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. The foxhole accelerating structure

    SciTech Connect

    Fernow, R.C.; Claus, J.

    1992-07-17

    This report examines some properties of a new type of open accelerating structure. It consists of a series of rectangular cavities, which we call foxholes, joined by a beam channel. The power for accelerating the particles comes from an external radiation source and enters the cavities through their open upper surfaces. Analytic and computer calculations are presented showing that the foxhole is a suitable structure for accelerating relativistic electrons.

  3. 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.

  4. 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.

  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. Accelerating Adverse Outcome Pathway (AOP) development ...

    EPA Pesticide Factsheets

    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. However, the conventional process for assembly of these AOPs is time and resource intensive, and has been a rate limiting step for AOP use and development. Therefore computational approaches to accelerate the process need to be developed. We previously developed a method for generating computationally predicted AOPs (cpAOPs) by association mining and integration of data from publicly available databases. In this work, a cpAOP network of ~21,000 associations was established between 105 phenotypes from TG-GATEs rat liver data from different time points (including microarray, pathological effects and clinical chemistry data), 994 REACTOME pathways, 688 High-throughput assays from ToxCast and 194 chemicals. A second network of 128,536 associations was generated by connecting 255 biological target genes from ToxCast to 4,980 diseases from CTD using either HT screening activity from ToxCast for 286 chemicals or CTD gene expression changes in response to 2,330 chemicals. Both networks were separately evaluated through manual extraction of disease-specific cpAOPs and comparison with expert curation of the relevant literature. By employing data integration strategies that involve the weighting of n

  7. 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. |

    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.

  8. 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.

  9. Vibrational Stability of NLC Linac accelerating structure

    SciTech Connect

    Le Pimpec, Frederic

    2002-09-25

    The vibration of components of the NLC linac, such as accelerating structures and girders, is being studied both experimentally and analytically. Various effects are being considered including structural resonances and vibration caused by cooling water in the accelerating structure. This paper reports the status of ongoing work.

  10. 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.

  11. Comparison of high group velocity accelerating structures

    SciTech Connect

    Farkas, Z.D.; Wilson, P.B.

    1987-02-01

    It is well known that waveguides with no perturbations have phase velocities greater than the velocity of light c. If the waveguide dimensions are chosen so that the phase velocity is only moderately greater than c, only small perturbations are required to reduce the phase velocity to be synchronous with a high energy particle bunch. Such a lightly loaded accelerator structure will have smaller longitudinal and transverse wake potentials and hence will lead to lower emittance growth in an accelerated beam. Since these structures are lightly loaded, their group velocities are only slightly less than c and not in the order of 0.01c, as is the case for the standard disk-loaded structures. To ascertain that the peak and average power requirements for these structures are not prohibitive, we examine the elastance and the Q for several traveling wave structures: phase slip structures, bellows-like structures, and lightly loaded disk-loaded structures.

  12. 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.

  13. The grating as an accelerating structure

    SciTech Connect

    Fernow, R.C.

    1991-02-01

    This report considers the use of a diffraction grating as an accelerating structure for charged particle beams. We examine the functional dependence of the electromagnetic fields above the surface of a grating. Calculations are made of the strength of the accelerating modes for structures with {pi} and 2{pi} phase advance per period and for incident waves polarized with either the E or H vector along the grooves of the grating. We consider examples of using gratings in a laser linac and in a grating lens. We also briefly examine previous results published about this subject. 36 refs.

  14. Multi-Mode Cavity Accelerator Structure

    SciTech Connect

    Jiang, Yong; Hirshfield, Jay Leonard

    2016-11-10

    This project aimed to develop a prototype for a novel accelerator structure comprising coupled cavities that are tuned to support modes with harmonically-related eigenfrequencies, with the goal of reaching an acceleration gradient >200 MeV/m and a breakdown rate <10-7/pulse/meter. Phase I involved computations, design, and preliminary engineering of a prototype multi-harmonic cavity accelerator structure; plus tests of a bimodal cavity. A computational procedure was used to design an optimized profile for a bimodal cavity with high shunt impedance and low surface fields to maximize the reduction in temperature rise ΔT. This cavity supports the TM010 mode and its 2nd harmonic TM011 mode. Its fundamental frequency is at 12 GHz, to benchmark against the empirical criteria proposed within the worldwide High Gradient collaboration for X-band copper structures; namely, a surface electric field Esurmax< 260 MV/m and pulsed surface heating ΔTmax< 56 °K. With optimized geometry, amplitude and relative phase of the two modes, reductions are found in surface pulsed heating, modified Poynting vector, and total RF power—as compared with operation at the same acceleration gradient using only the fundamental mode.

  15. Accelerator Structure Development for NLC/GLC

    SciTech Connect

    Wang, J

    2004-03-05

    The NLC (Next Linear Collider) and GLC (Global Linear Collider) [1,2] are e{sup +}e{sup -} linear collider proposals based on room-temperature accelerator technology--so called ''warm machines'' in comparison with the TESLA ''cold machine'' that is based on superconducting accelerator technology. There have been two major challenges in developing X-band (11.4 GHz) accelerator structures for the GLC/NLC. The first is to demonstrate stable, long-term operation at the high gradient (65 MV/m) that is required to optimize the machine cost. The second is to strongly suppress the beam induced long-range wakefields, which is required to achieve high luminosity. The development of high gradient structures has been a high priority in recent years. Nearly thirty X-band structures with various rf parameters, cavity shapes and coupler types have been fabricated and tested since 2000. This program has been a successful collaborative effort among groups at SLAC, KEK, FNAL and other labs. A summary of the main achievements and experiences are presented in this paper as well as a status report on the structure design, high power performance, manufacturing techniques, and other structure related issues.

  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.

  17. Advanced accelerator and mm-wave structure research at LANL

    SciTech Connect

    Simakov, Evgenya Ivanovna

    2016-06-22

    This document outlines acceleration projects and mm-wave structure research performed at LANL. The motivation for PBG research is described first, with reference to couplers for superconducting accelerators and structures for room-temperature accelerators and W-band TWTs. These topics are then taken up in greater detail: PBG structures and the MIT PBG accelerator; SRF PBG cavities at LANL; X-band PBG cavities at LANL; and W-band PBG TWT at LANL. The presentation concludes by describing other advanced accelerator projects: beam shaping with an Emittance Exchanger, diamond field emitter array cathodes, and additive manufacturing of novel accelerator structures.

  18. Micromechanical structures and microelectronics for acceleration sensing

    NASA Astrophysics Data System (ADS)

    Davies, Brady R.; Montague, Stephen; Smith, James H.; Lemkin, Mark

    1997-09-01

    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 microelectronics 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 approximately equals 25 G accelerometer) will be discussed in the paper (where 1 G approximately equals 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.

  19. 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...

  20. Locating Bound Structures in the Accelerating Universe

    NASA Astrophysics Data System (ADS)

    Pearson, David; Batuski, D. J.

    2013-01-01

    Given the overwhelming evidence of the universe’s accelerating expansion, the question of what structures are gravitationally bound becomes one of utmost interest. Dunner et al. 2006 (D06) and Busha et al. 2003 (B03) set out to answer this question analytically, and they arrived at fairly different answers owing to the differences in their assumptions of velocities at the present epoch. Applying their criteria to different superclusters, it’s possible to make predictions about what structures may be bound. We apply the criteria of D06 and B03 to the Aquarius, Microscopium, Corona Borealis, and Shapley superclusters to make predictions about what structures might be bound and compare with the results of simple N-body simulations to determine which method is a better predictor and to determine the likelihood that parts or all of the superclusters listed above are bound. We find that D06 tend to predict more structure to be bound than B03, and the results of the N-body simulations usually lie somewhere in between the two sets of predictions. Observational evidence, and simulation data suggests that pairs of clusters in Aquarius and Microscopium are gravitationally bound, and that Shapley contains a large complex of clusters that are bound, along with some additional bound pairs. The likelihood that any of the clusters in Corona Borealis are bound to one another is very small, contrary to the claims of Small et al. 1998, who claimed that the entire supercluster is likely gravitationally bound. Busha M. T., Adams F. C., Wechsler R. H., Evrard A. E., 2003, ApJ, 596, 713 Dunner R., Araya P. A., Meza A., Reisenegger A., 2006, MNRAS, 306, 803 Small T. A., Ma C., Sargent W. L. W., Hamilton D., 1998, ApJ, 492, 45

  1. 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.

  2. Progress Toward NLC/GLC Prototype Accelerator Structures

    SciTech Connect

    Wang, J

    2004-09-13

    The accelerator structure groups for NLC (Next Linear Collider) and GLC (Global Linear Colliders) have successfully collaborated on the research and development of a major series of advanced accelerator structures based on room-temperature technology at X-band frequency. The progress in design, simulation, microwave measurement and high gradient tests are summarized in this paper. The recent effort in design and fabrication of the accelerator structure prototype for the main linac is presented in detail including HOM (High Order Mode) suppression and design of HOM couplers and fundamental mode couplers, optimized accelerator cavities as well as plans for future structures.

  3. 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...

  4. Operational experience with room temperature continuous wave accelerator structures

    NASA Astrophysics Data System (ADS)

    Alimov, A. S.; Ishkhanov, B. S.; Piskarev, I. M.; Shvedunov, V. I.; Tiunov, A. V.

    1993-05-01

    The paper reports the results of the computer simulation of parameters of the on-axis coupled accelerator structure for the continuous wave racetrack microtron. The operational experience with the accelerating sections on the basis of the on-axis coupled structure is described.

  5. 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.

  6. Manifold damping of the NLC detuned accelerating structure

    NASA Astrophysics Data System (ADS)

    Kroll, N.; Thompson, K.; Bane, K.; Gluckstern, R.; Ko, K.; Miller, R.; Ruth, R.

    1995-06-01

    In order to mitigate the reappearance of the HOM wakefield of a detuned accelerator structure and relax tolerance requirements, we propose to provide low level damping by coupling all cavities to several identical and symmetrically located waveguides (manifolds) which run parallel to each accelerator structure and are terminated at each end by matched loads. The waveguides are designed such that all modes which couple to the acceleration mode are non-propagating at the acceleration mode frequency. Hence the coupling irises can be designed to provide large coupling to higher frequency modes without damping the acceleration mode. Because the higher order modes are detuned, they are localized and have a broad spectrum of phase velocities of both signs. They are therefore capable of coupling effectively to all propagating modes in the waveguides. Methods of analyzing and results obtained for the very complex system of modes in the accelerating structure and manifolds are presented.

  7. Manifold damping of the NLC detuned accelerating structure

    SciTech Connect

    Kroll, N.; Thompson, K.; Bane, K.; Ko, K.; Miller, R.; Ruth, R.; Gluckstern, R.

    1994-09-01

    In order to investigate the reappearance of the HOM wakefield of a detuned accelerator structure and relax tolerance requirements, we propose to provide low level damping by coupling all cavities to several identical and symmetrically located waveguides (manifolds) which run parallel to each accelerator structure and are terminated at each end by matched loads. The waveguides are designed such that all modes which couple to the acceleration mode are non-propagating at the acceleration mode frequency. Hence the coupling irises can be designed to provide large coupling to higher frequency modes without damping the acceleration mode. Because the higher order modes are detuned, they are localized and have a broad spectrum of phase velocities of both signs. They are therefore capable of coupling effectively to all propagating modes in the waveguides. Methods of analyzing and results obtained for the very complex system of modes in the accelerating structure and manifolds are presented.

  8. 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.

  9. Particle accelerations and current structures of Weibel and Filamentation instabilities

    NASA Astrophysics Data System (ADS)

    Ryu, C. M.; Huynh, C. T.

    2015-12-01

    Particle accelerations of the Wibel instability (WI) and the Filamentation instability(FI) are studied by using PIC simuations, comparing them side-by-side. Although two instabilities are almost identical in the linear growth phase, significant differences are found in the nonlinear phase in their particle accelerations and current structures. The FI shows enhanced electron acceleration, whereas particle acceleration is almost absent in the WI. The different particle accelerations between the FI and the WI seem to be associated with their different current structures; a hollow electron current structure for the FI and a center filled current structure for that of the WI. Different electron distributions seem to bring in different current filament structures, eventually leading to different magnetic characteristics.

  10. 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.

  11. 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.

  12. Multipactor Physics, Acceleration, and Breakdown in Dielectric-Loaded Accelerating Structures

    SciTech Connect

    Fischer, Richard P.; Gold, Steven H.

    2016-07-01

    The objective of this 3-year program is to study the physics issues associated with rf acceleration in dielectric-loaded accelerating (DLA) structures, with a focus on the key issue of multipactor loading, which has been found to cause very significant rf power loss in DLA structures whenever the rf pulsewidth exceeds the multipactor risetime (~10 ns). The experiments are carried out in the X-band magnicon laboratory at the Naval Research Laboratory (NRL) in collaboration with Argonne National Laboratory (ANL) and Euclid Techlabs LLC, who develop the test structures with support from the DoE SBIR program. There are two main elements in the research program: (1) high-power tests of DLA structures using the magnicon output (20 MW @11.4 GHz), and (2) tests of electron acceleration in DLA structures using relativistic electrons from a compact X-band accelerator. The work during this period has focused on a study of the use of an axial magnetic field to suppress multipactor in DLA structures, with several new high power tests carried out at NRL, and on preparation of the accelerator for the electron acceleration experiments.

  13. 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).

  14. Helical Pulse Line Structures for Ion Acceleration

    SciTech Connect

    Briggs, R.J.; Reginato, L.L.; Waldron, W.L.

    2005-05-01

    The basic concept of the ''Pulse Line Ion Accelerator'' is presented, where pulse power sources create a ramped traveling wave voltage pulse on a helical pulse line. Ions can surf on this traveling wave and achieve energy gains much larger than the peak applied voltage. Tapered and untapered lines are compared, and a transformer coupling technique for launching the wave is described.

  15. 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.

  16. 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.

  17. High-performance computing in accelerating structure design and analysis

    NASA Astrophysics Data System (ADS)

    Li, Zenghai; Folwell, Nathan; Ge, Lixin; Guetz, Adam; Ivanov, Valentin; Kowalski, Marc; Lee, Lie-Quan; Ng, Cho-Kuen; Schussman, Greg; Stingelin, Lukas; Uplenchwar, Ravindra; Wolf, Michael; Xiao, Liling; Ko, Kwok

    2006-03-01

    Future high-energy accelerators such as the Next Linear Collider (NLC) will accelerate multi-bunch beams of high current and low emittance to obtain high luminosity, which put stringent requirements on the accelerating structures for efficiency and beam stability. While numerical modeling has been quite standard in accelerator R&D, designing the NLC accelerating structure required a new simulation capability because of the geometric complexity and level of accuracy involved. Under the US DOE Advanced Computing initiatives (first the Grand Challenge and now SciDAC), SLAC has developed a suite of electromagnetic codes based on unstructured grids and utilizing high-performance computing to provide an advanced tool for modeling structures at accuracies and scales previously not possible. This paper will discuss the code development and computational science research (e.g. domain decomposition, scalable eigensolvers, adaptive mesh refinement) that have enabled the large-scale simulations needed for meeting the computational challenges posed by the NLC as well as projects such as the PEP-II and RIA. Numerical results will be presented to show how high-performance computing has made a qualitative improvement in accelerator structure modeling for these accelerators, either at the component level (single cell optimization), or on the scale of an entire structure (beam heating and long-range wakefields).

  18. High-Performance Computing in Accelerating Structure Design And Analysis

    SciTech Connect

    Li, Z.H.; Folwell, N.; Ge, Li-Xin; Guetz, A.; Ivanov, V.; Kowalski, M.; Lee, L.Q.; Ng, C.K.; Schussman, G.; Stingelin, L.; Uplenchwar, R.; Wolf, M.; Xiao, L.L.; Ko, K.; /SLAC /PSI, Villigen /Illinois U., Urbana

    2006-06-27

    Future high-energy accelerators such as the Next Linear Collider (NLC) will accelerate multi-bunch beams of high current and low emittance to obtain high luminosity, which put stringent requirements on the accelerating structures for efficiency and beam stability. While numerical modeling has been quite standard in accelerator R&D, designing the NLC accelerating structure required a new simulation capability because of the geometric complexity and level of accuracy involved. Under the US DOE Advanced Computing initiatives (first the Grand Challenge and now SciDAC), SLAC has developed a suite of electromagnetic codes based on unstructured grids and utilizing high performance computing to provide an advanced tool for modeling structures at accuracies and scales previously not possible. This paper will discuss the code development and computational science research (e.g. domain decomposition, scalable eigensolvers, adaptive mesh refinement) that have enabled the large-scale simulations needed for meeting the computational challenges posed by the NLC as well as projects such as the PEP-II and RIA. Numerical results will be presented to show how high performance computing has made a qualitative improvement in accelerator structure modeling for these accelerators, either at the component level (single cell optimization), or on the scale of an entire structure (beam heating and long range wakefields).

  19. ELECTROMAGNETIC SIMULATIONS OF DIELECTRIC WALL ACCELERATOR STRUCTURES FOR ELECTRON BEAM ACCELERATION

    SciTech Connect

    Nelson, S D; Poole, B R

    2005-05-05

    Dielectric Wall Accelerator (DWA) technology incorporates the energy storage mechanism, the switching mechanism, and the acceleration mechanism for electron beams. Electromagnetic simulations of DWA structures includes these effects and also details of the switch configuration and how that switch time affects the electric field pulse which accelerates the particle beam. DWA structures include both bi-linear and bi-spiral configurations with field gradients on the order of 20MV/m and the simulations include the effects of the beampipe, the beampipe walls, the DWA High Gradient Insulator (HGI) insulating stack, wakefield impedance calculations, and test particle trajectories with low emittance gain. Design trade-offs include the transmission line impedance (typically a few ohms), equilibration ring optimization, driving switch inductances, and layer-to-layer coupling effects and the associated affect on the acceleration pulse's peak value.

  20. Three-Year MD Programs: Perspectives From the Consortium of Accelerated Medical Pathway Programs (CAMPP).

    PubMed

    Cangiarella, Joan; Fancher, Tonya; Jones, Betsy; Dodson, Lisa; Leong, Shou Ling; Hunsaker, Matthew; Pallay, Robert; Whyte, Robert; Holthouser, Amy; Abramson, Steven B

    2017-04-01

    In the last decade, there has been renewed interest in three-year MD pathway programs. In 2015, with support from the Josiah Macy Jr., Foundation, eight North American medical schools with three-year accelerated medical pathway programs formed the Consortium of Accelerated Medical Pathway Programs (CAMPP). The schools are two campuses of the Medical College of Wisconsin; McMaster University Michael G. DeGroote School of Medicine; Mercer University School of Medicine; New York University School of Medicine; Penn State College of Medicine; Texas Tech University Health Sciences Center School of Medicine; University of California, Davis School of Medicine; and University of Louisville School of Medicine. These programs vary in size and medical specialty focus but all include the reduction of student debt from savings in tuition costs. Each school's mission to create a three-year pathway program differs; common themes include the ability to train physicians to practice in underserved areas or to allow students for whom the choice of specialty is known to progress more quickly. Compared with McMaster, these programs are small, but most capitalize on training and assessing competency across the undergraduate medical education-graduate medical education continuum and include conditional acceptance into an affiliated residency program. This article includes an overview of each CAMPP school with attention to admissions, curriculum, financial support, and regulatory challenges associated with the design of an accelerated pathway program. These programs are relatively new, with a small number of graduates; this article outlines opportunities and challenges for schools considering the development of accelerated programs.

  1. Blind protein structure prediction using accelerated free-energy simulations

    PubMed Central

    Perez, Alberto; Morrone, Joseph A.; Brini, Emiliano; MacCallum, Justin L.; Dill, Ken A.

    2016-01-01

    We report a key proof of principle of a new acceleration method [Modeling Employing Limited Data (MELD)] for predicting protein structures by molecular dynamics simulation. It shows that such Boltzmann-satisfying techniques are now sufficiently fast and accurate to predict native protein structures in a limited test within the Critical Assessment of Structure Prediction (CASP) community-wide blind competition. PMID:27847872

  2. 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.

  3. 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

  4. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2006-11-01

    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 ˜ 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 ˜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.

  6. rf breakdown tests of 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.

    2016-01-01

    We are exploring the physics and frequency-scaling of vacuum rf breakdowns at sub-THz frequencies. We present the experimental results of rf tests performed in metallic mm-wave accelerating structures. These experiments were carried out at the facility for advanced accelerator experimental tests (FACET) at the SLAC National Accelerator Laboratory. The rf fields were excited by the FACET ultrarelativistic electron beam. We compared the performances of metal structures made with copper and stainless steel. The rf frequency of the fundamental accelerating mode, propagating in the structures at the speed of light, varies from 115 to 140 GHz. The traveling wave structures are 0.1 m long and composed of 125 coupled cavities each. We determined the peak electric field and pulse length where the structures were not damaged by rf breakdowns. We calculated the electric and magnetic field correlated with the rf breakdowns using the FACET bunch parameters. The wakefields were calculated by a frequency domain method using periodic eigensolutions. Such a method takes into account wall losses and is applicable to a large variety of geometries. The maximum achieved accelerating gradient is 0.3 GV /m with a peak surface electric field of 1.5 GV /m and a pulse length of about 2.4 ns.

  7. 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.

  8. 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.

  9. Transverse wake field simulations for the ILC acceleration structure

    SciTech Connect

    Solyak, N.; Lunin, A.; Yakovlev, V.; /Fermilab

    2008-06-01

    Details of wake potential simulation in the acceleration structure of ILC, including the RF cavities and input/HOM couplers are presented. Transverse wake potential dependence is described versus the bunch length. Beam emittance dilution caused by main and HOM couplers is estimated, followed by a discussion of possible structural modifications allowing a reduction of transverse wake potential.

  10. COAXIAL WIRE MEASUREMENTS IN NLC ACCELERATING STRUCTURES

    SciTech Connect

    Jones, Roger M

    2002-06-20

    The coaxial wire method provides an experimental way of measuring wake fields without the need for a particle beam. A special setup has been designed and is in the process of being fabricated at SLAC to measure the loss factors and synchronous frequencies of dipole modes in both traveling and standing wave structures for the Next Linear Collider (NLC). The method is described and predictions based on electromagnetic field simulations are discussed.

  11. Design of High Gradient Accelerating Structure for CLIC

    NASA Astrophysics Data System (ADS)

    Grudiev, A.; Wuensch, W.

    2006-01-01

    A new CLIC main-linac accelerating-structure design, HDS (Hybrid Damped Structure), with improved high-gradient performance, efficiency and simplicity of fabrication is presented. The gains are achieved in part through a new cell design which includes fully-profiled rf surfaces optimized to minimize surface fields, and hybrid damping using both iris slots and radial waveguides. The slotted irises allow a simple structure fabrication in quadrants with no rf currents across joints, a reduced number of pieces per structure (only 4) and a reduced surface requiring precise machining. Further gains are achieved through a new structure optimization procedure, which simultaneously balances surface fields, power flow, short and long-range transverse wakefields and rf-to-beam efficiency. The optimization of a 30 GHz structure with a loaded accelerating gradient of 150 MV/m results in a bunch spacing of eight rf cycles and 31 % rf-to-beam efficiency.

  12. 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.

  13. 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

  14. 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.

  15. 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

  16. Progress on Diamond-Based Cylindrical Dielectric Accelerating Structures

    NASA Astrophysics Data System (ADS)

    Kanareykin, A.; Schoessow, P.; Conde, M.; Gai, W.

    2006-11-01

    The development of a high gradient diamond-based cylindrical dielectric loaded accelerator (DLA) is presented. A diamond-loaded DLA can potentially sustain accelerating gradients far in excess of the limits experimentally observed for conventional metallic accelerating structures. The electrical and mechanical properties of diamond make it an ideal candidate material for use in dielectric accelerators: high rf breakdown level, extremely low dielectric losses and the highest available thermoconductive coefficient. We used the hot-filament Chemical Vapor Deposition (CVD) process to produce high quality 5-10 cm long cylindrical diamond layers. Our collaboration has also been developing a new method of CVD diamond surface preparation that reduces the secondary electron emission coefficient below unity. Special attention was paid to the numerical optimization of the waveguide to structure rf coupling section, where the surface magnetic and electric fields were minimized relative to the accelerating gradient and within known metal surface breakdown limits. We conclude with a brief overview of the use of diamond microstructures for use in compact rf sources.

  17. Structure of Accelerated Learning Program (ALP) Efforts, 2000-01.

    ERIC Educational Resources Information Center

    Baenen, Nancy; Yaman, Kimberly

    This report focuses on the structure of instructional assistance available through the Accelerated Learning Program (ALP) to students who show low achievement in the Wake County Public School System (WCPSS), North Carolina. Context information is also provided on other programs available to these students. Reports on ALP student participation,…

  18. 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.

  19. 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.

  20. Structural Biology of the Purine Biosynthetic Pathway

    PubMed Central

    Zhang, Yang; Morar, Mariya; Ealick, Steven E.

    2008-01-01

    Purine biosynthesis requires ten enzymatic transformations to generate inosine monophosphate. PurF, PurD, PurL, PurM, PurC, and PurB are common to all pathways, while PurN or PurT, PurK/PurE-I or PurE-II, PurH or PurP, and PurJ or PurO catalyze the same steps in different organisms. X-ray crystal structures are available for all 15 purine biosynthetic enzymes, including seven ATP-dependent enzymes, two amidotransferases and two tetrahydrofolate-dependent enzymes. Here we summarize the structures of the purine biosynthetic enzymes, discuss similarities and differences, and present arguments for pathway evolution. Four of the ATP-dependent enzymes belong to the ATP-grasp superfamily and two to the PurM superfamily. The amidotransferases are unrelated with one utilizing an NTN-glutaminase and the other utilizing a triad glutaminase. Likewise the tetrahydrofolate-dependent enzymes are unrelated. Ancestral proteins may have included a broad specificity enzyme instead of PurD, PurT, PurK, PurC, and PurP, and a separate enzyme instead of PurM and PurL. PMID:18712276

  1. Ion Bombardment of Microprotrusions in High Gradient Accelerating Structures

    SciTech Connect

    Nusinovich, Gregory S.; Kashyn, Dmytro; Antonsen, Thomas Jr.; Haber, Irving

    2010-11-04

    This paper starts from a brief overview of theoretical studies of high-gradient accelerating structures at the University of Maryland. The rest of the paper is devoted to the analysis of ion bombardment of small protrusions in such structures. First, this problem is studied analytically. Then, some results of particle-in-cell simulations performed with the use of code WARP are presented and discussed.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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

  8. On radiative acceleration in spine-sheath structured blazar jets

    NASA Astrophysics Data System (ADS)

    Chhotray, A.; Nappo, F.; Ghisellini, G.; Salafia, O. S.; Tavecchio, F.; Lazzati, D.

    2017-04-01

    It has been proposed that blazar jets are structured, with a fast spine surrounded by a slower sheath or layer. This structured jet model explains some properties of their emission and morphology. Because of their relative motion, the radiation produced by one component is seen amplified by the other, thus enhancing the inverse Compton emission of both. Radiation is emitted anisotropically in the comoving frames and causes the emitting plasma to recoil. As seen in the observer frame, this corresponds to a deceleration of the fastest component (the spine) and an acceleration of the slower one (the layer). While the deceleration of the spine has already been investigated, here we study for the first time the acceleration of the sheath and find self-consistent velocity profile solutions for both the spine and the sheath while accounting for radiative cooling. We find that the sheath can be accelerated to the velocities required by the observations if its leptons remain energetic in the acceleration region, assumed to be of the order of ∼100 Schwarzschild radii, demanding continuous injection of energetic particles in that region.

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. 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.

  14. Summary report of working group 3: Laser and high-gradient structure-based acceleration

    NASA Astrophysics Data System (ADS)

    Andonian, Gerard; Simakov, Evgenya

    2017-03-01

    High-gradient particle acceleration with reduced power demands is essential for miniaturization and cost reduction of future accelerators. Applications for compact accelerators span collider research for High Energy Physics, light source development for Basic Energy Sciences and National Security, and industrial accelerators for Energy and Environmental Applications. Working Group 3 discussed and surveyed the recent advances in achieving higher gradients and better acceleration efficiency in externally powered, structure-based accelerators. The topics covered in Working Group 3 included dielectric laser acceleration, millimeter-wave accelerators, breakdown phenomena, exotic topologies such as photonic band-gap structures, artificial materials, and nanostructures, and novel rf technology.

  15. 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.

  16. On the resonant behavior of laminated accelerating structures

    NASA Astrophysics Data System (ADS)

    Ivanyan, M. I.; Avagyan, V. Sh.; Danielyan, V. A.; Tsakanian, A. V.; Vardanyan, A. S.; Zakaryan, V. S.

    2017-03-01

    The laminated round metallic waveguide is one of the promising options for high frequency single-mode accelerating structures. Under certain conditions the longitudinal impedance of such type structures has a narrow-band resonance that corresponds to slowly propagating synchronous TM01 fundamental mode. In this paper the resonant properties of two parallel plates and rectangular cavity with laminated walls are studied. The first measurement results performed for the copper cavity of rectangular cross section with inner germanium layers at top and bottom walls are presented. The measurements show the existence of a dedicated resonant frequency being in a good agreement with the one predicted for the corresponding laminated parallel plates.

  17. 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.

  18. Dark Current Simulation for Linear Collider Accelerator Structures

    SciTech Connect

    Ng, C.K.; Li, Z.; Zhan, X.; Srinivas, V.; Wang, J.; Ko, K.; /SLAC

    2011-08-25

    The dynamics of field-emitted electrons in the traveling wave fields of a constant gradient (tapered) disk-loaded waveguide is followed numerically. Previous simulations have been limited to constant impedance (uniform) structures for sake of simplicity since only the fields in a unit cell is needed. Using a finite element field solver on a parallel computer, the fields in the tapered structure can now be readily generated. We will obtain the characteristics of the dark current emitted from both structure types and compare the two results with and without the effect of secondary electrons. The NLC and JLC detuned structures are considered to study if dark current may pose a problem for high gradient acceleration in the next generation of Linear Colliders.

  19. On the relationship between collisionless shock structure and energetic particle acceleration

    NASA Technical Reports Server (NTRS)

    Kennel, C. F.

    1983-01-01

    Recent experimental research on bow shock structure and theoretical studies of quasi-parallel shock structure and shock acceleration of energetic particles were reviewed, to point out the relationship between structure and particle acceleration. The phenomenological distinction between quasi-parallel and quasi-perpendicular shocks that has emerged from bow shock research; present efforts to extend this work to interplanetary shocks; theories of particle acceleration by shocks; and particle acceleration to shock structures using multiple fluid models were discussed.

  20. Fabrication of x-band accelerating structures at Fermilab

    SciTech Connect

    Tug T Arkan et al.

    2004-07-20

    The RF Technology Development group at Fermilab is working together with the NLC and GLC groups at SLAC and KEK on developing technology for room temperature X-band accelerating structures for a future linear collider. We built six 60-cm long, high phase advance, detuned structures (HDS or FXB series). These structures have 150 degrees phase advance per cell, and are intended for high gradient tests. The structures were brazed in a vacuum furnace with a partial pressure of argon, rather than in a hydrogen atmosphere. We have also begun to build 60-cm long, damped and detuned structures (HDDS or FXC/FXD series). We have built 5 FXC and 1 FXD structures. Our goal was to build six structures for the 8-pack test at SLAC by the end of March 2004, as part of the GLC/NLC effort to demonstrate the readiness of room temperature RF technology for a linear collider. This paper describes the RF structure factory infrastructure (clean rooms, vacuum furnaces, vacuum equipment, RF equipment etc.), and the fabrication techniques utilized (the machining of copper cells/couplers, quality control, etching, vacuum brazing, cleanliness requirements etc.) for the production of FXB and FXC/FXD structures.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

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

    NASA Astrophysics Data System (ADS)

    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

    2016-02-01

    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.

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

    DOE PAGES

    Simakov, Evgenya I.; Arsenyev, Sergey A.; Buechler, Cynthia E.; ...

    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

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

    SciTech Connect

    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. We 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.

  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. 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

  10. Design of a 30 GHz Damped Detuned Accelerating Structure

    NASA Astrophysics Data System (ADS)

    Dehler, M.; Wilson, I.; Wuensch, W.; Jones, R. M.; Kroll, N. M.; Miller, R. H.

    1997-05-01

    Within the framework of the SLAC/CERN studies of 30 GHz linear colliders, an attempt has been made to scale the existing X-band NLC damped detuned accelerating structure to 30 GHz. A simple scaling was not chosen because of anticipated manufacturing difficulties. The new manifold-damped design has 101 cells and a minimum aperture of 3.4 mm. In order to obtain acceptably small values for both the single-bunch transverse wakefield and the long-range multibunch wakefield a relatively large non-linear variation of the iris thickness was introduced in addition to the iris diameter variation. The resulting short-range wakefield is 1270 V/pC/mm/m decreasing to less than 1after 1 ns.

  11. Deamidation accelerates amyloid formation and alters amylin fiber structure

    PubMed Central

    Dunkelberger, Emily B.; Buchanan, Lauren E.; Marek, Peter; Cao, Ping; Raleigh, Daniel P.; Zanni, Martin T.

    2012-01-01

    Deamidation of asparagine and glutamine is the most common non-enzymatic, post-translational modification. Deamidation can influence the structure, stability, folding, and aggregation of proteins and has been proposed to play a role in amyloid formation. However there are no structural studies of the consequences of deamidation on amyloid fibers, in large part because of the difficulty of studying these materials using conventional methods. Here we examine the effects of deamidation on the kinetics of amyloid formation by amylin, the causative agent of type 2 diabetes. We find that deamidation accelerates amyloid formation and the deamidated material is able to seed amyloid formation by unmodified amylin. Using site-specific isotope labeling and two-dimensional infrared (2D IR) spectroscopy, we show that fibers formed by samples that contain deamidated polypeptide contain reduced amounts of β-sheet. Deamidation leads to disruption of the N-terminal β-sheet between Ala-8 and Ala-13, but β-sheet is still retained near Leu-16. The C-terminal sheet is disrupted near Leu-27. Analysis of potential sites of deamidation together with structural models of amylin fibers reveals that deamidation in the N-terminal β-sheet region may be the cause for the disruption of the fiber structure at both the N- and C-terminal β-sheet. Thus, deamidation is a post-translational modification that creates fibers which have an altered structure, but can still act as a template for amylin aggregation. Deamidation is very difficult to detect with standard methods used to follow amyloid formation, but isotope labeled IR spectroscopy provides a means for monitoring sample degradation and investigating the structural consequences of deamidation. PMID:22734583

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

    PubMed

    Grishin, Andrey M; Cygler, Miroslaw

    2015-06-12

    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.

  13. Superconducting Accelerating Structure for High-Current Cyclotrons for Accelerator-Driven Subcritical Fission

    NASA Astrophysics Data System (ADS)

    Pogue, Nathaniel; McIntyre, Peter; Sattarov, Akhdiyor

    2011-10-01

    An accelerator driven molten salt fission core is being designed to provide reliable power by subcritical nuclear fission for the next few millennia. Fission is driven by proton beams from a flux-coupled stack of three high-current cyclotrons. A key innovation in attaining the needed beam current and efficiency is a superconducting Niobium rf accelerating cavity that can accelerate bunches in the 200 orbits uniformly. The unique design allows for several cavities to be stacked, and also provides uniform acceleration and eliminates higher order modes in the cyclotron. The design and properties of the superconducting cavity will increase the efficiency of the cyclotron and the overall energy amplification from the molten salt core by an order of magnitude compared to conventional designs.

  14. 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.

  15. Thermodynamic constraints shape the structure of carbon fixation pathways.

    PubMed

    Bar-Even, Arren; Flamholz, Avi; Noor, Elad; Milo, Ron

    2012-09-01

    Thermodynamics impose a major constraint on the structure of metabolic pathways. Here, we use carbon fixation pathways to demonstrate how thermodynamics shape the structure of pathways and determine the cellular resources they consume. We analyze the energetic profile of prototypical reactions and show that each reaction type displays a characteristic change in Gibbs energy. Specifically, although carbon fixation pathways display a considerable structural variability, they are all energetically constrained by two types of reactions: carboxylation and carboxyl reduction. In fact, all adenosine triphosphate (ATP) molecules consumed by carbon fixation pathways - with a single exception - are used, directly or indirectly, to power one of these unfavorable reactions. When an indirect coupling is employed, the energy released by ATP hydrolysis is used to establish another chemical bond with high energy of hydrolysis, e.g. a thioester. This bond is cleaved by a downstream enzyme to energize an unfavorable reaction. Notably, many pathways exhibit reduced ATP requirement as they couple unfavorable carboxylation or carboxyl reduction reactions to exergonic reactions other than ATP hydrolysis. In the most extreme example, the reductive acetyl coenzyme A (acetyl-CoA) pathway bypasses almost all ATP-consuming reactions. On the other hand, the reductive pentose phosphate pathway appears to be the least ATP-efficient because it is the only carbon fixation pathway that invests ATP in metabolic aims other than carboxylation and carboxyl reduction. Altogether, our analysis indicates that basic thermodynamic considerations accurately predict the resource investment required to support a metabolic pathway and further identifies biochemical mechanisms that can decrease this requirement.

