vulnerable populations. Both canine distemper virus (CDV) and rabies virus (RABV) cause lethal disease in wild and domestic carnivores. While RABV vaccines are inactivated, the live-attenuated CDV vaccines retain residual virulence for highly susceptible wildlife species. In this study, we developed recombinant bivalent vaccine candidates based on recombinant vaccine strain rabies virus particles, which concurrently display the protective CDV and RABV glycoprotein antigens. The recombinant viruses replicated to near-wild-type titers, and the heterologous glycoproteins were efficiently expressed and incorporated in the viral particles. Immunization of ferrets with beta-propiolactone-inactivated recombinant virus particles elicited protective RABV antibody titers, and animals immunized with a combination of CDV attachment protein- and fusion protein-expressing recombinant viruses were protected from lethal CDV challenge. However, animals that were immunized with only a RABV expressing the attachment protein of CDV vaccine strain Onderstepoort succumbed to infection with a more recent wild-type strain, indicating that immune responses to the more conserved fusion protein contribute to protection against heterologous CDV strains. IMPORTANCE Rabies virus and canine distemper virus (CDV) cause high mortality rates and death in many carnivores. While rabies vaccines are inactivated and thus have an excellent safety profile and high stability, live-attenuated CDV vaccines can retain residual virulence in highly susceptible species. Here we generated recombinant inactivated rabies viruses that carry one of the CDV glycoproteins on their surface. Ferrets immunized twice with a mix of recombinant rabies viruses carrying the CDV fusion and attachment glycoproteins were protected from lethal CDV challenge, whereas all animals that received recombinant rabies viruses carrying only the CDV attachment protein according to the same immunization scheme died. Irrespective of the CDV antigens used, all animals developed protective titers against rabies virus, illustrating that a bivalent rabies virus-based vaccine against CDV induces protective immune responses against both pathogens. Copyright © 2017 American Society for Microbiology.

Environmental conditions affect transcription of the pectinase genes of Erwinia chrysanthemi 3937.

PubMed Central

Hugouvieux-Cotte-Pattat, N; Dominguez, H; Robert-Baudouy, J

1992-01-01

To depolymerize plant pectin, the phytopathogenic enterobacterium Erwinia chrysanthemi produces a series of enzymes which include a pectin-methyl-esterase encoded by the pem gene and five isoenzymes of pectate lyases encoded by the five genes pelA, pelB, pelC, pelD, and pelE. We have constructed transcriptional fusions between the pectinase gene promoters and the uidA gene, encoding beta-glucuronidase, to study the regulation of these E. chrysanthemi pectinase genes individually. The transcription of the pectinase genes is dependent on many environmental conditions. All the fusions were induced by pectic catabolic products and responded, to different degrees, to growth phase, catabolite repression, temperature, and nitrogen starvation. Transcription of pelA, pelD, and pelE was also increased in anaerobic growth conditions. High osmolarity of the culture medium increased expression of pelE but decreased that of pelD; the other pectinase genes were not affected. The level of expression of each gene was different. Transcription of pelA was very low under all growth conditions. The expression of the pelB, pelC, and pem genes was intermediate. The pelE gene had a high basal level of expression. Expression of pelD was generally the most affected by changes in culture conditions and showed a low basal level but very high induced levels. These differences in the expression of the pectinase genes of E. chrysanthemi 3937 presumably reflect their role during infection of plants, because the degradation of pectic polymers of the plant cell walls is the main determinant of tissue maceration caused by soft rot erwiniae. PMID:1447147

Evaluating the effectiveness of using electroencephalogram power indices to measure visual fatigue.

PubMed

Hsu, Bin-Wei; Wang, Mao-Jiun J

2013-02-01

Electroencephalography (EEG) is widely used in cognitive and behavioral research. This study evaluates the effectiveness of using the EEG power index to measure visual fatigue. Three common visual fatigue measures, critical-flicker fusion (CFF), near-point accommodation (NPA), and subjective eye-fatigue rating, were used for comparison. The study participants were 20 men with a mean age of 20.4 yr. (SD = 1.5). The experimental task was a car-racing video game. Results indicated that the EEG power indices were valid as a visual fatigue measure and the sensitivity of the objective measures (CFF and EEG power index) was higher than the subjective measure. The EEG beta and EEG alpha were effective for measuring visual fatigue in short- and long-duration tasks, respectively. EEG beta/alpha were the most effective power indexes for the visual fatigue measure.

Using MASHA+TIMEPIX Setup for Registration Beta Decay Isotopes Produced in Heavy Ion Induced Reactions

NASA Astrophysics Data System (ADS)

Rodin, A. M.; Belozerov, A. V.; Chernysheva, E. V.; Dmitriev, S. N.; Gulyaev, A. V.; Gulyaeva, A. V.; Itkis, M. G.; Novoselov, A. S.; Oganessian, Yu. Ts.; Salamatin, V. S.; Stepantsov, S. V.; Vedeneev, V. Yu.; Yukhimchuk, S. A.; Krupa, L.; Granja, C.; Pospisil, S.; Kliman, J.; Motycak, S.; Sivacek, I.

2015-06-01

Radon and mercury isotopes were produced in multi nucleon transfer (48Ca + 232Th) and complete fusion (48Ca + naturalNd) reactions, respectively. The isotopes with given masses were detected using two detectors: a multi-strip detector of the well-type (made in CANBERRA) and a position-sensitive quantum counting hybrid pixel detector of the TIMEPIX type. The isotopes implanted into the detectors then emit alpha- and betaparticles until reaching the long lived isotopes. The position of the isotopes, the tracks, the time and energy of beta-particles were measured and analyzed. A new software for the particle recognition and data analysis of experimental results was developed and used. It was shown that MASHA+ TIMEPIX setup is a powerful instrument for investigation of neutron-rich isotopes far from stability limits.

Rat leucine-rich protein binds and activates the promoter of the beta isoform of Ca2+/calmodulin-dependent protein kinase II gene.

PubMed

Ochiai, Nagahiro; Masumoto, Shuji; Sakagami, Hiroyuki; Yoshimura, Yoshiyuki; Yamauchi, Takashi

2007-05-01

We previously found the neuronal cell-type specific promoter and binding partner of the beta isoform of Ca(2+)/calmodulin-dependent protein kinase II (beta CaM kinase II) in rat brain [Donai, H., Morinaga, H., Yamauchi, T., 2001. Genomic organization and neuronal cell type specific promoter activity of beta isoform of Ca(2+)/calmodulin-dependent protein kinase II of rat brain. Mol. Brain Res. 94, 35-47]. In the present study, we purified a protein that binds specifically a promoter region of beta CaM kinase II gene from a nuclear extract of the rat cerebellum using DEAE-cellulose column chromatography, ammonium sulfate fractionation, gel filtration and polyacrylamide gel electrophoresis. The purified protein was identified as rat leucine-rich protein 157 (rLRP157) using tandem mass spectrometry. Then, we prepared its cDNA by reverse transcriptase-polymerase chain reaction (RT-PCR) from poly(A)(+)RNA of rat cerebellum. The rLRP157 cDNA was introduced into mouse neuroblastomaxrat glioma hybrid NG108-15 cells, and cells stably expressing rLRP157 (NG/LRP cells) were isolated. Binding of rLRP157 with the promoter sequence was confirmed by electrophoretic mobility shift assay using nuclear extract of NG/LRP cells. A luciferase reporter gene containing a promoter of beta CaM kinase II was transiently expressed in NG/LRP cells. Under the conditions, the promoter activity was enhanced about 2.6-fold in NG/LRP cells as compared with wild-type cells. The expression of rLRP157 mRNA was paralleled with that of beta CaM kinase II in the adult and embryo rat brain detected by in situ hybridization. Nuclear localization of rLRP157 was confirmed using GFP-rLRP157 fusion protein investigated under a confocal microscope. These results indicate that rLRP157 is one of the proteins binding to, and regulating the activity of, the promoter of beta CaM kinase II.

Structure of the beta-galactosidase gene from Thermus sp. strain T2: expression in Escherichia coli and purification in a single step of an active fusion protein.

PubMed

Vian, A; Carrascosa, A V; García, J L; Cortés, E

1998-06-01

The nucleotide sequence of both the bgaA gene, coding for a thermostable beta-galactosidase of Thermus sp. strain T2, and its flanking regions was determined. The deduced amino acid sequence of the enzyme predicts a polypeptide of 645 amino acids (Mr, 73,595). Comparative analysis of the open reading frames located in the flanking regions of the bgaA gene revealed that they might encode proteins involved in the transport and hydrolysis of sugars. The observed homology between the deduced amino acid sequences of BgaA and the beta-galactosidase of Bacillus stearothermophilus allows us to classify the new enzyme within family 42 of glycosyl hydrolases. BgaA was overexpressed in its active form in Escherichia coli, but more interestingly, an active chimeric beta-galactosidase was constructed by fusing the BgaA protein to the choline-binding domain of the major pneumococcal autolysin. This chimera illustrates a novel approach for producing an active and thermostable hybrid enzyme that can be purified in a single step by affinity chromatography on DEAE-cellulose, retaining the catalytic properties of the native enzyme. The chimeric enzyme showed a specific activity of 191,000 U/mg at 70 degrees C and a Km value of 1.6 mM with o-nitrophenyl-beta-D-galactopyranoside as a substrate, and it retained 50% of its initial activity after 1 h of incubation at 70 degrees C.

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.

Observation of the hot electron interchange instability in a high beta dipolar confined plasma

NASA Astrophysics Data System (ADS)

Ortiz, Eugenio Enrique

In this thesis the first study of the high beta, hot electron interchange (HEI) instability in a laboratory, dipolar confined plasma is presented. The Levitated Dipole Experiment (LDX) is a new research facility that explores the confinement and stability of plasma created within the dipole field produced by a strong superconducting magnet. In initial experiments long-pulse, quasi-steady state microwave discharges lasting more than 10 sec have been produced with equilibria having peak beta values of 20%. Creation of high-pressure, high beta plasma is possible only when intense HEI instabilities are stabilized by sufficiently high background plasma density. LDX plasma exist within one of three regimes characterized by its response to heating and fueling. The observed HEI instability depends on the regime and can take one of three forms: as quasiperiodic bursts during the low density, low beta plasma regime, as local high beta relaxation events in the high beta plasma regime, and as global, intense energy relaxation bursts, both in the high beta and afterglow plasma regimes. Measurements of the HEI instability are made using high-impedance, floating potential probes and fast Mirnov coils. Analysis of these signals reveals the extent of the transport during high beta plasmas. During intense high beta HEI instabilities, fluctuations at the edge significantly exceed the magnitude of the equilibrium field generated by the high beta electrons and energetic electron confinement ends in under 100 musec. For heated plasmas, one of the consequences of the observed high beta transport is the presence of hysteresis in the neutral gas fueling required to stabilize and maintain the high beta plasma. Finally, a nonlinear, self-consistent numerical simulation of the growth and saturation of the HEI instability has been adapted for LDX and compared to experimental observations.

Role of mammalian homologue of Caenorhabditis elegans unc-13-1 (Munc13-1) in the recruitment of newcomer insulin granules in both first and second phases of glucose-stimulated insulin secretion in mouse islets.

PubMed

Xie, L; Zhu, D; Gaisano, H Y

2012-10-01

We have previously reported that the haplodeficient Munc13-1(+/-) mouse exhibits impaired biphasic glucose-stimulated insulin secretion (GSIS), causing glucose intolerance mimicking type 2 diabetes. Glucagon-like peptide-1 (GLP-1) can bypass these insulin-secretory defects in type 2 diabetes, but the mechanism of exocytotic events mediated by GLP-1 in rescuing insulin secretion is unclear. The total internal reflection fluorescence microscopy (TIRFM) technique was used to examine single insulin granule fusion events in mouse islet beta cells. There was no difference in the density of docked granules in the resting state between Munc13-1(+/+) and Munc13-1(+/-) mouse islet beta cells. While exocytosis of previously docked granules in Munc13-1(+/-) beta cells is reduced during high-K(+) stimulation as expected, we now find a reduction in additional exocytosis events that account for the major portion of GSIS, namely two types of newcomer granules, one which has a short docking time (short-dock) and another undergoing no docking before exocytosis (no-dock). As mammalian homologue of Caenorhabditis elegans unc-13-1 (Munc13-1) is a phorbol ester substrate, phorbol ester could partially rescue biphasic GSIS in Munc13-1-deficient beta cells by enhancing recruitment of short-dock newcomer granules for exocytosis. The more effective rescue of biphasic GSIS by GLP-1 than by phorbol was due to increased recruitment of both short-dock and no-dock newcomer granules. Phorbol ester and GLP-1 potentiation of biphasic GSIS are brought about by recruitment of distinct populations of newcomer granules for exocytosis, which may be mediated by Munc13-1 interaction with syntaxin-SNARE complexes other than that formed by syntaxin-1A.

Physics and Control of Locked Modes in the DIII-D Tokamak

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

Volpe, Francesco

This Final Technical Report summarizes an investigation, carried out under the auspices of the DOE Early Career Award, of the physics and control of non-rotating magnetic islands (“locked modes”) in tokamak plasmas. Locked modes are one of the main causes of disruptions in present tokamaks, and could be an even bigger concern in ITER, due to its relatively high beta (favoring the formation of Neoclassical Tearing Mode islands) and low rotation (favoring locking). For these reasons, this research had the goal of studying and learning how to control locked modes in the DIII-D National Fusion Facility under ITER-relevant conditions ofmore » high pressure and low rotation. Major results included: the first full suppression of locked modes and avoidance of the associated disruptions; the demonstration of error field detection from the interaction between locked modes, applied rotating fields and intrinsic errors; the analysis of a vast database of disruptive locked modes, which led to criteria for disruption prediction and avoidance.« less

A Global Approach for Quantitative Super Resolution and Electron Microscopy on Cryo and Epoxy Sections Using Self-labeling Protein Tags.

PubMed

Müller, Andreas; Neukam, Martin; Ivanova, Anna; Sönmez, Anke; Münster, Carla; Kretschmar, Susanne; Kalaidzidis, Yannis; Kurth, Thomas; Verbavatz, Jean-Marc; Solimena, Michele

2017-02-02

Correlative light and electron microscopy (CLEM) is a powerful approach to investigate the molecular ultrastructure of labeled cell compartments. However, quantitative CLEM studies are rare, mainly due to small sample sizes and the sensitivity of fluorescent proteins to strong fixatives and contrasting reagents for EM. Here, we show that fusion of a self-labeling protein to insulin allows for the quantification of age-distinct insulin granule pools in pancreatic beta cells by a combination of super resolution and transmission electron microscopy on Tokuyasu cryosections. In contrast to fluorescent proteins like GFP organic dyes covalently bound to self-labeling proteins retain their fluorescence also in epoxy resin following high pressure freezing and freeze substitution, or remarkably even after strong chemical fixation. This enables for the assessment of age-defined granule morphology and degradation. Finally, we demonstrate that this CLEM protocol is highly versatile, being suitable for single and dual fluorescent labeling and detection of different proteins with optimal ultrastructure preservation and contrast.

Activation of mTor Signaling by Gene Transduction to Induce Axon Regeneration in the Central Nervous System Following Neural Injury

DTIC Science & Technology

2014-03-01

bundle (MFB); quantification by confocal optical dissection of either GFP-positive axons in the MFB in transgenic TH- GFP mice or of Tomato -positive...axons following transduction with anterograde tracer Tomato -Tau. As anticipated, based on anatomical evidence showing an inability of AAV eIF4E to re...which the axon-targeted fusion protein Tomato -Tau is delivered to SN neurons by AAV and expression is driven by the robust chicken-beta actin promoter

Can Surgeon Demographic Factors Predict Postoperative Complication Rates After Elective Spinal Fusion?

PubMed

Chun, Danielle S; Cook, Ralph W; Weiner, Joseph A; Schallmo, Michael S; Barth, Kathryn A; Singh, Sameer K; Freshman, Ryan D; Patel, Alpesh A; Hsu, Wellington K

2018-03-01

Retrospective cohort. Determine whether surgeon demographic factors influence postoperative complication rates after elective spine fusion procedures. Surgeon demographic factors have been shown to impact decision making in the management of degenerative disease of the lumbar spine. Complication rates are frequently reported outcome measurements used to evaluate surgical treatments, quality-of-care, and determine health care reimbursements. However, there are few studies investigating the association between surgeon demographic factors and complication outcomes after elective spine fusions. A database of US spine surgeons with corresponding postoperative complications data after elective spine fusions was compiled utilizing public data provided by the Centers for Medicare and Medicaid Services (2011-2013) and ProPublica Surgeon Scorecard (2009-2013). Demographic data for each surgeon was collected and consisted of: surgical specialty (orthopedic vs. neurosurgery), years in practice, practice setting (private vs. academic), type of medical degree (MD vs. DO), medical school location (United States vs. foreign), sex, and geographic region of practice. General linear mixed models using a Beta distribution with a logit link and pairwise comparison with post hoc Tukey-Kramer were used to assess the relationship between surgeon demographics and complication rates. 2110 US-practicing spine surgeons who performed spine fusions on 125,787 Medicare patients from 2011 to 2013 met inclusion criteria for this study. None of the surgeon demographic factors analyzed were found to significantly affect overall complication rates in lumbar (posterior approach) or cervical spine fusion. Publicly available complication rates for individual spine surgeons are being utilized by hospital systems and patients to assess aptitude and gauge expectations. The increasing demand for transparency will likely lead to emphasis of these statistics to improve outcomes. We conclude that none of the surgeon demographic factors analyzed in this study are associated with differences in overall complications rates in patients undergoing elective spine fusion as published by the ProPublica Surgeon Scorecard. Level 3.

Platelet-derived growth factor-dependent association of the GTPase-activating protein of Ras and Src.

PubMed Central

Schlesinger, T K; Demali, K A; Johnson, G L; Kazlauskas, A

1999-01-01

Here we report that the platelet-derived growth factor beta receptor (betaPDGFR) is not the only tyrosine kinase able to associate with the GTPase-activating protein of Ras (RasGAP). The interaction of non-betaPDGFR kinase(s) with RasGAP was dependent on stimulation with platelet-derived growth factor (PDGF) and seemed to require tyrosine phosphorylation of RasGAP. Because the tyrosine phosphorylation site of RasGAP is in a sequence context that is favoured by the Src homology 2 ('SH2') domain of Src family members, we tested the possibility that Src was the kinase that associated with RasGAP. Indeed, Src interacted with phosphorylated RasGAP fusion proteins; immunodepletion of Src markedly decreased the recovery of the RasGAP-associated kinase activity. Thus PDGF-dependent tyrosine phosphorylation of RasGAP results in the formation of a complex between RasGAP and Src. To begin to address the relevance of these observations, we focused on the consequences of the interaction of Src and RasGAP. We found that a receptor mutant that did not activate Src was unable to efficiently mediate the tyrosine phosphorylation of phospholipase Cgamma (PLCgamma). Taken together, these observations support the following hypothesis. When RasGAP is recruited to the betaPDGFR, it is phosphorylated and associates with Src. Once bound to RasGAP, Src is no longer able to promote the phosphorylation of PLCgamma. This hypothesis offers a mechanistic explanation for our previously published findings that the recruitment of RasGAP to the betaPDGFR attenuates the tyrosine phosphorylation of PLCgamma. Finally, these findings suggest a novel way in which RasGAP negatively regulates signal relay by the betaPDGFR. PMID:10567236

Micro-power dissipation device described

NASA Astrophysics Data System (ADS)

Mao, X.; Zhou, L.; Zhou, J.

1985-11-01

The common-emitter current gain beta of a common two-pole transistor is generally below 250. They are referred to as high-beta or high gain transistors when the beta of such transistors exceeds 300. When the beta of a transistor is higher than 1,000, it is called a super-beta transistor (SBT) or supergain transistor. The micropower dissipation type has the widest applications among the high-beta. Micropower dissipation high-beta means that there is a high gain or a superhigh gain under a microcurrent. The device is widely used in small signal-detection systems and stereo audio equipment because of their characteristics of high gain, low frequency and low noise under small signals.

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

PubMed

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

2011-03-01

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

The Flavivirus Precursor Membrane-Envelope Protein Complex: Structure and Maturation

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

Li, Long; Lok, Shee-Mei; Yu, I-Mei

2008-09-17

Many viruses go through a maturation step in the final stages of assembly before being transmitted to another host. The maturation process of flaviviruses is directed by the proteolytic cleavage of the precursor membrane protein (prM), turning inert virus into infectious particles. We have determined the 2.2 angstrom resolution crystal structure of a recombinant protein in which the dengue virus prM is linked to the envelope glycoprotein E. The structure represents the prM-E heterodimer and fits well into the cryo-electron microscopy density of immature virus at neutral pH. The pr peptide {beta}-barrel structure covers the fusion loop in E, preventingmore » fusion with host cell membranes. The structure provides a basis for identifying the stages of its pH-directed conformational metamorphosis during maturation, ending with release of pr when budding from the host.« less

Identification and characterization of the Myxococcus xanthus bsgA gene product.

PubMed Central

Gill, R E; Bornemann, M C

1988-01-01

The bsgA mutants of Myxococcus xanthus are blocked at a very early stage of the developmental program. They fail to produce fruiting bodies or to sporulate under normal conditions but can be rescued by extracellular complementation in mixtures with wild-type cells. A bsgA-lacZ gene fusion was constructed and expressed in Escherichia coli. The resulting fusion protein, which has beta-galactosidase enzyme activity, was partially purified by affinity chromatography and preparative polyacrylamide gel electrophoresis. The protein was used to immunize mice, which produced a hybridoma secreting monoclonal antibody that was specific for the bsgA gene product. The monoclonal antibody was used in Western blot (immunoblot) experiments to determine the apparent cellular location of the bsgA protein in M. xanthus and to compare the level of this protein at various times in the Myxococcus life cycle. Images PMID:2846515

A short introduction to the status and motivation for reversed field pinch and compact toroid research

NASA Astrophysics Data System (ADS)

Dreicer, H.

1987-09-01

Potential commercial fusion power systems must be acceptable from a safety and environmental standpoint. They must also promise to be competitive with other sources of energy (i.e., fossil, fission, etc.) when considered from the standpoint of the cost of electricity (COE) and the unit direct cost (UDC) in dollars/kWe. These costs are affected by a host of factors including recirculating power, plant availability, construction time, capital cost, etc., and are influenced by technological complexity. In an attempt to meet these requirements, the emphasis of fusion research in the United States has been moving toward smaller, lower-cost systems. There is increased interest in higher beta tokamaks and stellarators, and in compact alternate concepts such as the Reversed Field Pinch (RFP) and the Compact Toroids (CTs) which are, in part, the subject of this paper.

Expression of the nifBfdxNnifOQ region of Azotobacter vinelandii and its role in nitrogenase activity.

PubMed Central

Rodríguez-Quiñones, F; Bosch, R; Imperial, J

1993-01-01

The nifBQ transcriptional unit of Azotobacter vinelandii has been previously shown to be required for activity of the three nitrogenase systems, Mo nitrogenase, V nitrogenase, and Fe nitrogenase, present in this organism. We studied regulation of expression and the role of the nifBQ region by means of translational beta-galactosidase fusions to each of the five open reading frames: nifB, orf2 (fdxN), orf3 (nifO), nifQ, and orf5. Expression of the first three open reading frames was observed under all three diazotrophic conditions; expression of orf5 was never observed. Genes nifB and fdxN were expressed at similar levels. With Mo, expression of nifO and nifQ was approximately 20- and approximately 400-fold lower than that of fdxN, respectively. Without Mo, expression of nifB dropped three- to fourfold and that of nifQ dropped to the detection limit. However, expression of nifO increased threefold. The products of nifB, fdxN, nifO, and nifQ have been visualized in A. vinelandii as beta-galactosidase fusion proteins with the expected molecular masses. The NifB- fusion lacked activity for any of the three nitrogenase systems and showed an iron-molybdenum cofactor-deficient phenotype in the presence of Mo. The FdxN- mutation resulted in reduced nitrogenase activities, especially when V was present. Dinitrogenase activity in extracts was similarly affected, suggesting a role of FdxN in iron-molybdenum cofactor synthesis. The NifO(-)-producing mutation did not affect any of the nitrogenases under standard diazotrophic conditions. The NifQ(-)-producing mutation resulted in an increased (approximately 1,000-fold) Mo requirement for Mo nitrogenase activity, a phenotype already observed with Klebsiella pneumoniae. No effect of the NifQ(-)-producing mutation on V or Fe nitrogenase was found; this is consistent with its very low expression under those conditions. Mutations in orf5 had no effect on nitrogenase activity. Images PMID:8491713

Cloning of the Pseudomonas aeruginosa outer membrane porin protein P gene: evidence for a linked region of DNA homology.

PubMed Central

Siehnel, R J; Worobec, E A; Hancock, R E

1988-01-01

The gene encoding the outer membrane phosphate-selective porin protein P from Pseudomonas aeruginosa was cloned into Escherichia coli. The protein product was expressed and transported to the outer membrane of an E. coli phoE mutant and assembled into functional trimers. Expression of a product of the correct molecular weight was confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot (immunoblot) analysis, using polyclonal antibodies to protein P monomer and trimer forms. Protein P trimers were partially purified from the E. coli clone and shown to form channels with the same conductance as those formed by protein P from P. aeruginosa. The location and orientation of the protein P-encoding (oprP) gene on the cloned DNA was identified by three methods: (i) mapping the insertion point of transposon Tn501 in a previously isolated P. aeruginosa protein P-deficient mutant; (ii) hybridization of restriction fragments from the cloned DNA to an oligonucleotide pool synthesized on the basis of the amino-terminal protein sequence of protein P; and (iii) fusion of a PstI fragment of the cloned DNA to the amino terminus of the beta-galactosidase gene of pUC8, producing a fusion protein that contained protein P-antigenic epitopes. Structural analysis of the cloned DNA and P. aeruginosa chromosomal DNA revealed the presence of two adjacent PstI fragments which cross-hybridized, suggesting a possible gene duplication. The P-related (PR) region hybridized to the oligonucleotide pool described above. When the PstI fragment which contained the PR region was fused to the beta-galactosidase gene of pUC8, a fusion protein was produced which reacted with a protein P-specific antiserum. However, the restriction endonuclease patterns of the PR region and the oprP gene differed significantly beyond the amino-terminal one-third of the two genes. Images PMID:2834340

Generation and characterization of recombinant bivalent fusion protein r-Cpib for immunotherapy against Clostridium perfringens beta and iota toxemia.

PubMed

Das, Shreya; Majumder, Saugata; Kingston, Joseph J; Batra, Harsh V

2016-02-01

Clostridium perfringens beta (CPB) and iota (CPI) toxaemias result in some of the most lethal forms of haemorrhagic and necrotic enteritis and sudden death syndrome affecting especially neonates. While CPB enterotoxemia is one of the most common forms of clostridial enterotoxemia, CPI enterotoxemia though putatively considered to be rare is an emerging cause of concern. The similarities in clinical manifestation, gross and histopathology findings of both types of toxaemias coupled to the infrequency of CPI toxaemia might lead to symptomatic misidentification with Type C resulting in therapeutic failure due to habitual administration of CPB anti-toxin which is ineffective against CPI. Therefore in the present study, to generate a composite anti-toxin capable of neutralizing both toxaemias, a novel bivalent chimera r-Cpib was constructed by splicing the non-toxic C terminal binding regions of CPB and CPI, via a flexible glycine linker (G4S) by overlap-extension PCR. The fusion protein was characterized for its therapeutic abilities toward CPI and CPB toxin neutralizations. The r-Cpib was found to be non-toxic and could competitively inhibit binding of CPB to host cell receptors thereby reducing its cytotoxicity. Immunization of mice with r-Cpib generated specific antibodies capable of neutralizing the above toxaemias both in vitro and in vivo. Caco-2 cells exposed to a mixture of anti-r-Cpib sera and native CPI or CPB, displayed significantly superior protection against the respective toxins while passive challenge of mice with a similar mixture resulted in 83 and 91% protection against CPI and CPB respectively. Alternatively, mice exposed to a mixture of sham sera and native toxins died within 2-3 days. This work thus demonstrates r-Cpib as a novel bivalent fusion protein capable of efficient immunotherapy against C. perfringens CPI and CPB toxaemia. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Dermatophagoides farinae group 22 allergen: cloning and expression in Escherichia coli.

PubMed

Cui, Yu-bao; Cai, Hong-xing; Zhou, Ying; Wang, Nan; Yu, Li-li; Yang, Li; Zhang, Cheng-bo

2015-09-01

Dermatophagoides farinae (Hughes) (Acari: Pyroglyphidae) and other domestic mites produce allergens that affect people worldwide. Here, the complementary DNA (cDNA) coding for group 22 allergen of D. farinae (Der f 22) from China was cloned, sequenced, and expressed successfully. The cDNA encoding Der f 22 was synthesized by reverse transcription polymerase chain reaction (RT-PCR), then ligated to the pCold-TF for expression in Escherichia coli BL21 cells. The purified recombinant fusion protein was identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), Western-blotting, and tandem matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF/TOF). The full-length cDNA comprised 468 nucleotides and was 99.57% (466/468) identical with the reference sequence (GenBank: DQ643992). After the plasmid pCold-TF-Der f 22 was transformed into E. coli BL21 and expressed with the induction of IPTG, SDS-PAGE showed a specific band for the recombinant fusion protein. The recombinant fusion protein, which was purified by chromatography, bound with a His-tagged antibody by Western blotting. MALDI-TOF/TOF mass spectrometry revealed that the structure of the recombinant protein was identical to the predicted Der f 22 structure. The hydrophilic protein contains a signal peptide of 20 amino acids, and the mature Der f 22 consists of 135 amino acid residues with a molecular weight of 14.7 kDa and theoretical isoelectric points (pI) of 6.38. Its secondary structure comprises an alpha helix (38.5%), beta-sheet (45.9%), random coils (11.85%), and beta-turns (11.1%). This work represents the first reported full-length sequence and successful cloning of Der f 22 from D. farinae in China; bioinformatics analysis can be used to further study the allergenicity and clinical utility of the recombinant Der f 22. © 2015 ARS-AAOA, LLC.

Membrane-anchored plakoglobins have multiple mechanisms of action in Wnt signaling.

PubMed

Klymkowsky, M W; Williams, B O; Barish, G D; Varmus, H E; Vourgourakis, Y E

1999-10-01

In Wnt signaling, beta-catenin and plakoglobin transduce signals to the nucleus through interactions with TCF-type transcription factors. However, when plakoglobin is artificially engineered to restrict it to the cytoplasm by fusion with the transmembrane domain of connexin (cnxPg), it efficiently induces a Wnt-like axis duplication phenotype in Xenopus. In Xenopus embryos, maternal XTCF3 normally represses ventral expression of the dorsalizing gene Siamois. Two models have been proposed to explain the Wnt-like activity of cnxPg: 1) that cnxPg inhibits the machinery involved in the turnover of cytosolic beta-catenin, which then accumulates and inhibits maternal XTCF3, and 2) that cnxPg directly acts to inhibit XTCF3 activity. To distinguish between these models, we created a series of N-terminal deletion mutations of cnxPg and examined their ability to induce an ectopic axis in Xenopus, activate a TCF-responsive reporter (OT), stabilize beta-catenin, and colocalize with components of the Wnt signaling pathway. cnxPg does not colocalize with the Wnt pathway component Dishevelled, but it does lead to the redistribution of APC and Axin, two proteins involved in the regulation of beta-catenin turnover. Expression of cnxPg increases levels of cytosolic beta-catenin; however, this effect does not completely explain its signaling activity. Although cnxPg and Wnt-1 stabilize beta-catenin to similar extents, cnxPg activates OT to 10- to 20-fold higher levels than Wnt-1. Moreover, although LEF1 and TCF4 synergize with beta-catenin and plakoglobin to activate OT, both suppress the signaling activity of cnxPg. In contrast, XTCF3 suppresses the signaling activity of both beta-catenin and cnxPg. Both exogenous XLEF1 and XTCF3 are sequestered in the cytoplasm of Xenopus cells by cnxPg. Based on these data, we conclude that, in addition to its effects on beta-catenin, cnxPg interacts with other components of the Wnt pathway, perhaps TCFs, and that these interactions contribute to its signaling activity.

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.

Immunoreactivity of polyclonal antibodies generated against the carboxy terminus of the predicted amino acid sequence of the Huntington disease gene

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

Alkatib, G.; Graham, R.; Pelmear-Telenius, A.

1994-09-01

A cDNA fragment spanning the 3{prime}-end of the Huntington disease gene (from 8052 to 9252) was cloned into a prokaryotic expression vector containing the E. Coli lac promoter and a portion of the coding sequence for {beta}-galactosidase. The truncated {beta}-galactosidase gene was cleaved with BamHl and fused in frame to the BamHl fragment of the Huntington disease gene 3{prime}-end. Expression analysis of proteins made in E. Coli revealed that 20-30% of the total cellular proteins was represented by the {beta}-galactosidase-huntingtin fusion protein. The identity of the Huntington disease protein amino acid sequences was confirmed by protein sequence analysis. Affinity chromatographymore » was used to purify large quantities of the fusion protein from bacterial cell lysates. Affinity-purified proteins were used to immunize New Zealand white rabbits for antibody production. The generated polyclonal antibodies were used to immunoprecipitate the Huntington disease gene product expressed in a neuroblastoma cell line. In this cell line the antibodies precipitated two protein bands of apparent gel migrations of 200 and 150 kd which together, correspond to the calculated molecular weight of the Huntington disease gene product (350 kd). Immunoblotting experiments revealed the presence of a large precursor protein in the range of 350-750 kd which is in agreement with the predicted molecular weight of the protein without post-translational modifications. These results indicate that the huntingtin protein is cleaved into two subunits in this neuroblastoma cell line and implicate that cleavage of a large precursor protein may contribute to its biological activity. Experiments are ongoing to determine the precursor-product relationship and to examine the synthesis of the huntingtin protein in freshly isolated rat brains, and to determine cellular and subcellular distribution of the gene product.« less

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

PubMed

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

2018-01-01

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

Beer Law Constants and Vapor Pressures of HgI2 over HgI2(s,l)

NASA Technical Reports Server (NTRS)

Su, Ching-Hua; Zhu, Shen; Ramachandran, N.; Burger, A.; Whitaker, Ann F. (Technical Monitor)

2001-01-01

The optical absorption spectra of the vapor phase over HgI2(s,l) were measured for wavelengths between 200 and 600 nm. The spectra show that the sample sublimed congruently into HgI2 with no Hg or I2 absorption spectrum observed. The Beer's Law constants for 15 wavelengths between 200 and 440 nm were determined. From these constants the vapor pressure of H912, P, was established as a function of temperatures for the liquid and the solid Beta-phases. The expressions correspond to the enthalpies of vaporization and sublimation of 15.30 and 20.17 Kcal/mole, respectively, for the liquid and the Beta-phase HgI2. The difference in the enthalpies gives an enthalpy of fusion of 4.87 Kcal/mole and the intersection of the two expressions gives a melting point of 537 K.

Kinetic electromagnetic instabilities in an ITB plasma with weak magnetic shear

NASA Astrophysics Data System (ADS)

Chen, W.; Yu, D. L.; Ma, R. R.; Shi, P. W.; Li, Y. Y.; Shi, Z. B.; Du, H. R.; Ji, X. Q.; Jiang, M.; Yu, L. M.; Yuan, B. S.; Li, Y. G.; Yang, Z. C.; Zhong, W. L.; Qiu, Z. Y.; Ding, X. T.; Dong, J. Q.; Wang, Z. X.; Wei, H. L.; Cao, J. Y.; Song, S. D.; Song, X. M.; Liu, Yi.; Yang, Q. W.; Xu, M.; Duan, X. R.

2018-05-01

Kinetic Alfvén and pressure gradient driven instabilities are very common in magnetized plasmas, both in space and the laboratory. These instabilities will be easily excited by energetic particles (EPs) and/or pressure gradients in present-day fusion and future burning plasmas. This will not only cause the loss and redistribution of the EPs, but also affect plasma confinement and transport. Alfvénic ion temperature gradient (AITG) instabilities with the frequency ω_BAE<ω<ω_TAE and the toroidal mode numbers n=2{-}8 are found to be unstable in NBI internal transport barrier plasmas with weak shear and low pressure gradients, where ω_BAE and ω_TAE are the frequencies of the beta- and toroidicity-induced Alfvén eigenmodes, respectively. The measured results are consistent with the general fishbone-like dispersion relation and kinetic ballooning mode equation, and the modes become more unstable the smaller the magnetic shear is in low pressure gradient regions. The interaction between AITG activity and EPs also needs to be investigated with greater attention in fusion plasmas, such as ITER (Tomabechi and The ITER Team 1991 Nucl. Fusion 31 1135), since these fluctuations can be enhanced by weak magnetic shear and EPs.

