Science.gov

Sample records for accelerated structured pathways

  1. Cornerstones of Completion: State Policy Support for Accelerated, Structured Pathways to College Credentials and Transfer

    ERIC Educational Resources Information Center

    Couturier, Lara K.

    2012-01-01

    In spring 2012, after a year of intensive data analysis and planning, the colleges participating in Completion by Design announced strategies for creating clear, structured routes through college for more students, often referred to as accelerated, structured pathways to completion. These strategies contain elements unique to each college, but all…

  2. Fiber Accelerating Structures

    SciTech Connect

    Hammond, Andrew P.; /Reed Coll. /SLAC

    2010-08-25

    One of the options for future particle accelerators are photonic band gap (PBG) fiber accelerators. PBG fibers are specially designed optical fibers that use lasers to excite an electric field that is used to accelerate electrons. To improve PBG accelerators, the basic parameters of the fiber were tested to maximize defect size and acceleration. Using the program CUDOS, several accelerating modes were found that maximized these parameters for several wavelengths. The design of multiple defects, similar to having closely bound fibers, was studied to find possible coupling or the change of modes. The amount of coupling was found to be dependent on distance separated. For certain distances accelerating coupled modes were found and examined. In addition, several non-periodic fiber structures were examined using CUDOS. The non-periodic fibers produced several interesting results and promised more modes given time to study them in more detail.

  3. Dielectric assist accelerating structure

    NASA Astrophysics Data System (ADS)

    Satoh, D.; Yoshida, M.; Hayashizaki, N.

    2016-01-01

    A higher-order TM02 n mode accelerating structure is proposed based on a novel concept of dielectric loaded rf cavities. This accelerating structure consists of ultralow-loss dielectric cylinders and disks with irises which are periodically arranged in a metallic enclosure. Unlike conventional dielectric loaded accelerating structures, most of the rf power is stored in the vacuum space near the beam axis, leading to a significant reduction of the wall loss, much lower than that of conventional normal-conducting linac structures. This allows us to realize an extremely high quality factor and a very high shunt impedance at room temperature. A simulation of a 5 cell prototype design with an existing alumina ceramic indicates an unloaded quality factor of the accelerating mode over 120 000 and a shunt impedance exceeding 650 M Ω /m at room temperature.

  4. Twisted waveguide accelerating structure.

    SciTech Connect

    Kang, Y. W.

    2000-08-15

    A hollow waveguide with a uniform cross section may be used for accelerating charged particles if the phase velocity of an accelerating mode is equal to or less than the free space speed of light. Regular straight hollow waveguides have phase velocities of propagating electromagnetic waves greater than the free-space speed of light. if the waveguide is twisted, the phase velocities of the waveguide modes become slower. The twisted waveguide structure has been modeled and computer simulated in 3-D electromagnetic solvers to show the slow-wave properties for the accelerating mode.

  5. Plasma-based accelerator structures

    SciTech Connect

    Schroeder, Carl B.

    1999-12-01

    Plasma-based accelerators have the ability to sustain extremely large accelerating gradients, with possible high-energy physics applications. This dissertation further develops the theory of plasma-based accelerators by addressing three topics: the performance of a hollow plasma channel as an accelerating structure, the generation of ultrashort electron bunches, and the propagation of laser pulses is underdense plasmas.

  6. Accelerator structure work for NLC

    SciTech Connect

    Miller, R.H.; Adolphsen, C.; Bane, K.L.F.; Deruyter, H.; Farkas, Z.D.; Hoag, H.A.; Holtkamp, N.; Lavine, T.; Loew, G.A.; Nelson, E.M.; Palmer, R.B.; Paterson, J.M.; Ruth, R.D.; Thompson, K.A.; Vlieks, A.; Wang, J.W.; Wilson, P.B. ); Gluckstern, R. ); Ko, K.; Kroll, N. (Stanford Linear Accelerator Ce

    1992-07-01

    The NLC design achieves high luminosity with multiple bunches in each RF pulse. Acceleration of a train of bunches without emittance growth requires control of long range dipole wakefields. SLAC is pursuing a structure design which suppresses the effect of wakefields by varying the physical dimensions of successive cells of the disk-loaded traveling wave structure in a manner which spreads the frequencies of the higher mode while retaining the synchronism between the electrons and the accelerating mode. The wakefields of structures incorporating higher mode detuning have been measured at the Accelerator Test Facility at Argonne. Mechanical design and brazing techniques which avoid getting brazing alloy into the interior of the accelerator are being studied. A test facility for high-power testing of these structures is complete and high power testing has begun.

  7. Medium Beta Superconducting Accelerating Structures

    SciTech Connect

    Jean Delayen

    2001-09-01

    While, originally, the development of superconducting structures was cleanly divided between low-beta resonators for heavy ions and beta=1 resonators for electrons, recent interest in protons accelerators (high and low current, pulsed and cw) has necessitated the development of structures that bridge the gap between the two. These activities have resulted both in new geometries and in the adaptation of well-known geometries optimized to this intermediate velocity range. Their characteristics and properties are reviewed.

  8. Accelerator structure development for NLC

    SciTech Connect

    Hoag, H.A.; Deruyter, H.; Pearson, C.; Ruth, R.D.; Wang, J.W.; Schaefer, J.

    1993-04-01

    In the program of work directed towards the development of an X-Band Next Linear Collider accelerator structure, two different test accelerator sections have been completed, and a third is being fabricated. The first is a simple 30-cell constant-impedance section in which no special attention was given to surface finish, pumping, and alignment. The second is an 86-cell section in which the cells were precision diamond-turned by Texas Instruments Inc. The structure has internal water-cooling and vacuum pumping manifolds. Some design details are given for the third section, which is a 206-cell structure with cavities dimensioned to give a Gaussian distribution of dipole mode frequencies. It has conventional-machining surface finishes and external water and pumping manifolds. Component design, fabrication, and assembly brazing are described for the first two experimental sections.

  9. Photonic Crystal Laser Accelerator Structures

    SciTech Connect

    Cowan, Benjamin M

    2003-05-21

    Photonic crystals have great potential for use as laser-driven accelerator structures. A photonic crystal is a dielectric structure arranged in a periodic geometry. Like a crystalline solid with its electronic band structure, the modes of a photonic crystal lie in a set of allowed photonic bands. Similarly, it is possible for a photonic crystal to exhibit one or more photonic band gaps, with frequencies in the gap unable to propagate in the crystal. Thus photonic crystals can confine an optical mode in an all-dielectric structure, eliminating the need for metals and their characteristic losses at optical frequencies. We discuss several geometries of photonic crystal accelerator structures. Photonic crystal fibers (PCFs) are optical fibers which can confine a speed-of-light optical mode in vacuum. Planar structures, both two- and three-dimensional, can also confine such a mode, and have the additional advantage that they can be manufactured using common microfabrication techniques such as those used for integrated circuits. This allows for a variety of possible materials, so that dielectrics with desirable optical and radiation-hardness properties can be chosen. We discuss examples of simulated photonic crystal structures to demonstrate the scaling laws and trade-offs involved, and touch on potential fabrication processes.

  10. CVD Diamond Dielectric Accelerating Structures

    SciTech Connect

    Schoessow, P.; Kanareykin, A.; Gat, R.

    2009-01-22

    The electrical and mechanical properties of diamond make it an ideal candidate material for use in dielectric accelerating structures: high RF breakdown field, extremely low dielectric losses and the highest available thermoconductive coefficient. Using chemical vapor deposition (CVD) cylindrical diamond structures have been manufactured with dimensions corresponding to fundamental TM{sub 01} mode frequencies in the GHz to THz range. Surface treatments are being developed to reduce the secondary electron emission (SEE) coefficient below unity to reduce the possibility of multipactor. The diamond CVD cylindrical waveguide technology developed here can be applied to a variety of other high frequency, large-signal applications.

  11. EM Structure Based and Vacuum Acceleration

    SciTech Connect

    Colby, E.R.; /SLAC

    2005-09-27

    The importance of particle acceleration may be judged from the number of applications which require some sort of accelerated beam. In addition to accelerator-based high energy physics research, non-academic applications include medical imaging and treatment, structural biology by x-ray diffraction, pulse radiography, cargo inspection, material processing, food and medical instrument sterilization, and so on. Many of these applications are already well served by existing technologies and will profit only marginally from developments in accelerator technology. Other applications are poorly served, such as structural biology, which is conducted at synchrotron radiation facilities, and medical treatment using proton accelerators, the machines for which are rare because they are complex and costly. Developments in very compact, high brightness and high gradient accelerators will change how accelerators are used for such applications, and potentially enable new ones. Physical and technical issues governing structure-based and vacuum acceleration of charged particles are reviewed, with emphasis on practical aspects.

  12. Photonic Crystal Laser-Driven Accelerator Structures

    SciTech Connect

    Cowan, Benjamin M.

    2007-08-22

    Laser-driven acceleration holds great promise for significantly improving accelerating gradient. However, scaling the conventional process of structure-based acceleration in vacuum down to optical wavelengths requires a substantially different kind of structure. We require an optical waveguide that (1) is constructed out of dielectric materials, (2) has transverse size on the order of a wavelength, and (3) supports a mode with speed-of-light phase velocity in vacuum. Photonic crystals---structures whose electromagnetic properties are spatially periodic---can meet these requirements. We discuss simulated photonic crystal accelerator structures and describe their properties. We begin with a class of two-dimensional structures which serves to illustrate the design considerations and trade-offs involved. We then present a three-dimensional structure, and describe its performance in terms of accelerating gradient and efficiency. We discuss particle beam dynamics in this structure, demonstrating a method for keeping a beam confined to the waveguide. We also discuss material and fabrication considerations. Since accelerating gradient is limited by optical damage to the structure, the damage threshold of the dielectric is a critical parameter. We experimentally measure the damage threshold of silicon for picosecond pulses in the infrared, and determine that our structure is capable of sustaining an accelerating gradient of 300 MV/m at 1550 nm. Finally, we discuss possibilities for manufacturing these structures using common microfabrication techniques.

  13. Photonic Crystal Laser-Driven Accelerator Structures

    SciTech Connect

    Cowan, B.; /SLAC

    2005-09-19

    We discuss simulated photonic crystal structure designs for laser-driven particle acceleration, focusing on three-dimensional planar structures based on the so-called ''woodpile'' lattice. We demonstrate guiding of a speed-of-light accelerating mode by a defect in the photonic crystal lattice and discuss the properties of this mode. We also discuss particle beam dynamics in the structure, presenting a novel method for focusing the beam. In addition we describe some potential coupling methods for the structure.

  14. Variable energy constant current accelerator structure

    DOEpatents

    Anderson, O.A.

    1988-07-13

    A variable energy, constant current ion beam accelerator structure is disclosed comprising an ion source capable of providing the desired ions, a pre-accelerator for establishing an initial energy level, a matching/pumping module having means for focusing means for maintaining the beam current, and at least one main accelerator module for continuing beam focus, with means capable of variably imparting acceleration to the beam so that a constant beam output current is maintained independent of the variable output energy. In a preferred embodiment, quadrupole electrodes are provided in both the matching/pumping module and the one or more accelerator modules, and are formed using four opposing cylinder electrodes which extend parallel to the beam axis and are spaced around the beam at 90/degree/ intervals with opposing electrodes maintained at the same potential. 12 figs., 3 tabs.

  15. Variable energy constant current accelerator structure

    DOEpatents

    Anderson, Oscar A.

    1990-01-01

    A variable energy, constant current ion beam accelerator structure is disclosed comprising an ion source capable of providing the desired ions, a pre-accelerator for establishing an initial energy level, a matching/pumping module having means for focusing means for maintaining the beam current, and at least one main accelerator module for continuing beam focus, with means capable of variably imparting acceleration to the beam so that a constant beam output current is maintained independent of the variable output energy. In a preferred embodiment, quadrupole electrodes are provided in both the matching/pumping module and the one or more accelerator modules, and are formed using four opposing cylinder electrodes which extend parallel to the beam axis and are spaced around the beam at 90.degree. intervals with opposing electrodes maintained at the same potential. Adjacent cylinder electrodes of the quadrupole structure are maintained at different potentials to thereby reshape the cross section of the charged particle beam to an ellipse in cross section at the mid point along each quadrupole electrode unit in the accelerator modules. The beam is maintained in focus by alternating the major axis of the ellipse along the x and y axis respectively at adjacent quadrupoles. In another embodiment, electrostatic ring electrodes may be utilized instead of the quadrupole electrodes.

  16. Accelerating Adverse Outcome Pathway Development Using Publicly Available Data Sources.

    PubMed

    Oki, Noffisat O; Nelms, Mark D; Bell, Shannon M; Mortensen, Holly M; Edwards, Stephen W

    2016-03-01

    The adverse outcome pathway (AOP) concept links molecular perturbations with organism and population-level outcomes to support high-throughput toxicity (HTT) testing. International efforts are underway to define AOPs and store the information supporting these AOPs in a central knowledge base; however, this process is currently labor-intensive and time-consuming. Publicly available data sources provide a wealth of information that could be used to define computationally predicted AOPs (cpAOPs), which could serve as a basis for creating expert-derived AOPs in a much more efficient way. Computational tools for mining large datasets provide the means for extracting and organizing the information captured in these public data sources. Using cpAOPs as a starting point for expert-derived AOPs should accelerate AOP development. Coupling this with tools to coordinate and facilitate the expert development efforts will increase the number and quality of AOPs produced, which should play a key role in advancing the adoption of HTT testing, thereby reducing the use of animals in toxicity testing and greatly increasing the number of chemicals that can be tested. PMID:26809562

  17. Preliminary results on open accelerating structures

    SciTech Connect

    Palmer, R.B.; Giordano, S.

    1985-01-07

    In this paper we consider periodic structures consisting of rows of spherical conductors. In a plasma linac, these spherical conductors would be formed from liquid droplets on whose surfaces a plasma would be formed. For this paper, the field configurations have been investigated using copper spheres approximately 11 cm diameter and microwave radiation of approximately 30 cm wavelength. No suitable accelerating mode was found for relativistic particles using a single row of spheres, but with two parallel rows of spheres both accelerating and focusing modes were found. In Section II we re-examine the accelerating modes over a grating surface, including a grating of parallel conducting rods. In Section III we discuss the coupling of these structures to incoming radiation. 3 refs., 6 figs.

  18. Design of the detuned accelerator structure

    SciTech Connect

    Wang, J.W.; Nelson, E.M.

    1993-05-01

    This is a summary of the design procedure for the detuned accelerator structure for SLAC's Next Linear Collider (NLC) program. The 11.424 GHz accelerating mode of each cavity must be synchronous with the beam. The distribution of the disk thicknesses and lowest synchronous dipole mode frequencies of the cavities in the structure is Gaussian in order to reduce the effect of wake fields. The finite element field solver YAP calculated the accelerating mode frequency and the lowest synchronous dipole mode frequency for various cavity diameters, aperture diameters and disk thicknesses. Polynomial 3-parameter fits are used to calculate the dimensions for a 1.8 m detuned structure. The program SUPERFISH was used to calculate the shunt impedances, quality factors and group velocities. The RF parameters of the section like filling time, attenuation factor, accelerating gradient and maximum surface field along the section are evaluated. Error estimates will be discussed and comparisons with conventional constant gradient and constant impedance structures will be presented.

  19. Design of the detuned accelerator structure

    SciTech Connect

    Wang, J.W.; Nelson, E.M.

    1993-05-01

    This is a summary of the design procedure for the detuned accelerator structure for SLAC`s Next Linear Collider (NLC) program. The 11.424 GHz accelerating mode of each cavity must be synchronous with the beam. The distribution of the disk thicknesses and lowest synchronous dipole mode frequencies of the cavities in the structure is Gaussian in order to reduce the effect of wake fields. The finite element field solver YAP calculated the accelerating mode frequency and the lowest synchronous dipole mode frequency for various cavity diameters, aperture diameters and disk thicknesses. Polynomial 3-parameter fits are used to calculate the dimensions for a 1.8 m detuned structure. The program SUPERFISH was used to calculate the shunt impedances, quality factors and group velocities. The RF parameters of the section like filling time, attenuation factor, accelerating gradient and maximum surface field along the section are evaluated. Error estimates will be discussed and comparisons with conventional constant gradient and constant impedance structures will be presented.

  20. Accelerating Adverse Outcome Pathway Development via Systems Approaches

    EPA Science Inventory

    The Adverse Outcome Pathway has emerged as an internationally harmonized mechanism for organizing biological information in a chemical agnostic manner. This construct is valuable for interpreting the results from high-throughput toxicity (HTT) assessment by providing a mechanisti...

  1. Computing folding pathways between RNA secondary structures.

    PubMed

    Dotu, Ivan; Lorenz, William A; Van Hentenryck, Pascal; Clote, Peter

    2010-03-01

    Given an RNA sequence and two designated secondary structures A, B, we describe a new algorithm that computes a nearly optimal folding pathway from A to B. The algorithm, RNAtabupath, employs a tabu semi-greedy heuristic, known to be an effective search strategy in combinatorial optimization. Folding pathways, sometimes called routes or trajectories, are computed by RNAtabupath in a fraction of the time required by the barriers program of Vienna RNA Package. We benchmark RNAtabupath with other algorithms to compute low energy folding pathways between experimentally known structures of several conformational switches. The RNApathfinder web server, source code for algorithms to compute and analyze pathways and supplementary data are available at http://bioinformatics.bc.edu/clotelab/RNApathfinder. PMID:20044352

  2. SIMULATING ACCELERATOR STRUCTURE OPERATION AT HIGH POWER

    SciTech Connect

    Ivanov, V

    2004-09-15

    The important limiting factors in high-gradient accelerator structure operation are dark current capture, RF breakdown and electron multipacting. These processes involve both primary and secondary electron field emission and produce plasma and X-rays. To better understand these phenomena, they have simulated dark current generation and transport in a linac structure and a square-bend waveguide, both high power tested at SLAC. For these simulations, they use the parallel, time-domain, unstructured-grid code Tau3P and the particle tracking module Track3P. In this paper, they present numerical results and their comparison with measurements on energy spectrum of electrons transmitted in a 30-cell structure and of X-rays emitted from the square-bend waveguide.

  3. Multi-GPU Accelerated Simulation of Dynamically Evolving Fluid Pathways

    NASA Astrophysics Data System (ADS)

    Räss, Ludovic; Omlin, Samuel; Moulas, Evangelos; Simon, Nina S. C.; Podladchikov, Yuri

    2014-05-01

    Fluid flow in porous rocks, both naturally occurring and caused by reservoir operations, mostly takes place along localized high permeability pathways. Pervasive flooding of the rock matrix is rarely observed, in particular for low permeability rocks. The pathways appear to form dynamically in response to the fluid flow itself; the amount of pathways, their location and their hydraulic conductivity may change in time. We propose a physically and thermodynamically consistent model that describes the formation and evolution of fluid pathways. The model consists of a system of equations describing poro-elasto-viscous deformation and flow. We have implemented the strongly coupled equations into a numerical model. Nonlinearity of the solid rheology is also taken into account. We have developed a fully three-dimensional numerical MATLAB application based on an iterative finite difference scheme. We have ported it to C-CUDA using MPI to run it on multi-GPU clusters. Numerical tuning of the application based on memory bandwidth throughput allows to approach hardware peak performance. Conducted high-resolution three-dimensional simulations predict the formation of dynamically evolving high porosity and permeability pathways as a natural outcome of porous flow coupled with rock deformation.

  4. Accelerating Adverse Outcome Pathway Development Using Publicly Available Data Sources

    EPA Science Inventory

    The adverse outcome pathway (AOP) concept links molecular perturbations with organism and population-level outcomes to support high-throughput toxicity testing. International efforts are underway to define AOPs and store the information supporting these AOPs in a central knowledg...

  5. High charge short electron bunches for wakefield accelerator structures development.

    SciTech Connect

    Conde, M. E.

    1998-09-25

    The Argonne Wakefield Accelerator group develops accelerating structures based on dielectric loaded waveguides. We use high charge short electron bunches to excite wakefields in dielectric loaded structures, and a second (low charge) beam to probe the wakefields left behind by the drive beam. We report measurements of beam parameters and also initial results of the dielectric loaded accelerating structures. We have studied acceleration of the probe beam in these structures and we have also made measurements on the RF pulses that are generated by the drive beam. Single drive bunches, as well as multiple bunches separated by an integer number of RF periods have been used to generate the accelerating wakefields.

  6. Micromechanical structures and microelectronics for acceleration sensing

    SciTech Connect

    Davies, B.R.; Montague, S.; Smith, J.H.; Lemkin, M.

    1997-08-01

    MEMS is an enabling technology that may provide low-cost devices capable of sensing motion in a reliable and accurate manner. This paper describes work in MEMS accelerometer development at Sandia National Laboratories. This work leverages a process for integrating both the micromechanical structures and microelectronis circuitry of a MEMS accelerometer on the same chip. The design and test results of an integrated MEMS high-g accelerometer will be detailed. Additionally a design for a high-g fuse component (low-G or {approx} 25 G accelerometer) will be discussed in the paper (where 1 G {approx} 9.81 m/s). In particular, a design team at Sandia was assembled to develop a new micromachined silicon accelerometer which would be capable of surviving and measuring high-g shocks. Such a sensor is designed to be cheaper and more reliable than currently available sensors. A promising design for a suspended plate mass sensor was developed and the details of that design along with test data will be documented in the paper. Future development in this area at Sandia will focus on implementing accelerometers capable of measuring 200 kilo-g accelerations. Accelerometer development at Sandia will also focus on multi-axis acceleration measurement with integrated microelectronics.

  7. SETDB1 accelerates tumorigenesis by regulating WNT signaling pathway

    PubMed Central

    Sun, Qiao-Yang; Ding, Ling-Wen; Xiao, Jin-Fen; Chien, Wenwen; Lim, Su-Lin; Hattori, Norimichi; Goodglick, Lee; Chia, David; Mah, Vei; Alavi, Mohammad; Kim, Sara R.; Doan, Ngan B.; Said, Jonathan W.; Loh, Xin-Yi; Xu, Liang; Liu, Li-Zhen; Yang, Henry; Hayano, Takahide; Shi, Shuo; Xie, Dong; Lin, De-Chen; Koeffler, H. Phillip

    2014-01-01

    We investigated the oncogenic role of SETDB1 focusing on non-small cell lung cancer (NSCLC) having high expression of this protein. A total of 387 lung cancer cases were examined by immunohistochemistry, 72% of NSCLC samples were positive for SETDB1 staining, compared to 46% samples of normal bronchial epithelium (106 cases) (p<0.0001). Percent positive cells and intensity of staining increased significantly with increased grade of disease. Forced expression of SETDB1 in NSCLC cell lines enhanced their clonogenic growth in vitro and markedly increased tumor size in a murine xenograft model; while silencing (shRNA) SETDB1 in NSCLC cells slowed their proliferation. SETDB1 positively stimulated activity of the WNT/β-catenin pathway and diminished P53 expression resulting in enhanced NSCLC growth in vitro and in vivo. Our finding suggests therapeutic targeting SETDB1 may benefit patients whose tumors express high levels of SETDB1. PMID:25404354

  8. The fabrication of millimeter-wavelength accelerating structures

    SciTech Connect

    Chou, P.J.; Bowden, G.B.; Copeland, M.R.

    1996-11-01

    There is a growing interest in the development of high gradient ({ge} 1 GeV/m) accelerating structures. The need for high gradient acceleration based on current microwave technology requires the structures to be operated in the millimeter wavelength. Fabrication of accelerating structures at millimeter scale with sub-micron tolerances poses great challenges. The accelerating structures impose strict requirements on surface smoothness and finish to suppress field emission and multipactor effects. Various fabrication techniques based on conventional machining and micromachining have been evaluated and tested. These will be discussed and measurement results presented.

  9. The fabrication of millimeter-wavelength accelerating structures

    SciTech Connect

    Chou, P.J.; Bowden, G.B.; Copeland, M.R.; Farvid, A.; Kirby, R.E.; Menegat, A.; Pearson, C.; Shere, L.; Siemann, R.H.; Spencer, J.E.; Whittum, D.H.

    1997-03-01

    There is a growing interest in the research of high gradient ({ge}1GeV/m) accelerating structures. The need for high gradient acceleration based on current microwave technology requires the structures to be operated in the millimeter wavelength. Fabrication of accelerating structures at millimeter scale with sub-micron tolerances poses great challenges. The accelerating structures impose strict requirements on surface smoothness and finish to suppress field emission and multipactor effects. Various fabrication techniques based on conventional machining and micromachining have been evaluated and tested. These will be discussed and measurement results presented. {copyright} {ital 1997 American Institute of Physics.}

  10. Building Integrated Pathways to Sustainable Careers: An Introduction to the Accelerated Opportunity Initiative

    ERIC Educational Resources Information Center

    Pleasants, Rachel

    2011-01-01

    "Accelerating Opportunity" responds to the nation's growing need for improved pathways from Adult Basic Education (ABE) to credentials of value in the labor market. It builds on promising practices developed in "Breaking Through," an initiative of Jobs for the Future and the National Council for Workforce Education, and Washington State's…

  11. S-band accelerating structures for the PAL-XFEL

    NASA Astrophysics Data System (ADS)

    Lee, Heung-Soo; Park, Young Jung; Joo, Young-Do; Heo, Hoon; Heo, Jinyul; Kim, Sang-Hee; Park, Soung-Soo; Hwang, Woon Ha; Kang, Heung-Sik; Kim, Kwang-woo; Ko, In-Soo; Oh, Kyoung-Min; Noh, Sung-Joo; Bak, Yong Hwan; Matsumoto, Hiroshi

    2015-02-01

    One hundred seventy-two accelerating structures are required for the Pohang Accelerator Laboratory X-ray free-electron laser's (PAL-XFEL's) 10-GeV main linear accelerator. So far, we have purchased 80 structures from Mitsubishi Heavy Industry (MHI), which have quasi-symmetric couplers in the accelerating structure to reduce the quadruple and the sextuple components of the electric field in the coupling cavity. High-power tests have been conducted for the first structure of the MHI structure, and Research Instruments (RI) has developed a 3-m long accelerating structure that has an operating frequency of 2856 MHz and in/out couplers of quasi-symmetric racetrack shape for the PAL-XFEL linear accelerator. This structure also has been tested by PAL and RI in the Pohang accelerator laboratory (PAL) to check the maximum available electric field gradient. We will describe the test results of these structures and the current status for the fabrication of the other accelerating structures in this paper.

  12. R&D of Accelerator Structures at SLAC

    SciTech Connect

    Wang, J.W.; /SLAC

    2007-01-17

    The research activities for accelerator structures at SLAC are reviewed including the achievement via the main linac design for the Next Linear Collider (NLC), the program adjustment after the decision of the International Linear Collider (ILC) to be based on superconducting technology, and the work progress for the ILC, photon science at SLAC and basic accelerator structure studies.

  13. Compact Couplers for Photonic Crystal Laser-Driven Accelerator Structures

    SciTech Connect

    Cowan, Benjamin; Lin, M.C.; Schwartz, Brian; Byer, Robert; McGuinness, Christopher; Colby, Eric; England, Robert; Noble, Robert; Spencer, James; /SLAC

    2012-07-02

    Photonic crystal waveguides are promising candidates for laser-driven accelerator structures because of their ability to confine a speed-of-light mode in an all-dielectric structure. Because of the difference between the group velocity of the waveguide mode and the particle bunch velocity, fields must be coupled into the accelerating waveguide at frequent intervals. Therefore efficient, compact couplers are critical to overall accelerator efficiency. We present designs and simulations of high-efficiency coupling to the accelerating mode in a three-dimensional photonic crystal waveguide from a waveguide adjoining it at 90{sup o}. We discuss details of the computation and the resulting transmission. We include some background on the accelerator structure and photonic crystal-based optical acceleration in general.

  14. High frequency single mode traveling wave structure for particle acceleration

    NASA Astrophysics Data System (ADS)

    Ivanyan, M. I.; Danielyan, V. A.; Grigoryan, B. A.; Grigoryan, A. H.; Tsakanian, A. V.; Tsakanov, V. M.; Vardanyan, A. S.; Zakaryan, S. V.

    2016-09-01

    The development of the new high frequency slow traveling wave structures is one of the promising directions in accomplishment of charged particles high acceleration gradient. The disc and dielectric loaded structures are the most known structures with slowly propagating modes. In this paper a large aperture high frequency metallic two-layer accelerating structure is studied. The electrodynamical properties of the slowly propagating TM01 mode in a metallic tube with internally coated low conductive thin layer are examined.

  15. Advanced Accelerating Structures and Their Interaction with Electron Beams

    SciTech Connect

    Gai Wei

    2009-01-22

    In this paper, we give a brief description of several advanced accelerating structures, such as dielectric loaded waveguides, photonic band gap, metamaterials and improved iris-loaded cavities. We describe wakefields generated by passing high current electron beams through these structures, and applications of wakefields to advanced accelerator schemes. One of the keys to success for high gradient wakefield acceleration is to develop high current drive beam sources. As an example, the high current RF photo injector at the Argonne Wakefield Accelerator, passed a {approx}80 nC electron beam through a high gradient dielectric loaded structure to achieve a 100 MV/m gradient. We will summarize recent related experiments on beam-structure interactions and also discuss high current electron beam generation and propagation and their applications to wakefield acceleration.

  16. Advanced accelerating structures and their interaction with electron beams.

    SciTech Connect

    Gai, W.; High Energy Physics

    2008-01-01

    In this paper, we give a brief description of several advanced accelerating structures, such as dielectric loaded waveguides, photonic band gap, metamaterials and improved iris-loaded cavities. We describe wakefields generated by passing high current electron beams through these structures, and applications of wakefields to advanced accelerator schemes. One of the keys to success for high gradient wakefield acceleration is to develop high current drive beam sources. As an example, the high current RF photo injector at the Argonne Wakefield Accelerator, passed a {approx}80 nC electron beam through a high gradient dielectric loaded structure to achieve a 100 MV/m gradient. We will summarize recent related experiments on beam-structure interactions and also discuss high current electron beam generation and propagation and their applications to wakefield acceleration.

  17. Investigations of the plasma and structure based accelerators

    SciTech Connect

    Shvets, Gennady

    2012-08-30

    The objective of our research during the reported period was three-fold: (a) theoretical investigation of novel mechanisms of injection into laser wake field accelerators; (b) theoretical investigation of single-shot frequency domain diagnostics of relativistic plasma wakes, specifically in the context of spatio-temporal evolution of the plasma bubble;(c) experimental and theoretical investigation of laser-driven accelerating structure, specifically in the context of the Surface Wave Accelerator Based on SiC (SWABSIC).

  18. A structural pathway for activation of the kinesin motor ATPase

    PubMed Central

    Yun, Mikyung; Zhang, Xiaohua; Park, Cheon-Gil; Park, Hee-Won; Endow, Sharyn A.

    2001-01-01

    Molecular motors move along actin or microtubules by rapidly hydrolyzing ATP and undergoing changes in filament-binding affinity with steps of the nucleotide hydrolysis cycle. It is generally accepted that motor binding to its filament greatly increases the rate of ATP hydrolysis, but the structural changes in the motor associated with ATPase activation are not known. To identify the conformational changes underlying motor movement on its filament, we solved the crystal structures of three kinesin mutants that decouple nucleotide and microtubule binding by the motor, and block microtubule-activated, but not basal, ATPase activity. Conformational changes in the structures include a disordered loop and helices in the switch I region and a visible switch II loop, which is disordered in wild-type structures. Switch I moved closer to the bound nucleotide in two mutant structures, perturbing water-mediated interactions with the Mg2+. This could weaken Mg2+ binding and accelerate ADP release to activate the motor ATPase. The structural changes we observe define a signaling pathway within the motor for ATPase activation that is likely to be essential for motor movement on microtubules. PMID:11387196

  19. A compact accelerating structure for stacked isochronous cyclotrons

    NASA Astrophysics Data System (ADS)

    Meitzler, C. R.; Byeon, J.; McIntyre, P. M.; Rogers, Bob; Sattarov, A.

    2003-03-01

    An accelerator-driven thorium cycle power reactor is being developed, based on a flux-coupled stack of isochronous cyclotrons. (IC) The stack consists of seven independent accelerators (total beam power 15 MW at 1 GeV), stacked on a spacing ˜ 20 cm. The close spacing poses unique problems for the design of the accelerating cavities. We have invented a 4-bar RF dipole structure for the purpose. We have built a cold model and are studying its operating characteristics. The structure will be described. We present measurements of the resonant frequency, parasitic capacitances, and electric and magnetic field distributions in the structure.

  20. Experimental demonstration of wakefield acceleration in a tunable dielectric loaded accelerating structure.

    PubMed

    Jing, C; Kanareykin, A; Power, J G; Conde, M; Liu, W; Antipov, S; Schoessow, P; Gai, W

    2011-04-22

    We report on a collinear wakefield experiment using the first tunable dielectric loaded accelerating structure. By introducing an extra layer of nonlinear ferroelectric, which has a dielectric constant sensitive to temperature and dc bias, the frequency of a dielectric loaded accelerating structure can be tuned. During the experiment, the energy of a witness bunch at a fixed delay with respect to the drive beam was measured while the temperature of the structure was scanned over a 50 °C range. The energy change corresponded to a change of more than half of the nominal structure wavelength. PMID:21599371

  1. Experimental demonstration of Wakefield acceleration in a tunable dielectric loaded accelerating structure.

    SciTech Connect

    Liu, W.; Power, J. G.; Conde, M.; Antipov, S.; Schoessow, P.; Gai, W.; Jing, C.; Kanareykin, A.; Schoessow, P.

    2011-04-21

    We report on a collinear wakefield experiment using the first tunable dielectric loaded accelerating structure. By introducing an extra layer of nonlinear ferroelectric, which has a dielectric constant sensitive to temperature and dc bias, the frequency of a dielectric loaded accelerating structure can be tuned. During the experiment, the energy of a witness bunch at a fixed delay with respect to the drive beam was measured while the temperature of the structure was scanned over a 50 C range. The energy change corresponded to a change of more than half of the nominal structure wavelength.

  2. Experimental Demonstration of Wakefield Acceleration in a Tunable Dielectric Loaded Accelerating Structure

    SciTech Connect

    Jing, C.; Antipov, S.; Kanareykin, A.; Schoessow, P.; Power, J. G.; Conde, M.; Liu, W.; Gai, W.

    2011-04-22

    We report on a collinear wakefield experiment using the first tunable dielectric loaded accelerating structure. By introducing an extra layer of nonlinear ferroelectric, which has a dielectric constant sensitive to temperature and dc bias, the frequency of a dielectric loaded accelerating structure can be tuned. During the experiment, the energy of a witness bunch at a fixed delay with respect to the drive beam was measured while the temperature of the structure was scanned over a 50 deg. C range. The energy change corresponded to a change of more than half of the nominal structure wavelength.

  3. Three-Dimensional Photonic Crystal Laser-Driven Accelerator Structures

    SciTech Connect

    Cowan, B.; /SLAC

    2006-09-07

    We discuss simulated photonic crystal structure designs for laser-driven particle acceleration, focusing on three-dimensional planar structures based on the so-called ''woodpile'' lattice. We describe guiding of a speed-of-light accelerating mode by a defect in the photonic crystal lattice and discuss the properties of this mode, including particle beam dynamics and potential coupling methods for the structure. We also discuss possible materials and power sources for this structure and their effects on performance parameters, as well as possible manufacturing techniques and the required tolerances. In addition we describe the computational technique and possible improvements in numerical modeling that would aid development of photonic crystal structures.

  4. Mutational Pathway Determines Whether Drug Gradients Accelerate Evolution of Drug-Resistant Cells

    NASA Astrophysics Data System (ADS)

    Greulich, Philip; Waclaw, Bartłomiej; Allen, Rosalind J.

    2012-08-01

    Drug gradients are believed to play an important role in the evolution of bacteria resistant to antibiotics and tumors resistant to anticancer drugs. We use a statistical physics model to study the evolution of a population of malignant cells exposed to drug gradients, where drug resistance emerges via a mutational pathway involving multiple mutations. We show that a nonuniform drug distribution has the potential to accelerate the emergence of resistance when the mutational pathway involves a long sequence of mutants with increasing resistance, but if the pathway is short or crosses a fitness valley, the evolution of resistance may actually be slowed down by drug gradients. These predictions can be verified experimentally, and may help to improve strategies for combating the emergence of resistance.

  5. Alignment issues of the SLC linac accelerating structure

    SciTech Connect

    Seeman, J.T.; Adolphsen, C.; Decker, F.J.; Fischer, G.; Hodgson, J.; Pennacchi, R.; Perkins, C.; Pietryka, M.

    1991-05-01

    The accelerating structure of the Stanford Linear Collider (SLC) is required to be aligned to 100--200 {mu}m rms. Alignment at such a level will reduce transverse wakefield effects sufficiently so that only a small emittance enlargement of the beam is expected during acceleration to 50 GeV with up to 7 {times} 10{sup 10} particles per bunch. This report describes many aspects of the alignment including global alignment, local alignment, construction of the accelerating cavities, active controls of the structure alignment, external constraints, temperature and airflow effects, and alignment stability. 9 refs., 8 figs.

  6. Minimal metabolic pathway structure is consistent with associated biomolecular interactions

    PubMed Central

    Bordbar, Aarash; Nagarajan, Harish; Lewis, Nathan E; Latif, Haythem; Ebrahim, Ali; Federowicz, Stephen; Schellenberger, Jan; Palsson, Bernhard O

    2014-01-01

    Pathways are a universal paradigm for functionally describing cellular processes. Even though advances in high-throughput data generation have transformed biology, the core of our biological understanding, and hence data interpretation, is still predicated on human-defined pathways. Here, we introduce an unbiased, pathway structure for genome-scale metabolic networks defined based on principles of parsimony that do not mimic canonical human-defined textbook pathways. Instead, these minimal pathways better describe multiple independent pathway-associated biomolecular interaction datasets suggesting a functional organization for metabolism based on parsimonious use of cellular components. We use the inherent predictive capability of these pathways to experimentally discover novel transcriptional regulatory interactions in Escherichia coli metabolism for three transcription factors, effectively doubling the known regulatory roles for Nac and MntR. This study suggests an underlying and fundamental principle in the evolutionary selection of pathway structures; namely, that pathways may be minimal, independent, and segregated. PMID:24987116

  7. Minimal metabolic pathway structure is consistent with associated biomolecular interactions.

    PubMed

    Bordbar, Aarash; Nagarajan, Harish; Lewis, Nathan E; Latif, Haythem; Ebrahim, Ali; Federowicz, Stephen; Schellenberger, Jan; Palsson, Bernhard O

    2014-01-01

    Pathways are a universal paradigm for functionally describing cellular processes. Even though advances in high-throughput data generation have transformed biology, the core of our biological understanding, and hence data interpretation, is still predicated on human-defined pathways. Here, we introduce an unbiased, pathway structure for genome-scale metabolic networks defined based on principles of parsimony that do not mimic canonical human-defined textbook pathways. Instead, these minimal pathways better describe multiple independent pathway-associated biomolecular interaction datasets suggesting a functional organization for metabolism based on parsimonious use of cellular components. We use the inherent predictive capability of these pathways to experimentally discover novel transcriptional regulatory interactions in Escherichia coli metabolism for three transcription factors, effectively doubling the known regulatory roles for Nac and MntR. This study suggests an underlying and fundamental principle in the evolutionary selection of pathway structures; namely, that pathways may be minimal, independent, and segregated. PMID:24987116

  8. Development of X-Band Dielectric-Loaded Accelerating Structures

    SciTech Connect

    Gold, S. H.; Jing, C.; Kanareykin, A.; Gai, W.; Konecny, R.; Power, J. G.; Kinkead, A. K.

    2010-11-04

    This paper presents a progress report on the development and testing of X-band dielectric-loaded accelerating structures. Recent tests on several quartz DLA structures with different inner diameters are reported. Designs for gap-free DLA structures are presented. Also, planned new experiments are discussed, including higher gradient traveling-wave and standing-wave structures and special grooved structures for multipactor suppression.

  9. Fabrication and Characterization of Woodpile Structures for Direct Laser Acceleration

    SciTech Connect

    McGuinness, C.; Peralta, E.; Soong, K.; Colby, E.; England, R. J.; Ng, J.; Noble, R. J.; Spencer, J.; Walz, D.; Cowan, B.; Byer, R. L.

    2010-11-04

    Eight and nine layer three dimensional photonic crystals with a defect designed specifically for accelerator applications have been fabricated. The structures were fabricated using a combination of nanofabrication techniques, including low pressure chemical vapor deposition, optical lithography, and chemical mechanical polishing. Limits imposed by the optical lithography set the minimum feature size to 400 nm, corresponding to a structure with a bandgap centered at 4.26 {mu}m. Reflection spectroscopy reveal a peak in reflectivity about the predicted region, and good agreement with simulation is shown. The eight and nine layer structures will be aligned and bonded together to form the complete seventeen layer woodpile accelerator structure.

  10. Fabrication and Characterization of Woodpile Structures for Direct Laser Acceleration

    SciTech Connect

    McGuinness, C.; Colby, E.; England, R.J.; Ng, J.; Noble, R.J.; Peralta, E.; Soong, K.; Spencer, J.; Walz, D.; Byer, R.L.

    2010-08-26

    An eight and nine layer three dimensional photonic crystal with a defect designed specifically for accelerator applications has been fabricated. The structures were fabricated using a combination of nanofabrication techniques, including low pressure chemical vapor deposition, optical lithography, and chemical mechanical polishing. Limits imposed by the optical lithography set the minimum feature size to 400 nm, corresponding to a structure with a bandgap centered at 4.26 {micro}m. Reflection spectroscopy reveal a peak in reflectivity about the predicted region, and good agreement with simulation is shown. The eight and nine layer structures will be aligned and bonded together to form the complete seventeen layer woodpile accelerator structure.

  11. High frequency planar accelerating structures for future linear colliders

    SciTech Connect

    Yu, D.; Ben-Menahem, S.; Wilson, P.; Miller, R.; Ruth, R.; Nassiri, A.

    1994-12-31

    Modern microfabrication techniques based on deep etch x-ray lithography, e.g., LIGA, can be used to produce large-aspect-ratio, metallic or dielectric, planar structures suitable for high-frequency RF acceleration of charged particle beams. Specifically, these techniques offer significant advantages over conventional manufacturing methods for future linear colliders (beyond NLC, the Next Linear Collider) because of several unique systems requirements. First, to have the required ac wall plug power within reasonable limits, such future linear colliders (5 TeV) must operate at high frequency (30 GHz). Secondly, luminosity requirements suggest the use of multi-bunch acceleration of electrons and positrons in the linear collider. Thirdly, in order to clearly discriminate physics events in the final interaction point at which electrons and positrons collide, it is required that secondary particle production from beamstrahlung be minimized. Flat electron and positron beams with a large aspect ratio will be beneficial in reducing beamstrahlung in the final focus region, but cause the beam to be more sensitive to wakefields in the vertical dimension. In principle, a flat beam can be accelerated in a planar structure with reduced wakefield in the vertical direction for the entire length of the accelerator. The LIGA process is particularly suitable for manufacturing miniaturized, planar, asymmetric cavities at high frequency. The main advantages of the LIGA process are fabrication of structures with high aspect ratio, small dimensional tolerances, and arbitrary mask shape (cross-section). Other advantages include mass-production with excellent repeatability and precision of up to an entire section of an accelerating structure consisting of a number of cells. It eliminates the need of tedious machining and brazing, for example, of individual disks and cups in conventional disk-loaded structures. Also, planar input/output couplers for the accelerating structure can be easily

  12. Experimental demonstration of dielectric structure based two beam acceleration.

    SciTech Connect

    Gai, W.; Conde, M. E.; Konecny, R.; Power, J. G.; Schoessow, P.; Sun, X.; Zou, P.

    2000-11-28

    We report on the experimental results of the dielectric based two beam accelerator (step-up transformer). By using a single high charge beam, we have generated and extracted a high power RF pulse from a 7.8 GHz primary dielectric structure and then subsequently transferred to a second accelerating structure with higher dielectric constant and smaller transverse dimensions. We have measured the energy change of a second (witness) beam passing through the acceleration stage. The measured gradient is >4 times the deceleration gradient. The detailed experiment of set-up and results of the measurements are dimmed. Future plans for the development of a 100 MeV demonstration accelerator based on this technique is presented.

  13. The structural response of a rail accelerator

    NASA Technical Reports Server (NTRS)

    Wang, S. Y.

    1983-01-01

    The transient response of a 0.4 by 0.6 cm rectangular bore rail accelerator was analyzed by a three dimensional finite element code. The copper rail deflected to a peak value of 0.08 mm in compression and then oscillated at an amplitude of 0.02 mm. Simultaneously the insulating side wall of glass fabric base, epoxy resin laminate (G-1o) was compressed to a peak value of 0.13 mm and rebounded to a steady state in extension. Projectile pinch or blowby due to the rail extension or compression, respectively, can be identified by examining the time history of the rail displacement. The effect of blowby was most significant at the side wall characterized by mm size displacement in compression. Dynamic stress calculations indicate that the G-10 supporting material behind the rail is subjected to over 21 MPa at which the G-10 could fail if the laminate was not carefully oriented. Results for a polycarbonate resin (Lexan) side wall show much larger displacements and stresses than for G-10. The tradeoff between the transparency of Lexan and the mechanical strength of G-10 for sidewall material is obvious. Displacement calculations from the modal method are smaller than the results from the direct integration method by almost an order of magnitude, because the high frequency effect is neglected.

  14. The structural response of a rail acceleration

    NASA Technical Reports Server (NTRS)

    Wang, S. Y.

    1984-01-01

    The transient response of a 0.4 by 0.6 cm rectangular bore rail accelerator was analyzed by a three dimensional finite element code. The copper rail deflected to a peak value of 0.08 mm in compression and then oscillated at an amplitude of 0.02 mm. Simultaneously the insulating side wall of glass fabric base, epoxy resin laminate (G-10) was compressed to a peak value of 0.13 mm and rebounded to a steady state in extension. Projectile pinch or blowby due to the rail extension or compression, respectively, can be identified by examining the time history of the rail displacement. The effect of blowby was most significant at the side wall characterized by mm size displacement in compression. Dynamic stress calculations indicate that the G-10 supporting material behind the rail is subjected to over 21 MPa at which the G-10 could fail if the laminate was not carefully oriented. Results for a polycarbonate resin (Lexan) side wall show much larger displacements and stresses than for G-10. The tradeoff between the transparency of Lexan and the mechanical strength of G-10 for sidewall material is obvious. Displacement calculations from the modal method are smaller than the results from the direct integration method by almost an order of magnitude, because the high frequency effect is neglected. Previously announced in STAR as N83-35412

  15. Rectangular Dielectric-loaded Structures for Achieving High Acceleration Gradients

    SciTech Connect

    Wang Changbiao; Yakovlev, V. P.; Marshall, T. C.; LaPointe, M. A.; Hirshfield, J. L.

    2006-11-27

    Rectangular dielectric-loaded structures are described that may sustain higher acceleration gradients than conventional all-metal structures with similar apertures. One structure is a test cavity designed to ascertain the breakdown limits of dielectrics, while a second structure could be the basis for a two-beam accelerator. CVD diamond is an attractive dielectric for a high-gradient structure, since the published DC breakdown limit for CVD diamond is {approx} 2 GV/m, although the limit has never been determined for RF fields. Here we present a design of a diamond-lined test cavity to measure the breakdown limit. The designed cavity operates at 34 GHz, where with 10-MW input power it is expected to produce an {approx}800 MV/m field on the diamond surface - provided breakdown is avoided. The two channel rectangular dielectric-loaded waveguide could be a two-beam accelerator structure, in which a drive beam is in one channel and an accelerated beam is in the other. The RF power produced by drive bunches in the drive channel is continuously coupled to the acceleration channel. The ratio of fields in the channels (transformer ratio) for the operating mode can be designed by adjusting the dimensions of the structure. An example of the two-channel structure is described, in which a train of five 3-nC drive bunches excites wake fields in the accelerator channel of up to 1.3 GV/m with a transformer ratio of 10 for the design mode.

  16. Gradient Limitations in Room Temperature and Superconducting Acceleration Structures

    SciTech Connect

    Solyak, N. A.

    2009-01-22

    Accelerating gradient is a key parameter of the accelerating structure in large linac facilities, like future Linear Collider. In room temperature accelerating structures the gradient is limited mostly by breakdown phenomena, caused by high surface electric fields or pulse surface heating. High power processing is a necessary procedure to clean surface and improve the gradient. In the best tested X-band structures the achieved gradient is exceed 100 MV/m in of {approx}200 ns pulses for breakdown rate of {approx}10{sup -7}. Gradient limit depends on number of factors and no one theory which can explain all sets of experimental results and predict gradient in new accelerating structure. In paper we briefly overview the recent experimental results of breakdown studies, progress in understanding of gradient limitations and scaling laws. Although superconducting rf technology has been adopted throughout the world for ILC, it has frequently been difficult to reach the predicted performance in these structures due to a number of factors: multipactoring, field emission, Q-slope, thermal breakdown. In paper we are discussing all these phenomena and the ways to increase accelerating gradient in SC cavity, which are a part of worldwide R and D program.

  17. Gradient limitations in room temperature and superconducting acceleration structures

    SciTech Connect

    Solyak, N.A.; /Fermilab

    2008-10-01

    Accelerating gradient is a key parameter of the accelerating structure in large linac facilities, like future Linear Collider. In room temperature accelerating structures the gradient is limited mostly by breakdown phenomena, caused by high surface electric fields or pulse surface heating. High power processing is a necessary procedure to clean surface and improve the gradient. In the best tested X-band structures the achieved gradient is exceed 100 MV/m in of {approx}200 ns pulses for breakdown rate of {approx} 10{sup -7}. Gradient limit depends on number of factors and no one theory which can explain all sets of experimental results and predict gradient in new accelerating structure. In paper we briefly overview the recent experimental results of breakdown studies, progress in understanding of gradient limitations and scaling laws. Although superconducting rf technology has been adopted throughout the world for ILC, it has frequently been difficult to reach the predicted performance in these structures due to a number of factors: multipactoring, field emission, Q-slope, thermal breakdown. In paper we are discussing all these phenomena and the ways to increase accelerating gradient in SC cavity, which are a part of worldwide R&D program.

  18. HEART Pathway Accelerated Diagnostic Protocol Implementation: Prospective Pre-Post Interrupted Time Series Design and Methods

    PubMed Central

    Wells, Brian J

    2016-01-01

    Background Most patients presenting to US Emergency Departments (ED) with chest pain are hospitalized for comprehensive testing. These evaluations cost the US health system >$10 billion annually, but have a diagnostic yield for acute coronary syndrome (ACS) of <10%. The history/ECG/age/risk factors/troponin (HEART) Pathway is an accelerated diagnostic protocol (ADP), designed to improve care for patients with acute chest pain by identifying patients for early ED discharge. Prior efficacy studies demonstrate that the HEART Pathway safely reduces cardiac testing, while maintaining an acceptably low adverse event rate. Objective The purpose of this study is to determine the effectiveness of HEART Pathway ADP implementation within a health system. Methods This controlled before-after study will accrue adult patients with acute chest pain, but without ST-segment elevation myocardial infarction on electrocardiogram for two years and is expected to include approximately 10,000 patients. Outcomes measures include hospitalization rate, objective cardiac testing rates (stress testing and angiography), length of stay, and rates of recurrent cardiac care for participants. Results In pilot data, the HEART Pathway decreased hospitalizations by 21%, decreased hospital length (median of 12 hour reduction), without increasing adverse events or recurrent care. At the writing of this paper, data has been collected on >5000 patient encounters. The HEART Pathway has been fully integrated into health system electronic medical records, providing real-time decision support to our providers. Conclusions We hypothesize that the HEART Pathway will safely reduce healthcare utilization. This study could provide a model for delivering high-value care to the 8-10 million US ED patients with acute chest pain each year. ClinicalTrial Clinicaltrials.gov NCT02056964; https://clinicaltrials.gov/ct2/show/NCT02056964 (Archived by WebCite at http://www.webcitation.org/6ccajsgyu) PMID:26800789

  19. Microbially-accelerated consolidation of oil sands tailings. Pathway II: solid phase biogeochemistry

    PubMed Central

    Siddique, Tariq; Kuznetsov, Petr; Kuznetsova, Alsu; Li, Carmen; Young, Rozlyn; Arocena, Joselito M.; Foght, Julia M.

    2014-01-01

    Consolidation of clay particles in aqueous tailings suspensions is a major obstacle to effective management of oil sands tailings ponds in northern Alberta, Canada. We have observed that microorganisms indigenous to the tailings ponds accelerate consolidation of mature fine tailings (MFT) during active metabolism by using two biogeochemical pathways. In Pathway I, microbes alter porewater chemistry to indirectly increase consolidation of MFT. Here, we describe Pathway II comprising significant, direct and complementary biogeochemical reactions with MFT mineral surfaces. An anaerobic microbial community comprising Bacteria (predominantly Clostridiales, Synergistaceae, and Desulfobulbaceae) and Archaea (Methanolinea/Methanoregula and Methanosaeta) transformed FeIII minerals in MFT to amorphous FeII minerals during methanogenic metabolism of an added organic substrate. Synchrotron analyses suggested that ferrihydrite (5Fe2O3. 9H2O) and goethite (α-FeOOH) were the dominant FeIII minerals in MFT. The formation of amorphous iron sulfide (FeS) and possibly green rust entrapped and masked electronegative clay surfaces in amended MFT. Both Pathways I and II reduced the surface charge potential (repulsive forces) of the clay particles in MFT, which aided aggregation of clays and formation of networks of pores, as visualized using cryo-scanning electron microscopy (SEM). These reactions facilitated the egress of porewater from MFT and increased consolidation of tailings solids. These results have large-scale implications for management and reclamation of oil sands tailings ponds, a burgeoning environmental issue for the public and government regulators. PMID:24711806

  20. Exploring ligand dissociation pathways from aminopeptidase N using random acceleration molecular dynamics simulation.

    PubMed

    Liu, Ya; Tu, GuoGang; Lai, XiaoPing; Kuang, BinHai; Li, ShaoHua

    2016-10-01

    Aminopeptidase N (APN) is a zinc-dependent ectopeptidase involved in cell proliferation, secretion, invasion, and angiogenesis, and is widely recognized as an important cancer target. However, the mechanisms whereby ligands leave the active site of APN remain unknown. Investigating ligand dissociation processes is quite difficult, both in classical simulation methods and in experimental approaches. In this study, random acceleration molecular dynamics (RAMD) simulation was used to investigate the potential dissociation pathways of ligand from APN. The results revealed three pathways (channels A, B and C) for ligand release. Channel A, which matches the hypothetical channel region, was the most preferred region for bestatin to dissociate from the enzyme, and is probably the major channel for the inner bound ligand. In addition, two alternative channels (channels B and C) were shown to be possible pathways for ligand egression. Meanwhile, we identified key residues controlling the dynamic features of APN channels. Identification of the dissociation routes will provide further mechanistic insights into APN, which will benefit the development of more promising APN inhibitors. Graphical Abstract The release pathways of bestatin inside active site of aminopeptidase N were simulated using RAMD simulation. PMID:27624165

  1. The signaling pathways by which the Fas/FasL system accelerates oocyte aging.

    PubMed

    Zhu, Jiang; Lin, Fei-Hu; Zhang, Jie; Lin, Juan; Li, Hong; Li, You-Wei; Tan, Xiu-Wen; Tan, Jing-He

    2016-02-01

    In spite of great efforts, the mechanisms for postovulatory oocyte aging are not fully understood. Although our previous work showed that the FasL/Fas signaling facilitated oocyte aging, the intra-oocyte signaling pathways are unknown. Furthermore, the mechanisms by which oxidative stress facilitates oocyte aging and the causal relationship between Ca2+ rises and caspase-3 activation and between the cell cycle and apoptosis during oocyte aging need detailed investigations. Our aim was to address these issues by studying the intra-oocyte signaling pathways for Fas/FasL to accelerate oocyte aging. The results indicated that sFasL released by cumulus cells activated Fas on the oocyte by increasing reactive oxygen species via activating NADPH oxidase. The activated Fas triggered Ca2+ release from the endoplasmic reticulum by activating phospholipase C-γ pathway and cytochrome c pathway. The cytoplasmic Ca2+ rises activated calcium/calmodulin-dependent protein kinase II (CaMKII) and caspase-3. While activated CaMKII increased oocyte susceptibility to activation by inactivating maturation-promoting factor (MPF) through cyclin B degradation, the activated caspase-3 facilitated further Ca2+releasing that activates more caspase-3 leading to oocyte fragmentation. Furthermore, caspase-3 activation and fragmentation were prevented in oocytes with a high MPF activity, suggesting that an oocyte must be in interphase to undergo apoptosis. PMID:26869336

  2. The signaling pathways by which the Fas/FasL system accelerates oocyte aging

    PubMed Central

    Zhu, Jiang; Lin, Fei-Hu; Zhang, Jie; Lin, Juan; Li, Hong; Li, You-Wei; Tan, Xiu-Wen; Tan, Jing-He

    2016-01-01

    In spite of great efforts, the mechanisms for postovulatory oocyte aging are not fully understood. Although our previous work showed that the FasL/Fas signaling facilitated oocyte aging, the intra-oocyte signaling pathways are unknown. Furthermore, the mechanisms by which oxidative stress facilitates oocyte aging and the causal relationship between Ca2+ rises and caspase-3 activation and between the cell cycle and apoptosis during oocyte aging need detailed investigations. Our aim was to address these issues by studying the intra-oocyte signaling pathways for Fas/FasL to accelerate oocyte aging. The results indicated that sFasL released by cumulus cells activated Fas on the oocyte by increasing reactive oxygen species via activating NADPH oxidase. The activated Fas triggered Ca2+ release from the endoplasmic reticulum by activating phospholipase C-γ pathway and cytochrome c pathway. The cytoplasmic Ca2+ rises activated calcium/calmodulin-dependent protein kinase II (CaMKII) and caspase-3. While activated CaMKII increased oocyte susceptibility to activation by inactivating maturation-promoting factor (MPF) through cyclin B degradation, the activated caspase-3 facilitated further Ca2+ releasing that activates more caspase-3 leading to oocyte fragmentation. Furthermore, caspase-3 activation and fragmentation were prevented in oocytes with a high MPF activity, suggesting that an oocyte must be in interphase to undergo apoptosis. PMID:26869336

  3. Grating-based deflecting, focusing, and diagnostic dielectric laser accelerator structures

    SciTech Connect

    Soong, Ken; Byer, R. L.; Colby, E. R.; England, R. J.; Peralta, E. A.

    2012-12-21

    Recent technological advances has made possible the realization of the first laser-driven particle accelerator structure to be fabricated lithographically. However, a complete particle accelerator requires more than just accelerating elements. In this paper, we present a grating-based design for three other quintessential accelerator elements: the focusing structure, the deflecting structure, and the diagnostic structure.

  4. Visual Outcome in Meningiomas Around Anterior Visual Pathways Treated With Linear Accelerator Fractionated Stereotactic Radiotherapy

    SciTech Connect

    Stiebel-Kalish, Hadas; Reich, Ehud; Gal, Lior; Rappaport, Zvi Harry; Nissim, Ouzi; Pfeffer, Raphael; Spiegelmann, Roberto

    2012-02-01

    Purpose: Meningiomas threatening the anterior visual pathways (AVPs) and not amenable for surgery are currently treated with multisession stereotactic radiotherapy. Stereotactic radiotherapy is available with a number of devices. The most ubiquitous include the gamma knife, CyberKnife, tomotherapy, and isocentric linear accelerator systems. The purpose of our study was to describe a case series of AVP meningiomas treated with linear accelerator fractionated stereotactic radiotherapy (FSRT) using the multiple, noncoplanar, dynamic conformal rotation paradigm and to compare the success and complication rates with those reported for other techniques. Patients and Methods: We included all patients with AVP meningiomas followed up at our neuro-ophthalmology unit for a minimum of 12 months after FSRT. We compared the details of the neuro-ophthalmologic examinations and tumor size before and after FSRT and at the end of follow-up. Results: Of 87 patients with AVP meningiomas, 17 had been referred for FSRT. Of the 17 patients, 16 completed >12 months of follow-up (mean 39). Of the 16 patients, 11 had undergone surgery before FSRT and 5 had undergone FSRT as first-line management. Tumor control was achieved in 14 of the 16 patients, with three meningiomas shrinking in size after RT. Two meningiomas progressed, one in an area that was outside the radiation field. The visual function had improved in 6 or stabilized in 8 of the 16 patients (88%) and worsened in 2 (12%). Conclusions: Linear accelerator fractionated RT using the multiple noncoplanar dynamic rotation conformal paradigm can be offered to patients with meningiomas that threaten the anterior visual pathways as an adjunct to surgery or as first-line treatment, with results comparable to those reported for other stereotactic RT techniques.

  5. Two-beam, Multi-mode Detuned Accelerating Structure

    SciTech Connect

    Kazakov, S. Yu.; Kuzikov, S. V.; Yakovlev, V. P.; Hirshfield, J. L.

    2009-01-22

    A two-beam accelerator structure is described having several novel features including all metal construction, no transfer structures required between the drive and accelerator channels, symmetric fields at the axes of each channel, RF micropulse widths on cavity irises that are less than half those for a conventional cavity at the same fundamental frequency by virtue of using several harmonically-related cavity modes, and a transformer ratio much greater than unity by the use of detuned cavities. Detuning is also shown to allow either parallel or anti-parallel directions for the drive and accelerated beams. A preliminary calculation for the dilution of emittance due to short-range wakes for drive beam parameters similar to those for CLIC shows this effect to be acceptably small.

  6. Acceleration of stable interface structure searching using a kriging approach

    NASA Astrophysics Data System (ADS)

    Kiyohara, Shin; Oda, Hiromi; Tsuda, Koji; Mizoguchi, Teruyasu

    2016-04-01

    Crystalline interfaces have a tremendous impact on the properties of materials. Determination of the atomic structure of the interface is crucial for a comprehensive understanding of the interface properties. Despite this importance, extensive calculation is necessary to determine even one interface structure. In this study, we apply a technique called kriging, borrowed from geostatistics, to accelerate the determination of the interface structure. The atomic structure of simplified coincidence-site lattice interfaces were determined using the kriging approach. Our approach successfully determined the most stable interface structure with an efficiency almost 2 orders of magnitude better than the traditional “brute force” approach.

  7. Dielectric-Lined High-Gradient Accelerator Structure

    SciTech Connect

    Jay L. Hirshfield

    2012-04-24

    Rectangular particle accelerator structures with internal planar dielectric elements have been studied, with a view towards devising structures with lower surface fields for a given accelerating field, as compared with structures without dielectrics. Success with this concept is expected to allow operation at higher accelerating gradients than otherwise on account of reduced breakdown probabilities. The project involves studies of RF breakdown on amorphous dielectrics in test cavities that could enable high-gradient structures to be built for a future multi-TeV collider. The aim is to determine what the limits are for RF fields at the surfaces of selected dielectrics, and the resulting acceleration gradient that could be achieved in a working structure. The dielectric of principal interest in this study is artificial CVD diamond, on account of its advertised high breakdown field ({approx}2 GV/m for dc), low loss tangent, and high thermal conductivity. Experimental studies at mm-wavelengths on materials and structures for achieving high acceleration gradient were based on the availability of the 34.3 GHz third-harmonic magnicon amplifier developed by Omega-P, and installed at the Yale University Beam Physics Laboratory. Peak power from the magnicon was measured to be about 20 MW in 0.5 {micro}s pulses, with a gain of 54 dB. Experiments for studying RF high-field effects on CVD diamond samples failed to show any evidence after more than 10{sup 5} RF pulses of RF breakdown up to a tangential surface field strength of 153 MV/m; studies at higher fields were not possible due to a degradation in magnicon performance. A rebuild of the tube is underway at this writing. Computed performance for a dielectric-loaded rectangular accelerator structure (DLA) shows highly competitive properties, as compared with an existing all-metal structure. For example, comparisons were made of a DLA structure having two planar CVD diamond elements with a all-metal CERN structure HDS

  8. Overexpression of protein O-fucosyltransferase 1 accelerates hepatocellular carcinoma progression via the Notch signaling pathway.

    PubMed

    Ma, Lijie; Dong, Pingping; Liu, Longzi; Gao, Qiang; Duan, Meng; Zhang, Si; Chen, She; Xue, Ruyi; Wang, Xiaoying

    2016-04-29

    Aberrant activation of Notch signaling frequently occurs in liver cancer, and is associated with liver malignancies. However, the mechanisms regulating pathologic Notch activation in hepatocellular carcinoma (HCC) remain unclear. Protein O-fucosyltransferase 1 (Pofut1) catalyzes the addition of O-linked fucose to the epidermal growth factor-like repeats of Notch. In the present study, we detected the expression of Pofut1 in 8 HCC cell lines and 253 human HCC tissues. We reported that Pofut1 was overexpressed in HCC cell lines and clinical HCC tissues, and Pofut1 overexpression clinically correlated with the unfavorable survival and high disease recurrence in HCC. The in vitro assay demonstrated that Pofut1 overexpression accelerated the cell proliferation and migration in HCC cells. Furthermore, Pofut1 overexpression promoted the binding of Notch ligand Dll1 to Notch receptor, and hence activated Notch signaling pathway in HCC cells, indicating that Pofut1 overexpression could be a reason for the aberrant activation of Notch signaling in HCC. Taken together, our findings indicated that an aberrant activated Pofut1-Notch pathway was involved in HCC progression, and blockage of this pathway could be a promising strategy for the therapy of HCC. PMID:27003260

  9. Two-Channel Rectangular Dielectric Wake Field Accelerator Structure Experiment

    SciTech Connect

    Sotnikov, G. V.; Marshall, T. C.; Shchelkunov, S. V.; Didenko, A.; Hirshfield, J. L.

    2009-01-22

    A design is presented for a two-channel 30-GHz rectangular dielectric wake field accelerator structure being built for experimental tests at Argonne National Laboratory (ANL). This structure allows for a transformer ratio T much greater than two, and permits continuous coupling of energy from drive bunches to accelerated bunches. It consists of three planar slabs of cordierite ceramic ({epsilon} = 4.7) supported within a rectangular copper block, forming a drive channel 12 mmx6 mm, and an accelerator channel 2 mmx6 mm. When driven by a 50 nC, 14 MeV single bunch available at ANL, theory predicts an acceleration field of 6 MeV/m, and T = 12.6. Inherent transverse wake forces introduce deflections and some distortion of bunch profiles during transit through the structure that are estimated to be tolerable. Additionally, a cylindrical two-channel DWFA is introduced which shares many advantages of the rectangular structure including high T, and the added virtue of axisymmetry that eliminates lowest-order transverse deflecting forces.

  10. The Organizational Culture and Structure of Accelerated Schools.

    ERIC Educational Resources Information Center

    Steaffens, Susan; McCarthy, Jane; Putney, LeAnn; Steinhoff, Carl

    This paper describes the organizational culture and structure of five accelerated schools in the Clark County School District in Nevada, focusing on the similarities and differences among these schools. The cultural aspects of the schools under comparison included the guiding principles, the central values, and the learning philosophy, whereas the…

  11. RF ACCELERATING STRUCTURE FOR THE MUON COOLING EXPERIMENT.

    SciTech Connect

    CORLETT,J.; GREEN,M.; LI,D.; HOLTKAMP,N.; MORETTI,A.; KIRK,H.G.; PALMER,R.B.; ZHAO,Y.; SUMMERS,D.

    1999-03-29

    The ionization cooling of muons requires longitudinal acceleration of the muons after scattering in a hydrogen target. In order to maximize the accelerating voltage, we propose using linear accelerating structures with cells bounded by thin beryllium metal foils. This produces an on-axis field equivalent to the maximum surface field, whereas with beam-pipes the accelerating field is approximately half that of the peak surface field in the cavity. The muons interact only weakly with the thin foils. A {pi}/2 interleaved cavity structure has been chosen, with alternate cells coupled together externally, and the two groups of cells fed in quadrature. At present they are considering an operating temperature of 77K to gain a factor of at least two in Q-value over room temperature. The authors describe the design of the {pi}/2 interleaved cavity structure, design of an alternative {pi}-mode open structure, preliminary experimental results from a low-power test cavity, and plans for high-power testing.

  12. Photonic Band Gap structures: A new approach to accelerator cavities

    SciTech Connect

    Kroll, N. |; Smith, D.R.; Schultz, S.

    1992-12-31

    We introduce a new accelerator cavity design based on Photonic Band Gap (PGB) structures. The PGB cavity consists of a two-dimensional periodic array of high dielectric, low loss cylinders with a single removal defect, bounded on top and bottom by conducting sheets. We present the results of both numerical simulations and experimental measurements on the PGB cavity.

  13. Improved input and output couplers for SC acceleration structure

    SciTech Connect

    Solyak, N.; Gonin, I.; Latina, A.; Lunin, A.; Poloubotko, V.; Yakovlev, V.; /Fermilab

    2009-04-01

    Different couplers are described that allow the reduction of both transverse wake potential and RF kick in the SC acceleration structure of ILC. A simple rotation of the couplers reducing the RF kick and transverse wake kick is discussed for both the main linac and bunch compressors, along with possible limitations of this method. Designs of a coupler unit are presented which preserve axial symmetry of the structure, and provide reduced both the RF kick and transverse wake field.

  14. Calculation of structural dynamic forces and stresses using mode acceleration

    NASA Technical Reports Server (NTRS)

    Blelloch, Paul

    1989-01-01

    While the standard mode acceleration formulation in structural dynamics has often been interpreted to suggest that the reason for improved convergence obtainable is that the dynamic correction factor is divided by the modal frequencies-squared, an alternative formulation is presented which clearly indicates that the only difference between mode acceleration and mode displacement data recovery is the addition of a static correction term. Attention is given to the advantages in numerical implementation associated with this alternative, as well as to an illustrative example.

  15. Woodpile Structure Fabrication for Photonic Crystal Laser Acceleration

    SciTech Connect

    McGuinness, C.; Colby, E.; England, R. J.; Noble, R. J.; Sears, C. M.; Siemann, R.; Spencer, J.; Waltz, D.; Byer, R. L.; Plettner, T.; Cowan, B. M.

    2009-01-22

    We describe initial steps at fabricating a dielectric photonic bandgap accelerator structure designed to operate at near IR frequencies. Such a structure operating at these frequencies requires extremely small, sub-micron sized features, forcing one to use lithographic means for fabrication. A process based upon lithographic equipment at the Stanford Nanofabrication Facility has been developed and a four layer test structure has been fabricated. Unexpected problems with the final etch step, and corresponding modifications to the process flow addressing these problems, are described. Spectroscopic measurements of the structure have been taken and are compared to simulations.

  16. Woodpile Structure Fabrication for Photonic Crystal Laser Acceleration

    SciTech Connect

    McGuinness, C.; Byer, R.L.; Colby, E.; Cowan, B.M.; England, R.J.; Noble, R.J.; Plettner, T.; Sears, C.M.; Siemann, R.; Spencer, J.; Waltz, D.; /SLAC

    2010-06-30

    We describe initial steps at fabricating a dielectric photonic bandgap accelerator structure designed to operate at near IR frequencies. Such a structure operating at these frequencies requires extremely small, sub-micron sized features, forcing one to use lithographic means for fabrication. A process based upon lithographic equipment at the Stanford Nanofabrication Facility has been developed and a four layer test structure has been fabricated. Unexpected problems with the final etch step, and corresponding modifications to the process flow addressing these problems, are described. Spectroscopic measurements of the structure have been taken and are compared to simulations.

  17. Simulations of Relativistic Collisionless Shocks: Shock Structure and Particle Acceleration

    SciTech Connect

    Spitkovsky, Anatoly; /KIPAC, Menlo Park

    2006-04-10

    We discuss 3D simulations of relativistic collisionless shocks in electron-positron pair plasmas using the particle-in-cell (PIC) method. The shock structure is mainly controlled by the shock's magnetization (''sigma'' parameter). We demonstrate how the structure of the shock varies as a function of sigma for perpendicular shocks. At low magnetizations the shock is mediated mainly by the Weibel instability which generates transient magnetic fields that can exceed the initial field. At larger magnetizations the shock is dominated by magnetic reflections. We demonstrate where the transition occurs and argue that it is impossible to have very low magnetization collisionless shocks in nature (in more than one spatial dimension). We further discuss the acceleration properties of these shocks, and show that higher magnetization perpendicular shocks do not efficiently accelerate nonthermal particles in 3D. Among other astrophysical applications, this may pose a restriction on the structure and composition of gamma-ray bursts and pulsar wind outflows.

  18. Comparison of the conditioning of high gradient accelerating structures

    NASA Astrophysics Data System (ADS)

    Degiovanni, Alberto; Wuensch, Walter; Giner Navarro, Jorge

    2016-03-01

    Accelerating gradients in excess of 100 MV /m , at very low breakdown rates, have been successfully achieved in numerous prototype CLIC accelerating structures. The conditioning and operational histories of several structures, tested at KEK and CERN, have been compared and there is clear evidence that the conditioning progresses with the number of rf pulses and not with the number of breakdowns. This observation opens the possibility that the optimum conditioning strategy, which minimizes the total number of breakdowns the structure is subject to without increasing conditioning time, may be to never exceed the breakdown rate target for operation. The result is also likely to have a strong impact on efforts to understand the physical mechanism underlying conditioning and may lead to preparation procedures which reduce conditioning time.

  19. Analysis and Design of Optical Bragg Acceleration Structures

    SciTech Connect

    Mizrahi, Amit; Schaechter, Levi

    2004-12-07

    It is demonstrated that a Bragg waveguide consisting of a series of dielectric layers may form an excellent optical acceleration structure. Confinement of the accelerating fields is achieved for both planar and cylindrical configurations by adjusting the first dielectric layer width. A typical structure made of Silica and Zirconia may support gradients of the order of 1 GV/m with an interaction impedance of a few hundreds of Ohms and with an energy velocity of less than 0.5c. An interaction impedance of about one thousand Ohms may be obtained by replacing the Zirconia with a (fictitious) material of {epsilon} = 25. Special attention is paid to the wake-field developing in such a structure. In case of a relatively small number of layers, a qualitative approach shows that the emitted power is inversely proportional to the number of micro-bunches. Quantitative results are given for a higher number of dielectric layers, showing that in comparison to a structure bounded by metallic walls, the emitted power is significantly smaller due to propagation bands allowing electromagnetic energy to escape. The efficiency of the acceleration structures is investigated and shown to have an optimum as a function of the vacuum core dimension.