  16. 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

  17. 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.

  18. 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.

  19. Electron acceleration by an electromagnetic wave propagating across a magnetic field in periodic structures

    NASA Astrophysics Data System (ADS)

    Buts, V. A.; Ognivenko, V. V.

    1990-05-01

    The possibility of the acceleration of charged particles captured by an electromagnetic wave propagating across a constant magnetic field in periodic slow-wave structures is demonstrated. A plane waveguide with perfectly conducting walls is examined as an example of an electrodynamic structure in which such an acceleration mechanism is possible. The acceleration rate is determined, and the stability of captured particle motion is investigated.

  20. 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.

  1. 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

  2. Exploration of the antagonist CP-376395 escape pathway for the corticotropin-releasing factor receptor 1 by random acceleration molecular dynamics simulations.

    PubMed

    Bai, Qifeng; Shi, Danfeng; Zhang, Yang; Liu, Huanxiang; Yao, Xiaojun

    2014-07-01

    Corticotropin-releasing factor receptor 1 (CRF1R), a member of class B G-protein-coupled receptors (GPCRs), plays an important role in the treatment of osteoporosis, diabetes, depression, migraine and anxiety. To explore the escape pathway of the antagonist CP-376395 in the binding pocket of CRF1R, molecular dynamics (MD) simulations, dynamical network analysis, random acceleration molecular dynamics (RAMD) simulations and adaptive biasing force (ABF) calculations were performed on the crystal structure of CRF1R in complex with CP-376395. The results of dynamical network analysis show that TM7 of CRF1R has the strongest edges during MD simulation. The bent part of TM7 forms a V-shape pocket with Gly356(7.50). Asn283(5.50) has high hydrogen bond occupancy during 100 ns MD simulations and is the key interaction residue with the antagonist in the binding pocket of CRF1R. RAMD simulation has identified three possible pathways (PW1, PW2 and PW3) for CP-376395 to escape from the binding pocket of CRF1R. The PW3 pathway was proved to be the most likely escape pathway for CP-376395. The free energy along the PW3 pathway was calculated by using ABF simulations. Two energy barriers were found along the reaction coordinates. Residues Leu323(6.49), Asn283(5.50) and Met206(3.47) contribute to the steric hindrance for the first energy barrier. Residues His199(3.40) and Gln355(7.49) contribute to the second energy barrier through the hydrogen bonding interaction between CP-376395 and CRF1R. The results of our study can not only provide useful information to understand the interaction mechanism between CP-376395 and CRF1R, but also provide the details about the possible escape pathway and the free energy profile of CP-376395 in the pocket of CRF1R.

  3. Formation of electrostatic structures by wakefield acceleration in ultrarelativistic plasma flows: Electron acceleration to cosmic ray energies

    SciTech Connect

    Dieckmann, M.E.; Shukla, P.K.; Eliasson, B.

    2006-06-15

    The ever increasing performance of supercomputers is now enabling kinetic simulations of extreme astrophysical and laser produced plasmas. Three-dimensional particle-in-cell (PIC) simulations of relativistic shocks have revealed highly filamented spatial structures and their ability to accelerate particles to ultrarelativistic speeds. However, these PIC simulations have not yet revealed mechanisms that could produce particles with tera-electron volt energies and beyond. In this work, PIC simulations in one dimension (1D) of the foreshock region of an internal shock in a gamma ray burst are performed to address this issue. The large spatiotemporal range accessible to a 1D simulation enables the self-consistent evolution of proton phase space structures that can accelerate particles to giga-electron volt energies in the jet frame of reference, and to tens of tera-electron volt in the Earth's frame of reference. One potential source of ultrahigh energy cosmic rays may thus be the thermalization of relativistically moving plasma.

  4. 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...

  5. 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.

  6. 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.

  7. Computer simulation of the coupling slots effects for on-axis coupled accelerating structures.

    NASA Astrophysics Data System (ADS)

    Salakhoutdinov, A. F.; Shvedunov, V. I.

    1997-05-01

    The presence of coupling elements in accelerating structures leads to the violation of axial symmetry of accelerating field and it may cause displacement, defocusing and non-linear distortion of phase space. As a result the growth of transverse emittance occures. From the other hand, these effects may be used for designing of RF- focusing accelerating structure for electron accelerators of various types. The numerical simulation of electrodynamical properties of on-axis coupled accelerating structure taking into account the coupling slots have been made. The characteristics of fields excited within the coupling cell have been investigated. The numerical estimations of various multipolarity components of transverse forces acting upon a particle inside the coupling cell have been achieved.

  8. 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.

  9. Particle motion of accelerated electrons in standing-wave RF structures

    NASA Astrophysics Data System (ADS)

    Hammen, A. F. J.; Corstens, J. M.; Botman, J. I. M.; Hagedoorn, H. L.; Theuws, W. H. C.

    1999-05-01

    A Hamiltonian theory has been formulated, which is used to calculate accelerated particle motion in standing-wave RF structures. In particular, these calculations have been applied to the Eindhoven racetrack microtron accelerating cavity. The calculations are in excellent agreement with simulations performed by particle-tracking codes.

  10. 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.

  11. 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.

  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

    2007-10-02

    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+.

  13. 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.

  14. Technological issues and high gradient test results on X-band molybdenum accelerating structures

    NASA Astrophysics Data System (ADS)

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

    2011-11-01

    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 ( Kō Enerugī Kasokuki Kenkyū Kikō). The technological issues to build both sections are discussed.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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

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

    DOE PAGES

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

    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

  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. RF Processing of X-Band Accelerator Structures at the NLCTA

    SciTech Connect

    Adolphsen, Chris

    2000-08-24

    During the initial phase of operation, the linacs of the Next Linear Collider (NLC) will contain roughly 5,000 X-Band accelerator structures that will accelerate beams of electrons and positrons to 250 GeV. These structures will nominally operate at an unloaded gradient of 72 MV/m. As part of the NLC R and D program, several prototype structures have been built and operated at the Next Linear Collider Test Accelerator (NLCTA) at SLAC. Here, the effect of high gradient operation on the structure performance has been studied. Significant progress was made during the past year after the NLCTA power sources were upgraded to reliably produce the required NLC power levels and beyond. This paper describes the structures, the processing methodology and the observed effects of high gradient operation.

  3. Strain-Specific Proteogenomics Accelerates Discovery of Natural Products Via Their Biosynthetic Pathways

    PubMed Central

    Albright, Jessica C.; Goering, Anthony W.; Doroghazi, James R.; Metcalf, William W.; Kelleher, Neil L.

    2014-01-01

    The use of proteomics for direct detection of expressed pathways producing natural products has yielded many new compounds, even when used in a screening mode without a bacterial genome sequence available. Here we quantify the advantages of having draft DNA-sequence available for strain-specific proteomics using the latest in ultrahigh-resolution mass spectrometry (MS) for both proteins and the small molecules they generate. Using the draft sequence of Streptomyces lilacinus NRRL B-1968, we show a >10-fold increase in the number of peptide identifications vs. using publicly available databases. Detected in this strain were six expressed gene clusters with varying homology to those known. To date, we have identified three of these clusters as encoding for the production of griseobactin (known), rakicidin D (an orphan NRPS/PKS hybrid cluster), and a putative thr and DHB-containing siderophore produced by a new non-ribosomal peptide sythetase gene cluster. The remaining three clusters show lower homology to those known, and likely encode enzymes for production of novel compounds. Using an interpreted strain-specific DNA sequence enables deep proteomics for the detection of multiple pathways and their encoded natural products in a single cultured bacterium. PMID:24242000

  4. Bacterial membrane lipids: diversity in structures and pathways.

    PubMed

    Sohlenkamp, Christian; Geiger, Otto

    2016-01-01

    For many decades, Escherichia coli was the main model organism for the study of bacterial membrane lipids. The results obtained served as a blueprint for membrane lipid biochemistry, but it is clear now that there is no such thing as a typical bacterial membrane lipid composition. Different bacterial species display different membrane compositions and even the membrane composition of cells belonging to a single species is not constant, but depends on the environmental conditions to which the cells are exposed. Bacterial membranes present a large diversity of amphiphilic lipids, including the common phospholipids phosphatidylglycerol, phosphatidylethanolamine and cardiolipin, the less frequent phospholipids phosphatidylcholine, and phosphatidylinositol and a variety of other membrane lipids, such as for example ornithine lipids, glycolipids, sphingolipids or hopanoids among others. In this review, we give an overview about the membrane lipid structures known in bacteria, the different metabolic pathways involved in their formation, and the distribution of membrane lipids and metabolic pathways across taxonomical groups.

  5. 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.

  6. Pathways of risk for accelerated heavy alcohol use among adolescent children of alcoholic parents.

    PubMed

    Hussong, A M; Curran, P J; Chassin, L

    1998-12-01

    The current study examined two questions. First, do internalizing symptoms and externalizing behavior each mediate the relations between parent psychopathology (alcoholism, antisocial personality disorder, and affective disorder) and growth in adolescent heavy alcohol use? Second, are there gender differences in these mediated pathways? Using latent curve analyses, we examined these questions in a high-risk sample of 439 families (53% children of alcoholic parents; 47% female). Collapsing across gender, adolescent-reported externalizing behavior mediated both the relation between parent alcoholism and growth in heavy alcohol use and the relation between parent antisociality and growth in heavy alcohol use. Parent-reported externalizing behavior only mediated the relation between parent antisociality and growth in heavy alcohol use in males. No support was found for internalizing symptoms as a mediator of these relations. Avenues are suggested for further exploring and integrating information about different mediating processes accounting for children of alcoholics' risk for heavy alcohol use.

  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.

  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. Design and fabrication of a traveling-wave muffin-tin accelerating structure at 90 GHz

    SciTech Connect

    Chou, P.J.; Bowden, G.B.; Copeland, M.R.; Menegat, A.; Siemann, R.H.; Henke, H.

    1997-05-01

    A prototype of a muffin-tin accelerating structure operating at 32 times the SLAC frequency (2.856 GHz) was built for research in high gradient acceleration. A traveling-wave design with single input and output feeds was chosen for the prototype which was fabricated by wire electrodischarge machining. Features of the mechanical design for the prototype are described. Design improvements are presented including considerations of cooling and vacuum.

  10. 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.

  11. 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

    2015-02-10

    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

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

    SciTech Connect

    Neilson, Jeffrey; Tantawi, Sami; Dolgashev, Valery

    2010-11-04

    We are investigating a standing wave structure with an 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

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

    DOE PAGES

    Tooker, Brian C.; Brindley, Stephen M.; Chiarappa-Zucca, Marina L.; ...

    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

  19. 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.

  20. Challenges to self-acceleration in modified gravity from gravitational waves and large-scale structure

    NASA Astrophysics Data System (ADS)

    Lombriser, Lucas; Lima, Nelson A.

    2017-02-01

    With the advent of gravitational-wave astronomy marked by the aLIGO GW150914 and GW151226 observations, a measurement of the cosmological speed of gravity will likely soon be realised. We show that a confirmation of equality to the speed of light as indicated by indirect Galactic observations will have important consequences for a very large class of alternative explanations of the late-time accelerated expansion of our Universe. It will break the dark degeneracy of self-accelerated Horndeski scalar-tensor theories in the large-scale structure that currently limits a rigorous discrimination between acceleration from modified gravity and from a cosmological constant or dark energy. Signatures of a self-acceleration must then manifest in the linear, unscreened cosmological structure. We describe the minimal modification required for self-acceleration with standard gravitational-wave speed and show that its maximum likelihood yields a 3σ poorer fit to cosmological observations compared to a cosmological constant. Hence, equality between the speeds challenges the concept of cosmic acceleration from a genuine scalar-tensor modification of gravity.

  1. 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.

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

    DOE PAGES

    Bulanov, S. S.; Esarey, E.; Schroeder, C. B.; ...

    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

  3. 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.

  4. USE OF ACOUSTIC EMISSION TO DIAGNOSE BREAKDOWN IN ACCELERATOR RF STRUCTURES

    SciTech Connect

    Nelson, Janice L.

    2003-05-12

    Accelerator structures of a wide variety have been damaged by RF breakdowns. Very little is known about the mechanisms that cause the breakdown and the damage although there has been theoretical work [1,2]. Using an array of ultrasonic acoustic emission sensors we have been able to locate and classify breakdown events more accurately than possible using microwave techniques. Data from the technique has led to improvements in the design of the NLC X-band RF structure. We report results of acoustic emission studies at the DESY TESLA Test Facility and the SLAC NLC Test Accelerator.

  5. Using Machine Learning to Accelerate Complex Atomic Structure Elucidation

    NASA Astrophysics Data System (ADS)

    Brouwer, William; Calderin, Lazaro; Sofo, Jorge

    2012-02-01

    Workers in various scientific disciplines seek to develop chemical models for extended and molecular systems. The modeling process revolves around the gradual refinement of model assumptions, through comparison of experimental and computational results. Solid state Nuclear Magnetic Resonance (NMR) is one such experimental technique, providing great insight into chemical order over Angstrom length scales. However, interpretation of spectra for complex materials is difficult, often requiring intensive simulations. Similarly, working forward from the model in order to produce experimental quantities via ab initio is computationally demanding. The work involved in these two significant steps, compounded by the need to iterate back and forth, drastically slows the discovery process for new materials. There is thus great motivation for the derivation of structural models directly from complex experimental data, the subject of this work. Using solid state NMR experimental datasets, in conjunction with ab initio calculations of measurable NMR parameters, a network of machine learning kernels are trained to rapidly yield structural details, on the basis of input NMR spectra. Results for an environmentally relevant material will be presented, and directions for future work.

  6. Comparison of accelerating structures for the first cavity of the main part of the INR linac

    NASA Astrophysics Data System (ADS)

    Rybakov, I. V.; Kalinin, Y. Z.; Leontev, V. N.; Naboka, A. N.; Paramonov, V. V.; Serov, V. L.; Feschenko, A. V.

    2016-09-01

    For the beam power improvement of the hydrogen-ion INR linac replacement of the first four-section cavity in the main part of linac is required. Existent cavity is realized using DAW structure on 991 MHz operating frequency. The new cavity should at least not lose in parameters to the current structure and essential changes in other linac systems are not wish able. Parameters of accelerating structures possible for such application are compared.

  7. 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.

  8. A single dose mass balance study of the Hedgehog pathway inhibitor vismodegib (GDC-0449) in humans using accelerator mass spectrometry.

    PubMed

    Graham, Richard A; Lum, Bert L; Morrison, Glenn; Chang, Ilsung; Jorga, Karin; Dean, Brian; Shin, Young G; Yue, Qin; Mulder, Teresa; Malhi, Vikram; Xie, Minli; Low, Jennifer A; Hop, Cornelis E C A

    2011-08-01

    Vismodegib (GDC-0449), a small-molecule Hedgehog pathway inhibitor, was well tolerated in patients with solid tumors and showed promising efficacy in advanced basal cell carcinoma in a Phase I trial. The purpose of the study presented here was to determine routes of elimination and the extent of vismodegib metabolism, including assessment and identification of metabolites in plasma, urine, and feces. Six healthy female subjects of nonchildbearing potential were enrolled; each received a single 30-ml oral suspension containing 150 mg of vismodegib with 6.5 μg of [(14)C]vismodegib to yield a radioactivity dose of approximately 37 kBq (1000 nCi). Plasma, urine, and feces samples were collected over 56 days to permit sample collection for up to 5 elimination half-lives. Nonradioactive vismodegib was measured in plasma using liquid chromatographic-tandem mass spectrometry, and total radioactivity in plasma, urine, and feces was measured using accelerator mass spectrometry. Vismodegib was slowly eliminated by a combination of metabolism and excretion of parent drug, most of which was recovered in feces. The estimated excretion of the administered dose was 86.6% on average, with 82.2 and 4.43% recovered in feces and urine, respectively. Vismodegib was predominant in plasma, with concentrations representing >98% of the total circulating drug-related components. Metabolic pathways of vismodegib in humans included oxidation, glucuronidation, and uncommon pyridine ring cleavage. We conclude that vismodegib and any associated metabolic products are mainly eliminated through feces after oral administration in healthy volunteers.

  9. Increasing temperature accelerates protein unfolding without changing the pathway of unfolding.

    PubMed

    Day, Ryan; Bennion, Brian J; Ham, Sihyun; Daggett, Valerie

    2002-09-06

    We have traditionally relied on extremely elevated temperatures (498K, 225 degrees C) to investigate the unfolding process of proteins within the timescale available to molecular dynamics simulations with explicit solvent. However, recent advances in computer hardware have allowed us to extend our thermal denaturation studies to much lower temperatures. Here we describe the results of simulations of chymotrypsin inhibitor 2 at seven temperatures, ranging from 298K to 498K. The simulation lengths vary from 94ns to 20ns, for a total simulation time of 344ns, or 0.34 micros. At 298K, the protein is very stable over the full 50ns simulation. At 348K, corresponding to the experimentally observed melting temperature of CI2, the protein unfolds over the first 25ns, explores partially unfolded conformations for 20ns, and then refolds over the last 35ns. Above its melting temperature, complete thermal denaturation occurs in an activated process. Early unfolding is characterized by sliding or breathing motions in the protein core, leading to an unfolding transition state with a weakened core and some loss of secondary structure. After the unfolding transition, the core contacts are rapidly lost as the protein passes on to the fully denatured ensemble. While the overall character and order of events in the unfolding process are well conserved across temperatures, there are substantial differences in the timescales over which these events take place. We conclude that 498K simulations are suitable for elucidating the details of protein unfolding at a minimum of computational expense.

  10. Free-electron laser as a power source for a high-gradient accelerating structure

    SciTech Connect

    Sessler, A.M.

    1982-02-01

    A two beam colliding linac accelerator is proposed in which one beam is intense (approx. = 1KA), of low energy (approx. = MeV), and long (approx. = 100 ns) and provides power at 1 cm wavelength through a free-electron-laser-mechanism to the second beam of a few electrons (approx. = 10/sup 11/), which gain energy at the rate of 250 MeV/m in a high-gradient accelerating structure and hence reach 375 GeV in 1.5 km. The intense beam is given energy by induction units and gains, and losses by radiation, 250 keV/m thus supplying 25 J/m to the accelerating structure. The luminosity, L, of two such linacs would be, at a repetition rate of 1 kHz, L = 4. x 10/sup 32/ cm/sup -2/ s/sup -1/.

  11. Capturing Structural Dynamics in Crystalline Silicon Using Chirped Electrons from a Laser Wakefield Accelerator.

    PubMed

    He, Z-H; Beaurepaire, B; Nees, J A; Gallé, G; Scott, S A; Pérez, J R Sánchez; Lagally, M G; Krushelnick, K; Thomas, A G R; Faure, J

    2016-11-08

    Recent progress in laser wakefield acceleration has led to the emergence of a new generation of electron and X-ray sources that may have enormous benefits for ultrafast science. These novel sources promise to become indispensable tools for the investigation of structural dynamics on the femtosecond time scale, with spatial resolution on the atomic scale. Here, we demonstrate the use of laser-wakefield-accelerated electron bunches for time-resolved electron diffraction measurements of the structural dynamics of single-crystal silicon nano-membranes pumped by an ultrafast laser pulse. In our proof-of-concept study, we resolve the silicon lattice dynamics on a picosecond time scale by deflecting the momentum-time correlated electrons in the diffraction peaks with a static magnetic field to obtain the time-dependent diffraction efficiency. Further improvements may lead to femtosecond temporal resolution, with negligible pump-probe jitter being possible with future laser-wakefield-accelerator ultrafast-electron-diffraction schemes.

  12. Capturing Structural Dynamics in Crystalline Silicon Using Chirped Electrons from a Laser Wakefield Accelerator

    NASA Astrophysics Data System (ADS)

    He, Z.-H.; Beaurepaire, B.; Nees, J. A.; Gallé, G.; Scott, S. A.; Pérez, J. R. Sánchez; Lagally, M. G.; Krushelnick, K.; Thomas, A. G. R.; Faure, J.

    2016-11-01

    Recent progress in laser wakefield acceleration has led to the emergence of a new generation of electron and X-ray sources that may have enormous benefits for ultrafast science. These novel sources promise to become indispensable tools for the investigation of structural dynamics on the femtosecond time scale, with spatial resolution on the atomic scale. Here, we demonstrate the use of laser-wakefield-accelerated electron bunches for time-resolved electron diffraction measurements of the structural dynamics of single-crystal silicon nano-membranes pumped by an ultrafast laser pulse. In our proof-of-concept study, we resolve the silicon lattice dynamics on a picosecond time scale by deflecting the momentum-time correlated electrons in the diffraction peaks with a static magnetic field to obtain the time-dependent diffraction efficiency. Further improvements may lead to femtosecond temporal resolution, with negligible pump-probe jitter being possible with future laser-wakefield-accelerator ultrafast-electron-diffraction schemes.

  13. Future accelerators (?)

    SciTech Connect

    John Womersley

    2003-08-21

    I describe the future accelerator facilities that are currently foreseen for electroweak scale physics, neutrino physics, and nuclear structure. I will explore the physics justification for these machines, and suggest how the case for future accelerators can be made.

  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. 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.

  16. Novel Anti-Microbial Peptide SR-0379 Accelerates Wound Healing via the PI3 Kinase/Akt/mTOR Pathway

    PubMed Central

    Tomioka, Hideki; Nakagami, Hironori; Tenma, Akiko; Saito, Yoshimi; Kaga, Toshihiro; Kanamori, Toshihide; Tamura, Nao; Tomono, Kazunori; Kaneda, Yasufumi; Morishita, Ryuichi

    2014-01-01

    We developed a novel cationic antimicrobial peptide, AG30/5C, which demonstrates angiogenic properties similar to those of LL-37 or PR39. However, improvement of its stability and cost efficacy are required for clinical application. Therefore, we examined the metabolites of AG30/5C, which provided the further optimized compound, SR-0379. SR-0379 enhanced the proliferation of human dermal fibroblast cells (NHDFs) via the PI3 kinase-Akt-mTOR pathway through integrin-mediated interactions. Furthermore SR-0379 promoted the tube formation of human umbilical vein endothelial cells (HUVECs) in co-culture with NHDFs. This compound also displays antimicrobial activities against a number of bacteria, including drug-resistant microbes and fungi. We evaluated the effect of SR-0379 in two different would-healing models in rats, the full-thickness defects under a diabetic condition and an acutely infected wound with full-thickness defects and inoculation with Staphylococcus aureus. Treatment with SR-0379 significantly accelerated wound healing when compared to fibroblast growth factor 2 (FGF2). The beneficial effects of SR-0379 on wound healing can be explained by enhanced angiogenesis, granulation tissue formation, proliferation of endothelial cells and fibroblasts and antimicrobial activity. These results indicate that SR-0379 may have the potential for drug development in wound repair, even under especially critical colonization conditions. PMID:24675668

  17. 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.

  18. 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.

  19. Damped accelerator structures for future linear e/sup/plus minus// colliders

    SciTech Connect

    Deruyter, H.; Hoag, H.A.; Lisin, A.V.; Loew, G.A.; Palmer, R.B.; Paterson, J.M.; Rago, C.E.; Wang, J.W.

    1989-03-01

    This paper describes preliminary work on accelerator structures for future TeV linear colliders which use trains of e/sup +-/ bunches to reach the required luminosity. These bunch trains, if not perfectly aligned with respect to the accelerator axis, induce transverse wake field modes into the structure. Unless they are sufficiently damped, these modes cause cummulative beam deflections and emittance growth. The envisaged structures, originally proposed by R. B. Palmer, are disk-loaded waveguides in which the disks are slotted radially into quadrants. Wake field energy is coupled via the slots and double-ridged waveguides into a lossy region which is external to the accelerator structure. The requirement is that the Q of the HEM/sub 11/ mode be reduced to a value of less than 30. The work done so far includes MAFIA code computations and low power rf measurements to study the fields. A four-cavity 2..pi../3 mode standing-wave structure has been built to find whether the slots lower the electric breakdown thresholds below those reached with conventional disk-loaded structures. We set out to assess the microwave properties of the structure and the problems which might be encountered in fabricating it. 4 refs., 7 figs.

  20. 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.

  1. Simulation of variation characteristics at thermostabilization of 27 GHz biperiodical accelerating structure

    NASA Astrophysics Data System (ADS)

    Kluchevskaya, Y. D.; Polozov, S. M.

    2016-07-01

    It was proposed to develop the biperiodical accelerating structure with operating frequency of 27 GHz to assess the possibility of design a compact accelerating structure for medical application. It is necessary to do the more careful simulation of variation characteristics this case because of decrease of wavelength 3-10 times in comparison with conventional structures 10 and 3 cm ranges. Results of such study are presented in the article. Also a combination of high electromagnetic fields and long pulses at a high operating frequency leads to the temperature increase in the structure, thermal deformation and significant change of the resonator characteristics, including the frequency of the RF pulse. Development results of three versions of system of temperature stabilization also discuses.

  2. Photosynthetic pathway alters hydraulic structure and function in woody plants.

    PubMed

    Kocacinar, Ferit; Sage, Rowan F

    2004-04-01

    Xylem structure and function is proposed to reflect an evolutionary balance between demands for efficient movement of water to the leaf canopy and resistance to cavitation during high xylem tension. Water use efficiency (WUE) affects this balance by altering the water cost of photosynthesis. Therefore species of greater WUE, such as C(4) plants, should have altered xylem properties. To evaluate this hypothesis, we assessed the hydraulic and anatomical properties of 19 C(3) and C(4) woody species from arid regions of the American west and central Asia. Specific conductivity of stem xylem ( K(s) ) was 16%-98% lower in the C(4) than C(3) shrubs from the American west. In the Asian species, the C(3) Nitraria schoberi had similar and Halimodendron halodendron higher K(s) values compared with three C(4) species. Leaf specific conductivity ( K(L); hydraulic conductivity per leaf area) was 60%-98% lower in the C(4) than C(3) species, demonstrating that the presence of the C(4) pathway alters the relationship between leaf area and the ability of the xylem to transport water. C(4) species produced similar or smaller vessels than the C(3) shrubs except in Calligonum, and most C(4) shrubs exhibited higher wood densities than the C(3) species. Together, smaller conduit size and higher wood density indicate that in most cases, the C(4) shrubs exploited higher WUE by altering xylem structure to enhance safety from cavitation. In a minority of cases, the C(4) shrubs maintained similar xylem properties but enhanced the canopy area per branch. By establishing a link between C(4) photosynthesis and xylem structure, this study indicates that other phenomena that affect WUE, such as atmospheric CO(2) variation, may also affect the evolution of wood structure and function.

  3. 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.

  4. A two-fluid model for black-hole accretion flows: particle acceleration and disc structure

    NASA Astrophysics Data System (ADS)

    Lee, Jason P.; Becker, Peter A.

    2017-02-01

    Hot, tenuous advection-dominated accretion flows around black holes are ideal sites for the Fermi acceleration of relativistic particles at standing shock waves in the accretion disc. Previous work has demonstrated that the shock-acceleration process can be efficient enough to power the observed, strong outflows in radio-loud active galaxies such as M87. However, the dynamical effect (back-reaction) on the flow, exerted by the pressure of the relativistic particles, has not been previously considered, and this effect can have a significant influence on the disc structure. We reexamine the problem by developing a new, two-fluid model for the structure of the accretion disc that includes the dynamical effect of the relativistic particle pressure, combined with the pressure of the background (thermal) gas. The new model is analogous to the two-fluid model of cosmic ray acceleration in supernova-driven shock waves. As part of the model, we also develop a new set of shock jump conditions, which are solved along with the hydrodynamic conservation equations to determine the structure of the accretion disc. The solutions include the formation of a mildly relativistic outflow (jet) at the shock radius, driven by the relativistic particles accelerated in the disc. One of our main conclusions is that in the context of the new two-fluid accretion model, global smooth (shock-free) solutions do not exist, and the disc must always contain a standing shock wave, at least in the inviscid case considered here.

  5. Particle Acceleration Affected by the Evolving Velocity Structures in the Solar Wind

    NASA Astrophysics Data System (ADS)

    Tsubouchi, K.

    2015-12-01

    It is accepted that high-energy particles are efficiently generated during their crossing of shocks in space, where the diffusive shock acceleration is the most standard process to explain the observed energy spectrum beyond the order of a gigaelectronvolt. In contrast, recent spacecraft observations have shown different characteristics in a lower energy range (a kilo- to megaelectronvolt): particles in the heliosphere have a power-law spectrum in particle speed with a spectral index of -5, which is commonly found in any solar wind conditions. This is a puzzling result that the shocks are not a necessary element responsible for accelerating particles. The alternative mechanism, a pump acceleration, is proposed where particles are accelerated in a region containing large-scale compressions and expansions (e.g., Fisk and Gloeckler, JGR 2014). In the present study, we elucidate the validity of this mechanism by performing hybrid simulations to investigate the particle, particularly pickup ions, dynamics in various situations of non-uniform velocity field, such as a simple fast/slow flow interaction, sinusoidal structures, or random profiles, and to compare the velocity spectrum of suprathermal particles in each case. We also study the scale dependence of acceleration processes by comparing the spectrum of the energetic H+, He+, and O+.

  6. Dynamic behavior of time-delayed acceleration feedback controller for active vibration control of flexible structures

    NASA Astrophysics Data System (ADS)

    An, Fang; Chen, Wei-dong; Shao, Min-qiang

    2014-09-01

    This paper addresses the design problem of the controller with time-delayed acceleration feedback. On the basis of the reduction method and output state-derivative feedback, a time-delayed acceleration feedback controller is proposed. Stability boundaries of the closed-loop system are determined by using Hurwitz stability criteria. Due to the introduction of time delay into the controller with acceleration feedback, the proposed controller has the feature of not only changing the mass property but also altering the damping property of the controlled system in the sense of equivalent structural modification. With this feature, the closed-loop system has a greater logarithmic decrement than the uncontrolled one, and in turn, the control behavior can be improved. In this connection, the time delay in the acceleration feedback control is a positive factor when satisfying some given conditions and it could be actively utilized. On the ground of the analysis, the developed controller is implemented on a cantilever beam for different controller gain-delay combinations, and the control performance is evaluated with the comparison to that of pure acceleration feedback controller. Simulation and experimental results verify the ability of the controller to attenuate the vibration resulting from the dominant mode.

  7. Diamond field emitter array cathodes and possibilities of employing additive manufacturing for dielectric laser accelerating structures

    NASA Astrophysics Data System (ADS)

    Simakov, Evgenya I.; Andrews, Heather L.; Herman, Matthew J.; Hubbard, Kevin M.; Weis, Eric

    2017-03-01

    Demonstration of a stand-alone practical dielectric laser accelerator (DLA) requires innovation in two major critical components: high-current ultra-low-emittance cathodes and efficient laser accelerator structures. LANL develops two technologies that in our opinion are applicable to the novel DLA architectures: diamond field emitter array (DFEA) cathodes and additive manufacturing of photonic band-gap (PBG) structures. This paper discusses the results of testing of DFEA cathodes in the field-emission regime and the possibilities for their operation in the photoemission regime, and compares their emission characteristics to the specific needs of DLAs. We also describe recent advances in additive manufacturing of dielectric woodpile structures using a Nanoscribe direct laser-writing device capable of maskless lithography and additive manufacturing, and the development of novel infrared dielectric materials compatible with additive manufacturing.

  8. Wire Measurement of Impedance of an X-Band Accelerating Structure

    SciTech Connect

    Baboi, N

    2004-09-02

    Several tens of thousands of accelerator structures will be needed for the next generation of normal conducting linear colliders known as the GLC/NLC (Global Linear Collider/Next Linear Collider). To prevent the beam being driven into a disruptive BBU (Beam Break-Up) mode or at the very least, the emittance being significantly diluted, it is important to damp down the wakefield left by driving bunches to a manageable level. Manufacturing errors and errors in design need to be measured and compared with prediction. In this paper a bench-top method of measuring transverse impedances in X-band accelerating structures is described. Utilizing an off-axis wire the S parameters are measured and converted to impedance. Measurements in a damped and detuned structure built for GLC/NLC are presented and the results are discussed.

  9. Diamond field emitter array cathodes and possibilities for employing additive manufacturing for dielectric laser accelerating structures

    SciTech Connect

    Simakov, Evgenya Ivanovna; Andrews, Heather Lynn; Herman, Matthew Joseph; Hubbard, Kevin Mark; Weis, Eric

    2016-09-20

    These are slides for a presentation at Stanford University. The outline is as follows: Motivation: customers for compact accelerators, LANL's technologies for laser acceleration, DFEA cathodes, and additive manufacturing of micron-size structures. Among the stated conclusions are the following: preliminary study identified DFEA cathodes as promising sources for DLAs--high beam current and small emittance; additive manufacturing with Nanoscribe Professional GT can produce structures with the right scale features for a DLA operating at micron wavelengths (fabrication tolerances need to be studied, DLAs require new materials). Future plans include DLA experiment with a beam produced by the DFEA cathode with field emission, demonstration of photoemission from DFEAs, and new structures to print and test.

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

    SciTech Connect

    Downer, Michael C.

    2014-04-30

    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

  11. 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

  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. 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.

  14. 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.

  15. Determination of the acceleration region size in a loop-structured solar flare

    NASA Astrophysics Data System (ADS)

    Guo, J.; Emslie, A. G.; Kontar, E. P.; Benvenuto, F.; Massone, A. M.; Piana, M.

    2012-07-01

    Aims: To study the acceleration and propagation of bremsstrahlung-producing electrons in solar flares, we analyze the evolution of the flare loop size with respect to energy at a variety of times. A GOES M3.7 loop-structured flare starting around 23:55 on 2002 April 14 is studied in detail using Ramaty High Energy Solar Spectroscopic Imager (RHESSI) observations. Methods: We construct photon and mean-electron-flux maps in 2-keV energy bins by processing observationally-deduced photon and electron visibilities, respectively, through several image-processing methods: a visibility-based forward-fit (FWD) algorithm, a maximum entropy (MEM) procedure and the uv-smooth (UVS) approach. We estimate the sizes of elongated flares (i.e., the length and width of flaring loops) by calculating the second normalized moments of the intensity in any given map. Employing a collisional model with an extended acceleration region, we fit the loop lengths as a function of energy in both the photon and electron domains. Results: The resulting fitting parameters allow us to estimate the extent of the acceleration region which is between ~ 13 arcsec and ~19 arcsec. Both forward-fit and uv-smooth algorithms provide substantially similar results with a systematically better fit in the electron domain. Conclusions: The consistency of the estimates from these methods provides strong support that the model can reliably determine geometric parameters of the acceleration region. The acceleration region is estimated to be a substantial fraction (~1/2) of the loop extent, indicating that this dense flaring loop incorporates both acceleration and transport of electrons, with concurrent thick-target bremsstrahlung emission.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. Spatial structure of the neck and acceleration processes in a micropinch

    NASA Astrophysics Data System (ADS)

    Dolgov, A. N.; Klyachin, N. A.; Prokhorovich, D. E.

    2016-12-01

    It is shown that the spatial structure of the micropinch neck during the transition from magnetohydrodynamic to radiative compression and the bremsstrahlung spectrum of the discharge in the photon energy range of up to 30 keV depend on the configuration of the inner electrode of the coaxial electrode system of the micropinch discharge. Analysis of the experimental results indicates that the acceleration processes in the electron component of the micropinch plasma develop earlier than radiative compression.

  1. Functional diversity and structural disorder in the human ubiquitination pathway.

    PubMed

    Bhowmick, Pallab; Pancsa, Rita; Guharoy, Mainak; Tompa, Peter

    2013-01-01

    The ubiquitin-proteasome system plays a central role in cellular regulation and protein quality control (PQC). The system is built as a pyramid of increasing complexity, with two E1 (ubiquitin activating), few dozen E2 (ubiquitin conjugating) and several hundred E3 (ubiquitin ligase) enzymes. By collecting and analyzing E3 sequences from the KEGG BRITE database and literature, we assembled a coherent dataset of 563 human E3s and analyzed their various physical features. We found an increase in structural disorder of the system with multiple disorder predictors (IUPred - E1: 5.97%, E2: 17.74%, E3: 20.03%). E3s that can bind E2 and substrate simultaneously (single subunit E3, ssE3) have significantly higher disorder (22.98%) than E3s in which E2 binding (multi RING-finger, mRF, 0.62%), scaffolding (6.01%) and substrate binding (adaptor/substrate recognition subunits, 17.33%) functions are separated. In ssE3s, the disorder was localized in the substrate/adaptor binding domains, whereas the E2-binding RING/HECT-domains were structured. To demonstrate the involvement of disorder in E3 function, we applied normal modes and molecular dynamics analyses to show how a disordered and highly flexible linker in human CBL (an E3 that acts as a regulator of several tyrosine kinase-mediated signalling pathways) facilitates long-range conformational changes bringing substrate and E2-binding domains towards each other and thus assisting in ubiquitin transfer. E3s with multiple interaction partners (as evidenced by data in STRING) also possess elevated levels of disorder (hubs, 22.90% vs. non-hubs, 18.36%). Furthermore, a search in PDB uncovered 21 distinct human E3 interactions, in 7 of which the disordered region of E3s undergoes induced folding (or mutual induced folding) in the presence of the partner. In conclusion, our data highlights the primary role of structural disorder in the functions of E3 ligases that manifests itself in the substrate/adaptor binding functions as well

  2. Structural dynamics of the monoamine transporter homolog LeuT from accelerated conformational sampling and channel analysis.