Titration of DnaA protein by oriC DnaA-boxes increases dnaA gene expression in Escherichia coli.

PubMed Central

Hansen, F G; Koefoed, S; Sørensen, L; Atlung, T

1987-01-01

Binding of the DnaA protein to its binding sites, the DnaA-boxes (TTATCCACA), was measured by a simple physiological approach. The presence of extra DnaA-boxes in growing cells leads to a derepression of dnaA gene expression, measured as beta-galactosidase activity of a dnaA-lacZ fusion polypeptide. Different DnaA-boxes caused different degrees of derepression indicating that the DnaA protein requires sequences in addition to the DnaA-box for efficient binding. The DnaA-boxes in oriC might act cooperatively in binding of the DnaA protein. The derepressed levels of DnaA protein obtained in a strain carrying an oriC+-pBR322 chimera were very high and sufficient to activate oriC on the chimeric plasmid, which was maintained at a copy number more than three times that of pBR322. PMID:3034578

Scrape-off-layer characterization and current-control of kink modes in HBT-EP

NASA Astrophysics Data System (ADS)

Brooks, John; Stewart, Ian; Levesque, Jeffrey; Mauel, Mike; Navratil, Gerald

2017-10-01

Scrape-off layer (SOL) currents and their paths through tokamaks are not well understood, but their control may prove crucial to the success of ITER and future fusion energy devices. We extend Columbia University's High Beta Tokamak-Extended Pulse (HBT-EP) experiment and active GPU feedback system to study the SOL and control MHD kink instabilities by actively controlling these currents. First, the radial plasma profiles and the edge structure of kink instabilities are measured with two triple probes. Second, we use active feedback control of a radially adjustable biased electrode to change the rotation and magnitude of slowly growing kink instabilities. By changing the phase between the probe's voltage and the edge instability with active feedback, we study its ability to influence and control plasma MHD structures. This work is in preparation for a planned 2018 multi-electrode SOL control upgrade. Supported by U.S. DOE Grant DE-FG02-86ER53222.

Rotational excitation of the Hoyle state in 12C

NASA Astrophysics Data System (ADS)

Garg, R.; Barton, C.; Diget, C. Aa; Courtin, S.; Fruet, G.; Fynbo, H. O. U.; Howard, A.; Illana, A.; Jenkins, D. G.; Marroquin, I.; Kirsebom, O. S.; Lund, M. V.; Moore, I.; Perea, A.; Refsgaard, J.; Riley, J. E.; Rinta-Antila, S.; Sinclair, L.; Tengblad, O.; IGISOL Collaboration

2018-01-01

12C is synthesised in stars by fusion of three α particles. This process occurs through a resonance in the 12C nucleus, famously known as the Hoyle state. In this state, the 12C nucleus exists as a cluster of α particles. The state is the band-head for a rotational band with the 2+ rotational excitation predicted in the energy region 9 - 11 MeV. This rotational excitation can affect the triple-α process reaction rate by more than an order of magnitude at high temperatures (109 K). Depending on the energy of the resonance, the knowledge of the state can also help determine the structure of the Hoyle state. In the work presented here, the state of interest is populated by beta decay of radioactive 12N ion beam delivered by the IGISOL facility at JYFL, Jyväskylä.

Developmental Changes is Expression of Beta-Adrenergic Receptors in Cultures of C2C12 Skeletal Muscle Cells

NASA Technical Reports Server (NTRS)

Young, Ronald B.; Bridge, K. Y.; Vaughn, J. R.

2000-01-01

beta-Adrenergic receptor (bAR) agonists have been reported to modulate growth in several mammalian and avian species, and bAR agonists presumably exert their physiological action on skeletal muscle cells through this receptor. Because of the importance of bAR regulation on muscle protein metabolism in muscle cells, the objectives of this study were to determine the developmental expression pattern of the bAR population in C2C12 skeletal muscle cells, and to analyze changes in both the quantity and isoform expression of the major muscle protein, myosin. The number of bAR in mononucleated C2C12 cells was approximately 8,000 bAR per cell, which is comparable with the population reported in several other nonmuscle cell types. However, the bar population increased after myoblast fusion to greater than 50,000 bAR per muscle cell equivalent. The reasons for this apparent over-expression of bAR in C2C12 cells is not known. The quantity of myosin also increased after C2C12 myoblast fusion, but the quantity of myosin was less than that reported in primary muscle cell cultures. Finally, at least five different isoforms of myosin heavy chain could be resolved in C2C12 cells, and three of these exhibited either increased or decreased developmental regulation relative to the others. Thus, C2C12 myoblasts undergo developmental regulation of bAR population and myosin heavy chain isoform expression.

Induction of bphA, encoding biphenyl dioxygenase, in two polychlorinated biphenyl-degrading bacteria, psychrotolerant Pseudomonas strain Cam-1 and mesophilic Burkholderia strain LB400.

PubMed

Master, E R; Mohn, W W

2001-06-01

We investigated induction of biphenyl dioxygenase in the psychrotolerant polychlorinated biphenyl (PCB) degrader Pseudomonas strain Cam-1 and in the mesophilic PCB degrader Burkholderia strain LB400. Using a counterselectable gene replacement vector, we inserted a lacZ-Gm(r) fusion cassette between chromosomal genes encoding the large subunit (bphA) and small subunit (bphE) of biphenyl dioxygenase in Cam-1 and LB400, generating Cam-10 and LB400-1, respectively. Potential inducers of bphA were added to cell suspensions of Cam-10 and LB400-1 incubated at 30 degrees C, and then beta-galactosidase activity was measured. Biphenyl induced beta-galactosidase activity in Cam-10 to a level approximately six times greater than the basal level in cells incubated with pyruvate. In contrast, the beta-galactosidase activities in LB400-1 incubated with biphenyl and in LB400-1 incubated with pyruvate were indistinguishable. At a concentration of 1 mM, most of the 40 potential inducers tested were inhibitory to induction by biphenyl of beta-galactosidase activity in Cam-10. The exceptions were naphthalene, salicylate, 2-chlorobiphenyl, and 4-chlorobiphenyl, which induced beta-galactosidase activity in Cam-10, although at levels that were no more than 30% of the levels induced by biphenyl. After incubation for 24 h at 7 degrees C, biphenyl induced beta-galactosidase activity in Cam-10 to a level approximately four times greater than the basal level in cells incubated with pyruvate. The constitutive level of beta-galactosidase activity in LB400-1 grown at 15 degrees C was approximately five times less than the level in LB400-1 grown at 30 degrees C. Thus, there are substantial differences in the effects of physical and chemical environmental conditions on genetic regulation of PCB degradation in different bacteria.

Progression of degenerative mitral stenosis: insights from a cohort of 254 patients.

PubMed

Tyagi, Gaurav; Dang, Patricia; Pasca, Ioana; Patel, Reena; Pai, Ramdas G

2014-11-01

Degenerative mitral stenosis (DMS) is an increasingly common echocardiographic finding, yet the clinical and biological behavior and rate of progression of the condition are unknown. A total of 254 patients was identified from the authors' echocardiographic database with DMS, defined as severe mitral annular calcification with extension into the mitral leaflets resulting in transmitral flow acceleration with a mean diastolic gradient of >2 mmHg in the absence of commissural fusion. Each patient required paired echocardiograms to have been recorded at least three months apart. Clinical, biochemical and pharmacological data were collected from each patient and related to the annualized rate of increase in mean diastolic mitral gradient and stenosis severity on a scale of 0 to 3. The characteristics of the patients were as follows: mean age 71 +/- 15 years; female gender 73%; and left ventricular ejection fraction 66 +/- 13%. Diabetes was present in 50% of patients, renal insufficiency in 40%, and coronary artery disease in 50%. Over a follow up period of 2.6 +/- 2.2 years, the mean gradient was increased by 0.8 +/- 2.4 mmHg (range: 0-15 mmHg) per year, while the stenosis grade was increased by 0.18 +/- 0.5 (range: 0-3) per year. The rate of progression was faster in patients with lesser degrees of stenosis (p = 0.01) and low serum albumen levels (p = 0.04), and slower in those receiving beta-blockers (p = 0.01). Milder stenosis, diabetes mellitus and lack of beta-blocker use were independent predictors of faster DMS progression. DMS progression is highly variable, but generally slow; its progression is accelerated in the presence of diabetes mellitus, but is retarded by beta-blocker use. DMS may be an active biological process offering potentially modifiable targets for intervention.

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

In vitro binding of the asialoglycoprotein receptor to the beta adaptin of plasma membrane coated vesicles.

PubMed Central

Beltzer, J P; Spiess, M

1991-01-01

The asialoglycoprotein (ASGP) receptor was used to probe total clathrin-coated vesicle proteins and purified adaptor proteins (APs) which had been fractionated by gel electrophoresis and transferred to nitrocellulose. The receptor was found to interact with proteins of approximately 100 kDa. The cytoplasmic domain of the ASGP receptor subunit H1 fused to dihydrofolate reductase competed for receptor binding to the 100 kDa polypeptide in the plasma membrane-type AP complexes (AP-2). A fusion protein containing the cytoplasmic domain of the endocytic mutant haemagglutinin HA-Y543 also competed, but a protein with the wild-type haemagglutinin sequence did not. This indicates that the observed interaction is specific for the cytoplasmic domain of the receptor and involves the tyrosine signal for endocytosis. When fractionated by gel electrophoresis in the presence of urea, the ASGP receptor binding polypeptide displayed a characteristic shift in electrophoretic mobility identifying it as the beta adaptin. Partial proteolysis of the AP-2 preparation followed by the receptor binding assay revealed that the aminoterminal domain of the beta adaptin contains the binding site for receptors. Images PMID:1935897

Host cell recognition by the henipaviruses: Crystal structures of the Nipah G attachment glycoprotein and its complex with ephrin-B3

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

Xu, Kai; Rajashankar, Kanagalaghatta R.; Chan, Yee-Peng

2008-07-28

Nipah virus (NiV) and Hendra virus are the type species of the highly pathogenic paramyxovirus genus Henipavirus, which can cause severe respiratory disease and fatal encephalitis infections in humans, with case fatality rates approaching 75%. NiV contains two envelope glycoproteins, the receptor-binding G glycoprotein (NiV-G) that facilitates attachment to host cells and the fusion (F) glycoprotein that mediates membrane merger. The henipavirus G glycoproteins lack both hemagglutinating and neuraminidase activities and, instead, engage the highly conserved ephrin-B2 and ephrin-B3 cell surface proteins as their entry receptors. Here, we report the crystal structures of the NiV-G both in its receptor-unbound statemore » and in complex with ephrin-B3, providing, to our knowledge, the first view of a paramyxovirus attachment complex in which a cellular protein is used as the virus receptor. Complex formation generates an extensive protein-protein interface around a protruding ephrin loop, which is inserted in the central cavity of the NiV-G {beta}-propeller. Analysis of the structural data reveals the molecular basis for the highly specific interactions of the henipavirus G glycoproteins with only two members (ephrin-B2 and ephrin-B3) of the very large ephrin family and suggests how they mediate in a unique fashion both cell attachment and the initiation of membrane fusion during the virus infection processes. The structures further suggest that the NiV-G/ephrin interactions can be effectively targeted to disrupt viral entry and provide the foundation for structure-based antiviral drug design.« less

The use of electrochemistry for the synthesis of 17 alpha-hydroxyprogesterone by a fusion protein containing P450c17.

PubMed

Estabrook, R W; Shet, M S; Faulkner, K; Fisher, C W

1996-11-01

A method has been developed for the commercial application of the unique oxygen chemistry catalyzed by various cytochrome P450s. This is illustrated here for the synthesis of hydroxylated steroids. This method requires the preparation of large amounts of enzymatically functional P450 proteins that can serve as catalysts and a technique for providing electrons at an economically acceptable cost. To generate large amounts of enzymatically active recombinant P450s we have engineered the cDNAs for various P450s, including bovine adrenal P450c17, by linking them to a modified cDNA for rat NADPH-P450 reductase and placing them in the plasmid pCWori+. Transformation of E. coli results in the high level expression of an enzymatically active protein that can be easily purified by affinity chromatography. Incubation of the purified enzyme with steroid in a reaction vessel containing a platinum electrode and a Ag/AgCl electrode couple poised at -650 mV, together with the electromotively active redox mediator, cobalt sepulchrate, results in the 17 alpha-hydroxylation of progesterone at rates as high as 25 nmoles of progesterone hydroxylated/min/nmole of P450. Thus, high concentrations of hydroxylated steroids can be produced with incubation conditions of hours duration without the use of costly NADPH. Similar experiments have been carried out for the generation of the 6 beta-hydroxylation product of testosterone (using a fusion protein containing human P450 3A4). It is apparent that this method is applicable to many other P450 catalyzed reactions for the synthesis of large amounts of hydroxylated steroid metabolites. The electrochemical system is also applicable to drug discovery studies for the characterization of drug metabolites.

Beta Emission and Bremsstrahlung

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

Karpius, Peter Joseph

2017-11-13

Bremsstrahlung is continuous radiation produced by beta particles decelerating in matter; different beta emitters have different endpoint energies; high-energy betas interacting with high-Z materials will more likely produce bremsstrahlung; depending on the data, sometimes all you can say is that a beta emitter is present.

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

NASA Astrophysics Data System (ADS)

Jortner, Joshua; Last, Isidore

2017-09-01

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

Overexpression of an endo-1,4-β-glucanase V gene (EGV) from Trichoderma reesei leads to the accumulation of cellulase activity in transgenic rice.

PubMed

Li, X Y; Liu, F; Hu, Y F; Xia, M; Cheng, B J; Zhu, S W; Ma, Q

2015-12-21

The ectopic expression of cellulase in biomass can reduce the cost of biofuel conversion. This trait modification technique is highly beneficial for biofuel production. In this study, we isolated an endo-1,4-beta-glucanase gene (EGV) from Trichoderma reesei and inserted this gene downstream of a fragment encoding the signal peptide Apo-SP in a modified pCAMBIA1301 vector to obtain an Apo-SP and AsRed fusion protein. Transient expression of this fusion protein in onion epidermal cells showed that the Apo-SP signal was localized to the plastids. EGV transgenic rice plants that did not carry screening marker genes were obtained through overexpression of the pDTB double T-DNA vector. Western blotting showed that EGV was expressed in the dry straw of T0 generation transgenic rice plants and in fresh leaves of the T1 generation. More importantly, our results also showed that the peptide product of EGV in the transgenic plants folded correctly and was capable of digesting the cellulase substrate CMC. Additionally, cellulase activity remained stable in the straw that had been dried at room temperature for three months. This study presents an important technical approach for the development of transgenic rice straw that has stable cellulase activity and can be used for biofuel conversion.

EDITORIAL: Safety aspects of fusion power plants

NASA Astrophysics Data System (ADS)

Kolbasov, B. N.

2007-07-01

This special issue of Nuclear Fusion contains 13 informative papers that were initially presented at the 8th IAEA Technical Meeting on Fusion Power Plant Safety held in Vienna, Austria, 10-13 July 2006. Following recommendation from the International Fusion Research Council, the IAEA organizes Technical Meetings on Fusion Safety with the aim to bring together experts to discuss the ongoing work, share new ideas and outline general guidance and recommendations on different issues related to safety and environmental (S&E) aspects of fusion research and power facilities. Previous meetings in this series were held in Vienna, Austria (1980), Ispra, Italy (1983), Culham, UK (1986), Jackson Hole, USA (1989), Toronto, Canada (1993), Naka, Japan (1996) and Cannes, France (2000). The recognized progress in fusion research and technology over the last quarter of a century has boosted the awareness of the potential of fusion to be a practically inexhaustible and clean source of energy. The decision to construct the International Thermonuclear Experimental Reactor (ITER) represents a landmark in the path to fusion power engineering. Ongoing activities to license ITER in France look for an adequate balance between technological and scientific deliverables and complying with safety requirements. Actually, this is the first instance of licensing a representative fusion machine, and it will very likely shape the way in which a more common basis for establishing safety standards and policies for licensing future fusion power plants will be developed. Now that ITER licensing activities are underway, it is becoming clear that the international fusion community should strengthen its efforts in the area of designing the next generations of fusion power plants—demonstrational and commercial. Therefore, the 8th IAEA Technical Meeting on Fusion Safety focused on the safety aspects of power facilities. Some ITER-related safety issues were reported and discussed owing to their potential importance for the fusion power plant research programmes. The objective of this Technical Meeting was to examine in an integrated way all the safety aspects anticipated to be relevant to the first fusion power plant prototype expected to become operational by the middle of the century, leading to the first generation of economically viable fusion power plants with attractive S&E features. After screening by guest editors and consideration by referees, 13 (out of 28) papers were accepted for publication. They are devoted to the following safety topics: power plant safety; fusion specific operational safety approaches; test blanket modules; accident analysis; tritium safety and inventories; decommissioning and waste. The paper `Main safety issues at the transition from ITER to fusion power plants' by W. Gulden et al (EU) highlights the differences between ITER and future fusion power plants with magnetic confinement (off-site dose acceptance criteria, consequences of accidents inside and outside the design basis, occupational radiation exposure, and waste management, including recycling and/or final disposal in repositories) on the basis of the most recent European fusion power plant conceptual study. Ongoing S&E studies within the US inertial fusion energy (IFE) community are focusing on two design concepts. These are the high average power laser (HAPL) programme for development of a dry-wall, laser-driven IFE power plant, and the Z-pinch IFE programme for the production of an economically-attractive power plant using high-yield Z-pinch-driven targets. The main safety issues related to these programmes are reviewed in the paper `Status of IFE safety and environmental activities in the US' by S. Reyes et al (USA). The authors propose future directions of research in the IFE S&E area. In the paper `Recent accomplishments and future directions in the US Fusion Safety & Environmental Program' D. Petti et al (USA) state that the US fusion programme has long recognized that the S&E potential of fusion can be attained by prudent materials selection, judicious design choices, and integration of safety requirements into the design of the facility. To achieve this goal, S&E research is focused on understanding the behaviour of the largest sources of radioactive and hazardous materials in a fusion facility, understanding how energy sources in a fusion facility could mobilize those materials, developing integrated state-of-the-art S&E computer codes and risk tools for safety assessment, and evaluating and improving fusion facility design in terms of accident safety, worker safety, and waste disposal. There are three papers considering safety issues of the test blanket modules (TBM) producing tritium to be installed in ITER. These modules represent different concepts of demonstration fusion power facilities (DEMO). L. Boccaccini et al (Germany) analyses the possibility of jeopardizing the ITER safety under specific accidents in the European helium-cooled pebble-bed TBM, e.g. pressurization of the vacuum vessel (VV), hydrogen production from the Be-steam reaction, the possible interconnection between the port cell and VV causing air ingress. Safety analysis is also presented for Chinese TBM with a helium-cooled solid breeder to be tested in ITER by Z. Chen et al (China). Radiological inventories, afterheat, waste disposal ratings, electromagnetic characteristics, LOCA and tritium safety management are considered. An overview of a preliminary safety analysis performed for a US proposed TBM is presented by B. Merrill et al (USA). This DEMO relevant dual coolant liquid lead-lithium TBM has been explored both in the USA and EU. T. Pinna et al (Italy) summarize the six-year development of a failure rate database for fusion specific components on the basis of data coming from operating experience gained in various fusion laboratories. The activity began in 2001 with the study of the Joint European Torus vacuum and active gas handling systems. Two years later the neutral beam injectors and the power supply systems were considered. This year the ion cyclotron resonant heating system is under evaluation. I. Cristescu et al (Germany) present the paper `Tritium inventories and tritium safety design principles for the fuel cycle of ITER'. She and her colleagues developed the dynamic mathematical model (TRIMO) for tritium inventory evaluation within each system of the ITER fuel cycle in various operational scenarios. TRIMO is used as a tool for trade-off studies within the fuel cycle systems with the final goal of global tritium inventory minimization. M. Matsuyama et al (Japan) describes a new technique for in situ quantitative measurements of high-level tritium inventory and its distribution in the VV and tritium systems of ITER and future fusion reactors. This technique is based on utilization of x-rays induced by beta-rays emitting from tritium species. It was applied to three physical states of high-level tritium: to gaseous, aqueous and solid tritium retained on/in various materials. Finally, there are four papers devoted to safety issues in fusion reactor decommissioning and waste management. A paper by R. Pampin et al (UK) provides the revised radioactive waste analysis of two models in the PPCS. Another paper by M. Zucchetti (Italy), S.A. Bartenev (Russia) et al describes a radiochemical extraction technology for purification of V-Cr-Ti alloy components from activation products to the dose rate of 10 µSv/h allowing their clearance or hands-on recycling which has been developed and tested in laboratory stationary conditions. L. El-Guebaly (USA) and her colleagues submitted two papers. In the first paper she optimistically considers the possibility of replacing the disposal of fusion power reactor waste with recycling and clearance. Her second paper considers the implications of new clearance guidelines for nuclear applications, particularly for slightly irradiated fusion materials.

Alternative preparation of inclusion bodies excludes interfering non-protein contaminants and improves the yield of recombinant proinsulin.

PubMed

Mackin, Robert B

2014-01-01

The goal of simple, high-yield expression and purification of recombinant human proinsulin has proven to be a considerable challenge. First, proinsulin forms inclusion bodies during bacterial expression. While this phenomenon can be exploited as a capture step, conventionally prepared inclusion bodies contain significant amounts of non-protein contaminants that interfere with subsequent chromatographic purification. Second, the proinsulin molecules within the inclusion bodies are incorrectly folded, and likely cross-linked to one another, making it difficult to quantify the amount of expressed proinsulin. Third, proinsulin is an intermediate between the initial product of ribosomal translation (preproinsulin) and the final product secreted by pancreatic beta cells (insulin). Therefore, to be efficiently produced in bacteria, it must be produced as an N-terminally extended fusion protein, which has to be converted to authentic proinsulin during the purification scheme. To address all three of these problems, while simultaneously streamlining the procedure and increasing the yield of recombinant proinsulin, we have made three substantive modifications to our previous method for producing proinsulin:.•Conditions for the preparation of inclusion bodies have been altered so contaminants that interfere with semi-preparative reversed-phase chromatography are excluded while the proinsulin fusion protein is retained at high yield.•Aliquots are taken following important steps in the procedure and the quantity of proinsulin-related polypeptide in the sample is compared to the amount present prior to that step.•Final purification is performed using a silica-based reversed-phase matrix in place of a polystyrene-divinylbenzene-based matrix.

Alternative preparation of inclusion bodies excludes interfering non-protein contaminants and improves the yield of recombinant proinsulin

PubMed Central

Mackin, Robert B.

2014-01-01

The goal of simple, high-yield expression and purification of recombinant human proinsulin has proven to be a considerable challenge. First, proinsulin forms inclusion bodies during bacterial expression. While this phenomenon can be exploited as a capture step, conventionally prepared inclusion bodies contain significant amounts of non-protein contaminants that interfere with subsequent chromatographic purification. Second, the proinsulin molecules within the inclusion bodies are incorrectly folded, and likely cross-linked to one another, making it difficult to quantify the amount of expressed proinsulin. Third, proinsulin is an intermediate between the initial product of ribosomal translation (preproinsulin) and the final product secreted by pancreatic beta cells (insulin). Therefore, to be efficiently produced in bacteria, it must be produced as an N-terminally extended fusion protein, which has to be converted to authentic proinsulin during the purification scheme. To address all three of these problems, while simultaneously streamlining the procedure and increasing the yield of recombinant proinsulin, we have made three substantive modifications to our previous method for producing proinsulin:.•Conditions for the preparation of inclusion bodies have been altered so contaminants that interfere with semi-preparative reversed-phase chromatography are excluded while the proinsulin fusion protein is retained at high yield.•Aliquots are taken following important steps in the procedure and the quantity of proinsulin-related polypeptide in the sample is compared to the amount present prior to that step.•Final purification is performed using a silica-based reversed-phase matrix in place of a polystyrene-divinylbenzene-based matrix. PMID:26150942

Review of fusion synfuels

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

Fillo, J.A.

1980-01-01

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

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.

Effects of administration of beta-carotene, ascorbic acid, persimmons, and pods on antioxidative ability in UV-irradiated ODS rats.

PubMed

Hosotani, Keisuke; Yoshida, Minoru; Kitagawa, Masahiro

2005-07-01

To evaluate the effects of supplementing diets with carotenoid and ascorbic acid (AsA) on the antioxidative ability of Osteogenic Disorder-Shionogi (ODS) rats, we added synthetic beta-carotene (betaC), AsA, and powders of persimmon (Ka) and pods (Po) containing betaC and AsA to the diet and obtained the following results. The urinary 8-hydroxydeoxyguanosine (8-OHdG) concentration was low in the -betaC.AsA and +AsA groups but high in the +betaC.AsA, +Ka, and +Po groups. The thiobarbituric acid-reactive substances (TBARS) in both the liver and skin were higher in the -betaC.AsA group than in the +betaC.AsA group and were low in the +Ka and +Po groups. As antioxidant enzymes, glutathione peroxidase (GSH-Px) activity was high in the +betaC.AsA group, low in the -beta3C.AsA group in both the skin and liver, and also high in the + Ka and +Po group in the liver. Superoxide dismutase (SOD) activity was high in the -betaC.AsA group and low in the +betaC.AsA and +Ka groups in both the skin and liver. Catalase (CAT) activity in the liver was low in the -betaC.AsA, +AsA, and +betaC groups and high in the +betaC.AsA and +Po groups. These results confirmed that the administration of betaC, AsA, and persimmons and pods increases antioxidative ability in the skin and liver of ultraviolet-b(UV-B)-irradiated ODS rats.

Myostatin signals through Pax7 to regulate satellite cell self-renewal

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

McFarlane, Craig; Department of Biological Sciences, University of Waikato, Hamilton; Hennebry, Alex

2008-01-15

Myostatin, a Transforming Growth Factor-beta (TGF-{beta}) super-family member, has previously been shown to negatively regulate satellite cell activation and self-renewal. However, to date the mechanism behind Myostatin function in satellite cell biology is not known. Here we show that Myostatin signals via a Pax7-dependent mechanism to regulate satellite cell self-renewal. While excess Myostatin inhibited Pax7 expression via ERK1/2 signaling, an increase in Pax7 expression was observed following both genetic inactivation and functional antagonism of Myostatin. As a result, we show that either blocking or inactivating Myostatin enhances the partitioning of the fusion-incompetent self-renewed satellite cell lineage (high Pax7 expression, lowmore » MyoD expression) from the pool of actively proliferating myogenic precursor cells. Consistent with this result, over-expression of Pax7 in C2C12 myogenic cells resulted in increased self-renewal through a mechanism which slowed both myogenic proliferation and differentiation. Taken together, these results suggest that increased expression of Pax7 promotes satellite cell self-renewal, and furthermore Myostatin may control the process of satellite cell self-renewal through regulation of Pax7. Thus we speculate that, in addition to the intrinsic factors (such as Pax7), extrinsic factors both positive and negative in nature, will play a major role in determining the stemness of skeletal muscle satellite cells.« less

Joint DIII-D/EAST research on the development of a high poloidal beta scenario for the steady state missions of ITER and CFETR

NASA Astrophysics Data System (ADS)

Garofalo, A. M.; Gong, X. Z.; Ding, S. Y.; Huang, J.; McClenaghan, J.; Pan, C. K.; Qian, J.; Ren, Q. L.; Staebler, G. M.; Chen, J.; Cui, L.; Grierson, B. A.; Hanson, J. M.; Holcomb, C. T.; Jian, X.; Li, G.; Li, M.; Pankin, A. Y.; Peysson, Y.; Zhai, X.; Bonoli, P.; Brower, D.; Ding, W. X.; Ferron, J. R.; Guo, W.; Lao, L. L.; Li, K.; Liu, H.; Lyv, B.; Xu, G.; Zang, Q.

2018-01-01

Experimental and modeling investigations on the DIII-D and EAST tokamaks show the attractive transport and stability properties of fully noninductive, high poloidal-beta (β P ) plasmas, and their suitability for steady-state operating scenarios in ITER and CFETR. A key feature of the high-β P regime is the large-radius (ρ > 0.6) internal transport barrier (ITB), often observed in all channels (ne, Te, Ti, rotation), and responsible for both excellent energy confinement quality and excellent stability properties. Experiments on DIII-D have shown that, with a large-radius ITB, very high β N and β P values (both ≥ 4) can be reached by taking advantage of the stabilizing effect of a nearby conducting wall. Synergistically, higher plasma pressure provides turbulence suppression by Shafranov shift, leading to ITB sustainment independent of the plasma rotation. Experiments on EAST have been used to assess the long pulse potential of the high-β P regime. Using RF-only heating and current drive, EAST achieved minute-long fully noninductive steady state H-mode operation with strike points on an ITER-like tungsten divertor. Improved confinement (relative to standard H-mode) and steady state ITB features are observed with a monotonic q-profile with q min ˜ 1.5. Separately, experiments have shown that increasing the density in plasmas driven by lower hybrid wave broadens the q-profile, a technique that could enable a large radius ITB. These experimental results have been used to validate MHD, current drive, and turbulent transport models, and to project the high-β P regime to a burning plasma. These projections suggest the Shafranov shift alone will not suffice to provide improved confinement (over standard H-mode) without rotation and rotation shear. However, increasing the negative magnetic shear (higher q on axis) provides a similar turbulence suppression mechanism to Shafranov shift, and can help devices such as ITER and CFETR achieve their steady-state fusion goals.

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

PubMed Central

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

2012-01-01

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

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

PubMed

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

2012-09-01

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

Differential secretion pathways of proteins fused to the Escherichia coli maltose binding protein (MBP) in Pichia pastoris.

PubMed

Moua, Pachai S; Gonzalez, Alfonso; Oshiro, Kristin T; Tam, Vivian; Li, Zhiguo Harry; Chang, Jennifer; Leung, Wilson; Yon, Amy; Thor, Der; Venkatram, Sri; Franz, Andreas H; Risser, Douglas D; Lin-Cereghino, Joan; Lin-Cereghino, Geoff P

2016-08-01

The Escherichia coli maltose binding protein (MBP) is an N-terminal fusion partner that was shown to enhance the secretion of some heterologous proteins from the yeast Pichia pastoris, a popular host for recombinant protein expression. The amount of increase in secretion was dependent on the identity of the cargo protein, and the fusions were proteolyzed prior to secretion, limiting its use as a purification tag. In order to overcome these obstacles, we used the MBP as C-terminal partner for several cargo peptides. While the Cargo-MBP proteins were no longer proteolyzed in between these two moieties when the MBP was in this relative position, the secretion efficiency of several fusions was lower than when MBP was located at the opposite end of the cargo protein (MBP-Cargo). Furthermore, fluorescence analysis suggested that the MBP-EGFP and EGFP-MBP proteins followed different routes within the cell. The effect of several Pichia pastoris beta-galactosidase supersecretion (bgs) strains, mutants showing enhanced secretion of select reporters, was also investigated on both MBP-EGFP and EGFP-MBP. While the secretion efficiency, proteolysis and localization of the MBP-EGFP was influenced by the modified function of Bgs13, EGFP-MBP behavior was not affected in the bgs strain. Taken together, these results indicate that the location of the MBP in a fusion affects the pathway and trans-acting factors regulating secretion in P. pastoris. Copyright © 2016 Elsevier Inc. All rights reserved.

Fusion and quality analysis for remote sensing images using contourlet transform

NASA Astrophysics Data System (ADS)

Choi, Yoonsuk; Sharifahmadian, Ershad; Latifi, Shahram

2013-05-01

Recent developments in remote sensing technologies have provided various images with high spatial and spectral resolutions. However, multispectral images have low spatial resolution and panchromatic images have low spectral resolution. Therefore, image fusion techniques are necessary to improve the spatial resolution of spectral images by injecting spatial details of high-resolution panchromatic images. The objective of image fusion is to provide useful information by improving the spatial resolution and the spectral information of the original images. The fusion results can be utilized in various applications, such as military, medical imaging, and remote sensing. This paper addresses two issues in image fusion: i) image fusion method and ii) quality analysis of fusion results. First, a new contourlet-based image fusion method is presented, which is an improvement over the wavelet-based fusion. This fusion method is then applied to a case study to demonstrate its fusion performance. Fusion framework and scheme used in the study are discussed in detail. Second, quality analysis for the fusion results is discussed. We employed various quality metrics in order to analyze the fusion results both spatially and spectrally. Our results indicate that the proposed contourlet-based fusion method performs better than the conventional wavelet-based fusion methods.

Properties of a herpes simplex virus multiple immediate-early gene-deleted recombinant as a vaccine vector

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

Watanabe, Daisuke; Brockman, Mark A.; Ndung'u, Thumbi

2007-01-20

Herpes simplex virus (HSV) recombinants induce durable immune responses in rhesus macaques and mice and have induced partial protection in rhesus macaques against mucosal challenge with virulent simian immunodeficiency virus (SIV). In this study, we evaluated the properties of a new generation HSV vaccine vector, an HSV-1 multiple immediate-early (IE) gene deletion mutant virus, d106, which contains deletions in the ICP4, ICP27, ICP22, and ICP47 genes. Because several of the HSV IE genes have been implicated in immune evasion, inactivation of the genes encoding these proteins was expected to result in enhanced immunogenicity. The d106 virus expresses few HSV genemore » products and shows minimal cytopathic effect in cultured cells. When d106 was inoculated into mice, viral DNA accumulated at high levels in draining lymph nodes, consistent with an ability to transduce dendritic cells and activate their maturation and movement to lymph nodes. A d106 recombinant expressing Escherichia coli {beta}-galactosidase induced durable {beta}-gal-specific IgG and CD8{sup +} T cell responses in naive and HSV-immune mice. Finally, d106-based recombinants have been constructed that express simian immunodeficiency virus (SIV) gag, env, or a rev-tat-nef fusion protein for several days in cultured cells. Thus, d106 shows many of the properties desirable in a vaccine vector: limited expression of HSV gene products and cytopathogenicity, high level expression of transgenes, ability to induce durable immune responses, and an ability to transduce dendritic cells and induce their maturation and migration to lymph nodes.« less

Airborne Infrared and Visible Image Fusion Combined with Region Segmentation

PubMed Central

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

2017-01-01

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

Airborne Infrared and Visible Image Fusion Combined with Region Segmentation.

PubMed

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

2017-05-15

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

Supplementation of a high-carbohydrate breakfast with barley beta-glucan improves postprandial glycaemic response for meals but not beverages.

PubMed

Poppitt, Sally D; van Drunen, Jenneke D E; McGill, Anne-Thea; Mulvey, Tom B; Leahy, Fiona E

2007-01-01

There is growing support for the protective role of soluble fibre in type II diabetes. Soluble fibre beta-glucan found in cereal products including oats and barley may be the active component. There is evidence of postprandial blunting of blood glucose and insulin responses to dietary carbohydrates when oat soluble fibre is supplemented into the diet but few trials have been carried out using natural barley or enriched barley beta-glucan products. The aim of this trial was to investigate the postprandial effect of a highly enriched barley beta -glucan product on blood glucose, insulin and lipids when given with a high-CHO food and a high-CHO drink. 18 lean, healthy men completed a 4 treatment intervention trial comprising (i) high-CHO(food control), (ii) high-CHO(food+fibre), (iii) high-CHO(drink control), (iv) high-CHO(drink+fibre) where a 10g dose of barley beta-glucan fibre supplement (Cerogen) containing 6.31g beta-glucan was added to food and drink controls. There was an increase of glucose and insulin following all 4 treatments. Addition of the beta -glucan supplement significantly blunted the glycaemic and insulinaemic responses on the food (p<0.05) but not drink (p>0.05) treatments when compared to controls. The high-CHO breakfasts decreased total, LDL- and HDL-cholesterol from baseline to 60 mins postprandially but there were no differential effects of beta-glucan treatment on circulating lipids. We conclude that a high dose barley beta-glucan supplement can improve glucose control when added to a high-CHO starchy food, probably due to increased gastro-intestinal viscosity, but not when added to a high-CHO beverage where rapid absorption combined with decreased beta-glucan concentration and viscosity may obviate this mechanism.

Characterization of a beta-glycosidase highly active on disaccharides and of a beta-galactosidase from Tenebrio molitor midgut lumen.