  20. Kidney injury accelerates cystogenesis via pathways modulated by heme oxygenase and complement.

    PubMed

    Zhou, Juling; Ouyang, Xiaosen; Schoeb, Trenton R; Bolisetty, Subhashini; Cui, Xiangqin; Mrug, Sylvie; Yoder, Bradley K; Johnson, Martin R; Szalai, Alexander J; Mrug, Michal

    2012-07-01

    AKI accelerates cystogenesis. Because cystogenic mutations induce strong transcriptional responses similar to those seen after AKI, these responses may accelerate the progression of cystic renal disease. Here, we modulated the severity of the AKI-like response in Cys1(cpk/cpk) mice, a model that mimics autosomal recessive polycystic kidney disease. Specifically, we induced or inhibited activity of the renoprotective enzyme heme oxygenase (HO) and determined the effects on renal cystogenesis. We found that induction of HO attenuated both renal injury and the rate of cystogenesis, whereas inhibition of HO promoted cystogenesis. HO activity mediated the response of NFκB, which is a hallmark transcriptional feature common to both cystogenesis and AKI. Among the HO-modulated effects we measured, expression of complement component 3 (C3) strongly correlated with cystogenesis, a functionally relevant association as suggested by Cys1(cpk/cpk) mice with genetically induced C3 deficiency. Because both C3 deficiency and HO induction reduce cyst number and cyst areas, these two factors define an injury-stimulated cystogenic pathway that may provide therapeutic targets to slow the formation of new renal cysts and the growth of existing cysts. PMID:22518005

  1. Structural Organization of Enzymes of the Phenylacetate Catabolic Hybrid Pathway

    PubMed Central

    Grishin, Andrey M.; Cygler, Miroslaw

    2015-01-01

    Aromatic compounds are the second most abundant class of molecules on the earth and frequent environmental pollutants. They are difficult to metabolize due to an inert chemical structure, and of all living organisms, only microbes have evolved biochemical pathways that can open an aromatic ring and catabolize thus formed organic molecules. In bacterial genomes, the phenylacetate (PA) utilization pathway is abundant and represents the central route for degradation of a variety of organic compounds, whose degradation reactions converge at this pathway. The PA pathway is a hybrid pathway and combines the dual features of aerobic metabolism, i.e., usage of both oxygen to open the aromatic ring and of anaerobic metabolism—coenzyme A derivatization of PA. This allows the degradation process to be adapted to fluctuating oxygen conditions. In this review we focus on the structural and functional aspects of enzymes and their complexes involved in the PA degradation by the catabolic hybrid pathway. We discuss the ability of the central PaaABCE monooxygenase to reversibly oxygenate PA, the controlling mechanisms of epoxide concentration by the pathway enzymes, and the similarity of the PA utilization pathway to the benzoate utilization Box pathway and β-oxidation of fatty acids. PMID:26075354

  2. Epidermal stem cells (ESCs) accelerate diabetic wound healing via the Notch signalling pathway

    PubMed Central

    Yang, Rong-Hua; Qi, Shao-Hai; Shu, Bin; Ruan, Shu-Bin; Lin, Ze-Peng; Lin, Yan; Shen, Rui; Zhang, Feng-Gang; Chen, Xiao-Dong; Xie, Ju-Lin

    2016-01-01

    Chronic, non-healing wounds are a major complication of diabetes. Recently, various cell therapies have been reported for promotion of diabetic wound healing. Epidermal stem cells (ESCs) are considered a powerful tool for tissue therapy. However, the effect and the mechanism of the therapeutic properties of ESCs in the diabetic wound healing are unclear. Herein, to determine the ability of ESCs to diabetic wound healing, a dorsal skin defect in a streptozotocin (STZ)-induced diabetes mellitus (DM) mouse model was used. ESCs were isolated from mouse skin. We found that both the mRNA and protein levels of a Notch ligand Jagged1 (Jag1), Notch1 and Notch target gene Hairy Enhancer of Split-1 (Hes1) were significantly increased at the wound margins. In addition, we observed that Jag1 was high expressed in ESCs. Overexpression of Jag1 promotes ESCs migration, whereas knockdown Jag1 resulted in a significant reduction in ESCs migration in vitro. Importantly, Jag1 overexpression improves diabetic wound healing in vivo. These results provide evidence that ESCs accelerate diabetic wound healing via the Notch signalling pathway, and provide a promising potential for activation of the Notch pathway for the treatment of diabetic wound. PMID:27129289

  3. Epidermal stem cells (ESCs) accelerate diabetic wound healing via the Notch signalling pathway.

    PubMed

    Yang, Rong-Hua; Qi, Shao-Hai; Shu, Bin; Ruan, Shu-Bin; Lin, Ze-Peng; Lin, Yan; Shen, Rui; Zhang, Feng-Gang; Chen, Xiao-Dong; Xie, Ju-Lin

    2016-08-01

    Chronic, non-healing wounds are a major complication of diabetes. Recently, various cell therapies have been reported for promotion of diabetic wound healing. Epidermal stem cells (ESCs) are considered a powerful tool for tissue therapy. However, the effect and the mechanism of the therapeutic properties of ESCs in the diabetic wound healing are unclear. Herein, to determine the ability of ESCs to diabetic wound healing, a dorsal skin defect in a streptozotocin (STZ)-induced diabetes mellitus (DM) mouse model was used. ESCs were isolated from mouse skin. We found that both the mRNA and protein levels of a Notch ligand Jagged1 (Jag1), Notch1 and Notch target gene Hairy Enhancer of Split-1 (Hes1) were significantly increased at the wound margins. In addition, we observed that Jag1 was high expressed in ESCs. Overexpression of Jag1 promotes ESCs migration, whereas knockdown Jag1 resulted in a significant reduction in ESCs migration in vitro Importantly, Jag1 overexpression improves diabetic wound healing in vivo These results provide evidence that ESCs accelerate diabetic wound healing via the Notch signalling pathway, and provide a promising potential for activation of the Notch pathway for the treatment of diabetic wound. PMID:27129289

  4. Sulfated Glycosaminoglycans Accelerate Transthyretin Amyloidogenesis by Quaternary Structural Conversion†

    PubMed Central

    Bourgault, Steve; Solomon, James P.; Reixach, Natàlia; Kelly, Jeffery W.

    2011-01-01

    Glycosaminoglycans (GAGs), which are found in association with all extracellular amyloid deposits in humans, are known to accelerate the aggregation of various amyloidogenic proteins in vitro. However, the precise molecular mechanism(s) by which GAGs accelerate amyloidogenesis remains elusive. Herein, we show that sulfated GAGs, especially heparin, accelerate transthyretin (TTR) amyloidogenesis by quaternary structural conversion. The clustering of sulfate groups on heparin and its polymeric nature are essential features for accelerating TTR amyloidogenesis. Heparin does not influence TTR tetramer stability or TTR dissociation kinetics, nor does it alter the folded monomer – misfolded monomer equilibrium directly. Instead, heparin accelerates the conversion of preformed TTR oligomers into larger aggregates. The more rapid disappearance of monomeric TTR in the presence of heparin likely reflects the fact that the monomer–misfolded amyloidogenic monomer–oligomer–TTR fibril equilibria are all linked—a hypothesis that is strongly supported by the light scattering data. TTR aggregates prepared in presence of heparin showed a higher resistance to trypsin and proteinase K proteolysis and a lower exposure of hydrophobic side chains comprising hydrophobic clusters, suggesting an active role in amyloidogenesis. Our data suggest that heparin accelerates TTR aggregation by a scaffold-based mechanism, in which the sulfate groups comprising GAGs interact primarily with TTR oligomers through electrostatic interactions, concentrating and orienting the oligomers, facilitating the formation of higher molecular weight aggregates. This model raises the possibility that GAGs may play a protective role in human amyloid diseases by interacting with proteotoxic oligomers and promoting their association into less toxic amyloid fibrils. PMID:21194234

  5. Enhanced Ion Acceleration from Micro-tube Structured Targets

    NASA Astrophysics Data System (ADS)

    Snyder, Joseph; Ji, Liangliang; Akli, Kramer

    2015-11-01

    We present an enhanced ion acceleration method that leverages recent advancements in 3D printing for target fabrication. Using the three-dimensional Particle-in-Cell simulation code Virtual Laser-Plasma Lab (VLPL), we model the interaction of a short pulse, high intensity laser with a micro-tube plasma (MTP) structured target. When compared to flat foils, the MTP target enhances the maximum proton energy by a factor of about 4. The ion enhancement is attributed to two main factors: high energy electrons extracted from the tube structure enhancing the accelerating field and light intensification within the MTP target increasing the laser intensity at the location of the foil. We also present results on ion energy scaling with micro-tube diameter and incident laser pulse intensity. This work was supported by the AFOSR under contract No. FA9550-14-1-0085.

  6. Research and Development for Ultra-High Gradient Accelerator Structures

    NASA Astrophysics Data System (ADS)

    Tantawi, Sami G.; Dolgashev, Valery; Higashi, Yasuo; Spataro, Bruno

    2010-11-01

    Research on the basic physics of high-gradient, high frequency accelerator structures and the associated RF/microwave technology are essential for the future of discovery science, medicine and biology, energy and environment, and national security. We will review the state-of-the-art for the development of high gradient linear accelerators. We will present the research activities aimed at exploring the basic physics phenomenon of RF breakdown. We present the experimental results of a true systematic study in which the surface processing, geometry, and materials of the structures have been varied, one parameter at a time. The breakdown rate or alternatively, the probability of breakdown/pulse/meter has been recorded for different operating parameters. These statistical data reveal a strong dependence of breakdown probability on surface magnetic field, or alternatively on surface pulsed heating. This is in contrast to the classical view of electric field dependence.

  7. High-performance insulator structures for accelerator applications

    SciTech Connect

    Sampayan, S.E.; Caporaso, G.J.; Sanders, D.M.; Stoddard, R.D.; Trimble, D.O.; Elizondo, J.; Krogh, M.L.; Wieskamp, T.F.

    1997-05-01

    A new, high gradient insulator technology has been developed for accelerator systems. The concept involves the use of alternating layers of conductors and insulators with periods of order 1 mm or less. These structures perform many times better (about 1.5 to 4 times higher breakdown electric field) than conventional insulators in long pulse, short pulse, and alternating polarity applications. We describe our ongoing studies investigating the degradation of the breakdown electric field resulting from alternate fabrication techniques, the effect of gas pressure, the effect of the insulator-to-electrode interface gap spacing, and the performance of the insulator structure under bi-polar stress.

  8. Development of Dielectric-Based High Gradient Accelerating Structures

    SciTech Connect

    Jing, C.; Gai, W.; Konecny, R.; Power, J.; Liu, W.; Gold, S. H.; Kinkead, A. K.; Kanareykin, A.; Kazakov, S.

    2006-11-27

    High gradient accelerating structures using dielectric-lined circular waveguides have been developed for a number of years at Argonne National Laboratory. In this article, we first report the experimental results of high power rf testing on the quartz based Dielectric-Loaded Accelerating (DLA) structure carried out on Feb. 2006 at the Naval Research Laboratory. The motivation for this experiment is to test the multipactor effect on different materials under high power and high vacuum condition. Up to 12 MW pulsed rf went through the tube without breakdown. Multipactor appeared during the experiment but with different features compared to other materials like alumina. Photomultiplier Tube (PMT) measurements were introduced into the experiment for the first time to observe the light emission time and intensity. In the second part of this paper, ways to achieve higher gradient for DLA structures are proposed: 1) smaller ID and longitudinal gap free DLA structures to reduce multipactor and obtain higher gradient; 2) new coaxial type coupler to avoid dielectric gap and improve impedance matching; 3) double layered DLA structure to reduce rf loss and enhance shunt impedance as well.

  9. The coupled dipole modes of the NLC accelerator structure

    SciTech Connect

    Bane, K.L.F.; Gluckstern, R.; Holtkamp, N.

    1992-03-01

    The proposed accelerator cavity of the Next Linear Collider (NLC) is a disk-loaded structure composed of 200 cells, operating at 11.42 GHz. The proposed mode of operation is to accelerate bunches in trains of 10, with a bunch spacing of 42 cm. One problem is that one bunch in a train can excite transverse wakefields in the accelerator cavity which, in turn, can deflect following bunches and result in emittance growth. A method of curing this problem is to detune the transverse modes of the cavity. Beam dynamics simulations for the NLC have shown that by keeping the transverse wakefield at the positions of the nine trailing bunches at or below 1 MW/nC/m{sup 2} we can void emittance growth. Earlier, approximate calculations of the wakefields, which did not include the cell-to-cell coupling of the modes, have shown that by the proper Gaussian detuning the above level of cancellation can be achieved. A specific goal of this report is to see if this conclusion still holds when coupling is included in the calculation. Note that in this paper we focus on the modes belonging to the first dipole passband, which are the most important. A special feature of these modes in the detuned NLC cavity is that the cell-to-cell coupling changes sign somewhere in the middle of the structure.

  10. Blood glucose fluctuation accelerates renal injury involved to inhibit the AKT signaling pathway in diabetic rats.

    PubMed

    Ying, Changjiang; Zhou, Xiaoyan; Chang, Zhenzhen; Ling, Hongwei; Cheng, Xingbo; Li, Wei

    2016-07-01

    Blood glucose fluctuation is associated with diabetic nephropathy. However, the mechanism by which blood glucose fluctuation accelerates renal injury is not fully understood. The aim of the present study was to assess the effects of blood glucose fluctuation on diabetic nephropathy in rats and investigate its underlying mechanism. Diabetes in the rats was induced by a high sugar, high-fat diet, and a single dose of STZ (35 mg/kg)-injected intraperitoneally. Unstable blood sugar models were induced by subcutaneous insulin injection and intravenous glucose injection alternately. Body weight, glycosylated hemoglobin A1c (HbAlc), blood urea nitrogen (BUN), serum creatinine (Scr), and Creatinine clearance (Ccr) were assessed. T-SOD activity and MDA level were measured by assay kit. Change in renal tissue ultrastructure was observed by light microscopy and electron microscopy. Phosphorylated ser/thr protein kinase (p-AKT) (phosphor-Ser473), phosphorylated glycogen synthase kinase-3 beta (p-GSK-3β) (phosphor-Ser9), Bcl-2-associated X protein (BAX), B cell lymphoma/leukemia 2 (BCL-2), and cleaved-cysteinyl aspartate-specific proteinase-3 (caspase-3) levels were detected by immunohistochemistry and Western blot. We observed that BUN and Scr were increased in diabetic rats, and Ccr was decreased. Furthermore, blood glucose fluctuations could exacerbate the Ccr changes. Renal tissue ultrastructure was also seriously injured by glucose variability in diabetic rats. In addition, glucose fluctuation increased the oxidative stress of renal tissue. Moreover, fluctuating blood glucose decreased p-AKT level and BCL-2, and increased p-GSK-3β, BAX, cleaved-caspase-3 levels, and ratio of BAX/BCL-2 in the kidneys of diabetic rats. In conclusion, these results suggest that blood glucose fluctuation accelerated renal injury is due, at least in part to its oxidative stress promoting and inhibiting the AKT signaling pathway in diabetic rats. PMID:26860515

  11. Characteristics of large beam hole biperiodic accelerator structures

    SciTech Connect

    Chan, K.C.D.; Schriber, S.O.

    1985-10-01

    Large beam hole biperiodic rf structures operating at ..pi../2 mode with a/R of 0.31 and 0.51 have been studied. A larger beam hole reduces the amount of higher order mode excitations for modes with frequencies below the beam pipe cutoff frequency. Further reductions can be made by reducing the accelerating cell lengths. Endcell effects can be corrected by detuning the endcell; a residual field imbalance in the endcell remains because of the reduced coupling coefficient caused by field leakage into the beam pipe. The dependence of the coupling coefficient and cell frequency of a detuned cell has to be taken into account when a structure with a large tuning range is analyzed using a RLC equivalent circuit model. The reductions in the first neighbour coupling coefficient in the two structures with aperture radius 8 cm and 13 cm are respectively 0.023% and 0.056% per MHz increase in cell frequency. A comparison with a singly periodic structure operating in the ..pi.. mode shows that: The additional couplers in a biperiodic structure increase the energy loss slightly (9% in this case). Although the field flatness of a ..pi.. mode structure is worse than that of a ..pi../2 mode structure close to the design frequency, a singly periodic structure, which has no lossy couplers, may be preferred if a large tuning range is required. An 'idle' biperiodic structure can be detuned to reduce the Q and therefore cause less disturbance than a singly periodic structure.

  12. Development of a dual layered dielectric-loaded accelerating structure.

    SciTech Connect

    Gai, W.; Liu, W.; Jing, C.; Kanareykin, A.; Antipov, S.; Nenasheva, E.; Schoessow, P.; High Energy Physics; Euclid Techlabs, LLC; Illinois Inst. of Tech.; KEK

    2008-09-01

    Due to the high magnetic field-induced surface currents on its conducting sleeve, a conventional single layer Dielectric-Loaded Accelerating (DLA) structure exhibits a relatively high RF loss. One possible way to solve this problem is to use multilayered DLA structures. In these devices, the RF power attenuation is reduced by making use of the Bragg Fiber concept: the EM fields are well confined by multiple reflections from multiple dielectric layers. This paper presents the design of an X-band dual layer DLA structure as well as the results of bench tests of the device. We will also present results on the design, numerical modeling, and fabrication of structures for coupling RF into multilayer DLAs such as a novel TM{sub 03} mode launcher and a TM{sub 01}-TM{sub 03} mode converter using dielectric-loaded corrugated waveguide.

  13. Design of Accelerator Online Simulator Server Using Structured Data

    SciTech Connect

    Shen, Guobao; Chu, Chungming; Wu, Juhao; Kraimer, Martin; /Argonne

    2012-07-06

    Model based control plays an important role for a modern accelerator during beam commissioning, beam study, and even daily operation. With a realistic model, beam behaviour can be predicted and therefore effectively controlled. The approach used by most current high level application environments is to use a built-in simulation engine and feed a realistic model into that simulation engine. Instead of this traditional monolithic structure, a new approach using a client-server architecture is under development. An on-line simulator server is accessed via network accessible structured data. With this approach, a user can easily access multiple simulation codes. This paper describes the design, implementation, and current status of PVData, which defines the structured data, and PVAccess, which provides network access to the structured data.

  14. Sulphasalazine accelerates apoptosis in neutrophils exposed to immune complex: Role of caspase pathway.

    PubMed

    Bertolotto, M; Dallegri, F; Dapino, P; Quercioli, A; Pende, A; Ottonello, L; Montecucco, Fabrizio

    2009-11-01

    1. Neutrophils release several histotoxic molecules that cause tissue injury. Neutrophil apoptosis is a crucial process that governs the persistence of inflammatory disorders and tissue damage. Thus, in the present study, we investigated whether the anti-inflammatory drug sulphasalazine (SSZ) affects neutrophil apoptosis in the presence of insoluble immune complex (IC). 2. Neutrophils were obtained from healthy donors. Neutrophils were resuspended in incubation medium and incubated for 2-12 h with or without 10, 30 or 100 micromol/L SSZ and 25 microg/mL IC. In some experiments, cells were co-incubated with 20 micromol/L Z-IETD-fmk (a caspase 8 inhibitor) or 20 micromol/L Z-LEHD-fmk (a caspase 9 inhibitor). Apoptosis was evaluated morphologically on cytological preparations stained with May-Grünwald-Giemsa as well as by flow cytometry analysis of annexin V and propidium iodide staining. Caspase 3 activity was determined spectrophotometrically. 3. At 100 micromol/L, SSZ significantly accelerated IC-induced neutrophil apoptosis. Treatment of neutrophils with 20 micromol/L of the caspase 8 or 9 inhibitors Z-IETD-fmk or Z-LEHD-fmk, respectively, demonstrated that the SSZ-induced pro-apoptotic effect was mediated by a caspase 8- but not caspase 9-dependent pathway. The caspase 3 activity assay showed that treatment with 100 micromol/L SSZ increased caspase 3 activation. 4. In conclusion, the results of the present study indicate that it is possible that the molecular mechanism underlying SSZ protection against neutrophil-mediated tissue injury inflammatory disorders, such as rheumatoid arthritis and inflammatory bowel diseases, involves a caspase 8-dependent pathway. PMID:19473188

  15. Summary report of working group 3: High gradient and laser-structure based acceleration

    SciTech Connect

    Solyak, N.; Cowan, B.M.; /Tech-X, Boulder

    2010-01-01

    The charge for the working group on high gradient and laser-structure based acceleration was to assess the current challenges involved in developing an advanced accelerator based on electromagnetic structures, and survey state-of-the-art methods to address those challenges. The topics of more than 50 presentations in the working group covered a very broad range of issues, from ideas, theoretical models and simulations, to design and manufacturing of accelerating structures and, finally, experimental results on obtaining extremely high accelerating gradients in structures from conventional microwave frequency range up to THz and laser frequencies. Workshop discussion topics included advances in the understanding of the physics of breakdown and other phenomena, limiting high gradient performance of accelerating structures. New results presented in this workshop demonstrated significant progress in the fields of conventional vacuum structure-based acceleration, dielectric wakefield acceleration, and laser-structure acceleration.

  16. Sodium humate accelerates cutaneous wound healing by activating TGF-β/Smads signaling pathway in rats

    PubMed Central

    Ji, Yuanyuan; Zhang, Aijun; Chen, Xiaobin; Che, Xiaoxia; Zhou, Kai; Wang, Zhidong

    2016-01-01

    Sodium humate (HA-Na) has been topically used as a wound healing and anti-inflammatory agent in folk medicine. In the present study, HA-Na was investigated for cutaneous wound healing in Sprague–Dawley rats. HA-Na solution (1.0%, w/v) was topically administered to rats undergoing excision wound models. Healing was assessed with a recombinant bovine basic fibroblast growth factor for external use as positive control. Wound healing rates were calculated on Day 3, 6, 9, 14 and 21 after injury, and tissues were also harvested after the same intervals for histological analysis. In addition, tissue hydroxyproline levels were measured. Furthermore, mRNA levels and protein expressions of transforming growth factor-β1, 2, 3 (TGF-β1, 2, 3) were determined by RT-PCR and western blot. Protein expression levels of Smad-2, -3, -4 and -7 were also detected by western blot. Our study demonstrates that HA-Na has the capacity to promote wound healing in rats via accelerated wound contraction and increased hydroxyproline content. More importantly, these wound healing effects of HA-Na might be mediated through the TGF-β/Smad signaling pathway. HA-Na may be an effective agent for enhanced wound healing. PMID:27006897

  17. Prompt Gas Desorption Due to Ion Impact on Accelerator Structures

    NASA Astrophysics Data System (ADS)

    Vijay, Sagar; Seidl, Peter A.; Faltens, Andy; Lidia, Steven M.

    2011-10-01

    The repetition rate and peak current of high intensity ion accelerators for inertial fusion or other applications may be limited under certain conditions by the desorption of gas molecules and atoms due to stray ions striking the accelerator structure. We have measured the prompt yield of atoms in close proximity to the point of impact of the ions on a surface. Using the 300-keV, K+ ion beam of the Neutralized Drift Compression Experiment (NDCX-I), ions strike a metal target in a 5-10 microsecond bunch. The collector of a Bayert-Alpert style ionization gauge is used to detect the local pressure burst several centimeters away. Pressure transients are observed on a micro-second time scale due to the initial burst of desorbed gas, and on a much longer (~1 second) timescale, corresponding to the equilibration of the pressure after many ``bounces'' of atoms in the vacuum chamber. We report on these time dependent pressure measurements, modeling of the pressure transient, and implications for high-intensity ion accelerators. Work performed under auspices of U.S. DOE by LBNL under Contract DE-AC02-05CH1123.

  18. Multipactor discharge in a dielectric-loaded accelerating structure

    NASA Astrophysics Data System (ADS)

    Wu, L.; Ang, L. K.

    2007-01-01

    This paper presents a Monte-Carlo model to explain the multipactor discharge and its high-power absorption in a dielectric-loaded accelerating (DLA) structure reported recently [J. G. Power et al., Phys. Rev. Lett. 92, 164801 (2004)]. Susceptibility diagrams are constructed. Dynamic calculations for beam loading and its power absorption by the multipactor discharge are performed. It is found that the fraction of power absorbed by multipactor discharge at saturation is much larger than the case of a simple rf window, and it is sensitive to the incident power, which confirms the prior experimental results. This enhanced power absorption is due to the fact that the length of a DLA structure is much larger than the radius of the structure. A resonant condition of a maximum growth region has also been determined numerically and analytically. The difference between the resonant condition and saturation (due to beam loading) is clarified.

  19. Numerical studies of multipactor in dielectric-loaded accelerator structures

    NASA Astrophysics Data System (ADS)

    Sinitsyn, Oleksandr; Nusinovich, Gregory; Antonsen, Thomas

    2009-11-01

    Multipactor (MP) is known as the avalanche growth of the number of secondary electrons emitted from a solid surface exposed to an rf electric field under vacuum conditions. MP may occur in various microwave and rf systems such as microwave tubes, rf windows and launchers, accelerating structures, and rf satellite payloads. In this work we present results of MP analysis in dielectric-loaded accelerator (DLA) structures. The starting point of our work was experimental and theoretical studies of DLA structures jointly done by Argonne National Laboratory and Naval Research Laboratory (J. G. Power et al., Phys. Rev. Lett. 92, 164801 (2004); J. G. Power et al., AIP Conf. Proc. 877, 362 (2006)). In the theoretical model developed during those studies the space-charge field due to the total number of particles is taken into account as a parameter. We perform our studies using a self-consistent approach with the help of time-dependent two-dimensional code developed at the University of Maryland (O. V. Sinitsyn et al., Phys. Plasmas 16, 073102 (2009)). Results include analysis of MP evolution at an early stage, detailed studies of individual electron trajectories, analysis of MP onset time under various conditions and comparison of some results with the experimental data.

  20. Low-Field Accelerator Structure Couplers and Design Techniques

    SciTech Connect

    Nantista, C

    2004-07-29

    Recent experience with X-band accelerator structure development has shown the rf input coupler to be the region most prone to rf breakdown and degradation, effectively limiting the operating gradient. A major factor in this appears to be high magnetic fields at the sharp edges of the coupling irises. As a first response to this problem, couplers with rounded and thickened iris horns have been employed and successfully tested at high power. To further reduce fields for higher power flow, conceptually new coupler designs have been developed, in which power is coupled through the broadwall of the feed waveguide, rather than through terminating irises. A 'mode launcher' coupler, which launches the TM{sub 01} mode in circular waveguide before coupling through a matching cell into the main structure, has been tested with great success. With peak surface fields below those in the body of the structure, this coupler represented a break-through in the NLC structure program. The design of this coupler and of variations which use beamline space more efficiently are described here. The latter include a coupler in which power passes directly through an iris in the broad wall of the rectangular waveguide into a matching cell, also successfully implemented, and a variation which makes the waveguide itself an accelerating cell. The authors also discuss in some detail a couple of techniques for matching such couplers to travelling-wave structures using a field solver. The first exploits the cell number independence of a travelling-wave match, and the second optimizes using the fields of an internally driven structure.

  1. Thyrotropin-releasing hormone accelerates fetal mouse lung ultrastructural maturation via stimulation of extra thyroidal pathway.

    PubMed

    Ansari, M A; Demello, D E; Polk, D H; Devaskar, U P

    1997-11-01

    ) showed increased numbers of lamellar bodies per type II cell, an increase in the alveolar/parenchymal ratio, larger air spaces, thinner alveolar septa, presence of tubular myelin, and increased numbers of air-blood barriers. We conclude that the effect of TRH in accelerating fetal mouse lung maturation is at least in part mediated via stimulation of extra thyroidal pathways. PMID:9357947

  2. Studying Radiation Damage in Structural Materials by Using Ion Accelerators

    NASA Astrophysics Data System (ADS)

    Hosemann, Peter

    2011-02-01

    Radiation damage in structural materials is of major concern and a limiting factor for a wide range of engineering and scientific applications, including nuclear power production, medical applications, or components for scientific radiation sources. The usefulness of these applications is largely limited by the damage a material can sustain in the extreme environments of radiation, temperature, stress, and fatigue, over long periods of time. Although a wide range of materials has been extensively studied in nuclear reactors and neutron spallation sources since the beginning of the nuclear age, ion beam irradiations using particle accelerators are a more cost-effective alternative to study radiation damage in materials in a rather short period of time, allowing researchers to gain fundamental insights into the damage processes and to estimate the property changes due to irradiation. However, the comparison of results gained from ion beam irradiation, large-scale neutron irradiation, and a variety of experimental setups is not straightforward, and several effects have to be taken into account. It is the intention of this article to introduce the reader to the basic phenomena taking place and to point out the differences between classic reactor irradiations and ion irradiations. It will also provide an assessment of how accelerator-based ion beam irradiation is used today to gain insight into the damage in structural materials for large-scale engineering applications.

  3. DNA damage tolerance by recombination: Molecular pathways and DNA structures.

    PubMed

    Branzei, Dana; Szakal, Barnabas

    2016-08-01

    Replication perturbations activate DNA damage tolerance (DDT) pathways, which are crucial to promote replication completion and to prevent fork breakage, a leading cause of genome instability. One mode of DDT uses translesion synthesis polymerases, which however can also introduce mutations. The other DDT mode involves recombination-mediated mechanisms, which are generally accurate. DDT occurs prevalently postreplicatively, but in certain situations homologous recombination is needed to restart forks. Fork reversal can function to stabilize stalled forks, but may also promote error-prone outcome when used for fork restart. Recent years have witnessed important advances in our understanding of the mechanisms and DNA structures that mediate recombination-mediated damage-bypass and highlighted principles that regulate DDT pathway choice locally and temporally. In this review we summarize the current knowledge and paradoxes on recombination-mediated DDT pathways and their workings, discuss how the intermediate DNA structures may influence genome integrity, and outline key open questions for future research. PMID:27236213

  4. Observation of Wakefield Suppression in a Photonic-Band-Gap Accelerator Structure

    DOE PAGESBeta

    Simakov, Evgenya I.; Arsenyev, Sergey A.; Buechler, Cynthia E.; Edwards, Randall L.; Romero, William P.; Conde, Manoel; Ha, Gwanghui; Power, John G.; Wisniewski, Eric E.; Jing, Chunguang

    2016-02-10

    We report experimental observation of higher order mode (HOM) wakefield suppression in a room-temperature traveling-wave photonic band gap (PBG) accelerating structure at 11.700 GHz. It has been long recognized that PBG structures have potential for reducing long-range wakefields in accelerators. The first ever demonstration of acceleration in a room-temperature PBG structure was conducted in 2005. Since then, the importance of PBG accelerator research has been recognized by many institutions. However, the full experimental characterization of the wakefield spectrum and demonstration of wakefield suppression when the accelerating structure is excited by an electron beam has not been performed to date. Wemore » conducted an experiment at the Argonne Wakefield Accelerator (AWA) test facility and observed wakefields excited by a single high charge electron bunch when it passes through a PBG accelerator structure. Lastly, excellent HOM suppression properties of the PBG accelerator were demonstrated in the beam test.« less

  5. Observation of Wakefield Suppression in a Photonic-Band-Gap Accelerator Structure.

    PubMed

    Simakov, Evgenya I; Arsenyev, Sergey A; Buechler, Cynthia E; Edwards, Randall L; Romero, William P; Conde, Manoel; Ha, Gwanghui; Power, John G; Wisniewski, Eric E; Jing, Chunguang

    2016-02-12

    We report experimental observation of higher order mode (HOM) wakefield suppression in a room-temperature traveling-wave photonic-band-gap (PBG) accelerating structure at 11.700 GHz. It has been long recognized that PBG structures have the potential for reducing long-range wakefields in accelerators. The first ever demonstration of acceleration in a room-temperature PBG structure was conducted in 2005. Since then, the importance of PBG accelerator research has been recognized by many institutions. However, the full experimental characterization of the wakefield spectrum and demonstration of wakefield suppression when the accelerating structure is excited by an electron beam has not been performed to date. We conducted an experiment at the Argonne Wakefield Accelerator test facility and observed wakefields excited by a single high charge electron bunch when it passes through a PBG accelerator structure. Excellent HOM suppression properties of the PBG accelerator were demonstrated in the beam test. PMID:26918995

  6. Reduced-Order Simulation of Large Accelerator Structures

    NASA Astrophysics Data System (ADS)

    Cooke, Simon

    2007-11-01

    Simulating electromagnetic waves inside finite periodic or almost periodic three-dimensional structures is important to research in linear particle acceleration, high power microwave generation, and photonic bandgap structures. While eigenmodes of periodic structures can be determined from analysis of a single unit cell, based on Floquet theory, the general case of aperiodic structures, with defects or non-uniform properties, typically requires 3D electromagnetic simulation of the entire structure. When the structure is large and high accuracy is necessary this can require high-performance computing techniques to obtain even a few eigenmodes [1]. To confront this problem, we describe an efficient, field-based algorithm that can accurately determine the complete eigenmode spectrum for extended aperiodic structures, up to some chosen frequency limit. The new method combines domain decomposition with a non-traditional, dual eigenmode representation of the fields local to each cell of the structure. Two related boundary value eigenproblems are solved numerically in each cell, with (a) electrically shielded, and (b) magnetically shielded interfaces, to determine a combined set of basis fields. By using the dual solutions in our field representation we accurately represent both the electric and magnetic surface currents that mediate coupling at the interfaces between adjacent cells. The solution is uniformly convergent, so that typically only a few modes are used in each cell. We present results from 3D simulations that demonstrate the speed and low computational needs of the algorithm. [1] Z. Li, et al, Nucl. Instrum. Methods Phys. Res., Sect. A 558 (2006), 168-174.

  7. Conceptual design of an L-band recirculating superconducting traveling wave accelerating structure for ILC

    SciTech Connect

    Avrakhov, P.; Kanareykin, A.; Liu, Z.; Kazakov, S.; Solyak, N.; Yakovlev, V.; Gai, W.; /Argonne

    2007-06-01

    With this paper, we propose the conceptual design of a traveling wave accelerating structure for a superconducting accelerator. The overall goal is to study a traveling wave (TW) superconducting (SC) accelerating structure for ILC that allows an increased accelerating gradient and, therefore reduction of the length of the collider. The conceptual studies were performed in order to optimize the acceleration structure design by minimizing the surface fields inside the cavity of the structure, to make the design compatible with existing technology, and to determine the maximum achievable gain in the accelerating gradient. The proposed solution considers RF feedback system redirecting the accelerating wave that passed through the superconducting traveling wave acceleration (STWA) section back to the input of the accelerating structure. The STWA structure has more cells per unit length than a TESLA structure but provides an accelerating gradient higher than a TESLA structure, consequently reducing the cost. In this paper, the STWA cell shape optimization, coupler cell design and feedback waveguide solution are considered. We also discuss the field flatness in the superconducting TW structure, the HOM modes and multipactor performance have been studied as well. The proposed TW structure design gives an overall 46% gain over the SW ILC structure if the 10 m long TW structure is employed.

  8. RF properties of periodic accelerating structures for linear colliders

    SciTech Connect

    Wang, J.W.

    1989-07-01

    With the advent of the SLAC electron-positron linear collider (SLC) in the 100 GeV center-of-mass energy range, research and development work on even higher energy machines of this type has started in several laboratories in the United States, Europe, the Soviet Union and Japan. These linear colliders appear to provide the only promising approach to studying e/sup /plus//e/sup /minus// physics at center-of-mass energies approaching 1 TeV. This thesis concerns itself with the study of radio frequency properties of periodic accelerating structures for linear colliders and their interaction with bunched beams. The topics that have been investigated are: experimental measurements of the energy loss of single bunches to longitudinal modes in two types of structures, using an equivalent signal on a coaxial wire to simulate the beam; a method of canceling the energy spread created within a single bunch by longitudinal wakefields, through appropriate shaping of the longitudinal charge distribution of the bunch; derivation of the complete transient beam-loading equation for a train of bunches passing through a constant-gradient accelerator section, with application to the calculation and minimization of multi-bunch energy spread; detailed study of field emission and radio frequency breakdown in disk-loaded structures at S-, C- and X-band frequencies under extremely high-gradient conditions, with special attention to thermal effects, radiation, sparking, emission of gases, surface damage through explosive emission and its possible control through RF-gas processing. 53 refs., 49 figs., 9 tabs.

  9. Comparative study of medium damped and detuned linear accelerator structures

    SciTech Connect

    Jean-Francois Ostiguy et al.

    2001-08-22

    Long range wakefields are a serious concern for a future linear collider based on room temperature accelerating structures. They can be suppressed either by detuning and or local damping or with some combination of both strategies. Detuning relies on precisely phasing the contributions of the dipole modes excited by the passage of a single bunch. This is accomplished by controlling individual mode frequencies, a process which dictates individual cell dimensional tolerances. Each mode must be excited with the correct strength; this in turn, determines cell-to-cell alignment tolerances. In contrast, in a locally damped structure, the modes are attenuated at the cell level. Clearly, mode frequencies and relative excitation become less critical in that context; mechanical fabrication tolerances can be relaxed. While local damping is ideal from the stand-point of long range wakefield suppression, this comes at the cost of reducing the shunt impedance and possibly unacceptable localized heating. Recently, the Medium Damped Structure (MDS), a compromise between detuning and local damping, has generated some interest. In this paper, we compare a hypothetical MDS to the NLC Rounded Damped Detuned Structure (RDDS) and investigate possible advantages from the standpoint fabrication tolerances and their relation to beam stability and emittance preservation.

  10. Exploring inhibitor release pathways in histone deacetylases using random acceleration molecular dynamics simulations.

    PubMed

    Kalyaanamoorthy, Subha; Chen, Yi-Ping Phoebe

    2012-02-27

    Molecular channel exploration perseveres to be the prominent solution for eliciting structure and accessibility of active site and other internal spaces of macromolecules. The volume and silhouette characterization of these channels provides answers for the issues of substrate access and ligand swapping between the obscured active site and the exterior of the protein. Histone deacetylases (HDACs) are metal-dependent enzymes that are involved in the cell growth, cell cycle regulation, and progression, and their deregulations have been linked with different types of cancers. Hence HDACs, especially the class I family, are widely recognized as the important cancer targets, and the characterizations of their structures and functions have been of special interest in cancer drug discovery. The class I HDACs are known to possess two different protein channels, an 11 Å and a 14 Å (named channels A and B1, respectively), of which the former is a ligand or substrate occupying tunnel that leads to the buried active site zinc ion and the latter is speculated to be involved in product release. In this work, we have carried out random acceleration molecular dynamics (RAMD) simulations coupled with the classical molecular dynamics to explore the release of the ligand, N-(2-aminophenyl) benzamide (LLX) from the active sites of the recently solved X-ray crystal structure of HDAC2 and the computationally modeled HDAC1 proteins. The RAMD simulations identified significant structural and dynamic features of the HDAC channels, especially the key 'gate-keeping' amino acid residues that control these channels and the ligand release events. Further, this study identified a novel and unique channel B2, a subchannel from channel B1, in the HDAC1 protein structure. The roles of water molecules in the LLX release from the HDAC1 and HDAC2 enzymes are also discussed. Such structural and dynamic properties of the HDAC protein channels that govern the ligand escape reactions will provide

  11. Nicotinamide Riboside Kinase Structures Reveal New Pathways to NAD+

    PubMed Central

    Bogan, Katrina L; Belenky, Peter; Wojcik, Marzena; Seidle, Heather F; Nedyalkova, Lyudmila; Yang, Tianle; Sauve, Anthony A; Park, Hee-Won; Brenner, Charles

    2007-01-01

    The eukaryotic nicotinamide riboside kinase (Nrk) pathway, which is induced in response to nerve damage and promotes replicative life span in yeast, converts nicotinamide riboside to nicotinamide adenine dinucleotide (NAD+) by phosphorylation and adenylylation. Crystal structures of human Nrk1 bound to nucleoside and nucleotide substrates and products revealed an enzyme structurally similar to Rossmann fold metabolite kinases and allowed the identification of active site residues, which were shown to be essential for human Nrk1 and Nrk2 activity in vivo. Although the structures account for the 500-fold discrimination between nicotinamide riboside and pyrimidine nucleosides, no enzyme feature was identified to recognize the distinctive carboxamide group of nicotinamide riboside. Indeed, nicotinic acid riboside is a specific substrate of human Nrk enzymes and is utilized in yeast in a novel biosynthetic pathway that depends on Nrk and NAD+ synthetase. Additionally, nicotinic acid riboside is utilized in vivo by Urh1, Pnp1, and Preiss-Handler salvage. Thus, crystal structures of Nrk1 led to the identification of new pathways to NAD+. PMID:17914902

  12. Nicotinamide riboside kinase structures reveal new pathways to NAD+.

    PubMed

    Tempel, Wolfram; Rabeh, Wael M; Bogan, Katrina L; Belenky, Peter; Wojcik, Marzena; Seidle, Heather F; Nedyalkova, Lyudmila; Yang, Tianle; Sauve, Anthony A; Park, Hee-Won; Brenner, Charles

    2007-10-01

    The eukaryotic nicotinamide riboside kinase (Nrk) pathway, which is induced in response to nerve damage and promotes replicative life span in yeast, converts nicotinamide riboside to nicotinamide adenine dinucleotide (NAD+) by phosphorylation and adenylylation. Crystal structures of human Nrk1 bound to nucleoside and nucleotide substrates and products revealed an enzyme structurally similar to Rossmann fold metabolite kinases and allowed the identification of active site residues, which were shown to be essential for human Nrk1 and Nrk2 activity in vivo. Although the structures account for the 500-fold discrimination between nicotinamide riboside and pyrimidine nucleosides, no enzyme feature was identified to recognize the distinctive carboxamide group of nicotinamide riboside. Indeed, nicotinic acid riboside is a specific substrate of human Nrk enzymes and is utilized in yeast in a novel biosynthetic pathway that depends on Nrk and NAD+ synthetase. Additionally, nicotinic acid riboside is utilized in vivo by Urh1, Pnp1, and Preiss-Handler salvage. Thus, crystal structures of Nrk1 led to the identification of new pathways to NAD+. PMID:17914902

  13. Particle acceleration and turbulence in cosmic Ray shocks: possible pathways beyond the Bohm limit

    NASA Astrophysics Data System (ADS)

    Malkov, M. A.; Diamond, P. H.

    2007-08-01

    Diffusive shock acceleration is discussed in terms of its potential to accelerate cosmic rays (CR) to 1018 eV (beyond the ``knee,'' as observations suggest) and in terms of the related observational signatures (spectral features). One idea to reach this energy is to resonantly generate a turbulent magnetic field via accelerated particles much in excess of the background field. We identify difficulties with this scenario and suggest two separate mechanisms that can work in concert with one another leading to a significant acceleration enhancement. The first mechanism is based on a nonlinear modification of the flow ahead of the shock supported by particles already accelerated to some specific (knee) momentum. The particles gain energy by bouncing off converging magnetic irregularities frozen into the flow in the shock precursor and not so much by re-crossing the shock itself. The acceleration rate is determined by the gradient of the flow velocity and turns out to be formally independent of the particle mean free path. The velocity gradient is set by the knee-particles. The acceleration rate of particles above the knee does not decrease with energy, unlike in the linear acceleration regime. The knee (spectrum steepening) forms because particles above it are effectively confined to the shock only if they are within limited domains in the momentum space, while other particles fall into ``loss-islands'', similar to the ``loss-cone'' of magnetic traps. This also maintains the steep velocity gradient and high acceleration rate. The second mechanism is based on the generation of Alfven waves at the gyroradius scale at the background field level, with a subsequent transfer to longer scales via interaction with strong acoustic turbulence in the shock precursor. The acoustic turbulence in turn, may be generated by Drury instability or by parametric instability of the Alfven (A) waves.

  14. A THz Coaxial Two-Channel Dielectric Wakefield Structure for High Gradient Acceleration

    SciTech Connect

    Marshall, T. C.; Sotnikov, G. V.; Hirshfield, J. L.

    2010-11-04

    A coaxial two-channel dielectric wakefield structure is examined for use as a high gradient accelerator. A THz design, having radius {approx}1 mm, is shown to provide GeV/m--level acceleration gradient, high transformer ratio, and stable accelerated bunch motion when excited by a stable-moving 5-GeV 6-nC annular drive bunch.

  15. A THz Coaxial Two-Channel Dielectric Wakefield Structure for High Gradient Acceleration

    NASA Astrophysics Data System (ADS)

    Marshall, T. C.; Sotnikov, G. V.; Hirshfield, J. L.

    2010-11-01

    A coaxial two-channel dielectric wakefield structure is examined for use as a high gradient accelerator. A THz design, having radius ˜1 mm, is shown to provide GeV/m—level acceleration gradient, high transformer ratio, and stable accelerated bunch motion when excited by a stable-moving 5-GeV 6-nC annular drive bunch.

  16. THE SPECIFIC ACCELERATION RATE IN LOOP-STRUCTURED SOLAR FLARES-IMPLICATIONS FOR ELECTRON ACCELERATION MODELS

    SciTech Connect

    Guo, Jingnan; Emslie, A. Gordon; Piana, Michele E-mail: piana@dima.unige.it

    2013-03-20

    We analyze electron flux maps based on RHESSI hard X-ray imaging spectroscopy data for a number of extended coronal-loop flare events. For each event, we determine the variation of the characteristic loop length L with electron energy E, and we fit this observed behavior with models that incorporate an extended acceleration region and an exterior 'propagation' region, and which may include collisional modification of the accelerated electron spectrum inside the acceleration region. The models are characterized by two parameters: the plasma density n in, and the longitudinal extent L{sub 0} of, the acceleration region. Determination of the best-fit values of these parameters permits inference of the volume that encompasses the acceleration region and of the total number of particles within it. It is then straightforward to compute values for the emission filling factor and for the specific acceleration rate (electrons s{sup -1} per ambient electron above a chosen reference energy). For the 24 events studied, the range of inferred filling factors is consistent with a value of unity. The inferred mean value of the specific acceleration rate above E{sub 0} = 20 keV is {approx}10{sup -2} s{sup -1}, with a 1{sigma} spread of about a half-order-of-magnitude above and below this value. We compare these values with the predictions of several models, including acceleration by large-scale, weak (sub-Dreicer) fields, by strong (super-Dreicer) electric fields in a reconnecting current sheet, and by stochastic acceleration processes.

  17. Comparisons of radio frequency technology for superconducting accelerating structures

    NASA Astrophysics Data System (ADS)

    Kimber, Andrew J.

    2015-12-01

    Since the introduction of radiofrequency (RF) accelerating cavities, normal conducting as well as superconducting, there has been a need to drive them with RF power. At first glance, the function of an RF drive system may seem simple and straightforward, but this belies subtleties that greatly affect the performance of the cavity itself, diminishing efforts in perfecting techniques in design and manufacture. It can also contribute to a significant portion of the initial capital and ongoing running costs of a facility, maintenance labor, downtime and future expenditure as the system ages. The RF `system', should be thought of as just that, the entire collection of components from wall plug to cavity. Following this integrated approach will enable the system to meet or exceed its design goals. This paper seeks to review the current state of RF technology for superconducting structures and to compare these technologies, looking at what has traditionally been used, developments that have enabled higher efficiencies and higher reliabilities as well as looking towards future technologies. It will concentrate on superconducting applications, but much of the narrative is equally applicable to normal conducting structures as well.

  18. Development of a chemical structure comparison method for integrated analysis of chemical and genomic information in the metabolic pathways.

    PubMed

    Hattori, Masahiro; Okuno, Yasushi; Goto, Susumu; Kanehisa, Minoru

    2003-10-01

    Cellular functions result from intricate networks of molecular interactions, which involve not only proteins and nucleic acids but also small chemical compounds. Here we present an efficient algorithm for comparing two chemical structures of compounds, where the chemical structure is treated as a graph consisting of atoms as nodes and covalent bonds as edges. On the basis of the concept of functional groups, 68 atom types (node types) are defined for carbon, nitrogen, oxygen, and other atomic species with different environments, which has enabled detection of biochemically meaningful features. Maximal common subgraphs of two graphs can be found by searching for maximal cliques in the association graph, and we have introduced heuristics to accelerate the clique finding and to detect optimal local matches (simply connected common subgraphs). Our procedure was applied to the comparison and clustering of 9383 compounds, mostly metabolic compounds, in the KEGG/LIGAND database. The largest clusters of similar compounds were related to carbohydrates, and the clusters corresponded well to the categorization of pathways as represented by the KEGG pathway map numbers. When each pathway map was examined in more detail, finer clusters could be identified corresponding to subpathways or pathway modules containing continuous sets of reaction steps. Furthermore, it was found that the pathway modules identified by similar compound structures sometimes overlap with the pathway modules identified by genomic contexts, namely, by operon structures of enzyme genes. PMID:14505407

  19. Design study of double-layer beam trajectory accelerator based on the Rhodotron structure

    NASA Astrophysics Data System (ADS)

    Jabbari, Iraj; Poursaleh, Ali Mohammad; Khalafi, Hossein

    2016-08-01

    In this paper, the conceptual design of a new structure of industrial electron accelerator based on the Rhodotron accelerator is presented and its properties are compared with those of Rhodotron-TT200 accelerator. The main goal of this study was to reduce the power of RF system of accelerator at the same output electron beam energy. The main difference between the new accelerator structure with the Rhodotron accelerator is the length of the coaxial cavity that is equal to the wavelength at the resonant frequency. Also two sets of bending magnets were used around the acceleration cavity in two layers. In the new structure, the beam crosses several times in the coaxial cavity by the bending magnets around the cavity at the first layer and then is transferred to the second layer using the central bending magnet. The acceleration process in the second layer is similar to the first layer. Hence, the energy of the electron beam will be doubled. The electrical power consumption of the RF system and magnet system were calculated and simulated for the new accelerator structure and TT200. Comparing the calculated and simulated results of the TT200 with those of experimental results revealed good agreement. The results showed that the overall electrical power consumption of the new accelerator structure was less than that of the TT200 at the same energy and power of the electron beam. As such, the electrical efficiency of the new structure was improved.

  20. Accelerating Adverse Outcome Pathway (AOP) development via computationally predicted AOP networks

    EPA Science Inventory

    The Adverse Outcome Pathway (AOP) framework is increasingly being adopted as a tool for organizing and summarizing the mechanistic information connecting molecular perturbations by environmental stressors with adverse outcomes relevant for ecological and human health outcomes. Ho...

  1. Get with the Program ... and Finish It: Building Guided Pathways to Accelerate Student Completion

    ERIC Educational Resources Information Center

    Jenkins, Davis; Cho, Sung-Woo

    2013-01-01

    In this chapter, we describe efforts by growing number of colleges and universities to redesign academic programs and support services to create "guided pathways" designed to increase the rate at which students enter and complete a program of study.

  2. Durability analysis of composite structures using the accelerated testing methodology

    NASA Astrophysics Data System (ADS)

    Kuraishi, Akira

    The applications of composite materials are increasing significantly due to their excellent properties and design flexibility, and composite materials have completely replaced conventional metals in several applications. However, much larger opportunities will be likely to occur when physical bases for durability characterization become established. Polymeric composite materials are in general viscoelastic, and their stiffness and strength depend on temperature and loading rate. These effects play an important role in the long-term durability of the composite materials, and therefore it is important to develop a durability analysis method for composite structures that considers these effects. The present approach is based on three components, a new accelerated material characterization methodology, statistical analysis of this methodology, and conventional design tools tailored for the temperature and loading rate dependence. The material characterization methodology uses series of short-term tests at elevated temperatures to predict life for wide ranges of temperature and loading conditions. This methodology is based on the empirical relation between the effects of temperature and loading rate on the stiffness and strength of polymeric composite materials. The statistical analysis allows us to create the confidence interval of the prediction, which is essential in generating the design allowables. Common design tools such as failure criteria and cumulative damage laws can be tailored to consider the temperature and loading rate dependence. These components are integrated into the proposed durability analysis and design method for composite structures. The durability design of a composite rotor for the flywheel energy storage system is shown as an example. This example demonstrates that the proposed design method is not significantly different from conventional designs in terms of complexity and required effort.

  3. Solution structure of ligands involved in purine salvage pathway.

    PubMed

    Karnawat, Vishakha; Puranik, Mrinalini

    2015-12-01

    Analogues of intermediates involved in the purine salvage pathway can be exploited as potential drug molecules against enzymes of protozoan parasites. To develop such analogues we need knowledge of the solution structures, predominant tautomer at physiological pH and protonation-state of the corresponding natural ligand. In this regard, we have employed ultraviolet resonance Raman spectroscopy (UVRR) in combination with density functional theory (DFT) to study the solution structures of two relatively unexplored intermediates, 6-phosphoryl IMP (6-pIMP) and succinyl adenosine-5'-monophosphate (sAMP), of purine salvage pathway. These molecules are intermediates in a two step enzymatic process that converts inosine-5'-monpophosphate (IMP) to adenosine-5'-monophosphate (AMP). Experimental data on the molecular structure of these ligands is lacking. We report UVRR spectra of these two ligands, obtained at an excitation wavelength of 260 nm. Using isotope induced shifts and DFT calculations we assigned observed spectra to computed normal modes. We find that sAMP exists as neutral species at physiological pH and the predominant tautomer in solution bears proton at N10 position of purine ring. Though transient in solution, 6-pIMP is captured in the enzyme-bound form. This work provides the structural information of these ligands in solution state at physiological pH. We further compare these structures with the structures of AMP and IMP. Despite the presence of similar purine rings in AMP and sAMP, their UVRR spectra are found to be very different. Similarly, though the purine ring in 6-pIMP resembles that of IMP, UVRR spectra of the two molecules are distinct. These differences in the vibrational spectra provide direct information on the effects of exocyclic groups on the skeletal structures of these molecules. Our results identify key bands in the vibrational spectra of these ligands which may serve as markers of hydrogen bonding interactions upon binding to the active

  4. Two Channel Dielectric-Lined Rectangular High Transformer Ratio Accelerator Structure Experiment

    SciTech Connect

    Shchelkunov, S. V.; LaPointe, M. A.; Hirshfield, J. L.; Marshall, T. C.; Sotnikov, G.; Gai, Wei; Conde, M.; Power, J.; Mihalcea, D.

    2010-11-04

    Current status of a two-channel cm-scale rectangular dielectric lined wakefield accelerator structure is described. This structure is installed at the Argonne Wakefield Accelerator facility (AWA), and is presently being evaluated. The device has a transformer ratio of {approx}12.5:1. When driven by a {approx}50 nC single drive bunch it is expected to obtain {approx}6 MV/m acceleration gradient. Related issues are discussed.

  5. Development of High-Gradient Dielectric Laser-Driven Particle Accelerator Structures

    SciTech Connect

    Byer, Robert L.

    2013-11-07

    The thrust of Stanford's program is to conduct research on high-gradient dielectric accelerator structures driven with high repetition-rate, tabletop infrared lasers. The close collaboration between Stanford and SLAC (Stanford Linear Accelerator Center) is critical to the success of this project, because it provides a unique environment where prototype dielectric accelerator structures can be rapidly fabricated and tested with a relativistic electron beam.

  6. Design of RF Feed System for Standing-Wave Accelerator Structures

    SciTech Connect

    Neilson, J.; Tantawi, S.; Dolgashev, V.; /SLAC

    2012-05-25

    We are investigating a standing wave accelerator structure that uses a rf feed to each individual cell. This approach minimizes rf power flow and electromagnetic energy absorbed by an rf breakdown. The objective of this work is a robust high-gradient (above 100 MV/m) X-band accelerator structure.

  7. The trabecular meshwork outflow pathways: structural and functional aspects.

    PubMed

    Tamm, Ernst R

    2009-04-01

    The major drainage structures for aqueous humor (AH) are the conventional or trabecular outflow pathways, which are comprised of the trabecular meshwork (made up by the uveal and corneoscleral meshworks), the juxtacanalicular connective tissue (JCT), the endothelial lining of Schlemm's canal (SC), the collecting channels and the aqueous veins. The trabecular meshwork (TM) outflow pathways are critical in providing resistance to AH outflow and in generating intraocular pressure (IOP). Outflow resistance in the TM outflow pathways increases with age and primary open-angle glaucoma. Uveal and corneoscleral meshworks form connective tissue lamellae or beams that are covered by flat TM cells which rest on a basal lamina. TM cells in the JCT are surrounded by fibrillar elements of the extracellular matrix (ECM) to form a loose connective tissue. In contrast to the other parts of the TM, JCT cells and ECM fibrils do not form lamellae, but are arranged more irregularly. SC inner wall endothelial cells form giant vacuoles in response to AH flow, as well as intracellular and paracellular pores. In addition, minipores that are covered with a diaphragm are observed. There is considerable evidence that normal AH outflow resistance resides in the inner wall region of SC, which is formed by the JCT and SC inner wall endothelium. Modulation of TM cell tone by the action of their actomyosin system affects TM outflow resistance. In addition, the architecture of the TM outflow pathways and consequently outflow resistance appear to be modulated by contraction of ciliary muscle and scleral spur cells. The scleral spur contains axons that innervate scleral spur cells or that have the ultrastructural characteristics of mechanosensory nerve endings. PMID:19239914

  8. Simulation Studies of the Dielectric Grating as an Accelerating and Focusing Structure

    SciTech Connect

    Soong, Ken; Peralta, E.A.; Byer, R.L.; Colby, E.; /SLAC

    2011-08-12

    A grating-based design is a promising candidate for a laser-driven dielectric accelerator. Through simulations, we show the merits of a readily fabricated grating structure as an accelerating component. Additionally, we show that with a small design perturbation, the accelerating component can be converted into a focusing structure. The understanding of these two components is critical in the successful development of any complete accelerator. The concept of accelerating electrons with the tremendous electric fields found in lasers has been proposed for decades. However, until recently the realization of such an accelerator was not technologically feasible. Recent advances in the semiconductor industry, as well as advances in laser technology, have now made laser-driven dielectric accelerators imminent. The grating-based accelerator is one proposed design for a dielectric laser-driven accelerator. This design, which was introduced by Plettner, consists of a pair of opposing transparent binary gratings, illustrated in Fig. 1. The teeth of the gratings serve as a phase mask, ensuring a phase synchronicity between the electromagnetic field and the moving particles. The current grating accelerator design has the drive laser incident perpendicular to the substrate, which poses a laser-structure alignment complication. The next iteration of grating structure fabrication seeks to monolithically create an array of grating structures by etching the grating's vacuum channel into a fused silica wafer. With this method it is possible to have the drive laser confined to the plane of the wafer, thus ensuring alignment of the laser-and-structure, the two grating halves, and subsequent accelerator components. There has been previous work using 2-dimensional finite difference time domain (2D-FDTD) calculations to evaluate the performance of the grating accelerator structure. However, this work approximates the grating as an infinite structure and does not accurately model a

  9. Female puberty acceleration by male odour in mice: neural pathway and behavioural consequences.

    PubMed

    Jouhanneau, Mélanie; Szymanski, Laura A; Keller, Matthieu

    2014-08-01

    In female mice, exposure to male chemosignals results in early puberty onset characterized by advanced vaginal opening and higher uterine weight. Evidence suggests that the male chemosignals responsible for acceleration of female puberty are androgen-dependent, but not all of the compounds that contribute to puberty acceleration have been identified. The male chemosignals are primarily detected and processed by the vomeronasal system including the vomeronasal organ, the accessory olfactory bulb and the medial amygdala. By contrast, the mechanism by which this olfactory information is integrated in the hypothalamus is poorly understood. In this context, the recent identification of the neuropeptide kisspeptin as a gatekeeper of puberty onset may provide a good candidate neuropeptide system for the transmission of chemosensory information to the gonadotrope axis. PMID:25109972

  10. Accelerate!

    PubMed

    Kotter, John P

    2012-11-01

    The old ways of setting and implementing strategy are failing us, writes the author of Leading Change, in part because we can no longer keep up with the pace of change. Organizational leaders are torn between trying to stay ahead of increasingly fierce competition and needing to deliver this year's results. Although traditional hierarchies and managerial processes--the components of a company's "operating system"--can meet the daily demands of running an enterprise, they are rarely equipped to identify important hazards quickly, formulate creative strategic initiatives nimbly, and implement them speedily. The solution Kotter offers is a second system--an agile, networklike structure--that operates in concert with the first to create a dual operating system. In such a system the hierarchy can hand off the pursuit of big strategic initiatives to the strategy network, freeing itself to focus on incremental changes to improve efficiency. The network is populated by employees from all levels of the organization, giving it organizational knowledge, relationships, credibility, and influence. It can Liberate information from silos with ease. It has a dynamic structure free of bureaucratic layers, permitting a level of individualism, creativity, and innovation beyond the reach of any hierarchy. The network's core is a guiding coalition that represents each level and department in the hierarchy, with a broad range of skills. Its drivers are members of a "volunteer army" who are energized by and committed to the coalition's vividly formulated, high-stakes vision and strategy. Kotter has helped eight organizations, public and private, build dual operating systems over the past three years. He predicts that such systems will lead to long-term success in the 21st century--for shareholders, customers, employees, and companies themselves. PMID:23155997

  11. Accelerating structure design and fabrication for KIPT and PAL XFEL

    NASA Astrophysics Data System (ADS)

    Hou, Mi; He, Xiang; Pei, Shi-Lun; Na, Bin; Chi, Yun-Long

    2015-05-01

    ANL (Argonne National Laboratory) and the National Science Center “Kharkov Institute of Physics Technology” (NSC KIPT, Kharkov, Ukraine) jointly propose to design and build a 100 MeV/100 kW linear accelerator which will be used to drive the neutron source subcritical assembly. The linac has almost finished assembly in KIPT by a team from the Institute of High Energy Physics (IHEP, Beijing, China). The design and measurement result of the accelerating system of the linac will be described in this paper.

  12. Auroral ion acceleration from lower hybrid solitary structures: A summary of sounding rocket observations

    NASA Astrophysics Data System (ADS)

    Lynch, K. A.; Arnoldy, R. L.; Kintner, P. M.; Schuck, P.; Bonnell, J. W.; Coffey, V.

    In this paper we present a review of sounding rocket observations of the ion acceleration seen in nightside auroral zone lower hybrid solitary structures. Observations from Topaz3, Amicist, and Phaze2 are presented on various spatial scales, including the two-point measurements of the Amicist mission. From this collection of observations we will demonstrate the following characteristics of transverse acceleration of ions (TAI) in lower hybrid solitary structures (LHSS). The ion acceleration process is narrowly confined to 90° pitch angle, in spatially confined regions of up to a few hundred meters across B. The acceleration process does not affect the thermal core of the ambient distribution and does not directly create a measurable effect on the ambient ion population outside the LHSS themselves. This precludes observation with these data of any nonlinear feedback between the ion acceleration and the existence or evolution of the density irregularities on which these LHSS events grow. Within the LHSS region the acceleration process creates a high-energy tail beginning at a few times the thermal ion speed. The ion acceleration events are closely associated with localized wave events. Accelerated ions bursts are also seen without a concurrent observation of a localized wave event, for two possible reasons. In some cases, the pitch angles of the accelerated tail ions are elevated above perpendicular; that is, the acceleration occurred below the observer and the mirror force has begun to act upon the distribution, moving it upward from the source. In other cases, the accelerated ion structure is spatially larger than the wave event structure, and the observation catches only the ion event. The occurrence rate of these ion acceleration events is related to the ambient environment in two ways: its altitude dependence can be modeled with the parameter B2/ne, and it is highest in regions of intense VLF activity. The cumulative ion outflow from these LHSS TAI is

  13. Development and low power test of the parallel coupled accelerating structure

    NASA Astrophysics Data System (ADS)

    Andrianov, A. V.; Barnyakov, A. M.; Levichev, A. E.; Maltseva, M. V.; Nikiforov, D. A.; Samoylov, S. L.

    2016-06-01

    The parallel coupled accelerating structure with a frequency of 2856 MHz is described. The cavities and the power propagation efficiencies are calculated. The results of the structure tuning are described. Analysis of the measurements and comparison with calculated data are provided. On the base of the measured parameters of the parallel coupled accelerating structure the beam energy under different meanings of the current is predicted.

  14. Road Map for Studies to Produce Consistent and High Performance SRF Accelerator Structures

    SciTech Connect

    Ganapati Rao Myneni; John F. O’Hanlon

    2007-06-20

    Superconducting Radio Frequency (SRF) accelerator structures made from high purity niobium are becoming the technological choice for a large number of future accelerators and energy recovery LINAC’s (ERL). Most of the presently planned accelerators and ERL requirements will be met with some effort by the current SRF technology where accelerating gradients of about 20 MV/m can be produced on a routine basis with an acceptable yield. However, the XFEL at DESY and the planned ILC require acceleration gradients more than 28 MV/m and 35 MV/m respectively. At the recent ILC meeting at Snowmass (2005) concern was expressed regarding the wide spread in the achieved accelerator gradients and the relatively low yields. For obtaining accelerating gradients of 35 MV/m in SRF accelerator structures consistently, a deeper understanding of the causes for the spread has to be gained and advances have to be made in many scientific and high technology fields, including materials, surface and vacuum sciences, application of reliable processes and procedures, which provide contamination –free surfaces and avoid recontamination and cryogenics related technologies. In this contribution a road map for studies needed to produce consistent and high performance SRF accelerator structures from the needed materials development to clean and non-recontaminating processes and procedures will be presented.

  15. Superconducting accelerating structures for very low velocity ion beams

    SciTech Connect

    Xu, J.; Shepard, K.W.; Ostroumov, P.N.; Fuerst, J.D.; Waldschmidt, G.; Gonin, I.V.; /Fermilab

    2008-01-01

    This paper presents designs for four types of very-low-velocity superconducting accelerating cavity capable of providing several MV of accelerating potential per cavity, and suitable for particle velocities in the range 0.006 < v/c < 0.06. Superconducting TEM-class cavities have been widely applied to CW acceleration of ion beams. SC linacs can be formed as an array of independently-phased cavities, enabling a variable velocity profile to maximize the output energy for each of a number of different ion species. Several laboratories in the US and Europe are planning exotic beam facilities based on SC linacs. The cavity designs presented here are intended for the front-end of such linacs, particularly for the post-acceleration of rare isotopes of low charge state. Several types of SC cavities have been developed recently to cover particle velocities above 0.06c. Superconducting four-gap quarter-wave resonators for velocities 0.008 < {beta} = v/c < 0.05 were developed about two decades ago and have been successfully operated at the ATLAS SC linac at Argonne National Laboratory. Since that time, progress in simulation tools, cavity fabrication and processing have increased SC cavity gradients by a factor of 3-4. This paper applies these tools to optimize the design of a four-gap quarter-wave resonator for exotic beam facilities and other low-velocity applications.

  16. Numerically optimized structures for dielectric asymmetric dual-grating laser accelerators

    SciTech Connect

    Aimidula, A.; Bake, M. A.; Wan, F.; Xie, B. S.; Welsch, C. P.; Xia, G.; Mete, O.; Uesaka, M.; Matsumura, Y.; Yoshida, M.; Koyama, K.

    2014-02-15

    Optical scale dielectric structures are promising candidates to realize future compact, low cost particle accelerators, since they can sustain high acceleration gradients in the range of GeV/m. Here, we present numerical simulation results for a dielectric asymmetric dual-grating accelerator. It was found that the asymmetric dual-grating structures can efficiently modify the laser field to synchronize it with relativistic electrons, therefore increasing the average acceleration gradient by ∼10% in comparison to symmetric structures. The optimum pillar height which was determined by simulation agrees well with that estimated analytically. The effect of the initial kinetic energy of injected electrons on the acceleration gradient is also discussed. Finally, the required laser parameters were calculated analytically and a suitable laser is proposed as energy source.

  17. Experimental demonstration of wakefield effects in a THz planar diamond accelerating structure

    SciTech Connect

    Antipov, S.; Jing, C.; Kanareykin, A.; Butler, J. E.; Yakimenko, V.; Fedurin, M.; Kusche, K.; Gai, W.

    2012-03-26

    We have directly measured THz wakefields induced by a subpicosecond, intense relativistic electron bunch in a diamond loaded accelerating structure via the wakefield acceleration method. We present here the beam test results from the diamond based structure. Diamond has been chosen for its high breakdown threshold and unique thermoconductive properties. Fields produced by a leading (drive) beam were used to accelerate a trailing (witness) electron bunch, which followed the drive bunch at a variable distance. The energy gain of a witness bunch as a function of its separation from the drive bunch describes the time structure of the generated wakefield.

  18. SLAB symmetric dielectric micron scale structures for high gradient electron acceleration.

    SciTech Connect

    Rosenzweig, J. B.; Schoessow, P. V.

    1999-06-12

    A class of planar microstructure is proposed which provide high accelerating gradients when excited by an infrared laser pulse. These structures consist of parallel dielectric slabs separated by a vacuum gap; the dielectric or the outer surface coating are spatially modulated at the laser wavelength along the beam direction so as to support a standing wave accelerating field. We have developed numerical and analytic models of the accelerating mode fields in the structure. We show an optimized coupling scheme such that this mode is excited resonantly with a large quality factor. The status of planned experiments on fabricating and measuring these planar structures will be described.

  19. The development of a TESLA recirculator with superconducting accelerating structures in Ukraine

    NASA Astrophysics Data System (ADS)

    Guk, I. S.; Dovbnya, A. N.

    2008-12-01

    The recirculator project, which is to be built at the National Science Center, Kharkov Institute of Physics and Technology (NSC KIPT), is presented. The basic solutions incorporated in the design are given. The TESLA superconducting section is chosen as the accelerating structure of an accelerating complex.

  20. e-/e+ Accelerating Structure with Cyclic Variation of Azimuth Asymmetry

    SciTech Connect

    Krasnykh, A.; /SLAC

    2007-03-05

    A classical electron/positron accelerating structure is a disk-loaded cylindrical waveguide. The accelerator structure here has azimuth symmetry. The proposed structure contains a disk-loaded cylindrical waveguide where there is a periodical change of RF-field vs. azimuth. The modulation deforms the rf-field in such a manner that the accelerated particles undergo transverse focusing forces. The new class of accelerator structures covers the initial part of e+/e- linacs where a bunch is not rigid and additional transverse focusing fields are necessary. We discuss a bunch formation with a high transverse aspect ratio in the proposed structure and particularly in the photoinjector part of a linac.

  1. Glucocorticoids accelerate maturation of the heme pathway in fetal liver through effects on transcription and DNA methylation

    PubMed Central

    Khulan, Batbayar; Liu, Lincoln; Rose, Catherine M.; Boyle, Ashley K.; Manning, Jonathan R.; Drake, Amanda J.

    2016-01-01

    ABSTRACT Glucocorticoids are widely used in threatened preterm labor to promote maturation in many organ systems in preterm babies and have significant beneficial effects on morbidity and mortality. We performed transcriptional profiling in fetal liver in a rat model of prenatal glucocorticoid exposure and identified marked gene expression changes in heme biosynthesis, utilization, and degradation pathways in late gestation. These changes in gene expression associated with alterations in DNA methylation and with a reduction in hepatic heme concentration. There were no persistent differences in gene expression, DNA methylation, or heme concentrations at 4 weeks of age, suggesting that these are transient effects. Our findings are consistent with glucocorticoid-induced accelerated maturation of the haematopoietic system and support the hypothesis that glucocorticoids can drive changes in gene expression in association with alterations in DNA methylation. PMID:26889791

  2. Microbially-accelerated consolidation of oil sands tailings. Pathway I: changes in porewater chemistry

    PubMed Central

    Siddique, Tariq; Kuznetsov, Petr; Kuznetsova, Alsu; Arkell, Nicholas; Young, Rozlyn; Li, Carmen; Guigard, Selma; Underwood, Eleisha; Foght, Julia M.

    2014-01-01

    Dispersed clay particles in mine tailings and soft sediments remain suspended for decades, hindering consolidation and challenging effective management of these aqueous slurries. Current geotechnical engineering models of self-weight consolidation of tailings do not consider microbial contribution to sediment behavior, however, here we show that microorganisms indigenous to oil sands tailings change the porewater chemistry and accelerate consolidation of oil sands tailings. A companion paper describes the role of microbes in alteration of clay chemistry in tailings. Microbial metabolism in mature fine tailings (MFT) amended with an organic substrate (hydrolyzed canola meal) produced methane (CH4) and carbon dioxide (CO2). Dissolution of biogenic CO2 lowered the pH of amended MFT to pH 6.4 vs. unamended MFT (pH 7.7). About 12% more porewater was recovered from amended than unamended MFT during 2 months of active microbial metabolism, concomitant with consolidation of tailings. The lower pH in amended MFT dissolved carbonate minerals, thereby releasing divalent cations including calcium (Ca2+) and magnesium (Mg2+) and increasing bicarbonate (HCO−3) in porewater. The higher concentrations increased the ionic strength of the porewater, in turn reducing the thickness of the diffuse double layer (DDL) of clay particles by reducing the surface charge potential (repulsive forces) of the clay particles. The combination of these processes accelerated consolidation of oil sands tailings. In addition, ebullition of biogenic gases created transient physical channels for release of porewater. In contrast, saturating the MFT with non-biogenic CO2 had little effect on consolidation. These results have significant implications for management and reclamation of oil sands tailings ponds and broad importance in anaerobic environments such as contaminated harbors and estuaries containing soft sediments rich in clays and organics. PMID:24711805

  3. Linear particle accelerator with seal structure between electrodes and insulators

    DOEpatents

    Broadhurst, John H.

    1989-01-01

    An electrostatic linear accelerator includes an electrode stack comprised of primary electrodes formed or Kovar and supported by annular glass insulators having the same thermal expansion rate as the electrodes. Each glass insulator is provided with a pair of fused-in Kovar ring inserts which are bonded to the electrodes. Each electrode is designed to define a concavo-convex particle trap so that secondary charged particles generated within the accelerated beam area cannot reach the inner surface of an insulator. Each insulator has a generated inner surface profile which is so configured that the electrical field at this surface contains no significant tangential component. A spark gap trigger assembly is provided, which energizes spark gaps protecting the electrodes affected by over voltage to prevent excessive energy dissipation in the electrode stack.

  4. Free electron laser using Rf coupled accelerating and decelerating structures

    DOEpatents

    Brau, Charles A.; Swenson, Donald A.; Boyd, Jr., Thomas J.

    1984-01-01

    A free electron laser and free electron laser amplifier using beam transport devices for guiding an electron beam to a wiggler of a free electron laser and returning the electron beam to decelerating cavities disposed adjacent to the accelerating cavities of the free electron laser. Rf energy is generated from the energy depleted electron beam after it emerges from the wiggler by means of the decelerating cavities which are closely coupled to the accelerating cavities, or by means of a second bore within a single set of cavities. Rf energy generated from the decelerated electron beam is used to supplement energy provided by an external source, such as a klystron, to thereby enhance overall efficiency of the system.

  5. Potential structures and particle acceleration on auroral field lines

    NASA Astrophysics Data System (ADS)

    Gorney, D. J.

    1985-05-01

    In the 1970's major advances in the understanding of auroral processes were brought about by observations of plasmas and electric fields within the regions of space responsible for auroral particle acceleration. The major contribution of these observations was the verification of the existence of electric fields with components parallel to the magnetic field over large regions of altitude (1000 to 20000 kilometers). These electric fields constitute potential drops of several kilovolts, accelerating magnetospheric electrons downward to form the aurora and ionospheric ions upward, where they contribute significantly to the magnetospheric hot ion population. Perpendicular spatial scales of about 100 kilometers are most common, although finer scales have been observed embedded, and individual small amplitude double layers occur on much smaller parallel spatial scales. More recently, the same data sets have revealed the existance of about 100 V electric potential drops directed downward in return current regions. Downward electric fields are in a direction to accelerate electrons out of the ionsphere and tend to retard the propagation of ions upward. An association between upflowing electron beams and transversely heated ions at low altitude has been noted, and a casual relationship between downward electric fields and ion conics is suggested.

  6. Rosiglitazone impedes Porphyromonas gingivalis-accelerated atherosclerosis by downregulating the TLR/NF-κB signaling pathway in atherosclerotic mice.