    PubMed

    Thomas, James R; Gedeon, Patrick C; Madura, Jeffry D

    2014-10-01

    The bacterial leucine transporter LeuT retains significant secondary structure similarities to the human monoamine transporters (MAT) such as the dopamine and serotonin reuptake proteins. The primary method of computational study of the MATs has been through the use of the crystallized LeuT structure. Different conformations of LeuT can give insight into mechanistic details of the MAT family. A conformational sampling performed through accelerated molecular dynamics simulations testing different combinations of the leucine substrate and bound sodium ions revealed seven distinct conformational clusters. Further analysis has been performed to target salt-bridge residues R30-D404, Y108-F253, and R5-D369 and transmembrane domains on both the seven isolated structures and the total trajectories. In addition, solvent accessibility of LeuT and its substrate binding pockets has been analyzed using a program for calculating channel radii. Occupation of the Na2 site stabilizes the outward conformation and should bind to the open outward conformation before the leucine and Na1 sodium while two possible pathways were found to be available for intracellular transport.

  3. 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

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

    SciTech Connect

    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.

    2016-08-16

    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. Lastly, these results bode well for high-gradient, high-efficiency acceleration of electron bunches while preserving their emittance in such a cavity.

  5. Structure-Based Drug Discovery Accelerated by Many-Core Devices.

    PubMed

    Feinstein, Wei; Brylinski, Michal

    2016-01-01

    Computer-aided design is one of the critical components of modern drug discovery. Drug development is routinely streamlined using computational approaches to improve hit identification and lead selection, enhance bioavailability, and reduce toxicity. A mounting body of genomic knowledge accumulated during the last decade or so presents great opportunities for pharmaceutical research. However, new challenges also arose because processing this large volume of data demands unprecedented computing resources. On the other hand, the state-of-the-art heterogeneous systems deliver petaflops of peak performance to accelerate scientific discovery. In this communication, we review modern parallel accelerator architectures, mainly focusing on Intel Xeon Phi many-core devices. Xeon Phi is a relatively new platform that features tens of computing cores with hundreds of threads offering massively parallel capabilities for a broad range of application. We also discuss common parallel programming frameworks targeted to this accelerator, including OpenMP, OpenCL, MPI and HPX. Recent advances in code development for many-core devices are described to demonstrate the advantages of heterogeneous implementations over the traditional, serial computing. Finally, we highlight selected algorithms, eFindSite, a ligand binding site predictor, a force field for bio-molecular simulations, and BUDE, a structure-based virtual screening engine, to demonstrate how modern drug discovery is accelerated by heterogeneous systems equipped with parallel computing devices.

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

    DOE PAGES

    Clayton, C. E.; Adli, E.; Allen, J.; ...

    2016-08-16

    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.).more » 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. Lastly, these results bode well for high-gradient, high-efficiency acceleration of electron bunches while preserving their emittance in such a cavity.« less

  7. Enhancing Target Normal Sheath Accelerated Ions with Micro-structured Targets

    NASA Astrophysics Data System (ADS)

    George, Kevin; Snyder, Joseph; Ji, Liangliang; Rubin, Trevor; Handler, Abraham; Poole, Patrick; Willis, Christopher; Daskalova, Rebecca; Cochran, Ginevra; Schumacher, Douglass

    2016-10-01

    Laser driven target normal sheath acceleration (TNSA) of ions has been widely studied due to its fundamental importance, use as a probe, and for possible applications such as cancer therapy and neutron generation. Much of this work has been conducted on thin foils with peak ion energy and yield optimized using laser parameters such as energy and spot size. Micro-structured targets, however, have demonstrated increased peak ion energy and yield by controlling and enhancing mechanisms preferential to TNSA. Novel micro-structured targets were developed using optical lithography techniques on thin substrates at the OSU NanoSystem Laboratory. Variable structure height (0.5-2 micron) and transverse patterning (up to 1 micron resolution) permit the survey of a range of structured target variables in the study of ion acceleration. We describe the development of these targets and an experiment investigating the enhancement of TNSA ions from lithography produced micro-structured targets conducted at the Scarlet Laser Facility. Experimental results show increased proton and Carbon yield >2 MeV and higher peak Carbon energy from structured targets. This work was supported by the Air Force Office of Scientific Research.

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

    SciTech Connect

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

    2016-05-09

    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.

  9. 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.

  10. 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.

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

    NASA Astrophysics Data System (ADS)

    Jing, Chunguang; Kanareykin, Alexei; Kazakov, Sergey; Liu, Wanming; Nenasheva, Elizaveta; Schoessow, Paul; Gai, Wei

    2008-09-01

    rf Power attenuation is a critical problem in the development of dielectric-loaded structures for particle acceleration. In a previous paper [C. Jing, W. Liu, W. Gai, J. Power, T. Wong, Nucl. Instr. Meth. A 539 (2005) 445] we suggested the use of a Multilayer Dielectric-Loaded Accelerating Structure (MDLA) as a possible approach for reducing the rf losses in a single layer device. The MDLA is based on the principle of Bragg reflection familiar from optics that is used to partially confine the fields inside the dielectric layers and reduce the wall current losses at the outer boundary. We report here on the design, construction and testing of a prototype X-band double-layer structure (2DLA). The measurements show an rf power attenuation for the 2DLA more than ten times smaller than that of a comparable single-layer structure, in good agreement with the analytic results. Testing and operation of MDLAs also requires efficient power coupling from test equipment or rf power systems to the device. We describe the design and construction of two novel structures: a TM 03 mode launcher for cold testing and a power coupler for planned high-gradient experiments.

  12. 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.

  13. 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.

  14. Capturing Structural Dynamics in Crystalline Silicon Using Chirped Electrons from a Laser Wakefield Accelerator

    PubMed Central

    He, Z.-H.; Beaurepaire, B.; Nees, J. A.; Gallé, G.; Scott, S. A.; Pérez, J. R. Sánchez; Lagally, M. G.; Krushelnick, K.; Thomas, A. G. R.; Faure, J.

    2016-01-01

    Recent progress in laser wakefield acceleration has led to the emergence of a new generation of electron and X-ray sources that may have enormous benefits for ultrafast science. These novel sources promise to become indispensable tools for the investigation of structural dynamics on the femtosecond time scale, with spatial resolution on the atomic scale. Here, we demonstrate the use of laser-wakefield-accelerated electron bunches for time-resolved electron diffraction measurements of the structural dynamics of single-crystal silicon nano-membranes pumped by an ultrafast laser pulse. In our proof-of-concept study, we resolve the silicon lattice dynamics on a picosecond time scale by deflecting the momentum-time correlated electrons in the diffraction peaks with a static magnetic field to obtain the time-dependent diffraction efficiency. Further improvements may lead to femtosecond temporal resolution, with negligible pump-probe jitter being possible with future laser-wakefield-accelerator ultrafast-electron-diffraction schemes. PMID:27824086

  15. Measurements of ultimate accelerating gradients in the SLAC disk-loaded structure

    SciTech Connect

    Wang, J.W.; Loew, G.A.

    1985-03-01

    This paper is a status report on an on-going program at SLAC to study accelerator structures under high-gradient electric field conditions. The study is a part of a much broader program dealing with future linear colliders. The accelerating gradient that might be achievable in such machines is a crucial parameter because once the beam energy is selected, the gradient determines the length of the linac and directly or indirectly affects the choice of many other parameters. To reach 100 MV/m in a conventional 3 m constant-gradient section without SLED, one would need a klystron with a peak power output of 900 MW. Since such a tube is not available, we decided to use a short standing-wave section in which the resonant fields can build up. The design criteria for this section, the fabrication, matching and tuning, the experimental set-up and the results are described. 6 refs., 5 figs., 1 tab.

  16. Spectroscopic characterization of the oligomeric surface structures on polyamide materials formed during accelerated aging.

    PubMed

    Chernev, Boril S; Eder, Gabriele C

    2011-10-01

    Crystalline surface species were observed at the surface of polyamide 12 materials upon accelerated aging. After detection of the depositions with scanning electron microscopy (SEM), the crystalline surface precipitations were analyzed with Fourier transform infrared (FT-IR) and Raman imaging microscopy. These surface species were supposed to be cyclic oligomers (dimer and trimer) of the PA12 monomer laurolactam, which are usually present in polyamide materials and tend to migrate to the surface when the material is subjected to accelerated aging. The evidence for the chemical identity of the crystalline surface structures to be mainly the cyclic dimer and trimer of laurolactam was given by melting-point identification and mass spectroscopic analysis of the methanol eluate of the surface. The Raman and FT-IR spectra of the mixture were extracted from the recorded images.

  17. 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.

  18. Recent Progress in R& D of Advanced Room Temperature Accelerator Structures

    SciTech Connect

    Wang, Juwen

    2003-08-11

    The NLC and JLC groups face two major challenges in designing X-Band accelerator structures for an electron-positron linear collider. The first is to demonstrate stable, long-term operation at a 70 MV/m gradient, which is required to keep the machine cost low, and the second is to strongly suppress the structure long-range wakefield, which is required to achieve high luminosity. During the past 2 years, the major emphasis has been on proving high gradient operation, although dipole wakefield suppression studies are continuing. This paper describes high gradient test results from a series of prototype TW and SW structures being developed for the NLC/JLC. Schemes for damping and detuning the dipole modes of these structures are also presented.

  19. 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.

  20. Accelerated cryo-EM structure determination with parallelisation using GPUs in RELION-2

    PubMed Central

    Kimanius, Dari; Forsberg, Björn O; Scheres, Sjors HW; Lindahl, Erik

    2016-01-01

    By reaching near-atomic resolution for a wide range of specimens, single-particle cryo-EM structure determination is transforming structural biology. However, the necessary calculations come at large computational costs, which has introduced a bottleneck that is currently limiting throughput and the development of new methods. Here, we present an implementation of the RELION image processing software that uses graphics processors (GPUs) to address the most computationally intensive steps of its cryo-EM structure determination workflow. Both image classification and high-resolution refinement have been accelerated more than an order-of-magnitude, and template-based particle selection has been accelerated well over two orders-of-magnitude on desktop hardware. Memory requirements on GPUs have been reduced to fit widely available hardware, and we show that the use of single precision arithmetic does not adversely affect results. This enables high-resolution cryo-EM structure determination in a matter of days on a single workstation. DOI: http://dx.doi.org/10.7554/eLife.18722.001 PMID:27845625

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

    DOE PAGES

    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

  2. Fine-grained parallelism accelerating for RNA secondary structure prediction with pseudoknots based on FPGA.

    PubMed

    Xia, Fei; Jin, Guoqing

    2014-06-01

    PKNOTS is a most famous benchmark program and has been widely used to predict RNA secondary structure including pseudoknots. It adopts the standard four-dimensional (4D) dynamic programming (DP) method and is the basis of many variants and improved algorithms. Unfortunately, the O(N(6)) computing requirements and complicated data dependency greatly limits the usefulness of PKNOTS package with the explosion in gene database size. In this paper, we present a fine-grained parallel PKNOTS package and prototype system for accelerating RNA folding application based on FPGA chip. We adopted a series of storage optimization strategies to resolve the "Memory Wall" problem. We aggressively exploit parallel computing strategies to improve computational efficiency. We also propose several methods that collectively reduce the storage requirements for FPGA on-chip memory. To the best of our knowledge, our design is the first FPGA implementation for accelerating 4D DP problem for RNA folding application including pseudoknots. The experimental results show a factor of more than 50x average speedup over the PKNOTS-1.08 software running on a PC platform with Intel Core2 Q9400 Quad CPU for input RNA sequences. However, the power consumption of our FPGA accelerator is only about 50% of the general-purpose micro-processors.

  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. Accelerating adiabatic quantum transfer for three-level Λ-type structure systems via picture transformation

    NASA Astrophysics Data System (ADS)

    Kang, Yi-Hao; Wu, Qi-Cheng; Chen, Ye-Hong; Shi, Zhi-Cheng; Song, Jie; Xia, Yan

    2017-04-01

    In this paper, we investigate the quantum transfer for the system with three-level Λ-type structure, and construct a shortcut to the adiabatic passage via picture transformation to speed up the evolution. We can design the pulses directly without any additional couplings. Moreover, by choosing suitable control parameters, the Rabi frequencies of pulses can be expressed by the linear superpositions of Gaussian functions, which could be easily realized in experiments. Compared with the previous works using the stimulated Raman adiabatic passage, the quantum transfer can be significantly accelerated with the present scheme.

  5. 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.

  6. Structure to function of an α-glucan metabolic pathway that promotes Listeria monocytogenes pathogenesis.

    PubMed

    Light, Samuel H; Cahoon, Laty A; Halavaty, Andrei S; Freitag, Nancy E; Anderson, Wayne F

    2016-11-07

    Here we employ a 'systems structural biology' approach to functionally characterize an unconventional α-glucan metabolic pathway from the food-borne pathogen Listeria monocytogenes (Lm). Crystal structure determination coupled with basic biochemical and biophysical assays allowed for the identification of anabolic, transport, catabolic and regulatory portions of the cycloalternan pathway. These findings provide numerous insights into cycloalternan pathway function and reveal the mechanism of repressor, open reading frame, kinase (ROK) transcription regulators. Moreover, by developing a structural overview we were able to anticipate the cycloalternan pathway's role in the metabolism of partially hydrolysed starch derivatives and demonstrate its involvement in Lm pathogenesis. These findings suggest that the cycloalternan pathway plays a role in interspecies resource competition-potentially within the host gastrointestinal tract-and establish the methodological framework for characterizing bacterial systems of unknown function.

  7. 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.

  8. Stress signalling pathways that impair prefrontal cortex structure and function

    PubMed Central

    2010-01-01

    The prefrontal cortex (PFC)—the most evolved brain region—subserves our highest-order cognitive abilities. However, it is also the brain region that is most sensitive to the detrimental effects of stress exposure. Even quite mild acute uncontrollable stress can cause a rapid and dramatic loss of prefrontal cognitive abilities, and more prolonged stress exposure causes architectural changes in prefrontal dendrites. Recent research has begun to reveal the intracellular signalling pathways that mediate the effects of stress on the PFC. This research has provided clues as to why genetic or environmental insults that disinhibit stress signalling pathways can lead to symptoms of profound prefrontal cortical dysfunction in mental illness. PMID:19455173

  9. 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.

  10. 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.

  11. 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

  12. Methodology for the structural design of single spoke accelerating cavities at Fermilab

    NASA Astrophysics Data System (ADS)

    Passarelli, Donato; Wands, Robert H.; Merio, Margherita; Ristori, Leonardo

    2016-10-01

    Fermilab is planning to upgrade its accelerator complex to deliver a more powerful and intense proton-beam for neutrino experiments. In the framework of the so-called Proton Improvement Plan-II (PIP-II), we are designing and developing a cryomodule containing superconducting accelerating cavities, the Single Spoke Resonators of type 1 (SSR1). In this paper, we present the sequence of analysis and calculations performed for the structural design of these cavities, using the rules of the American Society of Mechanical Engineers (ASME) Boiler and Pressure Vessel Code (BPVC). The lack of an accepted procedure for addressing the design, fabrication, and inspection of such unique pressure vessels makes the task demanding and challenging every time. Several factors such as exotic materials, unqualified brazing procedures, limited nondestructive examination, and the general R&D nature of these early generations of cavity design, conspire to make it impractical to obtain full compliance with all ASME BPVC requirements. However, the presented approach allowed us to validate the design of this new generation of single spoke cavities with values of maximum allowable working pressure that exceeds the safety requirements. This set of rules could be used as a starting point for the structural design and development of similar objects.

  13. Methodology for the structural design of single spoke accelerating cavities at Fermilab

    DOE PAGES

    Passarelli, Donato; Wands, Robert H.; Merio, Margherita; ...

    2016-10-01

    Fermilab is planning to upgrade its accelerator complex to deliver a more powerful and intense proton-beam for neutrino experiments. In the framework of the so-called Proton Improvement Plan-II (PIP-II), we are designing and developing a cryomodule containing superconducting accelerating cavities, the Single Spoke Resonators of type 1 (SSR1). In this paper, we present the sequence of analysis and calculations performed for the structural de- sign of these cavities, using the rules of the American Society of Mechanical Engineers (ASME) Boiler and Pressure Vessel Code (BPVC). The lack of an accepted procedure for addressing the design, fabrication, and inspection of suchmore » unique pressure vessels makes the task demanding and challenging every time. Several factors such as exotic materials, unqualified brazing procedures, limited nondestructive examination, and the general R&D nature of these early generations of cavity design, conspire to make it impractical to obtain full compliance with all ASME BPVC requirements. However, the presented approach allowed us to validate the design of these new generation of single spoke cavities with values of maximum allowable working pressure that exceed the safety requirements. This set of rules could be used as a starting point for the structural design and development of similar objects.« less

  14. Methodology for the structural design of single spoke accelerating cavities at Fermilab

    SciTech Connect

    Passarelli, Donato; Wands, Robert H.; Merio, Margherita; Ristori, Leonardo

    2016-10-01

    Fermilab is planning to upgrade its accelerator complex to deliver a more powerful and intense proton-beam for neutrino experiments. In the framework of the so-called Proton Improvement Plan-II (PIP-II), we are designing and developing a cryomodule containing superconducting accelerating cavities, the Single Spoke Resonators of type 1 (SSR1). In this paper, we present the sequence of analysis and calculations performed for the structural de- sign of these cavities, using the rules of the American Society of Mechanical Engineers (ASME) Boiler and Pressure Vessel Code (BPVC). The lack of an accepted procedure for addressing the design, fabrication, and inspection of such unique pressure vessels makes the task demanding and challenging every time. Several factors such as exotic materials, unqualified brazing procedures, limited nondestructive examination, and the general R&D nature of these early generations of cavity design, conspire to make it impractical to obtain full compliance with all ASME BPVC requirements. However, the presented approach allowed us to validate the design of these new generation of single spoke cavities with values of maximum allowable working pressure that exceed the safety requirements. This set of rules could be used as a starting point for the structural design and development of similar objects.

  15. A fast "kicker" using a two-channel rectangular dielectric wakefield accelerator structure

    NASA Astrophysics Data System (ADS)

    Marshall, Thomas C.; Shchelkunov, Sergey V.; Sotnikov, Gennadij V.; Hirshfield, Jay L.

    2017-03-01

    A method is proposed to select and eject bunches of electrons or positrons from a high energy train of charged bunches, based on proven dielectric wakefield accelerator technology. The kicker structure, consisting of a pair of adjacent rectangular dielectric-lined waveguides, permits the coupling of the wakefield that is generated from a train of low-energy (˜6 MeV) "drive bunches" moving in one waveguide to the adjacent waveguide where a portion of a train of high energy "witness bunches" needs to be diverted. A very fast response time (˜1 ns) for bunch deflection is estimated, and a structure as short as 10-30 cm would suffice to impart to the diverted bunches a transverse kick of an interest to high-energy accelerator application, e.g. 150 keV/c. The witness bunch width must be less than 0.2 - 0.3 mm to have an emittance dilution that makes the deflected bunch suitable for e.g. FEL applications.

  16. 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.

  17. 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...

  18. 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.

  19. High power breakdown testing of a photonic band-gap accelerator structure with elliptical rods

    NASA Astrophysics Data System (ADS)

    Munroe, Brian J.; Cook, Alan M.; Shapiro, Michael A.; Temkin, Richard J.; Dolgashev, Valery A.; Laurent, Lisa L.; Lewandowski, James R.; Yeremian, A. Dian; Tantawi, Sami G.; Marsh, Roark A.

    2013-01-01

    An improved single-cell photonic band-gap (PBG) structure with an inner row of elliptical rods (PBG-E) was tested with high power at a 60 Hz repetition rate at X-band (11.424 GHz), achieving a gradient of 128MV/m at a breakdown probability of 3.6×10-3 per pulse per meter at a pulse length of 150 ns. The tested standing-wave structure was a single high-gradient cell with an inner row of elliptical rods and an outer row of round rods; the elliptical rods reduce the peak surface magnetic field by 20% and reduce the temperature rise of the rods during the pulse by several tens of degrees, while maintaining good damping and suppression of high order modes. When compared with a single-cell standing-wave undamped disk-loaded waveguide structure with the same iris geometry under test at the same conditions, the PBG-E structure yielded the same breakdown rate within measurement error. The PBG-E structure showed a greatly reduced breakdown rate compared with earlier tests of a PBG structure with round rods, presumably due to the reduced magnetic fields at the elliptical rods vs the fields at the round rods, as well as use of an improved testing methodology. A post-testing autopsy of the PBG-E structure showed some damage on the surfaces exposed to the highest surface magnetic and electric fields. Despite these changes in surface appearance, no significant change in the breakdown rate was observed in testing. These results demonstrate that PBG structures, when designed with reduced surface magnetic fields and operated to avoid extremely high pulsed heating, can operate at breakdown probabilities comparable to undamped disk-loaded waveguide structures and are thus viable for high-gradient accelerator applications.

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

    PubMed

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

    2016-01-25

    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.

  1. 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

  2. High Gradient Performance of NLC/GLC X-band Accelerating Structures

    SciTech Connect

    Doebert, S.; Adolphsen, C.; Bowden, G.; Burke, D.; Chan, J.; Dolgashev, V.; Frisch, J.; Jobe, K.; Jones, R.; Lewandowski, J.; Kirby, R.; Li, Z.; McCormick, D.; Miller, R.; Nantista, C.; Nelson, J.; Pearson, C.; Ross, M.; Schultz, D.; Smith, T.; Tantawi, S.; /SLAC /Fermilab /KEK, Tsukuba

    2005-05-17

    During the past five years, there has been a concerted program at SLAC and KEK to develop accelerator structures that meet the high gradient (65 MV/m) performance requirements for the Next Linear Collider (NLC) and Global Linear Collider (GLC) initiatives. The design that resulted is a 60-cm-long, traveling-wave structure with low group velocity and 150 degree per cell phase advance. It has an average iris size that produces an acceptable short-range wakefield, and dipole mode damping and detuning that adequately suppresses the long-range wakefield. More than eight such structures have operated at a 60 Hz repetition rate over 1000 hours at 65 MV/m with 400 ns long pulses, and have reached breakdown rate levels below the limit for the linear collider. Moreover, the structures are robust in that the rates continue to decrease over time, and if the structures are briefly exposed to air, the rates recover to their low levels within a few days. This paper presents a summary of the results from this program, which effectively ended last August with the selection of ''cold'' technology for an International Linear Collider (ILC).

  3. Beam Position Monitoring using the HOM-Signals from a Damped and Detuned Accelerating Structure

    SciTech Connect

    Dobert, S; Adolphsen, C.; Jones, R.; Lewandowski, J.; Li, Z.; Pivi, M.; Wang, J.; Higo, T.; /KEK, Tsukuba

    2005-05-17

    The Next and Global Linear Collider (NLC/GLC) designs require precision alignment of the beam in the accelerator structures to reduce short range wakefields. The moderately damped and detuned structures themselves provide suitable higher order mode (HOM) signals to measure this alignment. The modes in the lowest dipole band, whose frequencies range from 14-16 GHz, provide the strongest signals. To determine the position resolution they provide, an NLC/GLC prototype structure that was installed in the ASSET facility of the SLAC Linac was instrumented to downmix and digitize these signals. The beam position within the structure was determined by simultaneously measuring the signals at three frequencies (14.3, 15, 15.7 GHz) corresponding to modes localized at the beginning, the middle and the end of the 60 cm long structure. A resolution of 1 micron was achieved even with 28 dB signal attenuation, which is better than the 5 micron resolution required for the NLC/GLC.

  4. The Effects of Structured Transfer Pathways in Community Colleges

    ERIC Educational Resources Information Center

    Baker, Rachel

    2016-01-01

    Most of the students who set out to earn degrees in community colleges never do. Interventions that simplify the complex organizational structures of these schools are promising solutions to this problem. This article is the first to provide rigorous evidence of the effects of structured transfer programs, one such intervention. Leveraging the…

  5. 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

  6. Discovery of new enzymes and metabolic pathways by using structure and genome context.

    PubMed

    Zhao, Suwen; Kumar, Ritesh; Sakai, Ayano; Vetting, Matthew W; Wood, B McKay; Brown, Shoshana; Bonanno, Jeffery B; Hillerich, Brandan S; Seidel, Ronald D; Babbitt, Patricia C; Almo, Steven C; Sweedler, Jonathan V; Gerlt, John A; Cronan, John E; Jacobson, Matthew P

    2013-10-31

    Assigning valid functions to proteins identified in genome projects is challenging: overprediction and database annotation errors are the principal concerns. We and others are developing computation-guided strategies for functional discovery with 'metabolite docking' to experimentally derived or homology-based three-dimensional structures. Bacterial metabolic pathways often are encoded by 'genome neighbourhoods' (gene clusters and/or operons), which can provide important clues for functional assignment. We recently demonstrated the synergy of docking and pathway context by 'predicting' the intermediates in the glycolytic pathway in Escherichia coli. Metabolite docking to multiple binding proteins and enzymes in the same pathway increases the reliability of in silico predictions of substrate specificities because the pathway intermediates are structurally similar. Here we report that structure-guided approaches for predicting the substrate specificities of several enzymes encoded by a bacterial gene cluster allowed the correct prediction of the in vitro activity of a structurally characterized enzyme of unknown function (PDB 2PMQ), 2-epimerization of trans-4-hydroxy-L-proline betaine (tHyp-B) and cis-4-hydroxy-D-proline betaine (cHyp-B), and also the correct identification of the catabolic pathway in which Hyp-B 2-epimerase participates. The substrate-liganded pose predicted by virtual library screening (docking) was confirmed experimentally. The enzymatic activities in the predicted pathway were confirmed by in vitro assays and genetic analyses; the intermediates were identified by metabolomics; and repression of the genes encoding the pathway by high salt concentrations was established by transcriptomics, confirming the osmolyte role of tHyp-B. This study establishes the utility of structure-guided functional predictions to enable the discovery of new metabolic pathways.

  7. 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.

  8. 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.

  9. TLR/MyD88 and liver X receptor alpha signaling pathways reciprocally control Chlamydia pneumoniae-induced acceleration of atherosclerosis.

    PubMed

    Naiki, Yoshikazu; Sorrentino, Rosalinda; Wong, Michelle H; Michelsen, Kathrin S; Shimada, Kenichi; Chen, Shuang; Yilmaz, Atilla; Slepenkin, Anatoly; Schröder, Nicolas W J; Crother, Timothy R; Bulut, Yonca; Doherty, Terence M; Bradley, Michelle; Shaposhnik, Zory; Peterson, Ellena M; Tontonoz, Peter; Shah, Prediman K; Arditi, Moshe

    2008-11-15

    Experimental and clinical studies link Chlamydia pneumoniae infection to atherogenesis and atherothrombotic events, but the underlying mechanisms are unclear. We tested the hypothesis that C. pneumoniae-induced acceleration of atherosclerosis in apolipoprotein E (ApoE)(-/-) mice is reciprocally modulated by activation of TLR-mediated innate immune and liver X receptor alpha (LXRalpha) signaling pathways. We infected ApoE(-/-) mice and ApoE(-/-) mice that also lacked TLR2, TLR4, MyD88, or LXRalpha intranasally with C. pneumoniae followed by feeding of a high fat diet for 4 mo. Mock-infected littermates served as controls. Atherosclerosis was assessed in aortic sinuses and in en face preparation of whole aorta. The numbers of activated dendritic cells (DCs) within plaques and the serum levels of cholesterol and proinflammatory cytokines were also measured. C. pneumoniae infection markedly accelerated atherosclerosis in ApoE-deficient mice that was associated with increased numbers of activated DCs in aortic sinus plaques and higher circulating levels of MCP-1, IL-12p40, IL-6, and TNF-alpha. In contrast, C. pneumoniae infection had only a minimal effect on atherosclerosis, accumulation of activated DCs in the sinus plaques, or circulating cytokine increases in ApoE(-/-) mice that were also deficient in TLR2, TLR4, or MyD88. However, C. pneumoniae-induced acceleration of atherosclerosis in ApoE(-/-) mice was further enhanced in ApoE(-/-)LXRalpha(-/-) double knockout mice and was accompanied by higher serum levels of IL-6 and TNF-alpha. We conclude that C. pneumoniae infection accelerates atherosclerosis in hypercholesterolemic mice predominantly through a TLR/MyD88-dependent mechanism and that LXRalpha appears to reciprocally modulate and reduce the proatherogenic effects of C. pneumoniae infection.

  10. Development of a Laser-Powered Dielectric Structure-Based Accelerator as a Stand-Alone Particle Source

    NASA Astrophysics Data System (ADS)

    Yoder, R. B.; Travish, G.; Arab, E. R.; Fong, D.; Hoyer, Z.; Lacroix, U. H.; Vartanian, N.; Rosenzweig, J. B.

    2010-11-01

    An experimental program to develop and build a dielectric-based slab-symmetric structure (the micro-accelerator platform, or MAP) for generating and accelerating low-energy electrons is underway at UCLA and Manhattanville College. This optical acceleration structure is effectively a resonant cavity powered by a side-coupled laser, and has applications as a radiation source for medicine or industry. We present recent experimental and computational results on the accelerator, and progress toward its incorporation into a self-contained particle source. Such a particle source would incorporate a micron-scale electron emitter and a non-relativistic capture region to enable self-injection into the synchronous field within the accelerator. A prototype of the accelerator itself has been constructed from candidate dielectric materials using micromanufacturing techniques; the current status of the testing program is described. A novel electron emitter incorporating pyroelectric crystals with field-enhancing tips has been demonstrated to produce steady currents; the results are dependent on tip geometry, and appear suitable for injection into a microstructure. Extension of the MAP concept to non-relativistic velocities, as in the stand-alone source, requires a tapered structure that gives rise to numerous complications including beam defocusing and manufacturing challenges; approaches for addressing these complications are mentioned.

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

    NASA Astrophysics Data System (ADS)

    Park, John J.; Buksa, John J.

    1995-09-01

    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.

  12. Structural disorder provides increased adaptability for vesicle trafficking pathways.

    PubMed

    Pietrosemoli, Natalia; Pancsa, Rita; Tompa, Peter

    2013-01-01

    Vesicle trafficking systems play essential roles in the communication between the organelles of eukaryotic cells and also between cells and their environment. Endocytosis and the late secretory route are mediated by clathrin-coated vesicles, while the COat Protein I and II (COPI and COPII) routes stand for the bidirectional traffic between the ER and the Golgi apparatus. Despite similar fundamental organizations, the molecular machinery, functions, and evolutionary characteristics of the three systems are very different. In this work, we compiled the basic functional protein groups of the three main routes for human and yeast and analyzed them from the structural disorder perspective. We found similar overall disorder content in yeast and human proteins, confirming the well-conserved nature of these systems. Most functional groups contain highly disordered proteins, supporting the general importance of structural disorder in these routes, although some of them seem to heavily rely on disorder, while others do not. Interestingly, the clathrin system is significantly more disordered (~23%) than the other two, COPI (~9%) and COPII (~8%). We show that this structural phenomenon enhances the inherent plasticity and increased evolutionary adaptability of the clathrin system, which distinguishes it from the other two routes. Since multi-functionality (moonlighting) is indicative of both plasticity and adaptability, we studied its prevalence in vesicle trafficking proteins and correlated it with structural disorder. Clathrin adaptors have the highest capability for moonlighting while also comprising the most highly disordered members. The ability to acquire tissue specific functions was also used to approach adaptability: clathrin route genes have the most tissue specific exons encoding for protein segments enriched in structural disorder and interaction sites. Overall, our results confirm the general importance of structural disorder in vesicle trafficking and suggest

  13. 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

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

    PubMed

    Tamaki, Naofumi; 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.

  15. 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.

  16. 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.

  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. Structural connectivity for visuospatial attention: significance of ventral pathways.

    PubMed

    Umarova, Roza M; Saur, Dorothee; Schnell, Susanne; Kaller, Christoph P; Vry, Magnus-Sebastian; Glauche, Volkmar; Rijntjes, Michel; Hennig, Jürgen; Kiselev, Valerij; Weiller, Cornelius

    2010-01-01

    In the present study, we identified the most probable trajectories of point-to-point segregated connections between functional attentional centers using a combination of functional magnetic resonance imaging and a novel diffusion tensor imaging-based algorithm for pathway extraction. Cortical regions activated by a visuospatial attention task were subsequently used as seeds for probabilistic fiber tracking in 26 healthy subjects. Combining probability maps of frontal and temporoparietal regions yielded a network that consisted of dorsal and ventral connections. The dorsal connections linked temporoparietal cortex with the frontal eye field and area 44 of the inferior frontal gyrus (IFG). Traveling along superior longitudinal and arcuate fascicles, these fibers are well described in relation to spatial attention. However, the ventral connections, which traveled in the white matter between insula (INS) cortex and putamen parallel to the sylvian fissure, were not previously described for visuospatial attention. Linking temporoparietal cortex with anterior INS and area 45 of IFG, these connections may provide an anatomical substrate for crossmodal cortical integration needed for stimulus perception and response in relation to current intention. The newly anatomically described integral network for visuospatial attention might improve the understanding of spatial attention deficits after white matter lesions.

  19. 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…

  20. Structural dynamics control the MicroRNA maturation pathway

    PubMed Central

    Dallaire, Paul; Tan, Huiping; Szulwach, Keith; Ma, Christopher; Jin, Peng; Major, François

    2016-01-01

    MicroRNAs (miRNAs) are crucial gene expression regulators and first-order suspects in the development and progression of many diseases. Comparative analysis of cancer cell expression data highlights many deregulated miRNAs. Low expression of miR-125a was related to poor breast cancer prognosis. Interestingly, a single nucleotide polymorphism (SNP) in miR-125a was located within a minor allele expressed by breast cancer patients. The SNP is not predicted to affect the ground state structure of the primary transcript or precursor, but neither the precursor nor mature product is detected by RT-qPCR. How this SNP modulates the maturation of miR-125a is poorly understood. Here, building upon a model of RNA dynamics derived from nuclear magnetic resonance studies, we developed a quantitative model enabling the visualization and comparison of networks of transient structures. We observed a high correlation between the distances between networks of variants with that of their respective wild types and their relative degrees of maturation to the latter, suggesting an important role of transient structures in miRNA homeostasis. We classified the human miRNAs according to pairwise distances between their networks of transient structures. PMID:27651454

  1. Accelerating Convolutional Sparse Coding for Curvilinear Structures Segmentation by Refining SCIRD-TS Filter Banks.

    PubMed

    Annunziata, Roberto; Trucco, Emanuele

    2016-11-01

    Deep learning has shown great potential for curvilinear structure (e.g., retinal blood vessels and neurites) segmentation as demonstrated by a recent auto-context regression architecture based on filter banks learned by convolutional sparse coding. However, learning such filter banks is very time-consuming, thus limiting the amount of filters employed and the adaptation to other data sets (i.e., slow re-training). We address this limitation by proposing a novel acceleration strategy to speed-up convolutional sparse coding filter learning for curvilinear structure segmentation. Our approach is based on a novel initialisation strategy (warm start), and therefore it is different from recent methods improving the optimisation itself. Our warm-start strategy is based on carefully designed hand-crafted filters (SCIRD-TS), modelling appearance properties of curvilinear structures which are then refined by convolutional sparse coding. Experiments on four diverse data sets, including retinal blood vessels and neurites, suggest that the proposed method reduces significantly the time taken to learn convolutional filter banks (i.e., up to -82%) compared to conventional initialisation strategies. Remarkably, this speed-up does not worsen performance; in fact, filters learned with the proposed strategy often achieve a much lower reconstruction error and match or exceed the segmentation performance of random and DCT-based initialisation, when used as input to a random forest classifier.

  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. 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.

  4. Structure of a strong supernova shock wave and rapid electron acceleration confined in its transition region

    SciTech Connect

    Shimada, N.; Hoshino, M.; Amano, T.