PubMed

Ferreira, Alexandre H P; Terra, Walter R; Ferreira, Clélia

2003-02-01

The midgut of the yellow mealworm, Tenebrio molitor L. (Coleoptera: Tenebrionidae) larvae has four beta-glycosidases. The properties of two of these enzymes (betaGly1 and betaGly2) have been described elsewhere. In this paper, the characterization of the other two glycosidases (betaGly3 and betaGly4) is described. BetaGly3 has one active site, hydrolyzes disaccharides, cellodextrins, synthetic substrates and beta-glucosides produced by plants. The enzyme is inhibited by amygdalin, cellotriose, cellotetraose and cellopentaose in high concentrations, probably due to transglycosylation. betaGly3 hydrolyzes beta 1,4-glycosidic linkages with a catalytic rate independent of the substrate polymerization degree (k(int)) of 11.9 s(-1). Its active site is formed by four subsites, where subsites +1 and -1 bind glucose residues with higher affinity than subsite +2. The main role of betaGly3 seems to be disaccharide hydrolysis. BetaGly4 is a beta-galactosidase, since it has highest activity against beta-galactosides. It can also hydrolyze fucosides, but not glucosides, and has Triton X-100 as a non-essential activator (K(a)=15 microM, pH 4.5). betaGly4 has two active sites that can hydrolyze p-nitrophenyl beta-galactoside (NPbetaGal). The one hydrolyzing NPbetaGal with more efficiency is also active against methylumbellipheryl beta-D-galactoside and lactose. The other active site hydrolyzes NPbetaFucoside and binds NPbetaGal weakly. BetaGly4 hydrolyzes hydrophobic substrates with high catalytical efficiency and is able to bind octyl-beta-thiogalactoside in its active site with high affinity. The betaGly4 physiological role is supposed to be the hydrolysis of galactolipids that are found in membranes from vegetal tissues. As the enzyme has a hydrophobic site where Triton X-100 can bind, it might be activated by membrane lipids, thus becoming fully active only at the surface of cell membranes.

Generation of a Stable Transgenic Swine Model Expressing a Porcine Histone 2B-eGFP Fusion Protein for Cell Tracking and Chromosome Dynamics Studies

PubMed Central

Simpson, Sean; Collins, Bruce; Sommer, Jeff; Petters, Robert M.; Caballero, Ignacio; Platt, Jeff L.

2017-01-01

Transgenic pigs have become an attractive research model in the field of translational research, regenerative medicine, and stem cell therapy due to their anatomic, genetic and physiological similarities with humans. The development of fluorescent proteins as molecular tags has allowed investigators to track cell migration and engraftment levels after transplantation. Here we describe the development of two transgenic pig models via SCNT expressing a fusion protein composed of eGFP and porcine Histone 2B (pH2B). This fusion protein is targeted to the nucleosomes resulting a nuclear/chromatin eGFP signal. The first model (I) was generated via random insertion of pH2B-eGFP driven by the CAG promoter (chicken beta actin promoter and rabbit Globin poly A; pCAG-pH2B-eGFP) and protected by human interferon-β matrix attachment regions (MARs). Despite the consistent, high, and ubiquitous expression of the fusion protein pH2B-eGFP in all tissues analyzed, two independently generated Model I transgenic lines developed neurodegenerative symptoms including Wallerian degeneration between 3–5 months of age, requiring euthanasia. A second transgenic model (II) was developed via CRISPR-Cas9 mediated homology-directed repair (HDR) of IRES-pH2B-eGFP into the endogenous β-actin (ACTB) locus. Model II transgenic animals showed ubiquitous expression of pH2B-eGFP on all tissues analyzed. Unlike the pCAG-pH2B-eGFP/MAR line, all Model II animals were healthy and multiple pregnancies have been established with progeny showing the expected Mendelian ratio for the transmission of the pH2B-eGFP. Expression of pH2B-eGFP was used to examine the timing of the maternal to zygotic transition after IVF, and to examine chromosome segregation of SCNT embryos. To our knowledge this is the first viable transgenic pig model with chromatin-associated eGFP allowing both cell tracking and the study of chromatin dynamics in a large animal model. PMID:28081156

Structure and regulation of KGD1, the structural gene for yeast alpha-ketoglutarate dehydrogenase.

PubMed

Repetto, B; Tzagoloff, A

1989-06-01

Nuclear respiratory-defective mutants of Saccharomyces cerevisiae have been screened for lesions in the mitochondrial alpha-ketoglutarate dehydrogenase complex. Strains assigned to complementation group G70 were ascertained to be deficient in enzyme activity due to mutations in the KGD1 gene coding for the alpha-ketoglutarate dehydrogenase component of the complex. The KGD1 gene has been cloned by transformation of a representative kgd1 mutant, C225/U1, with a recombinant plasmid library of wild-type yeast nuclear DNA. Transformants containing the gene on a multicopy plasmid had three- to four-times-higher alpha-ketoglutarate dehydrogenase activity than did wild-type S. cerevisiae. Substitution of the chromosomal copy of KGD1 with a disrupted allele (kgd1::URA3) induced a deficiency in alpha-ketoglutarate dehydrogenase. The sequence of the cloned region of DNA which complements kgd1 mutants was found to have an open reading frame of 3,042 nucleotides capable of coding for a protein of Mw 114,470. The encoded protein had 38% identical residues with the reported sequence of alpha-ketoglutarate dehydrogenase from Escherichia coli. Two lines of evidence indicated that transcription of KGD1 is catabolite repressed. Higher steady-state levels of KGD1 mRNA were detected in wild-type yeast grown on the nonrepressible sugar galactose than in yeast grown on high glucose. Regulation of KGD1 was also studied by fusing different 5'-flanking regions of KGD1 to the lacZ gene of E. coli and measuring the expression of beta-galactosidase in yeast. Transformants harboring a fusion of 693 nucleotides of the 5'-flanking sequence expressed 10 times more beta-galactosidase activity when grown under derepressed conditions. The response to the carbon source was reduced dramatically when the same lacZ fusion was present in a hap2 or hap3 mutant. The promoter element(s) responsible for the regulated expression of KGD1 has been mapped to the -354 to -143 region. This region contained several putative activation sites with sequences matching the core element proposed to be essential for binding of the HAP2 and HAP3 regulatory proteins.

Linkage study of nonsyndromic cleft lip with or without cleft palate using candidate genes and mapped polymorphic markers

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

Stein, J.D.; Nelson, L.D.; Conner, B.J.

1994-09-01

Nonsyndromic cleft lip with or without cleft palate (CL(P)) involves fusion or growth failure of facial primordia during development. Complex segregation analysis of clefting populations suggest that an autosomal dominant gene may play a role in this common craniofacial disorder. We have ascertained 16 multigenerational families with CL(P) and tested linkage to 29 candidate genes and 139 mapped short tandem repeat markers. The candidate genes were selected based on their expression in craniofacial development or were identified through murine models. These include: TGF{alpha}, TGF{beta}1, TGF{beta}2, TGF{beta}3, EGF, EGFR, GRAS, cMyc, FGFR, Jun, JunB, PDFG{alpha}, PDGF{beta}, IGF2R, GCR Hox7, Hox8, Hox2B,more » twirler, 5 collagen and 3 extracellular matrix genes. Linkage was tested assuming an autosomal dominant model with sex-specific decreased penetrance. Linkage to all of the candidate loci was excluded in 11 families. RARA was tested and was not informative. However, haplotype analysis of markers flanking RARA on 17q allowed exclusion of this candidate locus. We have previously excluded linkage to 61 STR markers in 11 families. Seventy-eight mapped short tandem repeat markers have recently been tested in 16 families and 30 have been excluded. The remaining are being analyzed and an exclusion map is being developed based on the entire study results.« less

Transcriptional repression mediated by the KRAB domain of the human C2H2 zinc finger protein Kox1/ZNF10 does not require histone deacetylation.

PubMed

Lorenz, P; Koczan, D; Thiesen, H J

2001-04-01

The KRAB domain of human Kox1, a member of the KRAB C2H2 zinc finger family, confers strong transcriptional repressor activities even to remote promoter positions. Here, HDAC inhibitors were used to demonstrate that histone deacetylation is not required for mediating transcriptional repression of KRAB zinc finger proteins. Two reporter systems with either stably integrated or transiently transfected templates, both under control of strong viral promoters, were analyzed. Under all circumstances, HDAC inhibition did not alter the repression potential of the KRAB domain. In case of the stably integrated luciferase reporter gene system, neither expression levels of the KRAB fusion protein nor complex formation with its putative co-repressor TIF1beta were significantly changed. Furthermore, the TIF1beta/KRAB complex was devoid of mSin3A and HDAC1. In the transient transfection system, the transcriptional repression induced by TIF1beta and HP1alpha was not diminished by HDAC inhibitors, whereas the repressory activity of TIF1alpha was significantly affected. Thus, KRAB, TIF1beta and HP1alpha are likely to be functionally linked. In conclusion, HDAC activity is not essential for the strong transcriptional repressor activity mediated by the KRAB domain of Kox1 in particular and, presumably, by KRAB domains in general. This feature might be helpful in identifying and characterizing target genes under the control of

Effect of interleukin 13 on bronchial hyperresponsiveness and the bronchoprotective effect of beta-adrenergic bronchodilators and corticosteroids.

PubMed

Townley, Robert G; Gendapodi, Pradeep R; Qutna, Nidal; Evans, Joseph; Romero, Francisco A; Abel, Peter

2009-03-01

Fluticasone affects airway bronchial hyperresponsiveness (BHR) and enhances bronchodilation and bronchoprotection induced by beta-adrenergic agonists. Interleukin 13 (IL-13), however, induces BHR. To test the hypotheses that fluticasone inhibits BHR after either allergen sensitization or IL-13 administration and that fluticasone restores the bronchodilation and bronchoprotective effects of beta-agonists. The BHR to methacholine induced by IL-13 or ovalbumin was determined in BALB/c mice, and the provocation concentration of methacholine that caused an increase in enhanced pause in expiration of 200% (PC200) was calculated. We compared this response to methacholine in control mice with the response after treatment with IL-13 receptor alpha 2-IgGFc fusion protein (IL-13R alpha 2) (an IL-13 blocker), fluticasone, albuterol, salmeterol, fluticasone-albuterol, and fluticasone-salmeterol. IL-13R alpha 2 (PC200, 17.59) completely blocks the BHR-induced effects of IL-13 (PC200, 7.28; P < .005). After IL-13 therapy (PC200, 5.90; P < .005), 1 mg/mL of albuterol (PC200, 3.38; P = .33), fluticasone (PC200, 4.59; P = .40), or fluticasone plus 50 microg/mL of salmeterol (PC200, 5.59; P = .11) showed no significant bronchoprotection. In nonsensitized mice, fluticasone plus 0.25 microg/mL of salmeterol (PC200, 25.90; P < .005) showed significantly greater bronchoprotection than did salmeterol alone (PC200, 11.08; P = .26). Fluticasone plus 0.3 mg/mL of albuterol and fluticasone plus 1 mg/mL of albuterol were significantly more protective than was fluticasone or albuterol alone in ovalbumin-sensitized mice. The protective effects of fluticasone, beta-agonists, and fluticasone plus beta-agonists are significantly less in IL-13-treated mice than in nonsensitized or ovalbumin-sensitized mice.

Human MI-ER1 alpha and beta function as transcriptional repressors by recruitment of histone deacetylase 1 to their conserved ELM2 domain.

PubMed

Ding, Zhihu; Gillespie, Laura L; Paterno, Gary D

2003-01-01

mi-er1 (previously called er1) was first isolated from Xenopus laevis embryonic cells as a novel fibroblast growth factor-regulated immediate-early gene. Xmi-er1 was shown to encode a nuclear protein with an N-terminal acidic transcription activation domain. The human orthologue of mi-er1 (hmi-er1) displays 91% similarity to the Xenopus sequence at the amino acid level and was shown to be upregulated in breast carcinoma cell lines and tumors. Alternative splicing at the 3' end of hmi-er1 produces two major isoforms, hMI-ER1alpha and hMI-ER1beta, which contain distinct C-terminal domains. In this study, we investigated the role of hMI-ER1alpha and hMI-ER1beta in the regulation of transcription. Using fusion proteins of hMI-ER1alpha or hMI-ER1beta tethered to the GAL4 DNA binding domain, we show that both isoforms, when recruited to the G5tkCAT minimal promoter, function to repress transcription. We demonstrate that this repressor activity is due to interaction and recruitment of a trichostatin A-sensitive histone deacetylase 1 (HDAC1). Furthermore, deletion analysis revealed that recruitment of HDAC1 to hMI-ER1alpha and hMI-ER1beta occurs through their common ELM2 domain. The ELM2 domain was first described in the Caenorhabditis elegans Egl-27 protein and is present in a number of SANT domain-containing transcription factors. This is the first report of a function for the ELM2 domain, highlighting its role in the regulation of transcription.

Revisiting the JDL Model for Information Exploitation

DTIC Science & Technology

2013-07-01

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

Interactions of the sulfonylurea receptor 1 subunit in the molecular assembly of beta-cell K(ATP) channels.

PubMed

Mikhailov, M V; Ashcroft, S J

2000-02-04

We have investigated protein interactions involved in pancreatic beta-cell ATP-sensitive potassium channel assembly. These channels, which are of key importance for control of insulin release, are a hetero-oligomeric complex of pore-forming Kir6.2 subunits and sulfonylurea receptor (SUR1) subunits with two nucleotide-binding domains (NBD1 and NBD2). We divided SUR1 into two halves at Pro-1042. Expression of either the individual N- or C-terminal domain in a baculovirus expression system did not lead to glibenclamide binding activity, although studies with green fluorescent protein fusion proteins showed that both half-molecules were inserted into the plasma membrane. However, significant glibenclamide binding activity was observed when the half-molecules were co-expressed (even when NBD2 was deleted from the C-terminal half-molecule). Simultaneous expression of Kir6.2 resulted in enhanced glibenclamide binding activity. We conclude that the glibenclamide-binding site includes amino acid residues from both halves of the molecule, that there is strong interaction between different regions of SUR1, that NBD2 is not essential for glibenclamide binding, and that interactions between Kir6.2 and SUR1 participate in ATP-sensitive potassium channel assembly. Investigation of NBD1-green fluorescent protein fusion protein distribution inside insect cells expressing C-terminal halves of SUR1 demonstrated strong interaction between NBD1 and NBD2. We also expressed and purified NBD1 from Escherichia coli. Purified NBD1 was found to exist as a tetramer indicating strong homomeric attractions and a possible role for NBD1 in SUR1 assembly.

Transforming properties of the Huntingtin interacting protein 1/ platelet-derived growth factor beta receptor fusion protein.

PubMed

Ross, T S; Gilliland, D G

1999-08-06

We have previously reported that the Huntingtin interacting protein 1 (HIP1) gene is fused to the platelet-derived growth factor beta receptor (PDGFbetaR) gene in a patient with chronic myelomonocytic leukemia. We now show that HIP1/PDGFbetaR oligomerizes, is constitutively tyrosine-phosphorylated, and transforms the murine hematopoietic cell line, Ba/F3, to interleukin-3-independent growth. A kinase-inactive mutant is neither tyrosine-phosphorylated nor able to transform Ba/F3 cells. Oligomerization and kinase activation required the 55-amino acid carboxyl-terminal TALIN homology region but not the leucine zipper domain. Tyrosine phosphorylation of a 130-kDa protein and STAT5 correlates with transformation in cells expressing HIP1/PDGFbetaR and related mutants. A deletion mutant fusion protein that contains only the TALIN homology region of HIP1 fused to PDGFbetaR is incapable of transforming Ba/F3 cells and does not tyrosine-phosphorylate p130 or STAT5, although it is itself constitutively tyrosine-phosphorylated. We have also analyzed cells expressing Tyr --> Phe mutants of HIP1/PDGFbetaR in the known PDGFbetaR SH2 docking sites and report that none of these sites are necessary for STAT5 activation, p130 phosphorylation, or Ba/F3 transformation. The correlation of factor-independent growth of hematopoietic cells with p130 and STAT5 phosphorylation/activation in both the HIP1/PDGFbetaR Tyr --> Phe and deletion mutational variants suggests that both STAT5 and p130 are important for transformation mediated by HIP1/PDGFbetaR.

Possible application of electromagnetic guns to impact fusion

NASA Astrophysics Data System (ADS)

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

1982-01-01

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

[Rumination and cognitive fusion in dementia family caregivers].

PubMed

Romero-Moreno, Rosa; Márquez-González, María; Losada, Andrés; Fernández-Fernández, Virginia; Nogales-González, Celia

2015-01-01

Rumination has been described as a dysfunctional coping strategy related to emotional distress. Recently, it has been highlighted from the Acceptance and Commitment Therapy therapeutic approach, the negative role that cognitive fusion (the extent to which we are psychologically tangled with and dominated by the form or content of our thoughts) has on the explanation of distress. The aim of this study is to simultaneously analyze the role of rumination and cognitive fusion in the caregiving stress process. The sample of 176 dementia caregivers was divided in four groups, taking into account their levels of rumination and cognitive fusion: HRHF=high rumination+high cognitive fusion; HRLF=high rumination+low cognitive fusion; LRHF= low rumination+high cognitive fusion; and LRLC=low rumination and low cognitive fusion. Caregiver stress factors, frequency of pleasant events, experiential avoidance, coherence and satisfaction with personal values, depression, anxiety and satisfaction with life, were measured. The HRHF group showed higher levels of depression, anxiety, experiential avoidance and lower levels of satisfaction with life, frequency of pleasant events, coherence and satisfaction with personal values, than the other three groups. Considering simultaneously rumination and cognitive fusion may contribute to a better understanding of caregiver coping and distress. Copyright © 2014 SEGG. Published by Elsevier Espana. All rights reserved.

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

NASA Astrophysics Data System (ADS)

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

2016-03-01

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

Fusion of multi-spectral and panchromatic images based on 2D-PWVD and SSIM

NASA Astrophysics Data System (ADS)

Tan, Dongjie; Liu, Yi; Hou, Ruonan; Xue, Bindang

2016-03-01

A combined method using 2D pseudo Wigner-Ville distribution (2D-PWVD) and structural similarity(SSIM) index is proposed for fusion of low resolution multi-spectral (MS) image and high resolution panchromatic (PAN) image. First, the intensity component of multi-spectral image is extracted with generalized IHS transform. Then, the spectrum diagrams of the intensity components of multi-spectral image and panchromatic image are obtained with 2D-PWVD. Different fusion rules are designed for different frequency information of the spectrum diagrams. SSIM index is used to evaluate the high frequency information of the spectrum diagrams for assigning the weights in the fusion processing adaptively. After the new spectrum diagram is achieved according to the fusion rule, the final fusion image can be obtained by inverse 2D-PWVD and inverse GIHS transform. Experimental results show that, the proposed method can obtain high quality fusion images.

Positron emission tomography with [ 18F]-FDG in oncology

NASA Astrophysics Data System (ADS)

Talbot, J. N.; Petegnief, Y.; Kerrou, K.; Montravers, F.; Grahek, D.; Younsi, N.

2003-05-01

Positron Emission Tomography (PET) is a several decade old imaging technique that has more recently demonstrated its utility in clinical applications. The imaging agents used for PET contain a positron emmiter coupled to a molecule that drives the radionuclide to target organs or to tissues performing the targetted biological function. PET is then part of functional imaging. As compared to conventional scintigraphy that uses gamma photons, the coincidence emission of two 511 keV annihilation photons in opposite direction that finally results from by beta plus decay makes it possible for PET to get rid of the collimators that greatly contribute to the poor resolution of scintigraphy. In this article, the authors describe the basics of physics for PET imaging and report on the clinical performances of the most commonly used PET tracer: [ 18F]-fluorodeoxyglucose (FDG). A recent and promising development in this field is fusion of images coming from different imaging modalities. New PET machines now include a CT and this fusion is therefore much easier.

Physicsdesign point for a 1MW fusion neutron source

NASA Astrophysics Data System (ADS)

Woodruff, Simon; Melnik, Paul; Sieck, Paul; Stuber, James; Romero-Talamas, Carlos; O'Bryan, John; Miller, Ronald

2016-10-01

We are developing a design point for a spheromak experiment heated by adiabatic compression for use as a compact neutron source. We utilize the CORSICA and NIMROD MHD codes as well as analytic modeling to assess a concept with target parameters R0 =0.5m, Rf =0.17m, T0 =1keV, Tf =8keV, n0 =2e20m-3 and nf = 5e21m-3, with radial convergence of C =R0/Rf =3. We present results from CORSICA showing the placement of coils and passive structure to ensure stability during compression. We specify target parameters for the compression in terms of plasma beta, formation efficiency and energy confinement. We present results simulations of magnetic compression using the NIMROD code to examine the role of rotation on the stability and confinement of the spheromak as it is compressed. Supported by DARPA Grant N66001-14-1-4044 and IAEA CRP on Compact Fusion Neutron Sources.

Prospective Randomized Controlled Trial of Hindfoot and Ankle Fusions Treated With rhPDGF-BB in Combination With a β-TCP-Collagen Matrix.

PubMed

Daniels, Timothy R; Younger, Alastair S E; Penner, Murray J; Wing, Kevin J; Le, Ian L D; Russell, Iain S; Lalonde, Karl-André; Evangelista, Peter T; Quiton, Jovelyn D; Glazebrook, Mark; DiGiovanni, Christopher W

2015-07-01

Ankle and hindfoot arthrodesis is often supplemented with autograft to promote bony union. Autograft harvest can lead to increased perioperative morbidity. Purified recombinant human platelet-derived growth factor BB homodimer (rhPDGF-BB) has stimulated bone formation in mandibular defects and hindfoot fusion. This randomized controlled trial evaluated the efficacy and safety of rhPDGF-BB combined with an injectable, osteoconductive beta-tricalcium phosphate (β-TCP)-collagen matrix versus autograft in ankle and hindfoot fusions. Seventy-five patients requiring ankle or hindfoot fusion were randomized 5:1 for rhPDGF-BB/β-TCP-collagen (treatment, n = 63) or autograft (control, n = 12). Prospective analysis included 142 autograft control subjects from another clinical trial with identical study protocols. Standardized operative and postoperative protocols were used. Patients underwent standard internal fixation augmented with autograft or 0.3 mg/mL rhPDGF-BB/β-TCP-collagen. Radiologic, clinical, and quality-of-life outcomes were assessed over 52 weeks. Primary outcome was joint fusion (50% or more osseous bridging on computed tomography) at 24 weeks. Secondary outcomes included radiographs, clinical healing status, visual analog scale pain score, American Orthopaedic Foot & Ankle Society Ankle-Hindfoot Scale score, Foot Function Index score, and Short Form-12 score. Noninferiority P values were calculated. Complete fusion of all involved joints at 24 weeks as indicated by computed tomography was achieved in 53 of 63 (84%) rhPDGF-BB/β-TCP-collagen-treated patients and 100 of 154 (65%) autograft-treated patients (P < .001). Mean time to fusion was 14.3 ± 8.9 weeks for rhPDGF-BB/β-TCP-collagen patients versus 19.7 ± 11.5 weeks for autograft patients (P < .01). Clinical success at 52 weeks was achieved in 57 of 63 (91%) rhPDGF-BB/β-TCP-collagen patients and 120 of 154 (78%) autograft patients (P < .001). Safety-related outcomes were equivalent. Autograft controls had 2 bone graft harvest infections. Application of rhPDGF-BB/β-TCP-collagen was a safe, effective alternative to autograft for ankle and hindfoot fusions, eliminating the pain and morbidity associated with autograft harvesting. Level I, prospective randomized study. © The Author(s) 2015.

Reduced and high molecular weight barley beta-glucans decrease plasma total and non-HDL-cholesterol in hypercholesterolemic Syrian golden hamsters.

PubMed

Wilson, Thomas A; Nicolosi, Robert J; Delaney, Bryan; Chadwell, Kim; Moolchandani, Vikas; Kotyla, Timothy; Ponduru, Sridevi; Zheng, Guo-Hua; Hess, Richard; Knutson, Nathan; Curry, Leslie; Kolberg, Lore; Goulson, Melanie; Ostergren, Karen

2004-10-01

Consumption of concentrated barley beta-glucan lowers plasma cholesterol because of its soluble dietary fiber nature. The role of molecular weight (MW) in lowering serum cholesterol is not well established. Prior studies showed that enzymatic degradation of beta-glucan eliminates the cholesterol-lowering activity; however, these studies did not evaluate the MW of the beta-glucan. The current study was conducted to evaluate whether barley beta-glucan concentrates, partially hydrolyzed to reduce MW, possess cholesterol-lowering and antiatherogenic activities. The reduced MW fraction was compared with a high MW beta-glucan concentrate from the same barley flour. Concentrated beta-glucan preparations were evaluated in Syrian Golden F(1)B hamsters fed a hypercholesterolemic diet (HCD) with cholesterol, hydrogenated coconut oil, and cellulose. After 2 wk, hamsters were fed HCD or diets that contained high or reduced MW beta-glucan at a concentration of 8 g/100 g at the expense of cellulose. Decreases in plasma total cholesterol (TC) and non-HDL-cholesterol (non-HDL-C) concentrations occurred in the hamsters fed reduced MW and high MW beta-glucan diets. Plasma HDL-C concentrations did not differ. HCD-fed hamsters had higher plasma triglyceride concentrations. Liver TC, free cholesterol, and cholesterol ester concentrations did not differ. Aortic cholesterol ester concentrations were lower in the reduced MW beta-glucan-fed hamsters. Consumption of either high or reduced MW beta-glucan increased concentrations of fecal total neutral sterols and coprostanol, a cholesterol derivative. Fecal excretion of cholesterol was greater than in HCD-fed hamsters only in those fed the reduced MW beta-glucan. Study results demonstrate that the cholesterol-lowering activity of barley beta-glucan may occur at both lower and higher MW.

Correlation of beta-catenin localization with cyclooxygenase-2 expression and CpG island methylator phenotype (CIMP) in colorectal cancer.

PubMed

Kawasaki, Takako; Nosho, Katsuhiko; Ohnishi, Mutsuko; Suemoto, Yuko; Kirkner, Gregory J; Dehari, Reiko; Meyerhardt, Jeffrey A; Fuchs, Charles S; Ogino, Shuji

2007-07-01

The WNT/beta-catenin (CTNNB1) pathway is commonly activated in the carcinogenic process. Cross-talks between the WNT and cyclooxygenase-2 (COX-2 or PTGS2)/prostaglandin pathways have been suggested. The relationship between beta-catenin activation and microsatellite instability (MSI) in colorectal cancer has been controversial. The CpG island methylator phenotype (CIMP or CIMP-high) with widespread promoter methylation is a distinct epigenetic phenotype in colorectal cancer, which is associated with MSI-high. However, no study has examined the relationship between beta-catenin activation and CIMP status. Using 832 population-based colorectal cancer specimens, we assessed beta-catenin localization by immunohistochemistry. We quantified DNA methylation in eight CIMP-specific promoters [CACNA1G, CDKN2A(p16), CRABP1, IGF2, MLH1, NEUROG1, RUNX3, and SOCS1] by real-time polymerase chain reaction (MethyLight). MSI-high, CIMP-high, and BRAF mutation were associated inversely with cytoplasmic and nuclear beta-catenin expressions (i.e., beta-catenin activation) and associated positively with membrane expression. The inverse relation between beta-catenin activation and CIMP was independent of MSI. COX-2 overexpression correlated with cytoplasmic beta-catenin expression (even after tumors were stratified by CIMP status), but did not correlate significantly with nuclear or membrane expression. In conclusion, beta-catenin activation is inversely associated with CIMP-high independent of MSI status. Cytoplasmic beta-catenin is associated with COX-2 overexpression, supporting the role of cytoplasmic beta-catenin in stabilizing PTGS2 (COX-2) mRNA.

The Physics of Advanced High-Gain Targets for Inertial Fusion Energy

NASA Astrophysics Data System (ADS)

Perkins, L. John

2010-11-01

In ca. 2011-2012, the National Ignition Facility is poised to demonstrate fusion ignition and gain in the laboratory for the first time. This key milestone in the development of inertial confinement fusion (ICF) can be expected to engender interest in the development of inertial fusion energy (IFE) and expanded efforts on a number of advanced targets that may achieve high fusion energy gain at lower driver energies. In this tutorial talk, we will discuss the physics underlying ICF ignition and thermonuclear burn, examine the requirements for high gain, and outline candidate R&D programs that will be required to assess the performance of these target concepts under various driver systems including lasers, heavy-ions and pulsed power. Such target concepts include those operating by fast ignition, shock ignition, impact ignition, dual-density, magnetically-insulated, one- and two-sided drive, etc., some of which may have potential to burn advanced, non-DT fusion fuels. We will then delineate the role of such targets in their application to the production of high average fusion power. Here, systems studies of IFE economics suggest that we should strive for target fusion gains of around 100 at drive energies of 1MJ, together with corresponding rep-rates of up to 10Hz and driver electrical efficiencies around 15%. In future years, there may be exciting opportunities to study such ``innovative confinement concepts'' with prospects of fielding them on facilities such as NIF to obtain high fusion energy gains on a single shot basis.

Preadipocyte 11beta-hydroxysteroid dehydrogenase type 1 is a keto-reductase and contributes to diet-induced visceral obesity in vivo.

PubMed

De Sousa Peixoto, R A; Turban, S; Battle, J H; Chapman, K E; Seckl, J R; Morton, N M

2008-04-01

Glucocorticoid excess promotes visceral obesity and cardiovascular disease. Similar features are found in the highly prevalent metabolic syndrome in the absence of high levels of systemic cortisol. Although elevated activity of the glucocorticoid-amplifying enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) within adipocytes might explain this paradox, the potential role of 11beta-HSD1 in preadipocytes is less clear; human omental adipose stromal vascular (ASV) cells exhibit 11beta-dehydrogenase activity (inactivation of glucocorticoids) probably due to the absence of cofactor provision by hexose-6-phosphate dehydrogenase. To clarify the depot-specific impact of 11beta-HSD1, we assessed whether preadipocytes in ASV from mesenteric (as a representative of visceral adipose tissue) and sc tissue displayed 11beta-HSD1 activity in mice. 11beta-HSD1 was highly expressed in freshly isolated ASV cells, predominantly in preadipocytes. 11beta-HSD1 mRNA and protein levels were comparable between ASV and adipocyte fractions in both depots. 11beta-HSD1 was an 11beta-reductase, thus reactivating glucocorticoids in ASV cells, consistent with hexose-6-phosphate dehydrogenase mRNA expression. Unexpectedly, glucocorticoid reactivation was higher in intact mesenteric ASV cells despite a lower expression of 11beta-HSD1 mRNA and protein (homogenate activity) levels than sc ASV cells. This suggests a novel depot-specific control over 11beta-HSD1 enzyme activity. In vivo, high-fat diet-induced obesity was accompanied by increased visceral fat preadipocyte differentiation in wild-type but not 11beta-HSD1(-/-) mice. The results suggest that 11beta-HSD1 reductase activity is augmented in mouse mesenteric preadipocytes where it promotes preadipocyte differentiation and contributes to visceral fat accumulation in obesity.

A local approach for focussed Bayesian fusion

NASA Astrophysics Data System (ADS)

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

2009-04-01

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

Use of an in vivo titration method to study a global regulator: effect of varying Lrp levels on expression of gltBDF in Escherichia coli.

PubMed

Borst, D W; Blumenthal, R M; Matthews, R G

1996-12-01

Most studies of global regulatory proteins are performed in vitro or involve phenotypic comparisons between wild-type and mutant strains. We report the use of strains in which the gene for the leucine-responsive regulatory protein (lrp) is transcribed from isopropyl-beta-D-thiogalactopyranoside (IPTG)-inducible promoters for the purpose of continuously varying the in vivo concentration of Lrp. To obtain a broad range of Lrp concentrations, strains were employed that contained the lrp fusion either in the chromosome (I. C. Blomfield, P. J. Calie, K. J. Eberhardt, M. S. McClain, and B. I. Eisenstein, J. Bacteriol. 175:27-36, 1993) or on a multicopy plasmid. Western blot (immunoblot) analysis with polyclonal antiserum to Lrp confirmed that Lrp levels could be varied more than 70-fold by growing the strains in glucose minimal 3-(N-morpholino)propanesulfonic acid (MOPS) medium containing different amounts of IPTG. Expression of an Lrp-regulated gltB::lacZ operon fusion was measured over this range of Lrp concentrations. beta-Galactosidase activity rose with increasing Lrp levels up to the level of Lrp found in wild-type strains, at which point expression is maximal. The presence of leucine in the medium increased the level of Lrp necessary to achieve half-maximal expression of the gltB::lacZ fusion, as predicted by earlier in vitro studies (B. R. Ernsting, J. W. Denninger, R. M. Blumenthal, and R. G. Matthews, J. Bacteriol. 175:7160-7169, 1993). Interestingly, levels of Lrp greater than those in wild-type cells interfered with activation of gltB::lacZ expression. The growth rate of cultures correlated with the intracellular Lrp concentration: levels of Lrp either lower or higher than wild-type levels resulted in significantly slower growth rates. Thus, the level of Lrp in the cell appears to be optimal for rapid growth in minimal medium, and the gltBDF control region is designed to give maximal expression at this Lrp level.

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.

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

NASA Astrophysics Data System (ADS)

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

2017-09-01

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

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

PubMed

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

2016-07-01

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

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

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

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

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

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

Finley, V.L.; Wiezcorek, M.A.

This report gives the results of the environmental activities and monitoring programs at the Princeton Plasma Physics Laboratory (PPPL) for CY93. The report is prepared to provide the U.S. Department of Energy (DOE) and the public with information on the level of radioactive and non-radioactive pollutants, if any, added to the environment as a result of PPPL operations, as well as environmental initiatives, assessments, and programs that were undertaken in 1993. The objective of the Annual Site Environmental Report is to document evidence that DOE facility environmental protection programs adequately protect the environment and the public health. The Princeton Plasmamore » Physics Laboratory has engaged in fusion energy research since 1951. The long-range goal of the U.S. Magnetic Fusion Energy Research Program is to develop and demonstrate the practical application of fusion power as an alternate energy source. In 1993, PPPL had both of its two large tokamak devices in operation; the Tokamak Fusion Test Reactor (TFTR) and the Princeton Beta Experiment-Modification (PBX-M). PBX-M completed its modifications and upgrades and resumed operation in November 1991. TFTR began the deuterium-tritium (D-T) experiments in December 1993 and set new records by producing over six million watts of energy. The engineering design phase of the Tokamak Physics Experiment (TPX), which replaced the cancelled Burning Plasma Experiment in 1992 as PPPL`s next machine, began in 1993 with the planned start up set for the year 2001. In 1993, the Environmental Assessment (EA) for the TFRR Shutdown and Removal (S&R) and TPX was prepared for submittal to the regulatory agencies.« less

Viral membrane fusion

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

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

2015-05-15

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

High power beta electron device - Beyond betavoltaics

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

Ayers, William M.; Gentile, Charles A.

Developing watt level power sources with beta emitting radioisotopes has been limited by the inability to utilize high energy (> 100 KeV) beta emitters at high radioisotope loadings without damaging the energy conversion materials. A new type of beta electron power source is described that removes those restrictions. This approach contains the radioisotope in a beta transparent titanium tube and confines beta electrons emitted through the tube wall to spiral trajectories around the tube with an axial magnetic field. The confined beta electrons dissipate energy though multiple interactions with surrounding excimer precursor gas atoms to efficiently generate photons. Photovoltaic cellsmore » convert the photons to electrical power. Since the beta electrons dissipate energy in the excimer precursor gas, the device can be loaded with more than 10 13 Bq of radioisotope to generate 100 milliwatt to watt levels of electrical power without damaging the device materials or degrading its performance. Furthermore, the power source can use a variety of beta radioisotopes and scales by stacking the devices.« less

High power beta electron device - Beyond betavoltaics

DOE PAGES

Ayers, William M.; Gentile, Charles A.

2017-11-10

Developing watt level power sources with beta emitting radioisotopes has been limited by the inability to utilize high energy (> 100 KeV) beta emitters at high radioisotope loadings without damaging the energy conversion materials. A new type of beta electron power source is described that removes those restrictions. This approach contains the radioisotope in a beta transparent titanium tube and confines beta electrons emitted through the tube wall to spiral trajectories around the tube with an axial magnetic field. The confined beta electrons dissipate energy though multiple interactions with surrounding excimer precursor gas atoms to efficiently generate photons. Photovoltaic cellsmore » convert the photons to electrical power. Since the beta electrons dissipate energy in the excimer precursor gas, the device can be loaded with more than 10 13 Bq of radioisotope to generate 100 milliwatt to watt levels of electrical power without damaging the device materials or degrading its performance. Furthermore, the power source can use a variety of beta radioisotopes and scales by stacking the devices.« less

High power beta electron device - Beyond betavoltaics.