    PubMed

    Pan, Shengbo; Lei, Lang; Chen, Shuai; Li, Houxuan; Yan, Fuhua

    2014-12-01

    Porphyromonas gingivalis,a predominant periodontal pathogen, is known to accelerate atherosclerosis in hyperlipidemic animals via aberrant inflammatory responses. Peroxisome proliferator-activated receptor gamma (PPARγ) agonists have been reported to exert anti-inflammatory effects in vitro. The purpose of the present study was to investigate the potential protective role of the PPARγ agonist rosiglitazone in pathogen accelerated atherosclerosis in an apolipoprotein E-deficient (ApoE-/-) mouse model. ApoE-/- mice were inoculated intravenously with live P. gingivalis (strain 33277) or the buffer vehicle and treated with rosiglitazone or saline over a 10-week period. Their atherosclerotic status in aortic artery was assessed through histomorphometric analysis, inflammatory agent and lipid profiles in blood was determined by ELISA, and levels of relevant cytokines and Toll-like receptors (TLRs) in aortic tissues were evaluated using immunohistochemistry and quantitative PCR. P. gingivalis inoculation was associated with increased atherosclerotic plaque formation in the aorta and higher levels of serum pro-inflammatory cytokines (tumor necrosis factor-α, monocyte chemotactic protein-1 and interleukin-1β), but the serum lipid profile was not affected by P. gingivalis infection. Levels of tumor necrosis factor-α, monocyte chemotactic protein-1 intercellular cell adhesion molecule-1 and TLRs were higher in the aortic tissues of mice exposed to P. gingivalis, and activation of nuclear factor-κB was also observed. In both P. gingivalis-treated and -untreated ApoE-/- mice, rosiglitazone treatment was associated with less atherosclerotic plaque formation; lower serum inflammatory cytokines, total cholesterol, and low density lipoprotein cholesterol; higher levels of PPARγ, lower amounts of TLR2/4 and downregulated nuclear factor-κB activity in aortic tissues. These findings suggest that rosiglitazone mitigates or prevents P. gingivalis-accelerated atherosclerosis by

  7. The Low Energy-Coupling Respiration in Zymomonas mobilis Accelerates Flux in the Entner-Doudoroff Pathway.

    PubMed

    Rutkis, Reinis; Strazdina, Inese; Balodite, Elina; Lasa, Zane; Galinina, Nina; Kalnenieks, Uldis

    2016-01-01

    Performing oxidative phosphorylation is the primary role of respiratory chain both in bacteria and eukaryotes. Yet, the branched respiratory chains of prokaryotes contain alternative, low energy-coupling electron pathways, which serve for functions other than oxidative ATP generation (like those of respiratory protection, adaptation to low-oxygen media, redox balancing, etc.), some of which are still poorly understood. We here demonstrate that withdrawal of reducing equivalents by the energetically uncoupled respiratory chain of the bacterium Zymomonas mobilis accelerates its fermentative catabolism, increasing the glucose consumption rate. This is in contrast to what has been observed in other respiring bacteria and yeast. This effect takes place after air is introduced to glucose-consuming anaerobic cell suspension, and can be simulated using a kinetic model of the Entner-Doudoroff pathway in combination with a simple net reaction of NADH oxidation that does not involve oxidative phosphorylation. Although aeration hampers batch growth of respiring Z. mobilis culture due to accumulation of toxic byproducts, nevertheless under non-growing conditions respiration is shown to confer an adaptive advantage for the wild type over the non-respiring Ndh knock-out mutant. If cells get occasional access to limited amount of glucose for short periods of time, the elevated glucose uptake rate selectively improves survival of the respiring Z. mobilis phenotype. PMID:27100889

  8. The Low Energy-Coupling Respiration in Zymomonas mobilis Accelerates Flux in the Entner-Doudoroff Pathway

    PubMed Central

    Rutkis, Reinis; Strazdina, Inese; Balodite, Elina; Lasa, Zane; Galinina, Nina; Kalnenieks, Uldis

    2016-01-01

    Performing oxidative phosphorylation is the primary role of respiratory chain both in bacteria and eukaryotes. Yet, the branched respiratory chains of prokaryotes contain alternative, low energy-coupling electron pathways, which serve for functions other than oxidative ATP generation (like those of respiratory protection, adaptation to low-oxygen media, redox balancing, etc.), some of which are still poorly understood. We here demonstrate that withdrawal of reducing equivalents by the energetically uncoupled respiratory chain of the bacterium Zymomonas mobilis accelerates its fermentative catabolism, increasing the glucose consumption rate. This is in contrast to what has been observed in other respiring bacteria and yeast. This effect takes place after air is introduced to glucose-consuming anaerobic cell suspension, and can be simulated using a kinetic model of the Entner-Doudoroff pathway in combination with a simple net reaction of NADH oxidation that does not involve oxidative phosphorylation. Although aeration hampers batch growth of respiring Z. mobilis culture due to accumulation of toxic byproducts, nevertheless under non-growing conditions respiration is shown to confer an adaptive advantage for the wild type over the non-respiring Ndh knock-out mutant. If cells get occasional access to limited amount of glucose for short periods of time, the elevated glucose uptake rate selectively improves survival of the respiring Z. mobilis phenotype. PMID:27100889

  9. Structural basis for autoinhibition and its relief of MOB1 in the Hippo pathway

    PubMed Central

    Kim, Sun-Yong; Tachioka, Yuka; Mori, Tomoyuki; Hakoshima, Toshio

    2016-01-01

    MOB1 protein is a key regulator of large tumor suppressor 1/2 (LATS1/2) kinases in the Hippo pathway. MOB1 is present in an autoinhibited form and is activated by MST1/2-mediated phosphorylation, although the precise mechanisms responsible for autoinhibition and activation are unknown due to lack of an autoinhibited MOB1 structure. Here, we report on the crystal structure of full-length MOB1B in the autoinhibited form and a complex between the MOB1B core domain and the N-terminal regulation (NTR) domain of LATS1. The structure of full-length MOB1B shows that the N-terminal extension forms a short β-strand, the SN strand, followed by a long conformationally flexible positively-charged linker and α-helix, the Switch helix, which blocks the LATS1 binding surface of MOB1B. The Switch helix is stabilized by β-sheet formation of the SN strand with the S2 strand of the MOB1 core domain. Phosphorylation of Thr12 and Thr35 residues structurally accelerates dissociation of the Switch helix from the LATS1-binding surface by the “pull-the-string” mechanism, thereby enabling LATS1 binding. PMID:27335147

  10. Structural basis for autoinhibition and its relief of MOB1 in the Hippo pathway.

    PubMed

    Kim, Sun-Yong; Tachioka, Yuka; Mori, Tomoyuki; Hakoshima, Toshio

    2016-01-01

    MOB1 protein is a key regulator of large tumor suppressor 1/2 (LATS1/2) kinases in the Hippo pathway. MOB1 is present in an autoinhibited form and is activated by MST1/2-mediated phosphorylation, although the precise mechanisms responsible for autoinhibition and activation are unknown due to lack of an autoinhibited MOB1 structure. Here, we report on the crystal structure of full-length MOB1B in the autoinhibited form and a complex between the MOB1B core domain and the N-terminal regulation (NTR) domain of LATS1. The structure of full-length MOB1B shows that the N-terminal extension forms a short β-strand, the SN strand, followed by a long conformationally flexible positively-charged linker and α-helix, the Switch helix, which blocks the LATS1 binding surface of MOB1B. The Switch helix is stabilized by β-sheet formation of the SN strand with the S2 strand of the MOB1 core domain. Phosphorylation of Thr12 and Thr35 residues structurally accelerates dissociation of the Switch helix from the LATS1-binding surface by the "pull-the-string" mechanism, thereby enabling LATS1 binding. PMID:27335147

  11. Acceleration of the GAMESS-UK electronic structure package on graphical processing units.

    PubMed

    Wilkinson, Karl A; Sherwood, Paul; Guest, Martyn F; Naidoo, Kevin J

    2011-07-30

    The approach used to calculate the two-electron integral by many electronic structure packages including generalized atomic and molecular electronic structure system-UK has been designed for CPU-based compute units. We redesigned the two-electron compute algorithm for acceleration on a graphical processing unit (GPU). We report the acceleration strategy and illustrate it on the (ss|ss) type integrals. This strategy is general for Fortran-based codes and uses the Accelerator compiler from Portland Group International and GPU-based accelerators from Nvidia. The evaluation of (ss|ss) type integrals within calculations using Hartree Fock ab initio methods and density functional theory are accelerated by single and quad GPU hardware systems by factors of 43 and 153, respectively. The overall speedup for a single self consistent field cycle is at least a factor of eight times faster on a single GPU compared with that of a single CPU. PMID:21541963

  12. H-mode accelerating structures with PMQ focusing for low-beta ion beams

    SciTech Connect

    Kurennoy, Sergey S; O' Hara, James F; Olivas, Eric R; Rybarcyk, Lawrence J

    2010-01-01

    We are developing high-efficiency normal-conducting RF accelerating structures based on inter-digital H-mode (IH) cavities and the transverse beam focusing with permanent-magnet quadrupoles (PMQ), for beam velocities in the range of a few percent of the speed of light. Such IH-PMQ accelerating structures following a short RFQ can be used in the front end of ion linacs or in stand-alone applications, e.g. a compact deuteron-beam accelerator up to the energy of several MeV. Results of combined 3-D modeling for a full IH-PMQ accelerator tank - electromagnetic computations, beam-dynamics simulations with high currents, and thermal-stress analysis - are presented. The accelerating field profile in the tank is tuned to provide the best beam propagation using coupled iterations of electromagnetic and beam-dynamics modeling. A cold model of the IH-PMQ tank is being manufactured.

  13. Recommendations for the development of rare disease drugs using the accelerated approval pathway and for qualifying biomarkers as primary endpoints.

    PubMed

    Kakkis, Emil D; O'Donovan, Mary; Cox, Gerald; Hayes, Mark; Goodsaid, Federico; Tandon, P K; Furlong, Pat; Boynton, Susan; Bozic, Mladen; Orfali, May; Thornton, Mark

    2015-01-01

    For rare serious and life-threatening disorders, there is a tremendous challenge of transforming scientific discoveries into new drug treatments. This challenge has been recognized by all stakeholders who endorse the need for flexibility in the regulatory review process for novel therapeutics to treat rare diseases. In the United States, the best expression of this flexibility was the creation of the Accelerated Approval (AA) pathway. The AA pathway is critically important for the development of treatments for diseases with high unmet medical need and has been used extensively for drugs used to treat cancer and infectious diseases like HIV.In 2012, the AA provisions were amended to enhance the application of the AA pathway to expedite the development of drugs for rare disorders under the Food and Drug Administration Safety and Innovation Act (FDASIA). FDASIA, among many provisions, requires the development of a more relevant FDA guidance on the types of evidence that may be acceptable in support of using a novel surrogate endpoint. The application of AA to rare diseases requires more predictability to drive greater access to appropriate use of AA for more rare disease treatments that might not be developed otherwise.This white paper proposes a scientific framework for assessing biomarker endpoints to enhance the development of novel therapeutics for rare and devastating diseases currently without adequate treatment and is based on the opinions of experts in drug development and rare disease patient groups. Specific recommendations include: 1) Establishing regulatory rationale for increased AA access in rare disease programs; 2) Implementing a Biomarker Qualification Request Process to provide the opportunity for an early determination of biomarker acceptance; and 3) A proposed scientific framework for qualifying biomarkers as primary endpoints. The paper's final section highlights case studies of successful examples that have incorporated biomarker endpoints into

  14. Technological Issues and High Gradient Test Results on X-Band Molybdenum Accelerating Structures

    SciTech Connect

    Spataro, B.; Alesini, D.; Chimenti, V.; Dolgashev, V.; Haase, A.; Tantawi, S.G.; Higashi, Y.; Marrelli, C.; Mostacci, A.; Parodi, R.; Yeremian, A.D.; /SLAC

    2012-04-24

    Two 11.424 GHz single cell standing wave accelerating structures have been fabricated for high gradient RF breakdown studies. Both are brazed structures: one made from copper and the other from sintered molybdenum bulk. The tests results are presented and compared to those of similar devices constructed at SLAC (Stanford Linear Accelerator Center) and KEK (Ko Enerugi Kasokuki Kenkyu Kiko). The technological issues to build both sections are discussed.

  15. Theory of factors limiting high gradient operation of warm accelerating structures

    SciTech Connect

    Nusinovich, Gregory S.

    2014-07-22

    This report consists of two parts. In the first part we describe a study of the heating of microprotrusions on surfaces of accelerating structures. This ;process is believed to lead to breakdown in these structures. Our study revealed that for current accelerator parameters melting should not occur due to space charge limitations of the current emitted by a protrusion. The second part describes a novel concept to develop THz range sources based on harmonic cyclotron masers for driving future colliders. This work was stimulated by a recent request of SLAC to develop high power, high-efficiency sources of sub-THz radiation for future high-gradient accelerators.

  16. Potential structures and particle acceleration on auroral field lines

    NASA Astrophysics Data System (ADS)

    Gorney, D. J.

    Observations of plasmas and electric field activity within regions of auroral particle acceleration have verified the existence of electric fields with components parallel to the magnetic field over large altitude regions. Evidence is presented which indicates that small-ampliatude double layers along the auroral magnetic field lines may provide a mechanism for the maintenance of auroral ion potential. Evidence is also presented of downward-directed parallel electric fields along the magnetic field lines in the return current region. It is suggested that the downward electric fields may have significant effects on ion trajectories, and further theoretical investigation of the effects of downward parallel electric fields on ion conic formation is recommended.

  17. Progress toward externally powered x-band dielectric-loaded accelerating structures.

    SciTech Connect

    Gai, W.; Power, J. G.; Liu, W.; Jing, C.; Gold, S. H.; Kinead, A. K.; Tantawi, S. G.; Dolgashev, V.; Kanareykin, A.; Konecny, R.; Wanming, L.

    2010-06-01

    We summarize recent progress in a program to develop externally powered dielectric-loaded accelerating (DLA) structures that can sustain high accelerating gradients. High-power RF tests of earlier structures showed strong multipactor loading. In addition, arcing at dielectric joints between the uniform DLA structure and matching sections at either end limited the achievable gradient. In this paper, we study the onset of multipactor in a DLA structure. We also study the effect of thin-film TiN coatings applied by atomic layer deposition and the effect of a reduction in the inner diameter of the structure. Test results of these structures show significant decreases in multipactor loading. We also test new structure designs that eliminate separate dielectric matching sections and, thus, the requirement for dielectric joints, including a DLA structure using a coaxial coupler and a clamped DLA structure. The clamped structure demonstrated a significantly improved gradient without breakdown.

  18. Efficient low-beta H-mode accelerating structures with PMQ focusing

    SciTech Connect

    Kurennoy, Sergey S; O' Hara, James F; Olivas, Eric R; Rybarcyk, Lawrence J

    2008-01-01

    We are developing high-efficiency room-temperature RF accelerating structures for beam velocities in the range of a few percent of the speed of light by merging two well-known ideas: H-mode cavities and the transverse beam focusing with permanent-magnet quadrupoles (PMQ). Combining electromagnetic 3-D modeling with beam dynamics simulations and thermal-stress analysis, we have found that the H-mode structures with PMQ focusing provide a very efficient and practical accelerator for light-ion beams of considerable currents. Such accelerating structures following a short RFQ can be used in the front end of ion linacs or in stand-alone applications such as a compact deuteron-beam accelerator up to the energy of a few MeV.

  19. Laser Acceleration in Vacuum with an Open Iris-Loaded Structure

    SciTech Connect

    Xie, Ming

    1997-07-01

    An open iris-loaded waveguide structure is considered for laser acceleration of highly relativistic particle in vacuum. Complete characterization of eigenmodes are given in analytical form for the structure. In particular acceleration performance of the dominant TM mode is evaluated in detail. Transparent scaling laws are derived, and through which significant advantages over other vacuum laser acceleration schemes are demonstrated. The entire parameter space is searched and it is found that below the laser damage threshold of the structure an acceleration gradient around 1 GV/m can be obtained over a phase slippage length of 10s of cm with TWs laser in the wavelength range from 1 to 10 {micro}m.

  20. Modelling the Structure and Dynamics of Biological Pathways

    PubMed Central

    O’Hara, Laura; Livigni, Alessandra; Chen, Sz-Hau; Raza, Sobia; Digard, Paul; Smith, Lee B.; Freeman, Tom C.

    2016-01-01

    There is a need for formalised diagrams that both summarise current biological pathway knowledge and support modelling approaches that explain and predict their behaviour. Here, we present a new, freely available modelling framework that includes a biologist-friendly pathway modelling language (mEPN), a simple but sophisticated method to support model parameterisation using available biological information; a stochastic flow algorithm that simulates the dynamics of pathway activity; and a 3-D visualisation engine that aids understanding of the complexities of a system’s dynamics. We present example pathway models that illustrate of the power of approach to depict a diverse range of systems. PMID:27509052

  1. Modelling the Structure and Dynamics of Biological Pathways.

    PubMed

    O'Hara, Laura; Livigni, Alessandra; Theo, Thanos; Boyer, Benjamin; Angus, Tim; Wright, Derek; Chen, Sz-Hau; Raza, Sobia; Barnett, Mark W; Digard, Paul; Smith, Lee B; Freeman, Tom C

    2016-08-01

    There is a need for formalised diagrams that both summarise current biological pathway knowledge and support modelling approaches that explain and predict their behaviour. Here, we present a new, freely available modelling framework that includes a biologist-friendly pathway modelling language (mEPN), a simple but sophisticated method to support model parameterisation using available biological information; a stochastic flow algorithm that simulates the dynamics of pathway activity; and a 3-D visualisation engine that aids understanding of the complexities of a system's dynamics. We present example pathway models that illustrate of the power of approach to depict a diverse range of systems. PMID:27509052

  2. Accelerator mass spectrometry detection of beryllium ions in the antigen processing and presentation pathway.

    PubMed

    Tooker, Brian C; Brindley, Stephen M; Chiarappa-Zucca, Marina L; Turteltaub, Kenneth W; Newman, Lee S

    2015-01-01

    Exposure to small amounts of beryllium (Be) can result in beryllium sensitization and progression to Chronic Beryllium Disease (CBD). In CBD, beryllium is presented to Be-responsive T-cells by professional antigen-presenting cells (APC). This presentation drives T-cell proliferation and pro-inflammatory cytokine (IL-2, TNFα, and IFNγ) production and leads to granuloma formation. The mechanism by which beryllium enters an APC and is processed to become part of the beryllium antigen complex has not yet been elucidated. Developing techniques for beryllium detection with enough sensitivity has presented a barrier to further investigation. The objective of this study was to demonstrate that Accelerator Mass Spectrometry (AMS) is sensitive enough to quantify the amount of beryllium presented by APC to stimulate Be-responsive T-cells. To achieve this goal, APC - which may or may not stimulate Be-responsive T-cells - were cultured with Be-ferritin. Then, by utilizing AMS, the amount of beryllium processed for presentation was determined. Further, IFNγ intracellular cytokine assays were performed to demonstrate that Be-ferritin (at levels used in the experiments) could stimulate Be-responsive T-cells when presented by an APC of the correct HLA type (HLA-DP0201). The results indicated that Be-responsive T-cells expressed IFNγ only when APC with the correct HLA type were able to process Be for presentation. Utilizing AMS, it was determined that APC with HLA-DP0201 had membrane fractions containing 0.17-0.59 ng Be and APC with HLA-DP0401 had membrane fractions bearing 0.40-0.45 ng Be. However, HLA-DP0401 APC had 20-times more Be associated with the whole cells (57.68-61.12 ng) than HLA-DP0201 APC (0.90-3.49 ng). As these findings demonstrate, AMS detection of picogram levels of Be processed by APC is possible. Further, regardless of form, Be requires processing by APC to successfully stimulate Be-responsive T-cells to generate IFNγ. PMID:24932923

  3. Accelerator mass spectrometry detection of beryllium ions in the antigen processing and presentation pathway

    SciTech Connect

    Tooker, Brian C.; Brindley, Stephen M.; Chiarappa-Zucca, Marina L.; Turteltaub, Kenneth W.; Newman, Lee S.

    2014-06-16

    We report that exposure to small amounts of beryllium (Be) can result in beryllium sensitization and progression to Chronic Beryllium Disease (CBD). In CBD, beryllium is presented to Be-responsive T-cells by professional antigen-presenting cells (APC). This presentation drives T-cell proliferation and pro-inflammatory cytokine (IL-2, TNFα, and IFNγ) production and leads to granuloma formation. The mechanism by which beryllium enters an APC and is processed to become part of the beryllium antigen complex has not yet been elucidated. Developing techniques for beryllium detection with enough sensitivity has presented a barrier to further investigation. The objective of this study was to demonstrate that Accelerator Mass Spectrometry (AMS) is sensitive enough to quantify the amount of beryllium presented by APC to stimulate Be-responsive T-cells. To achieve this goal, APC - which may or may not stimulate Be-responsive T-cells - were cultured with Be-ferritin. Then, by utilizing AMS, the amount of beryllium processed for presentation was determined. Further, IFNγ intracellular cytokine assays were performed to demonstrate that Be-ferritin (at levels used in the experiments) could stimulate Be-responsive T-cells when presented by an APC of the correct HLA type (HLA-DP0201). The results indicated that Be-responsive T-cells expressed IFNγ only when APC with the correct HLA type were able to process Be for presentation. Utilizing AMS, we determined that APC with HLA-DP0201 had membrane fractions containing 0.17-0.59 ng Be and APC with HLA-DP0401 had membrane fractions bearing 0.40-0.45 ng Be. However, HLA-DP0401 APC had 20-times more Be associated with the whole cells (57.68-61.12 ng) then HLA-DP0201 APC (0.90-3.49 ng). As these findings demonstrate, AMS detection of picogram levels of Be processed by APC is possible. Further, regardless of form, Be requires processing by APC to successfully stimulate Be-responsive T-cells to generate IFNγ.

  4. Accelerator Mass Spectrometry Detection of Beryllium Ions in the Antigen Processing and Presentation Pathway

    PubMed Central

    Tooker, Brian C.; Brindley, Stephen M.; Chiarappa-Zucca, Marina L.; Turteltaub, Kenneth W.; Newman, Lee S.

    2015-01-01

    Exposure to small amounts of beryllium (Be) can result in beryllium sensitization and progression to Chronic Beryllium Disease (CBD). In CBD, beryllium is presented to Be-responsive T-cells by professional antigen-presenting cells (APC). This presentation drives T-cell proliferation and pro-inflammatory cytokine (IL-2, TNFα, and IFNγ) production and leads to granuloma formation. The mechanism by which beryllium enters an APC and is processed to become part of the beryllium antigen complex has not yet been elucidated. Developing techniques for beryllium detection with enough sensitivity has presented a barrier to further investigation. The objective of this study was to demonstrate that Accelerator Mass Spectrometry (AMS) is sensitive enough to quantify the amount of beryllium presented by APC to stimulate Be-responsive T-cells. To achieve this goal, APC - which may or may not stimulate Be-responsive T-cells - were cultured with Be-ferritin. Then, by utilizing AMS, the amount of beryllium processed for presentation was determined. Further, IFNγ intracellular cytokine assays were performed to demonstrate that Be-ferritin (at levels used in the experiments) could stimulate Be-responsive T-cells when presented by an APC of the correct HLA type (HLA-DP0201). The results indicated that Be-responsive T-cells expressed IFNγ only when APC with the correct HLA type were able to process Be for presentation. Utilizing AMS, it was determined that APC with HLA-DP0201 had membrane fractions containing 0.17-0.59 ng Be and APC with HLA-DP0401 had membrane fractions bearing 0.40-0.45 ng Be. However, HLA-DP0401 APC had 20-times more Be associated with the whole cells (57.68-61.12 ng) then HLA-DP0201 APC (0.90-3.49 ng). As these findings demonstrate, AMS detection of picogram levels of Be processed by APC is possible. Further, regardless of form, Be requires processing by APC to successfully stimulate Be-responsive T-cells to generate IFNγ. PMID:24932923

  5. Accelerator mass spectrometry detection of beryllium ions in the antigen processing and presentation pathway

    DOE PAGESBeta

    Tooker, Brian C.; Brindley, Stephen M.; Chiarappa-Zucca, Marina L.; Turteltaub, Kenneth W.; Newman, Lee S.

    2014-06-16

    We report that exposure to small amounts of beryllium (Be) can result in beryllium sensitization and progression to Chronic Beryllium Disease (CBD). In CBD, beryllium is presented to Be-responsive T-cells by professional antigen-presenting cells (APC). This presentation drives T-cell proliferation and pro-inflammatory cytokine (IL-2, TNFα, and IFNγ) production and leads to granuloma formation. The mechanism by which beryllium enters an APC and is processed to become part of the beryllium antigen complex has not yet been elucidated. Developing techniques for beryllium detection with enough sensitivity has presented a barrier to further investigation. The objective of this study was to demonstratemore » that Accelerator Mass Spectrometry (AMS) is sensitive enough to quantify the amount of beryllium presented by APC to stimulate Be-responsive T-cells. To achieve this goal, APC - which may or may not stimulate Be-responsive T-cells - were cultured with Be-ferritin. Then, by utilizing AMS, the amount of beryllium processed for presentation was determined. Further, IFNγ intracellular cytokine assays were performed to demonstrate that Be-ferritin (at levels used in the experiments) could stimulate Be-responsive T-cells when presented by an APC of the correct HLA type (HLA-DP0201). The results indicated that Be-responsive T-cells expressed IFNγ only when APC with the correct HLA type were able to process Be for presentation. Utilizing AMS, we determined that APC with HLA-DP0201 had membrane fractions containing 0.17-0.59 ng Be and APC with HLA-DP0401 had membrane fractions bearing 0.40-0.45 ng Be. However, HLA-DP0401 APC had 20-times more Be associated with the whole cells (57.68-61.12 ng) then HLA-DP0201 APC (0.90-3.49 ng). As these findings demonstrate, AMS detection of picogram levels of Be processed by APC is possible. Further, regardless of form, Be requires processing by APC to successfully stimulate Be-responsive T-cells to generate IFNγ.« less

  6. Studies of Multipactor in Dielectric-Loaded Accelerator Structures: Comparison of Simulation Results with Experimental Data

    SciTech Connect

    Sinitsyn, Oleksandr; Nusinovich, Gregory; Antonsen, Thomas Jr.

    2010-11-04

    In this paper new results of numerical studies of multipactor in dielectric-loaded accelerator structures are presented. The results are compared with experimental data obtained during recent studies of such structures performed by Argonne National Laboratory, the Naval Research Laboratory, SLAC National Accelerator Laboratory and Euclid TechLabs, LLC. Good agreement between the theory and experiment was observed for the structures with larger inner diameter, however the structures with smaller inner diameter demonstrated a discrepancy between the two. Possible reasons for such discrepancy are discussed.

  7. Particle Acceleration at Filamentary Structures Downstream of Collisionless Shocks in the Heliosphere.

    NASA Astrophysics Data System (ADS)

    Kucharek, H.; Pogorelov, N. V.; Gamayunov, K. V.

    2015-12-01

    Collisionless shocks are an important feature in astrophysical, heliospheric and magnetospheric settings. At these structures plasma is heated, the properties of flows are changed, and particles are accelerated to high energies. Particles are accelerated throughout the heliosphere. There are no times or conditions where suprathermal ions forming tails are not present on the solar wind ion distribution, and given the low speeds of these particles they must be accelerated locally in the heliosphere. Coronal mass ejections (CMEs) and co-rotating interaction regions (CIRs) accelerate particles up to 10s of MeV/nucleon. The termination shock of the solar and the heliosheath produce energetic particles including the Anomalous Cosmic Rays (ACRs), with energies in excess of 100 MeV. In the last few years' very interesting observations at low energies showing power laws that cannot be explained with commonly accepted acceleration mechanisms and thus increased the need for alternative acceleration processes. Fully consistent kinetic particle simulations such as hybrid simulations appear to be a powerful tool to investigated ion acceleration. Nowadays these simulations can be performed in 3D and relative large simulation domains covering up to hundreds of ion inertial length in size and thus representing the MHD scale. These 3D hybrid simulations show filamentary magnetic and density structures, which could be interpreted as small-scale flux ropes. The growth of these small-scale structures is also associated with ion acceleration. In this talk we will discuss properties of these filamentary structures, their spatial and temporal evolution and the particle dynamics during the acceleration process. The results of this study may be of particular importance for future high resolution magnetospheric and heliospheric mission such as THOR.

  8. Generation of periodic accelerating structures in plasma by colliding laser pulses.

    PubMed

    Shvets, G; Fisch, N J; Pukhov, A; Meyer-Ter-Vehn, J

    1999-08-01

    A mechanism for generating large (>1 GeV/m) accelerating wakes in a plasma is proposed. Two slightly detuned counterpropagating laser beams, an ultrashort timing pulse and a long pump, exchange photons and deposit the recoil momentum in plasma electrons. This produces a localized region of electron current, which acts as a virtual electron beam, inducing intense plasma wakes with phase velocity equal to the group velocity of the short pulse. Modulating the pumping beam generates periodic accelerating structures in the plasma ("plasma linac") which can be used for particle acceleration unlimited by the dephasing between the particles and the wake. An important difference between this type of plasma accelerator and the conventional wakefield accelerators is that this type can be achieved with laser intensities I<10(18) W/cm(2). PMID:11970016

  9. Laser acceleration and deflection of 963 keV electrons with a silicon dielectric structure

    DOE PAGESBeta

    Leedle, Kenneth J.; Pease, R. Fabian; Byer, Robert L.; Harris, James S.

    2015-02-12

    Radio frequency particle accelerators are ubiquitous in ultrasmall and ultrafast science, but their size and cost have prompted exploration of compact and scalable alternatives such as the dielectric laser accelerator. We present the first demonstration, to the best of our knowledge, of high gradient laser acceleration and deflection of electrons with a silicon structure. Driven by a 5 nJ, 130 fs mode-locked Ti:sapphire laser at 907 nm wavelength, our devices achieve accelerating gradients in excess of 200 MeV/m and suboptical cycle streaking of 96.30 keV electrons. These results pave the way for high gradient silicon dielectric laser accelerators using commercialmore » lasers and subfemtosecond electron beam experiments.« less

  10. A Structural Model of Alcohol Use Pathways among Latino Youth

    ERIC Educational Resources Information Center

    Yan, Fang Alice; Beck, Kenneth H.; Howard, Donna; Shattuck, Teresa Downs; Kerr, Melissa Hallmark

    2008-01-01

    Objectives: To determine the pathways to alcohol use among adolescents. Methods: A cross-sectional study of risk and protective factors among a sample of Latino youth (aged 11-13) was conducted. Results: Peer norms and school connectedness had direct pathways to alcohol use. Self-concept was related to peer norms. Youth who were less acculturated…

  11. Electron acceleration by femtosecond laser interaction with micro-structured plasmas

    NASA Astrophysics Data System (ADS)

    Goers, Andy James

    Laser-driven accelerators are a promising and compact alternative to RF accelerator technology for generating relativistic electron bunches for medical, scientific, and security applications. This dissertation presents three experiments using structured plasmas designed to advance the state of the art in laser-based electron accelerators, with the goal of reducing the energy of the drive laser pulse and enabling higher repetition rate operation with current laser technology. First, electron acceleration by intense femtosecond laser pulses in He-like nitrogen plasma waveguides is demonstrated. Second, significant progress toward a proof of concept realization of quasi-phasematched direct acceleration (QPM-DLA) is presented. Finally, a laser wakefield accelerator at very high plasma density is studied, enabling relativistic electron beam generation with ˜10 mJ pulse energies. Major results from these experiments include: • Acceleration of electrons up to 120 MeV from an ionization injected wakefield accelerator driven in a 1.5 mm long He-like nitrogen plasma waveguide • Guiding of an intense, quasi-radially polarized femtosecond laser pulse in a 1 cm plasma waveguide. This pulse provides a strong drive field for the QPM-DLA concept. • Wakefield acceleration of electrons up to ˜10 MeV with sub-terawatt, ˜10 mJ pulses interacting with a thin (˜200 mum), high density (>1020 cm-3) plasma. • Observation of an intense, coherent, broadband wave breaking radiation flash from a high plasma density laser wakefield accelerator. The flash radiates > 1% of the drive laser pulse energy in a bandwidth consistent with half-cycle (˜1 fs) emission from violent unidirectional acceleration of electron bunches from rest. These results open the way to high repetition rate (>˜kHz) laser-driven generation of relativistic electron beams with existing laser technology.

  12. On a theory of two-beam mechanisms of charged particle acceleration in electrodynamic structures

    SciTech Connect

    Ostrovsky, A.O.

    1993-09-01

    This work is devoted to the theoretical studies of two-beam mechanisms of charged particle acceleration in electronic structures. The first section continues the outline of results of theoretical studies commenced in the intermediate report and considers the two-beam scheme of acceleration in the plasma waveguide. According to this scheme the strong current relativistic electron beam (REB) excites the intensive plasma waves accelerating the electrons of the second beam. The driving beam is assumed to be density-modulated. The preliminary modulation of the driving REB is shown to enhance substantially the acceleration efficiency of relativistic electrons of the driven beam. The second section deals with the two-beam acceleration in the vacuum corrugated waveguide. According to this scheme the excitation of electromagnetic waves and acceleration of driven beam electrons by them is accomplished under different Cherenkov resonances between the particles of beams and the corrugated waveguide field. The electromagnetic field in the periodic structure is known to be the superposition of spatial harmonics. With the small depth of the periodic nonuniformity the amplitudes of these harmonics decrease fast with their number increasing. Therefore, if the driving beam is in the Cherenkov resonance with the first spatial harmonic and the driven beam is in resonance with the zero space harmonic then the force accelerating the driven beam would be considerably bigger than the force decelerating the driving beam electrons.

  13. Variable frequency heavy-ion linac, RILAC I. Design, construction and operation of its accelerating structure

    NASA Astrophysics Data System (ADS)

    Odera, Masatoshi; Chiba, Yoshiaki; Tonuma, Tadao; Hemmi, Masatake; Miyazawa, Yoshitoshi; Inoue, Toshihiko; Kambara, Tadashi; Kase, Masayuki; Kubo, Toshiyuki; Yoshida, Fusako

    1984-11-01

    A variable frequency linear accelerator at RIKEN (IPCR), which is named RILAC, is designed to accelerate ions of almost every element in the periodic table. In this report, the design, construction and performance of the resonator cavities of this linac are described. A new accelerating structure was developed for the variable frequency scheme. The principal aim of the development was to obtain a configuration within the cavity to keep a uniform voltage distribution along the accelerating axis over the wide range of resonant frequencies required. The final form adopted is a coaxial quarter-wave type resonator with a race-track-like cross section for its coaxial inner and outer conductors. It has a movable shorting device as a frequency tuner and its open end is enlarged and loaded with drift tubes, connected to the inner and outer conductors alternatingly. The structure can maintain the required uniformity of the accelerating voltage within 10% in spite of resonant frequency tuning between 17 and 45 MHz. A relatively modest accelerating gradient was chosen so that cw operation could be realized. The RILAC is composed of six such cavities which are independently excited and it succeeded in the acceleration of a beam through all the cavities in 1981.

  14. INTERNAL STRUCTURE OF PROTOCLUSTER GALAXIES: ACCELERATED STRUCTURAL EVOLUTION IN OVERDENSE ENVIRONMENTS?

    SciTech Connect

    Zirm, Andrew W.; Toft, Sune; Tanaka, Masayuki E-mail: sune@dark-cosmology.dk

    2012-01-10

    We present a high spatial resolution Hubble Space Telescope/NICMOS imaging survey in the field of a known protocluster surrounding the powerful radio galaxy MRC1138-262 at z = 2.16. Previously, we have shown that this field exhibits a substantial surface overdensity of red J-H galaxies. Here we focus on the stellar masses and galaxy effective radii in an effort to compare and contrast the properties of likely protocluster galaxies with their field counterparts and to look for correlations between galaxy structure and (projected) distance relative to the radio galaxy. We find a hint that quiescent, cluster galaxies are on average less dense than quiescent field galaxies of similar stellar mass and redshift. In fact, we find that only two (of eight) quiescent protocluster galaxies are of similar density to the majority of the massive, quiescent compact galaxies (Semi-Evolved Elephantine Dense galaxies; SEEDs) found in several field surveys. Furthermore, there is some indication that the structural Sersic n parameter is higher (n {approx} 3-4) on average for cluster galaxies compared to the field SEEDs (n {approx} 1-2). This result may imply that the accelerated galaxy evolution expected (and observed) in overdense regions also extends to structural evolution presuming that massive galaxies began as dense (low n) SEEDs and have already evolved to be more in line with local galaxies of the same stellar mass.

  15. An Update on the DOE Early Career Project on Photonic Band Gap Accelerator Structures

    SciTech Connect

    Simakov, Evgenya I.; Edwards, Randall L.; Haynes, William B.; Madrid, Michael A.; Romero, Frank P.; Tajima, Tsuyoshi; Tuzel, Walter M.; Boulware , Chase H.; Grimm, Terry

    2012-06-07

    We performed fabrication of two SRF PBG resonators at 2.1 GHz and demonstrated their proof-of-principle operation at high gradients. Measured characteristics of the resonators were in good agreement with theoretical predictions. We demonstrated that SRF PBG cavities can be operated at 15 MV/m accelerating gradients. We completed the design and started fabrication of the 16-cell PBG accelerating structure at 11.7 GHz for wakefield testing at AWA.

  16. Summary Report of Working Group 7: Electromagnetic-Structure Based Accelerators

    SciTech Connect

    Colby, E.; Musumeci, P.; /INFN, Rome

    2007-04-02

    We detail the most pressing physics and technical issues confronting short-wavelength acceleration. We review new acceleration concepts that are proposed and under development, and recent progress on technical issues such as structure fabrication and material damage. We outline key areas where work is still needed before a reliable assessment of the value of working at wavelengths below 1 cm can be made. Possible ways to enhance collaboration and progress in this important area are also discussed.

  17. Beam dynamics and wakefield simulations of the double grating accelerating structure

    SciTech Connect

    Najafabadi, B. Montazeri; Byer, R. L.; Ng, C. K.; England, R. J.; Peralta, E. A.; Soong, K.; Noble, R.; Wu, Z.

    2012-12-21

    Laser-driven acceleration in dielectric structures can provide gradients on the order of GeV/m. The small transverse dimension and tiny feature sizes introduce challenges in design, fabrication, and simulation studies of these structures. In this paper we present the results of beam dynamic simulation and short range longitudinal wakefield simulation of the double grating structure. We show the linear trend of acceleration in a dielectric accelerator design and calculate the maximum achievable gradient equal to 0.47E{sub 0} where E0 is maximum electric field of the laser excitation. On the other hand, using wakefield simulations, we show that the loss factor of the structure with 400nm gap size will be 0.12GV/m for a 10fC, 100as electron bunch which is an order of magnitude less than expected gradient near damage threshold of the device.

  18. Proposed Few-optical Cycle Laser-driven ParticleAccelerator Structure

    SciTech Connect

    Plettner, T.; Lu, P.; Byer, R.L.; /Stanford U., Ginzton Lab.

    2006-10-06

    We describe a transparent dielectric grating accelerator structure that is designed for ultra-short laser pulse operation. The structure is based on the principle of periodic field reversal to achieve phase synchronicity for relativistic particles, however to preserve ultra-short pulse operation it does not resonate the laser field in the vacuum channel. The geometry of the structure appears well suited for application with high average power lasers and high thermal loading. Finally, it shows potential for an unloaded gradient of 10 GeV/m with 10 fsec laser pulses and the possibility to accelerate 10{sup 6} electrons per bunch at an efficiency of 8%. The fabrication procedure and a proposed near term experiment with this accelerator structure are presented.

  19. CPU-GPU hybrid accelerating the Zuker algorithm for RNA secondary structure prediction applications

    PubMed Central

    2012-01-01

    Background Prediction of ribonucleic acid (RNA) secondary structure remains one of the most important research areas in bioinformatics. The Zuker algorithm is one of the most popular methods of free energy minimization for RNA secondary structure prediction. Thus far, few studies have been reported on the acceleration of the Zuker algorithm on general-purpose processors or on extra accelerators such as Field Programmable Gate-Array (FPGA) and Graphics Processing Units (GPU). To the best of our knowledge, no implementation combines both CPU and extra accelerators, such as GPUs, to accelerate the Zuker algorithm applications. Results In this paper, a CPU-GPU hybrid computing system that accelerates Zuker algorithm applications for RNA secondary structure prediction is proposed. The computing tasks are allocated between CPU and GPU for parallel cooperate execution. Performance differences between the CPU and the GPU in the task-allocation scheme are considered to obtain workload balance. To improve the hybrid system performance, the Zuker algorithm is optimally implemented with special methods for CPU and GPU architecture. Conclusions Speedup of 15.93× over optimized multi-core SIMD CPU implementation and performance advantage of 16% over optimized GPU implementation are shown in the experimental results. More than 14% of the sequences are executed on CPU in the hybrid system. The system combining CPU and GPU to accelerate the Zuker algorithm is proven to be promising and can be applied to other bioinformatics applications. PMID:22369626

  20. Frequency Domain Tomography Of Evolving Laser-Plasma Accelerator Structures

    SciTech Connect

    Dong Peng; Reed, Stephen; Kalmykov, Serguei; Shvets, Gennady; Downer, Mike

    2009-01-22

    Frequency Domain Holography (FDH), a technique for visualizing quasistatic objects propagating near the speed of light, has produced 'snapshots' of laser wakefields, but they are averaged over structural variations that occur during propagation through the plasma medium. Here we explore via simulations a generalization of FDH--that we call Frequency Domain Tomography (FDT)--that can potentially record a time sequence of quasistatic snapshots, like the frames of a movie, of the wake structure as it propagates through the plasma. FDT utilizes a several probe-reference pulse pairs that propagate obliquely to the drive pulse and wakefield, along with tomographic reconstruction algorithms similar to those used in medical CAT scans.

  1. Update on the development of externally powered dielectric-loaded accelerating structures.

    SciTech Connect

    Jing, C.; Gai, W.; Konecny, R.; Power, J. G.; Liu, W.; Kanareykin, A.; Gold, S.; Kinkead, A. K.; High Energy Physics; EuclidTechlabs,; Naval Research Lab.; Icarus Research

    2009-01-01

    We report on recent progress in a program to develop an RF-driven Dielectric-Loaded Accelerating (DLA) structure, capable of supporting high gradient acceleration. Previous high power tests revealed that the earlier DLA structures suffered from multipactor and arcing at the dielectric joint. A few new DLA structures have been designed to alleviate this limitation including the coaxial coupler based DLA structure and the clamped DLA structure. These structures were recently fabricated and high power tested at the NRL X-band Magnicon facility. Results show the multipactor can be reduced by the TiN coating on the dielectric surface. Gradient of 15 MV/m has also been tested without dielectric breakdown in the test of the clamped DLA structure. Detailed results are reported, and future plans discussed.

  2. Active vibration suppression through positive acceleration feedback on a building-like structure: An experimental study

    NASA Astrophysics Data System (ADS)

    Enríquez-Zárate, J.; Silva-Navarro, G.; Abundis-Fong, H. F.

    2016-05-01

    This work deals with the structural and dynamic analysis of a building-like structure consisting of a three-story building with one active vibration absorber. The base of the structure is perturbed using an electromagnetic shaker, which provides forces with a wide range of excitation frequencies, including some resonance frequencies of the structure. One beam-column of the structure is coupled with a PZT stack actuator to reduce the vibrations. The overall mechanical structure is modeled using Euler-Lagrange methodology and validated using experimental modal analysis and Fine Element Method (FEM) techniques. The active control laws are synthesized to actively attenuate the vibration system response via the PZT stack actuator, caused by excitation forces acting on the base of the structure. The control scheme is obtained using Positive Acceleration Feedback (PAF) and Multiple Positive Acceleration Feedback (MPAF) to improve the closed-loop system response. Some experimental results are included to illustrate the overall system performance.

  3. Update on the Development of Externally Powered Dielectric-Loaded Accelerating Structures

    SciTech Connect

    Jing, C.; Kanareykin, A.; Gai, W.; Konecny, R.; Power, J. G.; Liu, W.; Gold, S. H.; Kinkead, A. K.

    2009-01-22

    We report on recent progress in a program to develop an RF-driven Dielectric-Loaded Accelerating (DLA) structure, capable of supporting high gradient acceleration. Previous high power tests revealed that the earlier DLA structures suffered from multipactor and arcing at the dielectric joint. A few new DLA structures have been designed to alleviate this limitation including the coaxial coupler based DLA structure and the clamped DLA structure. These structures were recently fabricated and high power tested at the NRL X-band Magnicon facility. Results show the multipactor can be reduced by the TiN coating on the dielectric surface. Gradient of 15 MV/m has also been tested without dielectric breakdown in the test of the clamped DLA structure. Detailed results are reported, and future plans discussed.

  4. Latest Development in Superconducting RF Structures for beta=1 Particle Acceleration

    SciTech Connect

    Peter Kneisel

    2006-06-26

    Superconducting RF technology is since nearly a decade routinely applied to different kinds of accelerating devices: linear accelerators, storage rings, synchrotron light sources and FEL's. With the technology recommendation for the International Linear Collider (ILC) a year ago, new emphasis has been placed on improving the performance of accelerating cavities both in Q-value and in accelerating gradients with the goal to achieve performance levels close to the fundamental limits given by the material parameters of the choice material, niobium. This paper will summarize the challenges to SRF technology and will review the latest developments in superconducting structure design. Additionally, it will give an overview of the newest results and will report on the developments in alternative materials and technologies.

  5. Enhancement of maximum attainable ion energy in the radiation pressure acceleration regime using a guiding structure

    DOE PAGESBeta

    Bulanov, S. S.; Esarey, E.; Schroeder, C. B.; Bulanov, S. V.; Esirkepov, T. Zh.; Kando, M.; Pegoraro, F.; Leemans, W. P.

    2015-03-13

    Radiation Pressure Acceleration is a highly efficient mechanism of laser driven ion acceleration, with the laser energy almost totally transferrable to the ions in the relativistic regime. There is a fundamental limit on the maximum attainable ion energy, which is determined by the group velocity of the laser. In the case of a tightly focused laser pulses, which are utilized to get the highest intensity, another factor limiting the maximum ion energy comes into play, the transverse expansion of the target. Transverse expansion makes the target transparent for radiation, thus reducing the effectiveness of acceleration. Utilization of an external guidingmore » structure for the accelerating laser pulse may provide a way of compensating for the group velocity and transverse expansion effects.« less

  6. Enhancement of maximum attainable ion energy in the radiation pressure acceleration regime using a guiding structure

    SciTech Connect

    Bulanov, S. S.; Esarey, E.; Schroeder, C. B.; Bulanov, S. V.; Esirkepov, T. Zh.; Kando, M.; Pegoraro, F.; Leemans, W. P.

    2015-03-13

    Radiation Pressure Acceleration is a highly efficient mechanism of laser driven ion acceleration, with the laser energy almost totally transferrable to the ions in the relativistic regime. There is a fundamental limit on the maximum attainable ion energy, which is determined by the group velocity of the laser. In the case of a tightly focused laser pulses, which are utilized to get the highest intensity, another factor limiting the maximum ion energy comes into play, the transverse expansion of the target. Transverse expansion makes the target transparent for radiation, thus reducing the effectiveness of acceleration. Utilization of an external guiding structure for the accelerating laser pulse may provide a way of compensating for the group velocity and transverse expansion effects.

  7. Three-dimensional Dielectric Photonic Crystal Structures for Laser-driven Acceleration

    SciTech Connect

    Cowan, Benjamin M.; /Tech-X, Boulder /SLAC

    2007-12-14

    We present the design and simulation of a three-dimensional photonic crystal waveguide for linear laser-driven acceleration in vacuum. The structure confines a synchronous speed-of-light accelerating mode in both transverse dimensions. We report the properties of this mode, including sustainable gradient and optical-to-beam efficiency. We present a novel method for confining a particle beam using optical fields as focusing elements. This technique, combined with careful structure design, is shown to have a large dynamic aperture and minimal emittance growth, even over millions of optical wavelengths.

  8. Experimental measurements of rf breakdowns and deflecting gradients in mm-wave metallic accelerating structures

    NASA Astrophysics Data System (ADS)

    Dal Forno, Massimo; Dolgashev, Valery; Bowden, Gordon; Clarke, Christine; Hogan, Mark; McCormick, Doug; Novokhatski, Alexander; Spataro, Bruno; Weathersby, Stephen; Tantawi, Sami G.

    2016-05-01

    We present an experimental study of a high gradient metallic accelerating structure at sub-THz frequencies, where we investigated the physics of rf breakdowns. Wakefields in the structure were excited by an ultrarelativistic electron beam. We present the first quantitative measurements of gradients and metal vacuum rf breakdowns in sub-THz accelerating cavities. When the beam travels off axis, a deflecting field is induced in addition to the longitudinal field. We measured the deflecting forces by observing the displacement and changes in the shape of the electron bunch. This behavior can be exploited for subfemtosecond beam diagnostics.

  9. Cosmic microwave background anisotropy from nonlinear structures in accelerating universes

    SciTech Connect

    Sakai, Nobuyuki; Inoue, Kaiki Taro

    2008-09-15

    We study the cosmic microwave background (CMB) anisotropy due to spherically symmetric nonlinear structures in flat universes with dust and a cosmological constant. By modeling a time-evolving spherical compensated void/lump by Lemaitre-Tolman-Bondi spacetimes, we numerically solve the null geodesic equations with the Einstein equations. We find that a nonlinear void redshifts the CMB photons that pass through it regardless of the distance to it. In contrast, a nonlinear lump blueshifts (or redshifts) the CMB photons if it is located near (or sufficiently far from) us. The present analysis comprehensively covers previous works based on a thin-shell approximation and a linear/second-order perturbation method and the effects of shell thickness and full nonlinearity. Our results indicate that, if quasilinear and large (> or approx.100 Mpc) voids/lumps would exist, they could be observed as cold or hot spots with temperature variance > or approx. 10{sup -5} K in the CMB sky.

  10. Comparison of accelerated T1-weighted whole-brain structural-imaging protocols.

    PubMed

    Falkovskiy, Pavel; Brenner, Daniel; Feiweier, Thorsten; Kannengiesser, Stephan; Maréchal, Bénédicte; Kober, Tobias; Roche, Alexis; Thostenson, Kaely; Meuli, Reto; Reyes, Denise; Stoecker, Tony; Bernstein, Matt A; Thiran, Jean-Philippe; Krueger, Gunnar

    2016-01-01

    Imaging in neuroscience, clinical research and pharmaceutical trials often employs the 3D magnetisation-prepared rapid gradient-echo (MPRAGE) sequence to obtain structural T1-weighted images with high spatial resolution of the human brain. Typical research and clinical routine MPRAGE protocols with ~1mm isotropic resolution require data acquisition time in the range of 5-10min and often use only moderate two-fold acceleration factor for parallel imaging. Recent advances in MRI hardware and acquisition methodology promise improved leverage of the MR signal and more benign artefact properties in particular when employing increased acceleration factors in clinical routine and research. In this study, we examined four variants of a four-fold-accelerated MPRAGE protocol (2D-GRAPPA, CAIPIRINHA, CAIPIRINHA elliptical, and segmented MPRAGE) and compared clinical readings, basic image quality metrics (SNR, CNR), and automated brain tissue segmentation for morphological assessments of brain structures. The results were benchmarked against a widely-used two-fold-accelerated 3T ADNI MPRAGE protocol that served as reference in this study. 22 healthy subjects (age=20-44yrs.) were imaged with all MPRAGE variants in a single session. An experienced reader rated all images of clinically useful image quality. CAIPIRINHA MPRAGE scans were perceived on average to be of identical value for reading as the reference ADNI-2 protocol. SNR and CNR measurements exhibited the theoretically expected performance at the four-fold acceleration. The results of this study demonstrate that the four-fold accelerated protocols introduce systematic biases in the segmentation results of some brain structures compared to the reference ADNI-2 protocol. Furthermore, results suggest that the increased noise levels in the accelerated protocols play an important role in introducing these biases, at least under the present study conditions. PMID:26297848

  11. Topical N-Acetylcysteine Accelerates Wound Healing in Vitro and in Vivo via the PKC/Stat3 Pathway

    PubMed Central

    Tsai, Min-Ling; Huang, Hui-Pei; Hsu, Jeng-Dong; Lai, Yung-Rung; Hsiao, Yu-Ping; Lu, Fung-Jou; Chang, Horng-Rong

    2014-01-01

    N-Acetylcysteine (Nac) is an antioxidant administered in both oral and injectable forms. In this study, we used Nac topically to treat burn wounds in vitro and in vivo to investigate mechanisms of action. In vitro, we monitored glutathione levels, cell proliferation, migration, scratch-wound healing activities and the epithelialization-related proteins, matrixmetalloproteinase-1 (MMP-1) and proteins involved in regulating the expression of MMP-1 in CCD-966SK cells treated with Nac. Various Nac concentrations (0.1, 0.5, and 1.0 mM) increased glutathione levels, cell viability, scratch-wound healing activities and migration abilities of CCD-966SK cells in a dose-dependent manner. The MMP-1 expression of CCD-966SK cells treated with 1.0 mM Nac for 24 h was significantly increased. Levels of phosphatidylinositol 3-kinase (PI3K), protein kinase C (PKC), janus kinase 1 (Jak1), signal transducer and activator of transcription 3 (Stat3), c-Fos and Jun, but not extracellular signal-regulated protein kinases 1 and 2 (Erk1/2), were also significantly increased in a dose-dependent manner compared to the controls. In addition, Nac induced collagenous expression of MMP-1 via the PKC/Stat3 signaling pathway. In vivo, a burn wound healing rat model was applied to assess the stimulation activity and histopathological effects of Nac, with 3.0% Nac-treated wounds being found to show better characteristics on re-epithelialization. Our results demonstrated that Nac can potentially promote wound healing activity, and may be a promising drug to accelerate burn wound healing. PMID:24798751

  12. Observation of wakefields in a beam-driven photonic band gap accelerating structure.

    SciTech Connect

    Conde, M.; Yusof, Z.; Power, J. G.; Jing, C.; Gao, F.; Antipov, S.; Xu, P.; Zheng, S.; Chen, H.; Tang, C.; Gai, W.; High Energy Physics; Euclid Techlabs LLC; Tsinghua Univ.

    2009-12-01

    Wakefield excitation has been experimentally studied in a three-cell X-band standing wave photonic band gap (PBG) accelerating structure. Major monopole (TM{sub 01}- and TM{sub 02}-like) and dipole (TM{sub 11}- and TM{sub 12}-like) modes were identified and characterized by precisely controlling the position of beam injection. The quality factor Q of the dipole modes was measured to be {approx}10 times smaller than that of the accelerating mode. A charge sweep, up to 80 nC, has been performed, equivalent to {approx} 30 MV/m accelerating field on axis. A variable delay low charge witness bunch following a high charge drive bunch was used to calibrate the gradient in the PBG structure by measuring its maximum energy gain and loss. Experimental results agree well with numerical simulations.

  13. X-Band Photonic Band-Gap Accelerator Structure Breakdown Experiment

    SciTech Connect

    Marsh, Roark A.; Shapiro, Michael A.; Temkin, Richard J.; Dolgashev, Valery A.; Laurent, Lisa L.; Lewandowski, James R.; Yeremian, A.Dian; Tantawi, Sami G.; /SLAC

    2012-06-11

    In order to understand the performance of photonic band-gap (PBG) structures under realistic high gradient, high power, high repetition rate operation, a PBG accelerator structure was designed and tested at X band (11.424 GHz). The structure consisted of a single test cell with matching cells before and after the structure. The design followed principles previously established in testing a series of conventional pillbox structures. The PBG structure was tested at an accelerating gradient of 65 MV/m yielding a breakdown rate of two breakdowns per hour at 60 Hz. An accelerating gradient above 110 MV/m was demonstrated at a higher breakdown rate. Significant pulsed heating occurred on the surface of the inner rods of the PBG structure, with a temperature rise of 85 K estimated when operating in 100 ns pulses at a gradient of 100 MV/m and a surface magnetic field of 890 kA/m. A temperature rise of up to 250 K was estimated for some shots. The iris surfaces, the location of peak electric field, surprisingly had no damage, but the inner rods, the location of the peak magnetic fields and a large temperature rise, had significant damage. Breakdown in accelerator structures is generally understood in terms of electric field effects. These PBG structure results highlight the unexpected role of magnetic fields in breakdown. The hypothesis is presented that the moderate level electric field on the inner rods, about 14 MV/m, is enhanced at small tips and projections caused by pulsed heating, leading to breakdown. Future PBG structures should be built to minimize pulsed surface heating and temperature rise.

  14. Observation of multipactor suppression in a dielectric-loaded accelerating structure using an applied axial magnetic field

    SciTech Connect

    Jing, C.; Konecny, R.; Antipov, S.; Chang, C.; Gold, S. H.; Schoessow, P.; Kanareykin, A.; Gai, W.

    2013-11-18

    Efforts by a number of institutions to develop a Dielectric-Loaded Accelerating (DLA) structure capable of supporting high gradient acceleration when driven by an external radio frequency source have been ongoing over the past decade. Single surface resonant multipactor has been previously identified as one of the major limitations on the practical application of DLA structures in electron accelerators. In this paper, we report the results of an experiment that demonstrated suppression of multipactor growth in an X-band DLA structure through the use of an applied axial magnetic field. This represents an advance toward the practical use of DLA structures in many accelerator applications.

  15. Observation of multipactor suppression in a dielectric-loaded accelerating structure using an applied axial magnetic field

    NASA Astrophysics Data System (ADS)

    Jing, C.; Chang, C.; Gold, S. H.; Konecny, R.; Antipov, S.; Schoessow, P.; Kanareykin, A.; Gai, W.

    2013-11-01

    Efforts by a number of institutions to develop a Dielectric-Loaded Accelerating (DLA) structure capable of supporting high gradient acceleration when driven by an external radio frequency source have been ongoing over the past decade. Single surface resonant multipactor has been previously identified as one of the major limitations on the practical application of DLA structures in electron accelerators. In this paper, we report the results of an experiment that demonstrated suppression of multipactor growth in an X-band DLA structure through the use of an applied axial magnetic field. This represents an advance toward the practical use of DLA structures in many accelerator applications.

  16. Accelerated safety analyses - structural analyses Phase I - structural sensitivity evaluation of single- and double-shell waste storage tanks

    SciTech Connect

    Becker, D.L.

    1994-11-01

    Accelerated Safety Analyses - Phase I (ASA-Phase I) have been conducted to assess the appropriateness of existing tank farm operational controls and/or limits as now stipulated in the Operational Safety Requirements (OSRs) and Operating Specification Documents, and to establish a technical basis for the waste tank operating safety envelope. Structural sensitivity analyses were performed to assess the response of the different waste tank configurations to variations in loading conditions, uncertainties in loading parameters, and uncertainties in material characteristics. Extensive documentation of the sensitivity analyses conducted and results obtained are provided in the detailed ASA-Phase I report, Structural Sensitivity Evaluation of Single- and Double-Shell Waste Tanks for Accelerated Safety Analysis - Phase I. This document provides a summary of the accelerated safety analyses sensitivity evaluations and the resulting findings.

  17. Temporal and Spatial Characteristics of Acceleration Structures in the Auroral Return Current Region

    NASA Astrophysics Data System (ADS)

    Marklund, G. T.; Karlsson, T.; Figueiredo, S.; Johansson, T.; Buchert, S.

    2003-12-01

    Temporal and spatial characteristics of high-altitude auroral electric fields, and, in particular, those which are related to quasi-static auroral electric potential structures, are discussed using Cluster multi-point observations from auroral field line crossings at geocentric distances of about 5 RE. Intense and narrow-structured diverging electric fields, associated with upward accelerated electrons, being fingerprints of quasi-static acceleration structures in the auroral return current region, appear more frequently at these altitudes than their counterpart, converging electric fields, on auroral field lines, for reasons not yet understood. The time needed for evacuating ionospheric electrons at the ionospheric end of the return current flux tube, which depend on the field-aligned current density, represent one characteristic time scale for the accelerating electric fields. We present results from four Cluster encounters with such acceleration structures and how these and their associated field-aligned current and electron distributions, evolve on the different time scales given by different inter-spacecraft separation distances.

  18. Alignment tolerance of accelerating structures and corrections for future linear colliders

    SciTech Connect

    Kubo, K.; Adolphsen, C.; Bane, K.L.F.; Raubenheimer, T.O.; Thompson, K.A.

    1995-06-01

    The alignment tolerance of accelerating structures is estimated by tracking simulations. Both single-bunch and multi-bunch effects are taken into account. Correction schemes for controlling the single and multi-bunch emittance growth in the case of large misalignment are also tested by simulations.

  19. Design of 57.5 MHz cw RFQ structure for the rare isotope accelerator facility.

    SciTech Connect

    Ostroumov, P. N.; Kolomiets, A. A.; Kashinsky, D. A.; Minaev, S. A.; Pershin, V. I.; Yaramishev, S. G.; Tretyakova, T. E.

    2002-01-29

    The Rare Isotope Accelerator (RIA) facility includes a driver linac for production of 400 kW CW heavy-ion beams. The initial acceleration of heavy-ions delivered from an ECR ion source can be effectively performed by a 57.5 MHz four-meter long RFQ. The principal specifications of the RFQ are: (1) formation of extremely low longitudinal emittance; (2) stable operation over a wide range of voltage for acceleration of various ion species needed for RIA operation; (3) simultaneous acceleration of two-charge states of uranium ions. CW operation of an accelerating structure leads to a number of requirements for the resonators such as high shunt impedance, efficient water cooling of all parts of the resonant cavity, mechanical stability together with precise alignment, reliable rf contacts, a stable operating mode and fine tuning of the resonant frequency during operation. To satisfy these requirements a new resonant structure has been developed. This paper discusses beam dynamics and electrodynamics design of the RFQ cavity, as well as, some aspects of the mechanical design of this low-frequency CW RFQ.

  20. Proposal for a study of laser acceleration of electrons using micrograting structures at ATF (Phase 1)

    SciTech Connect

    Chen, W.; Claus, J.; Fernow, R.C.; Fischer, J.; Gallardo, J.C.; Kirk, H.G.; Kramer, H.; Li, Z.; Palmer, R.B.; Rogers, J.; Shrinvasan-Rao, T.; Tsang, T.; Ulc, S.; Veligdan, J.; Warren, J.; Bigio, I.; Kurnit, N.; Shimada, T.; Wang, X.; McDonald, K.T.; Russell, D.P.; Los Alamos National Lab., NM; Princeton Univ., NJ; California Univ., Los Angeles, CA )

    1989-10-29

    We propose to investigate new methods of particle acceleration using a short-pulse CO{sub 2} laser as the power source and grating-like structures as accelerator cavities''. Phase I of this program is intended to demonstrate the principle of the method. We will focus the laser light to a 3 mm line on the surface of the microstructure. The structure is used to transform the electric field pattern of the incoming transversely polarized laser beam to a mode which has a component along the electron beam direction in the vicinity of the surface. With 6 mJ of laser energy and a 6 ps pulse length, the electric field in the spot will be around 1 GV/m. The electron beam from the Brookhaven Accelerator Test Facility (ATF) will be focused transversely within the few micron transverse dimension of the microstructure. The maximum expected acceleration for a 1 GV/m field and a 3 mm acceleration length is 3 MeV. 17 refs., 11 figs., 2 tabs.

  1. Rapid analysis of scattering from periodic dielectric structures using accelerated Cartesian expansions

    SciTech Connect

    Baczewski, Andrew David; Miller, Nicholas C.; Shanker, Balasubramaniam

    2012-03-22

    Here, the analysis of fields in periodic dielectric structures arise in numerous applications of recent interest, ranging from photonic bandgap structures and plasmonically active nanostructures to metamaterials. To achieve an accurate representation of the fields in these structures using numerical methods, dense spatial discretization is required. This, in turn, affects the cost of analysis, particularly for integral-equation-based methods, for which traditional iterative methods require Ο(Ν2) operations, Ν being the number of spatial degrees of freedom. In this paper, we introduce a method for the rapid solution of volumetric electric field integral equations used in the analysis of doubly periodic dielectric structures. The crux of our method is the accelerated Cartesian expansion algorithm, which is used to evaluate the requisite potentials in Ο(Ν) cost. Results are provided that corroborate our claims of acceleration without compromising accuracy, as well as the application of our method to a number of compelling photonics applications.

  2. Summary report : working group 5 on 'electron beam-driven plasma and structure based acceleration concepts'.

    SciTech Connect

    Conde, M. E.; Katsouleas, T.

    2000-10-19

    The talks presented and the work performed on electron beam-driven accelerators in plasmas and structures are summarized. Highlights of the working group include new experimental results from the E-157 Plasma Wakefield Experiment, the E-150 Plasma Lens Experiment and the Argonne Dielectric Structure Wakefield experiments. The presentations inspired discussion and analysis of three working topics: electron hose instability, ion channel lasers and the plasma afterburner.

  3. Near Catastrophic Accelerated Structural Degeneration of the Perimount Magna Pericardial Bioprosthesis in Children.

    PubMed

    Philip, Ranjit; Kumar, T K Susheel; Waller, B Rush; McCoy, Mia; Knott-Craig, Christopher J

    2016-07-01

    Experience with pericardial bioprostheses in young patients is limited. Accelerated degeneration of the Mitroflow valve has recently been reported. We report early accelerated structural valve degeneration with the Perimount Magna bioprosthesis, which has not been previously reported. Young patients with the Magna bioprosthesis are at high risk for rapid progression to severe stenosis, which underscores their need for more vigilant surveillance. The benefits and risks of these bioprosthetic valves must be weighed carefully when options for replacement in these young patients are discussed. PMID:27343502

  4. Design and RF Measurements of AN X-Band Accelerating Structure for the Sparc Project

    NASA Astrophysics Data System (ADS)

    Alesini, D.; Bacci, A.; Falone, A.; Migliorati, M.; Mostacci, A.; Palpini, F.; Palumbo, L.; Spataro, B.

    The paper presents the design of an X-band accelerating section for linearizing the longitudinal phase space in the Frascati Linac Coherent Light Source (SPARC). The nine cells structure, operating on the π standing wave mode, is fed by a central coupler and has been designed to obtain a 42 MV/m accelerating gradient. The 2D profile has been obtained using the electromagnetic codes Superfish and Oscar2D while the coupler has been designed using HFSS. Bead-pull measurements made on a copper prototype have been performed and the results are illustrated and compared with the numerical predictions.

  5. Design and RF Measurements of AN X-Band Accelerating Structure for the Sparc Project

    NASA Astrophysics Data System (ADS)

    Alesini, D.; Bacci, A.; Falone, A.; Migliorati, M.; Mostacci, A.; Palpini, F.; Palumbo, L.; Spataro, B.

    2007-09-01

    The paper presents the design of an X-band accelerating section for linearizing the longitudinal phase space in the Frascati Linac Coherent Light Source (SPARC). The nine cells structure, operating on the π standing wave mode, is fed by a central coupler and has been designed to obtain a 42 MV/m accelerating gradient. The 2D profile has been obtained using the electromagnetic codes Superfish and Oscar2D while the coupler has been designed using HFSS. Bead-pull measurements made on a copper prototype have been performed and the results are illustrated and compared with the numerical predictions.

  6. DEPOSITION DISTRICUTION AMONG THE PARALLEL PATHWAYS IN THE HUMAN LUNG CONDUCTING AIRWAY STRUCTURE.

    EPA Science Inventory

    DEPOSITION DISTRIBUTION AMONG THE PARALLEL PATHWAYS IN THE HUMAN LUNG CONDUCTING AIRWAY STRUCTURE. Chong S. Kim*, USEPA National Health and Environmental Effects Research Lab. RTP, NC 27711; Z. Zhang and C. Kleinstreuer, Department of Mechanical and Aerospace Engineering, North C...

  7. Statistical model for field emitter activation on metallic surfaces used in high-gradient accelerating structures

    NASA Astrophysics Data System (ADS)

    Lagotzky, S.; Müller, G.

    2016-01-01

    Both super- and normal-conducting high-gradient linear accelerators are limited by enhanced field emission (EFE) in the accelerating structures, e.g. due to power loss or ignition of discharges. We discuss the dependence of the number density of typical emitters, i.e. particulates and surface defects, on the electric field level at which they are activated for naturally oxidized metallic surfaces. This activation is explained by the transition of a metal-insulator interface into geometric features that enhance the EFE process. A statistical model is successfully compared to systematic studies of niobium and copper relevant for recent and future linear accelerators. Our results show that the achievable surface quality of Nb might be sufficient for the suppression of EFE in the superconducting accelerating structures for the actual European XFEL but not for the planned International Linear Collider. Moreover, some effort will be required to reduce EFE and thus the breakdown rate of the normal conducting Cu structures for the Compact Linear Collider.

  8. H-mode Accelerating Structures with PMQ Focusing for Low-Beta Beams

    SciTech Connect

    Kurennoy, Sergey S.; O'Hara, James F.; Olivas, Eric R.; Rybarcyk, Lawrence J.

    2011-01-01

    We report on results of the project developing high-efficiency normal-conducting RF accelerating structures based on inter-digital H-mode (IH) cavities and the transverse beam focusing with permanent-magnet quadrupoles (PMQ), for beam velocities in the range of a few percent of the speed of light. The shunt impedance of IH-PMQ structures is 10-20 times higher than that of a conventional drift-tube linac, while the transverse size is 4-5 times smaller. The H-PMQ accelerating structures following a short RFQ can be used both in the front end of ion linacs or in stand-alone applications. Results of the combined 3-D modeling -- electromagnetic computations, beam-dynamics simulations with high currents, and thermal-stress analysis -- for a full IH-PMQ accelerator tank are presented. The accelerating field profile in the tank is tuned to provide the best propagation of a 50-mA deuteron beam using coupled iterations of EM and beamdynamics modeling. Multi-particle simulations withParmela and CST Particle Studio have been used to confirm the design. Measurement results of a cold model of the IH-PMQ tank are presented.

  9. A model for earthquake acceleration monitoring with wireless sensor networks in a structure

    NASA Astrophysics Data System (ADS)

    Fujiwara, Takahiro; Nakamura, Yugo; Jinno, Kousei; Matsubara, Taku; Uehara, Hideyuki

    2014-03-01

    Wireless sensor networks (WSNs) technologies have attracted much attention to collect damage information in a natural disaster. WSNs to monitor temperature or humidity usually collect data once in some seconds or some minutes. Since structural health monitoring (SHM), meanwhile, aims to make a diagnosis for the state of a structure based on detected acceleration, WSNs are a promising technology to collect acceleration data. One concern to employ WSNs in SHM is to detect phenomena at a high sampling rate under energy-aware condition. In this paper, we describe a model for seismic acceleration monitoring, configured with multi-layer networks: WSNs, a wireless distribution system (WDS) and a database server, where the WDS is mainly operating in a wireless local area network (WLAN). Examining the performance in the test bed for the monitoring system, the results showed the system was capable of collecting acceleration at a rate of 100 sampling per second (sps) even in the fashion of intermittent operation, and capable of storing data into a database. We also suggest that the method using intermittent operation with appropriate sampling rate is effective in providing a long time operation for the system by considering in the response motion of a structure.

  10. The influence of acceleration forces on dendritic growth and grain structure

    NASA Technical Reports Server (NTRS)

    Johnston, M. H.; Parr, R. A.

    1982-01-01

    The results of experiments on the tin-15 wt pct lead system are presented, showing the effects on microstructure of solidification in the presence of acceleration forces from 0.0001 to 5 g for three cooling rates. An increase in the acceleration level is shown to drive fluid flow and cause dendrite remelting, fragmentation, and macrosegregation. The cooling rate impacts the final structure through its control of dendrite arm spacings and permeability to fluid flow. At the low (0.0001 g) acceleration, dendrite arm spacings deviated from the predicted relationship to cooling rate. An explanation for this anomaly is given which considers the temperature and concentration gradients in the low-gravity environment.

  11. Daintain/AIF-1 accelerates the activation of insulin-like growth factor-1 receptor signaling pathway in HepG2 cells.

    PubMed

    Jia, Shaohui; Du, Zhongxia; Jiang, Hua; Huang, Xingyuan; Chen, Zhengwang; Chen, Ning

    2015-07-01

    Daintain/allograft inflammatory factor-1 (AIF-1), as a novel inflammatory factor, has been reported to accelerate the proliferation and migration of breast cancer cells. However, the effect of daintain/AIF-1 on hepatocarcinogenesis remains unclear. In order to explore the effect of daintain/AIF-1 on the progression of hepatocellular carcinoma (HCC), enzyme-linked immunosorbent assay (ELISA) and reverse transcription polymerase chain reaction (RT-PCR) were performed to examine the secretion and gene expression of (IGF)-1, IGF-2 and IGFBP-3. The expression of IGF-1R and its downstream targets was evaluated by western blotting. In addition, the proliferation and cell-cycle progression of HepG2 cells was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenylterazolium bromide (MTT) and flow cytometric analysis. The results showed that HepG2 cells subjected to daintain/AIF-1 treatment revealed an obvious increase in the secretion of IGF-1 and IGF-2, and a reduction in the secretion of IGFBP-3. Moreover, daintain/AIF-1 accelerated the activation of IGF-1-induced IGF-1R and its downstream AKT signaling pathway, and subsequently promoted the activation of cyclin D1 pathway, thus accelerating the progression of the cell cycle and eventually promoting the proliferation of HepG2 cells. In conclusion, daintain/AIF-1 promoted the proliferation of HepG2 cells by accelerating the activation of IGF-1R and its downstream signaling pathway, which confirms that daintain/AIF-1 plays a crucial role in the development of HCC. PMID:25998745

  12. New Features of Time Domain Electric-Field Structures in the Auroral Acceleration Region

    SciTech Connect

    Mozer, F.S.; Ergun, R.; Temerin, M.; Cattell, C.; Dombeck, J.; Wygant, J.

    1997-08-01

    The Polar Satellite carries the first three-axis electric field detector flown in the magnetosphere. Its direct measurement of electric field components perpendicular and parallel to the local magnetic field has revealed new classes and features of electric field structures associated with the plasma acceleration that produces discrete auroras and that populates the magnetosphere with plasma of ionospheric origin. These structures, associated with the hydrogen ion cyclotron mode, include very large solitary waves, spiky field structures, wave envelopes of parallel electric fields, and very large amplitude, nonlinear, coherent ion cyclotron waves. {copyright} {ital 1997} {ital The American Physical Society}

  13. Loss of c-Met accelerates development of liver fibrosis in response to CCl(4) exposure through deregulation of multiple molecular pathways.

    PubMed

    Marquardt, Jens U; Seo, Daekwan; Gómez-Quiroz, Luis E; Uchida, Koichi; Gillen, Matthew C; Kitade, Mitsuteru; Kaposi-Novak, Pal; Conner, Elizabeth A; Factor, Valentina M; Thorgeirsson, Snorri S

    2012-06-01

    HGF/c-Met signaling plays a pivotal role in hepatocyte survival and tissue remodeling during liver regeneration. HGF treatment accelerates resolution of fibrosis in experimental animal models. Here, we utilized Met(fl/fl);Alb-Cre(+/-) conditional knockout mice and a carbon tetrachloride(CCl(4))-induced liver fibrosis model to formally address the role of c-Met signaling in hepatocytes in the context of chronic tissue injury. Histological changes during injury (4weeks) and healing phase (4weeks) were monitored by immunohistochemistry; expression levels of selected key fibrotic molecules were evaluated by western blotting, and time-dependent global transcriptomic changes were examined using a microarray platform. Loss of hepatocyte c-Met signaling altered hepatic microenvironment and aggravated hepatic fibrogenesis. Greater liver damage was associated with decreased hepatocyte proliferation, excessive stellate cell activation and rapid dystrophic calcification of necrotic areas. Global transcriptome analysis revealed a broad impact of c-Met on critical signaling pathways associated with fibrosis. Loss of hepatocyte c-Met caused a strong deregulation of chemotactic and inflammatory signaling (MCP-1, RANTES, Cxcl10) in addition to modulation of genes involved in reorganization of the cytoskeletal network (Actb, Tuba1a, Tuba8), intercellular communications and adhesion (Adam8, Icam1, Itgb2), control of cell proliferation (Ccng2, Csnk2a, Cdc6, cdk10), DNA damage and stress response (Rad9, Rad52, Ercc4, Gsta1 and 2, Jun). Our study demonstrates that deletion of c-Met receptor in hepatocytes results in pronounced changes in hepatic metabolism and microenvironment, and establishes an essential role for c-Met in maintaining the structural integrity and adaptive plasticity of the liver under adverse conditions. PMID:22386877

  14. Magnetosheath Filamentary Structures Formed by Ion Acceleration at the Quasi-Parallel Bow Shock

    NASA Technical Reports Server (NTRS)

    Omidi, N.; Sibeck, D.; Gutynska, O.; Trattner, K. J.