    2010-03-15

    A new rapid energization process within a supernova shock transition region (STR) is reported by utilizing numerical simulation. Although the scale of a STR as a main dissipation region is only several hundreds of thousands of kilometers, several interesting structures are found relating to the generation of a root of the energetic particles. The nonlinear evolution of plasma instabilities leads to a dynamical change in the ion phase space distribution, which associates with change in the field properties. As a result, different types of large-amplitude field structures appear. One is the leading wave packet, and another is a series of magnetic solitary humps. Each field structure has a microscopic scale (that is, the ion inertia length). Through the multiple nonlinear scattering between these large-amplitude field structures, electrons are accelerated directly. Within a STR, quick thermalization realizes energy equipartition between the ion and electron; hot electrons play an important role in keeping these large-amplitude field structures on the ion-acoustic mode. The hot electron shows non-Maxwellian distribution and could be the seed of further nonthermal population. The 'shock system', where fresh incoming and reflected ions are supplied constantly, play an essential role in our result. With a perpendicular shock geometry, the maximum energy of the electron is estimated by equating a width of the STR to a length of the Larmor radius of the energetic electron. Under some realistic condition of M{sub A}=170 and omega{sub pe}/OMEGA{sub ce}=120, maximum energy is estimated to be approx10 MeV at an instant only within the STR.

  5. Galectin-3 accelerates the progression of oral tongue squamous cell carcinoma via a Wnt/β-catenin-dependent pathway.

    PubMed

    Wang, Li-Ping; Chen, Shu-Wei; Zhuang, Shi-Min; Li, Huan; Song, Ming

    2013-07-01

    The purpose of this study was to elucidate the clinicopathological significance and mechanism of action of galectin-3 in oral tongue squamous cell carcinoma (OTSCC). Here, the expression of galectin-3 was quantified in OTSCC (n = 68) and paired OTSCC and normal surrounding tissues (n = 10) using immunohistochemical staining. Tca8113 OTSCC cells were transfected with a plasmid expressing galectin-3 cDNA or siRNA against galectin-3. Cell proliferation, migration and invasion were measured using the MTT assay, Matrigel-coated Transwell migration assay and wound healing assay. The effect of galectin-3 on the Wnt/β-catenin signaling pathway and epithelial mesenchymal transition (EMT) were investigated using a plasmid expressing the Wnt antagonist dickkopf 1 (DKK1) and Western blotting. Galectin-3 was expressed at significantly higher levels in OTSCC than the normal adjacent tissues; galectin-3 expression correlated strongly with pathological stage, pathological grade and lymph node invasion in OTSCC. Overexpression of galectin-3 promoted Tca8113 cell proliferation, migration and invasion, upregulated Wnt protein expression, activated β-catenin and induced the EMT; knockdown of galectin-3 had the opposite effects. Co-transfection of Tca8113 cells overexpressing galectin-3 with the Wnt antagonist DKK1 reduced the ability of galectin-3 to increase cell proliferation, migration and invasion, reduced upregulation of Wnt, inhibited β-catenin activation and abrogated the EMT, demonstrating that the Wnt/β-catenin signaling pathway mediated the effects of galectin-3. Galectin-3 plays an important role in the progression of OTSCC via activation of the Wnt/β-catenin signaling pathway.

  6. The Fanconi anemia DNA repair pathway: structural and functional insights into a complex disorder.

    PubMed

    Walden, Helen; Deans, Andrew J

    2014-01-01

    Mutations in any of at least sixteen FANC genes (FANCA-Q) cause Fanconi anemia, a disorder characterized by sensitivity to DNA interstrand crosslinking agents. The clinical features of cytopenia, developmental defects, and tumor predisposition are similar in each group, suggesting that the gene products participate in a common pathway. The Fanconi anemia DNA repair pathway consists of an anchor complex that recognizes damage caused by interstrand crosslinks, a multisubunit ubiquitin ligase that monoubiquitinates two substrates, and several downstream repair proteins including nucleases and homologous recombination enzymes. We review progress in the use of structural and biochemical approaches to understanding how each FANC protein functions in this pathway.

  7. Choosing the right path: enhancement of biologically relevant sets of genes or proteins using pathway structure

    PubMed Central

    Thomas, Reuben; Gohlke, Julia M; Stopper, Geffrey F; Parham, Frederick M; Portier, Christopher J

    2009-01-01

    A method is proposed that finds enriched pathways relevant to a studied condition using the measured molecular data and also the structural information of the pathway viewed as a network of nodes and edges. Tests are performed using simulated data and genomic data sets and the method is compared to two existing approaches. The analysis provided demonstrates the method proposed is very competitive with the current approaches and also provides biologically relevant results. PMID:19393085

  8. VLA Observations of ζ Aurigae: Confirmation of the Slow Acceleration Wind Density Structure

    NASA Astrophysics Data System (ADS)

    Harper, Graham M.; Brown, Alexander; Bennett, Philip D.; Baade, Robert; Walder, Rolf; Hummel, Christian A.

    2005-02-01

    Studies of the winds from single K and early M evolved stars indicate that these flows typically reach a significant fraction of their terminal velocity within the first couple of stellar radii. The most detailed spatially resolved information of the extended atmospheres of these spectral types comes from the ζ Aur eclipsing binaries. However, the wind acceleration inferred for the evolved primaries in these systems appears significantly slower than for stars of similar spectral type. Since there are no successful theories for mass loss from K and early M evolved stars, it is important to place strong empirical constraints on potential models and determine whether this difference in acceleration is real or an artifact of the analyses. We have undertaken a radio continuum monitoring study of ζ Aurigae (K4 Ib + B5 V) using the Very Large Array to test the wind density model of Baade et al. that is based on Hubble Space Telescope (HST) Goddard High Resolution Spectrograph ultraviolet spectra. ζ Aur was monitored at centimeter wavelengths over a complete orbital cycle, and flux variations during the orbit are found to be of similar magnitude to variations at similar orbital phases in the adjacent orbit. During eclipse, the flux does not decrease, showing that the radio emission originates from a volume substantially larger than R3K~(150Rsolar)3 surrounding the B star. Using the one-dimensional density model of the K4 Ib primary's wind derived from HST spectral line profile modeling and electron temperature estimates from previous optical and new HST studies, we find that the predicted radio fluxes are consistent with those observed. Three-dimensional hydrodynamic simulations indicate that the accretion flow perturbations near the B star do not contribute significantly to the total radio flux from the system, consistent with the radio eclipse observations. Our radio observations confirm the slow wind acceleration for the evolved K4 Ib component. ζ Aur's velocity

  9. Exogenous hydrogen sulfide exerts proliferation, anti-apoptosis, migration effects and accelerates cell cycle progression in multiple myeloma cells via activating the Akt pathway.

    PubMed

    Zheng, Dong; Chen, Ziang; Chen, Jingfu; Zhuang, Xiaomin; Feng, Jianqiang; Li, Juan

    2016-10-01

    Hydrogen sulfide (H2S), regarded as the third gaseous transmitter, mediates and induces various biological effects. The present study investigated the effects of H2S on multiple myeloma cell progression via amplifying the activation of Akt pathway in multiple myeloma cells. The level of H2S produced in multiple myeloma (MM) patients and healthy subjects was measured using enzyme-linked immunosorbent assay (ELISA). MM cells were treated with 500 µmol/l NaHS (a donor of H2S) for 24 h. The expression levels of phosphorylated-Akt (p-Akt), Bcl-2 and caspase-3 were measured by western blot assay. Cell viability was detected by Cell Counting Kit 8 (CCK-8). The cell cycle was analyzed by flow cytometry. Our results show that the concentration of H2S was higher in MM patients and that it increased in parallel with disease progression. Treating MM cells with 500 µmol/l NaHS for 24 h markedly increased the expression level of Bcl-2 and the activation of p-Akt, however, the expression level of caspase-3 was decreased, cell viability was increased, and cell cycle progression was accelerated in MM cells. NaHS also induced migration in MM cells in transwell migration assay. Furthermore, co-treatment of MM cells with 500 µmol/l NaHS and 50 µmol/l LY294002 for 24 h significantly overset these effects. In conclusion, our findings demonstrate that the Akt pathway contributes to NaHS-induced cell proliferation, migration and acceleration of cell cycle progression in MM cells.

  10. Structure and Assembly Pathway of the Ribosome Quality Control Complex

    PubMed Central

    Shao, Sichen; Brown, Alan; Santhanam, Balaji; Hegde, Ramanujan S.

    2015-01-01

    Summary During ribosome-associated quality control, stalled ribosomes are split into subunits and the 60S-housed nascent polypeptides are poly-ubiquitinated by Listerin. How this low-abundance ubiquitin ligase targets rare stall-generated 60S among numerous empty 60S is unknown. Here, we show that Listerin specificity for nascent chain-60S complexes depends on nuclear export mediator factor (NEMF). The 3.6 Å cryo-EM structure of a nascent chain-containing 60S-Listerin-NEMF complex revealed that NEMF makes multiple simultaneous contacts with 60S and peptidyl-tRNA to sense nascent chain occupancy. Structural and mutational analyses showed that ribosome-bound NEMF recruits and stabilizes Listerin’s N-terminal domain, while Listerin’s C-terminal RWD domain directly contacts the ribosome to position the adjacent ligase domain near the nascent polypeptide exit tunnel. Thus, highly specific nascent chain targeting by Listerin is imparted by the avidity gained from a multivalent network of context-specific individually weak interactions, highlighting a new principle of client recognition during protein quality control. PMID:25578875

  11. Zinc promotes clot stability by accelerating clot formation and modifying fibrin structure.

    PubMed

    Henderson, Sara J; Xia, Jing; Wu, Huayin; Stafford, Alan R; Leslie, Beverly A; Fredenburgh, James C; Weitz, David A; Weitz, Jeffrey I

    2016-03-01

    Zinc released from activated platelets binds fibrin(ogen) and attenuates fibrinolysis. Although zinc also affects clot formation, the mechanism and consequences are poorly understood. To address these gaps, the effect of zinc on clot formation and structure was examined in the absence or presence of factor (F) XIII. Zinc accelerated a) plasma clotting by 1.4-fold, b) fibrinogen clotting by 3.5- and 2.3-fold in the absence or presence of FXIII, respectively, c) fragment X clotting by 1.3-fold, and d) polymerisation of fibrin monomers generated with thrombin or batroxobin by 2.5- and 1.8-fold, respectively. Whereas absorbance increased up to 3.3-fold when fibrinogen was clotted in the presence of zinc, absorbance of fragment X clots was unaffected by zinc, consistent with reports that zinc binds to the αC-domain of fibrin(ogen). Scanning electron microscopic analysis revealed a two-fold increase in fibre diameter in the presence of zinc and in permeability studies, zinc increased clot porosity by 30-fold with or without FXIII. Whereas FXIII increased clot stiffness from 128 ± 19 Pa to 415 ± 27 Pa in rheological analyses, zinc reduced clot stiffness by 10- and 8.5-fold in the absence and presence of FXIII, respectively. Clots formed in the presence of zinc were more stable and resisted rupture with or without FXIII. Therefore, zinc accelerates clotting and reduces fibrin clot stiffness in a FXIII-independent manner, suggesting that zinc may work in concert with FXIII to modulate clot strength and stability.

  12. An accelerated stochastic vortex structure method for particle collision and agglomeration in homogeneous turbulence

    NASA Astrophysics Data System (ADS)

    Dizaji, Farzad F.; Marshall, Jeffrey S.

    2016-11-01

    Modeling the response of interacting particles, droplets, or bubbles to subgrid-scale fluctuations in turbulent flows is a long-standing challenge in multiphase flow simulations using the Reynolds-Averaged Navier-Stokes approach. The problem also arises for large-eddy simulation for sufficiently small values of the Kolmogorov-scale particle Stokes number. This paper expands on a recently proposed stochastic vortex structure (SVS) method for modeling of turbulence fluctuations for colliding or otherwise interacting particles. An accelerated version of the SVS method was developed using the fast multipole expansion and local Taylor expansion approach, which reduces computation speed by two orders of magnitude compared to the original SVS method. Detailed comparisons are presented showing close agreement of the energy spectrum and probability density functions of various fields between the SVS computational model, direct numerical simulation (DNS) results, and various theoretical and experimental results found in the literature. Results of the SVS method for particle collision rate and related measures of particle interaction exhibit excellent agreement with DNS predictions for homogeneous turbulent flows. The SVS method was also used with adhesive particles to simulate formation of particle agglomerates with different values of the particle Stokes and adhesion numbers, and various measures of the agglomerate structure are compared to the DNS results.

  13. 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.

  14. 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.

  15. 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.

  16. 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

    2016-04-18

    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.

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

    PubMed

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

    2014-07-02

    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.

  18. The downregulation of thioredoxin accelerated Neuro2a cell apoptosis induced by advanced glycation end product via activating several pathways.

    PubMed

    Ren, Xiang; Ma, Haiying; Qiu, Yuanyuan; Liu, Bo; Qi, Hui; Li, Zeyu; Kong, Hui; Kong, Li

    2015-08-01

    Thioredoxin (Trx), a 12 kDa protein, has different functions in different cellular environments, playing important anti-oxidative and anti-apoptotic roles and regulating the expression of transcription factors. Advanced glycation end products (AGEs) are a heterogeneous group of irreversible adducts from glucose-protein condensation reactions and are considered crucial to the development of diabetic nephropathy, retinopathy, neurodegeneration and atherosclerosis. The aim of this study was to use a Trx inhibitor to investigate the effects and mechanism of Trx down-regulation on AGE-induced Neuro2a cell apoptosis. Neuro2a cells were cultured in vitro and treated with different conditions. The apoptosis and proliferation of Neuro2a cells were detected using flow cytometry, DNA-Ladder and CCK8 assays. Rho 123 was used to detect the mitochondrial membrane potential. ROS generation and caspase3 activity were detected using a DCFH-DA probe and micro-plate reader. Western blotting and real-time PCR were used to detect the expression of proteins and genes. We found that the down-regulation of thioredoxin could accelerate AGE-induced apoptosis in Neuro2a cells. A possible underlying mechanism is that the down-regulation of thioredoxin stimulated the up-regulation of ASK1, p-JNK, PTEN, and Txnip, as well as the down-regulation of p-AKT, ultimately increasing ROS levels and caspase3 activity.

  19. Acceleration of bone regeneration by activating Wnt/β-catenin signalling pathway via lithium released from lithium chloride/calcium phosphate cement in osteoporosis.

    PubMed

    Li, Li; Peng, Xiaozhong; Qin, Yongbao; Wang, Renchong; Tang, Jingli; Cui, Xu; Wang, Ting; Liu, Wenlong; Pan, Haobo; Li, Bing

    2017-03-24

    By virtue of its excellent bioactivity and osteoconductivity, calcium phosphate cement (CPC) has been applied extensively in bone engineering. Doping a trace element into CPC can change physical characteristics and enhance osteogenesis. The trace element lithium has been demonstrated to stimulate the proliferation and differentiation of osteoblasts. We investigated the fracture-healing effect of osteoporotic defects with lithium-doped calcium phosphate cement (Li/CPC) and the underlying mechanism. Li/CPC bodies immersed in simulated body fluid converted gradually to hydroxyapatite. Li/CPC extracts stimulated the proliferation and differentiation of osteoblasts upon release of lithium ions (Li(+)) at 25.35 ± 0.12 to 50.74 ± 0.13 mg/l through activation of the Wnt/β-catenin pathway in vitro. We also examined the effect of locally administered Li(+) on defects in rat tibia between CPC and Li/CPC in vivo. Micro-computed tomography and histological staining showed that Li/CPC had better osteogenesis by increasing bone mass and promoting repair in defects compared with CPC (P < 0.05). Li/CPC also showed better osteoconductivity and osseointegration. These findings suggest that local release of Li(+) from Li/CPC may accelerate bone regeneration from injury through activation of the Wnt/β-catenin pathway in osteoporosis.

  20. Acceleration of bone regeneration by activating Wnt/β-catenin signalling pathway via lithium released from lithium chloride/calcium phosphate cement in osteoporosis

    NASA Astrophysics Data System (ADS)

    Li, Li; Peng, Xiaozhong; Qin, Yongbao; Wang, Renchong; Tang, Jingli; Cui, Xu; Wang, Ting; Liu, Wenlong; Pan, Haobo; Li, Bing

    2017-03-01

    By virtue of its excellent bioactivity and osteoconductivity, calcium phosphate cement (CPC) has been applied extensively in bone engineering. Doping a trace element into CPC can change physical characteristics and enhance osteogenesis. The trace element lithium has been demonstrated to stimulate the proliferation and differentiation of osteoblasts. We investigated the fracture-healing effect of osteoporotic defects with lithium-doped calcium phosphate cement (Li/CPC) and the underlying mechanism. Li/CPC bodies immersed in simulated body fluid converted gradually to hydroxyapatite. Li/CPC extracts stimulated the proliferation and differentiation of osteoblasts upon release of lithium ions (Li+) at 25.35 ± 0.12 to 50.74 ± 0.13 mg/l through activation of the Wnt/β-catenin pathway in vitro. We also examined the effect of locally administered Li+ on defects in rat tibia between CPC and Li/CPC in vivo. Micro-computed tomography and histological staining showed that Li/CPC had better osteogenesis by increasing bone mass and promoting repair in defects compared with CPC (P < 0.05). Li/CPC also showed better osteoconductivity and osseointegration. These findings suggest that local release of Li+ from Li/CPC may accelerate bone regeneration from injury through activation of the Wnt/β-catenin pathway in osteoporosis.

  1. Acceleration of bone regeneration by activating Wnt/β-catenin signalling pathway via lithium released from lithium chloride/calcium phosphate cement in osteoporosis

    PubMed Central

    Li, Li; Peng, Xiaozhong; Qin, Yongbao; Wang, Renchong; Tang, Jingli; Cui, Xu; Wang, Ting; Liu, Wenlong; Pan, Haobo; Li, Bing

    2017-01-01

    By virtue of its excellent bioactivity and osteoconductivity, calcium phosphate cement (CPC) has been applied extensively in bone engineering. Doping a trace element into CPC can change physical characteristics and enhance osteogenesis. The trace element lithium has been demonstrated to stimulate the proliferation and differentiation of osteoblasts. We investigated the fracture-healing effect of osteoporotic defects with lithium-doped calcium phosphate cement (Li/CPC) and the underlying mechanism. Li/CPC bodies immersed in simulated body fluid converted gradually to hydroxyapatite. Li/CPC extracts stimulated the proliferation and differentiation of osteoblasts upon release of lithium ions (Li+) at 25.35 ± 0.12 to 50.74 ± 0.13 mg/l through activation of the Wnt/β-catenin pathway in vitro. We also examined the effect of locally administered Li+ on defects in rat tibia between CPC and Li/CPC in vivo. Micro-computed tomography and histological staining showed that Li/CPC had better osteogenesis by increasing bone mass and promoting repair in defects compared with CPC (P < 0.05). Li/CPC also showed better osteoconductivity and osseointegration. These findings suggest that local release of Li+ from Li/CPC may accelerate bone regeneration from injury through activation of the Wnt/β-catenin pathway in osteoporosis. PMID:28338064

  2. The 3D velocity structure beneath Iceland: Identifying melt pathways

    NASA Astrophysics Data System (ADS)

    Allen, R.

    2003-04-01

    The integration of various seismic datasets, recorded by the broadband HOTSPOT network deployed across Iceland, provides one of the highest resolution studies of the crust and mantle structure associated with a plume-ridge system. The mantle P- and S-velocity models (ICEMAN), derived from teleseismic body-wave and surface wave analysis, show a vertical, cylindrical low velocity anomaly ˜200 km in diameter extending from ˜400 km, the maximum depth of resolution, up to ˜200 km above which low velocity material is present beneath all of Iceland. The maximum P- and S-velocity anomalies of -2% and -4% respectively are found beneath the northwestern edge of Vatnajokull. The crustal S-velocity model (ICECRTb) is constrained by local surface waves, refraction experiments and receiver functions, and shows significant variation in crustal thickness. The thinnest, ˜15 km, crust is found around coastal regions, the thickest crust is beneath northwestern Vatnajokull where it reaches a thickness of 45 km. Within this thick crustal root is a vertical low velocity anomaly connecting the core of the mantle anomaly to horizontal low velocity regions that extend along the western and eastern volcanic zones but not the northern volcanic zone. These crustal low velocity zones are interpreted as regions through which melt is fed from the mantle to shallow magma chambers beneath the rift zones, where crustal formation occurs. The pipework between the core of the mantle anomaly and the southern rift zones is responsible for ˜30 km thick crust. Its absence to the north results in relatively thin, ˜20 km thick, crust.

  3. Design, realization and test of C-band accelerating structures for the SPARC_LAB linac energy upgrade

    NASA Astrophysics Data System (ADS)

    Alesini, D.; Bellaveglia, M.; Biagini, M. E.; Boni, R.; Brönnimann, M.; Cardelli, F.; Chimenti, P.; Clementi, R.; Di Pirro, G.; Di Raddo, R.; Ferrario, M.; Ficcadenti, L.; Gallo, A.; Kalt, R.; Lollo, V.; Palumbo, L.; Piersanti, L.; Schilcher, T.

    2016-11-01

    The energy upgrade of the SPARC_LAB photo-injector at LNF-INFN (Frascati, Italy) has been originally conceived replacing one low gradient (13 MV/m) 3 m long SLAC type S-band traveling wave (TW) section with two 1.4 m long C-band accelerating sections. Due to the higher gradients reached by such structures, a higher energy beam can be obtained within the same accelerator footprint length. The use of C-band structures for electron acceleration has been adopted in a few FEL linacs in the world, among others, the Japanese Free Electron Laser at SPring-8 and the SwissFEL at Paul Scherrer Institute (PSI). The C-band sections are traveling wave, constant impedance structures with symmetric input and output axial couplers. Their design has been optimized for the operation with a SLED RF pulse compressor. In this paper we briefly review their design criteria and we focus on the construction, tuning, low and high-power RF tests. We also illustrate the design and realization of the dedicated low level RF system that has been done in collaboration with PSI in the framework of the EU TIARA project. Preliminary experimental results appear to confirm the operation of such structures with accelerating gradients larger than 35 MV/m.

  4. 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

  5. Structural enzymology of Helicobacter pylori methylthioadenosine nucleosidase in the futalosine pathway.

    PubMed

    Kim, Robbert Q; Offen, Wendy A; Davies, Gideon J; Stubbs, Keith A

    2014-01-01

    The recently discovered futalosine pathway is a promising target for the development of new antibiotics. The enzymes involved in this pathway are crucial for the biosynthesis of the essential prokaryotic respiratory compound menaquinone, and as the pathway is limited to few bacterial species such as the gastric pathogen Helicobacter pylori it is a potential target for specific antibiotics. In this report, the crystal structure of an H. pylori methylthioadenosine nucleosidase (MTAN; an enzyme with broad specificity and activity towards 6-amino-6-deoxyfutalosine), which is involved in the second step of menaquinone biosynthesis, has been elucidated at a resolution of 1.76 Å and refined with R factors of Rwork = 17% and Rfree = 21%. Activity studies on the wild type and active-site mutants show that the hydrolysis of 6-amino-6-deoxyfutalosine follows a mechanism similar to that of Escherichia coli MTAN. Further evidence for this mode of action is supplied by the crystal structures of active-site mutants. Through the use of reaction intermediates, the structures give additional evidence for the previously proposed nucleosidase mechanism. These structures and the confirmed reaction mechanism will provide a structural basis for the design of new inhibitors targeting the futalosine pathway.

  6. Structure of mycobacterial maltokinase, the missing link in the essential GlgE-pathway

    PubMed Central

    Fraga, Joana; Maranha, Ana; Mendes, Vitor; Pereira, Pedro José Barbosa; Empadinhas, Nuno; Macedo-Ribeiro, Sandra

    2015-01-01

    A novel four-step pathway identified recently in mycobacteria channels trehalose to glycogen synthesis and is also likely involved in the biosynthesis of two other crucial polymers: intracellular methylglucose lipopolysaccharides and exposed capsular glucan. The structures of three of the intervening enzymes - GlgB, GlgE, and TreS - were recently reported, providing the first templates for rational drug design. Here we describe the structural characterization of the fourth enzyme of the pathway, mycobacterial maltokinase (Mak), uncovering a eukaryotic-like kinase (ELK) fold, similar to methylthioribose kinases and aminoglycoside phosphotransferases. The 1.15 Å structure of Mak in complex with a non-hydrolysable ATP analog reveals subtle structural rearrangements upon nucleotide binding in the cleft between the N- and the C-terminal lobes. Remarkably, this new family of ELKs has a novel N-terminal domain topologically resembling the cystatin family of protease inhibitors. By interfacing with and restraining the mobility of the phosphate-binding region of the N-terminal lobe, Mak's unusual N-terminal domain might regulate its phosphotransfer activity and represents the most likely anchoring point for TreS, the upstream enzyme in the pathway. By completing the gallery of atomic-detail models of an essential pathway, this structure opens new avenues for the rational design of alternative anti-tubercular compounds. PMID:25619172

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

    SciTech Connect

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

    2016-01-15

    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 SO{sub 4}{sup 2−} anion NO{sup −} are more efficient. The mentioned additives according to accelerating effect belong to the following succession: K{sub 2}SO{sub 4} > Na{sub 2}SO{sub 4} > FeSO{sub 4} > MgSO{sub 4}. 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.

  8. 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.

  9. 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.

  10. Structural Shielding Design of a 6 MV Flattening Filter Free Linear Accelerator: Indian Scenario

    PubMed Central

    Mishra, Bibekananda; Selvam, T. Palani; Sharma, P. K. Dash

    2017-01-01

    Detailed structural shielding of primary and secondary barriers for a 6 MV medical linear accelerator (LINAC) operated with flattening filter (FF) and flattening filter free (FFF) modes are calculated. The calculations have been carried out by two methods, one using the approach given in National Council on Radiation Protection (NCRP) Report No. 151 and the other based on the monitor units (MUs) delivered in clinical practice. Radiation survey of the installations was also carried out. NCRP approach suggests that the primary and secondary barrier thicknesses are higher by 24% and 26%. respectively, for a LINAC operated in FF mode to that of a LINAC operated in both FF and FFF modes with an assumption that only 20% of the workload is shared in FFF mode. Primary and secondary barrier thicknesses calculated from MUs delivered on clinical practice method also show the same trend and are higher by 20% and 19%, respectively, for a LINAC operated in FF mode to that of a LINAC operated in both FF and FFF modes. Overall, the barrier thickness for a LINAC operated in FF mode is higher about 20% to that of a LINAC operated in both FF and FFF modes.

  11. 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.

  12. 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.

  13. FACET ORIENTATION AND TROPISM: ASSOCIATION WITH ACCELERATED DEGENERATION OF STABILIZING STRUCTURES IN LOWER LUMBAR SPINE.

    PubMed

    Jelec, Vjekoslav; Turner, Rajka; Franić, Miljenko; Korušić, Anđelko; Rotim, Krešimir

    2016-03-01

    The influence of facet orientation and tropism on the process of spinal degeneration has been extensively studied during the last few decades, but there are still many controversies and conflicting results in this field of research. The biomechanical cause of accelerated degeneration of stabilizing structures in lower lumbar spine lies within the combination of several factors, but two most important ones are compressive load and more coronal facet orientation that offers less resistance against torsional loading. Axial rotation of lower lumbar spine is undoubtedly associated with higher strain in disc annulus, and enhanced range of secondary rotational movements may be even more significant for the progression of annular degeneration. Accordingly, more pronounced facet tropism could be having part in faster progression of disc degeneration in lower lumbar spine, as indicated by a number of recent studies. More sagittal facet orientation in patients with a higher facet osteoarthritis score at lower lumbar segments is very likely related to arthritic remodeling commonly seen in other synovial joints. There is also a possibility that it could be associated with the adaptation to partial loss of lumbar lordosis, as both coincide with advanced age.

  14. 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.

  15. A Study of Higher-Band Dipole Wakefields in X-Band Accelerating Structures for the G/NLC

    SciTech Connect

    Jones, R

    2004-09-02

    The X-band linacs for the G/NLC (Global/Next Linear Collider) have evolved from the DDS (Damped Detuned Structure) series. The present accelerating structures are 60 cm in length and incorporate damping and detuning of the dipole modes which comprise the wakefield. In order to adequately damp the wakefield, frequencies of adjacent structures are interleaved. Limited analysis has been done previously on the higher order dipole bands. Here, we calculate the contribution of higher order bands of interleaved structures to the wakefield. Beam dynamics issues are also studied.

  16. Structural basis for the transformation pathways of the sodium naproxen anhydrate-hydrate system.

    PubMed

    Bond, Andrew D; Cornett, Claus; Larsen, Flemming H; Qu, Haiyan; Raijada, Dhara; Rantanen, Jukka

    2014-09-01

    Crystal structures are presented for two dihydrate polymorphs (DH-I and DH-II) of the non-steroidal anti-inflammatory drug sodium (S)-naproxen. The structure of DH-I is determined from twinned single crystals obtained by solution crystallization. DH-II is obtained by solid-state routes, and its structure is derived using powder X-ray diffraction, solid-state (13)C and (23)Na MAS NMR, and molecular modelling. The validity of both structures is supported by dispersion-corrected density functional theory (DFT-D) calculations. The structures of DH-I and DH-II, and in particular their relationships to the monohydrate (MH) and anhydrate (AH) structures, provide a basis to rationalize the observed transformation pathways in the sodium (S)-naproxen anhydrate-hydrate system. All structures contain Na(+)/carboxylate/H2O sections, alternating with sections containing the naproxen molecules. The structure of DH-I is essentially identical to MH in the naproxen region, containing face-to-face arrangements of the naphthalene rings, whereas the structure of DH-II is comparable to AH in the naproxen region, containing edge-to-face arrangements of the naphthalene rings. This structural similarity permits topotactic transformation between AH and DH-II, and between MH and DH-I, but requires re-organization of the naproxen molecules for transformation between any other pair of structures. The topotactic pathways dominate at room temperature or below, while the non-topotactic pathways become active at higher temperatures. Thermochemical data for the dehydration processes are rationalized in the light of this new structural information.

  17. First-principles prediction of stable SiC cage structures and their synthesis pathways

    NASA Astrophysics Data System (ADS)

    Pochet, Pascal; Genovese, Luigi; Caliste, Damien; Rousseau, Ian; Goedecker, Stefan; Deutsch, Thierry

    2010-07-01

    In this paper we use density functional theory calculations to investigate the structure and the stability of different SiC cagelike clusters. In addition to the fullerene family and the mixed four and six membered ring family, we introduce a family based on reconstructed nanotube slices. We propose an alternative synthesis pathway starting from SiC nanotubes.

  18. Schooling in Times of Acceleration

    ERIC Educational Resources Information Center

    Buddeberg, Magdalena; Hornberg, Sabine

    2017-01-01

    Modern societies are characterised by forms of acceleration, which influence social processes. Sociologist Hartmut Rosa has systematised temporal structures by focusing on three categories of social acceleration: technical acceleration, acceleration of social change, and acceleration of the pace of life. All three processes of acceleration are…

  19. Understanding specificity in metabolic pathways--structural biology of human nucleotide metabolism.

    PubMed

    Welin, Martin; Nordlund, Pär

    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.

  20. 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.

  1. An introduction to acceleration mechanisms

    SciTech Connect

    Palmer, R.B.

    1987-05-01

    This paper discusses the acceleration of charged particles by electromagnetic fields, i.e., by fields that are produced by the motion of other charged particles driven by some power source. The mechanisms that are discussed include: Ponderamotive Forces, Acceleration, Plasma Beat Wave Acceleration, Inverse Free Electron Laser Acceleration, Inverse Cerenkov Acceleration, Gravity Acceleration, 2D Linac Acceleration and Conventional Iris Loaded Linac Structure Acceleration. (LSP)

  2. Structural characterization of the enzymes composing the arginine deiminase pathway in Mycoplasma penetrans.

    PubMed

    Gallego, Pablo; Planell, Raquel; Benach, Jordi; Querol, Enrique; Perez-Pons, Josep A; Reverter, David

    2012-01-01

    The metabolism of arginine towards ATP synthesis has been considered a major source of energy for microorganisms such as Mycoplasma penetrans in anaerobic conditions. Additionally, this pathway has also been implicated in pathogenic and virulence mechanism of certain microorganisms, i.e. protection from acidic stress during infection. In this work we present the crystal structures of the three enzymes composing the gene cluster of the arginine deiminase pathway from M. penetrans: arginine deiminase (ADI), ornithine carbamoyltransferase (OTC) and carbamate kinase (CK). The arginine deiminase (ADI) structure has been refined to 2.3 Å resolution in its apo-form, displaying an "open" conformation of the active site of the enzyme in comparison to previous complex structures with substrate intermediates. The active site pocket of ADI is empty, with some of the catalytic and binding residues far from their active positions, suggesting major conformational changes upon substrate binding. Ornithine carbamoyltransferase (OTC) has been refined in two crystal forms at 2.5 Å and 2.6 Å resolution, respectively, both displaying an identical dodecameric structure with a 23-point symmetry. The dodecameric structure of OTC represents the highest level of organization in this protein family and in M.penetrans it is constituted by a novel interface between the four catalytic homotrimers. Carbamate kinase (CK) has been refined to 2.5 Å resolution and its structure is characterized by the presence of two ion sulfates in the active site, one in the carbamoyl phosphate binding site and the other in the β-phosphate ADP binding pocket of the enzyme. The CK structure also shows variations in some of the elements that regulate the catalytic activity of the enzyme. The relatively low number of metabolic pathways and the relevance in human pathogenesis of Mycoplasma penetrans places the arginine deiminase pathway enzymes as potential targets to design specific inhibitors against this human

  3. 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.

  4. Highly symmetric interfacial coherent structures in Rayleigh Taylor instability with time-dependent acceleration

    NASA Astrophysics Data System (ADS)

    Bhowmick, Aklant K.; Abarzhi, Snezhana

    2016-11-01

    Rayleigh Taylor instability in a power-law time dependent acceleration field is investigated theoretically for a flow with the symmetry group p6mm (hexagon) in the plane normal to acceleration. In the nonlinear regime, regular asymptotic solutions form a one-parameter family. The physically significant solution is identified with the one having the fastest growth and being stable (bubble tip velocity). Two distinct regimes are identified depending on the acceleration exponent. Particularly, the RM-type regime, where the dynamics is identical to conventional RM instability and is dominated by initial conditions, and the RT-type regime where the dynamics is dominated by the acceleration term. For the latter, the time dependence has profound effects on the dynamics. In the RT non-linear regime, the time dependence has no consequence on the morphology of the bubbles; the growth rate (bubble tip velocity) evolves as power law with the exponent set by the acceleration. The solutions for a one-parameter family, and are convergent with exponential decay of Fourier amplitudes. The solutions are stable at maximum tip velocity, whereas flat bubbles are unstable, and the growth/decay of perturbations is no longer purely exponential and depends on the acceleration exponent. The work is supported by the US National Science Foundation.

  5. Highly symmetric interfacial structures in Rayleigh Taylor instability with time-dependent acceleration

    NASA Astrophysics Data System (ADS)

    Bhowmick, Aklant K.; Abarzhi, Snezhana

    2016-10-01

    Rayleigh Taylor instability in a power-law time dependent acceleration field is investigated for a flow with the symmetry group p6mm (hexagonal) in the plane normal to acceleration. The Regular asymptotic solutions form a one-parameter family and the physically significant solution is identified with the one having the fastest growth and being stable (bubble tip velocity). Two distinct regimes are identified dependent on the acceleration exponent, the RM-type regime, where the dynamics is identical to conventional RM instability and is dominated by initial conditions, and the RT-type regime where the dynamics is dominated by the acceleration term. For the latter, the time dependence has profound effects on the dynamics. In the RT non-linear regime, the time dependence has no consequence on the morphology of the bubbles but the growth rate (bubble tip velocity) evolves as power law with the exponent set by the acceleration. The solutions for a one-parameter family, and are convergent with exponential decay of Fourier amplitudes close to the physical solution. The solutions are stable at maximum tip velocity and flat bubbles are unstable, and the growth/decay of perturbations is no longer purely exponential and depends on the acceleration exponent. The work is supported by the US National Science Foundation.

  6. 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

  7. 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.

  8. Structural pathways of cytokines may illuminate their roles in regulation of cancer development and immunotherapy.

    PubMed

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

    2014-03-25

    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).

  9. 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.

  10. High-frequency sonophoresis: permeation pathways and structural basis for enhanced permeability.

    PubMed

    Menon, G K; Bommannan, D B; Elias, P M

    1994-01-01

    The mechanism of stratum corneum (SC) permeabilization by ultrasound (sonophoresis) is unknown. We studied here permeation pathways, and SC intercellular structural organization following applications of high-frequency sonophoresis to hairless mouse skin. Ruthenium tetroxide post-fixation and tracer solutions of LaNO3 and FITC-dextrans were employed to examine SC lamellar bilayers, lamellar body morphology and subcellular permeation pathways. Sonophoresis disrupted the compact organization of SC bilayers and LB-derived contents at the stratum granulosum (SG)-SC interface, leading to domain separation between 0 and 20 h, reverting by 48 h. Post-sonophoresis, tracers traversed the SC via lacunae within the lamellar bilayers, and via lamellae in sites that displayed domain separation. These studies provide insights about the penetration pathways, permeabilizing mechanisms, and kinetics of sonophoresis on the epidermis.