PubMed

Ayers, William M; Gentile, Charles A

2018-01-01

Developing watt level power sources with beta emitting radioisotopes has been limited by the inability to utilize high energy (> 100KeV) beta emitters at high radioisotope loadings without damaging the energy conversion materials. A new type of beta electron power source is described that removes those restrictions. The approach contains the radioisotope in a beta transparent titanium tube and confines beta electrons emitted through the tube wall to spiral trajectories around the tube with an axial magnetic field. The confined beta electrons dissipate energy though multiple interactions with surrounding excimer precursor gas atoms to efficiently generate photons. Photovoltaic cells convert the photons to electrical power. Since the beta electrons dissipate energy in the excimer precursor gas, the device can be loaded with more than 10 13 Bq of radioisotope to generate 100 milliwatt to watt levels of electrical power without damaging the device materials or degrading its performance. The power source can use a variety of beta radioisotopes and scales by stacking the devices. Copyright © 2017. Published by Elsevier Ltd.

Whole organism high content screening identifies stimulators of pancreatic beta-cell proliferation.

PubMed

Tsuji, Naoki; Ninov, Nikolay; Delawary, Mina; Osman, Sahar; Roh, Alex S; Gut, Philipp; Stainier, Didier Y R

2014-01-01

Inducing beta-cell mass expansion in diabetic patients with the aim to restore glucose homeostasis is a promising therapeutic strategy. Although several in vitro studies have been carried out to identify modulators of beta-cell mass expansion, restoring endogenous beta-cell mass in vivo has yet to be achieved. To identify potential stimulators of beta-cell replication in vivo, we established transgenic zebrafish lines that monitor and allow the quantification of cell proliferation by using the fluorescent ubiquitylation-based cell cycle indicator (FUCCI) technology. Using these new reagents, we performed an unbiased chemical screen, and identified 20 small molecules that markedly increased beta-cell proliferation in vivo. Importantly, these structurally distinct molecules, which include clinically-approved drugs, modulate three specific signaling pathways: serotonin, retinoic acid and glucocorticoids, showing the high sensitivity and robustness of our screen. Notably, two drug classes, retinoic acid and glucocorticoids, also promoted beta-cell regeneration after beta-cell ablation. Thus, this study establishes a proof of principle for a high-throughput small molecule-screen for beta-cell proliferation in vivo, and identified compounds that stimulate beta-cell proliferation and regeneration.

Estrogen receptor signaling in prostate cancer: Implications for carcinogenesis and tumor progression.

PubMed

Bonkhoff, Helmut

2018-01-01

The androgen receptor (AR) is the classical target for prostate cancer prevention and treatment, but more recently estrogens and their receptors have also been implicated in prostate cancer development and tumor progression. Recent experimental and clinical data were reviewed to elucidate pathogenetic mechanisms how estrogens and their receptors may affect prostate carcinogenesis and tumor progression. The estrogen receptor beta (ERβ) is the most prevalent ER in the human prostate, while the estrogen receptor alpha (ERα) is restricted to basal cells of the prostatic epithelium and stromal cells. In high grade prostatic intraepithelial neoplasia (HGPIN), the ERα is up-regulated and most likely mediates carcinogenic effects of estradiol as demonstrated in animal models. The partial loss of the ERβ in HGPIN indicates that the ERβ acts as a tumor suppressor. The tumor promoting function of the TMPRSS2-ERG fusion, a major driver of prostate carcinogenesis, is triggered by the ERα and repressed by the ERβ. The ERβ is generally retained in hormone naïve and metastatic prostate cancer, but is partially lost in castration resistant disease. The progressive emergence of the ERα and ERα-regulated genes (eg, progesterone receptor (PR), PS2, TMPRSS2-ERG fusion, and NEAT1) during prostate cancer progression and hormone refractory disease suggests that these tumors can bypass the AR by using estrogens and progestins for their growth. In addition, nongenomic estrogen signaling pathways mediated by orphan receptors (eg, GPR30 and ERRα) has also been implicated in prostate cancer progression. Increasing evidences demonstrate that local estrogen signaling mechanisms are required for prostate carcinogenesis and tumor progression. Despite the recent progress in this research topic, the translation of the current information into potential therapeutic applications remains highly challenging and clearly warrants further investigation. © 2017 Wiley Periodicals, Inc.

Movement-related beta oscillations show high intra-individual reliability.

PubMed

Espenhahn, Svenja; de Berker, Archy O; van Wijk, Bernadette C M; Rossiter, Holly E; Ward, Nick S

2017-02-15

Oscillatory activity in the beta frequency range (15-30Hz) recorded from human sensorimotor cortex is of increasing interest as a putative biomarker of motor system function and dysfunction. Despite its increasing use in basic and clinical research, surprisingly little is known about the test-retest reliability of spectral power and peak frequency measures of beta oscillatory signals from sensorimotor cortex. Establishing that these beta measures are stable over time in healthy populations is a necessary precursor to their use in the clinic. Here, we used scalp electroencephalography (EEG) to evaluate intra-individual reliability of beta-band oscillations over six sessions, focusing on changes in beta activity during movement (Movement-Related Beta Desynchronization, MRBD) and after movement termination (Post-Movement Beta Rebound, PMBR). Subjects performed visually-cued unimanual wrist flexion and extension. We assessed Intraclass Correlation Coefficients (ICC) and between-session correlations for spectral power and peak frequency measures of movement-related and resting beta activity. Movement-related and resting beta power from both sensorimotor cortices was highly reliable across sessions. Resting beta power yielded highest reliability (average ICC=0.903), followed by MRBD (average ICC=0.886) and PMBR (average ICC=0.663). Notably, peak frequency measures yielded lower ICC values compared to the assessment of spectral power, particularly for movement-related beta activity (ICC=0.386-0.402). Our data highlight that power measures of movement-related beta oscillations are highly reliable, while corresponding peak frequency measures show greater intra-individual variability across sessions. Importantly, our finding that beta power estimates show high intra-individual reliability over time serves to validate the notion that these measures reflect meaningful individual differences that can be utilised in basic research and clinical studies. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Molecular cloning and characterization of two mouse peroxisome proliferator-activated receptor alpha (PPARalpha)-regulated peroxisomal acyl-CoA thioesterases.

PubMed

Westin, Maria A K; Alexson, Stefan E H; Hunt, Mary C

2004-05-21

Peroxisomes are organelles that function in the beta-oxidation of long- and very long-chain acyl-CoAs, bile acid-CoA intermediates, prostaglandins, leukotrienes, thromboxanes, dicarboxylic fatty acids, pristanic acid, and xenobiotic carboxylic acids. The very long- and long-chain acyl-CoAs are mainly chain-shortened and then transported to mitochondria for further metabolism. We have now identified and characterized two peroxisomal acyl-CoA thioesterases, named PTE-Ia and PTE-Ic, that hydrolyze acyl-CoAs to the free fatty acid and coenzyme A. PTE-Ia and PTE-Ic show 82% sequence identity at the amino acid level, and a putative peroxisomal type 1 targeting signal of -AKL was identified at the carboxyl-terminal end of both proteins. Localization experiments using green fluorescent fusion protein showed PTE-Ia and PTE-Ic to be localized in peroxisomes. Despite their high level of sequence identity, we show that PTE-Ia is mainly active on long-chain acyl-CoAs, whereas PTE-Ic is mainly active on medium-chain acyl-CoAs. Lack of regulation of enzyme activity by free CoASH suggests that PTE-Ia and PTE-Ic regulate intraperoxisomal levels of acyl-CoA, and they may have a function in termination of beta-oxidation of fatty acids of different chain lengths. Tissue expression studies revealed that PTE-Ia is highly expressed in kidney, whereas PTE-Ic is most highly expressed in spleen, brain, testis, and proximal and distal intestine. Both PTE-Ia and PTE-Ic were highly up-regulated in mouse liver by treatment with the peroxisome proliferator WY-14,643 and by fasting in a peroxisome proliferator-activated receptor alpha-dependent manner. These data show that PTE-Ia and PTE-Ic have different functions based on different substrate specificities and tissue expression.

Axisymmetric Tandem Mirrors: Stabilization and Confinement Studies

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

Post, R.F.; Fowler, T.K.; Bulmer, R.

2005-01-15

The 'Kinetic Stabilizer' has been proposed as a means of MHD stabilizing an axisymmetric tandem mirror system. The K-S concept is based on theoretical studies by Ryutov, confirmed experimentally in the Gas Dynamic Trap experiment in Novosibirsk. In the K-S beams of ions are directed into the end of an 'expander' region outside the outer mirror of a tandem mirror. These ions, slowed, stagnated, and reflected as they move up the magnetic gradient, produce a low-density stabilizing plasma.At the Lawrence Livermore National Laboratory we have been conducting theoretical and computational studies of the K-S Tandem Mirror. These studies have employedmore » a low-beta code written especially to analyze the beam injection/stabilization process,and a new code SYMTRAN (by Hua and Fowler)that solves the coupled radial and axial particle and energy transport in a K-S T-M. Also, a 'legacy' MHD stability code, FLORA, has been upgraded and employed to benchmark the injection/stabilization code and to extend its results to high beta values.The FLORA code studies so far have confirmed the effectiveness of the K-S in stabilizing high-beta (40%) plasmas with stabilizer plasmas the peak pressures of which are several orders of magnitude smaller than those of the confined plasma.Also the SYMTRAN code has shown D-T plasma ignition from alpha particle energy deposition in T-M regimes with strong end plugging.Our studies have confirmed the viability of the K-S T-M concept with respect to MHD stability and radial and axial confinement. We are continuing these studies in order to optimize the parameters and to examine means for the stabilization of possible residual instability modes, such as drift modes and 'trapped-particle' modes. These modes may in principle be controlled by tailoring the stabilizer plasma distribution and/or the radial potential distribution.In the paper the results to date of our studies are summarized and projected to scope out possible fusion-power versions of the K-S T-M.« less

Axisymmetric Tandem Mirrors: Stabilization and Confinement Studies

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

Post, R F; Fowler, T K; Bulmer, R

2004-07-15

The 'Kinetic Stabilizer' has been proposed as a means of MHD stabilizing an axisymmetric tandem mirror system. The K-S concept is based on theoretical studies by Ryutov, confirmed experimentally in the Gas Dynamic Trap experiment in Novosibirsk. In the K-S beams of ions are directed into the end of an 'expander' region outside the outer mirror of a tandem mirror. These ions, slowed, stagnated, and reflected as they move up the magnetic gradient, produce a low-density stabilizing plasma. At the Lawrence Livermore National Laboratory we have been conducting theoretical and computational studies of the K-S Tandem Mirror. These studies havemore » employed a low-beta code written especially to analyze the beam injection/stabilization process, and a new code SYMTRAN (by Hua and Fowler) that solves the coupled radial and axial particle and energy transport in a K-S TM. Also, a 'legacy' MHD stability code, FLORA, has been upgraded and employed to benchmark the injection/stabilization code and to extend its results to high beta values. The FLORA code studies so far have confirmed the effectiveness of the K-S in stabilizing high-beta (40%) plasmas with stabilizer plasmas the peak pressures of which are several orders of magnitude smaller than those of the confined plasma. Also the SYMTRAN code has shown D-T plasma ignition from alpha particle energy deposition in T-M regimes with strong end plugging. Our studies have confirmed the viability of the K-S-T-M concept with respect to MHD stability and radial and axial confinement. We are continuing these studies in order to optimize the parameters and to examine means for the stabilization of possible residual instability modes, such as drift modes and 'trapped-particle' modes. These modes may in principle be controlled by tailoring the stabilizer plasma distribution and/or the radial potential distribution. In the paper the results to date of our studies are summarized and projected to scope out possible fusion-power versions of the K-S T-M« less

Impaired activation of adenylyl cyclase in lung of the Basenji-greyhound model of airway hyperresponsiveness: decreased numbers of high affinity beta-adrenoceptors.

PubMed Central

Emala, C. W.; Aryana, A.; Hirshman, C. A.

1996-01-01

1. To evaluate mechanisms involved in the impaired beta-adrenoceptor stimulation of adenylyl cyclase in tissues from the Basenji-greyhound (BG) dog model of airway hyperresponsiveness, we compared agonist and antagonist binding affinity of beta-adrenoceptors, beta-adrenoceptor subtypes, percentage of beta-adrenoceptors sequestered, and coupling of the beta-adrenoceptor to Gs alpha in lung membranes from BG and control mongrel dogs. We found that lung membranes from the BG dog had higher total numbers of beta-adrenoceptors with a greater percentage of receptors of the beta 2 subtype as compared to mongrel lung membranes. 2. Agonist and antagonist binding affinity and the percentage of beta-adrenoceptors sequestered were not different in BG and mongrel dog lung membranes. However, the percentage of beta-adrenoceptors in the high affinity state for agonist was decreased in BG lung membranes suggesting an uncoupling of the receptor from Gs alpha. 3. Impaired coupling between the beta-adrenoceptor and G protein documented by the decreased numbers of beta-adrenoceptors in the high affinity state in BG lung membranes, is a plausible explanation for the reduced stimulation of adenylyl cyclase and the resultant reduction in airway smooth muscle relaxation in this model. PMID:8864536

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

NASA Astrophysics Data System (ADS)

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

2014-04-01

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

[High non-specific binding of the beta(1) -selective radioligand 2-(125)I-ICI-H].

PubMed

Riemann, B; Law, M P; Kopka, K; Wagner, St; Luthra, S; Pike, V W; Neumann, J; Kirchhefer, U; Schmitz, W; Schober, O; Schäfers, M

2003-08-01

As results of cardiac biopsies suggest, myocardial beta(1) -adrenoceptor density is reduced in patients with chronic heart failure. However, changes in cardiac beta(2)-adrenoceptors vary. With suitable radiopharmaceuticals single photon emission computed tomography (SPECT) and positron emission tomography (PET) offer the opportunity to assess beta-adrenoceptors non-invasively. Among the novel racemic analogues of the established beta(1)-selective adrenoceptor antagonist ICI 89.406 the iodinated 2-I-ICI-H showed high affinity and selectivity to beta(1)-adrenoceptors in murine ventricular membranes. The aim of this study was its evaluation as a putative sub-type selective beta(1)-adrenergic radioligand in cardiac imaging. Competition studies in vitro and in vivo were used to investigate the kinetics of 2-I-ICI-H binding to cardiac beta-adrenoceptors in mice and rats. In addition, the radiosynthesis of 2-(125)I-ICI-H from the silylated precursor 2-SiMe(3)-ICI-H was established. The specific activity was 80 GBq/ micro mol, the radiochemical yield ranged from 70 to 80%. The unlabelled compound 2-I-ICI-H showed high beta(1)-selectivity and -affinity in the in vitro competition studies. In vivo biodistribution studies apparently showed low affinity to cardiac beta-adrenoceptors. The radiolabelled counterpart 2-(125)I-ICI-H showed a high degree of non-specific binding in vitro and no specific binding to cardiac beta(1)-adrenoceptors in vivo. Because of its high non-specific binding 2-(125)I-ICI-H is no suitable radiotracer for imaging in vivo.

Proposal for a novel type of small scale aneutronic fusion reactor

NASA Astrophysics Data System (ADS)

Gruenwald, J.

2017-02-01

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

Solid-solid phase transformation via internal stress-induced virtual melting, significantly below the melting temperature. Application to HMX energetic crystal.

PubMed

Levitas, Valery I; Henson, Bryan F; Smilowitz, Laura B; Asay, Blaine W

2006-05-25

We theoretically predict a new phenomenon, namely, that a solid-solid phase transformation (PT) with a large transformation strain can occur via internal stress-induced virtual melting along the interface at temperatures significantly (more than 100 K) below the melting temperature. We show that the energy of elastic stresses, induced by transformation strain, increases the driving force for melting and reduces the melting temperature. Immediately after melting, stresses relax and the unstable melt solidifies. Fast solidification in a thin layer leads to nanoscale cracking which does not affect the thermodynamics or kinetics of the solid-solid transformation. Thus, virtual melting represents a new mechanism of solid-solid PT, stress relaxation, and loss of coherence at a moving solid-solid interface. It also removes the athermal interface friction and deletes the thermomechanical memory of preceding cycles of the direct-reverse transformation. It is also found that nonhydrostatic compressive internal stresses promote melting in contrast to hydrostatic pressure. Sixteen theoretical predictions are in qualitative and quantitative agreement with experiments conducted on the PTs in the energetic crystal HMX. In particular, (a) the energy of internal stresses is sufficient to reduce the melting temperature from 551 to 430 K for the delta phase during the beta --> delta PT and from 520 to 400 K for the beta phase during the delta --> beta PT; (b) predicted activation energies for direct and reverse PTs coincide with corresponding melting energies of the beta and delta phases and with the experimental values; (c) the temperature dependence of the rate constant is determined by the heat of fusion, for both direct and reverse PTs; results b and c are obtained both for overall kinetics and for interface propagation; (d) considerable nanocracking, homogeneously distributed in the transformed material, accompanies the PT, as predicted by theory; (e) the nanocracking does not change the PT thermodynamics or kinetics appreciably for the first and the second PT beta <--> delta cycles, as predicted by theory; (f) beta <--> delta PTs start at a very small driving force (in contrast to all known solid-solid transformations with large transformation strain), that is, elastic energy and athermal interface friction must be negligible; (g) beta --> alpha and alpha --> beta PTs, which are thermodynamically possible in the temperature range 382.4 < theta < 430 K and below 382.4 K, respectively, do not occur.

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

NASA Technical Reports Server (NTRS)

Schenker, Paul S. (Editor)

1990-01-01

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

Regulation of Serratia marcescens ompF and ompC porin genes in response to osmotic stress, salicylate, temperature and pH.

PubMed

Begic, Sanela; Worobec, Elizabeth A

2006-02-01

Serratia marcescens is a Gram-negative enterobacterium that has become an important opportunistic pathogen, largely due to its high degree of natural antibiotic resistance. One factor contributing to this natural antibiotic resistance is reduced outer membrane permeability, which is controlled in part by OmpC and OmpF porin proteins. OmpF expression is regulated by micF, an RNA transcript encoded upstream of the ompC gene, which hybridizes with the ompF transcript to inhibit its translation. Regulation of S. marcescens porin gene expression, as well as that of micF, was investigated using beta-galactosidase reporter gene fusions in response to 5, 8 and 10 % sucrose, 1, 5 and 8 mM salicylate, and different pH and temperature values. beta-Galactosidase activity assays revealed that a lower growth temperature (28 degrees C), a more basic pH (pH 8), and an absence of sucrose and salicylate induce the transcription of the ompF gene, whereas the induction of ompC is stimulated at a higher growth temperature (42 degrees C), acidic pH (pH 6), and maximum concentrations of sucrose (10 %) and salicylate (8 mM). In addition, when multiple conditions were tested, temperature had the predominant effect, followed by pH. In this study, it was found that the MicF regulatory mechanism does not play a role in the osmoregulation of the ompF and ompC genes, whereas MicF does repress OmpF expression in the presence of salicylate and high growth temperature, and under low pH conditions.

Statistical algorithms improve accuracy of gene fusion detection

PubMed Central

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

2017-01-01

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

Ultrahigh field magnetic resonance and colour Doppler real-time fusion imaging of the orbit--a hybrid tool for assessment of choroidal melanoma.

PubMed

Walter, Uwe; Niendorf, Thoralf; Graessl, Andreas; Rieger, Jan; Krüger, Paul-Christian; Langner, Sönke; Guthoff, Rudolf F; Stachs, Oliver

2014-05-01

A combination of magnetic resonance images with real-time high-resolution ultrasound known as fusion imaging may improve ophthalmologic examination. This study was undertaken to evaluate the feasibility of orbital high-field magnetic resonance and real-time colour Doppler ultrasound image fusion and navigation. This case study, performed between April and June 2013, included one healthy man (age, 47 years) and two patients (one woman, 57 years; one man, 67 years) with choroidal melanomas. All cases underwent 7.0-T magnetic resonance imaging using a custom-made ocular imaging surface coil. The Digital Imaging and Communications in Medicine volume data set was then loaded into the ultrasound system for manual registration of the live ultrasound image and fusion imaging examination. Data registration, matching and then volume navigation were feasible in all cases. Fusion imaging provided real-time imaging capabilities and high tissue contrast of choroidal tumour and optic nerve. It also allowed adding a real-time colour Doppler signal on magnetic resonance images for assessment of vasculature of tumour and retrobulbar structures. The combination of orbital high-field magnetic resonance and colour Doppler ultrasound image fusion and navigation is feasible. Multimodal fusion imaging promises to foster assessment and monitoring of choroidal melanoma and optic nerve disorders. • Orbital magnetic resonance and colour Doppler ultrasound real-time fusion imaging is feasible • Fusion imaging combines the spatial and temporal resolution advantages of each modality • Magnetic resonance and ultrasound fusion imaging improves assessment of choroidal melanoma vascularisation.

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

Ono, Kenji; Fuma, Kazuya; Tabata, Kaori

Magnetic resonance imaging (MRI) is a minimally invasive way to provide high spatial resolution tomograms. However, MRI has been considered to be useless for gene expression imaging compared to optical imaging. In this study, we used a ferritin reporter, binding with biogenic iron, to make it a powerful tool for gene expression imaging in MRI studies. GL261 mouse glioma cells were over-expressed with dual-reporter ferritin-DsRed under {beta}-actin promoter, then gene expression was observed by optical imaging and MRI in a brain tumor model. GL261 cells expressing ferritin-DsRed fusion protein showed enhanced visualizing effect by reducing T2-weighted signal intensity for inmore » vitro and in vivo MRI studies, as well as DsRed fluorescence for optical imaging. Furthermore, a higher contrast was achieved on T2-weighted images when permeating the plasma membrane of ferritin-DsRed-expressing GL261. Thus, a ferritin expression vector can be used as an MRI reporter to monitor in vivo gene expression.« less

Fishbone Mode Excited by Deeply Trapped Energetic Beam Ions in EAST

NASA Astrophysics Data System (ADS)

Zheng, Ting; Wu, Bin; Xu, Liqing; Hu, Chundong; Zang, Qing; Ding, Siye; Li, Yingying; Wu, Xingquan; Wang, Jinfang; Shen, Biao; Zhong, Guoqiang; Li, Hao; Shi, Tonghui; EAST Team

2016-06-01

This paper describes the fishbone mode phenomena during the injection of high-power neutral beams in EAST (Experimental Advanced Superconducting Tokamak). The features of the fishbone mode are presented. The change in frequency of the mode during a fishbone burst is from 1 kHz to 6 kHz. The nonlinear behavior of the fishbone mode is analyzed by using a prey-predator model, which is consistent with the experimental results. This model indicates that the periodic oscillations of the fishbone mode always occur near the critical value of fast ion beta. Furthermore, the neutral beam analysis for the discharge is done by using the NUBEAM module of the TRANSP code. According to the numerical simulation results and theoretical calculation, it can be concluded that the fishbone mode is driven by the deeply trapped energetic beam ions in EAST. supported by the National Magnetic Confinement Fusion Science Program of China (Nos. 2013GB101001, 2014DFG61950 and 2013GB112003) and National Natural Science Foundation of China (Nos. 11175211 and 11275233)

Genomic response to Wnt signalling is highly context-dependent - Evidence from DNA microarray and chromatin immunoprecipitation screens of Wnt/TCF targets

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

Railo, Antti; Pajunen, Antti; Itaeranta, Petri

2009-10-01

Wnt proteins are important regulators of embryonic development, and dysregulated Wnt signalling is involved in the oncogenesis of several human cancers. Our knowledge of the downstream target genes is limited, however. We used a chromatin immunoprecipitation-based assay to isolate and characterize the actual gene segments through which Wnt-activatable transcription factors, TCFs, regulate transcription and an Affymetrix microarray analysis to study the global transcriptional response to the Wnt3a ligand. The anti-{beta}-catenin immunoprecipitation of DNA-protein complexes from mouse NIH3T3 fibroblasts expressing a fusion protein of {beta}-catenin and TCF7 resulted in the identification of 92 genes as putative TCF targets. GeneChip assays ofmore » gene expression performed on NIH3T3 cells and the rat pheochromocytoma cell line PC12 revealed 355 genes in NIH3T3 and 129 genes in the PC12 cells with marked changes in expression after Wnt3a stimulus. Only 2 Wnt-regulated genes were shared by both cell lines. Surprisingly, Disabled-2 was the only gene identified by the chromatin immunoprecipitation approach that displayed a marked change in expression in the GeneChip assay. Taken together, our approaches give an insight into the complex context-dependent nature of Wnt pathway transcriptional responses and identify Disabled-2 as a potential new direct target for Wnt signalling.« less

Structural and Functional Properties of Peptides Based on the N-terminus of HIV-1 gp41 and the C-terminus of the Amyloid-Beta Protein

PubMed Central

Gordon, Larry M.; Nisthal, Alex; Lee, Andy B.; Eskandari, Sepehr; Ruchala, Piotr; Jung, Chun-Ling; Waring, Alan J.; Mobley, Patrick W.

2008-01-01

Given their high alanine and glycine levels, plaque formation, α-helix to β-sheet interconversion and fusogenicity, FP (i.e., the N-terminal fusion peptide of HIV-1 gp41; 23 residues) and amyloids were proposed as belonging to the same protein superfamily. Here, we further test whether FP may exhibit ‘amyloid-like’ characteristics, by contrasting its structural and functional properties with those of Aβ(26–42), a 17-residue peptide from the C-terminus of the amyloid-beta protein responsible for Alzheimer’s. FTIR spectroscopy, electron microscopy, light scattering and predicted amyloid structure aggregation (PASTA) indicated that aqueous FP and Aβ(26–42) formed similar networked β-sheet fibrils, although the FP fibril interactions were weaker. FP and Aβ(26–42) both lysed and aggregated human erythrocytes, with the hemolysis-onsets correlated with the conversion of α-helix to β-sheet for each peptide in liposomes. Congo red (CR), a marker of amyloid plaques in situ, similarly inhibited either FP- or Aβ(26–42)-induced hemolysis, and surface plasmon resonance indicated that this may be due to direct CR-peptide binding. These findings suggest that membrane-bound β-sheets of FP may contribute to the cytopathicity of HIV in vivo through an amyloid-type mechanism, and support the classification of HIV-1 FP as an ‘amyloid homolog’ (or ‘amylog’). PMID:18515070

Reciprocal expression of integration host factor and HU in the developmental cycle and infectivity of Legionella pneumophila.

PubMed

Morash, Michael G; Brassinga, Ann Karen C; Warthan, Michelle; Gourabathini, Poornima; Garduño, Rafael A; Goodman, Steven D; Hoffman, Paul S

2009-04-01

Legionella pneumophila is an intracellular parasite of protozoa that differentiates late in infection into metabolically dormant cysts that are highly infectious. Regulation of this process is poorly understood. Here we report that the small DNA binding regulatory proteins integration host factor (IHF) and HU are reciprocally expressed over the developmental cycle, with HU expressed during exponential phase and IHF expressed postexponentially. To assess the role of these regulatory proteins in development, chromosomal deletions were constructed. Single (ihfA or ihfB) and double deletion (Deltaihf) IHF mutants failed to grow in Acanthamoeba castellanii unless complemented in trans when expressed temporally from the ihfA promoter but not under P(tac) (isopropyl-beta-d-thiogalactopyranoside). In contrast, IHF mutants were infectious for HeLa cells, though electron microscopic examination revealed defects in late-stage cyst morphogenesis (thickened cell wall, intracytoplasmic membranes, and inclusions of poly-beta-hydroxybutyrate), and were depressed for the developmental marker MagA. Green fluorescent protein promoter fusion assays indicated that IHF and the stationary-phase sigma factor RpoS were required for full postexponential expression of magA. Finally, defects in cyst morphogenesis noted for Deltaihf mutants in HeLa cells correlated with a loss of both detergent resistance and hyperinfectivity compared with results for wild-type cysts. These studies establish IHF and HU as markers of developmental stages and show that IHF function is required for both differentiation and full virulence of L. pneumophila in natural amoebic hosts.

SH2 domains of the p85 alpha subunit of phosphatidylinositol 3-kinase regulate binding to growth factor receptors.

PubMed Central

McGlade, C J; Ellis, C; Reedijk, M; Anderson, D; Mbamalu, G; Reith, A D; Panayotou, G; End, P; Bernstein, A; Kazlauskas, A

1992-01-01

The binding of cytoplasmic signaling proteins such as phospholipase C-gamma 1 and Ras GTPase-activating protein to autophosphorylated growth factor receptors is directed by their noncatalytic Src homology region 2 (SH2) domains. The p85 alpha regulatory subunit of phosphatidylinositol (PI) 3-kinase, which associates with several receptor protein-tyrosine kinases, also contains two SH2 domains. Both p85 alpha SH2 domains, when expressed individually as fusion proteins in bacteria, bound stably to the activated beta receptor for platelet-derived growth factor (PDGF). Complex formation required PDGF stimulation and was dependent on receptor tyrosine kinase activity. The bacterial p85 alpha SH2 domains recognized activated beta PDGF receptor which had been immobilized on a filter, indicating that SH2 domains contact autophosphorylated receptors directly. Several receptor tyrosine kinases within the PDGF receptor subfamily, including the colony-stimulating factor 1 receptor and the Steel factor receptor (Kit), also associate with PI 3-kinase in vivo. Bacterially expressed SH2 domains derived from the p85 alpha subunit of PI 3-kinase bound in vitro to the activated colony-stimulating factor 1 receptor and to Kit. We infer that the SH2 domains of p85 alpha bind to high-affinity sites on these receptors, whose creation is dependent on receptor autophosphorylation. The SH2 domains of p85 are therefore primarily responsible for the binding of PI 3-kinase to activated growth factor receptors. Images PMID:1372092

NIMROD Simulations of the HIT-SI and HIT-SI3 Devices

NASA Astrophysics Data System (ADS)

Morgan, Kyle; Jarboe, Tom; Hossack, Aaron; Chandra, Rian; Everson, Chris

2017-10-01

The Helicity Injected Torus with Steady Inductive helicity injection (HIT-SI) experiment uses a set of inductively driven helicity injectors to apply non-axisymmetric current drive on the edge of the plasma, driving an axisymmetric spheromak equilibrium in a central confinement volume. Significant improvements have been made to extended MHD modeling of HIT-SI, with both the resolution of disagreement at high injector frequencies in HIT-SI in addition to successes with the new upgraded HIT-SI3 device. Previous numerical studies of HIT-SI, using a zero-beta eMHD model, focused on operations with a drive frequency of 14.5 kHz, and found reduced agreement with both the magnetic profile and current amplification at higher frequencies (30-70 kHz). HIT-SI3 has three helicity injectors which are able to operate with different mode structures of perturbations through the different relative temporal phasing of the injectors. Simulations that allow for pressure gradients have been performed in the parameter regimes of both devices using the NIMROD code and show improved agreement with experimental results, most notably capturing the observed Shafranov-shift due to increased beta observed at higher finj in HIT-SI and the variety of toroidal perturbation spectra available in HIT-SI3. This material is based upon work supported by the U.S. Department of Energy, Office of Science, Office of Fusion Energy Sciences under Award Number DE-FG02- 96ER54361.

Analysis of betaS and betaA genes in a Mexican population with African roots.

PubMed

Magaña, María Teresa; Ongay, Zoyla; Tagle, Juan; Bentura, Gilberto; Cobián, José G; Perea, F Javier; Casas-Castañeda, Maricela; Sánchez-López, Yoaly J; Ibarra, Bertha

2002-01-01

To investigate the origin of the beta(A) and beta(S) genes in a Mexican population with African roots and a high frequency of hemoglobin S, we analyzed 467 individuals (288 unrelated) from different towns in the states of Guerrero and Oaxaca in the Costa Chica region. The frequency of the sickle-cell trait was 12.8%, which may represent a public health problem. The frequencies of the beta-haplotypes were determined from 350 nonrelated chromosomes (313 beta(A) and 37 beta(S)). We observed 15 different beta(A) haplotypes, the most common of which were haplotypes 1 (48.9%), 2 (13.4%), and 3 (13.4%). The calculation of pairwise distributions and Nei's genetic distance analysis using 32 worldwide populations showed that the beta(A) genes are more closely related to those of Mexican Mestizos and North Africans. Bantu and Benin haplotypes and haplotype 9 were related to the beta(S) genes, with frequencies of 78.8, 18.2, and 3.0%, respectively. Comparison of these haplotypes with 17 other populations revealed a high similitude with the population of the Central African Republic. These data suggest distinct origins for the beta(A) and beta(S) genes in Mexican individuals from the Costa Chica region.

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

PubMed

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

2000-03-10

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

Satellite image fusion based on principal component analysis and high-pass filtering.

PubMed

Metwalli, Mohamed R; Nasr, Ayman H; Allah, Osama S Farag; El-Rabaie, S; Abd El-Samie, Fathi E

2010-06-01

This paper presents an integrated method for the fusion of satellite images. Several commercial earth observation satellites carry dual-resolution sensors, which provide high spatial resolution or simply high-resolution (HR) panchromatic (pan) images and low-resolution (LR) multi-spectral (MS) images. Image fusion methods are therefore required to integrate a high-spectral-resolution MS image with a high-spatial-resolution pan image to produce a pan-sharpened image with high spectral and spatial resolutions. Some image fusion methods such as the intensity, hue, and saturation (IHS) method, the principal component analysis (PCA) method, and the Brovey transform (BT) method provide HR MS images, but with low spectral quality. Another family of image fusion methods, such as the high-pass-filtering (HPF) method, operates on the basis of the injection of high frequency components from the HR pan image into the MS image. This family of methods provides less spectral distortion. In this paper, we propose the integration of the PCA method and the HPF method to provide a pan-sharpened MS image with superior spatial resolution and less spectral distortion. The experimental results show that the proposed fusion method retains the spectral characteristics of the MS image and, at the same time, improves the spatial resolution of the pan-sharpened image.

Alterations in the mitochondrial regulatory pathways constituted by the nuclear co-factors PGC-1alpha or PGC-1beta and mitofusin 2 in skeletal muscle in type 2 diabetes.

PubMed

Zorzano, Antonio; Hernández-Alvarez, María Isabel; Palacín, Manuel; Mingrone, Geltrude

2010-01-01

Muscle mitochondrial metabolism is regulated by a number of factors, many of which are responsible for the transcription of nuclear genes encoding mitochondrial proteins such as PPARdelta, PGC-1alpha or PGC-1beta. Recent evidence indicates that proteins participating in mitochondrial dynamics also regulate mitochondrial metabolism. Thus, in cultured cells the mitochondrial fusion protein mitofusin 2 (Mfn2) stimulates respiration, substrate oxidation and the expression of subunits involved in respiratory complexes. Mitochondrial dysfunction has been reported in skeletal muscle of type 2 diabetic patients. Reduced mitochondrial mass and defective activity has been proposed to explain this dysfunction. Alterations in mitochondrial metabolism may be crucial to account for some of the pathophysiological traits that characterize type 2 diabetes. Skeletal muscle of type 2 diabetic patients shows reduced expression of PGC-1alpha, PGC-1beta, and Mfn2. In addition, a differential response to bilio-pancreatic diversion-induced weight loss in non-diabetic and type 2 diabetic patients has been reported. While non-diabetic morbidly obese subjects showed an increased expression of genes encoding Mfn2, PGC-1alpha, PGC-1beta, PPARdelta or SIRT1 in response to bariatric surgery-induced weight loss, no effect was detected in type 2 diabetic patients. These observations suggest the existence of a heritable component responsible for the abnormal control of the expression of genes encoding for modulators of mitochondrial biogenesis/metabolism, and which may participate in the development of the disease. Copyright © 2010 Elsevier B.V. All rights reserved.

Design Considerations for Clean QED Fusion Propulsion Systems

NASA Astrophysics Data System (ADS)

Bussard, Robert W.; Jameson, Lorin W.

1994-07-01

The direct production of electric power appears possible from fusion reactions between fuels whose products consist solely of charged particles and thus do not present radiation hazards from energetic neutron production, as do reactions involving deuteron-bearing fuels. Among these are the fuels p, 11B, 3He, and 6Li. All of these can be ``burned'' in inertial-electrostatic-fusion (IEF) devices to power QED fusion-electric rocket engines. These IEF sources provide direct-converted electrical power at high voltage (MeV) to drive e-beams for efficient propellant heating to extreme temperatures, with resulting high specific impulse performance capabilities. IEF/QED engine systems using p11B can outperform all other advanced concepts for controlled fusion propulsion by 2-3 orders of magnitude, while 6Li6Li fusion yields one order of magnitude less advance. Either of these fusion rocket propulsion systems can provide very rapid transit for solar system missions, with high payload fractions in single-stage vehicles. The 3He3He reaction can not be used practically for direct electric conversion because of the wide spread in energy of its fusion products. However, it may eventually prove useful for thermal/electrical power generation in central station power plants, or for direct-fusion-product (DFP) propellant heatingin advanced deep-space rocket engines.

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.