    2014-01-01

    Results from 2.5-D electromagnetic hybrid simulations show the formation of field-aligned, filamentary plasma structures in the magnetosheath. They begin at the quasi-parallel bow shock and extend far into the magnetosheath. These structures exhibit anticorrelated, spatial oscillations in plasma density and ion temperature. Closer to the bow shock, magnetic field variations associated with density and temperature oscillations may also be present. Magnetosheath filamentary structures (MFS) form primarily in the quasi-parallel sheath; however, they may extend to the quasi-perpendicular magnetosheath. They occur over a wide range of solar wind Alfvénic Mach numbers and interplanetary magnetic field directions. At lower Mach numbers with lower levels of magnetosheath turbulence, MFS remain highly coherent over large distances. At higher Mach numbers, magnetosheath turbulence decreases the level of coherence. Magnetosheath filamentary structures result from localized ion acceleration at the quasi-parallel bow shock and the injection of energetic ions into the magnetosheath. The localized nature of ion acceleration is tied to the generation of fast magnetosonic waves at and upstream of the quasi-parallel shock. The increased pressure in flux tubes containing the shock accelerated ions results in the depletion of the thermal plasma in these flux tubes and the enhancement of density in flux tubes void of energetic ions. This results in the observed anticorrelation between ion temperature and plasma density.

  15. Magnetosheath filamentary structures formed by ion acceleration at the quasi-parallel bow shock

    NASA Astrophysics Data System (ADS)

    Omidi, N.; Sibeck, D.; Gutynska, O.; Trattner, K. J.

    2014-04-01

    Results from 2.5-D electromagnetic hybrid simulations show the formation of field-aligned, filamentary plasma structures in the magnetosheath. They begin at the quasi-parallel bow shock and extend far into the magnetosheath. These structures exhibit anticorrelated, spatial oscillations in plasma density and ion temperature. Closer to the bow shock, magnetic field variations associated with density and temperature oscillations may also be present. Magnetosheath filamentary structures (MFS) form primarily in the quasi-parallel sheath; however, they may extend to the quasi-perpendicular magnetosheath. They occur over a wide range of solar wind Alfvénic Mach numbers and interplanetary magnetic field directions. At lower Mach numbers with lower levels of magnetosheath turbulence, MFS remain highly coherent over large distances. At higher Mach numbers, magnetosheath turbulence decreases the level of coherence. Magnetosheath filamentary structures result from localized ion acceleration at the quasi-parallel bow shock and the injection of energetic ions into the magnetosheath. The localized nature of ion acceleration is tied to the generation of fast magnetosonic waves at and upstream of the quasi-parallel shock. The increased pressure in flux tubes containing the shock accelerated ions results in the depletion of the thermal plasma in these flux tubes and the enhancement of density in flux tubes void of energetic ions. This results in the observed anticorrelation between ion temperature and plasma density.

  16. Development of an S-band accelerating structure with quasi-symmetric single-feed racetrack couplers

    NASA Astrophysics Data System (ADS)

    Heo, Hoon; Joo, Young-Do; Park, Yong-Jung; Kang, Heung-Sik; Lee, Heung-Soo; Oh, Kyoung-Min; Seo, Hyung-Seok; Noh, Sung-Ju

    2015-03-01

    We developed an S-band traveling-wave accelerating structure for the Pohang Accelerator Laboratory's X-ray free-electron laser (PAL-XFEL), and we fabricated and tested a full-scale prototype. In order to reduce the field asymmetry inside the coupler cavity, we used the SUPERFISH code and the CST MWS electromagnetic field solvers to design the constant-gradient traveling-wave accelerator to use quasi-symmetric single-feed racetrack couplers. The RF measurement results indicate that the accelerating gradient of the prototype structure is as high as 27 MV/m for an input RF power of 65 MW.

  17. An L-Band Superconducting Traveling Wave Accelerating Structure With Feedback

    SciTech Connect

    Kanareykin, A.; Avrakhov, P.; Yakovlev, V. P.; Solyak, N.; Kazakov, S.

    2009-01-22

    The most severe problem of the International Linear Collider is its high cost, resulting in part from the enormous length of the collider. This length is determined mainly by the achievable accelerating gradient in the RF system of the ILC. In the ILC project the required accelerating gradient is higher than 30 MeV/m. Further improvement of the coupling to the beam may be achieved by using a Traveling Wave SC structure [1]. We have demonstrated that an additional gradient increase of up to 46% may be possible if a {pi}/2 TW SC structure is employed. However, a TW SC structure requires a SC feedback waveguide to return the few GW of circulating RF power from the structure output back to the structure input. The test cavity with feedback is designed to demonstrate the possibility of achieving a significantly higher gradient than existing SC structures. The double-coupler powering excitation and tuning have been studied numerically and the corresponding model results are presented. The proposed double-coupler powering scheme significantly reduces the tuning requirements as long as any of the partial modes of given magnitude and phase are excited independently, providing a clear traveling wave regime of structure operation.

  18. Advances in X-Band TW Accelerator Structures Operating in the 100 MV/M Regime

    SciTech Connect

    Higo, Toshiyasu; Higashi, Yasuo; Matsumoto, Shuji; Yokoyama, Kazue; Adolphsen, Chris; Dolgashev, Valery; Jensen, Aaron; Laurent, Lisa; Tantawi, Sami; Wang, Faya; Wang, Juwen; Dobert, Steffen; Grudiev, Alexej; Riddone, Germana; Wuensch, Walter; Zennaro, Riccardo; /CERN

    2012-07-05

    A CERN-SLAC-KEK collaboration on high gradient X-band accelerator structure development for CLIC has been ongoing for three years. The major outcome has been the demonstration of stable 100 MV/m gradient operation of a number of CLIC prototype structures. These structures were fabricated using the technology developed from 1994 to 2004 for the GLC/NLC linear collider initiative. One of the goals has been to refine the essential parameters and fabrication procedures needed to realize such a high gradient routinely. Another goal has been to develop structures with stronger dipole mode damping than those for GLC/NLC. The latter requires that the surface temperature rise during the pulse be higher, which may increase the breakdown rate. One structure with heavy damping has been RF processed and another is nearly finished. The breakdown rates of these structures were found to be higher by two orders of magnitude compared to those with equivalent acceleration mode parameters but without the damping features. This paper presents these results together with some of the earlier results from non-damped structures.

  19. APS linac klystron and accelerating structure gain measurements and klystron PFN voltage regulation requirements

    SciTech Connect

    Sereno, N.S.

    1997-07-01

    This note details measurements of the APS positron linac klystron and accelerating structure gain and presents an analysis of the data using fits to simple mathematical models. The models are used to investigate the sensitivity of the energy dependence of the output positron beam to klystron parameters. The gain measurements are separated into two parts: first, the energy gains of the accelerating structures of the positron linac are measured as a function of output power of the klystron; second, the klystron output power is measured as a function of input drive power and pulse forming network (PFN) voltage. This note concentrates on the positron linac rf and its performance as it directly affects the energy stability of the positron beam injected into the positron accumulator ring (PAR). Ultimately it is important to be able to minimize beam energy variations to maximize the PAR accumulation efficiency.

  20. Parallel Computation of Integrated Electromagnetic, Thermal and Structural Effects for Accelerator Cavities

    SciTech Connect

    Akcelik, V.; Candel, A.E.; Kabel, A.C.; Ko, K.; Lee, L.; Li, Z.; Ng, C.K.; Xiao, L.; /SLAC

    2011-11-02

    The successful operation of accelerator cavities has to satisfy both rf and mechanical requirements. It is highly desirable that electromagnetic, thermal and structural effects such as cavity wall heating and Lorentz force detuning in superconducting rf cavities can be addressed in an integrated analysis. Based on the SLAC parallel finite-element code infrastructure for electromagnetic modeling, a novel multi-physics analysis tool has been developed to include additional thermal and mechanical effects. The parallel computation enables virtual prototyping of accelerator cavities on computers, which would substantially reduce the cost and time of a design cycle. The multi-physics tool is applied to the LCLS rf gun for electromagnetic, thermal and structural analyses.

  1. Parallel Computation of Intergrated Electronmagnetic, Thermal and Structural Effects for Accelerator Cavities

    SciTech Connect

    Akcelik, V.; Candel, A.; Kabel, A.; Lee, L-Q.; Li, Z.; Ng, C-K.; Xiao, L.; Ko, K.

    2008-07-02

    The successful operation of accelerator cavities has to satisfy both rf and mechanical requirements. It is highly desirable that electromagnetic, thermal and structural effects such as cavity wall heating and Lorentz force detuning in superconducting rf cavities can be addressed in an integrated analysis. Based on the SLAC parallel finite-element code infrastructure for electromagnetic modeling, a novel multi-physics analysis tool has been developed to include additional thermal and mechanical effects. The parallel computation enables virtual prototyping of accelerator cavities on computers, which would substantially reduce the cost and time of a design cycle. The multi-physics tool is applied to the LCLS rf gun for electromagnetic, thermal and structural analyses.

  2. Acceleration response spectrum for prediction of structural vibration due to individual bouncing

    NASA Astrophysics Data System (ADS)

    Chen, Jun; Wang, Lei; Racic, Vitomir; Lou, Jiayue

    2016-08-01

    This study is designed to develop an acceleration response spectrum that can be used in vibration serviceability assessment of civil engineering structures, such as floors and grandstands those are dynamically excited by individual bouncing. The spectrum is derived from numerical simulations and statistical analysis of acceleration responses of a single degree of freedom system with variable natural frequency and damping under a large number of experimentally measured individual bouncing loads. Its mathematical representation is fit for fast yet reliable application in design practice and is comprised of three equations that describe three distinct frequency regions observed in the actual data: the first resonant plateau (2-3.5 Hz), the second resonant plateau (4-7 Hz) and a descension region (7-15 Hz). Finally, this paper verifies the proposed response spectrum approach to predict structural vibration by direct comparison against numerical simulations and experimental results.

  3. PI3K/Akt pathway restricts epithelial adhesion of Dr+ Escherichia coli by down-regulating the expression of Decay Accelerating Factor (DAF)

    PubMed Central

    Banadakoppa, Manu; Goluszko, Pawel; Liebenthal, Daniel; Nowicki, Bogdan J.; Nowicki, Stella; Yallampalli, Chandra

    2014-01-01

    The urogenital microbial infection in pregnancy is an important cause of maternal and neonatal morbidity and mortality. Uropathogenic Escherichia coli strains which express Dr fimbriae (Dr+) are associated with unique gestational virulence and they utilize cell surface decay accelerating factor (DAF or CD55) as one of the cellular receptor before invading the epithelial cells. Previous studies in our laboratory established that nitric oxide reduces the rate of E. coli invasion by delocalizing the DAF protein from cell surface lipid rafts and down-regulating its expression. The phosphoinositide 3-kinase/ protein kinase B (PI3K/Akt) cell signal pathway plays an important role in host-microbe interaction because many bacteria including E. coli activate this pathway in order to establish infection. In the present study we showed that the PI3K/Akt pathway negatively regulates the expression of DAF on the epithelial cell surface and thus inhibits the adhesion of Dr+ E. coli to epithelial cells. Initially, using two human cell lines Ishikawa and HeLa which differ in constitutive activity of PI3K/Akt we showed that DAF levels were associated with the PI3K/Akt pathway. We then showed that the DAF gene expression was up-regulated and the Dr+ E. coli adhesion increased after the suppression of PI3K/Akt pathway in Ishikawa cells using inhibitor LY-294002, and a plasmid which allowed the expression of PI3K/Akt regulatory protein PTEN. The down-regulation of PTEN protein using PTEN-specific siRNA activated the PI3K/Akt pathway, down-regulated the DAF and decreased the adhesion of Dr+ E. coli. We conclude that the PI3K/Akt pathway regulated the DAF expression in a nitric oxide independent manner. PMID:24599886

  4. Structural activation pathways from dynamic olfactory receptor-odorant interactions.

    PubMed

    Lai, Peter C; Singer, Michael S; Crasto, Chiquito J

    2005-11-01

    We have simulated an odor ligand's dynamic behavior in the binding region of an olfactory receptor (OR). Our short timescale computational studies (up to 200 ps) have helped identify unprecedented postdocking ligand behavior of ligands. From in vacuo molecular dynamics simulations of interactions between models of rat OR I7 and 10 aldehyde ligands, we have identified a dissociative pathway along which the ligand exits and enters the OR-binding pocket--a transit event. The ligand's transit through the receptor's binding region may mark the beginning of a signal transduction cascade leading to odor recognition. We have graphically traced the rotameric changes in key OR amino acid side chains during the transit. Our results have helped substantiate or refute previously held notions of amino acid contribution to ligand stability in the binding pocket. Our observations of ligand activity when compared to those of experimental (electroolfactogram response) OR-activation studies provide a view to predicting the stability of ligands in the binding pocket as a precursor to OR activation by the ligand. PMID:16243965

  5. Studies of coupled cavity LINAC (CCL) accelerating structures with 3-D codes

    SciTech Connect

    Spalek, G.

    2000-08-01

    The cw CCL being designed for the Accelerator Production of Tritium (APT) project accelerates protons from 96 MeV to 211 MeV. It consists of 99 segments each containing up to seven accelerating cavities. Segments are coupled by intersegment coupling cavities and grouped into supermodules. The design method needs to address not only basic cavity sizing for a given coupling and pi/2 mode frequency, but also the effects of high power densities on the cavity frequency, mechanical stresses, and the structure's stop band during operation. On the APT project, 3-D RF (Ansoft Corp.'s HFSS) and coupled RF/structural (Ansys Inc.'s ANSYS) codes are being used. to develop tools to address the above issues and guide cooling channel design. The code's predictions are being checked against available low power Aluminum models. Stop band behavior under power will be checked once the tools are extended to CCDTL structures that have been tested at high power. A summary of calculations made to date and agreement with measured results will be presented.

  6. Laser Wakefield Acceleration: Structural and Dynamic Studies. Final Technical Report ER40954

    SciTech Connect

    Downer, Michael C.

    2014-12-19

    Particle accelerators enable scientists to study the fundamental structure of the universe, but have become the largest and most expensive of scientific instruments. In this project, we advanced the science and technology of laser-plasma accelerators, which are thousands of times smaller and less expensive than their conventional counterparts. In a laser-plasma accelerator, a powerful laser pulse exerts light pressure on an ionized gas, or plasma, thereby driving an electron density wave, which resembles the wake behind a boat. Electrostatic fields within this plasma wake reach tens of billions of volts per meter, fields far stronger than ordinary non-plasma matter (such as the matter that a conventional accelerator is made of) can withstand. Under the right conditions, stray electrons from the surrounding plasma become trapped within these “wake-fields”, surf them, and acquire energy much faster than is possible in a conventional accelerator. Laser-plasma accelerators thus might herald a new generation of compact, low-cost accelerators for future particle physics, x-ray and medical research. In this project, we made two major advances in the science of laser-plasma accelerators. The first of these was to accelerate electrons beyond 1 gigaelectronvolt (1 GeV) for the first time. In experimental results reported in Nature Communications in 2013, about 1 billion electrons were captured from a tenuous plasma (about 1/100 of atmosphere density) and accelerated to 2 GeV within about one inch, while maintaining less than 5% energy spread, and spreading out less than ½ milliradian (i.e. ½ millimeter per meter of travel). Low energy spread and high beam collimation are important for applications of accelerators as coherent x-ray sources or particle colliders. This advance was made possible by exploiting unique properties of the Texas Petawatt Laser, a powerful laser at the University of Texas at Austin that produces pulses of 150 femtoseconds (1 femtosecond is 10

  7. Structuring Contexts: Pathways toward Un-Obstructing Race-Consciousness

    ERIC Educational Resources Information Center

    Berchini, Christina

    2016-01-01

    This research is situated in second-wave White Teacher Identity studies and investigates the ways context structures a high school English teacher's white identity, practices, and race-consciousness. Working with detailed data and vignettes from a single case study, the author highlights the teaching of a unit on the Holocaust. Using the required…

  8. GPU-Accelerated Analysis and Visualization of Large Structures Solved by Molecular Dynamics Flexible Fitting

    PubMed Central

    McGreevy, Ryan; Isralewitz, Barry

    2014-01-01

    Hybrid structure fitting methods combine data from cryo-electron microscopy and X-ray crystallography with molecular dynamics simulations for the determination of all-atom structures of large biomolecular complexes. Evaluating the quality-of-fit obtained from hybrid fitting is computationally demanding, particularly in the context of a multiplicity of structural conformations that must be evaluated. Existing tools for quality-of-fit analysis and visualization have previously targeted small structures and are too slow to be used interactively for large biomolecular complexes of particular interest today such as viruses or for long molecular dynamics trajectories as they arise in protein folding. We present new data-parallel and GPU-accelerated algorithms for rapid interactive computation of quality-of-fit metrics linking all-atom structures and molecular dynamics trajectories to experimentally determined density maps obtained from cryo-electron microscopy or X-ray crystallography. We evaluate the performance and accuracy of the new quality-of-fit analysis algorithms vis-a-vis existing tools, examine algorithm performance on GPU-accelerated desktop workstations and supercomputers, and describe new visualization techniques for results of hybrid structure fitting methods. PMID:25340325

  9. Studies of beam induced dipole-mode signals in accelerating structures at the SLC

    SciTech Connect

    Seidel, M.

    1997-06-01

    Beam emittance dilution by self induced transverse fields (wakefields) in accelerating structures is a key problem in linear accelerators. To minimize the wakefield effects the beam trajectory must be precisely centered within the structures. An efficient way to achieve this is to detect beam induced microwave signals in the lowest dipole mode band and to steer the beam by minimizing these signals. This paper briefly covers some experiences from SLC S-band structures, but mainly concentrates on results of a wakefield instrumentation scheme applied to a NLC prototype X-band structure and tested with beam in the SLC linac. A beam based in-situ structure straightness measurement is shown as well as results of beam steering experiments based on phase and amplitude detection of two separated modes in the structure. After centering the beam the reduction of the wakefield was demonstrated independently by probing it with a test bunch that is deflected by the residual wakefield at a short distance behind the drive bunch.

  10. Self-mapping the longitudinal field structure of a nonlinear plasma accelerator cavity

    PubMed Central

    Clayton, C. E.; Adli, E.; Allen, J.; An, W.; Clarke, C. I.; Corde, S.; Frederico, J.; Gessner, S.; Green, S. Z.; Hogan, M. J.; Joshi, C.; Litos, M.; Lu, W.; Marsh, K. A.; Mori, W. B.; Vafaei-Najafabadi, N.; Xu, X.; Yakimenko, V.

    2016-01-01

    The preservation of emittance of the accelerating beam is the next challenge for plasma-based accelerators envisioned for future light sources and colliders. The field structure of a highly nonlinear plasma wake is potentially suitable for this purpose but has not been yet measured. Here we show that the longitudinal variation of the fields in a nonlinear plasma wakefield accelerator cavity produced by a relativistic electron bunch can be mapped using the bunch itself as a probe. We find that, for much of the cavity that is devoid of plasma electrons, the transverse force is constant longitudinally to within ±3% (r.m.s.). Moreover, comparison of experimental data and simulations has resulted in mapping of the longitudinal electric field of the unloaded wake up to 83 GV m−1 to a similar degree of accuracy. These results bode well for high-gradient, high-efficiency acceleration of electron bunches while preserving their emittance in such a cavity. PMID:27527569

  11. Self-mapping the longitudinal field structure of a nonlinear plasma accelerator cavity.

    PubMed

    Clayton, C E; Adli, E; Allen, J; An, W; Clarke, C I; Corde, S; Frederico, J; Gessner, S; Green, S Z; Hogan, M J; Joshi, C; Litos, M; Lu, W; Marsh, K A; Mori, W B; Vafaei-Najafabadi, N; Xu, X; Yakimenko, V

    2016-01-01

    The preservation of emittance of the accelerating beam is the next challenge for plasma-based accelerators envisioned for future light sources and colliders. The field structure of a highly nonlinear plasma wake is potentially suitable for this purpose but has not been yet measured. Here we show that the longitudinal variation of the fields in a nonlinear plasma wakefield accelerator cavity produced by a relativistic electron bunch can be mapped using the bunch itself as a probe. We find that, for much of the cavity that is devoid of plasma electrons, the transverse force is constant longitudinally to within ±3% (r.m.s.). Moreover, comparison of experimental data and simulations has resulted in mapping of the longitudinal electric field of the unloaded wake up to 83 GV m(-1) to a similar degree of accuracy. These results bode well for high-gradient, high-efficiency acceleration of electron bunches while preserving their emittance in such a cavity. PMID:27527569

  12. Acceleration ground test program to verify GAS payload No. 559 structure/support avionics and experiment structural integrity

    NASA Technical Reports Server (NTRS)

    Cassanto, John M.; Cassanto, Valerie A.

    1988-01-01

    Acceleration ground tests were conducted on the Get Away Special (GAS) payload 559 to verify the structural integrity of the structure/support avionics and two of the planned three flight experiments. The ITA (Integrated Test Area) Standardized Experiment Module (ISEM) structure was modified to accommodate the experiments for payload 559. The ISEM avionics consisted of a heavy duty sliver zinc power supply, three orthogonal-mounted low range microgravity accelerometers, a tri-axis high range accelerometer, a solid state recorder/programmer sequencer, and pressure and temperature sensors. The tests were conducted using the Gravitational Plant Physiology Laboratory Centrifuge of the University City Science Center in Philadelphia, PA. The launch-powered flight steady state acceleration profile of the shuttle was simulated from lift-off through jettison of the External Tank (3.0 g's). Additional tests were conducted at twice the nominal powered flight acceleration levels (6 g's) and an over-test condition of four times the powered flight loads to 12.6 g's. The present test program has demonstrated the value of conducting ground tests to verify GAS payload experiment integrity and operation before flying on the shuttle.

  13. Complete multipactor suppression in an X-band dielectric-loaded accelerating structure

    NASA Astrophysics Data System (ADS)

    Jing, C.; Gold, S. H.; Fischer, Richard; Gai, W.

    2016-05-01

    Multipactor is a major issue limiting the gradient of rf-driven Dielectric-Loaded Accelerating (DLA) structures. Theoretical models have predicted that an axial magnetic field applied to DLA structures may completely block the multipactor discharge. However, previous attempts to demonstrate this magnetic field effect in an X-band traveling-wave DLA structure were inconclusive, due to the axial variation of the applied magnetic field, and showed only partial suppression of the multipactor loading [Jing et al., Appl. Phys. Lett. 103, 213503 (2013)]. The present experiment has been performed under improved conditions with a uniform axial magnetic field extending along the length of an X-band standing-wave DLA structure. Multipactor loading began to be continuously reduced starting from 3.5 kG applied magnetic field and was completely suppressed at ˜8 kG. Dependence of multipactor suppression on the rf gradient inside the DLA structure was also measured.

  14. Structural details, pathways, and energetics of unfolding apomyoglobin.

    PubMed

    Onufriev, Alexey; Case, David A; Bashford, Donald

    2003-01-17

    Protein folding is often difficult to characterize experimentally because of the transience of intermediate states, and the complexity of the protein-solvent system. Atomistic simulations, which could provide more detailed information, have had to employ highly simplified models or high temperatures, to cope with the long time scales of unfolding; direct simulation of folding is even more problematic. We report a fully atomistic simulation of the acid-induced unfolding of apomyoglobin in which the protonation of acidic side-chains to simulate low pH is sufficient to induce unfolding at room temperature with no added biasing forces or other unusual conditions; and the trajectory is validated by comparison to experimental characterization of intermediate states. Novel insights provided by their analysis include: characterization of a dry swollen globule state forming a barrier to initial unfolding or final folding; observation of cooperativity in secondary and tertiary structure formation and its explanation in terms of dielectric environments; and structural details of the intermediate and the completely unfolded states. These insights involve time scales and levels of structural detail that are presently beyond the range of experiment, but come within reach through the simulation methods described here. An implicit solvation model is used to analyze the energetics of protein folding at various pH and ionic strength values, and a reasonable estimate of folding free energy is obtained. Electrostatic interactions are found to disfavor folding. PMID:12498802

  15. Ion acceleration and coherent structures generated by lower hybrid shear-driven instabilities

    NASA Technical Reports Server (NTRS)

    Romero, H.; Ganguli, G.; Lee, Y. C.

    1992-01-01

    It is shown that if k = omega(S)/omega(LH) greater than 1 (omega(S) and omega(LH) are the shear and lower hybrid frequencies), a sheared electron cross-field flow excites the electron-ion-hybrid mode, causing significant perpendicular ion acceleration. The electric potential develops coherent structures (vortexlike) longer than the electron Larmor radius, rho(e). For k less than 1, a smooth transition occurs where the wavelength becomes of the order of rho(e), the lower hybrid drift instability dominates, and the formation of vortexlike structures is no longer observed. The results are relevant to laboratory, laser-produced, and space plasmas.

  16. Theory of factors limiting high gradient operation of warm accelerating structures

    SciTech Connect

    Nusinovich, Gregory S.; Antonsen, Thomas M.; Kishek, Rami

    2014-07-25

    This final report summarizes the research performed during the time period from 8/1/2010 to 7/31/2013. It consists of two parts describing our studies in two directions: (a) analysis of factors limiting operation of dielectric-loaded accelerating (DLA) structures where the main problem is the occurrence of multipactor on dielectric surfaces, and (b) studies of effects associated with either RF magnetic or RF electric fields which may cause the RF breakdown in high-gradient metallic accelerating structures. In the studies of DLA structures, at least, two accomplishments should be mentioned: the development of a 3D non-stationary, self-consistent code describing the multipactor phenomena and yielding very good agreement with some experimental data obtained in joint ANL/NRL experiments. In the metallic structures, such phenomena as the heating and melting of micro-particles (metallic dust) by RF electric and magnetic fields in single-shot and rep-rate regimes is analyzed. Also, such processes in micro-protrusions on the structure surfaces as heating and melting due to the field emitted current and the Nottingham effect are thoroughly investigated with the account for space charge of emitted current on the field emission from the tip.

  17. FPGA accelerator for protein secondary structure prediction based on the GOR algorithm

    PubMed Central

    2011-01-01

    Background Protein is an important molecule that performs a wide range of functions in biological systems. Recently, the protein folding attracts much more attention since the function of protein can be generally derived from its molecular structure. The GOR algorithm is one of the most successful computational methods and has been widely used as an efficient analysis tool to predict secondary structure from protein sequence. However, the execution time is still intolerable with the steep growth in protein database. Recently, FPGA chips have emerged as one promising application accelerator to accelerate bioinformatics algorithms by exploiting fine-grained custom design. Results In this paper, we propose a complete fine-grained parallel hardware implementation on FPGA to accelerate the GOR-IV package for 2D protein structure prediction. To improve computing efficiency, we partition the parameter table into small segments and access them in parallel. We aggressively exploit data reuse schemes to minimize the need for loading data from external memory. The whole computation structure is carefully pipelined to overlap the sequence loading, computing and back-writing operations as much as possible. We implemented a complete GOR desktop system based on an FPGA chip XC5VLX330. Conclusions The experimental results show a speedup factor of more than 430x over the original GOR-IV version and 110x speedup over the optimized version with multi-thread SIMD implementation running on a PC platform with AMD Phenom 9650 Quad CPU for 2D protein structure prediction. However, the power consumption is only about 30% of that of current general-propose CPUs. PMID:21342582

  18. Structural Basis for Accelerated Cleavage of Bovine Pancreatic Trypsin Inhibitor (BPTI) by Human Mesotrypsin

    SciTech Connect

    Salameh,M.; Soares, A.; Hockla, A.; Radisky, E.

    2008-01-01

    Human mesotrypsin is an isoform of trypsin that displays unusual resistance to polypeptide trypsin inhibitors and has been observed to cleave several such inhibitors as substrates. Whereas substitution of arginine for the highly conserved glycine 193 in the trypsin active site has been implicated as a critical factor in the inhibitor resistance of mesotrypsin, how this substitution leads to accelerated inhibitor cleavage is not clear. Bovine pancreatic trypsin inhibitor (BPTI) forms an extremely stable and cleavage-resistant complex with trypsin, and thus provides a rigorous challenge of mesotrypsin catalytic activity toward polypeptide inhibitors. Here, we report kinetic constants for mesotrypsin and the highly homologous (but inhibitor sensitive) human cationic trypsin, describing inhibition by, and cleavage of BPTI, as well as crystal structures of the mesotrypsin-BPTI and human cationic trypsin-BPTI complexes. We find that mesotrypsin cleaves BPTI with a rate constant accelerated 350-fold over that of human cationic trypsin and 150,000-fold over that of bovine trypsin. From the crystal structures, we see that small conformational adjustments limited to several side chains enable mesotrypsin-BPTI complex formation, surmounting the predicted steric clash introduced by Arg-193. Our results show that the mesotrypsin-BPTI interface favors catalysis through (a) electrostatic repulsion between the closely spaced mesotrypsin Arg-193 and BPTI Arg-17, and (b) elimination of two hydrogen bonds between the enzyme and the amine leaving group portion of BPTI. Our model predicts that these deleterious interactions accelerate leaving group dissociation and deacylation.

  19. Survivability of integrated PVDF film sensors to accelerated ageing conditions in aeronautical/aerospace structures

    NASA Astrophysics Data System (ADS)

    Guzman, E.; Cugnoni, J.; Gmür, T.; Bonhôte, P.; Schorderet, A.

    2013-06-01

    This work validates the use of integrated polyvinylidene fluoride (PVDF) film sensors for dynamic testing, even after being subjected to UV-thermo-hygro-mechanical accelerated ageing conditions. The verification of PVDF sensors’ survivability in these environmental conditions, typically confronted by civil and military aircraft, is the main concern of the study. The evaluation of survivability is made by a comparison of dynamic testing results provided by the PVDF patch sensors subjected to an accelerated ageing protocol, and those provided by neutral non-aged sensors (accelerometers). The available measurements are the time-domain response signals issued from a modal analysis procedure, and the corresponding frequency response functions (FRF). These are in turn used to identify the constitutive properties of the samples by extraction of the modal parameters, in particular the natural frequencies. The composite specimens in this study undergo different accelerated ageing processes. After several weeks of experimentation, the samples exhibit a loss of stiffness, represented by a decrease in the elastic moduli down to 10%. Despite the ageing, the integrated PVDF sensors, subjected to the same ageing conditions, are still capable of providing reliable data to carry out a close followup of these changes. This survivability is a determinant asset in order to use integrated PVDF sensors to perform structural health monitoring (SHM) in the future of full-scale composite aeronautical structures.

  20. Conceptual Design of Dielectric Accelerating Structures for Intense Neutron and Monochromatic X-ray Sources

    SciTech Connect

    Blanovsky, Anatoly

    2004-12-07

    Bright compact photon sources, which utilize electron beam interaction with periodic structures, may benefit a broad range of medical, industrial and scientific applications. A class of dielectric-loaded periodic structures for hard and soft X-ray production has been proposed that would provide a high accelerating gradient when excited by an external RF and/or primary electron beam. Target-distributed accelerators (TDA), in which an additional electric field compensates for lost beam energy in internal targets, have been shown to provide the necessary means to drive a high flux subcritical reactor (HFSR) for nuclear waste transmutation. The TDA may also be suitable for positron and nuclear isomer production, X-ray lithography and monochromatic computer tomography. One of the early assumptions of the theory of dielectric wake-field acceleration was that, in electrodynamics, the vector potential was proportional to the scalar potential. The analysis takes into consideration a wide range of TDA design aspects including the wave model of observed phenomena, a layered compound separated by a Van der Waals gap and a compact energy source based on fission electric cells (FEC) with a multistage collector. The FEC is a high-voltage power source that directly converts the kinetic energy of the fission fragments into electrical potential of about 2MV.

  1. Numerical simulations of input and output couplers for linear accelerator structures

    SciTech Connect

    Ng, C.K.; Ko, K.

    1993-04-01

    We present the numerical procedures involved in the design of coupler cavities for accelerator sections for linear colliders. The MAFIA code is used to simulate an X-band accelerator section with a symmetrical double-input coupler at each end. The transmission properties of the structure are calculated in the time domain and the dimensions of the coupler cavities are adjusted until the power coupling is optimized and frequency synchronism is obtained. We compare the performance of the symmetrical double-input design with that of the conventional single-input type by evaluating the field amplitude and phase asymmetries. We also evaluate the peak gradient in the coupler and discuss the implication of pulse rise time on dark current generation.

  2. Beam Based HOM Analysis of Accelerating Structures at the TESLA Test Facility Linac

    SciTech Connect

    Wendt, M.; Schreiber, S.; Castro, P.; Gossel, A.; Huning, M.; Devanz, G.; Jablonka, M.; Magne, C.; Napoly, O.; Baboi, N.; /SLAC

    2005-08-09

    The beam emittance in future linear accelerators for high energy physics and SASE-FEL applications depends highly on the field performance in the accelerating structures, i.e. the damping of higher order modes (HOM). Besides theoretical and laboratory analysis, a beam based analysis technique was established [1] at the TESLA Test Facility (TTF) linac. It uses a charge modulated beam of variable modulation frequency to excite dipole modes. This causes a modulation of the transverse beam displacement, which is observed at a downstream BPM and associated with a direct analysis of the modes at the HOM-couplers. A brief introduction of eigenmodes of a resonator and the concept of the wake potential is given. Emphasis is put on beam instrumentation and signal analysis aspects, required for this beam based HOM measurement technique.

  3. Comparative metabolomics and structural characterizations illuminate colibactin pathway-dependent small molecules.

    PubMed

    Vizcaino, Maria I; Engel, Philipp; Trautman, Eric; Crawford, Jason M

    2014-07-01

    The gene cluster responsible for synthesis of the unknown molecule "colibactin" has been identified in mutualistic and pathogenic Escherichia coli. The pathway endows its producer with a long-term persistence phenotype in the human bowel, a probiotic activity used in the treatment of ulcerative colitis, and a carcinogenic activity under host inflammatory conditions. To date, functional small molecules from this pathway have not been reported. Here we implemented a comparative metabolomics and targeted structural network analyses approach to identify a catalog of small molecules dependent on the colibactin pathway from the meningitis isolate E. coli IHE3034 and the probiotic E. coli Nissle 1917. The structures of 10 pathway-dependent small molecules are proposed based on structural characterizations and network relationships. The network will provide a roadmap for the structural and functional elucidation of a variety of other small molecules encoded by the pathway. From the characterized small molecule set, in vitro bacterial growth inhibitory and mammalian CNS receptor antagonist activities are presented. PMID:24932672

  4. Planar-Dielectric-Wakefield Accelerator Structure Using Bragg-Reflector Boundaries

    NASA Astrophysics Data System (ADS)

    Andonian, G.; Williams, O.; Barber, S.; Bruhwiler, D.; Favier, P.; Fedurin, M.; Fitzmorris, K.; Fukasawa, A.; Hoang, P.; Kusche, K.; Naranjo, B.; O'Shea, B.; Stoltz, P.; Swinson, C.; Valloni, A.; Rosenzweig, J. B.

    2014-12-01

    We report experimental measurements of narrow-band, single-mode excitation, and drive beam energy modulation, in a dielectric wakefield accelerating structure with planar geometry and Bragg-reflector boundaries. A short, relativistic electron beam (˜1 ps ) with moderate charge (˜100 pC ) is used to drive the wakefields in the structure. The fundamental mode of the structure is reinforced by constructive interference in the alternating dielectric layers at the boundary, and is characterized by the spectral analysis of the emitted coherent Cherenkov radiation signal. Data analysis shows a narrow-band peak at 210 GHz corresponding to the fundamental mode of the structure. Simulations in both 2D and 3D provide insight into the propagating fields and reproduction of the electron beams dynamics observables and emitted radiation characteristics.

  5. The buncher optimization for the biperiodic accelerating structure with the high-frequency focusing

    NASA Astrophysics Data System (ADS)

    Fadin, A. I.

    2006-03-01

    The bunching part optimization results of an on-axis-coupled biperiodic accelerating structure for electron linac with high-frequency focusing are presented. System is intended for operation in the continuous regime at operating frequency of 2856 MHz and input power 5.5 MW. The basic development challenge for such installations on average input currents is the effective beam transfer through the structure. Some variants of the bunching sections distinguished by number of bunching cells were considered. The optimum capture ratio and an acceptable spectrum are provided by structure with five bunching cells. Optimization was carried out by means of dynamics simulation code PARMELA and a package of applied programs for the axial symmetric structures calculation SUPERFISH. Taking into account, space-charge limitation, the maximum capture ratio is 55%.

  6. HOM-Free Linear Accelerating Structure for e+ e- Linear Collider at C-Band

    SciTech Connect

    Kubo, Kiyoshi

    2003-07-07

    HOM-free linear acceleration structure using the choke mode cavity (damped cavity) is now under design for e{sup +}e{sup -} linear collider project at C-band frequency (5712 MHz). Since this structure shows powerful damping effect on most of all HOMs, there is no multibunch problem due to long range wakefields. The structure will be equipped with the microwave absorbers in each cells and also the in-line dummy load in the last few cells. The straightness tolerance for 1.8 m long structure is closer than 30 {micro}m for 25% emittance dilution limit, which can be achieved by standard machining and braising techniques. Since it has good vacuum pumping conductance through annular gaps in each cell, instabilities due to the interaction of beam with the residual-gas and ions can be minimized.

  7. Planar-dielectric-wakefield accelerator structure using Bragg-reflector boundaries.

    PubMed

    Andonian, G; Williams, O; Barber, S; Bruhwiler, D; Favier, P; Fedurin, M; Fitzmorris, K; Fukasawa, A; Hoang, P; Kusche, K; Naranjo, B; O'Shea, B; Stoltz, P; Swinson, C; Valloni, A; Rosenzweig, J B

    2014-12-31

    We report experimental measurements of narrow-band, single-mode excitation, and drive beam energy modulation, in a dielectric wakefield accelerating structure with planar geometry and Bragg-reflector boundaries. A short, relativistic electron beam (∼1  ps) with moderate charge (∼100  pC) is used to drive the wakefields in the structure. The fundamental mode of the structure is reinforced by constructive interference in the alternating dielectric layers at the boundary, and is characterized by the spectral analysis of the emitted coherent Cherenkov radiation signal. Data analysis shows a narrow-band peak at 210 GHz corresponding to the fundamental mode of the structure. Simulations in both 2D and 3D provide insight into the propagating fields and reproduction of the electron beams dynamics observables and emitted radiation characteristics. PMID:25615344

  8. Experimental high gradient testing of a 17.1 GHz photonic band-gap accelerator structure

    NASA Astrophysics Data System (ADS)

    Munroe, Brian J.; Zhang, JieXi; Xu, Haoran; Shapiro, Michael A.; Temkin, Richard J.

    2016-03-01

    We report the design, fabrication, and high gradient testing of a 17.1 GHz photonic band-gap (PBG) accelerator structure. Photonic band-gap (PBG) structures are promising candidates for electron accelerators capable of high-gradient operation because they have the inherent damping of high order modes required to avoid beam breakup instabilities. The 17.1 GHz PBG structure tested was a single cell structure composed of a triangular array of round copper rods of radius 1.45 mm spaced by 8.05 mm. The test assembly consisted of the test PBG cell located between conventional (pillbox) input and output cells, with input power of up to 4 MW from a klystron supplied via a TM01 mode launcher. Breakdown at high gradient was observed by diagnostics including reflected power, downstream and upstream current monitors and visible light emission. The testing procedure was first benchmarked with a conventional disc-loaded waveguide structure, which reached a gradient of 87 MV /m at a breakdown probability of 1.19 ×10-1 per pulse per meter. The PBG structure was tested with 100 ns pulses at gradient levels of less than 90 MV /m in order to limit the surface temperature rise to 120 K. The PBG structure reached up to 89 MV /m at a breakdown probability of 1.09 ×10-1 per pulse per meter. These test results show that a PBG structure can simultaneously operate at high gradients and low breakdown probability, while also providing wakefield damping.

  9. Rapid analysis of scattering from periodic dielectric structures using accelerated Cartesian expansions

    DOE PAGESBeta

    Baczewski, Andrew David; Miller, Nicholas C.; Shanker, Balasubramaniam

    2012-03-22

    Here, the analysis of fields in periodic dielectric structures arise in numerous applications of recent interest, ranging from photonic bandgap structures and plasmonically active nanostructures to metamaterials. To achieve an accurate representation of the fields in these structures using numerical methods, dense spatial discretization is required. This, in turn, affects the cost of analysis, particularly for integral-equation-based methods, for which traditional iterative methods require Ο(Ν2) operations, Ν being the number of spatial degrees of freedom. In this paper, we introduce a method for the rapid solution of volumetric electric field integral equations used in the analysis of doubly periodic dielectricmore » structures. The crux of our method is the accelerated Cartesian expansion algorithm, which is used to evaluate the requisite potentials in Ο(Ν) cost. Results are provided that corroborate our claims of acceleration without compromising accuracy, as well as the application of our method to a number of compelling photonics applications.« less

  10. Accelerating Content-Based Image Retrieval via GPU-Adaptive Index Structure

    PubMed Central

    2014-01-01

    A tremendous amount of work has been conducted in content-based image retrieval (CBIR) on designing effective index structure to accelerate the retrieval process. Most of them improve the retrieval efficiency via complex index structures, and few take into account the parallel implementation of them on underlying hardware, making the existing index structures suffer from low-degree of parallelism. In this paper, a novel graphics processing unit (GPU) adaptive index structure, termed as plane semantic ball (PSB), is proposed to simultaneously reduce the work of retrieval process and exploit the parallel acceleration of underlying hardware. In PSB, semantics are embedded into the generation of representative pivots and multiple balls are selected to cover more informative reference features. With PSB, the online retrieval of CBIR is factorized into independent components that are implemented on GPU efficiently. Comparative experiments with GPU-based brute force approach demonstrate that the proposed approach can achieve high speedup with little information loss. Furthermore, PSB is compared with the state-of-the-art approach, random ball cover (RBC), on two standard image datasets, Corel 10 K and GIST 1 M. Experimental results show that our approach achieves higher speedup than RBC on the same accuracy level. PMID:24782668

  11. Acceleration of Vascular Sprouting from Fabricated Perfusable Vascular-Like Structures

    PubMed Central

    Osaki, Tatsuya; Kakegawa, Takahiro; Kageyama, Tatsuto; Enomoto, Junko; Nittami, Tadashi; Fukuda, Junji

    2015-01-01

    Fabrication of vascular networks is essential for engineering three-dimensional thick tissues and organs in the emerging fields of tissue engineering and regenerative medicine. In this study, we describe the fabrication of perfusable vascular-like structures by transferring endothelial cells using an electrochemical reaction as well as acceleration of subsequent endothelial sprouting by two stimuli: phorbol 12-myristate 13-acetate (PMA) and fluidic shear stress. The electrochemical transfer of cells was achieved using an oligopeptide that formed a dense molecular layer on a gold surface and was then electrochemically desorbed from the surface. Human umbilical vein endothelial cells (HUVECs), adhered to gold-coated needles (ϕ600 μm) via the oligopeptide, were transferred to collagen gel along with electrochemical desorption of the molecular layer, resulting in the formation of endothelial cell-lined vascular-like structures. In the following culture, the endothelial cells migrated into the collagen gel and formed branched luminal structures. However, this branching process was strikingly slow (>14 d) and the cell layers on the internal surfaces became disrupted in some regions. To address these issues, we examined the effects of the protein kinase C (PKC) activator, PMA, and shear stress generated by medium flow. Addition of PMA at an optimum concentration significantly accelerated migration, vascular network formation, and its stabilization. Exposure to shear stress reoriented the cells in the direction of the medium flow and further accelerated vascular network formation. Because of the synergistic effects, HUVECs began to sprout as early as 3 d of perfusion culture and neighboring vascular-like structures were bridged within 5 d. Although further investigations of vascular functions need to be performed, this approach may be an effective strategy for rapid fabrication of perfusable microvascular networks when engineering three-dimensional fully vascularized

  12. Loss of CAR promotes migration and proliferation of HaCaT cells, and accelerates wound healing in rats via Src-p38 MAPK pathway

    PubMed Central

    Su, Linlin; Fu, Lanqing; Li, Xiaodong; Zhang, Yue; Li, Zhenzhen; Wu, Xue; Li, Yan; Bai, Xiaozhi; Hu, Dahai

    2016-01-01

    The coxsackie and adenovirus receptor (CAR) is a cell adhesion molecule mostly localized to cell-cell contacts in epithelial and endothelial cells. CAR is known to regulate tumor progression, however, its physiological role in keratinocyte migration and proliferation, two essential steps in re-epithelialization during wound healing, has less been investigated. Here we showed that CAR was predominantly expressed in the epidermis of human skin, CAR knockdown by RNAi significantly accelerated HaCaT cell migration and proliferation. In addition, knockdown of CAR in vitro increased p-Src, p-p38, and p-JNK protein levels; however, Src inhibitor PP2 prevented the increase of p-Src and p-p38 induced by CAR RNAi, but not p-JNK, and decelerated cell migration and proliferation. More intriguingly, in vivo CAR RNAi on the skin area surrounding the wounds on rat back visually accelerated wound healing and re-epithelialization process, while treatment with PP2 or p38 inhibitor SB203580 obviously inhibited these effects. By contrast, overexpressing CAR in HaCaT cells significantly decelerated cell migration and proliferation. Above results demonstrate that suppression of CAR could accelerate HaCaT cell migration and proliferation, and promote wound healing in rat skin, probably via Src-p38 MAPK pathway. CAR thus might serve as a novel therapeutic target for facilitating wound healing. PMID:26804208

  13. Accelerated Tumor Growth Mediated by Sub-lytic Levels of Antibody-Induced Complement Activation is Associated with Activation of the PI3K/AKT Survival Pathway

    PubMed Central

    Wu, Xiaohong; Ragupathi, Govind; Panageas, Katherine; Hong, Feng; Livingston, Philip O.

    2013-01-01

    Purpose We addressed the possibility that low levels of tumor cell bound antibodies targeting gangliosides might accelerate tumor growth. Experimental Design To test this hypothesis, we treated mice with a range of mAb doses against GM2, GD2, GD3 and CD20 after challenge with tumors expressing these antigens and tested the activity of the same mAbs in-vitro. We also explored the mechanisms behind the complement-mediated tumor growth acceleration that we observed and an approach to overcome it. Results Serologically detectable levels of IgM-mAb against GM2 are able to delay or prevent tumor growth of high GM2-expressing cell lines both in-vitro and in a SCID mouse model, while very low levels of this mAb resulted in slight but consistent acceleration of tumor growth in both settings. Surprisingly, this is not restricted to IgM antibodies targeting GM2 but consistent against IgG-mAb targeting GD3 as well. These findings were mirrored by in-vitro studies with antibodies against these antigens as well as GD2 and CD20 (with Rituxan), and shown to be complement-dependent in all cases. Complement-mediated accelerated growth of cultured tumor cell lines initiated by low mAb levels was associated with activation of the PI3K/AKT survival pathway and significantly elevated levels of both p-AKT and p-PRAS40. This complement-mediated PI3K-activation and accelerated tumor growth in-vitro and in-vivo are eliminated by PI3K-inhibitors NVP-BEZ235 and Wortmannin. These PI3K-inhibitors also significantly increased efficacy of high doses of these 4 mAbs. Conclusion Our findings suggest that manipulation of the PI3K/AKT pathway and its signaling network can significantly increase the potency of passively administered mAbs and vaccine-induced-antibodies targeting a variety of tumor-cell-surface-antigens. PMID:23833306

  14. Origins of Highly Structured Distribution Functions in Magnetic Reconnection Exhausts: Understanding Electron Acceleration and Heating

    NASA Astrophysics Data System (ADS)

    Shuster, J. R.; Wang, S.; Chen, L. J.; Bessho, N.; Guo, R.; Torbert, R. B.; Daughton, W. S.

    2014-12-01

    Electron velocity distribution functions (VDFs) during reconnection with negligible guide field from particle in cell (PIC) simulations and Cluster observations are studied to further understand electron acceleration and heating. Until recently, electrons in the exhaust of reconnection with negligible guide field were thought to be isotropic. PIC simulation results with zero guide field reveal that near the time of peak reconnection, VDFs become highly structured in magnetic islands and open exhausts. Ring, arc, and counterstreaming populations are generic and lasting constituents of exhaust electron VDFs. Analyses of particle trajectories indicate that a number of mechanisms including Fermi acceleration, the parallel potential, and adiabatic heating contribute to the energization of exhaust electrons. Near the electron diffusion region (EDR), exhaust electrons exhibit large Te⊥ due to ring and arc populations of electrons accelerated in the EDR. Farther away from the EDR, the VDFs show a mixture of electrons from the EDR and those crossing the separatrix from the inflow. Pitch angle scattering is effective near the exhaust midplane, away from the EDR and before reaching the magnetic pileup region, producing isotropic, high-energy electrons, while the low energy exhaust electrons exhibit the anisotropy Te// > Te⊥ characteristic of the inflow. The work done on the electrons by the perpendicular electric field between the end of EDR and the magnetic pileup region is due to Fermi acceleration which leads to a net increase in the electron's parallel velocity. For the net increase of electrons' v⊥ beyond the EDR, pitch angle scattering effectively converts v// gained by acceleration from the parallel potential into v⊥. Electron's v⊥ further increases downstream through adiabatic heating from the increasing magnetic field in addition to less efficient pitch angle scattering. The parallel potential and the magnetic bottle together determine the trapped

  15. Acceleration of bone development and regeneration through the Wnt/β-catenin signaling pathway in mice heterozygously deficient for GSK-3β

    SciTech Connect

    Arioka, Masaki; Takahashi-Yanaga, Fumi; Sasaki, Masanori; Yoshihara, Tatsuya; Morimoto, Sachio; Takashima, Akihiko; Mori, Yoshihide; Sasaguri, Toshiyuki

    2013-11-01

    Highlights: •The Wnt/β-catenin signaling pathway was activated in GSK-3β{sup +/−} mice. •The cortical and trabecular bone volumes were increased in GSK-3β{sup +/−} mice. •Regeneration of a partial bone defect was accelerated in GSK-3β{sup +/−} mice. -- Abstract: Glycogen synthase kinase (GSK)-3β plays an important role in osteoblastogenesis by regulating the Wnt/β-catenin signaling pathway. Therefore, we investigated whether GSK-3β deficiency affects bone development and regeneration using mice heterozygously deficient for GSK-3β (GSK-3β{sup +/−}). The amounts of β-catenin, c-Myc, cyclin D1, and runt-related transcription factor-2 (Runx2) in the bone marrow cells of GSK-3β{sup +/−} mice were significantly increased compared with those of wild-type mice, indicating that Wnt/β-catenin signals were enhanced in GSK-3β{sup +/−} mice. Microcomputed tomography of the distal femoral metaphyses demonstrated that the volumes of both the cortical and trabecular bones were increased in GSK-3β{sup +/−} mice compared with those in wild-type mice. Subsequently, to investigate the effect of GSK-3β deficiency on bone regeneration, we established a partial bone defect in the femur and observed new bone at 14 days after surgery. The volume and mineral density of the new bone were significantly higher in GSK-3β{sup +/−} mice than those in wild-type mice. These results suggest that bone formation and regeneration in vivo are accelerated by inhibition of GSK-3β, probably through activation of the Wnt/β-catenin signaling pathway.

  16. Dielectric Wakefield Accelerating Structure as a Source of Terahertz Coherent Cerenkov Radiation

    SciTech Connect

    Cook, A. M.; Rosenzweig, J. B.; Badakov, H.; Travish, G.; Tikhoplav, R.; Williams, O. B.; England, R. J.; Thompson, M. C.

    2006-11-27

    We discuss future experimental work proposed to study the performance of a cylindrical dielectric wakefield accelerating structure as a coherent Cerenkov radiation source at the Neptune laboratory at UCLA. The Cerenkov wakefield acceleration experiment carried out recently by UCLA/SLAC/USC, using the ultrashort and high charge beam (Q = 3 nC, {sigma}z = 20 micron) at the SLAC FFTB, demonstrated electromagnetic wakes at the few GV/m level. The motivation of our prospective experiment is to investigate the operation of a similar scenario using the comparatively long pulse, low charge beam (Q = 0.5 nC, {sigma}z = 200 micron) at UCLA Neptune. The field amplitude produced in this setup would be one to two orders of magnitude lower, at the few tens to few 100 MV/m level. Such a decelerating field would extract a significant amount of energy from a low-energy beam in a distance on the order of a few centimeters, allowing the use of short dielectric structures. We discuss details of the geometry and composition of the structures to be used in the experiment. We also examine the possibility of a future dedicated facility at UCLA Neptune based on a hybrid photoinjector currently in development. The intrinsic bunch compression capabilities and improved beam parameters ({sigma}z = 100 micron, Q = 1 nC) of the photoinjector would allow the creation of a high power radiation source in the terahertz regime.

  17. The ANL experiment for a wake field accelerator using an rf structure

    SciTech Connect

    Ruggiero, A.G.; Schoessow, P.; Simpson, J.

    1986-08-27

    Experiments are planned at ANL to study a new accelerating concept that has been developed during the last few years named the WAKEATRON. This requires a very special, simple configuration of the beams and of the rf structure involved. The basic concepts are explained. Like most proposed experimental work, this too was initiated by a considerable amount of computational work, both analytical and numerical, on which we would like to report. We will then describe details of the planned experiments we will carry out at ANL to check some of our predictions for this concept. These experiments concentrate on beam and cavity geometry applicable to the Wakeatron.

  18. A STUDY ON APPLICABILITY OF GROUND RESPONSE ACCELERATION METHOD TO DEEP VERTICAL UNDERGROUND STRUCTURES

    NASA Astrophysics Data System (ADS)

    Matsumoto, Mai; Shiba, Yukio; Watanabe, Kazuaki

    This paper discusses the applicability of ground response acceleration method to seismic analysis for deep vertical underground structures. To examine the applicability, an analysis of relationships between response of ground and the shaft was conducted. It was found from the analysis that vertical axial stress of the shaft was not correspond with shear stress of ground. Accordingly, it was concluded that the axial stress was not evaluated correctly by the existing method. Therefore, to extend the applicability of the method, ground responses correlated with the axial stress were analyzed and a new method using these ground responses was proposed.

  19. Laser Wakefield Structures and Electron Acceleration in Gas Jet and Capillary Discharge Plasmas

    NASA Astrophysics Data System (ADS)

    Maksimchuk, Anatoly

    2007-11-01

    Laser-driven plasma wakefield accelerators have the potential to become the next generation of particle accelerators because of the very high acceleration gradients. The beam quality from such accelerators depends critically on the details plasma wave spatial structures. In experiments at the University of Michigan it was possible in a single shot by frequency domain holography (FDH) to visualize individual plasma waves produced by the 40 TW, 30 fs Hercules laser focused to the intensity of 10^19 W/cm^2 onto a supersonic He gas jet [1]. These holographic ``snapshots'' capture the evolution of multiple wake periods, and resolve wavefront curvature seen previously only in simulations. High-energy quasi-monoenergetic electron beams for plasma density in the specific range 1.5x10^19<=ne<=3.5x10^19 cm-3 were generated [2]. The experiments show that the energy, charge, divergence and pointing stability of the beam can be controlled by changing ne, and that higher electron energies and more stable beams are produced for lower densities. An optimized quasi-monoenergetic beam of over 300 MeV and 10 mrad angular divergence is demonstrated at a plasma density of ne=1.5x10^19 cm-3. The resulted relativistic electron beams have been used to perform gamma-neutron activation of ^12C and ^63Cu and photo-fission of ^238U with a record high reaction yields of ˜5x10^5/Joule [3]. Experiments performed with ablative capillary discharge plasma demonstrate stable guiding for laser power up to 10 TW with the transmission of 50% and guided intensity of ˜10^17 W/cm^2. Study of the staged electron acceleration have been performed which uses ablated plasma in front of the capillary to inject electrons into the wakefield structures. [1] N. H. Matlis et. al., Nature Physics 2, 749 (2006). [2] A. Maksimchuk et. al., Journal de Physique IV 133, 1123 (2006). [3] S. A. Reed et. al., Appl. Phys. Lett. 89, 231107 (2006).

  20. Temporal evolution and electric potential structure of the auroral acceleration region from multispacecraft measurements

    NASA Astrophysics Data System (ADS)

    Forsyth, C.; Fazakerley, A. N.; Walsh, A. P.; Watt, C. E.; Garza, K.; Owen, C. J.; Constantinescu, D. O.; Dandouras, I. S.; Fornacon, K.; Lucek, E. A.; Marklund, G. T.; Sadeghi, S. S.; Khotyaintsev, Y. V.; Masson, A.; Doss, N.

    2013-12-01

    Bright aurorae can be excited by the acceleration of electrons into the atmosphere in violation of ideal magnetohydrodynamics. Modelling studies predict that the accelerating electric potential consists of electric double layers at the boundaries of an acceleration region but observations suggest that particle acceleration occurs throughout this region. Using multispacecraft observations from Cluster, we have examined two upward current regions on 14 December 2009. Our observations show that the potential difference below C4 and C3 changed by up to 1.7 kV between their respective crossings, which were separated by 150 s. The field-aligned current density observed by C3 was also larger than that observed by C4. The potential drop above C3 and C4 was approximately the same in both crossings. Using a novel technique of quantitively comparing the electron spectra measured by Cluster 1 and 3, which were separated in altitude, we determine when these spacecraft made effectively magnetically conjugate observations, and we use these conjugate observations to determine the instantaneous distribution of the potential drop in the AAR. Our observations show that an average of 15% of the potential drop in the AAR was located between C1 at 6235 km and C3 at 4685 km altitude, with a maximum potential drop between the spacecraft of 500 V, and that the majority of the potential drop was below C3. Assuming a spatial invariance along the length of the upward current region, we discuss these observations in terms of temporal changes and the vertical structure of the electrostatic potential drop and in the context of existing models and previous single- and multispacecraft observations.

  1. Temporal evolution and electric potential structure of the auroral acceleration region from multispacecraft measurements

    NASA Astrophysics Data System (ADS)

    Forsyth, C.; Fazakerley, A. N.; Walsh, A. P.; Watt, C. E. J.; Garza, K. J.; Owen, C. J.; Constantinescu, D.; Dandouras, I.; FornaçOn, K.-H.; Lucek, E.; Marklund, G. T.; Sadeghi, S. S.; Khotyaintsev, Y.; Masson, A.; Doss, N.

    2012-12-01

    Bright aurorae can be excited by the acceleration of electrons into the atmosphere in violation of ideal magnetohydrodynamics. Modeling studies predict that the accelerating electric potential consists of electric double layers at the boundaries of an acceleration region but observations suggest that particle acceleration occurs throughout this region. Using multispacecraft observations from Cluster, we have examined two upward current regions on 14 December 2009. Our observations show that the potential difference below C4 and C3 changed by up to 1.7 kV between their respective crossings, which were separated by 150 s. The field-aligned current density observed by C3 was also larger than that observed by C4. The potential drop above C3 and C4 was approximately the same in both crossings. Using a novel technique of quantitively comparing the electron spectra measured by Cluster 1 and 3, which were separated in altitude, we determine when these spacecraft made effectively magnetically conjugate observations, and we use these conjugate observations to determine the instantaneous distribution of the potential drop in the AAR. Our observations show that an average of 15% of the potential drop in the AAR was located between C1 at 6235 km and C3 at 4685 km altitude, with a maximum potential drop between the spacecraft of 500 V, and that the majority of the potential drop was below C3. Assuming a spatial invariance along the length of the upward current region, we discuss these observations in terms of temporal changes and the vertical structure of the electrostatic potential drop and in the context of existing models and previous single- and multispacecraft observations.

  2. Hydrogen-Rich Water Intake Accelerates Oral Palatal Wound Healing via Activation of the Nrf2/Antioxidant Defense Pathways in a Rat Model

    PubMed Central

    Orihuela-Campos, Rita Cristina; Fukui, Makoto; Ito, Hiro-O

    2016-01-01

    The wound healing process attempts to restore the integrity and function of the injured tissue. Additionally, proinflammatory cytokines, growth factors, and oxidative stress play important roles in wound healing. The aim of this study was to determine whether hydrogen-rich water intake induces the activation of the Nrf2/antioxidant defense pathway in rat palatal tissue, thereby reducing systemic oxidative stress and proinflammatory cytokine levels and promoting healing-associated genes. A circular excisional wound was created in the oral palatal region, and the wound healing process was observed. The rats were divided into two experimental groups in which either hydrogen-rich water or distilled water was consumed. In the drinking hydrogen-rich water, the palatal wound healing process was accelerated compared to that in the control group. As molecular hydrogen upregulated the Nrf2 pathway, systemic oxidative stresses were decreased by the activation of antioxidant activity. Furthermore, hydrogen-rich water intake reduced proinflammatory cytokine levels and promoted the expression of healing-associated factors in rat palatal tissue. In conclusion, hydrogen-rich water intake exhibited multiple beneficial effects through activation of the Nrf2/antioxidant defense pathway. The results of this study support the hypothesis that oral administration of hydrogen-rich water benefits the wound healing process by decreasing oxidative stress and inflammatory responses. PMID:26798423

  3. Uniform Plasma Etching of Complex Shaped Three Dimensional Niobium Structures for Particle Accelerators

    NASA Astrophysics Data System (ADS)

    Upadhyay, Janardan; Im, Do; Peshl, Jeremy; Popovic, Svetozar; Vuskovic, Lepsha; Phillips, Larry; Valente-Felliciano, Anne-Marie

    2014-10-01

    Complex shaped three dimensional niobium structures are used in particle accelerators as super conducting radio frequency (SRF) cavities. The inner surfaces of these structures have to be chemically etched for better performance, as SRF performance parameters are very sensitive to their properties. Plasma etching of inner surface of three dimensional niobium structures has not been reported even though plasma etching of niobium has been reported earlier for Josephson junction and other applications. We are proposing an RF capacitively coupled coaxial (ccp) plasma etching method for nano machining of niobium structures for SRF applications. We are using gas mixture of Argon and Chlorine. We report the effects of the pressure, RF power, gas concentration, shape and size of the inner electrode, temperature of the structure, DC bias voltage and residence time on the etch rate of the niobium. We also show the method to reduce the asymmetry effect in coaxial ccp by changing the shape of the inner electrode in cylindrical structure, as well as a method to overcome the severe loading effect in etching of 3D structures for uniform mass removal purpose. Supported by DOE under Grant No. DE-SC0007879. J.U. acknowledges support by JSA/DOE via DE-AC05-06OR23177.

  4. Investigating perturbed pathway modules from gene expression data via structural equation models

    PubMed Central

    2014-01-01

    Background It is currently accepted that the perturbation of complex intracellular networks, rather than the dysregulation of a single gene, is the basis for phenotypical diversity. High-throughput gene expression data allow to investigate changes in gene expression profiles among different conditions. Recently, many efforts have been made to individuate which biological pathways are perturbed, given a list of differentially expressed genes (DEGs). In order to understand these mechanisms, it is necessary to unveil the variation of genes in relation to each other, considering the different phenotypes. In this paper, we illustrate a pipeline, based on Structural Equation Modeling (SEM) that allowed to investigate pathway modules, considering not only deregulated genes but also the connections between the perturbed ones. Results The procedure was tested on microarray experiments relative to two neurological diseases: frontotemporal lobar degeneration with ubiquitinated inclusions (FTLD-U) and multiple sclerosis (MS). Starting from DEGs and dysregulated biological pathways, a model for each pathway was generated using databases information biological databases, in order to design how DEGs were connected in a causal structure. Successively, SEM analysis proved if pathways differ globally, between groups, and for specific path relationships. The results confirmed the importance of certain genes in the analyzed diseases, and unveiled which connections are modified among them. Conclusions We propose a framework to perform differential gene expression analysis on microarray data based on SEM, which is able to: 1) find relevant genes and perturbed biological pathways, investigating putative sub-pathway models based on the concept of disease module; 2) test and improve the generated models; 3) detect a differential expression level of one gene, and differential connection between two genes. This could shed light, not only on the mechanisms affecting variations in gene

  5. Acceleration of solar wind ions to 1 MeV by electromagnetic structures upstream of the Earth's bow shock

    NASA Astrophysics Data System (ADS)

    Stasiewicz, K.; Markidis, S.; Eliasson, B.; Strumik, M.; Yamauchi, M.

    2013-05-01

    We present measurements from the ESA/NASA Cluster mission that show in situ acceleration of ions to energies of 1 MeV outside the bow shock. The observed heating can be associated with the presence of electromagnetic structures with strong spatial gradients of the electric field that lead to ion gyro-phase breaking and to the onset of chaos in ion trajectories. It results in rapid, stochastic acceleration of ions in the direction perpendicular to the ambient magnetic field. The electric potential of the structures can be compared to a field of moguls on a ski slope, capable of accelerating and ejecting the fast running skiers out of piste. This mechanism may represent the universal mechanism for perpendicular acceleration and heating of ions in the magnetosphere, the solar corona and in astrophysical plasmas. This is also a basic mechanism that can limit steepening of nonlinear electromagnetic structures at shocks and foreshocks in collisionless plasmas.

  6. GeauxDock: Accelerating Structure-Based Virtual Screening with Heterogeneous Computing

    PubMed Central

    Fang, Ye; Ding, Yun; Feinstein, Wei P.; Koppelman, David M.; Moreno, Juana; Jarrell, Mark; Ramanujam, J.; Brylinski, Michal

    2016-01-01

    Computational modeling of drug binding to proteins is an integral component of direct drug design. Particularly, structure-based virtual screening is often used to perform large-scale modeling of putative associations between small organic molecules and their pharmacologically relevant protein targets. Because of a large number of drug candidates to be evaluated, an accurate and fast docking engine is a critical element of virtual screening. Consequently, highly optimized docking codes are of paramount importance for the effectiveness of virtual screening methods. In this communication, we describe the implementation, tuning and performance characteristics of GeauxDock, a recently developed molecular docking program. GeauxDock is built upon the Monte Carlo algorithm and features a novel scoring function combining physics-based energy terms with statistical and knowledge-based potentials. Developed specifically for heterogeneous computing platforms, the current version of GeauxDock can be deployed on modern, multi-core Central Processing Units (CPUs) as well as massively parallel accelerators, Intel Xeon Phi and NVIDIA Graphics Processing Unit (GPU). First, we carried out a thorough performance tuning of the high-level framework and the docking kernel to produce a fast serial code, which was then ported to shared-memory multi-core CPUs yielding a near-ideal scaling. Further, using Xeon Phi gives 1.9× performance improvement over a dual 10-core Xeon CPU, whereas the best GPU accelerator, GeForce GTX 980, achieves a speedup as high as 3.5×. On that account, GeauxDock can take advantage of modern heterogeneous architectures to considerably accelerate structure-based virtual screening applications. GeauxDock is open-sourced and publicly available at www.brylinski.org/geauxdock and https://figshare.com/articles/geauxdock_tar_gz/3205249. PMID:27420300

  7. GeauxDock: Accelerating Structure-Based Virtual Screening with Heterogeneous Computing.

    PubMed

    Fang, Ye; Ding, Yun; Feinstein, Wei P; Koppelman, David M; Moreno, Juana; Jarrell, Mark; Ramanujam, J; Brylinski, Michal

    2016-01-01

    Computational modeling of drug binding to proteins is an integral component of direct drug design. Particularly, structure-based virtual screening is often used to perform large-scale modeling of putative associations between small organic molecules and their pharmacologically relevant protein targets. Because of a large number of drug candidates to be evaluated, an accurate and fast docking engine is a critical element of virtual screening. Consequently, highly optimized docking codes are of paramount importance for the effectiveness of virtual screening methods. In this communication, we describe the implementation, tuning and performance characteristics of GeauxDock, a recently developed molecular docking program. GeauxDock is built upon the Monte Carlo algorithm and features a novel scoring function combining physics-based energy terms with statistical and knowledge-based potentials. Developed specifically for heterogeneous computing platforms, the current version of GeauxDock can be deployed on modern, multi-core Central Processing Units (CPUs) as well as massively parallel accelerators, Intel Xeon Phi and NVIDIA Graphics Processing Unit (GPU). First, we carried out a thorough performance tuning of the high-level framework and the docking kernel to produce a fast serial code, which was then ported to shared-memory multi-core CPUs yielding a near-ideal scaling. Further, using Xeon Phi gives 1.9× performance improvement over a dual 10-core Xeon CPU, whereas the best GPU accelerator, GeForce GTX 980, achieves a speedup as high as 3.5×. On that account, GeauxDock can take advantage of modern heterogeneous architectures to considerably accelerate structure-based virtual screening applications. GeauxDock is open-sourced and publicly available at www.brylinski.org/geauxdock and https://figshare.com/articles/geauxdock_tar_gz/3205249. PMID:27420300

  8. Understanding specificity in metabolic pathways-Structural biology of human nucleotide metabolism

    SciTech Connect

    Welin, Martin; Nordlund, Paer

    2010-05-21

    Interactions are the foundation of life at the molecular level. In the plethora of activities in the cell, the evolution of enzyme specificity requires the balancing of appropriate substrate affinity with a negative selection, in order to minimize interactions with other potential substrates in the cell. To understand the structural basis for enzyme specificity, the comparison of structural and biochemical data between enzymes within pathways using similar substrates and effectors is valuable. Nucleotide metabolism is one of the largest metabolic pathways in the human cell and is of outstanding therapeutic importance since it activates and catabolises nucleoside based anti-proliferative drugs and serves as a direct target for anti-proliferative drugs. In recent years the structural coverage of the enzymes involved in human nucleotide metabolism has been dramatically improved and is approaching completion. An important factor has been the contribution from the Structural Genomics Consortium (SGC) at Karolinska Institutet, which recently has solved 33 novel structures of enzymes and enzyme domains in human nucleotide metabolism pathways and homologs thereof. In this review we will discuss some of the principles for substrate specificity of enzymes in human nucleotide metabolism illustrated by a selected set of enzyme families where a detailed understanding of the structural determinants for specificity is now emerging.

  9. Accelerated electronic structure-based molecular dynamics simulations of shock-induced chemistry

    NASA Astrophysics Data System (ADS)

    Cawkwell, Marc

    2015-06-01

    The initiation and progression of shock-induced chemistry in organic materials at moderate temperatures and pressures are slow on the time scales available to regular molecular dynamics simulations. Accessing the requisite time scales is particularly challenging if the interatomic bonding is modeled using accurate yet expensive methods based explicitly on electronic structure. We have combined fast, energy conserving extended Lagrangian Born-Oppenheimer molecular dynamics with the parallel replica accelerated molecular dynamics formalism to study the relatively sluggish shock-induced chemistry of benzene around 13-20 GPa. We model interatomic bonding in hydrocarbons using self-consistent tight binding theory with an accurate and transferable parameterization. Shock compression and its associated transient, non-equilibrium effects are captured explicitly by combining the universal liquid Hugoniot with a simple shrinking-cell boundary condition. A number of novel methods for improving the performance of reactive electronic structure-based molecular dynamics by adapting the self-consistent field procedure on-the-fly will also be discussed. The use of accelerated molecular dynamics has enabled us to follow the initial stages of the nucleation and growth of carbon clusters in benzene under thermodynamic conditions pertinent to experiments.

  10. 2D and 3D multipactor modeling in dielectric-loaded accelerator structures

    NASA Astrophysics Data System (ADS)

    Sinitsyn, Oleksandr; Nusinovich, Gregory; Antonsen, Thomas

    2010-11-01

    Multipactor (MP) is known as the avalanche growth of the number of secondary electrons emitted from a solid surface exposed to an RF electric field under vacuum conditions. MP is a severe problem in modern rf systems and, therefore, theoretical and experimental studies of MP are of great interest to the researchers working in various areas of physics and engineering. In this work we present results of MP studies in dielectric-loaded accelerator (DLA) structures. First, we show simulation results obtained with the use of the 2D self-consistent MP model (O. V. Sinitsyn, et. al., Phys. Plasmas, vol. 16, 073102 (2009)) and compare those to experimental ones obtained during recent extensive studies of DLA structures performed by Argonne National Laboratory, Naval Research Laboratory, SLAC National Accelerator Laboratory and Euclid TechLabs (C. Jing, et al., IEEE Trans. Plasma Sci., vol. 38, pp. 1354-1360 (2010)). Then we present some new results of 3D analysis of MP which include studies of particle trajectories and studies of MP development at the early stage.

  11. Fabrication Technologies of the High Gradient Accelerator Structures at 100MV/M Range

    SciTech Connect

    Wang, Juwen; Lewandowski, James; Van Pelt, John; Yoneda, Charles; Gudkov, Boris; Riddone, Germana; Higo, Toshiyasu; Takatomi, Toshikazu; /KEK, Tsukuba

    2012-07-03

    A CERN-SLAC-KEK collaboration on high gradient X-band structure research has been established in order to demonstrate the feasibility of the CLIC baseline design for the main linac stably operating at more than 100 MV/m loaded accelerating gradient. Several prototype CLIC structures were successfully fabricated and high power tested. They operated at 105 MV/m with a breakdown rate that meets the CLIC linear collider specifications of < 5 x 10{sup -7}/pulse/m. This paper summarizes the fabrication technologies including the mechanical design, precision machining, chemical cleaning, diffusion bonding as well as vacuum baking and all related assembly technologies. Also, the tolerances control, tuning and RF characterization will be discussed.

  12. Confirmatory evidence for a direct parasympathetic pathway to internal eye structures.

    PubMed Central

    Parelman, J J; Fay, M T; Burde, R M

    1984-01-01

    The hypothesis that a direct neural pathway exists between the midbrain and the intrinsic musculature was investigated. Wheat germ agglutinin labeled with HRP and WG-HRP were injected intraocularly into the ciliary muscle of rabbits and cynomolgus monkeys, and their retrograde movement was monitored. Sparse, but definite labeling was found in the AM nuclei, the EW nuclei, and Perlia's nucleus of the monkey, confirming the existence of a nonsynapsing pathway between intraocular structures and the midbrain in the primate. Images FIGURE 1 A FIGURE 1 B FIGURE 1 C PMID:6549517

  13. Development of structural health assessment system for steel and reinforced concrete structures using acceleration data

    NASA Astrophysics Data System (ADS)

    Suzuki, Yu; Mita, Akira

    2014-03-01

    Because of the repeated earthquake and the problem such as the aging of buildings, a number of studies of Structural Health Monitoring (SHM) is have been done. Now, the writer is developing structural health assessment system for steel and reinforced concrete structures aiming for completion in 2014. In this system, following three programs for automatically estimating the physical quantity that is important for assessing the integrity of the structure are planned. First program is what automatically estimate the modal parameters (natural frequency and damping ratio) of the structure by the time history by using the subspace method. Second program is what automatically estimate the inter-layer parameters (stiffness and damping coefficient) by the time history by using the adaptive Kalman filter. Third program is what automatically estimate the story drift angle by time history by using the adaptive Kalman filter. The proposed method is expected to be estimated in consideration of the higher order modes than the conventional method by reverse modal analysis.