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

    SciTech Connect

    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.

  12. 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

    2016-02-05

    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 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.

  13. 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.

  14. Interaction of an ultrarelativistic electron bunch train with a W-band accelerating structure: High power and high gradient

    DOE PAGES

    Wang, D.; Antipov, S.; Jing, C.; ...

    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

  15. Interaction of an ultrarelativistic electron bunch train with a W-band accelerating structure: High power and high gradient

    SciTech Connect

    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.

    2016-02-05

    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 the 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.

  16. Folding pathways of proteins with increasing degree of sequence identities but different structure and function.

    PubMed

    Giri, Rajanish; Morrone, Angela; Travaglini-Allocatelli, Carlo; Jemth, Per; Brunori, Maurizio; Gianni, Stefano

    2012-10-30

    Much experimental work has been devoted in comparing the folding behavior of proteins sharing the same fold but different sequence. The recent design of proteins displaying very high sequence identities but different 3D structure allows the unique opportunity to address the protein-folding problem from a complementary perspective. Here we explored by Φ-value analysis the pathways of folding of three different heteromorphic pairs, displaying increasingly high-sequence identity (namely, 30%, 77%, and 88%), but different structures called G(A) (a 3-α helix fold) and G(B) (an α/β fold). The analysis, based on 132 site-directed mutants, is fully consistent with the idea that protein topology is committed very early along the pathway of folding. Furthermore, data reveals that when folding approaches a perfect two-state scenario, as in the case of the G(A) domains, the structural features of the transition state appear very robust to changes in sequence composition. On the other hand, when folding is more complex and multistate, as for the G(B)s, there are alternative nuclei or accessible pathways that can be alternatively stabilized by altering the primary structure. The implications of our results in the light of previous work on the folding of different members belonging to the same protein family are discussed.

  17. 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.

  18. Representation of gravity-aligned scene structure in ventral pathway visual cortex

    PubMed Central

    Vaziri, Siavash; Connor, Charles E.

    2016-01-01

    Summary 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, 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/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, 4, 5]. Our results, like the recent discovery of object weight representation [6], imply the ventral pathway is involved not just in recognition but also in physical understanding of objects and scenes. PMID:26923785

  19. Impact of the α-Synuclein Initial Ensemble Structure on Fibrillation Pathways and Kinetics.

    PubMed

    Bai, Jia; Cheng, Kai; Liu, Maili; Li, Conggang

    2016-03-31

    The presence of intracellular filamentous α-synuclein (αS) aggregates is a common feature in Parkinson's disease. Recombinant expressed and purified human αS is also capable of forming fibrils in vitro. Many studies have shown that solution conditions heavily influence αS fibrillation kinetics, fibril structure, and morphology that exhibit differential biological effects. Nevertheless, the αS ensemble structure in various solution conditions is not well characterized; furthermore, how the initial solution ensemble structures impact αS assembly kinetics and pathways that result in diverse fibril structure and morphology remains elusive. Here, we mainly employed NMR spectroscopy to characterize the initial ensemble structure of αS in the presence or absence of a 150 mM sodium chloride (NaCl) solution, where two polymorphs of αS were demonstrated in previous studies. Our data show that αS exhibits distinct conformations and fibrillation kinetics in these two solutions. αS adopts a more compact and rigid ensemble structure that has faster fibrillation kinetics in the absence of NaCl. On the basis of the ensemble structure and dynamics, we proposed a possible molecular mechanism in which αS forms different polymorphs under these two conditions. Our results provide novel insights into how the initial conformation impacts fibrillation pathways and kinetics, suggesting that a microenvironment can be used to regulate the intrinsically disordered proteins assembly.

  20. IMPEDANCE MEASUREMENT SETUP FOR HIGHER-ORDER MODE STUDIES IN NLC ACCELERATING STRUCTURES WITH THE WIRE METHOD

    SciTech Connect

    Baboi, Nicoleta

    2002-09-19

    Dipole modes are the main cause of transverse emittance dilution in the Japanese Linear Collider/Next Linear Collider (JLC/NLC). A diagnostic setup has been built in order to investigate them. The method is based on using a coaxial wire to excite and measure electromagnetic modes of accelerating structures. This method can offer a more efficient and less expensive procedure than the ASSET facility. Initial measurements have been made and are presented in this paper.

  1. Superconducting accelerating structure for particle velocities from 0. 12 to 0. 23 c

    SciTech Connect

    Shepard, K.W.; Zinkann, G.P.

    1983-01-01

    A split-ring resonator has been designed for an optimum particle velocity ..beta.. = v/c = 0.16 and a frequency of 145.5 MHz. The ratio of peak-surface electric field to effective accelerating field in the resonator has been reduced 20% from the value obtained in previously developed split-ring resonators. The improved design results from the use of elliptically-sectioned loading arms and drift tubes, which have been enlarged to reduce peak-surface fields and also shaped to eliminate beam-steering effects in the resonator. All fabrication problems presented by the more-complex geometry have been solved, and a prototype superconducting niobium resonator has been completed. An accelerating field of 3.3 MV/m at 4 watts rf input has been so far achieved, corresponding to an effective accelerating potential of 1.17 MV per resonator.

  2. Integrative Approaches to Enhance Understanding of Plant Metabolic Pathway Structure and Regulation1

    PubMed Central

    Tohge, Takayuki; Scossa, Federico; Fernie, Alisdair R.

    2015-01-01

    Huge insight into molecular mechanisms and biological network coordination have been achieved following the application of various profiling technologies. Our knowledge of how the different molecular entities of the cell interact with one another suggests that, nevertheless, integration of data from different techniques could drive a more comprehensive understanding of the data emanating from different techniques. Here, we provide an overview of how such data integration is being used to aid the understanding of metabolic pathway structure and regulation. We choose to focus on the pairwise integration of large-scale metabolite data with that of the transcriptomic, proteomics, whole-genome sequence, growth- and yield-associated phenotypes, and archival functional genomic data sets. In doing so, we attempt to provide an update on approaches that integrate data obtained at different levels to reach a better understanding of either single gene function or metabolic pathway structure and regulation within the context of a broader biological process. PMID:26371234

  3. 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

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

    PubMed

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

    2011-10-25

    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.

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

    PubMed Central

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

    2011-01-01

    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. PMID:21987796

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. Success Structure for Accelerated Acquisition of English by Young ESL Learners

    ERIC Educational Resources Information Center

    Mohamed, Abdul Rashid; Tumin, Mahani; Omar, Hamzah

    2008-01-01

    This is an investigation into the accelerated acquisition of English among young ESL learners in an International School. It employed an ethnographic case study approach where data were gathered through non-participant observations, unstructured interviews, relevant documents, students' portfolios, field notes and biographical details. The sample…

  13. 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.

  14. Existence of Different Structural Intermediates on the Fibrillation Pathway of Human Serum Albumin

    PubMed Central

    Juárez, Josué; Taboada, Pablo; Mosquera, Víctor

    2009-01-01

    The fibrillation propensity of the multidomain protein human serum albumin (HSA) was analyzed under different solution conditions. The aggregation kinetics, protein conformational changes upon self-assembly, and structure of the different intermediates on the fibrillation pathway were determined by means of thioflavin T (ThT) fluorescence and Congo Red absorbance; far- and near-ultraviolet circular dichroism; tryptophan fluorescence; Fourier transform infrared spectroscopy; x-ray diffraction; and transmission electron, scanning electron, atomic force, and microscopies. HSA fibrillation extends over several days of incubation without the presence of a lag phase, except for HSA samples incubated at acidic pH and room temperature in the absence of electrolyte. The absence of a lag phase occurs if the initial aggregation is a downhill process that does not require a highly organized and unstable nucleus. The fibrillation process is accompanied by a progressive increase in the β-sheet (up to 26%) and unordered conformation at the expense of α-helical conformation, as revealed by ThT fluorescence and circular dichroism and Fourier transform infrared spectroscopies, but changes in the secondary structure contents depend on solution conditions. These changes also involve the presence of different structural intermediates in the aggregation pathway, such as oligomeric clusters (globules), bead-like structures, and ring-shaped aggregates. We suggest that fibril formation may take place through the role of association-competent oligomeric intermediates, resulting in a kinetic pathway via clustering of these oligomeric species to yield protofibrils and then fibrils. The resultant fibrils are elongated but curly, and differ in length depending on solution conditions. Under acidic conditions, circular fibrils are commonly observed if the fibrils are sufficiently flexible and long enough for the ends to find themselves regularly in close proximity to each other. These fibrils

  15. Structural Conservation of Ligand Binding Reveals a Bile Acid-like Signaling Pathway in Nematodes*

    PubMed Central

    Zhi, Xiaoyong; Zhou, X. Edward; Melcher, Karsten; Motola, Daniel L.; Gelmedin, Verena; Hawdon, John; Kliewer, Steven A.; Mangelsdorf, David J.; Xu, H. Eric

    2012-01-01

    Bile acid-like molecules named dafachronic acids (DAs) control the dauer formation program in Caenorhabditis elegans through the nuclear receptor DAF-12. This mechanism is conserved in parasitic nematodes to regulate their dauer-like infective larval stage, and as such, the DAF-12 ligand binding domain has been identified as an important therapeutic target in human parasitic hookworm species that infect more than 600 million people worldwide. Here, we report two x-ray crystal structures of the hookworm Ancylostoma ceylanicum DAF-12 ligand binding domain in complex with DA and cholestenoic acid (a bile acid-like metabolite), respectively. Structure analysis and functional studies reveal key residues responsible for species-specific ligand responses of DAF-12. Furthermore, DA binds to DAF-12 mechanistically and is structurally similar to bile acids binding to the mammalian bile acid receptor farnesoid X receptor. Activation of DAF-12 by cholestenoic acid and the cholestenoic acid complex structure suggest that bile acid-like signaling pathways have been conserved in nematodes and mammals. Together, these results reveal the molecular mechanism for the interplay between parasite and host, provide a structural framework for DAF-12 as a promising target in treating nematode parasitism, and provide insight into the evolution of gut parasite hormone-signaling pathways. PMID:22170062

  16. Simplified Protein Models: Predicting Folding Pathways and Structure Using Amino Acid Sequences

    NASA Astrophysics Data System (ADS)

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

    2013-07-01

    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 nativelike 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 nativelike propensities in the unfolded state do not necessarily determine the order of structure formation, a departure from a major conclusion of the molecular dynamics 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.

  17. 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.

  18. Structures of the ozonolysis products and ozonolysis pathway of aflatoxin B1 in acetonitrile solution.

    PubMed

    Diao, Enjie; Shan, Changpo; Hou, Hanxue; Wang, Shanshan; Li, Minghua; Dong, Haizhou

    2012-09-12

    The ozonolysis of aflatoxin B(1) (400 μg/mL) in acetonitrile solution was conducted with an ozone concentration of 6.28 mg/L at the flow rate of 60 mL/min for different times. The results showed that ozone was an effective detoxification agent because of its powerful oxidative role. Thin-layer chromatography and liquid chromatography-quadrupole time-of-flight mass spectra were applied to confirm and identify the ozonolysis products of aflatoxin B(1). A total of 13 products were identified, and 6 of them were main products. The structural identification of these products provided effective information for understanding the ozonolysis pathway of aflatoxin B(1). Two ozonolysis pathways were proposed on the basis of the accurate mass and molecular formulas of these product ions. Nine ozonolysis products came from the first oxidative pathway based on the Criegee mechanism, and the other four products were produced from the second pathway based on the oxidative and electrophilic reactions of ozone. According to the toxicity mechanism of aflatoxin B(1) to animals, the toxicity of aflatoxin B(1) was significantly reduced because of the disappearance of the double bond on the terminal furan ring or the lactone moiety on the benzene ring.

  19. 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.

  20. Structurally similar estradiol analogs uniquely alter the regulation of intracellular signaling pathways.

    PubMed

    Yarger, James G; Babine, Robert E; Bittner, Michael; Shanle, Erin; Xu, Wei; Hershberger, Pamela; Nye, Steven H

    2013-02-01

    Ligand structure can affect the activation of nuclear receptors, such as estrogen receptors (ERs), and their control of signaling pathways for cellular responses including death and differentiation. We hypothesized that distinct biological functions of similar estradiol (E(2)) analogs could be identified by integrating gene expression patterns obtained from human tumor cell lines with receptor binding and functional data for the purpose of developing compounds for treatment of a variety of diseases. We compared the estrogen receptor subtype selectivity and impact on signaling pathways for three distinct, but structurally similar, analogs of E(2). Modifications in the core structure of E(2) led to pronounced changes in subtype selectivity for estrogen receptors, ER-α or ER-β, along with varying degrees of ER dimerization and activation. While all three E(2) analogs are predominantly ER-β agonists, the cell growth inhibitory activity commonly associated with this class of compounds was detected for only two of the analogs and might be explained by a ligand-specific pattern of gene transcription. Microarray studies using three different human tumor cell lines demonstrated that the analogs distinctly affect the transcription of genes in signaling pathways for chromosome replication, cell death, and oligodendrocyte progenitor cell differentiation. That the E(2) analogs could lower tumor cell viability and stimulate neuronal differentiation confirmed that gene expression data could accurately distinguish biological activity of the E(2) analogs. The findings reported here confirm that cellular responses can be regulated by making key structural alterations to the core structure of endogenous ER ligands.

  1. 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.

  2. Gas density structure of supersonic flows impinged on by thin blades for laser-plasma accelerators

    NASA Astrophysics Data System (ADS)

    Mao, H.-S.; Swanson, K. K.; Tsai, H.-E.; Barber, S. K.; Steinke, S.; van Tilborg, J.; Geddes, C. G. R.; Leemans, W. P.

    2017-03-01

    Density transition injection is an effective technique for controllably loading electrons into a trapped phase for laser-plasma accelerators. One common technique to achieve this fluid phenomenon is to impinge a thin blade on the plume of a supersonic nozzle. 2-D simulations show that the density transition accessible to a transverse laser is produced by a rapid re-expansion of the high pressure region behind the initial bow shock, and not by the bow shock produced by the blade, as is commonly thought. This pressure mismatched re-expansion generates compression waves that could coalesce into shock-fronts as they interact with the surrounding ambient gas. This has consequences when interpreting the electron injection mechanism. In the simulations presented here, the fluid dynamics of a supersonic nozzle impinged on by a thin, flat object is explored, along with the implications for electron beam injectors in laser-plasma accelerators.

  3. Structural basis of YAP recognition by TEAD4 in the Hippo pathway

    PubMed Central

    Chen, Liming; Chan, Siew Wee; Zhang, XiaoQian; Walsh, Martin; Lim, Chun Jye; Hong, Wanjin; Song, Haiwei

    2010-01-01

    The Hippo signaling pathway controls cell growth, proliferation, and apoptosis by regulating the expression of target genes that execute these processes. Acting downstream from this pathway is the YAP transcriptional coactivator, whose biological function is mediated by the conserved TEAD family transcription factors. The interaction of YAP with TEADs is critical to regulate Hippo pathway-responsive genes. Here, we describe the crystal structure of the YAP-interacting C-terminal domain of TEAD4 in complex with the TEAD-interacting N-terminal domain of YAP. The structure reveals that the N-terminal region of YAP is folded into two short helices with an extended loop containing the PXXΦP motif in between, while the C-terminal domain of TEAD4 has an immunoglobulin-like fold. YAP interacts with TEAD4 mainly through the two short helices. Point mutations of TEAD4 indicate that the residues important for YAP interaction are required for its transforming activity. Mutagenesis reveals that the PXXΦP motif of YAP, although making few contacts with TEAD4, is important for TEAD4 interaction as well as for the transforming activity. PMID:20123908

  4. Structural analysis of human FANCL, the E3 ligase in the Fanconi anemia pathway.

    PubMed

    Hodson, Charlotte; Cole, Ambrose R; Lewis, Laurence P C; Miles, Jennifer A; Purkiss, Andrew; Walden, Helen

    2011-09-16

    The Fanconi anemia (FA) pathway is essential for the repair of DNA interstrand cross-links. At the heart of this pathway is the monoubiquitination of the FANCI-FANCD2 (ID) complex by the multiprotein "core complex" containing the E3 ubiquitin ligase FANCL. Vertebrate organisms have the eight-protein core complex, whereas invertebrates apparently do not. We report here the structure of the central domain of human FANCL in comparison with the recently solved Drosophila melanogaster FANCL. Our data represent the first structural detail into the catalytic core of the human system and reveal that the central fold of FANCL is conserved between species. However, there are macromolecular differences between the FANCL proteins that may account for the apparent distinctions in core complex requirements between the vertebrate and invertebrate FA pathways. In addition, we characterize the binding of human FANCL with its partners, Ube2t, FANCD2, and FANCI. Mutational analysis reveals which residues are required for substrate binding, and we also show the domain required for E2 binding.

  5. Application of Rate Theory to Accelerated Durability Testing of Structural Adhesives

    DTIC Science & Technology

    1980-03-01

    comes too late to impact on material selection or design considerations. The analytical approach, coupled with an accelerated 10 testing program, is...estimated range and then evaluating the impact of each parameter on the failure rate and expected service life. The life-limiting components and the...interest of processing economy can be identified. This information can then be fed back into the system design process and the analyses repeated to

  6. The Effects of High Sustained Acceleration on the Acoustic Phonetic Structure of Speech. A Preliminary Investigation.

    DTIC Science & Technology

    1986-05-21

    displacement of the articulators. The effect is most clearly present for the second formant which is traditionally associated with tongue advancement. Diphthong...words produced at 1 G in both spectral and durational characteristics. The formant shifts observed were similar for both speakers. The first formant ...increased for the majority of vowels. The second formant tended to be lower for the front vowels /i, J/ and higher for the back vowel (u). Acceleration

  7. Strong current sheet at a magnetosheath jet: Kinetic structure and electron acceleration

    NASA Astrophysics Data System (ADS)

    Eriksson, E.; Vaivads, A.; Graham, D. B.; Khotyaintsev, Yu. V.; Yordanova, E.; Hietala, H.; André, M.; Avanov, L. A.; Dorelli, J. C.; Gershman, D. J.; Giles, B. L.; Lavraud, B.; Paterson, W. R.; Pollock, C. J.; Saito, Y.; Magnes, W.; Russell, C.; Torbert, R.; Ergun, R.; Lindqvist, P.-A.; Burch, J.

    2016-10-01

    Localized kinetic-scale regions of strong current are believed to play an important role in plasma thermalization and particle acceleration in turbulent plasmas. We present a detailed study of a strong localized current, 4900 nA m-2, located at a fast plasma jet observed in the magnetosheath downstream of a quasi-parallel shock. The thickness of the current region is ˜3 ion inertial lengths and forms at a boundary separating magnetosheath-like and solar wind-like plasmas. On ion scales the current region has the shape of a sheet with a significant average normal magnetic field component but shows strong variations on smaller scales. The dynamic pressure within the magnetosheath jet is over 3 times the solar wind dynamic pressure. We suggest that the current sheet is forming due to high velocity shears associated with the jet. Inside the current sheet we observe local electron acceleration, producing electron beams, along the magnetic field. However, there is no clear sign of ongoing reconnection. At higher energies, above the beam energy, we observe a loss cone consistent with part of the hot magnetosheath-like electrons escaping into the colder solar wind-like plasma. This suggests that the acceleration process within the current sheet is similar to the one that occurs at shocks, where electron beams and loss cones are also observed. Therefore, electron beams observed in the magnetosheath do not have to originate from the bow shock but can also be generated locally inside the magnetosheath.

  8. Optimization of radiation acceleration regime and the target structure in laser plasma interaction

    NASA Astrophysics Data System (ADS)

    Dudnikova, Galina; Lui, Chuan; Papadopoulos, Dennis; Sagdeev, Roald; Zigler, Ari

    2009-11-01

    Recent work [1,2] indicates that under proper conditions the interaction of ultra-short, high power lasers with thin foils can generate ion beams in the 100-200 MeV energy range with relatively low velocity dispersion. This technology can have major implications to medical ion proton cancer therapy since it can provide a relatively inexpensive table-top alternative to the current used traditional cyclotrons. This paper presents a simulation trade-off study of laser driven generation of quasi-monochromatic ion beams in the thin-foil Radiation Pressure Acceleration (RPA) regime. The radiation pressure accelerates the electron cloud, which in its turn transfers accelerates the ions due to the induced longitudinal charge separation fields. A series of two and three-dimensional PIC simulations are presented with emphasis on stabilizing the target plasma against Raleigh-Taylor and modulational instabilities. Such instabilities are known as the main obstacles in achieving monochromatic beams. [4pt] [1] B. Eliasson, C. Lui, et al. New Jour. Phys., 11, 2009.[0pt] [2] F. Pegoraro, S.V. Bulanov. Laser Phys., v19, N 2, 2009.

  9. Gas-phase Structure and Fragmentation Pathways of Singly Protonated Peptides with N-terminal Arginine

    PubMed Central

    Bythell, Benjamin J.; Csonka, István P.; Suhai, Sándor; Barofsky, Douglas F.; Paizs, Béla

    2010-01-01

    The gas-phase structures and fragmentation pathways of the singly protonated peptide arginylglycylaspartic acid (RGD) are investigated by means of collision-induced-dissociation (CID) and detailed molecular mechanics and density functional theory (DFT) calculations. It is demonstrated that despite the ionizing proton being strongly sequestered at the guanidine group, protonated RGD can easily be fragmented on charge directed fragmentation pathways. This is due to facile mobilization of the C-terminal or aspartic acid COOH protons thereby generating salt-bridge (SB) stabilized structures. These SB intermediates can directly fragment to generate b2 ions or facilely rearrange to form anhydrides from which both b2 and b2+H2O fragments can be formed. The salt-bridge stabilized and anhydride transition structures (TSs) necessary to form b2 and b2+H2O are much lower in energy than their traditional charge solvated counterparts. These mechanisms provide compelling evidence of the role of SB and anhydride structures in protonated peptide fragmentation which complements and supports our recent findings for tryptic systems (Bythell, B. J.; Suhai, S.; Somogyi, A.; Paizs, B. J. Am. Chem. Soc., 2009, 131, 14057–14065.). In addition to these findings we also report on the mechanisms for the formation of the b1 ion, neutral loss (H2O, NH3, guanidine) fragment ions and the d3 ion. PMID:20973555

  10. [3D structure of DKK1 indicates its involvement in both canonical and non-canonical Wnt pathways].

    PubMed

    Khalili, S; Rasaee, M J; Bamdad, T

    2017-01-01

    Dikkoppf-1 (DKK1) is an antagonist of the canonical Wnt signaling pathway. The importance of DKK1 as a diagnostic and therapeutic agent in a wide range of diseases along with its significance in a variety of biological processes accentuate the necessity to decipher its 3D structure that would pave the way towards the development of relevant selective inhibitors. A DKK1 structure model predicted by the Robetta server with structural refinements including a 10 ns molecular dynamics run was subjected to functional and docking analyses. We hypothesize that the N-terminal region of the DKK1 molecule could be functionally important for both canonical and noncanonical Wnt pathways. Moreover, it seems that DKK1 could be involved in interactions with the Frizzled receptors, leading to the activation of the Planar Cell Polarity (PCP) pathway (activation of Jun N-terminal kinase (JNK) Pathway) and Wnt/Ca^(2+) pathway (activation of CamKII).

  11. 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

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

    DOE PAGES

    Faraji, Mojdeh; Fonseca, Luis L.; Escamilla-Treviño, Luis; ...

    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

  13. Parallel Readout of Pathway-Specific Inputs to Laminated Brain Structures

    PubMed Central

    Makarova, Julia; Ibarz, José M.; Makarov, Valeri A.; Benito, Nuria; Herreras, Oscar

    2011-01-01

    Local field potentials (LFPs) capture the electrical activity produced by principal cells during integration of converging synaptic inputs from multiple neuronal populations. However, since synaptic currents mix in the extracellular volume, LFPs have complex spatiotemporal structure, making them hard to exploit. Here we propose a biophysical framework to identify and separate LFP-generators. First we use a computational multineuronal model that scales up single cell electrogenesis driven by several synaptic inputs to realistic aggregate LFPs. This approach relies on the fixed but distinct locations of synaptic inputs from different presynaptic populations targeting a laminated brain structure. Thus the LFPs are contributed by several pathway-specific LFP-generators, whose electrical activity is defined by the spatial distribution of synaptic terminals and the time course of synaptic currents initiated in target cells by the corresponding presynaptic population. Then we explore the efficacy of independent component analysis to blindly separate converging sources and reconstruct pathway-specific LFP-generators. This approach can optimally locate synaptic inputs with subcellular accuracy while the reconstructed time course of pathway-specific LFP-generators is reliable in the millisecond scale. We also describe few cases where the non-linear intracellular interaction of strongly overlapping LFP-generators may lead to a significant cross-contamination and the appearance of derivative generators. We show that the approach reliably disentangle ongoing LFPs in the hippocampus into contribution of several LFP-generators. We were able to readout in parallel the pathway-specific presynaptic activity of projection cells in the entorhinal cortex and pyramidal cells in the ipsilateral and contralateral CA3. Thus we provide formal mathematical and experimental support for parallel readout of the activity of converging presynaptic populations in working neuronal circuits from

  14. 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.

  15. Structural basis for leucine sensing by the Sestrin2-mTORC1 pathway.

    PubMed

    Saxton, Robert A; Knockenhauer, Kevin E; Wolfson, Rachel L; Chantranupong, Lynne; Pacold, Michael E; Wang, Tim; Schwartz, Thomas U; Sabatini, David M

    2016-01-01

    Eukaryotic cells coordinate growth with the availability of nutrients through the mechanistic target of rapamycin complex 1 (mTORC1), a master growth regulator. Leucine is of particular importance and activates mTORC1 via the Rag guanosine triphosphatases and their regulators GATOR1 and GATOR2. Sestrin2 interacts with GATOR2 and is a leucine sensor. Here we present the 2.7 angstrom 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.

  16. 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

  17. Structural basis for leucine sensing by the Sestrin2-mTORC1 pathway

    SciTech Connect

    Saxton, Robert A.; Knockenhauer, Kevin E.; Wolfson, Rachel L.; Chantranupong, Lynne; Pacold, Michael E.; Wang, Tim; Schwartz, Thomas U.; Sabatini, David M.

    2015-11-19

    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. Lastly, these results provide a structural mechanism of amino acid sensing by the mTORC1 pathway.

  18. 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.

  19. Structure and function of the silk production pathway in the spider Nephila edulis.

    PubMed

    Vollrath, F; Knight, D P

    1999-01-01

    Our observations on the major ampullate gland of the spider Nephila edulis indicate that the exceptionally tough and strong core and coat composite structure of the dragline thread is formed by the co-drawing of two feedstocks through a single die. The cuticle that lines the gland's duct has the structure of an advanced hollow fibre dialysis membrane and is thought to facilitate a rapid removal of water and change in ionic composition involved in the spinning process. A structure previously termed the 'valve' is thought to advance the broken thread and act as a pump to restart spinning after the accidental internal rupture of a thread. Together, these observations indicate that the spider silk production pathway is highly optimised for the production of silk threads and shows considerable biomimetic potential.

  20. Mediation pathways and effects of green structures on respiratory mortality via reducing air pollution

    PubMed Central

    Shen, Yu-Sheng; Lung, Shih-Chun Candice

    2017-01-01

    Previous studies have shown both health and environmental benefits of green spaces, especially in moderating temperature and reducing air pollution. However, the characteristics of green structures have been overlooked in previous investigations. In addition, the mediation effects of green structures on respiratory mortality have not been assessed. This study explores the potential mediation pathways and effects of green structure characteristics on respiratory mortality through temperature, primary and secondary air pollutants separately using partial least squares model with data from Taiwan. The measurable characteristics of green structure include the largest patch percentage, landscape proportion, aggregation, patch distance, and fragmentation. The results showed that mortality of pneumonia and chronic lower respiratory diseases could be reduced by minimizing fragmentation and increasing the largest patch percentage of green structure, and the mediation effects are mostly through reducing air pollutants rather than temperature. Moreover, a high proportion of but fragmented green spaces would increase secondary air pollutants and enhance health risks; demonstrating the deficiency of traditional greening policy with primary focus on coverage ratio. This is the first research focusing on mediation effects of green structure characteristics on respiratory mortality, revealing that appropriate green structure planning can be a useful complementary strategy in environmental health management. PMID:28230108

  1. Mediation pathways and effects of green structures on respiratory mortality via reducing air pollution

    NASA Astrophysics Data System (ADS)

    Shen, Yu-Sheng; Lung, Shih-Chun Candice

    2017-02-01

    Previous studies have shown both health and environmental benefits of green spaces, especially in moderating temperature and reducing air pollution. However, the characteristics of green structures have been overlooked in previous investigations. In addition, the mediation effects of green structures on respiratory mortality have not been assessed. This study explores the potential mediation pathways and effects of green structure characteristics on respiratory mortality through temperature, primary and secondary air pollutants separately using partial least squares model with data from Taiwan. The measurable characteristics of green structure include the largest patch percentage, landscape proportion, aggregation, patch distance, and fragmentation. The results showed that mortality of pneumonia and chronic lower respiratory diseases could be reduced by minimizing fragmentation and increasing the largest patch percentage of green structure, and the mediation effects are mostly through reducing air pollutants rather than temperature. Moreover, a high proportion of but fragmented green spaces would increase secondary air pollutants and enhance health risks; demonstrating the deficiency of traditional greening policy with primary focus on coverage ratio. This is the first research focusing on mediation effects of green structure characteristics on respiratory mortality, revealing that appropriate green structure planning can be a useful complementary strategy in environmental health management.

  2. Mediation pathways and effects of green structures on respiratory mortality via reducing air pollution.

    PubMed

    Shen, Yu-Sheng; Lung, Shih-Chun Candice

    2017-02-23

    Previous studies have shown both health and environmental benefits of green spaces, especially in moderating temperature and reducing air pollution. However, the characteristics of green structures have been overlooked in previous investigations. In addition, the mediation effects of green structures on respiratory mortality have not been assessed. This study explores the potential mediation pathways and effects of green structure characteristics on respiratory mortality through temperature, primary and secondary air pollutants separately using partial least squares model with data from Taiwan. The measurable characteristics of green structure include the largest patch percentage, landscape proportion, aggregation, patch distance, and fragmentation. The results showed that mortality of pneumonia and chronic lower respiratory diseases could be reduced by minimizing fragmentation and increasing the largest patch percentage of green structure, and the mediation effects are mostly through reducing air pollutants rather than temperature. Moreover, a high proportion of but fragmented green spaces would increase secondary air pollutants and enhance health risks; demonstrating the deficiency of traditional greening policy with primary focus on coverage ratio. This is the first research focusing on mediation effects of green structure characteristics on respiratory mortality, revealing that appropriate green structure planning can be a useful complementary strategy in environmental health management.

  3. 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.

  4. 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%).

  5. IDENTIFYING MUTATION SPECIFIC CANCER PATHWAYS USING A STRUCTURALLY RESOLVED PROTEIN INTERACTION NETWORK

    PubMed Central

    ENGIN, H. BILLUR; HOFREE, MATAN; CARTER, HANNAH

    2014-01-01

    Here we present a method for extracting candidate cancer pathways from tumor ‘omics data while explicitly accounting for diverse consequences of mutations for protein interactions. Disease-causing mutations are frequently observed at either core or interface residues mediating protein interactions. Mutations at core residues frequently destabilize protein structure while mutations at interface residues can specifically affect the binding energies of protein-protein interactions. As a result, mutations in a protein may result in distinct interaction profiles and thus have different phenotypic consequences. We describe a protein structure-guided pipeline for extracting interacting protein sets specific to a particular mutation. Of 59 cancer genes with 3D co-complexed structures in the Protein Data Bank, 43 showed evidence of mutations with different functional consequences. Literature survey reciprocated functional predictions specific to distinct mutations on APC, ATRX, BRCA1, CBL and HRAS. Our analysis suggests that accounting for mutation-specific perturbations to cancer pathways will be essential for personalized cancer therapy. PMID:25592571

  6. Structure of DnmZ, a nitrososynthase in the Streptomyces peucetius anthracycline biosynthetic pathway

    PubMed Central

    Sartor, Lauren; Ibarra, Charmaine; Al-Mestarihi, Ahmad; Bachmann, Brian O.; Vey, Jessica L.

    2015-01-01

    The anthracyclines are a class of highly effective natural product chemotherapeutics and are used to treat a range of cancers, including leukemia. The toxicity of the anthracyclines has stimulated efforts to further diversify the scaffold of the natural product, which has led to renewed interest in the biosynthetic pathway responsible for the formation and modification of this family of molecules. DnmZ is an N-hydroxylating flavin monooxygenase (a nitrososynthase) that catalyzes the oxidation of the exocyclic amine of the sugar nucleotide dTDP-l-epi-vancosamine to its nitroso form. Its specific role in the anthracycline biosynthetic pathway involves the synthesis of the seven-carbon acetal moiety attached to C4 of l-daunosamine observed in the anthracycline baumycin. Here, X-ray crystallography was used to elucidate the three-dimensional structure of DnmZ. Two crystal structures of DnmZ were yielded: that of the enzyme alone, solved to 3.00 Å resolution, and that of the enzyme in complex with thymidine diphosphate, the nucleotide carrier portion of the substrate, solved to 2.74 Å resolution. These models add insights into the structural features involved in substrate specificity and conformational changes involved in thymidine diphosphate binding by the nitrososynthases. PMID:26457508

  7. 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.

  8. 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

  9. 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.

  10. Patterns of Individual Variation in Visual Pathway Structure and Function in the Sighted and Blind

    PubMed Central

    Datta, Ritobrato; Benson, Noah C.; Prasad, Sashank; Jacobson, Samuel G.; Cideciyan, Artur V.; Bridge, Holly; Watkins, Kate E.; Butt, Omar H.; Dain, Aleksandra S.; Brandes, Lauren; Gennatas, Efstathios D.

    2016-01-01

    Many structural and functional brain alterations accompany blindness, with substantial individual variation in these effects. In normally sighted people, there is correlated individual variation in some visual pathway structures. Here we examined if the changes in brain anatomy produced by blindness alter the patterns of anatomical variation found in the sighted. We derived eight measures of central visual pathway anatomy from a structural image of the brain from 59 sighted and 53 blind people. These measures showed highly significant differences in mean size between the sighted and blind cohorts. When we examined the measurements across individuals within each group we found three clusters of correlated variation, with V1 surface area and pericalcarine volume linked, and independent of the thickness of V1 cortex. These two clusters were in turn relatively independent of the volumes of the optic chiasm and lateral geniculate nucleus. This same pattern of variation in visual pathway anatomy was found in the sighted and the blind. Anatomical changes within these clusters were graded by the timing of onset of blindness, with those subjects with a post-natal onset of blindness having alterations in brain anatomy that were intermediate to those seen in the sighted and congenitally blind. Many of the blind and sighted subjects also contributed functional MRI measures of cross-modal responses within visual cortex, and a diffusion tensor imaging measure of fractional anisotropy within the optic radiations and the splenium of the corpus callosum. We again found group differences between the blind and sighted in these measures. The previously identified clusters of anatomical variation were also found to be differentially related to these additional measures: across subjects, V1 cortical thickness was related to cross-modal activation, and the volume of the optic chiasm and lateral geniculate was related to fractional anisotropy in the visual pathway. Our findings show that

  11. Patterns of Individual Variation in Visual Pathway Structure and Function in the Sighted and Blind.

    PubMed

    Aguirre, Geoffrey K; Datta, Ritobrato; Benson, Noah C; Prasad, Sashank; Jacobson, Samuel G; Cideciyan, Artur V; Bridge, Holly; Watkins, Kate E; Butt, Omar H; Dain, Aleksandra S; Brandes, Lauren; Gennatas, Efstathios D

    2016-01-01

    Many structural and functional brain alterations accompany blindness, with substantial individual variation in these effects. In normally sighted people, there is correlated individual variation in some visual pathway structures. Here we examined if the changes in brain anatomy produced by blindness alter the patterns of anatomical variation found in the sighted. We derived eight measures of central visual pathway anatomy from a structural image of the brain from 59 sighted and 53 blind people. These measures showed highly significant differences in mean size between the sighted and blind cohorts. When we examined the measurements across individuals within each group we found three clusters of correlated variation, with V1 surface area and pericalcarine volume linked, and independent of the thickness of V1 cortex. These two clusters were in turn relatively independent of the volumes of the optic chiasm and lateral geniculate nucleus. This same pattern of variation in visual pathway anatomy was found in the sighted and the blind. Anatomical changes within these clusters were graded by the timing of onset of blindness, with those subjects with a post-natal onset of blindness having alterations in brain anatomy that were intermediate to those seen in the sighted and congenitally blind. Many of the blind and sighted subjects also contributed functional MRI measures of cross-modal responses within visual cortex, and a diffusion tensor imaging measure of fractional anisotropy within the optic radiations and the splenium of the corpus callosum. We again found group differences between the blind and sighted in these measures. The previously identified clusters of anatomical variation were also found to be differentially related to these additional measures: across subjects, V1 cortical thickness was related to cross-modal activation, and the volume of the optic chiasm and lateral geniculate was related to fractional anisotropy in the visual pathway. Our findings show that

  12. 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.