Analytic, High-beta Solutions of the Helical Grad-Shafranov Equation

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

D.R. Smith; A.H. Reiman

We present analytic, high-beta ({beta} {approx} O(1)), helical equilibrium solutions for a class of helical axis configurations having large helical aspect ratio, with the helix assumed to be tightly wound. The solutions develop a narrow boundary layer of strongly compressed flux, similar to that previously found in high beta tokamak equilibrium solutions. The boundary layer is associated with a strong localized current which prevents the equilibrium from having zero net current.

Fusion of infrared and visible images based on BEMD and NSDFB

NASA Astrophysics Data System (ADS)

Zhu, Pan; Huang, Zhanhua; Lei, Hai

2016-07-01

This paper presents a new fusion method based on the adaptive multi-scale decomposition of bidimensional empirical mode decomposition (BEMD) and the flexible directional expansion of nonsubsampled directional filter banks (NSDFB) for visible-infrared images. Compared with conventional multi-scale fusion methods, BEMD is non-parametric and completely data-driven, which is relatively more suitable for non-linear signals decomposition and fusion. NSDFB can provide direction filtering on the decomposition levels to capture more geometrical structure of the source images effectively. In our fusion framework, the entropies of the two patterns of source images are firstly calculated and the residue of the image whose entropy is larger is extracted to make it highly relevant with the other source image. Then, the residue and the other source image are decomposed into low-frequency sub-bands and a sequence of high-frequency directional sub-bands in different scales by using BEMD and NSDFB. In this fusion scheme, two relevant fusion rules are used in low-frequency sub-bands and high-frequency directional sub-bands, respectively. Finally, the fused image is obtained by applying corresponding inverse transform. Experimental results indicate that the proposed fusion algorithm can obtain state-of-the-art performance for visible-infrared images fusion in both aspects of objective assessment and subjective visual quality even for the source images obtained in different conditions. Furthermore, the fused results have high contrast, remarkable target information and rich details information that are more suitable for human visual characteristics or machine perception.

The Relationship between Serum Vitamin D Levels and Spinal Fusion Success: A Quantitative Analysis

PubMed Central

Metzger, Melodie F.; Kanim, Linda E.; Zhao, Li; Robinson, Samuel T.; Delamarter, Rick B.

2015-01-01

Study Design An in vivo dosing study of vitamin D in a rat posterolateral spinal fusion model with autogenous bone grafting. Rats randomized to four levels of Vitamin D adjusted rat chow, longitudinal serum validation, surgeons/observers blinded to dietary conditions, and rats followed prospectively for fusion endpoint. Objective To assess the impact of dietary and serum levels of Vitamin D on fusion success, consolidation of fusion mass, and biomechanical stiffness after posterolateral spinal fusion procedure. Summary of Background Data Metabolic risk factors, including vitamin D insufficiency, are often overlooked by spine surgeons. Currently there are no published data on the causal effect of insufficient or deficient vitamin D levels on the success of establishing solid bony union after a spinal fusion procedure. Methods 50 rats were randomized to four experimentally controlled rat chow diets: normal control, vitamin D-deficient, vitamin-D insufficient, and a non-toxic high dose of vitamin D, four weeks prior to surgery and maintained post-surgery until sacrifice. Serum levels of 25(OH)D were determined at surgery and sacrifice using radioimmunoassay. Posterolateral fusion surgery with tail autograft was performed. Rats were sacrificed 12 weeks post-operatively and fusion was evaluated via manual palpation, high resolution radiographs, μCT, and biomechanical testing. Results Serum 25(OH)D and calcium levels were significantly correlated with vitamin-D adjusted chow (p<0.001). There was a dose dependent relationship between vitamin D adjusted chow and manual palpation fusion with greatest differences found in measures of radiographic density between high and deficient vitamin D (p<0.05). Adequate levels of vitamin D (high and normal control) yielded stiffer fusion than inadequate levels (insufficient and deficient) (p<0.05). Conclusions Manual palpation fusion rates increased with supplementation of dietary vitamin D. Biomechanical stiffness, bone volume and density were also positively-related to vitamin D, and calcium. PMID:25627287

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

DTIC Science & Technology

1992-02-01

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

Expansion of the octarepeat domain alters the misfolding pathway but not the folding pathway of the prion protein.

PubMed

Leliveld, S Rutger; Stitz, Lothar; Korth, Carsten

2008-06-10

A misfolded conformation of the prion protein (PrP), PrP (Sc), is the essential component of prions, the infectious agents that cause transmissible neurodegenerative diseases. Insertional mutations that lead to an increase in the number of octarepeats (ORs) in PrP are linked to familial human prion disease. In this study, we investigated how expansion of the OR domain causes PrP to favor a prion-like conformation. Therefore, we compared the conformational and aggregation modulating properties of wild-type versus expanded OR domains, either as a fusion construct with the protein G B1 domain (GB1-OR) or as an integral part of full-length mouse PrP (MoPrP). Using circular dichroism spectroscopy, we first demonstrated that ORs are not unfolded but exist as an ensemble of three distinct conformers: polyproline helix-like, beta-turn, and "Trp-related". Domain expansion had little effect on the conformation of GB1-OR fusion proteins. When part of MoPrP however, OR domain expansion changed PrP's folding landscape, not by hampering the production of native alpha-helical monomers but by greatly reducing the propensity to form amyloid and by altering the assembly of misfolded, beta-rich aggregates. These features may relate to subtle pH-dependent conformational differences between wild-type and mutant monomers. In conclusion, we propose that PrP insertional mutations are pathogenic because they enhance specific misfolding pathways of PrP rather than by undermining native folding. This idea was supported by a trial bioassay in transgenic mice overexpressing wild-type MoPrP, where intracerebral injection of recombinant MoPrP with an expanded OR domain but not wild-type MoPrP caused prion disease.

Structural requirements of oleosin domains for subcellular targeting to the oil body.

PubMed Central

van Rooijen, G J; Moloney, M M

1995-01-01

We have investigated the protein domains responsible for the correct subcellular targeting of plant seed oleosins. We have attempted to study this targeting in vivo using "tagged" oleosins in transgenic plants. Different constructs were prepared lacking gene sequences encoding one of three structural domains of natural oleosins. Each was fused in frame to the Escherichia coli uid A gene encoding beta-glucuronidase (GUS). These constructs were introduced into Brassica napus using Agrobacterium-mediated transformation. GUS activity was measured in washed oil bodies and in the soluble protein fraction of the transgenic seeds. It was found that complete Arabidopsis oleosin-GUS fusions undergo correct subcellular targeting in transgenic Brassica seeds. Removal of the C-terminal domain of the Arabidopsis oleosin comprising the last 48 amino acids had no effect on overall subcellular targeting. In contrast, loss of the first 47 amino acids (N terminus) or amino acids 48 to 113 (which make up a lipophilic core) resulted in impaired targeting of the fusion protein to the oil bodies and greatly reduced accumulation of the fusion protein. Northern blotting revealed that this reduction is not due to differences in mRNA accumulation. Results from these measurements indicated that both the N-terminal and central oleosin domain are important for targeting to the oil body and show that there is a direct correlation between the inability to target to the oil body and protein stability. PMID:8539295

Production of three-dimensional tissue-engineered cartilage through mutual fusion of chondrocyte pellets.

PubMed

Hoshi, K; Fujihara, Y; Mori, Y; Asawa, Y; Kanazawa, S; Nishizawa, S; Misawa, M; Numano, T; Inoue, H; Sakamoto, T; Watanabe, M; Komura, M; Takato, T

2016-09-01

In this study, the mutual fusion of chondrocyte pellets was promoted in order to produce large-sized tissue-engineered cartilage with a three-dimensional (3D) shape. Five pellets of human auricular chondrocytes were first prepared, which were then incubated in an agarose mold. After 3 weeks of culture in matrix production-promoting medium under 5.78g/cm(2) compression, the tissue-engineered cartilage showed a sufficient mechanical strength. To confirm the usefulness of these methods, a transplantation experiment was performed using beagles. Tissue-engineered cartilage prepared with 50 pellets of beagle chondrocytes was transplanted subcutaneously into the cell-donor dog for 2 months. The tissue-engineered cartilage of the beagles maintained a rod-like shape, even after harvest. Histology showed fair cartilage regeneration. Furthermore, 20 pellets were made and placed on a beta-tricalcium phosphate prism, and this was then incubated within the agarose mold for 3 weeks. The construct was transplanted into a bone/cartilage defect in the cell-donor beagle. After 2 months, bone and cartilage regeneration was identified on micro-computed tomography and magnetic resonance imaging. This approach involving the fusion of small pellets into a large structure enabled the production of 3D tissue-engineered cartilage that was close to physiological cartilage tissue in property, without conventional polyper scaffolds. Copyright © 2016. Published by Elsevier Ltd.

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

PubMed Central

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

2017-01-01

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

Mathematical Fundamentals of Probabilistic Semantics for High-Level Fusion

DTIC Science & Technology

2013-12-02

understanding of the fundamental aspects of uncertainty representation and reasoning that a theory of hard and soft high-level fusion must encompass...representation and reasoning that a theory of hard and soft high-level fusion must encompass. Successful completion requires an unbiased, in-depth...and soft information is the lack of a fundamental HLIF theory , backed by a consistent mathematical framework and supporting algorithms. Although there

Multi-focus image fusion based on area-based standard deviation in dual tree contourlet transform domain

NASA Astrophysics Data System (ADS)

Dong, Min; Dong, Chenghui; Guo, Miao; Wang, Zhe; Mu, Xiaomin

2018-04-01

Multiresolution-based methods, such as wavelet and Contourlet are usually used to image fusion. This work presents a new image fusion frame-work by utilizing area-based standard deviation in dual tree Contourlet trans-form domain. Firstly, the pre-registered source images are decomposed with dual tree Contourlet transform; low-pass and high-pass coefficients are obtained. Then, the low-pass bands are fused with weighted average based on area standard deviation rather than the simple "averaging" rule. While the high-pass bands are merged with the "max-absolute' fusion rule. Finally, the modified low-pass and high-pass coefficients are used to reconstruct the final fused image. The major advantage of the proposed fusion method over conventional fusion is the approximately shift invariance and multidirectional selectivity of dual tree Contourlet transform. The proposed method is compared with wavelet- , Contourletbased methods and other the state-of-the art methods on common used multi focus images. Experiments demonstrate that the proposed fusion framework is feasible and effective, and it performs better in both subjective and objective evaluation.

Fusion Studies in Japan

NASA Astrophysics Data System (ADS)

Ogawa, Yuichi

2016-05-01

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

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

PubMed

Chen, Meiling; Tao, Ling; Qian, Zhiyu

2009-08-01

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

An Overview of INEL Fusion Safety R&D Facilities

NASA Astrophysics Data System (ADS)

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

1997-06-01

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

Phenotypic Characterization of Multidrug-resistant Escherichia Coli with Special Reference to Extended-spectrum-beta-lactamases and Metallo-beta-lactamases in a Tertiary Care Center.

PubMed

Shrestha, B; Shrestha, S; Mishra, S K; Kattel, H P; Tada, T; Ohara, H; Kirikae, T; Rijal, B P; Sherchand, J B; Pokhrel, B M

2015-01-01

The increasing reports on extended-spectrum-beta-lactamase and metallo-beta-lactamase producing Escherichia coli have addressed a potential threat to global health since it is found to be highly resistance to most of the currently available antibiotics including carbapenems. The present study was aimed to determine the antibiogram of extended-spectrum-beta-lactamase and metallo-beta-lactamase producing MDR E. coli isolates from various clinical samples. This was a cross-sectional study conducted over a period of seven months from December 2013 to July 2014 at bacteriology laboratory of Tribhuvan University Teaching Hospital. A total of 250 clinical specimens (urine, pus, sputum, blood, body fluid, bile, tissue and central venous pressure line tip) were processed from inpatients, with multidrug-resistant Escherichia coli infections. Standard microbiological techniques were used for isolation and identification of the isolates. The presence of extended-spectrum-beta-lactamase was detected by phenotypic confirmatory test recommended by Clinical and Laboratory Standards Institute and imipenem (IMP) /EDTA combined disc method was performed to detect metallo-beta-lactamase mediated resistance mechanism. We found high level of beta lactamase mediated resistance mechanism as part of multidrug resistance. Among 250 MDR isolates, 60% isolates were extended-spectrum-beta-lactamase producers and 17.2% isolates were metallo-beta-lactamase producers. Co-existence of extended-spectrum-beta-lactamase and metallo-beta-lactamase identified in 6.8% isolates. Beta-lactamase mediated resistance mechanisms are accounting very high in the multidrug resistant isolates of E. coli. Therefore, early detection of beta lactamase mediated resistant strains and their current antibiotic susceptibility pattern is necessary to avoid treatment failure and prevent the spread of MDR.

High-energy krypton fluoride lasers for inertial fusion.

PubMed

Obenschain, Stephen; Lehmberg, Robert; Kehne, David; Hegeler, Frank; Wolford, Matthew; Sethian, John; Weaver, James; Karasik, Max

2015-11-01

Laser fusion researchers have realized since the 1970s that the deep UV light from excimer lasers would be an advantage as a driver for robust high-performance capsule implosions for inertial confinement fusion (ICF). Most of this research has centered on the krypton-fluoride (KrF) laser. In this article we review the advantages of the KrF laser for direct-drive ICF, the history of high-energy KrF laser development, and the present state of the art and describe a development path to the performance needed for laser fusion and its energy application. We include descriptions of the architecture and performance of the multi-kilojoule Nike KrF laser-target facility and the 700 J Electra high-repetition-rate KrF laser that were developed at the U.S. Naval Research Laboratory. Nike and Electra are the most advanced KrF lasers for inertial fusion research and energy applications.

chimeraviz: a tool for visualizing chimeric RNA.

PubMed

Lågstad, Stian; Zhao, Sen; Hoff, Andreas M; Johannessen, Bjarne; Lingjærde, Ole Christian; Skotheim, Rolf I

2017-09-15

Advances in high-throughput RNA sequencing have enabled more efficient detection of fusion transcripts, but the technology and associated software used for fusion detection from sequencing data often yield a high false discovery rate. Good prioritization of the results is important, and this can be helped by a visualization framework that automatically integrates RNA data with known genomic features. Here we present chimeraviz , a Bioconductor package that automates the creation of chimeric RNA visualizations. The package supports input from nine different fusion-finder tools: deFuse, EricScript, InFusion, JAFFA, FusionCatcher, FusionMap, PRADA, SOAPfuse and STAR-FUSION. chimeraviz is an R package available via Bioconductor ( https://bioconductor.org/packages/release/bioc/html/chimeraviz.html ) under Artistic-2.0. Source code and support is available at GitHub ( https://github.com/stianlagstad/chimeraviz ). rolf.i.skotheim@rr-research.no. Supplementary data are available at Bioinformatics online. © The Author(s) 2017. Published by Oxford University Press.

Automated image-based assay for evaluation of HIV neutralization and cell-to-cell fusion inhibition.

PubMed

Sheik-Khalil, Enas; Bray, Mark-Anthony; Özkaya Şahin, Gülsen; Scarlatti, Gabriella; Jansson, Marianne; Carpenter, Anne E; Fenyö, Eva Maria

2014-08-30

Standardized techniques to detect HIV-neutralizing antibody responses are of great importance in the search for an HIV vaccine. Here, we present a high-throughput, high-content automated plaque reduction (APR) assay based on automated microscopy and image analysis that allows evaluation of neutralization and inhibition of cell-cell fusion within the same assay. Neutralization of virus particles is measured as a reduction in the number of fluorescent plaques, and inhibition of cell-cell fusion as a reduction in plaque area. We found neutralization strength to be a significant factor in the ability of virus to form syncytia. Further, we introduce the inhibitory concentration of plaque area reduction (ICpar) as an additional measure of antiviral activity, i.e. fusion inhibition. We present an automated image based high-throughput, high-content HIV plaque reduction assay. This allows, for the first time, simultaneous evaluation of neutralization and inhibition of cell-cell fusion within the same assay, by quantifying the reduction in number of plaques and mean plaque area, respectively. Inhibition of cell-to-cell fusion requires higher quantities of inhibitory reagent than inhibition of virus neutralization.

URREF Reliability Versus Credibility in Information Fusion

DTIC Science & Technology

2013-07-01

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

High-beta spherical tokamak startup in TS-4 merging experiment by use of toroidal field ramp-up

NASA Astrophysics Data System (ADS)

Kaminou, Yasuhiro; , Toru, II; Kato, Joji; Inomoto, Michiaki; Ono, Yasushi; TS Group Team; National InstituteFusion Science Collaboration

2014-10-01

We demonstrated the formation method of an ultrahigh-beta spherical tokamak by use of a field-reversed configuration and a spheromak in TS-4 device (R ~ 0.5 m, A ~ 1.5, Ip ~ 30-100 kA, B ~ 100 mT). This method is composed of the following steps: 1. Two spheromaks are merged together and a high-beta spheromak or FRC is formed by reconnection heating. 2. External toroidal magnetic field is added (current rising time ~50 μs), and spherical tokamak-like configuration is formed. In this way, the ultrahigh-beta ST is formed. The ultrahigh-beta ST formed by FRC has a diamagnetic toroidal field, and it presumed to be in a second-stable state for ballooning stability, and the one formed by spheromak has a weak paramagnetic toroidal magnetic field, while a spheormak has a strong paramagnetic toroidal magnetic field. This diamagnetic current derives from inductive electric field by ramping up the external toroidal magnetic field, and the diamagnetic current sustains high thermal pressure of the ultrahigh-beta spherical tokamak. And the beta of the ultrahigh-beta ST formed by FRC reaches about 50%. To sustain the high-beta state, 0.6 MW neutral beam injection and center solenoid coils are installed to the TS-4 device. In the poster, we report the experimental results of ultrahigh-beta spherical tokamak startup and sustainment by NBI and CS current driving experiment.

A study of thermal hydraulic and kinetic phenomena in HYLIFE-2: An inertial confinement fusion reactor

NASA Astrophysics Data System (ADS)

Chen, Xiang Ming

1993-01-01

Researchers have studied the different aspects of commercial fusion energy for several decades. A variety of inertial confinement fusion (ICF) reactors have been proposed. Different from the magnetic confinement fusion concept, inertial confinement fusion does not need long-term confinement of the fusion fuel but achieves fusion reaction in a short microexplosion under a high density, high temperature condition. The HYLIFE-2 reactor design started in 1987 is based on the study of a previous concept called HYLIFE (High Yield Lithium Injection Fusion Energy). Similar to the old concept, the HYLIFE-2 design uses a vacuum chamber in which D-T fusion pellets are injected and ignited by high energy beams shot into the reactor through different ports. The reactor vessel is protected from explosion radiations by a liquid fall (blanket) that also breeds tritium through the (n, alpha) reaction of lithium and conveys the fusion energy to the power cycle. In addition to some geometric chances, the new design replaces liquid metal lithium with the molten salt Flibe (Li2BeF4) as the protective blanket material. The objective was to remove the possibility of fire hazard. The important thermal hydraulic issues in the design are (1) equation of state of Flibe; (2) liquid relaxation after isochoric (constant volume) heating; (3) ablation and gas dynamics; (4) interaction of the vapor and liquid; and (5) condensation of the vaporized material. The first four issues have to do with the internal relaxation after the fusion microexplosion in the chamber. Vaporized material, as well as liquid, may assert strong impulses on the chamber wall during the process of relaxing after absorbing the energy from the microexplosion. Item (5) is related to the rapid vacuum recovery between the ignitions. Some aspects of the first four issues are studied.

Osteocalcin protects pancreatic beta cell function and survival under high glucose conditions

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

Kover, Karen, E-mail: kkover@cmh.edu; University of Missouri-Kansas City School of Medicine, Kansas City, MO 64108; Yan, Yun

Diabetes is characterized by progressive beta cell dysfunction and loss due in part to oxidative stress that occurs from gluco/lipotoxicity. Treatments that directly protect beta cell function and survival in the diabetic milieu are of particular interest. A growing body of evidence suggests that osteocalcin, an abundant non-collagenous protein of bone, supports beta cell function and proliferation. Based on previous gene expression data by microarray, we hypothesized that osteocalcin protects beta cells from glucose-induced oxidative stress. To test our hypothesis we cultured isolated rat islets and INS-1E cells in the presence of normal, high, or high glucose ± osteocalcin for up tomore » 72 h. Oxidative stress and viability/mitochondrial function were measured by H{sub 2}O{sub 2} assay and Alamar Blue assay, respectively. Caspase 3/7 activity was also measured as a marker of apoptosis. A functional test, glucose stimulated insulin release, was conducted and expression of genes/protein was measured by qRT-PCR/western blot/ELISA. Osteocalcin treatment significantly reduced high glucose-induced H{sub 2}O{sub 2} levels while maintaining viability/mitochondrial function. Osteocalcin also significantly improved glucose stimulated insulin secretion and insulin content in rat islets after 48 h of high glucose exposure compared to untreated islets. As expected sustained high glucose down-regulated gene/protein expression of INS1 and BCL2 while increasing TXNIP expression. Interestingly, osteocalcin treatment reversed the effects of high glucose on gene/protein expression. We conclude that osteocalcin can protect beta cells from the negative effects of glucose-induced oxidative stress, in part, by reducing TXNIP expression, thereby preserving beta cell function and survival. - Highlights: • Osteocalcin reduces glucose-induced oxidative stress in beta cells. • Osteocalcin preserves beta cell function and survival under stress conditions. • Osteocalcin reduces glucose-induced TXNIP expression in beta cells.« less

Paratesticular desmoplastic small round cell tumour: an unusual tumour with an unusual fusion; cytogenetic and molecular genetic analysis combining RT-PCR and COBRA-FISH.

PubMed

Cliteur, Vincent Pm; Szuhai, Károly; Baelde, Hans J; van Dam, Jurriaan; Gelderblom, Hans; Hogendoorn, Pancras Cw

2012-01-25

Desmoplastic small round cell tumour is a rare malignant tumour with a male to female ratio of 4:1. It manifests mostly at serosal sites. Here we present a case of a 28-year-old male patient, who presented with a fast growing paratesticular mass. On biopsy nests and cords of small round cells, without a clear morphological lineage of differentiation were seen. Occasionally desmoplatic small round cell tumour shows different lines of differentiation. An unequivocal histological diagnosis might be difficult in such cases. Here we demonstrate by a combination of methods the characteristic immunohistochemical profile and - albeit unusual - molecular background and discuss the eventual link with Ewing sarcoma.Immunohistochemical studies showed a membranous staining of Keratine AE1/3 and a dot-like staining of Desmine, confirming its diagnosis. Using COBRA-FISH following a metaphase approach we demonstrated a balanced translocation, t(11;22)(p13;q12) and in RT-PCR formation of the EWSR1-WT1 fusion product, a specific translocation of desmoplastic round cell tumour. The fusion involves exon 9 of EWSR1 to exon 8 of WT1, an unusual fusion product, though earlier described in a case of a desmoplastic small round cell tumour of the hand. The EWSR1-WT1 chimera seems to function as an oncogenic transcription factor. Here the zinc finger domain of the WT1 acts with affinity with certain promoter domains influencing the expression of various downstream proteins such as: PDGFA, PAX2, insulin-like growth factor 1 receptor, epidermal growth factor receptor, IL2 receptor beta, BAIAP3, MLF1, TALLA-1, LRRC15 and ENT. We discuss their potential oncogenic roles and potential therapeutic consequences.

Paratesticular desmoplastic small round cell tumour: an unusual tumour with an unusual fusion; cytogenetic and molecular genetic analysis combining RT-PCR and COBRA-FISH

PubMed Central

2012-01-01

Desmoplastic small round cell tumour is a rare malignant tumour with a male to female ratio of 4:1. It manifests mostly at serosal sites. Here we present a case of a 28-year-old male patient, who presented with a fast growing paratesticular mass. On biopsy nests and cords of small round cells, without a clear morphological lineage of differentiation were seen. Occasionally desmoplatic small round cell tumour shows different lines of differentiation. An unequivocal histological diagnosis might be difficult in such cases. Here we demonstrate by a combination of methods the characteristic immunohistochemical profile and - albeit unusual - molecular background and discuss the eventual link with Ewing sarcoma. Immunohistochemical studies showed a membranous staining of Keratine AE1/3 and a dot-like staining of Desmine, confirming its diagnosis. Using COBRA-FISH following a metaphase approach we demonstrated a balanced translocation, t(11;22)(p13;q12) and in RT-PCR formation of the EWSR1-WT1 fusion product, a specific translocation of desmoplastic round cell tumour. The fusion involves exon 9 of EWSR1 to exon 8 of WT1, an unusual fusion product, though earlier described in a case of a desmoplastic small round cell tumour of the hand. The EWSR1-WT1 chimera seems to function as an oncogenic transcription factor. Here the zinc finger domain of the WT1 acts with affinity with certain promoter domains influencing the expression of various downstream proteins such as: PDGFA, PAX2, insulin-like growth factor 1 receptor, epidermal growth factor receptor, IL2 receptor beta, BAIAP3, MLF1, TALLA-1, LRRC15 and ENT. We discuss their potential oncogenic roles and potential therapeutic consequences. PMID:22587803

Fusion of Huntingtin interacting protein 1 to platelet-derived growth factor beta receptor (PDGFbetaR) in chronic myelomonocytic leukemia with t(5;7)(q33;q11.2).

PubMed

Ross, T S; Bernard, O A; Berger, R; Gilliland, D G

1998-06-15

We report the fusion of the Huntingtin interactin protein 1 (HIP1) gene to the platelet-derived growth factor betareceptor (PDGFbetaR) gene in a patient with chronic myelomonocytic leukemia (CMML) with a t(5;7)(q33;q11.2) translocation. Southern blot analysis of patient bone marrow cells with a PDGFbetaR gene probe demonstrated rearrangement of the PDGFbetaR gene. Anchored polymerase chain reaction using PDGFbetaR primers identified a chimeric transcript containing the HIP1 gene located at 7q11.2 fused to the PDGFbetaR gene on 5q33. HIP1 is a 116-kD protein recently cloned by yeast two-hybrid screening for proteins that interact with Huntingtin, the mutated protein in Huntington's disease. The consequence of t(5;7)(q33;q11.2) is an HIP1/PDGFbetaR fusion gene that encodes amino acids 1 to 950 of HIP1 joined in-frame to the transmembrane and tyrosine kinase domains of the PDGFbetaR. The reciprocal PDGFbetaR/HIP1 transcript is not expressed. HIP1/PDGFbetaR is a 180-kD protein when expressed in the murine hematopoietic cell line, Ba/F3, and is constitutively tyrosine phosphorylated. Furthermore, HIP1/PDGFbetaR transforms the Ba/F3 cells to interleukin-3-independent growth. These data are consistent with an alternative mechanism for activation of PDGFbetaR tyrosine kinase activity by fusion with HIP1, leading to transformation of hematopoietic cells, and may implicate Huntingtin or HIP1 in the pathogenesis of hematopoietic malignancies.

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

Finley, V.L.; Wieczorek, M.A.

This report gives the results of the environmental activities and monitoring programs at the Princeton Plasma Physics Laboratory (PPPL) for CY94. The report is prepared to provide the US Department of Energy (DOE) and the public with information on the level of radioactive and nonradioactive pollutants, if any, added to the environment as a result of PPPL operations, as well as environmental initiatives, assessments, and programs that were undertaken in 1994. The objective of the Annual Site Environmental Report is to document evidence that PPPL`s environmental protection programs adequately protect the environment and the public health. The Princeton Plasma Physicsmore » Laboratory has engaged in fusion energy research since 195 1. The long-range goal of the US Magnetic Fusion Energy Research Program is to develop and demonstrate the practical application of fusion power as an alternate energy source. In 1994, PPPL had one of its two large tokamak devices in operation-the Tokamak Fusion Test Reactor (TFTR). The Princeton Beta Experiment-Modification or PBX-M completed its modifications and upgrades and resumed operation in November 1991 and operated periodically during 1992 and 1993; it did not operate in 1994 for funding reasons. In December 1993, TFTR began conducting the deuterium-tritium (D-T) experiments and set new records by producing over ten @on watts of energy in 1994. The engineering design phase of the Tokamak Physics Experiment (T?X), which replaced the cancelled Burning Plasma Experiment in 1992 as PPPL`s next machine, began in 1993 with the planned start up set for the year 2001. In December 1994, the Environmental Assessment (EA) for the TFTR Shutdown and Removal (S&R) and TPX was submitted to the regulatory agencies, and a finding of no significant impact (FONSI) was issued by DOE for these projects.« less

Cellular localization and expression of template-activating factor I in different cell types.

PubMed

Nagata, K; Saito, S; Okuwaki, M; Kawase, H; Furuya, A; Kusano, A; Hanai, N; Okuda, A; Kikuchi, A

1998-05-01

Template-activating factors I (TAF-I) alpha and beta have been identified as chromatin remodeling factors from human HeLa cells. TAF-I beta corresponds to the protein encoded by the set gene, which was found in an acute undifferentiated leukemia as a fusion version with the can gene via chromosomal translocation. To determine the localization of TAF-I, we raised both polyclonal and monoclonal antibodies against TAF-I. The proteins that react to the antibodies are present not only in human cells but also in mouse, frog, insect, and yeast cells. The mouse TAF-I homologue is ubiquitous in a variety of tissue cells, including liver, kidney, spleen, lung, heart, and brain. It is of interest that the amounts of TAF-I alpha and beta vary among hemopoietic cells and some specific cell types do not contain TAF-I alpha. The level of the TAF-I proteins does not change significantly during the cell cycle progression in either HeLa cells synchronized with an excess concentration of thymidine or NIH 3T3 cells released from the serum-depleted state. TAF-I is predominantly located in nuclei, while TAF-I that is devoid of its acidic region, the region which is essential for the TAF-I activity, shows both nuclear and cytoplasmic localization. The localization of TAF-I in conjunction with the regulation of its activity is discussed.

Isolation of human hexosaminidase. cap alpha. cDNA and expression of. cap alpha. chains in E. coli

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

Wiktorowicz, J.E.; Whitman, J.M.

1986-05-01

Pooled antisera against homogeneous, glutaraldehyde cross-linked hexosaminidase (hex) A was adsorbed with E. coli lysate insolubilized on Sepharose 4B. Aliquots of a human liver lambdagtll cDNA library (50,000-100,000 pfu) were plated on E. coli Y1090. Expression of cloned cDNA, after sufficient plaque growth at 42/sup 0/, was accomplished by induction with isopropylthiogalactoside soaked nitrocellulose filters. Identification of hex cDNA clones was performed by incubation of the filters with purified antisera. Protein A labelled with I-125 was used to develop the reactive plaques. Positive plaques, identified by autoradiography, were picked, replated at a lower density, and rescreened. This was repeated severalmore » more times until all plaques yielded positive signals. Identification of the clones as containing ..cap alpha.. or ..beta.. cDNA was accomplished by replating the purified phage and rescreening the plaques with anti-hex B antiserum preadsorbed with E. coli lysate. According to this protocol several hex ..cap alpha.. clones have been identified. While these clones generate ..beta..-galactosidase: hex ..cap alpha.. fusion proteins, these findings suggest that in the future it may be possible to obtain large quantities of unmodified hex ..cap alpha.. and ..beta.. polypeptides from E. coli for the study of the structural and enzymatic properties of these polypeptides and for diagnostic purposes in the GM2 gangliosidoses.« less

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

Liu, Ying, E-mail: yingliu@doheny.org; Sun Yet-sen University, Zhongshan Ophthalmic Center, State Key Ophthalmic Laboratory, Guangzhou 510060; Kawai, Kirio

Research highlights: {yields} Inactivation of Smad4 caused disruption in the development of the anterior segment. {yields} Inactivation of Smad4 failed to disrupt early lens development. {yields} Smad4 controlled lens cell cycle and cell death processes. {yields} Smad4 may regulate actin stress fiber assembly and eyelid epithelial movement. -- Abstract: Purpose: Signaling by members of the TGF{beta} superfamily of molecules is essential for embryonic development and homeostasis. Smad4, a key intracellular mediator in TGF{beta} signaling, forms transcriptional activator complexes with Activin-, BMP-, and TGF{beta}-restricted Smad proteins. However, the functional role of Smad4 in controlling different visual system compartments has not beenmore » fully investigated. Methods: Using the Pax6 promoter-driven Cre transgenic, smad4 was conditionally inactivated in the lens, cornea and ectoderm of the eyelids. Standard histological and molecular analytical approaches were employed to reveal morphological and cellular changes. Results: Inactivation of Smad4 in the lens led to microphthalmia and cataract formation in addition to the persistent adhesion of the retina to the lens and the iris to the cornea. Inactivation of Smad4 from the ectoderm of the eyelid and cornea caused disruption to eyelid fusion and proper development of the corneal epithelium and corneal stroma. Conclusions: Smad4 is required for the development and maintenance of the lens in addition to the proper development of the cornea, eyelids, and retina.« less

Fluorescence Microspectroscopy for Testing the Dimerization Hypothesis of BACE1 Protein in Cultured HEK293 Cells

NASA Astrophysics Data System (ADS)

Gardeen, Spencer; Johnson, Joseph L.; Heikal, Ahmed A.

2016-06-01

Alzheimer's Disease (AD) is a neurodegenerative disorder that results from the formation of beta-amyloid plaques in the brain that trigger the known symptoms of memory loss in AD patients. The beta-amyloid plaques are formed by the proteolytic cleavage of the amyloid precursor protein (APP) by the proteases BACE1 and gamma-secretase. These enzyme-facilitated cleavages lead to the production of beta-amyloid fragments that aggregate to form plaques, which ultimately lead to neuronal cell death. Recent detergent protein extraction studies suggest that BACE1 protein forms a dimer that has significantly higher catalytic activity than its monomeric counterpart. In this contribution, we examine the dimerization hypothesis of BACE1 in cultured HEK293 cells using complementary fluorescence spectroscopy and microscopy methods. Cells were transfected with a BACE1-EGFP fusion protein construct and imaged using confocal, and differential interference contrast to monitor the localization and distribution of intracellular BACE1. Complementary fluorescence lifetime and anisotropy measurements enabled us to examine the conformational and environmental changes of BACE1 as a function of substrate binding. Using fluorescence correlation spectroscopy, we also quantified the diffusion coefficient of BACE1-EGFP on the plasma membrane as a means to test the dimerization hypothesis as a fucntion of substrate-analog inhibitition. Our results represent an important first towards examining the substrate-mediated dimerization hypothesis of BACE1 in live cells.

Effects of exendin-4 on glucose tolerance, insulin secretion, and beta-cell proliferation depend on treatment dose, treatment duration and meal contents

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

Arakawa, Masayuki; Ebato, Chie; Mita, Tomoya

2009-12-18

Beta-cell proliferation is regulated by various metabolic demands including peripheral insulin resistance, obesity, and hyperglycemia. In addition to enhancement of glucose-induced insulin secretion, agonists for glucagon-like peptide-1 receptor (GLP-1R) stimulate proliferation and inhibit apoptosis of beta-cells, thereby probably preserve beta-cell mass. To evaluate the beta-cell preserving actions of GLP-1R agonists, we assessed the acute and chronic effects of exendin-4 on beta-cell proliferation, mass and glucose tolerance in C57BL/6J mice under various conditions. Short-term administration of high-dose exendin-4 transiently stimulated beta-cell proliferation. Comparative transcriptomic analysis showed upregulation of IGF-1 receptor and its downstream effectors in islets. Treatment of mice with exendin-4more » daily for 4 weeks (long-term administration) and feeding high-fat diet resulted in significant inhibition of weight gain and improvement of glucose tolerance with reduced insulin secretion and beta-cell mass. These findings suggest that long-term GLP-1 treatment results in insulin sensitization of peripheral organs, rather than enhancement of beta-cell proliferation and function, particularly when animals are fed high-fat diet. Thus, the effects of exendin-4 on glucose tolerance, insulin secretion, and beta-cell proliferation largely depend on treatment dose, duration of treatment and meal contents. While GLP-1 enhances proliferation of beta-cells in some diabetic mice models, our results suggest that GLP-1 stimulates beta-cell growth only when expansion of beta-cell mass is required to meet metabolic demands.« less

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

PubMed

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

2016-09-01

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

Multiplexed transcriptome analysis to detect ALK, ROS1 and RET rearrangements in lung cancer

PubMed Central

Rogers, Toni-Maree; Arnau, Gisela Mir; Ryland, Georgina L.; Huang, Stephen; Lira, Maruja E.; Emmanuel, Yvette; Perez, Omar D.; Irwin, Darryl; Fellowes, Andrew P.; Wong, Stephen Q.; Fox, Stephen B.