  14. Convergence acceleration for partitioned simulations of the fluid-structure interaction in arteries

    NASA Astrophysics Data System (ADS)

    Radtke, Lars; Larena-Avellaneda, Axel; Debus, Eike Sebastian; Düster, Alexander

    2016-06-01

    We present a partitioned approach to fluid-structure interaction problems arising in analyses of blood flow in arteries. Several strategies to accelerate the convergence of the fixed-point iteration resulting from the coupling of the fluid and the structural sub-problem are investigated. The Aitken relaxation and variants of the interface quasi-Newton -least-squares method are applied to different test cases. A hybrid variant of two well-known variants of the interface quasi-Newton-least-squares method is found to perform best. The test cases cover the typical boundary value problem faced when simulating the fluid-structure interaction in arteries, including a strong added mass effect and a wet surface which accounts for a large part of the overall surface of each sub-problem. A rubber-like Neo Hookean material model and a soft-tissue-like Holzapfel-Gasser-Ogden material model are used to describe the artery wall and are compared in terms of stability and computational expenses. To avoid any kind of locking, high-order finite elements are used to discretize the structural sub-problem. The finite volume method is employed to discretize the fluid sub-problem. We investigate the influence of mass-proportional damping and the material model chosen for the artery on the performance and stability of the acceleration strategies as well as on the simulation results. To show the applicability of the partitioned approach to clinical relevant studies, the hemodynamics in a pathologically deformed artery are investigated, taking the findings of the test case simulations into account.

  15. Convergence acceleration for partitioned simulations of the fluid-structure interaction in arteries

    NASA Astrophysics Data System (ADS)

    Radtke, Lars; Larena-Avellaneda, Axel; Debus, Eike Sebastian; Düster, Alexander

    2016-02-01

    We present a partitioned approach to fluid-structure interaction problems arising in analyses of blood flow in arteries. Several strategies to accelerate the convergence of the fixed-point iteration resulting from the coupling of the fluid and the structural sub-problem are investigated. The Aitken relaxation and variants of the interface quasi-Newton -least-squares method are applied to different test cases. A hybrid variant of two well-known variants of the interface quasi-Newton-least-squares method is found to perform best. The test cases cover the typical boundary value problem faced when simulating the fluid-structure interaction in arteries, including a strong added mass effect and a wet surface which accounts for a large part of the overall surface of each sub-problem. A rubber-like Neo Hookean material model and a soft-tissue-like Holzapfel-Gasser-Ogden material model are used to describe the artery wall and are compared in terms of stability and computational expenses. To avoid any kind of locking, high-order finite elements are used to discretize the structural sub-problem. The finite volume method is employed to discretize the fluid sub-problem. We investigate the influence of mass-proportional damping and the material model chosen for the artery on the performance and stability of the acceleration strategies as well as on the simulation results. To show the applicability of the partitioned approach to clinical relevant studies, the hemodynamics in a pathologically deformed artery are investigated, taking the findings of the test case simulations into account.

  16. CAVER 3.0: a tool for the analysis of transport pathways in dynamic protein structures.

    PubMed

    Chovancova, Eva; Pavelka, Antonin; Benes, Petr; Strnad, Ondrej; Brezovsky, Jan; Kozlikova, Barbora; Gora, Artur; Sustr, Vilem; Klvana, Martin; Medek, Petr; Biedermannova, Lada; Sochor, Jiri; Damborsky, Jiri

    2012-01-01

    Tunnels and channels facilitate the transport of small molecules, ions and water solvent in a large variety of proteins. Characteristics of individual transport pathways, including their geometry, physico-chemical properties and dynamics are instrumental for understanding of structure-function relationships of these proteins, for the design of new inhibitors and construction of improved biocatalysts. CAVER is a software tool widely used for the identification and characterization of transport pathways in static macromolecular structures. Herein we present a new version of CAVER enabling automatic analysis of tunnels and channels in large ensembles of protein conformations. CAVER 3.0 implements new algorithms for the calculation and clustering of pathways. A trajectory from a molecular dynamics simulation serves as the typical input, while detailed characteristics and summary statistics of the time evolution of individual pathways are provided in the outputs. To illustrate the capabilities of CAVER 3.0, the tool was applied for the analysis of molecular dynamics simulation of the microbial enzyme haloalkane dehalogenase DhaA. CAVER 3.0 safely identified and reliably estimated the importance of all previously published DhaA tunnels, including the tunnels closed in DhaA crystal structures. Obtained results clearly demonstrate that analysis of molecular dynamics simulation is essential for the estimation of pathway characteristics and elucidation of the structural basis of the tunnel gating. CAVER 3.0 paves the way for the study of important biochemical phenomena in the area of molecular transport, molecular recognition and enzymatic catalysis. The software is freely available as a multiplatform command-line application at http://www.caver.cz. PMID:23093919

  17. Structural investigation of inhibitor designs targeting 3-dehydroquinate dehydratase from the shikimate pathway of Mycobacterium tuberculosis

    SciTech Connect

    Dias, Marcio V.B.; Snee, William C.; Bromfield, Karen M.; Payne, Richard J.; Palaninathan, Satheesh K.; Ciulli, Alessio; Howard, Nigel I.; Abell, Chris; Sacchettini, James C.; Blundell, Tom L.

    2011-09-06

    The shikimate pathway is essential in Mycobacterium tuberculosis and its absence from humans makes the enzymes of this pathway potential drug targets. In the present paper, we provide structural insights into ligand and inhibitor binding to 3-dehydroquinate dehydratase (dehydroquinase) from M. tuberculosis (MtDHQase), the third enzyme of the shikimate pathway. The enzyme has been crystallized in complex with its reaction product, 3-dehydroshikimate, and with six different competitive inhibitors. The inhibitor 2,3-anhydroquinate mimics the flattened enol/enolate reaction intermediate and serves as an anchor molecule for four of the inhibitors investigated. MtDHQase also forms a complex with citrazinic acid, a planar analogue of the reaction product. The structure of MtDHQase in complex with a 2,3-anhydroquinate moiety attached to a biaryl group shows that this group extends to an active-site subpocket inducing significant structural rearrangement. The flexible extensions of inhibitors designed to form {pi}-stacking interactions with the catalytic Tyr{sup 24} have been investigated. The high-resolution crystal structures of the MtDHQase complexes provide structural evidence for the role of the loop residues 19-24 in MtDHQase ligand binding and catalytic mechanism and provide a rationale for the design and efficacy of inhibitors.

  18. Structural Pathways of Cytokines May Illuminate Their Roles in Regulation of Cancer Development and Immunotherapy

    PubMed Central

    Guven-Maiorov, Emine; Acuner-Ozbabacan, Saliha Ece; Keskin, Ozlem; Gursoy, Attila; Nussinov, Ruth

    2014-01-01

    Cytokines are messengers between tissues and the immune system. They play essential roles in cancer initiation, promotion, metastasis, and immunotherapy. Structural pathways of cytokine signaling which contain their interactions can help understand their action in the tumor microenvironment. Here, our aim is to provide an overview of the role of cytokines in tumor development from a structural perspective. Atomic details of protein-protein interactions can help in understanding how an upstream signal is transduced; how higher-order oligomerization modes of proteins can influence their function; how mutations, inhibitors or antagonists can change cellular consequences; why the same protein can lead to distinct outcomes, and which alternative parallel pathways can take over. They also help to design drugs/inhibitors against proteins de novo or by mimicking natural antagonists as in the case of interferon-γ. Since the structural database (PDB) is limited, structural pathways are largely built from a series of predicted binary protein-protein interactions. Below, to illustrate how protein-protein interactions can help illuminate roles played by cytokines, we model some cytokine interaction complexes exploiting a powerful algorithm (PRotein Interactions by Structural Matching—PRISM). PMID:24670367

  19. Pathway-Level Acceleration of Glycogen Catabolism by a Response Regulator in the Cyanobacterium Synechocystis Species PCC 68031[W

    PubMed Central

    Osanai, Takashi; Oikawa, Akira; Numata, Keiji; Kuwahara, Ayuko; Iijima, Hiroko; Doi, Yoshiharu; Saito, Kazuki; Hirai, Masami Yokota

    2014-01-01

    Response regulators of two-component systems play pivotal roles in the transcriptional regulation of responses to environmental signals in bacteria. Rre37, an OmpR-type response regulator, is induced by nitrogen depletion in the unicellular cyanobacterium Synechocystis species PCC 6803. Microarray and quantitative real-time polymerase chain reaction analyses revealed that genes related to sugar catabolism and nitrogen metabolism were up-regulated by rre37 overexpression. Protein levels of GlgP(slr1367), one of the two glycogen phosphorylases, in the rre37-overexpressing strain were higher than those of the parental wild-type strain under both nitrogen-replete and nitrogen-depleted conditions. Glycogen amounts decreased to less than one-tenth by rre37 overexpression under nitrogen-replete conditions. Metabolome analysis revealed that metabolites of the sugar catabolic pathway and amino acids were altered in the rre37-overexpressing strain after nitrogen depletion. These results demonstrate that Rre37 is a pathway-level regulator that activates the metabolic flow from glycogen to polyhydroxybutyrate and the hybrid tricarboxylic acid and ornithine cycle, unraveling the mechanism of the transcriptional regulation of primary metabolism in this unicellular cyanobacterium. PMID:24521880

  20. Acceleration Data Reveal Highly Individually Structured Energetic Landscapes in Free-Ranging Fishers (Pekania pennanti)

    PubMed Central

    Scharf, Anne K.; LaPoint, Scott; Wikelski, Martin; Safi, Kamran

    2016-01-01

    Investigating animal energy expenditure across space and time may provide more detailed insight into how animals interact with their environment. This insight should improve our understanding of how changes in the environment affect animal energy budgets and is particularly relevant for animals living near or within human altered environments where habitat change can occur rapidly. We modeled fisher (Pekania pennanti) energy expenditure within their home ranges and investigated the potential environmental and spatial drivers of the predicted spatial patterns. As a proxy for energy expenditure we used overall dynamic body acceleration (ODBA) that we quantified from tri-axial accelerometer data during the active phases of 12 individuals. We used a generalized additive model (GAM) to investigate the spatial distribution of ODBA by associating the acceleration data to the animals' GPS-recorded locations. We related the spatial patterns of ODBA to the utilization distributions and habitat suitability estimates across individuals. The ODBA of fishers appears highly structured in space and was related to individual utilization distribution and habitat suitability estimates. However, we were not able to predict ODBA using the environmental data we selected. Our results suggest an unexpected complexity in the space use of animals that was only captured partially by re-location data-based concepts of home range and habitat suitability. We suggest future studies recognize the limits of ODBA that arise from the fact that acceleration is often collected at much finer spatio-temporal scales than the environmental data and that ODBA lacks a behavioral correspondence. Overcoming these limits would improve the interpretation of energy expenditure in relation to the environment. PMID:26840399

  1. Acceleration Data Reveal Highly Individually Structured Energetic Landscapes in Free-Ranging Fishers (Pekania pennanti).

    PubMed

    Scharf, Anne K; LaPoint, Scott; Wikelski, Martin; Safi, Kamran

    2016-01-01

    Investigating animal energy expenditure across space and time may provide more detailed insight into how animals interact with their environment. This insight should improve our understanding of how changes in the environment affect animal energy budgets and is particularly relevant for animals living near or within human altered environments where habitat change can occur rapidly. We modeled fisher (Pekania pennanti) energy expenditure within their home ranges and investigated the potential environmental and spatial drivers of the predicted spatial patterns. As a proxy for energy expenditure we used overall dynamic body acceleration (ODBA) that we quantified from tri-axial accelerometer data during the active phases of 12 individuals. We used a generalized additive model (GAM) to investigate the spatial distribution of ODBA by associating the acceleration data to the animals' GPS-recorded locations. We related the spatial patterns of ODBA to the utilization distributions and habitat suitability estimates across individuals. The ODBA of fishers appears highly structured in space and was related to individual utilization distribution and habitat suitability estimates. However, we were not able to predict ODBA using the environmental data we selected. Our results suggest an unexpected complexity in the space use of animals that was only captured partially by re-location data-based concepts of home range and habitat suitability. We suggest future studies recognize the limits of ODBA that arise from the fact that acceleration is often collected at much finer spatio-temporal scales than the environmental data and that ODBA lacks a behavioral correspondence. Overcoming these limits would improve the interpretation of energy expenditure in relation to the environment. PMID:26840399

  2. Titanium α-ω phase transformation pathway and a predicted metastable structure

    DOE PAGESBeta

    Zarkevich, Nickolai A.; Johnson, Duane D.

    2016-01-15

    A titanium is a highly utilized metal for structural lightweighting and its phases, transformation pathways (transition states), and structures have scientific and industrial importance. Using a proper solid-state nudged elastic band method employing two climbing images combined with density functional theory DFT + U methods for accurate energetics, we detail the pressure-induced α (ductile) to ω (brittle) transformation at the coexistence pressure. We also find two transition states along the minimal-enthalpy path and discover a metastable body-centered orthorhombic structure, with stable phonons, a lower density than the end-point phases, and decreasing stability with increasing pressure.

  3. Titanium α -ω phase transformation pathway and a predicted metastable structure

    NASA Astrophysics Data System (ADS)

    Zarkevich, N. A.; Johnson, D. D.

    2016-01-01

    As titanium is a highly utilized metal for structural lightweighting, its phases, transformation pathways (transition states), and structures have scientific and industrial importance. Using a proper solid-state nudged elastic band method employing two climbing images combined with density functional theory DFT + U methods for accurate energetics, we detail the pressure-induced α (ductile) to ω (brittle) transformation at the coexistence pressure. We find two transition states along the minimal-enthalpy path and discover a metastable body-centered orthorhombic structure, with stable phonons, a lower density than the end-point phases, and decreasing stability with increasing pressure.

  4. Representation of Gravity-Aligned Scene Structure in Ventral Pathway Visual Cortex.

    PubMed

    Vaziri, Siavash; Connor, Charles E

    2016-03-21

    The ventral visual pathway in humans and non-human primates is known to represent object information, including shape and identity [1]. Here, we show the ventral pathway also represents scene structure aligned with the gravitational reference frame in which objects move and interact. We analyzed shape tuning of recently described macaque monkey ventral pathway neurons that prefer scene-like stimuli to objects [2]. Individual neurons did not respond to a single shape class, but to a variety of scene elements that are typically aligned with gravity: large planes in the orientation range of ground surfaces under natural viewing conditions, planes in the orientation range of ceilings, and extended convex and concave edges in the orientation range of wall/floor/ceiling junctions. For a given neuron, these elements tended to share a common alignment in eye-centered coordinates. Thus, each neuron integrated information about multiple gravity-aligned structures as they would be seen from a specific eye and head orientation. This eclectic coding strategy provides only ambiguous information about individual structures but explicit information about the environmental reference frame and the orientation of gravity in egocentric coordinates. In the ventral pathway, this could support perceiving and/or predicting physical events involving objects subject to gravity, recognizing object attributes like animacy based on movement not caused by gravity, and/or stabilizing perception of the world against changes in head orientation [3-5]. Our results, like the recent discovery of object weight representation [6], imply that the ventral pathway is involved not just in recognition, but also in physical understanding of objects and scenes. PMID:26923785

  5. Dynamic Transmission of Protein Allostery without Structural Change: Spatial Pathways or Global Modes?

    PubMed

    McLeish, Tom C B; Cann, Martin J; Rodgers, Thomas L

    2015-09-15

    We examine the contrast between mechanisms for allosteric signaling that involve structural change, and those that do not, from the perspective of allosteric pathways. In particular we treat in detail the case of fluctuation-allostery by which amplitude modulation of the thermal fluctuations of the elastic normal modes conveys the allosteric signal, and address the question of what an allosteric pathway means in this case. We find that a perturbation theory of thermal elastic solids and nonperturbative approach (by super-coarse-graining elasticity into internal bending modes) have opposite signatures in their structure of correlated pathways. We illustrate the effect from analysis of previous results from GlxR of Corynebacterium glutamicum, an example of the CRP/FNR transcription family of allosteric homodimers. We find that the visibility of both correlated pathways and disconnected sites of correlated motion in this protein suggests that mechanisms of local elastic stretch and bend are recruited for the purpose of creating and controlling allosteric cooperativity. PMID:26338443

  6. SOFIA-EXES: Probing the Thermal Structure of M Supergiant Wind Acceleration Zones

    NASA Astrophysics Data System (ADS)

    Harper, Graham M.; O'Gorman, Eamon; Guinan, Edward F.; EXES Instrument Team, EXES Science Team

    2016-01-01

    There is no standard model for mass loss from cool evolved stars, particularly for non-pulsating giants and supergiants. For the early-M supergiants, radiation pressure, convective ejections, magnetic fields, and Alfven waves have all been put forward as potential mass loss mechanisms. A potential discriminator between these ideas is the thermal structure resulting from the heating-cooling balance in the acceleration zone - the most important region to study mass loss physics.We present mid-IR [Fe II] emission line profiles of Betelgeuse and Antares obtained with NASA-DLR SOFIA-EXES and NASA IRTF-TEXES that were obtained as part of a GO program (Harper: Cycle 2-0004) and EXES instrument commissioning observations. The intra-term transitions sample a range of excitation conditions, Texc=540K, 3,400K, and 11,700K, i.e., from the warm chromospheric plasma, that also emits in the cm-radio and ultraviolet, to the cold inner circumstellar envelope. The spectrally-resolved profiles, when combined with VLA cm-radio observations, provide new constraints on the temperature and flow velocity in the outflow accelerating region. The semi-empirical energy balance can be used to test theoretical predictions of wind heating.

  7. PARTICLE ACCELERATION IN PLASMOID EJECTIONS DERIVED FROM RADIO DRIFTING PULSATING STRUCTURES

    SciTech Connect

    Nishizuka, N.; Karlický, M.; Bárta, M.; Janvier, M.

    2015-02-01

    We report observations of slowly drifting pulsating structures (DPSs) in the 0.8-4.5 GHz frequency range of the RT4 and RT5 radio spectrographs at Ondřejov Observatory, between 2002 and 2012. We found 106 events of DPSs, which we classified into four cases: (I) single events with a constant frequency drift (12 events), (II) multiple events occurring in the same flare with constant frequency drifts (11 events), (III) single or multiple events with increasing or decreasing frequency drift rates (52 events), and (IV) complex events containing multiple events occurring at the same time in a different frequency range (31 events). Many DPSs are associated with hard X-ray (HXR) bursts (15-25 keV) and soft X-ray (SXR) gradient peaks, as they typically occurred at the beginning of HXR peaks. This indicates that DPS events are related to the processes of fast energy release and particle acceleration. Furthermore, interpreting DPSs as signatures of plasmoids, we measured their ejection velocity, their width, and their height from the DPS spectra, from which we also estimated the reconnection rate and the plasma beta. In this interpretation, constant frequency drift indicates a constant velocity of a plasmoid, and an increasing/decreasing frequency drift indicates a deceleration/acceleration of a plasmoid ejection. The reconnection rate shows a good positive correlation with the plasmoid velocity. Finally we confirmed that some DPS events show plasmoid counterparts in Solar Dynamics Observatory/Atmospheric Imaging Assembly images.

  8. Muscle mass, structural and functional investigations of senescence-accelerated mouse P8 (SAMP8)

    PubMed Central

    Guo, An Yun; Leung, Kwok Sui; Siu, Parco Ming Fai; Qin, Jiang Hui; Chow, Simon Kwoon Ho; Qin, Ling; Li, Chi Yu; Cheung, Wing Hoi

    2015-01-01

    Sarcopenia is an age-related systemic syndrome with progressive deterioration in skeletal muscle functions and loss in mass. Although the senescence-accelerated mouse P8 (SAMP8) was reported valid for muscular ageing research, there was no report on the details such as sarcopenia onset time. Therefore, this study was to investigate the change of muscle mass, structure and functions during the development of sarcopenia. Besides the average life span, muscle mass, structural and functional measurements were also studied. Male SAMP8 animals were examined at month 6, 7, 8, 9, and 10, in which the right gastrocnemius was isolated and tested for ex vivo contractile properties and fatigability while the contralateral one was harvested for muscle fiber cross-sectional area (FCSA) and typing assessments. Results showed that the peak of muscle mass appeared at month 7 and the onset of contractility decline was observed from month 8. Compared with month 8, most of the functional parameters at month 10 decreased significantly. Structurally, muscle fiber type IIA made up the largest proportion of the gastrocnemius, and the fiber size was found to peak at month 8. Based on the altered muscle mass, structural and functional outcomes, it was concluded that the onset of sarcopenia in SAMP8 animals was at month 8. SAMP8 animals at month 8 should be at pre-sarcopenia stage while month 10 at sarcopenia stage. It is confirmed that SAMP8 mouse can be used in sarcopenia research with established time line in this study. PMID:26193895

  9. Selection of flowing liquid lead target structural materials for accelerator driven transmutation applications

    SciTech Connect

    Park, J.J.; Buksa, J.J.

    1994-08-01

    The beam entry window and container for a liquid lead spallation target will be exposed to high fluxes of protons and neutrons that are both higher in magnitude and energy than have been experienced in proton accelerators and fission reactors, as well as in a corrosive environment. The structural material of the target should have a good compatibility with liquid lead, a sufficient mechanical strength at elevated temperatures, a good performance under an intense irradiation environment, and a low neutron absorption cross section; these factors have been used to rank the applicability of a wide range of materials for structural containment Nb-1Zr has been selected for use as the structural container for the LANL ABC/ATW molten lead target. Corrosion and mass transfer behavior for various candidate structural materials in liquid lead are reviewed, together with the beneficial effects of inhibitors and various coatings to protect substrate against liquid lead corrosion. Mechanical properties of some candidate materials at elevated temperatures and the property changes resulting from 800 MeV proton irradiation are also reviewed.

  10. Multiple quasi-monoenergetic electron beams from laser-wakefield acceleration with spatially structured laser pulse

    SciTech Connect

    Ma, Y.; Li, M. H.; Li, Y. F.; Wang, J. G.; Tao, M. Z.; Han, Y. J.; Zhao, J. R.; Huang, K.; Yan, W. C.; Ma, J. L.; Li, Y. T.; Chen, L. M.; Li, D. Z.; Chen, Z. Y.; Sheng, Z. M.; Zhang, J.

    2015-08-15

    By adjusting the focus geometry of a spatially structured laser pulse, single, double, and treble quasi-monoenergetic electron beams were generated, respectively, in laser-wakefield acceleration. Single electron beam was produced as focusing the laser pulse to a single spot. While focusing the laser pulse to two spots that are approximately equal in energy and size and intense enough to form their own filaments, two electron beams were produced. Moreover, with a proper distance between those two focal spots, three electron beams emerged with a certain probability owing to the superposition of the diffractions of those two spots. The energy spectra of the multiple electron beams are quasi-monoenergetic, which are different from that of the large energy spread beams produced due to the longitudinal multiple-injection in the single bubble.

  11. Determination of molecular-ion structures through the use of accelerated beams

    SciTech Connect

    Gemmell, D.S.

    1987-01-01

    In this talk we report on recent research on molecular-ion structures using fast molecular-ion beams provided by Argonne's 5-MV Dynamitron accelerator. The method has become known as the ''Coulomb-explosion'' technique. When molecular-ion projectiles travelling at velocities of a few percent of the velocity of light strike a foil, the electrons that bind the molecular projectiles are almost always totally stripped off within the first few Angstroms of penetration into the solid target. This leaves a cluster of bare (or nearly bare) nuclei which separate rapidly as a result of their mutual Coulomb repulsion. This violent dissociation process in which the initial electrostatic potential energy is converted into kinetic energy of relative motion in the center-of-mass, has been termed a ''Coulomb explosion.'' 4 refs., 2 figs.

  12. Relativistic magnetosonic shock waves in synchrotron sources - Shock structure and nonthermal acceleration of positrons

    NASA Technical Reports Server (NTRS)

    Hoshino, Masahiro; Arons, Jonathan; Gallant, Yves A.; Langdon, A. B.

    1992-01-01

    The theoretical properties of relativistic, transverse, magnetosonic collisionless shock waves in electron-positron-heavy ion plasmas of relevance to astrophysical sources of synchrotron radiation are investigated. Both 1D electromagnetic particle-in-cell simulations and quasi-linear theory are used to examine the spatial and kinetic structure of these nonlinear flows. A new process of shock acceleration of nonthermal positrons, in which the gyrating reflected heavy ions dissipate their energy in the form of collectively emitted, left-handed magnetosonic waves which are resonantly absorbed by the positrons immediately behind the ion reflection region, is described. Applications of the results to the termination shocks of pulsar winds and to the termination shocks of jets emanating from the AGN are outlined.

  13. Influence of solidification accelerators on structure formation of anhydrite-containing binders

    NASA Astrophysics Data System (ADS)

    Anikanova, L.; Volkova, O.; Kudyakov, A.; Sarkisov, Y.; Tolstov, D.

    2016-01-01

    The article presents results of scientific analysis of chemical additives influence on acid fluoride binder. It was found that the influence of sulfate nature additives on the process of hydration and solidification of the binder is similar to influence of additives on indissoluble anhydrite. Additives with SO42- anion NO- are more efficient. The mentioned additives according to accelerating effect belong to the following succession: K2SO4 > Na2SO4 > FeSO4 > MgSO4. Facilitation of the process of hydration and solidification of the binder, increase in density and durability of the binder (32 MPa) is to the greatest extent achieved with the introduction of 2% sodium sulfate additive of the binder's mass into the composition of the binder along with the ultrasonic treatment of water solution. Directed crystal formation process with healing of porous structure by new growths presented as calcium sulfate dehydrate and hydroglauberite provides positive effect.

  14. Thin current sheets in collisionless plasma: Equilibrium structure, plasma instabilities, and particle acceleration

    SciTech Connect

    Zelenyi, L. M.; Malova, H. V.; Artemyev, A. V.; Popov, V. Yu.; Petrukovich, A. A.

    2011-02-15

    The review is devoted to plasma structures with an extremely small transverse size, namely, thin current sheets that have been discovered and investigated by spacecraft observations in the Earth's magnetotail in the last few decades. The formation of current sheets is attributed to complicated dynamic processes occurring in a collisionless space plasma during geomagnetic perturbations and near the magnetic reconnection regions. The models that describe thin current structures in the Earth's magnetotail are reviewed. They are based on the assumption of the quasi-adiabatic ion dynamics in a relatively weak magnetic field of the magnetotail neutral sheet, where the ions can become unmagnetized. It is shown that the ion distribution can be represented as a function of the integrals of particle motion-the total energy and quasi-adiabatic invariant. Various modifications of the initial equilibrium are considered that are obtained with allowance for the currents of magnetized electrons, the contribution of oxygen ions, the asymmetry of plasma sources, and the effects related to the non-Maxwellian particle distributions. The theoretical results are compared with the observational data from the Cluster spacecraft mission. Various plasma instabilities developing in thin current sheets are investigated. The evolution of the tearing mode is analyzed, and the parameter range in which the mode can grow are determined. The paradox of complete stabilization of the tearing mode in current sheets with a nonzero normal magnetic field component is thereby resolved based on the quasi-adiabatic model. It is shown that, over a wide range of current sheet parameters and the propagation directions of large-scale unstable waves, various modified drift instabilities-kink and sausage modes-can develop in the system. Based on the concept of a turbulent electromagnetic field excited as a result of the development and saturation of unstable waves, a mechanism for charged particle acceleration in

  15. Response to comment on "the geometric structure of the brain fiber pathways".

    PubMed

    Wedeen, Van J; Rosene, Douglas L; Wang, Ruopeng; Dai, Guangping; Mortazavi, Farzad; Hagmann, Patric; Kaas, Jon H; Tseng, Wen-Yih I

    2012-09-28

    In response to Catani et al., we show that corticospinal pathways adhere via sharp turns to two local grid orientations; that our studies have three times the diffusion resolution of those compared; and that the noted technical concerns, including crossing angles, do not challenge the evidence of mathematically specific geometric structure. Thus, the geometric thesis gives the best account of the available evidence. PMID:23019633

  16. Structural and Functional Characterization of a Caenorhabditis elegans Genetic Interaction Network within Pathways

    PubMed Central

    Boucher, Benjamin; Lee, Anna Y.; Hallett, Michael; Jenna, Sarah

    2016-01-01

    A genetic interaction (GI) is defined when the mutation of one gene modifies the phenotypic expression associated with the mutation of a second gene. Genome-wide efforts to map GIs in yeast revealed structural and functional properties of a GI network. This provided insights into the mechanisms underlying the robustness of yeast to genetic and environmental insults, and also into the link existing between genotype and phenotype. While a significant conservation of GIs and GI network structure has been reported between distant yeast species, such a conservation is not clear between unicellular and multicellular organisms. Structural and functional characterization of a GI network in these latter organisms is consequently of high interest. In this study, we present an in-depth characterization of ~1.5K GIs in the nematode Caenorhabditis elegans. We identify and characterize six distinct classes of GIs by examining a wide-range of structural and functional properties of genes and network, including co-expression, phenotypical manifestations, relationship with protein-protein interaction dense subnetworks (PDS) and pathways, molecular and biological functions, gene essentiality and pleiotropy. Our study shows that GI classes link genes within pathways and display distinctive properties, specifically towards PDS. It suggests a model in which pathways are composed of PDS-centric and PDS-independent GIs coordinating molecular machines through two specific classes of GIs involving pleiotropic and non-pleiotropic connectors. Our study provides the first in-depth characterization of a GI network within pathways of a multicellular organism. It also suggests a model to understand better how GIs control system robustness and evolution. PMID:26871911

  17. Structure Loaded Vacuum Laser-Driven Particle Acceleration Experiments at SLAC

    SciTech Connect

    Plettner, T.; Byer, R.L.; Colby, E.R.; Cowan, B.M.; Ischebeck, R.; McGuinness, C.; Lincoln, M.R.; Sears, C.M.; Siemann, R.H.; Spencer, J.E.; /SLAC /Stanford U., Phys. Dept.

    2007-04-09

    We present an overview of the future laser-driven particle acceleration experiments. These will be carried out at the E163 facility at SLAC. Our objectives include a reconfirmation of the proof-of-principle experiment, a staged buncher laser-accelerator experiment, and longer-term future experiments that employ dielectric laser-accelerator microstructures.

  18. Complete set of glycosyltransferase structures in the calicheamicin biosynthetic pathway reveals the origin of regiospecificity

    SciTech Connect

    Chang, Aram; Singh, Shanteri; Helmich, Kate E.; Goff, Randal D.; Bingman, Craig A.; Thorson, Jon S.; Phillips, Jr., George N.

    2012-03-15

    Glycosyltransferases are useful synthetic catalysts for generating natural products with sugar moieties. Although several natural product glycosyltransferase structures have been reported, design principles of glycosyltransferase engineering for the generation of glycodiversified natural products has fallen short of its promise, partly due to a lack of understanding of the relationship between structure and function. Here, we report structures of all four calicheamicin glycosyltransferases (CalG1, CalG2, CalG3, and CalG4), whose catalytic functions are clearly regiospecific. Comparison of these four structures reveals a conserved sugar donor binding motif and the principles of acceptor binding region reshaping. Among them, CalG2 possesses a unique catalytic motif for glycosylation of hydroxylamine. Multiple glycosyltransferase structures in a single natural product biosynthetic pathway are a valuable resource for understanding regiospecific reactions and substrate selectivities and will help future glycosyltransferase engineering.

  19. Partitioning the effects of an ecosystem engineer: kangaroo rats control community structure via multiple pathways.

    PubMed

    Prugh, Laura R; Brashares, Justin S

    2012-05-01

    1. Ecosystem engineers impact communities by altering habitat conditions, but they can also have strong effects through consumptive, competitive and other non-engineering pathways. 2. Engineering effects can lead to fundamentally different community dynamics than non-engineering effects, but the relative strengths of these interactions are seldom quantified. 3. We combined structural equation modelling and exclosure experiments to partition the effects of a keystone engineer, the giant kangaroo rat (Dipodomys ingens), on plants, invertebrates and vertebrates in a semi-arid California grassland. 4. We separated the effects of burrow creation from kangaroo rat density and found that kangaroo rats increased the diversity and abundance of other species via both engineering and non-engineering pathways. 5. Engineering was the primary factor structuring plant and small mammal communities, whereas non-engineering effects structured invertebrate communities and increased lizard abundance. 6. These results highlight the importance of the non-engineering effects of ecosystem engineers and shed new light on the multiple pathways by which strong-interactors shape communities. PMID:22098534

  20. Structural inhibition and reactivation of Escherichia coli septation by elements of the SOS and TER pathways

    SciTech Connect

    Dopazo, A.; Tormo, A.; Aldea, M.; Vicente, M.

    1987-04-01

    The inhibition of cell division caused by induction of the SOS pathway in Escherichia coli structurally blocks septation, as deduced from two sets of results. Potential septation sites active at the time of SOS induction became inactivated, while those initiated during the following doubling time were active. Penicillin resistance increased in wild-type UV light-irradiated cells, a behavior similar to that observed in mutants in which structural blocks were introduced by inactivation of FtsA. Potential septation sites that have been structurally blocked by either the SOS division inhibitor, furazlocillin inhibition of PBP3, or inactivation of a TER pathway component, FtsA3, could be reactivated one doubling time after removal of the inhibitory agent in the presence of an active lon gene product. Reactivation of potential septation sites blocked by the presence of an inactivated FtsA3 was significantly lower when the lon protease was not active, suggesting that Lon plays a role in the removal of inactivated TER pathway products from the blocked potential septation sites.

  1. L2-Proficiency-Dependent Laterality Shift in Structural Connectivity of Brain Language Pathways.

    PubMed

    Xiang, Huadong; van Leeuwen, Tessa Marije; Dediu, Dan; Roberts, Leah; Norris, David G; Hagoort, Peter

    2015-08-01

    Diffusion tensor imaging (DTI) and a longitudinal language learning approach were applied to investigate the relationship between the achieved second language (L2) proficiency during L2 learning and the reorganization of structural connectivity between core language areas. Language proficiency tests and DTI scans were obtained from German students before and after they completed an intensive 6-week course of the Dutch language. In the initial learning stage, with increasing L2 proficiency, the hemispheric dominance of the Brodmann area (BA) 6-temporal pathway (mainly along the arcuate fasciculus) shifted from the left to the right hemisphere. With further increased proficiency, however, lateralization dominance was again found in the left BA6-temporal pathway. This result is consistent with reports in the literature that imply a stronger involvement of the right hemisphere in L2 processing especially for less proficient L2 speakers. This is the first time that an L2 proficiency-dependent laterality shift in the structural connectivity of language pathways during L2 acquisition has been observed to shift from left to right and back to left hemisphere dominance with increasing L2 proficiency. The authors additionally find that changes in fractional anisotropy values after the course are related to the time elapsed between the two scans. The results suggest that structural connectivity in (at least part of) the perisylvian language network may be subject to fast dynamic changes following language learning. PMID:25594261

  2. Track Structure and the Biological Effectiveness of Accelerated Particles for the Induction of Chromosome Damage

    NASA Technical Reports Server (NTRS)

    George, K.; Hada, M.; Chappell, L.; Cucinotta, F. A.

    2011-01-01

    Track structure models predict that at a fixed value of LET, particles with lower charge number, Z will have a higher biological effectiveness compared to particles with a higher Z. In this report we investigated how track structure effects induction of chromosomal aberration in human cells. Human lymphocytes were irradiated in vitro with various energies of accelerated iron, silicon, neon, or titanium ions and chromosome damage was assessed in using three color FISH chromosome painting in chemically induced PCC samples collected a first cell division post irradiation. The LET values for these ions ranged from 30 to195 keV/micron. Of the particles studied, Neon ions have the highest biological effectiveness for induction of total chromosome damage, which is consistent with track structure model predictions. For complex-type exchanges 64 MeV/ u Neon and 450 MeV/u Iron were equally effective and induced the most complex damage. In addition we present data on chromosomes exchanges induced by six different energies of protons (5 MeV/u to 2.5 GeV/u). The linear dose response term was similar for all energies of protons suggesting that the effect of the higher LET at low proton energies is balanced by the production of nuclear secondaries from the high energy protons.

  3. Beam-based measurements of long-range transverse wakefields in the Compact Linear Collider main-linac accelerating structure

    NASA Astrophysics Data System (ADS)

    Zha, Hao; Latina, Andrea; Grudiev, Alexej; De Michele, Giovanni; Solodko, Anastasiya; Wuensch, Walter; Schulte, Daniel; Adli, Erik; Lipkowitz, Nate; Yocky, Gerald S.

    2016-01-01

    The baseline design of CLIC (Compact Linear Collider) uses X-band accelerating structures for its main linacs. In order to maintain beam stability in multibunch operation, long-range transverse wakefields must be suppressed by 2 orders of magnitude between successive bunches, which are separated in time by 0.5 ns. Such strong wakefield suppression is achieved by equipping every accelerating structure cell with four damping waveguides terminated with individual rf loads. A beam-based experiment to directly measure the effectiveness of this long-range transverse wakefield and benchmark simulations was made in the FACET test facility at SLAC using a prototype CLIC accelerating structure. The experiment showed good agreement with the simulations and a strong suppression of the wakefields with an unprecedented minimum resolution of 0.1 V /(pC mm m ) .

  4. Microbial structures, functions, and metabolic pathways in wastewater treatment bioreactors revealed using high-throughput sequencing.

    PubMed

    Ye, Lin; Zhang, Tong; Wang, Taitao; Fang, Zhiwei

    2012-12-18

    The objective of this study was to explore microbial community structures, functional profiles, and metabolic pathways in a lab-scale and a full-scale wastewater treatment bioreactors. In order to do this, over 12 gigabases of metagenomic sequence data and 600,000 paired-end sequences of bacterial 16S rRNA gene were generated with the Illumina HiSeq 2000 platform, using DNA extracted from activated sludge in the two bioreactors. Three kinds of sequences (16S rRNA gene amplicons, 16S rRNA gene sequences obtained from metagenomic sequencing, and predicted proteins) were used to conduct taxonomic assignments. Specially, relative abundances of ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB) were analyzed. Compared with quantitative real-time PCR (qPCR), metagenomic sequencing was demonstrated to be a better approach to quantify AOA and AOB in activated sludge samples. It was found that AOB were more abundant than AOA in both reactors. Furthermore, the analysis of the metabolic profiles indicated that the overall patterns of metabolic pathways in the two reactors were quite similar (73.3% of functions shared). However, for some pathways (such as carbohydrate metabolism and membrane transport), the two reactors differed in the number of pathway-specific genes. PMID:23151157

  5. Simplified protein models can rival all atom simulations in predicting folding pathways and structure

    PubMed Central

    Adhikari, Aashish N.; Freed, Karl F.; Sosnick, Tobin R.

    2014-01-01

    We demonstrate the ability of simultaneously determining a protein’s folding pathway and structure using a properly formulated model without prior knowledge of the native structure. Our model employs a natural coordinate system for describing proteins and a search strategy inspired by the observation that real proteins fold in a sequential fashion by incrementally stabilizing native-like substructures or "foldons". Comparable folding pathways and structures are obtained for the twelve proteins recently studied using atomistic molecular dynamics simulations [K. Lindorff-Larsen, S. Piana, R.O. Dror, D. E. Shaw, Science 334, 517 (2011)], with our calculations running several orders of magnitude faster. We find that native-like propensities in the unfolded state do not necessarily determine the order of structure formation, a departure from a major conclusion of the MD study. Instead, our results support a more expansive view wherein intrinsic local structural propensities may be enhanced or overridden in the folding process by environmental context. The success of our search strategy validates it as an expedient mechanism for folding both in silico and in vivo. PMID:23889448

  6. On the reaction pathways and determination of transition-state structures for retaining alpha-galactosyltransferases.

    PubMed

    André, Isabelle; Tvaroska, Igor; Carver, Jeremy P

    2003-04-22

    The catalytic mechanism of retaining glycosyltransferases is not yet completely understood, but one possible mechanism, by analogy with retaining glycosidases, is a double-displacement mechanism via a covalent glycosyl-enzyme intermediate (CGE). We have investigated various reaction pathways for this mechanism using non-empirical quantum mechanical methods. Because a double-displacement mechanism presumes a reaction happening in two steps, we have used predefined reaction coordinates to calculate the potential energy surface describing each step of the mechanism. By investigating several potential candidates to act as a catalytic base, this study attempts to shed some light on the unclear mechanism of the second step of the reaction. All intermediates and transition states on the reaction pathways were characterized using basis sets up to the DFT/B3LYP/6-311++G**//DFT/B3LYP/6-31G* level. Reaction pathways and structural changes were compared with the results previously obtained for inverting glycosyltransferases. The outcome of this study indicates, that among the reaction models investigated, the energetically favorable one is also the most plausible given the existing experimental data. This model requires the presence of only one catalytic acid in the active site with the UDP functioning as a general base in the second step of the reaction. This mechanism is in agreement with both kinetic data in the literature and the description of X-ray structures of retaining glycosyltransferases solved up to today. PMID:12681911

  7. Analysis of a Symmetric Terahertz Dielectric-Lined Rectangular Structure for High Gradient Acceleration

    SciTech Connect

    Marshall, T. C.; Sotnikov, G. V.; Shchelkunov, S. V.; Hirshfield, J. L.

    2009-01-22

    We study, using computational methods based on analytic theory as well as a PIC code, the wakefields set up in a seven-zone symmetric rectangular THZ structure, and find that for overall transverse x/y dimensions 2.121 mmx0.6 mm, two 5-GeV drive bunches (3 nC, with x/y/z dimensions 0.3/0.3/0.12 mm{sup 3} as available at SLAC) will set up an axial wakefield {approx}350 MV/m in the witness channel, with a transformer ratio {approx}18-20. The symmetry of the structure ensures not only that small transverse forces are imposed on the witness bunch, but also that the two components of transverse force are equal and opposite at the bunch location so as to enable dynamical stabilization in an accelerator comprising many modules. Transverse forces on the drive bunch tails may allow bunches to move {approx}0.5-1 m without suffering excessive erosion.

  8. Structural analysis of mevalonate-3-kinase provides insight into the mechanisms of isoprenoid pathway decarboxylases

    PubMed Central

    Vinokur, Jeffrey M; Korman, Tyler P; Sawaya, Michael R; Collazo, Michael; Cascio, Duillio; Bowie, James U

    2015-01-01

    In animals, cholesterol is made from 5-carbon building blocks produced by the mevalonate pathway. Drugs that inhibit the mevalonate pathway such as atorvastatin (lipitor) have led to successful treatments for high cholesterol in humans. Another potential target for the inhibition of cholesterol synthesis is mevalonate diphosphate decarboxylase (MDD), which catalyzes the phosphorylation of (R)-mevalonate diphosphate, followed by decarboxylation to yield isopentenyl pyrophosphate. We recently discovered an MDD homolog, mevalonate-3-kinase (M3K) from Thermoplasma acidophilum, which catalyzes the identical phosphorylation of (R)-mevalonate, but without concomitant decarboxylation. Thus, M3K catalyzes half the reaction of the decarboxylase, allowing us to separate features of the active site that are required for decarboxylation from features required for phosphorylation. Here we determine the crystal structure of M3K in the apo form, and with bound substrates, and compare it to MDD structures. Structural and mutagenic analysis reveals modifications that allow M3K to bind mevalonate rather than mevalonate diphosphate. Comparison to homologous MDD structures show that both enzymes employ analogous Arg or Lys residues to catalyze phosphate transfer. However, an invariant active site Asp/Lys pair of MDD previously thought to play a role in phosphorylation is missing in M3K with no functional replacement. Thus, we suggest that the invariant Asp/Lys pair in MDD may be critical for decarboxylation rather than phosphorylation. PMID:25422158

  9. Computational inference of the structure and regulation of the lignin pathway in Panicum virgatum

    SciTech Connect

    Faraji, Mojdeh; Fonseca, Luis L.; Escamilla-Treviño, Luis; Dixon, Richard A.; Voit, Eberhard O.

    2015-09-17

    Switchgrass is a prime target for biofuel production from inedible plant parts and has been the subject of numerous investigations in recent years. Yet, one of the main obstacles to effective biofuel production remains to be the major problem of recalcitrance. Recalcitrance emerges in part from the 3-D structure of lignin as a polymer in the secondary cell wall. Lignin limits accessibility of the sugars in the cellulose and hemicellulose polymers to enzymes and ultimately decreases ethanol yield. Monolignols, the building blocks of lignin polymers, are synthesized in the cytosol and translocated to the plant cell wall, where they undergo polymerization. The biosynthetic pathway leading to monolignols in switchgrass is not completely known, and difficulties associated with in vivo measurements of these intermediates pose a challenge for a true understanding of the functioning of the pathway. In this study, a systems biological modeling approach is used to address this challenge and to elucidate the structure and regulation of the lignin pathway through a computational characterization of alternate candidate topologies. The analysis is based on experimental data characterizing stem and tiller tissue of four transgenic lines (knock-downs of genes coding for key enzymes in the pathway) as well as wild-type switchgrass plants. These data consist of the observed content and composition of monolignols. The possibility of a G-lignin specific metabolic channel associated with the production and degradation of coniferaldehyde is examined, and the results support previous findings from another plant species. The computational analysis suggests regulatory mechanisms of product inhibition and enzyme competition, which are well known in biochemistry, but so far had not been reported in switchgrass. By including these mechanisms, the pathway model is able to represent all observations. In conclusion, the results show that the presence of the coniferaldehyde channel is necessary

  10. Computational inference of the structure and regulation of the lignin pathway in Panicum virgatum

    DOE PAGESBeta

    Faraji, Mojdeh; Fonseca, Luis L.; Escamilla-Treviño, Luis; Dixon, Richard A.; Voit, Eberhard O.

    2015-09-17

    Switchgrass is a prime target for biofuel production from inedible plant parts and has been the subject of numerous investigations in recent years. Yet, one of the main obstacles to effective biofuel production remains to be the major problem of recalcitrance. Recalcitrance emerges in part from the 3-D structure of lignin as a polymer in the secondary cell wall. Lignin limits accessibility of the sugars in the cellulose and hemicellulose polymers to enzymes and ultimately decreases ethanol yield. Monolignols, the building blocks of lignin polymers, are synthesized in the cytosol and translocated to the plant cell wall, where they undergomore » polymerization. The biosynthetic pathway leading to monolignols in switchgrass is not completely known, and difficulties associated with in vivo measurements of these intermediates pose a challenge for a true understanding of the functioning of the pathway. In this study, a systems biological modeling approach is used to address this challenge and to elucidate the structure and regulation of the lignin pathway through a computational characterization of alternate candidate topologies. The analysis is based on experimental data characterizing stem and tiller tissue of four transgenic lines (knock-downs of genes coding for key enzymes in the pathway) as well as wild-type switchgrass plants. These data consist of the observed content and composition of monolignols. The possibility of a G-lignin specific metabolic channel associated with the production and degradation of coniferaldehyde is examined, and the results support previous findings from another plant species. The computational analysis suggests regulatory mechanisms of product inhibition and enzyme competition, which are well known in biochemistry, but so far had not been reported in switchgrass. By including these mechanisms, the pathway model is able to represent all observations. In conclusion, the results show that the presence of the coniferaldehyde channel is

  11. Guided post-acceleration of laser-driven ions by a miniature modular structure

    NASA Astrophysics Data System (ADS)

    Kar, Satyabrata; Ahmed, Hamad; Prasad, Rajendra; Cerchez, Mirela; Brauckmann, Stephanie; Aurand, Bastian; Cantono, Giada; Hadjisolomou, Prokopis; Lewis, Ciaran L. S.; Macchi, Andrea; Nersisyan, Gagik; Robinson, Alexander P. L.; Schroer, Anna M.; Swantusch, Marco; Zepf, Matt; Willi, Oswald; Borghesi, Marco

    2016-04-01

    All-optical approaches to particle acceleration are currently attracting a significant research effort internationally. Although characterized by exceptional transverse and longitudinal emittance, laser-driven ion beams currently have limitations in terms of peak ion energy, bandwidth of the energy spectrum and beam divergence. Here we introduce the concept of a versatile, miniature linear accelerating module, which, by employing laser-excited electromagnetic pulses directed along a helical path surrounding the laser-accelerated ion beams, addresses these shortcomings simultaneously. In a proof-of-principle experiment on a university-scale system, we demonstrate post-acceleration of laser-driven protons from a flat foil at a rate of 0.5 GeV m-1, already beyond what can be sustained by conventional accelerator technologies, with dynamic beam collimation and energy selection. These results open up new opportunities for the development of extremely compact and cost-effective ion accelerators for both established and innovative applications.

  12. Effect of gravitational acceleration, hypokinesia and hypodynamia on the structure of the intestinal vascular bed

    NASA Technical Reports Server (NTRS)

    Nikitin, M. V.

    1980-01-01

    A series of experiments comparing single and combined effects of hypokinesia and gravitational acceleration on morphology of intestinal blood vessels are discussed. Results indicate that hypokinesia has a whole body nonspecific effect reflected even in an organ whose activity shows little or no change due to hypokinesia. In early hypokinetic stages blood redistribution caused anorexia, intestinal atonia, and secretory disruption. Destructive changes from further exposure include aneurisms, varicoses, extravascular movement of blood elements, and vascular wall muscle fiber degeneration. The effect of acceleration is greatest in the ventrodorsal direction. Changes due to acceleration then hypokinesia are like those due to hypokinesia alone; changes due to acceleration before and after hypokinesia are like those due to acceleration. Adaptation raises acceleration tolerance but the effects do not survive four-week hypokinesia.

  13. PDE2-mediated cAMP hydrolysis accelerates cardiac fibroblast to myofibroblast conversion and is antagonized by exogenous activation of cGMP signaling pathways.

    PubMed

    Vettel, C; Lämmle, S; Ewens, S; Cervirgen, C; Emons, J; Ongherth, A; Dewenter, M; Lindner, D; Westermann, D; Nikolaev, V O; Lutz, S; Zimmermann, W H; El-Armouche, A

    2014-04-15

    Recent studies suggest that the signal molecules cAMP and cGMP have antifibrotic effects by negatively regulating pathways associated with fibroblast to myofibroblast (MyoCF) conversion. The phosphodiesterase 2 (PDE2) has the unique property to be stimulated by cGMP, which leads to a remarkable increase in cAMP hydrolysis and thus mediates a negative cross-talk between both pathways. PDE2 has been recently investigated in cardiomyocytes; here we specifically addressed its role in fibroblast conversion and cardiac fibrosis. PDE2 is abundantly expressed in both neonatal rat cardiac fibroblasts (CFs) and cardiomyocytes. The overexpression of PDE2 in CFs strongly reduced basal and isoprenaline-induced cAMP synthesis, and this decrease was sufficient to induce MyoCF conversion even in the absence of exogenous profibrotic stimuli. Functional stress-strain experiments with fibroblast-derived engineered connective tissue (ECT) demonstrated higher stiffness in ECTs overexpressing PDE2. In regard to cGMP, neither basal nor atrial natriuretic peptide-induced cGMP levels were affected by PDE2, whereas the response to nitric oxide donor sodium nitroprusside was slightly but significantly reduced. Interestingly, despite persistently depressed cAMP levels, both cGMP-elevating stimuli were able to completely prevent the PDE2-induced MyoCF phenotype, arguing for a double-tracked mechanism. In conclusion, PDE2 accelerates CF to MyoCF conversion, which leads to greater stiffness in ECTs. Atrial natriuretic peptide- and sodium nitroprusside-mediated cGMP synthesis completely reverses PDE2-induced fibroblast conversion. Thus PDE2 may augment cardiac remodeling, but this effect can also be overcome by enhanced cGMP. The redundant role of cAMP and cGMP as antifibrotic meditators may be viewed as a protective mechanism in heart failure. PMID:24531807

  14. ConnectViz: Accelerated Approach for Brain Structural Connectivity Using Delaunay Triangulation.

    PubMed

    Adeshina, A M; Hashim, R

    2016-03-01

    Stroke is a cardiovascular disease with high mortality and long-term disability in the world. Normal functioning of the brain is dependent on the adequate supply of oxygen and nutrients to the brain complex network through the blood vessels. Stroke, occasionally a hemorrhagic stroke, ischemia or other blood vessel dysfunctions can affect patients during a cerebrovascular incident. Structurally, the left and the right carotid arteries, and the right and the left vertebral arteries are responsible for supplying blood to the brain, scalp and the face. However, a number of impairment in the function of the frontal lobes may occur as a result of any decrease in the flow of the blood through one of the internal carotid arteries. Such impairment commonly results in numbness, weakness or paralysis. Recently, the concepts of brain's wiring representation, the connectome, was introduced. However, construction and visualization of such brain network requires tremendous computation. Consequently, previously proposed approaches have been identified with common problems of high memory consumption and slow execution. Furthermore, interactivity in the previously proposed frameworks for brain network is also an outstanding issue. This study proposes an accelerated approach for brain connectomic visualization based on graph theory paradigm using compute unified device architecture, extending the previously proposed SurLens Visualization and computer aided hepatocellular carcinoma frameworks. The accelerated brain structural connectivity framework was evaluated with stripped brain datasets from the Department of Surgery, University of North Carolina, Chapel Hill, USA. Significantly, our proposed framework is able to generate and extract points and edges of datasets, displays nodes and edges in the datasets in form of a network and clearly maps data volume to the corresponding brain surface. Moreover, with the framework, surfaces of the dataset were simultaneously displayed with the

  15. A piezo-driven micro-inclination stage for calibration of a micro-acceleration transducer: structure and control strategy

    NASA Astrophysics Data System (ADS)

    Shao, Shubao; Song, Siyang; Xu, Minglong; Xie, Shilin; Li, Liang

    2016-02-01

    In some space applications, such as space navigation and vibration control of the large space structures, micro-acceleration transducers are required and have to be calibrated accurately. Unfortunately, providing extremely small static and quasi-static stimuli (accelerations) for the calibration of the micro-acceleration transducer has been a challenging task. This paper proposes a novel piezo-driven micro-inclination stage (PMIS) that can produce both discrete and continuous tumbles in a gravity field so that extremely small static and quasi-static stimuli (accelerations) can be obtained from a tiny component of the gravity constant. The proposed PMIS, which is driven by the lead zirconate titanate (PZT) stack, employs a rhombic mechanism to provide the PZT stack with a proper preload for the purpose of outputting a bidirectional force. To produce accurate static and quasi-static stimuli, the hysteresis non-linearity inherent in PZT stack is compensated by employing the strain feedback based adaptive control where the hysteresis property is identified online using the controlled auto-regressive moving average model. Furthermore, to improve the resolution of strain feedback, the strain sensitivity is maximized through structure optimization of the rhombic mechanism. The experimental results demonstrated that the proposed PMIS can produce minimal micro-inclination of {{0.1}\\prime \\prime} (corresponding to the induced micro-acceleration of 0.5μ g ) with the frequency ranging from 0 (DC) to 2 Hz.

  16. Pathways of information transmission among wild songbirds follow experimentally imposed changes in social foraging structure.

    PubMed

    Firth, Josh A; Sheldon, Ben C; Farine, Damien R

    2016-06-01

    Animals regularly use information from others to shape their decisions. Yet, determining how changes in social structure affect information flow and social learning strategies has remained challenging. We manipulated the social structure of a large community of wild songbirds by controlling which individuals could feed together at automated feeding stations (selective feeders). We then provided novel ephemeral food patches freely accessible to all birds and recorded the spread of this new information. We demonstrate that the discovery of new food patches followed the experimentally imposed social structure and that birds disproportionately learnt from those whom they could forage with at the selective feeders. The selective feeders reduced the number of conspecific information sources available and birds subsequently increased their use of information provided by heterospecifics. Our study demonstrates that changes to social systems carry over into pathways of information transfer and that individuals learn from tutors that provide relevant information in other contexts. PMID:27247439

  17. Pathways of information transmission among wild songbirds follow experimentally imposed changes in social foraging structure

    PubMed Central

    Sheldon, Ben C.

    2016-01-01

    Animals regularly use information from others to shape their decisions. Yet, determining how changes in social structure affect information flow and social learning strategies has remained challenging. We manipulated the social structure of a large community of wild songbirds by controlling which individuals could feed together at automated feeding stations (selective feeders). We then provided novel ephemeral food patches freely accessible to all birds and recorded the spread of this new information. We demonstrate that the discovery of new food patches followed the experimentally imposed social structure and that birds disproportionately learnt from those whom they could forage with at the selective feeders. The selective feeders reduced the number of conspecific information sources available and birds subsequently increased their use of information provided by heterospecifics. Our study demonstrates that changes to social systems carry over into pathways of information transfer and that individuals learn from tutors that provide relevant information in other contexts. PMID:27247439

  18. Structural basis for leucine sensing by the Sestrin2-mTORC1 pathway

    PubMed Central

    Saxton, Robert A.; Knockenhauer, Kevin E.; Wolfson, Rachel L.; Chantranupong, Lynne; Pacold, Michael E.; Wang, Tim; Schwartz, Thomas U.; Sabatini, David M.

    2015-01-01

    Eukaryotic cells coordinate growth with the availability of nutrients through mTOR complex 1 (mTORC1), a master growth regulator. Leucine is of particular importance and activates mTORC1 via the Rag GTPases and their regulators GATOR1 and GATOR2. Sestrin2 interacts with GATOR2 and is a leucine sensor. We present the 2.7-Å crystal structure of Sestrin2 in complex with leucine. Leucine binds through a single pocket that coordinates its charged functional groups and confers specificity for the hydrophobic side chain. A loop encloses leucine and forms a lid-latch mechanism required for binding. A structure-guided mutation in Sestrin2 that decreases its affinity for leucine leads to a concomitant increase in the leucine concentration required for mTORC1 activation in cells. These results provide a structural mechanism of amino acid sensing by the mTORC1 pathway. PMID:26586190

  19. Ion Acceleration at Earth, Saturn and Jupiter and its Global Impact on Magnetospheric Structure

    NASA Astrophysics Data System (ADS)

    Brandt, Pontus

    2016-07-01

    The ion plasma pressures at Earth, Saturn and Jupiter are significant players in the electrodynamic force-balance that governs the structure and dynamics of these magnetospheres. There are many similarities between the physical mechanisms that are thought to heat the ion plasma to temperatures that even exceed those of the solar corona. In this presentation we compare the ion acceleration mechanisms at the three planetary magnetospheres and discuss their global impacts on magnetopsheric structure. At Earth, bursty-bulk flows, or "bubbles", have been shown to accelerate protons and O+ to high energies by the earthward moving magnetic dipolarization fronts. O+ ions display a more non-adiabatic energization in response to these fronts than protons do as they are energized and transported in to the ring-current region where they reach energies of several 100's keV. We present both in-situ measurements from the NASA Van Allen Probes Mission and global Energetic Neutral (ENA) images from the High-Energy Neutral Atom (HENA) Camera on board the IMAGE Mission, that illustrate these processes. The global impact on the magnetospheric structure is explored by comparing the empirical magnetic field model TS07d for given driving conditions with global plasma pressure distributions derived from the HENA images. At Saturn, quasi-periodic energization events, or large-scale injections, occur beyond about 9 RS around the post-midnight sector, clearly shown by the Ion and Neutral Atom Camera (INCA) on board the Cassini mission. In contrast to Earth, the corotational drift dominates even the energetic ion distributions. The large-scale injections display similar dipolarization front features can be found and there are indications that like at Earth the O+ responds more non-adiabatically than protons do. However, at Saturn there are also differences in that there appears to be energization events deep in the inner magnetosphere (6-9 RS) preferentially occurring in the pre

  20. A new structural relaxation pathway of low-density amorphous ice.

    PubMed

    Shephard, Jacob J; Klotz, Stefan; Vickers, Martin; Salzmann, Christoph G

    2016-05-28

    Low-density amorphous (LDA) ice is involved in critical cosmological processes and has gained prominence as one of the at least two distinct amorphous forms of ice. Despite these accolades, we still have an incomplete understanding of the structural diversity that is encompassed within the LDA state and the dynamic processes that take place upon heating LDA. Heating the high-pressure ice VIII phase at ambient pressure is a remarkable example of temperature-induced amorphisation yielding LDA. We investigate this process in detail using X-ray diffraction and Raman spectroscopy and show that the LDA obtained from ice VIII is structurally different from the more "traditional" states of LDA which are approached upon thermal annealing. This new structural relaxation pathway involves an increase of structural order on the intermediate range length scale. In contrast with other LDA materials the local structure is more ordered initially and becomes slightly more disordered upon annealing. We also show that the cascade of phase transitions upon heating ice VIII at ambient pressure includes the formation of ice IX which may be connected with the structural peculiarities of LDA from ice VIII. Overall, this study shows that LDA is a structurally more diverse material than previously appreciated. PMID:27250311

  1. Distinct Structural Pathways Coordinate the Activation of AMPA Receptor-Auxiliary Subunit Complexes

    PubMed Central

    Dawe, G. Brent; Musgaard, Maria; Aurousseau, Mark R.P.; Nayeem, Naushaba; Green, Tim; Biggin, Philip C.; Bowie, Derek

    2016-01-01

    Summary Neurotransmitter-gated ion channels adopt different gating modes to fine-tune signaling at central synapses. At glutamatergic synapses, high and low activity of AMPA receptors (AMPARs) is observed when pore-forming subunits coassemble with or without auxiliary subunits, respectively. Whether a common structural pathway accounts for these different gating modes is unclear. Here, we identify two structural motifs that determine the time course of AMPAR channel activation. A network of electrostatic interactions at the apex of the AMPAR ligand-binding domain (LBD) is essential for gating by pore-forming subunits, whereas a conserved motif on the lower, D2 lobe of the LBD prolongs channel activity when auxiliary subunits are present. Accordingly, channel activity is almost entirely abolished by elimination of the electrostatic network but restored via auxiliary protein interactions at the D2 lobe. In summary, we propose that activation of native AMPAR complexes is coordinated by distinct structural pathways, favored by the association/dissociation of auxiliary subunits. PMID:26924438

  2. Pathway structure determination in complex stochastic networks with non-exponential dwell times

    SciTech Connect

    Li, Xin; Kolomeisky, Anatoly B.; Valleriani, Angelo

    2014-05-14

    Analysis of complex networks has been widely used as a powerful tool for investigating various physical, chemical, and biological processes. To understand the emergent properties of these complex systems, one of the most basic issues is to determine the structure and topology of the underlying networks. Recently, a new theoretical approach based on first-passage analysis has been developed for investigating the relationship between structure and dynamic properties for network systems with exponential dwell time distributions. However, many real phenomena involve transitions with non-exponential waiting times. We extend the first-passage method to uncover the structure of distinct pathways in complex networks with non-exponential dwell time distributions. It is found that the analysis of early time dynamics provides explicit information on the length of the pathways associated to their dynamic properties. It reveals a universal relationship that we have condensed in one general equation, which relates the number of intermediate states on the shortest path to the early time behavior of the first-passage distributions. Our theoretical predictions are confirmed by extensive Monte Carlo simulations.

  3. Distinct Structural Pathways Coordinate the Activation of AMPA Receptor-Auxiliary Subunit Complexes.

    PubMed

    Dawe, G Brent; Musgaard, Maria; Aurousseau, Mark R P; Nayeem, Naushaba; Green, Tim; Biggin, Philip C; Bowie, Derek

    2016-03-16

    Neurotransmitter-gated ion channels adopt different gating modes to fine-tune signaling at central synapses. At glutamatergic synapses, high and low activity of AMPA receptors (AMPARs) is observed when pore-forming subunits coassemble with or without auxiliary subunits, respectively. Whether a common structural pathway accounts for these different gating modes is unclear. Here, we identify two structural motifs that determine the time course of AMPAR channel activation. A network of electrostatic interactions at the apex of the AMPAR ligand-binding domain (LBD) is essential for gating by pore-forming subunits, whereas a conserved motif on the lower, D2 lobe of the LBD prolongs channel activity when auxiliary subunits are present. Accordingly, channel activity is almost entirely abolished by elimination of the electrostatic network but restored via auxiliary protein interactions at the D2 lobe. In summary, we propose that activation of native AMPAR complexes is coordinated by distinct structural pathways, favored by the association/dissociation of auxiliary subunits. PMID:26924438

  4. Structural insights into the initiating complex of the lectin pathway of complement activation.

    PubMed

    Kjaer, Troels R; Le, Le T M; Pedersen, Jan Skov; Sander, Bjoern; Golas, Monika M; Jensenius, Jens Christian; Andersen, Gregers R; Thiel, Steffen

    2015-02-01

    The proteolytic cascade of the complement system is initiated when pattern-recognition molecules (PRMs) bind to ligands, resulting in the activation of associated proteases. In the lectin pathway of complement, the complex of mannan-binding lectin (MBL) and MBL-associated serine protease-1 (MASP-1) initiates the pathway by activating a second protease, MASP-2. Here we present a structural study of a PRM/MASP complex and derive the overall architecture of the 450 kDa MBL/MASP-1 complex using small-angle X-ray scattering and electron microscopy. The serine protease (SP) domains from the zymogen MASP-1 dimer protrude from the cone-like MBL tetramer and are separated by at least 20 nm. This suggests that intracomplex activation within a single MASP-1 dimer is unlikely and instead supports intercomplex activation, whereby the MASP SP domains are accessible to nearby PRM-bound MASPs. This activation mechanism differs fundamentally from the intracomplex initiation models previously proposed for both the lectin and the classical pathway. PMID:25579818

  5. Structure and function of enterotoxigenic Escherichia coli fimbriae from differing assembly pathways.

    PubMed

    Mortezaei, Narges; Epler, Chelsea R; Shao, Paul P; Shirdel, Mariam; Singh, Bhupender; McVeigh, Annette; Uhlin, Bernt Eric; Savarino, Stephen J; Andersson, Magnus; Bullitt, Esther

    2015-01-01

    Pathogenic enterotoxigenic Escherichia coli (ETEC) are the major bacterial cause of diarrhea in young children in developing countries and in travelers, causing significant mortality in children. Adhesive fimbriae are a prime virulence factor for ETEC, initiating colonization of the small intestinal epithelium. Similar to other Gram-negative bacteria, ETEC express one or more diverse fimbriae, some assembled by the chaperone-usher pathway and others by the alternate chaperone pathway. Here, we elucidate structural and biophysical aspects and adaptations of each fimbrial type to its respective host niche. CS20 fimbriae are compared with colonization factor antigen I (CFA/I) fimbriae, which are two ETEC fimbriae assembled via different pathways, and with P-fimbriae from uropathogenic E. coli. Many fimbriae unwind from their native helical filament to an extended linear conformation under force, thereby sustaining adhesion by reducing load at the point of contact between the bacterium and the target cell. CFA/I fimbriae require the least force to unwind, followed by CS20 fimbriae and then P-fimbriae, which require the highest unwinding force. We conclude from our electron microscopy reconstructions, modeling and force spectroscopy data that the target niche plays a central role in the biophysical properties of fimbriae that are critical for bacterial pathophysiology. PMID:25355550

  6. Pesticide residue transfer in Thai farmer families: using structural equation modeling to determine exposure pathways.

    PubMed

    Liu, Hanhua; Hanchenlaksh, Chalalai; Povey, Andrew C; de Vocht, Frank

    2015-01-01

    Use of pesticides in agriculture may lead to downstream exposure of farmers' families to pesticide residues inadvertently taken home. Identification of the independent contribution of different exposure pathways from the farmer to their children can provide clear targets to reduce exposure of farmers' children. Individual contributions of different pesticide transfer exposure pathways were investigated using structural equation modeling methods, and the benefits of these methods compared to standard multiple regression are described. A total of 72 Thai families, consisting of a farmer, a spouse, and a child, participated in this study. Family members completed a questionnaire and self-collected three spot morning urine samples in the spraying season. Urine samples were analyzed for diethyl phosphate, diethyl thiophosphate, diethyl dithiophosphate, dimethyl phosphate, dimethyl thiophosphate, and dimethyl dithiophosphate. A path model was developed based on an a priori hypothesized framework to examine the individual contributions of different exposure pathways that may directly or indirectly affect transfer of pesticide residues from farmers to their children. Transfer from the farmer to the child occurs indirectly, primarily through transfer to the spouse in the first instance, but also through contamination of the home environment. Clear targets for interventions are directly the reduction of farmers' take-home exposures and indirectly frequent cleaning of the home to avoid buildup of pesticide residues. PMID:25407029

  7. Structure and function of Enterotoxigenic Escherichia coli fimbriae from differing assembly pathways

    PubMed Central

    Mortezaei, Narges; Epler, Chelsea R.; Shao, Paul P.; Shirdel, Mariam; Singh, Bhupender; McVeigh, Annette; Uhlin, Bernt Eric; Savarino, Stephen J.; Andersson, Magnus; Bullitt, Esther

    2014-01-01

    Pathogenic enterotoxigenic Escherichia coli (ETEC) are the major bacterial cause of diarrhea in young children in developing countries and in travelers, causing significant mortality in children. Adhesive fimbriae are a prime virulence factor for ETEC, initiating colonization of the small intestinal epithelium. Similar to other Gram-negative bacteria, ETEC express one or more diverse fimbriae, some assembled by the chaperone-usher pathway and others by the alternate chaperone pathway. Here we elucidate structural and biophysical aspects and adaptations of each fimbrial type to its respective host niche. CS20 fimbriae are compared to CFA/I fimbriae, which are two ETEC fimbriae assembled via different pathways, and to P-fimbriae from uropathogenic E. coli. Many fimbriae unwind from their native helical filament to an extended linear conformation under force, thereby sustaining adhesion by reducing load at the point of contact between the bacterium and the target cell. CFA/I fimbriae require the least force to unwind, followed by CS20 fimbriae and then P-fimbriae, which require the highest unwinding force. We conclude from our electron microscopy reconstructions, modeling, and force spectroscopy data that the target niche plays a central role in the biophysical properties of fimbriae that are critical for bacterial pathophysiology. PMID:25355550

  8. Biochemical and Structural Characterization of a Ureidoglycine Aminotransferase in the Klebsiella pneumoniae Uric Acid Catabolic Pathway

    SciTech Connect

    French, Jarrod B.; Ealick, Steven E.

    2010-09-03

    Many plants, fungi, and bacteria catabolize allantoin as a mechanism for nitrogen assimilation. Recent reports have shown that in plants and some bacteria the product of hydrolysis of allantoin by allantoinase is the unstable intermediate ureidoglycine. While this molecule can spontaneously decay, genetic analysis of some bacterial genomes indicates that an aminotransferase may be present in the pathway. Here we present evidence that Klebsiella pneumoniae HpxJ is an aminotransferase that preferentially converts ureidoglycine and an {alpha}-keto acid into oxalurate and the corresponding amino acid. We determined the crystal structure of HpxJ, allowing us to present an explanation for substrate specificity.

  9. Accelerated Life Structural Benchmark Testing for a Stirling Convertor Heater Head

    NASA Astrophysics Data System (ADS)

    Krause, David L.; Kantzos, Pete T.

    2006-01-01

    For proposed long-duration NASA Space Science missions, the Department of Energy, Lockheed Martin, Infinia Corporation, and NASA Glenn Research Center are developing a high-efficiency, 110-watt Stirling Radioisotope Generator (SRG110). A structurally significant limit state for the SRG110 heater head component is creep deformation induced at high material temperature and low stress level. Conventional investigations of creep behavior adequately rely on experimental results from uniaxial creep specimens, and a wealth of creep data is available for the Inconel 718 material of construction. However, the specified atypical thin heater head material is fine-grained with a heat treatment that limits precipitate growth, and little creep property data for this microstructure is available in the literature. In addition, the geometry and loading conditions apply a multiaxial stress state on the component, far from the conditions of uniaxial testing. For these reasons, an extensive experimental investigation is ongoing to aid in accurately assessing the durability of the SRG110 heater head. This investigation supplements uniaxial creep testing with pneumatic testing of heater head-like pressure vessels at design temperature with stress levels ranging from approximately the design stress to several times that. This paper presents experimental results, post-test microstructural analyses, and conclusions for four higher-stress, accelerated life tests. Analysts are using these results to calibrate deterministic and probabilistic analytical creep models of the SRG110 heater head.

  10. Aggressive, accelerated subdomain smoothers for Stokes flow with highly heterogeneous viscosity structure

    NASA Astrophysics Data System (ADS)

    Sanan, Patrick; May, Dave; Schenk, Olaf; Rupp, Karl

    2016-04-01

    Scalable solvers for mantle convection and lithospheric dynamics with highly heterogeneous viscosity structure typically require the use of a multigrid method. To leverage new hybrid CPU-accelerator architectures on leadership compute clusters, multigrid hierarchies which can reduce communication and use high available arithmetic intensity are at a premium, motivating more aggressive coarsening schemes and smoothers. We present results of a comparative study of two competitive GPU-enabled subdomain smoothers within an additive Schwarz method. Chebyshev-Jacobi smoothing has been shown to be an effective smoother, and its nature as a low-communication method built from basic linear algebra routines allows its use on a wide range of devices with current libraries. ILU smoothing is also of interest and is known to provide robust smoothing in some cases, but has traditionally been difficult to use in a fine-grained parallel environment. However, a recently-introduced variant by Chow and Patel allows for incomplete factorizations to be computed and applied in these environments, hence allowing us to study them as well. We use and extend the pTatin3D, PETSc, and ViennaCL libraries to integrate promising methods into a realistic application framework.

  11. Accelerated dynamic MRI exploiting sparsity and low-rank structure: k-t SLR.

    PubMed

    Lingala, Sajan Goud; Hu, Yue; DiBella, Edward; Jacob, Mathews

    2011-05-01

    We introduce a novel algorithm to reconstruct dynamic magnetic resonance imaging (MRI) data from under-sampled k-t space data. In contrast to classical model based cine MRI schemes that rely on the sparsity or banded structure in Fourier space, we use the compact representation of the data in the Karhunen Louve transform (KLT) domain to exploit the correlations in the dataset. The use of the data-dependent KL transform makes our approach ideally suited to a range of dynamic imaging problems, even when the motion is not periodic. In comparison to current KLT-based methods that rely on a two-step approach to first estimate the basis functions and then use it for reconstruction, we pose the problem as a spectrally regularized matrix recovery problem. By simultaneously determining the temporal basis functions and its spatial weights from the entire measured data, the proposed scheme is capable of providing high quality reconstructions at a range of accelerations. In addition to using the compact representation in the KLT domain, we also exploit the sparsity of the data to further improve the recovery rate. Validations using numerical phantoms and in vivo cardiac perfusion MRI data demonstrate the significant improvement in performance offered by the proposed scheme over existing methods. PMID:21292593

  12. Accelerated Life Structural Benchmark Testing for a Stirling Convertor Heater Head

    SciTech Connect

    Krause, David L.; Kantzos, Pete T.

    2006-01-20

    For proposed long-duration NASA Space Science missions, the Department of Energy, Lockheed Martin, Infinia Corporation, and NASA Glenn Research Center are developing a high-efficiency, 110-watt Stirling Radioisotope Generator (SRG110). A structurally significant limit state for the SRG110 heater head component is creep deformation induced at high material temperature and low stress level. Conventional investigations of creep behavior adequately rely on experimental results from uniaxial creep specimens, and a wealth of creep data is available for the Inconel 718 material of construction. However, the specified atypical thin heater head material is fine-grained with a heat treatment that limits precipitate growth, and little creep property data for this microstructure is available in the literature. In addition, the geometry and loading conditions apply a multiaxial stress state on the component, far from the conditions of uniaxial testing. For these reasons, an extensive experimental investigation is ongoing to aid in accurately assessing the durability of the SRG110 heater head. This investigation supplements uniaxial creep testing with pneumatic testing of heater head-like pressure vessels at design temperature with stress levels ranging from approximately the design stress to several times that. This paper presents experimental results, post-test microstructural analyses, and conclusions for four higher-stress, accelerated life tests. Analysts are using these results to calibrate deterministic and probabilistic analytical creep models of the SRG110 heater head.