  13. Polynomial chaos expansion in structural dynamics: Accelerating the convergence of the first two statistical moment sequences

    NASA Astrophysics Data System (ADS)

    Jacquelin, E.; Adhikari, S.; Sinou, J.-J.; Friswell, M. I.

    2015-11-01

    Polynomial chaos solution for the frequency response of linear non-proportionally damped dynamic systems has been considered. It has been observed that for lightly damped systems the convergence of the solution can be very poor in the vicinity of the deterministic resonance frequencies. To address this, Aitken's transformation and its generalizations are suggested. The proposed approach is successfully applied to the sequences defined by the first two moments of the responses, and this process significantly accelerates the polynomial chaos convergence. In particular, a 2-dof system with respectively 1 and 2 parameter uncertainties has been studied. The first two moments of the frequency response were calculated by Monte Carlo simulation, polynomial chaos expansion and Aitken's transformation of the polynomial chaos expansion. Whereas 200 polynomials are required to have a good agreement with Monte Carlo results around the deterministic eigenfrequencies, less than 50 polynomials transformed by the Aitken's method are enough. This latter result is improved if a generalization of Aitken's method (recursive Aitken's transformation, Shank's transformation) is applied. With the proposed convergence acceleration, polynomial chaos may be reconsidered as an efficient method to estimate the first two moments of a random dynamic response.

  14. 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.

  15. 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.

  16. 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

  17. Design and optimization of Compact Linear Collider main linac accelerating structure

    NASA Astrophysics Data System (ADS)

    Zha, Hao; Grudiev, Alexej

    2016-11-01

    The Compact Linear Collider (CLIC) main linac uses waveguide damped structure as its baseline design. The current baseline structure design written in the CLIC Conceptual Design Report is named "CLIC-G." Recent activities on the CLIC-G design including high power tests on structure prototypes and the study of machining cost assessment had raised the need of reoptimizing the structure design to minimize the machining cost and the pulse surface temperature rise. This work presents optimization of the structure geometry, high-order-mode (HOM) damping loads and the design of a HOM-free power splitter for the input coupler. Compared to the current baseline design CLIC-G, the new structure design reduced the pulse surface temperature rise, input power and manufacturing cost and achieves better suppression to the long range transverse wakefield. Cell disks and damping loads for the new structure design are also more compact than those of the CLIC-G design.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. Structure of the FANCI-FANCD2 complex: insights into the Fanconi anemia DNA repair pathway.

    PubMed

    Joo, Woo; Xu, Guozhou; Persky, Nicole S; Smogorzewska, Agata; Rudge, Derek G; Buzovetsky, Olga; Elledge, Stephen J; Pavletich, Nikola P

    2011-07-15

    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 ~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.

  4. Biodegradation of antibiotic ciprofloxacin: pathways, influential factors, and bacterial community structure.

    PubMed

    Liao, Xiaobin; Li, Bingxin; Zou, Rusen; Dai, Yu; Xie, Shuguang; Yuan, Baoling

    2016-04-01

    Antibiotic ciprofloxacin is ubiquitous in the environment. However, little is known about ciprofloxacin dissipation by microbial community. The present study investigated the biodegradation potential of ciprofloxacin by mixed culture and the influential factors and depicted the structure of ciprofloxacin-degrading microbial community. Both the original microbiota from drinking water biofilter and the microbiota previously acclimated to high levels of ciprofloxacin could utilize ciprofloxacin as sole carbon and nitrogen sources, while the acclimated microbiota had a much stronger removal capacity. Temperature rise and the presence of carbon or nitrogen sources favored ciprofloxacin biodegradation. Many novel biotransformation products were identified, and four different metabolic pathways for ciprofloxacin were proposed. Bacterial community structure illustrated a profound shift with ciprofloxacin biodegradation. The ciprofloxacin-degrading bacterial community was mainly composed of classes Gammaproteobacteria, Bacteroidia, and Betaproteobacteria. Microorganisms from genera Pseudoxanthomonas, Stenotrophomonas, Phenylobacterium, and Leucobacter might have links with the dissipation of ciprofloxacin. This work can provide some new insights towards ciprofloxacin biodegradation.

  5. Central obesity and insulin resistance in the cardiometabolic syndrome: pathways to preclinical cardiovascular structure and function.

    PubMed

    Klaus, Johanna R; Hurwitz, Barry E; Llabre, Maria M; Skyler, Jay S; Goldberg, Ronald B; Marks, Jennifer B; Bilsker, Martin S; Schneiderman, Neil

    2009-01-01

    The cardiometabolic syndrome (CMS) has been an organizing conceptual framework for subclinical cardiovascular pathophysiology. Using cross-sectional data from 338 healthy men and women aged 18 to 55 years, the study examined the role of central adiposity and insulin sensitivity and assessed potential relationships with other metabolic indices (insulin sensitivity, glucose tolerance, fibrinolysis, lipidemia, endothelial function, and inflammation) and measures of cardiac structure and function (cardiac mass, compliance and contractility, myocardial oxygen demand, and blood pressure). Structural equation modeling analyses, which controlled for sex, age, and race, demonstrated good fit to the data. The derived relationships provided a physiologically consistent model of CMS, with an initiating role for central adiposity and insulin resistance. The model accounted for 30% and 82% of the variance in diastolic blood pressure and myocardial oxygen demand, respectively. The findings suggest predominant pathways through which subclinical metabolic processes may exert pathogenic impact on the heart and vasculature.

  6. The Rcs signal transduction pathway is triggered by enterobacterial common antigen structure alterations in Serratia marcescens.

    PubMed

    Castelli, María E; Véscovi, Eleonora García

    2011-01-01

    The enterobacterial common antigen (ECA) is a highly conserved exopolysaccharide in Gram-negative bacteria whose role remains largely uncharacterized. In a previous work, we have demonstrated that disrupting the integrity of the ECA biosynthetic pathway imposed severe deficiencies to the Serratia marcescens motile (swimming and swarming) capacity. In this work, we show that alterations in the ECA structure activate the Rcs phosphorelay, which results in the repression of the flagellar biogenesis regulatory cascade. In addition, a detailed analysis of wec cluster mutant strains, which provoke the disruption of the ECA biosynthesis at different levels of the pathway, suggests that the absence of the periplasmic ECA cyclic structure could constitute a potential signal detected by the RcsF-RcsCDB phosphorelay. We also identify SMA1167 as a member of the S. marcescens Rcs regulon and show that high osmolarity induces Rcs activity in this bacterium. These results provide a new perspective from which to understand the phylogenetic conservation of ECA among enterobacteria and the basis for the virulence attenuation detected in wec mutant strains in other pathogenic bacteria.

  7. Breakdown pathways during oral processing of different breads: impact of crumb and crust structures.

    PubMed

    Jourdren, S; Panouillé, M; Saint-Eve, A; Déléris, I; Forest, D; Lejeune, P; Souchon, I

    2016-03-01

    Oral processing during bread consumption is a key process related to the dynamics of texture perceptions, sensory stimuli release and starch digestion. The aim of this study was to determine the respective contribution of bread properties (composition and structure of crumb and crust) and of the oral physiology of subjects to the breakdown pathways in the mouth. The properties of the in vivo bread bolus obtained from eight healthy subjects were studied at three key points in time during their oral processing. The progressive lubrication and breakdown of bread were observed, as well as the beginning of the enzymatic degradation of starch. The study showed that "time" was the factor responsible for the greatest variability in bolus properties. Breakdown pathways were established for crumbs with and without crust. The presence of crust modified the oral processing, increasing, for instance, the heterogeneity of particle size at the middle of the oral processing sequence. Moreover, the hydration capacity of crust contributed to high starch degradation at swallowing time, in comparison with crumb alone. The main subject characteristics impacting bolus properties were the in-mouth duration, the individual masticatory index and the mouth volume, while the main bread properties explaining the bolus properties were the initial composition and the water-absorbing capacity. We concluded that both crumb and crust structures had an impact on the oral processing, affecting the capacity of hydration, the rheology and the breakdown degree of the bolus.

  8. Structural adjustment and health: A conceptual framework and evidence on pathways.

    PubMed

    Kentikelenis, Alexander E

    2017-02-23

    Economic reform programs designed by the International Monetary Fund and the World Bank-so-called 'structural adjustment programs'-have formed one of the most influential policy agendas of the past four decades. To gain access to financial support from these organizations, countries-often in economic crisis-have reduced public spending, limited the role of the state, and deregulated economic activity. This article identifies the multiple components of structural adjustment, and presents a conceptual framework linking them to health systems and outcomes. Based on a comprehensive review of the academic literature, the article identifies three main pathways through which structural adjustment affects health: policies directly targeting health systems; policies indirectly impacting health systems; and policies affecting the social determinants of health. The cogency of the framework is illustrated by revisiting Greece's recent experience with structural adjustment, drawing on original IMF reports and secondary literature. Overall, the framework offers a lens through which to analyze the health consequences of structural adjustment across time, space and levels of socioeconomic development, and can be utilized in ex ante health impact assessments of these policies.

  9. Multistep Aggregation Pathway of Human Interleukin-1 Receptor Antagonist: Kinetic, Structural, and Morphological Characterization

    PubMed Central

    Krishnan, Sampathkumar; Raibekas, Andrei A.

    2009-01-01

    Abstract The complex, multistep aggregation kinetic and structural behavior of human recombinant interleukin-1 receptor antagonist (IL-1ra) was revealed and characterized by spectral probes and techniques. At a certain range of protein concentration (12–27 mg/mL) and temperature (44–48°C), two sequential aggregation kinetic transitions emerge, where the second transition is preceded by a lag phase and is associated with the main portion of the aggregated protein. Each kinetic transition is linked to a different type of aggregate population, referred to as type I and type II. The aggregate populations, isolated at a series of time points and analyzed by Fourier-transform infrared spectroscopy, show consecutive protein structural changes, from intramolecular (type I) to intermolecular (type II) β-sheet formation. The early type I protein spectral change resembles that seen for IL-1ra in the crystalline state. Moreover, Fourier-transform infrared data demonstrate that type I protein assembly alone can undergo a structural rearrangement and, consequently, convert to the type II aggregate. The aggregated protein structural changes are accompanied by the aggregate morphological changes, leading to a well-defined population of interacting spheres, as detected by scanning electron microscopy. A nucleation-driven IL-1ra aggregation pathway is proposed, and assumes two major activation energy barriers, where the second barrier is associated with the type I → type II aggregate structural rearrangement that, in turn, serves as a pseudonucleus triggering the second kinetic event. PMID:19134476

  10. 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.

  11. 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.

  12. 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

  13. 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

  14. BEAM LOADING AND HIGHER-BAND LONGITUDINAL WAKES IN HIGH PHASE ADVANCE TRAVELING WAVE ACCELERATOR STRUCTURES FOR THE GLC/NLC

    SciTech Connect

    Jones, R

    2004-07-30

    A multi-bunch beam, traversing travelling wave accelerator structures, each with a 5{pi}/6 phase advance per cell, is accelerated at a frequency that is synchronous with the fundamental mode frequency. As per design, the main interaction occurs at the working frequency of 11.424 GHz. However, modes with frequencies surrounding the dominant accelerating mode are also excited and these give rise to additional modal components to the wakefield. Here, we consider the additional modes in the context of X-band accelerator structures for the GLC/NLC (Global Linear Collider/Next Linear Collider). Finite element simulations and field mode-matching models are employed in order to calculate the wakefield.

  15. 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

  16. 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

  17. Structural Basis of Vta1 Function in the Multivesicular Body Sorting Pathway

    SciTech Connect

    Xiao, Junyu; Xia, Hengchuan; Zhou, Jiahai; Azmi, Ishara F.; Davies, Brian A.; Katzmann, David J.; Xu, Zhaohui

    2008-05-01

    The MVB pathway plays essential roles in several eukaryotic cellular processes. Proper function of the MVB pathway requires reversible membrane association of the ESCRTs, a process catalyzed by Vps4 ATPase. Vta1 regulates the Vps4 activity, but its mechanism of action was poorly understood. We report the high-resolution crystal structures of the Did2- and Vps60-binding N-terminal domain and the Vps4-binding C-terminal domain of S. cerevisiae Vta1. The C-terminal domain also mediates Vta1 dimerization and both subunits are required for its function as a Vps4 regulator. Emerging from our analysis is a mechanism of regulation by Vta1 in which the C-terminal domain stabilizes the ATP-dependent double ring assembly of Vps4. In addition, the MIT motif-containing N-terminal domain, projected by a long disordered linker, allows contact between the Vps4 disassembly machinery and the accessory ESCRT-III proteins. This provides an additional level of regulation and coordination for ESCRT-III assembly and disassembly.

  18. Is structured observation a valid technique to measure handwashing behavior? Use of acceleration sensors embedded in soap to assess reactivity to structured observation.

    PubMed

    Ram, Pavani K; Halder, Amal K; Granger, Stewart P; Jones, Therese; Hall, Peter; Hitchcock, David; Wright, Richard; Nygren, Benjamin; Islam, M Sirajul; Molyneaux, John W; Luby, Stephen P

    2010-11-01

    Structured observation is often used to evaluate handwashing behavior. We assessed reactivity to structured observation in rural Bangladesh by distributing soap containing acceleration sensors and performing structured observation 4 days later. Sensors recorded the number of times soap was moved. In 45 participating households, the median number of sensor soap movements during the 5-hour time block on pre-observation days was 3.7 (range 0.3-10.6). During the structured observation, the median number of sensor soap movements was 5.0 (range 0-18.0), a 35% increase, P = 0.0004. Compared with the same 5-hour time block on pre-observation days, the number of sensor soap movements increased during structured observation by ≥ 20% in 62% of households, and by ≥ 100% in 22% of households. The increase in sensor soap movements during structured observation, compared with pre-observation days, indicates substantial reactivity to the presence of the observer. These findings call into question the validity of structured observation for measurement of handwashing behavior.

  19. Expression of Wnt pathway genes in polyps and medusa-like structures of Ectopleura larynx (Cnidaria: Hydrozoa).

    PubMed

    Nawrocki, Annalise M; Cartwright, Paulyn

    2013-01-01

    The canonical Wnt signaling pathway is conserved in its role in axial patterning throughout Metazoa. In some hydrozoans (Phylum Cnidaria), Wnt signaling is implicated in oral-aboral patterning of the different life cycle stages-the planula, polyp and medusa. Unlike most hydrozoans, members of Aplanulata lack a planula larva and the polyp instead develops directly from a brooded or encysted embryo. The Aplanulata species Ectopleura larynx broods such embryos within gonophores. These gonophores are truncated medusae that remain attached to the polyps from which they bud, and retain evolutionary remnants of medusa structures. In E. larynx, gonophores differ between males and females in their degree of medusa truncation, making them an ideal system for examining truncated medusa development. Using next-generation sequencing, we isolated genes from Wnt signaling pathways and examined their expression in E. larynx. Our data are consistent with the Wnt pathway being involved in axial patterning of the polyp and truncated medusa. Changes in the spatial expression of Wnt pathway genes are correlated with the development of different oral structures in male and female gonophores. The absence of expression of components of the Wnt pathway and presence of a Wnt pathway antagonist SFRP in the developing anterior end of the gonophore suggest that downregulation of the Wnt pathway could play a role in medusa reduction in E. larynx.

  20. The Afferent Visual Pathway: Designing a Structural-Functional Paradigm of Multiple Sclerosis

    PubMed Central

    Costello, Fiona

    2013-01-01

    Multiple sclerosis (MS) is a disease of the central nervous system (CNS) believed to arise from a dysfunctional immune-mediated response in a genetically susceptible host. The actual cause of MS is not known, and there is ongoing debate about whether this CNS disorder is predominantly an inflammatory versus a degenerative condition. The afferent visual pathway (AVP) is frequently involved in MS, such that one in every five individuals affected presents with acute optic neuritis (ON). As a functionally eloquent system, the AVP is amenable to interrogation with highly reliable and reproducible tests that can be used to define a structural-functional paradigm of CNS injury. The AVP has numerous unique advantages as a clinical model of MS. In this review, the parameters and merits of the AVP model are highlighted. Moreover, the roles the AVP model may play in elucidating mechanisms of brain injury and repair in MS are described. PMID:24288622

  1. High Gradient Accelerator Research

    SciTech Connect

    Temkin, Richard

    2016-07-12

    The goal of the MIT program of research on high gradient acceleration is the development of advanced acceleration concepts that lead to a practical and affordable next generation linear collider at the TeV energy level. Other applications, which are more near-term, include accelerators for materials processing; medicine; defense; mining; security; and inspection. The specific goals of the MIT program are: • Pioneering theoretical research on advanced structures for high gradient acceleration, including photonic structures and metamaterial structures; evaluation of the wakefields in these advanced structures • Experimental research to demonstrate the properties of advanced structures both in low-power microwave cold test and high-power, high-gradient test at megawatt power levels • Experimental research on microwave breakdown at high gradient including studies of breakdown phenomena induced by RF electric fields and RF magnetic fields; development of new diagnostics of the breakdown process • Theoretical research on the physics and engineering features of RF vacuum breakdown • Maintaining and improving the Haimson / MIT 17 GHz accelerator, the highest frequency operational accelerator in the world, a unique facility for accelerator research • Providing the Haimson / MIT 17 GHz accelerator facility as a facility for outside users • Active participation in the US DOE program of High Gradient Collaboration, including joint work with SLAC and with Los Alamos National Laboratory; participation of MIT students in research at the national laboratories • Training the next generation of Ph. D. students in the field of accelerator physics.

  2. The Structural Basis of Functional Group Activation by Sulfotransferases in Complex Metabolic Pathways

    PubMed Central

    McCarthy, Jennifer Gehret; Eisman, Eli B.; Kulkarni, Sarang; Gerwick, Lena; Gerwick, William H.; Wipf, Peter; Sherman, David H.; Smith, Janet L.

    2012-01-01

    Sulfated molecules with diverse functions are common in biology, but sulfonation as a method to activate a metabolite for chemical catalysis is rare. Catalytic activity was characterized and crystal structures were determined for two such “activating” sulfotransferases (STs) that sulfonate β-hydroxyacyl thioester substrates. The CurM polyketide synthase (PKS) ST domain from the curacin A biosynthetic pathway of Moorea producens and the olefin synthase (OLS) ST from a hydrocarbon-producing system of Synechococcus PCC 7002 both occur as a unique acyl carrier protein (ACP), ST and thioesterase (TE) tridomain within a larger polypeptide. During pathway termination, these cyanobacterial systems introduce a terminal double bond into the β-hydroxyacyl-ACP-linked substrate by the combined action of the ST and TE. Under in vitro conditions, CurM PKS ST and OLS ST acted on β-hydroxy fatty acyl-ACP substrates; however, OLS ST was not reactive toward analogs of the natural PKS ST substrate bearing a C5-methoxy substituent. The crystal structures of CurM ST and OLS ST revealed that they are members of a distinct protein family relative to other prokaryotic and eukaryotic sulfotransferases. A common binding site for the sulfonate donor 3'-phosphoadenosine-5'-phosphosulfate was visualized in complexes with the product 3'-phosphoadenosine-5'-phosphate. Critical functions for several conserved amino acids in the active site were confirmed by site-directed mutagenesis, including a proposed glutamate catalytic base. A dynamic active-site flap unique to the “activating” ST family affects substrate selectivity and product formation, based on the activities of chimeras of the PKS and OLS STs with exchanged active-site flaps. PMID:22991895

  3. Functional and structural insight into properdin control of complement alternative pathway amplification.

    PubMed

    Pedersen, Dennis V; Roumenina, Lubka; Jensen, Rasmus K; Gadeberg, Trine Af; Marinozzi, Chiara; Picard, Capucine; Rybkine, Tania; Thiel, Steffen; Sørensen, Uffe Bs; Stover, Cordula; Fremeaux-Bacchi, Veronique; Andersen, Gregers R

    2017-03-06

    Properdin (FP) is an essential positive regulator of the complement alternative pathway (AP) providing stabilization of the C3 and C5 convertases, but its oligomeric nature challenges structural analysis. We describe here a novel FP deficiency (E244K) caused by a single point mutation which results in a very low level of AP activity. Recombinant FP E244K is monomeric, fails to support bacteriolysis, and binds weakly to C3 products. We compare this to a monomeric unit excised from oligomeric FP, which is also dysfunctional in bacteriolysis but binds the AP proconvertase, C3 convertase, C3 products and partially stabilizes the convertase. The crystal structure of such a FP-convertase complex suggests that the major contact between FP and the AP convertase is mediated by a single FP thrombospondin repeat and a small region in C3b. Small angle X-ray scattering indicates that FP E244K is trapped in a compact conformation preventing its oligomerization. Our studies demonstrate an essential role of FP oligomerization in vivo while our monomers enable detailed structural insight paving the way for novel modulators of complement.

  4. Structural Plasticity in Globins: Role of Protein Dynamics in Defining Ligand Migration Pathways.

    PubMed

    Estarellas, C; Capece, L; Seira, C; Bidon-Chanal, A; Estrin, D A; Luque, F J

    2016-01-01

    Globins are a family of proteins characterized by the presence of the heme prosthetic group and involved in variety of biological functions in the cell. Due to their biological relevance and widespread distribution in all kingdoms of life, intense research efforts have been devoted to disclosing the relationships between structural features, protein dynamics, and function. Particular attention has been paid to the impact of differences in amino acid sequence on the topological features of docking sites and cavities and to the influence of conformational flexibility in facilitating the migration of small ligands through these cavities. Often, tunnels are carved in the interior of globins, and ligand exchange is regulated by gating residues. Understanding the subtle intricacies that relate the differences in sequence with the structural and dynamical features of globins with the ultimate aim of rationalizing the thermodynamics and kinetics of ligand binding continues to be a major challenge in the field. Due to the evolution of computational techniques, significant advances into our understanding of these questions have been made. In this review we focus our attention on the analysis of the ligand migration pathways as well as the function of the structural cavities and tunnels in a series of representative globins, emphasizing the synergy between experimental and theoretical approaches to gain a comprehensive knowledge into the molecular mechanisms of this diverse family of proteins.

  5. Structural basis for leucine sensing by the Sestrin2-mTORC1 pathway

    DOE PAGES

    Saxton, Robert A.; Knockenhauer, Kevin E.; Wolfson, Rachel L.; ...

    2015-11-19

    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 leucinemore » leads to a concomitant increase in the leucine concentration required for mTORC1 activation in cells. Lastly, these results provide a structural mechanism of amino acid sensing by the mTORC1 pathway.« less

  6. Frequency-Domain Streak Camera and Tomography for Ultrafast Imaging of Evolving and Channeled Plasma Accelerator Structures

    SciTech Connect

    Li Zhengyan; Zgadzaj, Rafal; Wang Xiaoming; Reed, Stephen; Dong Peng; Downer, Michael C.

    2010-11-04

    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.

  7. Radiography with cosmic-ray and compact accelerator muons; Exploring inner-structure of large-scale objects and landforms.

    PubMed

    Nagamine, Kanetada

    2016-01-01

    Cosmic-ray muons (CRM) arriving from the sky on the surface of the earth are now known to be used as radiography purposes to explore the inner-structure of large-scale objects and landforms, ranging in thickness from meter to kilometers scale, such as volcanic mountains, blast furnaces, nuclear reactors etc. At the same time, by using muons produced by compact accelerators (CAM), advanced radiography can be realized for objects with a thickness in the sub-millimeter to meter range, with additional exploration capability such as element identification and bio-chemical analysis. In the present report, principles, methods and specific research examples of CRM transmission radiography are summarized after which, principles, methods and perspective views of the future CAM radiography are described.

  8. Radiography with cosmic-ray and compact accelerator muons; Exploring inner-structure of large-scale objects and landforms

    PubMed Central

    NAGAMINE, Kanetada

    2016-01-01

    Cosmic-ray muons (CRM) arriving from the sky on the surface of the earth are now known to be used as radiography purposes to explore the inner-structure of large-scale objects and landforms, ranging in thickness from meter to kilometers scale, such as volcanic mountains, blast furnaces, nuclear reactors etc. At the same time, by using muons produced by compact accelerators (CAM), advanced radiography can be realized for objects with a thickness in the sub-millimeter to meter range, with additional exploration capability such as element identification and bio-chemical analysis. In the present report, principles, methods and specific research examples of CRM transmission radiography are summarized after which, principles, methods and perspective views of the future CAM radiography are described. PMID:27725469

  9. 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.

  10. Human Sinoatrial Node Structure: 3D Microanatomy of Sinoatrial Conduction Pathways

    PubMed Central

    Csepe, Thomas A.; Zhao, Jichao; Hansen, Brian J.; Li, Ning; Sul, Lidiya V.; Lim, Praise; Wang, Yufeng; Simonetti, Orlando P.; Kilic, Ahmet; Mohler, Peter J.; Janssen, Paul ML.; Fedorov, Vadim V.

    2016-01-01

    Introduction Despite a century of extensive study on the human sinoatrial node (SAN), the structure-to-function features of specialized SAN conduction pathways (SACP) are still unknown and debated. We report a new method for direct analysis of the SAN microstructure in optically-mapped human hearts with and without clinical history of SAN dysfunction. Methods Two explanted donor human hearts were coronary-perfused and optically-mapped. Structural analyses of histological sections parallel to epicardium (~13-21μm intervals) were integrated with optical maps to create 3D computational reconstructions of the SAN complex. High-resolution fiber fields were obtained using 3D Eigen-analysis of the structure tensor, and used to analyze SACP microstructure with a fiber-tracking approach. Results Optical mapping revealed normal SAN activation of the atria through a lateral SACP proximal to the crista terminalis in Heart #1 but persistent SAN exit block in diseased Heart #2. 3D structural analysis displayed a functionally-observed SAN border composed of fibrosis, fat, and/or discontinuous fibers between SAN and atria, which was only crossed by several branching myofiber tracts in SACP regions. Computational 3D fiber-tracking revealed that myofiber tracts of SACPs created continuous connections between SAN #1 and atria, but in SAN #2, SACP region myofiber tracts were discontinuous due to fibrosis and fat. Conclusions We developed a new integrative functional, structural and computational approach that allowed for the resolution of the specialized 3D microstructure of human SACPs for the first time. Application of this integrated approach will shed new light on the role of the specialized SAN microanatomy in maintaining sinus rhythm. PMID:26743207

  11. 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

  12. 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.

  13. Oxygen transport pathways in Ruddlesden–Popper structured oxides revealed via in situ neutron diffraction

    DOE PAGES

    Tomkiewicz, Alex C.; Tamimi, Mazin; Huq, Ashfia; ...

    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

  14. 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

  15. 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

  16. Predicting the equilibrium protein folding pathway: structure-based analysis of staphylococcal nuclease.

    PubMed

    Hilser, V J; Freire, E

    1997-02-01

    The equilibrium folding pathway of staphylococcal nuclease (SNase) has been approximated using a statistical thermodynamic formalism that utilizes the high-resolution structure of the native state as a template to generate a large ensemble of partially folded states. Close to 400,000 different states ranging from the native to the completely unfolded states were included in the analysis. The probability of each state was estimated using an empirical structural parametrization of the folding energetics. It is shown that this formalism predicts accurately the stability of the protein, the cooperativity of the folding/unfolding transition observed by differential scanning calorimetry (DSC) or urea denaturation and the thermodynamic parameters for unfolding. More importantly, this formalism provides a quantitative account of the experimental hydrogen exchange protection factors measured under native conditions for SNase. These results suggest that the computer-generated distribution of states approximates well the ensemble of conformations existing in solution. Furthermore, this formalism represents the first model capable of quantitatively predicting within a unified framework the probability distribution of states seen under native conditions and its change upon unfolding.

  17. 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.

  18. Hydrophobin Film Structure for HFBI and HFBII and Mechanism for Accelerated Film Formation

    PubMed Central

    Magarkar, Aniket; Mele, Nawel; Abdel-Rahman, Noha; Butcher, Sarah; Torkkeli, Mika; Serimaa, Ritva; Paananen, Arja; Linder, Markus; Bunker, Alex

    2014-01-01

    Hydrophobins represent an important group of proteins from both a biological and nanotechnological standpoint. They are the means through which filamentous fungi affect their environment to promote growth, and their properties at interfaces have resulted in numerous applications. In our study we have combined protein docking, molecular dynamics simulation, and electron cryo-microscopy to gain atomistic level insight into the surface structure of films composed of two class II hydrophobins: HFBI and HFBII produced by Trichoderma reesei. Together our results suggest a unit cell composed of six proteins; however, our computational results suggest P6 symmetry, while our experimental results show P3 symmetry with a unit cell size of 56 Å. Our computational results indicate the possibility of an alternate ordering with a three protein unit cell with P3 symmetry and a smaller unit cell size, and we have used a Monte Carlo simulation of a spin model representing the hydrophobin film to show how this alternate metastable structure may play a role in increasing the rate of surface coverage by hydrophobin films, possibly indicating a mechanism of more general significance to both biology and nanotechnology. PMID:25079355

  19. GPU-accelerated computing for Lagrangian coherent structures of multi-body gravitational regimes

    NASA Astrophysics Data System (ADS)

    Lin, Mingpei; Xu, Ming; Fu, Xiaoyu

    2017-04-01

    Based on a well-established theoretical foundation, Lagrangian Coherent Structures (LCSs) have elicited widespread research on the intrinsic structures of dynamical systems in many fields, including the field of astrodynamics. Although the application of LCSs in dynamical problems seems straightforward theoretically, its associated computational cost is prohibitive. We propose a block decomposition algorithm developed on Compute Unified Device Architecture (CUDA) platform for the computation of the LCSs of multi-body gravitational regimes. In order to take advantage of GPU's outstanding computing properties, such as Shared Memory, Constant Memory, and Zero-Copy, the algorithm utilizes a block decomposition strategy to facilitate computation of finite-time Lyapunov exponent (FTLE) fields of arbitrary size and timespan. Simulation results demonstrate that this GPU-based algorithm can satisfy double-precision accuracy requirements and greatly decrease the time needed to calculate final results, increasing speed by approximately 13 times. Additionally, this algorithm can be generalized to various large-scale computing problems, such as particle filters, constellation design, and Monte-Carlo simulation.

  20. 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.

  1. Accelerating Nanoscale Research with Neutron Total Scattering: Linking Structure and Function in Finite Materials

    NASA Astrophysics Data System (ADS)

    Page, Katharine

    2012-10-01

    h -abstract-pard In contrast to bulk materials, nanomaterials and nanoparticles, comprised of a few hundred to tens of thousands of atoms, require every atom's position to be located in order to understand their structure-property relationships. New behavior can arise with a constricted, expanded, or distorted lattice, variation in surface termination structure, ligand capping or stabilization, or with the increasingly diverse set of shapes and architectures appearing in nanoscience literature today: tubes, pyramids, stars, core-shell and matrix-confined particles, multilayer films, etc. Pair distribution function (PDF) analysis, based on spallation neutron or synchrotron x-ray total scattering data, has emerged as a very promising characterization method for nanomaterials in recent years. Total scattering methods provide information about every pair of atoms probed in a diffraction experiment and thus contain an unexploited wealth of information for finite systems. In this contribution we will present our work establishing the influence of particle size and shape on the nature and correlation of local atomic dipoles in finite ferroelectric systems. We also review current data-driven modeling capabilities and outline the need for evolution of robust computational tools to follow other complex nanoscale phenomena with scattering data. pard-/abstract-

  2. 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.

  3. 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.

  4. Wake fields in 9-cell TESLA accelerating structures : Spectral Element Discontinuous Galerkin (SEDG) simulations.

    SciTech Connect

    Min, M.; Fischer, P. F.; Chae, Y.-C.

    2007-01-01

    Using our recently developed high-order accurate Maxwell solver, NEKCEM, we carried out longitudinal wakefield calculations for a 9-cell TESLA cavity structure in 3D. Indirect method is used for wake potential calculations. Computational results with NEKCEM are compared with those of GdfidL. NEKCEM uses a spectral element discontinuous Galerkin (SEDG) method based on a domain decomposition approach using spectral-element discretizations on Gauss-Lobatto-Legendre grids with body-conforming hexahedral meshes. The numerical scheme is designed to ensure high-order spectral accuracy, using the discontinuous Galerkin form with boundary conditions weakly enforced through a flux term between elements. Concerns related to implementation on wake potential calculations are discussed, and wake potential calculations with indirect method by NEKCEM compared with the results of the finite difference time-domain code GdfidL.

  5. Accelerated structure-based design of chemically diverse allosteric modulators of a muscarinic G protein-coupled receptor

    PubMed Central

    Miao, Yinglong; Goldfeld, Dahlia Anne; Moo, Ee Von; Sexton, Patrick M.; Christopoulos, Arthur; McCammon, J. Andrew; Valant, Celine

    2016-01-01

    Design of ligands that provide receptor selectivity has emerged as a new paradigm for drug discovery of G protein-coupled receptors, and may, for certain families of receptors, only be achieved via identification of chemically diverse allosteric modulators. Here, the extracellular vestibule of the M2 muscarinic acetylcholine receptor (mAChR) is targeted for structure-based design of allosteric modulators. Accelerated molecular dynamics (aMD) simulations were performed to construct structural ensembles that account for the receptor flexibility. Compounds obtained from the National Cancer Institute (NCI) were docked to the receptor ensembles. Retrospective docking of known ligands showed that combining aMD simulations with Glide induced fit docking (IFD) provided much-improved enrichment factors, compared with the Glide virtual screening workflow. Glide IFD was thus applied in receptor ensemble docking, and 38 top-ranked NCI compounds were selected for experimental testing. In [3H]N-methylscopolamine radioligand dissociation assays, approximately half of the 38 lead compounds altered the radioligand dissociation rate, a hallmark of allosteric behavior. In further competition binding experiments, we identified 12 compounds with affinity of ≤30 μM. With final functional experiments on six selected compounds, we confirmed four of them as new negative allosteric modulators (NAMs) and one as positive allosteric modulator of agonist-mediated response at the M2 mAChR. Two of the NAMs showed subtype selectivity without significant effect at the M1 and M3 mAChRs. This study demonstrates an unprecedented successful structure-based approach to identify chemically diverse and selective GPCR allosteric modulators with outstanding potential for further structure-activity relationship studies. PMID:27601651

  6. Structural insights into how Yrb2p accelerates the assembly of the Xpo1p nuclear export complex.

    PubMed

    Koyama, Masako; Shirai, Natsuki; Matsuura, Yoshiyuki

    2014-11-06

    Proteins and ribonucleoproteins containing a nuclear export signal (NES) assemble with the exportin Xpo1p (yeast CRM1) and Gsp1p-GTP (yeast Ran-GTP) in the nucleus and exit through the nuclear pore complex. In the cytoplasm, Yrb1p (yeast RanBP1) displaces NES from Xpo1p. Efficient export of NES-cargoes requires Yrb2p (yeast RanBP3), a primarily nuclear protein containing nucleoporin-like phenylalanine-glycine (FG) repeats and a low-affinity Gsp1p-binding domain (RanBD). Here, we show that Yrb2p strikingly accelerates the association of Gsp1p-GTP and NES to Xpo1p. We have solved the crystal structure of the Xpo1p-Yrb2p-Gsp1p-GTP complex, a key assembly intermediate that can bind cargo rapidly. Although the NES-binding cleft of Xpo1p is closed in this intermediate, our data suggest that preloading of Gsp1p-GTP onto Xpo1p by Yrb2p, conformational flexibility of Xpo1p, and the low affinity of RanBD enable active displacement of Yrb2p RanBD by NES to occur effectively. The structure also reveals the major binding sites for FG repeats on Xpo1p.