2017-01-01

ALK, ROS1 and RET gene fusions are important predictive biomarkers for tyrosine kinase inhibitors in lung cancer. Currently, the gold standard method for gene fusion detection is Fluorescence In Situ Hybridization (FISH) and while highly sensitive and specific, it is also labour intensive, subjective in analysis, and unable to screen a large numbers of gene fusions. Recent developments in high-throughput transcriptome-based methods may provide a suitable alternative to FISH as they are compatible with multiplexing and diagnostic workflows. However, the concordance between these different methods compared with FISH has not been evaluated. In this study we compared the results from three transcriptome-based platforms (Nanostring Elements, Agena LungFusion panel and ThermoFisher NGS fusion panel) to those obtained from ALK, ROS1 and RET FISH on 51 clinical specimens. Overall agreement of results ranged from 86–96% depending on the platform used. While all platforms were highly sensitive, both the Agena panel and Thermo Fisher NGS fusion panel reported minor fusions that were not detectable by FISH. Our proof–of–principle study illustrates that transcriptome-based analyses are sensitive and robust methods for detecting actionable gene fusions in lung cancer and could provide a robust alternative to FISH testing in the diagnostic setting. PMID:28181564

Highly mesoporous single-crystalline zeolite beta synthesized using a nonsurfactant cationic polymer as a dual-function template.

PubMed

Zhu, Jie; Zhu, Yihan; Zhu, Liangkui; Rigutto, Marcello; van der Made, Alexander; Yang, Chengguang; Pan, Shuxiang; Wang, Liang; Zhu, Longfeng; Jin, Yinying; Sun, Qi; Wu, Qinming; Meng, Xiangju; Zhang, Daliang; Han, Yu; Li, Jixue; Chu, Yueying; Zheng, Anmin; Qiu, Shilun; Zheng, Xiaoming; Xiao, Feng-Shou

2014-02-12

Mesoporous zeolites are useful solid catalysts for conversion of bulky molecules because they offer fast mass transfer along with size and shape selectivity. We report here the successful synthesis of mesoporous aluminosilicate zeolite Beta from a commercial cationic polymer that acts as a dual-function template to generate zeolitic micropores and mesopores simultaneously. This is the first demonstration of a single nonsurfactant polymer acting as such a template. Using high-resolution electron microscopy and tomography, we discovered that the resulting material (Beta-MS) has abundant and highly interconnected mesopores. More importantly, we demonstrated using a three-dimensional electron diffraction technique that each Beta-MS particle is a single crystal, whereas most previously reported mesoporous zeolites are comprised of nanosized zeolitic grains with random orientations. The use of nonsurfactant templates is essential to gaining single-crystalline mesoporous zeolites. The single-crystalline nature endows Beta-MS with better hydrothermal stability compared with surfactant-derived mesoporous zeolite Beta. Beta-MS also exhibited remarkably higher catalytic activity than did conventional zeolite Beta in acid-catalyzed reactions involving large molecules.

Expression and affinity purification of recombinant proteins from plants

NASA Technical Reports Server (NTRS)

Desai, Urvee A.; Sur, Gargi; Daunert, Sylvia; Babbitt, Ruth; Li, Qingshun

2002-01-01

With recent advances in plant biotechnology, transgenic plants have been targeted as an inexpensive means for the mass production of proteins for biopharmaceutical and industrial uses. However, the current plant purification techniques lack a generally applicable, economic, large-scale strategy. In this study, we demonstrate the purification of a model protein, beta-glucuronidase (GUS), by employing the protein calmodulin (CaM) as an affinity tag. In the proposed system, CaM is fused to GUS. In the presence of calcium, the calmodulin fusion protein binds specifically to a phenothiazine-modified surface of an affinity column. When calcium is removed with a complexing agent, e.g., EDTA, calmodulin undergoes a conformational change allowing the dissociation of the calmodulin-phenothiazine complex and, therefore, permitting the elution of the GUS-CaM fusion protein. The advantages of this approach are the fast, efficient, and economical isolation of the target protein under mild elution conditions, thus preserving the activity of the target protein. Two types of transformation methods were used in this study, namely, the Agrobacterium-mediated system and the viral-vector-mediated transformation system. Copyright 2002 Elsevier Science (USA).

Glycoprotein D actively induces rapid internalization of two nectin-1 isoforms during herpes simplex virus entry

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

Stiles, Katie M., E-mail: stileskm@mail.med.upenn.ed; Krummenacher, Claude

2010-03-30

Entry of herpes simplex virus (HSV) occurs either by fusion at the plasma membrane or by endocytosis and fusion with an endosome. Binding of glycoprotein D (gD) to a receptor such as nectin-1 is essential in both cases. We show that virion gD triggered the rapid down-regulation of nectin-1 with kinetics similar to those of virus entry. In contrast, nectin-1 was not constitutively recycled from the surface of uninfected cells. Both the nectin-1alpha and beta isoforms were internalized in response to gD despite having different cytoplasmic tails. However, deletion of the nectin-1 cytoplasmic tail slowed down-regulation of nectin-1 and internalizationmore » of virions. These data suggest that nectin-1 interaction with a cytoplasmic protein is not required for its down-regulation. Overall, this study shows that gD binding actively induces the rapid internalization of various forms of nectin-1. We suggest that HSV activates a nectin-1 internalization pathway to use for endocytic entry.« less

Regulation of glutamine synthetase II activity in Rhizobium meliloti 104A14.

PubMed Central

Shatters, R G; Somerville, J E; Kahn, M L

1989-01-01

Most rhizobia contain two glutamine synthetase (GS) enzymes: GSI, encoded by glnA, and GSII, encoded by glnII. We have found that WSU414, a Rhizobium meliloti 104A14 glutamine auxotroph derived from a glnA parental strain, is an ntrA mutant. The R. meliloti glnII promoter region contains DNA sequences similar to those found in front of other genes that require ntrA for their transcription. No GSII was found in the glnA ntrA mutant, and when a translational fusion of glnII to the Escherichia coli lacZ gene was introduced into WSU414, no beta-galactosidase was expressed. These results indicate that ntrA is required for glnII expression. The ntrA mutation did not prevent the expression of GSI. In free-living culture, the level of GSII and of the glnII-lacZ fusion protein was regulated by altering transcription in response to available nitrogen. No GSII protein was detected in alfalfa, pea, or soybean nodules when anti-GSII-specific antiserum was used. Images PMID:2570059

Chimeric L2-Based Virus-Like Particle (VLP) Vaccines Targeting Cutaneous Human Papillomaviruses (HPV).

PubMed

Huber, Bettina; Schellenbacher, Christina; Shafti-Keramat, Saeed; Jindra, Christoph; Christensen, Neil; Kirnbauer, Reinhard

2017-01-01

Common cutaneous human papillomavirus (HPV) types induce skin warts, whereas species beta HPV are implicated, together with UV-radiation, in the development of non-melanoma skin cancer (NMSC) in immunosuppressed patients. Licensed HPV vaccines contain virus-like particles (VLP) self-assembled from L1 major capsid proteins that provide type-restricted protection against mucosal HPV infections causing cervical and other ano-genital and oro-pharyngeal carcinomas and warts (condylomas), but do not target heterologous HPV. Experimental papillomavirus vaccines have been designed based on L2 minor capsid proteins that contain type-common neutralization epitopes, to broaden protection to heterologous mucosal and cutaneous HPV types. Repetitive display of the HPV16 L2 cross-neutralization epitope RG1 (amino acids (aa) 17-36) on the surface of HPV16 L1 VLP has greatly enhanced immunogenicity of the L2 peptide. To more directly target cutaneous HPV, L1 fusion proteins were designed that incorporate the RG1 homolog of beta HPV17, the beta HPV5 L2 peptide aa53-72, or the common cutaneous HPV4 RG1 homolog, inserted into DE surface loops of HPV1, 5, 16 or 18 L1 VLP scaffolds. Baculovirus expressed chimeric proteins self-assembled into VLP and VLP-raised NZW rabbit immune sera were evaluated by ELISA and L1- and L2-based pseudovirion (PsV) neutralizing assays, including 12 novel beta PsV types. Chimeric VLP displaying the HPV17 RG1 epitope, but not the HPV5L2 aa53-72 epitope, induced cross-neutralizing humoral immune responses to beta HPV. In vivo cross-protection was evaluated by passive serum transfer in a murine PsV challenge model. Immune sera to HPV16L1-17RG1 VLP (cross-) protected against beta HPV5/20/24/38/96/16 (but not type 76), while antisera to HPV5L1-17RG1 VLP cross-protected against HPV20/24/96 only, and sera to HPV1L1-4RG1 VLP cross-protected against HPV4 challenge. In conclusion, RG1-based VLP are promising next generation vaccine candidates to target cutaneous HPV infections.

Beta1-integrin and IL-1alpha expression as bystander effect of medium from irradiated cells: the pilot study.

PubMed

Osterreicher, Jan; Skopek, Jirí; Jahns, Juta; Hildebrandt, Guido; Psutka, Jan; Vilasová, Zdenka; Tanner, Judith Maria; Vogt, Jürgen; Butz, Tilman

2003-01-01

Bystander effects have been proposed as a third action pathway of ionising radiation besides direct and indirect effects. The purpose of the study was to investigate whether expression of interleukin-1alpha (IL-1alpha) and beta1-integrin is elevated in bystander cells as a marker for bystander effects in comparison with classical markers such as the clonogenic assay, apoptosis and the presence of micronuclei. The hybrid cell line E.A. hy.926 obtained by fusion of HUVEC cells with the epithelial cell line A 459 was irradiated with 0-5 Gy. Bystander effects were established via medium transfer at 45 min and 4 h after irradiation from irradiated to nonirradiated cell populations. In order to exclude effects of the irradiated medium itself, irradiated medium only was also used for transfer to nonirradiated cells. Then, cells were fixed at 1, 2, 6, and 24 h after irradiation or medium transport and IL-1alpha and beta1-integrin were detected and evaluated. A higher number of beta1-integrin-positive cells was observed in both irradiated and bystander cell populations than in the control group at 1 and 24 h after irradiation with 1 Gy or medium transfer. Significantly higher numbers of IL-1alpha-positive cells were found at 1, 2, and 6 h after irradiation with 1 Gy or medium transfer as well as at 2 and 6 h after irradiation with 5 Gy or medium transfer. Clonogenic survival decreased dependently on the dose in irradiated cells but did not show any significant difference between the bystander cell populations and sham-irradiated cells. The irradiated medium itself did not have any effect. It is concluded that beta1-integrin and IL-1alpha expression may serve as more sensitive markers of post-irradiation responses in bystander cell populations than the classical radiobiological markers. Moreover, overexpression of beta1-integrin and IL-1alpha may induce increased susceptibility to inflammation of bystander cells.

High LET Radiation Can Enhance TGF(Beta) Induced EMT and Cross-Talk with ATM Pathways

NASA Technical Reports Server (NTRS)

Wang, Minli; Hada, Megumi; Huff, Janice; Pluth, Janice M.; Anderson, Janniffer; ONeill, Peter; Cucinotta, Francis A.

2010-01-01

The TGF(Beta) pathway has been shown to regulate or directly interact with the ATM pathway in the response to radiation in mammary epithelial cells. We investigated possible interactions between the TGF(Beta) and ATM pathways following simulated space radiation using hTERT immortalized human esophageal epithelial cells (EPC-hTERT), mink lung epithelial cells (Mv1lu), and several human fibroblast cell lines. TGF(Beta) is a key modulator of the Epithelial-Mesenchymal Transition (EMT), important in cancer progression and metastasis. The implication of EMT by radiation also has several lines of developing evidence, however is poorly understood. The identification of TGF(Beta) induced EMT can be shown in changes to morphology, related gene over expression or down regulation, which can be detected by RT-PCR, and immunostaining and western blotting. In this study, we have observed morphologic and molecular alternations consistent with EMT after Mv1lu cells were treated with TGF(Beta) High LET radiation enhanced TGF(Beta) mediated EMT with a dose as low as 0.1Gy. In order to consider the TGF(Beta) interaction with ATM we used a potent ATM inhibitor Ku55933 and investigated gene expression changes and Smad signaling kinetics. Ku559933 was observed to reverse TGF(Beta) induced EMT, while this was not observed in dual treated cells (radiation+TGF(Beta)). In EPC-hTERT cells, TGF(Beta) alone was not able to induce EMT after 3 days of application. A combined treatment with high LET, however, significantly caused the alteration of EMT markers. To study the function of p53 in the process of EMT, we knocked down P53 through RNA interference. Morphology changes associated with EMT were observed in epithelial cells with silenced p53. Our study indicates: high LET radiation can enhance TGF(Beta) induced EMT; while ATM is triggering the process of TGF(Beta)-induced EMT, p53 might be an essential repressor for EMT phenotypes.

[Metapneumovirus expands the understanding of Paramyxovirus cell fusion--a review].

PubMed

Liu, Xiaoyu; Zhang, Xiaodong; Wei, Yongwei

2014-04-04

For most viruses in Paramyxoviridae, cell fusion requires both attachment protein and fusion protein. The attachment protein is responsible for the binding to its cognate receptors, while the interaction between fusion protein and attachment protein triggers the fusion protein which is responsible for the fusion. However, the Metapneumovirus fusion in Pneumovirinae subfamily displayed different mechanism where the attachment protein is not required. The cell fusion is accomplished by fusion protein alone without the help of the attachment protein. Recent studies indicate that low pH is required for cell fusion promoted by some hMPV strains. The fusion protein of aMPV type A is highly fusogenic, whereas that of type B is low. The original fusion models for Paramyxovirus cannot explain the phenomenon above. The mechanism to regulate the cell fusion of Metapneumovirus is poorly understood. It is becoming a hot spot for the study of cell fusion triggered by Paramyxovirus where it enlarged the traditional scope of Paramyxovirus fusion. In this review, we discuss the new achievements and advances in the understanding of cell fusion triggered by Metapneumovirus.

The High Field Path to Practical Fusion Energy

NASA Astrophysics Data System (ADS)

Mumgaard, Robert; Whyte, D.; Greenwald, M.; Hartwig, Z.; Brunner, D.; Sorbom, B.; Marmar, E.; Minervini, J.; Bonoli, P.; Irby, J.; Labombard, B.; Terry, J.; Vieira, R.; Wukitch, S.

2017-10-01

We propose a faster, lower cost development path for fusion energy enabled by high temperature superconductors, devices at high magnetic field, innovative technologies and modern approaches to technology development. Timeliness, scale, and economic-viability are the drivers for fusion energy to combat climate change and aid economic development. The opportunities provided by high-temperature superconductors, innovative engineering and physics, and new organizational structures identified over the last few years open new possibilities for realizing practical fusion energy that could meet mid-century de-carbonization needs. We discuss re-factoring the fusion energy development path with an emphasis on concrete risk retirement strategies utilizing a modular approach based on the high-field tokamak that leverages the broader tokamak physics understanding of confinement, stability, and operational limits. Elements of this plan include development of high-temperature superconductor magnets, simplified immersion blankets, advanced long-leg divertors, a compact divertor test tokamak, efficient current drive, modular construction, and demountable magnet joints. An R&D plan culminating in the construction of an integrated pilot plant and test facility modeled on the ARC concept is presented.

Overview of MST Research

NASA Astrophysics Data System (ADS)

Sarff, J. S.; MST Team

2011-10-01

MST progress in advancing the RFP for (1) fusion plasma confinement with minimal external magnetization, (2) toroidal confinement physics, and (3) basic plasma physics is summarized. New tools and diagnostics are accessing physics barely studied in the RFP. Several diagnostic advances are important for ITER/burning plasma. A 1 MW neutral beam injector operates routinely for fast ion, heating, and transport investigations. Energetic ions are also created spontaneously by tearing mode reconnection, reminiscent of astrophysical plasmas. Classical confinement of impurity ions is measured in reduced-tearing plasmas. Fast ion slowing-down is also classical. Alfven-eigenmode-like activity occurs with NBI, but apparently not TAE. Stellarator-like helical structure appears in the core of high current plasmas, with improved confinement characteristics. FIR interferometry, Thomson scattering, and HIBP diagnostics are beginning to explore microturbulence scales, an opportunity to exploit the RFP's high beta and strong magnetic shear parameter space. A programmable power supply for the toroidal field flexibly explores scenarios from advanced inductive profile control to low current tokamak operation. A 1 MW 5.5 GHz source for electron Bernstein wave injection is nearly complete to investigate heating and current drive in over-dense plasmas. Supported by DOE and NSF.

Fusion method of SAR and optical images for urban object extraction

NASA Astrophysics Data System (ADS)

Jia, Yonghong; Blum, Rick S.; Li, Fangfang

2007-11-01

A new image fusion method of SAR, Panchromatic (Pan) and multispectral (MS) data is proposed. First of all, SAR texture is extracted by ratioing the despeckled SAR image to its low pass approximation, and is used to modulate high pass details extracted from the available Pan image by means of the á trous wavelet decomposition. Then, high pass details modulated with the texture is applied to obtain the fusion product by HPFM (High pass Filter-based Modulation) fusion method. A set of image data including co-registered Landsat TM, ENVISAT SAR and SPOT Pan is used for the experiment. The results demonstrate accurate spectral preservation on vegetated regions, bare soil, and also on textured areas (buildings and road network) where SAR texture information enhances the fusion product, and the proposed approach is effective for image interpret and classification.

Specific beta1-adrenergic receptor silencing with small interfering RNA lowers high blood pressure and improves cardiac function in myocardial ischemia.

PubMed

Arnold, Anne-Sophie; Tang, Yao Liang; Qian, Keping; Shen, Leping; Valencia, Valery; Phillips, Michael Ian; Zhang, Yuan Clare

2007-01-01

Beta-blockers are widely used and effective for treating hypertension, acute myocardial infarction (MI) and heart failure, but they present side-effects mainly due to antagonism of beta2-adrenergic receptor (AR). Currently available beta-blockers are at best selective but not specific for beta1 or beta2-AR. To specifically inhibit the expression of the beta1-AR, we developed a small interfering RNA (siRNA) targeted to beta1-AR. Three different sequences of beta1 siRNA were delivered into C6-2B cells with 90% efficiency. One of the three sequences reduced the level of beta1-AR mRNA by 70%. The siRNA was highly specific for beta1-AR inhibition with no overlap with beta2-AR. To test this in vivo, systemic injection of beta1 siRNA complexed with liposomes resulted in efficient delivery into the heart, lung, kidney and liver, and effectively reduced beta1-AR expression in the heart without altering beta2-AR. beta1 siRNA significantly lowered blood pressure of spontaneously hypertensive rats (SHR) for at least 12 days and reduced cardiac hypertrophy following a single injection. Pretreatment with beta1 siRNA 3 days before induction of MI in Wistar rats significantly improved cardiac function, as demonstrated by dP/dt and electrocardiogram following the MI. The protective mechanism involved reduction of cardiomyocyte apoptosis in the beta1 siRNA-treated hearts. The present study demonstrates the possibility of using siRNA for treating cardiovascular diseases and may represent a novel beta-blocker specific for beta1-AR.

Proton Spectra from He 3 + T and He 3 + He 3 Fusion at Low Center-of-Mass Energy, with Potential Implications for Solar Fusion Cross Sections

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

Zylstra, A. B.; Frenje, J. A.; Gatu Johnson, M.

Few-body nuclear physics often relies upon phenomenological models, with new efforts at the ab initio theory reported recently; both need high-quality benchmark data, particularly at low center-of-mass energies. We use high-energy-density plasmas to measure the proton spectra from 3He + T and 3He + 3He fusion. The data disagree with R -matrix predictions constrained by neutron spectra from T + T fusion. Here, we present a new analysis of the 3He + 3He proton spectrum; these benchmarked spectral shapes should be used for interpreting low-resolution data, such as solar fusion cross-section measurements.

Proton Spectra from 3He + T and 3He + 3He Fusion at Low Center-of-Mass Energy, with Potential Implications for Solar Fusion Cross Sections

NASA Astrophysics Data System (ADS)

Zylstra, A. B.; Frenje, J. A.; Gatu Johnson, M.; Hale, G. M.; Brune, C. R.; Bacher, A.; Casey, D. T.; Li, C. K.; McNabb, D.; Paris, M.; Petrasso, R. D.; Sangster, T. C.; Sayre, D. B.; Séguin, F. H.

2017-12-01

Few-body nuclear physics often relies upon phenomenological models, with new efforts at the ab initio theory reported recently; both need high-quality benchmark data, particularly at low center-of-mass energies. We use high-energy-density plasmas to measure the proton spectra from 3He +T and 3He + 3He fusion. The data disagree with R -matrix predictions constrained by neutron spectra from T +T fusion. We present a new analysis of the 3He + 3He 3 proton spectrum; these benchmarked spectral shapes should be used for interpreting low-resolution data, such as solar fusion cross-section measurements.

Proton Spectra from He 3 + T and He 3 + He 3 Fusion at Low Center-of-Mass Energy, with Potential Implications for Solar Fusion Cross Sections

DOE PAGES

Zylstra, A. B.; Frenje, J. A.; Gatu Johnson, M.; ...

2017-11-29

Few-body nuclear physics often relies upon phenomenological models, with new efforts at the ab initio theory reported recently; both need high-quality benchmark data, particularly at low center-of-mass energies. We use high-energy-density plasmas to measure the proton spectra from 3He + T and 3He + 3He fusion. The data disagree with R -matrix predictions constrained by neutron spectra from T + T fusion. Here, we present a new analysis of the 3He + 3He proton spectrum; these benchmarked spectral shapes should be used for interpreting low-resolution data, such as solar fusion cross-section measurements.

Mutants of Agrobacterium tumefaciens with elevated vir gene expression

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

Pazour, G.J.; Ta, C.N.; Das, A.

1991-08-15

Expression of Agrobacterium tumefaciens virulence (vir) genes requires virA, virG, and a plant-derived inducing compound such as acetosyringone. To identify the critical functional domains of virA and virG, a mutational approach was used. Agrobacterium A136 harboring plasmid pGP159, which contains virA, virG, and a reporter virB:lacZ gene fusion, was mutagenized with UV light or nitrosoguanidine. Survivors that formed blue colonies on a plate containing 5-bromo-4-chloro-3-indolyl beta-D-galactoside were isolated and analyzed. Quantification of beta-galactosidase activity in liquid assays identified nine mutant strains. By plasmid reconstruction and other procedures, all mutations mapped to the virA locus. These mutations caused an 11- tomore » 560-fold increase in the vegetative level of virB:lacZ reporter gene expression. DNA sequence analysis showed that the mutations are located in four regions of VirA: transmembrane domain one, the active site, a glycine-rich region with homology to ATP-binding sites, and a region at the C terminus that has homology to the N terminus of VirG.« less

Penning trap mass spectrometry Q-value determinations for highly forbidden β-decays

NASA Astrophysics Data System (ADS)

Sandler, Rachel; Bollen, Georg; Eibach, Martin; Gamage, Nadeesha; Gulyuz, Kerim; Hamaker, Alec; Izzo, Chris; Kandegedara, Rathnayake; Redshaw, Matt; Ringle, Ryan; Valverde, Adrian; Yandow, Isaac; Low Energy Beam Ion Trap Team

2017-09-01

Over the last several decades, extremely sensitive, ultra-low background beta and gamma detection techniques have been developed. These techniques have enabled the observation of very rare processes, such as highly forbidden beta decays e.g. of 113Cd, 50V and 138La. Half-life measurements of highly forbidden beta decays provide a testing ground for theoretical nuclear models, and the comparison of calculated and measured energy spectra could enable a determination of the values of the weak coupling constants. Precision Q-value measurements also allow for systematic tests of the beta-particle detection techniques. We will present the results and current status of Q value determinations for highly forbidden beta decays. The Q values, the mass difference between parent and daughter nuclides, are measured using the high precision Penning trap mass spectrometer LEBIT at the National Superconducting Cyclotron Laboratory.

High beta-N experiments at JET

NASA Astrophysics Data System (ADS)

Challis, Clive

2007-11-01

JET has investigated the performance potential and limitations of highly triangular plasmas relevant to fully non-inductive tokamak operation. The q-profile shape has been varied from cases with highly negative core magnetic shear to low shear with q0 close to 1, allowing the effect on confinement and stability to be studied. Operation with beta-N above the no-wall `limit' has been demonstrated for durations comparable with the resistive time and direct measurements of the no-wall beta have been developed as a tool for systematic performance optimization. Regimes have been developed with ITBs at reduced plasma current and toroidal field (1.2-1.5MA/2.3-2.7T) to obtain high values of beta-N and beta-P with either impurity seeding or quasi-double-null plasma configurations used to mitigate ELMs. The importance of the q-profile shape for performance optimization has been demonstrated in plasmas without ITBs (1.2MA/1.8T) with low values of minimum q (1-2) providing access to the highest beta-N (above 3).

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.

Clinical outcome of trans-sacral interbody fusion after partial reduction for high-grade l5-s1 spondylolisthesis.

PubMed

Smith, J A; Deviren, V; Berven, S; Kleinstueck, F; Bradford, D S

2001-10-15

A clinical retrospective study was conducted. To evaluate the clinical and radiographic outcome of reduction followed by trans-sacral interbody fusion for high-grade spondylolisthesis. In situ posterior interbody fusion with fibula allograft has improved the fusion rates for patients with high-grade spondylolisthesis. The use of this technique in conjunction with partial reduction has not been reported. Nine consecutive patients underwent treatment of high-grade (Grade 3 or 4) spondylolisthesis with partial reduction followed by posterior interbody fusion using cortical allograft. The average age at the time of surgery was 27 years (range, 8-51 years), and the average follow-up period was 43 months (range, 24-72 months). Before surgery, eight patients had low back pain, seven patients had radiating leg pain, and five patients had hamstring tightness. The average grade of spondylolisthesis by Meyerding grading was 3.9 (range, 3-5). Charts and radiographs were evaluated, and outcomes were collected by use of the modified SRS outcomes instrument. Radiographic indexes demonstrated significant improvement with partial reduction and fusion. The slip angle, as measured from the inferior endplate of L5, improved from 41.2 degrees (range, 24-82 degrees ) before surgery to 21 degrees (range, 5-40 degrees ) after surgery. All the patients were extremely or somewhat satisfied with surgery. The two patients who underwent this operation without initial instrumentation experienced fractures of their interbody grafts. Both of these patients underwent repair of the pseudarthrosis with placement of trans-sacral pedicle screw instrumentation and subsequent fusion. Partial reduction followed by posterior interbody fusion is an effective technique for the management of high-grade spondylolisthesis in pediatric and adult patient populations, as assessed by radiographic and clinical criteria. Pedicle screw instrumentation with the sacral screws capturing L5 is recommended when this technique is used for the treatment of high-grade spondylolisthesis. According to the clinical and radiographic results from this study, partial reduction and posterior fibula interbody fusion supplemented with pedicle screw instrumentation is an effective technique for select patients with high-grade spondylolisthesis at L5-S1.

Genome-wide analysis of DNA methylation variations caused by chronic glucolipotoxicity in beta-cells.

PubMed

Hu, Y; Xu, X-H; He, K; Zhang, L-L; Wang, S-K; Pan, Y-Q; He, B-S; Feng, T-T; Mao, X-M

2014-02-01

There is a growing body of literature suggesting the role of interactions between genes and the environment in development of type 2 diabetes mellitus (T2DM). However, the interplay between environment and genetic in developing and progressing T2MD is not fully understood. To determine the effects of high-glucose-lipid on the status of DNA methylation in beta cells, and clarify the mechanism of glucolipotoxicity on beta-cell deterioration, the DNA methylation profile was detected in beta-cells cultured with high-glucose-lipid medium.We utilized a high throughput NimbleGen RN34 CpG Island & Promoter Microarray to investigate the DNA methylation profile in beta-cells cultured with high-glucose-lipid medium. To validate the results of microarray, the immunoprecipitation (MeDIP) PCR was used to test the methylation status of some selected genes. The mRNA and protein expression of insulin and Tcf7l2 in these cells were quantified by RT-PCR and western blot, respectively.We have identified a lot of loci which experienced aberrant DNA methylation in beta-cells cultured with high-glucose-lipid medium. The results of MeDIP PCR were consistency to the microarray. An opposite regulation in transcription and translation of Tcf7l2 gene was found. Furthermore, the insulin mRNA and protein expression in beta-cells also decreased after cultured with high-glucose-lipid medium compared with the control cells.We conclude that chronic glucolipotoxicity could induce aberrant DNA methylation of some genes and may affect these genes expression in beta-cells, which might contribute to beta-cell function failure in T2DM and be helpful to explain, at least partially, the mechanism of glucolipotoxicity on beta-cells deterioration. © J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York.

The VISTA spacecraft: Advantages of ICF (Inertial Confinement Fusion) for interplanetary fusions propulsion applications

NASA Technical Reports Server (NTRS)

Orth, Charles D.; Klein, Gail; Sercel, Joel; Hoffman, Nate; Murray, Kathy; Chang-Diaz, Franklin

1987-01-01

Inertial Confinement Fusion (ICF) is an attractive engine power source for interplanetary manned spacecraft, especially for near-term missions requiring minimum flight duration, because ICF has inherent high power-to-mass ratios and high specific impulses. We have developed a new vehicle concept called VISTA that uses ICF and is capable of round-trip manned missions to Mars in 100 days using A.D. 2020 technology. We describe VISTA's engine operation, discuss associated plasma issues, and describe the advantages of DT fuel for near-term applications. Although ICF is potentially superior to non-fusion technologies for near-term interplanetary transport, the performance capabilities of VISTA cannot be meaningfully compared with those of magnetic-fusion systems because of the lack of a comparable study of the magnetic-fusion systems. We urge that such a study be conducted.

Biological functions of hCG and hCG-related molecules

PubMed Central

2010-01-01

Background hCG is a term referring to 4 independent molecules, each produced by separate cells and each having completely separate functions. These are hCG produced by villous syncytiotrophoblast cells, hyperglycosylated hCG produced by cytotrophoblast cells, free beta-subunit made by multiple primary non-trophoblastic malignancies, and pituitary hCG made by the gonadotrope cells of the anterior pituitary. Results and discussion hCG has numerous functions. hCG promotes progesterone production by corpus luteal cells; promotes angiogenesis in uterine vasculature; promoted the fusion of cytotrophoblast cell and differentiation to make syncytiotrophoblast cells; causes the blockage of any immune or macrophage action by mother on foreign invading placental cells; causes uterine growth parallel to fetal growth; suppresses any myometrial contractions during the course of pregnancy; causes growth and differentiation of the umbilical cord; signals the endometrium about forthcoming implantation; acts on receptor in mother's brain causing hyperemesis gravidarum, and seemingly promotes growth of fetal organs during pregnancy. Hyperglycosylated hCG functions to promote growth of cytotrophoblast cells and invasion by these cells, as occurs in implantation of pregnancy, and growth and invasion by choriocarcinoma cells. hCG free beta-subunit is produced by numerous non-trophoblastic malignancies of different primaries. The detection of free beta-subunit in these malignancies is generally considered a sign of poor prognosis. The free beta-subunit blocks apoptosis in cancer cells and promotes the growth and malignancy of the cancer. Pituitary hCG is a sulfated variant of hCG produced at low levels during the menstrual cycle. Pituitary hCG seems to mimic luteinizing hormone actions during the menstrual cycle. PMID:20735820

Fragrant dioxane derivatives identify beta1-subunit-containing GABAA receptors.

PubMed

Sergeeva, Olga A; Kletke, Olaf; Kragler, Andrea; Poppek, Anja; Fleischer, Wiebke; Schubring, Stephan R; Görg, Boris; Haas, Helmut L; Zhu, Xin-Ran; Lübbert, Hermann; Gisselmann, Günter; Hatt, Hanns

2010-07-30

Nineteen GABA(A) receptor (GABA(A)R) subunits are known in mammals with only a restricted number of functionally identified native combinations. The physiological role of beta1-subunit-containing GABA(A)Rs is unknown. Here we report the discovery of a new structural class of GABA(A)R positive modulators with unique beta1-subunit selectivity: fragrant dioxane derivatives (FDD). At heterologously expressed alpha1betaxgamma2L (x-for 1,2,3) GABA(A)R FDD were 6 times more potent at beta1- versus beta2- and beta3-containing receptors. Serine at position 265 was essential for the high sensitivity of the beta1-subunit to FDD and the beta1N286W mutation nearly abolished modulation; vice versa the mutation beta3N265S shifted FDD sensitivity toward the beta1-type. In posterior hypothalamic neurons controlling wakefulness GABA-mediated whole-cell responses and GABAergic synaptic currents were highly sensitive to FDD, in contrast to beta1-negative cerebellar Purkinje neurons. Immunostaining for the beta1-subunit and the potency of FDD to modulate GABA responses in cultured hypothalamic neurons was drastically diminished by beta1-siRNA treatment. In conclusion, with the help of FDDs we reveal a functional expression of beta1-containing GABA(A)Rs in the hypothalamus, offering a new tool for studies on the functional diversity of native GABA(A)Rs.

Magnetized Target Fusion

NASA Technical Reports Server (NTRS)

Griffin, Steven T.

2002-01-01

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

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

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

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

2013-03-15

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

Antibody-independent Targeted Quantification of TMPRSS2-ERG Fusion Protein Products in Prostate Cancer

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

He, Jintang; Sun, Xuefei; Shi, Tujin

2014-10-01

Fusions between the transmembrane protease serine 2 (TMPRSS2) and ETS related gene (ERG) represent one of the most specific biomarkers that define a distinct molecular subtype of prostate cancer. The studies on TMPRSS2-ERG gene fusions have seldom been performed at the protein level, primarily due to the lack of high-quality antibodies or an antibody-independent method that is sufficiently sensitive for detecting the truncated ERG protein products resulting from TMPRSS2-ERG gene fusions and alternative splicing. Herein, we applied a recently developed PRISM (high-pressure high-resolution separations with intelligent selection and multiplexing)-SRM (selected reaction monitoring) strategy for quantifying ERG protein in prostate cancermore » cell lines and tumors. The highly sensitive PRISM-SRM assays led to confident detection of 6 unique ERG peptides in either the TMPRSS2-ERG positive cell lines or tissues but not in the negative controls, indicating that ERG protein expression is highly correlated with TMPRSS2-ERG gene rearrangements. Significantly, our results demonstrated for the first time that at least two groups of ERG protein isoforms were simultaneously expressed at variable levels in TMPRSS2-ERG positive samples as evidenced by concomitant detection of two mutually exclusive peptides. Three peptides shared across almost all fusion protein products were determined to be the most abundant peptides, and hence can be used as “signature” peptides for detecting ERG overexpression resulting from TMPRSS2-ERG gene fusion. These PRISM-SRM assays provide valuable tools for studying TMPRSS2-ERG gene fusion protein products, thus improving our understanding of the role of TMPRSS2-ERG gene fusion in the biology of prostate cancer.« less

Subthalamic nucleus phase–amplitude coupling correlates with motor impairment in Parkinson’s disease

PubMed Central

van Wijk, Bernadette C.M.; Beudel, Martijn; Jha, Ashwani; Oswal, Ashwini; Foltynie, Tom; Hariz, Marwan I.; Limousin, Patricia; Zrinzo, Ludvic; Aziz, Tipu Z.; Green, Alexander L.; Brown, Peter; Litvak, Vladimir

2016-01-01

Objective High-amplitude beta band oscillations within the subthalamic nucleus are frequently associated with Parkinson’s disease but it is unclear how they might lead to motor impairments. Here we investigate a likely pathological coupling between the phase of beta band oscillations and the amplitude of high-frequency oscillations around 300 Hz. Methods We analysed an extensive data set comprising resting-state recordings obtained from deep brain stimulation electrodes in 33 patients before and/or after taking dopaminergic medication. We correlated mean values of spectral power and phase–amplitude coupling with severity of hemibody bradykinesia/rigidity. In addition, we used simultaneously recorded magnetoencephalography to look at functional interactions between the subthalamic nucleus and ipsilateral motor cortex. Results Beta band power and phase–amplitude coupling within the subthalamic nucleus correlated positively with severity of motor impairment. This effect was more pronounced within the low-beta range, whilst coherence between subthalamic nucleus and motor cortex was dominant in the high-beta range. Conclusions We speculate that the beta band might impede pro-kinetic high-frequency activity patterns when phase–amplitude coupling is prominent. Furthermore, results provide evidence for a functional subdivision of the beta band into low and high frequencies. Significance Our findings contribute to the interpretation of oscillatory activity within the cortico-basal ganglia circuit. PMID:26971483

Double Beta Decays and Neutrinos - Experiments and MOON

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

Ejiri, H.; National Institute of Radiological Sciences, Chiba, 263-8555

2008-01-24

This is a brief review of the present and future experiments of neutrino-less double beta decays (0{nu}{beta}{beta}) and the MOON (Mo Observatory Of Neutrinos) project. High sensitivity 0{nu}{beta}{beta} experiments are unique and realistic probes for studying the Majorana nature of neutrinos and the absolute mass scale as suggested by neutrino oscillation experiments. MOON aims at spectroscopic 0{nu}{beta}{beta} studies with the {nu}-mass sensitivity of 100-30 meV by means of a super ensemble of multilayer modules of scintillator plates and tracking detector planes.