  13. Beta/A4 proteinlike immunoreactive granular structures in the brain of senescence-accelerated mouse.

    PubMed Central

    Takemura, M.; Nakamura, S.; Akiguchi, I.; Ueno, M.; Oka, N.; Ishikawa, S.; Shimada, A.; Kimura, J.; Takeda, T.

    1993-01-01

    The immunohistochemical localization of amyloid beta/A4 protein in the senescence-accelerated mouse brain was studied using six different antisera against human amyloid precursor protein peptides. beta/A4 proteinlike immunoreactivity was observed in the form of granular structures (beta-LIGS) in various regions, including the medial septum, cerebral cortex, hippocampus, cerebellum, and some cranial nerve roots. beta-LIGS were 1.5 to 2.5 mu in diameter and irregularly shaped. They increased significantly in number with aging, predominantly in animals with a phenotype of age-related deterioration of memory and learning abilities. Congo red and thioflavine S did not stain the granules. On immunoblots, the main immunoreactive bands were observed at 14 to 18 kd. The staining intensities of these bands also increased with advancing age. We consider that beta-LIGS are not only a new morphological manifestation of senescence in mice, but also a pertinent clue in understanding the mechanisms of amyloid deposition. Images Figure 1 Figure 3 Figure 4 PMID:8506956

  14. Accelerated Life Structural Benchmark Testing for a Stirling Convertor Heater Head

    NASA Technical Reports Server (NTRS)

    Krause, David L.; Kantzos, Pete T.

    2006-01-01

    For proposed long-duration NASA Space Science missions, the Department of Energy, Lockheed Martin, Infinia Corporation, and NASA Glenn Research Center are developing a high-efficiency, 110 W Stirling Radioisotope Generator (SRG110). A structurally significant limit state for the SRG110 heater head component is creep deformation induced at high material temperature and low stress level. Conventional investigations of creep behavior adequately rely on experimental results from uniaxial creep specimens, and a wealth of creep data is available for the Inconel 718 material of construction. However, the specified atypical thin heater head material is fine-grained with a heat treatment that limits precipitate growth, and little creep property data for this microstructure is available in the literature. In addition, the geometry and loading conditions apply a multiaxial stress state on the component, far from the conditions of uniaxial testing. For these reasons, an extensive experimental investigation is ongoing to aid in accurately assessing the durability of the SRG110 heater head. This investigation supplements uniaxial creep testing with pneumatic testing of heater head-like pressure vessels at design temperature with stress levels ranging from approximately the design stress to several times that. This paper presents experimental results, post-test microstructural analyses, and conclusions for four higher-stress, accelerated life tests. Analysts are using these results to calibrate deterministic and probabilistic analytical creep models of the SRG110 heater head.

  15. Magnetic and structural design of a 15 T Nb3Sn accelerator dipole model

    NASA Astrophysics Data System (ADS)

    Kashikhin, V. V.; Andreev, N.; Barzi, E.; Novitski, I.; Zlobin, A. V.

    2015-12-01

    Hadron Colliders (HC) are the most powerful discovery tools in modern high energy physics. A 100 TeV scale HC with a nominal operation field of at least 15 T is being considered for the post-LHC era. The choice of a 15 T nominal field requires using the Nb3Sn technology. Practical demonstration of this field level in an accelerator-quality magnet and substantial reduction of the magnet costs are the key conditions for realization of such a machine. FNAL has started the development of a 15 T Nb3Sn dipole demonstrator for a 100 TeV scale HC. The magnet design is based on 4-layer shell type coils, graded between the inner and outer layers to maximize the performance. The experience gained during the 11-T dipole R&D campaign is applied to different aspects of the magnet design. This paper describes the magnetic and structural designs and parameters of the 15 T Nb3Sn dipole and the steps towards the demonstration model.

  16. Magnetic and Structural Design of a 15 T $Nb_3Sn$ Accelerator Depole Model

    SciTech Connect

    Kashikhin, V. V.; Andreev, N.; Barzi, E.; Novitski, I.; Zlobin, A. V.

    2015-01-01

    Hadron Colliders (HC) are the most powerful discovery tools in modern high energy physics. A 100 TeV scale HC with a nominal operation field of at least 15 T is being considered for the post-LHC era. The choice of a 15 T nominal field requires using the Nb3Sn technology. Practical demonstration of this field level in an accelerator-quality magnet and substantial reduction of the magnet costs are the key conditions for realization of such a machine. FNAL has started the development of a 15 T $Nb_{3}Sn$ dipole demonstrator for a 100 TeV scale HC. The magnet design is based on 4-layer shell type coils, graded between the inner and outer layers to maximize the performance. The experience gained during the 11-T dipole R&D campaign is applied to different aspects of the magnet design. This paper describes the magnetic and structural designs and parameters of the 15 T $Nb_3Sn$ dipole and the steps towards the demonstration model.

  17. GPU-accelerated model for fast, three-dimensional fluid-structure interaction computations.

    PubMed

    Nita, Cosmin; Itu, Lucian; Mihalef, Viorel; Sharma, Puneet; Rapaka, Saikiran

    2015-08-01

    In this paper we introduce a methodology for performing one-way Fluid-Structure interaction (FSI), i.e. where the motion of the wall boundaries is imposed. We use a Graphics Processing Unit (GPU) accelerated Lattice-Boltzmann Method (LBM) implementation and present an efficient workflow for embedding the moving geometry, given as a set of polygonal meshes, in the LBM computation. The proposed method is first validated in a synthetic experiment: a vessel which is periodically expanding and contracting. Next, the evaluation focuses on the 3D Peristaltic flow problem: a fluid flows inside a flexible tube, where a periodic wave-like deformation produces a fluid motion along the centerline of the tube. Different geometry configurations are used and results are compared against previously published solutions. The efficient approach leads to an average execution time of approx. one hour per computation, whereas 50% of it is required for the geometry update operations. Finally, we also analyse the effect of changing the Reynolds number on the flow streamlines: the flow regime is significantly affected by the Reynolds number. PMID:26736424

  18. Estimating double tuned mass dampers for structures under ground acceleration using a novel optimum criterion

    NASA Astrophysics Data System (ADS)

    Li, Chunxiang; Zhu, Bilei

    2006-11-01

    The double tuned mass dampers (DTMD), consisting of one larger mass block (i.e. one larger tuned mass damper (TMD)) and one smaller mass block (i.e. one smaller TMD), have been proposed to seek for the mass dampers with high effectiveness and robustness for the reduction of the undesirable vibrations of structures under the ground acceleration. The structure is represented by the mode-generalized system corresponding to the specific vibration mode that needs to be controlled. In light of the developed dynamic magnification factors (DMF) of the DTMD structure system, the criterion used for assessing the optimum parameters and effectiveness of the DTMD is selected as the minimization of the minimum values of the maximum DMF of the structure with the DTMD. With resorting to the maximum DMF of both the larger and smaller TMDs in the DTMD, the stroke of the DTMD is simultaneously investigated too. It is highlighted that a novel optimum objective function has been proposed in order to acquire high robust control system. Consequently, the two types of optimum goal functions (including the optimum goal function commonly used) have been applied for the optimum searching of the DTMD. The numerical results indicate that the DTMD designed in terms of the second type of optimum objective functions (i.e. the novel optimum objective function) practically provides the same effectiveness and robustness to the changes in the drift frequency ratio (DFR) as the multiple tuned mass dampers (MTMD) with the distributed natural frequencies with the total number of the TMD units equal to five and with equal total mass ratio. Likewise, the DTMD designed with resort to the second type of optimum objective functions can practically attain the same effectiveness as the TMD with equal total mass ratio. More importantly, in the robustness to the changes in the DFR, the DTMD is significantly better than the TMD, whereas in the robustness to the natural frequency tuning (NFT), measured by the

  19. Rational design of self-assembly pathways for complex multicomponent structures.

    PubMed

    Jacobs, William M; Reinhardt, Aleks; Frenkel, Daan

    2015-05-19

    The field of complex self-assembly is moving toward the design of multiparticle structures consisting of thousands of distinct building blocks. To exploit the potential benefits of structures with such "addressable complexity," we need to understand the factors that optimize the yield and the kinetics of self-assembly. Here we use a simple theoretical method to explain the key features responsible for the unexpected success of DNA-brick experiments, which are currently the only demonstration of reliable self-assembly with such a large number of components. Simulations confirm that our theory accurately predicts the narrow temperature window in which error-free assembly can occur. Even more strikingly, our theory predicts that correct assembly of the complete structure may require a time-dependent experimental protocol. Furthermore, we predict that low coordination numbers result in nonclassical nucleation behavior, which we find to be essential for achieving optimal nucleation kinetics under mild growth conditions. We also show that, rather surprisingly, the use of heterogeneous bond energies improves the nucleation kinetics and in fact appears to be necessary for assembling certain intricate 3D structures. This observation makes it possible to sculpt nucleation pathways by tuning the distribution of interaction strengths. These insights not only suggest how to improve the design of structures based on DNA bricks, but also point the way toward the creation of a much wider class of chemical or colloidal structures with addressable complexity. PMID:25941388

  20. Rational design of self-assembly pathways for complex multicomponent structures

    PubMed Central

    Jacobs, William M.; Reinhardt, Aleks; Frenkel, Daan

    2015-01-01

    The field of complex self-assembly is moving toward the design of multiparticle structures consisting of thousands of distinct building blocks. To exploit the potential benefits of structures with such “addressable complexity,” we need to understand the factors that optimize the yield and the kinetics of self-assembly. Here we use a simple theoretical method to explain the key features responsible for the unexpected success of DNA-brick experiments, which are currently the only demonstration of reliable self-assembly with such a large number of components. Simulations confirm that our theory accurately predicts the narrow temperature window in which error-free assembly can occur. Even more strikingly, our theory predicts that correct assembly of the complete structure may require a time-dependent experimental protocol. Furthermore, we predict that low coordination numbers result in nonclassical nucleation behavior, which we find to be essential for achieving optimal nucleation kinetics under mild growth conditions. We also show that, rather surprisingly, the use of heterogeneous bond energies improves the nucleation kinetics and in fact appears to be necessary for assembling certain intricate 3D structures. This observation makes it possible to sculpt nucleation pathways by tuning the distribution of interaction strengths. These insights not only suggest how to improve the design of structures based on DNA bricks, but also point the way toward the creation of a much wider class of chemical or colloidal structures with addressable complexity. PMID:25941388

  1. Methionine Oxidation Perturbs the Structural Core of the Prion Protein and Suggests a Generic Misfolding Pathway*

    PubMed Central

    Younan, Nadine D.; Nadal, Rebecca C.; Davies, Paul; Brown, David R.; Viles, John H.

    2012-01-01

    Oxidative stress and misfolding of the prion protein (PrPC) are fundamental to prion diseases. We have therefore probed the effect of oxidation on the structure and stability of PrPC. Urea unfolding studies indicate that H2O2 oxidation reduces the thermodynamic stability of PrPC by as much as 9 kJ/mol. 1H-15N NMR studies indicate methionine oxidation perturbs key hydrophobic residues on one face of helix-C as follows: Met-205, Val-209, and Met-212 together with residues Val-160 and Tyr-156. These hydrophobic residues pack together and form the structured core of the protein, stabilizing its ternary structure. Copper-catalyzed oxidation of PrPC causes a more significant alteration of the structure, generating a monomeric molten globule species that retains its native helical content. Further copper-catalyzed oxidation promotes extended β-strand structures that lack a cooperative fold. This transition from the helical molten globule to β-conformation has striking similarities to a misfolding intermediate generated at low pH. PrP may therefore share a generic misfolding pathway to amyloid fibers, irrespective of the conditions promoting misfolding. Our observations support the hypothesis that oxidation of PrP destabilizes the native fold of PrPC, facilitating the transition to PrPSc. This study gives a structural and thermodynamic explanation for the high levels of oxidized methionine in scrapie isolates. PMID:22654104

  2. Fragmentation pathways and structural characterization of 14 nerve agent compounds by electrospray ionization tandem mass spectrometry.

    PubMed

    Housman, Kathleen J; Swift, Austin T; Oyler, Jonathan M

    2015-03-01

    Organophosphate nerve agents (OPNAs) are some of the most widely used and proliferated chemical warfare agents. As evidenced by recent events in Syria, these compounds remain a serious military and terrorist threat to human health because of their toxicity and the ease with which they can be used, produced and stored. There are over 2,000 known, scheduled compounds derived from common parent structures with many more possible. To address medical, forensic, attribution, remediation and other requirements, laboratory systems have been established to provide the capability to analyze 'unknown' samples for the presence of these compounds. Liquid chromatography/mass spectrometric methods have been validated and are routinely used in the analysis of samples for a very limited number of these compounds, but limited data exist characterizing the electrospray ionization (ESI) and mass spectrometric fragmentation pathways of the compound families. This report describes results from direct infusion ESI/MS, ESI/MS(2) and ESI/MS(3) analysis of 14 G and V agents, the major OPNA families, using an AB Sciex 4000 QTrap. Using a range of conditions, spectra were acquired and characteristic fragments identified. The results demonstrated that the reproducible and predictable fragmentation of these compounds by ESI/MS, ESI/MS(2) and ESI/MS(3) can be used to describe systematic fragmentation pathways specific to compound structural class. These fragmentation pathways, in turn, may be useful as a predictive tool in the analysis of samples by screening and confirmatory laboratories to identify related compounds for which authentic standards are not readily available. PMID:25519457

  3. Harnessing the complexity of gene expression data from cancer: from single gene to structural pathway methods

    PubMed Central

    2012-01-01

    High-dimensional gene expression data provide a rich source of information because they capture the expression level of genes in dynamic states that reflect the biological functioning of a cell. For this reason, such data are suitable to reveal systems related properties inside a cell, e.g., in order to elucidate molecular mechanisms of complex diseases like breast or prostate cancer. However, this is not only strongly dependent on the sample size and the correlation structure of a data set, but also on the statistical hypotheses tested. Many different approaches have been developed over the years to analyze gene expression data to (I) identify changes in single genes, (II) identify changes in gene sets or pathways, and (III) identify changes in the correlation structure in pathways. In this paper, we review statistical methods for all three types of approaches, including subtypes, in the context of cancer data and provide links to software implementations and tools and address also the general problem of multiple hypotheses testing. Further, we provide recommendations for the selection of such analysis methods. Reviewers This article was reviewed by Arcady Mushegian, Byung-Soo Kim and Joel Bader. PMID:23227854

  4. Biochemical and structural characterization of Klebsiella pneumoniae oxamate amidohydrolase in the uric acid degradation pathway.

    PubMed

    Hicks, Katherine A; Ealick, Steven E

    2016-06-01

    HpxW from the ubiquitous pathogen Klebsiella pneumoniae is involved in a novel uric acid degradation pathway downstream from the formation of oxalurate. Specifically, HpxW is an oxamate amidohydrolase which catalyzes the conversion of oxamate to oxalate and is a member of the Ntn-hydrolase superfamily. HpxW is autoprocessed from an inactive precursor to form a heterodimer, resulting in a 35.5 kDa α subunit and a 20 kDa β subunit. Here, the structure of HpxW is presented and the substrate complex is modeled. In addition, the steady-state kinetics of this enzyme and two active-site variants were characterized. These structural and biochemical studies provide further insight into this class of enzymes and allow a mechanism for catalysis consistent with other members of the Ntn-hydrolase superfamily to be proposed. PMID:27303801

  5. Structure of the FANCI-FANCD2 Complex: Insights into the Fanconi Anemia DNA Repair Pathway

    SciTech Connect

    Joo, Woo; Xu, Guozhou; Persky, Nicole S.; Smogorzewska, Agata; Rudge, Derek G.; Buzovetsky, Olga; Elledge, Stephen J.; Pavletich, Nikola P.

    2011-08-29

    Fanconi anemia is a cancer predisposition syndrome caused by defects in the repair of DNA interstrand cross-links (ICLs). Central to this pathway is the Fanconi anemia I-Fanconi anemia D2 (FANCI-FANCD2) (ID) complex, which is activated by DNA damage-induced phosphorylation and monoubiquitination. The 3.4 angstrom crystal structure of the {approx}300 kilodalton ID complex reveals that monoubiquitination and regulatory phosphorylation sites map to the I-D interface, suggesting that they occur on monomeric proteins or an opened-up complex and that they may serve to stabilize I-D heterodimerization. The 7.8 angstrom electron-density map of FANCI-DNA crystals and in vitro data show that each protein has binding sites for both single- and double-stranded DNA, suggesting that the ID complex recognizes DNA structures that result from the encounter of replication forks with an ICL.

  6. Structure of the FANCI-FANCD2 Complex: Insights into the Fanconi Anemia DNA Repair Pathway

    SciTech Connect

    W Joo; G Xu; n Persky; A Smogorzewska; D Rudge; O Buzovetsky; S Elledge; N Pavletich

    2011-12-31

    Fanconi anemia is a cancer predisposition syndrome caused by defects in the repair of DNA interstrand cross-links (ICLs). Central to this pathway is the Fanconi anemia I-Fanconi anemia D2 (FANCI-FANCD2) (ID) complex, which is activated by DNA damage-induced phosphorylation and monoubiquitination. The 3.4 angstrom crystal structure of the {approx}300 kilodalton ID complex reveals that monoubiquitination and regulatory phosphorylation sites map to the I-D interface, suggesting that they occur on monomeric proteins or an opened-up complex and that they may serve to stabilize I-D heterodimerization. The 7.8 angstrom electron-density map of FANCI-DNA crystals and in vitro data show that each protein has binding sites for both single- and double-stranded DNA, suggesting that the ID complex recognizes DNA structures that result from the encounter of replication forks with an ICL.

  7. Structural Snapshots of Escherichia coli Histidinol Phosphate Phosphatase along the Reaction Pathway

    SciTech Connect

    Rangarajan,E.; Proteau, A.; Wagner, J.; Hung, M.; Matte, A.; Cygler, M.

    2006-01-01

    HisB from Escherichia coli is a bifunctional enzyme catalyzing the sixth and eighth steps of L-histidine biosynthesis. The N-terminal domain (HisB-N) possesses histidinol phosphate phosphatase activity, and its crystal structure shows a single domain with fold similarity to the haloacid dehalogenase (HAD) enzyme family. HisB-N forms dimers in the crystal and in solution. The structure shows the presence of a structural Zn{sup 2+} ion stabilizing the conformation of an extended loop. Two metal binding sites were also identified in the active site. Their presence was further confirmed by isothermal titration calorimetry. HisB-N is active in the presence of Mg{sup 2+}, Mn{sup 2+}, Co{sup 2+}, or Zn{sup 2+}, but Ca{sup 2+} has an inhibitory effect. We have determined structures of several intermediate states corresponding to snapshots along the reaction pathway, including that of the phosphoaspartate intermediate. A catalytic mechanism, different from that described for other HAD enzymes, is proposed requiring the presence of the second metal ion not found in the active sites of previously characterized HAD enzymes, to complete the second half-reaction. The proposed mechanism is reminiscent of two-Mg{sup 2+} ion catalysis utilized by DNA and RNA polymerases and many nucleases. The structure also provides an explanation for the inhibitory effect of Ca{sup 2+}.

  8. Magnetized Plasma-filled Waveguide: A New High-Gradient Accelerating Structure

    SciTech Connect

    Avitzour, Yoav; Shvets, Gennady

    2009-01-22

    Electromagnetic waves confined between the metal plates of a plasma-filled waveguide are investigated. It is demonstrated that when the plasma is magnetized along the metallic plates, there exists a luminous accelerating wave propagating with a very slow group velocity. It is shown that the magnetized plasma 'isolates' the metal wall from the transverse electric field, thereby reducing potential breakdown problems. Applications of the metallic plasma-filled waveguide to particle accelerations and microwave pulse manipulation are described.

  9. 3D visualization of deformation structures and potential fluid pathways at the Grimsel Test Site

    NASA Astrophysics Data System (ADS)

    Schneeberger, Raphael; Kober, Florian; Berger, Alfons; Spillmann, Thomas; Herwegh, Marco

    2015-04-01

    Knowledge on the ability of fluids to infiltrate subsurface rocks is of major importance for underground constructions, geothermal or radioactive waste disposal projects. In this study, we focus on the characterization of water infiltration pathways, their 3D geometries and origins. Based on surface and subsurface mapping in combination with drill core data, we developed by the use of MoveTM (Midland Valley Exploration Ltd.) a 3D structural model of the Grimsel Test Site (GTS). GTS is an underground laboratory operated by NAGRA, the Swiss organisation responsible for the management of nuclear waste. It is located within a suite of post-Variscan magmatic bodies comprising former granitic and granodioritic melts, which are dissected by mafic and aplitic dikes. During Alpine orogeny, the suite was tectonically overprinted within two stages of ductile deformation (Wehrens et al., in prep.) followed by brittle overprint of some of the shear zones during the retrograde exhumation history. It is this brittle deformation, which controls today's water infiltration network. However, the associated fractures, cataclasites and fault gouges are controlled themselves by aforementioned pre-existing mechanical discontinuities, whose origin ranges back as far as to the magmatic stage. For example, two sets of vertically oriented mafic dikes (E-W and NW-SE striking) and compositional heterogeneities induced by magmatic segregation processes in the plutonic host rocks served as nucleation sites for Alpine strain localization. Subsequently, NE-SW, E-W and NW-SE striking ductile shear zones were formed, in combination with high temperature fracturing while dissecting the host rocks in a complex 3D pattern (Wehrens et al, in prep.). Whether the ductile shear zones have been subjected to brittle reactivation and can serve as infiltration pathways or not, depends strongly on their orientations with respect to the principal stress field. Especially where deformation structures intersect

  10. The solar wind structures associated with cosmic ray decreases and particle acceleration in 1978-1982

    NASA Technical Reports Server (NTRS)

    Cane, H. V.; Richardson, I. G.; Vonrosenvinge, T. T.

    1992-01-01

    The time histories of particles in the energy range 1 MeV to 1 GeV at times of all greater than 3 percent cosmic ray decreases in the years 1978 to 1982 are studied. Essentially all 59 of the decreases commenced at or before the passages of interplanetary shocks, the majority of which accelerated energetic particles. We use the intensity-time profiles of the energetic particles to separate the cosmic ray decreases into four classes which we subsequently associate with four types of solar wind structures. Decreases in class 1 (15 events) and class 2 (26 events) can be associated with shocks which are driven by energetic coronal mass ejections. For class 1 events the ejecta is detected at 1 AU whereas this is not the case for class 2 events. The shock must therefore play a dominant role in producing the depression of cosmic rays in class 2 events. In all class 1 and 2 events (which comprise 69 percent of the total) the departure time of the ejection from the sun (and hence the location) can be determined from the rapid onset of energetic particles several days before the shock passage at Earth. The class 1 events originate from within 50 deg of central meridian. Class 3 events (10 decreases) can be attributed to less energetic ejections which are directed towards the Earth. In these events the ejecta is more important than the shock in causing a depression in the cosmic ray intensity. The remaining events (14 percent of the total) can be attributed to corotating streams which have ejecta material embedded in them.

  11. Guided post-acceleration of laser-driven ions by a miniature modular structure

    PubMed Central

    Kar, Satyabrata; Ahmed, Hamad; Prasad, Rajendra; Cerchez, Mirela; Brauckmann, Stephanie; Aurand, Bastian; Cantono, Giada; Hadjisolomou, Prokopis; Lewis, Ciaran L. S.; Macchi, Andrea; Nersisyan, Gagik; Robinson, Alexander P. L.; Schroer, Anna M.; Swantusch, Marco; Zepf, Matt; Willi, Oswald; Borghesi, Marco

    2016-01-01

    All-optical approaches to particle acceleration are currently attracting a significant research effort internationally. Although characterized by exceptional transverse and longitudinal emittance, laser-driven ion beams currently have limitations in terms of peak ion energy, bandwidth of the energy spectrum and beam divergence. Here we introduce the concept of a versatile, miniature linear accelerating module, which, by employing laser-excited electromagnetic pulses directed along a helical path surrounding the laser-accelerated ion beams, addresses these shortcomings simultaneously. In a proof-of-principle experiment on a university-scale system, we demonstrate post-acceleration of laser-driven protons from a flat foil at a rate of 0.5 GeV m−1, already beyond what can be sustained by conventional accelerator technologies, with dynamic beam collimation and energy selection. These results open up new opportunities for the development of extremely compact and cost-effective ion accelerators for both established and innovative applications. PMID:27089200

  12. Guided post-acceleration of laser-driven ions by a miniature modular structure.

    PubMed

    Kar, Satyabrata; Ahmed, Hamad; Prasad, Rajendra; Cerchez, Mirela; Brauckmann, Stephanie; Aurand, Bastian; Cantono, Giada; Hadjisolomou, Prokopis; Lewis, Ciaran L S; Macchi, Andrea; Nersisyan, Gagik; Robinson, Alexander P L; Schroer, Anna M; Swantusch, Marco; Zepf, Matt; Willi, Oswald; Borghesi, Marco

    2016-01-01

    All-optical approaches to particle acceleration are currently attracting a significant research effort internationally. Although characterized by exceptional transverse and longitudinal emittance, laser-driven ion beams currently have limitations in terms of peak ion energy, bandwidth of the energy spectrum and beam divergence. Here we introduce the concept of a versatile, miniature linear accelerating module, which, by employing laser-excited electromagnetic pulses directed along a helical path surrounding the laser-accelerated ion beams, addresses these shortcomings simultaneously. In a proof-of-principle experiment on a university-scale system, we demonstrate post-acceleration of laser-driven protons from a flat foil at a rate of 0.5 GeV m(-1), already beyond what can be sustained by conventional accelerator technologies, with dynamic beam collimation and energy selection. These results open up new opportunities for the development of extremely compact and cost-effective ion accelerators for both established and innovative applications. PMID:27089200

  13. Design and RF measurements of an X-band accelerating structure for linearizing the longitudinal emittance at SPARC

    NASA Astrophysics Data System (ADS)

    Alesini, D.; Falone, A.; Migliorati, M.; Mostacci, A.; Palpini, F.; Palumbo, L.; Spataro, B.

    2005-12-01

    The paper presents the design of an X-band accelerating section for linearizing the longitudinal phase space in the Frascati Linac Coherent Light Source (SPARC). The nine cells structure, operating on the π standing wave mode, is fed by a central coupler and has been designed to obtain a 42 MV/m accelerating gradient. The two-dimensional (2D) profile has been obtained using the electromagnetic codes Superfish and Oscar-2D while the coupler has been designed using HFSS. Bead-pull measurements made on a copper prototype have been performed and the results are illustrated and compared with the numerical predictions. Mechanical details of the realized prototype and RF properties of the structure as a function of the assembly characteristics are also discussed.

  14. Interaction of an Ultrarelativistic Electron Bunch Train with a W-Band Accelerating Structure: High Power and High Gradient.

    PubMed

    Wang, D; Antipov, S; Jing, C; Power, J G; Conde, M; Wisniewski, E; Liu, W; Qiu, J; Ha, G; Dolgashev, V; Tang, C; Gai, W

    2016-02-01

    Electron beam interaction with high frequency structures (beyond microwave regime) has a great impact on future high energy frontier machines. We report on the generation of multimegawatt pulsed rf power at 91 GHz in a planar metallic accelerating structure driven by an ultrarelativistic electron bunch train. This slow-wave wakefield device can also be used for high gradient acceleration of electrons with a stable rf phase and amplitude which are controlled by manipulation of the bunch train. To achieve precise control of the rf pulse properties, a two-beam wakefield interferometry method was developed in which the rf pulse, due to the interference of the wakefields from the two bunches, was measured as a function of bunch separation. Measurements of the energy change of a trailing electron bunch as a function of the bunch separation confirmed the interferometry method. PMID:26894715

  15. Interaction of an ultrarelativistic electron bunch train with a W-band accelerating structure: High power and high gradient

    DOE PAGESBeta

    Wang, D.; Antipov, S.; Jing, C.; Power, J. G.; Conde, M.; Wisniewski, E.; Liu, W.; Qiu, J.; Ha, G.; Dolgashev, V.; et al

    2016-02-05

    Electron beam interaction with high frequency structures (beyond microwave regime) has a great impact on future high energy frontier machines. We report on the generation of multimegawatt pulsed rf power at 91 GHz in a planar metallic accelerating structure driven by an ultrarelativistic electron bunch train. This slow-wave wakefield device can also be used for high gradient acceleration of electrons with a stable rf phase and amplitude which are controlled by manipulation of the bunch train. To achieve precise control of the rf pulse properties, a two-beam wakefield interferometry method was developed in which the rf pulse, due to themore » interference of the wakefields from the two bunches, was measured as a function of bunch separation. As a result, measurements of the energy change of a trailing electron bunch as a function of the bunch separation confirmed the interferometry method.« less

  16. Interaction of an Ultrarelativistic Electron Bunch Train with a W -Band Accelerating Structure: High Power and High Gradient

    NASA Astrophysics Data System (ADS)

    Wang, D.; Antipov, S.; Jing, C.; Power, J. G.; Conde, M.; Wisniewski, E.; Liu, W.; Qiu, J.; Ha, G.; Dolgashev, V.; Tang, C.; Gai, W.

    2016-02-01

    Electron beam interaction with high frequency structures (beyond microwave regime) has a great impact on future high energy frontier machines. We report on the generation of multimegawatt pulsed rf power at 91 GHz in a planar metallic accelerating structure driven by an ultrarelativistic electron bunch train. This slow-wave wakefield device can also be used for high gradient acceleration of electrons with a stable rf phase and amplitude which are controlled by manipulation of the bunch train. To achieve precise control of the rf pulse properties, a two-beam wakefield interferometry method was developed in which the rf pulse, due to the interference of the wakefields from the two bunches, was measured as a function of bunch separation. Measurements of the energy change of a trailing electron bunch as a function of the bunch separation confirmed the interferometry method.

  17. Bidirectional Expression of Metabolic, Structural, and Immune Pathways in Early Myopia and Hyperopia

    PubMed Central

    Riddell, Nina; Giummarra, Loretta; Hall, Nathan E.; Crewther, Sheila G.

    2016-01-01

    Myopia (short-sightedness) affects 1.45 billion people worldwide, many of whom will develop sight-threatening secondary disorders. Myopic eyes are characterized by excessive size while hyperopic (long-sighted) eyes are typically small. The biological and genetic mechanisms underpinning the retina's local control of these growth patterns remain unclear. In the present study, we used RNA sequencing to examine gene expression in the retina/RPE/choroid across 3 days of optically-induced myopia and hyperopia induction in chick. Data were analyzed for differential expression of single genes, and Gene Set Enrichment Analysis (GSEA) was used to identify gene sets correlated with ocular axial length and refraction across lens groups. Like previous studies, we found few single genes that were differentially-expressed in a sign-of-defocus dependent manner (only BMP2 at 1 day). Using GSEA, however, we are the first to show that more subtle shifts in structural, metabolic, and immune pathway expression are correlated with the eye size and refractive changes induced by lens defocus. Our findings link gene expression with the morphological characteristics of refractive error, and suggest that physiological stress arising from metabolic and inflammatory pathway activation could increase the vulnerability of myopic eyes to secondary pathologies. PMID:27625591

  18. Bidirectional Expression of Metabolic, Structural, and Immune Pathways in Early Myopia and Hyperopia.

    PubMed

    Riddell, Nina; Giummarra, Loretta; Hall, Nathan E; Crewther, Sheila G

    2016-01-01

    Myopia (short-sightedness) affects 1.45 billion people worldwide, many of whom will develop sight-threatening secondary disorders. Myopic eyes are characterized by excessive size while hyperopic (long-sighted) eyes are typically small. The biological and genetic mechanisms underpinning the retina's local control of these growth patterns remain unclear. In the present study, we used RNA sequencing to examine gene expression in the retina/RPE/choroid across 3 days of optically-induced myopia and hyperopia induction in chick. Data were analyzed for differential expression of single genes, and Gene Set Enrichment Analysis (GSEA) was used to identify gene sets correlated with ocular axial length and refraction across lens groups. Like previous studies, we found few single genes that were differentially-expressed in a sign-of-defocus dependent manner (only BMP2 at 1 day). Using GSEA, however, we are the first to show that more subtle shifts in structural, metabolic, and immune pathway expression are correlated with the eye size and refractive changes induced by lens defocus. Our findings link gene expression with the morphological characteristics of refractive error, and suggest that physiological stress arising from metabolic and inflammatory pathway activation could increase the vulnerability of myopic eyes to secondary pathologies. PMID:27625591

  19. A Structure-Toxicity Study of Aß42 Reveals a New Anti-Parallel Aggregation Pathway

    PubMed Central

    Vignaud, Hélène; Bobo, Claude; Lascu, Ioan; Sörgjerd, Karin Margareta; Zako, Tamotsu; Maeda, Mizuo; Salin, Benedicte; Lecomte, Sophie; Cullin, Christophe

    2013-01-01

    Amyloid beta (Aβ) peptides produced by APP cleavage are central to the pathology of Alzheimer’s disease. Despite widespread interest in this issue, the relationship between the auto-assembly and toxicity of these peptides remains controversial. One intriguing feature stems from their capacity to form anti-parallel ß-sheet oligomeric intermediates that can be converted into a parallel topology to allow the formation of protofibrillar and fibrillar Aβ. Here, we present a novel approach to determining the molecular aspects of Aß assembly that is responsible for its in vivo toxicity. We selected Aß mutants with varying intracellular toxicities. In vitro, only toxic Aß (including wild-type Aß42) formed urea-resistant oligomers. These oligomers were able to assemble into fibrils that are rich in anti-parallel ß-sheet structures. Our results support the existence of a new pathway that depends on the folding capacity of Aß . PMID:24244667

  20. X-band accelerator structures: On going R&D at the INFN

    NASA Astrophysics Data System (ADS)

    Gatti, G.; Marcelli, A.; Spataro, B.; Dolgashev, V.; Lewandowski, J.; Tantawi, S. G.; Yeremian, A. D.; Higashi, Y.; Rosenzweig, J.; Sarti, S.; Caliendo, C.; Castorina, G.; Cibin, G.; Carfora, L.; Leonardi, O.; Rigato, V.; Campostrini, M.

    2016-09-01

    The next generation of accelerators, from the compact to the large infrastructure dedicated to high energy physics, is highly demanding in terms of accelerating gradients. To upgrade performances of X band linacs at 11.424 GHz many resources are devoted to achieve high accelerating gradients and at the same time to obtain a high reliability. In the framework of a three-year funded project by the Vth Committee of the INFN to the Laboratori Nazionali di Frascati (LNF) and to the Laboratori Nazionali di Legnaro (LNL). Within a broad international collaboration the LNF has been involved in the design, manufacture and test of compact high power standing wave (SW) sections operating at high frequency while LNL is actively involved in the development of new materials and multilayers using PVD (Physical Vapor Deposition) methods. We will report about the status of the accelerating device and of the different ongoing R&D activities and characterization procedures such as tests of different materials and metallic coatings.

  1. Development of millimeter-wave accelerating structures using precision metal forming technology

    SciTech Connect

    2003-06-03

    High gradients in radio-frequency (RF) driven accelerators require short wavelengths that have the concomitant requirements of small feature size and high tolerances, 1-2 {micro}m for millimeter wavelengths. Precision metal-forming stampling has the promise of meeting those tolerances with high production rates. This STI will evaluate that promise.

  2. 805 MHz Beta = 0.47 Elliptical Accelerating Structure R & D

    SciTech Connect

    S. Bricker; C. Compton; W. Hartung; M. Johnson; F. Marti; J. Popierlarski; R. C. York; et al

    2008-09-22

    A 6-cell 805 MHz superconducting cavity for acceleration in the velocity range of about 0.4 to 0.53 times the speed of light was designed. After single-cell prototyping, three 6-cell niobium cavities were fabricated. In vertical RF tests of the 6-cell cavities, the measured quality factors (Q{sub 0}) were between 7 {center_dot} 10{sup 9} and 1.4 {center_dot} 10{sup 10} at the design field (accelerating gradient of 8 to 10 MV/m). A rectangular cryomodule was designed to house 4 cavities per cryomodule. The 4-cavity cryomodule could be used for acceleration of ions in a linear accelerator, with focusing elements between the cryomodules. A prototype cryomodule was fabricated to test 2 cavities under realistic operating conditions. Two of the 6-cell cavities were equipped with helium tanks, tuners, and input coupler and installed into the cryomodule. The prototype cryomodule was used to verify alignment, electromagnetic performance, frequency tuning, cryogenic performance, low-level RF control, and control of microphonics.

  3. Functional upregulation of the H2S/Cav3.2 channel pathway accelerates secretory function in neuroendocrine-differentiated human prostate cancer cells.

    PubMed

    Fukami, Kazuki; Sekiguchi, Fumiko; Yasukawa, Miku; Asano, Erina; Kasamatsu, Ryuji; Ueda, Mai; Yoshida, Shigeru; Kawabata, Atsufumi

    2015-10-01

    Neuroendocrine-differentiated prostate cancer cells may contribute to androgen-independent proliferation of surrounding cells through Ca(2+)-dependent secretion of mitogenic factors. Human prostate cancer LNCaP cells, when neuroendocrine-differentiated, overexpress Cav3.2 T-type Ca(2+) channels that contribute to Ca(2+)-dependent secretion. Given evidence for the acceleration of Cav3.2 activity by hydrogen sulfide (H2S), we examined the roles of the H2S/Cav3.2 pathway and then analyzed the molecular mechanisms of the Cav3.2 overexpression in neuroendocrine-differentiated LNCaP cells. LNCaP cells were differentiated by dibutyryl cyclic AMP. Protein levels and T-type Ca(2+) channel-dependent currents (T-currents) were measured by immunoblotting and whole-cell pacth-clamp technique, respectively. Spontaneous release of prostatic acid phosphatase (PAP) was monitored to evaluate secretory function. The differentiated LNCaP cells exhibited neurite outgrowth, androgen-independent proliferation and upregulation of mitogenic factors, and also showed elevation of Cav3.2 expression or T-currents. Expression of cystathionine-γ-lyase (CSE) and cystathionine-β-synthase (CBS), H2S-forming enzymes, and spontaneous secretion of PAP increased following the differentiation. The augmented T-currents were enhanced by H2S donors and suppressed by inhibitors of CSE, but not CBS. The PAP secretion was reduced by inhibition of CSE or T-type Ca(2+) channels. During differentiation, Egr-1 and REST, positive and negative transcriptional regulators for Cav3.2, were upregulated and downregulated, respectively, and Egr-1 knockdown prevented the Cav3.2 overexpression. Our data suggest that, in neuroendocrine-differentiated LNCaP cells, H2S formed by the upregulated CSE promotes the activity of the upregulated Cav3.2, leading to the elevated secretory functions. The overexpression of Cav3.2 appears to involve upregulation of Egr-1 and downregulation of REST. PMID:26256074

  4. In vivo evolution of metabolic pathways: Assembling old parts to build novel and functional structures

    PubMed Central

    Luque, Alejandro; Sebai, Sarra C; Sauveplane, Vincent; Ramaen, Odile; Pandjaitan, Rudy

    2014-01-01

    In our recent article “In vivo evolution of metabolic pathways by homeologous recombination in mitotic cells” we proposed a useful alternative to directed evolution methods that permits the generation of yeast cell libraries containing recombinant metabolic pathways from counterpart genes. The methodology was applied to generate single mosaic genes and intragenic mosaic pathways. We used flavonoid metabolism genes as a working model to assembly and express evolved pathways in DNA repair deficient cells. The present commentary revises the principles of gene and pathway mosaicism and explores the scope and perspectives of our results as an additional tool for synthetic biology. PMID:25482082

  5. Oxygen transport pathways in Ruddlesden–Popper structured oxides revealed via in situ neutron diffraction

    DOE PAGESBeta

    Tomkiewicz, Alex C.; Tamimi, Mazin; Huq, Ashfia; McIntosh, Steven

    2015-09-21

    Ruddlesden-Popper structured oxides, general form An+1BnO3n+1, consist of n-layers of the perovskite structure stacked in between rock-salt layers, and have potential application in solid oxide electrochemical cells and ion transport membrane reactors. Three materials with constant Co/Fe ratio, LaSrCo0.5Fe0.5O4-δ (n = 1), La0.3Sr2.7CoFeO7-δ (n = 2), and LaSr3Co1.5Fe1.5O10-δ (n = 3) were synthesized and studied via in situ neutron powder diffraction between 765 K and 1070 K at a pO2 of 10-1 atm. Then, the structures were fit to a tetragonal I4/mmm space group, and were found to have increased total oxygen vacancy concentration in the order La0.3Sr2.7CoFeO7-δ > LaSr3Co1.5Fe1.5O10-δmore » > LaSrCo0.5Fe0.5O4-δ, following the trend predicted for charge compensation upon increasing Sr2+/La3+ ratio. The oxygen vacancies within the material were almost exclusively located within the perovskite layers for all of the crystal structures with only minimal vacancy formation in the rock-salt layer. Finally, analysis of the concentration of these vacancies at each distinct crystallographic site and the anisotropic atomic displacement parameters for the oxygen sites reveals potential preferred oxygen transport pathways through the perovskite layers.« less

  6. Ecohydrological responses of dense canopies to environmental variability: 1. Interplay between vertical structure and photosynthetic pathway

    NASA Astrophysics Data System (ADS)

    Drewry, D. T.; Kumar, P.; Long, S.; Bernacchi, C.; Liang, X.-Z.; Sivapalan, M.

    2010-12-01

    Vegetation acclimation to changing climate, in particular elevated atmospheric concentrations of carbon dioxide (CO2), has been observed to include modifications to the biochemical and ecophysiological functioning of leaves and the structural components of the canopy. These responses have the potential to significantly modify plant carbon uptake and surface energy partitioning, and have been attributed with large-scale changes in surface hydrology over recent decades. While the aggregated effects of vegetation acclimation can be pronounced, they often result from subtle changes in canopy properties that require the resolution of physical, biochemical and ecophysiological processes through the canopy for accurate estimation. In this paper, the first of two, a multilayer canopy-soil-root system model developed to capture the emergent vegetation responses to environmental change is presented. The model incorporates both C3 and C4 photosynthetic pathways, and resolves the vertical radiation, thermal, and environmental regimes within the canopy. The tight coupling between leaf ecophysiological functioning and energy balance determines vegetation responses to climate states and perturbations, which are modulated by soil moisture states through the depth of the root system. The model is validated for three growing seasons each for soybean (C3) and maize (C4) using eddy-covariance fluxes of CO2, latent, and sensible heat collected at the Bondville (Illinois) Ameriflux tower site. The data set provides an opportunity to examine the role of important environmental drivers and model skill in capturing variability in canopy-atmosphere exchange. Vertical variation in radiative states and scalar fluxes over a mean diurnal cycle are examined to understand the role of canopy structure on the patterns of absorbed radiation and scalar flux magnitudes and the consequent differences in sunlit and shaded source/sink locations through the canopies. An analysis is made of the impact of

  7. Developing Measures of Pathways that May Link Macro Social/Structural Changes with HIV Epidemiology.

    PubMed

    Pouget, Enrique R; Sandoval, Milagros; Nikolopoulos, Georgios K; Mateu-Gelabert, Pedro; Rossi, Diana; Smyrnov, Pavlo; Jones, Yolanda; Friedman, Samuel R

    2016-08-01

    Macro-social/structural events ("big events") such as wars, disasters, and large-scale changes in policies can affect HIV transmission by making risk behaviors more or less likely or by changing risk contexts. The purpose of this study was to develop new measures to investigate hypothesized pathways between macro-social changes and HIV transmission. We developed novel scales and indexes focused on topics including norms about sex and drug injecting under different conditions, involvement with social groups, helping others, and experiencing denial of dignity. We collected data from 300 people who inject drugs in New York City during 2012-2013. Most investigational measures showed evidence of validity (Pearson correlations with criterion variables range = 0.12-0.71) and reliability (Cronbach's alpha range = 0.62-0.91). Research is needed in different contexts to evaluate whether these measures can be used to better understand HIV outbreaks and help improve social/structural HIV prevention intervention programs. PMID:26796384

  8. Crystal structure of SEL1L: Insight into the roles of SLR motifs in ERAD pathway

    PubMed Central

    Jeong, Hanbin; Sim, Hyo Jung; Song, Eun Kyung; Lee, Hakbong; Ha, Sung Chul; Jun, Youngsoo; Park, Tae Joo; Lee, Changwook

    2016-01-01

    Terminally misfolded proteins are selectively recognized and cleared by the endoplasmic reticulum-associated degradation (ERAD) pathway. SEL1L, a component of the ERAD machinery, plays an important role in selecting and transporting ERAD substrates for degradation. We have determined the crystal structure of the mouse SEL1L central domain comprising five Sel1-Like Repeats (SLR motifs 5 to 9; hereafter called SEL1Lcent). Strikingly, SEL1Lcent forms a homodimer with two-fold symmetry in a head-to-tail manner. Particularly, the SLR motif 9 plays an important role in dimer formation by adopting a domain-swapped structure and providing an extensive dimeric interface. We identified that the full-length SEL1L forms a self-oligomer through the SEL1Lcent domain in mammalian cells. Furthermore, we discovered that the SLR-C, comprising SLR motifs 10 and 11, of SEL1L directly interacts with the N-terminus luminal loops of HRD1. Therefore, we propose that certain SLR motifs of SEL1L play a unique role in membrane bound ERAD machinery. PMID:27064360

  9. Evolution of structure and properties of VVER-1000 RPV steels under accelerated irradiation up to beyond design fluences

    NASA Astrophysics Data System (ADS)

    Gurovich, B.; Kuleshova, E.; Shtrombakh, Ya.; Fedotova, S.; Maltsev, D.; Frolov, A.; Zabusov, O.; Erak, D.; Zhurko, D.

    2015-01-01

    In this paper comprehensive studies of structure and properties of VVER-1000 RPV steels after the accelerated irradiation to fluences corresponding to extended lifetime up to 60 years or more as well as comparative studies of materials irradiated with different fluxes were carried out. The significant flux effect is confirmed for the weld metal (nickel concentration ⩾1.35%) which is mainly due to development of reversible temper brittleness. The rate of radiation embrittlement of VVER-1000 RPV steels under operation up to 60 years and more (based on the results of accelerated irradiation considering flux effect for weld metal) is expected not to differ significantly from the observed rate under irradiation within surveillance specimens.

  10. Structural and functional evolution of isopropylmalate dehydrogenases in the leucine and glucosinolate pathways of Arabidopsis thaliana

    SciTech Connect

    He, Yan; Galant, Ashley; Pang, Qiuying; Strul, Johanna M.; Balogun, Sherifat F.; Jez, Joseph M.; Chen, Sixue

    2012-10-24

    The methionine chain-elongation pathway is required for aliphatic glucosinolate biosynthesis in plants and evolved from leucine biosynthesis. In Arabidopsis thaliana, three 3-isopropylmalate dehydrogenases (AtIPMDHs) play key roles in methionine chain-elongation for the synthesis of aliphatic glucosinolates (e.g. AtIPMDH1) and leucine (e.g. AtIPMDH2 and AtIPMDH3). Here we elucidate the molecular basis underlying the metabolic specialization of these enzymes. The 2.25 {angstrom} resolution crystal structure of AtIPMDH2 was solved to provide the first detailed molecular architecture of a plant IPMDH. Modeling of 3-isopropylmalate binding in the AtIPMDH2 active site and sequence comparisons of prokaryotic and eukaryotic IPMDH suggest that substitution of one active site residue may lead to altered substrate specificity and metabolic function. Site-directed mutagenesis of Phe-137 to a leucine in AtIPMDH1 (AtIPMDH1-F137L) reduced activity toward 3-(2'-methylthio)ethylmalate by 200-fold, but enhanced catalytic efficiency with 3-isopropylmalate to levels observed with AtIPMDH2 and AtIPMDH3. Conversely, the AtIPMDH2-L134F and AtIPMDH3-L133F mutants enhanced catalytic efficiency with 3-(2'-methylthio)ethylmalate {approx}100-fold and reduced activity for 3-isopropylmalate. Furthermore, the altered in vivo glucosinolate profile of an Arabidopsis ipmdh1 T-DNA knock-out mutant could be restored to wild-type levels by constructs expressing AtIPMDH1, AtIPMDH2-L134F, or AtIPMDH3-L133F, but not by AtIPMDH1-F137L. These results indicate that a single amino acid substitution results in functional divergence of IPMDH in planta to affect substrate specificity and contributes to the evolution of specialized glucosinolate biosynthesis from the ancestral leucine pathway.

  11. Assessment of the utility of contact-based restraints in accelerating the prediction of protein structure using molecular dynamics simulations.

    PubMed

    Raval, Alpan; Piana, Stefano; Eastwood, Michael P; Shaw, David E

    2016-01-01

    Molecular dynamics (MD) simulation is a well-established tool for the computational study of protein structure and dynamics, but its application to the important problem of protein structure prediction remains challenging, in part because extremely long timescales can be required to reach the native structure. Here, we examine the extent to which the use of low-resolution information in the form of residue-residue contacts, which can often be inferred from bioinformatics or experimental studies, can accelerate the determination of protein structure in simulation. We incorporated sets of 62, 31, or 15 contact-based restraints in MD simulations of ubiquitin, a benchmark system known to fold to the native state on the millisecond timescale in unrestrained simulations. One-third of the restrained simulations folded to the native state within a few tens of microseconds-a speedup of over an order of magnitude compared with unrestrained simulations and a demonstration of the potential for limited amounts of structural information to accelerate structure determination. Almost all of the remaining ubiquitin simulations reached near-native conformations within a few tens of microseconds, but remained trapped there, apparently due to the restraints. We discuss potential methodological improvements that would facilitate escape from these near-native traps and allow more simulations to quickly reach the native state. Finally, using a target from the Critical Assessment of protein Structure Prediction (CASP) experiment, we show that distance restraints can improve simulation accuracy: In our simulations, restraints stabilized the native state of the protein, enabling a reasonable structural model to be inferred. PMID:26266489

  12. Electron Acceleration and Structure in the Quasi-perpendicular Collisionless Shock

    SciTech Connect

    Burgess, D.

    2005-08-01

    Electron acceleration at quasi-perpendicular shocks is a key problem in collisionless shock physics, in the context of the Earth's bow shock and other astrophysical situations. Fast Fermi acceleration, or reflection by adiabatic mirroring is a robust mechanism, but predicts that the highest energies are produced over a very small shock angle range, close to perpendicular where the reflected flux is decreasingly small. Pitch angle scattering has been shown to be effective in broadening the parameter range where this process is important. Using 2D hybrid simulations and electron test particle simulations, we show that ripples and oscillations of the shock surface are efficient scatters of suprathermal electrons. The results indicate that power law energy distributions can be obtained for both upstream and downstream energetic electrons, over a reasonably wide range of shock angles.

  13. Modeling the double-trough structure observed in broad absorption line QSOs using radiative acceleration

    NASA Technical Reports Server (NTRS)

    Arav, Nahum; Begelman, Mitchell C.

    1994-01-01

    We present a model explaining the double trough, separated by delta v approximately = 5900 km/s, observed in the C IV lambda-1549 broad absorption line (BAL) in a number of BALQSOs. The model is based on radiative acceleration of the BAL outflow, and the troughs result from modulations in the radiative force. Specifically, where the strong flux from the Lyman-alpha lambda-1215 broad emission line is redshifted to the frequency of the N V lambda-1240 resonance line, in the rest frame of the accelerating N V ions, the acceleration increases and the absorption is reduced. At higher velocities the Lyman-alpha emission is redshifted out of the resonance and the N V ions experience a declining flux which causes the second absorption trough. A strongly nonlinear relationship between changes in the flux and the optical depth in the lines is shown to amplify the expected effect. This model produces double troughs for which the shallowest absorption between the two troughs occurs at v approximately = 5900 km/s. Indeed, we find that a substantial number of the observed objects show this feature. A prediction of the model is that all BALQSOs that show a double-trough signature will be found to have an intrinsic sharp drop in their spectra shortward of approximately 1200 A.

  14. Theoretical Studies on Structures, Properties and Dominant Debromination Pathways for Selected Polybrominated Diphenyl Ethers

    PubMed Central

    Li, Lingyun; Hu, Jiwei; Shi, Xuedan; Ruan, Wenqian; Luo, Jin; Wei, Xionghui

    2016-01-01

    The B3LYP/6-311+G(d)-SDD method, which considers the relativistic effect of bromine, was adopted for the calculations of the selected polybrominated diphenyl ethers (PBDEs) in the present study, in which the B3LYP/6-311+G(d) method was also applied. The calculated values and experimental data for structural parameters of the selected PBDEs were compared to find the suitable theoretical methods for their structural optimization. The results show that the B3LYP/6-311+G(d) method can give the better results (with the root mean square errors (RMSEs) of 0.0268 for the C–Br bond and 0.0161 for the C–O bond) than the B3LYP/6-311+G(d)-SDD method. Then, the B3LYP/6-311+G(d) method was applied to predict the structures for the other selected PBDEs (both neutral and anionic species). The lowest unoccupied molecular orbital (LUMO) and the electron affinity are of a close relationship. The electron affinities (vertical electron affinity and adiabatic electron affinity) were discussed to study their electron capture abilities. To better estimate the conversion of configuration for PBDEs, the configuration transition states for BDE-5, BDE-22 and BDE-47 were calculated at the B3LYP/ 6-311+G(d) level in both gas phase and solution. The possible debromination pathway for BDE-22 were also studied, which have bromine substituents on two phenyl rings and the bromine on meta-position prefers to depart from the phenyl ring. The reaction profile of the electron-induced reductive debromination for BDE-22 were also shown in order to study its degradation mechanism. PMID:27322242

  15. Theoretical Studies on Structures, Properties and Dominant Debromination Pathways for Selected Polybrominated Diphenyl Ethers.

    PubMed

    Li, Lingyun; Hu, Jiwei; Shi, Xuedan; Ruan, Wenqian; Luo, Jin; Wei, Xionghui

    2016-01-01

    The B3LYP/6-311+G(d)-SDD method, which considers the relativistic effect of bromine, was adopted for the calculations of the selected polybrominated diphenyl ethers (PBDEs) in the present study, in which the B3LYP/6-311+G(d) method was also applied. The calculated values and experimental data for structural parameters of the selected PBDEs were compared to find the suitable theoretical methods for their structural optimization. The results show that the B3LYP/6-311+G(d) method can give the better results (with the root mean square errors (RMSEs) of 0.0268 for the C-Br bond and 0.0161 for the C-O bond) than the B3LYP/6-311+G(d)-SDD method. Then, the B3LYP/6-311+G(d) method was applied to predict the structures for the other selected PBDEs (both neutral and anionic species). The lowest unoccupied molecular orbital (LUMO) and the electron affinity are of a close relationship. The electron affinities (vertical electron affinity and adiabatic electron affinity) were discussed to study their electron capture abilities. To better estimate the conversion of configuration for PBDEs, the configuration transition states for BDE-5, BDE-22 and BDE-47 were calculated at the B3LYP/ 6-311+G(d) level in both gas phase and solution. The possible debromination pathway for BDE-22 were also studied, which have bromine substituents on two phenyl rings and the bromine on meta-position prefers to depart from the phenyl ring. The reaction profile of the electron-induced reductive debromination for BDE-22 were also shown in order to study its degradation mechanism. PMID:27322242

  16. Molecular crowding of collagen: a pathway to produce highly-organized collagenous structures.

    PubMed

    Saeidi, Nima; Karmelek, Kathryn P; Paten, Jeffrey A; Zareian, Ramin; DiMasi, Elaine; Ruberti, Jeffrey W

    2012-10-01

    organizational control of structure not only makes de novo tissue engineering a possibility, but also suggests a clearer pathway to organization for fibroblasts than direct matrix printing. PMID:22846420

  17. Use of spectral acceleration data for determination of three-dimensional attenuation structure in the Pithoragarh region of Kumaon Himalaya

    NASA Astrophysics Data System (ADS)

    Joshi, A.; Mohanty, M.; Bansal, A. R.; Dimri, V. P.; Chadha, R. K.

    2010-04-01

    Three-dimensional attenuation structures are related to the subsurface heterogeneities present in the earth crust. An algorithm for estimation of three-dimensional attenuation structure in the part of Garhwal Himalaya, India has been presented by Joshi (Curr Sci 90:581-585, 2006b; Nat Hazards 43:129-146, 2007). In continuation of our earlier approach, we have presented a method in which strong motion data have been used to estimate frequency-dependent three-dimensional attenuation structure of the region. The border district of Pithoragarh in the Higher Himalaya, India, lies in the central seismic gap region of Himalaya. This region falls in the seismic zones IV and V of the seismic zoning map of India. A dense network consisting of eight accelerographs has been installed in this region. This network has recorded several local events. An algorithm based on inversion of strong motion digital data is developed in this paper to estimate attenuation structure at different frequencies using the data recorded by this network. Twenty strong motion records observed at five stations have been used to estimate the site amplification factors using inversion algorithm defined in this paper. Site effects obtained from inversion has been compared with that obtained using Nakamura (1988) and Lermo et al. (Bull Seis Soc Am 83:1574-1594, 1993) approach. The obtained site amplification term has been used for correcting spectral acceleration data at different stations. The corrected spectral acceleration data have been used as an input to the developed algorithm to avoid effect of near-site soil amplification term. The attenuation structure is estimated by dividing the entire area in several three-dimensional block of different frequency-dependent shear wave quality factor Q β ( f). The input to this algorithm is the spectral acceleration of S phase of the corrected accelerogram. The outcome of the algorithm is given in terms of attenuation coefficient and source acceleration

  18. Accelerating Rates of Discontinuous Permafrost Thaw Associated with Ground Surface Morphology and Changing Vegetation Structures Determined from Multi-Temporal LIDAR Data

    NASA Astrophysics Data System (ADS)

    Chasmer, L.; Hopkinson, C.

    2015-12-01

    Rates of permafrost thaw within the discontinuous permafrost zone are expected to accelerate with permafrost fragmentation. However quantification of drivers of permafrost change remain elusive due to the non-linearity of feedbacks in space and time. Given the extent of permafrost in Canada, there is significant interest in the mechanisms associated with land cover change as climate change and disturbance intensifies.We quantify the variability of rates of thaw associated with structural characteristics of the land surface within a discontinuous permafrost watershed in the NWT, Canada. Results are compared to an isolated permafrost watershed in Alberta, which may exemplify the northern discontinuous landscape in ~350 years. Three airborne Light Detection And Ranging (LiDAR) datasets have been collected in 2008, 2011 and 2015, coincident with digital photogrammetry (2008), thermal infrared (2011) and bathymetry (2015) within both watersheds. Rates of change of land elevation associated with permafrost thaw within plateaus and peatlands are quantified using non-linear spatial regression, and compared with topographic and vegetation derivatives. Results indicate that increasing fragmentation of discontinuous permafrost plateaus results in exponential thaw. Rates of thaw become linear with decreasing complexity. Accelerating thaw is related to substantial Picea mariana mortality (up to 45%), increased gap fraction within 1-2 m of plateau edges, and shrub succession (average growth ~0.2 m yr—1) at the 0-2m boundary within the 7-year period. Thaw rate in parts is also complicated by understory succession within the area of local convexity between the plateau and slope edge and linear thaw pathways. Greatest rates of thaw and vegetation mortality (~30-50%) are found on plateaus with populous tremuloides. In the central boreal watershed, vegetation succession at peatland margins is associated with increased drying and changes to runoff trends over the last 40 years

  19. Signature of recent ice flow acceleration in the radar attenuation and temperature structure of Thwaites Glacier, West Antarctica

    NASA Astrophysics Data System (ADS)

    Schroeder, Dustin; Seroussi, Helene; Chu, Winnie; Young, Duncan

    2016-04-01

    Englacial temperature structure exerts significant control on the rheology and flow of glaciers and ice sheets. It is however logistically prohibitive to directly measure at the glacier-catchment scale. As a result, numerical ice sheet models often make broad assumptions about englacial temperatures based on contemporary ice surface velocities. However, this assumption might break down in regions - like the Amundsen Sea Embayment - that have experienced recent acceleration since temperature and rheology do not respond instantaneously to changes in ice flow regime. To address this challenge, we present a new technique for estimating englacial attenuation rates using bed echoes from radar sounding data. We apply this technique to an airborne survey of Thwaites Glacier and compare the results to temperature and attenuation structures modeled using the numerical Ice Sheet System Model (ISSM) for three surface velocity scenarios. These include contemporary surface velocities, surface velocities from the early 1970s, and ice-sheet balance velocities. We find that the observed attenuation structure is much closer to those modeled with pre-acceleration surface velocities. This suggests that ice sheet models initialized with contemporary surface velocities are likely overestimating the temperature and underestimating the rheology of the fast-flowing trunk and grounding zone of Thwaites Glacier.

  20. Time Domain Structures: Generation Mechanisms and Their Role for Electron Acceleration in the Earth's Outer Radiation Belt

    NASA Astrophysics Data System (ADS)

    Mozer, F.; Artemyev, A.; Agapitov, O. V.; Drake, J. F.; Krasnoselskikh, V.; Lejosne, S.; Mournas, D.; Vasko, I.

    2015-12-01

    Time Domain Structures (TDS) is the generic name for short duration (~msec) electric field pulses that occur in streams and that have significant components parallel to the background magnetic field. Examples of TDS are electrostatic or electromagnetic double layers, electron holes, and non-linear whistlers. They are found in copious quantities in the Earth's outer radiation belt and on auroral zone magnetic field lines, in the tail, the plasma sheet, the plasma sheet boundary layer, at shocks, at magnetic field reconnection sites, in the solar wind and at Saturn. Mechanisms for the generation of TDS and their role in accelerating radiation belt electrons will be described.

  1. Production of Multi-Terawatt Time-Structured CO{sub 2} Laser Pulses for Ion Acceleration

    SciTech Connect

    Haberberger, Dan; Tochitsky, Sergei; Gong Chao; Joshi, Chan

    2010-11-04

    The UCLA Neptune Laboratory CO{sub 2} laser system has been recently upgraded to produce 3ps multi-terawatt 10{mu}m laser pulses. The laser energy is distributed over several 3 ps pulses separated by 18 ps. These temporally structured pulses are applied for laser driven ion acceleration in an H{sub 2} gas jet at a measured plasma density of 2x10{sup 19} cm{sup -3}. Protons in excess of 20 MeV have been observed in the forward direction and with energy spreads ({Delta}E/E{approx}10%).

  2. Macrophage Receptor with Collagenous Structure (MARCO) Is Processed by either Macropinocytosis or Endocytosis-Autophagy Pathway

    PubMed Central

    Hirano, Seishiro; Kanno, Sanae

    2015-01-01

    The Macrophage Receptor with COllagenous structure (MARCO) protein is a plasma membrane receptor for un-opsonized or environmental particles on phagocytic cells. Here, we show that MARCO was internalized either by ruffling of plasma membrane followed by macropinocytosis or by endocytosis followed by fusion with autophagosome in CHO-K1 cells stably transfected with GFP-MARCO. The macropinocytic process generated large vesicles when the plasma membrane subsided. The endocytosis/autophagosome (amphisome) generated small fluorescent puncta which were visible in the presence of glutamine, chloroquine, bafilomycin, ammonia, and other amines. The small puncta, but not the large vesicles, co-localized with LC3B and lysosomes. The LC3-II/LC3-I ratio increased in the presence of glutamine, ammonia, and chloroquine in various cells. The small puncta trafficked between the peri-nuclear region and the distal ends of cells back and forth at rates of up to 2–3 μm/sec; tubulin, but not actin, regulated the trafficking of the small puncta. Besides phagocytosis MARCO, an adhesive plasma membrane receptor, may play a role in incorporation of various extracellular materials into the cell via both macropinocytic and endocytic pathways. PMID:26545255

  3. A structured approach for the engineering of biochemical network models, illustrated for signalling pathways.

    PubMed

    Breitling, Rainer; Gilbert, David; Heiner, Monika; Orton, Richard

    2008-09-01

    Quantitative models of biochemical networks (signal transduction cascades, metabolic pathways, gene regulatory circuits) are a central component of modern systems biology. Building and managing these complex models is a major challenge that can benefit from the application of formal methods adopted from theoretical computing science. Here we provide a general introduction to the field of formal modelling, which emphasizes the intuitive biochemical basis of the modelling process, but is also accessible for an audience with a background in computing science and/or model engineering. We show how signal transduction cascades can be modelled in a modular fashion, using both a qualitative approach--qualitative Petri nets, and quantitative approaches--continuous Petri nets and ordinary differential equations (ODEs). We review the major elementary building blocks of a cellular signalling model, discuss which critical design decisions have to be made during model building, and present a number of novel computational tools that can help to explore alternative modular models in an easy and intuitive manner. These tools, which are based on Petri net theory, offer convenient ways of composing hierarchical ODE models, and permit a qualitative analysis of their behaviour. We illustrate the central concepts using signal transduction as our main example. The ultimate aim is to introduce a general approach that provides the foundations for a structured formal engineering of large-scale models of biochemical networks. PMID:18573813

  4. Protein denaturation in vacuo: intrinsic unfolding pathways associated with the native tertiary structure of lysozyme

    NASA Astrophysics Data System (ADS)

    Arteca, Gustavo A.; Tapia, O.

    Using computer-simulated molecular dynamics, we study the effect of sequence mutation on the unfolding mechanism of a native fold. The system considered is the native fold of hen egg-white lysozyme, exposed to centrifugal unfolding in vacuo. This unfolding bias elicits configurational transitions that imitate the behaviour of anhydrous proteins diffusing after electrospraying from neutral-pH solutions. By changing the sequences threaded onto the native fold of lysozyme, we probe the role of disulfide bridges and the effect of a global mutation. We find that the initial denaturing steps share common characteristics for the tested sequences. Recurrent features are: (i) the presence of dumbbell conformers with significant residual secondary structure, (ii) the ubiquitous formation of hairpins and two-stranded β-sheets regardless of disulfide bridges, and (iii) an unfolding pattern where the reduction in folding complexity is highly correlated with the decrease in chain compactness. These findings appear to be intrinsic to the shape of the native fold, suggesting that similar unfolding pathways may be accessible to many protein sequences.

  5. Structural basis of lentiviral subversion of a cellular protein degradation pathway

    NASA Astrophysics Data System (ADS)

    Schwefel, David; Groom, Harriet C. T.; Boucherit, Virginie C.; Christodoulou, Evangelos; Walker, Philip A.; Stoye, Jonathan P.; Bishop, Kate N.; Taylor, Ian A.

    2014-01-01

    Lentiviruses contain accessory genes that have evolved to counteract the effects of host cellular defence proteins that inhibit productive infection. One such restriction factor, SAMHD1, inhibits human immunodeficiency virus (HIV)-1 infection of myeloid-lineage cells as well as resting CD4+ T cells by reducing the cellular deoxynucleoside 5'-triphosphate (dNTP) concentration to a level at which the viral reverse transcriptase cannot function. In other lentiviruses, including HIV-2 and related simian immunodeficiency viruses (SIVs), SAMHD1 restriction is overcome by the action of viral accessory protein x (Vpx) or the related viral protein r (Vpr) that target and recruit SAMHD1 for proteasomal degradation. The molecular mechanism by which these viral proteins are able to usurp the host cell's ubiquitination machinery to destroy the cell's protection against these viruses has not been defined. Here we present the crystal structure of a ternary complex of Vpx with the human E3 ligase substrate adaptor DCAF1 and the carboxy-terminal region of human SAMHD1. Vpx is made up of a three-helical bundle stabilized by a zinc finger motif, and wraps tightly around the disc-shaped DCAF1 molecule to present a new molecular surface. This adapted surface is then able to recruit SAMHD1 via its C terminus, making it a competent substrate for the E3 ligase to mark for proteasomal degradation. The structure reported here provides a molecular description of how a lentiviral accessory protein is able to subvert the cell's normal protein degradation pathway to inactivate the cellular viral defence system.

  6. Structural basis of lentiviral subversion of a cellular protein degradation pathway

    PubMed Central

    Schwefel, David; Groom, Harriet C. T.; Boucherit, Virginie C.; Christodoulou, Evangelos; Walker, Philip A.; Stoye, Jonathan P.; Bishop, Kate N.; Taylor, Ian A.

    2013-01-01

    Lentiviruses contain accessory genes that have evolved to counteract the effects of host cellular defence proteins that inhibit productive infection. One such restriction factor, SAMHD1, inhibits HIV-1 infection of myeloid-lineage cells 1,2 as well as resting CD4+ T cells 3,4 by reducing the cellular dNTP concentration to a level where the viral reverse transcriptase cannot function 5,6. In other lentiviruses, including HIV-2 and related SIVs, SAMHD1 restriction is overcome by the action of viral accessory protein x (Vpx) or the related viral protein r (Vpr) that target and recruit SAMHD1 for proteasomal degradation 7,8. The molecular mechanism by which these viral proteins are able to usurp the host cell’s ubiquitination machinery to destroy the cell’s protection against these viruses has not been defined. We present here the crystal structure of a ternary complex of Vpx with the host cell’s E3 ligase substrate adaptor DCAF1 and the C-terminal region of SAMHD1. Vpx is made up of a three-helical bundle, stabilised by a zinc finger motif and wraps tightly around the disc-shaped DCAF1 molecule to present a new molecular surface. This adapted surface is then able to recruit SAMHD1 via its C-terminus making it a competent substrate for the E3 ligase to mark for proteasomal degradation. The structure provides the first description of how a lentiviral accessory protein is able to subvert the cell’s normal protein degradation pathway to inactivate the cellular viral defence system. PMID:24336198

  7. Oxygen transport pathways in Ruddlesden–Popper structured oxides revealed via in situ neutron diffraction

    SciTech Connect

    Tomkiewicz, Alex C.; Tamimi, Mazin; Huq, Ashfia; McIntosh, Steven

    2015-09-21

    Ruddlesden-Popper structured oxides, general form An+1BnO3n+1, consist of n-layers of the perovskite structure stacked in between rock-salt layers, and have potential application in solid oxide electrochemical cells and ion transport membrane reactors. Three materials with constant Co/Fe ratio, LaSrCo0.5Fe0.5O4-δ (n = 1), La0.3Sr2.7CoFeO7-δ (n = 2), and LaSr3Co1.5Fe1.5O10-δ (n = 3) were synthesized and studied via in situ neutron powder diffraction between 765 K and 1070 K at a pO2 of 10-1 atm. Then, the structures were fit to a tetragonal I4/mmm space group, and were found to have increased total oxygen vacancy concentration in the order La0.3Sr2.7CoFeO7-δ > LaSr3Co1.5Fe1.5O10-δ > LaSrCo0.5Fe0.5O4-δ, following the trend predicted for charge compensation upon increasing Sr2+/La3+ ratio. The oxygen vacancies within the material were almost exclusively located within the perovskite layers for all of the crystal structures with only minimal vacancy formation in the rock-salt layer. Finally, analysis of the concentration of these vacancies at each distinct crystallographic site and the anisotropic atomic displacement parameters for the oxygen sites reveals potential preferred oxygen transport pathways through the perovskite layers.

  8. Electron acceleration at localized wave structures in the solar corona (German Title: Elektronenbeschleunigung an lokalen Wellenstrukturen in der Sonnenkorona)

    NASA Astrophysics Data System (ADS)

    Miteva, Rositsa Stoycheva

    2007-07-01

    Our dynamic Sun manifests its activity by different phenomena: from the 11-year cyclic sunspot pattern to the unpredictable and violent explosions in the case of solar flares. During flares, a huge amount of the stored magnetic energy is suddenly released and a substantial part of this energy is carried by the energetic electrons, considered to be the source of the nonthermal radio and X-ray radiation. One of the most important and still open question in solar physics is how the electrons are accelerated up to high energies within (the observed in the radio emission) short time scales. Because the acceleration site is extremely small in spatial extent as well (compared to the solar radius), the electron acceleration is regarded as a local process. The search for localized wave structures in the solar corona that are able to accelerate electrons together with the theoretical and numerical description of the conditions and requirements for this process, is the aim of the dissertation. Two models of electron acceleration in the solar corona are proposed in the dissertation: I. Electron acceleration due to the solar jet interaction with the background coronal plasma (the jet--plasma interaction) A jet is formed when the newly reconnected and highly curved magnetic field lines are relaxed by shooting plasma away from the reconnection site. Such jets, as observed in soft X-rays with the Yohkoh satellite, are spatially and temporally associated with beams of nonthermal electrons (in terms of the so-called type III metric radio bursts) propagating through the corona. A model that attempts to give an explanation for such observational facts is developed here. Initially, the interaction of such jets with the background plasma leads to an (ion-acoustic) instability associated with growing of electrostatic fluctuations in time for certain range of the jet initial velocity. During this process, any test electron that happen to feel this electrostatic wave field is drawn to co

  9. Structure, function and regulation of the enzymes in the starch biosynthetic pathway.

    SciTech Connect

    Geiger, Jim

    2013-11-30

    structure of ADP- Glucose pyrophosphorylase from potato in its inhibited conformation, and bound to both ATP and ADP-glucose. In addition, we have determined the first structure of glycogen synthase in its "closed", catalytically active conformation bound to ADP-glucose. We also determined the structure of glycogen synthase bound to malto-oligosaccharides, showing for the first time that an enzyme in the starch biosynthetic pathway recognizes glucans not just in its active site but on binding sites on the surface of the enzyme ten’s of Angstroms from the active site. In addition our structure of a glycogen branching enzyme bound to malto-oligosaccharides identified seven distinct binding sites distributed about the surface of the enzyme. We will now determine the function of these sites to get a molecular-level picture of exactly how these enzymes interact with their polymeric substrates and confer specificity leading to the complex structure of the starch granule. We will extend our studies to other isoforms of the enzymes, to understand how their structures give rise to their distinct function. Our goal is to understand what accounts for the various functional differences between SS and SBE isoforms at a molecular level.