  7. Role of Nottingham and Thomson effects in heating of micro-protrusion in high-gradient accelerating structures

    NASA Astrophysics Data System (ADS)

    Keser, Aydin; Nusinovich, Gregory; Kashyn, Dmytro; Antonsen, Thomas

    2012-10-01

    It is widely accepted that one of the reasons for appearance of the RF breakdown which limits operation of high-gradient accelerating structures is the electron dark current [1]. This field emitted current, usually considered as a precursor of the breakdown, can be emitted from apexes of micro-protrusions on a structure surface. Therefore field and thermal processes in such protrusions deserve careful studies [2, 3]. The goal of our first study [3] was to analyze 2D process of RF field penetration inside protrusion of a metal with finite conductivity and to study corresponding Joule heating. In the current study, it is found that space charges can have a stabilizing effect on the electric field. We include a modification of the 1D model described in [4]. Moreover, we include into consideration, first, the Nottingham effect which may significantly change the protrusion heating. We also investigate the interplay between high temperature gradients and electric fields (Thomson heating).[4pt] [1] Wang and Loew, SLAC PUB 7684 October 1997.[0pt] [2] K.L. Jensen, Y.Y. Lau, D.W. Feldman, P.G. O'Shea, Phys. Rev. ST Accel. Beams 11, 081001(2008).[0pt] [3] Kashyn et al, AAC-2010.[0pt] [4] K.L. Jensen, J. LEbowitz, Y.Y. LAu, J. Luginsland, Journal of Applied Physics 111, 054917(2012).

  8. Structural and mechanistic insights into an extracytoplasmic copper trafficking pathway in Streptomyces lividans.

    PubMed

    Blundell, Katie L I M; Hough, Michael A; Vijgenboom, Erik; Worrall, Jonathan A R

    2014-05-01

    In Streptomyces lividans an extracytoplasmic copper-binding Sco protein plays a role in two unlinked processes: (i) initiating a morphological development switch and (ii) facilitating the co-factoring of the CuA domain of CcO (cytochrome c oxidase). How Sco obtains copper once secreted to the extracytoplasmic environment is unknown. In the present paper we report on a protein possessing an HX₆MX₂₁HXM motif that binds a single cuprous ion with subfemtomolar affinity. High-resolution X-ray structures of this extracytoplasmic copper chaperone-like protein (ECuC) in the apo- and Cu(I)-bound states reveal that the latter possesses a surface-accessible cuprous-ion-binding site located in a dish-shaped region of β-sheet structure. A cuprous ion is transferred under a favourable thermodynamic gradient from ECuC to Sco with no back transfer occurring. The ionization properties of the cysteine residues in the Cys⁸⁶xxxCys⁹⁰ copper-binding motif of Sco, together with their positional locations identified from an X-ray structure of Sco, suggests a role for Cys⁸⁶ in initiating an inter-complex ligand-exchange reaction with Cu(I)-ECuC. Generation of the genetic knockouts, Δsco, Δecuc and Δsco/ecuc, and subsequent in vivo assays lend support to the existence of a branched extracytoplasmic copper-trafficking pathway in S. lividans. One branch requires both Sco and to a certain extent ECuC to cofactor the CuA domain, whereas the other uses only Sco to deliver copper to a cuproenzyme to initiate morphological development.

  9. 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

  10. 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

    2016-06-16

    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.

  11. 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.

  12. 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.

  13. 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.

  14. The folding pathway of glycosomal triosephosphate isomerase: structural insights into equilibrium intermediates.

    PubMed

    Guzman-Luna, Valeria; Garza-Ramos, Georgina

    2012-06-01

    The guanidine hydrochloride-induced conformational transitions of glycosomal triosephosphate isomerase (TIM) were monitored with functional, spectroscopic, and hydrodynamic measurements. The equilibrium folding pathway was found to include two intermediates (N(2) ↔I(2) ↔2M↔2U). According to this model, the conformational stability parameters of TIM are as follows: ΔG(I2-N2) = 5.5 ± 0.6, ΔG(2M-I2) =19.6 ± 1.6, and ΔG(2U-2M) = 14.7 ± 3.1 kcal mol(-1) . The I(2) state is compact (α(SR) = 0.8); it is able to bind 8-anilinonaphthalene-1-sulfonic acid ANS and it is composed of ∼45% of α-helix and tertiary structure content compared with the native enzyme; however, it is unable to bind the transition-state analog 2-phosphoglycolate. Conversely, the 2M state lacks detectable tertiary contacts, possesses ∼10% of the native α-helical content, is significantly expanded (α(SR) = 0.2), and has low affinity for ANS. We studied the effect of mutating cysteine residues on the structure and stability of I(2) and 2M. Three mutants were made: C39A, C126A, and C39A/C126A. The replacement of C39, which is located at β(2) , was found to be neutral. The I(2) -C126A state, however, was prone to aggregation and exhibited an emission maximum that was 3-nm red-shifted compared with the I(2) -wild type, indicating solvent exposure of W90 at β(4) . Our results suggest that the I(2) state comprises the (βα)(1-4) β(5) module in which the conserved C126 residue located at β(5) defines the boundary of the folded segment. We propose a folding pathway that highlights the remarkable thermodynamic stability of this glycosomal enzyme.

  15. Biological/biomedical accelerator mass spectrometry targets. 2. Physical, morphological, and structural characteristics.

    PubMed

    Kim, Seung-Hyun; Kelly, Peter B; Clifford, Andrew J

    2008-10-15

    The number of biological/biomedical applications that require AMS to achieve their goals is increasing, and so is the need for a better understanding of the physical, morphological, and structural traits of high quality of AMS targets. The metrics of quality included color, hardness/texture, and appearance (photo and SEM), along with FT-IR, Raman, and powder X-ray diffraction spectra that correlate positively with reliable and intense ion currents and accuracy, precision, and sensitivity of fraction modern ( F m). Our previous method produced AMS targets of gray-colored iron-carbon materials (ICM) 20% of the time and of graphite-coated iron (GCI) 80% of the time. The ICM was hard, its FT-IR spectra lacked the sp (2) bond, its Raman spectra had no detectable G' band at 2700 cm (-1), and it had more iron carbide (Fe 3C) crystal than nanocrystalline graphite or graphitizable carbon (g-C). ICM produced low and variable ion current whereas the opposite was true for the graphitic GCI. Our optimized method produced AMS targets of graphite-coated iron powder (GCIP) 100% of the time. The GCIP shared some of the same properties as GCI in that both were black in color, both produced robust ion current consistently, their FT-IR spectra had the sp (2) bond, their Raman spectra had matching D, G, G', D +G, and D '' bands, and their XRD spectra showed matching crystal size. GCIP was a powder that was easy to tamp into AMS target holders that also facilitated high throughput. We concluded that AMS targets of GCIP were a mix of graphitizable carbon and Fe 3C crystal, because none of their spectra, FT-IR, Raman, or XRD, matched exactly those of the graphite standard. Nevertheless, AMS targets of GCIP consistently produced the strong, reliable, and reproducible ion currents for high-throughput AMS analysis (270 targets per skilled analyst/day) along with accurate and precise F m values.

  16. Solution phase parallel synthesis and evaluation of MAPK inhibitory activities of close structural analogues of a Ras pathway modulator.

    PubMed

    Lu, Yingchun; Sakamuri, Sukumar; Chen, Quin-Zene; Keng, Yen-Fang; Khazak, Vladimir; Illgen, Katrin; Schabbert, Silke; Weber, Lutz; Menon, Sanjay R

    2004-08-02

    A solution phase parallel synthesis approach was undertaken to rapidly explore the structure-activity relationship of an inhibitor of the Ras/Raf protein interaction identified from a small molecule compound library. Evaluation of the MAPK pathway signaling inhibitory activity of the synthesized analogues as well as their antiproliferative activity and ability to inhibit soft agar growth were performed.

  17. FFAGS for rapid acceleration

    SciTech Connect

    Carol J. Johnstone and Shane Koscielniak

    2002-09-30

    When large transverse and longitudinal emittances are to be transported through a circular machine, extremely rapid acceleration holds the advantage that the beam becomes immune to nonlinear resonances because there is insufficient time for amplitudes to build up. Uncooled muon beams exhibit large emittances and require fast acceleration to avoid decay losses and would benefit from this style of acceleration. The approach here employs a fixed-field alternating gradient or FFAG magnet structure and a fixed frequency acceleration system. Acceptance is enhanced by the use only of linear lattice elements, and fixed-frequency rf enables the use of cavities with large shunt resistance and quality factor.

  18. Structural elements of the signal propagation pathway in squid rhodopsin and bovine rhodopsin.

    PubMed

    Sugihara, Minoru; Fujibuchi, Wataru; Suwa, Makiko

    2011-05-19

    Squid and bovine rhodopsins are G-protein coupled receptors (GPCRs) that activate Gq- and Gt-type G-proteins, respectively. To understand the structural elements of the signal propagation pathway, we performed molecular dynamics (MD) simulations of squid and bovine rhodopsins plus a detailed sequence analysis of class A GPCRs. The computations indicate that although the geometry of the retinal is similar in bovine and squid rhodopsins, the important interhelical hydrogen bond networks are different. In squid rhodopsin, an extended hydrogen bond network that spans ∼13 Å to Tyr315 on the cytoplasmic site is present regardless of the protonation state of Asp80. In contrast, the extended hydrogen bond network is interrupted at Tyr306 in bovine rhodopsin. Those differences in the hydrogen bond network may play significant functional roles in the signal propagation from the retinal binding site to the cytoplasmic site, including transmembrane helix (TM) 6 to which the G-protein binds. The MD calculations demonstrate that the elongated conformation of TM6 in squid rhodopsin is stabilized by salt bridges formed with helix (H) 9. Together with the interhelical hydrogen bonds, the salt bridges between TM6 and H9 stabilize the protein conformation of squid rhodopsin and may hinder the occurrence of large conformational changes that are observed upon activation of bovine rhodopsin.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. Near-planar Solution Structures of Mannose-binding Lectin Oligomers Provide Insight on Activation of Lectin Pathway of Complement

    PubMed Central

    Miller, Ami; Phillips, Anna; Gor, Jayesh; Wallis, Russell; Perkins, Stephen J.

    2012-01-01

    The complement system is a fundamental component of innate immunity that orchestrates complex immunological and inflammatory processes. Complement comprises over 30 proteins that eliminate invading microorganisms while maintaining host cell integrity. Protein-carbohydrate interactions play critical roles in both the activation and regulation of complement. Mannose-binding lectin (MBL) activates the lectin pathway of complement via the recognition of sugar arrays on pathogenic surfaces. To determine the solution structure of MBL, synchrotron x-ray scattering and analytical ultracentrifugation experiments showed that the carbohydrate-recognition domains in the MBL dimer, trimer, and tetramer are positioned close to each other in near-planar fan-like structures. These data were subjected to constrained modeling fits. A bent structure for the MBL monomer was identified starting from two crystal structures for its carbohydrate-recognition domain and its triple helical region. The MBL monomer structure was used to identify 10–12 near-planar solution structures for each of the MBL dimers, trimers, and tetramers starting from 900 to 6,859 randomized structures for each. These near-planar fan-like solution structures joined at an N-terminal hub clarified how the carbohydrate-recognition domain of MBL binds to pathogenic surfaces. They also provided insight on how MBL presents a structural template for the binding and auto-activation of the MBL-associated serine proteases to initiate the lectin pathway of complement activation. PMID:22167201

  9. 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.

  10. 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.

  11. mzGroupAnalyzer-Predicting Pathways and Novel Chemical Structures from Untargeted High-Throughput Metabolomics Data

    PubMed Central

    Wang, Lei; Engelmeier, Doris; Lyon, David; Weckwerth, Wolfram

    2014-01-01

    The metabolome is a highly dynamic entity and the final readout of the genotype x environment x phenotype (GxExP) relationship of an organism. Monitoring metabolite dynamics over time thus theoretically encrypts the whole range of possible chemical and biochemical transformations of small molecules involved in metabolism. The bottleneck is, however, the sheer number of unidentified structures in these samples. This represents the next challenge for metabolomics technology and is comparable with genome sequencing 30 years ago. At the same time it is impossible to handle the amount of data involved in a metabolomics analysis manually. Algorithms are therefore imperative to allow for automated m/z feature extraction and subsequent structure or pathway assignment. Here we provide an automated pathway inference strategy comprising measurements of metabolome time series using LC- MS with high resolution and high mass accuracy. An algorithm was developed, called mzGroupAnalyzer, to automatically explore the metabolome for the detection of metabolite transformations caused by biochemical or chemical modifications. Pathways are extracted directly from the data and putative novel structures can be identified. The detected m/z features can be mapped on a van Krevelen diagram according to their H/C and O/C ratios for pattern recognition and to visualize oxidative processes and biochemical transformations. This method was applied to Arabidopsis thaliana treated simultaneously with cold and high light. Due to a protective antioxidant response the plants turn from green to purple color via the accumulation of flavonoid structures. The detection of potential biochemical pathways resulted in 15 putatively new compounds involved in the flavonoid-pathway. These compounds were further validated by product ion spectra from the same data. The mzGroupAnalyzer is implemented in the graphical user interface (GUI) of the metabolomics toolbox COVAIN (Sun & Weckwerth, 2012, Metabolomics 8: 81

  12. Coordinated Activation of VEGF/VEGFR-2 and PPARδ Pathways by a Multi-Component Chinese Medicine DHI Accelerated Recovery from Peripheral Arterial Disease in Type 2 Diabetic Mice

    PubMed Central

    He, Shuang; Zhao, Tiechan; Guo, Hao; Meng, Yanzhi; Qin, Gangjian; Goukassian, David A.; Han, Jihong; Gao, Xuimei; Zhu, Yan

    2016-01-01

    Diabetic mellitus (DM) patients are at an increased risk of developing peripheral arterial disease (PAD). Danhong injection (DHI) is a Chinese patent medicine widely used for several cardiovascular indications but the mechanism of action is not well-understood. We investigated the therapeutic potential of DHI on experimental PAD in mice with chemically induced as well as genetic (KKAy) type 2 DM and the overlapping signaling pathways regulating both therapeutic angiogenesis and glucose homeostasis. Compared with normal genetic background wild type (WT) mice, both DM mice showed impaired perfusion recovery in hind-limb ischemia (HLI) model. DHI treatment significantly accelerated perfusion recovery, lowered blood glucose and improved glucose tolerance in both DM models. Bioluminescent imaging demonstrated a continuous ischemia-induced vascular endothelial growth factor receptor 2 (VEGFR-2) gene expressions with a peak time coincident with the maximal DHI stimulation. Flow cytometry analysis showed a DHI-mediated increase in endothelial progenitor cell (EPC) mobilization from bone marrow to circulating peripheral blood. DHI administration upregulated the expression of vascular endothelial growth factor A (VEGF-A) and VEGF receptor-2 (VEGFR-2) in ischemic muscle. A cross talk between ischemia-induced angiogenesis and glucose tolerance pathways was analyzed by Ingenuity Pathway Analysis (IPA) which suggested an interaction of VEGF-A/VEGFR-2 and peroxisome proliferator-activated receptor δ (PPARδ)/peroxisome proliferator-activated receptor γ (PPARγ) genes. We confirmed that upregulation of VEGF-A/VEGFR-2 by DHI promoted PPARδ gene expression in both type 2 diabetic mice. Our findings demonstrated that a multi-component Chinese medicine DHI effectively increased blood flow recovery after tissue ischemia in diabetic mice by promoting angiogenesis and improving glucose tolerance through a concomitant activation of VEGF-A/VEGFR-2 and PPARδ signaling pathways. PMID

  13. Structural and Ultrastructural Alterations in Human Olfactory Pathways and Possible Associations with Herpesvirus 6 Infection

    PubMed Central

    Skuja, Sandra; Zieda, Anete; Ravina, Kristine; Chapenko, Svetlana; Roga, Silvija; Teteris, Ojars; Groma, Valerija; Murovska, Modra

    2017-01-01

    Structural and ultrastructural alterations in human olfactory pathways and putative associations with human herpesvirus 6 (HHV-6) infection were studied. The olfactory bulb/tract samples from 20 subjects with an unspecified encephalopathy determined by pathomorphological examination of the brain autopsy, 17 healthy age-matched and 16 younger controls were used. HHV-6 DNA was detected in 60, 29, and 19% of cases in these groups, respectively. In the whole encephalopathy group, significantly more HHV-6 positive neurons and oligodendrocytes were found in the gray matter, whereas, significantly more HHV-6 positive astrocytes, oligodendrocytes, microglia/macrophages and endothelial cells were found in the white matter. Additionally, significantly more HHV-6 positive astrocytes and, in particular, oligodendrocytes were found in the white matter when compared to the gray matter. Furthermore, when only HHV-6 PCR+ encephalopathy cases were studied, we observed similar but stronger associations between HHV-6 positive oligodendrocytes and CD68 positive cells in the white matter. Cellular alterations were additionally evidenced by anti-S100 immunostaining, demonstrating a significantly higher number of S100 positive cells in the gray matter of the whole encephalopathy group when compared to the young controls, and in the white matter when compared to both control groups. In spite the decreased S100 expression in the PCR+ encephalopathy group when compared to PCR- cases and controls, groups demonstrated significantly higher number of S100 positive cells in the white compared to the gray matter. Ultrastructural changes confirming the damage of myelin included irregularity of membranes and ballooning of paranodal loops. This study shows that among the cellular targets of the nervous system, HHV-6 most severely affects oligodendrocytes and the myelin made by them. PMID:28072884

  14. 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.

  15. A Structure-Based Approach for Mapping Adverse Drug Reactions to the Perturbation of Underlying Biological Pathways

    PubMed Central

    Wallach, Izhar; Jaitly, Navdeep; Lilien, Ryan

    2010-01-01

    Adverse drug reactions (ADR), also known as side-effects, are complex undesired physiologic phenomena observed secondary to the administration of pharmaceuticals. Several phenomena underlie the emergence of each ADR; however, a dominant factor is the drug's ability to modulate one or more biological pathways. Understanding the biological processes behind the occurrence of ADRs would lead to the development of safer and more effective drugs. At present, no method exists to discover these ADR-pathway associations. In this paper we introduce a computational framework for identifying a subset of these associations based on the assumption that drugs capable of modulating the same pathway may induce similar ADRs. Our model exploits multiple information resources. First, we utilize a publicly available dataset pairing drugs with their observed ADRs. Second, we identify putative protein targets for each drug using the protein structure database and in-silico virtual docking. Third, we label each protein target with its known involvement in one or more biological pathways. Finally, the relationships among these information sources are mined using multiple stages of logistic-regression while controlling for over-fitting and multiple-hypothesis testing. As proof-of-concept, we examined a dataset of 506 ADRs, 730 drugs, and 830 human protein targets. Our method yielded 185 ADR-pathway associations of which 45 were selected to undergo a manual literature review. We found 32 associations to be supported by the scientific literature. PMID:20808786

  16. The genome-scale metabolic extreme pathway structure in Haemophilus influenzae shows significant network redundancy.

    PubMed

    Papin, Jason A; Price, Nathan D; Edwards, Jeremy S; Palsson B, Bernhard Ø

    2002-03-07

    Genome-scale metabolic networks can be characterized by a set of systemically independent and unique extreme pathways. These extreme pathways span a convex, high-dimensional space that circumscribes all potential steady-state flux distributions achievable by the defined metabolic network. Genome-scale extreme pathways associated with the production of non-essential amino acids in Haemophilus influenzae were computed. They offer valuable insight into the functioning of its metabolic network. Three key results were obtained. First, there were multiple internal flux maps corresponding to externally indistinguishable states. It was shown that there was an average of 37 internal states per unique exchange flux vector in H. influenzae when the network was used to produce a single amino acid while allowing carbon dioxide and acetate as carbon sinks. With the inclusion of succinate as an additional output, this ratio increased to 52, a 40% increase. Second, an analysis of the carbon fates illustrated that the extreme pathways were non-uniformly distributed across the carbon fate spectrum. In the detailed case study, 45% of the distinct carbon fate values associated with lysine production represented 85% of the extreme pathways. Third, this distribution fell between distinct systemic constraints. For lysine production, the carbon fate values that represented 85% of the pathways described above corresponded to only 2 distinct ratios of 1:1 and 4:1 between carbon dioxide and acetate. The present study analysed single outputs from one organism, and provides a start to genome-scale extreme pathways studies. These emergent system-level characterizations show the significance of metabolic extreme pathway analysis at the genome-scale.

  17. Induction linear accelerators

    NASA Astrophysics Data System (ADS)

    Birx, Daniel

    1992-03-01

    Among the family of particle accelerators, the Induction Linear Accelerator is the best suited for the acceleration of high current electron beams. Because the electromagnetic radiation used to accelerate the electron beam is not stored in the cavities but is supplied by transmission lines during the beam pulse it is possible to utilize very low Q (typically<10) structures and very large beam pipes. This combination increases the beam breakup limited maximum currents to of order kiloamperes. The micropulse lengths of these machines are measured in 10's of nanoseconds and duty factors as high as 10-4 have been achieved. Until recently the major problem with these machines has been associated with the pulse power drive. Beam currents of kiloamperes and accelerating potentials of megavolts require peak power drives of gigawatts since no energy is stored in the structure. The marriage of liner accelerator technology and nonlinear magnetic compressors has produced some unique capabilities. It now appears possible to produce electron beams with average currents measured in amperes, peak currents in kiloamperes and gradients exceeding 1 MeV/meter, with power efficiencies approaching 50%. The nonlinear magnetic compression technology has replaced the spark gap drivers used on earlier accelerators with state-of-the-art all-solid-state SCR commutated compression chains. The reliability of these machines is now approaching 1010 shot MTBF. In the following paper we will briefly review the historical development of induction linear accelerators and then discuss the design considerations.

  18. NLRX1 accelerates cisplatin-induced ototoxity in HEI-OC1 cells via promoting generation of ROS and activation of JNK signaling pathway

    PubMed Central

    Yin, Haiyan; Sun, Gaoying; Yang, Qianqian; Chen, Chen; Qi, Qi; Wang, Haibo; Li, Jianfeng

    2017-01-01

    Nucleotide-binding domain and leucine-rich-repeat-containing family member X1 (NLRX1), located in mitochondria, can recognize cytoplasmic pattern recognition receptors and is tightly related to reactive oxygen species (ROS) production, mitochondrial function, apoptosis and inflammation. The present study was designed to explore whether NLRX1 expresses in HEI-OC1 cells and, if so, to investigate the possible correlations between NLRX1 and cisplatin-induced ototoxity in vitro. Here, we report that NLRX1 was specifically localized to mitochondria in the cytoplasm of HEI-OC1 cells and its expression was increased concurrent with the increase of ROS production and occurrence of apoptosis in HEI-OC1 cells in response to cisplatin stimulus. NLRX1 overexpression led to a higher apoptosis in HEI-OC1 cells treated with cisplatin, whereas, NLRX silencing decreased cisplatin induced apoptosis. Mechanistic studies showed that NLRX1 activated mitochondrial apoptosis pathway as well as promoted ROS generation and JNK activation. Either inhibition of ROS generation or JNK signaling significantly prevented NLRX1-mediated mitochondrial apoptosis in HEI-OC1cells. In addition, NLRX1 expression was confirmed in cochlear explants. The findings from this work reveal that NLRX1 sensitizes HEI-OC1 cells to cisplatin-induced apoptosis via activation of ROS/JNK signaling pathway, suggesting that NLRX1 acts as an important regulator of the cisplatin-elicited ototoxity. PMID:28287190

  19. 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.

  20. Structure and Composition of the Distant Lunar Exosphere: Constraints from ARTEMIS Observations of Ion Acceleration in Time-Varying Fields

    NASA Technical Reports Server (NTRS)

    Halekas, J. S.; Poppe, A. R.; Farrell, W. M.; McFadden, J. P.

    2016-01-01

    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.

  1. 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.

  2. Crystal Structure of Schistosoma mansoni Adenosine Phosphorylase/5’-Methylthioadenosine Phosphorylase and Its Importance on Adenosine Salvage Pathway

    PubMed Central

    Torini, Juliana Roberta; Brandão-Neto, José; DeMarco, Ricardo; Pereira, Humberto D'Muniz

    2016-01-01

    Schistosoma mansoni do not have de novo purine pathways and rely on purine salvage for their purine supply. It has been demonstrated that, unlike humans, the S. mansoni is able to produce adenine directly from adenosine, although the enzyme responsible for this activity was unknown. In the present work we show that S. mansoni 5´-deoxy-5´-methylthioadenosine phosphorylase (MTAP, E.C. 2.4.2.28) is capable of use adenosine as a substrate to the production of adenine. Through kinetics assays, we show that the Schistosoma mansoni MTAP (SmMTAP), unlike the mammalian MTAP, uses adenosine substrate with the same efficiency as MTA phosphorolysis, which suggests that this enzyme is part of the purine pathway salvage in S. mansoni and could be a promising target for anti-schistosoma therapies. Here, we present 13 SmMTAP structures from the wild type (WT), including three single and one double mutant, and generate a solid structural framework for structure description. These crystal structures of SmMTAP reveal that the active site contains three substitutions within and near the active site when compared to it mammalian counterpart, thus opening up the possibility of developing specific inhibitors to the parasite MTAP. The structural and kinetic data for 5 substrates reveal the structural basis for this interaction, providing substract for inteligent design of new compounds for block this enzyme activity. PMID:27935959

  3. Finding off-targets, biological pathways, and target diseases for chymase inhibitors via structure-based systems biology approach.

    PubMed

    Arooj, Mahreen; Sakkiah, Sugunadevi; Cao, Guang Ping; Kim, Songmi; Arulalapperumal, Venkatesh; Lee, Keun Woo

    2015-07-01

    Off-target binding connotes the binding of a small molecule of therapeutic significance to a protein target in addition to the primary target for which it was proposed. Progressively such off-targeting is emerging to be regular practice to reveal side effects. Chymase is an enzyme of hydrolase class that catalyzes hydrolysis of peptide bonds. A link between heart failure and chymase is ascribed, and a chymase inhibitor is in clinical phase II for treatment of heart failure. However, the underlying mechanisms of the off-target effects of human chymase inhibitors are still unclear. Here, we develop a robust computational strategy that is applicable to any enzyme system and that allows the prediction of drug effects on biological processes. Putative off-targets for chymase inhibitors were identified through various structural and functional similarity analyses along with molecular docking studies. Finally, literature survey was performed to incorporate these off-targets into biological pathways and to establish links between pathways and particular adverse effects. Off-targets of chymase inhibitors are linked to various biological pathways such as classical and lectin pathways of complement system, intrinsic and extrinsic pathways of coagulation cascade, and fibrinolytic system. Tissue kallikreins, granzyme M, neutrophil elastase, and mesotrypsin are also identified as off-targets. These off-targets and their associated pathways are elucidated for the effects of inflammation, cancer, hemorrhage, thrombosis, and central nervous system diseases (Alzheimer's disease). Prospectively, our approach is helpful not only to better understand the mechanisms of chymase inhibitors but also for drug repurposing exercises to find novel uses for these inhibitors.

  4. The shikimate pathway: review of amino acid sequence, function and three-dimensional structures of the enzymes.

    PubMed

    Mir, Rafia; Jallu, Shais; Singh, T P

    2015-06-01

    The aromatic compounds such as aromatic amino acids, vitamin K and ubiquinone are important prerequisites for the metabolism of an organism. All organisms can synthesize these aromatic metabolites through shikimate pathway, except for mammals which are dependent on their diet for these compounds. The pathway converts phosphoenolpyruvate and erythrose 4-phosphate to chorismate through seven enzymatically catalyzed steps and chorismate serves as a precursor for the synthesis of variety of aromatic compounds. These enzymes have shown to play a vital role for the viability of microorganisms and thus are suggested to present attractive molecular targets for the design of novel antimicrobial drugs. This review focuses on the seven enzymes of the shikimate pathway, highlighting their primary sequences, functions and three-dimensional structures. The understanding of their active site amino acid maps, functions and three-dimensional structures will provide a framework on which the rational design of antimicrobial drugs would be based. Comparing the full length amino acid sequences and the X-ray crystal structures of these enzymes from bacteria, fungi and plant sources would contribute in designing a specific drug and/or in developing broad-spectrum compounds with efficacy against a variety of pathogens.

  5. Structural modeling and analysis of signaling pathways based on Petri nets.

    PubMed

    Li, Chen; Suzuki, Shunichi; Ge, Qi-Wei; Nakata, Mitsuru; Matsuno, Hiroshi; Miyano, Satoru

    2006-10-01

    The purpose of this paper is to discuss how to model and analyze signaling pathways by using Petri net. Firstly, we propose a modeling method based on Petri net by paying attention to the molecular interactions and mechanisms. Then, we introduce a new notion "activation transduction component" in order to describe an enzymic activation process of reactions in signaling pathways and shows its correspondence to a so-called elementary T-invariant in the Petri net models. Further, we design an algorithm to effectively find basic enzymic activation processes by obtaining a series of elementary T-invariants in the Petri net models. Finally, we demonstrate how our method is practically used in modeling and analyzing signaling pathway mediated by thrombopoietin as an example.

  6. Peptide Ligand Structure and I-Aq Binding Avidity Influence T Cell Signaling Pathway Utilization

    PubMed Central

    Myers, Linda K; Cullins, David L; Park, Jeoung-Eun; Yi, Ae-Kyung; Brand, David D; Rosloniec, Edward F; Stuart, John M; Kang, Andrew H

    2015-01-01

    Factors that drive T cells to signal through differing pathways remain unclear. We have shown that an altered peptide ligand (A9) activates T cells to utilize an alternate signaling pathway which is dependent upon FcRγ and Syk. However, it remains unknown whether the affinity of peptide binding to MHC drives this selection. To answer this question we developed a panel of peptides designed so that amino acids interacting with the p6 and p9 predicted MHC binding pockets were altered. Analogs were tested for binding to I-Aq using a competitive binding assay and selected analogs were administered to arthritic mice. Using the collagen-induced arthritis (CIA) model, arthritis severity was correlated with T cell cytokine production and molecular T cell signaling responses. We establish that reduced affinity of interaction with the MHC correlates with T cell signaling through the alternative pathway, leading ultimately to secretion of suppressive cytokine and attenuation of arthritis. PMID:25982319

  7. Trapping and Structural Elucidation of a Very Advanced Intermediate in the Lesion-Extrusion Pathway of hOGG1

    SciTech Connect

    Lee, Seongmin; Radom, Christopher T.; Verdine, Gregory L.

    2008-07-28

    Here we present the first structure of a very advanced intermediate in the lesion-extrusion pathway of a DNA glycosylase, human 8-oxoguanine DNA glycosylase (hOGG1), and a substrate DNA containing a mutagenic lesion, 8-oxoguanine (oxoG). The structure was obtained by irradiation and flash-freezing of a disulfide-cross-linked (DXLed) complex of hOgg1 bound to DNA containing a novel photocaged derivative of oxoG. The X-ray structure reveals that, upon irradiation, the oxoG lesion has transited from the exosite to the active site pocket, but has not undergone cleavage by the enzyme. Furthermore, all but one of the specificity-determining interactions between the lesion and the enzyme are unformed in the flashed complex (FC), because active site functionality and elements of the DNA backbone are mispositioned. This structure thus provides a first glimpse into the structure of a very late-stage intermediate in the lesion-extrusion pathway -- the latest observed to date for any glycosylase -- in which the oxoG has undergone insertion into the enzyme active site following photodeprotection, but the enzyme and DNA have not yet completed the slower process of adjusting to the presence of the lesion in the active site.

  8. Vibration control in accelerators

    SciTech Connect

    Montag, C.

    2011-01-01

    In the vast majority of accelerator applications, ground vibration amplitudes are well below tolerable magnet jitter amplitudes. In these cases, it is necessary and sufficient to design a rigid magnet support structure that does not amplify ground vibration. Since accelerator beam lines are typically installed at an elevation of 1-2m above ground level, special care has to be taken in order to avoid designing a support structure that acts like an inverted pendulum with a low resonance frequency, resulting in untolerable lateral vibration amplitudes of the accelerator components when excited by either ambient ground motion or vibration sources within the accelerator itself, such as cooling water pumps or helium flow in superconducting magnets. In cases where ground motion amplitudes already exceed the required jiter tolerances, for instance in future linear colliders, passive vibration damping or active stabilization may be considered.

  9. Associations between Proprioceptive Neural Pathway Structural Connectivity and Balance in People with Multiple Sclerosis.

    PubMed

    Fling, Brett W; Dutta, Geetanjali Gera; Schlueter, Heather; Cameron, Michelle H; Horak, Fay B

    2014-01-01

    Mobility and balance impairments are a hallmark of multiple sclerosis (MS), affecting nearly half of patients at presentation and resulting in decreased activity and participation, falls, injuries, and reduced quality of life. A growing body of work suggests that balance impairments in people with mild MS are primarily the result of deficits in proprioception, the ability to determine body position in space in the absence of vision. A better understanding of the pathophysiology of balance disturbances in MS is needed to develop evidence-based rehabilitation approaches. The purpose of the current study was to (1) map the cortical proprioceptive pathway in vivo using diffusion-weighted imaging and (2) assess associations between proprioceptive pathway white matter microstructural integrity and performance on clinical and behavioral balance tasks. We hypothesized that people with MS (PwMS) would have reduced integrity of cerebral proprioceptive pathways, and that reduced white matter microstructure within these tracts would be strongly related to proprioceptive-based balance deficits. We found poorer balance control on proprioceptive-based tasks and reduced white matter microstructural integrity of the cortical proprioceptive tracts in PwMS compared with age-matched healthy controls (HC). Microstructural integrity of this pathway in the right hemisphere was also strongly associated with proprioceptive-based balance control in PwMS and controls. Conversely, while white matter integrity of the right hemisphere's proprioceptive pathway was significantly correlated with overall balance performance in HC, there was no such relationship in PwMS. These results augment existing literature suggesting that balance control in PwMS may become more dependent upon (1) cerebellar-regulated proprioceptive control, (2) the vestibular system, and/or (3) the visual system.

  10. Design of On-chip Power Transport and Coupling Components for a Silicon Woodpile Accelerator

    SciTech Connect

    Wu, Ziran; Ng, C.; McGuinness, C.; Colby, E.; /SLAC

    2011-05-23

    Three-dimensional woodpile photonic bandgap (PBG) waveguide enables high-gradient and efficient laser driven acceleration, while various accelerator components, including laser couplers, power transmission lines, woodpile accelerating and focusing waveguides, and energy recycling resonators, can be potentially integrated on a single monolithic structure via lithographic fabrications. This paper will present designs of this on-chip accelerator based on silicon-on-insulator (SOI) waveguide. Laser power is coupled from free-space or fiber into SOI waveguide by grating structures on the silicon surface, split into multiple channels to excite individual accelerator cells, and eventually gets merged into the power recycle pathway. Design and simulation results will be presented regarding various coupling components involved in this network.

  11. 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

  12. 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

    2016-06-07

    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.

  13. 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.

  14. LINEAR ACCELERATOR

    DOEpatents

    Colgate, S.A.

    1958-05-27

    An improvement is presented in linear accelerators for charged particles with respect to the stable focusing of the particle beam. The improvement consists of providing a radial electric field transverse to the accelerating electric fields and angularly introducing the beam of particles in the field. The results of the foregoing is to achieve a beam which spirals about the axis of the acceleration path. The combination of the electric fields and angular motion of the particles cooperate to provide a stable and focused particle beam.

  15. Coupled biotic-abiotic Mn(II) oxidation pathway mediates the formation and structural evolution of biogenic Mn oxides

    NASA Astrophysics Data System (ADS)

    Learman, D. R.; Wankel, S. D.; Webb, S. M.; Martinez, N.; Madden, A. S.; Hansel, C. M.

    2011-10-01

    Manganese (Mn) oxides are among the strongest oxidants and sorbents in the environment, impacting the transport and speciation of metals, cycling of carbon, and flow of electrons within soils and sediments. The oxidation of Mn(II) to Mn(III/IV) oxides has been primarily attributed to biological processes, due in part to the faster rates of bacterial Mn(II) oxidation compared to observed mineral-induced and other abiotic rates. Here we explore the reactivity of biogenic Mn oxides formed by a common marine bacterium ( Roseobacter sp. AzwK-3b), which has been previously shown to oxidize Mn(II) via the production of extracellular superoxide. Oxidation of Mn(II) by superoxide results in the formation of highly reactive colloidal birnessite with hexagonal symmetry. The colloidal oxides induce the rapid oxidation of Mn(II), with dramatically accelerated rates in the presence of organics, presumably due to mineral surface-catalyzed organic radical generation. Mn(II) oxidation by the colloids is further accelerated in presence of both organics and light, implicating reactive oxygen species in aiding abiotic oxidation. Indeed, the enhancement of Mn(II) oxidation is negated when the colloids are reacted with Mn(II) in the presence of superoxide dismutase, an enzyme that scavenges the reactive oxygen species (ROS) superoxide. The reactivity of the colloidal phase is short-lived due to the rapid evolution of the birnessite from hexagonal to pseudo-orthogonal symmetry. The secondary particulate triclinic birnessite phase exhibits a distinct lack of Mn(II) oxidation and subsequent Mn oxide formation. Thus, the evolution of initial reactive hexagonal birnessite to non-reactive triclinic birnessite imposes the need for continuous production of new colloidal hexagonal particles for Mn(II) oxidation to be sustained, illustrating an intimate dependency of enzymatic and mineral-based reactions in Mn(II) oxidation. Further, the coupled enzymatic and mineral-induced pathways are linked

  16. Acceleration switch

    DOEpatents

    Abbin, Jr., Joseph P.; Devaney, Howard F.; Hake, Lewis W.