MicroRNA Detection by DNA-Mediated Liposome Fusion.

PubMed

Jumeaux, Coline; Wahlsten, Olov; Block, Stephan; Kim, Eunjung; Chandrawati, Rona; Howes, Philip D; Höök, Fredrik; Stevens, Molly M

2018-03-02

Membrane fusion is a process of fundamental importance in biological systems that involves highly selective recognition mechanisms for the trafficking of molecular and ionic cargos. Mimicking natural membrane fusion mechanisms for the purpose of biosensor development holds great potential for amplified detection because relatively few highly discriminating targets lead to fusion and an accompanied engagement of a large payload of signal-generating molecules. In this work, sequence-specific DNA-mediated liposome fusion is used for the highly selective detection of microRNA. The detection of miR-29a, a known flu biomarker, is demonstrated down to 18 nm within 30 min with high specificity by using a standard laboratory microplate reader. Furthermore, one order of magnitude improvement in the limit of detection is demonstrated by using a novel imaging technique combined with an intensity fluctuation analysis, which is coined two-color fluorescence correlation microscopy. © 2018 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

Low dose radiation interactions with the transformation growth factor (TFG)-beta pathway

NASA Astrophysics Data System (ADS)

Maslowski, Amy Jesse

A major limiting factor for long-term, deep-space missions is the radiation dose to astronauts. Because the dose to the astronauts is a mixed field of low- and high-LET radiation, there is a need to understand the effects of both radiation types on whole tissue; however, there are limited published data on the effects of high-LET (linear-energy-transfer) radiation on tissue. Thus, we designed a perfusion chamber system for rat trachea in order to mimic in vivo respiratory tissue. We successfully maintained the perfused tracheal tissue ex vivo in a healthy and viable condition for up to three days. In addition, this project studied the effects of high-LET Fe particles on the overall transformation growth factor (TGF)-beta response after TGF-beta inactivation and compared the results to the TGF-beta response post x-ray irradiation. It was found that a TGF-beta response could be measured in the perfused tracheal tissue, for x-ray and Fe particle irradiations, despite the high autofluorescent background intrinsic to tissue. However, after comparing the TGF-beta response of x-ray irradiation to High-Z-High-energy (HZE) irradiation, there was not a significant difference in radiation types. The TGF-beta response in x-ray and HZE irradiated perfusion chambers was also measured over time post irradiation. It was found that for 6 hour and 8 hour post irradiation, the TGF-beta response was higher for lower doses of radiation than for higher doses. This is in contrast to the 0 hour fixation which found the TGF-beta response to increase with increased dose. The inverse relationship found for 6 hour and 8 hour fixation times may indicate a threshold response for TGF-beta response; i.e., for low doses, a threshold of dose must be reached for an immediate TGF-beta response, otherwise the tissue responds more slowly to the irradiation damage. This result was unexpected and will require further investigation to determine if the threshold can be determined for the 250 kVp x-rays and 1 Gev Fe particles.

Center for the Study of Plasma Microturbulence

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

Parker, Scott E.

We have discovered a possible "natural fueling" mechanism in tokamak fusion reactors using large scale gyrokinetic turbulence simulation. In the presence of a heat flux dominated tokamak plasma, cold ions naturally pinch radially inward. If cold DT fuel is introduced near the edge using shallow pellet injection, the cold fuel will pinch inward, at the expense of hot helium ash going radially outward. By adjusting the cold DT fuel concentration, the core DT density profiles can be maintained. We have also shown that cold source ions from edge recycling of cold neutrals are pinched radially inward. This mechanism may bemore » important for fully understanding the edge pedestal buildup after an ELM crash. Work includes benchmarking the gyrokinetic turbulence codes in the electromagnetic regime. This includes cyclone base case parameters with an increasing plasma beta. The code comparisons include GEM, GYRO and GENE. There is good linear agreement between the codes using the Cyclone base case, but including electromagnetics and scanning the plasma beta. All the codes have difficulty achieving nonlinear saturation as the kinetic ballooning limit is approached. GEM does not saturate well when beta gets above about 1/2 of the ideal ballooning limit. We find that the lack of saturation is due to the long wavelength k{sub y} modes being nonlinearly pumped to high levels. If the fundamental k{sub y} mode is zeroed out, higher values of beta nonlinearly saturate well. Additionally, there have been studies to better understand CTEM nonlinear saturation and the importance of zonal flows. We have continued our investigation of trapped electron mode (TEM) turbulence. More recently, we have focused on the nonlinear saturation of TEM turbulence. An important feature of TEM is that in many parameter regimes, the zonal flow is unimportant. We find that when zonal flows are unimportant, zonal density is the dominant saturation mechanism. We developed a simple theory that agrees with the simulation and predicts zonal density generation and feedback stabilization of the most unstable mode even in the absence of zonal flow. We are using GEM to simulate NSTX discharges. We have also done verification and validation on DIII-D. Good agreement with GYRO and DIII-D flux levels were reported in the core region.« less

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.

Classical sickle beta-globin haplotypes exhibit a high degree of long-range haplotype similarity in African and Afro-Caribbean populations.

PubMed

Hanchard, Neil; Elzein, Abier; Trafford, Clare; Rockett, Kirk; Pinder, Margaret; Jallow, Muminatou; Harding, Rosalind; Kwiatkowski, Dominic; McKenzie, Colin

2007-08-10

The sickle (betas) mutation in the beta-globin gene (HBB) occurs on five "classical" betas haplotype backgrounds in ethnic groups of African ancestry. Strong selection in favour of the betas allele - a consequence of protection from severe malarial infection afforded by heterozygotes - has been associated with a high degree of extended haplotype similarity. The relationship between classical betas haplotypes and long-range haplotype similarity may have both anthropological and clinical implications, but to date has not been explored. Here we evaluate the haplotype similarity of classical betas haplotypes over 400 kb in population samples from Jamaica, The Gambia, and among the Yoruba of Nigeria (Hapmap YRI). The most common betas sub-haplotype among Jamaicans and the Yoruba was the Benin haplotype, while in The Gambia the Senegal haplotype was observed most commonly. Both subtypes exhibited a high degree of long-range haplotype similarity extending across approximately 400 kb in all three populations. This long-range similarity was significantly greater than that seen for other haplotypes sampled in these populations (P < 0.001), and was independent of marker choice and marker density. Among the Yoruba, Benin haplotypes were highly conserved, with very strong linkage disequilibrium (LD) extending a megabase across the betas mutation. Two different classical betas haplotypes, sampled from different populations, exhibit comparable and extensive long-range haplotype similarity and strong LD. This LD extends across the adjacent recombination hotspot, and is discernable at distances in excess of 400 kb. Although the multi-centric geographic distribution of betas haplotypes indicates strong subdivision among early Holocene sub-Saharan populations, we find no evidence that selective pressures imposed by falciparum malaria varied in intensity or timing between these subpopulations. Our observations also suggest that cis-acting loci, which may influence outcomes in sickle cell disease, could lie considerable distances away from beta-globin.

Shock ignition: a new approach to high gain inertial confinement fusion on the national ignition facility.

PubMed

Perkins, L J; Betti, R; LaFortune, K N; Williams, W H

2009-07-24

Shock ignition, an alternative concept for igniting thermonuclear fuel, is explored as a new approach to high gain, inertial confinement fusion targets for the National Ignition Facility (NIF). Results indicate thermonuclear yields of approximately 120-250 MJ may be possible with laser drive energies of 1-1.6 MJ, while gains of approximately 50 may still be achievable at only approximately 0.2 MJ drive energy. The scaling of NIF energy gain with laser energy is found to be G approximately 126E (MJ);{0.510}. This offers the potential for high-gain targets that may lead to smaller, more economic fusion power reactors and a cheaper fusion energy development path.

Overview of the present progress and activities on the CFETR

NASA Astrophysics Data System (ADS)

Wan, Yuanxi; Li, Jiangang; Liu, Yong; Wang, Xiaolin; Chan, Vincent; Chen, Changan; Duan, Xuru; Fu, Peng; Gao, Xiang; Feng, Kaiming; Liu, Songlin; Song, Yuntao; Weng, Peide; Wan, Baonian; Wan, Farong; Wang, Heyi; Wu, Songtao; Ye, Minyou; Yang, Qingwei; Zheng, Guoyao; Zhuang, Ge; Li, Qiang; CFETR Team

2017-10-01

The China Fusion Engineering Test Reactor (CFETR) is the next device in the roadmap for the realization of fusion energy in China, which aims to bridge the gaps between the fusion experimental reactor ITER and the demonstration reactor (DEMO). CFETR will be operated in two phases. Steady-state operation and self-sufficiency will be the two key issues for Phase I with a modest fusion power of up to 200 MW. Phase II aims for DEMO validation with a fusion power over 1 GW. Advanced H-mode physics, high magnetic fields up to 7 T, high frequency electron cyclotron resonance heating and lower hybrid current drive together with off-axis negative-ion neutral beam injection will be developed for achieving steady-state advanced operation. The recent detailed design, research and development (R&D) activities including integrated modeling of operation scenarios, high field magnet, material, tritium plant, remote handling and future plans are introduced in this paper.

Flexible responses to visual and olfactory stimuli by foraging Manduca sexta: larval nutrition affects adult behaviour.

PubMed

Goyret, Joaquín; Kelber, Almut; Pfaff, Michael; Raguso, Robert A

2009-08-07

Here, we show that the consequences of deficient micronutrient (beta-carotene) intake during larval stages of Manduca sexta are carried across metamorphosis, affecting adult behaviour. Our manipulation of larval diet allowed us to examine how developmental plasticity impacts the interplay between visual and olfactory inputs on adult foraging behaviour. Larvae of M. sexta were reared on natural (Nicotiana tabacum) and artificial laboratory diets containing different concentrations of beta-carotene (standard diet, low beta-carotene, high beta-carotene and cornmeal). This vitamin-A precursor has been shown to be crucial for photoreception sensitivity in the retina of M. sexta. After completing development, post-metamorphosis, starved adults were presented with artificial feeders that could be either scented or unscented. Regardless of their larval diet, adult moths fed with relatively high probabilities on scented feeders. When feeders were unscented, moths reared on tobacco were more responsive than moths reared on beta-carotene-deficient artificial diets. Strikingly, moths reared on artificial diets supplemented with increasing amounts of beta-carotene (low beta and high beta) showed increasing probabilities of response to scentless feeders. We discuss these results in relationship to the use of complex, multi-modal sensory information by foraging animals.

Short-term scheduling of crude oil operations in refinery with high-fusion-point oil and two transportation pipelines

NASA Astrophysics Data System (ADS)

Wu, NaiQi; Zhu, MengChu; Bai, LiPing; Li, ZhiWu

2016-07-01

In some refineries, storage tanks are located at two different sites, one for low-fusion-point crude oil and the other for high one. Two pipelines are used to transport different oil types. Due to the constraints resulting from the high-fusion-point oil transportation, it is challenging to schedule such a system. This work studies the scheduling problem from a control-theoretic perspective. It proposes to use a hybrid Petri net method to model the system. It then finds the schedulability conditions by analysing the dynamic behaviour of the net model. Next, it proposes an efficient scheduling method to minimize the cost of high-fusion-point oil transportation. Finally, it gives a complex industrial case study to show its application.

beta-Endorphin-induced analgesia is inhibited by synthetic analogs of beta-endorphin.

PubMed

Nicolas, P; Hammonds, R G; Li, C H

1984-05-01

Competitive antagonism of human beta-endorphin (beta h-EP)-induced analgesia by synthetic beta h-EP analogs with high in vitro opiate receptor binding to in vivo analgesic potency ratio has been demonstrated. A parallel shift of the dose-response curve for analgesia to the right was observed when either beta h-EP or [ Trp27 ] -beta h-EP was coinjected with various doses of [Gln8, Gly31 ]-beta h-EP-Gly-Gly-NH2, [Arg9,19,24,28,29]-beta h-EP, or [ Cys11 ,26, Phe27 , Gly31 ]-beta h-EP. It was estimated that the most potent antagonist, [Gln8, Gly31 ]-beta h-EP-Gly-NH2, is at least 200 times more potent than naloxone.

Advanced Concepts: Aneutronic Fusion Power and Propulsion

NASA Technical Reports Server (NTRS)

Chapman, John J.

2012-01-01

Aneutronic Fusion for In-Space thrust, power. Clean energy & potential nuclear gains. Fusion plant concepts, potential to use advanced fuels. Methods to harness ionic momentum for high Isp thrust plus direct power conversion into electricity will be presented.

Occurrence of high-beta superthermal plasma events in the close environment of Jupiter's bow shock as observed by Ulysses

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

Marhavilas, P. K.; Sarris, E. T.; Anagnostopoulos, G. C.

2011-01-04

The ratio of the plasma pressure to the magnetic field pressure (or of their energy densities) which is known as the plasma parameter 'beta'({beta}) has important implications to the propagation of energetic particles and the interaction of the solar wind with planetary magnetospheres. Although in the scientific literature the contribution of the superthermal particles to the plasma pressure is generally assumed negligible, we deduced, by analyzing energetic particles and magnetic field measurements recorded by the Ulysses spacecraft, that in a series of events, the energy density contained in the superthermal tail of the particle distribution is comparable to or evenmore » higher than the energy density of the magnetic field, creating conditions of high-beta plasma. More explicitly, in this paper we analyze Ulysses/HI-SCALE measurements of the energy density ratio (parameter {beta}{sub ep}) of the energetic ions'(20 keV to {approx}5 MeV) to the magnetic field's in order to find occurrences of high-beta ({beta}{sub ep}>1) superthermal plasma conditions in the environment of the Jovian magnetosphere, which is an interesting plasma laboratory and an important source of emissions in our solar system. In particular, we examine high-beta ion events close to Jupiter's bow shock, which are produced by two processes: (a) bow shock ion acceleration and (b) ion leakage from the magnetosphere.« less

Mechanistic studies of cancer cell mitochondria- and NQO1-mediated redox activation of beta-lapachone, a potentially novel anticancer agent

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

Li, Jason Z.; Ke, Yuebin; Misra, Hara P.

Beta-lapachone (beta-Lp) derived from the Lapacho tree is a potentially novel anticancer agent currently under clinical trials. Previous studies suggested that redox activation of beta-Lp catalyzed by NAD(P)H:quinone oxidoreductase 1 (NQO1) accounted for its killing of cancer cells. However, the exact mechanisms of this effect remain largely unknown. Using chemiluminescence and electron paramagnetic resonance (EPR) spin-trapping techniques, this study for the first time demonstrated the real-time formation of ROS in the redox activation of beta-lapachone from cancer cells mediated by mitochondria and NQO1 in melanoma B16–F10 and hepatocellular carcinoma HepG2 cancer cells. ES936, a highly selective NQO1 inhibitor, and rotenone,more » a selective inhibitor of mitochondrial electron transport chain (METC) complex I were found to significantly block beta-Lp meditated redox activation in B16–F10 cells. In HepG2 cells ES936 inhibited beta-Lp-mediated oxygen radical formation by ∼ 80% while rotenone exerted no significant effect. These results revealed the differential contribution of METC and NQO1 to beta-lapachone-induced ROS formation and cancer cell killing. In melanoma B16–F10 cells that do not express high NQO1 activity, both NOQ1 and METC play a critical role in beta-Lp redox activation. In contrast, in hepatocellular carcinoma HepG2 cells expressing extremely high NQO1 activity, redox activation of beta-Lp is primarily mediated by NQO1 (METC plays a minor role). These findings will contribute to our understanding of how cancer cells are selectively killed by beta-lapachone and increase our ability to devise strategies to enhance the anticancer efficacy of this potentially novel drug while minimizing its possible adverse effects on normal cells. - Highlights: • Both isolated mitochondria and purified NQO1 are able to generate ROS by beta-Lp. • The differential roles of mitochondria and NQO1 in mediating redox activation of beta-Lp • In cancer cells with low NQO1 expression, mitochondria play a critical role in beta-Lp redox activation. • In cancer cells with high NQO1 activity, redox activation of beta-Lp is primarily mediated by NQO1.« less

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

PubMed

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

2009-09-29

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

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

PubMed Central

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

2016-01-01

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

Chimeric Amino Acid Rearrangements as Immune Targets in Prostate Cancer

DTIC Science & Technology

2016-05-01

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

[Increase of beta 2-microglobulin in drug addicts with anti-HIV antibodies and high risk of AIDS].

PubMed

D'Angelo, G; Giardini, C; Zanco, M D; Calvano, D; Crovetti, G; De Filippo, C

1991-01-01

The beta 2-Microglobulin is a polypeptide present on the surface membrane of both B and T cells and is integrated into the structure of HLA antigenes. The beta 2-Microglobulin concentration have been used as a reliable indicator of glomerular and tubular function of the kidney. Increased serum concentration of beta 2-Microglobulin are observed also in lymphoproliferative disorders with high cell proliferation rates. More recently, increased concentration of beta 2-Microglobulin was shown in patients with anti-HIV antibodies with or without symptomatic AIDS. We have determined beta 2-Microglobulin in 61 subjects: 40 between the ages of 25 and 35 and seemingly healthy, 21 patients between the ages of 22 and 32 and intravenous drug abuser with anti-HIV antibodies and at high-risk for AIDS. In all subjects we have tested: BUN, creatinine, beta 2-Microglobulin and T4/T8 ratio. In 40 subjects as normal controls, beta 2-Microglobulin average was means = 1.07 mg/L (SD = 0.39), T4/T8 ratio average: means = 1.06 (SD = 0.119). In 21 patients drug abuser with anti-HIV antibodies, the beta 2-Microglobulin average was cleanly increased: means = 4.72 mg/L (SD = 2.23), the T4/T8 ratio average cleanly decreased: means = 0.54 (SD = 0.21). We believe the beta 2-Microglobulin quantitation, even if not specific for patient with symptomatic AIDS, used in conjunction with other laboratory tests, principally T4/T8 ratio, will be a useful marker for recognizing persons with possible asymptomatic AIDS who are members of populations known to be at high-risk for AIDS.

Expression of class III beta tubulin in cervical cancer patients administered preoperative radiochemotherapy: correlation with response to treatment and clinical outcome.

PubMed

Ferrandina, Gabriella; Martinelli, Enrica; Zannoni, Gian Franco; Distefano, Mariagrazia; Paglia, Amelia; Ferlini, Cristiano; Scambia, Giovanni

2007-02-01

Alterations of the beta subunit of tubulin have been reported to be predictive of resistance to radiation and antitubulin agents in several solid tumors. The aim of the study was to investigate the clinical role of beta III tubulin expression as prognostic factor for survival and as a predictive parameter of response to preoperative radiochemotherapy in a single institutional series of locally advanced cervical cancer (LACC) patients. The study included 98 LACC patients admitted to the Gynecologic Oncology Unit, Catholic University of Rome and Campobasso between January 1998 and January 2005. Immunohistochemistry was performed by using the polyclonal rabbit anti-beta III tubulin antibody (Covance, Princeton, NJ, USA). The value of 10% immunostained tumor cells was arbitrarily chosen as cut-off value to distinguish cases with high versus low beta III tubulin content. In the whole series, beta III tubulin immunoreaction was detectable in 66/98 cases (67.3%), and the percentage of positively stained cells ranged from 0 to 100% (median=10%). The percentages of cases with high beta III tubulin expression were shown not to be differently distributed according to clinico-pathological characteristics. There was no statistically significant difference in the distribution of cases with high beta III tubulin expression according to clinical and pathological response to treatment. During the follow-up period, recurrence and death of disease occurred in 15 and 13 cases, respectively. There was no difference in disease-free and overall survival in cases with high versus low beta III tubulin expression. The assessment of class III beta tubulin status seems of little usefulness in order to identify LACC patients with poor chance of response to concomitant radiochemotherapy and unfavorable prognosis.

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

PubMed

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

2015-10-01

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

Generation of fusion protein EGFRvIII-HBcAg and its anti-tumor effect in vivo

PubMed Central

Duan, Xiao-yi; Han, Dong-gang; Zhang, Ming-xin; Wang, Jian-sheng

2009-01-01

The epidermal growth factor receptor variant III (EGFRvIII) is the most common variation of EGFR. Because it shows a high frequency in several different types of tumor and has not been detected in normal tissues, it is an ideal target for tumor specific therapy. In this study, we prepared EGFRvIII-HBcAg fusion protein. After immunization with fusion protein, HBcAg or PBS, the titers of antibody in BALB/c mice immunized with fusion protein reached 2.75 × 105. Western blot analysis demonstrated that the fusion protein had specific antigenicity against anti-EGFRvIII antibody. Further observation showed fusion protein induced a high frequency of IFN-γ-secreting lymphocytes. CD4+T cells rather than CD8+T cells were associated with the production of IFN-γ. Using Renca-vIII(+) cell as specific stimulator, we observed remarkable cytotoxic activity in splenocytes from mice immunized with fusion protein. Mice were challenged with Renca-vIII(+) cells after five times immunization. In fusion protein group, three of ten mice failed to develop tumor and all survived at the end of the research. The weight of tumors in fusion protein were obviously lighter than that in other two groups (t = 4.73, P = 0.044;t = 6.89, P = 0.040). These findings demonstrated that EGFRvIII-HBcAg fusion protein triggered protective responses against tumor expressing EGFRvIII. PMID:19788747

Superconducting Prototype Cavities for the Spallation Neutron Source (SNS) Project

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

G. Ciovati; P. Kneisel; K. Davis

2002-06-01

The Spallation Neutron Source project includes a superconducting linac section in the energy range from 186 MeV to 1000 MeV operating at a frequency of 805 MHz at 2.1 K. For this energy range two types of cavities are needed with geometrical Beta-values of Beta=0.61 and Beta=0.81. An aggressive cavity prototyping program is being pursued at JLab, which calls for fabricating and testing of four Beta=0.61 cavities and two Beta=0.81 cavities. Both types consist of six cells made from high purity niobium and feature one HOM coupler of the TESLA type on each beam pipe and a port for amore » high power coaxial input coupler. Three of the four Beta=0.61 cavities will be used for a cryomodule test in early 2002. At this time, four medium beta cavities and one high beta cavity have been completed and tested at JLab. In addition, the three medium beta cavities for the prototype cryomodule have been equipped with the integrated Ti-Helium vessel, successfully retested and will be assembled into a cavity string. Results from the cryo-module test should be available by the time of the conference. The tests on the Beta=0.61 cavity and the Beta=0.81 cavity exceeded the design values for gradient and Q - value: E{sub acc} =10.1 MV/m and Q = 5 x 10{sup 9} at 2.1K for Beta=0.61 and E{sub acc} = 12.3 MV/m and Q=5 x 10{sup 9} at 2.1K for Beta = 0.81. The medium beta cavities reached gradients between E{sub acc} = 15 MV/m and 21 MV/m. This paper will describe the test results obtained with the various cavities, some aspects of the HOM damping at cryogenic temperatures, results from microphonics and Lorentz force detuning tests and the cavity string assembly at the time of this workshop.« less

Transportation fuel production by combination of LDPE thermal cracking and catalytic hydroreforming

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

Escola, J.M., E-mail: josemaria.escola.saez@urjc.es; Aguado, J.; Serrano, D.P.

2014-11-15

Highlights: • h-Beta samples were impregnated with Ni nitrate to achieve Ni contents of 1.5%, 4%, 7% and 10%. • Larger and more easily reducible metal particles were obtained on Ni 7%/h-Beta and Ni 10%/h-Beta. • Higher Ni contents increased the amount of gases at the expenses of diesel fractions. • Maximum selectivity to automotive fuels (∼81%) was obtained with Ni 7%/h-Beta. • Ni loading also enhanced olefins saturation up to Ni 7%/h-Beta. - Abstract: Fuel production from plastics is a promising way to reduce landfilling rates while obtaining valuable products. The usage of Ni-supported hierarchical Beta zeolite (h-Beta) formore » the hydroreforming of the oils coming from LDPE thermal cracking has proved to produce high selectivities to gasoline and diesel fuels (>80%). In the present work, the effect of the Ni loading on Ni/h-Beta is investigated in the hydroreforming of the oils form LDPE thermal cracking. h-Beta samples were impregnated with Ni nitrate, calcined and reduced in H{sub 2} up to 550 °C to achieve different Ni contents: 1.5%, 4%, 7% and 10%. Larger and more easily reducible metal particles were obtained on Ni 7%/h-Beta and Ni 10%/h-Beta. Hydroreforming tests were carried out in autoclave reactor at 310 °C, under 20 bar H{sub 2}, for 45 min. Ni content progressively increased the amount of gases at the expenses of diesel fractions, while gasoline remained approximately constant about 52–54%. Maximum selectivity to automotive fuels (∼81%) was obtained with Ni 7%/h-Beta. Ni loading also enhanced olefins saturation up to Ni 7%/h-Beta. High cetane indices (71–86) and octane numbers (89–91) were obtained over all the catalysts. Regarding the different studied Ni contents, Ni 7%/h-Beta constitutes a rather promising catalyst for obtaining high quality fuels from LDPE thermal cracking oils.« less

Greetings from the new Editor-in-Chief, Ronald Stambaugh Greetings from the new Editor-in-Chief, Ronald Stambaugh

NASA Astrophysics Data System (ADS)

Stambaugh, Ronald

2012-04-01

I am very pleased to join the outstanding leadership team for the journal Nuclear Fusion as Scientific Editor. The journal's high position in the field of fusion energy research derives in no small measure from the efforts of the IAEA team in Vienna, the production and marketing of IOP Publishing, the Board of Editors led by its chairman Mitsuru Kikuchi, the Associate Editor for Inertial Confinement Max Tabak and the outgoing Scientific Editor, Paul Thomas. During Paul's five year tenure submissions have grown by over 40%. The usage of the electronic journal has grown year by year with about 300 000 full text downloads of Nuclear Fusion articles in 2011, an impressive figure due in part to the launch of the full 50 year archive. High quality has been maintained while times for peer review and publishing have been reduced and the journal achieved some of the highest impact factors ever (as high as 4.27). The journal has contributed greatly to building the international scientific basis for fusion. I was privileged to serve from 2003 to 2010 as chairman of the Coordinating Committee for the International Tokamak Physics Activity (ITPA) which published in Nuclear Fusion the first ITER Physics Basis (1999) and its later update (2007). The scientific basis that has been developed to date for fusion has led to the construction of major facilities to demonstrate the production of power-plant relevant levels of fusion reactions. We look forward to the journal continuing to play a key role in the international effort toward fusion energy as these exciting major facilities and the various approaches to fusion continue to be developed. It is clear that Nuclear Fusion maintains its position in the field because of the perceived high quality of the submissions, the refereeing and the editorial processes, and the availability and utility of the online journal. The creation of the Nuclear Fusion Prize, led by the Board of Editors chairman Mitsuru Kikuchi, for the most outstanding paper published in the journal each year has furthered the submission and recognition of papers of the highest quality. The accomplishments of the journal's team over the last five years will be a tough act to follow but I look forward to working with this competent and dedicated group to continue the journal's high standards and ensure that Nuclear Fusion remains the journal of choice for authors and readers alike.

New precursors for direct synthesis of single phase Na- and K-{beta}{double_prime}-aluminas for use in AMTEC systems

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

Cook, R.L.; MacQueen, D.B.; Bader, K.E.

1997-12-31

Alkali Metal Thermoelectric Converters (AMTEC) are efficient direct energy conversion devices that depend on the use of highly conductive beta-alumina membranes for their operation. The key component of the AMTEC system is a highly conductive Na-{beta}{double_prime}-alumina solid electrolyte which conducts sodium ions from the high to low temperature zone, thereby generating electricity. AMTEC cells convert thermal to electrical energy by using heat to produce and maintain an alkali metal concentration gradient across the ion transporting BASE membrane. They have developed a method for producing pure phase Na-{beta}{double_prime}-alumina and K-{beta}{double_prime}-alumina powders from single phase nano-sized carboxylato-alumoxanes precursors. Sodium or potassium ionsmore » (the mobile ions) and either Mg{sup 2+} or Li{sup +} ions (which stabilize the {beta}{double_prime}-alumina structure) can be atomically dispersed into the carboxylato-alumoxane lattice at low (< 100 C) temperature. Calculation of the carboxylato-alumoxane precursors at 1,200--1,500 C produces pure phase {beta}{double_prime}-alumina powders.« less

Self-regulation of 70-kilodalton heat shock proteins in Saccharomyces cerevisiae.

PubMed Central

Stone, D E; Craig, E A

1990-01-01

To determine whether the 70-kilodalton heat shock proteins of Saccharomyces cerevisiae play a role in regulating their own synthesis, we studied the effect of overexpressing the SSA1 protein on the activity of the SSA1 5'-regulatory region. The constitutive level of Ssa1p was increased by fusing the SSA1 structural gene to the GAL1 promoter. A reporter vector consisting of an SSA1-lacZ translational fusion was used to assess SSA1 promoter activity. In a strain producing approximately 10-fold the normal heat shock level of Ssa1p, induction of beta-galactosidase activity by heat shock was almost entirely blocked. Expression of a transcriptional fusion vector in which the CYC1 upstream activating sequence of a CYC1-lacZ chimera was replaced by a sequence containing a heat shock upstream activating sequence (heat shock element 2) from the 5'-regulatory region of SSA1 was inhibited by excess Ssa1p. The repression of an SSA1 upstream activating sequence by the SSA1 protein indicates that SSA1 self-regulation is at least partially mediated at the transcriptional level. The expression of another transcriptional fusion vector, containing heat shock element 2 and a lesser amount of flanking sequence, is not inhibited when Ssa1p is overexpressed. This suggests the existence of an element, proximal to or overlapping heat shock element 2, that confers sensitivity to the SSA1 protein. Images PMID:2181281

Research on HDR image fusion algorithm based on Laplace pyramid weight transform with extreme low-light CMOS

NASA Astrophysics Data System (ADS)

Guan, Wen; Li, Li; Jin, Weiqi; Qiu, Su; Zou, Yan

2015-10-01

Extreme-Low-Light CMOS has been widely applied in the field of night-vision as a new type of solid image sensor. But if the illumination in the scene has drastic changes or the illumination is too strong, Extreme-Low-Light CMOS can't both clearly present the high-light scene and low-light region. According to the partial saturation problem in the field of night-vision, a HDR image fusion algorithm based on the Laplace Pyramid was researched. The overall gray value and the contrast of the low light image is very low. We choose the fusion strategy based on regional average gradient for the top layer of the long exposure image and short exposure image, which has rich brightness and textural features. The remained layers which represent the edge feature information of the target are based on the fusion strategy based on regional energy. In the process of source image reconstruction with Laplacian pyramid image, we compare the fusion results with four kinds of basal images. The algorithm is tested using Matlab and compared with the different fusion strategies. We use information entropy, average gradient and standard deviation these three objective evaluation parameters for the further analysis of the fusion result. Different low illumination environment experiments show that the algorithm in this paper can rapidly get wide dynamic range while keeping high entropy. Through the verification of this algorithm features, there is a further application prospect of the optimized algorithm. Keywords: high dynamic range imaging, image fusion, multi-exposure image, weight coefficient, information fusion, Laplacian pyramid transform.

A simple approach for assessing equilibrated Kt/V beta 2-M on a routine basis.

PubMed

Casino, Francesco G; Pedrini, Luciano A; Santoro, Antonio; Mandolfo, Salvatore; David, Salvatore; De Cristofaro, Vincenzo; Teatini, Ugo; Lomonte, Carlo; Lopez, Teodoro

2010-09-01

Large observational studies have shown a reduction in morbidity and mortality in patients on high-flux haemodialysis (HD) or convective techniques, compared with low-flux HD. An index to evaluate treatment efficiency in middle molecule (MM) removal would be recommended. Since beta-2-microglobulin (beta2-M) is a recognized MM marker, we evaluated an easy approach for Kt/V(beta2-M) assessment on a routine basis, avoiding other complex methods. An equation that estimates single-pool (sp) Kt/V(beta2-M) was derived from Leypoldt's formula, which calculates beta2-M dialyser clearance (K(beta2-M)) from the post/pre-dialysis beta2-M concentration (C(t)/C(0)) ratio and the weight loss/end-dialysis weight (Delta W/W) ratio. Our equation, spKt/V(beta2-M) = 6.12 Delta W/W [1 - ln(C(t)/C(0))/ln(1 + 6.12 Delta W/W)], was derived by assuming urea distribution volume (V(u)) as 49% of W and beta2-M volume (V(beta2-M)) as V(u)/3, in agreement with the average patient values in the HEMO Study. The spKt/V(beta2-M) values calculated with our equation (F) in 129 patients on 407 sessions of different high-flux treatments were compared with those calculated with the method applied in the HEMO Study (HM). Equilibrated beta2-M concentration (C(eq)) of the same sessions was also estimated with the equation for C(eq) by Tattersall, and equilibrated Kt/V (eKt/V(beta2-M)) was calculated by introducing Tattersall's equation into our simplified spKt/V(beta2-M) formula. Mean results of our spKt/V(beta2-M) equation (F) were very close to those of the HM method (1.48 +/- 0.38 vs 1.47 +/- 0.37). The difference was less than +/-0.1 in 95% of cases. A mean end-session beta2-M rebound of 44 +/- 14% was predicted, which caused a mean reduction in actual Kt/V(beta2-M) of ~27% (eKt/V(beta2-M) = 1.08 +/- 0.26). The method proposed to estimate spKt/V(beta2-M) and eKt/V(beta2-M) could become a simple tool to monitor the efficiency of high-flux HD and convective techniques and to evaluate the adequacy of treatments in terms of MM removal. Moreover, it might help to better understand the effects of different dialysis schedules. Validation on a larger dialysis population is required.

Circulating form of beta-2-microglobulin in dialysis patients.

PubMed

Gagnon, R F; Somerville, P; Thomson, D M

1988-01-01

The circulating profile of beta-2-microglobulin (beta 2M) was determined in 8 end-stage renal disease patients on long-term dialysis (6 on hemodialysis, 2 on CAPD) by measuring beta 2M in different fraction after molecular sieve separation of their sera. Four patients had carpal tunnel syndrome with demonstrated amyloid in excised wrist tissues of which 2 were positive for beta 2M. In all patients despite very high blood levels (34.3-63.1 mg/l), beta 2M eluted exclusively as a single peak in the molecular weight region of about 12,000 daltons on a calibrated Sephacryl S-200 column. Recoveries from within the peak accounted for 96% of the applied beta 2M serum concentrations. These results were confirmed by molecular sieve separation of the enriched beta 2M-containing fractions by high-pressure liquid chromatography. We conclude that immunoreactive beta 2M in dialysis patients circulates as an intact monomer without evidence for the formation of aggregates or fragments. The pathogenesis of tissue deposition of this low-molecular-weight protein and its polymerisation to form a specific amyloid remains to be defined.

The activity of hydrolases of larval stages of Anisakis simplex (Nematoda).

PubMed

Lopieńska-Biernat, Elzbieta; Zółtowska, Krystyna; Rokicki, Jerzy

2004-01-01

Activity of hydrolases during the third and fourth larval stage of Anisakis simplex was identified by applying the API ZYM test method. In A. simplex larvae the activity of phosphatases was high, particularly that of acid phosphatase (40 nmol/mg(-1)). Among esterases lack of activity of lipase (C14) is worth noticing while the activity of esterases (C4) and (C8) was high. The activity of those later two enzymes was higher in L3 larvae than in L4 larvae. The highest activity in the subclass of glucosidases was recorded for beta-fucosidase and N-acetyl-beta-glucosaminidase. A higher activity in L3 larvae than in L4 larvae was recorded for: beta-glucuronidase and N-acetyl-beta-glucosaminidase (2-fold) and beta-fucosidase (3-fold). Differently the activity of beta-galactosidase and beta-glucosidase was higher in L4 larvae than in L3 larvae. The tests did not show activity of alpha-galactosidase, beta-glucosidase and alpha-mannosidase on both larval forms.

The rate of transient beta frequency events predicts behavior across tasks and species

PubMed Central

Law, Robert; Tsutsui, Shawn; Moore, Christopher I; Jones, Stephanie R

2017-01-01

Beta oscillations (15-29Hz) are among the most prominent signatures of brain activity. Beta power is predictive of healthy and abnormal behaviors, including perception, attention and motor action. In non-averaged signals, beta can emerge as transient high-power 'events'. As such, functionally relevant differences in averaged power across time and trials can reflect changes in event number, power, duration, and/or frequency span. We show that functionally relevant differences in averaged beta power in primary somatosensory neocortex reflect a difference in the number of high-power beta events per trial, i.e. event rate. Further, beta events occurring close to the stimulus were more likely to impair perception. These results are consistent across detection and attention tasks in human magnetoencephalography, and in local field potentials from mice performing a detection task. These results imply that an increased propensity of beta events predicts the failure to effectively transmit information through specific neocortical representations. PMID:29106374

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.