  10. Novel 14,21-dihydroxy-docosahexaenoic acids: structures, formation pathways, and enhancement of wound healing

    PubMed Central

    Lu, Yan; Tian, Haibin; Hong, Song

    2010-01-01

    Chronic wounds remain a medical challenge, where well-coordinated cellular and molecular processes required by optimal healing are impaired by diabetes, aging, or other diseases. In determining mechanisms that regulate wound healing, we found that wounding induced formation of novel endogenous 14S,21S-dihydroxy-docosa-4Z,7Z,10Z,12E,16Z,19Z-hexaenoic acids (14S,21S-diHDHA);14R,21R-diHDHA; 14S,21R-diHDHA; and/or 14R,21S-diHDHA. 12-lipoxygenase and cytochrome P450 catalysis in tandem converted docosahexaenoic acid to 14S,21R-diHDHA and 14S,21S-diHDHA through the intermediacy of 14S-HDHA; P450 also converted 14R-HDHA to novel 14R,21R-diHDHA and 14R,21S-diHDHA. Macrophages function as the combination of 12-lipoxgenase and P450 to generate these 14,21-diHDHA stereoisomers, as well as their intermediates 14S-HDHA, 14R-HDHA, and 21-HDHA. The structure and formation pathways of 14,21-diHDHA stereoisomers were further confirmed by macrophage biosynthesis of 14,21-diHDHA-21,22,22,22-d4 stereoisomers, 14S-HDHA-d5, 14R-HDHA-d5, and 21-HDHA-d4 from DHA-21,21,22,22,22-d5. We found that 14S,21-diHDHA and 14R,21-diHDHA enhanced wound closure, reepithelialization, granulation tissue growth, and capillary vasculature formation of murine wounds. 14S,21-diHDHA and 14R,21-diHDHA produced by macrophages may partially represent the molecular mechanisms for macrophage pro-healing function. Taken together, 14,21-dihydroxy-DHA stereoisomers and their formation pathways may represent a novel mechanism in the orchestration of wound healing processes, which may provide new insight for developing novel therapeutic modalities that counteract impairments to wound healing. PMID:19965612

  11. Novel 14,21-dihydroxy-docosahexaenoic acids: structures, formation pathways, and enhancement of wound healing.

    PubMed

    Lu, Yan; Tian, Haibin; Hong, Song

    2010-05-01

    Chronic wounds remain a medical challenge, where well-coordinated cellular and molecular processes required by optimal healing are impaired by diabetes, aging, or other diseases. In determining mechanisms that regulate wound healing, we found that wounding induced formation of novel endogenous 14S,21S-dihydroxy-docosa-4Z,7Z,10Z,12E,16Z,19Z-hexaenoic acids (14S,21S-diHDHA);14R,21R-diHDHA; 14S,21R-diHDHA; and/or 14R,21S-diHDHA. 12-lipoxygenase and cytochrome P450 catalysis in tandem converted docosahexaenoic acid to 14S,21R-diHDHA and 14S,21S-diHDHA through the intermediacy of 14S-HDHA; P450 also converted 14R-HDHA to novel 14R,21R-diHDHA and 14R,21S-diHDHA. Macrophages function as the combination of 12-lipoxgenase and P450 to generate these 14,21-diHDHA stereoisomers, as well as their intermediates 14S-HDHA, 14R-HDHA, and 21-HDHA. The structure and formation pathways of 14,21-diHDHA stereoisomers were further confirmed by macrophage biosynthesis of 14,21-diHDHA-21,22,22,22-d(4) stereoisomers, 14S-HDHA-d(5), 14R-HDHA-d(5), and 21-HDHA-d(4) from DHA-21,21,22,22,22-d(5). We found that 14S,21-diHDHA and 14R,21-diHDHA enhanced wound closure, reepithelialization, granulation tissue growth, and capillary vasculature formation of murine wounds. 14S,21-diHDHA and 14R,21-diHDHA produced by macrophages may partially represent the molecular mechanisms for macrophage pro-healing function. Taken together, 14,21-dihydroxy-DHA stereoisomers and their formation pathways may represent a novel mechanism in the orchestration of wound healing processes, which may provide new insight for developing novel therapeutic modalities that counteract impairments to wound healing. PMID:19965612

  12. Thermodynamics and Kinetics for the Free Radical Oxygen Protein Oxidation Pathway in a Model for β-Structured Peptides.

    PubMed

    Green, Mandy C; Dubnicka, Laura J; Davis, Alex C; Rypkema, Heather A; Francisco, Joseph S; Slipchenko, Lyudmila V

    2016-04-28

    Oxidative stress plays a role in many biological phenomena, but involved mechanisms and individual reactions are not well understood. Correlated electronic structure calculations with the MP2, MP4, and CCSD(T) methods detail thermodynamic and kinetic information for the free radical oxygen protein oxidation pathway studied in a trialanine model system. The pathway includes aerobic, anaerobic and termination reactions. The course of the oxidation process depends on local conditions and availability of specific reactive oxygen species (ROS). A chemical mechanism is proposed for how oxidative stress promotes β-structure formation in the amyloid diseases. The work can be used to aid experimentalists as they explore individual reactions and mechanisms involving oxygen free radicals and oxidative stress in β-structured proteins. PMID:27055125

  13. CyanoPhyChe: A Database for Physico-Chemical Properties, Structure and Biochemical Pathway Information of Cyanobacterial Proteins

    PubMed Central

    Arun, P. V. Parvati Sai; Bakku, Ranjith Kumar; Subhashini, Mranu; Singh, Pankaj; Prabhu, N. Prakash; Suzuki, Iwane; Prakash, Jogadhenu S. S.

    2012-01-01

    CyanoPhyChe is a user friendly database that one can browse through for physico-chemical properties, structure and biochemical pathway information of cyanobacterial proteins. We downloaded all the protein sequences from the cyanobacterial genome database for calculating the physico-chemical properties, such as molecular weight, net charge of protein, isoelectric point, molar extinction coefficient, canonical variable for solubility, grand average hydropathy, aliphatic index, and number of charged residues. Based on the physico-chemical properties, we provide the polarity, structural stability and probability of a protein entering in to an inclusion body (PEPIB). We used the data generated on physico-chemical properties, structure and biochemical pathway information of all cyanobacterial proteins to construct CyanoPhyChe. The data can be used for optimizing methods of expression and characterization of cyanobacterial proteins. Moreover, the ‘Search’ and data export options provided will be useful for proteome analysis. Secondary structure was predicted for all the cyanobacterial proteins using PSIPRED tool and the data generated is made accessible to researchers working on cyanobacteria. In addition, external links are provided to biological databases such as PDB and KEGG for molecular structure and biochemical pathway information, respectively. External links are also provided to different cyanobacterial databases. CyanoPhyChe can be accessed from the following URL: http://bif.uohyd.ac.in/cpc. PMID:23185330

  14. Wake field accelerators

    SciTech Connect

    Wilson, P.B.

    1986-02-01

    In a wake field accelerator a high current driving bunch injected into a structure or plasma produces intense induced fields, which are in turn used to accelerate a trailing charge or bunch. The basic concepts of wake field acceleration are described. Wake potentials for closed cavities and periodic structures are derived, as are wake potentials on a collinear path with a charge distribution. Cylindrically symmetric structures excited by a beam in the form of a ring are considered. (LEW)

  15. Accelerated Testing Methodology in Constant Stress-Rate Testing for Advanced Structural Ceramics: A Preloading Technique

    NASA Technical Reports Server (NTRS)

    Choi, Sung R.; Gyekenyesi, John P.; Huebert, Dean; Bartlett, Allen; Choi, Han-Ho

    2001-01-01

    Preloading technique was used as a means of an accelerated testing methodology in constant stress-rate (dynamic fatigue) testing for two different brittle materials. The theory developed previously for fatigue strength as a function of preload was further verified through extensive constant stress-rate testing for glass-ceramic and CRT glass in room temperature distilled water. The preloading technique was also used in this study to identify the prevailing failure mechanisms at elevated temperatures, particularly at lower test rates in which a series of mechanisms would be associated simultaneously with material failure, resulting in significant strength increase or decrease. Two different advanced ceramics including SiC whisker-reinforced composite silicon nitride and 96 wt% alumina were used at elevated temperatures. It was found that the preloading technique can be used as an additional tool to pinpoint the dominant failure mechanism that is associated with such a phenomenon of considerable strength increase or decrease.

  16. Accelerated Testing Methodology in Constant Stress-Rate Testing for Advanced Structural Ceramics: A Preloading Technique

    NASA Technical Reports Server (NTRS)

    Choi, Sung R.; Gyekenyesi, John P.; Huebert, Dean; Bartlett, Allen; Choi, Han-Ho

    2001-01-01

    Preloading technique was used as a means of an accelerated testing methodology in constant stress-rate ('dynamic fatigue') testing for two different brittle materials. The theory developed previously for fatigue strength as a function of preload was further verified through extensive constant stress-rate testing for glass-ceramic and CRT glass in room temperature distilled water. The preloading technique was also used in this study to identify the prevailing failure mechanisms at elevated temperatures, particularly at lower test rate in which a series of mechanisms would be associated simultaneously with material failure, resulting in significant strength increase or decrease. Two different advanced ceramics including SiC whisker-reinforced composite silicon nitride and 96 wt% alumina were used at elevated temperatures. It was found that the preloading technique can be used as an additional tool to pinpoint the dominant failure mechanism that is associated with such a phenomenon of considerable strength increase or decrease.

  17. Studies of laser wakefield structures and electron acceleration in underdense plasmas

    SciTech Connect

    Maksimchuk, A.; Reed, S.; Bulanov, S. S.; Chvykov, V.; Kalintchenko, G.; Matsuoka, T.; McGuffey, C.; Mourou, G.; Naumova, N.; Nees, J.; Rousseau, P.; Yanovsky, V.; Krushelnick, K.; Matlis, N. H.; Kalmykov, S.; Shvets, G.; Downer, M. C.; Vane, C. R.; Beene, J. R.; Stracener, D.

    2008-05-15

    Experiments on electron acceleration and optical diagnostics of laser wakes were performed on the HERCULES facility in a wide range of laser and plasma parameters. Using frequency domain holography we demonstrated single shot visualization of individual plasma waves, produced by 40 TW, 30 fs laser pulses focused to the intensity of 10{sup 19} W/cm{sup 2} onto a supersonic He gas jet with plasma densities n{sub e}<10{sup 19} cm{sup -3}. These holographic 'snapshots' capture the variation in shape of the plasma wave with distance behind the driver, and resolve wave front curvature seen previously only in simulations. High-energy quasimonoenergetic electron beams were generated using plasma density in the range 1.5x10{sup 19}{<=}n{sub e}{<=}3.5x10{sup 19} cm{sup -3}. These experiments demonstrated that the energy, charge, divergence, and pointing stability of the beam can be controlled by changing n{sub e}, and that higher electron energies and more stable beams are produced for lower densities. An optimized quasimonoenergetic beam of over 300 MeV and 10 mrad angular divergence is demonstrated at a plasma density of n{sub e}{approx_equal}1.5x10{sup 19} cm{sup -3}. The resultant relativistic electron beams have been used to perform photo-fission of {sup 238}U with a record high reaction yields of {approx}3x10{sup 5}/J. The results of initial experiments on electron acceleration at 70 TW are discussed.

  18. First high-power model of the annular-ring coupled structure for use in the Japan Proton Accelerator Research Complex linac

    NASA Astrophysics Data System (ADS)

    Ao, Hiroyuki; Yamazaki, Yoshishige

    2012-01-01

    A prototype cavity for the annular-ring coupled structure (ACS) for use in the Japan Proton Accelerator Research Complex (J-PARC) linac has been developed to confirm the feasibility of achieving the required performance. This prototype cavity is a buncher module, which includes ten accelerating cells in total. The ACS cavity is formed by the silver brazing of ACS half-cell pieces stacked in a vacuum furnace. The accelerating cell of the ACS is surrounded by a coupling cell. We, therefore, tuned the frequencies of the accelerating and coupling cells by an ultraprecision lathe before brazing, taking into account the frequency shift due to brazing. The prototype buncher module was successfully conditioned up to 600 kW, which corresponds to an accelerating field that is higher than the designed field of 4.1MV/m by 30%. We describe the frequency-tuning results for the prototype buncher module and its high-power conditioning.

  19. Linear Accelerators

    NASA Astrophysics Data System (ADS)

    Sidorin, Anatoly

    2010-01-01

    In linear accelerators the particles are accelerated by either electrostatic fields or oscillating Radio Frequency (RF) fields. Accordingly the linear accelerators are divided in three large groups: electrostatic, induction and RF accelerators. Overview of the different types of accelerators is given. Stability of longitudinal and transverse motion in the RF linear accelerators is briefly discussed. The methods of beam focusing in linacs are described.

  20. Linear Accelerators

    SciTech Connect

    Sidorin, Anatoly

    2010-01-05

    In linear accelerators the particles are accelerated by either electrostatic fields or oscillating Radio Frequency (RF) fields. Accordingly the linear accelerators are divided in three large groups: electrostatic, induction and RF accelerators. Overview of the different types of accelerators is given. Stability of longitudinal and transverse motion in the RF linear accelerators is briefly discussed. The methods of beam focusing in linacs are described.

  1. Structure and Function of Vps15 in the Endosomal G Protein Signaling Pathway

    SciTech Connect

    Heenan, Erin J.; Vanhooke, Janeen L.; Temple, Brenda R.; Betts, Laurie; Sondek, John E.; Dohlman, Henrik G.

    2009-09-11

    G protein-coupled receptors mediate cellular responses to a wide variety of stimuli, including taste, light, and neurotransmitters. In the yeast Saccharomyces cerevisiae, activation of the pheromone pathway triggers events leading to mating. The view had long been held that the G protein-mediated signal occurs principally at the plasma membrane. Recently, it has been shown that the G protein {alpha} subunit Gpa1 can promote signaling at endosomes and requires two components of the sole phosphatidylinositol-3-kinase in yeast, Vps15 and Vps34. Vps15 contains multiple WD repeats and also binds to Gpa1 preferentially in the GDP-bound state; these observations led us to hypothesize that Vps15 may function as a G protein {beta} subunit at the endosome. Here we show an X-ray crystal structure of the Vps15 WD domain that reveals a seven-bladed propeller resembling that of typical G{beta} subunits. We show further that the WD domain is sufficient to bind Gpa1 as well as to Atg14, a potential G{gamma} protein that exists in a complex with Vps15. The Vps15 kinase domain together with the intermediate domain (linking the kinase and WD domains) also contributes to Gpa1 binding and is necessary for Vps15 to sustain G protein signaling. These findings reveal that the Vps15 G{beta}-like domain serves as a scaffold to assemble Gpa1 and Atg14, whereas the kinase and intermediate domains are required for proper signaling at the endosome.

  2. Morphometric changes in subcortical structures of the central auditory pathway in mice with bilateral nodular heterotopia.

    PubMed

    Truong, Dongnhu T; Rendall, Amanda R; Rosen, Glenn D; Fitch, R Holly

    2015-04-01

    Malformations of cortical development (MCD) have been observed in human reading and language impaired populations. Injury-induced MCD in rodent models of reading disability show morphological changes in the auditory thalamic nucleus (medial geniculate nucleus; MGN) and auditory processing impairments, thus suggesting a link between MCD, MGN, and auditory processing behavior. Previous neuroanatomical examination of a BXD29 recombinant inbred strain (BXD29-Tlr4(lps-2J)/J) revealed MCD consisting of bilateral subcortical nodular heterotopia with partial callosal agenesis. Subsequent behavioral characterization showed a severe impairment in auditory processing-a deficient behavioral phenotype seen across both male and female BXD29-Tlr4(lps-2J)/J mice. In the present study we expanded upon the neuroanatomical findings in the BXD29-Tlr4(lps-2J)/J mutant mouse by investigating whether subcortical changes in cellular morphology are present in neural structures critical to central auditory processing (MGN, and the ventral and dorsal subdivisions of the cochlear nucleus; VCN and DCN, respectively). Stereological assessment of brain tissue of male and female BXD29-Tlr4(lps-2J)/J mice previously tested on an auditory processing battery revealed overall smaller neurons in the MGN of BXD29-Tlr4(lps-2J)/J mutant mice in comparison to BXD29/Ty coisogenic controls, regardless of sex. Interestingly, examination of the VCN and DCN revealed sexually dimorphic changes in neuronal size, with a distribution shift toward larger neurons in female BXD29-Tlr4(lps-2J)/J brains. These effects were not seen in males. Together, the combined data set supports and further expands the observed co-occurrence of MCD, auditory processing impairments, and changes in subcortical anatomy of the central auditory pathway. The current stereological findings also highlight sex differences in neuroanatomical presentation in the presence of a common auditory behavioral phenotype. PMID:25549859

  3. Particle acceleration

    NASA Technical Reports Server (NTRS)

    Vlahos, L.; Machado, M. E.; Ramaty, R.; Murphy, R. J.; Alissandrakis, C.; Bai, T.; Batchelor, D.; Benz, A. O.; Chupp, E.; Ellison, D.

    1986-01-01

    Data is compiled from Solar Maximum Mission and Hinothori satellites, particle detectors in several satellites, ground based instruments, and balloon flights in order to answer fundamental questions relating to: (1) the requirements for the coronal magnetic field structure in the vicinity of the energization source; (2) the height (above the photosphere) of the energization source; (3) the time of energization; (4) transistion between coronal heating and flares; (5) evidence for purely thermal, purely nonthermal and hybrid type flares; (6) the time characteristics of the energization source; (7) whether every flare accelerates protons; (8) the location of the interaction site of the ions and relativistic electrons; (9) the energy spectra for ions and relativistic electrons; (10) the relationship between particles at the Sun and interplanetary space; (11) evidence for more than one acceleration mechanism; (12) whether there is single mechanism that will accelerate particles to all energies and also heat the plasma; and (13) how fast the existing mechanisms accelerate electrons up to several MeV and ions to 1 GeV.

  4. Structural and biochemical characterization of Chlamydia trachomatis hypothetical protein CT263 supports that menaquinone synthesis occurs through the futalosine pathway.

    PubMed

    Barta, Michael L; Thomas, Keisha; Yuan, Hongling; Lovell, Scott; Battaile, Kevin P; Schramm, Vern L; Hefty, P Scott

    2014-11-14

    The obligate intracellular human pathogen Chlamydia trachomatis is the etiological agent of blinding trachoma and sexually transmitted disease. Genomic sequencing of Chlamydia indicated this medically important bacterium was not exclusively dependent on the host cell for energy. In order for the electron transport chain to function, electron shuttling between membrane-embedded complexes requires lipid-soluble quinones (e.g. menaquionone or ubiquinone). The sources or biosynthetic pathways required to obtain these electron carriers within C. trachomatis are poorly understood. The 1.58Å crystal structure of C. trachomatis hypothetical protein CT263 presented here supports a role in quinone biosynthesis. Although CT263 lacks sequence-based functional annotation, the crystal structure of CT263 displays striking structural similarity to 5'-methylthioadenosine nucleosidase (MTAN) enzymes. Although CT263 lacks the active site-associated dimer interface found in prototypical MTANs, co-crystal structures with product (adenine) or substrate (5'-methylthioadenosine) indicate that the canonical active site residues are conserved. Enzymatic characterization of CT263 indicates that the futalosine pathway intermediate 6-amino-6-deoxyfutalosine (kcat/Km = 1.8 × 10(3) M(-1) s(-1)), but not the prototypical MTAN substrates (e.g. S-adenosylhomocysteine and 5'-methylthioadenosine), is hydrolyzed. Bioinformatic analyses of the chlamydial proteome also support the futalosine pathway toward the synthesis of menaquinone in Chlamydiaceae. This report provides the first experimental support for quinone synthesis in Chlamydia. Menaquinone synthesis provides another target for agents to combat C. trachomatis infection. PMID:25253688

  5. Structural Basis for the Function of Complement Component C4 within the Classical and Lectin Pathways of Complement.

    PubMed

    Mortensen, Sofia; Kidmose, Rune T; Petersen, Steen V; Szilágyi, Ágnes; Prohászka, Zoltan; Andersen, Gregers R

    2015-06-01

    Complement component C4 is a central protein in the classical and lectin pathways within the complement system. During activation of complement, its major fragment C4b becomes covalently attached to the surface of pathogens and altered self-tissue, where it acts as an opsonin marking the surface for removal. Moreover, C4b provides a platform for assembly of the proteolytically active convertases that mediate downstream complement activation by cleavage of C3 and C5. In this article, we present the crystal and solution structures of the 195-kDa C4b. Our results provide the molecular details of the rearrangement accompanying C4 cleavage and suggest intramolecular flexibility of C4b. The conformations of C4b and its paralogue C3b are shown to be remarkably conserved, suggesting that the convertases from the classical and alternative pathways are likely to share their overall architecture and mode of substrate recognition. We propose an overall molecular model for the classical pathway C5 convertase in complex with C5, suggesting that C3b increases the affinity for the substrate by inducing conformational changes in C4b rather than a direct interaction with C5. C4b-specific features revealed by our structural studies are probably involved in the assembly of the classical pathway C3/C5 convertases and C4b binding to regulators. PMID:25911760

  6. Electron acceleration at localized wave structures in the solar corona (German Title: Elektronenbeschleunigung an lokalen Wellenstrukturen in der Sonnenkorona)

    NASA Astrophysics Data System (ADS)

    Miteva, Rositsa Stoycheva

    2007-07-01

    Our dynamic Sun manifests its activity by different phenomena: from the 11-year cyclic sunspot pattern to the unpredictable and violent explosions in the case of solar flares. During flares, a huge amount of the stored magnetic energy is suddenly released and a substantial part of this energy is carried by the energetic electrons, considered to be the source of the nonthermal radio and X-ray radiation. One of the most important and still open question in solar physics is how the electrons are accelerated up to high energies within (the observed in the radio emission) short time scales. Because the acceleration site is extremely small in spatial extent as well (compared to the solar radius), the electron acceleration is regarded as a local process. The search for localized wave structures in the solar corona that are able to accelerate electrons together with the theoretical and numerical description of the conditions and requirements for this process, is the aim of the dissertation. Two models of electron acceleration in the solar corona are proposed in the dissertation: I. Electron acceleration due to the solar jet interaction with the background coronal plasma (the jet--plasma interaction) A jet is formed when the newly reconnected and highly curved magnetic field lines are relaxed by shooting plasma away from the reconnection site. Such jets, as observed in soft X-rays with the Yohkoh satellite, are spatially and temporally associated with beams of nonthermal electrons (in terms of the so-called type III metric radio bursts) propagating through the corona. A model that attempts to give an explanation for such observational facts is developed here. Initially, the interaction of such jets with the background plasma leads to an (ion-acoustic) instability associated with growing of electrostatic fluctuations in time for certain range of the jet initial velocity. During this process, any test electron that happen to feel this electrostatic wave field is drawn to co

  7. Structure determination of chemisorbed chirality transfer complexes: Accelerated STM analysis and exchange-correlation functional sensitivity

    NASA Astrophysics Data System (ADS)

    Groves, M. N.; Goubert, G.; Rasmussen, A. M. H.; Dong, Y.; Lemay, J.-C.; Demers-Carpentier, V.; McBreen, P. H.; Hammer, B.

    2014-11-01

    Linking STM images to atomic positions determined by DFT calculations is an important step in characterizing the intermolecular interactions at play in many surface processes including asymmetric hydrogenation on heterogeneous catalysts. An accelerated data extraction method is used to collect STM information on the geometry of complexes formed between the two substrates, 2,2,2-trifluoroacetophenone (TFAP) and 3,3,3-methyltrifluoropyruvate (MTFP), and the chiral modifier (R)-(+)-1-(1-naphthyl)ethylamine ((R)-NEA) on Pt(111). We present new experimental data for complexes formed by MTFP and the (R)-NEA-1 conformer along with a new and enlarged set of reformulated STM data that extends what was reported in previously published studies of complexed MTFP and TFAP. Atomic geometries based on DFT calculations using PBE, M06-L, and optB88-vdW exchange-correlation functionals will also be presented. It will be shown that both substrates have well-defined complexation geometries when interacting with the modifier and that the relative complexation energies are not markedly sensitive to the functional employed.

  8. The structural alteration of gut microbiota in low-birth-weight mice undergoing accelerated postnatal growth.

    PubMed

    Wang, Jingjing; Tang, Huang; Wang, Xiaoxin; Zhang, Xu; Zhang, Chenhong; Zhang, Menghui; Zhao, Yufeng; Zhao, Liping; Shen, Jian

    2016-01-01

    The transient disruption of gut microbiota in infancy by antibiotics causes adult adiposity in mice. Accelerated postnatal growth (A) leads to a higher risk of adult metabolic syndrome in low birth-weight (LB) humans than in normal birth-weight (NB) individuals, but the underlying mechanism remains unclear. Here, we set up an experiment using LB + A mice, NB + A mice, and control mice with NB and normal postnatal growth. At 24 weeks of age (adulthood), while NB + A animals had a normal body fat content and glucose tolerance compared with controls, LB + A mice exhibited excessive adiposity and glucose intolerance. In infancy, more fecal bacteria implicated in obesity were increased in LB + A pups than in NB + A pups, including Desulfovibrionaceae, Enterorhabdus, and Barnesiella. One bacterium from the Lactobacillus genus, which has been implicated in prevention of adult adiposity, was enhanced only in NB + A pups. Besides, LB + A pups, but not NB + A pups, showed disrupted gut microbiota fermentation activity. After weaning, the fecal microbiota composition of LB + A mice, but not that of NB + A animals, became similar to that of controls by 24 weeks. In infancy, LB + A mice have a more dysbiotic gut microbiome compared to NB + A mice, which might increase their risk of adult metabolic syndrome. PMID:27277748

  9. The structural alteration of gut microbiota in low-birth-weight mice undergoing accelerated postnatal growth

    PubMed Central

    Wang, Jingjing; Tang, Huang; Wang, Xiaoxin; Zhang, Xu; Zhang, Chenhong; Zhang, Menghui; Zhao, Yufeng; Zhao, Liping; Shen, Jian

    2016-01-01

    The transient disruption of gut microbiota in infancy by antibiotics causes adult adiposity in mice. Accelerated postnatal growth (A) leads to a higher risk of adult metabolic syndrome in low birth-weight (LB) humans than in normal birth-weight (NB) individuals, but the underlying mechanism remains unclear. Here, we set up an experiment using LB + A mice, NB + A mice, and control mice with NB and normal postnatal growth. At 24 weeks of age (adulthood), while NB + A animals had a normal body fat content and glucose tolerance compared with controls, LB + A mice exhibited excessive adiposity and glucose intolerance. In infancy, more fecal bacteria implicated in obesity were increased in LB + A pups than in NB + A pups, including Desulfovibrionaceae, Enterorhabdus, and Barnesiella. One bacterium from the Lactobacillus genus, which has been implicated in prevention of adult adiposity, was enhanced only in NB + A pups. Besides, LB + A pups, but not NB + A pups, showed disrupted gut microbiota fermentation activity. After weaning, the fecal microbiota composition of LB + A mice, but not that of NB + A animals, became similar to that of controls by 24 weeks. In infancy, LB + A mice have a more dysbiotic gut microbiome compared to NB + A mice, which might increase their risk of adult metabolic syndrome. PMID:27277748

  10. Pathway-based outlier method reveals heterogeneous genomic structure of autism in blood transcriptome

    PubMed Central

    2013-01-01

    Background Decades of research strongly suggest that the genetic etiology of autism spectrum disorders (ASDs) is heterogeneous. However, most published studies focus on group differences between cases and controls. In contrast, we hypothesized that the heterogeneity of the disorder could be characterized by identifying pathways for which individuals are outliers rather than pathways representative of shared group differences of the ASD diagnosis. Methods Two previously published blood gene expression data sets – the Translational Genetics Research Institute (TGen) dataset (70 cases and 60 unrelated controls) and the Simons Simplex Consortium (Simons) dataset (221 probands and 191 unaffected family members) – were analyzed. All individuals of each dataset were projected to biological pathways, and each sample’s Mahalanobis distance from a pooled centroid was calculated to compare the number of case and control outliers for each pathway. Results Analysis of a set of blood gene expression profiles from 70 ASD and 60 unrelated controls revealed three pathways whose outliers were significantly overrepresented in the ASD cases: neuron development including axonogenesis and neurite development (29% of ASD, 3% of control), nitric oxide signaling (29%, 3%), and skeletal development (27%, 3%). Overall, 50% of cases and 8% of controls were outliers in one of these three pathways, which could not be identified using group comparison or gene-level outlier methods. In an independently collected data set consisting of 221 ASD and 191 unaffected family members, outliers in the neurogenesis pathway were heavily biased towards cases (20.8% of ASD, 12.0% of control). Interestingly, neurogenesis outliers were more common among unaffected family members (Simons) than unrelated controls (TGen), but the statistical significance of this effect was marginal (Chi squared P < 0.09). Conclusions Unlike group difference approaches, our analysis identified the samples within the case

  11. Methanogenic pathway and community structure in a thermophilic anaerobic digestion process of organic solid waste.

    PubMed

    Sasaki, Daisuke; Hori, Tomoyuki; Haruta, Shin; Ueno, Yoshiyuki; Ishii, Masaharu; Igarashi, Yasuo

    2011-01-01

    The methanogenic pathway and microbial community in a thermophilic anaerobic digestion process of organic solid waste were investigated in a continuous-flow stirred-tank reactor using artificial garbage slurry as a feedstock. The decomposition pathway of acetate, a significant precursor of CH(4) and a key intermediate metabolite in the anaerobic digestion process, was analyzed by using stable isotopes. A tracer experiment using (13)C-labeled acetate revealed that approximately 80% of the acetate was decomposed via a non-aceticlastic oxidative pathway, whereas the remainder was converted to methane via an aceticlastic pathway. Archaeal 16S rRNA analyses demonstrated that the hydrogenotrophic methanogens Methanoculleus spp. accounted for >90% of detected methanogens, and the aceticlastic methanogens Methanosarcina spp. were the minor constituents. The clone library targeting bacterial 16S rRNA indicated the predominance of the novel Thermotogales bacterium (relative abundance: ~53%), which is related to anaerobic acetate oxidizer Thermotoga lettingae TMO, although the sequence similarity was low. Uncultured bacteria that phylogenetically belong to municipal solid waste cluster I were also predominant in the microflora (~30%). These results imply that the microbial community in the thermophilic degrading process of organic solid waste consists exclusively of unidentified bacteria, which efficiently remove acetate through a non-aceticlastic oxidative pathway. PMID:20851673

  12. Structure-Based Design of Inhibitors of the Crucial Cysteine Biosynthetic Pathway Enzyme O-Acetyl Serine Sulfhydrylase.

    PubMed

    Mazumder, Mohit; Gourinath, Samudrala

    2016-01-01

    The cysteine biosynthetic pathway is of fundamental importance for the growth, survival, and pathogenicity of the many pathogens. This pathway is present in many species but is absent in mammals. The ability of pathogens to counteract the oxidative defences of a host is critical for the survival of these pathogens during their long latent phases, especially in anaerobic pathogens such as Entamoeba histolytica, Leishmania donovani, Trichomonas vaginalis, and Salmonella typhimurium. All of these organisms rely on the de novo cysteine biosynthetic pathway to assimilate sulphur and maintain a ready supply of cysteine. The de novo cysteine biosynthetic pathway, on account of its being important for the survival of pathogens and at the same time being absent in mammals, is an important drug target for diseases such as amoebiasis, trichomoniasis & tuberculosis. Cysteine biosynthesis is catalysed by two enzymes: serine acetyl transferase (SAT) followed by O-acetylserine sulfhydrylase (OASS). OASS is well studied, and with the availability of crystal structures of this enzyme in different conformations, it is a suitable template for structure-based inhibitor development. Moreover, OASS is highly conserved, both structurally and sequence-wise, among the above-mentioned organisms. There have been several reports of inhibitor screening and development against this enzyme from different organisms such as Salmonella typhimurium, Mycobacterium tuberculosis and Entamoeba histolytica. All of these inhibitors have been reported to display micromolar to nanomolar binding affinities for the open conformation of the enzyme. In this review, we highlight the structural similarities of this enzyme in different organisms and the attempts for inhibitor development so far. We also propose that the intermediate state of the enzyme may be the ideal target for the design of effective highaffinity inhibitors. PMID:26303427

  13. Magnetic stimulation modulates structural synaptic plasticity and regulates BDNF-TrkB signal pathway in cultured hippocampal neurons.

    PubMed

    Ma, Jun; Zhang, Zhanchi; Su, Yuhong; Kang, Lin; Geng, Dandan; Wang, Yanyong; Luan, Feng; Wang, Mingwei; Cui, Huixian

    2013-01-01

    Repetitive transcranial magnetic stimulation (rTMS) is a neuropsychiatric tool that can be used to investigate the neurobiology of learning and cognitive function. Few studies have examined the effects of low frequency (⩽1Hz) magnetic stimulation (MS) on structural synaptic plasticity of neurons in vitro, thus, the current study examined its effects on hippocampal neuron and synapse morphology, as well as synaptic protein markers and signaling pathways. Similarly, both intensities of low frequency magnetic stimulation (1Hz) activated brain-derived neurotrophic factor (BDNF) and tropomyosin-related kinase B (TrkB) pathways, including the pathways for mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) and for phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt). Specifically, low intensity magnetic stimulation (LIMS, 1.14Tesla, 1Hz) promoted more extensive dendritic and axonal arborization, as well as increasing synapses density, thickening PSD (post synaptic density) and upregulation of synaptophysin (SYN), growth associated protein 43 (GAP43) and post synaptic density 95 (PSD95). Conversely, high intensity magnetic stimulation (HIMS, 1.55Tesla, 1Hz) appeared to be detrimental, reducing dendritic and axonal arborization and causing apparent structural damage, including thinning of PSD, less synapses and disordered synaptic structure, as well as upregulation of GAP43 and PSD95, possibly for their ability to mitigate dysfunction. In conclusion, we infers that low frequency magnetic stimulation participates in regulating structural synaptic plasticity of hippocampal neurons via the activation of BDNF-TrkB signaling pathways. PMID:23201339

  14. Atomic oxygen ground-based accelerated tests of spacecraft materials and structures for long-term LEO missions

    NASA Astrophysics Data System (ADS)

    Chernik, Vladimir; Novikov, Lev; Smirnova, Tatyana; Shumov, Andrey

    Spacecraft materials are degradated during long-term low earth orbit (LEO) flight. The Internation Space Station (ISS) is planed to be prolonged the term of action up to 20-25 years. To specify so long life one requires a validation of spacecraft material behaviour conservation for the period. The LEO environment includes atomic oxygen (AO) destructive incident flow. The appropriate AO fluence is proposed to be as high as 10E22-10E23 atom O/sq cm. The simulative ground-based test is evident to be acceptable if its duration is not too long usually under several hundreds of hours. In that case the rate of the test acceleration exceeds 100-200. One way to accelerate test is to increase oxygen particles energy. We test materials under oxygen plasma beam, formed by a magnetoplasmadynamic accelerator, with the oxygen particle energy of 20 -30 eV. In this way we determine an AO effective fluence by a kapton equivalent technique. The beam varies from LEO incident flow by energy, flux and rates of the oxygen dissociation / ionization/ excitation. To evaluate the test adequacy we measured and compared with LEO data erosion yields of a number of polymer materials, applied on spacecraft external surfaces. There were: polyimide (kapton), polyamide (nylon), polyethylene, polyvinyl fluoride (tedlar), polysteren, polymethyl methacrylate, epoxy, polyethylene terephthalate (mylar), graphite. Their relative erosion yields, measured and normalized by polyimide in this way, practically coincide with the data of flight experiments on the ISS. The results ground to use our plasma mode for accelerated tests of spacecraft material durability for long-term LEO flights. We tested quite a number of polymer-based materials and structures usable on ISS and another LEO spacecrafts. The effective AO fluencies ran up to 3,5 10E22 atom O/sq cm corresponding to the ISS flight duration about 20 years. We studied material behaviors like mass and thickness losses, erosion yield, surface morphology

  15. Kinetic Analysis as a Tool to Distinguish Pathway Complexity in Molecular Assembly: An Unexpected Outcome of Structures in Competition.

    PubMed

    van der Zwaag, Daan; Pieters, Pascal A; Korevaar, Peter A; Markvoort, Albert J; Spiering, A J H; de Greef, Tom F A; Meijer, E W

    2015-10-01

    While the sensitive dependence of the functional characteristics of self-assembled nanofibers on the molecular structure of their building blocks is well-known, the crucial influence of the dynamics of the assembly process is often overlooked. For natural protein-based fibrils, various aggregation mechanisms have been demonstrated, from simple primary nucleation to secondary nucleation and off-pathway aggregation. Similar pathway complexity has recently been described in synthetic supramolecular polymers and has been shown to be intimately linked to their morphology. We outline a general method to investigate the consequences of the presence of multiple assembly pathways, and show how kinetic analysis can be used to distinguish different assembly mechanisms. We illustrate our combined experimental and theoretical approach by studying the aggregation of chiral bipyridine-extended 1,3,5-benzenetricarboxamides (BiPy-1) in n-butanol as a model system. Our workflow consists of nonlinear least-squares analysis of steady-state spectroscopic measurements, which cannot provide conclusive mechanistic information but yields the equilibrium constants of the self-assembly process as constraints for subsequent kinetic analysis. Furthermore, kinetic nucleation-elongation models based on one and two competing pathways are used to interpret time-dependent spectroscopic measurements acquired using stop-flow and temperature-jump methods. Thus, we reveal that the sharp transition observed in the aggregation process of BiPy-1 cannot be explained by a single cooperative pathway, but can be described by a competitive two-pathway mechanism. This work provides a general tool for analyzing supramolecular polymerizations and establishing energetic landscapes, leading to mechanistic insights that at first sight may seem unexpected and counterintuitive. PMID:26354151

  16. Molecule-optimized basis sets and Hamiltonians for accelerated electronic structure calculations of atoms and molecules.

    PubMed

    Gidofalvi, Gergely; Mazziotti, David A

    2014-01-16

    Molecule-optimized basis sets, based on approximate natural orbitals, are developed for accelerating the convergence of quantum calculations with strongly correlated (multireferenced) electrons. We use a low-cost approximate solution of the anti-Hermitian contracted Schrödinger equation (ACSE) for the one- and two-electron reduced density matrices (RDMs) to generate an approximate set of natural orbitals for strongly correlated quantum systems. The natural-orbital basis set is truncated to generate a molecule-optimized basis set whose rank matches that of a standard correlation-consistent basis set optimized for the atoms. We show that basis-set truncation by approximate natural orbitals can be viewed as a one-electron unitary transformation of the Hamiltonian operator and suggest an extension of approximate natural-orbital truncations through two-electron unitary transformations of the Hamiltonian operator, such as those employed in the solution of the ACSE. The molecule-optimized basis set from the ACSE improves the accuracy of the equivalent standard atom-optimized basis set at little additional computational cost. We illustrate the method with the potential energy curves of hydrogen fluoride and diatomic nitrogen. Relative to the hydrogen fluoride potential energy curve from the ACSE in a polarized triple-ζ basis set, the ACSE curve in a molecule-optimized basis set, equivalent in size to a polarized double-ζ basis, has a nonparallelity error of 0.0154 au, which is significantly better than the nonparallelity error of 0.0252 au from the polarized double-ζ basis set. PMID:24387056

  17. The measurement results of carbon ion beam structure extracted by bent crystal from U-70 accelerator

    NASA Astrophysics Data System (ADS)

    Afonin, A. G.; Barnov, E. V.; Britvich, G. I.; Chesnokov, Yu A.; Chirkov, P. N.; Durum, A. A.; Kostin, M. Yu; Maisheev, V. A.; Pitalev, V. I.; Reshetnikov, S. F.; Yanovich, A. A.; Nazhmudinov, R. M.; Kubankin, A. S.; Shchagin, A. V.

    2016-07-01

    The carbon ion +6C beam with energy 25 GeV/nucleon was extracted by bent crystal from the U-70 ring. The bent angle of silicon crystal was 85 mrad. About 2×105 particles for 109 circulated ions in the ring were observed in beam line 4a after bent crystal. Geometrical parameters, time structure and ion beam structure were measured. The ability of the bent monocrystal to extract and generate ion beam with necessary parameters for regular usage in physical experiments is shown in the first time.

  18. Circuit and Scattering Matrix Analysis of the Wire Measurement Method of Beam Impedance in Accelerating Structures

    SciTech Connect

    Jones, Roger M

    2003-05-23

    In order to measure the wakefield left behind multiple bunches of energetic electrons we have previously used the ASSET facility in the SLC [1]. However, in order to produce a more rapid and cost-effective determination of the wakefields we have designed a wire experimental method to measure the beam impedance and from the Fourier transform thereof, the wakefields. In this paper we present studies of the wire effect on the properties of X-band structures in study for the JLC/NLC (Japanese Linear Collider/Next Linear Collider) project. Simulations are made on infinite and finite periodical structures. The results are discussed.

  19. A cautionary tale of structure-guided inhibitor development against an essential enzyme in the aspartate-biosynthetic pathway.

    PubMed

    Pavlovsky, Alexander G; Thangavelu, Bharani; Bhansali, Pravin; Viola, Ronald E

    2014-12-01

    The aspartate pathway is essential for the production of the amino acids required for protein synthesis and of the metabolites needed in bacterial development. This pathway also leads to the production of several classes of quorum-sensing molecules that can trigger virulence in certain microorganisms. The second enzyme in this pathway, aspartate β-semialdehyde dehydrogenase (ASADH), is absolutely required for bacterial survival and has been targeted for the design of selective inhibitors. Fragment-library screening has identified a new set of inhibitors that, while they do not resemble the substrates for this reaction, have been shown to bind at the active site of ASADH. Structure-guided development of these lead compounds has produced moderate inhibitors of the target enzyme, with some selectivity observed between the Gram-negative and Gram-positive orthologs of ASADH. However, many of these inhibitor analogs and derivatives have not yet achieved the expected enhanced affinity. Structural characterization of these enzyme-inhibitor complexes has provided detailed explanations for the barriers that interfere with optimal binding. Despite binding in the same active-site region, significant changes are observed in the orientation of these bound inhibitors that are caused by relatively modest structural alterations. Taken together, these studies present a cautionary tale for issues that can arise in the systematic approach to the modification of lead compounds that are being used to develop potent inhibitors. PMID:25478842

  20. Magnetospheric Multiscale Satellite Observations of Parallel Electron Acceleration in Magnetic Field Reconnection by Fermi Reflection from Time Domain Structures

    NASA Astrophysics Data System (ADS)

    Mozer, F. S.; Agapitov, O. A.; Artemyev, A.; Burch, J. L.; Ergun, R. E.; Giles, B. L.; Mourenas, D.; Torbert, R. B.; Phan, T. D.; Vasko, I.

    2016-04-01

    The same time domain structures (TDS) have been observed on two Magnetospheric Multiscale Satellites near Earth's dayside magnetopause. These TDS, traveling away from the X line along the magnetic field at 4000 km /s , accelerated field-aligned ˜5 eV electrons to ˜200 eV by a single Fermi reflection of the electrons by these overtaking barriers. Additionally, the TDS contained both positive and negative potentials, so they were a mixture of electron holes and double layers. They evolve in ˜10 km of space or 7 ms of time and their spatial scale size is 10-20 km, which is much larger than the electron gyroradius (<1 km ) or the electron inertial length (4 km at the observation point, less nearer the X line).

  1. Magnetospheric Multiscale Satellite Observations of Parallel Electron Acceleration in Magnetic Field Reconnection by Fermi Reflection from Time Domain Structures.

    PubMed

    Mozer, F S; Agapitov, O A; Artemyev, A; Burch, J L; Ergun, R E; Giles, B L; Mourenas, D; Torbert, R B; Phan, T D; Vasko, I

    2016-04-01

    The same time domain structures (TDS) have been observed on two Magnetospheric Multiscale Satellites near Earth's dayside magnetopause. These TDS, traveling away from the X line along the magnetic field at 4000  km/s, accelerated field-aligned ∼5  eV electrons to ∼200  eV by a single Fermi reflection of the electrons by these overtaking barriers. Additionally, the TDS contained both positive and negative potentials, so they were a mixture of electron holes and double layers. They evolve in ∼10  km of space or 7 ms of time and their spatial scale size is 10-20 km, which is much larger than the electron gyroradius (<1  km) or the electron inertial length (4 km at the observation point, less nearer the X line). PMID:27104714

  2. Frequency-Domain Streak Camera and Tomography for Ultrafast Imaging of Evolving and Channeled Plasma Accelerator Structures

    NASA Astrophysics Data System (ADS)

    Li, Zhengyan; Zgadzaj, Rafal; Wang, Xiaoming; Reed, Stephen; Dong, Peng; Downer, Michael C.

    2010-11-01

    We demonstrate a prototype Frequency Domain Streak Camera (FDSC) that can capture the picosecond time evolution of the plasma accelerator structure in a single shot. In our prototype Frequency-Domain Streak Camera, a probe pulse propagates obliquely to a sub-picosecond pump pulse that creates an evolving nonlinear index "bubble" in fused silica glass, supplementing a conventional Frequency Domain Holographic (FDH) probe-reference pair that co-propagates with the "bubble". Frequency Domain Tomography (FDT) generalizes Frequency-Domain Streak Camera by probing the "bubble" from multiple angles and reconstructing its morphology and evolution using algorithms similar to those used in medical CAT scans. Multiplexing methods (Temporal Multiplexing and Angular Multiplexing) improve data storage and processing capability, demonstrating a compact Frequency Domain Tomography system with a single spectrometer.

  3. Structural basis of Ornithine Decarboxylase inactivation and accelerated degradation by polyamine sensor Antizyme1

    PubMed Central

    Wu, Donghui; Kaan, Hung Yi Kristal; Zheng, Xiaoxia; Tang, Xuhua; He, Yang; Vanessa Tan, Qianmin; Zhang, Neng; Song, Haiwei

    2015-01-01

    Ornithine decarboxylase (ODC) catalyzes the first and rate-limiting step of polyamine biosynthesis in humans. Polyamines are essential for cell proliferation and are implicated in cellular processes, ranging from DNA replication to apoptosis. Excessive accumulation of polyamines has a cytotoxic effect on cells and elevated level of ODC activity is associated with cancer development. To maintain normal cellular proliferation, regulation of polyamine synthesis is imposed by Antizyme1 (AZ1). The expression of AZ1 is induced by a ribosomal frameshifting mechanism in response to increased intracellular polyamines. AZ1 regulates polyamine homeostasis by inactivating ODC activity and enhancing its degradation. Here, we report the structure of human ODC in complex with N-terminally truncated AZ1 (cAZ1). The structure shows cAZ1 binding to ODC, which occludes the binding of a second molecule of ODC to form the active homodimer. Consequently, the substrate binding site is disrupted and ODC is inactivated. Structural comparison shows that the binding of cAZ1 to ODC causes a global conformational change of ODC and renders its C-terminal region flexible, therefore exposing this region for degradation by the 26S proteasome. Our structure provides the molecular basis for the inactivation of ODC by AZ1 and sheds light on how AZ1 promotes its degradation. PMID:26443277

  4. Miniaturization Techniques for Accelerators

    SciTech Connect

    Spencer, James E.

    2003-05-27

    The possibility of laser driven accelerators [1] suggests the need for new structures based on micromachining and integrated circuit technology because of the comparable scales. Thus, we are exploring fully integrated structures including sources, optics (for both light and particle) and acceleration in a common format--an accelerator-on-chip (AOC). Tests suggest a number of preferred materials and techniques but no technical or fundamental roadblocks at scales of order 1 {micro}m or larger.

  5. Can Accelerators Accelerate Learning?

    NASA Astrophysics Data System (ADS)

    Santos, A. C. F.; Fonseca, P.; Coelho, L. F. S.

    2009-03-01

    The 'Young Talented' education program developed by the Brazilian State Funding Agency (FAPERJ) [1] makes it possible for high-schools students from public high schools to perform activities in scientific laboratories. In the Atomic and Molecular Physics Laboratory at Federal University of Rio de Janeiro (UFRJ), the students are confronted with modern research tools like the 1.7 MV ion accelerator. Being a user-friendly machine, the accelerator is easily manageable by the students, who can perform simple hands-on activities, stimulating interest in physics, and getting the students close to modern laboratory techniques.

  6. PARTICLE ACCELERATOR

    DOEpatents

    Teng, L.C.

    1960-01-19

    ABS>A combination of two accelerators, a cyclotron and a ring-shaped accelerator which has a portion disposed tangentially to the cyclotron, is described. Means are provided to transfer particles from the cyclotron to the ring accelerator including a magnetic deflector within the cyclotron, a magnetic shield between the ring accelerator and the cyclotron, and a magnetic inflector within the ring accelerator.

  7. Final Report on "Development and Testing of Advanced Accelerator Structures and Technologies at 11.424 GHz"

    SciTech Connect

    Gold, Steven H.

    2013-10-13

    This is the final report on the research program ?Development and Testing of Advanced Accelerator Structures and Technologies at 11.424 GHz,? which was carried out by the Naval Research Laboratory (NRL) under Interagency Agreement DE?AI02?01ER41170 with the Department of Energy. The period covered by this report is 15 July 2010 ? 14 July 2013. The program included two principal tasks. Task 1 involved a study of the key physics issues related to the use of high gradient dielectric-loaded accelerating (DLA) structures in rf linear accelerators and was carried out in collaboration with Argonne National Laboratory (ANL) and Euclid Techlabs LLC. Task 2 involved a study of high power active microwave pulse compressors and was carried out in collaboration with Omega-P, Inc. and the Institute of Applied Physics of the Russian Academy of Sciences in Nizhny Novgorod. The studies under Task 1 were focused on rf-induced multipactor and breakdown in externally driven DLA structures at the 200-ns timescale. Suppression of multipactor and breakdown are essential to the practical application of dielectric structures in rf linear accelerators. The structures that were studied were developed by ANL and Euclid Techlabs and their performance was evaluated at high power in the X-band Magnicon Laboratory at NRL. Three structures were designed, fabricated, and tested, and the results analyzed in the first two years of the program: a clamped quartz traveling-wave (TW) structure, a externally copper-coated TW structure, and an externally copper-coated dielectric standing-wave (SW) structure. These structures showed that rf breakdown could be largely eliminated by eliminating dielectric joints in the structures, but that the multipactor loading was omnipresent. In the third year of the program, the focus of the program was on multipactor suppression using a strong applied axial magnetic field, as proposed by Chang et al. [C. Chang et al., J. Appl. Phys. 110, 063304 (2011).], and a

  8. Structural Incorporation of Uranium into Iron Oxides: A Competitive Secondary Sequestration Pathway Mediated by Fe(II)

    NASA Astrophysics Data System (ADS)

    Massey, M. S.; Lezama-Pacheco, J. S.; Nico, P. S.; Bargar, J.; Fendorf, S.

    2011-12-01

    Uranium retention and sequestration pathways determine the long-term fate of this important contaminant in soils and sediments. Direct, enzymatic U reduction and subsequent precipitation of UO2 is one potential sequestration pathway, but indirect U transformations can also occur as a result of reactions with microbially-generated Fe(II). Here we explored uranium retention mechanisms active during abiotic reduction of U(VI) by aqueous Fe(II), in the presence of ferrihydrite, in Ca and carbonate-bearing solutions. Ferrihydrite transformation and U reduction were studied in batch incubations containing Ca (0 and 4 mM), carbonate (3.8 mM), ferrihydrite (~180 mg/L), Fe(II) (0.3 mM), and a range of concentrations of uranyl (1 to 170 μM). Uranium retention pathways were differentiated using extended x-ray absorption fine structure (EXAFS) spectroscopy and synchrotron X-ray powder diffraction. At U concentrations >50 μM, U(VI) reduction to U(IV) and subsequent precipitation of UO2 was a dominant sequestration pathway. At lower U concentrations (1-10 μM), UO2 precipitation was not observed and incorporation into goethite, the secondary transformation product of ferrihydrite, was dominant. For groundwaters having micromolar U(VI) concentrations, U incorporation into ferrihydrite transformation products via microbially-produced Fe(II) may be an important sequestration process.

  9. Earthworms modify microbial community structure and accelerate maize stover decomposition during vermicomposting.

    PubMed

    Chen, Yuxiang; Zhang, Yufen; Zhang, Quanguo; Xu, Lixin; Li, Ran; Luo, Xiaopei; Zhang, Xin; Tong, Jin

    2015-11-01

    In the present study, maize stover was vermicomposted with the epigeic earthworm Eisenia fetida. The results showed that, during vermicomposting process, the earthworms promoted decomposition of maize stover. Analysis of microbial communities of the vermicompost by high-throughput pyrosequencing showed more complex bacterial community structure in the substrate treated by the earthworms than that in the control group. The dominant microbial genera in the treatment with the earthworms were Pseudoxanthomonas, Pseudomonas, Arthrobacter, Streptomyces, Cryptococcus, Guehomyces, and Mucor. Compared to the control group, the relative abundance of lignocellulose degradation microorganisms increased. The results indicated that the earthworms modified the structure of microbial communities during vermicomposting process, activated the growth of lignocellulose degradation microorganisms, and triggered the lignocellulose decomposition. PMID:26139410

  10. The Molecular Clock of Neutral Evolution Can Be Accelerated or Slowed by Asymmetric Spatial Structure

    PubMed Central

    Allen, Benjamin; Sample, Christine; Dementieva, Yulia; Medeiros, Ruben C.; Paoletti, Christopher; Nowak, Martin A.

    2015-01-01

    Over time, a population acquires neutral genetic substitutions as a consequence of random drift. A famous result in population genetics asserts that the rate, K, at which these substitutions accumulate in the population coincides with the mutation rate, u, at which they arise in individuals: K = u. This identity enables genetic sequence data to be used as a “molecular clock” to estimate the timing of evolutionary events. While the molecular clock is known to be perturbed by selection, it is thought that K = u holds very generally for neutral evolution. Here we show that asymmetric spatial population structure can alter the molecular clock rate for neutral mutations, leading to either Ku. Our results apply to a general class of haploid, asexually reproducing, spatially structured populations. Deviations from K = u occur because mutations arise unequally at different sites and have different probabilities of fixation depending on where they arise. If birth rates are uniform across sites, then K ≤ u. In general, K can take any value between 0 and Nu. Our model can be applied to a variety of population structures. In one example, we investigate the accumulation of genetic mutations in the small intestine. In another application, we analyze over 900 Twitter networks to study the effect of network topology on the fixation of neutral innovations in social evolution. PMID:25719560

  11. Acceleration of ions to suprathermal energies by turbulence in the plasmoid-like magnetic structures

    NASA Astrophysics Data System (ADS)

    Grigorenko, E. E.; Malykhin, A. Yu.; Kronberg, E. A.; Malova, Kh. V.; Daly, P. W.

    2015-08-01

    We study energetic spectra of H+, He+, and O+ ion fluxes in the energy range ≥130 keV measured by Cluster/Research with Adaptive Particle Imaging Detectors (RAPID) instruments during 37 intervals of the tailward bulk flow propagation in the near-Earth tail (at X ≤ -19 RE). In all events from our database, the plasmoid-like magnetic structures with the superimposed low-frequency magnetic and electric field fluctuations were observed along with the tailward bulk flows. The plasmoid-like structures were associated with the enhancements of energetic ion fluxes and the hardening of energy spectra of H+ and He+ ion components in 80% of events and of O+ ion component in 64% of events. The hardening of energy spectra was more pronounced for heavy ions than for protons. The analysis of the magnetic structures and power spectral density (PSD) of the magnetic and electric field fluctuations from our database revealed the following factors favorable for the ion energization: (1) the spatial scale of a plasmoid should exceed the thermal gyroradius of a given ion component in the neutral plane inside the plasmoid; (2) the PSD of the magnetic fluctuations near the gyrofrequency of a particular ion component should exceed ~ 50.0 nT2/Hz for oxygen ions; while the energization of helium ions and protons takes place for much lower values of the PSD. The kinetic analysis of ion dynamics in the plasmoid-like magnetic configuration similar to the observed one with the superimposed turbulence confirms the importance of ion resonant interactions with the low-frequency electromagnetic fluctuations for ion energization inside plasmoids.

  12. Analytical Study on the Cosmological Large-scale Structure in an Accelerating Universe

    NASA Astrophysics Data System (ADS)

    Wang, Xin

    2012-01-01

    Motivated by the roughly log-normal probability density distribution function (PDF) of the small scale density field, we develop cosmological perturbation theory for the power spectrum of a logarithmically transformed density field with the formalism which is developed in the context of the cosmological renormalized perturbation theory. Compared with the standard perturbation theory, our approach help to regulate the convergence behavior of the perturbation series, and of the Taylor series expansion we use for the logarithmic mapping. The perturbation calculation achieved good agreement with simulation results. Then we consider the topology of the iso-density contour of the density field, especially the genus. The genus is relatively insensitive to nonlinear gravitational evolution, clustering bias and redshift distortion, and is approximately conserved over time as structures grow in Einstein's general relativity, hence it can be used as a robust standard ruler for cosmological measurements. However, in modified gravity models where structures grow with different rates on different scales, the genus should change over time, and therefore it can be used to test the gravity models on large scales. We studied the case of the f(R) theory, DGP brane-world theory as well as phenomenological models. We also forecast how the modified gravity models can be constrained with optical/IR or 21cm surveys in the near future.

  13. Effective seismic acceleration measurements for low-cost Structural Health Monitoring

    NASA Astrophysics Data System (ADS)

    Pentaris, Fragkiskos; Makris, John P.

    2015-04-01

    There is increasing demand on cost effective Structural Health Monitoring systems for buildings as well as important and/or critical constructions. The front end for all these systems is the accelerometer. We present a comparative study of two low cost MEMS accelaration sensors against a very sensitive, high dynamic range strong motion accelerometer of force balance type but much more expensive. A real experiment was realized by deploying the three sesnors in a reinforced concrete building of the premises of TEI of Crete at Chania Crete, an earthquake prone region. The analysis of the collected accelararion data from many seismic events indicates that all sensors are able to efficiently reveal the seismic response of the construction in terms of PSD. Furthermore, it is shown that coherence diagrams between excitation and response of the building under study, depict structural characteristics but also the seismic energy distribution. This work is supported by the Archimedes III Program of the Ministry of Education of Greece, through the Operational Program "Educational and Lifelong Learning", in the framework of the project entitled "Interdisciplinary Multi-Scale Research of Earthquake Physics and Seismotectonics at the front of the Hellenic Arc (IMPACT-ARC)" and is co-financed by the European Union (European Social Fund) and Greek national funds.

  14. Structural Origins of Cholesterol Accelerated Lipid Flip-Flop Studied by Sum-Frequency Vibrational Spectroscopy.

    PubMed

    Allhusen, John S; Kimball, Dylan R; Conboy, John C

    2016-03-31

    The unique structure of cholesterol and its role in modulating lipid translocation (flip-flop) were examined using sum-frequency vibrational spectroscopy (SFVS). Two structural analogues of cholesterol--cholestanol and cholestene--were examined to explore the influence of ring rigidity and amphiphilicity on controlling distearoylphosphocholine (DSPC) flip-flop. Kinetic rates for DSPC flip-flop were determined as a function of sterol concentration and temperature. All three sterols increased the rate of DSPC flip-flop in a concentration-dependent manner following the order cholestene > cholestanol > cholesterol. Rates of DSPC flip-flop were used to calculate the thermodynamic activation free energy barrier (ΔG(‡)) in the presence of cholesterol, cholestanol, and cholestene. The acyl chain gauche content of DSPC, mean lipid area, and membrane compressibility were correlated to observed trends in ΔG(‡). ΔG(‡) for DSPC flip-flop showed a strong positive correlation with the molar compression modulus (K*) of the membrane, influenced by the type and concentration of the sterol added. Interestingly, cholesterol is distinctive in maintaining invariant membrane compressibility over the range of 2-10 mol %. The results in this study demonstrate that the compression modulus of a membrane plays a significant role in moderating ΔG(‡) and the kinetics of native, protein-free, lipid translocation in membranes. PMID:26978577

  15. Cosmic ray decreases and particle acceleration in 1978-1982 and the associated solar wind structures

    NASA Technical Reports Server (NTRS)

    Cane, H. V.; Richardson, I. G.; Von Rosenvinge, T. T.

    1993-01-01

    Results of a study of the time histories of particles in the energy range 1 MeV to 1 GeV at the times of greater than 3-percent cosmic ray decreases in the years 1978-1982 are presented. The intensity-time profiles of the particles are used to separate the cosmic ray decreases into four classes which are subsequently associated with three types of solar wind structures. Decreases in class 1 (15 events) and class 2 (26 events) are associated with shocks driven by energetic coronal mass ejections. For class 1 events, the ejecta are detected at 1 AU, whereas this is not usually the case for class 2 events. The shock must therefore play a dominant role in producing the cosmic ray depression in class 2 events. It is argued that since energetic particles (from MEV to GeV energies) seen at earth may respond to solar wind structures which are not detected at earth, consideration of particle observations over a wide range of energies is necessary for a full understanding of cosmic ray decreases.

  16. Theoretical Investigations of Plasma-Based Accelerators and Other Advanced Accelerator Concepts

    SciTech Connect

    Shuets, G.

    2004-05-21

    Theoretical investigations of plasma-based accelerators and other advanced accelerator concepts. The focus of the work was on the development of plasma based and structure based accelerating concepts, including laser-plasma, plasma channel, and microwave driven plasma accelerators.

  17. Structure of Arabidopsis Dehydroquinate Dhydratase-Shikimate Dehydrogeanse and Implications for Metabolic Channeling in the Shikimate Pathway

    SciTech Connect

    Singh,S.; Christendat, D.

    2006-01-01

    The bifunctional enzyme dehydroquinate dehydratase-shikimate dehydrogenase (DHQ-SDH) catalyzes the dehydration of dehydroquinate to dehydroshikimate and the reduction of dehydroshikimate to shikimate in the shikimate pathway. We report the first crystal structure of Arabidopsis DHQ-SDH with shikimate bound at the SDH site and tartrate at the DHQ site. The interactions observed in the DHQ-tartrate complex reveal a conserved mode for substrate binding between the plant and microbial DHQ dehydratase family of enzymes. The SDH-shikimate complex provides the first direct evidence of the role of active site residues in the catalytic mechanism. Site-directed mutagenesis and mechanistic analysis revealed that Asp 423 and Lys 385 are key catalytic groups and Ser 336 is a key binding group. The arrangement of the two functional domains reveals that the control of metabolic flux through the shikimate pathway is achieved by increasing the effective concentration of dehydroshikimate through the proximity of the two sites.

  18. The crystal structure of Neisseria gonorrhoeae PriB reveals mechanistic differences among bacterial DNA replication restart pathways

    SciTech Connect

    Dong, Jinlan; George, Nicholas P.; Duckett, Katrina L.; DeBeer, Madeleine A.P.; Lopper, Matthew E.

    2010-05-25

    Reactivation of repaired DNA replication forks is essential for complete duplication of bacterial genomes. However, not all bacteria encode homologs of the well-studied Escherichia coli DNA replication restart primosome proteins, suggesting that there might be distinct mechanistic differences among DNA replication restart pathways in diverse bacteria. Since reactivation of repaired DNA replication forks requires coordinated DNA and protein binding by DNA replication restart primosome proteins, we determined the crystal structure of Neisseria gonorrhoeae PriB at 2.7 {angstrom} resolution and investigated its ability to physically interact with DNA and PriA helicase. Comparison of the crystal structures of PriB from N. gonorrhoeae and E. coli reveals a well-conserved homodimeric structure consisting of two oligosaccharide/oligonucleotide-binding (OB) folds. In spite of their overall structural similarity, there is significant species variation in the type and distribution of surface amino acid residues. This correlates with striking differences in the affinity with which each PriB homolog binds single-stranded DNA and PriA helicase. These results provide evidence that mechanisms of DNA replication restart are not identical across diverse species and that these pathways have likely become specialized to meet the needs of individual organisms.

  19. The VP3 structural protein of foot-and-mouth disease virus inhibits the IFN-β signaling pathway.

    PubMed

    Li, Dan; Yang, Wenping; Yang, Fan; Liu, Huanan; Zhu, Zixiang; Lian, Kaiqi; Lei, Caoqi; Li, Shu; Liu, Xiangtao; Zheng, Haixue; Shu, Hongbing

    2016-05-01

    Foot-and-mouth disease is a frequently occurring disease of cloven-hoofed animals that is caused by infection with the foot-and-mouth virus (FMDV). FMDV circumvents the type-I IFN response by expressing proteins that antagonize cellular innate immunity, such as leader protease and 3C protease. We identified the FMDV structural protein VP3 as a negative regulator of the virus-triggered IFN-β signaling pathway. Expression of FMDV VP3 inhibited the Sendai virus-triggered activation of IFN regulatory factor-3 and the expression of retinoic acid-inducible gene-I/melanoma differentiation-associated protein-5. Transient transfection and coimmunoprecipitation confirmed that the structural protein VP3 interacts with virus-induced signaling adapter (VISA), which is dependent on the C-terminal aa 111-220 of VP3. In addition, we found that FMDV VP3 inhibits the expression of VISA by disrupting its mRNA. Taken together, our findings reveal a novel strategy used by the structural VP3 protein of FMDV to evade host innate immunity.-Li, D., Yang, W., Yang, F., Liu, H., Zhu, Z., Lian, K., Lei, C., Li, S., Liu, X., Zheng, H., Shu, H. The VP3 structural protein of foot-and-mouth disease virus inhibits the IFN-β signaling pathway. PMID:26813975

  20. Role of the XPA protein in the NER pathway: A perspective on the function of structural disorder in macromolecular assembly.

    PubMed

    Fadda, Elisa

    2016-01-01

    Lack of structure is often an essential functional feature of protein domains. The coordination of macromolecular assemblies in DNA repair pathways is yet another task disordered protein regions are highly implicated in. Here I review the available experimental and computational data and within this context discuss the functional role of structure and disorder in one of the essential scaffolding proteins in the nucleotide excision repair (NER) pathway, namely Xeroderma pigmentosum complementation group A (XPA). From the analysis of the current knowledge, in addition to protein-protein docking and secondary structure prediction results presented for the first time herein, a mechanistic framework emerges, where XPA builds the NER pre-incision complex in a modular fashion, as "beads on a string", where the protein-protein interaction "beads", or modules, are interconnected by disordered link regions. This architecture is ideal to avoid the expected steric hindrance constraints of the DNA expanded bubble. Finally, the role of the XPA structural disorder in binding affinity modulation and in the sequential binding of NER core factors in the pre-incision complex is also discussed. PMID:26865925

  1. In silico 3D structure analysis accelerates the solution of a real viral structure and antibodies docking mechanism

    PubMed Central

    Miki, Motohiro; Katayama, Kazuhiko

    2012-01-01

    Norwalk virus (NoV) is responsible for most outbreaks of non-bacterial gastroenteritis. NoV is genetically diverse and show antigenically variable. Recently, we produced a monoclonal antibody called 5B-18 that reacts broadly with NoV genogroup II (GII). We suspected the 5B-18 binds to a conformational epitope on 3D structure of virion. X-ray crystallography showed us that 5B-18 binds to NoV at the P domain, which protrudes from the capsid surface of the virion. However, there seems to be no space that would allow the IgG to approach the virion. To solve this problem, we used cryo-electron microscopy to examine NoV GII virus-like particles (VLPs). The P domain rises up higher in NoV GII than in NoV GI, and it seems to form an outer layer around the virion. Finally, using in silico modeling we found the 5B-18 Fab arms and NoV P region are quite flexible, so that 5B-18 can bind the NoV virion from bottom of P domain. This study demonstrates the shortcomings of studying biological phenomenon by only one technique. Each method has limitations. Multiple methods and modeling in silico are the keys to solving structural problems. PMID:23133439

  2. Resistive foil edge grading for accelerator and other high voltage structures

    DOEpatents

    Caporaso, George J.; Sampayan, Stephen F.; Sanders, David M.

    2014-06-10

    In a structure or device having a pair of electrical conductors separated by an insulator across which a voltage is placed, resistive layers are formed around the conductors to force the electric potential within the insulator to distribute more uniformly so as to decrease or eliminate electric field enhancement at the conductor edges. This is done by utilizing the properties of resistive layers to allow the voltage on the electrode to diffuse outwards, reducing the field stress at the conductor edge. Preferably, the resistive layer has a tapered resistivity, with a lower resistivity adjacent to the conductor and a higher resistivity away from the conductor. Generally, a resistive path across the insulator is provided, preferably by providing a resistive region in the bulk of the insulator, with the resistive layer extending over the resistive region.

  3. Structural and Biochemical Characterization of Chlamydia trachomatis Hypothetical Protein CT263 Supports That Menaquinone Synthesis Occurs through the Futalosine Pathway*

    PubMed Central

    Barta, Michael L.; Thomas, Keisha; Yuan, Hongling; Lovell, Scott; Battaile, Kevin P.; Schramm, Vern L.; Hefty, P. Scott

    2014-01-01

    The obligate intracellular human pathogen Chlamydia trachomatis is the etiological agent of blinding trachoma and sexually transmitted disease. Genomic sequencing of Chlamydia indicated this medically important bacterium was not exclusively dependent on the host cell for energy. In order for the electron transport chain to function, electron shuttling between membrane-embedded complexes requires lipid-soluble quinones (e.g. menaquionone or ubiquinone). The sources or biosynthetic pathways required to obtain these electron carriers within C. trachomatis are poorly understood. The 1.58Å crystal structure of C. trachomatis hypothetical protein CT263 presented here supports a role in quinone biosynthesis. Although CT263 lacks sequence-based functional annotation, the crystal structure of CT263 displays striking structural similarity to 5′-methylthioadenosine nucleosidase (MTAN) enzymes. Although CT263 lacks the active site-associated dimer interface found in prototypical MTANs, co-crystal structures with product (adenine) or substrate (5′-methylthioadenosine) indicate that the canonical active site residues are conserved. Enzymatic characterization of CT263 indicates that the futalosine pathway intermediate 6-amino-6-deoxyfutalosine (kcat/Km = 1.8 × 103 m−1 s−1), but not the prototypical MTAN substrates (e.g. S-adenosylhomocysteine and 5′-methylthioadenosine), is hydrolyzed. Bioinformatic analyses of the chlamydial proteome also support the futalosine pathway toward the synthesis of menaquinone in Chlamydiaceae. This report provides the first experimental support for quinone synthesis in Chlamydia. Menaquinone synthesis provides another target for agents to combat C. trachomatis infection. PMID:25253688

  4. Acceleration of Lung Regeneration by Platelet-Rich Plasma Extract through the Low-Density Lipoprotein Receptor-Related Protein 5-Tie2 Pathway.

    PubMed

    Mammoto, Tadanori; Chen, Zhao; Jiang, Amanda; Jiang, Elisabeth; Ingber, Donald E; Mammoto, Akiko

    2016-01-01

    Angiogenesis, the growth of new blood vessels, plays a key role in organ development, homeostasis, and regeneration. The cooperation of multiple angiogenic factors, rather than a single factor, is required for physiological angiogenesis. Recently, we have reported that soluble platelet-rich plasma (PRP) extract, which contains abundant angiopoietin-1 and multiple other angiogenic factors, stimulates angiogenesis and maintains vascular integrity in vitro and in vivo. In this report, we have demonstrated that mouse PRP extract increases phosphorylation levels of the Wnt coreceptor low-density lipoprotein receptor-related protein 5 (LRP5) and thereby activates angiogenic factor receptor Tie2 in endothelial cells (ECs) and accelerates EC sprouting and lung epithelial cell budding in vitro. PRP extract also increases phosphorylation levels of Tie2 in the mouse lungs and accelerates compensatory lung growth and recovery of exercise capacity after unilateral pneumonectomy in mice, whereas soluble Tie2 receptor or Lrp5 knockdown attenuates the effects of PRP extract. Because human PRP extract is generated from autologous peripheral blood and can be stored at -80°C, our findings may lead to the development of novel therapeutic interventions for various angiogenesis-related lung diseases and to the improvement of strategies for lung regeneration. PMID:26091161

  5. Diffusion bonding and brazing of high purity copper for linear collider accelerator structures

    NASA Astrophysics Data System (ADS)

    Elmer, J. W.; Klingmann, J.; van Bibber, K.

    2001-05-01

    is proposed for fabricating the NLC structures. The structure would be assembled with pure silver braze inserts using a self-aligning step joint design, then the assembly would be vacuum diffusion bonded at 700 °C and 3.45 MPa pressure to seal the critical inner portion of the assembly. Finally, during the same furnace cycle, the temperature would be increased to 800 °C in order to react the silver with the copper to form a liquid braze alloy that would join and seal the outer portion of the cells together.

  6. Exploration of multi-fold symmetry element-loaded superconducting radio frequency structure for reliable acceleration of low- & medium-beta ion species

    SciTech Connect

    Huang, Shichun; Geng, Rongli

    2015-09-01

    Reliable acceleration of low- to medium-beta proton or heavy ion species is needed for future high-current superconducting radio frequency (SRF) accelerators. Due to the high-Q nature of an SRF resonator, it is sensitive to many factors such as electron loading (from either the accelerated beam or from parasitic field emitted electrons), mechanical vibration, and liquid helium bath pressure fluctuation etc. To increase the stability against those factors, a mechanically strong and stable RF structure is desirable. Guided by this consideration, multi-fold symmetry element-loaded SRF structures (MFSEL), cylindrical tanks with multiple (n>=3) rod-shaped radial elements, are being explored. The top goal of its optimization is to improve mechanical stability. A natural consequence of this structure is a lowered ratio of the peak surface electromagnetic field to the acceleration gradient as compared to the traditional spoke cavity. A disadvantage of this new structure is an increased size for a fixed resonant frequency and optimal beta. This paper describes the optimization of the electro-magnetic (EM) design and preliminary mechanical analysis for such structures.

  7. Accelerating Atomic Orbital-based Electronic Structure Calculation via Pole Expansion plus Selected Inversion

    SciTech Connect

    Lin, Lin; Chen, Mohan; Yang, Chao; He, Lixin

    2012-02-10

    We describe how to apply the recently developed pole expansion plus selected inversion (PEpSI) technique to Kohn-Sham density function theory (DFT) electronic structure calculations that are based on atomic orbital discretization. We give analytic expressions for evaluating charge density, total energy, Helmholtz free energy and atomic forces without using the eigenvalues and eigenvectors of the Kohn-Sham Hamiltonian. We also show how to update the chemical potential without using Kohn-Sham eigenvalues. The advantage of using PEpSI is that it has a much lower computational complexity than that associated with the matrix diagonalization procedure. We demonstrate the performance gain by comparing the timing of PEpSI with that of diagonalization on insulating and metallic nanotubes. For these quasi-1D systems, the complexity of PEpSI is linear with respect to the number of atoms. This linear scaling can be observed in our computational experiments when the number of atoms in a nanotube is larger than a few hundreds. Both the wall clock time and the memory requirement of PEpSI is modest. This makes it even possible to perform Kohn-Sham DFT calculations for 10,000-atom nanotubes on a single processor. We also show that the use of PEpSI does not lead to loss of accuracy required in a practical DFT calculation.

  8. Structural characterization of intact proteins is enhanced by prevalent fragmentation pathways rarely observed for peptides.

    PubMed

    Cobb, Jennifer S; Easterling, Michael L; Agar, Jeffrey N

    2010-06-01

    While collisionally activated dissociation (CAD) pathways for peptides are well characterized, those of intact proteins are not. We systematically assigned CAD product ions of ubiquitin, myoglobin, and bovine serum albumin generated using high-yield, in-source fragmentation. Assignment of >98% of hundreds of product ions implies that the fragmentation pathways described are representative of the major pathways. Protein dissociation mechanisms were found to be modulated by both source declustering potential and precursor ion charge state. Like peptides, higher charge states of proteins fragmented at lower energies next to Pro, via mobile protons, while lower charge states fragmented at higher energies after Asp and Glu, via localized protons. Unlike peptides, however, predominant fragmentation channels of proteins occurred at intermediate charge states via non-canonical mechanisms and produced extensive internal fragmentation. The non-canonical mechanisms include prominent cleavages C-terminal to Pro and Asn, and N-terminal to Ile, Leu, and Ser; these cleavages, along with internal fragments, led to a 45% increase in sequence coverage, improving the specificity of top-down protein identification. Three applications take advantage of the different mechanisms of protein fragmentation. First, modulation of declustering potential selectively fragments different charge states, allowing the source region to be used as the first stage of a low-resolution tandem mass spectrometer, facilitating pseudo-MS(3) of product ions with known parent charge states. Second, development and integration of automated modulation of ion funnel declustering potential allows users access to a particular fragmentation mechanism, yielding facile cleavage on a liquid chromatography timescale. Third, augmentation of a top-down search engine improved protein characterization. PMID:20303285

  9. Oxygen diffusion pathways in brownmillerite SrCoO2.5: Influence of structure and chemical potential

    NASA Astrophysics Data System (ADS)

    Mitra, Chandrima; Meyer, Tricia; Lee, Ho Nyung; Reboredo, Fernando A.