    1982-08-17

    The disclosure relates to an improved integrating acceleration switch of the type having a mass suspended within a fluid filled chamber, with the motion of the mass initially opposed by a spring and subsequently not so opposed.

  17. Acceleration switch

    DOEpatents

    Abbin, J.P. Jr.; Devaney, H.F.; Hake, L.W.

    1979-08-29

    The disclosure relates to an improved integrating acceleration switch of the type having a mass suspended within a fluid filled chamber, with the motion of the mass initially opposed by a spring and subsequently not so opposed.

  18. ION ACCELERATOR

    DOEpatents

    Bell, J.S.

    1959-09-15

    An arrangement for the drift tubes in a linear accelerator is described whereby each drift tube acts to shield the particles from the influence of the accelerating field and focuses the particles passing through the tube. In one embodiment the drift tube is splii longitudinally into quadrants supported along the axis of the accelerator by webs from a yoke, the quadrants. webs, and yoke being of magnetic material. A magnetic focusing action is produced by energizing a winding on each web to set up a magnetic field between adjacent quadrants. In the other embodiment the quadrants are electrically insulated from each other and have opposite polarity voltages on adjacent quadrants to provide an electric focusing fleld for the particles, with the quadrants spaced sufficienily close enough to shield the particles within the tube from the accelerating electric field.

  19. Guided Pathways to Careers: Four Dimensions of Structure in Community College Career-Technical Programs

    ERIC Educational Resources Information Center

    Van Noy, Michelle; Trimble, Madeline; Jenkins, Davis; Barnett, Elisabeth; Wachen, John

    2016-01-01

    Objective: Some have hypothesized that community college programs are not sufficiently structured to support student success and that students would benefit from more highly structured programs. This study examines the specific ways that structure is expressed in policy and practice at representative community colleges. Method: Using data obtained…

  20. LINEAR ACCELERATOR

    DOEpatents

    Christofilos, N.C.; Polk, I.J.

    1959-02-17

    Improvements in linear particle accelerators are described. A drift tube system for a linear ion accelerator reduces gap capacity between adjacent drift tube ends. This is accomplished by reducing the ratio of the diameter of the drift tube to the diameter of the resonant cavity. Concentration of magnetic field intensity at the longitudinal midpoint of the external sunface of each drift tube is reduced by increasing the external drift tube diameter at the longitudinal center region.

  1. Cluster Multipoint Observations of the Spatial Structure and Time Development of Auroral Acceleration Region Field-aligned Current Systems, Potentials, and Plasma

    NASA Astrophysics Data System (ADS)

    Hull, A. J.; Chaston, C. C.; Fillingim, M. O.; Frey, H. U.; Bonnell, J. W.; Mozer, F.; Goldstein, M. L.

    2014-12-01

    The auroral acceleration region is an integral part of the magnetosphere-ionosphere electrodynamic system, and plays a key role in the transport of plasma and energy between Earth and space. This region is embedded with field-aligned currents that couple the magnetosphere to the ionosphere and is where parallel electric fields form that accelerate plasma to and from these regions. Though considerable progress has been made, the complex interplay between field-aligned current system formation, the development of parallel electric fields, changes in the plasma constituents, and auroral emissions consequences are not fully understood. The Cluster mission is well suited for studying the structure and dynamics of the auroral acceleration region. Over its lifetime, Cluster has sampled much of this region with closely spaced probes enabling the distinction between temporal effects from spatial variations. Moreover, this data when combined with auroral images from IMAGE or THEMIS GBO-ASI enable an assessment of the auroral emission response to spatial morphology and temporal development of structures seeded in the auroral acceleration region. In this study we present a survey of Cluster multi-point traversals within and just above the auroral acceleration region (≤ 3 Re altitude). In particular we highlight the spatial morphology and developmental sequence of auroral acceleration current systems, potentials and plasma constituents, with the aim of identifying controlling factors, and assessing ionospheric consequences under different conditions. Our results suggest that the "Alfvénic" activity may be an important precursor and perhaps may be playing an essential role in the development of "quasi-static" current systems during quiet and substorm active times. Such events are generally the result of an injection mediated process at or near the plasma sheet boundary layer, resulting in the local expansion of the plasma sheet. Key features of the conversion from Alfv

  2. D-galactose catabolism in Penicillium chrysogenum: Expression analysis of the structural genes of the Leloir pathway.

    PubMed

    Jónás, Ágota; Fekete, Erzsébet; Németh, Zoltán; Flipphi, Michel; Karaffa, Levente

    2016-09-01

    In this study, we analyzed the expression of the structural genes encoding the five enzymes comprising the Leloir pathway of D-galactose catabolism in the industrial cell factory Penicillium chrysogenum on various carbon sources. The genome of P. chrysogenum contains a putative galactokinase gene at the annotated locus Pc13g10140, the product of which shows strong structural similarity to yeast galactokinase that was expressed on lactose and D-galactose only. The expression profile of the galactose-1-phosphate uridylyl transferase gene at annotated locus Pc15g00140 was essentially similar to that of galactokinase. This is in contrast to the results from other fungi such as Aspergillus nidulans, Trichoderma reesei and A. niger, where the ortholog galactokinase and galactose-1-phosphate uridylyl transferase genes were constitutively expressed. As for the UDP-galactose-4-epimerase encoding gene, five candidates were identified. We could not detect Pc16g12790, Pc21g12170 and Pc20g06140 expression on any of the carbon sources tested, while for the other two loci (Pc21g10370 and Pc18g01080) transcripts were clearly observed under all tested conditions. Like the 4-epimerase specified at locus Pc21g10370, the other two structural Leloir pathway genes - UDP-glucose pyrophosphorylase (Pc21g12790) and phosphoglucomutase (Pc18g01390) - were expressed constitutively at high levels as can be expected from their indispensable function in fungal cell wall formation.

  3. CLASHING BEAM PARTICLE ACCELERATOR

    DOEpatents

    Burleigh, R.J.

    1961-04-11

    A charged-particle accelerator of the proton synchrotron class having means for simultaneously accelerating two separate contra-rotating particle beams within a single annular magnet structure is reported. The magnet provides two concentric circular field regions of opposite magnetic polarity with one field region being of slightly less diameter than the other. The accelerator includes a deflector means straddling the two particle orbits and acting to collide the two particle beams after each has been accelerated to a desired energy. The deflector has the further property of returning particles which do not undergo collision to the regular orbits whereby the particles recirculate with the possibility of colliding upon subsequent passages through the deflector.

  4. RF Measurements on DXRL (Deep X-ray Li-thog-ra-phy)-Fabricated mmWave Accelerating Cavity Structures at the Advanced Photon Source (APS)

    NASA Astrophysics Data System (ADS)

    Song, J. J.; Kang, Y. W.

    1997-05-01

    Recently rf structures have been proposed for frequencies in the mmwave (30--300 GHz) range. This miniaturization is feasible with a 3-D micromachining process known as LIGA (German acronym for lithographe, galvanoformung, und abformung) or DXRL (deep x-ray lithography).(J.J. Song, et. al, ``LIGA-Fabrication of mmWave Accelerating Cavity Structures at the Advanced Photon Source (APS),'' these proceedings.) A 32-cell 108-GHz constant-impedance cavity and a 66-cell 94-GHz constant-gradient cavity were fabricated using DXRL micromachining with the synchrotron radiation sources at NSLS and APS. Their eventual application could be parts of linear accelerators, microwave undulators, or free-electron lasers. Radiofrequency measurement on the structures was performed by the bead-perturbation method with e-beam sputtered aluminum beads. The form factor of the bead was measured with the pillbox cavity and compared with the calculation. This paper will describe the rf measur! ement on the mmwave cavity structure.

  5. Pathways of inhalation exposure to manganese in children living near a ferromanganese refinery: A structural equation modeling approach.

    PubMed

    Fulk, Florence; Succop, Paul; Hilbert, Timothy J; Beidler, Caroline; Brown, David; Reponen, Tiina; Haynes, Erin N

    2017-02-01

    Manganese (Mn) is both essential element and neurotoxicant. Exposure to Mn can occur from various sources and routes. Structural equation modeling was used to examine routes of exposure to Mn among children residing near a ferromanganese refinery in Marietta, Ohio. An inhalation pathway model to ambient air Mn was hypothesized. Data for model evaluation were obtained from participants in the Communities Actively Researching Exposure Study (CARES). These data were collected in 2009 and included levels of Mn in residential soil and dust, levels of Mn in children's hair, information on the amount of time the child spent outside, heat and air conditioning in the home and level of parent education. Hair Mn concentration was the primary endogenous variable used to assess the theoretical inhalation exposure pathways. The model indicated that household dust Mn was a significant contributor to child hair Mn (0.37). Annual ambient air Mn concentration (0.26), time children spent outside (0.24) and soil Mn (0.24) significantly contributed to the amount of Mn in household dust. These results provide a potential framework for understanding the inhalation exposure pathway for children exposed to ambient air Mn who live in proximity to an industrial emission source.

  6. Parallel processing in the honeybee olfactory pathway: structure, function, and evolution.

    PubMed

    Rössler, Wolfgang; Brill, Martin F

    2013-11-01

    Animals face highly complex and dynamic olfactory stimuli in their natural environments, which require fast and reliable olfactory processing. Parallel processing is a common principle of sensory systems supporting this task, for example in visual and auditory systems, but its role in olfaction remained unclear. Studies in the honeybee focused on a dual olfactory pathway. Two sets of projection neurons connect glomeruli in two antennal-lobe hemilobes via lateral and medial tracts in opposite sequence with the mushroom bodies and lateral horn. Comparative studies suggest that this dual-tract circuit represents a unique adaptation in Hymenoptera. Imaging studies indicate that glomeruli in both hemilobes receive redundant sensory input. Recent simultaneous multi-unit recordings from projection neurons of both tracts revealed widely overlapping response profiles strongly indicating parallel olfactory processing. Whereas lateral-tract neurons respond fast with broad (generalistic) profiles, medial-tract neurons are odorant specific and respond slower. In analogy to "what-" and "where" subsystems in visual pathways, this suggests two parallel olfactory subsystems providing "what-" (quality) and "when" (temporal) information. Temporal response properties may support across-tract coincidence coding in higher centers. Parallel olfactory processing likely enhances perception of complex odorant mixtures to decode the diverse and dynamic olfactory world of a social insect.

  7. TOP 1 and 2, polysaccharides from Taraxacum officinale, inhibit NFκB-mediated inflammation and accelerate Nrf2-induced antioxidative potential through the modulation of PI3K-Akt signaling pathway in RAW 264.7 cells.

    PubMed

    Park, Chung Mu; Cho, Chung Won; Song, Young Sun

    2014-04-01

    Anti-inflammatory and anti-oxidative activities of polysaccharides from Taraxacum officinale (TOP 1 and 2) were analyzed in RAW 264.7 cells. First, lipopolysaccharide (LPS) was applied to identify anti-inflammatory activity of TOPs, which reduced expression of inducible nitric oxide synthase (iNOS) and tumor necrosis factor (TNF)-α. TOPs treatment inhibited phosphorylation of inflammatory transcription factor, nuclear factor (NF)κB, and its upstream signaling molecule, PI3K/Akt. Second, cytoprotective potential of TOPs against oxidative stress was investigated via heme oxygenase (HO)-1 induction. HO-1, one of phase II enzymes shows antioxidative activity, was potently induced by TOPs treatment, which was in accordance with the nuclear translocation of nuclear factor-erythroid 2 p45-related factor 2 (Nrf2). In addition, TOPs treatment phosphorylated PI3K/Akt with slight activation of c-Jun NH2-terminal kinase (JNK). TOPs-mediated HO-1 induction protected macrophage cells from oxidative stress-induced cell death, which was confirmed by SnPP and CoPP (HO-1 inhibitor and inducer, respectively). Consequently, TOPs potently inhibited NFκB-mediated inflammation and accelerated Nrf2-mediated antioxidative potential through the modulation of PI3K/Akt pathway, which would contribute to their promising strategy for novel anti-inflammatory and anti-oxidative agents.

  8. Novel durable bio-photocatalyst purifiers, a non-heterogeneous mechanism: accelerated entrapped dye degradation into structural polysiloxane-shield nano-reactors.

    PubMed

    Dastjerdi, Roya; Montazer, Majid; Shahsavan, Shadi; Böttcher, Horst; Moghadam, M B; Sarsour, Jamal

    2013-01-01

    This research has designed innovative Ag/TiO(2) polysiloxane-shield nano-reactors on the PET fabric to develop novel durable bio-photocatalyst purifiers. To create these very fine nano-reactors, oppositely surface charged multiple size nanoparticles have been applied accompanied with a crosslinkable amino-functionalized polysiloxane (XPs) emulsion. Investigation of photocatalytic dye decolorization efficiency revealed a non-heterogeneous mechanism including an accelerated degradation of entrapped dye molecules into the structural polysiloxane-shield nano-reactors. In fact, dye molecules can be adsorbed by both Ag and XPs due to their electrostatic interactions and/or even via forming a complex with them especially with silver NPs. The absorbed dye and active oxygen species generated by TiO(2) were entrapped by polysiloxane shelter and the presence of silver nanoparticles further attract the negative oxygen species closer to the adsorbed dye molecules. In this way, the dye molecules are in close contact with concentrated active oxygen species into the created nano-reactors. This provides an accelerated degradation of dye molecules. This non-heterogeneous mechanism has been detected on the sample containing all of the three components. Increasing the concentration of Ag and XPs accelerated the second step beginning with an enhanced rate. Further, the treated samples also showed an excellent antibacterial activity.

  9. Neisseria gonorrhoeae O-linked pilin glycosylation: functional analyses define both the biosynthetic pathway and glycan structure

    PubMed Central

    Aas, Finn Erik; Vik, Åshild; Vedde, John; Koomey, Michael; Egge-Jacobsen, Wolfgang

    2007-01-01

    Neisseria gonorrhoeae expresses an O-linked protein glycosylation pathway that targets PilE, the major pilin subunit protein of the Type IV pilus colonization factor. Efforts to define glycan structure and thus the functions of pilin glycosylation (Pgl) components at the molecular level have been hindered by the lack of sensitive methodologies. Here, we utilized a ‘top-down’ mass spectrometric approach to characterize glycan status using intact pilin protein from isogenic mutants. These structural data enabled us to directly infer the function of six components required for pilin glycosylation and to define the glycan repertoire of strain N400. Additionally, we found that the N. gonorrhoeae pilin glycan is O-acetylated, and identified an enzyme essential for this unique modification. We also identified the N. gonorrhoeae pilin oligosaccharyltransferase using bioinformatics and confirmed its role in pilin glycosylation by directed mutagenesis. Finally, we examined the effects of expressing the PglA glycosyltransferase from the Campylobacter jejuni N-linked glycosylation system that adds N-acetylgalactosamine onto undecaprenylpyrophosphate-linked bacillosamine. The results indicate that the C. jejuni and N. gonorrhoeae pathways can interact in the synthesis of O-linked di- and trisaccharides, and therefore provide the first experimental evidence that biosynthesis of the N. gonorrhoeae pilin glycan involves a lipid-linked oligosaccharide precursor. Together, these findings underpin more detailed studies of pilin glycosylation biology in both N. gonorrhoeae and N. meningitidis, and demonstrate how components of bacterial O- and N-linked pathways can be combined in novel glycoengineering strategies. PMID:17608667

  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. Chordin and dickkopf-1b are essential for the formation of head structures through activation of the FGF signaling pathway in zebrafish.

    PubMed

    Tanaka, Shingo; Hosokawa, Hiroshi; Weinberg, Eric S; Maegawa, Shingo

    2017-04-15

    The ability of the Spemann organizer to induce dorsal axis formation is dependent on downstream factors of the maternal Wnt/β-catenin signaling pathway. The fibroblast growth factor (FGF) signaling pathway has been identified as one of the downstream components of the maternal Wnt/β-catenin signaling pathway. The ability of the FGF signaling pathway to induce the formation of a dorsal axis with a complete head structure requires chordin (chd) expression; however, the molecular mechanisms involved in this developmental process, due to activation of FGF signaling, remain unclear. In this study, we showed that activation of the FGF signaling pathway induced the formation of complete head structures through the expression of chd and dickkopf-1b (dkk1b). Using the organizer-deficient maternal mutant, ichabod, we identified dkk1b as a novel downstream factor in the FGF signaling pathway. We also demonstrate that dkk1b expression is necessary, after activation of the FGF signaling pathway, to induce neuroectoderm patterning along the anteroposterior (AP) axis and for formation of complete head structures. Co-injection of chd and dkk1b mRNA resulted in the formation of a dorsal axis with a complete head structure in ichabod embryos, confirming the role of these factors in this developmental process. Unexpectedly, we found that chd induced dkk1b expression in ichabod embryos at the shield stage. However, chd failed to maintain dkk1b expression levels in cells of the shield and, subsequently, in the cells of the prechordal plate after mid-gastrula stage. In contrast, activation of the FGF signaling pathway maintained the dkk1b expression from the beginning of gastrulation to early somitogenesis. In conclusion, activation of the FGF signaling pathway induces the formation of a dorsal axis with a complete head structure through the expression of chd and subsequent maintenance of dkk1b expression levels.

  12. An attempt to validate the ultra-accelerated microbar and the concrete performance test with the degree of AAR-induced damage observed in concrete structures

    SciTech Connect

    Leemann, Andreas; Merz, Christine

    2013-07-15

    There is little knowledge about the relation between AAR-induced damage observed in structures and the expansion potential obtained with accelerated tests. In this study, aggregates used in structures damaged by AAR were tested with the microbar test (MBT/AFNOR XP 18-594) and the concrete performance test (CPT/AFNOR P18-454). After the tests, the samples were examined using optical and scanning electron microscopy. Based on the results, the significance of the microbar test has to be examined very critically. The agreement of measured expansion, reacted rock types and the composition of the reaction products between the on-site concrete and the reproduced concrete subjected to the CPT clearly indicates that the reaction mechanisms in the structure and in the concrete performance test are comparable. As such, the concrete performance test seems to be an appropriate tool to test the potential reactivity of specific concrete mixtures.

  13. Biochemical and structural characterization of Klebsiella pneumoniae oxamate amidohydrolase in the uric acid degradation pathway

    SciTech Connect

    Hicks, Katherine A.; Ealick, Steven E.

    2016-05-25

    HpxW from the ubiquitous pathogenKlebsiella pneumoniaeis 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.

  14. Bacterial community structure and predicted alginate metabolic pathway in an alginate-degrading bacterial consortium.

    PubMed

    Kita, Akihisa; Miura, Toyokazu; Kawata, Satoshi; Yamaguchi, Takeshi; Okamura, Yoshiko; Aki, Tsunehiro; Matsumura, Yukihiko; Tajima, Takahisa; Kato, Junichi; Nishio, Naomichi; Nakashimada, Yutaka

    2016-03-01

    Methane fermentation is one of the effective approaches for utilization of brown algae; however, this process is limited by the microbial capability to degrade alginate, a main polysaccharide found in these algae. Despite its potential, little is known about anaerobic microbial degradation of alginate. Here we constructed a bacterial consortium able to anaerobically degrade alginate. Taxonomic classification of 16S rRNA gene, based on high-throughput sequencing data, revealed that this consortium included two dominant strains, designated HUA-1 and HUA-2; these strains were related to Clostridiaceae bacterium SK082 (99%) and Dysgonomonas capnocytophagoides (95%), respectively. Alginate lyase activity and metagenomic analyses, based on high-throughput sequencing data, revealed that this bacterial consortium possessed putative genes related to a predicted alginate metabolic pathway. However, HUA-1 and 2 did not grow on agar medium with alginate by using roll-tube method, suggesting the existence of bacterial interactions like symbiosis for anaerobic alginate degradation.

  15. A visual pathway links brain structures active during magnetic compass orientation in migratory birds.

    PubMed

    Heyers, Dominik; Manns, Martina; Luksch, Harald; Güntürkün, Onur; Mouritsen, Henrik

    2007-09-26

    The magnetic compass of migratory birds has been suggested to be light-dependent. Retinal cryptochrome-expressing neurons and a forebrain region, "Cluster N", show high neuronal activity when night-migratory songbirds perform magnetic compass orientation. By combining neuronal tracing with behavioral experiments leading to sensory-driven gene expression of the neuronal activity marker ZENK during magnetic compass orientation, we demonstrate a functional neuronal connection between the retinal neurons and Cluster N via the visual thalamus. Thus, the two areas of the central nervous system being most active during magnetic compass orientation are part of an ascending visual processing stream, the thalamofugal pathway. Furthermore, Cluster N seems to be a specialized part of the visual wulst. These findings strongly support the hypothesis that migratory birds use their visual system to perceive the reference compass direction of the geomagnetic field and that migratory birds "see" the reference compass direction provided by the geomagnetic field.

  16. Structural basis of the recognition of the dishevelled DEP domain in the Wnt signaling pathway.

    PubMed

    Wong, H C; Mao, J; Nguyen, J T; Srinivas, S; Zhang, W; Liu, B; Li, L; Wu, D; Zheng, J

    2000-12-01

    The DEP domain of Dishevelled (Dvl) proteins transduces signals to effector proteins downstream of Dvl in the Wnt pathway. Here we report that DEP-containing mutants inhibit Wnt-induced, but not Dvl-induced, activation of the transcription factor Lef-1. This inhibitory effect is weakened by a K434M mutation. Nuclear magnetic resonance spectroscopy revealed that the DEP domain of mouse Dvl1 comprises a three-helix bundle, a beta-hairpin 'arm' and two short beta-strands at the C-terminal region. Lys 434 is located at the tip of the beta-hairpin 'arm'. Based on our findings, we conclude that DEP interacts with regulators upstream of Dvl via a strong electric dipole on the molecule's surface created by Lys 434, Asp 445 and Asp 448; the electric dipole and the putative membrane binding site are at two different locations.

  17. 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

  18. Structural and electronic transformation pathways in morphotropic BiFeO3

    NASA Astrophysics Data System (ADS)

    Sharma, P.; Heo, Y.; Jang, B.-K.; Liu, Y. Y.; Li, J. Y.; Yang, C.-H.; Seidel, J.

    2016-09-01

    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.

  19. Crustal magma pathway beneath Aso caldera inferred from three-dimensional electrical resistivity structure

    NASA Astrophysics Data System (ADS)

    Hata, Maki; Takakura, Shinichi; Matsushima, Nobuo; Hashimoto, Takeshi; Utsugi, Mitsuru

    2016-10-01

    At Naka-dake cone, Aso caldera, Japan, volcanic activity is raised cyclically, an example of which was a phreatomagmatic eruption in September 2015. Using a three-dimensional model of electrical resistivity, we identify a magma pathway from a series of northward dipping conductive anomalies in the upper crust beneath the caldera. Our resistivity model was created from magnetotelluric measurements conducted in November-December 2015; thus, it provides the latest information about magma reservoir geometry beneath the caldera. The center of the conductive anomalies shifts from the north of Naka-dake at depths >10 km toward Naka-dake, along with a decrease in anomaly depths. The melt fraction is estimated at 13-15% at 2 km depth. Moreover, these anomalies are spatially correlated with the locations of earthquake clusters, which are distributed within resistive blocks on the conductive anomalies in the northwest of Naka-dake but distributed at the resistive sides of resistivity boundaries in the northeast.

  20. 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

  1. Single-shot, ultrafast diagnostics of light-speed plasma structures and accelerating GeV electrons

    NASA Astrophysics Data System (ADS)

    Chang, Yen-Yu; Shaw, Joseph M.; Welch, James; Weichman, Kathleen; Hannasch, Andrea; LaBerge, Maxwell; Henderson, Watson; Zgadzaj, Rafal; Bernstein, Aaron; Downer, Mike

    2017-03-01

    We have experimentally demonstrated ultrafast diagnostics to visualize the laser wakefield acceleration process in a single-shot mode. We measured the Faraday rotation of a probe pulse due to the magnetic field induced by GeV electrons in low-density plasmas. In addition, we improved the temporal resolution of Frequency Domain Streak Camera (FDSC) to ˜10 fs by broadening the bandwidth of the probe beam, enabling visualization of the bubble dynamics. A prototype experiment using the broad bandwidth FDSC was performed.

  2. Acceleration Studies

    NASA Technical Reports Server (NTRS)

    Rogers, Melissa J. B.

    1993-01-01

    Work to support the NASA MSFC Acceleration Characterization and Analysis Project (ACAP) was performed. Four tasks (analysis development, analysis research, analysis documentation, and acceleration analysis) were addressed by parallel projects. Work concentrated on preparation for and implementation of near real-time SAMS data analysis during the USMP-1 mission. User support documents and case specific software documentation and tutorials were developed. Information and results were presented to microgravity users. ACAP computer facilities need to be fully implemented and networked, data resources must be cataloged and accessible, future microgravity missions must be coordinated, and continued Orbiter characterization is necessary.

  3. Accelerators for America's Future

    NASA Astrophysics Data System (ADS)

    Bai, Mei

    2016-03-01

    Particle accelerator, a powerful tool to energize beams of charged particles to a desired speed and energy, has been the working horse for investigating the fundamental structure of matter and fundermental laws of nature. Most known examples are the 2-mile long Stanford Linear Accelerator at SLAC, the high energy proton and anti-proton collider Tevatron at FermiLab, and Large Hadron Collider that is currently under operation at CERN. During the less than a century development of accelerator science and technology that led to a dazzling list of discoveries, particle accelerators have also found various applications beyond particle and nuclear physics research, and become an indispensible part of the economy. Today, one can find a particle accelerator at almost every corner of our lives, ranging from the x-ray machine at the airport security to radiation diagnostic and therapy in hospitals. This presentation will give a brief introduction of the applications of this powerful tool in fundermental research as well as in industry. Challenges in accelerator science and technology will also be briefly presented

  4. Active vibration control of structure by Active Mass Damper and Multi-Modal Negative Acceleration Feedback control algorithm

    NASA Astrophysics Data System (ADS)

    Yang, Don-Ho; Shin, Ji-Hwan; Lee, HyunWook; Kim, Seoug-Ki; Kwak, Moon K.

    2017-03-01

    In this study, an Active Mass Damper (AMD) consisting of an AC servo motor, a movable mass connected to the AC servo motor by a ball-screw mechanism, and an accelerometer as a sensor for vibration measurement were considered. Considering the capability of the AC servo motor which can follow the desired displacement accurately, the Negative Acceleration Feedback (NAF) control algorithm which uses the acceleration signal directly and produces the desired displacement for the active mass was proposed. The effectiveness of the NAF control was proved theoretically using a single-degree-of-freedom (SDOF) system. It was found that the stability condition for the NAF control is static and it can effectively increase the damping of the target natural mode without causing instability in the low frequency region. Based on the theoretical results of the SDOF system, the Multi-Modal NAF (MMNAF) control is proposed to suppress the many natural modes of multi-degree-of-freedom (MDOF) systems using a single AMD. It was proved both theoretically and experimentally that the MMNAF control can suppress vibrations of the MDOF system.

  5. Prospects in Nuclear Structure and Reactions with New Generation of High Power Accelerators and Innovative Instrumentation in Europe

    NASA Astrophysics Data System (ADS)

    Gales, S.

    2014-09-01

    The advent of high power light and heavy ion accelerators producing intense secondary radioactive ion beams (RIB) made possible the exploration of a new territory of nuclei with extreme in Mass and/or N/Z ratios. To pursue the investigation of this "terra incognita" several projects, based on second generation accelerators producing intense stables and RIB, all aiming at the increase by several orders of magnitude of the RIB intensities are now under construction and/or planned for the end of this decade in the world. In Europe RIB production at SPES@Legnaro, SPIRAL2@GANIL, ALTO@Orsay and HIE-ISOLDE@CERN are based on the ISOL method, whereas FAIR@GSI with the new Super-FRS fragment-separator takes advantage of the "In Flight" technique. Projects of high intensity heavy ions, and low energy drivers (< 10 MeV/n) are also foreseen at Flerov Laboratory @DUBNA, GSI, and GANIL. Technical performances, innovative new instrumentation and methods, and keys experiments in connection with these second generation high intensity facilities will be reviewed.

  6. 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

  7. Plasma accelerator

    DOEpatents

    Wang, Zhehui; Barnes, Cris W.

    2002-01-01

    There has been invented an apparatus for acceleration of a plasma having coaxially positioned, constant diameter, cylindrical electrodes which are modified to converge (for a positive polarity inner electrode and a negatively charged outer electrode) at the plasma output end of the annulus between the electrodes to achieve improved particle flux per unit of power.

  8. Accelerated Achievement

    ERIC Educational Resources Information Center

    Ford, William J.

    2010-01-01

    This article focuses on the accelerated associate degree program at Ivy Tech Community College (Indiana) in which low-income students will receive an associate degree in one year. The three-year pilot program is funded by a $2.3 million grant from the Lumina Foundation for Education in Indianapolis and a $270,000 grant from the Indiana Commission…

  9. ACCELERATION INTEGRATOR

    DOEpatents

    Pope, K.E.

    1958-01-01

    This patent relates to an improved acceleration integrator and more particularly to apparatus of this nature which is gyrostabilized. The device may be used to sense the attainment by an airborne vehicle of a predetermined velocitv or distance along a given vector path. In its broad aspects, the acceleration integrator utilizes a magnetized element rotatable driven by a synchronous motor and having a cylin drical flux gap and a restrained eddy- current drag cap deposed to move into the gap. The angular velocity imparted to the rotatable cap shaft is transmitted in a positive manner to the magnetized element through a servo feedback loop. The resultant angular velocity of tae cap is proportional to the acceleration of the housing in this manner and means may be used to measure the velocity and operate switches at a pre-set magnitude. To make the above-described dcvice sensitive to acceleration in only one direction the magnetized element forms the spinning inertia element of a free gyroscope, and the outer housing functions as a gimbal of a gyroscope.

  10. NMR structure of bitistatin – a missing piece in the evolutionary pathway of snake venom disintegrins.

    PubMed

    Carbajo, Rodrigo J; Sanz, Libia; Perez, Alicia; Calvete, Juan J

    2015-01-01

    Extant disintegrins, as found in the venoms of Viperidae and Crotalidae snakes (vipers and rattlesnakes, represent a family of polypeptides that block the function of β1 and β3 integrin receptors, both potently and with a high degree of selectivity. This toxin family owes its origin to the neofunctionalization of the extracellular region of an ADAM (a disintegrin and metalloprotease) molecule recruited into the snake venom gland proteome in the Jurassic. The evolutionary structural diversification of the disintegrin scaffold, from the ancestral long disintegrins to the more recently evolved medium-sized, dimeric and short disintegrins, involved the stepwise loss of pairs of class-specific disulfide linkages and the processing of the N-terminal region. NMR and crystal structures of medium-sized, dimeric and short disintegrins have been solved. However, the structure of a long disintegrin remained unknown. The present study reports the NMR solution structures of two disulfide bond conformers of the long disintegrin bitistatin from the African puff adder Bitis arietans. The findings provide insight into how a structural domain of the extracellular region of an ADAM molecule, recruited into and selectively expressed in the snake venom gland proteome as a PIII metalloprotease in the Jurassic, has subsequently been tranformed into a family of integrin receptor antagonists.

  11. Advanced accelerator theory development

    SciTech Connect

    Sampayan, S.E.; Houck, T.L.; Poole, B.; Tishchenko, N.; Vitello, P.A.; Wang, I.

    1998-02-09

    A new accelerator technology, the dielectric wall accelerator (DWA), is potentially an ultra compact accelerator/pulsed power driver. This new accelerator relies on three new components: the ultra-high gradient insulator, the asymmetric Blumlein and low jitter switches. In this report, we focused our attention on the first two components of the DWA system the insulators and the asymmetric Blumlein. First, we sought to develop the necessary design tools to model and scale the behavior of the high gradient insulator. To perform this task we concentrated on modeling the discharge processes (i.e., initiation and creation of the surface discharge). In addition, because these high gradient structures exhibit favorable microwave properties in certain accelerator configurations, we performed experiments and calculations to determine the relevant electromagnetic properties. Second, we performed circuit modeling to understand energy coupling to dynamic loads by the asymmetric Blumlein. Further, we have experimentally observed a non-linear coupling effect in certain asymmetric Blumlein configurations. That is, as these structures are stacked into a complete module, the output voltage does not sum linearly and a lower than expected output voltage results. Although we solved this effect experimentally, we performed calculations to understand this effect more fully to allow better optimization of this DWA pulse-forming line system.

  12. Pathways to seeing music: enhanced structural connectivity in colored-music synesthesia.

    PubMed

    Zamm, Anna; Schlaug, Gottfried; Eagleman, David M; Loui, Psyche

    2013-07-01

    Synesthesia, a condition in which a stimulus in one sensory modality consistently and automatically triggers concurrent percepts in another modality, provides a window into the neural correlates of cross-modal associations. While research on grapheme-color synesthesia has provided evidence for both hyperconnectivity-hyperbinding and disinhibited feedback as potential underlying mechanisms, less research has explored the neuroanatomical basis of other forms of synesthesia. In the current study we investigated the white matter correlates of colored-music synesthesia. As these synesthetes report seeing colors upon hearing musical sounds, we hypothesized that they might show unique patterns of connectivity between visual and auditory association areas. We used diffusion tensor imaging to trace the white matter tracts in temporal and occipital lobe regions in 10 synesthetes and 10 matched non-synesthete controls. Results showed that synesthetes possessed hemispheric patterns of fractional anisotropy, an index of white matter integrity, in the inferior fronto-occipital fasciculus (IFOF), a major white matter pathway that connects visual and auditory association areas to frontal regions. Specifically, white matter integrity within the right IFOF was significantly greater in synesthetes than controls. Furthermore, white matter integrity in synesthetes was correlated with scores on audiovisual tests of the Synesthesia Battery, especially in white matter underlying the right fusiform gyrus. Our findings provide the first evidence of a white matter substrate of colored-music synesthesia, and suggest that enhanced white matter connectivity is involved in enhanced cross-modal associations.

  13. 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.

  14. 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…

  15. Bilingualism modulates the white matter structure of language-related pathways.

    PubMed

    Hämäläinen, Sini; Sairanen, Viljami; Leminen, Alina; Lehtonen, Minna

    2017-03-02

    Learning and speaking a second language (L2) may result in profound changes in the human brain. Here, we investigated local structural differences along two language-related white matter trajectories, the arcuate fasciculus and the inferior fronto-occipital fasciculus (IFOF), between early simultaneous bilinguals and late sequential bilinguals. We also examined whether early exposure to two languages might lead to a more bilateral structural organization of the arcuate fasciculus. Fractional anisotropy, mean and radial diffusivities (FA, MD, and RD respectively) were extracted to analyse tract-specific changes. Additionally, global voxel-wise effects were investigated with Tract-Based Spatial Statistics (TBSS). We found that relative to late exposure, early exposure to L2 leads to increased FA along a phonology-related segment of the arcuate fasciculus, but induces no modulations along the IFOF, associated to semantic processing. Late sequential bilingualism, however, was associated with decreased MD along the bilateral IFOF. Our results suggest that early vs. late bilingualism may lead to qualitatively different kind of changes in the structural language-related network. Furthermore, we show that early bilingualism contributes to the structural laterality of the arcuate fasciculus, leading to a more bilateral organization of these perisylvian language-related tracts.

  16. 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…

  17. Study of Structure and Deformation Pathways in Ti-7Al Using Atomistic Simulations, Experiments, and Characterization

    NASA Astrophysics Data System (ADS)

    Venkataraman, Ajey; Shade, Paul A.; Adebisi, R.; Sathish, S.; Pilchak, Adam L.; Viswanathan, G. Babu; Brandes, Matt C.; Mills, Michael J.; Sangid, Michael D.

    2017-03-01

    Ti-7Al is a good model material for mimicking the α phase response of near-α and α+β phases of many widely used titanium-based engineering alloys, including Ti-6Al-4V. In this study, three model structures of Ti-7Al are investigated using atomistic simulations by varying the Ti and Al atom positions within the crystalline lattice. These atomic arrangements are based on transmission electron microscopy observations of short-range order. The elastic constants of the three model structures considered are calculated using molecular dynamics simulations. Resonant ultrasound spectroscopy experiments are conducted to obtain the elastic constants at room temperature and a good agreement is found between the simulation and experimental results, providing confidence that the model structures are reasonable. Additionally, energy barriers for crystalline slip are established for these structures by means of calculating the γ-surfaces for different slip systems. Finally, the positions of Al atoms in regards to solid solution strengthening are studied using density functional theory simulations, which demonstrate a higher energy barrier for slip when the Al solute atom is closer to (or at) the fault plane. These results provide quantitative insights into the deformation mechanisms of this alloy.

  18. 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 com