High-Gain High-Field Fusion Plasma

PubMed Central

Li, Ge

2015-01-01

A Faraday wheel (FW)—an electric generator of constant electrical polarity that produces huge currents—could be implemented in an existing tokamak to study high-gain high-field (HGHF) fusion plasma, such as the Experimental Advanced Superconducting Tokamak (EAST). HGHF plasma can be realized in EAST by updating its pulsed-power system to compress plasma in two steps by induction fields; high gains of the Lawson trinity parameter and fusion power are both predicted by formulating the HGHF plasma. Both gain rates are faster than the decrease rate of the plasma volume. The formulation is checked by earlier ATC tests. Good agreement between theory and tests indicates that scaling to over 10 T at EAST may be possible by two-step compressions with a compression ratio of the minor radius of up to 3. These results point to a quick new path of fusion plasma study, i.e., simulating the Sun by EAST. PMID:26507314

Putting Beta-Diversity on the Map: Broad-Scale Congruence and Coincidence in the Extremes

PubMed Central

McKnight, Meghan W; White, Peter S; McDonald, Robert I; Lamoreux, John F; Sechrest, Wes; Ridgely, Robert S; Stuart, Simon N

2007-01-01

Beta-diversity, the change in species composition between places, is a critical but poorly understood component of biological diversity. Patterns of beta-diversity provide information central to many ecological and evolutionary questions, as well as to conservation planning. Yet beta-diversity is rarely studied across large extents, and the degree of similarity of patterns among taxa at such scales remains untested. To our knowledge, this is the first broad-scale analysis of cross-taxon congruence in beta-diversity, and introduces a new method to map beta-diversity continuously across regions. Congruence between amphibian, bird, and mammal beta-diversity in the Western Hemisphere varies with both geographic location and spatial extent. We demonstrate that areas of high beta-diversity for the three taxa largely coincide, but areas of low beta-diversity exhibit little overlap. These findings suggest that similar processes lead to high levels of differentiation in amphibian, bird, and mammal assemblages, while the ecological and biogeographic factors influencing homogeneity in vertebrate assemblages vary. Knowledge of beta-diversity congruence can help formulate hypotheses about the mechanisms governing regional diversity patterns and should inform conservation, especially as threat from global climate change increases. PMID:17927449

Grape seed procyanidin extract modulates proliferation and apoptosis of pancreatic beta-cells.

PubMed

Cedó, Lídia; Castell-Auví, Anna; Pallarès, Victor; Blay, Mayte; Ardévol, Anna; Arola, Lluís; Pinent, Montserrat

2013-05-01

Grape seed procyanidin extract (GSPE) modulates glucose homeostasis and insulinemia in several animal models. Under pathological conditions, insulin levels are dependent on pancreatic beta-cell functionality, as well as on the beta-cell mass expansion or apoptosis in the pancreas. In this study, we analysed the effects of GSPE on modulating apoptosis and proliferation in beta-cells. We tested the effects of GSPE in the INS-1E pancreatic beta-cell line, either under basal or altered conditions with high glucose, insulin or palmitate levels. GSPE enhanced the pro-apoptotic effect of high glucose and showed clear antiproliferative effects under high glucose, insulin and palmitate conditions. These antiproliferative effects are likely due to high molecular weight compounds contained in the extract. GSPE also modulated pro- and anti-apoptotic markers in the pancreas of rats fed a cafeteria diet, with the effect depending on the dose of GSPE and duration of treatment. Thus, GSPE is able to modulate apoptosis and proliferation of beta-cells under altered, but not basal, conditions. Copyright © 2012 Elsevier Ltd. All rights reserved.

The Beta Pictoris Phenomenon in A-Shell Stars: Detection of Accreting Gas

NASA Technical Reports Server (NTRS)

Grady, C. A.; Perez, Mario R.; Talavera, A.; McCollum, B.; Rawley, L. A.; England, M. N.; Schlegel, M.

1996-01-01

We present the results of an expanded survey of A-shell stars using IUE high-dispersion spectra and find accreting, circumstellar gas in the line of sight to nine stars, in addition to the previously identified beta Pic, HR 10, and 131 Tau, which can be followed to between +70 and 100 km/s relative to the star. Two of the program stars, HD 88195 and HD 148283, show variable high-velocity gas. Given the small number of IUE spectra for our program stars, detection of high-velocity, accreting gas in 2/3 of the A-shell stars sampled indicates that accretion is an intrinsic part of the A-shell phenomenon and that beta Pic is not unique among main-sequence A stars in exhibiting such activity. Our program stars, as a group, have smaller column densities of high-velocity gas and smaller near-IR excesses compared with beta Pic. These features are consistent with greater central clearing of a remnant debris disk, compared with beta Pic, and suggest that the majority of field A-shell stars are older than beta Pic.

Anodic Aluminum Oxide Membrane-Assisted Fabrication of beta-In(2)S(3) Nanowires.

PubMed

Shi, Jen-Bin; Chen, Chih-Jung; Lin, Ya-Ting; Hsu, Wen-Chia; Chen, Yu-Cheng; Wu, Po-Feng

2009-06-06

In this study, beta-In(2)S(3) nanowires were first synthesized by sulfurizing the pure Indium (In) nanowires in an AAO membrane. As FE-SEM results, beta-In(2)S(3) nanowires are highly ordered, arranged tightly corresponding to the high porosity of the AAO membrane used. The diameter of the beta-In(2)S(3) nanowires is about 60 nm with the length of about 6-8 mum. Moreover, the aspect ratio of beta-In(2)S(3) nanowires is up to 117. An EDS analysis revealed the beta-In(2)S(3) nanowires with an atomic ratio of nearly S/In = 1.5. X-ray diffraction and corresponding selected area electron diffraction patterns demonstrated that the beta-In(2)S(3) nanowire is tetragonal polycrystalline. The direct band gap energy (E(g)) is 2.40 eV from the optical measurement, and it is reasonable with literature.

Development of next generation tempered and ODS reduced activation ferritic/martensitic steels for fusion energy applications

DOE PAGES

Zinkle, S. J.; Boutard, J. L.; Hoelzer, D. T.; ...

2017-06-09

Reduced activation ferritic/martensitic steels are currently the most technologically mature option for the structural material of proposed fusion energy reactors. Advanced next-generation higher performance steels offer the opportunity for improvements in fusion reactor operational lifetime and reliability, superior neutron radiation damage resistance, higher thermodynamic efficiency, and reduced construction costs. The two main strategies for developing improved steels for fusion energy applications are based on (1) an evolutionary pathway using computational thermodynamics modelling and modified thermomechanical treatments (TMT) to produce higher performance reduced activation ferritic/martensitic (RAFM) steels and (2) a higher risk, potentially higher payoff approach based on powder metallurgy techniquesmore » to produce very high strength oxide dispersion strengthened (ODS) steels capable of operation to very high temperatures and with potentially very high resistance to fusion neutron-induced property degradation. The current development status of these next-generation high performance steels is summarized, and research and development challenges for the successful development of these materials are outlined. In conclusion, material properties including temperature-dependent uniaxial yield strengths, tensile elongations, high-temperature thermal creep, Charpy impact ductile to brittle transient temperature (DBTT) and fracture toughness behaviour, and neutron irradiation-induced low-temperature hardening and embrittlement and intermediate-temperature volumetric void swelling (including effects associated with fusion-relevant helium and hydrogen generation) are described for research heats of the new steels.« less

Development of next generation tempered and ODS reduced activation ferritic/martensitic steels for fusion energy applications

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

Zinkle, S. J.; Boutard, J. L.; Hoelzer, D. T.

Reduced activation ferritic/martensitic steels are currently the most technologically mature option for the structural material of proposed fusion energy reactors. Advanced next-generation higher performance steels offer the opportunity for improvements in fusion reactor operational lifetime and reliability, superior neutron radiation damage resistance, higher thermodynamic efficiency, and reduced construction costs. The two main strategies for developing improved steels for fusion energy applications are based on (1) an evolutionary pathway using computational thermodynamics modelling and modified thermomechanical treatments (TMT) to produce higher performance reduced activation ferritic/martensitic (RAFM) steels and (2) a higher risk, potentially higher payoff approach based on powder metallurgy techniquesmore » to produce very high strength oxide dispersion strengthened (ODS) steels capable of operation to very high temperatures and with potentially very high resistance to fusion neutron-induced property degradation. The current development status of these next-generation high performance steels is summarized, and research and development challenges for the successful development of these materials are outlined. In conclusion, material properties including temperature-dependent uniaxial yield strengths, tensile elongations, high-temperature thermal creep, Charpy impact ductile to brittle transient temperature (DBTT) and fracture toughness behaviour, and neutron irradiation-induced low-temperature hardening and embrittlement and intermediate-temperature volumetric void swelling (including effects associated with fusion-relevant helium and hydrogen generation) are described for research heats of the new steels.« less

Development of next generation tempered and ODS reduced activation ferritic/martensitic steels for fusion energy applications

NASA Astrophysics Data System (ADS)

Zinkle, S. J.; Boutard, J. L.; Hoelzer, D. T.; Kimura, A.; Lindau, R.; Odette, G. R.; Rieth, M.; Tan, L.; Tanigawa, H.

2017-09-01

Reduced activation ferritic/martensitic steels are currently the most technologically mature option for the structural material of proposed fusion energy reactors. Advanced next-generation higher performance steels offer the opportunity for improvements in fusion reactor operational lifetime and reliability, superior neutron radiation damage resistance, higher thermodynamic efficiency, and reduced construction costs. The two main strategies for developing improved steels for fusion energy applications are based on (1) an evolutionary pathway using computational thermodynamics modelling and modified thermomechanical treatments (TMT) to produce higher performance reduced activation ferritic/martensitic (RAFM) steels and (2) a higher risk, potentially higher payoff approach based on powder metallurgy techniques to produce very high strength oxide dispersion strengthened (ODS) steels capable of operation to very high temperatures and with potentially very high resistance to fusion neutron-induced property degradation. The current development status of these next-generation high performance steels is summarized, and research and development challenges for the successful development of these materials are outlined. Material properties including temperature-dependent uniaxial yield strengths, tensile elongations, high-temperature thermal creep, Charpy impact ductile to brittle transient temperature (DBTT) and fracture toughness behaviour, and neutron irradiation-induced low-temperature hardening and embrittlement and intermediate-temperature volumetric void swelling (including effects associated with fusion-relevant helium and hydrogen generation) are described for research heats of the new steels.

beta-Endorphin-induced analgesia is inhibited by synthetic analogs of beta-endorphin.

PubMed Central

Nicolas, P; Hammonds, R G; Li, C H

1984-01-01

Competitive antagonism of human beta-endorphin (beta h-EP)-induced analgesia by synthetic beta h-EP analogs with high in vitro opiate receptor binding to in vivo analgesic potency ratio has been demonstrated. A parallel shift of the dose-response curve for analgesia to the right was observed when either beta h-EP or [ Trp27 ] -beta h-EP was coinjected with various doses of [Gln8, Gly31 ]-beta h-EP-Gly-Gly-NH2, [Arg9,19,24,28,29]-beta h-EP, or [ Cys11 ,26, Phe27 , Gly31 ]-beta h-EP. It was estimated that the most potent antagonist, [Gln8, Gly31 ]-beta h-EP-Gly-NH2, is at least 200 times more potent than naloxone. PMID:6328494

High Temperature Stability of Potassium Beta Alumina

NASA Technical Reports Server (NTRS)

Williams, R. M.; Kisor, A.; Ryan, M. A.

1996-01-01

None. From Objectives section: Evaluate the stability of potassium beta alumina under potassium AMTEC operating conditions. Evaluate the stability regime in which potassium beta alumina can be fabricated.

Scalloped Hibachi and Vacuum-Pressure Foil for Electra: Electron Beam Pumped KrF Laser

DTIC Science & Technology

2007-06-01

confinement fusion energy (IFE) applications [1-8]. The foils are a critical part of this durability and efficiency. The electron beam, generated in a high...and A. W. Maschke, “Design descriptions of the Prometheus- L and -H inertial fusion energy drivers,” Fusion Engineering and Design, vol. 25, pp...inertial fusion energy ,” Fusion Engineering and Design, vol. 44, pp. 371-375, March 1999. [4] I. Okuda, e. Takahashi, and Y. Owadano, “A

Activation of Beta-Catenin Signaling in Androgen Receptor–Negative Prostate Cancer Cells

PubMed Central

Wan, Xinhai; Liu, Jie; Lu, Jing-Fang; Tzelepi, Vassiliki; Yang, Jun; Starbuck, Michael W.; Diao, Lixia; Wang, Jing; Efstathiou, Eleni; Vazquez, Elba S.; Troncoso, Patricia; Maity, Sankar N.; Navone, Nora M.

2012-01-01

Purpose To study Wnt/beta-catenin in castrate-resistant prostate cancer (CRPC) and understand its function independently of the beta-catenin–androgen receptor (AR) interaction. Experimental Design We performed beta-catenin immunocytochemical analysis, evaluated TOP-flash reporter activity (a reporter of beta-catenin–mediated transcription), and sequenced the beta-catenin gene in MDA PCa 118a, MDA PCa 118b, MDA PCa 2b, and PC-3 prostate cancer (PCa) cells. We knocked down beta-catenin in AR-negative MDA PCa 118b cells and performed comparative gene-array analysis. We also immunohistochemically analyzed beta-catenin and AR in 27 bone metastases of human CRPCs. Results Beta-catenin nuclear accumulation and TOP-flash reporter activity were high in MDA PCa 118b but not in MDA PCa 2b or PC-3 cells. MDA PCa 118a and 118b cells carry a mutated beta-catenin at codon 32 (D32G). Ten genes were expressed differently (false discovery rate, 0.05) in MDA PCa 118b cells with downregulated beta-catenin. One such gene, hyaluronan synthase 2 (HAS2), synthesizes hyaluronan, a core component of the extracellular matrix. We confirmed HAS2 upregulation in PC-3 cells transfected with D32G-mutant beta-catenin. Finally, we found nuclear localization of beta-catenin in 10 of 27 human tissue specimens; this localization was inversely associated with AR expression (P = 0.056, Fisher’s exact test), suggesting that reduced AR expression enables Wnt/beta-catenin signaling. Conclusion We identified a previously unknown downstream target of beta-catenin, HAS2, in PCa, and found that high beta-catenin nuclear localization and low or no AR expression may define a subpopulation of men with bone-metastatic PCa. These findings may guide physicians in managing these patients. PMID:22298898

Strong expression of the neuronal transcription factor FOXP2 is linked to an increased risk of early PSA recurrence in ERG fusion-negative cancers.

PubMed

Stumm, Laura; Burkhardt, Lia; Steurer, Stefan; Simon, Ronald; Adam, Meike; Becker, Andreas; Sauter, Guido; Minner, Sarah; Schlomm, Thorsten; Sirma, Hüseyin; Michl, Uwe

2013-07-01

Transcription factors of the forkhead box P (FOXP1-4) family have been implicated in various human cancer types before. The relevance and role of neuronal transcription factor FOXP2 in prostate cancer is unknown. A tissue microarray containing samples from more than 11 000 prostate cancers from radical prostatectomy specimens with clinical follow-up data was analysed for FOXP2 expression by immunohistochemistry. FOXP2 data were also compared with pre-existing ERG fusion (by fluorescence in situ hybridisation and immunohistochemistry) and cell proliferation (Ki67 labelling index) data. There was a moderate to strong FOXP2 protein expression in basal and secretory cells of normal prostatic glands. As compared with normal cells, FOXP2 expression was lost or reduced in 25% of cancers. Strong FOXP2 expression was linked to advanced tumour stage, high Gleason score, presence of lymph node metastases and early tumour recurrence (p<0.0001; each) in ERG fusion-negative, but not in ERG fusion-positive cancers. High FOXP2 expression was linked to high Ki67 labelling index (p<0.0001) in all cancers irrespective of ERG fusion status. These data demonstrate that similar high FOXP2 protein levels as in normal prostate epithelium exert a 'paradoxical' oncogenic role in 'non fusion-type' prostate cancer. It may be speculated that interaction of FOXP2 with members of pathways that are specifically activated in 'non fusion-type' cancers may be responsible for this phenomenon.

Sm14 of Schistosoma mansoni in Fusion with Tetanus Toxin Fragment C Induces Immunoprotection against Tetanus and Schistosomiasis in Mice

PubMed Central

Abreu, Patrícia A. E.; Miyasato, Patrícia A.; Vilar, Mônica M.; Dias, Waldely O.; Ho, Paulo L.; Tendler, Míriam; Nascimento, Ana L. T. O.

2004-01-01

We have constructed vectors that permit the expression in Escherichia coli of Schistosoma mansoni fatty acid-binding protein 14 (Sm14) in fusion with the nontoxic, but highly immunogenic, tetanus toxin fragment C (TTFC). The recombinant six-His-tagged proteins were purified by nickel affinity chromatography and used in immunization and challenge assays. Animals inoculated with TTFC in fusion with or coadministered with Sm14 showed high levels of tetanus toxin antibodies, while animals inoculated with Sm14 in fusion with or coadministered with TTFC showed high levels of Sm14 antibodies. In both cases, there were no changes in the type of immune response (Th2) obtained with the fusion proteins compared to those obtained with the nonfused proteins. Mice immunized with the recombinant proteins (TTFC in fusion with or coadministered with Sm14) survived the challenge with tetanus toxin and did not show any symptoms of the disease. Control animals inoculated with either phosphate-buffered saline (PBS) or Sm14 died with severe symptoms of tetanus after 24 h. Mice immunized with the recombinant proteins (Sm14 in fusion with or coadministered with TTFC) showed a 50% reduction in worm burden when they were challenged with S. mansoni cercariae, while control animals inoculated with either PBS or TTFC were not protected. The results show that the expression of other antigens in fusion at the carboxy terminus of TTFC is feasible for the development of a multivalent recombinant vaccine. PMID:15385496

Laser or charged-particle-beam fusion reactor with direct electric generation by magnetic flux compression

DOEpatents

Lasche, George P.

1988-01-01

A high-power-density laser or charged-particle-beam fusion reactor system maximizes the directed kinetic energy imparted to a large mass of liquid lithium by a centrally located fusion target. A fusion target is embedded in a large mass of lithium, of sufficient radius to act as a tritium breeding blanket, and provided with ports for the access of beam energy to implode the target. The directed kinetic energy is converted directly to electricity with high efficiency by work done against a pulsed magnetic field applied exterior to the lithium. Because the system maximizes the blanket thickness per unit volume of lithium, neutron-induced radioactivities in the reaction chamber wall are several orders of magnitude less than is typical of other fusion reactor systems.

Laser or charged-particle-beam fusion reactor with direct electric generation by magnetic flux compression

DOEpatents

Lasche, G.P.

1987-02-20

A high-power-density-laser or charged-particle-beam fusion reactor system maximizes the directed kinetic energy imparted to a large mass of liquid lithium by a centrally located fusion target. A fusion target is embedded in a large mass of lithium, of sufficient radius to act as a tritium breeding blanket, and provided with ports for the access of beam energy to implode the target. The directed kinetic energy is converted directly to electricity with high efficiency by work done against a pulsed magnetic field applied exterior to the lithium. Because the system maximizes the blanket thickness per unit volume of lithium, neutron-induced radioactivities in the reaction chamber wall are several orders of magnitude less than is typical of other fusion reactor systems. 25 figs.

High-gain magnetized inertial fusion.

PubMed

Slutz, Stephen A; Vesey, Roger A

2012-01-13

Magnetized inertial fusion (MIF) could substantially ease the difficulty of reaching plasma conditions required for significant fusion yields, but it has been widely accepted that the gain is not sufficient for fusion energy. Numerical simulations are presented showing that high-gain MIF is possible in cylindrical liner implosions based on the MagLIF concept [S. A. Slutz et al Phys. Plasmas 17, 056303 (2010)] with the addition of a cryogenic layer of deuterium-tritium (DT). These simulations show that a burn wave propagates radially from the magnetized hot spot into the surrounding much denser cold DT given sufficient hot-spot areal density. For a drive current of 60 MA the simulated gain exceeds 100, which is more than adequate for fusion energy applications. The simulated gain exceeds 1000 for a drive current of 70 MA.

Tissue strands as "bioink" for scale-up organ printing.

PubMed

Yu, Yin; Ozbolat, Ibrahim T

2014-01-01

Organ printing, takes tissue spheroids as building blocks together with additive manufacturing technique to engineer tissue or organ replacement parts. Although a wide array of cell aggregation techniques has been investigated, and gained noticeable success, the application of tissue spheroids for scale-up tissue fabrication is still worth investigation. In this paper, we introduce a new micro-fabrication technique to create tissue strands at the scale of 500-700μm as a "bioink" for future robotic tissue printing. Printable alginate micro-conduits are used as semi-permeable capsules for tissue strand fabrication. Mouse insulinoma beta TC3 cell tissue strands were formed upon 4 days post fabrication with reasonable mechanical strength, high cell viability close to 90%, and tissue specific markers expression. Fusion was readily observed between strands when placing them together as early as 24h. Also, tissue strands were deposited with human umbilical vein smooth muscle cells (HUVSMCs) vascular conduits together to fabricated miniature pancreatic tissue analog. Our study provided a novel technique using tissue strands as "bioink" for scale-up bioprinting of tissues or organs.

Laser Beat-Wave Magnetization of a Dense Plasma

NASA Astrophysics Data System (ADS)

Yates, Kevin; Hsu, Scott; Montgomery, David; Dunn, John; Langendorf, Samuel; Pollock, Bradley; Johnson, Timothy; Welch, Dale; Thoma, Carsten

2017-10-01

We present results from the first of a series of experiments to demonstrate and characterize laser beat-wave magnetization of a dense plasma, motivated by the desire to create high-beta targets with standoff for magneto-inertial fusion. The experiments are being conducted at the Jupiter Laser Facility (JLF) at LLNL. The experiment uses the JLF Janus 1 ω (1053 nm) beam and a standalone Nd:YAG (1064 nm) to drive the beat wave, and the Janus 2 ω (526.5 nm) beam to ionize/heat a gas-jet target as well as to provide Thomson-scattering (TS) measurements of the target density/temperature and scattered light from the beat wave. Streaked TS data captured electron-plasma-wave and ion-acoustic-wave features utilizing either nitrogen or helium gas jets. Effects of initial gas density as well as laser intensity on target have been measured, with electron densities ranging from 1E18 to 1E19 cm-3 with temperatures of tens to hundreds of eV, near the desired range for optimal field generation. LSP simulations were run to aid experimental design and data interpretation. LANL LDRD Program.

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

NASA Astrophysics Data System (ADS)

Dean, Stephen O.

1988-09-01

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

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

PubMed

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

2018-01-29

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

Discovering and understanding oncogenic gene fusions through data intensive computational approaches

PubMed Central

Latysheva, Natasha S.; Babu, M. Madan

2016-01-01

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

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

NASA Technical Reports Server (NTRS)

Dean, Stephen O.

1988-01-01

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

Superconducting Prototype Cavities for the Spallation Neutron Source (SNS) Project

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

G. Ciovati, P. Kneisel , J. Brawley, R. Bundy, I. Campisi, K. Davis; K. Macha; D. Machie

2001-09-01

The Spallation Neutron Source project includes a superconducting linac section in the energy range from 192 MeV to 1000 MeV, operating at a frequency of 805 MHz at 2.1 K. For this energy range two types of cavities are needed with geometrical beta - values of beta= 0.61 and beta= 0.81. An aggressive cavity prototyping program is being pursued at Jlab, which calls for fabricating and testing of four beta= 0.61 cavities and two beta= 0.81 cavities. Both types consist of six cells made from high purity niobium and feature one HOM coupler on each beam pipe and a portmore » for a high power coaxial input coupler. Three of the four beta= 0.61 cavities will be used for a cryomodule test in early 2002. At this time four medium beta cavities and one high beta cavity have been completed at JLab. The first tests on the beta=0.61 cavity and the beta= 0.81 exceeded the design values for gradient and Q - value: E{sub acc} = 1 0.3 MV/m and Q = 5 x 10{sup 9} at 2.1K for beta= 0.61 and E{sub acc} = 12.3 MV/m and Q = 5 x 10{sup 9} at 2.1K for beta= 0.81. One of the medium beta cavities has been equipped with an integrated helium vessel and measurements of the static and dynamic Lorentz force detuning will be done and compared to the ''bare'' cavities. In addition two single cell cavities have been fabricated, equipped with welded-on HOM couplers. They are being used to evaluate the HOM couplers with respect to multipacting, fundamental mode rejection and HOM damping as far as possible in a single cell. This paper will describe the cavity design with respect to electrical and mechanical features, the fabrication efforts and the results obtained with the different cavities existing at the time of this workshop.« less

Expression and putative function of fibronectin and its receptor (integrin alpha(5)beta(1)) in male and female gametes during bovine fertilization in vitro.

PubMed

Thys, Mirjan; Nauwynck, Hans; Maes, Dominiek; Hoogewijs, Maarten; Vercauteren, Dries; Rijsselaere, Tom; Favoreel, Herman; Van Soom, Ann

2009-09-01

Fibronectin (Fn) is a 440 kDa glycoprotein assumed to participate in sperm-egg interaction in human. Recently, it has been demonstrated that Fn--when present during bovine IVF--strongly inhibits sperm penetration. The present study was conducted firstly to evaluate the expression of Fn and its integrin receptor (alpha(5)beta(1)) on male and female bovine gametes using indirect immunofluorescence and secondly, to determine the function of Fn during bovine IVF. Endogenous Fn was detected underneath the zona pellucida (ZP) and integrin alpha(5) on the oolemma of cumulus-denuded oocytes. Bovine spermatozoa displayed integrin alpha(5) at their equatorial segment after acrosome reaction. We established that the main inhibitory effect of exogenously supplemented Fn was located at the sperm-oolemma binding, with a (concurrent) effect on fusion, and this can probably be attributed to the binding of Fn to spermatozoa at the equatorial segment, as shown by means of Alexa Fluor 488-conjugated Fn. Combining these results, the inhibitory effect of exogenously supplemented Fn seemed to be exerted on the male gamete by binding to the exposed integrin alpha(5)beta(1) receptor after acrosome reaction. The presence of endogenous Fn underneath the ZP together with integrin alpha(5) expression on oolemma and acrosome-reacted (AR) sperm cell surface suggests a 'velcro' interaction between the endogenous Fn ligand and corresponding receptors on both (AR) sperm cell and oolemma, initiating sperm-egg binding.

Synthesis of a beta-estradiol-biotin chimera that potently heterodimerizes estrogen receptor and streptavidin proteins in a yeast three-hybrid system.

PubMed

Hussey, Stephen L; Muddana, Smita S; Peterson, Blake R

2003-04-02

Small molecules that dimerize proteins in living cells provide powerful probes of biological processes and have potential as tools for the identification of protein targets of natural products. We synthesized 7-alpha-substituted derivatives of beta-estradiol tethered to the natural product biotin to regulate heterodimerization of estrogen receptor (ER) and streptavidin (SA) proteins expressed as components of a yeast three-hybrid system. Addition of an estradiol-biotin chimera bearing a 19-atom linker to yeast expressing DNA-bound ER-alpha or ER-beta LexA fusion proteins and wild-type SA protein fused to the B42 activation domain activated reporter gene expression by as much as 450-fold in vivo (10 muM ligand). Comparative analysis of lower affinity Y43A (biotin Kd approximately 100 pM) and W120A (biotin Kd approximately 100 nM) mutants of SA indicated that moderate affinity interactions can be readily detected with this system. Comparison of a 7-alpha-substituted estradiol-biotin chimera with a structurally similar dexamethasone-biotin chimera revealed that yeast expressing ER proteins can detect cognate ligands with up to 5-fold greater potency and 70-fold higher activity than yeast expressing analogous glucocorticoid receptor (GR) proteins. This approach may facilitate the identification of protein targets of biologically active small molecules screened against genetically encoded libraries of proteins expressed in yeast three-hybrid systems.

Selective, high-energy beta scintillation sensor for real-time, in situ characterization of uranium-238 and strontium-90

NASA Astrophysics Data System (ADS)

Schilk, A. J.; Abel, K. H.; Brown, D. P.; Thompson, R. C.; Knopf, M. A.; Hubbard, C. W.

1994-04-01

A novel scintillating-fiber sensor for detecting high-energy beta particles has been designed and built at the Pacific Northwest Laboratory to characterize U-238 and Sr-90 in surface soils. High-energy betas generate unique signals as they pass through multiple layers of scintillating fibers that make up the active region of the detector. Lower-energy beta particles, gamma rays, and cosmic-ray-generated particles comprise the majority of the background interferences. The resulting signals produced by these latter phenomena are effectively discriminated against due to the combination of the sensor's multilayer configuration and its interlayer coincidence/anticoincidence circuitry.

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

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

PubMed Central

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

2012-01-01

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

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

PubMed

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

2012-12-15

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

Magnetized Target Fusion Driven by Plasma Liners

NASA Technical Reports Server (NTRS)

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

2002-01-01

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

Practice advisory: The utility of EEG theta/beta power ratio in ADHD diagnosis

PubMed Central

Gloss, David; Varma, Jay K.; Pringsheim, Tamara; Nuwer, Marc R.

2016-01-01

Objective: To evaluate the evidence for EEG theta/beta power ratio for diagnosing, or helping to diagnose, attention-deficit/hyperactivity disorder (ADHD). Methods: We identified relevant studies and classified them using American Academy of Neurology criteria. Results: Two Class I studies assessing the ability of EEG theta/beta power ratio and EEG frontal beta power to identify patients with ADHD correctly identified 166 of 185 participants. Both studies evaluated theta/beta power ratio and frontal beta power in suspected ADHD or in syndromes typically included in an ADHD differential diagnosis. A bivariate model combining the diagnostic studies shows that the combination of EEG frontal beta power and theta/beta power ratio has relatively high sensitivity and specificity but is insufficiently accurate. Conclusions: It is unknown whether a combination of standard clinical examination and EEG theta/beta power ratio increases diagnostic certainty of ADHD compared with clinical examination alone. Recommendations: Level B: Clinicians should inform patients with suspected ADHD and their families that the combination of EEG theta/beta power ratio and frontal beta power should not replace a standard clinical evaluation. There is a risk for significant harm to patients from ADHD misdiagnosis because of the unacceptably high false-positive diagnostic rate of EEG theta/beta power ratio and frontal beta power. Level R: Clinicians should inform patients with suspected ADHD and their families that the EEG theta/beta power ratio should not be used to confirm an ADHD diagnosis or to support further testing after a clinical evaluation, unless such diagnostic assessments occur in a research setting. PMID:27760867

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).

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

Protective effects of melittin on transforming growth factor-{beta}1 injury to hepatocytes via anti-apoptotic mechanism

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

Lee, Woo-Ram; Park, Ji-Hyun; Kim, Kyung-Hyun

Melittin is a cationic, hemolytic peptide that is the main toxic component in the venom of the honey bee (Apis mellifera). Melittin has multiple effects, including anti-bacterial, anti-viral and anti-inflammatory, in various cell types. However, the anti-apoptotic mechanisms of melittin have not been fully elucidated in hepatocytes. Apoptosis contributes to liver inflammation and fibrosis. Knowledge of the apoptotic mechanisms is important to develop new and effective therapies for treatment of cirrhosis, portal hypertension, liver cancer, and other liver diseases. In the present study, we investigated the anti-apoptotic effect of melittin on transforming growth factor (TGF)-{beta}1-induced apoptosis in hepatocytes. TGF-{beta}1-treated hepatocytesmore » were exposed to low doses (0.5 and 1 {mu}g/mL) and high dose (2 {mu}g/mL) of melittin. The low doses significantly protected these cells from DNA damage in TGF-{beta}1-induced apoptosis compared to the high dose. Also, melittin suppressed TGF-{beta}1-induced apoptotic activation of the Bcl-2 family and caspase family of proteins, which resulted in the inhibition of poly-ADP-ribose polymerase (PARP) cleavage. These results demonstrate that TGF-{beta}1 induces hepatocyte apoptosis and that an optimal dose of melittin exerts anti-apoptotic effects against TGF-{beta}1-induced injury to hepatocytes via the mitochondrial pathway. These results suggest that an optimal dose of melittin can serve to protect cells against TGF-{beta}1-mediated injury. - Highlights: > We investigated the anti-apoptotic effect of melittin on TGF-{beta}1-induced hepatocyte. > TGF-{beta}1 induces hepatocyte apoptosis. > TGF-{beta}1-treated hepatocytes were exposed to low doses and high dose of melittin. > Optimal dose of melittin exerts anti-apoptotic effects to hepatocytes.« less

Control of a laser inertial confinement fusion-fission power plant

DOEpatents

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

2015-10-27

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

Development of fusogenic glass surfaces that impart spatiotemporal control over macrophage fusion: Direct visualization of multinucleated giant cell formation

PubMed Central

Faust, James J.; Christenson, Wayne; Doudrick, Kyle; Ros, Robert

2017-01-01

Implantation of synthetic material, including vascular grafts, pacemakers, etc. results in the foreign body reaction and the formation of multinucleated giant cells (MGCs) at the exterior surface of the implant. Despite the long-standing premise that fusion of mononucleated macrophages results in the formation of MGCs, to date, no published study has shown fusion in context with living specimens. This is due to the fact that optical-quality glass, which is required for the majority of live imaging techniques, does not promote macrophage fusion. Consequently, the morphological changes that macrophages undergo during fusion as well as the mechanisms that govern this process remain ill-defined. In this study, we serendipitously identified a highly fusogenic glass surface and discovered that the capacity to promote fusion was due to oleamide contamination. When adsorbed on glass, oleamide and other molecules that contain long-chain hydrocarbons promoted high levels of macrophage fusion. Adhesion, an essential step for macrophage fusion, was apparently mediated by Mac-1 integrin (CD11b/CD18, αMβ2) as determined by single cell force spectroscopy and adhesion assays. Micropatterned glass further increased fusion and enabled a remarkable degree of spatiotemporal control over MGC formation. Using these surfaces, we reveal the kinetics that govern MGC formation in vitro. We anticipate that the spatiotemporal control afforded by these surfaces will expedite studies designed to identify the mechanism(s) of macrophage fusion and MGC formation with implication for the design of novel biomaterials. PMID:28340410

Purification and Crystallization Reveal Two Types of Interactions of the Fusion Protein Homotrimer of Semliki Forest Virus

PubMed Central

Gibbons, Don L.; Reilly, Brigid; Ahn, Anna; Vaney, Marie-Christine; Vigouroux, Armelle; Rey, Felix A.; Kielian, Margaret

2004-01-01

The fusion proteins of the alphaviruses and flaviviruses have a similar native structure and convert to a highly stable homotrimer conformation during the fusion of the viral and target membranes. The properties of the alpha- and flavivirus fusion proteins distinguish them from the class I viral fusion proteins, such as influenza virus hemagglutinin, and establish them as the first members of the class II fusion proteins. Understanding how this new class carries out membrane fusion will require analysis of the structural basis for both the interaction of the protein subunits within the homotrimer and their interaction with the viral and target membranes. To this end we report a purification method for the E1 ectodomain homotrimer from the alphavirus Semliki Forest virus. The purified protein is trimeric, detergent soluble, retains the characteristic stability of the starting homotrimer, and is free of lipid and other contaminants. In contrast to the postfusion structures that have been determined for the class I proteins, the E1 homotrimer contains the fusion peptide region responsible for interaction with target membranes. This E1 trimer preparation is an excellent candidate for structural studies of the class II viral fusion proteins, and we report conditions that generate three-dimensional crystals suitable for analysis by X-ray diffraction. Determination of the structure will provide our first high-resolution views of both the low-pH-induced trimeric conformation and the target membrane-interacting region of the alphavirus fusion protein. PMID:15016874

Determination of pharmacological levels of harmane, harmine and harmaline in mammalian brain tissue, cerebrospinal fluid and plasma by high-performance liquid chromatography with fluorimetric detection.

PubMed

Moncrieff, J

1989-11-24

Increased blood aldehyde levels, as occur in alcohol intoxication, could lead to the formation of beta-carbolines such as harmane by condensation with indoleamines. Endogenous beta-carbolines, therefore, should occur in specific brain areas where indoleamine concentrations are high, whilst exogenous beta-carbolines should exhibit an even distribution. The author presents direct and sensitive methods for assaying the beta-carbolines harmane, harmine and harmaline in brain tissue, cerebrospinal fluid and plasma at picogram sample concentrations using reversed-phase high-performance liquid chromatography with fluorimetric detection and minimal sample preparation. Using these assay methods, it was found that the distribution of beta-carbolines from a source exogenous to the brain results in a relatively even distribution within the brain tissue.