    2014-08-01

    To design and discover new materials for next-generation energy materials such as solid-oxide fuel cells (SOFCs), a fundamental understanding of their ionic properties and behaviors is essential. The potential applicability of a material for SOFCs is critically determined by the activation energy barrier of oxygen along various diffusion pathways. In this work, we investigate interstitial-oxygen (Oi) diffusion in brownmillerite oxide SrCoO2.5, employing a first-principles approach. Our calculations indicate highly anisotropic ionic diffusion pathways, which result from its anisotropic crystal structure. The one-dimensional-ordered oxygen vacancy channels are found to provide the easiest diffusion pathway with an activation energy barrier height of 0.62 eV. The directions perpendicular to the vacancy channels have higher energy barriers for Oint diffusion. In addition, we have studied migration barriers for oxygen vacancies that could be present as point defects within the material. This in turn could also facilitate the transport of oxygen. Interestingly, for oxygen vacancies, the lowest barrier height was found to occur within the octahedral layer with an energy of 0.82 eV. Our results imply that interstitial migration would be highly one-dimensional in nature. Oxygen vacancy transport, on the other hand, could preferentially occur in the two-dimensional octahedral plane.

  10. Hypoxic Conditioned Medium from Human Amniotic Fluid-Derived Mesenchymal Stem Cells Accelerates Skin Wound Healing through TGF-β/SMAD2 and PI3K/Akt Pathways

    PubMed Central

    Jun, Eun Kyoung; Zhang, Qiankun; Yoon, Byung Sun; Moon, Jai-Hee; Lee, Gilju; Park, Gyuman; Kang, Phil Jun; Lee, Jung Han; Kim, Areee; You, Seungkwon

    2014-01-01

    In a previous study, we isolated human amniotic fluid (AF)-derived mesenchymal stem cells (AF-MSCs) and utilized normoxic conditioned medium (AF-MSC-norCM) which has been shown to accelerate cutaneous wound healing. Because hypoxia enhances the wound healing function of mesenchymal stem cell-conditioned medium (MSC-CM), it is interesting to explore the mechanism responsible for the enhancement of wound healing function. In this work, hypoxia not only increased the proliferation of AF-MSCs but also maintained their constitutive characteristics (surface marker expression and differentiation potentials). Notably, more paracrine factors, VEGF and TGF-β1, were secreted into hypoxic conditioned medium from AF-MSCs (AF-MSC-hypoCM) compared to AF-MSC-norCM. Moreover, AF-MSC-hypoCM enhanced the proliferation and migration of human dermal fibroblasts in vitro, and wound closure in a skin injury model, as compared to AF-MSC-norCM. However, the enhancement of migration of fibroblasts accelerated by AF-MSC-hypoCM was inhibited by SB505124 and LY294002, inhibitors of TGF-β/SMAD2 and PI3K/AKT, suggesting that AF-MSC-hypoCM-enhanced wound healing is mediated by the activation of TGF-β/SMAD2 and PI3K/AKT. Therefore, AF-MSC-hypoCM enhances wound healing through the increase of hypoxia-induced paracrine factors via activation of TGF-β/SMAD2 and PI3K/AKT pathways. PMID:24398984

  11. Exploring the N-glycosylation Pathway in Chlamydomonas reinhardtii Unravels Novel Complex Structures*

    PubMed Central

    Mathieu-Rivet, Elodie; Scholz, Martin; Arias, Carolina; Dardelle, Flavien; Schulze, Stefan; Le Mauff, François; Teo, Gavin; Hochmal, Ana Karina; Blanco-Rivero, Amaya; Loutelier-Bourhis, Corinne; Kiefer-Meyer, Marie-Christine; Fufezan, Christian; Burel, Carole; Lerouge, Patrice; Martinez, Flor; Bardor, Muriel; Hippler, Michael

    2013-01-01

    Chlamydomonas reinhardtii is a green unicellular eukaryotic model organism for studying relevant biological and biotechnological questions. The availability of genomic resources and the growing interest in C. reinhardtii as an emerging cell factory for the industrial production of biopharmaceuticals require an in-depth analysis of protein N-glycosylation in this organism. Accordingly, we used a comprehensive approach including genomic, glycomic, and glycoproteomic techniques to unravel the N-glycosylation pathway of C. reinhardtii. Using mass-spectrometry-based approaches, we found that both endogenous soluble and membrane-bound proteins carry predominantly oligomannosides ranging from Man-2 to Man-5. In addition, minor complex N-linked glycans were identified as being composed of partially 6-O-methylated Man-3 to Man-5 carrying one or two xylose residues. These findings were supported by results from a glycoproteomic approach that led to the identification of 86 glycoproteins. Here, a combination of in-source collision-induced dissodiation (CID) for glycan fragmentation followed by mass tag-triggered CID for peptide sequencing and PNGase F treatment of glycopeptides in the presence of 18O-labeled water in conjunction with CID mass spectrometric analyses were employed. In conclusion, our data support the notion that the biosynthesis and maturation of N-linked glycans in the endoplasmic reticulum and Golgi apparatus occur via a GnT I-independent pathway yielding novel complex N-linked glycans that maturate differently from their counterparts in land plants. PMID:23912651

  12. STRUCTURAL DESIGN CRITERIA FOR TARGET/BLANKET SYSTEM COMPONENT MATERIALS FOR THE ACCELERATOR PRODUCTION OF TRITIUM PROJECT

    SciTech Connect

    W. JOHNSON; R. RYDER; P. RITTENHOUSE

    2001-01-01

    The design of target/blanket system components for the Accelerator Production of Tritium (APT) plant is dependent on the development of materials properties data specified by the designer. These data are needed to verify that component designs are adequate. The adequacy of the data will be related to safety, performance, and economic considerations, and to other requirements that may be deemed necessary by customers and regulatory bodies. The data required may already be in existence, as in the open technical literature, or may need to be generated, as is often the case for the design of new systems operating under relatively unique conditions. The designers' starting point for design data needs is generally some form of design criteria used in conjunction with a specified set of loading conditions and associated performance requirements. Most criteria are aimed at verifying the structural adequacy of the component, and often take the form of national or international standards such as the ASME Boiler and Pressure Vessel Code (ASME B and PV Code) or the French Nuclear Structural Requirements (RCC-MR). Whether or not there are specific design data needs associated with the use of these design criteria will largely depend on the uniqueness of the conditions of operation of the component. A component designed in accordance with the ASME B and PV Code, where no unusual environmental conditions exist, will utilize well-documented, statistically-evaluated developed in conjunction with the Code, and will not be likely to have any design data needs. On the other hand, a component to be designed to operate under unique APT conditions, is likely to have significant design data needs. Such a component is also likely to require special design criteria for verification of its structural adequacy, specifically accounting for changes in materials properties which may occur during exposure in the service environment. In such a situation it is common for the design criteria and

  13. Stringent restriction from the growth of large-scale structure on apparent acceleration in inhomogeneous cosmological models.

    PubMed

    Ishak, Mustapha; Peel, Austin; Troxel, M A

    2013-12-20

    Probes of cosmic expansion constitute the main basis for arguments to support or refute a possible apparent acceleration due to different expansion rates in the Universe as described by inhomogeneous cosmological models. We present in this Letter a separate argument based on results from an analysis of the growth rate of large-scale structure in the Universe as modeled by the inhomogeneous cosmological models of Szekeres. We use the models with no assumptions of spherical or axial symmetries. We find that while the Szekeres models can fit very well the observed expansion history without a Λ, they fail to produce the observed late-time suppression in the growth unless Λ is added to the dynamics. A simultaneous fit to the supernova and growth factor data shows that the cold dark matter model with a cosmological constant (ΛCDM) provides consistency with the data at a confidence level of 99.65%, while the Szekeres model without Λ achieves only a 60.46% level. When the data sets are considered separately, the Szekeres with no Λ fits the supernova data as well as the ΛCDM does, but provides a very poor fit to the growth data with only 31.31% consistency level compared to 99.99% for the ΛCDM. This absence of late-time growth suppression in inhomogeneous models without a Λ is consolidated by a physical explanation. PMID:24483736

  14. Effects of fuel cetane number on the structure of diesel spray combustion: An accelerated Eulerian stochastic fields method

    NASA Astrophysics Data System (ADS)

    Jangi, Mehdi; Lucchini, Tommaso; Gong, Cheng; Bai, Xue-Song

    2015-09-01

    An Eulerian stochastic fields (ESF) method accelerated with the chemistry coordinate mapping (CCM) approach for modelling spray combustion is formulated, and applied to model diesel combustion in a constant volume vessel. In ESF-CCM, the thermodynamic states of the discretised stochastic fields are mapped into a low-dimensional phase space. Integration of the chemical stiff ODEs is performed in the phase space and the results are mapped back to the physical domain. After validating the ESF-CCM, the method is used to investigate the effects of fuel cetane number on the structure of diesel spray combustion. It is shown that, depending of the fuel cetane number, liftoff length is varied, which can lead to a change in combustion mode from classical diesel spray combustion to fuel-lean premixed burned combustion. Spray combustion with a shorter liftoff length exhibits the characteristics of the classical conceptual diesel combustion model proposed by Dec in 1997 (http://dx.doi.org/10.4271/970873), whereas in a case with a lower cetane number the liftoff length is much larger and the spray combustion probably occurs in a fuel-lean-premixed mode of combustion. Nevertheless, the transport budget at the liftoff location shows that stabilisation at all cetane numbers is governed primarily by the auto-ignition process.

  15. Does Grammatical Structure Accelerate Number Word Learning? Evidence from Learners of Dual and Non-Dual Dialects of Slovenian

    PubMed Central

    Plesničar, Vesna; Razboršek, Tina; Sullivan, Jessica; Barner, David

    2016-01-01

    How does linguistic structure affect children’s acquisition of early number word meanings? Previous studies have tested this question by comparing how children learning languages with different grammatical representations of number learn the meanings of labels for small numbers, like 1, 2, and 3. For example, children who acquire a language with singular-plural marking, like English, are faster to learn the word for 1 than children learning a language that lacks the singular-plural distinction, perhaps because the word for 1 is always used in singular contexts, highlighting its meaning. These studies are problematic, however, because reported differences in number word learning may be due to unmeasured cross-cultural differences rather than specific linguistic differences. To address this problem, we investigated number word learning in four groups of children from a single culture who spoke different dialects of the same language that differed chiefly with respect to how they grammatically mark number. We found that learning a dialect which features “dual” morphology (marking of pairs) accelerated children’s acquisition of the number word two relative to learning a “non-dual” dialect of the same language. PMID:27486802

  16. Does Grammatical Structure Accelerate Number Word Learning? Evidence from Learners of Dual and Non-Dual Dialects of Slovenian.

    PubMed

    Marušič, Franc; Žaucer, Rok; Plesničar, Vesna; Razboršek, Tina; Sullivan, Jessica; Barner, David

    2016-01-01

    How does linguistic structure affect children's acquisition of early number word meanings? Previous studies have tested this question by comparing how children learning languages with different grammatical representations of number learn the meanings of labels for small numbers, like 1, 2, and 3. For example, children who acquire a language with singular-plural marking, like English, are faster to learn the word for 1 than children learning a language that lacks the singular-plural distinction, perhaps because the word for 1 is always used in singular contexts, highlighting its meaning. These studies are problematic, however, because reported differences in number word learning may be due to unmeasured cross-cultural differences rather than specific linguistic differences. To address this problem, we investigated number word learning in four groups of children from a single culture who spoke different dialects of the same language that differed chiefly with respect to how they grammatically mark number. We found that learning a dialect which features "dual" morphology (marking of pairs) accelerated children's acquisition of the number word two relative to learning a "non-dual" dialect of the same language. PMID:27486802

  17. Laser acceleration with open waveguides

    SciTech Connect

    Xie, Ming

    1999-03-01

    A unified framework based on solid-state open waveguides is developed to overcome all three major limitations on acceleration distance and hence on the feasibility of two classes of laser acceleration. The three limitations are due to laser diffraction, acceleration phase slippage, and damage of waveguide structure by high power laser. The two classes of laser acceleration are direct-field acceleration and ponderomotive-driven acceleration. Thus the solutions provided here encompass all mainstream approaches for laser acceleration, either in vacuum, gases or plasmas.

  18. Mimicking the folding pathway to improve homology-free protein structure prediction

    NASA Astrophysics Data System (ADS)

    Freed, Karl; Debartolo, Joe; Colubri, Andres; Jha, Abhishek; Fitzgerald, James; Sosnick, Tobin

    2010-03-01

    Since demonstrating that a protein's sequence encodes its structure, the prediction of structure from sequence remains an outstanding problem that impacts numerous scientific disciplines including many genome projects. By iteratively fixing secondary structure assignments of residues during Monte Carlo simulations of folding, our coarse grained model without information concerning homology or explicit side chains outperforms current homology-based secondary structure prediction methods for many proteins. The computationally rapid algorithm using only single residue (phi, psi) dihedral angle moves also generates tertiary structures of comparable accuracy to existing all-atom methods for many small proteins, particularly ones with low homology. Hence, given appropriate search strategies and scoring functions, reduced representations can be used for accurately predicting secondary structure as well as providing three-dimensional structures, thereby increasing the size of proteins approachable by homology-free methods and the accuracy of template methods whose accuracy depends on the quality of the input secondary structure. Inclusion of information from evolutionarily related sequences enhances the statistics and the accuracy of the predictions.

  19. Structure of sheared and rotating turbulence: Multiscale statistics of Lagrangian and Eulerian accelerations and passive scalar dynamics

    NASA Astrophysics Data System (ADS)

    Jacobitz, Frank G.; Schneider, Kai; Bos, Wouter J. T.; Farge, Marie

    2016-01-01

    The acceleration statistics of sheared and rotating homogeneous turbulence are studied using direct numerical simulation results. The statistical properties of Lagrangian and Eulerian accelerations are considered together with the influence of the rotation to shear ratio, as well as the scale dependence of their statistics. The probability density functions (pdfs) of both Lagrangian and Eulerian accelerations show a strong and similar dependence on the rotation to shear ratio. The variance and flatness of both accelerations are analyzed and the extreme values of the Eulerian acceleration are observed to be above those of the Lagrangian acceleration. For strong rotation it is observed that flatness yields values close to three, corresponding to Gaussian-like behavior, and for moderate and vanishing rotation the flatness increases. Furthermore, the Lagrangian and Eulerian accelerations are shown to be strongly correlated for strong rotation due to a reduced nonlinear term in this case. A wavelet-based scale-dependent analysis shows that the flatness of both Eulerian and Lagrangian accelerations increases as scale decreases, which provides evidence for intermittent behavior. For strong rotation the Eulerian acceleration is even more intermittent than the Lagrangian acceleration, while the opposite result is obtained for moderate rotation. Moreover, the dynamics of a passive scalar with gradient production in the direction of the mean velocity gradient is analyzed and the influence of the rotation to shear ratio is studied. Concerning the concentration of a passive scalar spread by the flow, the pdf of its Eulerian time rate of change presents higher extreme values than those of its Lagrangian time rate of change. This suggests that the Eulerian time rate of change of scalar concentration is mainly due to advection, while its Lagrangian counterpart is only due to gradient production and viscous dissipation.

  20. Structure of sheared and rotating turbulence: Multiscale statistics of Lagrangian and Eulerian accelerations and passive scalar dynamics.

    PubMed

    Jacobitz, Frank G; Schneider, Kai; Bos, Wouter J T; Farge, Marie

    2016-01-01

    The acceleration statistics of sheared and rotating homogeneous turbulence are studied using direct numerical simulation results. The statistical properties of Lagrangian and Eulerian accelerations are considered together with the influence of the rotation to shear ratio, as well as the scale dependence of their statistics. The probability density functions (pdfs) of both Lagrangian and Eulerian accelerations show a strong and similar dependence on the rotation to shear ratio. The variance and flatness of both accelerations are analyzed and the extreme values of the Eulerian acceleration are observed to be above those of the Lagrangian acceleration. For strong rotation it is observed that flatness yields values close to three, corresponding to Gaussian-like behavior, and for moderate and vanishing rotation the flatness increases. Furthermore, the Lagrangian and Eulerian accelerations are shown to be strongly correlated for strong rotation due to a reduced nonlinear term in this case. A wavelet-based scale-dependent analysis shows that the flatness of both Eulerian and Lagrangian accelerations increases as scale decreases, which provides evidence for intermittent behavior. For strong rotation the Eulerian acceleration is even more intermittent than the Lagrangian acceleration, while the opposite result is obtained for moderate rotation. Moreover, the dynamics of a passive scalar with gradient production in the direction of the mean velocity gradient is analyzed and the influence of the rotation to shear ratio is studied. Concerning the concentration of a passive scalar spread by the flow, the pdf of its Eulerian time rate of change presents higher extreme values than those of its Lagrangian time rate of change. This suggests that the Eulerian time rate of change of scalar concentration is mainly due to advection, while its Lagrangian counterpart is only due to gradient production and viscous dissipation. PMID:26871161

  1. Enzyme-accelerated and structure-guided crystallization of calcium carbonate: role of the carbonic anhydrase in the homologous system.

    PubMed

    Müller, Werner E G; Schlossmacher, Ute; Schröder, Heinz C; Lieberwirth, Ingo; Glasser, Gunnar; Korzhev, Michael; Neufurth, Meik; Wang, Xiaohong

    2014-01-01

    The calcareous spicules from sponges, e.g. from Sycon raphanus, are composed of almost pure calcium carbonate. In order to elucidate the formation of those structural skeletal elements, the function of the enzyme carbonic anhydrase (CA), isolated from this species, during the in vitro calcium carbonate-based spicule formation, was investigated. It is shown that the recombinant sponge CA substantially accelerates calcium carbonate formation in the in vitro diffusion assay. A stoichiometric calculation revealed that the turnover rate of the sponge CA during the calcification process amounts to 25 CO2s(-1) × molecule CA(-1). During this enzymatically driven process, initially pat-like particles are formed that are subsequently transformed to rhomboid/rhombohedroid crystals with a dimension of ~50 μm. The CA-catalyzed particles are smaller than those which are formed in the absence of the enzyme. The Martens hardness of the particles formed is ~4 GPa, a value which had been determined for other biogenic calcites. This conclusion is corroborated by energy-dispersive X-ray spectroscopy, which revealed that the particles synthesized are composed predominantly of the elements calcium, oxygen and carbon. Surprising was the finding, obtained by light and scanning electron microscopy, that the newly formed calcitic crystals associate with the calcareous spicules from S. raphanus in a highly ordered manner; the calcitic crystals almost perfectly arrange in an array orientation along the two opposing planes of the spicules, leaving the other two plane arrays uncovered. It is concluded that the CA is a key enzyme controlling the calcium carbonate biomineralization process, which directs the newly formed particles to existing calcareous spicular structures. It is expected that with the given tools new bioinspired materials can be fabricated. PMID:23978410

  2. Plasma accelerators

    SciTech Connect

    Ruth, R.D.; Chen, P.

    1986-03-01

    In this paper we discuss plasma accelerators which might provide high gradient accelerating fields suitable for TeV linear colliders. In particular we discuss two types of plasma accelerators which have been proposed, the Plasma Beat Wave Accelerator and the Plasma Wake Field Accelerator. We show that the electric fields in the plasma for both schemes are very similar, and thus the dynamics of the driven beams are very similar. The differences appear in the parameters associated with the driving beams. In particular to obtain a given accelerating gradient, the Plasma Wake Field Accelerator has a higher efficiency and a lower total energy for the driving beam. Finally, we show for the Plasma Wake Field Accelerator that one can accelerate high quality low emittance beams and, in principle, obtain efficiencies and energy spreads comparable to those obtained with conventional techniques.

  3. The structure of ends determines the pathway choice and Mre11 nuclease dependency of DNA double-strand break repair.

    PubMed

    Liao, Shuren; Tammaro, Margaret; Yan, Hong

    2016-07-01

    The key event in the choice of repair pathways for DNA double-strand breaks (DSBs) is the initial processing of ends. Non-homologous end joining (NHEJ) involves limited processing, but homology-dependent repair (HDR) requires extensive resection of the 5' strand. How cells decide if an end is channeled to resection or NHEJ is not well understood. We hypothesize that the structure of ends is a major determinant and tested this hypothesis with model DNA substrates in Xenopus egg extracts. While ends with normal nucleotides are efficiently channeled to NHEJ, ends with damaged nucleotides or bulky adducts are channeled to resection. Resection is dependent on Mre11, but its nuclease activity is critical only for ends with 5' bulky adducts. CtIP is absolutely required for activating the nuclease-dependent mechanism of Mre11 but not the nuclease-independent mechanism. Together, these findings suggest that the structure of ends is a major determinant for the pathway choice of DSB repair and the Mre11 nuclease dependency of resection. PMID:27084932

  4. The structure of ends determines the pathway choice and Mre11 nuclease dependency of DNA double-strand break repair

    PubMed Central

    Liao, Shuren; Tammaro, Margaret; Yan, Hong

    2016-01-01

    The key event in the choice of repair pathways for DNA double-strand breaks (DSBs) is the initial processing of ends. Non-homologous end joining (NHEJ) involves limited processing, but homology-dependent repair (HDR) requires extensive resection of the 5′ strand. How cells decide if an end is channeled to resection or NHEJ is not well understood. We hypothesize that the structure of ends is a major determinant and tested this hypothesis with model DNA substrates in Xenopus egg extracts. While ends with normal nucleotides are efficiently channeled to NHEJ, ends with damaged nucleotides or bulky adducts are channeled to resection. Resection is dependent on Mre11, but its nuclease activity is critical only for ends with 5′ bulky adducts. CtIP is absolutely required for activating the nuclease-dependent mechanism of Mre11 but not the nuclease-independent mechanism. Together, these findings suggest that the structure of ends is a major determinant for the pathway choice of DSB repair and the Mre11 nuclease dependency of resection. PMID:27084932

  5. Structural Insight into Archaic and Alternative Chaperone-Usher Pathways Reveals a Novel Mechanism of Pilus Biogenesis

    PubMed Central

    Pakharukova, Natalia; Garnett, James A.; Tuittila, Minna; Paavilainen, Sari; Diallo, Mamou; Xu, Yingqi; Matthews, Steve J.; Zavialov, Anton V.

    2015-01-01

    Gram-negative pathogens express fibrous adhesive organelles that mediate targeting to sites of infection. The major class of these organelles is assembled via the classical, alternative and archaic chaperone-usher pathways. Although non-classical systems share a wider phylogenetic distribution and are associated with a range of diseases, little is known about their assembly mechanisms. Here we report atomic-resolution insight into the structure and biogenesis of Acinetobacter baumannii Csu and Escherichia coli ECP biofilm-mediating pili. We show that the two non-classical systems are structurally related, but their assembly mechanism is strikingly different from the classical assembly pathway. Non-classical chaperones, unlike their classical counterparts, maintain subunits in a substantially disordered conformational state, akin to a molten globule. This is achieved by a unique binding mechanism involving the register-shifted donor strand complementation and a different subunit carboxylate anchor. The subunit lacks the classical pre-folded initiation site for donor strand exchange, suggesting that recognition of its exposed hydrophobic core starts the assembly process and provides fresh inspiration for the design of inhibitors targeting chaperone-usher systems. PMID:26587649

  6. Structural Insight into Archaic and Alternative Chaperone-Usher Pathways Reveals a Novel Mechanism of Pilus Biogenesis.

    PubMed

    Pakharukova, Natalia; Garnett, James A; Tuittila, Minna; Paavilainen, Sari; Diallo, Mamou; Xu, Yingqi; Matthews, Steve J; Zavialov, Anton V

    2015-11-01

    Gram-negative pathogens express fibrous adhesive organelles that mediate targeting to sites of infection. The major class of these organelles is assembled via the classical, alternative and archaic chaperone-usher pathways. Although non-classical systems share a wider phylogenetic distribution and are associated with a range of diseases, little is known about their assembly mechanisms. Here we report atomic-resolution insight into the structure and biogenesis of Acinetobacter baumannii Csu and Escherichia coli ECP biofilm-mediating pili. We show that the two non-classical systems are structurally related, but their assembly mechanism is strikingly different from the classical assembly pathway. Non-classical chaperones, unlike their classical counterparts, maintain subunits in a substantially disordered conformational state, akin to a molten globule. This is achieved by a unique binding mechanism involving the register-shifted donor strand complementation and a different subunit carboxylate anchor. The subunit lacks the classical pre-folded initiation site for donor strand exchange, suggesting that recognition of its exposed hydrophobic core starts the assembly process and provides fresh inspiration for the design of inhibitors targeting chaperone-usher systems. PMID:26587649

  7. Structures of Pup Ligase PafA and Depupylase Dop of the Prokaryotic Ubiquitin-like Modification Pathway

    PubMed Central

    Özcelik, Dennis; Barandun, Jonas; Schmitz, Nikolaus; Sutter, Markus; Guth, Ethan; Damberger, Fred F.; Allain, Frédéric H.-T.; Ban, Nenad; Weber-Ban, Eilika

    2015-01-01

    Pupylation is a post-translational protein modification occurring in mycobacteria and other actinobacteria that is functionally analogous to ubiquitination. Here, we report the crystal structures of the modification enzymes involved in this pathway, the Pup ligase PafA and the depupylase/deamidase Dop. Both feature a larger N-terminal domain consisting of a central β-sheet packed against a cluster of helices, a fold characteristic for carboxylate-amine ligases, and a smaller C-terminal domain unique to PafA/Dop members. The active site is located on the concave surface of the β-sheet with the nucleotide bound in a deep pocket. A conserved groove leading into the active site could play a role in Pup-binding. NMR and biochemical experiments determine the region of Pup that interacts with PafA and Dop. Structural data and mutational studies identify crucial residues for catalysis of both enzymes. PMID:22910360

  8. Structural and electronic transformation pathways in morphotropic BiFeO3.

    PubMed

    Sharma, P; Heo, Y; Jang, B-K; Liu, Y Y; Li, J Y; Yang, C-H; Seidel, J

    2016-01-01

    Phase boundaries in multiferroics, in which (anti-)ferromagnetic, ferroelectric and ferroelastic order parameters coexist, enable manipulation of magnetism and electronic properties by external electric fields through switching of the polarization in the material. It has been shown that the strain-driven morphotropic phase boundaries in a single-phase multiferroic such as BiFeO3 (BFO) can exhibit distinct electronic conductivity. However, the control of ferroelectric and phase switching and its correlation with phase boundary conductivity in this material has been a significant challenge. Supported by a thermodynamic approach, here we report a concept to precisely control different switching pathways and the associated control of electronic conductivity in mixed phase BFO. This work demonstrates a critical step to control and use non-volatile strain-conductivity coupling at the nanoscale. Beyond this observation, it provides a framework for exploring a route to control multiple order parameters coupled to ferroelastic and ferroelectric order in multiferroic materials. PMID:27581222

  9. Structural and electronic transformation pathways in morphotropic BiFeO3

    PubMed Central

    Sharma, P.; Heo, Y.; Jang, B.-K.; Liu, Y. Y.; Li, J. Y.; Yang, C.-H.; Seidel, J.

    2016-01-01

    Phase boundaries in multiferroics, in which (anti-)ferromagnetic, ferroelectric and ferroelastic order parameters coexist, enable manipulation of magnetism and electronic properties by external electric fields through switching of the polarization in the material. It has been shown that the strain-driven morphotropic phase boundaries in a single-phase multiferroic such as BiFeO3 (BFO) can exhibit distinct electronic conductivity. However, the control of ferroelectric and phase switching and its correlation with phase boundary conductivity in this material has been a significant challenge. Supported by a thermodynamic approach, here we report a concept to precisely control different switching pathways and the associated control of electronic conductivity in mixed phase BFO. This work demonstrates a critical step to control and use non-volatile strain-conductivity coupling at the nanoscale. Beyond this observation, it provides a framework for exploring a route to control multiple order parameters coupled to ferroelastic and ferroelectric order in multiferroic materials. PMID:27581222

  10. Structural characterization of the reaction pathway in phosphoserine phosphatase: Crystallographic 'snapshots' of intermediate states.

    SciTech Connect

    Wang, Weiru; Cho, Ho S.; Kim, Rosalind; Jancarik, Jaru; Yokota, Hisao; Nguyen, Henry H.; Grigoriev, Igor V.; Wemmer, David E.; Kim, Sung-Hou

    2004-04-12

    Phosphoserine phosphatase (PSP) is a member of a large class of enzymes that catalyze phosphoester hydrolysis using a phosphoaspartate enzyme intermediate. PSP is a likely regulator of the steady-state-serine level in the brain, which is a critical co-agonist of the N-methyl--aspartate type of glutamate receptors. Here, we present high-resolution (1.5 1.9 Angstrom) structures of PSP from Methanococcus jannaschii, which define the open state prior to substrate binding, the complex with phosphoserine substrate bound (with a D to N mutation in the active site), and the complex with AlF3, a transition-state analog for the phospho-transfer steps in the reaction. These structures, together with those described for the BeF3- complex (mimicking the phospho-enzyme) and the enzyme with phosphate product in the active site, provide a detailed structural picture of the full reaction cycle. The structure of the apostate indicates partial unfolding of the enzyme to allow substrate binding, with refolding in the presence of substrate to provide specificity. Interdomain and active-site conformational changes are identified. The structure with the transition state analog bound indicates a ''tight'' intermediate. A striking structure homology, with significant sequence conservation, among PSP, P-type ATPases and response regulators suggests that the knowledge of the PSP reaction mechanism from the structures determined will provide insights into the reaction mechanisms of the other enzymes in this family.

  11. Inhibition of the ubiquitin-proteasome pathway does not protect against ventilator-induced accelerated proteolysis or atrophy in the diaphragm

    PubMed Central

    Smuder, Ashley J.; Nelson, W. Bradley; Hudson, Matthew B.; Kavazis, Andreas N.; Powers, Scott K.

    2014-01-01

    Background Mechanical ventilation (MV) is a life-saving intervention in patients with acute respiratory failure. However, prolonged MV results in ventilator-induced diaphragm dysfunction (VIDD), a condition characterized by both diaphragm fiber atrophy and contractile dysfunction. Previous work has shown calpain, caspase-3 and the ubiquitin-proteasome pathway (UPP) are all activated in the diaphragm during prolonged MV. However, while it is established that both calpain and caspase-3 are important contributors to VIDD, the role that the UPP plays in VIDD remains unknown. These experiments tested the hypothesis that inhibition of the UPP will protect the diaphragm against VIDD. Methods We tested this prediction in an established animal model of MV using a highly specific UPP inhibitor, epoxomicin, to prevent MV-induced activation of the proteasome in the diaphragm (n = 8/group). Results Our results reveal that inhibition of the UPP did not prevent ventilator-induced diaphragm muscle fiber atrophy and contractile dysfunction during 12 hours of MV. Also, inhibition of the UPP does not impact MV-induced increases in calpain and caspase-3 activity in the diaphragm. Finally, administration of the proteasome inhibitor did not protect against the MV-induced increases in the expression of the E3 ligases, MuRF1 and atrogin-1/MaFbx. Conclusions Collectively, these results indicate that proteasome activation does not play a required role in VIDD during the first 12 hours of MV. PMID:24681580

  12. The Structure of L-Tyrosine 2,3-Aminomutase frmo the C-1027 Enediyne Antitumor Antibiotic Biosynthetic Pathway

    SciTech Connect

    Christianson,C.; Montavon, T.; Van Lanen, S.; Shen, B.; Bruner, S.

    2007-01-01

    The SgcC4 L-tyrosine 2,3-aminomutase (SgTAM) catalyzes the formation of (S)-{beta}-tyrosine in the biosynthetic pathway of the enediyne antitumor antibiotic C-1027. SgTAM is homologous to the histidine ammonia lyase family of enzymes whose activity is dependent on the methylideneimidazole-5-one (MIO) cofactor. Unlike the lyase enzymes, SgTAM catalyzes additional chemical transformations resulting in an overall stereospecific 1,2-amino shift in the substrate L-tyrosine to generate (S)-{beta}-tyrosine. Previously, we provided kinetic, spectroscopic, and mutagenesis data supporting the presence of MIO in the active site of SgTAM [Christenson, S. D.; Wu, W.; Spies, A.; Shen, B.; and Toney, M. D. (2003) Biochemistry 42, 12708-12718]. Here we report the first X-ray crystal structure of an MIO-containing aminomutase, SgTAM, and confirm the structural homology of SgTAM to ammonia lyases. Comparison of the structure of SgTAM to the L-tyrosine ammonia lyase from Rhodobacter sphaeroides provides insight into the structural basis for aminomutase activity. The results show that SgTAM has a closed active site well suited to retain ammonia and minimize the formation of lyase elimination products. The amino acid determinants for substrate recognition and catalysis can be predicted from the structure, setting the framework for detailed mechanistic investigations.

  13. The structure of L-tyrosine 2,3-aminomutase from the C-1027 enediyne antitumor antibiotic biosynthetic pathway.

    PubMed

    Christianson, Carl V; Montavon, Timothy J; Van Lanen, Steven G; Shen, Ben; Bruner, Steven D

    2007-06-19

    The SgcC4 l-tyrosine 2,3-aminomutase (SgTAM) catalyzes the formation of (S)-beta-tyrosine in the biosynthetic pathway of the enediyne antitumor antibiotic C-1027. SgTAM is homologous to the histidine ammonia lyase family of enzymes whose activity is dependent on the methylideneimidazole-5-one (MIO) cofactor. Unlike the lyase enzymes, SgTAM catalyzes additional chemical transformations resulting in an overall stereospecific 1,2-amino shift in the substrate l-tyrosine to generate (S)-beta-tyrosine. Previously, we provided kinetic, spectroscopic, and mutagenesis data supporting the presence of MIO in the active site of SgTAM [Christenson, S. D.; Wu, W.; Spies, A.; Shen, B.; and Toney, M. D. (2003) Biochemistry 42, 12708-12718]. Here we report the first X-ray crystal structure of an MIO-containing aminomutase, SgTAM, and confirm the structural homology of SgTAM to ammonia lyases. Comparison of the structure of SgTAM to the l-tyrosine ammonia lyase from Rhodobacter sphaeroides provides insight into the structural basis for aminomutase activity. The results show that SgTAM has a closed active site well suited to retain ammonia and minimize the formation of lyase elimination products. The amino acid determinants for substrate recognition and catalysis can be predicted from the structure, setting the framework for detailed mechanistic investigations. PMID:17516659

  14. Structural basis of the heterodimerization of the MST and RASSF SARAH domains in the Hippo signalling pathway

    SciTech Connect

    Hwang, Eunha; Cheong, Hae-Kap; Mushtaq, Ameeq Ul; Kim, Hye-Yeon; Yeo, Kwon Joo; Kim, Eunhee; Lee, Woo Cheol; Hwang, Kwang Yeon; Cheong, Chaejoon; Jeon, Young Ho

    2014-07-01

    The heterodimeric structure of the MST1 and RASSF5 SARAH domains is presented. A comparison of homodimeric and heterodimeric interactions provides a structural basis for the preferential association of the SARAH heterodimer. Despite recent progress in research on the Hippo signalling pathway, the structural information available in this area is extremely limited. Intriguingly, the homodimeric and heterodimeric interactions of mammalian sterile 20-like (MST) kinases through the so-called ‘SARAH’ (SAV/RASSF/HPO) domains play a critical role in cellular homeostasis, dictating the fate of the cell regarding cell proliferation or apoptosis. To understand the mechanism of the heterodimerization of SARAH domains, the three-dimensional structures of an MST1–RASSF5 SARAH heterodimer and an MST2 SARAH homodimer were determined by X-ray crystallography and were analysed together with that previously determined for the MST1 SARAH homodimer. While the structure of the MST2 homodimer resembled that of the MST1 homodimer, the MST1–RASSF5 heterodimer showed distinct structural features. Firstly, the six N-terminal residues (Asp432–Lys437), which correspond to the short N-terminal 3{sub 10}-helix h1 kinked from the h2 helix in the MST1 homodimer, were disordered. Furthermore, the MST1 SARAH domain in the MST1–RASSF5 complex showed a longer helical structure (Ser438–Lys480) than that in the MST1 homodimer (Val441–Lys480). Moreover, extensive polar and nonpolar contacts in the MST1–RASSF5 SARAH domain were identified which strengthen the interactions in the heterodimer in comparison to the interactions in the homodimer. Denaturation experiments performed using urea also indicated that the MST–RASSF heterodimers are substantially more stable than the MST homodimers. These findings provide structural insights into the role of the MST1–RASSF5 SARAH domain in apoptosis signalling.

  15. Intracellular Delivery of a Planar DNA Origami Structure by the Transferrin-Receptor Internalization Pathway.

    PubMed

    Schaffert, David H; Okholm, Anders H; Sørensen, Rasmus S; Nielsen, Jesper S; Tørring, Thomas; Rosen, Christian B; Kodal, Anne Louise B; Mortensen, Michael R; Gothelf, Kurt V; Kjems, Jørgen

    2016-05-01

    DNA origami provides rapid access to easily functionalized, nanometer-sized structures making it an intriguing platform for the development of defined drug delivery and sensor systems. Low cellular uptake of DNA nanostructures is a major obstacle in the development of DNA-based delivery platforms. Herein, significant strong increase in cellular uptake in an established cancer cell line by modifying a planar DNA origami structure with the iron transport protein transferrin (Tf) is demonstrated. A variable number of Tf molecules are coupled to the origami structure using a DNA-directed, site-selective labeling technique to retain ligand functionality. A combination of confocal fluorescence microscopy and quantitative (qPCR) techniques shows up to 22-fold increased cytoplasmic uptake compared to unmodified structures and with an efficiency that correlates to the number of transferrin molecules on the origami surface. PMID:27032044

  16. Crystal structure of CmlI, the arylamine oxygenase from the chloramphenicol biosynthetic pathway.

    PubMed

    Knoot, Cory J; Kovaleva, Elena G; Lipscomb, John D

    2016-09-01

    The diiron cluster-containing oxygenase CmlI catalyzes the conversion of the aromatic amine precursor of chloramphenicol to the nitroaromatic moiety of the active antibiotic. The X-ray crystal structures of the fully active, N-terminally truncated CmlIΔ33 in the chemically reduced Fe(2+)/Fe(2+) state and a cis μ-1,2(η (1):η (1))-peroxo complex are presented. These structures allow comparison with the homologous arylamine oxygenase AurF as well as other types of diiron cluster-containing oxygenases. The structural model of CmlIΔ33 crystallized at pH 6.8 lacks the oxo-bridge apparent from the enzyme optical spectrum in solution at higher pH. In its place, residue E236 forms a μ-1,3(η (1):η (2)) bridge between the irons in both models. This orientation of E236 stabilizes a helical region near the cluster which closes the active site to substrate binding in contrast to the open site found for AurF. A very similar closed structure was observed for the inactive dimanganese form of AurF. The observation of this same structure in different arylamine oxygenases may indicate that there are two structural states that are involved in regulation of the catalytic cycle. Both the structural studies and single crystal optical spectra indicate that the observed cis μ-1,2(η (1):η (1))-peroxo complex differs from the μ-η (1):η (2)-peroxo proposed from spectroscopic studies of a reactive intermediate formed in solution by addition of O2 to diferrous CmlI. It is proposed that the structural changes required to open the active site also drive conversion of the µ-1,2-peroxo species to the reactive form. PMID:27229511

  17. Greek classicism in living structure? Some deductive pathways in animal morphology.

    PubMed

    Zweers, G A

    1985-01-01

    Classical temples in ancient Greece show two deterministic illusionistic principles of architecture, which govern their functional design: geometric proportionalism and a set of illusion-strengthening rules in the proportionalism's "stochastic margin". Animal morphology, in its mechanistic-deductive revival, applies just one architectural principle, which is not always satisfactory. Whether a "Greek Classical" situation occurs in the architecture of living structure is to be investigated by extreme testing with deductive methods. Three deductive methods for explanation of living structure in animal morphology are proposed: the parts, the compromise, and the transformation deduction. The methods are based upon the systems concept for an organism, the flow chart for a functionalistic picture, and the network chart for a structuralistic picture, whereas the "optimal design" serves as the architectural principle for living structure. These methods show clearly the high explanatory power of deductive methods in morphology, but they also make one open end most explicit: neutral issues do exist. Full explanation of living structure asks for three entries: functional design within architectural and transformational constraints. The transformational constraint brings necessarily in a stochastic component: an at random variation being a sort of "free management space". This variation must be a variation from the deterministic principle of the optimal design, since any transformation requires space for plasticity in structure and action, and flexibility in role fulfilling. Nevertheless, finally the question comes up whether for animal structure a similar situation exists as in Greek Classical temples. This means that the at random variation, that is found when the optimal design is used to explain structure, comprises apart from a stochastic part also real deviations being yet another deterministic part. This deterministic part could be a set of rules that governs

  18. Ghrelin accelerates wound healing through GHS-R1a-mediated MAPK-NF-κB/GR signaling pathways in combined radiation and burn injury in rats.

    PubMed

    Liu, Cong; Huang, Jiawei; Li, Hong; Yang, Zhangyou; Zeng, Yiping; Liu, Jing; Hao, Yuhui; Li, Rong

    2016-01-01

    The therapeutic effect of ghrelin on wound healing was assessed using a rat model of combined radiation and burn injury (CRBI). Rat ghrelin, anti-rat tumor necrosis factor (TNF) α polyclonal antibody (PcAb), or selective antagonists of p38 mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase (JNK), and growth hormone secretagogue receptor (GHS-R) 1a (SB203580, SP600125, and [D-Lys3]-GHRP-6, respectively), were administered for seven consecutive days. Levels of various signaling molecules were assessed in isolated rat peritoneal macrophages. The results showed that serum ghrelin levels and levels of macrophage glucocorticoid receptor (GR) decreased, while phosphorylation of p38MAPK, JNK, and p65 nuclear factor (NF) κB increased. Ghrelin inhibited the serum induction of proinflammatory mediators, especially TNF-α, and promoted wound healing in a dose-dependent manner. Ghrelin treatment decreased phosphorylation of p38MAPK, JNK, and p65NF-κB, and increased GR levels in the presence of GHS-R1a. SB203580 or co-administration of SB203580 and SP600125 decreased TNF-α level, which may have contributed to the inactivation of p65NF-κB and increase in GR expression, as confirmed by western blotting. In conclusion, ghrelin enhances wound recovery in CRBI rats, possibly by decreasing the induction of TNF-α or other proinflammatory mediators that are involved in the regulation of GHS-R1a-mediated MAPK-NF-κB/GR signaling pathways. PMID:27271793

  19. Ghrelin accelerates wound healing through GHS-R1a-mediated MAPK-NF-κB/GR signaling pathways in combined radiation and burn injury in rats

    PubMed Central

    Liu, Cong; Huang, Jiawei; Li, Hong; Yang, Zhangyou; Zeng, Yiping; Liu, Jing; Hao, Yuhui; Li, Rong

    2016-01-01

    The therapeutic effect of ghrelin on wound healing was assessed using a rat model of combined radiation and burn injury (CRBI). Rat ghrelin, anti-rat tumor necrosis factor (TNF) α polyclonal antibody (PcAb), or selective antagonists of p38 mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase (JNK), and growth hormone secretagogue receptor (GHS-R) 1a (SB203580, SP600125, and [D-Lys3]-GHRP-6, respectively), were administered for seven consecutive days. Levels of various signaling molecules were assessed in isolated rat peritoneal macrophages. The results showed that serum ghrelin levels and levels of macrophage glucocorticoid receptor (GR) decreased, while phosphorylation of p38MAPK, JNK, and p65 nuclear factor (NF) κB increased. Ghrelin inhibited the serum induction of proinflammatory mediators, especially TNF-α, and promoted wound healing in a dose-dependent manner. Ghrelin treatment decreased phosphorylation of p38MAPK, JNK, and p65NF-κB, and increased GR levels in the presence of GHS-R1a. SB203580 or co-administration of SB203580 and SP600125 decreased TNF-α level, which may have contributed to the inactivation of p65NF-κB and increase in GR expression, as confirmed by western blotting. In conclusion, ghrelin enhances wound recovery in CRBI rats, possibly by decreasing the induction of TNF-α or other proinflammatory mediators that are involved in the regulation of GHS-R1a-mediated MAPK-NF-κB/GR signaling pathways. PMID:27271793

  20. Age-related changes in the function and structure of the peripheral sensory pathway in mice.

    PubMed

    Canta, Annalisa; Chiorazzi, Alessia; Carozzi, Valentina Alda; Meregalli, Cristina; Oggioni, Norberto; Bossi, Mario; Rodriguez-Menendez, Virginia; Avezza, Federica; Crippa, Luca; Lombardi, Raffaella; de Vito, Giuseppe; Piazza, Vincenzo; Cavaletti, Guido; Marmiroli, Paola

    2016-09-01

    This study is aimed at describing the changes occurring in the entire peripheral nervous system sensory pathway along a 2-year observation period in a cohort of C57BL/6 mice. The neurophysiological studies evidenced significant differences in the selected time points corresponding to childhood, young adulthood, adulthood, and aging (i.e., 1, 7, 15, and 25 months of age), with a parabolic course as function of time. The pathological assessment allowed to demonstrate signs of age-related changes since the age of 7 months, with a remarkable increase in both peripheral nerves and dorsal root ganglia at the subsequent time points. These changes were mainly in the myelin sheaths, as also confirmed by the Rotating-Polarization Coherent-Anti-stokes-Raman-scattering microscopy analysis. Evident changes were also present at the morphometric analysis performed on the peripheral nerves, dorsal root ganglia neurons, and skin biopsies. This extensive, multimodal characterization of the peripheral nervous system changes in aging provides the background for future mechanistic studies allowing the selection of the most appropriate time points and readouts according to the investigation aims. PMID:27459934

  1. Nucleoprotein structure influences the response of the mouse mammary tumor virus promoter to activation of the cyclic AMP signalling pathway.

    PubMed Central

    Pennie, W D; Hager, G L; Smith, C L

    1995-01-01

    Recent studies have provided evidence of crosstalk between steroid receptors and cyclic AMP (cAMP) signalling pathways in the regulation of gene expression. A synergism between intracellular phosphorylation inducers and either glucocorticoids or progestins has been shown to occur during activation of the mouse mammary tumor virus (MMTV) promoter. We have investigated the effect of 8-Br-cAMP and okadaic acid, modulators of cellular kinases and phosphatases, on the hormone-induced activation of the MMTV promoter in two forms: a transiently transfected template with a disorganized, accessible nucleoprotein structure and a stably replicating template with an ordered, inaccessible nucleoprotein structure. Both okadaic acid and 8-Br-cAMP synergize significantly with either glucocorticoids or progestins in activating the transiently transfected MMTV template. In contrast, 8-Br-cAMP, but not okadaic acid, is antagonistic to hormone-induced activation of the stably replicating MMTV template. Nuclear run-on experiments demonstrate that this inhibition is a transcriptional effect on both hormone-induced transcription and basal transcription. Surprisingly, 8-Br-cAMP does not inhibit glucocorticoid-induced changes in restriction enzyme access and nuclear factor 1 binding. However, association of a complex with the TATA box region is inhibited in the presence of 8-Br-cAMP. Thus, cAMP treatment interferes with the initiation process but does not inhibit interaction of the receptor with the template. Since the replicated, ordered MMTV templates and the transfected, disorganized templates show opposite responses to 8-Br-cAMP treatment, we conclude that chromatin structure can influence the response of a promoter to activation of the cAMP signalling pathway. PMID:7891707

  2. Insights into the structural nature of the transition state in the Kir channel gating pathway.

    PubMed

    Fowler, Philip W; Bollepalli, Murali K; Rapedius, Markus; Nematian-Ardestani, Ehsan; Shang, Lijun; Sansom, Mark Sp; Tucker, Stephen J; Baukrowitz, Thomas

    2014-01-01

    In a previous study we identified an extensive gating network within the inwardly rectifying Kir1.1 (ROMK) channel by combining systematic scanning mutagenesis and functional analysis with structural models of the channel in the closed, pre-open and open states. This extensive network appeared to stabilize the open and pre-open states, but the network fragmented upon channel closure. In this study we have analyzed the gating kinetics of different mutations within key parts of this gating network. These results suggest that the structure of the transition state (TS), which connects the pre-open and closed states of the channel, more closely resembles the structure of the pre-open state. Furthermore, the G-loop, which occurs at the center of this extensive gating network, appears to become unstructured in the TS because mutations within this region have a 'catalytic' effect upon the channel gating kinetics. PMID:25483285

  3. Insights into the structural nature of the transition state in the Kir channel gating pathway

    PubMed Central

    Fowler, Philip W; Bollepalli, Murali K; Rapedius, Markus; Nematian-Ardestani, Ehsan; Shang, Lijun; Sansom, Mark SP; Tucker, Stephen J; Baukrowitz, Thomas

    2014-01-01

    In a previous study we identified an extensive gating network within the inwardly rectifying Kir1.1 (ROMK) channel by combining systematic scanning mutagenesis and functional analysis with structural models of the channel in the closed, pre-open and open states. This extensive network appeared to stabilize the open and pre-open states, but the network fragmented upon channel closure. In this study we have analyzed the gating kinetics of different mutations within key parts of this gating network. These results suggest that the structure of the transition state (TS), which connects the pre-open and closed states of the channel, more closely resembles the structure of the pre-open state. Furthermore, the G-loop, which occurs at the center of this extensive gating network, appears to become unstructured in the TS because mutations within this region have a ‘catalytic’ effect upon the channel gating kinetics. PMID:25483285

  4. Crystal Structure of Vancosaminyltransferase GtfD from the Vancomycin Biosynthetic Pathway: Interactions with Acceptor and Nucleotide Ligands

    SciTech Connect

    Mulichak, A.M.; Lu, W.; Losey, H.C.; Walsh, C.T.; Garavito, R.M.

    2010-03-08

    The TDP-vancosaminyltransferase GtfD catalyzes the attachment of L-vancosamine to a monoglucosylated heptapeptide intermediate during the final stage of vancomycin biosynthesis. Glycosyltransferases from this and similar antibiotic pathways are potential tools for the design of new compounds that are effective against vancomycin resistant bacterial strains. We have determined the X-ray crystal structure of GtfD as a complex with TDP and the natural glycopeptide substrate at 2.0 {angstrom} resolution. GtfD, a member of the bidomain GT-B glycosyltransferase superfamily, binds TDP in the interdomain cleft, while the aglycone acceptor binds in a deep crevice in the N-terminal domain. However, the two domains are more interdependent in terms of substrate binding and overall structure than was evident in the structures of closely related glycosyltransferases GtfA and GtfB. Structural and kinetic analyses support the identification of Asp13 as a catalytic general base, with a possible secondary role for Thr10. Several residues have also been identified as being involved in donor sugar binding and recognition.

  5. Structure and composition of the distant lunar exosphere: Constraints from ARTEMIS observations of ion acceleration in time-varying fields

    NASA Astrophysics Data System (ADS)

    Halekas, J. S.; Poppe, A. R.; Farrell, W. M.; McFadden, J. P.

    2016-06-01

    By analyzing the trajectories of ionized constituents of the lunar exosphere in time-varying electromagnetic fields, we can place constraints on the composition, structure, and dynamics of the lunar exosphere. Heavy ions travel slower than light ions in the same fields, so by observing the lag between field rotations and the response of ions from the lunar exosphere, we can place constraints on the composition of the ions. Acceleration, Reconnection, Turbulence, and Electrodynamics of Moon's Interaction with the Sun (ARTEMIS) provides an ideal platform to utilize such an analysis, since its two-probe vantage allows precise timing of the propagation of field discontinuities in the solar wind, and its sensitive plasma instruments can detect the ion response. We demonstrate the utility of this technique by using fully time-dependent charged particle tracing to analyze several minutes of ion observations taken by the two ARTEMIS probes ~3000-5000 km above the dusk terminator on 25 January 2014. The observations from this time period allow us to reach several interesting conclusions. The ion production at altitudes of a few hundred kilometers above the sunlit surface of the Moon has an unexpectedly significant contribution from species with masses of 40 amu or greater. The inferred distribution of the neutral source population has a large scale height, suggesting that micrometeorite impact vaporization and/or sputtering play an important role in the production of neutrals from the surface. Our observations also suggest an asymmetry in ion production, consistent with either a compositional variation in neutral vapor production or a local reduction in solar wind sputtering in magnetic regions of the surface.

  6. Structural snapshots along the reaction pathway of Yersinia pestis RipA, a putative butyryl-CoA transferase

    SciTech Connect

    Torres, Rodrigo; Lan, Benson; Latif, Yama; Chim, Nicholas; Goulding, Celia W.

    2014-04-01

    The crystal structures of Y. pestis RipA mutants were determined to provide insights into the CoA transferase reaction pathway. Yersinia pestis, the causative agent of bubonic plague, is able to survive in both extracellular and intracellular environments within the human host, although its intracellular survival within macrophages is poorly understood. A novel Y. pestis three-gene rip (required for intracellular proliferation) operon, and in particular ripA, has been shown to be essential for survival and replication in interferon γ-induced macrophages. RipA was previously characterized as a putative butyryl-CoA transferase proposed to yield butyrate, a known anti-inflammatory shown to lower macrophage-produced NO levels. RipA belongs to the family I CoA transferases, which share structural homology, a conserved catalytic glutamate which forms a covalent CoA-thioester intermediate and a flexible loop adjacent to the active site known as the G(V/I)G loop. Here, functional and structural analyses of several RipA mutants are presented in an effort to dissect the CoA transferase mechanism of RipA. In particular, E61V, M31G and F60M RipA mutants show increased butyryl-CoA transferase activities when compared with wild-type RipA. Furthermore, the X-ray crystal structures of E61V, M31G and F60M RipA mutants, when compared with the wild-type RipA structure, reveal important conformational changes orchestrated by a conserved acyl-group binding-pocket phenylalanine, Phe85, and the G(V/I)G loop. Binary structures of M31G RipA and F60M RipA with two distinct CoA substrate conformations are also presented. Taken together, these data provide CoA transferase reaction snapshots of an open apo RipA, a closed glutamyl-anhydride intermediate and an open CoA-thioester intermediate. Furthermore, biochemical analyses support essential roles for both the catalytic glutamate and the flexible G(V/I)G loop along the reaction pathway, although further research is required to fully

  7. Pathways to Parental Knowledge: The Role of Family Process and Family Structure

    ERIC Educational Resources Information Center

    Padilla-Walker, Laura M.; Harper, James M.; Bean, Roy A.

    2011-01-01

    The purpose of the current study was (a) to examine the role of family process on child disclosure, parental solicitation, and parental knowledge and (b) to examine how patterns might differ as a function of family structure. Data for this study were taken from the Flourishing Families Project, which consists of 353 two- and 147 single-parent…

  8. Structured Parenting of Toddlers at High versus Low Genetic Risk: Two Pathways to Child Problems

    ERIC Educational Resources Information Center

    Leve, Leslie D.; Harold, Gordon T.; Ge, Xiaojia; Neiderhiser, Jenae M.; Shaw, Daniel; Scaramella, Laura V.; Reiss, David

    2009-01-01

    Objective: Little is known about how parenting might offset genetic risk to prevent the onset of child problems during toddlerhood. We used a prospective adoption design to separate genetic and environmental influences and test whether associations between structured parenting and toddler behavior problems were conditioned by genetic risk for…

  9. The structure, function and properties of sirohaem decarboxylase - an enzyme with structural homology to a transcription factor family that is part of the alternative haem biosynthesis pathway

    PubMed Central

    Palmer, David J; Schroeder, Susanne; Lawrence, Andrew D; Deery, Evelyne; Lobo, Susana A; Saraiva, Ligia M; McLean, Kirsty J; Munro, Andrew W; Ferguson, Stuart J; Pickersgill, Richard W; Brown, David G; Warren, Martin J

    2014-01-01

    Some bacteria and archaea synthesize haem by an alternative pathway, which involves the sequestration of sirohaem as a metabolic intermediate rather than as a prosthetic group. Along this pathway the two acetic acid side-chains attached to C12 and C18 are decarboxylated by sirohaem decarboxylase, a heterodimeric enzyme composed of AhbA and AhbB, to give didecarboxysirohaem. Further modifications catalysed by two related radical SAM enzymes, AhbC and AhbD, transform didecarboxysirohaem into Fe-coproporphyrin III and haem respectively. The characterization of sirohaem decarboxylase is reported in molecular detail. Recombinant versions of Desulfovibrio desulfuricans, Desulfovibrio vulgaris and Methanosarcina barkeri AhbA/B have been produced and their physical properties compared. The D. vulgaris and M. barkeri enzyme complexes both copurify with haem, whose redox state influences the activity of the latter. The kinetic parameters of the D. desulfuricans enzyme have been determined, the enzyme crystallized and its structure has been elucidated. The topology of the enzyme reveals that it shares a structural similarity to the AsnC/Lrp family of transcription factors. The active site is formed in the cavity between the two subunits and a AhbA/B-product complex with didecarboxysirohaem has been obtained. A mechanism for the decarboxylation of the kinetically stable carboxyl groups is proposed. PMID:24865947

  10. Structure, pathways and dynamics of the East Greenland Current in eddy-resolving global ocean models and observations

    NASA Astrophysics Data System (ADS)

    Aksenov, Yevgeny; Bacon, Sheldon; Nurser, George; Coward, Andrew

    2013-04-01

    The fresh and cold East Greenland Current (EGC) transports Polar waters from the Arctic Ocean southward in the Nordic Seas and the North Atlantic, affecting deep convection in the Nordic and Labrador Seas with potential impacts on the meridional overturning circulation. The pathways of the EGC in Fram Strait and south of it are well documented by observations and model simulations. However, neither the EGC's pathways upstream of Fram Strait nor its sources in the central Arctic Ocean are known sufficiently well to attribute variability of the Arctic outflow to atmospheric or oceanic mechanisms. A set of eddy-permitting and eddy-resolving global Ocean General Circulation Models (OGCMs) run with dye tracers and observational data have been used to examine the structure and dynamics of the EGC. The Montgomery function on pseudo-neutral surfaces has been applied to the model results to investigate dynamics of the current and its inter-annual variability. The sources of the EGC and the covariance of Arctic fresh water sinks via Fram Strait and the Canadian Arctic Archipelago are investigated. The model results are compared with observations, and mechanisms driving the EGC are suggested.

  11. MEG3 long noncoding RNA regulates the TGF-β pathway genes through formation of RNA-DNA triplex structures.

    PubMed

    Mondal, Tanmoy; Subhash, Santhilal; Vaid, Roshan; Enroth, Stefan; Uday, Sireesha; Reinius, Björn; Mitra, Sanhita; Mohammed, Arif; James, Alva Rani; Hoberg, Emily; Moustakas, Aristidis; Gyllensten, Ulf; Jones, Steven J M; Gustafsson, Claes M; Sims, Andrew H; Westerlund, Fredrik; Gorab, Eduardo; Kanduri, Chandrasekhar

    2015-01-01

    Long noncoding RNAs (lncRNAs) regulate gene expression by association with chromatin, but how they target chromatin remains poorly understood. We have used chromatin RNA immunoprecipitation-coupled high-throughput sequencing to identify 276 lncRNAs enriched in repressive chromatin from breast cancer cells. Using one of the chromatin-interacting lncRNAs, MEG3, we explore the mechanisms by which lncRNAs target chromatin. Here we show that MEG3 and EZH2 share common target genes, including the TGF-β pathway genes. Genome-wide mapping of MEG3 binding sites reveals that MEG3 modulates the activity of TGF-β genes by binding to distal regulatory elements. MEG3 binding sites have GA-rich sequences, which guide MEG3 to the chromatin through RNA-DNA triplex formation. We have found that RNA-DNA triplex structures are widespread and are present over the MEG3 binding sites associated with the TGF-β pathway genes. Our findings suggest that RNA-DNA triplex formation could be a general characteristic of target gene recognition by the chromatin-interacting lncRNAs. PMID:26205790

  12. Prenatal inhibition of the kynurenine pathway leads to structural changes in the hippocampus of adult rat offspring

    PubMed Central

    Khalil, Omari S; Pisar, Mazura; Forrest, Caroline M; Vincenten, Maria C J; Darlington, L Gail; Stone, Trevor W

    2014-01-01

    Glutamate receptors for N-methyl-d-aspartate (NMDA) are involved in early brain development. The kynurenine pathway of tryptophan metabolism includes the NMDA receptor agonist quinolinic acid and the antagonist kynurenic acid. We now report that prenatal inhibition of the pathway in rats with 3,4-dimethoxy-N-[4-(3-nitrophenyl)thiazol-2-yl]benzenesulphonamide (Ro61-8048) produces marked changes in hippocampal neuron morphology, spine density and the immunocytochemical localisation of developmental proteins in the offspring at postnatal day 60. Golgi–Cox silver staining revealed decreased overall numbers and lengths of CA1 basal dendrites and secondary basal dendrites, together with fewer basal dendritic spines and less overall dendritic complexity in the basal arbour. Fewer dendrites and less complexity were also noted in the dentate gyrus granule cells. More neurons containing the nuclear marker NeuN and the developmental protein sonic hedgehog were detected in the CA1 region and dentate gyrus. Staining for doublecortin revealed fewer newly generated granule cells bearing extended dendritic processes. The number of neuron terminals staining for vesicular glutamate transporter (VGLUT)-1 and VGLUT-2 was increased by Ro61-8048, with no change in expression of vesicular GABA transporter or its co-localisation with vesicle-associated membrane protein-1. These data support the view that constitutive kynurenine metabolism normally plays a role in early embryonic brain development, and that interfering with it has profound consequences for neuronal structure and morphology, lasting into adulthood. PMID:24646396

  13. MEG3 long noncoding RNA regulates the TGF-β pathway genes through formation of RNA–DNA triplex structures

    PubMed Central

    Mondal, Tanmoy; Subhash, Santhilal; Vaid, Roshan; Enroth, Stefan; Uday, Sireesha; Reinius, Björn; Mitra, Sanhita; Mohammed, Arif; James, Alva Rani; Hoberg, Emily; Moustakas, Aristidis; Gyllensten, Ulf; Jones, Steven J.M.; Gustafsson, Claes M; Sims, Andrew H; Westerlund, Fredrik; Gorab, Eduardo; Kanduri, Chandrasekhar

    2015-01-01

    Long noncoding RNAs (lncRNAs) regulate gene expression by association with chromatin, but how they target chromatin remains poorly understood. We have used chromatin RNA immunoprecipitation-coupled high-throughput sequencing to identify 276 lncRNAs enriched in repressive chromatin from breast cancer cells. Using one of the chromatin-interacting lncRNAs, MEG3, we explore the mechanisms by which lncRNAs target chromatin. Here we show that MEG3 and EZH2 share common target genes, including the TGF-β pathway genes. Genome-wide mapping of MEG3 binding sites reveals that MEG3 modulates the activity of TGF-β genes by binding to distal regulatory elements. MEG3 binding sites have GA-rich sequences, which guide MEG3 to the chromatin through RNA–DNA triplex formation. We have found that RNA–DNA triplex structures are widespread and are present over the MEG3 binding sites associated with the TGF-β pathway genes. Our findings suggest that RNA–DNA triplex formation could be a general characteristic of target gene recognition by the chromatin-interacting lncRNAs. PMID:26205790

  14. Prenatal inhibition of the kynurenine pathway leads to structural changes in the hippocampus of adult rat offspring.

    PubMed

    Khalil, Omari S; Pisar, Mazura; Forrest, Caroline M; Vincenten, Maria C J; Darlington, L Gail; Stone, Trevor W

    2014-05-01

    Glutamate receptors for N-methyl-d-aspartate (NMDA) are involved in early brain development. The kynurenine pathway of tryptophan metabolism includes the NMDA receptor agonist quinolinic acid and the antagonist kynurenic acid. We now report that prenatal inhibition of the pathway in rats with 3,4-dimethoxy-N-[4-(3-nitrophenyl)thiazol-2-yl]benzenesulphonamide (Ro61-8048) produces marked changes in hippocampal neuron morphology, spine density and the immunocytochemical localisation of developmental proteins in the offspring at postnatal day 60. Golgi-Cox silver staining revealed decreased overall numbers and lengths of CA1 basal dendrites and secondary basal dendrites, together with fewer basal dendritic spines and less overall dendritic complexity in the basal arbour. Fewer dendrites and less complexity were also noted in the dentate gyrus granule cells. More neurons containing the nuclear marker NeuN and the developmental protein sonic hedgehog were detected in the CA1 region and dentate gyrus. Staining for doublecortin revealed fewer newly generated granule cells bearing extended dendritic processes. The number of neuron terminals staining for vesicular glutamate transporter (VGLUT)-1 and VGLUT-2 was increased by Ro61-8048, with no change in expression of vesicular GABA transporter or its co-localisation with vesicle-associated membrane protein-1. These data support the view that constitutive kynurenine metabolism normally plays a role in early embryonic brain development, and that interfering with it has profound consequences for neuronal structure and morphology, lasting into adulthood. PMID:24646396

  15. Computational study on the unbinding pathways of B-RAF inhibitors and its implication for the difference of residence time: insight from random acceleration and steered molecular dynamics simulations.

    PubMed

    Niu, Yuzhen; Li, Shuyan; Pan, Dabo; Liu, Huanxiang; Yao, Xiaojun

    2016-02-21

    B-RAF kinase is a clinically validated target implicated in melanoma and advanced renal cell carcinoma (RCC). PLX4720 and TAK-632 are promising inhibitors against B-RAF with different dissociation rate constants (k(off)), but the specific mechanism that determines the difference of their dissociation rates remains unclear. In order to understand the kinetically different behaviors of these two inhibitors, their unbinding pathways were explored by random acceleration and steered molecular dynamics simulations. The random acceleration molecular dynamics (RAMD) simulations show that PLX4720 dissociates along the ATP-channel, while TAK-632 dissociates along either the ATP-channel or the allosteric-channel. The steered molecular dynamics (SMD) simulations reveal that TAK-632 is more favorable to escape from the binding pocket through the ATP-channel rather than the allosteric-channel. The PMF calculations suggest that TAK-632 presents longer residence time, which is in qualitative agreement with the experimental k(off)(k(off) = 3.3 × 10(-2) s(-1) and ΔG(off) = -82.17 ± 0.29 kcal mol(-1) for PLX4720; k(off) = 1.9 × 10(-5) s(-1) and ΔG(off) = -39.73 ± 0.79 kcal mol(-1) for PLX4720). Furthermore, the binding free decomposition by MM/GBSA illustrates that the residues K36, E54, V57, L58, L120, I125, H127, G146 and D147 located around the allosteric binding pocket play important roles in determining the longer residence time of TAK-632 by forming stronger hydrogen bond and hydrophobic interactions. Our simulations provide valuable information to design selective B-RAF inhibitors with long residence time in the future. PMID:26862741

  16. Crystal Structure of UBA2[superscript ufd]-Ubc9: Insights into E1-E2 Interactions in Sumo Pathways

    SciTech Connect

    Wang, Jing; Taherbhoy, Asad M.; Hunt, Harold W.; Seyedin, Steven N.; Miller, David W.; Miller, Darcie J.; Huang, Danny T.; Schulman, Brenda A.

    2012-04-30

    Canonical ubiquitin-like proteins (UBLs) such as ubiquitin, Sumo, NEDD8, and ISG15 are ligated to targets by E1-E2-E3 multienzyme cascades. The Sumo cascade, conserved among all eukaryotes, regulates numerous biological processes including protein localization, transcription, DNA replication, and mitosis. Sumo conjugation is initiated by the heterodimeric Aos1-Uba2 E1 enzyme (in humans called Sae1-Uba2), which activates Sumo's C-terminus, binds the dedicated E2 enzyme Ubc9, and promotes Sumo C-terminal transfer between the Uba2 and Ubc9 catalytic cysteines. To gain insights into details of E1-E2 interactions in the Sumo pathway, we determined crystal structures of the C-terminal ubiquitin fold domain (ufd) from yeast Uba2 (Uba2{sup ufd}), alone and in complex with Ubc9. The overall structures of both yeast Uba2{sup ufd} and Ubc9 superimpose well on their individual human counterparts, suggesting conservation of fundamental features of Sumo conjugation. Docking the Uba2{sup ufd}-Ubc9 and prior full-length human Uba2 structures allows generation of models for steps in Sumo transfer from Uba2 to Ubc9, and supports the notion that Uba2 undergoes remarkable conformational changes during the reaction. Comparisons to previous structures from the NEDD8 cascade demonstrate that UBL cascades generally utilize some parallel E1-E2 interaction surfaces. In addition, the structure of the Uba2{sup ufd}-Ubc9 complex reveals interactions unique to Sumo E1 and E2. Comparison with a previous Ubc9-E3 complex structure demonstrates overlap between Uba2 and E3 binding sites on Ubc9, indicating that loading with Sumo and E3-catalyzed transfer to substrates are strictly separate steps. The results suggest mechanisms establishing specificity and order in Sumo conjugation cascades.

  17. Molecular Details of Olfactomedin Domains Provide Pathway to Structure-Function Studies

    PubMed Central

    Hill, Shannon E.; Donegan, Rebecca K.; Nguyen, Elaine; Desai, Tanay M.; Lieberman, Raquel L.

    2015-01-01

    Olfactomedin (OLF) domains are found within extracellular, multidomain proteins in numerous tissues of multicellular organisms. Even though these proteins have been implicated in human disorders ranging from cancers to attention deficit disorder to glaucoma, little is known about their structure(s) and function(s). Here we biophysically, biochemically, and structurally characterize OLF domains from H. sapiens olfactomedin-1 (npoh-OLF, also called noelin, pancortin, OLFM1, and hOlfA), and M. musculus gliomedin (glio-OLF, also called collomin, collmin, and CRG-L2), and compare them with available structures of myocilin (myoc-OLF) recently reported by us and R. norvegicus glio-OLF and M. musculus latrophilin-3 (lat3-OLF) by others. Although the five-bladed β-propeller architecture remains unchanged, numerous physicochemical characteristics differ among these OLF domains. First, npoh-OLF and glio-OLF exhibit prominent, yet distinct, positive surface charges and copurify with polynucleotides. Second, whereas npoh-OLF and myoc-OLF exhibit thermal stabilities typical of human proteins near 55°C, and most myoc-OLF variants are destabilized and highly prone to aggregation, glio-OLF is nearly 20°C more stable and significantly more resistant to chemical denaturation. Phylogenetically, glio-OLF is most similar to primitive OLFs, and structurally, glio-OLF is missing distinguishing features seen in OLFs such as the disulfide bond formed by N- and C- terminal cysteines, the sequestered Ca2+ ion within the propeller central hydrophilic cavity, and a key loop-stabilizing cation-π interaction on the top face of npoh-OLF and myoc-OLF. While deciphering the explicit biological functions, ligands, and binding partners for OLF domains will likely continue to be a challenging long-term experimental pursuit, we used structural insights gained here to generate a new antibody selective for myoc-OLF over npoh-OLF and glio-OLF as a first step in overcoming the impasse in detailed

  18. Molecular Details of Olfactomedin Domains Provide Pathway to Structure-Function Studies.

    PubMed

    Hill, Shannon E; Donegan, Rebecca K; Nguyen, Elaine; Desai, Tanay M; Lieberman, Raquel L

    2015-01-01

    Olfactomedin (OLF) domains are found within extracellular, multidomain proteins in numerous tissues of multicellular organisms. Even though these proteins have been implicated in human disorders ranging from cancers to attention deficit disorder to glaucoma, little is known about their structure(s) and function(s). Here we biophysically, biochemically, and structurally characterize OLF domains from H. sapiens olfactomedin-1 (npoh-OLF, also called noelin, pancortin, OLFM1, and hOlfA), and M. musculus gliomedin (glio-OLF, also called collomin, collmin, and CRG-L2), and compare them with available structures of myocilin (myoc-OLF) recently reported by us and R. norvegicus glio-OLF and M. musculus latrophilin-3 (lat3-OLF) by others. Although the five-bladed β-propeller architecture remains unchanged, numerous physicochemical characteristics differ among these OLF domains. First, npoh-OLF and glio-OLF exhibit prominent, yet distinct, positive surface charges and copurify with polynucleotides. Second, whereas npoh-OLF and myoc-OLF exhibit thermal stabilities typical of human proteins near 55°C, and most myoc-OLF variants are destabilized and highly prone to aggregation, glio-OLF is nearly 20°C more stable and significantly more resistant to chemical denaturation. Phylogenetically, glio-OLF is most similar to primitive OLFs, and structurally, glio-OLF is missing distinguishing features seen in OLFs such as the disulfide bond formed by N- and C- terminal cysteines, the sequestered Ca2+ ion within the propeller central hydrophilic cavity, and a key loop-stabilizing cation-π interaction on the top face of npoh-OLF and myoc-OLF. While deciphering the explicit biological functions, ligands, and binding partners for OLF domains will likely continue to be a challenging long-term experimental pursuit, we used structural insights gained here to generate a new antibody selective for myoc-OLF over npoh-OLF and glio-OLF as a first step in overcoming the impasse in detailed

  19. Lactobacillus fermentum AGR1487 cell surface structures and supernatant increase paracellular permeability through different pathways.

    PubMed

    Sengupta, Ranjita; Anderson, Rachel C; Altermann, Eric; McNabb, Warren C; Ganesh, Siva; Armstrong, Kelly M; Moughan, Paul J; Roy, Nicole C

    2015-08-01

    Lactobacillus fermentum is commonly found in food products, and some strains are known to have beneficial effects on human health. However, our previous research indicated that L. fermentum AGR1487 decreases in vitro intestinal barrier integrity. The hypothesis was that cell surface structures of AGR1487 are responsible for the observed in vitro effect. AGR1487 was compared to another human oral L. fermentum strain, AGR1485, which does not cause the same effect. The examination of phenotypic traits associated with the composition of cell surface structures showed that compared to AGR1485, AGR1487 had a smaller genome, utilized different sugars, and had greater tolerance to acid and bile. The effect of the two strains on intestinal barrier integrity was determined using two independent measures of paracellular permeability of the intestinal epithelial Caco-2 cell line. The transepithelial electrical resistance (TEER) assay specifically measures ion permeability, whereas the mannitol flux assay measures the passage of uncharged molecules. Both live and UV-inactivated AGR1487 decreased TEER across Caco-2 cells implicating the cell surfaces structures in the effect. However, only live AGR1487, and not UV-inactivated AGR1487, increased the rate of passage of mannitol, implying that a secreted component(s) is responsible for this effect. These differences in barrier integrity results are likely due to the TEER and mannitol flux assays measuring different characteristics of the epithelial barrier, and therefore imply that there are multiple mechanisms involved in the effect of AGR1487 on barrier integrity. PMID:25943073

  20. Structural modeling and analysis of dengue-mediated inhibition of interferon signaling pathway.

    PubMed

    Aslam, B; Ahmad, J; Ali, A; Paracha, R Z; Tareen, S H K; Khusro, S; Ahmad, T; Muhammad, S A; Niazi, U; Azevedo, V

    2015-01-01

    Dengue virus (DENV) belongs to the family Flaviviridae and can cause major health problems worldwide, including dengue fever and dengue shock syndrome. DENV replicon in human cells inhibits interferon α and β with the help of its non-structural proteins. Non-structural protein 5 (NS5) of DENV is responsible for the proteasome-mediated degradation of signal transducer and activator of transcription (STAT) 2 protein, which has been implicated in the development of resistance against interferon-mediated antiviral effect. This degradation of STAT2 primarily occurs with the help of E3 ubiquitin ligases. Seven in absentia homologue (SIAH) 2 is a host protein that can mediate the ubiquitination of proteins and is known for its interaction with NS5. In this study, comprehensive computational analysis was performed to characterize the protein-protein interactions between NS5, SIAH2, and STAT2 to gain insight into the residues and sites of interaction between these proteins. The objective of the study was to structurally characterize the NS5-STAT2, SIAH2-STAT2, and NS5-SIAH2 interactions along with the determination of the possible reaction pattern for the degradation of STAT2. Docking and physicochemical studies indicated that DENV NS5 may first interact with the host SIAH2, which can then proceed towards binding with STAT2 from the side of SIAH2. These implications are reported for the first time and require validation by wet-lab studies. PMID:25966194